A Behavioral and Electroencephalographic Study of Anesthetic State Induced by MK-801 Combined with Haloperidol, Ketamine and Riluzole in Mice.

BACKGROUND: Ketamine is an intravenous anesthetic that acts as a channel blocker on the N-methyl-d-aspartate (NMDA) receptor, a glutamate receptor subtype. MK-801 is the most potent compound among noncompetitive NMDA receptor antagonists. Ketamine induces loss of the righting reflex (LORR) in rodents, which is one of the indicators of unconsciousness, whereas high doses of MK-801 produce ataxia, but not LORR. In contrast, we previously reported that MK-801 combined with a low dose of the dopamine receptor antagonist haloperidol-induced LORR in mice. To assess a neurophysiologically distinct brain state and demonstrate unconsciousness, electroencephalograms (EEG) need to be examined together with LORR. Therefore, we herein investigated EEG changes after the systemic administration of MK-801 alone or in combination with haloperidol, and compared them with those induced by ketamine, the glutamate release inhibitor riluzole, and the γ-aminobutyric acid type A receptor agonist propofol. METHODS: All drugs were intraperitoneally administered to adult male ddY mice (n = 168). General anesthesia was evaluated based on the righting reflex test. Animals who exhibited no righting for more than 30 seconds were considered to have LORR. In a separate group of mice, EEG of the primary visual cortex was recorded before and after the administration of MK-801 (3.0 mg/kg) alone or in combination with haloperidol (0.2 mg/kg), ketamine (150 mg/kg), riluzole (30 mg/kg), or propofol (240 mg/kg). The waveforms recorded were analyzed using EEG power spectra and spectrograms. RESULTS: The high dose of MK-801 alone did not induce LORR, whereas MK-801 combined with haloperidol produced LORR in a dose-dependent manner. Ketamine, riluzole, and propofol also dose-dependently induced LORR. In the EEG study, MK-801 alone induced a significant increase in δ power, while MK-801 plus haloperidol exerted similar effects on not only δ, but also θ and α power during LORR, suggesting that increases in δ, θ, and α power were necessary for LORR. The results obtained on MK-801 plus haloperidol were similar to those on ketamine in the behavioral and EEG studies, except for an increase in γ power by ketamine during LORR. Propofol significantly increased δ, θ, α, and ß power during LORR. However, the EEG results obtained using riluzole, which produced a unique pattern of lower amplitude activity spanning most frequencies, markedly differed from those with the other drugs. CONCLUSIONS: This study revealed differences in EEG changes induced by various sedatives. The results obtained on MK-801 alone and MK-801 plus haloperidol suggest the importance of dopamine transmission in maintaining the righting reflex.

N-methyl-d-aspartate receptors and glycinergic transmission, respectively, mediate muscle relaxation and immobility of pentobarbital in mice.

Pentobarbital-induced anesthesia is believed to be mediated by enhancement of the inhibitory action of γ-aminobutyric acid (GABA)ergic neurons in the central nervous system. However, it is unclear whether all components of anesthesia induced by pentobarbital, such as muscle relaxation, unconsciousness, and immobility in response to noxious stimuli, are mediated only through GABAergic neurons. Thus, we examined whether the indirect GABA and glycine receptor agonists gabaculine and sarcosine, respectively, the neuronal nicotinic acetylcholine receptor antagonist mecamylamine, or the N-methyl-d-aspartate receptor channel blocker MK-801 could enhance pentobarbital-induced components of anesthesia. Muscle relaxation, unconsciousness, and immobility were evaluated by grip strength, the righting reflex, and loss of movement in response to nociceptive tail clamping, respectively, in mice. Pentobarbital reduced grip strength, impaired the righting reflex, and induced immobility in a dose-dependent manner. The change in each behavior induced by pentobarbital was roughly consistent with that in electroencephalographic power. A low dose of gabaculine, which significantly increased endogenous GABA levels in the central nervous system but had no effect on behaviors alone, potentiated muscle relaxation, unconsciousness, and immobility induced by low pentobarbital doses. A low dose of MK-801 augmented only the masked muscle-relaxing effects of pentobarbital among these components. Sarcosine enhanced only pentobarbital-induced immobility. Conversely, mecamylamine had no effect on any behavior. These findings suggest that each component of anesthesia induced by pentobarbital is mediated through GABAergic neurons and that pentobarbital-induced muscle relaxation and immobility may partially be associated with N-methyl-d-aspartate receptor antagonism and glycinergic neuron activation, respectively.

Difficult intubation and postoperative aspiration pneumonia associated with Moebius syndrome: a case report.

BACKGROUND: Moebius syndrome is a rare congenital disorder characterized by non-progressive palsy of the abducens (VI) and facial (VII) cranial nerves. Its common features include dysfunctions associated with other cranial nerves, orofacial abnormalities, skeletal muscle hypotonia, and other systemic disorders of differing severities. There are several concerns in the perioperative management of patients with Moebius syndrome. CASE PRESENTATION: We present a report on the management of general anesthesia of a 14-year-old male patient with Moebius syndrome who was scheduled for mandibular cystectomy. The patient was diagnosed with Moebius syndrome at the age of 7 years based on his clinical manifestations of nerve palsy since birth and cranial nerve palsy of the trigeminal (V), facial (VII), glossopharyngeal (IX), vagus (X), and sublingual nerves (XII). The patient's oral morphological abnormalities made intubation difficult. He also experienced dysphagia and aspiration pneumonia on a daily basis. Oral secretions were frequently suctioned postoperatively. However, after discharge, the patient developed aspiration pneumonia and was readmitted to the hospital. CONCLUSIONS: The main problem arising when administering general anesthesia to patients with this syndrome is difficult airway management. The oral abnormalities in these patients, such as small jaw and extreme dental stenosis, make mask ventilation and intubation difficult. Furthermore, this syndrome often involves respiratory impairment and dysphagia due to cerebral nerve palsy, so there is a high risk of postoperative respiratory complications. Since multiple organs are affected in patients with Moebius syndrome, appropriate perioperative management strategies must be prepared for these patients.

Prenatal exposure to valproic acid causes allodynia associated with spinal microglial activation.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction and the presence of restricted, repetitive behaviors. Additionally, difficulties in sensory processing commonly occur in ASD. Sensory abnormalities include heightened or reduced sensitivity to pain, but the mechanism underlying sensory phenotypes in ASD remain unknown. Emerging evidence suggests that microglia play an important role in forming and refining neuronal circuitry, and thus contribute to neuronal plasticity and nociceptive signaling. In the present study, we investigated the age-dependent tactile sensitivity in an animal model of ASD induced by prenatal exposure to valproic acid (VPA) and subsequently assessed the involvement of microglia in the spinal cord in pain processing. Pregnant ICR (CD1) mice were intraperitoneally injected with either saline or VPA (500 mg/kg) on embryonic day 12.5. Male offspring of VPA-treated mothers showed mechanical allodynia at both 4 and 8 weeks of age. In the spinal cord dorsal horn in prenatally VPA-treated mice, the numbers and staining intensities of ionized calcium-binding adapter molecule 1-positive cells were increased and the cell bodies became enlarged, indicating microglial activation. Treatment with PLX3397, a colony-stimulating factor 1 receptor inhibitor, for 10 days resulted in a decreased number of spinal microglia and attenuated mechanical allodynia in adult mice prenatally exposed to VPA. Additionally, intrathecal injection of Mac-1-saporin, a saporin-conjugated anti-CD11b antibody to deplete microglia, abolished mechanical allodynia. These findings suggest that prenatal VPA treatment causes allodynia and that spinal microglia contribute to the increased nociceptive responses.

Mirogabalin alleviates nociceptive hypersensitivity without causing sedation in a mouse model of post-traumatic trigeminal neuropathy.

Post-traumatic trigeminal neuropathy (PTTN) is a chronic sensory disorder that afflicts patients with nerve injury caused by orofacial and dental surgery or cervicofacial trauma. Currently, effective treatment strategies for PTTN are lacking, and patients treated with conventional drugs for PTTN experience adverse effects such as drowsiness and drug addiction. In the present study, we investigated whether mirogabalin, a novel gabapentinoid, could be an effective treatment for PTTN induced by distal infraorbital nerve chronic constriction injury (dIoN-CCI) in the mouse. Increased facial grooming time and hyper-responsiveness to acetone were observed in dIoN-CCI mice. These pain-related behaviors were attenuated by intraperitoneal injection of mirogabalin. In particular, mirogabalin significantly diminished the increase in facial grooming time. The analgesic effect of mirogabalin injection started 45 min after the injection and persisted for 6 h. Additionally, 10 mg/kg mirogabalin did not affect locomotor activity in the open field test, suggesting that it does not cause sedation. Together, the current findings suggest that mirogabalin could be a valuable therapeutic drug for PTTN following orofacial surgeries without sedative side effects.

Pentobarbital may protect against neurogenic inflammation after surgery via inhibition of substance P release from peripheral nerves of rats.

The inflammatory response related to surgery is considered surgical inflammation. Most anesthetic agents directly or indirectly suppress the immune response. However, the intravenous anesthetics pentobarbital and ketamine were reported to inhibit the lipopolysaccharide-induced inflammatory response such as cytokines formation. Neurogenic inflammation is inflammation originating from the local release of inflammatory mediators, such as substance P (SP), by primary afferent neurons after noxious stimuli like surgery. Thus, in this study, we examined whether pentobarbital and ketamine suppress SP release from cultured dorsal root ganglion (DRG) neurons. DRG cells were dissected from male Wistar rats. Released SP was measured by radioimmunoassay. We demonstrated that higher concentrations of pentobarbital (100-1,000 µM) significantly inhibited capsaicin (100 nM)-induced, but not high K+ (50 mM)-induced, SP release from DRG cells, although a high concentration of ketamine (1 mM) did not. This study revealed that pentobarbital functions between the activation of vanilloid receptor subtype 1 (TRPV1) receptors, to which capsaicin selectively binds, and the opening of voltage-operated Ca2+ channels (VOCC) in the nerve endings. Therefore, the anti-inflammatory action of pentobarbital is mediated through different mechanisms than those of ketamine. Thus, the inhibitory effect of pentobarbital on SP release from peripheral terminals may protect against neurogenic inflammation after surgery.

Real-time assessment of swallowing sound using an electronic stethoscope and an artificial intelligence system.

OBJECTIVES: Daily assessments of swallowing function and interventions such as rehabilitation and dietary adjustments are necessary to improve dysphagia. Cervical auscultation is convenient for health care providers for assessing swallowing ability. Although this method allows for swallowing sound evaluations, sensory evaluations with this method are difficult. Thus, we aimed to assess swallowing sound by the combined use of an electronic stethoscope and an artificial intelligence (AI) system that incorporates sound recognition. MATERIAL AND METHODS: Herein, 20 fifth-year dentistry student volunteers were included; each participant was drank 10 ml and then 20 ml of water in different positions (sitting and supine). We developed an algorithm for indexing bolus inflow sounds using AI, which compared the swallowing sounds and created a new index. RESULTS: The new index value used for swallowing sound was significantly higher in men than in women and in the sitting position than in the supine position. A software for acoustic analysis confirmed that the swallowing index was significantly higher in men than in women as well as in the sitting position than in the supine position. These results were similar to those obtained using the new index. However, the new index substantially differed between sexes in terms of posture compared with effective sound pressure. CONCLUSIONS: We developed a new algorithm for indexing swallowing sounds using a stethoscope and an AI system, which could identify swallowing sounds. For future research and development, evaluations of patients with dysphagia are necessary to determine the efficacy of the new index for bedside screening of swallowing conditions.

Efficacy of Chest Compressions Performed on Patients in Dental Chairs Versus on the Floor.

This study aimed to investigate the characteristics of chest compressions performed in dental chairs (DCs) with 2 different structural support designs and on the floor. This randomized prospective study was conducted to compare the effectiveness of chest compressions (rate and depth) using a feedback device and a manikin reporting system. The mean anterior chest wall motion measurements captured using the feedback device were significantly increased in the DCs than on the floor, whereas the percentage of net chest compression depths ≥5 cm as measured using the manikin reporting system were significantly decreased in the DCs than on the floor. These findings suggest that cardiopulmonary resuscitation performed in a DC without the use of a supporting stool or stiff backboard is not likely to be effective even if a DC design that incorporates a supportive steel column is utilized.

Pretreatment with High Mobility Group Box-1 Monoclonal Antibody Prevents the Onset of Trigeminal Neuropathy in Mice with a Distal Infraorbital Nerve Chronic Constriction Injury.

Persistent pain following orofacial surgery is not uncommon. High mobility group box 1 (HMGB1), an alarmin, is released by peripheral immune cells following nerve injury and could be related to pain associated with trigeminal nerve injury. Distal infraorbital nerve chronic constriction injury (dIoN-CCI) evokes pain-related behaviors including increased facial grooming and hyper-responsiveness to acetone (cutaneous cooling) after dIoN-CCI surgery in mice. In addition, dIoN-CCI mice developed conditioned place preference to mirogabalin, suggesting increased neuropathic pain-related aversion. Treatment of the infraorbital nerve with neutralizing antibody HMGB1 (anti-HMGB1 nAb) before dIoN-CCI prevented both facial grooming and hyper-responsiveness to cooling. Pretreatment with anti-HMGB1 nAb also blocked immune cell activation associated with trigeminal nerve injury including the accumulation of macrophage around the injured IoN and increased microglia activation in the ipsilateral spinal trigeminal nucleus caudalis. The current findings demonstrated that blocking of HMGB1 prior to nerve injury prevents the onset of pain-related behaviors, possibly through blocking the activation of immune cells associated with the nerve injury, both within the CNS and on peripheral nerves. The current findings further suggest that blocking HMGB1 before tissue injury could be a novel strategy to prevent the induction of chronic pain following orofacial surgeries.

Expression of PRIP, a phosphatidylinositol 4,5-bisphosphate binding protein, attenuates PI3K/AKT signaling and suppresses tumor growth in a xenograft mouse model.

Cancer is characterized by uncontrolled proliferation resulting from aberrant cell cycle progression. The activation of phosphatidylinositol 3-kinase (PI3K)/AKT signaling, a regulatory pathway for the cell cycle, stabilizes cyclin D1 in the G1 phase by inhibiting the activity of glycogen synthase kinase 3ß (GSK3ß) via phosphorylation. We previously reported that phospholipase C-related catalytically inactive protein (PRIP), a phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] binding protein, regulates PI3K/AKT signaling by competitively inhibiting substrate recognition by PI3K. Therefore, in this study, we investigated whether PRIP is involved in cell cycle progression. PRIP silencing in MCF-7 cells, a human breast cancer cell line, demonstrated PI(3,4,5)P3 signals accumulated at the cell periphery compared to that of the control. This suggests that PRIP reduction enhances PI(3,4,5)P3-mediated signaling. Consistently, PRIP silencing in MCF-7 cells exhibited increased phosphorylation of AKT and GSK3ß which resulted in cyclin D1 accumulation. In contrast, the exogenous expression of PRIP in MCF-7 cells evidenced stronger downregulation of AKT and GSK3ß phosphorylation, reduced accumulation of cyclin D1, and diminished cell proliferation in comparison to control cells. Flow cytometry analysis indicated that MCF-7 cells stably expressing PRIP attenuate cell cycle progression. Importantly, tumor growth of MCF-7 cells stably expressing PRIP was considerably prevented in an in vivo xenograft mouse model. In conclusion, PRIP expression downregulates PI3K/AKT/GSK3ß-mediated cell cycle progression and suppresses tumor growth. Therefore, we propose that PRIP is a new therapeutic target for anticancer therapy.

Syntaxin 3 interacts with serotonin transporter and regulates its function.

Herein, we investigated the functional association of the serotonin transporter (SERT) with syntaxin-3 (STX3). We first overexpressed SERT and STX3 in various cells and examined their interaction, localization, and functional association. Immunoprecipitation studies revealed that STX3 interacted with SERT when expressed in COS-7 cells. Immunocytochemical studies revealed that SERT and STX3 were colocalized in the endoplasmic reticulum (ER) and Golgi apparatus. STX3 overexpression significantly reduced the uptake activity of SERT by attenuating its plasma membrane expression, suggesting that overexpressed STX3 anchors SERT in the ER and Golgi apparatus. STX3 knockdown did not affect the uptake activity of SERT but altered its glycosylation state. To elucidate the association of STX3 with SERT under physiological conditions, rather than overexpressing cells, we investigated this interaction in polarized Caco-2 cells, which endogenously express both proteins. Immunocytochemical studies revealed that SERT and STX3 were localized in microvilli-like structures at the apical plasma membrane. STX3 knockdown marginally but significantly decreased the serotonin uptake activity of Caco-2 cells, suggesting that STX3 positively regulates SERT function in Caco-2 cells, as opposed to SERT regulation by STX3 in overexpressing cells. Collectively, STX3 may colocalize with SERT during SERT membrane trafficking and regulate SERT function in an STX3-expressing lesion-dependent manner.

Usefulness of Tranexamic Acid Administration During Sagittal Split Ramus Osteotomy.

ABSTRACT: Tranexamic acid has been used to reduce intraoperative bleeding; however, its effect on anti-inflammation and the amount of drainage after orthognathic surgery is yet to be determined. Therefore, we aimed to examine the effect of tranexamic acid on intraoperative bleeding volume and operation time, amount of drainage, and anti-inflammation after orthognathic surgery. Forty healthy women who underwent bilateral sagittal split ramus osteotomy under general anesthesia participated in this study. The amount of intraoperative bleeding, the operation time, the amount of drainage, and the C-reactive protein level were compared between patients intravenously administered with tranexamic acid before surgery (before-surgery group) and those administered with the drug after surgery (after-surgery group). All data were analyzed using the Student t-test. Results were considered to be statistically significant when P < 0.05. Although no significant difference was found in the amount of drainage between the groups (P > 0.05), significant variations were detected in the amount of bleeding during surgery (before-surgery group: 161.7 ±â€Š45.3 mL versus after-surgery group: 270.2 ±â€Š24.0 mL; P = 0.0009), operation time (before-surgery group: 141.3 ±â€Š16.8 min versus after-surgery group: 166.8 ±â€Š24.9 min; P = 0.03), and postoperative C-reactive protein level (before-surgery group: 3.77 ±â€Š0.40 mg/dL versus after-surgery group: 5.02 ±â€Š0.75 mg/dL; P = 0.012) between the groups. In conclusion, administering tranexamic acid before surgery was found to significantly decrease bleeding, reduce operation time, and suppress postoperative inflammation.

Component of nicotine-induced intracellular calcium elevation mediated through α3- and α5-containing nicotinic acetylcholine receptors are regulated by cyclic AMP in SH-SY 5Y cells.

The pathway from the medial habenular nucleus to the interpeduncular nucleus, in which nicotinic acetylcholine receptor (nAChR) including the α3 and α5 subunits (α3 * and α5 * nAChRs) are expressed, is implicated in nicotine dependence. We investigated whether α3 * and α5 * nAChRs are regulated by cAMP using SH-SY5Y cells to clarify the significance of these receptors in nicotine dependence. We analyzed the nicotine-induced elevation of intracellular Ca2+ ([Ca2+]i). Nicotine induces a concentration-dependent increase in [Ca2+]i. The elimination of Ca2+ from extracellular fluid or intracellular stores demonstrated that the nicotine-induced [Ca2+]i elevation was due to extracellular influx and intracellular mobilization. The effects of tubocurarine on nicotine-induced [Ca2+]i elevation and current suggest that intracellular mobilization is caused by plasma membrane-permeating nicotine. The inhibition of α3 *, α5 *, α7 nAChR and voltage-gated Ca2+ channels by using siRNAs and selective antagonists revealed the involvement of these nAChR subunits and channels in nicotine-induced [Ca2+]i elevation. To distinguish and characterize the α3 * and α5 * nAChR-mediated Ca2+ influx, we measured the [Ca2+]i elevation induced by nonmembrane-permeating acetylcholine when muscarinic receptors, α7nAChR and Ca2+ channels were blocked. Under this condition, the [Ca2+]i elevation was significantly inhibited with a 48-h treatment of dibutyryl cAMP, which was accompanied by the downregulation of α3 and ß4 mRNA. These findings suggest that α3 * and α5 * nAChR-mediated Ca2+ influx is possibly regulated by cAMP at the transcriptional level.

The indirect γ-aminobutyric acid (GABA) receptor agonist gabaculine-induced loss of the righting reflex may inhibit the descending analgesic pathway.

In the spinal cord, γ-aminobutyric acid (GABA) interneurons play an essential role in antinociception. However, not all actions of GABA favor antinociception at the supraspinal level. We previously reported that gabaculine, which increases endogenous GABA in the synaptic clefts, induces loss of the righting reflex (LORR) that is one indicator of hypnosis, but not immobility in response to noxious stimulus. A slow pain is transmitted to the spinal cord via C fibers and evokes substance P (SP) release from their terminals. However, the antinociceptive effects of gabaculine are still unknown. Our study examined whether the analgesic effects of the opioid morphine or the α2-adrenoceptor agonist dexmedetomidine, whose actions are mediated through facilitation of the descending analgesic pathway, are affected by gabaculine-induced LORR. We also explored the effects of GABA receptor agonists on SP release from cultured dorsal root ganglion (DRG) neurons. All drugs were administered systemically to mice. To assess antinociception, loss of nociceptive response (analgesia) and immobility were evaluated. DRG cells were dissected from rats. Gabaculine produced no analgesia. Either morphine or dexmedetomidine in combination with gabaculine induced immobility; however, the doses of each drug required to induce immobility were much higher than those required to induce analgesia. Capsaicin significantly increased SP release from DRG cells, but a high concentration (1 mM) of the GABA receptor agonist muscimol, propofol, gaboxadol, or baclofen did not inhibit the capsaicin-induced SP release, suggesting that their antinociceptive effects were not through this mechanism. Thus, the gabaculine-induced LORR may inhibit the descending analgesic pathway.

Phospholipase C-related catalytically inactive protein: A novel signaling molecule for modulating fat metabolism and energy expenditure.

BACKGROUND: Overweight and obesity are defined as excessive or abnormal fat accumulation in adipose tissues, and increase the risk of morbidity in many diseases, including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, and stroke, through pathophysiological mechanisms. There is strong evidence that weight loss reduces the risk of metabolic syndrome by limiting blood pressure and improving the levels of serum triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. To date, several attempts have been made to develop effective anti-obesity medication or weight-loss drugs; however, satisfactory drugs for clinical use have not yet been developed. Therefore, elucidation of the molecular mechanisms driving fat metabolism (adipogenesis and lipolysis) represents the first step in developing clinically useful drugs and/or therapeutic treatments to control obesity. HIGHLIGHT: In our previous study on intracellular signaling of phospholipase C-related catalytically inactive protein (PRIP), we generated and analyzed Prip-double knockout (Prip-DKO) mice. Prip-DKO mice showed tolerance against insulin resistance and a lean phenotype with low fat mass. Here, we therefore reviewed the involvement of PRIP in fat metabolism and energy expenditure. We conclude that PRIP, a protein phosphatase-binding protein, can modulate fat metabolism via phosphoregulation of adipose lipolysis-related molecules, and regulates non-shivering heat generation in brown adipocytes. CONCLUSION: We propose PRIP as a new therapeutic target for controlling obesity or developing novel anti-obesity drugs.

SKF-10047, a prototype Sigma-1 receptor agonist, augmented the membrane trafficking and uptake activity of the serotonin transporter and its C-terminus-deleted mutant via a Sigma-1 receptor-independent mechanism.

The serotonin transporter (SERT) is functionally regulated via membrane trafficking. Our previous studies have demonstrated that the SERT C-terminal deletion mutant (SERTΔCT) showed a robust decrease in its membrane trafficking and was retained in the endoplasmic reticulum (ER), suggesting that SERTΔCT is an unfolded protein that may cause ER stress. The Sigma-1 receptor (SigR1) has been reported to attenuate ER stress via its chaperone activity. In this study, we investigated the effects of SKF-10047, a prototype SigR1 agonist, on the membrane trafficking and uptake activity of SERT and SERTΔCT expressed in COS-7 cells. Twenty-four hours of SKF-10047 treatment (>200 µM) accelerated SERT membrane trafficking and robustly upregulated SERTΔCT activity. Interestingly, these effects of SKF-10047 on SERT functions were also found in cells in which SigR1 expression was knocked down by shRNA, suggesting that SKF-10047 exerted these effects on SERT via a mechanism independent of SigR1. A cDNA array study identified several candidate genes involved in the mechanism of action of SKF-10047. Among them, Syntaxin3, a member of the SNARE complex, was significantly upregulated by 48 h of SKF-10047 treatment. These results suggest that SKF-10047 is a candidate for ER stress relief.

Effective Postoperative Analgesia Using Intravenous Flurbiprofen and Acetaminophen.

PURPOSE: Management of postoperative pain is one of the most important components in postoperative care, because most patients have pain after dental surgery. The aim of this study was to evaluate whether acetaminophen could be an alternative to fentanyl in combination with a nonsteroidal anti-inflammatory drug (NSAID) as an analgesic after dental surgery in cases in which narcotic drugs were contraindicated. MATERIALS AND METHODS: Patients were 24- to 54-year-old men who underwent enucleation of a mandibular cyst under general anesthesia. The authors measured time from discontinuation of anesthetic administration until discharge from the operating room and postoperative pain during 4 hours after discharge. They compared these parameters between patients who were intravenously administered an NSAID such as flurbiprofen with fentanyl (NSAID/fentanyl group) and those administered an NSAID with acetaminophen (NSAID/acetaminophen group). Parametric data of time were analyzed using Student t test. Nonparametric data of the analgesic effect were analyzed using Mann-Whitney U test. RESULTS: Time until discharge from the operating room after discontinuation of anesthetics in the NSAID/fentanyl group was significantly longer than that in the NSAID/acetaminophen group (P < .05). In contrast, there was no significant difference in analgesic effect between the NSAID/acetaminophen and NSAID/fentanyl groups (P > .05). CONCLUSION: Although recovery time in the operating room of the flurbiprofen and acetaminophen group was markedly shorter than that of the flurbiprofen and fentanyl group, the postoperative analgesic effects of the 2 drugs were equipotent. Therefore, acetaminophen can be an alternative to fentanyl in cases in which narcotic drugs are contraindicated.

Propofol induced diverse and subtype-specific translocation of PKC families.

Propofol is the most commonly used anesthetic. Immunohistochemical studies have reported that propofol translocated protein kinase Cs (PKCs) in cardiomyocyte in a subtype-specific manner; however detailed features of the propofol-induced translocation of PKCs remain unknown. In this study, we performed real-time observation of propofol-induced PKC translocation in SH-SY5Y cells expressing PKCs fused with a fluorescent protein. Propofol unidirectionally translocated γPKC-GFP, a conventional PKC, and ζPKC-GFP, an atypical PKC, to the plasma membrane and nucleus, respectively, whereas the propofol-induced translocation of novel PKCs was diverse and subtype-specific among δPKC, εPKC and ηPKC. The propofol-induced translocation of εPKC-GFP was especially complicated and diverse, that is, 200 µM propofol first translocated εPKC-GFP to the perinuclear region. Thereafter, εPKC was translocated to the nucleus, followed by translocation to the plasma membrane. Analysis using a mutant εPKC in which the C1 domain was deleted demonstrated that the C1b domain of εPKC was indispensable for its translocation to the perinuclear region and plasma membrane, but not for its nuclear translocation. An in vitro kinase assay revealed that propofol increased the activities of the PKCs activities at the concentration that triggered the translocation. These results suggest that propofol could translocate PKCs to their appropriate target sites in a subtype-specific manner and concomitantly activated PKCs at these sites, contributing to its beneficial or adverse effects.

Management of an Internal Carotid Artery Injury Caused by a Displaced Titanium Plate With a Combination of Interventional Vascular Radiology and Surgery.

Treatment of pseudoaneurysms in the internal carotid artery (ICA) is associated with a high risk of cerebral infarction; therefore, vessel ligation for hemostasis must be avoided. A 66-year-old man had intraoral hemorrhaging. At the time of the initial examination, computed tomography angiography showed jaw plate displacement near the ICA. A more detailed image was obtained using digital-subtraction angiography. After evaluation of the image, a pseudoaneurysm was diagnosed. Six days later, there were concerns about aspiration and airway obstruction; therefore, tracheostomy was performed. Interventional vascular radiology (IVR) and surgery were planned to facilitate complete recovery, removal of the jaw plate, and repair of the pseudoaneurysm. Before surgery, it was confirmed that it would be possible to block blood flow for approximately 20 minutes. Surgery was performed with the patient under general anesthesia. Before plate removal, cardiovascular surgeons exposed the left large saphenous vein and prepared it so that it could be used to patch the vascular wall defect. A balloon type of embolic protection device was placed so that it could be inflated at any time after plate removal via oral surgery. The pseudoaneurysm was found directly under the plate; however, it had adhered to the scar tissue. As removal progressed, hemorrhaging occurred. To achieve hemostasis, the balloon embolic protection device was inflated. The pseudoaneurysm was removed, and a red thrombus was aspirated. On postoperative day 41, bleeding reoccurred. Two days later, embolization using a platinum coil and stent placement were performed through IVR monotherapy. Postoperative progress was favorable, and the patient was discharged 83 days after treatment without neurologic sequelae. ICA pseudoaneurysms located near the skull base are risky and challenging to repair. However, for traumatic aneurysms such as the one in this case, a combination of IVR therapy and surgery is useful for controlling intraoperative hemorrhage.

A Case With Deteriorating Palmoplantar Pustulosis and Hyperthyroidism After Simultaneous Bimaxillary Orthognathic Surgery.

A case of palmoplantar pustulosis and hyperthyroidism following orthognathic surgery is presented. Both diseases may have been related to allergic phenomena.