Clinical characteristics of persistent postural-perceptual dizziness and its visual subtype in Korean patients: A multicenter cross-sectional study.

OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. METHODS: Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. RESULTS: Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space-motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. CONCLUSION: This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.

A Rat Model for Oral Mucositis Induced by a Single Administration of 5-Fluorouracil.

BACKGROUND/AIM: This study aimed to develop a reliable chemotherapy-induced oral mucositis (CIOM) rat model by intraperitoneally administering a single dosage of 5-fluorouracil (5-FU) combined with a chemical stimulus. MATERIALS AND METHODS: The 5-FU dosage for CIOM development was determined by the survival rate of rats administrated 160 mg/kg, 200 mg/kg, and 240 mg/kg of 5-FU. Thirty rats were assigned to normal control (NC) and three experimental groups: i) ulcer formation without 5-FU administration (PBS/U+), ii) 5-FU administration without ulcer formation (5-FU/U-), and iii) ulcer formation after 5-FU administration (5-FU/U+). White blood cell count and weight were measured at the day of 5-FU administration (D0), ulcer formation (D2), and two days after ulcer formation (D4). The oral mucosa for histologic evaluations was obtained two (D4) and five days (D7) after ulcer formation. RESULTS: The 5-FU dosage for CIOM development was 200 mg/kg. White blood cell count (WBC) counts and weight of rats were significantly lower in 5-FU/U- (WBC, p<0.001; weight, p=0.002) and 5-FU/U+ (WBC, p<0.001; weight, p<0.001) groups compared to those in the NC group at D4. The number of Ki-67 positive cells in the oral epithelium was lower in 5-FU/U+ group compared to that in NC (p<0.001) and PBS/U+ (p=0.047) groups at D7. CONCLUSION: Single administration of 200 mg/kg of 5-FU combined with a chemical stimulus can lead to an immune-suppressive status, failure of weight gain, and impairment of epithelium regeneration as observed in a CIOM rat model.

Changes in the Laryngeal Mucosa After Thyroid Surgery: A Rat Model.

BACKGROUND/AIM: Thyroidectomy can cause various airway symptoms affecting the quality of life. We investigated the changes in extracellular matrix (ECM) composition and markers for inflammation and microcirculation of laryngeal mucosa. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were categorized into control and three surgical groups based on the extent of surgeries, 1) flap elevation (FE) group, 2) thyroid and trachea exposure (TE) group, and 3) thyroid isthmectomy (TI) group. We analyzed the expression of TGF-ß1, VEGFR-3, CD31, and MMP- 9 in relation to the inflammatory and microcirculatory changes in the lamina propria on postoperative days (PODs) 3, 7, and 21. ECM composition of hyaluronic acid (HA) and collagen in the subglottic area (SA) was also evaluated. RESULTS: All parameters increased in surgical groups at each postoperative phase except collagen deposition. On POD 3, TGF-ß1 expression and SA increased in relation to the surgical extent and decreased over time, but more than the control in all surgical groups on POD 21. Surgical groups had more HA and less collagen composition, causing a higher HA to collagen ratio in relation to the surgical extent. VEGFR-3 and CD31 expression increased with time at all postoperative phases according to the surgical extent. Expression of MMP-9 increased in TI groups compared to TE and FE groups on POD 7 and POD 21. CONCLUSION: This study demonstrated that thyroid surgery exposing the thyroid and trachea induces an increase in the SA with a higher HA and lesser collagen composition. Furthermore, the markers for acute inflammation and microcirculation with tissue remodeling increased in the laryngeal mucosa.

Restoration of Homeostasis in the Tracheal Mucosa After Thyroid Surgery in a Rat Model.

BACKGROUND/AIM: This study aimed to investigate the process of homeostatic restoration in the tracheal mucosa (TM) after thyroid surgery. MATERIALS AND METHODS: Fifty-four rats were divided into normal controls (NC) and three experimental groups: (i) flap elevation (FE), (ii) thyroid exposure (TE), and (iii) thyroid isthmusectomy (TI). Expression of mRNA and proteins of key factors regulating homeostasis were evaluated in the TM obtained 3, 7, and 21 days after thyroid surgery. RESULTS: Increased mRNA expression of transforming growth factor-ß1 (TGF-ß1), hypoxia-inducible factor-1α (HIF-1α), and matrix metalloproteinase-9 (MMP-9) were observed 21 days after thyroid surgery in all experimental groups compared to that of NC group. CONCLUSION: Thyroid surgery leads to an actual increase of TGF-ß1, HIF-1α, and MMP-9 expression in the TM. This increased expression of key regulators of homeostatic restoration in the TM lasts for a considerable period of time after surgery, especially if the extent of surgery increased.

Effects of allergic rhinitis on the progression and recovery of acute otitis media in a mouse model.

OBJECTIVES: The objective of this study was to evaluate the effects of allergic rhinitis (AR) on the development, progression, and recovery of acute otitis media (OM) in an animal model and investigate the secondary effects of bacterial infection. METHODS: BALB/c mice were divided into four groups: AR + OM, AR, OM, and control groups. AR + OM and AR groups were sensitized with ovalbumin (OVA) and alum and then challenged intranasally with OVA. Phosphate-buffered saline (PBS) was administered to the OM and control groups the same number of times. After AR induction, OM was induced by surgical inoculation of non-typeable Haemophilus influenza (NTHi) into the middle ear (ME) cavity of the mice in the AR + OM and OM groups. PBS was injected into the bulla in the AR and control groups. Each group was subdivided into sets of six mice, one for each of the four time points (0, 2, 7, and 10 days post-bacterial inoculation), at which point the mice were euthanized and ME and nasal cavity mucosa were obtained and evaluated. The occurrence of OM and the ME mucosa thickness were evaluated and compared among the four groups. Tissue expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in infected ME mucosa was assessed by immunohistochemical staining. We also investigated IgE, IL-4, and IL-5 in the nasal mucosa. RESULTS: Most of the ears showed OM on post-inoculation day 2 in both AR + OM and OM groups. In the AR + OM group, 58.3% of ears still had OM on post-inoculation day 10, while only 16.7% of the OM group had OM. The ME mucosa of all groups increased, and the AR + OM group exhibited the thickest mucosa. The OM group showed peak thickness on post-inoculation day 2 and then decreased, whereas the ME mucosa thickness of the AR + OM group continued to increase to day 7. In the OM group, the expression of IL-1ß, IL-6, and TNF-α in the ME also increased significantly, peaking on post-inoculation day 2, and then gradually decreased. In the AR + OM group, the expression of these proteins increased until day 7 and then decreased. The IgE and Th2 response (IL-4 and IL-5) cytokines were expressed at higher levels in the AR + OM and AR groups than in the OM and control groups. CONCLUSION: The inflammatory reaction to NTHi was more intense and lasted longer in the allergic group, which indicates that AR affects the progression and subsequent recovery of acute bacterial OM.

The Clinical Manifestations and Chest Computed Tomography Findings of Coronavirus Disease 2019 (COVID-19) Patients in China: A Proportion Meta-Analysis.

OBJECTIVES: The objectives of this study were to identify the clinical features and chest computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) patients and to compare the characteristics of patients diagnosed in Wuhan and in other areas of China by integrating the findings reported in previous studies. METHODS: We conducted a proportion meta-analysis to integrate the results of previous studies identified in online databases, and subsequently compared the overlapping of 95% confidence intervals (CIs) between locations of diagnosis. The heterogeneity of the results of the included studies was also demonstrated. RESULTS: Nine studies with level IV evidence were considered to be eligible for the meta-analysis, and a comparative analysis was only possible between patients diagnosed in Wuhan and outside of Wuhan in China. Fever (84.8%; 95% CI, 78.5% to 90.1%) was identified as the most common clinical manifestation in all COVID-19 patients, and signs of respiratory infection were also frequently present in these patients. When comparing the clinical features according to the location of diagnosis, fever and dyspnea were less frequent in patients diagnosed outside of Wuhan (fever: 78.1%; 95% CI, 73.2% to 82.7%; dyspnea: 3.80%; 95% CI, 0.13% to 12.22%) than in patients diagnosed in Wuhan (fever: 91.7%; 95% CI, 88.0% to 94.8%; dyspnea: 21.1%; 95% CI, 13.2% to 30.3%). The chest CT findings exhibited no significant differences between the groups. CONCLUSION: Fever was found to be the most common symptom in COVID-19, and respiratory infection signs were also commonly present. Fever and dyspnea were less frequently observed in the patients diagnosed outside of Wuhan, which should be considered in COVID-19 screening programs. These results may be attributable to the earlier diagnosis of the disease and the younger age of patients outside of Wuhan although further analysis is needed. The role of chest CT in COVID-19 diagnosis is inconclusive based on this study.

Changes in Tracheal Respiratory Mucosa After Thyroidectomy: A Rat Model.

BACKGROUND/AIM: This study aimed to investigate changes in the tracheal mucosa after thyroidectomy, that can be a cause of post-thyroidectomy discomfort. MATERIALS AND METHODS: Forty rats were divided into normal controls and 3 surgical groups: (i) thyroid isthmectomy with cauterization, (ii) isthmectomy by a cold instrument without hemostasis, and (iii) sham (exposure of the trachea and thyroid gland without thyroidectomy by dissection through pretracheal fascia). Animals were euthanized at 1 and 4 weeks. Mucosal edema and glandular hyperplasia were measured. Mucin production and basal cell activities were evaluated by mucin 5AC (MUC5AC) and keratin 5 (KRT5) using immunofluorescence staining. RESULTS: Larger mucosal areas were observed in all surgical groups at 1 and 4 weeks. More submucosal glandular hyperplasia was noted in the group with isthmectomy without hemostasis. MUC5AC and KRT5 expressions were significantly higher in the surgical groups. CONCLUSION: The tracheal mucosa may change after surgery, which could explain postoperative discomfort after thyroidectomy.

Effects of Amniotic Membrane Extract on the Hyperplastic Response of the Middle Ear Mucosa in a Bacterially-Induced Otitis Media Rat Model: A Preliminary Study.

OBJECTIVES: Human amniotic membrane extract (AME) is known to contain numerous bioactive factors and anti-inflammatory substances. However, the anti-inflammatory effects of AME on the middle ear (ME) mucosa are unclear. This study assessed the effects of AME on the growth of the ME mucosa in response to bacterially-induced otitis media (OM). METHODS: OM was induced by inoculating nontypeable Haemophilus influenzae (NTHi) into the ME cavity of rats. ME mucosal explants were cultured in AME concentrations of 0, 5, 10, or 50 µg/mL. The area of explant outgrowth was measured in culture and analyzed at 1, 3, 5, and 7 days after explantation. The expression of Ki-67, mucin 5AC (MUC5AC), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) in the explants was also evaluated using quantitative polymerase chain reaction (PCR) and immunocytochemistry (ICC). RESULTS: The NTHi-induced ME mucosa growth increased gradually over the 7-day culture period in all explants at different AME concentrations. There was a trend for mucosal growth inhibition at higher concentrations of AME, although the growth was not significantly different among the groups until day 5. The ME mucosal explants treated with the 50 µg/mL concentration of AME showed significantly suppressed growth on postexplantation day 7 compared with other explants on the same day. PCR and ICC staining revealed that the expression of Ki-67, MUC5AC, TNF-α, and IL-10 further decreased in the explants with higher concentrations of AME than in those with lower concentrations of AME. CONCLUSION: Our results showed that higher concentrations of AME reduced the mucosal proliferative response in bacterial OM in rats. These findings provide evidence that AME has an influence on the inflammatory and proliferative responses to NTHi infection in ME mucosa.

A comparison of single-dose and multiple divided daily-dose oral steroids for sudden sensorineural hearing loss / Comparação entre dose única e múltiplas doses diárias de corticoides para perda auditiva neurossensorial súbita

Abstract Introduction: Glucocorticoids are considered the first-line therapy for sudden sensorineural hearing loss. But there is currently no consensus on administering them as a single dose versus multiple divided daily doses. Objective: We aim to evaluate the treatment outcome of sudden sensorineural hearing loss between a single-dose and multiple divided daily doses of steroid treatment. Methods: A total of 94 patients who were diagnosed and treated for sudden sensorineural hearing loss and followed up for more than three months were reviewed retrospectively. Patients were divided into single-dose and multiple divided-dose groups, based on their medication regimens. Hearing thresholds were repeatedly measured: on the initial visit and 1 week, 1 month, and 3 months after the initial treatment. Treatment outcomes were analyzed by comparing hearing recovery rates and post-treatment audiometric changes. Results: The hearing threshold was significantly reduced at three months post-treatment in both groups. The hearing recovery rate of the single-dose group was significantly higher than that of the multiple divided-dose groups. Audiometric changes showed no statistical difference either in pure tone threshold or speech discrimination. Conclusion: When oral steroids are indicated for sudden sensorineural hearing loss, both a single dose and multiple divided doses can be effective for treatment and have comparable results. However, the single-dose regimen seems to be more efficacious than the divided-dose regimen.

Resumo Introdução: Os glicocorticoides são considerados terapia de primeira linha para perda auditiva neurossensorial súbita. Contudo, atualmente não há consenso em como para administrá-los, se em dose única ou múltiplas doses diárias. Objetivo: Nosso objetivo é avaliar o resultado do tratamento da perda auditiva neurossensorial súbita com uma dose única ou várias doses diárias de tratamento com esteróides. Método: Um total de 94 pacientes que foram diagnosticados e tratados para perda auditiva neurossensorial súbita e acompanhados por mais de três meses pós-tratamento foram avalia-dos retrospectivamente. Os pacientes foram divididos em grupos de dose única diária e dose diária dividida em múltiplas tomadas, baseado em seu regime medicamentoso. Os limiares auditivos foram medidos repetidamente: na visita inicial e em 1 semana, 1 mês e 3 meses após o tratamento inicial. Os resultados do tratamento foram analisados comparando-se as taxas de recuperação da audição e as alterações audiométricas pós-tratamento. Resultados: O limiar auditivo foi significativamente reduzido aos três meses pós-tratamento em ambos os grupos. A taxa de recuperação auditiva no grupo de dose única foi significativamente maior do que no grupo de dose diária dividida em múltiplas tomadas. As alterações audiométricas não mostraram diferença estatística, tanto no limiar de tom puro quanto na discriminação da fala. Conclusão: Quando esteroides orais são indicados para perda auditiva neurossensorial súbita, tanto uma dose única quanto múltiplas doses podem ser eficazes para o tratamento e têm resultados comparáveis. No entanto, o regime de dose única diária parece ser mais eficaz do que o regime de dose diária dividida em múltiplas tomadas.

A comparison of single-dose and multiple divided daily-dose oral steroids for sudden sensorineural hearing loss.

INTRODUCTION: Glucocorticoids are considered the first-line therapy for sudden sensorineural hearing loss. But there is currently no consensus on administering them as a single dose versus multiple divided daily doses. OBJECTIVE: We aim to evaluate the treatment outcome of sudden sensorineural hearing loss between a single-dose and multiple divided daily doses of steroid treatment. METHODS: A total of 94 patients who were diagnosed and treated for sudden sensorineural hearing loss and followed up for more than three months were reviewed retrospectively. Patients were divided into single-dose and multiple divided-dose groups, based on their medication regimens. Hearing thresholds were repeatedly measured: on the initial visit and 1 week, 1 month, and 3 months after the initial treatment. Treatment outcomes were analyzed by comparing hearing recovery rates and post-treatment audiometric changes. RESULTS: The hearing threshold was significantly reduced at three months post-treatment in both groups. The hearing recovery rate of the single-dose group was significantly higher than that of the multiple divided-dose groups. Audiometric changes showed no statistical difference either in pure tone threshold or speech discrimination. CONCLUSION: When oral steroids are indicated for sudden sensorineural hearing loss, both a single dose and multiple divided doses can be effective for treatment and have comparable results. However, the single-dose regimen seems to be more efficacious than the divided-dose regimen.

Expression of surfactant Protein-A in the Haemophilus influenzae-induced otitis media in a rat model.

The objective of this study was to investigate the expression and the role of surfactant protein A (SP-A) in the middle ear (ME) mucosa in response to bacterial infection in a rat model. Otitis media (OM) was induced by surgical inoculation of non-typeable Haemophilus influenza (NTHi) into the ME cavity of Sprague-Dawley rats. The rats were divided into an NTHi-induced OM group and a phosphate-buffered saline-injected control group. The NTHi-induced OM and control groups were subdivided into sets of 6 rats, one for each of the 6 time points (0, 1, 2, 4, 7, and 14 days post-inoculation), at which point the rats were euthanized after inoculation. The concentrations of SP-A in the ME effusion were determined by an enzyme-linked immunosorbent assay (ELISA). Tissue expression of SP-A, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in infected ME mucosa was assessed by immunohistochemical staining. For mRNA expression quantification, RNA was extracted from the ME mucosa and SP-A expression was monitored and compared between the control and OM groups using quantitative polymerase chain reaction (PCR). Expression of IL-1ß, IL-6, and TNF-α in the ME mucosa was also evaluated. SP-A expression was evaluated in the effusion of pediatric OM patients (70 ears) who received ventilation-tube insertion by ELISA. SP-A was detected in normal rat ME mucosa before bacterial inoculation. SP-A expression was up-regulated in the NTHi-induced OM group (p = 0.046). Immunohistochemical staining revealed increased SP-A expression on post-inoculation day 1, 2, and 4 in the OM group. Expression of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) in the ME also increased significantly on post-inoculation day 1, 2, and 4 in the OM group. It correlated with changes in SP-A expression. Expression of SP-A was also identified in the ME effusion of humans. SP-A exists in the ME of the rat and was up-regulated in the ME of NTHi-induced OM. Expression of IL-1ß, IL-6, and TNF-α was increased in the ME of the bacteria-induced OM in the rat model. The results suggest that SP-A may play a significant role in the early phase of OM induction and subsequent recovery from it.

Influence of Vitamin D Deficiency on Progression of Experimental Otitis Media in Rats.

BACKGROUND: Vitamin D plays an important role in the immune response against infection. The purpose of the present study was to investigate the influence of vitamin D deficiency on the progression of otitis media (OM) using an experimental rat model. METHODS: Four-week-old male Sprague-Dawley rats (n=72) were divided into two groups based on their diet: a control diet group (n=36) and a vitamin D-deficient diet group (n=36). After 8 weeks of diet, experimental OM was induced by inoculation of non-typeable Haemophilus influenzae in the middle ear cavity. The rats were evaluated with otomicroscopy to determine the inflammation in the middle ear mucosa on days 1, 2, 4, 7, and 14 post-inoculation. Bullae from sacrificed rats were collected and analyzed histologically. RESULTS: The middle ear mucosa from rats with vitamin D deficiency showed a significantly higher thickness than that of controls during the course of OM. The maximum mucosal thickness was 56.0±9.1 µm in the vitamin D deficiency group, and 43.9±9.8 µm in the control group, although there was no significant difference in the tympanic membrane score between the two groups evaluated with otomicroscopy. An immunohistochemical study showed increased expression of interleukin 6 (IL-6) and tumor necrosis factor α in rats manifesting vitamin D deficiency and decreased expression of IL-10 compared with controls. CONCLUSION: Our results showed that vitamin D deficiency may exacerbate the pathophysiological changes of OM via altered cytokine production. Therefore, maintaining vitamin D status in the optimal range may be beneficial for proper management of OM.

Effects of excessive fibrin deposit and polylactide adhesion barrier on wound healing in thyroidectomy murine wound model.

BACKGROUND: We hypothesize that excessive fibrin formation and inflammation induced by antiadhesive material, SurgiWrap (SW), would have an adverse effect on wound healing. It was evaluated by a thyroidectomy murine wound model. METHODS: Excessive fibrin formation was induced by isthmectomy without hemostasis. Rats were allocated into isthmectomy with SurgiWrap (I+SW+), I+SW-, I-SW+, I-SW-, and isthmectomy after electrocautery for hemostasis (I+C+SW-). The SWs were placed on the superficial and visceral layers for gross and microscopic evaluation. RESULTS: Microscopic examination showed collagen deposition occurred in the I-SW- sham group and at a higher level in I+C+SW-. The collagen deposition decreased in groups without SW with time but increased in groups with SW. Use of SW produced more inflammation and more collagen deposition. The I+SW + group developed the largest area of collagen deposition at 4 weeks and more collagen deposition than the I-SW + group. CONCLUSION: The SW induced more collagen deposition increasing with time. The collagen deposition produced by SW was worsened by excessive fibrin formation and inflammation.

Abnormalities of Otoacoustic Emissions in Myasthenia Gravis: Association With Serological and Electrophysiological Features.

Objective: To investigate whether otoacoustic emissions (OAEs) are impaired in patients with myasthenia gravis (MG) and whether such dysfunction is associated with serological and electrophysiological features of MG. Methods: We tested 15 patients with MG (30 ears) and 10 healthy age- and sex-matched subjects (20 ears) for transiently evoked OAE (TEOAE) and distortion product OAE (DPOAE). Results: Compared with controls, MG patients revealed a significant reduction in the amplitude of TEOAEs (p < 0.05) and DPOAEs at higher frequencies between 2,026 and 4,053 Hz (p < 0.05). In the subgroup analysis, TEOAE and DPOAE amplitudes were significantly lower in the acetylcholine receptor (AChR) antibody-positive group (p < 0.05) as well as in the repetitive nerve stimulation (RNS)-positive (p < 0.05) group. In particular, the OAE alteration significantly correlated with anti-AChR antibody titers. No significant difference of the OAEs was found between thymomatous and non-thymomatous MG or between purely ocular and generalized MG. Conclusions: Our study confirms that OAEs reveal subclinical dysfunction of the cholinergic neurotransmission of cochlear outer hair cells and correlate well with electrophysiological and serological characteristics of MG patients. Our findings imply that the measurement of OAEs might increase the diagnostic accuracy and help to monitor the severity of MG.

Both canonical and non-canonical NF-κB activation contribute to the proliferative response of the middle ear mucosa during bacterial infection.

A major aspect of pathology in otitis media (OM), the most common childhood bacterial disease, is hyperplasia of the middle ear mucosa. Activation of innate immune receptors during OM leads to the activation of NF-κB, a pleiotropic transcription factor involved both in inflammation and tissue growth. To explore the role of NF-κB in mucosal hyperplasia during OM, we evaluated the expression of genes involved in two modes of NF-κB activation during a complete episode of acute, bacterial OM in mice. We also determined the effects of inhibitors of each pathway on infection-stimulated mucosal growth in vitro. A majority of the genes that mediate both the canonical and the non-canonical pathways of NF-κB activation were regulated during OM, many with kinetics related to the time course of mucosal hyperplasia. Inhibition of either pathway reduced the growth of cultured mucosal explants in a dose-dependent manner. However, inhibition of the canonical pathway produced a greater effect, suggesting that this mode of NF-κB activation dominates mucosal hyperplasia during OM.

Role of group 3 innate lymphoid cells during experimental otitis media in a rat model.

The objective of this study was to evaluate the role of group 3 innate lymphoid cells (ILC3) in the middle ear (ME) mucosal response to bacterial infection in a rat model. To confirm the role of ILC3 in bacterially induced otitis media (OM), the serum concentrations of IL-17 and IL-22 were determined by ELISA, and the tissue expression of IL-17 and IL-22 in infected ME mucosa was assessed by immunohistochemical staining. Immunohistochemical staining of specific cell surface markers was also assessed to confirm the origin of the cells expressing IL-17 and IL-22. Twenty Sprague-Dawley rats were used in the surgically-induced animal model of OM. OM was induced by inoculation of non-typeable Haemophilus influenzae into the ME cavity of the rats. The rats were divided into four experimental groups: three infected groups and one control group. Infected groups were subdivided into sets of 5 rats, one for each of the three time points (1, 4 and 7 days post-inoculation). For determination of rat IL-17 and IL-22 levels in infected rats and control rats, infected or control ME mucosa sections were analyzed by immunohistochemistry with specific antibodies directed against IL-17 and IL-22. Immunohistochemical staining for CD3, RORγt, and NKp46 were also conducted on the samples to confirm the origin of cells expressing IL-17 and IL-22. IL-17 and IL-22 serum concentrations were significantly increased in the infected rats compared to control rats. Immunohistochemical staining revealed increased IL-17 and IL-22 expressions in all infected ME mucosae from the first day after inoculation. In addition, the results of tissue staining for the specific surface markers were negative for CD3 and NKp46, but were highly positive for RORγt. IL-17 and IL-22 revealed their association with the bacterially induced proliferative and hyperplastic responses of ME mucosa, which are characteristic features in pathogenesis of OM. Surface marker examination showed that the source cells for IL-17 and IL-22 seemed to be lymphoid tissue inducer (LTi) cells. The results suggest that LTi cells release IL-17 and IL-22, and play a significant role in both the early phase of OM induction and recovery from it.

Enhanced mucosal healing with curcumin in animal oral ulcer model.

OBJECTIVES/HYPOTHESIS: Oral ulcers are very common and can compromise the quality of life of patients with pain. The objective of this study was to evaluate mucosal healing with curcumin in an animal oral ulcer model. STUDY DESIGN: Experimental study. METHODS: Twenty New Zealand white rabbits were used. Round filter paper 6 mm in diameter was soaked with 15 µl 50% acetic acid and applied over the upper labial gingiva, creating a uniform circular ulcer. After creation of an oral ulcer, curcumin, the active substance in tumeric, was applied twice over the ulcer in the experimental group but not in the control group. The ulcer area was calculated by maximal (D) and minimal (d) diameter : π × D × d/4. All animals were weighed, and the area was measured on days 0, 7, and 14. On days 7 and 14, half of the animals were sacrificed and gingival specimens were acquired. RESULTS: Curcumin treatment exhibited accelerated healing such that the gross appearance of the ulcer demonstrated a recognizable difference in wound healing between the curcumin-treated and control groups with time. Weight loss was observed after the creation of oral ulcer in the control group. However, the curcumin-treated group gained weight with time, resulting in a significant weight difference. On day 14, epithelial regeneration was completed in the treated group but incomplete in the control group. CONCLUSION: Topical application of curcumin enhanced the wound-healing process of oral ulcer in the animal model, which implicate that curcumin can be used as an effective and safe medical tool in the treatment of oral ulcer. LEVEL OF EVIDENCE: NA.

Vocal fold augmentation with injectable polycaprolactone microspheres/pluronic F127 hydrogel: long-term in vivo study for the treatment of glottal insufficiency.

There is increasing demand for reconstruction of glottal insufficiency. Several injection materials have been examined for this purpose, but all had limitations, such as poor long-term durability, migration from the injection site, inflammation, granuloma formation, and interference with vocal fold vibration due to viscoelastic mismatch. Here, we developed a novel injection material, consisting of polycaprolactone (PCL) microspheres, which exhibits better viscoelasticity than conventional materials, and Pluronic F127 carrier, which decreases the migration of the injection materials. The material was injected into rabbits with glottal insufficiency and compared with the FDA-approved injection material, calcium hydroxylapatite (CaHA). Endoscopic and histological examinations indicated that PCL/Pluronic F127 remained at the injection site with no inflammatory response or granuloma formation, whereas CaHA leaked out and migrated from the injection site. Therefore, vocal fold augmentation was almost completely retained during the 12-month follow-up period in this study. Moreover, induced phonation and high-speed recording of vocal fold vibration showed decreased vocal fold gap area in the PCL/Pluronic F127 group. Our newly developed injection material, PCL/Pluronic F127, permits efficient augmentation of paralyzed vocal fold without complications, a concept that can be applied clinically, as demonstrated by the successful long-term follow-up.

Tracheal reconstruction with asymmetrically porous polycaprolactone/pluronic F127 membranes.

BACKGROUND: Congenital and acquired tracheal stenosis continues to be challenging problems. The purpose of this study was to evaluate the efficacy of an asymmetrically porous membrane (APM) to induce tracheal reconstruction by inhibition of granulation tissue growth into the tracheal lumen whereas minimizing graft failure. METHODS: The APM was fabricated with polycaprolactone (PCL) and pluronic F127 to have nano-size pores at top side, whereas the bottom side had micro-size pores. Fifteen rabbits underwent tracheal defect, which was then reconstructed with the APM. Rabbits were euthanized 1, 4, and 12 weeks postoperatively, and endoscopic, histologic, and radiologic evaluations were conducted. RESULTS: Endoscopy did not reveal granulation ingrowth into tracheal lumen. APM was well incorporated into the surrounding tissue on histologic evaluation. CT scans showed well maintained airways. CONCLUSION: Off-the-shelf use of APM for tracheal reconstruction seems to be a promising strategy in the treatment of tracheal defects.

Selective delivery of a therapeutic gene for treatment of head and neck squamous cell carcinoma using human neural stem cells.

OBJECTIVES: Based on studies of the extensive tropism of neural stem cells (NSCs) toward malignant brain tumor, we hypothesized that NSCs could also target head and neck squamous cell carcinoma (HNSCC) and could be used as a cellular therapeutic delivery system. METHODS: To apply this strategy to the treatment of HNSCC, we used a human NSC line expressing cytosine deaminase (HB1.F3-CD), an enzyme that converts 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU), an anticancer agent. HB1. F3-CD in combination with 5-FC were cocultured with the HNSCC (SNU-1041) to examine the cytotoxicity on target tumor cells in vitro. For in vivo studies, an HNSCC mouse model was created by subcutaneous implantation of human HNSCC cells into athymic nude mice. HB1.F3-CD cells were injected into mice using tumoral, peritumoral, or intravenous injections, followed by systemic 5-FC administration. RESULTS: In vitro, the HB1.F3-CD cells significantly inhibited the growth of an HNSCC cell line in the presence of the 5-FC. Independent of the method of injection, the HB1.F3-CD cells migrated to the HNSCC tumor, causing a significant reduction in tumor volume. In comparison to 5-FU administration, HB1.F3-CD cell injection followed by 5-FC administration reduced systemic toxicity, but achieved the same level of therapeutic efficacy. CONCLUSION: Transplantation of human NSCs that express the suicide enzyme cytosine deaminase combined with systemic administration of the prodrug 5-FC may be an effective regimen for the treatment of HNSCC.