RANKL+ senescent cells under mechanical stress: a therapeutic target for orthodontic root resorption using senolytics.

In dentistry, orthodontic root resorption is a long-lasting issue with no effective treatment strategy, and its mechanisms, especially those related to senescent cells, remain largely unknown. Here, we used an orthodontic intrusion tooth movement model with an L-loop in rats to demonstrate that mechanical stress-induced senescent cells aggravate apical root resorption, which was prevented by administering senolytics (a dasatinib and quercetin cocktail). Our results indicated that cementoblasts and periodontal ligament cells underwent cellular senescence (p21+ or p16+) and strongly expressed receptor activator of nuclear factor-kappa B (RANKL) from day three, subsequently inducing tartrate-resistant acid phosphatase (TRAP)-positive odontoclasts and provoking apical root resorption. More p21+ senescent cells expressed RANKL than p16+ senescent cells. We observed only minor changes in the number of RANKL+ non-senescent cells, whereas RANKL+ senescent cells markedly increased from day seven. Intriguingly, we also found cathepsin K+p21+p16+ cells in the root resorption fossa, suggesting senescent odontoclasts. Oral administration of dasatinib and quercetin markedly reduced these senescent cells and TRAP+ cells, eventually alleviating root resorption. Altogether, these results unveil those aberrant stimuli in orthodontic intrusive tooth movement induced RANKL+ early senescent cells, which have a pivotal role in odontoclastogenesis and subsequent root resorption. These findings offer a new therapeutic target to prevent root resorption during orthodontic tooth movement.

Perforation of the Nasal Septum Identified During a Preoperative Otorhinolaryngology Consultation: A Case Report.

Nasal intubation is often required during oral surgery; however, nasal intubation can cause various complications including bleeding associated with nasal mucosal trauma during intubation and obstruction of the endotracheal tube. Two days before surgery, a nasal septal perforation was identified using computed tomography during a preoperative otorhinolaryngology consultation for a patient planned to undergo a nasally intubated general anesthetic. Subsequently, nasotracheal intubation was successfully performed after confirming the size and location of the nasal septal perforation. We used a flexible fiber optic bronchoscope to safely perform the nasal intubation while assessing for inadvertent migration of the endotracheal tube or soft-tissue damage around the perforation site. Careful preoperative planning in cooperation with the otorhinolaryngology department and use of computed tomography is recommended when a nasal abnormality is suspected.

A Case of Nasal Mucosa Cautery With Reintubation Under Pharyngeal Suction for Massive Epistaxis After Extubation.

We describe a case of massive epistaxis that occurred after removal of a nasal endotracheal tube, prompting emergent reintubation. Mask ventilation could not be performed because the nasal cavity was packed with gauze and the airway was being evacuated with a suction catheter. Therefore, instead of inhalational anesthetics and muscle relaxants, boluses of midazolam and remifentanil were administered, and reintubation was promptly performed. Sedation was maintained with dexmedetomidine infusion and midazolam. Nasal cautery was performed near the left sphenopalatine foramen. The patient was extubated without agitation or additional hemorrhage. Immediate recognition of the potential for airway loss, sufficient control of active bleeding, and drug selection in accordance with the emergent circumstances enabled prompt resecuring of the airway without pulmonary aspiration of blood.

Severe gag reflex during dental treatment associated with hiatus hernia: A case report.

AIMS: This report presents a case wherein severe gagging during dental treatment was linked to hiatus hernia. METHODS AND RESULTS: A 22-year-old man with a severe gagging problem presented with a chief complaint of pain localized to the lower molars. Oral examination revealed inadequate plaque control, demineralization of the enamel surface on buccal-gingival margins of all teeth, and inflamed gingival tissue surrounding the coronal portion of both mandibular third molars; panoramic radiography revealed that they were horizontally impacted. As the patient reported experiencing vomiting and heartburn for the past two months, he was referred to the internal medicine department before scheduling surgical tooth extraction. Hiatus hernia and reflux esophagitis were diagnosed, and the severity of gagging was significantly reduced by modifying the patient's eating behavior and administering a proton pump inhibitor. Although intravenous sedation was still required for surgical extraction of the impacted third molars, preventive treatments, such as tooth cleaning and fluoride application, could be performed without the need for pharmacological intervention. CONCLUSION: While gagging is often attributed to conditioning responses and iatrogenic factors, interdisciplinary consultation for successful management may facilitate the elucidation of local anatomical and systemic causes.

Anesthetic Management of a Patient With Restless Legs Syndrome: A Case Report.

Restless legs syndrome (RLS) is a neurological sensory disorder associated with sensory and motor symptoms that most commonly occur at night and during periods of rest. It is characterized by altered or abnormal sensations primarily in the legs and the urge to move the associated limbs. Perioperative procedures, including general anesthesia, can cause exacerbations of RLS. This is a case report of a suspected RLS exacerbation in a 22-year-old woman who had no formal diagnosis of RLS despite reporting symptoms that met all essential diagnostic criteria by the International RLS Study Group. Despite her previous diagnoses of dehydration induced-muscle pain or nocturnal cramps, we suspected her to have RLS. The patient underwent general anesthesia for a bilateral sagittal split ramus osteotomy using a combined inhalational and intravenous anesthetic technique with sevoflurane, propofol, remifentanil, and dexmedetomidine. After successful completion of the surgery and returning to the ward, she began moving her lower extremities and complaining of unpleasant sensations in both ankles. Bed rest exacerbated the suspected RLS symptoms despite a continuous infusion of dexmedetomidine. The RLS symptoms continued to worsen and spread to her upper extremities. After increasing the dexmedetomidine infusion from 0.2 to 0.4 µg/kg/h, almost all symptoms improved, and she slept for 3 hours. Upon awakening, the unpleasant sensations were completely relieved by walking and stretching. The patient was formally diagnosed with RLS by a neurologist after discharge. In this case, an infusion of dexmedetomidine was helpful in successfully managing a suspected exacerbation of RLS.

Anesthetic Management of Patient With Dravet Syndrome: A Case Report.

Dravet syndrome (DS) is a rare and severe form of epilepsy that begins in infancy. This is particularly burdensome because repeated epileptic seizures lead to cognitive decline. We describe the case of a 12-year-old girl who was diagnosed with DS and was scheduled to have gingival reduction around her mandibular molars. Despite the patient being intellectually disabled, she was able to cooperate somewhat during medical procedures, including intravenous cannulation. Under the assumption that the major problem with anesthesia for DS would be the regulation of body temperature-induced seizures, we used body temperature management equipment to maintain the patient's body temperature during the procedure. We opted for intravenous sedation and administered a total dose of 4.5 mg midazolam throughout the procedure. Anesthesia was completed within 1 hour and 20 minutes without any adverse events. To the best of our knowledge, no previous studies have documented the anesthetic management of DS. In this case, no adverse events occurred perioperatively. However, the patient's temperature rose to that which indicated a slight fever despite the use of a standard cooling technique.

A Case of Cardiac Arrest for 31 Seconds During Recovery After Intravenous Sedation.

A 26-year-old woman with a history of feeling nauseated during dental local anesthesia presented to our clinic for tooth extraction under intravenous sedation. Although she had experienced episodes of neurally-mediated syncope, her symptoms were controlled well with drug therapy, stopped 3 years earlier. No syncope episodes developed over the previous 2 years. Tooth extraction was performed under intravenous sedation without incident. When she was returned to a sitting position after being roused, convulsion, loss of consciousness, and cardiac arrest developed. One week later, similar symptoms occurred immediately after suture removal. We suspect that the change in body position triggered these episodes. It is important to avoid abrupt changes in body position and any other triggers and to administer preventive drugs in patients at high risk of syncope.

Comparison of the Contact Force Exerted on Teeth by Conventional Macintosh Laryngoscope Versus Video Laryngoscopes.

During laryngoscopy, the laryngoscope blade sometimes comes in contact with the teeth, fracturing or dislocating them. However, no studies have compared the effects of newly marketed video laryngoscopes and the Macintosh laryngoscope (Mac) on teeth. In this study, we measured and compared the force exerted on the teeth of an intubating manikin by the Mac, the Airway Scope (Pentax), and the McGrath MAC (Covidien). The mean force exerted was 141.1 ± 15.7 kg by the Mac, 39.2 ± 10.3 kg by the Airway Scope, and 48.7 ± 6.7 kg by the McGrath MAC. No significant difference was observed between the Airway Scope and the McGrath MAC. When the Mac is inserted, the glottis has to be visually located from outside the oral cavity. However, a significant force is not necessary when inserting video laryngoscopes because a camera is mounted on the blade tip. In this laboratory model, the lower force exerted by the video laryngoscopes should contribute to a reduction in their impact on fracture or dislocation of teeth.

Recurrent Coronary Artery Spasm Induced by Vasopressors During Two Operations in the Same Patient Under General Anesthesia.

Variant angina is caused by coronary artery spasm (CAS) with ST-segment elevation. We herein report a case of recurrent CAS during 2 operations in the same patient. An 80-year-old woman was scheduled to undergo tracheostomy, submandibular dissection, left partial maxillectomy, and coronoidectomy. We administered ephedrine and phenylephrine to manage hypotension during general anesthesia. Immediately after the administration of these drugs, the ST segment elevated. We decided to cease the operation and transport the patient to the department of cardiology. Computed tomography angiography revealed pneumomediastinum. The cardiologists considered that the electrocardiography findings had changed secondary to pneumomediastinum. About 6 weeks later, a second operation was scheduled. We administered ephedrine and phenylephrine to manage hypotension during general anesthesia. Immediately after the administration of these drugs, ST-segment elevation occurred. We discontinued use of these drugs, and the ST-segment elevation did not recur. We considered that the cause of the ST-segment elevation was vasopressor-induced CAS because the vasopressors were administered immediately before the occurrence of CAS. Vasopressors such as ephedrine or phenylephrine are frequently used to manage hypotension during general anesthesia. Therefore, anesthesiologists should consider the occurrence of CAS before using vasopressors and know how to manage CAS well.

Functional recovery by application of human dedifferentiated fat cells on cerebral infarction mice model.

Elderly people whose daily activities have declined due to a cerebrovascular disorder may suffer from dysphagia and may find oral hygiene difficult. Therefore, it is important to establish an effective therapy for the underlying cerebrovascular disorder. Dedifferentiated fat cells (DFAT) were obtained from mature adipocytes isolated from human buccal adipose pads in a ceiling culture. DFAT expressed the neural markers Nestin and SOX2. Flow cytometric analysis revealed that the cells had properties similar to mesenchymal stem cells. Although the transplantation of DFAT did not change the infarction area and volume ratios in a murine cerebral infarction model, functional recovery was observed in behavioral tests. Furthermore, DFAT administered to mice were later detected in cerebral infarctions. It therefore appears that transplanted DFAT affect the brain after infarction and contribute to the promotion of functional recovery. This finding may provide new cell replacement therapy options for treating disorders of the central nervous system.

Junctional Rhythm Preoperatively and During General Anesthesia for Oral and Maxillofacial Surgery.

We report a case of junctional rhythm that occurred both preoperatively and later during a portion of general anesthesia. A 19-year-old woman was scheduled to undergo bilateral sagittal split ramus osteotomy after being diagnosed with a jaw deformity. Preoperative electrocardiography (ECG) revealed a junctional rhythm with a slow heart rate (HR). At 90 minutes after anesthesia induction, local anesthesia with 10 mL of 1% lidocaine and 1:100,000 adrenaline was administered. A junctional rhythm appeared 15 minutes after the local anesthesia. We believe that the atrioventricular nodal pacemaker cells accelerated because of the increased sympathetic activity due to the adrenaline. On the preoperative ECG, the junctional rhythm with slow HR appeared as an escaped beat caused by slowing of the primary pacemaker. Therefore, we think that the preoperative junctional rhythm and the junctional rhythm that appeared during general anesthesia were due to different causes. Understanding the cause of a junctional rhythm could lead to more appropriate treatment. We therefore believe that identifying the cause of the junctional rhythm is important in anesthetic management.

Tension Pneumothorax After Percutaneous Tracheostomy.

A 76-year-old woman with right mandibular gingival cancer was scheduled for surgery. A percutaneous tracheostomy kit was used for tracheostomy under intravenous sedation. After puncturing the cricothyroid membrane, a dilator was inserted along a guidewire. Bucking was observed at the time of insertion of the dilator, despite intratracheal lidocaine spray applied before insertion. After that, the tracheostomy tube was inserted, but no capnographic waveforms appeared when the tube was connected to the anesthesia circuit. Direct macroscopic observation revealed a perforation extending from the posterior wall of the trachea to the anterior wall of the esophagus, which prompted us to request assistance from a thoracic surgeon for treatment before reinserting the tracheostomy tube. After verifying capnographic waveforms on the monitor, anesthesia was induced. Because arterial oxygen saturation was 96% under the administration of pure oxygen, chest radiography was conducted revealing a right pneumothorax. A chest tube was inserted and the patient transported to a nearby general hospital. We suspect that pneumothorax was induced when the integrity of the mediastinal pleura was compromised by mediastinal emphysema because of the injury to the posterior tracheal wall complicated by bucking at the time of insertion of the dilator.

Anesthetic Management of a Patient With Multiple Sclerosis.

A 54-year-old woman diagnosed with multiple sclerosis (MS) at the age of 19 years was scheduled to undergo temporomandibular joint mobilization. She was currently in a remission phase from her MS but with persistent sequelae, including impaired eyesight and muscle weakness of the limbs. In addition, the blood vessels in her upper limbs were compromised by the formation of internal shunts secondary to vascular prosthesis replacements for plasma exchange therapy in MS. After a previous joint mobilization surgery, her temporomandibular joint developed adhesions with resultant trismus. One of the adverse effects of general anesthesia can be exacerbations of MS symptoms. Minimizing mental and physical stress caused by surgical and anesthetic procedures and maintenance of stable body temperature are important considerations. Awake intubation was performed under sedation with midazolam and fentanyl. After intubation, anesthesia was induced with propofol, remifentanil, and rocuronium. Maintenance of anesthesia was achieved with oxygen-N2O-sevoflurane, remifentanil, fentanyl, and rocuronium. In this case, no adverse events occurred intraoperatively. However, the patient experienced lingering weakness of the limbs in the postoperative period, and activities of daily living of the patient were affected.

Management of infusion reactions associated with cetuximab treatment: A case report.

Cetuximab is a drug targeting the epidermal growth factor receptor, which is indicated for the treatment of unresectable advanced or recurrent head and neck or colorectal cancer. Cetuximab also enhances the cytotoxic effects of radiation in squamous cell carcinoma. The severity of infusion reactions (IR) is categorized from grade 1 to 5; grades 3 and 4 are associated with life-threatening reactions (anaphylaxis), whereas grade 5 indicates death. The incidence of grade 3-4 IR with premedication is reported to be 1.1%. We herein describe a case of a 77-year-old man who developed IR during intravenous administration of cetuximab. The patient developed grade 3-4 anaphylaxis with pruritus, rash and urticaria, followed by hypotension and bradycardia. The timely diagnosis and treatment with intravenous infusion of a vasopressor drug and Ringer's acetate solution proved to be effective. The case presented herein demonstrated an unfeatured aspect of cetuximab-related IR as dermatological reactions over the entire body followed by circulatory collapse.

Induction of Perivascular Neural Stem Cells and Possible Contribution to Neurogenesis Following Transient Brain Ischemia/Reperfusion Injury.

Recent therapeutic advances have increased the likelihood of recanalizing the obstructed brain arteries in patients with stroke. Therefore, it is important to understand the fate of neural cells under transient ischemia/reperfusion injury. Accumulating evidence shows that neurogenesis occurs in perivascular regions following brain injury, although the precise mechanism and origin of these newborn neurons under transient ischemia/reperfusion injury remain unclear. Using a mouse model of transient brain ischemia/reperfusion injury, we found that neural stem cells (NSCs) develop within injured areas. This induction of NSCs following ischemia/reperfusion injury was observed even in response to nonlethal ischemia, although massive numbers of NSCs were induced by lethal ischemia. Immunohistochemical and immunoelectron microscopic studies indicated that platelet-derived growth factor receptor beta-positive (PDGFRß+) pericytes within injured areas following nonlethal ischemia began to express the NSC marker nestin as early as 3 days after transient ischemia/reperfusion. Some PDGFRß+ pericytes expressed the immature neuronal marker doublecortin at day 7. These findings indicate that brain pericytes are a potential source of the perivascular NSCs that generate neuronal cells under lethal and nonlethal ischemic conditions following transient ischemia/reperfusion. Thus, brain pericytes might be a target for neurogenesis mediation in patients with nonlethal and lethal ischemia following transient ischemia/reperfusion injury.

Anesthetic Management of a Patient With Ehlers-Danlos Syndrome.

We describe the case of a 37-year-old woman who had been diagnosed with Ehlers-Danlos syndrome (EDS) 4 years earlier and was scheduled to undergo removal of synovial chondromatosis in the temporomandibular joint. EDS is a heritable connective tissue disorder and has 6 types. In this case, the patient was classified into EDS hypermobility type. The major clinical feature of this type is joint hypermobility. The patient had sprain or subluxation of the elbows and ankles and dislocation of the knees. Anticipated problems during general anesthesia would be affected by the disease type. For this patient, extra attention was directed to positional injury-induced neuropathy and articular luxation, cutaneous injuries, injuries related to intubation and ventilation, and postoperative pain. Anesthesia was induced with propofol, remifentanil, and rocuronium and maintained with oxygen-air-desflurane, propofol, remifentanil, fentanyl, and rocuronium. In this case, the patient was safely managed without adverse events.

Anesthetic Management of a Patient With Charcot-Marie-Tooth Disease.

Charcot-Marie-Tooth disease (CMTD) is a hereditary peripheral neuropathy and is characterized by progressive muscle atrophy and motor-sensory disorders in all 4 limbs. Most reports have indicated that major challenges with general anesthetic administration in CMTD patients are the appropriate use of nondepolarizing muscle relaxants and preparation for malignant hyperthermia in neuromuscular disease. Moderate sedation may be associated with the same complications as those of general anesthesia, as well as dysfunction of the autonomic nervous system, reduced perioperative respiratory function, difficulty in positioning, and sensitivity to intravenous anesthetic agents. We decided to use intravenous sedation in a CMTD patient and administered midazolam initially and propofol continuously, with total doses of 1.5 mg and 300 mg, respectively. Anesthesia was completed in 3 hours and 30 minutes without adverse events. We suggest that dental anesthetic treatment with propofol and midazolam may be effective for patients with CMTD.

Sevoflurane induces cardioprotection through reactive oxygen species-mediated upregulation of autophagy in isolated guinea pig hearts.

PURPOSE: Sevoflurane increases reactive oxygen species (ROS), which mediate cardioprotection against myocardial ischemia-reperfusion injury. Emerging evidence suggests that autophagy is involved in cardioprotection. We examined whether reactive oxygen species mediate sevoflurane preconditioning through autophagy. METHODS: Isolated guinea pigs hearts were subjected to 30 min ischemia followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2 % sevoflurane for 10 min before ischemia (SEVO). The ROS-scavenger, N-(2-mercaptopropionyl) glycine (MPG, 1 mmol/l), was administered starting 30 min before ischemia to sevoflurane-treated (SEVO + MPG) or non-sevoflurane-treated (MPG) hearts. Infarct size was determined by triphenyltetrazolium chloride stain. Tissue samples were obtained after reperfusion to determine autophagy-related protein (microtubule-associated protein light chain I and II: LC3-I, -II) and 5' AMP-activated protein kinase (AMPK) expression using Western blot analysis. Electron microscopy was used to detect autophagosomes. RESULTS: Infarct size was significantly reduced and there were more abundant autophagosomes in SEVO compared with control. Western blot analysis revealed that the ratio of LC3-II/I and phosphorylation of AMPK were significantly increased in SEVO. These effects were abolished by MPG. CONCLUSIONS: Sevoflurane induces cardioprotection through ROS-mediated upregulation of autophagy.