Anesthetic management of a patient with Sturge-Weber syndrome in sagittal split ramus osteotomy surgery.

Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome characterized by angiomas. This report presents airway management using submental intubation in sagittal split ramus osteotomy under general anesthesia and aimed to explore better anesthetic management for avoiding the rupture of angiomas in a patient with SWS.

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.

Severe perioperative lactic acidosis in a pediatric patient with glycogen storage disease type Ia: a case report.

BACKGROUND: Glycogen storage disease (GSD) is a group of rare inherited metabolic disorders caused by enzyme deficiencies in glycogen catabolism. GSD type Ia is a congenital deficiency of the enzyme responsible for the final step in glucose production by glycolysis, resulting in impaired carbohydrate metabolism. CASE PRESENTATION: A 14-year-old boy with GSD type Ia was scheduled for a maxillary cystectomy under general anesthesia. He was taking oral sugars such as uncooked cornstarch regularly to prevent hypoglycemia. Perioperatively, glucose was administered via the peripheral vein for fasting; however, severe lactic acidosis occurred. He also developed hypercapnia because of intraoperative poor ventilation caused by hepatomegaly. CONCLUSIONS: We experienced a child with GSD type Ia who developed severe lactic acidosis despite continuous glucose infusion. Further studies are required to determine appropriate perioperative management for patients with GSD, including fasting glucose administration.

Usefulness of new acoustic respiratory sound monitoring with artificial intelligence for upper airway assessment in obese patients during monitored anesthesia care.

Monitored anesthesia care (MAC) often causes airway complications, particularly posing an elevated risk of aspiration and airway obstruction in obese patients. This study aimed to quantify the levels of aspiration and airway obstruction using an artificial intelligence (AI)-based acoustic analysis algorithm, assessing its utility in identifying airway complications in obese patients. To verify the correlation between the stridor quantitative value (STQV) calculated by acoustic analysis and body weight, and to further evaluate fluid retention and airway obstruction, STQV calculated exhaled breath sounds collected at the neck region, was compared before and after injection of 3 ml of water in the oral cavity and at the start and end of the MAC procedures. STQV measured immediately following the initiation of MAC exhibited a weak correlation with body mass index. Furhtermore, STQV values before and after water injection increased predominantly after injection, further increased at the end of MAC. AI-based analysis of cervical respiratory sounds can enhance the safety of airway management during MAC by quantifying airway obstruction and fluid retention in obese patients. J. Med. Invest. 70 : 430-435, August, 2023.

New acoustic monitoring system quantifying aspiration risk during monitored anaesthesia care.

Respiratory monitoring is crucial during monitored anaesthesia care (MAC) to ensure patient safety. Patients undergoing procedures like gastrointestinal endoscopy and dental interventions under MAC have a heightened risk of aspiration. Despite the risks, no current system or device can evaluate aspiration risk. This study presents a novel acoustic monitoring system designed to detect fluid retention in the upper airway during MAC. We conducted a prospective observational study with 60 participants undergoing dental treatment under MAC. We utilized a prototype acoustic monitoring system to assess fluid retention in the upper airway by analysing inspiratory sounds. Water was introduced intraorally in participants to simulate fluid retention; artificial intelligence (AI) analysed respiratory sounds pre and post-injection. We also compared respiratory sounds pre-treatment and during coughing events. Coughing was observed in 14 patients during MAC, and 31 instances of apnoea were detected by capnography. However, 27 of these cases had breath sounds. Notably, with intraoral water injection, the Stridor Quantitative Value (STQV) significantly increased; furthermore, the STQV was substantially higher immediately post-coughing in patients who coughed during MAC. In summary, the innovative acoustic monitoring system using AI provides accurate evaluations of fluid retention in the upper airway, offering potential to mitigate aspiration risks during MAC.Clinical trial number: jRCTs 062220054.

Efficacy and safety of remimazolam besilate for sedation in outpatients undergoing impacted third molar extraction: a prospective exploratory study.

BACKGROUND: Dental treatments often cause anxiety, fear, and stress in patients. Intravenous sedation is widely used to alleviate these concerns, and various agents are employed for sedation. However, it is important to find safer and more effective sedation agents, considering the adverse effects associated with current agents. This study aimed to investigate the efficacy and safety of remimazolam besilate (hereinafter called "remimazolam") and to determine the optimal dosages for sedation in outpatients undergoing dental procedures. METHODS: Thirty-one outpatients aged 18-65 years scheduled for impacted third molar extraction were included in the study. Remimazolam was administered as a single dose of 0.05 mg/kg followed by a continuous infusion at a rate of 0.35 mg/kg/h, with the infusion rate adjusted to maintain a sedation level at a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of 2-4. The primary endpoint was the sedation success rate with remimazolam monotherapy, and the secondary endpoints included induction time, recovery time, time until discharge, remimazolam dose, respiratory and circulatory dynamics, and frequency of adverse events. RESULTS: The sedation success rate with remimazolam monotherapy was 100%. The remimazolam induction dose was 0.08 (0.07-0.09) mg/kg, and the anesthesia induction time was 3.2 (2.6-3.9) min. The mean infusion rate of remimazolam during the procedure was 0.40 (0.38-0.42) mg/kg/h. The time from the end of remimazolam administration to awakening was 8.0 (6.7-9.3) min, and the time from the end of remimazolam administration to discharge was 14.0 (12.5-15.5) min. There were no significant respiratory or circulatory effects requiring intervention during sedation. CONCLUSIONS: Continuous intravenous administration of remimazolam can achieve optimal sedation levels without significantly affecting respiratory or circulatory dynamics. The study also provided guidance on the appropriate dosage of remimazolam for achieving moderate sedation during dental procedures. Additionally, the study findings suggest that electroencephalogram monitoring can be a reliable indicator of the level of sedation during dental procedural sedation with remimazolam. TRIAL REGISTRATION: The study was registered in the Japan Registry of Clinical Trials (No. jRCTs061220052) on 30/08/2022.

Spinal Muscular Atrophy Type III Recognized After Delayed Recovery From Neuromuscular Blockade After an Orthognathic Surgery.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by the degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. SMA is classified into types I-IV based on the age at symptom onset or maximum motor function achieved, and its clinical manifestations vary. SMA affects maxillofacial growth because of muscle dysfunction and results in abnormal maxillofacial morphology. In addition, definitive diagnosis is not often made because of the older onset age and symptoms are rarely severe. Therefore, the possibility of undiagnosed SMA in craniofacial surgeries must be considered. This report described a case of an SMA type III recognized after delayed recovery from the neuromuscular blockade in an orthognathic surgery under general anesthesia.

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.

Analgesia-based Sedation for Oral Surgery in Patients With Chronic Respiratory Obstructive Disease.

Chronic obstructive pulmonary disease (COPD) is a risk factor for postoperative cardiovascular and respiratory complications. Thus, intravenous sedation can be a better option than general anesthesia for surgery in patients with severe COPD. Herein, we present 2 cases of analgesia-based sedation in patients with severe COPD who underwent oral surgery. The current study aimed to discuss these cases to provide knowledge about the appropriate sedation management in patients with this disease. In the current cases, the patients received sufficient analgesia and minimum sedation (analgesia-based sedation). Moreover, dexmedetomidine was used for maintaining sedation and fentanyl for analgesic effects. Furthermore, we focused on providing the maximum analgesic effect of local anesthesia. The patients' vital signs were stable. They did not have any psychological or physical complaints, such as anxiety and pain, during the procedure. Then, they were discharged from the hospital without any complications. Thus, analgesia-based sedation can be an alternative option for oral surgery in patients with COPD.

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.

Imipramine prevents Porphyromonas gingivalis lipopolysaccharide-induced microglial neurotoxicity.

Porphyromonas gingivalis (P. gingivalis) is a Gram-negative anaerobe involved in the pathogenesis of chronic periodontitis, including local inflammation of the oral cavity. However, periodontal disease has recently been identified as a significant factor in the pathogenesis of neural diseases, including Alzheimer's disease. A virulence factor, P. gingivalis-lipopolysaccharide (LPS-PG), is involved in pro-inflammatory responses, not only in peripheral tissues but also in the brain. In this study, we examined whether P. gingivalis-induced brain inflammation could be ameliorated by pharmacotherapy, using in vivo and in vitro studies. In an animal experiment, peripheral administration of LPS-PG induced inflammation in the hippocampus via microglial activation, which was inhibited by pre-treatment with the antidepressant imipramine. Similarly, LPS-PG-induced inflammation in MG-6 cells, a mouse microglial cell line, was inhibited by pre-treatment with imipramine, which caused imipramine-induced inhibition of NF-κB signaling. Culture media obtained from LPS-PG-treated MG-6 cells induced neuronal cell death in Neuro-2A cells, a mouse neuroblastoma cell line, which was prevented by pre-treatment of MG-6 cells with imipramine. These results indicate that imipramine inhibits LPS-PG-induced inflammatory responses in microglia and ameliorates periodontal disease-related neural damage.

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.

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.

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 regulates lipopolysaccharide-induced hypothalamic inflammation-mediated anorexia in mice.

Peripheral lipopolysaccharide (LPS) injection induces systemic inflammation through the activation of the inhibitor of nuclear factor kappa B (NF-κB) kinase (IKK)/NF-κB signaling pathway, which promotes brain dysfunction resulting in conditions including anorexia. LPS-mediated reduction of food intake is associated with activation of NF-κB signaling and phosphorylation of the transcription factor signal transducer and activator of transcription 3 (STAT3) in the hypothalamus. We recently reported phospholipase C-related catalytically inactive protein (PRIP) as a new negative regulator of phosphatidylinositol 3-kinase/AKT signaling. AKT regulates the IKK/NF-κB signaling pathway; therefore, this study aimed to investigate the role of PRIP/AKT signaling in LPS-mediated neuroinflammation-induced anorexia. PRIP gene (Prip1 and Prip2) knockout (Prip-KO) mice intraperitoneally (ip) administered with LPS exhibited increased anorexia responses compared with wild-type (WT) controls. Although few differences were observed between WT and Prip-KO mice in LPS-elicited plasma pro-inflammatory cytokine elevation, hypothalamic pro-inflammatory cytokines were significantly upregulated in Prip-KO rather than WT mice. Hypothalamic AKT and IKK phosphorylation and IκB degradation were significantly increased in Prip-KO rather than WT mice, indicating further promotion of AKT-mediated NF-κB signaling. Consistently, hypothalamic STAT3 was further phosphorylated in Prip-KO rather than WT mice. Furthermore, suppressor of cytokine signaling 3 (Socs3), a negative feedback regulator for STAT3 signaling, and cyclooxogenase-2 (Cox2), a candidate molecule in LPS-induced anorexigenic responses, were upregulated in the hypothalamus in Prip-KO rather than WT mice. Pro-inflammatory cytokines were upregulated in hypothalamic microglia isolated from Prip-KO rather than WT mice. Together, these findings indicate that PRIP negatively regulates LPS-induced anorexia caused by pro-inflammatory cytokine expression in the hypothalamus, which is mediated by AKT-activated NF-κB signaling. Importantly, hypothalamic microglia participate in this PRIP-mediated process. Elucidation of PRIP-mediated neuroinflammatory responses may provide novel insights into the pathophysiology of many brain dysfunctions.

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.

General anesthetic actions on GABAA receptors in vivo are reduced in phospholipase C-related catalytically inactive protein knockout mice.

PURPOSE: The aim of this study was to investigate the action of general anesthetics in phospholipase C-related catalytically inactive protein (PRIP)-knockout (KO) mice that alter GABAA receptor signaling. METHODS: PRIP regulates the intracellular trafficking of ß subunit-containing GABAA receptors in vitro. In this study, we examined the effects of intravenous anesthetics, propofol and etomidate that act via ß subunit-containing GABAA receptors, in wild-type and Prip-KO mice. Mice were intraperitoneally injected with a drug, and a loss of righting reflex (LORR) assay and an electroencephalogram analysis were performed. RESULTS: The cell surface expression of GABAA receptor ß3 subunit detected by immunoblotting was decreased in Prip-knockout brain compared with that in wild-type brain without changing the expression of other GABAA receptor subunits. Propofol-treated Prip-KO mice exhibited significantly shorter duration of LORR and had lower total anesthetic score than wild-type mice in the LORR assay. The average duration of sleep time in an electroencephalogram analysis was shorter in propofol-treated Prip-KO mice than in wild-type mice. The hypnotic action of etomidate was also reduced in Prip-KO mice. However, ketamine, an NMDA receptor antagonist, had similar effects in the two genotypes. CONCLUSION: PRIP regulates the cell surface expression of the GABAA receptor ß3 subunit and modulates general anesthetic action in vivo. Elucidation of the involved regulatory mechanisms of GABAA receptor-dependent signaling would inform the development of safer anesthetic therapies for clinical applications.

Phospholipase C-related catalytically inactive protein can regulate obesity, a state of peripheral inflammation.

Obesity is defined as abnormal or excessive fat accumulation. Chronic inflammation in fat influences the development of obesity-related diseases. Many reports state that obesity increases the risk of morbidity in many diseases, including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, sleep apnea, and breast, prostate and colon cancers, leading to increased mortality. Obesity is also associated with chronic neuropathologic conditions such as depression and Alzheimer's disease. However, there is strong evidence that weight loss reduces these risks, by limiting blood pressure and improving levels of serum triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol. Prevention and control of obesity is complex, and requires a multifaceted approach. The elucidation of molecular mechanisms driving fat metabolism (adipogenesis and lipolysis) aims at developing clinical treatments to control obesity. We recently reported a new regulatory mechanism in fat metabolism: a protein phosphatase binding protein, phospholipase C-related catalytically inactive protein (PRIP), regulates lipolysis in white adipocytes and heat production in brown adipocytes via phosphoregulation. Deficiency of PRIP in mice led to reduced fat accumulation and increased energy expenditure, resulting in a lean phenotype. Here, we evaluate PRIP as a new therapeutic target for the control of obesity.