Language：English   Publishing type：Research paper (scientific journal)  

Anaesthetics may modify colorectal cancer cell biology which potentially affects long-term survival. This study aims to compare propofol and sevoflurane regarding with the direct anaesthetic effects on cancer malignancy and the indirect effects on host immunity in a cancer xenograft mode of mice. Cultured colon cancer cell (Caco-2) was injected subcutaneously to nude mice (day 1). Mice were exposed to either 1.5% sevoflurane for 1.5 h or propofol (20 μg g-1; ip injection) with or without 4 μg g-1 lipopolysaccharide (LPS; ip) from days 15 to 17, compared with those without anaesthetic exposure as controls. The clinical endpoints including tumour volumes over 70 mm3 were closely monitored up to day 28. Tumour samples from the other cohorts were collected on day 18 for PCR array, qRT-PCR, western blotting and immunofluorescent assessment. Propofol treatment reduced tumour size (mean ± SD; 23.0 ± 6.2mm3) when compared to sevoflurane (36.0 ± 0.3mm3) (p = 0.008) or control (23.6 ± 4.7mm3). Propofol decreased hypoxia inducible factor 1α (HIF1α), interleukin 1β (IL1β), and hepatocyte growth factor (HGF) gene expressions and increased tissue inhibitor of metalloproteinases 2 (TIMP-2) gene and protein expression in comparison to sevoflurane in the tumour tissue. LPS suppressed tumour growth in any conditions whilst increased TIMP-2 and anti-cancer neutrophil marker expressions and decreased macrophage marker expressions compared to those in the LPS-untreated groups. Our data indicated that sevoflurane increased cancer development when compared with propofol in vivo under non-surgical condition. Anaesthetics tested in this study did not alter the effects of LPS as an immune modulator in changing immunocyte phenotype and suppressing cancer development.

DOI： 10.1007/s10565-022-09747-9

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BACKGROUND: A growing number of older patients are undergoing surgeries. The reliable pre-operative predictive factors of surgical mortality among older patients remained unclear. This study compared the predictive factors for 30-day survival in patients over 90 years old after their non-cardiac surgery. METHODS: A retrospective study at Nippon Medical School hospital was performed for patients aged >90 years who underwent non-cardiac surgeries between 2010 and 2020. Measurements included age, gender, American Society of Anesthesiologists physical status (ASA-PS), pre-operative Charlson score, pre-operative fall risk assessment, Eastern Cooperative Oncology Group performance status (ECOG-PS), the modified 5-item frailty index (mFI-5), the presence of intra-operative transfusion, post-operative complications, and 30-day survival post-surgery. RESULTS: A total of 327 cases of elective surgery and 149 cases of emergency surgery were examined. The non-survival group (n=20, 4.2%) had significantly worse pre-operative ASA-PS in emergency cases (non-survival vs. survivor group, 2.8 [2-3] vs. 2.3 [1-4], p=0.045), ECOG-PS (3.0 [2-4] vs. 1.0 [0-4], p<0.001), and mFI-5 values (3.0 [1-4] vs. 1.0 [0-3], p<0.001), more emergency cases (75.0% vs. 36.2%, p=0.004), and a greater need for intra-operative transfusion (55.0% vs. 13.4%, p<0.001). Among the frailty assessment methods, ECOG-PS was the most efficient for 30-day mortality (area under curve, ECOG-PS: 0.98, p<0.001; mFI-5: 0.86, p<0.001; Charlson score: 0.53, p=0.71; fall risk assessment: 0.55, p=0.44). Kaplan-Maier curves and a multivariate logistic regression analysis demonstrated that ECOG-PS>3 was significantly associated with 30-day mortality (ECOG-PS: Kaplan-Maier curve, p<0.001, Log-rank test; odds ratio 1.71, 95%CI: 1.35-2.16, p<0.001). CONCLUSIONS: After non-cardiac surgery in patients >90 years old, ECOG-PS>3 was significantly correlated with 30-day mortality.

DOI： 10.1272/jnms.JNMS.2022_89-304

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Inhalational anesthetics was previously reported to suppress glioma cell malignancy but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNAs upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.

DOI： 10.3390/ijms22094355

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Language：Japanese   Publisher：日本医科大学医学会  

麻酔薬は遺伝子発現変化を介し生体に影響を与えることが明らかとなり、その研究過程で翻訳後修飾の主体としてmicroRNA(miRNA)をはじめとする小分子RNAの関与が示され、麻酔薬の作用にも関係していることが示唆された。周術期に疾患特有のmiRNAを抑制する麻酔薬の使用、あるいはmiRNA薬剤投与が生命予後改善をもたらす可能性がある。miRNAを介した術後疼痛、癌、臓器障害、麻酔(麻酔薬)への作用について解説した。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04260&link_issn=&doc_id=20210514340005&doc_link_id=%2Fcw1nimed%2F2021%2F001702%2F006%2F0072-0080%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw1nimed%2F2021%2F001702%2F006%2F0072-0080%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: microRNAs (miRNAs) are single-stranded and noncoding RNA molecules that control post-transcriptional gene regulation. miRNAs can be tumor suppressors or oncogenes through various mechanism including cancer cell biology, cell-to-cell communication, and anti-cancer immunity. MAIN BODY: Anesthetics can affect cell biology through miRNA-mediated regulation of messenger RNA (mRNA). Indeed, sevoflurane was reported to upregulate miR-203 and suppresses breast cancer cell proliferation. Propofol reduces matrix metalloproteinase expression through its impact on miRNAs, leading to anti-cancer microenvironmental changes. Propofol also modifies miRNA expression profile in circulating extracellular vesicles with their subsequent anti-cancer effects via modulating cell-to-cell communication. CONCLUSION: Inhalational and intravenous anesthetics can alter cancer cell biology through various cellular signaling pathways induced by miRNAs' modification. However, this area of research is insufficient and further study is needed to figure out optimal anesthesia regimens for cancer patients.

DOI： 10.1186/s12871-021-01294-w

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Inhalational anaesthetics were previously reported to promote ovarian cancer malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the role of sevoflurane- or desflurane-induced microRNA (miRNA) changes on ovarian cancer cell behaviour. The cultured SKOV3 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. Expression of miR-138, -210 and -335 was determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and Cell Counting Kit-8 (CCK8) assay with or without mimic miR-138/-210 transfections. The miRNA downstream effector, hypoxia inducible factor-1α (HIF-1α), was also analysed with immunofluorescent staining. Sevoflurane or desflurane exposure to cancer cells enhanced their proliferation and migration. miR-138 expression was suppressed by both sevoflurane and desflurane, while miR-210 expression was suppressed only by sevoflurane. miR-335 expression was not changed by either sevoflurane or desflurane exposure. The administration of mimic miR-138 or -210 reduced the promoting effects of sevoflurane and desflurane on cancer cell proliferation and migration, in line with the HIF-1α expression changes. These data indicated that inhalational agents sevoflurane and desflurane enhanced ovarian cancer cell malignancy via miRNA deactivation and HIF-1α. The translational value of this work needs further study.

DOI： 10.3390/ijms22041826

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PURPOSE: The purpose of this pre-post survey study was to assess the effect of the Patient SafetyNet system (Masimo Corp, Irvine, CA) on postoperative respiratory evaluation by nurses in general wards. Patient SafetyNet is a wireless monitoring system that evaluates respiratory rate and percutaneous oxygen saturation. DESIGN: Survey of nurses at a single medical center. METHODS: Staff nurses (n = 75) were queried using a questionnaire asking about methods and problems of postoperative respiratory monitoring, usefulness of this system, and suggestions about suitable cases of this system. FINDINGS: A total of 75 questionnaires were completed and returned. The nurses reported that central/remote (89.3%) or continuous (98.7%) monitoring was useful in the postquestionnaire. Moreover, the average frequency of clinical examination was reduced from 11.0 ± 2.3 to 5.1 ± 1.3. Using the Patient SafetyNet system led to a reported 61.3% reduction in nursing workload related to respiratory assessment postoperatively. CONCLUSIONS: Continuous monitoring of respiratory rate and percutaneous oxygen saturation after general anesthesia is recommended for patients' safety. Moreover, Patient SafetyNet can decrease the number of physical assessments of respiratory status for postoperative patients in the general wards, resulting in reduction of nurse's workload.

DOI： 10.1016/j.jopan.2020.03.005

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Budd-Chiari syndrome (BCS) is a rare congestive hepatopathy arising from hepatic venous outflow obstruction. The clinical presentation of BCS varies depending on the presence of collateral veins. The authors report a rare case of infective endocarditis and chronic primary BCS in a 50-year-old man who underwent open cardiac surgery. Due to the presence of dilated collateral veins flowing directly into the inferior vena cava, cardiopulmonary bypass was established by arterial cannulation of the ascending aorta, with venous cannulation of the upper portion of the superior vena cava, as well as the dilated collateral vein. Mitral valve replacement and tricuspid valvuloplasty were performed uneventfully, and the patient then was admitted to the intensive care unit. Patients with primary BCS need to be evaluated rigorously preoperatively and intraoperatively for collateral flow to establish cardiopulmonary bypass.

DOI： 10.1053/j.jvca.2020.11.063

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DOI： 10.1016/S0140-6736(20)30488-8

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There are concerns regarding overtreatment in papillary thyroid carcinoma (PTC). BRAF V600E and TERT promoter mutations play important roles in the development of PTC. However, initial surgical approaches for PTC based on genetic characteristics remain unclear. The present study aimed to identify genetic mutations as predictors of prognosis and to establish proper indications for lobectomy (LT) in patients with 1-4 cm intrathyroidal PTC. Prospectively accumulated data from 685 consecutive patients with PTC who underwent primary thyroid surgery at the Cancer Institute Hospital, Tokyo, Japan, between 2001 and 2012 were retrospectively reviewed. Of the 685 patients examined, 538 (78.5%) had BRAF V600E mutation and 133 (19.4%) had TERT promoter mutations. Patients with TERT promoter mutations displayed significantly worse outcomes than those without mutations (10-year cause-specific survival (CSS): 73.7% vs. 98.1%, p < 0.001; 10-year disease-free survival (DFS): 53.7% vs. 93.3%, p < 0.001). As for extent of thyroidectomy among TERT mutation-negative patients with 1-4 cm intrathyroidal PTC, patients who underwent LT showed no significant differences in 10-year CSS and 10-year DFS compared to patients who had total thyroidectomy (TT) under propensity score-matching. Avoiding TT for those patients indicates a possible pathway to prevent overtreatment and reduce postoperative complications.

DOI： 10.3390/cancers12082115

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The kidneys are prone to developing ischemia reperfusion injury (IRI) following certain renal surgeries and cardiovascular surgeries requiring cardiac arrest. Sevoflurane and ischemic preconditioning reportedly alleviate IRI, which is mediated via microRNAs. The present study compared anesthetic preconditioning (APC) and ischemic preconditioning (IPC) on microRNAs, which promote cell‑survival pathways in rats in a randomized controlled study. After undergoing right nephrectomy under general anesthesia, male Wistar rats (336±24 g) and were divided into four groups (IRI, APC, IPC and sham; n=7 each). The IRI group underwent 45 min clamping of the left renal vasculature, followed by 4 h of reperfusion. APC involved exposure to one minimum alveolar concentration sevoflurane for 15 min. IPC included three cycles of two‑min clamping and five‑min reperfusion. Blood and renal biopsy samples were assessed postoperatively to measure serum creatinine and to analyze renal microRNA (miR) expression using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) testing and their target pathways with Ingenuity Pathway Analysis™. The present study found that serum creatinine values in APC (0.71±0.08 mg/dl) and IPC (0.73±0.1 mg/dl) groups were lower than in the IRI group (0.96±0.13 mg/dl; P<0.05), indicating amelioration of IRI by APC and IPC. RT‑qPCR followed by pathway analysis indicated that APC and IPC affect 'protein kinase B (Akt)'. APC promoted miR‑17‑3p and suppressed miR‑27a. IPC promoted miR‑19a. All the miRs were predicted to regulate phosphorylated Akt, which promotes cell‑protection. Western blot analysis showed that expression of phosphorylated Akt increased and phosphatase and tensin homologue deleted from chromosome 10 (PTEN) decreased following APC and IPC. The present study concluded that APC and IPC affect different miRs, although they are estimated to similarly promote the PTEN/phosphoinositide 3‑kinase/Akt signaling pathway, resulting in reno‑protection.

DOI： 10.3892/ijmm.2020.4477

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DOI： 10.1007/s10877-019-00358-0

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Language：Japanese   Publisher：日本手術医学会  

本邦では周術期管理の向上により手術適応範囲が拡大し、全身麻酔症例は増加傾向にある。しかし、循環器合併症や抗血小板薬・抗凝固薬の休薬は手術決定に多大な影響を与え、手術中止の主因となっている。そのため、内科医、薬剤師など多職種による術前評価、周術期管理計画が必要である。今回、この2点を含め当院における周術期外来への取り組みをまとめる。周術期合併症として、循環器合併症、呼吸器合併症、感染などが挙げられる。その中でも周術期循環器合併症は、発生頻度は低いものの死亡率は高く重篤なものである。当院では本邦のガイドラインをベースに、循環器内科と共同で術前評価フローチャートを作成した。フローチャートは、外科外来で実施可能な簡便なものであること、循環器内科・麻酔科にコンサルトすべきかどうか明らかになることに要点を置いている。虚血性疾患、あるいは、不整脈の合併により抗血小板薬・抗凝固薬を内服している症例は増えている。これまで各科判断にて休薬をしていたが、不適切な休薬期間により手術を延期しなければならない症例があった。当院では周術期管理と区域麻酔における休薬プロトコールを定めた。これは区域麻酔など外科的止血ができない侵襲的手技において、より厳格な休薬を定め安全性を保つことを目的としている。薬剤師外来、病棟薬剤師、手術室薬剤師が連携し、これを基に全手術症例の薬剤内服状況を確認している。当院においては周術期外来として各専門科共同の外来は設置していない。しかし、重要チェック項目においてプロトコールを定め、評価が必要な症例が主科から循環器内科、薬剤師外来を経由し麻酔科による術前外来に至ることとなった。これにより適切な術前評価が可能となるとともに、重篤な症例については事前に関係各科で協議を行い周術期計画を立てることが可能となった。(著者抄録)

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DOI： 10.1007/s10877-019-00293-0

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DOI： 10.1007/s10877-019-00283-2

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：日本臨床麻酔学会  

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Language：Japanese   Publisher：日本臨床麻酔学会  

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Language：Japanese   Publisher：日本臨床麻酔学会  

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Language：Japanese   Publisher：日本臨床麻酔学会  

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Language：Japanese   Publisher：(一社)日本心臓血管麻酔学会  

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Language：Japanese   Publisher：日本臨床麻酔学会  

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Language：Japanese   Publisher：日本臨床麻酔学会  

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Language：Japanese   Publisher：(一社)日本心臓血管麻酔学会  

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AIM: Opioids are increasingly used to control postoperative pain via intravenous patient-controlled analgesia, with several advantages. The present study evaluated the effects of intravenous patient-controlled analgesia with different doses of fentanyl on postoperative pain and on the quality of physical/emotional recovery from surgery and anesthesia. METHODS: We retrospectively reviewed data from 288 patients, and evaluated whether intravenous patient-controlled analgesia with fentanyl correlated with the degree of postoperative pain. We then prospectively studied 47 patients who underwent elective laparoscopic cholecystectomy. The patients were randomized into 2 groups (15 or 30 μg/mL of fentanyl), and postoperative pain control was compared using a visual analog scale score. Furthermore, the Japanese 40-item quality of recovery (QoR-40J) score (global and dimensional) and Hospital Anxiety and Depression Scale (HADS) were used to assess the quality of recovery from surgery and anesthesia. RESULTS: Of 288 patients, 20% complained of intolerable pain and 18% experienced postoperative nausea and vomiting. In the prospective study, the visual analog scale pain score was lower in the Fentanyl 30 group than in the Fentanyl 15 group (p<0.05) on postoperative day 1. Dimensional QoR-40J pain subscales correlated with both the emotional state subscales (postoperative day 1, p<0.05; day 2, p<0.05) and global QoR-40 scores on both postoperative days (day 1, p<0.05; day 2, p<0.05). CONCLUSION: The postoperative pain as well as the physical and emotional quality of recovery in the patients who underwent laparoscopic cholecystectomy could be alleviated by sufficient doses of opioids.

DOI： 10.1272/jnms.83.158

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Previous reports have shown that electroconvulsive therapy (ECT) is efficacious in the treatment of neuropathic pain; however, its mechanism of action remains unclear. The present study aimed to understand these mechanisms by investigating the alterations in the expression of neuropeptide Y (NPY) and interleukin-1β (IL-1β) in the prefrontal cortex. A rat model of neuropathic pain produced by chronic constrictive injury of the sciatic nerve was used, and mechanical and thermal hyperalgesia were evaluated starting 2 days after the injury. Using a pulse generator, ECT was administered to the rodents for 6 days from days 7-12 after the injury. Thermal and mechanical stimulation were administered to assess pain thresholds. Quantitative polymerase chain reaction, used to measure gene expression levels in the prefrontal cortex, showed that NPY and IL-1β gene expression levels in the prefrontal cortex increased following the injury. The present results indicate that these gene expression level variations may be associated with the mechanisms underlying the effect of ECT in treating neuropathic pain.

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Language：English   Publishing type：Part of collection (book)   Publisher：Springer Japan  

Fluid management of neurosurgical patients has been a difficult problem for anesthesiologists. Cerebral edema may become a crisis of life. Although restrictive fluid management has been used for a long time, excessive fluid restriction may result in hypotension which can reduce cerebral perfusion pressure and cerebral blood flow. The goals of fluid management for neurosurgical patients include maintaining intravascular volume, preserving cerebral perfusion pressure, and minimizing cerebral edema. The blood-brain barrier prevents not only the movement of colloids but also small ions. Because there are so few protein molecules compared with the number of ions, the fluid movement is governed by crystalloid osmotic pressure rather than colloid oncotic pressure in the brain. Intraoperative fluid administration should be given at a rate sufficient to replace the urinary output, insensible losses, and blood loss, but a reduction of osmolality should be avoided. Fluid administration will not induce cerebral edema as long as normal serum osmolality and oncotic pressure are maintained, and cerebral hydrostatic pressures are not markedly increased.

DOI： 10.1007/978-4-431-54490-6_27

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Anaesthetic preconditioning (APC) and ischemic preconditioning (IPC) ameliorate liver ischemia- reperfusion (I/R) injury and are important for regulating hepatic I/R injury. MicroRNAs (miRNAs) are short, noncoding RNA molecules of 21-23 nucleotides in length, and are currently under intensive investigation regarding their ability to regulate gene expression in a wide range of species. miRNA activity is involved in controlling a wide range of biological functions and processes. We evaluated whether APC and IPC are mediated by the same miRNAs by performing comprehensive miRNA screening experiments in a rat model of hepatic I/R injury. Twenty-one rats were randomly divided into three groups (n = 7/group): control (mock preconditioning), APC, and IPC. Control rats were subjected to 60 min of hepatic ischemia followed by 4 h of reperfusion, whereas the APC and IPC groups were preconditioned with 2% sevoflurane and hepatic ischemia for 10 min prior to ischemia-reperfusion, respectively. Liver samples were collected to measure miRNA levels after 3 h of reperfusion, and gene networks and canonical pathways were identified using Ingenuity Pathway Analysis (IPA). Blood samples were collected to measure the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Although haemodynamic parameters did not vary among the groups, AST and ALT levels were significantly higher in the control group than in the APC and IPC groups. Comprehensive miRNA screening experiments revealed that most miRNAs altered in the APC group were common to those in the IPC group. IPA identified five miRNAs related to the Akt-glycogen synthase kinase-3 beta (GSK-3 beta)-cyclin D1 pathway that were significantly affected by both preconditioning strategies. The application of either APC or IPC to ameliorate hepatic I/R injury results in expression of several common miRNAs that are related to the Akt-GSK-cyclin D1 pathway.

DOI： 10.1371/journal.pone.0125866

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Volatile anesthetics have a lung protective effect in acute lung injury (ALI). Our previous study showed sevoflurane affects the expression of microRNA (miRNA) that control various physiological systems by regulating messenger RNA (mRNA) expression. However, the association between the anti-inflammatory effect of sevoflurane and miRNAs modulation remains unknown. The aim of the present study was to investigate the effect of sevoflurane and the expression of miRNAs in an endotoxin-induced ALI model in rats. Wistar rats were randomly assigned to three groups [lipopolysaccharide (LPS), LPS-sevoflurane and control; n=8/group]. All the rats were mechanically ventilated and intravenously-administered LPS (saline as control). Two hours post-injury, general anaesthesia was performed for 4 h with 2% sevoflurane (LPS-sevoflurane). The LPS and the control groups did not receive anaesthesia. The severity of ALI was evaluated by partial pressure of oxygen/fraction of inspired oxygen and the mRNA expression of inflammatory cytokine. The miRNA expression in lung tissue was analyzed by a reverse transcription-quantitative polymerase chain reaction. LPS caused ALI, evidenced by the impairment of pulmonary function and increased mRNA levels of tumor necrosis factor-α, interleukin-6 and nuclear factor-κB. Sevoflurane improved pulmonary function and inhibited the increased mRNAs. Of the 219 miRNAs detected, 15 and nine miRNAs were significantly changed in the LPS and LPS-sevoflurane group, respectively. In the LPS-sevoflurane group, the expression of several miRNAs that regulate inflammation was significantly changed compared to the LPS group. In conclusion, the present data showed that sevoflurane influences the expression of the miRNAs that regulate inflammation. This result suggests that the changes in miRNA expression are involved in the lung protective mechanisms of volatile anesthetics.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMEDICAL RESEARCH PRESS LTD  

Commonly used anesthetics adversely affect the developing brain, but the mechanisms remain unknown. We previously showed that the expressions of microRNAs (miRNAs) in major organs are affected by anesthetics. Therefore, we used TaqMan low-density array (TLDA) to analyze gene expression in the hippocampus of neonatal rats exposed to sevoflurane and performed behavioral tests after they reached adulthood to evaluate cognitive and memory function. Rat male pups at postnatal day 7 were exposed to 1.9% sevoflurane for 3 h, and the hippocampus-miRNA expression profile on postnatal day 8 was determined. Open field and fear conditioning tests conducted during postnatal weeks 7 and 8 indicated that sevoflurane-exposed rats, but not controls, exhibited anxiety- like disorders. TLDA analysis identified 20 differentially expressed miRNAs, which were not shared between postnatally and maturely sevoflurane-exposed rats. The level of rno-miR-632, which targets brain-derived neurotrophic factor and calcium channel, voltage-dependent, alpha 2/delta subunit 2, increased by 10-fold, indicating that exposure to sevoflurane during early neural development alters hippocampus-miRNA expression and may induce subsequent behavioral disorders.

DOI： 10.2220/biomedres.36.347

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMEDICAL RESEARCH PRESS LTD  

Commonly used anesthetics adversely affect the developing brain, but the mechanisms remain unknown. We previously showed that the expressions of microRNAs (miRNAs) in major organs are affected by anesthetics. Therefore, we used TaqMan low-density array (TLDA) to analyze gene expression in the hippocampus of neonatal rats exposed to sevoflurane and performed behavioral tests after they reached adulthood to evaluate cognitive and memory function. Rat male pups at postnatal day 7 were exposed to 1.9% sevoflurane for 3 h, and the hippocampus-miRNA expression profile on postnatal day 8 was determined. Open field and fear conditioning tests conducted during postnatal weeks 7 and 8 indicated that sevoflurane-exposed rats, but not controls, exhibited anxiety- like disorders. TLDA analysis identified 20 differentially expressed miRNAs, which were not shared between postnatally and maturely sevoflurane-exposed rats. The level of rno-miR-632, which targets brain-derived neurotrophic factor and calcium channel, voltage-dependent, alpha 2/delta subunit 2, increased by 10-fold, indicating that exposure to sevoflurane during early neural development alters hippocampus-miRNA expression and may induce subsequent behavioral disorders.

DOI： 10.2220/biomedres.36.347

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

General anesthesia is commonly used in the surgical arena, but little is known regarding its influence at the genomic and molecular levels. MicroRNAs (miRNAs) belong to a new class of non-coding RNA molecules which influence cell biology. In the present study, it was hypothesized that miRNAs alter gene expression levels under general anesthesia. The aim was to compare the miRNA expression profiles in the rat hippocampus in response to anesthesia with representative volatile (sevoflurane) and intravenous (propofol) anesthetics. Wistar Rats were randomly assigned to either a 2.4% sevoflurane, 600 mu g/kg/min propofol or control (without anesthetics) group. Total RNA from hippocampal samples which contained miRNA was subjected to quantitative reverse transcription-polymerase chain reaction and Taqman Low-Density Arrays (TLDA). A total of 373 miRNAs are associated with rats and the TLDA analysis revealed that 279 expressed miRNAs (74.8%) were expressed in all three groups. Significant differences in the levels of 33 of the 279 expressed miRNAs (11.8%) were observed among the three groups in response to the anesthetic agents, and when compared with the control group, significant differences were found in 26 of the 279 expressed miRNAs (9.3%). Following sevoflurane anesthesia, the levels of four miRNAs were significantly increased and those of 12 were significantly reduced. By contrast, following propofol anesthesia, the levels of 11 miRNAs were significantly reduced but no miRNAs exhibited significantly elevated levels. Fourteen miRNAs were significantly differentially expressed between the two anesthesia groups. In conclusion, sevoflurane and propofol exerted different effects on miRNA expression in the rat hippocampus.

DOI： 10.3892/mmr.2014.2038

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Spandidos Publications  

General anesthesia is commonly used in the surgical arena, but little is known regarding its influence at the genomic and molecular levels. MicroRNAs (miRNAs) belong to a new class of non-coding RNA molecules which influence cell biology. In the present study, it was hypothesized that miRNAs alter gene expression levels under general anesthesia. The aim was to compare the miRNA expression profiles in the rat hippocampus in response to anesthesia with representative volatile (sevoflurane) and intravenous (propofol) anesthetics. Wistar Rats were randomly assigned to either a 2.4% sevoflurane, 600 μg/kg/min propofol or control (without anesthetics) group. Total RNA from hippocampal samples which contained miRNA was subjected to quantitative reverse transcriptionpolymerase chain reaction and Taqman Low-Density Arrays (TLDA). A total of 373 miRNAs are associated with rats and the TLDA analysis revealed that 279 expressed miRNAs (74.8%) were expressed in all three groups. Significant differences in the levels of 33 of the 279 expressed miRNAs (11.8%) were observed among the three groups in response to the anesthetic agents, and when compared with the control group, significant differences were found in 26 of the 279 expressed miRNAs (9.3%). Following sevoflurane anesthesia, the levels of four miRNAs were significantly increased and those of 12 were significantly reduced. By contrast, following propofol anesthesia, the levels of 11 miRNAs were significantly reduced but no miRNAs exhibited significantly elevated levels. Fourteen miRNAs were significantly differentially expressed between the two anesthesia groups. In conclusion, sevoflurane and propofol exerted different effects on miRNA expression in the rat hippocampus.

DOI： 10.3892/mmr.2014.2038

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PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Objective We elaborated the rat hippocampi in order to assess for central nervous system changes following a peripheral neuropathic injury. Design, SettingSubjects We examined the gene changes in the hippocampi of chronic constriction injury (CCI) rats with TaqMan (R) low-density array analysis (TLDA) and quantitative real-time polymerase chain reaction (qRT-PCR) of miR-125b, -132, and messenger RNAs (mRNAs) of neuropeptide Y, brain-derived neural factor, N-methyl-D-aspartate glutamate 2A receptor, gamma-aminobutyric acid A a1 receptor, gamma-aminobutyric acid A b1 receptor, gamma-aminobutyric acid B b2 receptor, serotonin 1A receptor, serotonin 2A receptor, serotonin 2C receptor, and serotonin 3A receptor on days 0, 7, and 15 after surgery. Interventions None. Outcome Measures Two behavioral tests (thermal and mechanical stimulation tests) were performed three times at 5-minute intervals to assess pain thresholds. MicroRNA (miRNA) changes were examined by TLDA. mRNA changes were examined by qRT-PCR. Statistical significance was determined by TukeyKramer's method and paired t-test. Results All rats showed mechanical and thermal hypersensitivity on the ipsilateral side. Out of 373 miRNAs analyzed, 237 were expressed, and 51 changed their expressions after CCI. By TLDA, cluster analysis found obvious miRNA changes on day 7 that tended to recover by day 15. For miR-125b, the relative expression decreased to 0.70 +/- 0.30 at day 7 and recovered to 1.65 +/- 0.19 at day 15. The miR-132 relative expressions were 0.69 +/- 0.30 and 0.70 +/- 0.15, respectively. The mRNA changes followed the miRNA changes. Conclusions Our results showed that the peripheral nerve injury altered rat hippocampal miRNA.

DOI： 10.1111/pme.12066

Web of Science

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

Elucidation of the mechanisms underlying neuropathic pain is expected to aid in the discovery and selection of effective therapeutic methods. Currently, microRNA (miRNA) is thought to play an important role in the development and maintenance of the nervous system. We, therefore, hypothesized that miRNAs are involved in neuropathic pain, and investigated this possibility by analyzing miRNA expression in the dorsal horn of the spinal cord in a chronic constriction injury (CCI) rat model using the TaqMan (R) Low Density Array (TLDA). Neuropathic pain model rats were produced by CCI induced by ligation of the sciatic nerve. The miRNA expression in the dorsal horn of the spinal cord was analyzed in Day 0 rats, with no sciatic nerve ligation or sham operation, Day 7 rats, examined 7 days after sciatic nerve ligation or sham operation, and Day 14 rats, examined 14 days after sciatic nerve ligation or sham operation using TLDA. In this study, Ill miRNAs were significantly regulated in CCI rats in both the Day 7 and Day 14 groups compared with sham rats in both groups. Of these 111, there were 75 miRNAs (67.6%) that had been analyzed in previous reports and 36 miRNAs (32.4%) related to the development of tumors of the nervous system and neurodegenerative diseases. Certain miRNAs were reported to be related to neuropathic pain; miR-500, -221 and -21. The expression levels of a large number of miRNAs in the dorsal horn of the spinal cord in CCI rats changed. These results provide a step toward elucidation of the mechanisms underlying neuropathic pain.

DOI： 10.3892/ijmm.2012.1163

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Background: In previous studies, the authors showed that anesthetics affect the expression ratios of many genes in rat liver. microRNAs (miRNA) negatively regulate more than 30% of genes in cells, and control cell proliferation, inflammation, and metabolism. The authors hypothesized that anesthetics influence miRNA expression in the liver, and performed miRNA screening tests using TaqMan low-density arrays.
Methods: Rats were randomly assigned to the 2.4% sevoflurane group, the 600 mu g.kg(-1).min(-1) propofol group, and the control group without anesthetics. Rats were allowed to breathe spontaneously under anesthesia for 6 h. The miRNA expression profile of the liver was analyzed, and 15 representative miRNAs were validated by quantitative real-time reverse transcriptase polymerase chain reaction.
Results: TaqMan low-density arrays analysis showed 46 miRNAs that were differentially expressed by anesthetics. After sevoflurane treatment, 16 miRNAs were significantly increased and 11 were significantly decreased compared with controls, whereas after propofol treatment, 31 miRNAs were increased and 8 were decreased. Twenty expressed miRNAs were common to both anesthetics, whereas three miRNAs were differentially expressed. Bland-Altman analysis was performed across the validations to compare the fold changes measured by both methods, and they were equivalent (mean difference = 0.01, 95% CI = -0.26 to 0.27). This showed that the TaqMan low-density arrays results are accurate and can be confirmed using an independent experimental approach.
Conclusion: The results showed that anesthetics cause many miRNA expression changes, and the miRNA expression pattern was particular for each anesthetic. Further studies are needed to determine the functional consequence of miRNA modulation by anesthetics.

DOI： 10.1097/ALN.0b013e3182746676

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Language：English   Publishing type：Research paper (scientific journal)  

Reportedly, a large number of microRNAs (miRNAs) play an important role in inflammatory lung diseases such as asthma, idiopathic pulmonary fibrosis (IPF), acute respiratory distress syndrome (ARDS), and pulmonary arterial hypertension (PAH). Sevoflurane is routinely used to various patients, and its safety has been confirmed by clinical outcomes
however, its effects to lungs at the miRNA level have not been elucidated. In our previous genomic studies, we showed that sevoflurane anesthesia affected the expression of many genes and mRNAs in rat lungs. In this study, we comprehensively investigated changes in miRNA expression caused by sevoflurane anesthesia (2.0% and 4.0%). Sevoflurane anesthesia resulted in apparent changes in miRNA expression in rat lungs, and the pattern of 2.0% sevoflurane-induced changes in miRNA expression was similar to that of 4.0% sevoflurane. Some of the differentially expressed miRNAs are known to be involved in asthma, IPF, and PAH. Especially, miR-146a, the most up-regulated miRNA, is known to attenuate the toxic effects associated with LPS stimulation. We showed, for the first time, dynamic changes in miRNA expression caused by sevoflurane anesthesia, and moreover, our results were important to understand the influence of sevoflurane anesthesia on any patients suffered from various lung diseases.

DOI： 10.2220/biomedres.33.255

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Language：Japanese  

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：日本臨床麻酔学会  

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Language：Japanese   Publisher：日本臨床麻酔学会  

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Language：Japanese   Publisher：(一社)日本心臓血管麻酔学会  

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Language：Japanese   Publisher：(一社)日本心臓血管麻酔学会  

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Language：Japanese   Publisher：日本手術医学会  

新型コロナウイルス感染症は接触または飛沫により感染するが、エアロゾルが発生する可能性がある場合は空気感染対策が必要である。麻酔器はバクテリアフィルターと人工鼻を使用すること、エネルギーデバイスを使用する際は排煙装置を使用することで感染対策となる。人工心肺で使用する人工肺もエアロゾルが発生する可能性があるので工夫が必要である。手術室で使用する医療機器の特性を理解し、それぞれにあった感染対策をすることが必要である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：日本臨床麻酔学会  

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Language：Japanese   Publisher：日本臨床麻酔学会  

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Language：Japanese   Publisher：(一社)日本心臓血管麻酔学会  

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Language：Japanese   Publisher：日本臨床麻酔学会  

医療事故調査制度は、医療に起因あるいは疑われる予期せぬ死亡を対象に第三者機関が情報収集・分析し再発を防止することを目的としている。本制度施行からの9ヵ月間における相談件数は1,381例であり、約20%は患者遺族からの申し出であった。背景には不信と疑問があり、インフォームドコンセントの重要性がうかがわれる。起因となった医療は外科手術が最も多く、その管理を担当する麻酔科医にとっても無関係ではない。各施設においては、インフォームドコンセントのガイドラインを作成し、それに準じて行う必要がある。今回、医療事故調査制度における注意点、当院におけるインフォームドコンセントへの取り組みについて述べる。(著者抄録)

DOI： 10.2199/jjsca.38.63

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：日本臨床麻酔学会  

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：日本臨床麻酔学会  

麻酔科術前外来は術前リスクを評価するとともに,患者が麻酔について理解し信頼を深めることを目的としている.術前合併症は周術期トラブルの主要な原因であり,その役割は非常に重要である.しかし,短期間で行わなければならないため,他職種が連携し多角的な視点でアプローチをすることが必要である.当院においては,麻酔科,看護師,薬剤師,各科専門医による術前スクリーニングを行っている.現状では,別個に行われた各種評価を麻酔科医が統合,判断した上で周術期管理を行っている.今後,周術期管理チームとして一つにまとめ,さらに質の高い周術期管理を提供するよう取り組む必要がある.(著者抄録)

DOI： 10.2199/jjsca.36.590

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Language：Japanese   Publisher：(一社)日本心臓血管麻酔学会  

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本心臓血管麻酔学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本心臓血管麻酔学会  

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J-GLOBAL

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Language：Japanese   Publisher：日本循環制御医学会  

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Language：Japanese   Publisher：(一社)日本集中治療医学会  

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Language：Japanese   Publisher：日本医科大学医学会  

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Venue：東京  

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