Hyperpolarized 1- 13Cpyruvate Magnetic Resonance Spectroscopy Shows That Agmatine Increased Lactate Production in the Brain of Type 2 Diabetic Mice

Purpose@#Type 2 diabetes mellitus (T2DM) is associated with a 2-fold increased risk of developing Alzheimer’s disease. In earlier research, agmatine has been demonstrated to alleviate diabetes symptoms and increase cognitive performance. However, it is unclear whether the improvement of cognitive function is attributable to the reduction of diabetic symptoms or its direct influence on brain metabolism. Using hyperpolarized (HP) [1- 13C]pyruvate magnetic resonance spectroscopy (MRS), this study intends to evaluate the influence of agmatine on brain metabolism. @*Materials and Methods@#ICR mice were fed a high-fat diet and injected with streptozotocin to develop a T2DM animal model. During a 2-week period, T2DM mice were treated with normal saline or 100 mg/kg of agmatine, and brain HP [1- 13C]pyruvate MRS was performed. The effect of agmatine on lactate generation and NADH/NAD+ redox state was investigated using C6 and neuro-2a (N2a) cells. @*Results@#As a perfusion marker, the total 13C signals in the brain of T2DM mice (p=0.07) and agmatine-treated mice (p<0.05) were reduced. The conversion constant (Kpl) from [1- 13C]pyruvate to [1- 13C]lactate was not distinguishable in the brains of T2DM mice but was significantly increased in the brains of agmatine-treated T2DM mice. Treating C6 and N2a cells with agmatine increased NADH/NAD+ ratio and lactate generation. @*Conclusion@#Agmatine influences the NADH/NAD+ redox state in the brains of T2DM mice, which may be connected with enhanced cognitive performance and increased conversion of HP [1- 13C]pyruvate to HP [1- 13C]lactate.

Positional changes of the mandibular condyle in unilateral sagittal split ramus osteotomy combined with intraoral vertical ramus osteotomy for asymmetric class III malocclusion

Objectives@#In the present study, the effects of sagittal split ramus osteotomy (SSRO) combined with intraoral vertical ramus osteotomy (IVRO) for the treatment of asymmetric mandible in class Ⅲ malocclusion patients were assessed and the postoperative stability of the mandibular condyle and the symptoms of temporomandibular joint disorder (TMD) evaluated. @*Materials and Methods@#A total of 82 patients who underwent orthognathic surgery for the treatment of facial asymmetry or mandibular asymmetry at the Department of Oral and Maxillofacial Surgery, Dong-A University Hospital, from 2016 to 2021 were selected. The patients that underwent SSRO with IVRO were assigned to Group I (n=8) and patients that received bilateral SSRO (BSSRO) to Group II (n=10, simple random sampling). Preoperative and postoperative three-dimensional computed tomography (CT) axial images obtained for each group were superimposed. The condylar position changes and degree of rotation on the superimposed images were measured, and the changes in condyle based on the amount of chin movement for each surgical method were statistically analyzed. @*Results@#Group I showed a greater amount of postoperative chin movement. For the amount of mediolateral condylar displacement on the deviated side, Groups I and II showed an average lateral displacement of 0.07 mm and 1.62 mm, respectively, and statistically significantly correlated with the amount of chin movement (P=0.004). Most of the TMD symptoms in Group I patients who underwent SSRO with IVRO showed improvement. @*Conclusion@#When a large amount of mandibular rotation is required to match the menton to the midline of the face, IVRO on the deviated side is considered a technique to prevent condylar torque. In the present study, worsening of TMD symptoms did not occur after orthognathic surgery in any of the 18 patients.

Is distal segment ostectomy essential for stabilization of the condylar position in patients with facial asymmetry? / 대한악안면성형재건외과학회지

Background@#The purpose of this retrospective study was to evaluate the postoperative change in the position and stability of the mandibular condyle after bilateral sagittal split ramus osteotomy (BSSRO) and BSSRO with distal segmental ostectomy (DSO) in patients with facial asymmetry using 3D computed tomography. @*Methods@#The condyles of the patient diagnosed with facial asymmetry were divided into the deviated side (DS) and the non-deviated side (NDS). Group I, which was treated with BSSRO only, and Group II, which additionally received DSO along with BSSRO, were superimposed on the condyle using the pre-and postoperative 3D CT. The amount of condylar change in anteroposterior displacement, mediolateral displacement, and rotation was measured. The clinical symptoms of temporomandibular joint were also evaluated before and after surgery for each patient. @*Results@#Between Groups I and II, there was no statistically significant difference in the anteroposterior condylar position on both DS and NDS.And also, there was no statistical difference between the two groups in the mediolateral change on DS but, statistically significant difference on NDS. The change in the rotation of the condyle was observed to rotate inward from both condylar heads of Groups I and II, and a statistically significant difference was observed between the two groups on both DS and NDS. Moreover, no difference in clinical temporomandibular joint symptoms was observed after surgery in each DS and NDS condyle of the two groups. @*Conclusions@#As a result of analyzing the condylar position change of the group treated with BSSRO alone and the group treated with BSSRO and DSO in patients with facial asymmetry, there were statistically significant differences in the mediolateral displacement of NDS and the condyle rotation of NDS and DS. However, the anteroposterior condylar position did not show any difference in the bilateral condyles. In addition, since worsening clinical symptoms of bilateral temporomandibular joint were not observed before and after surgery in both groups, it is concluded that it is not necessary to accompany DSO in patients with facial asymmetry (minimum 3 mm, maximum 7 mm).

Maladaptive Alterations of Defensive Response Following Developmental Complex Stress in Rats

Objective@#Despite the etiological significance of complex developmental trauma in adult personality disorders and treatment-resistant depression, neurobiological studies have been rare due to the lack of useful animal models. As a first step, we devised an animal model to investigate the effects of multiple trauma-like stress during different developmental periods. @*Methods@#Twenty-one male Sprague-Dawley rats were classified into 3 groups based on the stress protocol: fear conditioning control (FCC, n = 6), complex stress (ComS, n = 9), and control (n = 6). While the ComS experienced three types of stress (maternal separation, juvenile isolation, electric foot shock), the FCC only experienced an electric foot shock stress and the control never experienced any. We compared fear responses at postnatal day (PND) 29 and PND 56 through freezing time per episode (FTpE), total freezing time (TFT), total freezing episodes (TFE), and ultrasonic vocalization (USV). @*Results@#ComS showed the longest FTpE in the conditioned fear response test. ComS and FCC exhibited the longer TFT and these two groups only displayed USV. ComS show difference TFE between PND 29 and PND 56. @*Conclusion@#The results of this investigation show that complex stress may affect not quantity of fear response but characteristics of fear response. Longer FTpE may be associated with tonic immobility which could be considered as a failed self-protective reaction and might be analogous to a sign of inappropriate coping strategy and self-dysregulation in complex trauma patients.

Carotid Arterial Calcium Scoring Using Upper Airway Computed Tomography in Patients with Obstructive Sleep Apnea: Efficacy as a Clinical Predictor of Cerebrocardiovascular Disease

OBJECTIVE: To evaluate the value of airway computed tomography (CT) in patients with obstructive sleep apnea (OSA) as a predictor of cerebrocardiovascular disease (CCVD) clinically, by quantitatively analyzing carotid arterial calcification (CarAC). MATERIALS AND METHODS: This study included 287 patients aged 40–80 years, who had undergone both polysomnography (PSG) and airway CT between March 2011 and October 2015. The carotid arterial calcium score (CarACS) was quantified using the modified Agatston method on each upper airway CT. The OSA severity was categorized as normal, mild, moderate, and severe using the PSG results. Clinical characteristics, comorbid diseases, and lipid profiles of all patients were analyzed, and the prevalence of CCVDs was investigated during the follow up period (52.2 ± 16.0 months). RESULTS: CCVD occurred in 27 patients (9.3%) at the end of follow-up, and the CCVD-present groups showed a significantly older mean age (57.5 years vs. 54.2 years), higher prevalence of hypertension (59% vs. 34%) and CarAC (51.9% vs. 20.8%), whereas sex, other comorbid diseases, and severity of OSA were not significantly different from the CCVD-absent group. A univariate analysis showed that age, hypertension, incidence of CarAC, and CarACS were risk factors for the occurrence of CCVD events. In a multivariate analysis, the incidence of CarAC was the only independent risk factor for CCVD. CONCLUSION: CarAC is an independent risk factor for CCVD, whereas the severity of OSA is not a contributory risk factor in patients with OSA. Therefore, additional analysis of CarACS based on airway CT scans may be useful for predicting CCVD.

Correlation between Carotid Arterial Calcium Score and Silent Cerebrovascular Lesions in Obstructive Sleep Apnea Patients: by Using Upper Airway CT and Brain MRI

PURPOSE@#To investigate the relationship between carotid arterial calcium score (CarACS) and silent cerebrovascular lesions in patients with obstructive sleep apnea (OSA).@*MATERIALS AND METHODS@#This study involved retrospective evaluation of 60 OSA patients who underwent both upper airway CT and brain MRI. Using polysomnography, several indicators, including apnea index (AI), were used to evaluate the relationship between OSA and silent cerebrovascular lesions. The CarACS was quantified on CT imaging using the modified Agatston method. Silent cerebrovascular lesions were evaluated on brain MRI by grading periventricular hyperintensity (PVH). Various clinical characteristics, including age, were analyzed in each patient.@*RESULTS@#The number of patients per PVH grade 0, 1, 2, 3, and 4 was 26 (43.3%), 14 (23.3%), 14 (23.3%), 4 (6.7%), and 2 (3.3%), respectively. The mean age, hypertension, smoking status, AI, and CarACS were significantly different among PVH groups (Ps < 0.05). In univariate analysis, the presence of carotid arterial calcification (β = 0.483, p < 0.01), CarACS (β = 0.482, p < 0.01), and age (β = 0.360, p < 0.01) showed a significant association with PVH grade. The mean AI and lowest O₂ saturation had statistically weak associations with PVH grade (β = 0.267, p < 0.01; β = −0.219, p < 0.14, respectively). In multivariate analysis, CarACS was the only factor affecting PVH grade (p < 0.04).@*CONCLUSION@#CarACS is associated with the severity of silent cerebrovascular lesions. Therefore, additional analysis of CarACS in OSA patients may provide more information on their cerebrovascular status.

Combined effect of recombinant human bone morphogenetic protein-2 and low level laser irradiation on bisphosphonate-treated osteoblasts

OBJECTIVES: The purpose of this study was to evaluate the synergic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) and low-level laser therapy (LLLT) on bisphosphonate-treated osteoblasts. MATERIALS AND METHODS: Human fetal osteoblast cells (hFOB 1.19) were cultured with 100 µM alendronate. Low-level Ga-Al-As laser alone or with 100 ng/mL rhBMP-2 was then applied. Cell viability was measured with MTT assay. The expression levels of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and osteoprotegerin (OPG) were analyzed for osteoblastic activity inducing osteoclastic activity. Collagen type and transforming growth factor beta-1 were also evaluated for bone matrix formation. RESULTS: The results showed that rhBMP-2 and LLLT had a synergic effect on alendronate-treated osteoblasts for enhancing osteoblastic activity and bone matrix formation. Between rhBMP-2 and LLLT, rhBMP-2 exhibited a greater effect, but did not show a significant difference. CONCLUSION: rhBMP-2 and LLLT have synergic effects on bisphosphonate-treated osteoblasts through enhancement of osteoblastic activity and bone formation activity.

Assessment of Cognitive Impairment in a Mouse Model of High-Fat Diet-Induced Metabolic Stress with Touchscreen-Based Automated Battery System

Obesity-related metabolic disorders can affect not only systemic health but also brain function. Recent studies have elucidated that amyloid beta deposition cannot satisfactorily explain the development of Alzheimer's disease (AD) and that dysregulation of glucose metabolism is a critical factor for the sporadic onset of non-genetic AD. Identifying the pathophysiology of AD due to changes in brain metabolism is crucial; however, it is limited in measuring changes in brain cognitive function due to metabolic changes in animal models. The touchscreen-based automated battery system, which is more accurate and less invasive than conventional behavioral test tools, is used to assess the cognition of mice with dysregulated metabolism. This system was introduced in humans to evaluate cognitive function and was recently back-translated in monkeys and rodents. We used outbred ICR mice fed on high-fat diet (HFD) and performed the paired associates learning (PAL) test to detect their visual memory and new learning ability loss as well as to assess memory impairment. The behavioral performance of the HFD mice was weaker than that of normal mice in the training but was not significantly associated with motivation. In the PAL test, the average number of trials completed and proportion of correct touches was significantly lower in HFD mice than in normal diet-fed mice. Our results reveal that HFD-induced metabolic dysregulation has detrimental effects on operant learning according to the percentage of correct responses in PAL. These findings establish that HFD-induced metabolic stress may have an effect in accelerating AD-like pathogenesis.

Removal of submandibular calculi by surgical method and hydraulic power with curved needle: a case report

Sialolithiasis, the most common salivary gland pathology, is caused by calculi in the gland itself and its duct. While patients with small sialoliths can undergo conservative treatment, those with standard-size or larger sialoliths require sialolithotomy. In the present case study, we removed two sialoliths located beneath the mucosa in the posterior and anterior regions of Wharton's duct, respectively. For the posterior calculus, we performed sialolithotomy via an intra-oral approach; thereafter, the small anterior calculus near the duct orifice was removed by hydraulic power. This method has not previously been reported. There were no complications either during the operation or postoperatively, and the salivary function of the gland remained normal.

Use of artificial palate for improving facial support in the fabrication of a maxillary obturator: A case report / 대한치과보철학회지

Patients with maxillectomy defects predisposed to not only difficulty in deglutition, mastication, speech but also psychological depression from impaired facial esthetics that affect life quality. Obturator prostheses play a important role in restoring the lost form, function and the quality of life for patients with maxillectomy defects. This clinical report presents the simplified approach to predict the degree of adequate facial support by Artificial palate which reflected from a maxillary interim obturator during the stabilization period after maxillectomy.

Overexpression of SOX2 Is Associated with Better Overall Survival in Squamous Cell Lung Cancer Patients Treated with Adjuvant Radiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to investigate the prognostic significance of SOX2 gene amplification and expression in patients with American Joint Committee on Cancer stage III lung squamous cell carcinoma (SCC) who underwent surgery followed by adjuvant radiotherapy. MATERIALS AND METHODS: Pathological specimens were obtained from 33 patients with stage III lung SCC treated with surgery followed by adjuvant radiotherapy between 1996 and 2008. SOX2 gene amplification and protein expression were analyzed using fluorescent in situ hybridization and immunohistochemistry, respectively. Patients were divided into two groups according to their SOX2 gene amplification and protein expression status. Kaplan-Meier estimates and a Cox proportional hazards model were used to identify the prognostic factors affecting patient survival. RESULTS: The median follow-up period for surviving patients was 58 months (range, 5 to 102 months). SOX2 gene amplification was observed in 22 patients and protein overexpression in 26 patients. SOX2 overexpression showed significant association with SOX2 gene amplification (p=0.002). In multivariate analysis, SOX2 overexpression was a significant prognostic factor for overall survival (OS) (hazard ratios [HR], 0.1; 95% confidence interval [CI], 0.002 to 0.5; p=0.005) and disease-free survival (DFS) (HR, 0.15; 95% CI, 0.04 to 0.65; p=0.01). Age (HR, 0.33; 95% CI, 0.11 to 0.98; p=0.046) and total radiation dose (HR, 0.13; 95% CI, 0.02 to 0.7; p=0.02) were the independent prognostic factors for OS and DFS. Patients with SOX2 amplification did not show a longer OS (p=0.95) and DFS (p=0.48). CONCLUSION: Our data suggested that SOX2 overexpression could be used as a positive prognostic factor in patients with stage III lung SCC receiving adjuvant radiotherapy.

Agmatine Ameliorates High Glucose-Induced Neuronal Cell Senescence by Regulating the p21 and p53 Signaling

Neuronal senescence caused by diabetic neuropathy is considered a common complication of diabetes mellitus. Neuronal senescence leads to the secretion of pro-inflammatory cytokines, the production of reactive oxygen species, and the alteration of cellular homeostasis. Agmatine, which is biosynthesized by arginine decarboxylation, has been reported in previous in vitro to exert a protective effect against various stresses. In present study, agmatine attenuated the cell death and the expression of pro-inflammatory cytokines such as IL-6, TNF-alpha and CCL2 in high glucose in vitro conditions. Moreover, the senescence associated-beta-galatosidase's activity in high glucose exposed neuronal cells was reduced by agmatine. Increased p21 and reduced p53 in high glucose conditioned cells were changed by agmatine. Ultimately, agmatine inhibits the neuronal cell senescence through the activation of p53 and the inhibition of p21. Here, we propose that agmatine may ameliorate neuronal cell senescence in hyperglycemia.

Full-mouth rehabilitation by immediate implantation combined with orthognathic surgery: a clinical report / 대한치과보철학회지

Clinical therapy that combines full-mouth rehabilitation with immediate implantation and orthognathic surgery poses a challenge to prosthodontists. This clinical report describes a multidisciplinary approach to the diagnosis and treatment of a patient presenting with skeletal discrepancy and rampant caries. The results thus achieved indicate that full-mouth rehabilitation by fixed immediate and early loading implantation accompanied by orthognathic surgery can be a predictable and effective treatment procedure.

Facial asymmetry: a case report of localized linear scleroderma patient with muscular strain and spasm / 대한악안면성형재건외과학회지

Facial asymmetry is found in patients with or without cosmetic facial alterations. Some patients have facial asymmetry that manifests underlying skeletal problems, while others have only limited soft-tissue facial asymmetry. Orthognathic surgery brings about a dermatic change, as soft tissue covers underlying bones. Limited soft-tissue asymmetry, meanwhile, is difficult to correct. The treatment modalities for the creation or restoration of an esthetically pleasing appearance were autogenous fat grafts, cartilage graft, and silicon injections. A young female patient had right-side facial asymmetry. The clinical assessment involved visual inspection of the face and palpation to differentiate soft tissue and bone. Although the extra-oral examination found facial asymmetry with skin atrophy, the radiographic findings revealed no mandibular atrophy or deviation. She was diagnosed as localized scleroderma with muscle spasm. In conclusion, facial asymmetry patients with skeletal asymmetry can be esthetically satisfied by orthognathic surgery; however, facial atrophy patients with skin or subdermal tissue contraction need treatment by cosmetic dermatological surgery and orthodontic correction.

Temporomandibular joint disorder from skull-base osteomyelitis: a case report / 대한악안면성형재건외과학회지

Skull-base osteomyelitis is a rare disease affecting the medulla of the temporal, sphenoid, and occipital bones. In general, it occurs due to external ear canal infections caused by malignant external otitis. Skull-base osteomyelitis usually affects elderly diabetic patients. The patient, a 58-year-old man, was referred for evaluation and management of the left jaw. Clinical examination of the patient revealed pain in the left jaw and mouth-opening deflection to the left. The maximum active mouth opening was measured to about 27 mm. Panoramic, CT, and CBCT revealed bone resorption patterns in the left condyle. Through control of diabetes, continued pharmacological treatment, arthrocentesis, and occlusal stabilization appliance therapy were carried out. The extent of active mouth opening was increased to 45 mm, and pain in the left jaw joint was alleviated. This was a case wherein complications caused by failure to control diabetes induced skull-base osteomyelitis. There is a need for continued discussion about the advantages and disadvantages of arthrocentesis with lavage for patients with skull-base osteomyelitis and other treatment options.

Reconstruction of extensive jaw defects induced by keratocystic odontogenic tumor via patient-customized devices / 대한악안면성형재건외과학회지

Keratocystic odontogenic tumors can occur in any area of the maxilla or mandible. According to their size, location, and relations with surrounding structures, they are treated by cyst enucleation or enucleation after either marsupialization or decompression. Enucleation is performed when cysts are not large and when only minor damage to adjacent anatomical structures is expected. Although marsupialization and decompression follow the same basic bone-regeneration principle, which is to say, by reducing the pressure within the cyst, the former leaves a large defect after healing due to the large fistula necessary to induce the conversion of the cyst-lining epithelia to oral epithelia; the latter leaves only a relatively small defect, because of the continuous washing carried out by means of a tube inserted into a small hole in the cyst. In the latter case too, a decompressor appropriate for the focal position is required, owing to the importance of maintaining the device and controlling for oral hygiene. We report herein decompression treatment with a patient-customized device for an extensive cyst in the anterior region of the mandible.

Complication rates in patients using absorbable collagen sponges in third molar extraction sockets: a retrospective study

OBJECTIVES: The purpose of this study is to retrospectively evaluate the postoperative complication rates for absorbable type-I collagen sponge (Ateloplug; Bioland) use in third molar extraction. MATERIALS AND METHODS: From January to August 2013, 2,697 total patients undergoing third molar extraction and type-I collagen sponge application in the Department of Oral and Maxillofacial Surgery at Yonsei University Dental Hospital (1,163 patients) and Dong-A University Hospital (1,534 patients) were evaluated in a retrospective study using their operation and medical records. RESULTS: A total of 3,869 third molars in 2,697 patients were extracted and the extraction sockets packed with type-I collagen sponges to prevent postoperative complications. As a result, the overall complication rate was 4.52%, with 3.00% experiencing surgical site infection (SSI), 1.14% showing alveolar osteitis, and 0.39% experiencing hematoma. Of the total number of complications, SSI accounted for more than a half at 66.29%. CONCLUSION: Compared to previous studies, this study showed a relatively low incidence of complications. The use of type-I collagen sponges is recommended for the prevention of complications after third molar extraction.

Effect of Endogenous Bone Marrow Derived Stem Cells Induced by AMD-3100 on Expanded Ischemic Flap

The purpose of this study was to devise an expanded ischemic flap model and to investigate the role of AMD-3100 (Plerixafor, chemokine receptor 4 inhibitor) in this model by confirming its effect on mobilization of stem cells from the bone marrow. Male Sprague-Dawley rats were used as an animal research model. The mobilization of stem cells from the bone marrow was confirmed in the AMD-3100-treated group. The fractions of endothelial progenitor cells (EPC) and the vascular endothelial growth factor receptor (VEGFR) 2+ cells in the peripheral blood were increased in groups treated with AMD-3100. The expression of vascular endothelial growth factor (VEGF) was increased in response to expansion or AMD injection. The expression of stromal cell derived factor (SDF)-1 and VEGFR2 were increased only in unexpanded flap treated with AMD-3100. Treatment with AMD-3100 increased both the number and area of blood vessels. However, there were no statistically significant differences in the survival area or physiologic microcirculation in rats from the other groups. This endogenous neovascularization induced by AMD-3100 may be a result of the increase in both the area and number of vessels, as well as paracrine augmentation of the expression of VEGF and EPCs. However, the presence of a tissue expander under the flap could block the neovascularization between the flap and the recipient regardless of AMD-3100 treatment and expansion.

Effect of recombinant human bone morphogenetic protein-2 on bisphosphonate-treated osteoblasts

OBJECTIVES: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphophonate therapy that has been reported in recent years. Osteoclastic inactivity by bisphosphonate is the known cause of BRONJ. Bone morphogenetic protein-2 (BMP-2) plays an important role in the development of bone. Recombinant human BMP-2 (rhBMP-2) is potentially useful as an activation factor for bone repair. We hypothesized that rhBMP-2 would enhance the osteoclast-osteoblast interaction related to bone remodeling. MATERIALS AND METHODS: Human fetal osteoblast cells (hFOB 1.19) were treated with 100 microM alendronate, and 100 ng/mL rhBMP-2 was added. Cells were incubated for a further 48 hours, and cell viability was measured using an MTT assay. Expression of the three cytokines from osteoblasts, receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), and macrophage colony-stimulating factor (M-CSF), were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Cell viability was decreased to 82.75%+/-1.00% by alendronate and then increased to 110.43%+/-1.35% after treatment with rhBMP-2 (P<0.05, respectively). OPG, RANKL, and M-CSF expression were all decreased by alendronate treatment. RANKL and M-CSF expression were increased, but OPG was not significantly affected by rhBMP-2. CONCLUSION: rhBMP2 does not affect OPG gene expression in hFOB, but it may increase RANKL and M-CSF gene expression.

Treatment of Keratocystic Odontogenic Tumors in Nevoid Basal Cell Carcinoma Syndrome