Takeshi Sugiura

Ketamine reduces amyloid β-protein degradation by suppressing neprilysin expression in primary cultured astrocytes

Pathological accumulation of cortical amyloid β-protein (Aβ) is an early and consistent feature of Alzheimers disease (AD). Aβ levels in the brain are determined by production and catabolism. Previous studies have suggested that deficits in the brain expression of neprilysin (NEP) and the insulin-degrading enzyme (IDE), which are both proteases involved in amyloid degradation, may promote Aβ deposition in patients with sporadic late-onset AD. Because the incidence of AD increases after surgical intervention, we examined whether ketamine, which is a general anaesthetic with neuroprotective properties for excitotoxic ischaemic damage, is associated with Aβ degradation by inducing NEP and IDE expression. The non-competitive N-methyl-d-aspartate receptor antagonist ketamine and MK801 significantly decreased the expression of NEP, but not IDE, in a concentration- and time-dependent manner through the dephosphorylation of p38 mitogen-activated protein kinase (MAPK) in cultured rat astrocytes. Furthermore, NEP-reduced reagents significantly suppressed the degradation of exogenous Aβ in cultured astrocytes. These results suggested that ketamine suppresses the Aβ degradation of NEP by reducing p38 MAPK-mediated pathway activity.

A New Enteral Diet, MHN-02, Which Contains Abundant Antioxidants and Whey Peptide, Protects Against Carbon Tetrachloride–Induced Hepatitis:

BACKGROUNDnInflammatory or oxidative stress is related to various diseases, including not only inflammatory diseases, but also diabetes, cancer, and atherosclerosis. The aim of this study was to evaluate the anti-inflammatory effects of a new enteral diet, MHN-02, which contains abundant antioxidants and whey peptide. The study also investigated the ability of MHN-02 to attenuate lethality, liver injury, the production of inflammatory cytokines, and the production of oxidized products using a carbon tetrachloride-induced rat model of severe fulminant hepatitis.nnnMETHODSnMale Sprague-Dawley rats were fed either a control diet or the MHN-02 diet for 14 days and injected with 2 mL/kg of carbon tetrachloride. Survival of rats was monitored from day 0 to day 3. To evaluate liver injury, inflammation, and oxidative stress, blood and liver samples were collected, and aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, interleukin 6, tumor necrosis factor-α, and superoxide dismutase activity as a free radical scavenger were measured. A portion of the liver was evaluated histologically.nnnRESULTSnThe survival rates of rats receiving the MHN-02 diet and the control diet were 90% and 55%, respectively. In the MHN-02 diet group, levels of serum liver enzymes and serum cytokines were significantly lower than in the control group. Superoxide dismutase activity in the MHN-02 diet was significantly higher in the MHN-02 group. Pathological lesions were significantly larger in the control group.nnnCONCLUSIONnSupplementation of enteral diets containing whey peptide and antioxidants may protect against severe hepatitis.

Markedly elevated procalcitonin in early postoperative period in pediatric open heart surgery: a prospective cohort study

BackgroundWe encountered markedly elevated procalcitonin (PCT) among pediatric patients during the early postoperative period of open heart surgery. The purpose of this study is to investigate what factors are associated with the PCT elevation.MethodsFifty-two pediatric patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) were enrolled. Plasma PCT, aspartate aminotransferase/alanine aminotransferase (AST/ALT), creatinine, lactate, and C-reactive protein (CRP) were measured on admission to ICU and during the postoperative period. The patients were categorized into high (group H) and low (group L) groups according to their peak PCT levels. Aorta cross-clamp (ACC), CPB time, ICU stay, mechanical ventilation period, peak AST/ALT, creatinine, lactate, and CRP levels were compared.ResultsACC and CPB times, ICU stay period, and mechanical ventilation period were significantly longer in group H compared with group L (118.7u2009±u200951.6 vs. 49.4u2009±u200943.5xa0min, 244.5u2009±u200965.7 vs. 122.9u2009±u200963.0xa0min, 7.9u2009±u20094.6 vs. 4.0u2009±u20094.5xa0days, and 6.3u2009±u20094.1 vs. 2.9u2009±u20094.2xa0days, respectively; pu2009<u20090.01). Peak AST and creatinine were significantly higher in group H compared with group L (999.0u2009±u20091,990.3 vs. 88.3u2009±u200943.0xa0U/l and 0.84u2009±u20090.77 vs. 0.41u2009±u20090.17xa0mg/dl, respectively; pu2009<u20090.05).ConclusionsACC and CPB time-related perioperative stress is associated with elevated PCT; an association between ICU stay and mechanical ventilation period, liver enzymes, and creatinine levels was observed. PCT may be a good predictor of postoperative severity and organ dysfunction.

Time progression from the patient's operating room entrance to incision: factors affecting anesthetic setup and surgical preparation times.

PurposeOwing to recent advances in surgical technology, substantial time is required for preparing surgical equipment before incision. The purpose of this study was to demonstrate the time progression from a patient’s operating room entrance to incision and to evaluate the duration of each anesthetic procedure and surgical preparation.MethodsWe marked the following seven points on the anesthetic chart: (1) entrance; (2) IV line placement; (3) preoxygenation; (4) intubation; (5) completion of patient positioning (Anesth-Set); (6) applying antiseptic solution; and (7) incision. Afterward, we analyzed the event time periods according to anesthetic procedure, patient position, surgical service, and surgical procedure (such as the utilization of endoscopy, navigation systems, and sentinel lymph node biopsy).ResultsOn average, it took approximately 3 min to start IV placement, 7 min until preoxygenation, 15 min until intubation, and 30 min until Anesth-Set. Epidural, arterial, and central venous catheterization required 15, 9, and 13 min, respectively. It took 20 min from Anesth-Set to incision, on average; 22, 4, and 5 min were required to prepare the navigation system, endoscope, and sentinel lymph node biopsy, respectively. In total, it took an average of 49.8 ± 17.1 min from entrance to incision, which was significantly longer (30.4 ± 8.8 min) than it took in 1985–1986.ConclusionThe mean time taken from the patient’s operating room entrance to incision is now significantly longer than before. This may be attributed, at least in part, to the preparation of equipment associated with new surgical technologies.

Postextubation airway management with nasal continuous positive airway pressure in a child with Down syndrome

We describe our experience with use of variable-flow nasal continuous positive airway pressure (NCPAP) to manage postextubation stridor in a 31-month-old child with Down syndrome (DS). Although it has been recognized that children with DS tend to develop obstruction of the upper airway postoperatively, little is known concerning appropriate management of this situation. Although there are surprisingly few reports of use of variable-flow NCPAP for children older than preterm infants, we successfully treated postextubation ventilatory complications by providing variable-flow NCPAP without complications such as pneumothorax.

Spinal cord stimulation for a woman with complex regional pain syndrome who wished to get pregnant

A woman with complex regional pain syndrome (CRPS) in the right lower extremity who wished to discontinue medications to get pregnant underwent implantation of a spinal cord stimulation system (SCS). An electrode lead was placed at Th10–11 in the epidural space, accessed via the L2–3 interspace with a paramedian approach, and a pulse generator was implanted in the left buttock. She kept the SCS on 24xa0h a day. After she had experienced several chemical abortions, finally she got pregnant via artificial insemination. She had an uneventful delivery of a healthy baby by cesarean resection under spinal anesthesia. In a patient with CRPS who has an implanted SCS system and wishes to get pregnant, the electrode lead into the low thoracic epidural space should be accessed via the high lumbar intervertebral space in consideration of a future requirement for spinal or epidural anesthesia for cesarean section. The generator should be placed in the buttock to prevent impairment of the SCS system being caused by the enlarged abdomen during pregnancy. Although we were apprehensive of adverse effects owing to the electromagnetic field force and change of blood flow in the pelvic viscera, our patient had a successful delivery. SCS is a favorable option for patients with CRPS who wish to get pregnant.

Midazolam inhibits the formation of amyloid fibrils and GM1 ganglioside-rich microdomains in presynaptic membranes through the gamma-aminobutyric acid A receptor

Recent studies have suggested that a positive correlation exists between surgical interventions performed under general anesthesia and the risk of developing Alzheimers disease (AD) in the late postoperative period. It has been reported that amyloid β-protein (Αβ) fibrillogenesis, which is closely related to AD, is accelerated by exposure to anesthetics. However, the mechanisms underlying these effects remain uncertain. This study was designed to investigate whether the anesthetic midazolam affects Αβ fibrillogenesis, and if so, whether it acts through GM1 ganglioside (GM1) on the neuronal surface. Midazolam treatment decreased GM1 expression in the detergent-resistant membrane microdomains of neurons, and these effects were regulated by the gamma-aminobutyric acid-A receptor. Midazolam inhibited Αβ fibril formation from soluble Αβ on the neuronal surface. In addition, midazolam suppressed GM1-induced fibril formation in a cell-free system. Moreover, midazolam inhibited the formation of Αβ assemblies in synaptosomes isolated from aged mouse brains. These finding suggested that midazolam has direct and indirect inhibitory effects on Αβ fibrillogenesis.

Before-after study of a restricted fluid infusion strategy for management of donor hepatectomy for living-donor liver transplantation

PurposeIntraoperative fluid infusion strategy remains controversial. Many animal model studies have shown that restricted fluid infusion reduces blood loss, though reports on this topic in humans are rare. The purpose of this study was to determine the effects on volume of blood loss of a restricted fluid infusion strategy for hepatectomy in donors for livingdonor liver transplantation.MethodsA before-after study design was used with prospective consecutive data collection. A total of 22 patients who underwent living-donor hepatectomy were enrolled. Eleven patients who were managed before the implementation of restricted-volume fluid administration comprised the standard-volume group, and 11 who were evaluated after the implementation of the restricted-volume infusion strategy comprised the restricted-volume group. In the standard-volume group, the donors were given 10 ml·kg−1·h−1 of lactated Ringer’s solution and additional plasma expander corresponding to blood loss. In the restricted-volume group, the donors received 5 ml·kg−1·h−1 of lactated Ringer’s solution until the resection of the hepatic graft, followed by 15 ml·kg−1·h−1 of lactated Ringer’s solution after the completion of resection until the end of the operation.ResultsIntraoperative blood loss was less in the restricted-volume group (445 ± 193 ml) than in the standard-volume group (1331 ± 602 ml; P < 0.01). Intraoperative fluid infusion was also less in the restricted-volume group (4130 ± 563 ml) than in the standard-volume group (5634 ± 1260 ml; P < 0.01). There were no differences in length of hospital stay or side effects between the two groups.ConclusionOur restricted-volume strategy reduced blood loss and had no adverse effects during living-donor hepatectomy.

Use of landiolol in the perioperative management of supraventricular tachycardia

was stable. Her blood pressure then dropped, although the IABP worked well. The vasoconstrictive effect of dopamine appeared to be required for maintaining a stable hemodynamic status. Landiolol was discontinued 10 h after her admission to the intensive care unit. The SVT recurred immediately, resulting in failure of IABP synchronization. Landiolol infusion was recommenced. As a result, her HR decreased to 90– 100 bpm and her hemodynamic status improved again. The landiolol infusion was continued for another 50 h, at the same rate. She remained stable and was discharged from the intensive care unit on the tenth postoperative day. We believe that landiolol is useful for the HR control of perioperative SVT in patients undergoing cardiac surgery and that the resultant slow cardiac rhythm aids the synchronization of IABP with the patient’s heartbeat. In this patient, landiolol was safely administered not only intraoperatively but also postoperatively for as long as 3 days. Landiolol is considered to be effective in treating perioperative SVT because of its similarity to esmolol, another cardioselective and ultra-shortacting β-blocker, which, it is claimed, is safe and efficacious [4,5]. Further, landiolol has been shown to have a less depressive effect on the cardiovascular system than esmolol in animals [6,7]. In humans, it appears that the blood pressure does not significantly decrease at the optimal dose of landiolol required for HR control [8]. This characteristic would be advantageous for administration to a patient with hypotension.

Intra-operative monitoring of vagal nerve activity with wire electrodes.

A monitoring system for tracking the electromyogram (EMG) of the vocal cords with wire electrodes embedded in an endotracheal tube was designed to identify the recurrent laryngeal nerve during thyroidectomy. Our recent experience in two cases suggests that vagal nerve activity can be correctly detected by recording of the EMG of the vocal cords using a special endotracheal tube embedded with wire electrodes.