dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses

German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma.

CpG Oligodeoxynucleotide Inhibits Cockroach-Induced Asthma via Induction of IFN-gamma+ Th1 Cells or Foxp3+ Regulatory T Cells in the Lung

PURPOSE: CpG oligodeoxynucleotide (CpG-ODN), a TLR9 agonist, activates innate immunity and induces Th1 response. Although the immune modulatory effect of CpG-ODN has been extensively studied, its function in cockroach extract-induced allergic asthma has not been studied. Here, we investigated the inhibitory function of CpG-ODN in cockroach extract-induced asthma in mice with different treatment schemes. METHODS: Scheme 1: BALB/C mice were intra-nasally co-administered by cockroach extract and CpG-ODN twice a week for 3 weeks; Scheme 2: The mice were intra-nasally pre-treated with CpG-ODN at day 0 and cockroach allergen challenge was performed from day 3 as in scheme 1. Scheme 3: Cockroach allergen challenge was performed as in scheme 1 and CpG-ODN was post-treated at day 21. Then, BAL cell count, flow cytometric analysis of alveolar macrophages, regulatory T cells, and lung tissue histology, Th1 and Th2 cytokines, serum IgE, cockroach specific IgE, IgG1/IgG2a ratio, and airway hyper-responsiveness were evaluated. RESULTS: Mice with repeated intra-nasal exposure to CpG-ODN showed a dramatic decrease in eosinophilic inflammation, goblet cell hyperplasia, and airway hyper-responsiveness with reduction of IL-13, IL-5, and serum IgE, cockroach specific IgE and IgG1/IgG2a ratio. This inhibitory function might be related to the up-regulation of IL-10 and CD4+Foxp3+ regulatory T cells in the lung. Interestingly, one-time challenge of CpG-ODN either prior or posterior to cockroach extract exposure could modulate airway inflammation and hyper-responsiveness via increase of Th1 response. CONCLUSIONS: Collectively, our data suggest that CpG-ODN treatment modulates Th2 inflammation in the lung by induction of regulatory T cells or Th1 response in a cockroach-induced asthma model.

Acute exposure to silica nanoparticles aggravate airway inflammation: different effects according to surface characteristics

Silica nanoparticles (SNPs) are widely used in many scientific and industrial fields despite the lack of proper evaluation of their potential toxicity. This study examined the effects of acute exposure to SNPs, either alone or in conjunction with ovalbumin (OVA), by studying the respiratory systems in exposed mouse models. Three types of SNPs were used: spherical SNPs (S-SNPs), mesoporous SNPs (M-SNPs), and PEGylated SNPs (P-SNPs). In the acute SNP exposure model performed, 6-week-old BALB/c female mice were intranasally inoculated with SNPs for 3 consecutive days. In the OVA/SNPs asthma model, the mice were sensitized two times via the peritoneal route with OVA. Additionally, the mice endured OVA with or without SNP challenges intranasally. Acute SNP exposure induced significant airway inflammation and airway hyper-responsiveness, particularly in the S-SNP group. In OVA/SNPs asthma models, OVA with SNP-treated group showed significant airway inflammation, more than those treated with only OVA and without SNPs. In these models, the P-SNP group induced lower levels of inflammation on airways than both the S-SNP or M-SNP groups. Interleukin (IL)-5, IL-13, IL-1beta and interferon-gamma levels correlated with airway inflammation in the tested models, without statistical significance. In the mouse models studied, increased airway inflammation was associated with acute SNPs exposure, whether exposed solely to SNPs or SNPs in conjunction with OVA. P-SNPs appear to be relatively safer for clinical use than S-SNPs and M-SNPs, as determined by lower observed toxicity and airway system inflammation.

Endotoxin Is Not Essential for the Development of Cockroach Induced Allergic Airway Inflammation

PURPOSE: Cockroach (CR) is an important inhalant allergen and can induce allergic asthma. However, the mechanism by which CR induces airway allergic inflammation and the role of endotoxin in CR extract are not clearly understood in regards to the development of airway inflammation. In this study, we evaluated whether endotoxin is essential to the development of CR induced airway allergic inflammation in mice. MATERIALS AND METHODS: Airway allergic inflammation was induced by intranasal administration of either CR extract, CR with additional endotoxin, or endotoxin depleted CR extract, respectively, in BALB/c wild type mice. CR induced inflammation was also evaluated with toll like receptor-4 (TLR-4) mutant (C3H/HeJ) and wild type (C3H/HeN) mice. RESULTS: Intranasal administration of CR extracts significantly induced airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation, as well as goblet cell hyperplasia in a dose-dependent manner. The addition of endotoxin along with CR allergen attenuated eosinophilic inflammation, interleukin (IL)-13 level, and goblet cell hyperplasia of respiratory epithelium; however, it did not affect the development of AHR. Endotoxin depletion in CR extract did not attenuate eosinophilic inflammation and lymphocytosis in BAL fluid, AHR and IL-13 expression in the lungs compared to CR alone. The attenuation of AHR, eosinophilic inflammation, and goblet cell hyperplasia induced by CR extract alone was not different between TLR-4 mutant and the wild type mice. In addition, heat inactivated CR extract administration induced attenuated AHR and eosinophilic inflammation. CONCLUSION: Endotoxin in CR extracts may not be essential to the development of airway inflammation.

Effect of an Air Cleaner with Electrostatic Filter on the Removal of Airborne House Dust Mite Allergens

PURPOSE: The effects of air cleaners on the removal of airborne indoor allergens, especially house dust mites (HDM), are still controversial. The objective of this study is to evaluate the effect of an air cleaner with an electrostatic filter on the removal of airborne mite allergens. MATERIALS AND METHODS: A dried HDM culture medium that contained mite body particles and excretions was dispersed in a chamber equipped with an electrostatic air cleaner. The number of airborne particles was recorded continuously by a dust spectrometer for 60 minutes. Airborne particles in the chamber were collected on a sampling filter at a flow rate of 10 L/min and the Der f 1 concentration in the filter extracts was measured by two-site ELISA. RESULTS: The air cleaner efficiently removed airborne HDM particles. The air cleaner removed airborne HDM particles (size 2-12.5 microm) 11.4 +/- 2.9 fold (cleaner operating for 15 minutes), 5.4 +/- 0.7 fold (cleaner operating for 30 minutes), and 2.4 +/- 0.2 fold (cleaner operating for 60 minutes) more than the removal of HDM particles by natural settle down. Removal kinetics differed according to the particle size of the airborne particles. The air cleaner decreased the concentration of Der f 1 in the extraction of airborne particles collected on the air sampling filter by 60.3%. CONCLUSION: The electrostatic air cleaner can remove airborne HDM allergens and may be useful as a supplementary environmental control tool for HDM sensitized respiratory allergic patients.

The Effects of Hypertonic Saline Irrigation on Nasal Mucus Secretion in Patient with Chronic Rhinosinusitis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Various saline solution formulae for nasal irrigation have been used frequently in patients with rhinosinusitis. However, there are not enough scientific evidences supporting the effect of irrigation of the nose with saline solution. We investigated the effects of saline irrigation on mucus secretion, subjective symptoms, and nasal cavity air-space volume changes in patients with rhinosinusitis. SUBJECTS AND METHOD: The nasal cavities of patients with rhinosinusitis were washed with 0.9%, 3%, and 6% of saline solutions consecutively with about 10 minute intervals. Lavage fluids were collected from the ipsilateral sides to determine the concentrations of mucin and lysozyme. Patients recorded subjective symptoms and each patient's nasal cavity air-space volume was assessed by acoustic rhinometry after each irrigations. RESULTS: The sensation of rhinorrhea, pain, and nasal blockage were increased as the concentration of saline increased. The concentrations of mucin increased with the increasing concentration of saline solution. However, the concentration of lysozyme decreased with the increase in the concentration of saline solution. Futhermore, hypertonic saline solution (6%) decreased the air-space volume significantly. CONCLUSION: The saline solution induces mucin secretion but not lysozyme secretion in patients with chronic rhinosinusitis. These changes in the secretion pattern may change the physical properties of mucus. The hypertonic saline solution may increase the edema of nasal cavity and decrease air-space vol

Clinical Review of Chronic Otitis Media in Patients with Contracted Mastoid / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: High resolution computed tomography (HRCT) helps locating the anatomical structure within the temporal bone preoperatively. Contracted mastoid has lots of changed anatomical structure and outside in technique tympanomastoidectomy procedure cannot provide safe and effective access. The aims of this study are to analyze changed anatomical structure and to suggest safer and more effective surgical procedures in chronic otitis media patients with contracted mastoid. SUBJECTS AND METHOD: We measured distances between important surgical landmarks and cross sectional area of pneumatized air cells in contracted mastoid, and compared with normal groups. We analyzed postoperative complications between outside in technique and inside out technique tympanomastoidectomy. RESULTS: The shortest distance between the posterior wall of external auditory canal and the anterior edge of the sigmoid sinus, the vertical shortest distance between the superior wall of external auditory canal and the tegmen, and the cross-sectional area of mastoid air cells were significantly small in contracted mastoid group (p<0.05). There were 2 cases of postoperative facial weakness by outside in technique tympanomastoidectomy. CONCLUSION: Contracted mastoid has lots of changed anatomical structure. We suggest that inside out technique tympanomastoidectomy procedure is safer and more effective in patients with contracted mastoid.

Effects of the Body Position Changes on Upper Airway Caliber in Obstructive Sleep Apnea during Sleep / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea (OSA) is the intermittent cessation of breathing during sleep due to the collapse of the pharyngeal airway. Pharyngeal collapsibility and oropharyngeal caliber are affected by the respiratory cycle and the body position. Several methods have been used to evaluate the states of upper airway in patients with OSA according to body positions during wakefulness, but there were no reports about the upper airway states according to body positions during sleep. The aim of this study is to evaluate the states of upper airway in patients with OSA according to body position changes during sleep. MATERIALS AND METHOD: Using a multi detector CT, we studied 10 patients with OSA. Each patient was scanned at supine position during the awake state and then induced to sleep using Midazolam. According to body positions (supine, decubitus, and prone), images were acquired during sleep state. The following 4 transverse levels were obtained to evaluate the minimal cross sectional area, collapsibility index, and airway volume: 1) high retropalate level, 2) low retropalate level, 3) high retroglossal level, 4) low retroglossal level. RESULTS: During sleep, the upper airway cross sectional area was decreased and the airway wall collapsibility was increased. Cross sectional area and airway volume were larger at prone and decubitus positions than supine position. Airway wall collapsibility index was lower at prone and decubitus positions than at the supine position. CONCLUSION: In this study, we confirm that the upper airway collapsibility decreases and the airway caliber increases according to body position changes (prone, decubitus) during sleep. Furthermore, the decubitus position is better than the prone position for improving upper airway patency during sleep.

Two Cases of Cerebral Aspergillosis Originated from Sphenoid Sinus / 대한이비인후과학회지

Sphenoid aspergillosis is unusual and more aggressive than other paranasal aspergillosis. Intacranial extension of sphenoid aspergillosis may occur via direct spread of invasive disease or along communicating veins despite intact sinus walls. This tends to occur in immunocompromised patients and once this occurs, mortality is high. Recently, itraconazole, a triazole derivatives with a broad antifungal spectrum, is used instead of conventional antifungal agent. We experienced two cases of cerebral aspergillosis, both of which originated from the sphenoid sinus. Of these cases, one resulted in complete resolution through therapy with high dose itraconazole after endoscorpic sinus surgery but the other one case failed to keep up with the high dose itraconazole therapy and was lost in follow-up because of side effects of drug. So, we report the important role and side effects of high dose itraconazole against cerebral aspergillosis with a review of the literature.

A Case of Primary Hepatocellular Carcinoma with Metastasis to The Spinal Cord / 대한간학회지

Hepatocellular carcinoma is one of the most common malignancies reported in Korean adult males. Hepatocellular carcinoma usually spreads to regional lymph nodes around porta hepatis via lymphatics and to distant metastasis via hematogenous spread. The lung is most common distant metastatic site, followed by the adrenal glands, local lymph nodes and bones. But metastasis to the spinal cord of hepatocellular carcinoma is very rare. Recently we experienced a patient with hepatocellular carcinoma who had suffered from lower leg weakness for 10 days. The patient was proved to have hepatocellular carcinoma with metastasis to the spinal cord. MRI showed an ovoid intracordal mass between the twelfth thoracic and first lumbar vertebra level. After emergency irradiation, the patient could recover.

The Correlation Between The Histologic Activity and Fibrosis and The Distribution of Intrahepatic HBsAg and HBcAg in Patients With Chronic Hepatitis B / 대한간학회지

BACKGROUND/AIMS: The purpose of this study was to assess the correlation between histologic activity and fibrosis and the distribution of intrahepatic hepatitis B core antigen (HBcAg) and surface antigen (HBsAg) in patients with chronic hepatitis B. METHODS: 141 patients (M:F=141:27) with biopsy-proven chronic hepatitis B, abnormal liver function, and a positive HBV viral marker (serum HBeAg, serum HBV DNA) were enrolled. RESULTS: HBcAg was expressed in 96 of 141 patients (68.1%), nHBcAg in 23 (16.3%), cHBcAg in 58 (41.2%), and n-cHBcAg in 15 (10.6%). In the cases of HBsAg, 114 of 141 patients (80.9%) were expressed as cHBsAg, 2 (1.4%) as mHBsAg, and 16 (11.3%) as m-cHBsAg. The presence of intrahepatic HBcAg and HBsAg according to Gudat's classification was not correlated with activity and fibrosis. But the groups with nuclear expression of HBcAg revealed less inflammatory activity (grade, p=0.003), and less fibrotic stage (p = 0.002) than with cytoplasmic or no expression of HBcAg. HBsAg was not. CONCLUSIONS: These observations suggest that inflammatory activity and fibrosis of chronic hepatitis B are related to the presence of HBcAg in hepatocytes and the expression of HBcAg. This is a very important finding in hepatocytolysis.

Insertion of Urethral Wallstent (MemothermR) at External Urethral Sphincter for the Treatment of Patients with Complicated Detrusor Sphincter Dyssynergia / 대한비뇨기과학회지

In patients with spinal cord injury, detrusor sphincter dyssynergia is a common and troublesome problem that may evoke progressive deterioration of upper urinary tract and urinary tract infection including sepsis. Instead of external sphincterotomy, urethral wallstent may be the useful treatment for the patients with detrusor sphincter dyssynergia refractory to conventional treatment. In addition, this method has some advantages of less invassive, less morbid and simpler technique than other treatment methods. We report our preliminary results of the urethral wallstent(MemothermR) for the treatment of 2 patients with complicated detrusor sphincter dyssynergia.

Early Urethroscopic Realignment of Ruptured Bulbous Urethra / 대한비뇨기과학회지

PURPOSE: To evaluate the efficacy of early urethroscopic realignment compared to initial suprapubic cystostomy in the management of bulbous urethral rupture caused by straddle injury. MATERIALS AND METHODS: From May 1995 to June 1996, early urethroscopic realignment was attempted on 16 consecutive patients with bulbous urethral rupture caused by straddle injury. These results were compared with those of 10 consecutive such patients who were managed initially with suprapubic cystostomy between July 1994 and April 1995. RESULTS: Thirteen of the 16 patients(81%), including 1 with a complete rupture, had successful early urethroscopic realignment of the urethra and catheter placement. Ten of these 13 patients(77%), including 9 of 12 partial ruptures and 1 of 1 complete rupture, did not develop stricture after catheter removal. Of the 6 patients with partial rupture who were managed with initial suprapubic cystostomy, 2(33%) had no secondary stricture. All 4 patients with complete rupture managed with initial suprapubic cystostomy alone had resulting stricture. CONCLUSIONS: Early urethroscopic realignment of the ruptured urethra is a simple, safe, rapid, and nontraumatic technique that can be done with sedation and intraurethral topical anesthesia, It reduces the incidence of secondary urethral stricture compared with initial suprapubic cystostomy alone. Therefore, it could be a valuable alternative in the management of bulbous urethral rupture caused by straddle injury.

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Spontaneously Ruptured Congenital Arteriovenous Malformation of Kidney with Renal Artery Aneurysm / 대한비뇨기과학회지

Arteriovenous malformations of the kidney with renal artery aneurysm are rare. Rupture of an congenital arteriovenous malformation in the kidney has been reported only in 4 cases and all cases were accompanied with pregnancy. We present a case of spontaneously ruptured congenital arteriovenous malformation of the kidney with renal artery aneurysm in a 39-year-old man with literature review.

Strangulation of the Penis by Metal Ring / 대한비뇨기과학회지

Strangulation developed after applying constricting objects around the penis is occasionally encountered in the emergency room. As this kind of strangulation can result in penile gangrene or urethral injury, removal of constricting objects should be urgent and presents a great challenge to the physician. We report a case of urinary retention and sepsis due to penile strangulation by metal ring in a 68-year-old man and review the literature.

Urinary Ascites with Urinoma Secondary to Ureteropelvic Junction Obstruction in an Infant: A Case Report / 대한비뇨기과학회지

Spontaneous intraperitoneal extravasation of urine is rare. Urinary ascites occurs mostly in patients with the common primary obstructive lesion being posterior urethral valves. The second most common cause of urinary ascites is hydronephrosis due to congenital ureteropelvic junction obstruction. We report a case of urinary ascites with urinoma resulting from a ureteropelvic junction obstruction in an infant.