Analgesic efficacy of modified thoracoabdominal nerves block through the perichondrial approach in laparoscopic cholecystectomy: A retrospective study with propensity analysis.

Modified thoracoabdominal nerves block through the perichondral approach (M-TAPA) was recently reported to provide broad analgesia with only a single injection of local anesthetics (LA) on each side. However, the effectiveness of M-TAPA in laparoscopic cholecystectomy (LC) is not often reported. We retrospectively evaluated the analgesic efficacy of M-TAPA in patients who underwent LC and compared it with conventional LA infiltration (LAI) by calculating the propensity score. The primary outcome was the frequency of analgesic use after surgery. Although there was no difference in the frequency of analgesic use within 48 hours (P = .063), there was significantly less analgesic use 24-48 hours after surgery in the TAPA group (P = .02). Intraoperative remifentanil administration also significantly decreased in the TAPA group (P < .001). We found that pre-incisional M-TAPA may have an advantage over LAI with respect to analgesia on postoperative day 1.

Dermal macrophages set pain sensitivity by modulating the amount of tissue NGF through an SNX25-Nrf2 pathway.

Cross-talk between peripheral neurons and immune cells is important in pain sensation. We identified Snx25 as a pain-modulating gene in a transgenic mouse line with reduced pain sensitivity. Conditional deletion of Snx25 in monocytes and macrophages, but not in peripheral sensory neurons, in mice (Snx25cKO mice) reduced pain responses in both normal and neuropathic conditions. Bone marrow transplantation using Snx25cKO and wild-type mice indicated that macrophages modulated pain sensitivity. Expression of sorting nexin (SNX)25 in dermal macrophages enhanced expression of the neurotrophic factor NGF through the inhibition of ubiquitin-mediated degradation of Nrf2, a transcription factor that activates transcription of Ngf. As such, dermal macrophages set the threshold for pain sensitivity through the production and secretion of NGF into the dermis, and they may cooperate with dorsal root ganglion macrophages in pain perception.

Synapsin-Promoted Caveolin-1 Overexpression Maintains Mitochondrial Morphology and Function in PSAPP Alzheimer's Disease Mice.

Mitochondrial dysfunction plays a pivotal role in the Alzheimer's Disease (AD) pathology. Disrupted mitochondrial dynamics (i.e., fusion/fission balance), which are essential for normal mitochondria structure and function, are documented in AD. Caveolin-1 (Cav-1), a membrane/lipid raft (MLR) scaffolding protein regulates metabolic pathways in several different cell types such as hepatocytes and cancer cells. Previously, we have shown decreased expression of Cav-1 in the hippocampus of 9-month (m) old PSAPP mice, while hippocampal overexpression of neuron-targeted Cav-1 using the synapsin promoter (i.e., SynCav1) preserved cognitive function, neuronal morphology, and synaptic ultrastructure in 9 and 12 m PSAPP mice. Considering the central role of energy production in maintaining normal neuronal and synaptic function and survival, the present study reveals that PSAPP mice exhibit disrupted mitochondrial distribution, morphometry, and respiration. In contrast, SynCav1 mitigates mitochondrial damage and loss and enhances mitochondrial respiration. Furthermore, by examining mitochondrial dynamics, we found that PSAPP mice showed a significant increase in the phosphorylation of mitochondrial dynamin-related GTPase protein (DRP1), resulting in excessive mitochondria fragmentation and dysfunction. In contrast, hippocampal delivery of SynCav1 significantly decreased p-DRP1 and augmented the level of the mitochondrial fusion protein, mitofusin1 (Mfn1) in PSAPP mice, a molecular event, which may mechanistically explain for the preserved balance of mitochondria fission/fusion and metabolic resilience in 12 m PSAPP-SynCav1 mice. Our data demonstrate the critical role for Cav-1 in maintaining normal mitochondrial morphology and function through affecting mitochondrial dynamics and explain a molecular and cellular mechanism underlying the previously reported neuroprotective and cognitive preservation induced by SynCav1 in PSAPP mouse model of AD.

Increased anxiety-like behaviour is an early symptom of vitamin E deficiency that is suppressed by adrenalectomy in rats.

We previously reported that dietary vitamin E deficiency increased anxiety-like behaviour in rats exposed to social isolation. Here, we performed a detailed investigation of this phenomenon and its underlying mechanism. First, we fed Wistar rats with a vitamin E-free diet for 3 d, 1 week or 2 weeks and found an increase in anxiety-like behaviour after 1 and 2 weeks of vitamin E deficiency based on behavioural indicators. Next, we examined the effect of a control diet (150 mg all-racemic α-tocopheryl acetate/kg) on anxiety-like behaviours in rats that received a 4-week vitamin E-free diet. We found that increased anxiety-like behaviour was reversed to control levels after refeeding vitamin E for 7 d but not for 1 or 3 d. Further, anxiety-like behaviour increased or decreased gradually based on the amount of vitamin E intake; however, it had a quicker progression than physical symptoms of vitamin E deficiency. Moreover, rats fed with excess vitamin E (500 mg all-racemic α-tocopherol/kg diet) showed less anxiety-like behaviour than control rats, indicating that vitamin E supplementation is effective for preventing anxiety increase under social isolation stress. Since plasma corticosterone levels were higher in vitamin E-deficient rats, we investigated the effect of adrenalectomy on anxiety-like behaviour and found that adrenal hormones played an essential role in the increased anxiety-like behaviour induced by vitamin E deficiency. In conclusion, increased anxiety-like behaviour is a symptom that emerges earlier than physical vitamin E deficiency and is caused by adrenal hormone-dependent mechanisms.

NGF and BDNF expression in mouse DRG after spared nerve injury.

Neuropathic pain is initiated by a primary lesion in the peripheral nervous system and spoils quality of life. Neurotrophins play important roles in the development and transmission of neuropathic pain. There are conflicting reports that the dorsal root ganglion (DRG) in an injured nerve contribute to neuropathic pain, whereas several studies have highlighted the important contribution of the DRG in a non-injured nerve. Clarifying the role of neurotrophins in neuropathic pain is problematic because we cannot distinguish injured and intact neurons in most peripheral nerve injury models. In the present study, to elicit neuropathic pain, we used the spared nerve injury (SNI) model, in which injured DRG neurons are distinguishable from intact ones, and mechanical allodynia develops in the intact sural nerve skin territory. We examined nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression in the DRGs of SNI model mice. NGF and BDNF levels increased in the injured L3 DRG, while NGF decreased in the intact L5 DRG. These data offer a new point of view on the role of these neurotrophins in neuropathic pain induced by peripheral nerve injury.

Propofol induces nuclear localization of Nrf2 under conditions of oxidative stress in cardiac H9c2 cells.

Oxidative stress contributes to myocardial ischemia-reperfusion injury, which causes cardiomyocyte death and precipitate life-threatening heart failure. Propofol has been proposed to protect cells or tissues against oxidative stress. However, the mechanisms underlying its beneficial effects are not fully elucidated. In the present study, we employed an in vitro oxidative injury model, in which rat cardiac H9c2 cells were treated with H2O2, and investigated roles of propofol against oxidative stress. Propofol treatment reduced H2O2-induced apoptotic cell death. While H2O2 induced expression of the antioxidant enzyme HO-1, propofol further increased HO-1 mRNA and protein levels. Propofol also promoted nuclear localization of Nrf2 in the presence of H2O2. Knockdown of Nrf2 using siRNA suppressed propofol-inducible Nrf2 and expression of Nrf2-downstream antioxidant enzyme. Knockdown of Nrf2 suppressed the propofol-induced cytoprotection. In addition, Nrf2 overexpression induced nuclear localization of Nrf2 and HO-1 expression. These results suggest that propofol exerts antioxidative effects by inducing nuclear localization of Nrf2 and expression of its downstream enzyme in cardiac cells. Finally, we examined the effect of propofol on cardiomyocytes using myocardial ischemia-reperfusion injury models. The expression level of Nrf2 protein was increased at 15 min after reperfusion in the ischemia-reperfusion and propofol group compared with ischemia-reperfusion group in penumbra region. These results suggest that propofol protects cells or tissues from oxidative stress via Nrf2/HO-1 cascade.

Olig2-Lineage Astrocytes: A Distinct Subtype of Astrocytes That Differs from GFAP Astrocytes.

Astrocytes are the most abundant glia cell type in the central nervous system (CNS), and are known to constitute heterogeneous populations that differ in their morphology, gene expression and function. Although glial fibrillary acidic protein (GFAP) is the cardinal cytological marker of CNS astrocytes, GFAP-negative astrocytes can easily be found in the adult CNS. Astrocytes are also allocated to spatially distinct regional domains during development. This regional heterogeneity suggests that they help to coordinate post-natal neural circuit formation and thereby to regulate eventual neuronal activity. Here, during lineage-tracing studies of cells expressing Olig2 using Olig2CreER; Rosa-CAG-LSL-eNpHR3.0-EYFP transgenic mice, we found Olig2-lineage mature astrocytes in the adult forebrain. Long-term administration of tamoxifen resulted in sufficient recombinant induction, and Olig2-lineage cells were found to be preferentially clustered in some adult brain nuclei. We then made distribution map of Olig2-lineage astrocytes in the adult mouse brain, and further compared the map with the distribution of GFAP-positive astrocytes visualized in GFAPCre; Rosa-CAG-LSL-eNpHR3.0-EYFP mice. Brain regions rich in Olig2-lineage astrocytes (e.g., basal forebrain, thalamic nuclei, and deep cerebellar nuclei) tended to lack GFAP-positive astrocytes, and vice versa. Even within a single brain nucleus, Olig2-lineage astrocytes and GFAP astrocytes frequently occupied mutually exclusive territories. These findings strongly suggest that there is a subpopulation of astrocytes (Olig2-lineage astrocytes) in the adult brain, and that it differs from GFAP-positive astrocytes in its distribution pattern and perhaps also in its function. Interestingly, the brain nuclei rich in Olig2-lineage astrocytes strongly expressed GABA-transporter 3 in astrocytes and vesicular GABA transporter in neurons, suggesting that Olig2-lineage astrocytes are involved in inhibitory neuronal transmission.

Voluntary Exercise Induces Astrocytic Structural Plasticity in the Globus Pallidus.

Changes in astrocyte morphology are primarily attributed to the fine processes where intimate connections with neurons form the tripartite synapse and participate in neurotransmission. Recent evidence has shown that neurotransmission induces dynamic synaptic remodeling, suggesting that astrocytic fine processes may adapt their morphologies to the activity in their environment. To illustrate such a neuron-glia relationship in morphological detail, we employed a double transgenic Olig2(CreER/WT); ROSA26-GAP43-EGFP mice, in which Olig2-lineage cells can be visualized and traced with membrane-targeted GFP. Although Olig2-lineage cells in the adult brain usually become mature oligodendrocytes or oligodendrocyte precursor cells with NG2-proteoglycan expression, we found a population of Olig2-lineage astrocytes with bushy morphology in several brain regions. The globus pallidus (GP) preferentially contains Olig2-lineage astrocytes. Since the GP exerts pivotal motor functions in the indirect pathway of the basal ganglionic circuit, we subjected the double transgenic mice to voluntary wheel running to activate the GP and examined morphological changes of Olig2-lineage astrocytes at both the light and electron microscopic levels. The double transgenic mice were divided into three groups: control group mice were kept in a cage with a locked running wheel for 3 weeks, Runner group were allowed free access to a running wheel for 3 weeks, and the Runner-Rest group took a sedentary 3-week rest after a 3-week running period. GFP immunofluorescence analysis and immunoelectron microscopy revealed that astrocytic fine processes elaborated complex arborization in the Runner mice, and reverted to simple morphology comparable to that of the Control group in the Runner-Rest group. Our results indicated that the fine processes of the Olig2-lineage astrocytes underwent plastic changes that correlated with overall running activities, suggesting that they actively participate in motor functions.

Highly spectral efficient networks based on grouped optical path routing.

In order to mitigate the signal spectrum narrowing caused by optical filtering at nodes, an adequate guard band is needed between optical channels, which degrades the frequency utilization of optical fibers. In this study, we propose a grouped routing based network architecture that minimizes spectrum narrowing while greatly improving spectral efficiency. Coarse granular routing at GRE (grouped routing entity) level is employed at each ROADM node, but fine granular add/drop is adopted to retain high frequency utilization. Optical channels are packed densely in each GRE, and sufficient guard bands are inserted between GREs. As a result, signal spectrum narrowing is minimized and efficient spectrum utilization is achieved. Network design/control algorithms that support both static and dynamic traffic growth are developed. Extensive simulations demonstrate the effectiveness of the proposed architecture. To implement the scheme, current LCOS-based ROADMs are applied without any hardware changes; only the control schema are modified.

[Comparison of Sedative and Analgesic Requirements in Children with and without Down Syndrome following Pediatric Cardiac Surgery].

BACKGROUND: Conflicting results have been reported on postoperative analgesia in pediatric patients with Down syndrome. We compared sedative and analgesic requirements following cardiac surgery between pediatric patients with and without Down syndrome. METHODS: Patients who underwent atrial septal defect closure, ventricular septal defect closure and repair of atrioventricular septal defect at the age between one month and 24 months in our institution for 2 years from 2011 to 2012 were recruited into the study. Patient's background and perioperative managements were investigated. Data collected included preoperative cardiac catheterization data, postoperative sedative and analgesic dosage, postoperative sedation scores and duration of mechanical ventilation. RESULTS: Eight Down syndrome (mean : weight 5.6 kg, age 7.9 months) and twelve non-Down syndrome (mean : weight 5.6 kg, age 5.6 months) patients were enrolled into the study. Pulmonary-systemic artery pressure ratio after cardiac repair and intraoperative anesthetic doses did not differ. Postoperative sedation score, duration of mechanical ventilation and stay in intensive care unit were equivalent. Maintenance and cumulative dose of midazolam, dexmedetomidine and fentanyl, and times of rescue administration did not differ between the groups. CONCLUSIONS: In our study, all enrolled patients received adequate sedation and analgesia after pediatric cardiac surgery. Sedative and analgesic doses following pediatric cardiac surgery were not different between the groups of Down syndrome and non-Down syndrome.

Hedgehog Signaling Modulates the Release of Gliotransmitters from Cultured Cerebellar Astrocytes.

Sonic hedgehog (Shh), a member of the Hedgehog (Hh) family, plays essential roles in the development of the central nervous system. Recent studies suggest that the Hh signaling pathway also functions in mature astrocytes under physiological conditions. We first examined the expression of genes encoding Hh signaling molecules in the adult mouse cerebellum by in situ hybridization histochemistry. mRNA for Patched homolog 1 (Ptch1), a receptor for Hh family members, was expressed in S100ß-positive astrocytes and Shh mRNA was expressed in HuC/D-positive neurons, implying that the Hh signaling pathway contributes to neuro-glial interactions. To test this hypothesis, we next examined the effects of recombinant SHH N-terminal protein (rSHH-N) on the functions of cultured cerebellar astrocytes. rSHH-N up-regulated Hh signal target genes such as Ptch1 and Gli-1, a key transcription factor of the Hh signaling pathway. Although activation of Hh signaling by rSHH-N or purmorphamine influenced neither glutamate uptake nor gliotransmitters release, inhibition of the Hh signaling pathway by cyclopamine, neutralizing antibody against SHH or intracellular Ca(2+) chelation decreased glutamate and ATP release from cultured cerebellar astrocytes. On the other hand, cyclopamine, neutralizing antibody against SHH or Ca(2+) chelator hardly affected D-serine secretion. Various kinase inhibitors attenuated glutamate and ATP release, while only U0126 reduced D-serine secretion from the astrocytes. These results suggested that the Hh signaling pathway sustains the release of glutamate and ATP and participates in neuro-glial interactions in the adult mouse brain. We also propose that signaling pathways distinct from the Hh pathway govern D-serine secretion from adult cerebellar astrocytes.

[Spontaneous Respiration Technique for Pediatric Microlaryngeal Surgery without Endotracheal Intubation].

We report the anesthetic management of microlaryngeal surgery in children using tubeless total intravenous anesthesia (TIVA) without endotracheal intubation under spontaneous breathing. In 9 patients (median age : 4.9 yr. range 1 months-14 years, body weight : 17 kg, range 3-61 kg), 19 procedures were performed with TIVA using propofol and remifentanil. The median time from the start of TIVA to rigid laryngoscope insertion was 11 minutes. Propofol 15.7 mg x kg(-1) x hr(-1) and remifentanil 0.05 µg x kg(-1) x min(-1) was infused in this interval. Laryngospasm was observed in two cases, but it responded to a bolus of propofol (0.5-1.0 mg x kg(-1)) and additional topical anesthesia with 1% lidocaine. Three children were found apneic after a bolus administration of remifentanil or after increasing the rate of remifentanil infusion accompanied with desaturation and their tracheae were intubated. The spontaneous respiration technique using TIVA without intubation provides an excellent view of the operative field while allowing stable anesthesia. Further studies are required to establish the optimal dose of propofol and remifentanil and the timing of rigid laryngoscope insertion.

[Outcome of the Pediatric Patients Who Required Repeated Cardiopulmonary Bypass during the Repair of Congenital Heart Disease].

BACKGROUND: We occasionally encounter clinical deterioration after discontinuation of cardiopulmonary bypass (CPB) and are forced to reinstitute CPB during cardiac surgery. Some reports describe such cases occurring in adults, but few in infants and children. We retrospectively investigated the causes and outcomes of children requiring repeated CPB during the repair of congenital heart anomalies. METHODS: Patients who required repeated CPB during the repair of congenital heart anomalies in our institution from 2007 to 2012 were recruited into the study. Patient's background, diagnosis, surgical procedures, durations of total CPB and aortic cross-clamping, indications for re-CPB, procedures or treatment added after reinstitution of CPB and outcomes were collected. RESULTS: Out of 600 pediatric patients who underwent the repair of congenital heart disease during the study period, 34 required repeated CPB and were enrolled into the study. Mean age was 2 years and mean body weight was 9.9 kg. Twenty-six patients of 34 were weaned from the CPB after additional surgical repair with re-bypass, one of whom died in the ICU. The remaining 8 patients were weaned from the CPB after medical treatment. One of 8 patients died in the ICU and 2 died after discharge from ICU. CONCLUSIONS: In cardiac surgery of congenital heart disease, pediatric patients who required repeated CPB showed high mortality but patients who received additional surgical repair to be weaned from CPB had better outcome compared with those who received medical treatment.

[Perioperative fibrinogen concentrations in cardiac surgery with cardiopulmonary bypass].

BACKGROUND: Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) need many blood products due to deficiency of coagulation factors. Blood transfusion therapy in patients with excessive bleeding after CPB is generally empiric. We checked and studied the fibrinogen concentration and transfusion, as well as bleeding amount in the perioperative period. METHODS: The study was approved by our institutional ethics committee. Thirty patients were studied. Blood samples were obtained at the induction of anesthesia (before CPB), at the end of CPB, at the end of operation, and on the next morning, or before the patient was given fresh frozen plasma in the intensive care unit. RESULTS: For all cases, fibrinogen concentration and platelet concentration were lowest at the end of CPB. Fibrinogen concentration rose up to before CPB level on the next morning. The group in which fibrinogen concentration was less than 150 mg x dl(-1) at the end of CPB consumed more blood products than the group with fibrinogen concentration of over 150 mg x dl(-1). CONCLUSIONS: Blood transfusion therapy based on fibrinogen concentration is needed to maintain adequacy of the perioperative blood transfusion and blood conservation in cardiac surgery.

Dietary vitamin E deficiency increases anxiety-like behavior in juvenile and adult rats.

Vitamin E deficiency from birth or infancy has recently been found to increase anxiety-like behavior in rodents. The present study was undertaken to elucidate the effect of dietary vitamin E deficiency on anxiety in adult rats in comparison with juvenile rats. Male Wistar rats, 3 or 10 weeks old, were divided into two groups and fed a control or vitamin E-deficient diet for 4 weeks. The results of behavioral analysis revealed that vitamin E-deficiency increased anxiety in both juvenile and adult rats. Plasma, liver, and brain α-tocopherol concentrations decreased significantly due to vitamin E deficiency in both age groups. Plasma corticosterone concentrations were higher in the vitamin E-deficient rats in response to the stress of a behavioral test. Based on these results, we conclude that dietary vitamin-E deficiency induces anxiety in adult rats as well as juvenile rats. This might be due to an elevated plasma corticosterone concentration.

The impact of postoperative intensive care on outcomes in elective neurosurgical patients in good physical condition: a single centre propensity case-matched study.

PURPOSE: In the last three years, all elective neurosurgical cases were performed by a single surgeon at Nara Medical University. For the last year and a half, all patients were transferred to a newly created neurosurgical intensive care unit. The purpose of this study was to evaluate the impact of admission to an intensive care unit after elective neurosurgery. METHODS: This study was conducted as a retrospective clinical chart review. Institutional ethics approval was waived, and we reviewed the charts of 296 neurosurgical patients who were American Society of Anesthesiologists' physical status I-II. To avoid channelling bias, propensity score analysis was used to generate a set of matched cases (patients transferred to the intensive care unit [ICU]) and controls (patients transferred to the neurosurgical ward). This process resulted in 104 matched pairs of elective surgical patients who did or did not have an ICU admission after surgery. Glasgow outcome scale (GOS) at discharge or at three months after the operation was compared as the primary outcome measure. As secondary outcome measures, we also compared rates of severe early complications and patient satisfaction regarding perioperative patient care. RESULTS: With an unmatched population, poor GOS tended to occur more often in the non-ICU group than in the ICU group (6.5% vs 2.3%, respectively). Mortality rates and severe early complication rates also tended to be higher in the non-ICU group than in the ICU group (2.4% and 5.3%, respectively, non-ICU group vs 0.8% and 2.3%, respectively, ICU group). However, after propensity score matching, there was no difference regarding the GOS between groups. Both groups showed very high good outcome percentages (98.1% ICU vs 97.1% non-ICU). With regard to mortality rates and severe early complications, both groups showed low mortality (0.96% vs 0.96%) and complication rates (2.89% ICU vs 3.85% non-ICU). Patient care in the ICU failed to increase patient satisfaction regarding the overall hospital care. CONCLUSION: The results of this analysis suggest that admission to an ICU after elective neurosurgery has little impact on outcomes.

[Patient scheduled for ligation of the contralateral internal jugular vein and its reconstruction following unilateral radical neck dissection].

A 76-year-old man who had previously undergone unilateral radical neck dissection (RND) was scheduled for contralateral radical neck dissection and reconstruction of the internal jugular vein (IJV) with the saphenous vein due to local recurrence of thyroid carcinoma infiltrating the IJV Reconstruction of the IJV was not necessary, however, because the preserved IJV was large enough to drain venous return after partial resection of the tumor-infiltrated part of the IJV. Reports of anesthetic management for bilateral RND are very rare. In this report, we discussed anesthetic management of bilateral RND including physiological changes and complications after bilateral IJV ligation and monitoring methods for disturbances of cerebral venous circulation.