[Show abstract][Hide abstract] ABSTRACT: Serine protease inhibitors are involved in immune development, anti-inflammatory mechanisms, and tissue repair. In the present study, the serine protease inhibitor 4-(2-aminoethyl) benzene sulfonyl fluoride hydrochloride (AEBSF) was evaluated for its prophylactic and therapeutic applications in a mouse model of allergic rhinitis (AR).
[Show abstract][Hide abstract] ABSTRACT: A nasoseptal flap is used to reconstruct defects in the skull base when cerebrospinal fluid (CSF) leaks after the endoscopic endonasal transsphenoidal approach (EETSA). We evaluated the usefulness of elevating bilateral nasoseptal flaps with the EETSA. Sixty-seven patients (71 procedures, including 4 revisions) underwent the EETSA with bilateral nasoseptal flap elevation. We retrospectively reviewed patients' medical records, including demographic data, surgical procedures, outcomes, and complications. The entire sellar floor was exposed after elevating bilateral nasoseptal flaps. We reconstructed the defect using a right nasoseptal flap in 14 cases with intraoperative CSF leakage. The denuded sphenoidal sinus was covered with a left nasoseptal flap in 13 cases with excessive loss of sphenoidal sinus mucosa. Unused flaps (57 right flaps and 58 left flaps) were repositioned in the original sites. No postoperative CSF leak occurred. All sphenoidal sinuses covered with the left nasoseptal flap healed well without excessive crust. Two patients experienced immediate postoperative bleeding. Septal perforation occurred in 1 patient who underwent a revision operation. Bilateral nasoseptal flap elevation provided good exposure of the sellar floor with the EETSA. The nasoseptal flap could be used to reconstruct the defect after the EETSA and to cover the denuded sphenoidal sinus. The unused flaps could be repositioned in their original sites to minimize the septal defect and could be reused in revision surgery. We suggest that elevating bilateral nasoseptal flaps is a useful surgical technique in a variety of settings with the EETSA.
The Journal of craniofacial surgery 09/2013; 24(5):1569-72. · 0.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES/HYPOTHESIS: For a wide exposure of skull base and preservation of septal mucosa, we have raised bilateral modified nasoseptal rescue flaps in the endoscopic endonasal transsphenoidal approach (EETSA) and evaluated the usefulness of these flaps elevation. STUDY DESIGN: Case series. METHODS: The study population comprised the patients who underwent EETSA with bilateral modified nasoseptal rescue flaps elevation between February 2009 and June 2012. We retrospectively reviewed patients' medical records. Patients underwent preoperative nasal evaluation using the Nasal Obstruction Symptom Evaluation (NOSE), Sino-Nasal Outcome Test (SNOT-20), and a visual analogue scale (VAS) to assess several nasal symptoms. Repeat testing was performed 6 months postoperatively. RESULTS: A total of 92 patients underwent the EETSA with bilateral modified nasoseptal rescue flaps elevation. A total of 17 patients had intraoperative cerebrospinal fluid (CSF) leakage. Three patients underwent extension of the modified nasoseptal rescue flap to a conventional nasoseptal flap. No patients underwent reoperation due to CSF leakage. There was no statistical difference between preoperative and postoperative total SNOT-20 and NOSE scores. According to the VAS, subjective olfaction function statistically worsened (P = 0.011) postoperatively. CONCLUSION: Bilateral modified nasoseptal rescue flaps elevation provided good exposure of the sellar floor, preserved the septal branch of sphenopalatine artery, and facilitated removal of sellar tumors. We could also preserve more septal mucosa by designing a novel incision and repositioning unused flaps to their original sites. Postoperative complications of the nasal cavity were thus minimized. We believe that this flap is very useful in a variety of settings during the EETSA. LEVEL OF EVIDENCE: 4. Laryngoscope, 2013.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES/HYPOTHESIS: Pneumococcal vaccines have been widely used, and Streptococcus pneumoniae has been suggested to be an effective therapeutic agent in allergic disease. OBJECTIVES: The present study was performed to evaluate the effects of pneumococcal polysaccharide vaccine (PV) and pneumococcal protein conjugate vaccine (PCV), and to examine differences between the vaccines in a murine model of allergic rhinitis. STUDY DESIGN: In vivo study using an animal model. SETTING: Catholic Research Institutes of Medical Science. METHODS: Allergic rhinitis was induced in 40 BALB/c mice by intraperitoneal sensitization and intranasal challenge with Dermatophagoides farinae (Derf). The animals were divided into four groups: control, Derf, PV, and PCV. Interferon-γ, interleukin-13, and interleukin-10 levels in nasal lavage fluid and Derf-specific immunoglobulin E levels in serum were measured. The levels of T-bet, GATA-3, and Foxp3 mRNA expression in splenic mononuclear cells were determined. The number of CD4(+) CD25(+) Foxp3(+) regulatory T cells in splenic mononuclear cells was compared between groups by flow cytometry. RESULTS: Allergic symptom scores, T-bet and GATA-3 mRNA levels, serum Derf-specific immunoglobulin E levels, and tissue eosinophil counts were lower in the PV and PCV groups than the Derf group (P < 0.05). The regulatory T (Treg) cell indicators, Foxp3 mRNA, and percentages of CD4(+) CD25(+) Foxp3(+) T cells were increased in the PV and PCV groups (P < 0.05). CONCLUSION AND CLINICAL RELEVANCE: Both PV and PCV suppressed the allergen-specific T helper 2 response and induced regulatory T cells in a murine model of allergic rhinitis. However, PV and PCV may activate Treg cells via different mechanisms. LEVEL OF EVIDENCE: N/A. Laryngoscope, 2013.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES/HYPOTHESIS: To evaluate the relationship between subjective symptoms of nasal obstruction and the corresponding nasal anatomical parameters using paranasal computed tomography (PNS CT). STUDY DESIGN: Retrospective chart review at a tertiary referral center. METHODS: We studied 277 patients who underwent evaluation by the Nasal Obstruction Symptom Evaluation scale and a visual analogue scale of nasal obstruction for preoperative evaluation; 197 patients with nasal obstruction who underwent septoplasty were enrolled in the study group, and 80 patients without nasal septal deviation and without nasal obstruction who underwent a trans-sphenoidal pituitary tumor operation were enrolled in the control group. A preoperative coronal CT image was used to calculate both nasal cavity cross-sectional areas and the septal deviation angle at the three levels (internal nasal valve, ostiomeatal unit [OMU], and choana). RESULTS: Differences between the study group and the control group were found in all nasal anatomical parameters at the internal nasal valve, OMU, and choana. In the study group, subjective nasal obstruction symptoms were correlated with the septal deviation angle and the nasal cavity cross-sectional area at the OMU and the choana levels. However, there was no correlation between subjective symptoms of nasal obstruction and anatomical factors at the nasal valve level (P < .05). CONCLUSIONS: Coronal PNS CT revealed a relationship between subjective nasal obstructive symptoms and anatomical factors at the middle and posterior nasal levels, especially in patients complaining of stuffy nose. When septoplasty is performed, we must pay attention to correction of middle and posterior nasal septal deviation. LEVEL OF EVIDENCE: 3.
[Show abstract][Hide abstract] ABSTRACT: Objectives
This study aimed to determine if pneumococcal polysaccharide vaccine (PPV) could suppress allergic inflammation in an allergic rhinitis mouse model and to explore whether differences exist regarding the effect of PPV according to timing of administration.Study DesignIn vivo study using an animal model.SettingCatholic Research Institutes of Medical Science.Subjects and MethodsBALB/c mice were divided into control, Der f, Pre-S, and Post-S groups. The allergen was Dermatophagoides farinae (Der f). Pneumococcal polysaccharide vaccine was administered before (Pre-S) or after (Post-S) sensitization. Allergic symptoms and eosinophils in nasal mucosa, interferon-γ, interleukin (IL)-13, and IL-10 in nasal lavage fluid and serum Der f-specific IgE were measured. T-bet, GATA-3, and Foxp3 mRNA in spleen were determined by real-time polymerase chain reaction. Flow cytometry of CD4(+)CD25(+)Foxp3(+) T cells in spleen was analyzed.ResultsIn the Pre-S group, symptom score, serum Der f-specific IgE, eosinophils, IL-13, and GATA-3 mRNA were decreased (P < .05), and IL-10, Foxp3 mRNA, and CD4(+)CD25(+)Foxp3(+) T cells were increased compared with those in Der f group (P < .05). In the Post-S group, symptom score, serum Der f-specific IgE, and GATA-3 mRNA were decreased (P < .05), and Foxp3 mRNA and CD4(+)CD25(+)Foxp3(+) T cells were increased compared with those in the Der f group (P < .05).Conclusion
These results suggest that PPV administered before or after sensitization suppresses Th2 response and enhanced induction of regulatory T cells in an allergic rhinitis model. In addition, there was no significant difference between the degrees of effects in these 2 conditions. In the future, we can consider PPV to be a preventative agent for allergic rhinitis.
Otolaryngology Head and Neck Surgery 01/2013; · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oral tolerance (OT) is considered as a preventive and therapeutic strategy for treating asthma and allergic rhinitis (AR). We investigated the preventive effects of OT on allergic inflammation and remodeling in the upper and lower airways in a mouse model of allergy.
BALB/c mice were divided into four groups: control, allergy, low-dose OT, and high-dose OT. To induce OT, mice were fed ovalbumin (OVA) before sensitization with OVA/Al(OH)(3) at a dose of 1 mg for 6 days in low-dose OT group and a single dose of 25 mg in high-dose OT group. After sensitization followed by OVA challenge, nasal symptoms, interleukin (IL)-13, interferon (IFN)-gamma, IL-10, and transforming growth factor (TGF) beta-1 levels in nasal lavage (NAL) and bronchoalveolar lavage (BAL) fluids were measured, and OVA-specific IgE, IgG1, and IgG2a levels were measured in the serum. The airway hyperresponsiveness (AHR) was measured by enhanced pause. The goblet cell hyperplasia and the thickness of lamina propria were observed in the upper and lower airways.
In the allergy group, the allergic behavior scores, AHR, and OVA-specific IgE, IgG1, and IgG2a levels; inflammatory cells; IFN-gamma levels; and IL-13 levels in NAL/BAL fluids were elevated compared with the control group, low-dose OT group, and high-dose OT group. The allergy group had higher levels of IL-10 and TGF-beta-1 in BAL fluids when compared with the other groups. The goblet cell hyperplasia and the thickness of the lamina propria were attenuated in both OT groups compared with the allergy group.
OT may effectively prevent AHR, allergic inflammation, and airway remodeling in the upper and lower airways.
American Journal of Rhinology and Allergy 01/2013; 27(1):11-6.
[Show abstract][Hide abstract] ABSTRACT: Objectives
The purpose of the present study was to investigate the effect of nucleotide-binding oligomerization domain 1 (NOD1), an innate immune sensor, on allergic inflammation and induction of regulatory T cells in a mouse model of allergic rhinitis. We also aimed to explore whether there were differences in the effect of NOD1 ligand according to the timing of administration.Study DesignAn in vivo study using an animal model.SettingCatholic Research Institutes of Medical Science.Subjects and Methods
Forty BALB/c mice were divided into 4 groups: control, OVA, pre-NOD1, and post-NOD1. Ovalbumin (OVA) was used for sensitization and challenge. The pre-NOD1 group received NOD1 ligand intranasally before sensitization, whereas the post-NOD1 group received it after sensitization. The effects of allergic inflammation and regulatory T cells were compared among the groups.ResultsIn the post-NOD1 group, serum OVA-specific IgE, eosinophil counts, interleukin (IL)-13 levels, and GATA-3 mRNA expression were significantly increased and Foxp3(+) mRNA expression and CD4(+) Foxp3(+) T cells were decreased compared with the OVA group. In the pre-NOD1 group, Foxp3 mRNA expression and CD4(+) Foxp3(+) T cells were significantly decreased compared with the OVA group. Although not significant, the pre-NOD1 group showed increases in serum OVA-specific IgE, eosinophil counts, IL-13 levels, and GATA-3 mRNA expression compared with the OVA group.Conclusion
The innate immune response through NOD1 enhances allergen-specific Th2 response and suppresses induction of regulatory T cells in a mouse model of allergic rhinitis, and the effects are different depending on the timing of exposure to NOD1 ligand.
Otolaryngology Head and Neck Surgery 10/2012; · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the volumetric relationship between the mastoid air cell (MAC) and paranasal sinus (PNS) in the pediatric population using three-dimensional reconstruction and the analysis technique of CT.
Retrospective cross-sectional study was conducted at a university-based, secondary referral hospital.
PNS CT imaging data of 62 children (40 boys and 22 girls; mean age=13.4±4.0 years) was reconstructed to the three-dimensional model with the surface-rendering algorithm (lower threshold of -1024HU and upper threshold of -318HU), and subsequently measuring the volume of the three PNSs (frontal, maxillary and sphenoid) and MAC. Hierarchical linear regression analysis was used to control the effect of age.
Controlling the effect of age, no significant linear regression relationship was found between the volume of MAC and PNSs. It was observed that PNSs and MAC showed a significant linear relationship with age. The regression slopes of PNSs were larger than that of MAC, especially the growth of maxillary and sphenoid sinuses was faster and larger than that of the frontal sinus and MAC. As the coefficient of determination was extremely small, the aging process itself could not effectively explain the volume variation of PNSs and MAC.
No interaction was observed in the pneumatization of the three PNSs (frontal, maxillary, and sphenoid) and MAC. It was found that the growths of PNSs and MAC are influenced by age. Further, maxillary and sphenoid sinuses tend to grow faster and become larger than the frontal sinus and mastoid air cell system. Thus, it is verified that environmental factors could be involved in the postnatal pneumatization process of the PNSs and MAC, which might influence MAC to a greater extent than the PNSs.
International journal of pediatric otorhinolaryngology 08/2012; 76(11):1642-6. · 0.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The management of allergic rhinitis (AR) encompasses education, pharmacotherapy, immunotherapy, and surgery. FK506 (tacrolimus) is an immunosuppressant that inhibits allergic reactions. The purpose of this study was to reveal whether FK506 treatment reduces allergic inflammation in an AR mouse model and to elucidate the mechanisms.
Forty mice were divided into four groups: control, AR, FK (FK506), and dexamethasone (DEX). All mice except for the control group were sensitized by an i.p. injection of ovalbumin (OVA). After sensitization, the FK and DEX groups were treated with FK506 and DEX intranasally. All sensitized mice were challenged intranasally with OVA. Allergic symptoms and tissue eosinophil counts were recorded. Interleukin (IL)-5, interferon gamma, and IL-10 levels in nasal lavage fluid (NALF) and serum OVA-specific IgE levels were measured. T-bet, GATA-3, and Foxp3 mRNA expression in splenic mononuclear cells were determined by real-time polymerase chain reaction.
In the FK group and DEX group, allergic symptoms, serum OVA-specific IgE, tissue eosinophil counts, IL-5 in NALF, and GATA-3 mRNAs expression decreased (p < 0.05), and IL-10 in NALF and Foxp3 mRNAs expression increased compared with the AR group (p < 0.05). No significant difference was observed between the FK group and the DEX group.
These results suggest that topical FK506 may reduce allergic inflammation and have potency equal to DEX in the AR model. This mechanism may involve not only Th2 cells but also regulatory T cells. Additional studies are needed on FK506, but in the future, we can consider FK506 as an alternative to topical steroids in the treatment of AR.
American Journal of Rhinology and Allergy 03/2012; 26(2):e71-5.
[Show abstract][Hide abstract] ABSTRACT: The Onodi cell is the posterior-most ethmoid air cell and an important anatomical variant because of the intimate spatial relationship with the optic nerve, internal carotid artery, and sellar floor during sphenoid sinus surgery. The authors evaluated the incidence of Onodi cells, their clinical importance, and the association between preoperative radiological findings and surgical findings.
Case series with chart review.
Tertiary care medical center.
The authors retrospectively reviewed the medical records of 162 cases, including preoperative paranasal sinus computed tomography (PNS CT) findings and the findings with the endoscopic endonasal transsphenoidal approach (EETSA). They evaluated the prevalence of Onodi cells and the clinical manifestations in the patients with these cells. They also examined the clinical significance of these cells during EETSA.
Onodi cells were identified in the preoperative PNS CT of 53 patients, whereas Onodi cells were observed in 54 (33.3%) of the 162 patients at EETSA. The Onodi cells were bilateral in 23 patients and unilateral in 31. In all cases, the Onodi cells limited the exposure of the sellar floor. Only after removing these cells was the entire sellar floor exposed so that the tumors could be removed completely.
Onodi cells were observed more frequently than in previous studies, and 98.1% of them were identified on preoperative PNS CT. When reviewing PNS CT images preoperatively, one needs to identify the presence of Onodi cells. The Onodi cells must be removed to completely resect tumors located in the sellar region during EETSA.
Otolaryngology Head and Neck Surgery 08/2011; 145(6):1040-2. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this pilot study was to investigate the effects of HR2 on allergen-specific immunotherapy in a mouse model of allergic rhinitis.
An in vivo study using an animal model.
Catholic Research Institutes of Medical Science.
Fifty mice were divided into 5 groups: control, allergic rhinitis (AR), immunotherapy (IT), immunotherapy with HR2 agonist (HI), and immunotherapy with HR2 antagonist (HB). All mice except for the control group were sensitized with ovalbumin (OVA). After 1 week, mice in the IT, HI, and HB groups underwent immunotherapy by intradermal injections of OVA. During immunotherapy, the HI group was injected with HR2 agonist, whereas the HB group was injected with HR2 antagonist. All sensitized mice were challenged with intranasal OVA. After the final challenge, allergic behavior was evaluated. Interleukin (IL)-13, interferon-γ, IL-10, and transforming growth factor (TGF)-β levels in nasal lavage fluid (NALF), as well as OVA-specific IgE levels in serum, were measured. The number of eosinophils in lamina propria was evaluated.
The levels of serum OVA-specific IgE and IL-13 in NALF were significantly increased in the HB group compared with the IT group (P < .05). Also, the tissue eosinophil counts were higher in the HB group than in the IT group (P < .05).
HR2 antagonist impaired OVA-specific immunotherapy in mice. Although confirmation of this preliminary result is needed, these findings suggest that HR2 receptors may have inhibitory effects on immune tolerance. The authors suggest that application of this property could enhance the efficiency of allergen-specific immunotherapy.
Otolaryngology Head and Neck Surgery 04/2011; 144(4):500-5. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Induction of oral tolerance (OT) is known to prevent allergic inflammation in models of asthma. This study investigated the preventive effect of OT and airway remodeling in a mouse model of allergic rhinitis (AR).
An in vivo study using an animal model.
Catholic Research Institutes of Medical Science.
Forty six-week-old, female BALB/c mice were divided into four groups: control, AR, low-dose OT, and high-dose OT. To induce OT, mice were fed ovalbumin (OVA) before sensitization with OVA/aluminum hydroxide, 1 mg for six days in the low-dose OT group and a 25 mg single dose in the high-dose OT group. Mice in the AR group were fed phosphate-buffered saline. After sensitization followed by challenges with OVA during six weeks, nasal behaviors, interleukin (IL)-13 and interferon gamma (IFN-gamma) levels in nasal lavage (NAL) fluids, as well as OVA-specific IgE levels in serum, were measured. The degree of goblet cell hyperplasia and thickness of lamina propria were observed in nasal tissues by periodic acid-Schiff and Masson's trichrome stain. A P value < 0.05 was accepted as statistically significant.
Both OT groups showed a significant decrease in inflammatory cells, IL-13 and IFN-gamma in NAL fluids, as well as OVA-specific IgE levels in serum compared with the AR group. In addition, the degree of goblet cell hyperplasia and thickness of lamina propria were attenuated in both OT groups compared with the AR group. Further, these alterations did not differ significantly between the two OT groups.
These results suggest that OT may effectively reduce allergic inflammation as well as airway remodeling in a mouse model of AR.
Otolaryngology Head and Neck Surgery 03/2010; 142(3):370-5. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We conducted a retrospective study to evaluate outcomes in patients with a craniopharyngioma who were managed via a transnasal transsphenoidal approach. Craniopharyngiomas exhibit histologically benign but "clinically malignant" features. Our study group was made up of 5 patients who underwent a total of 6 operations. The study population included 1 female and 5 males, aged 14 to 50 years (mean: 29.2). The overall rate of near-total tumor removal was 67%, but all patients eventually experienced a recurrence. Revision surgery to correct any severe postoperative complications was not required in any case. We found that the endoscopic transnasal transsphenoidal approach could be a safe and less invasive surgical option for the removal of craniopharyngiomas, although we were unable to remove all tumor or prevent recurrences.