Sung Moon Hong

Metformin reduces TGF-β1-induced extracellular matrix production in nasal polyp-derived fibroblasts.

Background and Objects Metformin is widely used to treat type 2 diabetes mellitus, and adenosine monophosphate–activated protein kinase (AMPK) is thought to be the target that mediates its effects. Recently, it has been demonstrated that metformin has antifibrotic effects beyond its antihyperglycemic action. The purposes of this study were to investigate the effect of metformin on TGF-β1–induced myofibroblast differentiation (α-smooth muscle actin [α-SMA]) and extracellular matrix (ECM) production and to determine the underlying mechanism of the action of metformin in nasal polyp–derived fibroblasts (NPDFs). Study Design Basic research. Setting The rhinology laboratory of Korea University Guro Hospital, Seoul, Korea. Methods NPDFs from 7 patients were incubated with TGF-β1 and treated with metformin or compound C, an inhibitor of AMPK. To determine the proliferation rate of nasal fibroblasts, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was performed. The expression levels of α-SMA and fibronectin were determined by reverse transcription–polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescent staining. Phosphorylation of AMPK and phosphorylation of Smad2/3 were evaluated by Western blot analysis. Results In TGF-β1–induced NPDFs, metformin inhibited the expression of α-SMA and fibronectin, as confirmed by both RT-PCR and Western blot analysis. Metformin increased the phosphorylation of AMPK and the expression levels of α-SMA and fibronectin. However, compound C reversed these effects. Metformin inhibited TGF-β1–induced phosphorylation of Smad2/3. Conclusions This study showed that metformin inhibits TGF-β1–induced myofibroblast differentiation and ECM production in NPDFs via the Smad2/3 pathway. AMPK can be a therapeutic target for the prevention of ECM remodeling in nasal polyps.

Coblation vs. Electrocautery Tonsillectomy: A Prospective Randomized Study Comparing Clinical Outcomes in Adolescents and Adults

Objectives Coblation is operated in low temperature, so it is proposed that tonsillectomy with coblation involves less postoperative pain and allows accelerated healing of the tonsillar fossae compared with other methods involving heat driven processes. However, the results of the previous studies showed that the effect of coblation tonsillectomy has been equivocal in terms of postoperative pain and hemorrhage. Though, most of the previous studies which evaluated coblation tonsillectomy were performed in children. Recently, electrocautery tonsillectomy has been used most widely because of the reduced intraoperative blood loss and shorter operative time compared to other techniques. This prospective study compared intraoperative records and postoperative clinical outcomes in adolescents and adults following coblation and electrocautery tonsillectomies. Methods Eighty patients over 16 years of age with histories of recurrent tonsillitis were enrolled. The patients were randomly allocated into coblation (n=40) and electrocautery tonsillectomy groups (n=40). All operations were performed by one surgeon who was skilled in both surgical techniques. Intraoperative parameters and postoperative outcomes were checked. Results Postoperative pain and otalgia were not significantly different between the two groups; however, there was a tendency towards reduced pain and otalgia in the coblation group. More cotton balls for swabbing the operative field were used introoperatively in the electrocautery group (P=0.00). There was no significant difference in postoperative hemorrhage, wound healing, commencement of a regular diet, and foreign body sensation between the groups. Conclusion Only cotton use, which represented the amount of blood loss, was less in the coblation tonsillectomy group. Coblation tonsillectomy warrants further study with respect to the decreased postoperative pain and otalgia.

Increased expression of high-mobility group protein B1 in chronic rhinosinusitis.

Background Chronic rhinosinusitis (CRS) is an inflammation of the sinonasal mucosa and many inflammatory cells and cytokines are involved in its pathogenesis. High-mobility group protein B1 (HMGB1) is a DNA-binding protein that has a proinflammatory function when secreted into extracellular space. The purpose of this study was to evaluate the expression of HMGB1 in paranasal sinus mucosa and to determine the difference of HMGB1 expression between CRS patients and normal controls. Methods Paranasal sinus mucosa was obtained from 10 patients with CRS and 10 patients without CRS. Semiquantitative reverse transcriptase–polymerase chain reaction (RT-PCR), real-time PCR and Western blot analysis were performed to detect mRNA and protein. Sections of the mucosa were immunostained for localization of HMGB1 and image analysis was performed. Results RT-PCR and real-time PCR showed that the expression level of HMGB1 mRNA was significantly increased in the tissues of patients with CRS compared with controls. Western blot analysis showed that the expression level of HMGB1 protein was significantly increased in the tissues of CRS. In immunohistochemical staining, the HMGB1 protein was expressed in epithelial cells and inflammatory cells and the expression intensity of HMGB1 protein was stronger in CRS. Conclusion HMGB1 is increased in the paranasal sinus mucosa of patients with CRS. These results suggest a possible contribution of HMGB1 in the pathophysiology of CRS.

Efficacy and safety of sublingual immunotherapy in Asian children

OBJECTIVE Sublingual immunotherapy is currently accepted as a suitable alternative to subcutaneous immunotherapy because of its easy and painless administration and improved safety. Many clinical trials have demonstrated that sublingual immunotherapy is an effective and safe treatment for pollen or mite allergic rhinitis. However, there have been very few studies overall on children with allergic rhinitis who are sensitized to house-dust mites in Asia. The purpose of the present study was to investigate the efficacy and safety of sublingual immunotherapy in children with allergic rhinitis to house-dust mites. METHODS A total of 112 patients under the age of 15 who had allergic rhinitis to Dermatophagoides pteronyssinus and Dermatophagoides farinae were included. All patients were treated with sublingual immunotherapy (Staloral(®)). Symptom scores and quality of life were evaluated by questionnaires until one year after sublingual immunotherapy. The medication score was assessed monthly using a diary medication card and serologic tests were evaluated before and 6 and 12 months after treatment. Adverse effects and compliance were also investigated. RESULTS All nasal and non-nasal symptoms and quality of life were significantly improved after treatment. The total medication score was decreased significantly after sublingual immunotherapy. There was no significant change in serologic tests. Some minor adverse effects were reported, however there were no systemic reactions. The drop-out rate was 21%. CONCLUSIONS Sublingual immunotherapy is a valuable therapy for the treatment of allergic rhinitis in Asian children sensitized to house-dust mites.

Sclerosing Polycystic Adenosis of the Nasal Septum: The Risk of Misdiagnosis

Sclerosing polycyctic adenosis (SPA) is a rare lesion of unknown etiology morphologically resembling fibrocystic changes of the breast. To date, approximately 41 cases of SPA have been reported. Most cases of SPA have originated in the parotid and submandibular glands, with a few cases of intra-oral minor salivary gland origin. This is the first reported case of sclerosing polycystic adenosis of nasal minor salivary gland origin. The differential diagnosis of SPA includes polycystic disease, sclerosing sialadenitis, and benign and malignant glandular neoplasias. Although atypia ranging from mild dysplasia to carcinoma in situ can occur in some cases, SPA has a favorable outcome. It is important to be familiar with SPA to avoid aggresive treatment that results from a misdiagnosis. We present a case of a 49-year-old man who had 1-year history of right nasal obstruction.

Caffeic acid phenethyl ester inhibits diesel exhaust particle-induced inflammation of human middle ear epithelial cells via NOX4 inhibition.

Objectives: Otitis media is one of the most common diseases in pediatric populations. Recent research on its pathogenesis has focused on air pollution. Chronic exposure to particulate air pollution is associated with the impairment of middle ear function. However, the mechanisms and the underlying inhibitory pathways, especially in the human middle ear, remain unknown. Caffeic acid phenethyl ester (CAPE) is a biologically active ingredient of propolis, a product of honeybee hives, which has anti-oxidative and anti-inflammatory activities. The aim of this study was to evaluate the inhibitory effect of CAPE on diesel exhaust particle (DEP)–induced inflammation of human middle ear epithelial cells and to determine the underlying pathway of the action of CAPE. Methods: The inflammatory damage caused by DEPs and the anti-inflammatory effects of CAPE were determined by measuring the levels of tumor necrosis factor α and nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4 with real-time reverse transcription polymerase chain reaction and Western blot analysis. The oxidative stress induced by DEPs and the anti-oxidative effects of CAPE were directly evaluated by measuring reactive oxygen species production by use of flow cytometric analysis of 2′,7′-dichlorofluorescein diacetate. The effects of CAPE were compared with those of N-acetyl-L-cysteine, which has anti-oxidative and anti-inflammatory effects. Results: Use of CAPE significantly inhibited DEP-induced up-regulation of tumor necrosis factor α and NOX4 expression in a dose- and time-dependent manner. The accumulation of reactive oxygen species induced by DEPs was decreased by pretreatment with CAPE. The anti-inflammatory and anti-oxidative effects of CAPE were similar to those of N-acetyl-L-cysteine. Conclusions: The inflammation induced by DEP is reduced by CAPE via the inhibition of NOX4 expression. These findings suggest that CAPE might be used as a therapeutic agent against DEP-induced inflammation of human middle ear epithelial cells.

A randomized, multi-center, single blind, active-controlled, matched pairs clinical study to evaluate prevention of adhesion formation and safety of hyfence in patients after endoscopic sinus surgery

Objectives Recurrent mucosal disease and anatomic obstruction are commonly cited causes of failed endoscopic sinus surgery (ESS). Hyaluronic acid (HA) has been reported to reduce scarring and to promote wound healing in sinonasal surgery. HyFence is HA stabilized by 1, 4-butandiol diglycidyl ether, which makes it less-water-soluble and highly viscoelastic. The purpose of this study is to examine the anti-adhesion effect of HyFence after ESS compared to that of HA-CMC (Guardix-Sol). Methods Seventy-four patients with chronic rhinosinusitis who underwent ESS were included in the study. After the ESS procedure, Merocel was placed in the ethmoidectomized areas of the both sides. Five milliliters of Guardix-Sol was then applied to the Merocel of one side and HyFence LV was applied to the other side. The effect of the agents was evaluated at one, two, and four weeks after surgery by endoscopic examination. The severity of adhesion, edema, infection and complications were evaluated. Results There was no significant difference in the incidence of postoperative adhesion between the HyFence group and the Guardix-Sol group (P>0.05). Mean postoperative grades of edema and infection showed no significant difference between groups (P>0.05). There was no significant postoperative complications associated with either anti-adhesion agent (P>0.05). Conclusion HyFence has equivalent anti-adhesion effect compared to Guardix-Sol following ESS.

Stimulatory effects of histamine on migration of nasal fibroblasts.

Fibroblast migration is crucial for normal wound repair after sinonasal surgery. Histamine is known to be involved in wound healing by its effects on cell proliferation and migration. This study aimed to determine whether histamine affects the migration of nasal fibroblasts and to investigate the mechanism of action of histamine on nasal fibroblasts.

Inhibitory effect of prostaglandin E(2) on the migration of nasal fibroblasts.

Background Fibroblast migration is crucial for normal wound repair after sinonasal surgery. Prostaglandin E2 (PGE2) is a potent inhibitor of fibroblast functions including chemotaxis, proliferation, and matrix production. The purpose of this study was to determine whether PGE2 affects the migration of nasal fibroblasts and to investigate the mechanism of action of PGE2 on nasal fibroblasts. Methods Primary cultures of nasal fibroblasts were established from inferior turbinate samples. Fibroblast migration was evaluated with scratch assays. Reverse-transcription polymerase chain reaction was performed for E prostanoid (EP) 1, EP2, EP3, and EP4 receptors. EP receptor–selective agonists and antagonists were used to evaluate receptor functions. Stimulatory G (Gs) proteins were activated to evaluate mechanisms. Intracellular cyclic adenosine monophosphate (cAMP) levels were measured by ELISA, and fibroblast cytoskeletal structures were visualized with immunocytochemistry. Results PGE2 significantly reduced the migration of nasal fibroblasts. Agonists selective for the EP2 and EP4 receptors significantly reduced the nasal fibroblast migration. Antagonists of the EP2 and EP4 receptors inhibited the effect of PGE2 on nasal fibroblast migration. Activation of Gs protein and adenyl cyclase reduced nasal fibroblast migration. Conclusion PGE2 inhibited the migration of nasal fibroblasts via the EP2 and EP4 receptors, and this inhibition was mediated by cAMP elevation. Targeting specific EP receptors could offer therapeutic opportunities for conditions such as delayed wound healing after nasal surgery.