NLRP3 Inflammasome as Therapeutic Targets in Inflammatory Diseases

Innate immunity is a first line defence system in the body which is for sensing signals of danger such as pathogenic microbes or host-derived signals of cellular stress. Pattern recognition receptors (PRR’s), which present in the cell memebrane, are suspect the infection through pathogen-associated molecular patterns (PAMP), and activate innate immunity with response to promote inflammation via inflammatory cells such as macrophages and neutrophils, and cytokines. Inflammasome are protein complexes which are part of innate immunity in inflammation to remove pathogens and repair damaged tissues. What is the important role of inflammation in disease? In this review, we are focused on the action mechanism of NLRP3 inflammasome in inflammatory diseases such as asthma, atopic dermatitis, and sepsis.

Cell Autonomous Circadian Systems and Their Relation to Inflammation

All living beings on earth have an important mechanism of 24-h periodicity, which controls their physiology, metabolism, and behavior. In humans, 24-h periodicity is regulated by the superchiasmatic nucleus (SCN) through external and environmental cues.Peripheral organs demonstrate circadian rhythms and circadian clock functions, and these are also observed in cultured cell lines.Every cell contains a CLOCK: BMAL1 loop for the generation of circadian rhythms. In this review, we focused on cell autonomous circadian rhythms in immune cells, the inflammatory diseases caused by disruption of circadian rhythms in hormones, and the role of clock genes in inflammatory diseases.

Changes in Cortical Auditory Evoked Potentials by Ipsilateral, Contralateral and Binaural Speech Stimulation in Normal-Hearing Adults

Objectives@#. Cortical auditory evoked potentials (CAEPs) have been used to examine auditory cortical development or changes in patients with hearing loss. However, there have been no studies analyzing CAEP responses to the different sound stimulation by different stimulation sides. We characterized changes in normal CAEP responses by stimulation sides in normal-hearing adults. @*Methods@#. CAEPs from the right auditory cortex were recorded in 16 adults following unilateral (ipsilateral and contralateral) and bilateral sound stimulation using three speech sounds (/m/, /g/, and /t/). Amplitudes and latencies of the CAEP peaks in three conditions were compared. @*Results@#. Contralateral stimulation elicited larger P2-N1 amplitudes (sum of P2 and N1 amplitudes) than ipsilateral stimulation regardless of the stimulation sounds, mostly due to the larger P2 amplitudes obtained, but elicited comparable P2-N1 amplitudes to bilateral stimulation. Although the P2-N1 amplitudes obtained with the three speech sounds were comparable following contralateral stimulation, the /m/ sound elicited the largest P2-N1 amplitude in ipsilateral stimulation condition due to the largest N1 amplitude obtained, whereas /t/ elicited larger a P2-N1 amplitude than/g/ in bilateral stimulation condition due to a larger P2 amplitude. @*Conclusion@#. Spectrally different speech sounds and input sides are encoded differently at the cortical level in normal-hearing adults. Standardized speech stimuli, as well as specific input sides of speech, are needed to examine normal development or rehabilitation-related changes of the auditory cortex in the future.

Assessment of Objective Audiometry to Predict Subjective Satisfaction in Patients With Hearing Aids

Objectives@#. To investigate the correlation of objective audiometry with user satisfaction as measured with the questionnaire scores. @*Methods@#. Twenty patients with hearing loss, who agreed to wear a hearing aid and were referred for hearing aid fitting, were included in this prospective clinical study. All patients used the in-the-canal type of Wide7 hearing aid provided by BSL Co., Ltd. We performed the Korean version of the Hearing Handicap Inventory for the Elderly (K-HHIE) and the International Outcome Inventory for Hearing Aids (K-IOI-HA) before and 1, 3, and 6 months after wearing the hearing aid. We also performed pure tone audiometry (PTA), speech audiometry (SA), functional gain (FG), hearing in noise test (HINT), and central auditory processing disorder tests, such as frequency pattern test (CA-f), duration pattern test (CA-d), and dichotic test (CA-Di). Patients were divided into two groups (group A-HHIE, improved; group B-HHIE, same or worse) by comparing the score of K-HHIE before and 6 months after wearing the hearing aid. In the 6-month K-IOI-HA questionnaire, 21 points were considered as the average score. Based on this, we further divided patients into two groups (group A-IOI, >21 points; group B-IOI, ≤21 points). @*Results@#. Group A-HHIE included six patients and group B-HHIE included 14 patients. In PTA, SA, HINT, CA-d, and CA-Di, group A-HHIE showed higher improvements than group B-HHIE, which were not statistically significant. Group A-IOI included 12 patients and group B-IOI included eight patients. No statistically significant difference was noted in the improvement of audiometric results over a period of 6 months after wearing the hearing aid between groups A-IOI and B-IOI. @*Conclusion@#. There were no significant and consistent audiometric results to reflect patient’s satisfaction with the hearing aid. Therefore, when analyzing the hearing aid-fitting outcome, both the objective audiometric tests and subjective questionnaire should be performed together for validating hearing aid performance.

Repositioned Drugs for Inflammatory Diseases such as Sepsis, Asthma, and Atopic Dermatitis

The process of drug discovery and drug development consumes billions of dollars to bring a new drug to the market. Drug development is time consuming and sometimes, the failure rates are high. Thus, the pharmaceutical industry is looking for a better option for new drug discovery. Drug repositioning is a good alternative technology that has demonstrated many advantages over de novo drug development, the most important one being shorter drug development timelines. In the last two decades, drug repositioning has made tremendous impact on drug development technologies. In this review, we focus on the recent advances in drug repositioning technologies and discuss the repositioned drugs used for inflammatory diseases such as sepsis, asthma, and atopic dermatitis.

Comparison of Binocular Function and Surgical Outcomes of Tenacious Proximal Fusion and High Accommodative Convergence/Accommodation Ratio Types of Intermittent Exotropia

PURPOSE: To compare the characteristics and surgical outcomes in patients with tenacious proximal fusion (TPF) and high accommodative convergence/accommodation ratio (AC/A) types of intermittent exotropia. METHODS: This study retrospectively enrolled 40 patients with intermittent exotropia, 23 with TPF and 17 with high AC/A. Binocular function was evaluated by Worth's 4-dot test. Patients underwent lateral rectus recession, and surgical outcomes were compared. Surgical success was defined as less than ±10 prism diopters (PD) at 12 months postoperatively. RESULTS: The proportion of diplopia at near, evaluated by Worth's 4-dot test, was significantly higher in patients with high AC/A than in those with TPF (35.3% vs. 4.3%, p = 0.029). The mean preoperative angles of deviation in TPF and high AC/A types were 28.3 ± 4.4 and 28.8 ± 4.5 PD at distances, and 14.7 ± 4.2 and 15.1 ± 4.1 PD at near. Twelve months after surgery, the mean angles of deviation in TPF and high AC/A types were 2.9 ± 9.8 and 1.2 ± 9.6 PD, respectively, at distance and 1.7 ± 7.7 and −1.3 ± 11.3 PD at near. The surgical success rates were similar in the TPF and high AC/A types (74.0% vs. 64.7%). Five (21.7%) patients with TPF and 2 (11.8%) with high AC/A type experienced recurrence, with consecutive esotropia occurring in 1 (4.3%) patient with TPF and 4 (23.5%) patients with high AC/A. CONCLUSIONS: The proportion of diplopia at near was higher in patients with high AC/A type than in those with TPF intermittent exotropia. However, the surgical success rates were not significantly different between the types.

Posterior Vitreous Structures Evaluated by Swept-source Optical Coherence Tomography with En Face Imaging

PURPOSE: To evaluate posterior vitreous structures using swept-source (SS) optical coherence tomography (OCT) with en face imaging. METHODS: We retrospectively reviewed OCT images of healthy individuals who did not have intra-ocular disease. We obtained high-definition horizontal and vertical line scans crossing the fovea and 3D scans using SS-OCT, with the 3D scan centered between the fovea and the optic-nerve head. An enhanced vitreous visualization function was used to highlight vitreous structures. En face mode was used to measure the area of Martegiani (AM) and bursa premacularis (BP). We performed all measurements using a built-in function of the viewing software. RESULTS: We enrolled 24 eyes from 12 healthy individuals. The mean patient age was 28.7 ± 4.6 years (range, 24 to 39 years). The mean AM and BP areas were 5.73 ± 0.88 and 18.76 ± 6.95 mm2, respectively. In en face imaging, AM shape was most frequently a vertical oval (18 / 22, 81.8%), while the predominant BP shape was round (16 / 20, 80.0%). AM was in contact with the optic disc, either at the temporal-disc margin (13 eyes, 59.1%) or the nasal optic-disc margin (9 eyes, 40.9%). CONCLUSIONS: Posterior vitreous structures, such as AM and BP, were readily visualized using en face imaging with SS-OCT. Investigating normal vitreous configuration might help in understanding changes in vitreous structures associated with retinal pathology.

Epinephrine-Induced Acute Pulmonary Edema during Septoplasty

Epinephrine is used with lidocaine to provide bloodless surgical field and to prolong the action of local anesthetics. But epinephrine also has many adverse reactions, such as agitation, restlessness, headache, tachycardia, hypertension, and some significantly more dangerous conditions including myocardial ischemia, ventricular arrhythmia, cerebral hemorrhage and pulmonary edema, cardiac arrest, etc. We have experienced epinephrine-induced acute pulmonary edema due to submucosal intranasal application of epinephrine soaked gauze during septoplasty. The patient was successfully treated in intensive care unit with positive pressure ventilation, diuretics, and inotropic support. He was extubated after 5 hours and discharged after 7 days without any complications.

FEA model analysis of the effects of the stress distribution of saddle-type implants on the alveolar bone and the structural/physical stability of implants / 대한악안면성형재건외과학회지

BACKGROUND: As dental implants receive masticatory stress, the distribution of stress is very important to peri-implant bone homeostasis and implant survival. In this report, we created a saddle-type implant and analyzed its stability and ability to distribute stress to the surrounding bone. METHODS: The implants were designed as a saddle-type implant (SI) that wrapped around the alveolar bone, and the sizes of the saddles were 2.5, 3.5, 4.5, and 5.5 mm. The X and Y displacement were compared to clarify the effects of the saddle structures. The control group consisted of dental implants without the saddle design (CI). Using finite element modeling (FEM), the stress distribution around the dental implants was analyzed. RESULTS: With saddle-type implants, saddles longer than 4.5 mm were more effective for stress distribution than CI. Regarding lateral displacement, a SI of 2.5 mm was effective for stress distribution compared to lateral displacement. ASI that was 5.6 mm in length was more effective for stress distribution than a CI that was 10 mm in length. CONCLUSIONS: The saddle-type implant could have a bone-gaining effect. Because it has stress-distributing effects, it might protect the newly formed bone under the implant.

Double-Layered Conjunctival Autograft and Amniotic Membrane Transplantation to Treat Restrictive Esotropia and Hypotropia

PURPOSE: To report a case of double-layered conjunctival autograft and amniotic membrane transplantation for the effective treatment of esotropia and hypotropia after removal of the recurrent pterygium. CASE SUMMARY: A 58-year-old male who had pterygium surgery of the right eye twice presented with diplopia on right gaze for 3 months. At the first visit, he had orthotropia in the primary position and right esotropia of 12 prism diopters (PD) on right gaze with limited abduction of -1 in the right eye. Fourteen months later, deviation was aggravated by esotropia of 30 PD and 12 PD of right hypotropia in the primary position at distance, and esotropia of 35 PD and 12 PD of right hypotropia at near with limited abduction of -2 and supraduction of -3 in the right eye. The patient complained of diplopia at all gazes and demonstrated chin-up posture. The conjunctival edge was recessed near the medial canthus and fornix, preventing conjunctival autograft after removal of subconjunctival scar tissue. Thus, 5 mm right medial rectus recession and additional half-sized conjunctival autograft were performed after amniotic membrane transplantation. The patient than showed no diplopia and orthotropia at both distance and near, with limited adduction of -1 in the right eye. He experienced no recurrence during 7 months of follow-up. CONCLUSIONS: To prevent poor epithelial regeneration and dehiscence of graft in the patients with severe restrictive strabismus and very extensive conjunctival defect, double-layered conjunctival autograft and amniotic membrane transplantation may be effective for the treatment of severe esotropia and hypotropia.

Oral cavity lipoma: a case report

Intraoral lipomas are a rare clinical entity, comprising only 0.1% to 5% of all benign tumors in the intraoral cavity. A 56-year-old woman suffering from diabetes presented with this relatively rare intraoral lipoma and was treated by surgical excision under general anesthesia. Because the mass was located adjacent to the mental foramen, a precise dissection was necessary to ensure minimal nerve damage. No abnormalities or recurrence was noted at 1-year follow-up and the patient did not complain of numbness. We studied the occurrence of oral lipoma in this diabetic patient and reviewed the relationship between oral lipoma and diabetes in the literature.

A Case of Facial Nerve Paralysis Following Parotid Abscess Treated by Catheter Drainage / 대한이비인후과학회지

Facial nerve paralysis is one of the complications of parotid abscess. Although a few cases of benign tumor and inflammatory condition of parotid gland with the facial nerve paralysis have been reported, the occurrence of facial nerve palsy following parotid abscess without coexisting tumor is very rare. The mechanism of facial nerve paralysis is not clear, but facial nerve paralysis is usually improved after the treatment of parotid abscess. The treatment of parotid abscess is composed of antibiotics based on proper culture study and drainages. Most of parotid abscess is drained by surgical approach, but catheter drainage is also recommended for selected patients. Here, we report a case of parotid abscess treated by pig-tail catheter drainage.

Results of High-Frequency and High-Acceleration Rotary Chair Test in Patients with Acute Unilateral Vestibular Neuritis / 대한평형의학회지

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the results of high-frequency and high-acceleration rotary chair test in patients with acute unilateral vestibular neuritis. MATERIALS AND METHODS: Twenty-four patients who were diagnosed as acute vestibular neuritis and underwent rotational chair and caloric tests during March 2012 to March 2013 were included. Slow harmonic acceleration (SHA) test was performed at 0.01, 0.04, 0.16, 0.64, 1.28, and 2.00 Hz. Step velocity tests at the peak velocity of 100degrees/sec (low-acceleration) and 240degrees/sec (high-acceleration) were performed. Gains and phases in SHA test and gains and time constants (Tc) in step velocity test were analyzed. RESULTS: In SHA test, decreased gain and phase lead was observed mostly in low frequencies. Gains (phases) at 0.01, 0.04, 0.16, 0.64, 1.28, and 2.00 Hz were 0.2+/-0.1 (62.2+/-15.4), 0.3+/-0.2 (24.5+/-13.0), 0.4+/-0.2 (7.2+/-18.8), 0.5+/-0.1 (7.2+/-11.3), 0.7+/-0.2 (11.0+/-7.5), and 0.8+/-0.3 (4.4+/-14.4), respectively. In step velocity (SV) test, gains stimulating the lesion side were significantly lower than those stimulating the intact side in both low- and high-acceleration SV test (p<0.05) and per-rotatory gain stimulating the lesion side in high-acceleration SV test was significantly lower than that in low-acceleration SV test. Tc stimulating the lesion side were significantly shorter than those stimulating the intact side in low- acceleration SV test (p<0.05) but not in high-acceleration SV test. Per- and post-rotatory Tc in high-acceleration SV test stimulating the intact side was significantly lower than those in low-acceleration SV test (p<0.05). CONCLUSION: At high-frequency SHA test, gain was pretty normal and phase lead was observed in some patients. High-acceleration SV test showed shortened Tc regardless of the sides, suggesting that high-acceleration SV test can reveal the impaired velocity storage system in patients with vestibular neuritis more frequently than low-acceleration SV test.

Bisphosphonates-related osteonecrosis of the jaw in Korea: a preliminary report

OBJECTIVES: Bisphosphonates (BP) are widely used in medicine for inhibiting bone resorption; however bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a major side effect of BP. To date, there have been no specific reports on the incidence of BRONJ among Koreans. This study investigated the preliminary results from a nationwide survey of BRONJ in the Departments of Oral and Maxillofacial Surgery (OMFS) at individual training hospitals. MATERIALS AND METHODS: A total of 15 OMFS departments (10 from dental schools, 4 from medical schools, and 1 from a dental hospital) participated in a multi-centric survey. This study assessed every BRONJ case diagnosed between January 2010 and December 2010. The patient age and BP type were evaluated. RESULTS: A total of 254 BRONJ cases were collected. The majority of BRONJ cases were associated with oral BP therapy, while 21.8% of the cases were associated with intravenous administration. Alendronate was the drug most frequently related to BRONJ (59.2% of cases), followed by risedronate (14.3%) and zolendronate (17.0%). The average age of BRONJ patients was 70.0+/-10.1 years, with a range of 38-88 years of age. With the number of BP patients in Korea reported to be around 600,000 in 2008, the estimated incidence of BRONJ is at least 0.04% or 1 per 2,300 BP patients. CONCLUSION: The results suggest that the estimated incidence of BRONJ in Korea is higher than the incidence of other countries. Future prospective studies should be carried out to investigate the exact epidemiological characteristics of BRONJ in Korea.

Bisphosphonates-related osteonecrosis of the jaw in Korea: a preliminary report

OBJECTIVES: Bisphosphonates (BP) are widely used in medicine for inhibiting bone resorption; however bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a major side effect of BP. To date, there have been no specific reports on the incidence of BRONJ among Koreans. This study investigated the preliminary results from a nationwide survey of BRONJ in the Departments of Oral and Maxillofacial Surgery (OMFS) at individual training hospitals. MATERIALS AND METHODS: A total of 15 OMFS departments (10 from dental schools, 4 from medical schools, and 1 from a dental hospital) participated in a multi-centric survey. This study assessed every BRONJ case diagnosed between January 2010 and December 2010. The patient age and BP type were evaluated. RESULTS: A total of 254 BRONJ cases were collected. The majority of BRONJ cases were associated with oral BP therapy, while 21.8% of the cases were associated with intravenous administration. Alendronate was the drug most frequently related to BRONJ (59.2% of cases), followed by risedronate (14.3%) and zolendronate (17.0%). The average age of BRONJ patients was 70.0+/-10.1 years, with a range of 38-88 years of age. With the number of BP patients in Korea reported to be around 600,000 in 2008, the estimated incidence of BRONJ is at least 0.04% or 1 per 2,300 BP patients. CONCLUSION: The results suggest that the estimated incidence of BRONJ in Korea is higher than the incidence of other countries. Future prospective studies should be carried out to investigate the exact epidemiological characteristics of BRONJ in Korea.

Study of a "wing-type" implant on stress distribution and bone resorption at the alveolar crest

OBJECTIVES: Implants connect the internal body to its external structure, and is mainly supported by alveolar bone. Stable osseointegration is therefore required when implants are inserted into bone to retain structural integrity. In this paper, we present an implant with a "wing" design on its area. This type of implant improved stress distribution patterns and promoted changes in bone remodeling. MATERIALS AND METHODS: Finite element analysis was performed on two types of implants. One implant was designed to have wings on its cervical area, and the other was a general root form type. On each implant, tensile and compressive forces (30 N/m2, 35 N/m2, 40 N/m2, and 45 N/m2) were loaded in the vertical direction. Stress distribution and displacement were subsequently measured. RESULTS: The maximum stresses measured for the compressive forces of the wing-type implant were 21.5979 N/m2, 25.1974 N/m2, 29.7971 N/m2, and 32.3967 N/m2 when 30 N/m2, 35 N/m2, 40 N/m2, and 45 N/m2 were loaded, respectively. The maximum stresses measured for the root form type were 23.0442 N/m2, 26.9950 N/m2, 30.7257 N/m2, and 34.5584 N/m2 when 30 N/m2, 35 N/m2, 40 N/m2, and 45 N/m2 were loaded, respectively. Thus, the maximum stresses measured for the tensile force of the root form implant were significantly higher (about three times greater) than the wing-type implant. The displacement of each implant showed no significant difference. Modifying the design of cervical implants improves the strength of bone structure surrounding these implants. In this study, we used the wing-type cervical design to reduce both compressive and tensile distribution forces loaded onto the surrounding structures. In future studies, we will optimize implant length and placement to improve results. CONCLUSION: 1. Changing the cervical design of implants improves stress distribution to the surrounding bone. 2. The wing-type implant yielded better results, in terms of stress distribution, than the former root-type implant.

Evaluation of Effect of Silvernanoparticle Treated Implant on Bone Formation

Effect of Combination Graft of Choukroun's Platelet-rich-fibrin with Silk Fibroin Powder in the Peri-implant Defects

Switching Genioplasty - a New Genioplasty Technique in Order to Resolve Asymmetry of Chin Area: Case Report

Blood-Brain Barrier Experiments with Clinical Magnetic Resonance Imaging and an Immunohistochemical Study

OBJECTIVE: The purpose of study was to evaluate the feasibility of brain magnetic resonance (MR) images of the rat obtained using a 1.5T MR machine in several blood-brain barrier (BBB) experiments. METHODS: Male Sprague-Dawley rats were used. MR images were obtained using a clinical 1.5T MR machine. A microcatheter was introduced via the femoral artery to the carotid artery. Normal saline (group 1, n = 4), clotted autologous blood (group 2, n = 4), triolein emulsion (group 3, n = 4), and oleic acid emulsion (group 4, n = 4) were infused into the carotid artery through a microcatheter. Conventional and diffusion-weighted images, the apparent coefficient map, perfusion-weighted images, and contrast-enhanced MR images were obtained. Brain tissue was obtained and triphenyltetrazolium chloride (TTC) staining was performed in group 2. Fluorescein isothiocyanate (FITC)-labeled dextran images and endothelial barrier antigen (EBA) studies were performed in group 4. RESULTS: The MR images in group 1 were of good quality. The MR images in group 2 revealed typical findings of acute cerebral infarction. Perfusion defects were noted on the perfusion-weighted images. The MR images in group 3 showed vasogenic edema and contrast enhancement, representing vascular damage. The rats in group 4 had vasogenic edema on the MR images and leakage of dextran on the FITC-labeled dextran image, representing increased vascular permeability. The immune reaction was decreased on the EBA study. CONCLUSION: Clinical 1.5T MR images using a rat depicted many informative results in the present study. These results can be used in further researches of the BBB using combined clinical MR machines and immunohistochemical examinations.