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Introduction The aim of this study was to assess the efficacy and safety of switching to teneligliptin from other dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes mellitus (T2DM) inadequately controlled despite treatment with a stable dose of other DPP-4 inhibitors. Methods Patients with glycosylated hemoglobin (HbA1c) ≥ 7% despite taking DPP-4 inhibitors other than teneligliptin, with or without other antidiabetic agents, for at least 3 months were enrolled in this study. Patients on DPP-4 inhibitors administered prior to participation in this study were switched to 20 mg teneligliptin once daily and the dose was maintained for the 52-week study period. The primary endpoint was the change in HbA1c at week 12. Fasting plasma glucose (FPG) and the blood lipid profile were also evaluated. Adverse events were monitored for safety assessment. Results At weeks 12, 24, and 52, the HbA1c values significantly decreased by − 0.39, − 0.44, and − 0.52%, respectively, compared to the baseline value (p

Various techniques have been used to reconstruct the temporomandibular joints, including autogenous transplants and alloplastic implants. Among autogenous grafts, costochondral grafts have mainly been used. A costochondral graft has many advantages over other autogenous grafts and alloplastic implants. Harvest is easy and has minimal impact on patients. The graft can bear functional load well and biocompatibility is excellent. A costochondral graft obviates foreign body reactions and further surgery for revision of alloplastic replacements if the graft takes well. Although long-term prognosis remains unclear, it appears that for autogenous condylar reconstruction, costochondral grafts can be used with few complications and acceptable results. This article describes cases and discusses surgical techniques and considerations related to costochondral grafts.

Ranula is a mucocele caused by extravasation of the sublingual gland on the floor of the mouth. The most common presentation is a cystic mass in the floor of the mouth. A portion of the sublingual gland could herniate through the mylohyoid muscle, and its extravasated mucin can spread along this hiatus into submandibular and submental spaces and cause cervical swelling. This phenomenon is called plunging ranula. A variety of treatments for ranula has been suggested and include aspiration of cystic fluid, sclerotherapy, marsupialization, incision and drainage, ranula excision only, and excision of the sublingual gland with or without ranula. Those various treatments have shown diverse results. Most surgeons agree that removal of the sublingual gland is necessary in oral and plunging ranula. Four patients with ranula were investigated retrospectively, and treatment methods based on literature review were attempted.

Introduction Teneligliptin, an antidiabetic agent classified as a class III dipeptidyl peptidase-4 (DPP-4) inhibitor, has a unique structural feature that provides strong binding to DPP-4 enzymes. We investigated the efficacy and safety of switching patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control on a stable dose of other DPP-4 inhibitors to teneligliptin. Methods Patients with T2DM whose glycosylated hemoglobin (HbA1c) levels were ≥ 7% despite taking DPP-4 inhibitors other than teneligliptin, with or without other hypoglycemic agents, for at least 3 months were enrolled. The DPP-4 inhibitors taken before participating in the study were switched to 20 mg qd teneligliptin, and this was to be maintained for 52 weeks. The primary end point was the change in HbA1c levels after 12 weeks. Metabolic parameters including fasting plasma glucose (FPG) and blood lipids were assessed also. To assess safety, adverse and hypoglycemic events were monitored. The data from baseline to week 12 were used for analysis in this interim report. Results The mean change in HbA1c levels from baseline to week 12 was − 0.44%. At week 12, the percentage of patients achieving HbA1c

Background/aim The aim of this study was to evaluate the effect of evodiamine alone or in combination with chemotherapeutic agents on thyroid carcinoma cells. Materials and methods TPC-1 and SW1736 thyroid carcinoma cells were used. Cell viability, cytotoxic activity, apoptosis and migration were examined by applying appropriate methods. Drug combination analysis was performed. Results Evodiamine treatment of cells decreased cell viability, and Bcl2 and phospho-AKT protein levels. Cytotoxic activity and the percentage of apoptotic cells increased. After co-treatment of wortmannin, cell viability, and phospho-AKT and Bcl2 protein levels decreased, and cytotoxic activity increased. In transforming growth factor-β-treated cells, evodiamine attenuated variations in morphology, growth and migration, and increased p21 and p53 protein levels, and decreased β-catenin, N-cadherin, vimentin, phospho-AKT, matrix metalloproteinase-2 and matrix metalloproteinase-9 protein levels. When cells were treated with both evodiamine and chemotherapeutic agents, all combination index values were lower than 1.0. Conclusion Evodiamine was cytotoxic towards thyroid carcinoma cells, and repression of AKT reinforced evodiamine-induced cytotoxicity. Furthermore, evodiamine ameliorated proliferation, migration and epithelial-mesenchymal transition, and synergized with chemotherapeutic agents.

BACKGROUND/AIM Heat shock protein 90 (HSP90) controls maturation of oncogenic client proteins of cancer cells, and thus we studied the effect of HSP 90 inhibitors on cell survival and survival-related mediators in thyroid carcinoma cells. MATERIALS AND METHODS Human TPC-1 and SW1736 thyroid carcinoma cells were utilized. Cell viability, cytotoxic activity and apoptosis were estimated using CCK-8 assay, cytotoxicity assay and FACS analysis, respectively. RESULTS AUY922, BIIB021 and SNX5422 decreased cell viability, and increased cytotoxic activity and the proportion of apoptotic cells. The protein levels of cleaved PARP, cleaved caspase-3, Bax and Bim were elevated, and Bcl2 protein levels were reduced. Knockdown of Bax did not change cell viability, cytotoxic activity, the proportion of apoptotic cells and cleaved caspase-3 protein levels. Meanwhile, knockdown of Bim enhanced cell viability, and diminished cytotoxic activity, the proportion of apoptotic cells and cleaved caspase-3 protein levels. AUY922, BIIB021 and SNX5422 increased the protein levels of phospho-AMPK, and decreased those of phospho-ERK1/2, and total and phospho-AKT. CONCLUSION AUY922, BIIB021 and SNX5422 induce cytotoxicity by modulating Bim and ERK1/2, AKT and AMPK signaling in thyroid carcinoma cells.

Background/aim The aim of the present study was to assess the role of enigma protein in survival of thyroid carcinoma cells. Materials and methods BCPAP and 8505C human thyroid carcinoma cells were used. Cell viability using CCK-8 assay, the percentage of dead cells using trypan blue assay, cytotoxic activity using cytotoxicity assay, cell growth rate and cell migration using wound-healing assay were performed. Results In enigma siRNA-transfected cells, cell viability, and the protein levels of AKT and survivin decreased. The percentage of dead cells, cytotoxic activity and cleaved poly (ADP-ribose) polymerase (PARP) protein levels increased. After transfection of p110α plasmid, the alterations in cell viability, the percentage of dead cells, cytotoxic activity, and protein levels of AKT, survivin and cleaved PARP were abrogated. Cell growth rate and cell migration were reduced with reduction of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) protein levels, as well as increased p53 and p21 protein levels. Conclusion Enigma affects cell survival through modulation of phosphatidylinositol-3 kinase/AKT signaling and survivin, and regulates cell proliferation and migration via involvement of MMP-2, MMP-9, p53 and p21 in thyroid carcinoma cells.

Once a submasseteric space infection is diagnosed, the key to resolving the infection is via surgical intervention to evacuate the pus. Although it is possible and occasionally practical to drain the submasseteric space via an intraoral approach, an extraoral approach may sometimes be required. Surgeons have encountered complications such as facial nerve damage during extraoral incision and drainage procedures, and they have felt that extraoral dissection was very difficult. As such, an easier and simpler technique is needed. Our department recently modified various drainage techniques for submasseteric space abscesses. Damage to the marginal branch of the facial nerve did not occur, and this technique was very simple and rapid, such that a novice physician could perform this procedure. This modified technique was possible with trismus and under local anesthesia. After intraorally checking the position of the drain, the intraoral wound is closed with an absorbable suture and the drain is fixed to the extraoral skin. When a masseteric space infection is diagnosed, multiple space involvement is ruled out, and dependent drainage is required, this modified drainage technique can be useful.

Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1.73 m(2) of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0.75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0.75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for >= 30 days) or end-stage kidney disease (eGFR = 90 days, chronic dialysis for >= 90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials. gov, number NCT01858532.Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2.2 years (IQR 1.4-2.9). 79 (6.0%) of 1325 patients in the atrasentan group and 105 (7.9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0.65 [95% CI 0.49-0.88]; p=0.0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3.5%) of 1325 patients in the atrasentan group and 34 (2.6%) of 1323 patients in the placebo group (HR 1.33 [95% CI 0.85-2.07]; p=0.208). 58 (4.4%) patients in the atrasentan group and 52 (3.9%) in the placebo group died (HR 1.09 [95% CI 0.75-1.59]; p=0.65).Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

The impact of evodiamine in combination with histone deacetylase (HDAC) inhibitors on survival of thyroid carcinoma cells was identified. TPC-1 and SW1736 human thyroid carcinoma cells were used. After treatment with evodiamine and PXD101, cell viability, the percentage of viable cells and Bcl2 protein levels decreased, whereas cytotoxic activity, the percentage of apoptotic cells, the protein levels of γH2AX, acetyl. histone H3 and cleaved PARP, and reactive oxygen species (ROS) production increased. In cells treated with both evodiamine and PXD101, compared with PXD101 alone, decrement of cell viability, the percentage of viable cells, and Bcl2 protein levels as well as increment of cytotoxic activity, the percentage of apoptotic cells, the protein levels of γH2AX and cleaved PARP, and ROS production were significant, causing decrement of Bcl2/Bax ratio. Furthermore, all of the combination index values were

Objectives The maxillary sinus mucosa is reported to recover to preoperative sterility after sinus floor elevation. However, when drainage of maxillary sinus is impaired, recovery can be delayed and maxillary sinusitis can occur. Therefore, in this study, we investigated the correlations between anatomic variants that can interrupt the ostium of the maxillary sinus and incidence of complication after sinus lifting. Materials and Methods The subjects are 81 patients who underwent sinus lifting in Wonkwang University Dental Hospital (Iksan, Korea). Computed tomography (CT) images of the subjects were reviewed for presence of nasal septum deviation, anatomic variants of the middle turbinate, and Haller cells. Correlations between anatomic variations and occurrence of maxillary sinusitis were statistically analyzed. Results Patients with anatomic variants of ostio-meatal units, such as deviated nasal septum, concha bullosa or paradoxical curvature of the middle turbinate, or Haller cells, showed a higher rate of complication. However, only presence of Haller cell showed statistically significant. Conclusion Before sinus lifting, CT images are recommended to detect anatomic variants of the ostio-meatal complex. If disadvantageous anatomic variants are detected, the use of nasal decongestants should be considered to reduce the risk of postoperative sinusitis.

AimsTo investigate associations of glomerular hyperfiltration with other metabolic factors in a nationally representative dataset.MethodsWe analyzed cross-sectional data from 15,918 subjects with estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2 and urine albumin creation ratio (ACR) ResultsPrevalence of hyperfiltration was 5.2% and that among normal, prediabetic, and diabetic subjects was 4.9%, 5.6%, and 7.3%, respectively, after adjusting for age, sex, and body weight (p for trend = 0.008). In a multiple logistic regression analysis, hyperfiltration was associated with a body mass index ≥30 kg/m2 [odds ratio (OR) = 3.461, pConclusionsIn a general Korean population, both hyperfiltration and ACR were associated with similar metabolic parameters, and hyperfiltration correlated independently with a high ACR. Longitudinal studies are needed to further explore risks of hyperfiltration and microalbuminuria.

Surgical approaches to the condylar fracture include intraoral, preauricular, submandibular, and retromandibular approaches. Each approach has its own advantages and disadvantages. When a patient needs esthetic results and an intraoral approach is not feasible, the transmasseteric antero-parotid facelift approach is considered. This approach permits direct exposure and allow the surgeon to fixate the fractured unit tangentially. Tangential fixation is critical to osteosynthesis. Disadvantages of the transmasseteric antero-parotid facelift approach include damage to the facial nerve and a longer operation time. However, after the initial learning curve, facial nerve damage can be avoided and operation time may decrease. We report three cases of subcondylar fractures that were treated with a transmasseteric antero-parotid facelift approach. Among these, two cases had trivial complications that were easily overcome. Instead of dissecting through the parotid gland parenchyma, the transmasseteric antero-parotid facelift approach uses transmasseteric dissection and reduces facial nerve damage more than the retromandibular transparotid approach. The esthetic result is superior to that of other approaches.

We aimed to elucidate the effect of herbimycin A (HMA), a heat shock protein 90 inhibitor, on cell growth and epithelial-mesenchymal transition (EMT) in anaplastic thyroid carcinoma (ATC) cells. HMA inhibited cell growth and migration concomitantly with increase of E-cadherin as well as decrease of N-cadherin and vimentin. Moreover, HMA upregulated p21 and p27, while it downregulated p53 and Akt. In HMA-treated condition, knockdown of E-cadherin and overexpression of p53 increased N-cadherin and vimentin, and mitigated the inhibitory effects of HMA on cell growth and migration. Furthermore, knockdown of p21 and p27 ameliorated inhibition of cell growth and reversal of EMT. In addition, the activation of Akt attenuated growth inhibition, cell death and EMT reversal. Therefore, we propose that HMA suppresses cell growth, and reverses EMT in conjunction with the activation of E-cadherin, p21 and p27 and the inactivation of p53 and PI3K/Akt signaling in ATC cells.

The effect of the dipeptidyl peptidase-IV inhibitor gemigliptin alone or in combination with the heat shock protein 90 inhibitor NVP-AUY922 (AUY922) on survival of thyroid carcinoma cells was elucidated. The SW1736 and TPC-1 human thyroid carcinoma cells were used. Cell viability, the percentage of viable cells, cytotoxic activity, the percentage of apoptotic cells, and mitochondrial membrane potential were measured. To evaluate the combined effect of gemigliptin with AUY922, the interactions were estimated by calculating combination index. Gemigliptin led to cell death in conjunction with overexpression of the phosphorylated protein levels of Akt, extracellular signal–regulated kinase 1/2, and adenosine monophosphate–activated protein kinase. In gemigliptin-treated cells, wortmannin augmented cell death, whereas AZD6244 and compound C did not affect cell survival. Wortmannin decreased phosphorylated adenosine monophosphate–activated protein kinase protein levels, and AZD6244 increased phosphorylated Akt protein levels. Meanwhile, cotreatment of both gemigliptin and AUY922, compared with treatment of AUY922 alone, potentiated cell death. All the combination index values were lower than 1.0, suggesting synergistic cytotoxicity of gemigliptin with AUY922. In treatment of both gemigliptin and AUY922, compared with AUY922 alone, the protein levels of total and phosphorylated Akt, phosphorylated extracellular signal–regulated kinase 1/2, and phosphorylated adenosine monophosphate–activated protein kinase increased without alteration in those of total extracellular signal–regulated kinase 1/2 and total adenosine monophosphate–activated protein kinase. The percentage of apoptotic cells increased. The protein levels of Bax and cleaved poly (ADP-ribose) polymerase increased, whereas Bcl2 protein levels were unchanged, resulting in increment of Bax/Bcl2 ratio. Transfection of Bax small interfering RNA did not cause any variation in cell viability, the percentage of viable cells and cytotoxic activity. Our results demonstrate that gemigliptin exerts a cytotoxic activity with concomitant alterations in expression of Akt, extracellular signal–regulated kinase 1/2, and adenosine monophosphate–activated protein kinase in thyroid carcinoma cells. Furthermore, gemigliptin synergizes with AUY922 in induction of cytotoxicity via regulation of Akt, extracellular signal–regulated kinase 1/2, and adenosine monophosphate–activated protein kinase as well as involvement of Bcl2 family proteins in thyroid carcinoma cells.

The influence of the dipeptidyl peptidase-IV inhibitor, gemigliptin alone or in combination with metformin on survival, proliferation, and migration of thyroid carcinoma cells was investigated. SW1736 and TPC-1 human thyroid carcinoma cells were used. Gemigliptin and metformin caused cell death in a dose-dependent manner. In cells treated with both gemigliptin and metformin, compared with metformin alone, all of the combination index values were lower than 1.0, suggesting synergistic cytotoxicity of two agents. Cell viability, the percentage of viable cells, ATP levels, and mitochondrial membrane potential decreased; however, cytotoxic activity, and the protein levels of cleaved PARP, phospho-Akt and phospho-AMP-activated protein kinase (AMPK) increased. Administration of wortmannin, but not compound C, further decreased cell viability, and further increased cytotoxic activity. Moreover, compared with control, cell proliferation and migration as well as the protein levels of p53, p21, vascular cell adhesion molecule-1 (VCAM-1), and phospho-extracellular signal-regulated kinase (ERK) 1/2 decreased. The decrement of matrix metalloproteinase-2 and matrix metalloproteinase-9 protein levels was cell specific. Our results demonstrate that gemigliptin induces cytotoxic activity, and has a synergistic activity with metformin in inducing cytotoxicity via regulation of Akt and AMPK in thyroid carcinoma cells. Furthermore, gemigliptin augments the inhibitory effect of metformin on proliferation and migration through involvement of matrix metalloproteinase-2, matrix metalloproteinase-9, p53, p21, VCAM-1, and ERK in thyroid carcinoma cells.

This study aimed to explore the relation of immunoglobulin G4 (IgG4) to clinical and laboratory characteristics of patients newly diagnosed with Graves' disease (GD) without or with Graves' ophthalmopathy (GO) and to analyze association of IgG4 with development and grade of GO in GD patients.Sixty-four GD patients and 64 sex- and age-matched euthyroid subjects were enrolled. Serum levels of thyroid hormones, thyroid autoantibodies, immunoglobulin G (IgG), and IgG4 were measured, and ophthalmological and ultrasonographical evaluation was performed.In GD patients compared with euthyroid subjects, levels of thyroid hormones, thyroid autoantibodies and IgG4 as well as the IgG4/IgG ratio were elevated. GD patients having GO in comparison to not having GO were characterized by a female predominance; a high incidence of smoking history; high levels of T3, free T4, TSH receptor autoantibody (TRAb) and IgG4; and a high IgG4/IgG ratio after adjusting for sex. In GD patients, the IgG4 level was the independent factor associated with GO development on multivariate analysis. When severity and activity of GO were classified using the European Group on Graves' Orbitopathy criteria in GD patients with GO, IgG4 levels and IgG4/IgG ratio were elevated in the moderate-to-severe group compared with the mild group and in the active group compared with the inactive group. IgG4 levels and IgG4/IgG ratio became elevated as clinical activity score increased. IgG4 levels were positively correlated with TRAb levels. The high IgG4 group in comparison to the normal IgG4 group had a high incidence of family history of autoimmune thyroid disease, high levels of free T4, TRAb and IgG4, a high IgG4/IgG ratio and extensive hypoechogenicity.These results suggest that IgG4 levels are elevated in newly diagnosed GD patients compared with euthyroid subjects and in the presence of GO compared with the absence of GO. Moreover, our findings suggest that IgG4 levels are associated with the development and grade of GO in GD patients.

The effect of 17-allylamino-17-demethoxygeldanamycin (17-AAG), an hsp90 inhibitor, alone or in combination with paclitaxel on survival of anaplastic thyroid carcinoma (ATC) was evaluated. In 8505C and CAL62 cells, after treatment of 17-AAG, cell viability decreased, and the percentage of dead cells increased. 17-AAG did not cause cleavage of caspase-3 protein, and change expression of IAPs. Pretreatment of z-VAD-fmk did not alter cell viability and the percentage of dead cells. In 17-AAG-treated cells, knockdown of p53 rescued growth inhibition, while cycloheximide attenuated cell death. When cells were treated with both 17-AAG and paclitaxel, all of the combination index values were higher than 1, indicating antagonism between 17-AAG and paclitaxel. In 17-AAG- and paclitaxel-treated cells, compared with paclitaxel alone-treated cells, the protein levels of hsp90, hsp70, and hsc70 increased. In conclusion, our results suggest that 17-AAG induces non-apoptotic cell death requiring de novo protein synthesis in ATC cells. Moreover, these results demonstrate that 17-AAG antagonizes paclitaxel with concomitant alterations in hsp90 client proteins in ATC cells.

Background Ultraviolet irradiation by sun exposure has been associated with both harms and benefits to metabolic health. Objective The objective of this study was to determine whether unprotected daily sun exposure is associated with the prevalence of diabetes and explore the underlying mechanism. Methods We analyzed the Korean National Health and Nutrition Survey V from 2010 to 2011. Participants 19–60 years of age were asked about the average amount of time they had been exposed to direct sunlight per day since the age of 19. We categorized participants into three groups with different levels of lifetime daily sun exposure and explored the association of sun exposure with the prevalence of diabetes. Results The risk of diabetes was higher in subjects with more than 5 h of unprotected sun exposure per day, with an odds ratio of 2.39 (95% CI 1.75–3.25), compared to those with less than 2 h of sun exposure, and the association remained significant after adjusting for diabetes risk factors. Long-term sun exposure was associated with increased central obesity and the possibility of an increase in visceral adiposity, especially among women, and with decrease in beta cell function and peripheral adiposity or percent body fat in men. Conclusions Our study provides a cutoff for upper limit of sun exposure and suggests unprotected daily sun exposure for more than 5 h should be avoided to prevent diabetes. Increased central adiposity and decreased beta cell function were observed in women and men, respectively, who had long-term unprotected daily sun exposure.

Bilateral coronoid hyperplasia causes painless progressive trismus, resulting from coronoid process impingement on the posterior aspect of the zygomatic bone. The etiology of coronoid hyperplasia is unclear, with various theories proposed. An endocrine stimulus, increased temporalis activity, trauma, genetic inheritance and familial occurrence have all been proposed, but no substantive evidence exists to support any of these hypotheses. Multiplanar reformatting of axial scans and 3-dimensional reconstruction permit precise reproduction of the shape and size of the coronoid and malar structures, and relationships of all structures of the temporal and infratemporal fossae. This case shows remarkably increased mouth opening by coronoidectomy in a patient who complained of trismus due to hyperplasia of coronoid process.

Hyperglycemia is not identified as a significant prognostic factor for idiopathic sudden sensorineural hearing loss in any literature. Therefore, we investigated the prognostic value of hyperglycemia in predicting hearing recovery.A retrospective cohort study.Tertiary university hospital.Patients were classified into 3 groups according to their glucose tolerance using the 75-gram oral glucose tolerance test and hemoglobin A1c test as follows: (1) a normal glucose tolerance group, (2) a prediabetes group, which included patients with impaired glucose tolerance and/or impaired fasting glucose levels, and (3) a diabetes mellitus group.Among 94 patients with idiopathic sudden sensorineural hearing loss, 45 were classified into the normal glucose tolerance group, 28 into the prediabetes group, and 21 into the diabetes mellitus group. The recovery rate of the normal glucose tolerance group was not higher than that of the diabetes mellitus group (P = .140). However, when the prediabetes and diabetes mellitus groups were collectively defined as the impaired glucose regulation (hyperglycemia) group, the hearing recovery rate of the normal glucose tolerance (normoglycemia) group was significantly better than that of the impaired glucose regulation group (P = .038).We suggest that hyperglycemia may be a potential negative prognostic factor for hearing recovery in idiopathic sudden sensorineural hearing loss. Further interventional studies should be followed to determine whether hearing outcomes of the impaired glucose regulation group may be improved to the same extent as those of the normal glucose tolerance group after strict glycemic control.

Epidemiologic studies have shown that low vitamin D levels are associated with reduced insulin sensitivity and increased risk of developing type 2 diabetes mellitus (T2DM). However, there is little evidence that vitamin D supplementation improves glucose intolerance. We evaluated the glucose-lowering effect of vitamin D in Korean T2DM subjects. We enrolled 158 T2DM patients who had stable glycemic control [hemoglobin A1c (HbA1c)

Frey syndrome is a disease characterized by abnormal sweating, facial redness, and rare pain by stimulation of taste sense on the limited area dominated by the auriculotemporal nerve and great auricular nerve. Although the developmental mechanism and histopathologic cause of Frey syndrome are still being debated, the most reliable theory is based on injury of the parathympathetic nerve connected to the auriculotemporal nerve continuing to abnormal regeneration. The other theory is that the sweat glands develop an increased sensitivity after degeneration of sympathetic fibers. Therapy of Frey syndrome includes drugs, radiographic treatment, and surgical treatment; however, in most cases, treatment is not satisfactory. This is a case report on a 24-year-old male patient with Frey syndrome caused by the fracture reduction with retromandibular approach after multiple facial traumas and spontaneous healing without any special treatment.

The possible involvement of glucocorticoid system in interleukin-1β (IL-1β)-induced nociception and the blood glucose level was studied in ICR mice. In the first experiment, mice were treated intrathecally (i.t.) with IL-1β (100 pg). Corticotrophin releasing hormone (CRH) mRNA (hypothalamus) and c-Fos mRNA (pituitary gland, spinal cord, and the adrenal gland) levels were measured at 30, 60 and 120 min after IL-1β administration. We found that i.t. injection with IL-1β increased CRH mRNA level in the hypothalamus. The IL-1β administered i.t. elevated c-Fos mRNA levels in the spinal cord, pituitary and adrenal glands. Furthermore, i.t. administration of IL-1β significantly increased the plasma corticosterone level up to 60 min. In addition, the adrenalectomy caused the reductions of the blood glucose level and pain behavior induced by IL-1β injected i.t. in normal and D -glucose-fed groups. Furthermore, intraperitoneal (i.p.) pretreatment with RU486 (100 mg/kg) attenuated the blood glucose level and pain behavior induced by IL-1β administered i.t. in normal and D -glucose-fed groups. Our results suggest that IL-1β administered i.t. increases the blood glucose level and pain behavior via an activation of the glucocorticoid system.

We report the case of a patient who experienced extreme recurrent gestational hyperlipidemia. She was diagnosed with partial lipoprotein lipase (LPL) deficiency but without an associated LPL gene mutation in the presence of the apolipoprotein E3/2 genotype. This is the first reported case of extreme gestational hyperlipidemia with a partial LPL deficiency in the absence of an LPL gene mutation and the apolipoprotein E 3/2 genotype. She was managed with strict dietary control and medicated with omega-3 acid ethyl esters. A patient with extreme hyperlipidemia that is limited to the gestational period should be considered partially LPL-deficient. Extreme instances of hyperlipidemia increase the risk of acute pancreatitis, and the effect of parturition on declining plasma lipid levels can be immediate and dramatic. Therefore, decisions regarding the timing and route of delivery with extreme gestational hyperlipidemia are critical and should be made carefully.

The possible roles of gamma-amino butyric acid (GABA) receptors located in the spinal cord for the regulation of the blood glucose level were studied in ICR mice. We found in the present study that intrathecal (i.t.) injection with baclofen (a GABAB receptor agonist; 1-10 μg/5 μl) or bicuculline (a GABAA receptor antagonist; 1-10 μg/5 μl) caused an elevation of the blood glucose level in a dose-dependent manner. The hyperglycemic effect induced by baclofen was more pronounced than that induced by bicuculline. However, muscimol (a GABAA receptor agonist; 1-5 μg/5 μl) or phaclofen (a GABAB receptor antagonist; 5-10 μg/5 μl) administered i.t. did not affect the blood glucose level. Baclofen-induced elevation of the blood glucose was dose-dependently attenuated by phaclofen. Furthermore, i.t. pretreatment with pertussis toxin (PTX; 0.05 or 0.1 μg/5 μl) for 6 days dose-dependently reduced the hyperglycemic effect induced by baclofen. Our results suggest that GABAB receptors located in the spinal cord play important roles for the elevation of the blood glucose level. Spinally located PTX-sensitive G-proteins appear to be involved in hyperglycemic effect induced by baclofen. Furthermore, inactivation of GABAA receptors located in the spinal cord appears to be responsible for tonic up-regulation of the blood glucose level.

Background Fracture of the zygomaticomaxillary complex (ZMC) is one of the most common facial injuries. A previous study has performed 3D analyses of the parallel and rotational displacements that occur in a fractured ZMC. However, few studies have investigated adequate fixation methods according to these displacements. Here, we assessed whether specific approaches and fixation methods for displacement of ZMC fractures produce esthetic results. Methods Hospital records and pre- and post-surgical computed tomographic scans of patients treated for ZMC fractures at the Department of Oral and Maxillofacial Surgery, College of Dentistry, Wonkwang University, between January 2010 and December 2015, were selected. Data were analyzed according to the direction of displacement and post-reduction prognosis using a 3D software. Results With ZMC fractures, displacement in the posterior direction occurred most frequently, while displacement in the superior-inferior direction was rare. A reduction using a transconjunctival approach and an intraoral approach was statistically better than that using an intraoral approach, Gillies approach, and lateral canthotomy approach for a posterior displacement (P

Background The aims of this study are to evaluate the lip morphology and change of lip commissure after mandibular setback surgery (MSS) for class III patients and analyze association between the amount of mandibular setback and change of lip morphology. Methods The samples consisted of 14 class III patients treated with MSS using bilateral sagittal split ramus osteotomy. Lateral cephalogram and cone-beam CT were taken before and about 6 months after MSS. Changes in landmarks and variables were measured with 3D software program Ondemand™. Paired and independent t tests were performed for statistical analysis. Results Landmarks in the mouth corner (cheilion, Ch) moved backward and downward (p < .005, p < .01). However, cheilion width was not statistically significantly changed. Landmark in labrale superius (Ls) was not altered significantly. Upper lip prominence angle (ChRt-Ls-ChLt °) became acute. Landmarks in stomion (Stm), labrale inferius (Li) moved backward (p < .005, p < .001). Lower lip prominence angle (ChRt-Li-ChLt °) became obtuse (p < .001). Height of the upper and lower lips was not altered significantly. Length of the upper lip vermilion was increased (p =< 0.01), and length of the lower lip vermilion was decreased (p < .05). Lip area on frontal view was not statistically significantly changed, but the upper lip area on lateral view was increased and change of the lower lip area decreased (p > .05, p < .005). On lateral view, upper lip prominent point (UP) moved downward and stomion moved backward and upward and the angle of Ls-UP-Stm (°) was decreased. Lower lip prominent point (LP) moved backward and downward, and the angle of Stm-LP-Li (°) was increased. Li moved backward. Finally, landmarks in the lower incisor tip (L1) moved backward and upward, but stomion moved downward. After surgery, lower incisor tip (L1) was positioned more superiorly than stomion (p < .05). There were significant associations between horizontal soft tissue and corresponding hard tissue. The posterior movement of L1 was related to statistically significantly about backward and downward movement of cheilion. Conclusions The lip morphology of patients with dento-skeletal class III malocclusion shows a significant improvement after orthognathic surgery. Three-dimensional lip morphology changes in class III patients after MSS exhibited that cheilion moved backward and downward, upper lip projection angle became acute, lower lip projection angle became obtuse, change of upper lip area on lateral view was increased, change of lower lip area decreased, and morphology of lower lip was protruding. L1 was concerned with the lip tissue change in statistically significant way.

The effec.t of BIIB021, a novel heat shock protein 90 (hsp90) inhibitor, on survival of thyroid carcinoma cells has not been evaluated. In this study, the impact of BIIB021 alone or in combination with the histone acetyltransferase inhibitor triptolide on survival of thyroid carcinoma cells was identified. In 8505C and TPC-1 thyroid carcinoma cells, BIIB021 caused cell death in conjunction with alterations in expression of hsp90 client proteins. Cotreatment of both BIIB021 and triptolide, compared with treatment of BIIB021 alone, decreased cell viability, and increased the percentage of dead cells and cytotoxic activity. All of the combination index values were lower than 1.0, suggesting synergistic activity of BIIB021 with triptolide in induction of cytotoxicity. In treatment of both BIIB021 and triptolide, compared with treatment of BIIB021 alone, the protein levels of total and phospho-p53, and cleaved caspase-3 were elevated, while those of total Akt, phospho-mTOR, phospho-4EBP1, phospho-S6K, phospho-NF-κB, survivin, X-linked inhibitor of apoptosis protein (xIAP), cellular inhibitor of apoptosis protein (cIAP) and acetyl. histone H4 were reduced. These results suggest that BIIB021 has a cytotoxic activity accompanied by regulation of hsp90 client proteins in thyroid carcinoma cells. Moreover, the synergism between BIIB021 and triptolide in induction of cytotoxicity is associated with the inhibition of PI3K/Akt/mTOR and NF-κB signal pathways, the underexpression of survivin and the activation of DNA damage response in thyroid carcinoma cells.

Background. We investigated the cardiac effects of TSH (thyroid-stimulating hormone) oversuppression in women with thyroidectomized differentiated thyroid cancer (DTC) during levothyroxine suppression therapy.Methods. Fourteen young female patients with DTC were enrolled. The duration of TSH-suppressive therapy was 5 to 9 years. They satisfied the following criteria: (1) a serum level of TSH < 0.1 mU/L in the intermediate-risk or TSH < 0.3 mU/L in the low-recurrence-risk group and (2) having been receiving a fixed dose of LT4 before the study. Controls matched for age, sex, and body mass index (BMI) were compared in terms of the levels of serum free T4, free T3, TSH, plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and cardiac functions and structures.Results. DTC patients and control subjects were well matched in heart rate and blood pressure. There were marked differences in serum TSH (P=0.001) and free T4 (P=0.002). However, there were no differences between the groups in serum free T3 and plasma NT-pro-BNP. Furthermore, there were nonsignificant differences in cardiac functions and structures between the groups.Conclusions. This study shows that TSH suppression therapy in women with DTC may be safe with respect to cardiac functions and structures despite intermittent oversuppression of TSH during long-term suppressive therapy.Trial Registration. This trial is registered with clinicaltrials.gov identifierNCT02645786.

Background In the present study, the possible anti-diabetic action of biguanide and thiazolidinediones administered supraspinally or spinally was studied in ICR mice. Methods Mice were intracerebroventricular (i.c.v.) or intrathecal (i.t.) treated with 20 or 30 μg metformin, pioglitazone and rosiglitazone in d -glucose fed and streptozotocin-treated models, and blood glucose levels was measured at 30, 60 and 120 min after i.c.v. or i.t. administration. Results We found that i.c.v. injection with metformin or rosiglitazone slightly attenuated the blood glucose level in d -glucose fed model, whereas pioglitazone showed no effect on the blood glucose level in d -glucose fed model. The i.t. administration with metformin, pioglitazone or rosiglitazone did not alter the blood glucose level in d -glucose fed model. We also assessed the possible roles of biguanide and thiazolidinedione in the regulation of the blood glucose level in streptozotocin-treated model. We found in the present study that i.c.v. or i.t. administration with metformin caused a pronounced attenuation of the blood glucose level in streptozotocin-treated model. However, rosiglitazone administered i.c.v. did not affect the blood glucose level in streptozotocin-treated model. Conclusions Our results suggest that the anti-diabetic actions of metformin and rosiglitazone appear to be mediated via the brain regions as revealed in d -glucose fed animal model. Furthermore, metformin administered supraspinally or spinally may be effective for treating type I diabetes mellitus as revealed in streptozotocin-treated mouse model.

The relationship between pain stimulation and the blood glucose level was studied in ICR mice. We examined the possible change of the blood glucose level after the pain stimulation induced by acetic acid injected intraperitoneally (i.p.),, formalin injected subcutaneously (s.c.) into the hind paw, or substance P (SP), glutamate, and pro-inflammatory cytokines (TNF-α and IFN-γ) injected intrathecally (i.t.). We found in the present study that acetic acid, formalin, SP, TNF-α, and IFN-γ increased the blood glucose level. The blood glucose level reached at maximal state 30 min and returned to normal level 2 h after the pain stimulation in a fasting group. Furthermore, acetic acid, formalin, SP, TNF-α, and IFN-γ caused the elevation of the blood glucose level in d-glucose-fed group only in an additive manner. However, i.t. injection of glutamate did not alter the blood glucose level in a fasting group. In contrast, i.t. injection of glutamate enhanced the blood glucose level in the d-glucose-fed grou...

The relationship between interleukin-1β (IL‐1β)‐induced nociception and the blood glucose level was studied in ICR mice. We found in the present study that intrathecal (i.t.) injection of IL‐1β increased pain behavior. In addition, i.t. IL‐1β injection caused an elevation of the blood glucose level. The time‐course study showed that maximal blood glucose level was observed 30 and 60 min after i.t. IL‐1β administration. Furthermore, i.t. injection of IL‐1β enhanced the blood glucose level when mice were orally fed with d ‐glucose. The i.t. administration of IL‐1β antagonist (AF12198) inhibited the hyperglycemia and pain behaviors induced by IL‐1β. We found in the present study that adrenal tyrosine hydroxylase (TH) mRNA level was also increased by i.t. IL‐1β injection. Furthermore, intraperitoneal (i.p.) pretreatment with phentolamine (an α1‐adrenergic blocker) or yohimbine (an α2‐adrenergic blocker) significantly attenuated the blood glucose level and pain behavior induced by IL‐1β administered i.t. However, the blood glucose level and pain behavior were not affected by butoxamine (a β2-adrenergic blocker), whereas metoprolol (a β2-adrenergic blocker) enhanced IL‐1β-induced blood glucose level and pain behavior in mice fed with d ‐glucose. However, its effect was not statistically significant. Our results suggest that IL‐1β administered i.t. increases the blood glucose level via an activation of α adrenergic nervous system.

We studied the effect of apigenin in combination with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on cell survival and the influence of AKT inhibition on the combined effect of apigenin with TRAIL in anaplastic thyroid carcinoma (ATC) cells.The human 8505C and CAL62 ATC cell lines were used.Apigenin in combination with TRAIL, compared to apigenin alone, reduced cell viability and Bcl2 protein levels, elevated the percentage of dead cells, as well as the protein levels of cleaved PARP and phospho-ERK1/2. The protein levels of Bcl-xL, Bax, Bid, total ERK1/2, and total and phospho-AKT were unchanged. Administration of wortmannin further reduced cell viability, and elevated the percentage of dead cells, cytotoxic activity and cleaved PARP protein levels.Apigenin synergizes with TRAIL through regulation of Bcl2 family proteins in inducing cytotoxicity, and suppression of AKT potentiates synergistic cytotoxicity of apigenin with TRAIL in ATC cells.

BACKGROUND Little is known about the relative contribution of long-term glycemic variability to the risk of macrovascular complications in type 2 diabetes. This study was conducted to evaluate the effect of A1C variability on the progression of carotid artery intima-media thickness (IMT) in type 2 diabetic patients. METHODS Among type 2 diabetic patients who visited Hallym University Sacred Heart Hospital from March 2007 to September 2009, 120 patients who had carotid artery IMT measured annually and A1C checked every three months for at least one year were analyzed. Individual A1C variability was defined as the standard deviation (SD) of five A1C levels taken every three months for approximately one year. Change in IMT was defined as an increase in IMT on follow-up measurement. The association between the SD of A1C and changes in IMT was evaluated. RESULTS With greater A1C variability, there was a greater increase in the mean IMT (r = 0.350, P < 0.001) of the carotid artery. After adjusting for confounding factors that may influence IMT, A1C variability was significantly associated with the progression of IMT (r = 0.222, P = 0.034). However, the SD of A1C was not a significant independent risk factor for the progression of IMT in multiple regression analysis (beta = 0.158, P = 0.093). CONCLUSION Higher A1C variability is associated with IMT progression in type 2 diabetic patients; however, it is not an independent predictor of IMT progression. Overall glycemic control is the most important factor in the progression of IMT.

In diabetic nephropathy, transforming growth factor beta1 (TGFbeta1) is related to p38 mitogen-activated protein kinase (MAPK) that induces production of fibronectin in mesangial cells. We investigated the effects of alpha-lipoic acid (ALA), a potent antioxidant, on proteinuria and TGFbeta1-p38 MAPK-fibronectin pathway in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After ALA treatment for 5 weeks in OLETF rats at 30 weeks of age, plasma malondialdehyde, urinary protein excretion, renal cortical TGFbeta1, and fibronectin protein levels were decreased; and urinary protein excretion was positively correlated with renal cortical TGFbeta1 and fibronectin protein levels. Phospho-form but not total-form levels as well as fold activations of each protein consisting of p38 MAPK pathway were also attenuated. These results suggest that ALA ameliorates proteinuria by attenuating expressions of TGFbeta1 and fibronectin proteins, and these favorable effects are related to inhibition of phosphorylating activation of p38 MAPK pathway in renal cortex of OLETF rats.

Knowledge about the current status of diabetes management is indispensable for the improvement of diabetes management. We performed a survey to investigate the current trend of diabetes management in elderly Koreans, at eight hospitals located throughout the country. A total of 539 patients with type 2 diabetes older than 65 years (men=224, women=315) were recruited. Their mean age was 71.5+/-4.9 years and BMI 24.3+/-3.4 (men=23.6+/-2.8, women=24.9+/-3.7)kg/m(2), and 38.2% of the patients were obese (BMIor =25 kg/m(2), men=29.5%, women=44.4%). The mean duration of the diabetes was 13.1+/-9.2 years. Although 37.3% of the patients had A1C below 7.0%, 33.8% of the patients had A1C more than 8.0%. Three hundred and sixty three patients (67.4%) were treated with oral hypoglycemic agents and 175 patients (32.5%) were treated with insulin or combination with oral agents. The glycemic control was better in patients treated with oral agents (oral agent group=7.7+/-4.6%, insulin group=8.5+/-1.9%). Although mean SBP and DBP were 131.4+/-16.7 and 75.9+/-10.4 mmHg, respectively, 67.4% of the patients had hypertension and 38.2% of the patients with hypertension did not reach the goal (130/80 mmHg). Of 539 elderly patients, 253 patients (47.4%) had dyslipidemia (LDL-Cor =4.1 mmol/l and/or triglycerideor =2.5 mmol/l and/or HDL-C1.1 mmol/l) and 72.7% of the patients with dyslipidemia took the lipid lowering agents. However, 47.4% of them did not achieve the goal (LDL-C2.6 mmol/l and/or triglyceride1.7 mmol/l and/or HDL-C1.1 mmol/l). Twenty-eight patients (5.5%) had been admitted to the hospital because of severe hypoglycemia. Half of the patients (57%) had microvascular complications (retinopathy, neuropathy or overt proteinuria), and 28% of the patients had macro-vascular complications (CVD, stroke or peripheral vascular disease). As elderly diabetic patients are usually polymorbid, diabetes mellitus in old age is needed a more comprehensive approach to not only the treatment of hyperglycemia but also of hypertension, dyslipidemia and other associated diseases.

The aim of the present study was to evaluate the effect of heat-shock protein 90 (HSP90) inhibitors, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and herbimycin A (HMA) on survival of anaplastic thyroid carcinoma (ATC) cells.Antitumor activities of 17-AAG and HMA were investigated in FRO ATC cells.In FRO ATC cells, 17-AAG and HMA caused cell death with concomitant changes in the expression of HSP90 client proteins, increased β-catenin protein levels, and inhibited PI3K/AKT signaling. The inactivation of β-catenin by β-catenin siRNA transfection and the activation of PI3K/AKT signaling by p110α plasmid transfection abrogated cell death caused by 17-AAG and HMA.17-AAG and HMA have cytotoxic activities accompanied by regulation of HSP90 client proteins, and cytotoxicity is associated with overexpression of β-catenin and suppression of PI3K/AKT signaling in FRO ATC cells.

The influence of the heat shock protein 90 (hsp90) inhibitor SNX5422 alone or in combination with the histone deacetylase (HDAC) inhibitors PXD101, suberoylanilide hydroxamic acid (SAHA), and trichostatin A (TSA) on survival of anaplastic thyroid carcinoma (ATC) cells was investigated. In 8505C and CAL62 cells, SNX5422 caused cell death with concomitant changes in the expression of hsp90 client proteins. After treatment of both SNX5422 and PXD101, SAHA and TSA, compared with treatment of SNX5422 alone, cell viability was diminished, whereas inhibition rate and cytotoxic activity were enhanced. All of the combination index values were lower than 1.0, suggesting the synergism between SNX5422 and PXD101, SAHA and TSA in induction of cell death. In cells treated with both SNX5422 and PXD101, SAHA and TSA, compared with cells treated with SNX5422 alone, the protein levels of Akt, phospho-4EBP1, phospho-S6 K, and survivin were diminished, while those of γH2AX, acetyl. histone H3, acetyl. histone H4, cleaved PARP, and cleaved caspase-3 were enhanced. In conclusion, these results demonstrate that SNX5422 has a cytotoxic activity in conjunction with alterations in the expression of hsp90 client proteins in ATC cells. Moreover, SNX5422 synergizes with HDAC inhibitors in induction of cytotoxicity accompanied by the suppression of PI3K/Akt/mTOR signaling and survivin, and the overexpression of DNA damage-related proteins in ATC cells.