Hoon Shik Yang

Smoking induces oropharyngeal narrowing and increases the severity of obstructive sleep apnea syndrome.

OBJECTIVE Smoking is a known risk factor for snoring, and is reported to be associated with an increased prevalence of obstructive sleep apnea syndrome (OSAS). The purpose of this was to determine the relationship of smoking to the severity of OSAS and examine what local histological changes in the uvular mucosa of OSAS patients might influence this relationship. STUDY DESIGN AND METHODS Fifty-seven OSAS subjects were included and classified according to smoking history and OSAS severity. Twenty-eight subjects were heavy smokers and 29 were nonsmokers; these 57 patients were divided according to moderate or severe OSAS. Histologic changes in the uvular mucosa were evaluated in all subjects as well as smoking duration and OSAS severity. RESULTS Among smokers, moderate-to-severe OSAS was more common, and apnea, hypopnea, and oxygen desaturation indices were higher. Moreover, smoking duration and OSAS severity were significantly correlated. Increased thickness and edema of the uvular mucosa lamina propria were observed in moderate and severe OSAS patients, and only smokers had significant changes in uvular mucosa histology. Positive staining for calcitonin gene-related peptide (CGRP), a neuroinflammatory marker for peripheral nerves, was increased in the uvular mucosa of smokers. CONCLUSIONS Our results suggest that smoking may worsen OSAS through exacerbation of upper airway collapse at the level of the uvula, and that histological changes of the uvular mucosa correlated with smoking might be due to increased CGRP-related neurogenic inflammation.

Depletion of ascorbic acid impairs NK cell activity against ovarian cancer in a mouse model

Ascorbic acid (Vitamin C) administration has been used to prevent infectious diseases in public or as a therapeutic agent by the physicians in treatment of several diseases. Ascorbic acid is also involved in immune cell functions and immune responses, although the mechanisms by which it exerts effects on immune cells against cancer cells are not fully understood at the normal plasma level. In this study, we used the mice lacking l-gulono-γ-lactone oxidase (Gulo), the enzyme required for the biosynthesis of ascorbic acid, to characterize the effects of ascorbic acid on NK cell cytotoxicity against ovarian cancer cells, MOSECs (murine ovarian surface epithelial cells). Gulo(-/-) mice depleted of ascorbic acid survived for a shorter time than the normal control or Gulo(-/-) mice supplemented with ascorbic acid after tumor challenge regardless of treatment with IL-2. CD69 and NKG2D expression was clearly reduced in NK cells isolated from mice depleted of ascorbic acid as compared to that in the normal control and the mice supplemented with ascorbic acid. We also observed that IFN-γ secretion by NK cells isolated from Gulo(-/-) mice depleted of ascorbic acid was decreased after NK cells were co-cultured with MOSECs. Furthermore, the mRNA expression of perforin and granzyme B genes was also significantly decreased in NK cells isolated from mice depleted of ascorbic acid. Taken together, our results suggest that ascorbic acid at the normal plasma concentration has an essential role in maintaining the NK cytotoxicity against cancer cells.

Age-related changes in the distribution of Kv1.1 and Kv3.1 in rat cochlear nuclei

Abstract Objectives: To identify age-related changes in voltage-gated K+ (Kv) channels that contribute to temporal processing in neurons of the central auditory system, we investigated the distribution of Kv1.1 and Kv3.1 in the auditory brainstem of adult and aged rats. Methods: Immunohistochemistry was performed in accordance with the free-floating method described earlier. Results: Among the auditory nuclei, only the posterior ventral cochlear nucleus (PVCN) showed age-related changes. Kv1.1 immunoreactivity was increased in the octopus cell bodies, while the staining intensity was significantly decreased in the neuropil. Image analysis demonstrated the specific increase in Kv1.1 immunoreactivity in aged cochlear nucleus neurons although the mean density of the entire selection was significantly decreased. In contrast, the number of Kv1.1-immunoreactive neurons was not significantly different between control and aged groups. The immunoreactivity for Kv3.1 was decreased in the octopus cells and neuropil of aged PVCN, which was confirmed by image analysis. The number of Kv3.1-positive cells was also significantly decreased in aged PVCN. Discussion: This study may provide useful data to compare age-related changes in Kv1.1 and Kv3.1 with known physiological properties of auditory neurons.

The Effect of Early Canalith Repositioning on Benign Paroxysmal Positional Vertigo on Recurrence

Objectives Benign paroxysmal positional vertigo (BPPV) can be treated using a simple repositioning maneuver. This study demonstrates the effects of early repositioning therapy in patients with BPPV, especially with regard to recurrence. Methods We enrolled 138 consecutive patients who had been diagnosed with BPPV in the emergency rooms and ENT out-patient clinics of Chung-Ang University Hospital and Samyook Medical Center from January to June 2009. All patients immediately underwent appropriate canalith repositioning procedures (CRPs) depending on canalith type and location. The CRPs were performed daily until the patients symptoms were resolved. The patients were classified into two groups according to the duration between symptom onset and initial treatment: less than 24 hours (early repositioning group, n=66) and greater 24 hours (delayed repositioning group, n=72). We prospectively compared the numbers of treatments received and the recurrence rates between the two groups. Results Follow-up periods ranged from 8 to 14 months, 77 cases involved posterior canal BPPV, 48 cases were lateral canal BPPV (of which 20 cases were cupulolithiasis), and 13 cases were multiple canal BPPV. BPPV recurrence was found in a total of 46 patients (33.3%). The necessary numbers of CRPs were 2.3 for the early repositioning group and 2.5 for the late repositioning group, a difference that was not statistically significant (P=0.582). The early repositioning group showed a recurrence rate of 19.7%, and the delayed repositioning group showed a recurrence rate of 45.8% (P=0.002). Conclusion Performing repositioning treatments as soon as possible after symptom onset may be an important factor in the prevention of BPVV recurrence.

Can Mitochondrial Dysfunction Be a Predictive Factor for Oxidative Stress in Patients with Obstructive Sleep Apnea

Mitochondrial dysfunction reflects a lifelong cumulative burden of cellular damage, and a decrease in mitochondrial DNA (mtDNA) copy number is associated with oxidative stress and chronic inflammation. The goal of this study was to assess whether mitochondrial dysfunction and a decrease in mtDNA copy number are common features of patients with obstructive sleep apnea syndrome (OSA). We compared mtDNA copy number between 20 healthy volunteers and 20 patients with OSA and investigated whether a significant attenuation of mtDNA copy number was observed in genomic DNA isolated from whole blood of OSA patients. Our observations lead to the hypothesis that mtDNA copy number is lower in whole blood DNA of OSA subjects and might be related to OSA severity, reflecting excessive oxidative stress in patients with OSA.

Clinical characteristics of acoustic trauma caused by gunshot noise in mass rifle drills without ear protection

One of the major occupational hazards of working in military service is being subjected to intense impulse noise. We analyzed the clinical presentation of acoustic traumas, induced by mass rifle gunshot noise during military training, in unprotected patients. We evaluated 189 soldiers who had otologic symptoms after rifle shooting exercises without using any hearing protection. All soldiers had been training on the K2 rifle. We took medical histories; conducted physical examinations and hearing evaluations (pure-tone audiometry, speech audiometry, and impedence audiometry); and distributed the Newmanns Tinnitus Handicap Inventory (THI) survey. In addition, we evaluated a normal control group of 64 subjects of similar age who had never fired a rifle. In the patient group, the most common and irritating reported symptom was tinnitus (94.2%), and the average THI score in the patient group was 39.51 ± 14.87, which was significantly higher than the control group score (0.56 ± 3.94) (p < 0.001). Average outcomes of post-exposure air conduction thresholds were 21.33 ± 13.25 dB HL in the affected ears. These levels also were significantly higher than those of the control group (9.16 ± 4.07dB HL) (p < 0.001). Hearing loss was most prominent at high frequencies. An asymmetry of hearing loss related to head position during shooting was not observed. Acoustic trauma induced by gunshot noise can cause permanent tinnitus and hearing loss. Hearing protection (bilateral earplugs) and environmental reform are necessary.

Oxidative Stress-induced Telomere Length Shortening of Circulating Leukocyte in Patients with Obstructive Sleep Apnea.

The main mechanism of pathogenesis which causes systemic complications in obstructive sleep apnea (OSA) patients is believed to be intermittent hypoxia-induced intermediary effect and it depends on the burden of oxidative stress during sleep. We aimed to search the predictive markers which reflect the burden of systemic oxidative stress in patients with OSA and whether excessive telomere length shortening is a characteristic feature that can assess oxidative stress levels. We used quantitative PCR to measure telomere length using peripheral blood genomic DNA. Telomere lengths were compared in an age- and body mass index (BMI)-dependent manner in 34 healthy volunteers and 43 OSA subjects. We also performed reactive oxygen species assay to measure the concentration of hydrogen peroxide in the peripheral blood of healthy volunteers and OSA subjects. We found that the serum concentration of hydrogen peroxide was considerably higher in OSA patients, and that this was closely related with the severity of OSA. Significantly shortened telomere length was observed in the circulating leukocytes of the peripheral blood of OSA patients, and telomere length shortening was aggravated more acutely in an age- and BMI-dependent manner. An inverse correlation was observed between the concentration of hydrogen peroxide and the telomere length of OSA patients and excessive telomere length shortening was also linked to severity of OSA. The results provided evidence that telomere length shortening or excessive cellular aging might be distinctive in circulating leukocyte of OSA patients and may be an predictive biomarker for reflect the burden of oxidative stress in the peripheral blood of OSA patients.

Expression of CAIII and Hsp70 Is Increased the Mucous Membrane of the Posterior Commissure in Laryngopharyngeal Reflux Disease

Purpose We tried to evaluate the difference in the expression of carbonic anhydrase (CA) III and heat shock protein (Hsp) 70 between laryngopharyngeal reflux disease (LPRD) and non-LPRD patients. Materials and Methods The study involved 28 patients who underwent laryngeal microsurgery due to benign laryngeal disease from March to August 2008. Reflux symptom index (RSI) and reflux finding score (RFS) were measured for each person, and they were assigned either to the LPRD group (n=10) or non-LPRD group (n=18). Tissue samples were obtained from the mucosa of posterior commissure, and immunohistochemistry (IHC) staining of CAIII and Hsp70 was performed. The IHC scores were measured and compared with clinical features including RSI and RFS. Results Total 10 patients were assigned as LPRD group, and 18 patients were as control group. The mean IHC score of CAIII and Hsp70 was 1.70±1.06 and 1.90±0.88, respectively, in LPRD patients, whereas the mean IHC score of CAIII and Hsp70 was 0.78±0.73 and 0.94±0.87, respectively, in non-LPRD patients. The difference between two groups was statistically significant (p<0.05). Conclusion CAIII and Hsp70 expressions were higher in LPRD patients that in non-LPRD patients, suggesting the possibility as one of biomomarker in LPRD diagnosis.

Therapeutic Effects of Carbogen Inhalation and Lipo-Prostaglandin E1 in Sudden Hearing Loss

Purpose Vascular disorders and viral infections are considered the main causes of sudden hearing loss (SHL), although its pathogenesis remain unclear. Treatments include carbogen inhalation and lipo-prostaglandin E1 (lipo-PGE1), both of which have circulation-enhancing effects. We investigated the effectiveness of carbogen inhalation and lipo-PGE1 in SHL. Materials and Methods This retrospective review included 202 patients with idiopathic SHL who visited our clinic within 14 days of symptom onset between January 2006 and June 2010. All patients received oral prednisolone for 10 days. Of the 202 patients, 44 received no additional treatment, 106 received additional carbogen inhalation, and 52 received additional lipo-PGE1. Hearing improvement was measured using Siegels criteria. Results Overall recovery rates were 67.9% in the carbogen group, 53.8% in the lipo-PGE1 group, and 52.3% in the steroid-only control group (p=0.097). Limited to type 1 and type 2 categories of Sigelss criteria, the carbogen group had a significantly higher recovery rate (53.8%) than the lipo-PGE1 group (26.9%) and the steroid-only control group (38.6%) (p=0.005). Conclusion Carbogen inhalation added to steroid was a more effective treatment than lipo-PGE1 added to steroid or steroid alone in patients with SHL.

N-acetylcysteine enhances neuronal differentiation of P19 embryonic stem cells via Akt and N-cadherin activation

We examined whether N-acetylcysteine (NAC) enhanced embryonic body (EB) formation and neuronal differentiation in terms of EB formation, neuronal marker (microtubule-associated protein 2; MAP-2) expression, and neuron maturation using P19 embryonic stem cells. The size and numbers of EBs were greatly increased, together with the up-regulated N-cadherin expression. Also, MAP-2 expression and neurite outgrowth were much increased with activation of serine/threonine protein kinase (Akt) and blocked by addition of an Akt inhibitor (LY294002). Our results suggested that NAC increased EB formation by up-regulating the N-cadherin expression. Furthermore, NAC-enhanced neuronal differentiation was mediated by activation of Akt.