Il Ho Park

Volumetric study in the development of paranasal sinuses by CT imaging in Asian: A Pilot study

BACKGROUND AND OBJECTIVES The volume of the air cavities in the paranasal sinuses is not only the simplest, but also the most important index for paranasal sinus evaluation. However, few volumetric studies have been performed in all age groups. The purpose of the current study was to outline the normal development of paranasal sinuses in all age groups, and to determine normal adult volumetric values by means of computed tomographic (CT) scan of paranasal sinus using volumetric procedures. MATERIALS AND METHODS A prospective volumetric CT study was conducted with 260 patients (520 sides) <25 years of age by means of three-dimensional reconstruction. RESULTS The frontal sinuses began to pneumatize at 2 years of age, exhibited a faster growth pattern between 6 and 19 years of age, and the mean volume after full growth was 3.46±0.78 cm(3). The maxillary sinuses were pneumatized at birth in all cases, exhibited a monomodal growth pattern increasing until 15 years of age, and the mean volume after full growth was 14.83±1.36 cm(3). The floor of the sinus was the same level as the floor of the nasal cavity was between 7 and 15 years of age. The ethmoid sinuses exhibited a faster initial tendency to increase until 7 years of age, were completed by 15-16 years of age, and the mean volume after full growth was 4.51±0.92 cm(3). The sphenoid sinuses exhibited a growth spurt between 6 and 10 years of age, were completed by 15 years of age, and the mean volume after full growth was 3.47±0.93 cm(3). CONCLUSION The results of this study are presented to provide the basis for an objective normal volume of sinus development and for studies involving diseases of the sinuses.

The effect of macrolides on myofibroblast differentiation and collagen production in nasal polyp-derived fibroblasts.

Background Macrolides are known to have anti-inflammatory, immunomodulatory, and tissue reparative effects. The purpose of this study was to determine the effect of macrolides (erythromycin [EM] and roxithromycin [RXM]) on the differentiation of fibroblasts into myofibroblasts and extracellular matrix accumulation in transforming growth factor (TGF) beta1–induced nasal polyp–derived fibroblasts (NPDFs) and to determine if NADPH oxidase (Nox) 4 and reactive oxygen species (ROS) are involved in the aforementioned processes. Methods Nasal polyps of six patients (three women and three men; 32.3 ± 5.2 years of age) were acquired during surgery and NPDFs were isolated from surgical tissues. NPDFs were pretreated with macrolides for 2 hours before differentiation induction by TGF-beta1. The mRNA expressions of alpha-smooth muscle actin (SMA), collagen types I and III, and Nox4 were determined by reverse-transcription–polymerase chain reaction, and the expression of alpha-SMA protein was determined by immunocytochemical staining. The amount of total collagen production was analyzed by SirCol collagen dye-binding assay. ROS activity was measured by nitroblue tetrazolium reduction assay and was visualized by fluorescent microscopy. Results In TGF-beta1–induced NPDFs, EM, and RXM significantly inhibited expressions of alpha-SMA and collagen types I and III mRNA and reduced alpha-SMA and collagen protein levels at concentrations of 5 and 10 μg/mL. EM and RXM also inhibited TGF-β1–induced ROS production and Nox4 mRNA expression at the same concentrations. Conclusion These results suggest the possibility that EM and RXM may play an important role in inhibiting the development of nasal polyps through their antioxidant effect.

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.

Human papillomavirus-related carcinoma with adenoid cystic-like features of the inferior turbinate: A case report

Sinonasal malignancies are uncommon, but are of many different histologic types. Recently, Human papillomavirus (HPV)-related carcinoma with adenoid cystic features was reported as a new histologic form. Although this histologic type resembles an adenoid cystic carcinoma, it differs from adenoid cystic carcinomas with regard to its association with HPV. Here, we present a case of HPV-related carcinoma with adenoid cystic features in the nasal cavity. We also review the histological characters of the tumor.

Correlation between skin-prick testing, individual specific IgE tests, and a multiallergen IgE assay for allergy detection in patients with chronic rhinitis.

Background Allergy test results can differ based on the method used. The most common tests include skin-prick testing (SPT) and in vitro tests to detect allergen-specific IgE. This study was designed to assess allergy test results using SPT, individual specific IgE tests, and a multiallergen IgE assay (multiple allergen simultaneous test) in patients with chronic rhinitis and controls. Methods One hundred forty total patients were prospectively enrolled in the study, including 100 patients with chronic rhinitis and 40 control patients without atopy. All eligible patients underwent SPT, serum analysis using individual specific IgE test, and multiple allergen simultaneous test against 10 common allergens. Allergy test results were then compared to identify correlation and interest agreement. Results There was an 81–97% agreement between SPT and individual specific IgE test in allergen detection and an 80–98% agreement between SPT and multiple allergen simultaneous test. Individual specific IgE test and multiple allergen simultaneous test allergy detection prevalence was generally similar to SPT in patients with chronic rhinitis. All control patients had negative SPT (0/40), but low positive results were found with both individual specific IgE test (5–12.5%) and multiple allergen simultaneous test (2.5–7.5%) to some allergens, especially cockroach, Dermatophagoides farina, and ragweed. Agreement and correlation between individual specific IgE test and multiple allergen simultaneous test were good to excellent for a majority of tested allergens. Conclusion This study shows good agreement and correlation between SPT with individual specific IgE test and multiple allergen simultaneous test on a majority of the tested allergens for patients with chronic rhinitis. Comparing the two in vitro tests, individual specific IgE test agrees with SPT better than multiple allergen simultaneous test.

Trichostatin A inhibits epithelial mesenchymal transition induced by TGF-β1 in airway epithelium

Background and Objectives Tissue remodeling is believed to cause recalcitrant chronic rhinosinusitis (CRS). Epithelial-mesenchymal transition (EMT) is a novel clinical therapeutic target in many chronic airway diseases related with tissue remodeling. The aim of this study was to investigate the effect of trichostatin A (TSA) on transforming growth factor (TGF)-β1-induced EMT in airway epithelium and nasal tissue. Materials and Methods A549 cells, primary nasal epithelial cells (PNECs), or inferior nasal turbinate organ culture were exposed to TSA prior to stimulation with TGF-β1. Expression levels of E-cadherin, vimentin, fibronectin, α-smooth muscle actin (SMA), histone deacetylase 2 (HDAC2), and HDAC4 were determined by western blotting and/or immunofluorescent staining. Hyperacetylation of histone H2 and H4 by TSA was measured by western blotting. After siHDAC transfection, the effects of HDAC2 and HDAC4 silencing on expression of E-cadherin, vimentin, fibronectin, α-SMA, HDAC2, and HDAC4 in TGF-β1-induced A549 were determined by RT-PCR and/or western blotting. We assessed the change in migration capacity of A549 cells by using cell migration assay and transwell invasion assay. Results TGF-β1 altered mRNA and protein expression levels of EMT markers including E-cadherin, vimentin, fibronectin, α-SMA, slug, and snail in A549 cells. Inhibition and silencing of HDAC2 and HDAC4 by TSA and siRNA enhanced TGF-β1-induced EMT in A549 cells. TSA blocked the effect of TGF-β1 on the migratory ability of A549 cells. In experiments using PNECs and inferior turbinate organ cultures, TSA suppressed expression of EMT markers induced by TGF-β1. Conclusions We showed that EMT is induced by TGF-β1 in airway epithelial cells and nasal tissue via activation of HDAC2 and HDAC4, and that inhibition of HDAC2 and HDAC4 by TSA reduces TGF-β1-induced EMT. This observation indicates that histone deacetylase inhibitors such as TSA could be potential candidates for treatment of recalcitrant CRS related with tissue remodeling.

Effects of histone deacetylase inhibitor on extracellular matrix production in human nasal polyp organ cultures.

Background Nasal polyposis is associated with a chronic inflammatory condition of the sinonasal mucosa and involves myofibroblast differentiation and extracellular matrix (ECM) accumulation. Epigenetic modulation by histone deacetylase (HDAC) inhibitors including trichostatin A (TSA) has been reported to have inhibitory effects on myofibroblast differentiation in lung and renal fibroblasts. The purpose of this study was to investigate the inhibitory effect of TSA on myofibroblast differentiation and ECM production in nasal polyp organ cultures. Methods Nasal polyp tissues from 18 patients were acquired during endoscopic sinus surgery. After organ culture, nasal polyps were stimulated with TGF-beta1 and then treated with TSA. Alpha-smooth muscle actin (α-SMA), fibronectin, and collagen type I expression levels were examined by reverse transcription–polymerase chain reaction (PCR), real-time PCR, Western blot, and immunofluorescent staining. HDAC2, HDAC4, and acetylated H4 expression levels were assayed by Western blot. Cytotoxicity was analyzed by the terminal deoxynucleotidyl transferase biotin–dUTP nick end labeling assay. Results The expression levels of α-SMA, fibronectin, and collagen type 1 were increased in nasal polyp after transforming growth factor (TGF) beta1 treatment. TSA-inhibited TGF-beta1 induced these gene and protein expression levels. Furthermore, TSA suppressed protein expression levels of HDAC2 and HDAC4. However, TSA induced hyperacetylation of histones H4. Treatment with TGF-beta1 with or without TSA did not have cytotoxic effect. Conclusion These findings provide novel insights into the epigenetic regulation in myofibroblast differentiation and ECM production of nasal polyp. TSA could be a candidate of a therapeutic agent for reversing the TGF-beta1–induced ECM synthesis that leads to nasal polyp development.

Effect of simvastatin on transforming growth factor beta-1-induced myofibroblast differentiation and collagen production in nasal polyp-derived fibroblasts.

Background Statins are the most commonly prescribed drugs for the treatment of hypercholesterolemia. Statins exert not only lipid-lowering but also other cellular effects, including antifibrotic properties. The purpose of this study was to determine the effect of simvastatin on transforming growth factor (TGF)-beta-1–induced myofibroblast differentiation and collagen production in nasal polyp-derived fibroblasts (NPDFs) and to verify the mechanism of the effect of simvastatin in TGF-beta-1–induced myofibroblast differentiation in NPDFs. Methods NPDFs were pretreated with simvastatin with or without mevalonate or Y-27643 for 2 hours before induction by TGF-beta-1. The expression of alpha-smooth muscle actin (SMA) and collagen type IV mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of alpha-SMA protein was determined by immunofluorescent cytochemical staining. Total soluble collagen production was analyzed by the SirCol collagen dye-binding assay (Biocolor, Belfast, U.K.). Phosphorylation of Smad 2/3 was evaluated by Western blot analysis. Results In TGF-beta-1–induced NPDFs, simvastatin significantly inhibited the expressions of α-SMA and collagen type IV mRNA and reduced alpha-SMA and collagen protein levels. Pretreatment with mevalonate reversed the effect of simvastatin. The expression of alpha-SMA mRNA and protein was significantly decreased by pretreatment with Y-27632. The TGF-beta-1–induced expression of pSmad 2/3 protein was notably decreased by pretreatment with simvastatin. Conclusion We showed that simvastatin inhibits TGF-beta-1–induced myofibroblast differentiation (expression of alpha-SMA) and collagen production in NPDFs and Rho/Rock and TGF-β/Smad signaling is involved as an underlying mechanism. The results of our study suggest that simvastatin is a possible candidate for the suppression of nasal polyp formation.

Thermomigration of tellurium precipitates in CdZnTe crystals grown by vertical Bridgman method

Te precipitates in CdZnTe have been characterized by x-ray diffraction at room and higher temperatures. From the x-ray results at room temperature, it has been confirmed that Te precipitates in CdZnTe have the same structural phase as observed in elemental Te under high pressure. The x-ray results at higher temperature indicate that Te precipitates melt around 440°C. CdZnTe samples containing Te precipitates have been annealed at temperatures below and above 440°C with thermal gradient of ∼70°C/cm. Results of the observation with infrared microscope before and after the annealings indicate distinct occurrence of thermomigration of Te precipitates in samples annealed at temperature above 440°C compared with ones annealed at temperature below 440°C. Thermomigration velocity obtained from these results is ∼50 μm/h. The average value for the effective diffusion coefficient of the metallic atoms in Te precipitates calculated by using the thermomigration velocity is ∼3 x 10−5 cm2/s.

Isolation and characterization of multipotent mesenchymal stem cells in nasal polyps

Mesenchymal stem cells (MSCs) are multipotent progenitor cells in adult tissues. This study aimed to investigate nasal polyp (NP) tissues as a potential new source of multipotent MSCs that maintain their stemness and differentiation potential following multiple rounds of passaging. NP tissues were obtained from 10 patients during endoscopic sinus surgery. After isolating and culturing NP-derived MSCs (npMSCs), the expression levels of the surface markers CD34, CD44, CD45, CD73, CD90, CD105, CD106, CD146 and human leukocyte antigens-class II DR antigen (HLA-DR) were estimated by flow cytometry. NpMSCs were cultured in chondrogenic, osteogenic, adipogenic, or neurogenic differentiation medium. The differentiation potential of npMSCs was analyzed by Alcian blue, alizarin red S, oil red O, and immunocytochemical staining and reverse transcription-polymerase chain reaction. The clonogenic potential of npMSCs was measured using a colony-forming unit assay. Cell proliferation of npMSCs was measured using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Flow cytometry analysis revealed that npMSCs were negative for hematopoietic lineage markers (CD34, CD45, and HLA-DR) and positive for MSC markers (CD44, CD73, CD90, and CD105). The npMSCs differentiated into osteogenic, adipogenic, chondrogenic, and neurogenic lineages, respectively. Chondrogenically differentiated npMSCs were stained with Alcian blue, osteogenically differentiated npMSCs were stained with alizarin red S, and adipogenically differentiated npMSCs were stained with oil red O. Real-time polymerase chain reaction results showed that the differentiated npMSCs expressed the respective differentiation markers (Sox 9 and Col2A for chondrogenesis, Runx2 and osteocalcin for osteogenesis, fatty acid-binding protein 4 and peroxisome proliferator-activated receptor γ for adipogenesis, TuJ1, neurofilament light chain, and neurofilament heavy chain for neurogenesis). There were no significant differences in the clonogenic potential and proliferation rate between early and late passage npMSCs. These results show that npMSCs possess the characteristics of MSCs in terms of morphology, multipotent differentiation capacity, cell surface marker expression, and clonogenicity. Thus, npMSCs may represent an alternative source of MSCs.