Self-Assembled Peptidyl Aggregates for the Fluorogenic Recognition of Mitochondrial DNA G-Quadruplexes.

The selective monitoring of G-quadruplex (G4) structures in living cells is important to elucidate their functions and reveal their value as diagnostic or therapeutic targets. Here we report a fluorogenic probe (CV2) able to selectively light-up parallel G4 DNA over antiparallel topologies. CV2 was constructed by conjugating the excimer-forming CV dye with a peptide sequence (l-Arg-l-Gly-glutaric acid) that specifically recognizes G4s. CV2 forms self-assembled, red excimer-emitting nanoaggregates in aqueous media, but specific binding to G4s triggers its disassembly into rigidified monomeric dyes, leading to a dramatic fluorescence enhancement. Moreover, selective permeation of CV2 stains G4s in mitochondria over the nucleus. CV2 was employed for tracking the folding and unfolding of G4s in living cells, and for monitoring mitochondrial DNA (mtDNA) damage. These properties make CV2 appealing to investigate the possible roles of mtDNA G4s in diseases that involve mitochondrial dysfunction.

Photoactivatable BODIPY Platform: Light-Triggered Anticancer Drug Release and Fluorescence Monitoring.

We report a photoactivatable fluorophore that relies on the conversion of a dark meso-ester-BODIPY to an emissive meso-carboxylate-BODIPY. The process is triggered by the photolysis of an aryl azide to an amine, which occurs in a high photochemical yield, and does not release toxic nitroso photoproducts. Its utility is demonstrated in platforms that simultaneously release upon irradiation both a bioactive molecule and an emissive dye, resulting in an approximate 1250-fold luminescence increase.

Protective effect of a purified polyphenolic extract from Ecklonia cava against noise-induced hearing loss: Prevention of temporary threshold shift.

OBJECTIVE: Noise is one of the most common causes of hearing loss. Approximately 16% of American teenagers (12-19 years) have hearing loss caused by loud noise. The implication of noise-induced hearing loss (NIHL) in teenagers has received increasing attention. Although temporary threshold shift (TTS), a type of NIHL, is a transient hearing loss, it can accelerate age-related hearing loss. Reactive oxygen species are a primary cause of TTS. As the polyphenols from Ecklonia cava are known to have potent antioxidant effects, we investigated the protective effects of a purified polyphenolic extract of Ecklonia cava (PPEE) against TTS in mice. METHODS: The radical-scavenging activity of PPEE was evaluated using the 1,1-diphenyl-2-picrylhydrazyl assay. The PPEE + Noise and Saline + Noise groups were administered intraperitoneal PPEE (100 mg/kg) and saline, respectively, for 5 days before exposure to noise at 100 dB SPL for 60 min. Hearing ability was assessed following noise exposure using auditory brainstem responses and distortion product otoacoustic emissions. RESULTS: PPEE exhibited significant radical scavenging activity. The ABR threshold shifts 1 day after exposure to noise at 16 kHz and 1, 7, and 14 days after exposure to noise at 32 kHz, were significantly less in the PPEE + Noise than in the Saline + Noise group. One day after noise exposure, mice in the PPEE + Noise group showed a significant degree of protection in relation to their DPOAE level at f2, 17, and 28 kHz. CONCLUSIONS: These findings suggest that PPEE may be a potential preventive agent against TTS. In addition, as a food ingredient approved by the United States Food and Drug Administration, PPEE may be administered to those who are exposed to noise inevitably with little likelihood of adverse effects, thereby contributing to the prevention of TTS.

Protective effects of the seaweed phlorotannin polyphenolic compound dieckol on gentamicin-induced damage in auditory hair cells.

OBJECTIVES: Drug-induced ototoxicity from compounds such as aminoglycosides and platinum can damage the inner ear resulting in hearing loss, tinnitus or balance problems and may be caused by the formation of reactive oxygen species (ROS). Dieckol is a phlorotannin polyphenolic compound with strong antioxidant effects found in edible brown algae. This study investigated the protective effects of dieckol on drug-induced ototoxicity in cochlear cultures obtained from neonatal mice. METHODS: Cochlear explants were pretreated with dieckol and exposed to gentamicin for 48h. The explants were then fixed and stained with fluorescein isothiocyanate-phalloidin and the intact hair cells counted. The free radical scavenging activity of dieckol was assessed using a 1,1-diphenyl-2-picrylhydrazyl assay. E. coli (Escherichia coli) cultures were used to evaluate the effect of dieckol on the antibiotic activity of gentamicin. RESULTS: Gentamicin treatment resulted in dose-dependent hair cell loss that was partially protected by dieckol. Moreover, at concentrations >67µM dieckol had significant radical scavenging activity. Dieckol did not compromise the antibiotic effect of gentamicin. CONCLUSIONS: These findings suggest that dieckol can be used as a therapeutic agent that reduces the damage caused by drug-induced ototoxicity.

Analysis of sinonasal anatomical variations associated with maxillary sinus fungal balls.

OBJECTIVE: The pathogenesis of MSFB development remains unclear, but it has been suggested that poor sinus ventilation is associated with disease development; such a ventilation is influenced by anatomical variation of the paranasal sinuses. Thus, we sought to determine whether sinonasal anatomical variations were associated with MSFB development. METHODS: Thirty-one patients with MSFB and 28 gender-matched control patients were included in the present study. The presence or absence of Haller cells and a concha bullosa were scored, and the angle of septal deviation and the minimal and maximal lengths of the infundibulum were measured on preoperative computed tomography images. RESULTS: In the MSFB group, both a concha bullosa (61.3% vs. 28.6%, p=0.006) and Haller cells (41.9% vs. 30.4%) were present at higher frequencies than in the control group, although the between-group difference in Haller cell occurrence was not statistically significant (p=0.348). In addition, MSFB patients had a significantly lower mean infundibular width (3.23±0.69mm vs. 3.99±1.17mm, p<0.001) and a longer infundibular length (9.71±1.43mm vs. 8.23±1.72mm, p<0.001) than controls. CONCLUSIONS: Sinonasal anatomical variations, especially the presence of a concha bullosa, and/or a narrow and long infundibulum, may play roles in the development of maxillary sinus fungal balls (MSFBs).

Cellular proliferation and angiogenesis in nasal polyps of young adult and geriatric patients.

BACKGROUND: Cellular proliferation and angiogenesis are associated with pathophysiology of nasal polyposis (NP). In a previous report, we showed that patient age is a predictive factor of surgical outcomes among patients with chronic rhinosinusitis and NP, and that geriatric patients exhibit better outcomes than pediatric and adult patients. We postulated that better outcomes in the geriatric population may be secondary to decreased proliferation and angiogenesis within polyps. Therefore, we evaluated the cellular proliferation and angiogenesis in young adult and geriatric patients with NP. This was a prospective case-control study. METHODS: Twenty patients were divided into 2 groups according to age (20 to 30 years vs ≥65 years of age). NP tissues were sampled during endoscopic sinus surgery and processed for immunohistochemistry. Cellular proliferation was evaluated with proliferating cell nuclear antigen and Ki67, and angiogenesis was assessed with vascular endothelial growth factor. We also compared objective surgical outcomes using endoscopy scores. RESULTS: Immunohistochemical analysis revealed significantly higher expression and positive reactivity of proliferating cell nuclear antigen and Ki67 in the polyps of young adults than in those of geriatric patients, whereas the expression of vascular endothelial growth factor was similar between the 2 groups. Endoscopy scores were better in the geriatric group. CONCLUSION: Geriatric patients have a lower cellular proliferative ability than young adults, and angiogenesis does not significantly differ between the 2 age groups. Cellular proliferation seems to be the cause of the different surgical outcomes between the 2 age groups, whereas angiogenesis has no significant influence on the postoperative course.

Long-term efficacy of inferior meatal antrostomy for treatment of postoperative maxillary mucoceles.

PURPOSE: Transnasal endoscopic marsupialization has replaced the conventional Caldwell-Luc operation for managing postoperative maxillary mucoceles. Inferior meatal antrostomy (IMA) may be an easier and more effective method than middle meatal antrostomy (MMA) because of anatomical and structural changes of the maxillary sinus. We evaluated the long-term efficacy and technical simplicity of both methods. METHODS: This study included 21 and 32 patients who underwent MMA and IMA, respectively. They were diagnosed with a unilateral postoperative maxillary mucocele, and medical records were reviewed for history, clinical presentation, radiographic findings, surgical intervention, complications, and outcomes. During follow-up, the size of the opening and stenosis or obstruction of the antrostomy site were evaluated. RESULTS: Preoperative symptoms and mean follow-up period were similar in both groups. All patients in the IMA group received the operation as planned, whereas in four MMA patients, the attempt to create an opening failed because of thick bones and anatomical changes from the previous operation; in these patients, IMA was performed. The opening remained large enough for ventilation and drainage between the mucocele and the nasal cavity in both groups. There were no major complications, such as profuse bleeding, wound infection, or orbital or nasolacrimal duct injury. CONCLUSIONS: Although both surgical procedures seem to be effective for managing postoperative maxillary mucoceles, IMA is easier to perform, and no instances of failure to create antrostomy openings occurred. We recommend IMA as the surgical technique of choice, but providing an opening of sufficient size is necessary to ensure long-term efficacy.

Usefulness of partial uncinectomy in patients with localized maxillary sinus pathology.

PURPOSE: Conventional total uncinectomy may be unnecessary in localized maxillary sinus lesion. Partial removal of the uncinate process and middle meatal antrostomy would be sufficient to eradicate the pathological condition. Therefore, we aimed to evaluate the efficacy of partial uncinectomy versus total removal of the uncinate process in patients with localized maxillary sinus disease. METHODS: In total, 25 patients were assigned randomly to partial and total uncinectomy groups. Preoperative computed tomography established that all patients had localized pathology in the maxillary sinus. The lower half of the uncinate process was removed in the partial uncinectomy group, while the total uncinectomy group underwent the conventional surgery. Time required for the uncinectomy, healing period for the uncinectomy site, incidence of lamina papyracea or nasolacrimal duct injury, obstruction or stenosis of the frontal recess, and incidence of synechia formation in the middle meatus were compared between the groups. RESULTS: All patients completed the follow-up and were included in the analysis. Surgical indications included chronic maxillary sinusitis, fungal sinusitis, antrochoanal polyp, and odontogenic sinusitis. Operation durations and healing periods were significantly shorter in the partial uncinectomy group. One patient had a minor injury to the lamina papyracea and two patients showed partial synechia formations in the total uncinectomy group. However, other parameters did not differ significantly between the groups. CONCLUSIONS: Partial uncinectomy may be useful in patients with pathological conditions confined to the maxillary sinus. Shorter operation duration, more rapid healing, and lower incidence of complications are advantages over a conventional total uncinectomy.

Overexpression of angiomotin in sinonasal inverted papilloma.

BACKGROUND: Although inverted papilloma (IP) is one of the most common sinonasal tumors, its etiology and factors associated with tumor progression have not been fully determined. Generally, tumorigenesis or tumor growth requires angiogenesis to feed tumor cells. Angiomotin is a recently discovered protein that regulates migration and tubule formation in endothelial cells. It has been reported that angiomotin affects angiostatin (circulating inhibitor of angiogenesis), resulting in promotion of angiogenesis. Thus, we evaluated the expression and distribution of angiomotin in sinonasal IP, compared to normal control tissue. METHODS: The study included 10 subjects with sinonasal IP and 5 normal controls. Ethmoid sinus mucosa obtained during reduction of blowout fractures was used as a normal control. Reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, immunohistochemistry, and Western blot analysis were used to assess the expression, intensity, and distribution of angiomotin in tissues. RESULTS: Positive bands for angiomotin were seen in all specimens by RT-PCR. The expression level of angiomotin was significantly upregulated in IP tissues versus normal sinus mucosa by real-time PCR. Immunohistochemistry revealed positive reactions on endothelial cells of capillaries and small vessels within the tumor and normal tissues, but the positivity was significantly stronger in IP. Western blot analysis showed that expression levels of angiomotin were increased in IP compared to normal sinus mucosa. CONCLUSION: Angiomotin, a novel protein in angiogenesis, was overexpressed in IP. Although it is not an etiological or initiating factor in tumor development, it seems to be associated with progression and growth of IP via promoting angiogenesis.

Effect of cold-water cooling of tonsillar fossa and pharyngeal mucosa on post-tonsillectomy pain.

PURPOSE: Post-tonsillectomy pain is a notable concern and thermal injury produced by electric surgical devices is considered a main cause. Intraoperative cooling of the tonsillar fossa and pharyngeal mucosa with cold water has effectively reduced postoperative pain, but no studies have fully evaluated the effects of this technique with a proper study design. We assessed mucosal cooling in two groups of patients undergoing the same surgical technique by a single surgeon, with one group receiving cold-water cooling and the other group as a control. METHODS: Forty patients who underwent monopolar electrocautery tonsillectomy were randomly assigned to two groups (n = 20 for each group). Group 1 received cooling of the tonsillar fossa and pharyngeal mucosa with 4 °C saline just after removal of each tonsil whereas Group 2 did not receive cooling. Postoperative pain was recorded on operation day and 1, 2, 4, 7, and 10 days postoperatively. Post-tonsillectomy pain, return to normal diet, and incidence of postoperative bleeding were compared between the groups. RESULTS: Post-tonsillectomy pain on 6 selected days and overall pain during the 10-day follow-up period were significantly lower in Group 1. However, return to normal diet and incidence of postoperative bleeding did not differ significantly between the groups. CONCLUSIONS: Intraoperative application of cold water after tonsillectomy significantly reduced postoperative pain. We recommend cooling the tonsillar fossa and pharyngeal mucosa with cold water during tonsillectomy to easily and effectively reduce post-tonsillectomy pain.

Effect of maxillary sinus packing with epinephrine hydrochloride-soaked cotton pledgets on complications after canine fossa puncture.

CONCLUSION: Bleeding control with epinephrine hydrochloride-soaked cotton packing in the maxillary sinus after canine fossa puncture (CFP) during operation is a simple method for reducing complications, especially those associated with blood leakage from the maxillary sinus into the subcutaneous tissue. OBJECTIVE: Although CFP is a useful method for extensive maxillary sinus disease, complications can occur associated with nerve injuries or mucosal bleeding. We evaluated whether maxillary sinus packing with epinephrine hydrochloride-soaked cotton pledgets would reduce complications after CFP. METHODS: Patients who met the inclusion criteria were randomly allocated to groups 1 (packing) and 2 (no packing). Patients underwent unilateral or bilateral CFP. We compared the disease entities, complication incidence, and average symptom duration between the groups. RESULTS: A total of 57 patients were included. Group 1 underwent 36 CFPs, and complications occurred in 20 sides of 17 patients. Group 2 had 39 CFPs, and 20 patients experienced complications in 26 sides. The total number of complications was 40 and 73 in groups 1 and 2, respectively. Incidence or duration of facial, dental, or gum numbness did not differ between groups. Tingling sensation, facial pain, facial swelling, and bruising showed significantly lower occurrence rates and shorter duration in group 1.

Canine fossa puncture for severe maxillary disease in unilateral chronic sinusitis with nasal polyp.

OBJECTIVES/HYPOTHESIS: To evaluate the efficacy of canine fossa puncture (CFP) by comparing patients with unilateral chronic rhinosinusitis (CRS) accompanying nasal polyposis (NP) who underwent CFP with those who underwent maxillary sinus clearance through a middle meatal antrostomy (MMA). STUDY DESIGN: Prospective randomized study. METHODS: Twenty-nine patients were randomly assigned to the CFP and MMA groups. Preoperative computed tomography (CT) established that all patients had severely diseased maxillary sinuses. Subjective outcomes were evaluated preoperatively and at 3, 6, and 12 months postoperatively using the Sino-Nasal Outcome Test 20 (SNOT-20) and a visual analogue scale (VAS). Additionally, mucosal thickening was measured as a percentage of total maxillary sinus volume on CT images taken 12 months postoperatively. RESULTS: Twenty-five patients who completed the follow-up, questionnaires, and postoperative CT evaluation were included in the analysis. SNOT-20 and VAS scores improved significantly at 3, 6, and 12 months postprocedure in both groups. However, significant improvement of SNOT-20 at 12 months and VAS scores for purulent discharge, foul odor, and postnasal drip at 6 and 12 months were observed in the CFP group compared with the MMA group. In addition, the volume of mucosal thickening was significantly greater in the MMA group than in the CFP group on postoperative CT images. CONCLUSIONS: CFP is a useful method for the removal of severe maxillary mucosal disease that cannot be reached through MMA, and is superior to conventional MMA for improving subjective and objective outcomes in patients with unilateral CRS accompanying NP.

A Case of Glomangiopericytoma of the Ethmoid Sinus / 대한이비인후과학회지

Glomangiopericytoma, a new term referring to the sinonasal type hemangiopericytoma, is a rare sinonasal tumor arising from modified perivascular glomus-like myoid cells. It is a borderline, low grade malignancy tumor, which has good prognosis following a complete surgical resection. Recently, we experienced a case of a glomangiopericytoma in a 68-year-old woman who presented with epistaxis and unilateral nasal obstruction. Endoscopic examinations revealed polypoid mass with bleeding tendency in the left middle meatus. The tumor was located mainly in the left ethmoid sinus and we removed it successfully by endoscopic approach. Histological examination and immunohistochemistry confirmed the diagnosis of glomangiopericytoma. We present the clinical and histological characteristics, therapeutic principles, and prognosis of this rare disease entity with a literature review.

Middle turbinate resection versus preservation in patients with chronic rhinosinusitis accompanying nasal polyposis: baseline disease burden and surgical outcomes between the groups.

OBJECTIVE: To evaluate baseline disease burden and surgical outcomes between middle turbinate resection and preservation groups consisting of patients diagnosed with chronic rhinosinusitis accompanying nasal polyposis (NP). STUDY DESIGN: Prospective, nonrandomized study. METHODS: The preoperative disease burden (extent of NP, Lund-Mackay scores, and subjective symptom scores) was evaluated using nasal endoscopy, computed tomography, and questionnaires. Objective and subjective surgical outcomes were assessed 12 months postoperatively based on endoscopic findings, the Sino-Nasal Outcome Test 20 (SNOT-20), and a visual analogue scale (VAS). RESULTS: The extent of NP, Lund-Mackay scores, and VAS scores for the two main symptoms were significantly greater in the resection group than in the preservation group. The preservation group had better objective outcomes. Preoperative SNOT-20 and VAS scores were improved significantly at 12 months postoperatively in both groups, and the improvement did not differ significantly between the groups. CONCLUSIONS: The middle turbinate resection group had greater baseline disease burden (severe polyposis, more extensive disease, and poorer symptom scores) than the preservation group. This may be the reason for the poorer objective surgical outcome in the resection group despite more radical surgery. However, the subjective outcomes were successful regardless of the middle turbinate resection or preservation.

Menopause and Sleep Related Breathing Disorders / 대한폐경학회지

Women after the menopause appear to be more susceptible to sleep related breathing disorders (SBDs). The increased prevalence of SBDs in postmenopausal women may be related to weight gain and the decline in female sex hormones levels. These conditions may cause upper airway obstruction, which can result in sleep disruption. Other sleep disorders, such as insomnia, depression, and fibromyalgia must be ruled out with SBDs in postmenopausal women with sleep difficulties. Once SBD is strongly suspected through medical history and precise physical examinations, polysomnogram is required for confirmatory diagnosis. In addition, other examinations besides polysomnogram should be performed to detect obstructed regions. Treatment of SBD can be classified into surgical method and non-surgical method. Treatment options must be carefully selected by considering the patient's clinical examinations, patient's preference, age and life style.

Fatty acid binding protein 1 is related with development of aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the ingestion of aspirin. Although alterations in eicosanoid metabolites play a role in AERD, other immune or inflammatory mechanisms may be involved. We aimed to identify proteins that were differentially expressed in nasal polyps between patients with AERD and aspirin-tolerant asthma (ATA). METHODOLOGY/PRINCIPAL FINDINGS: Two-dimensional electrophoresis was adopted for differential display proteomics. Proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS). Western blotting and immunohistochemical staining were performed to compare the amount of fatty acid-binding protein 1 (FABP1) in the nasal polyps of patients with AERD and ATA. Fifteen proteins were significantly up- (seven spots) or down-regulated in the nasal polyps of patients with AERD (n = 5) compared to those with ATA (n = 8). LC-MS revealed an increase in seven proteins expression and a decrease in eight proteins expression in patients with AERD compared to those with ATA (P = 0.003-0.045). FABP1-expression based on immunoblotting and immunohistochemical analysis was significantly higher in the nasal polyps of patients with AERD compared to that in patients with ATA. FABP1 was observed in epithelial, eosinophils, macrophages, and the smooth-muscle cells of blood vessels in the polyps. CONCLUSIONS/SIGNIFICANCE: Our results indicate that alterations in 15 proteins, including FABP1, may be related to the development of AERD.

Frequency of Nasal Septal Perforation at the Suture Fixation Site of a Silastic Sheet Inserted during Nasal Surgery

OBJECTIVE: This study was performed to evaluate the frequency of nasal septal perforation at the suture fixation site of a silastic sheet inserted during nasal surgery. METHODS: Seven hundred and twenty-one patients with silastic sheet insertion during common nasal surgeries were examined. The frequency of perforations and subjective symptoms of the patients were evaluated. RESULTS: Nasal septal perforation at the suture fixation site occurred in seven patients (0.97%). In three patients, perforations occurred immediately after removal of the sheet, while four patients developed perforations 2 to 4 weeks later. In most cases, perforations were small and did not exceed 2 to 3 mm in diameter. No patient complained of nasal symptoms related to the septal perforation postoperatively. CONCLUSION: The frequency of the septal perforation at the suture fixation site of a silastic sheet was very low and subjective symptoms were absent.

Outcomes after endoscopic sinus surgery for unilateral versus bilateral chronic rhinosinusitis with nasal polyposis.

BACKGROUND: Endoscopic sinus surgery (ESS) is a safe and reliable procedure for the treatment of chronic rhinosinusitis (CRS) and nasal polyposis (NP). Although most cases of CRS with NP occur bilaterally, we occasionally encounter patients with unilateral sinus disease with NP. Because no study has been conducted on the surgical outcomes between unilateral and bilateral CRS with NP after ESS, we evaluated subjective and objective outcomes between patients with unilateral and bilateral CRS with NP. METHODS: A total of 181 patients diagnosed with CRS with NP were enrolled. Twenty-three patients had unilateral CRS with NP and 158 patients had bilateral disease. The extent of NP, Lund-Mackay score, and involved sinuses were evaluated with nasal endoscopy and preoperative computed tomography (CT). Objective and subjective surgical outcomes were assessed 6 months after ESS, using endoscopic findings, the Sino-Nasal Outcome Test 20 (SNOT-20), and visual analog scales. RESULTS: The extent of NP and Lund-Mackay score did not differ significantly between the two groups. The SNOT-20 and six main symptom scores included in the questionnaire were significantly improved 6 months postoperatively in both groups, with no significant difference between the groups. However, the unilateral group showed significantly better objective outcomes than the bilateral group. CONCLUSION: Unilateral CRS with NP showed more favorable objective surgical outcomes than bilateral disease. We suggest that the developmental mechanisms of the two disease entities may be different and that bilateral CRS with NP may be more intimately associated with a patient's innate tendency to develop NP.