Dental and Occlusal Changes during Mandibular Advancement Device Therapy in Japanese Patients with Obstructive Sleep Apnea: Four Years Follow-Up.

Dentoskeletal changes caused by the long-term use of mandibular advancement devices (MADs) for obstructive sleep apnea (OSA) have rarely been investigated in Japan. We assessed the long-term dentofacial morphological changes in 15 Japanese patients with OSA who used two-piece MADs for an average of 4 years. Lateral cephalography analyses were performed initially and 4 years later (T1). The dental assessment included overjet, overbite, upper anterior facial height, lower anterior facial height (LAFH), total anterior facial height (TAFH), and anterior facial height ratio. Dental casts were digitized and analyzed using a 3D scanner. Changes in the apnea hypopnea index (AHI) and other sleep-assessment indices were assessed using polysomnography and out-of-center sleep testing. Radiography revealed lingual inclination of the maxillary central incisors, labial inclination of the mandibular central incisors, clockwise rotation of the mandible, and an increase in the TAFH and LAFH at T1. In the dental cast analysis, the diameter width and palatal depth tended to decrease and increase, respectively. There was a significant decrease in the AHI and other sleep assessment indices after using the MADs for approximately 4 years. However, these findings do not provide a strong basis and should be interpreted cautiously. Future studies should have a larger sample size and should further investigate the long-term occlusal and dental changes caused by the original MADs in Japanese patients with OSA.

Changes in airway patency and sleep-breathing in healthy skeletal Class II children undergoing functional activator therapy.

Purpose: Several studies agree that an abnormal maxilla-mandible relationship correlates better as an Obstructive Sleep Apnea (OSA) predictor, rather than obesity. One of the orthodontic therapies recommended for this kind of craniofacial deformity is to advance the mandible forward with an orthodontic activator, therefore, the aim of this study is to determine if healthy children that use this appliance experience a widening of the upper airway as well as an improvement in their sleep-breathing patterns. Materials and methods: 39 healthy children, 20 for activator group (10 boys and 10 girls, 4 mean age 10.9 + 0.9; BMI 16.2 + 1.4), 19 for control group (13 boys and 6 girls, mean age 5 9.8 + 1.4; BMI 17.6 + 2.1) participated in this study. They were required to submit 2 lateral cephalometric radiographs both at initial and final stages of evaluation, and finally three at- home sleep-breathing monitoring results for the activator group and one for the control group. Results: After radiographic evaluation, it was found that children in the activator group experienced an increase in all measured variables. After evaluation with the sleep monitor, an improvement of sleep-breathing was found in children from the activator group (p<0.05). Conclusion: The activator not only provides a harmonious occlusion and proper development of the mandible, but it also helps improve the quality of sleep-breathing through widening of the upper airway and reducing the number of disordered breathing events in children that undergo this therapy.

Masticatory Function Assessment of Adult Patients With Cleft Lip and Palate After Orthodontic Treatment.

OBJECTIVE: To determine whether orthodontically treated patients with cleft lip and palate (CLP) possess a different masticatory function than those of untreated patients with normal occlusion. DESIGN: Occlusal contact area, occlusal force, as well as masseter and anterior temporal muscular activity were measured during maximum voluntary clenching (MVC) tests. Mandibular left and right lateral movements during mastication were also assessed. To further elucidate the nature of masticatory function, especially to determine the rate of abnormal jaw movement patterns, a parametric error index (EI) was set. Finally, masticatory efficiency was evaluated with a glucose sensitive measuring device. PARTICIPANTS: Fifteen patients with CLP who had previously completed the orthodontic treatments required to achieve an acceptable and more harmonious occlusion accepted to volunteer in this study along with 21 untreated patients who already possessed a normal occlusion. RESULTS: Patients with CLP showed a significantly lower occlusal force, reduced occlusal contact area, and decreased masticatory efficiency as well as significantly higher EI value when compared with controls. However, there was no significant difference when analyzing muscle activity, although masticatory efficiency was significantly different between the 2 groups. Despite this result, the scores obtained by the patients with CLP in the masticatory efficiency tests were still in the normal range. CONCLUSIONS: Orthodontic treatment for adult patients with CLP provides a satisfactory result for the patients' masticatory ability albeit significantly less ideal compared with untreated patients with normal occlusion.

Multislice Computed Tomography Assessment of Airway Patency Changes Associated with Mandibular Advancement Appliance Therapy in Supine Patients with Obstructive Sleep Apnea.

The purpose of the present study was to measure the regional effects of the mandibular advancement appliance (MAA) on the upper airway of supine subjects with obstructive sleep apnea (OSA) using multislice computed tomography (MSCT). The subjects included 8 males and 5 females who were diagnosed with mild to moderate OSA and were referred to the Orthodontic Clinic of Hiroshima University Hospital, where they underwent MAA therapy. Using a CT scanner, baseline MSCT images were obtained from the subjects without the MAA for morphological analysis, and then the experimental images were obtained while wearing the MAA. To measure the anteroposterior diameter, width, and cross-sectional area of the oropharynx region of interest (ROI), five distance variables were first defined on each multiplanar reconstruction (MPR) image using OsiriX. Additionally, the volumes of the upper airway, bony hard tissue, and soft tissue (soft palate and tongue) in the oro-hypopharyngeal region were measured. In most of the assessed airway size variables, significant increases in the anteroposterior diameter and width were observed after MAA therapy. Regarding the upper airway cross-sectional area, all the upper airway size variables exhibited significant increases. In the volumetric analysis, a significant increase was observed in airway volume, whereas the soft tissue volume in the oro-hypopharyngeal region did not show the significant decrease after MMA therapy. However, from a different point of view, the volumes of the upper airway and soft tissue significantly increased and decreased, respectively, as demonstrated by the calculated ratio for the oro-hypopharyngeal region. We demonstrated that the proportional size of the soft tissue volume, i.e., the soft palate and tongue in the oro-hypopharyngeal region, significantly decreased during use of an MAA. This forward displacement of the soft tissue thereby increases the retroglossal airway space (except the nasopharynx) three-dimensionally.

Influence of Oral Appliances for Mandibular Advancement on Dentitions Using a Strain Gauge Analysis: A Pilot Study.

Introduction. This study aimed to evaluate the influence of oral appliances (OAs) on dentition using a strain gauge analysis. Materials/Methods. Eight volunteers, who were mild snorers, participated in this study. OAs were individually constructed, and advancement was defined as two-thirds of the maximum mandibular advancement. Strain gauges were mounted on the right first molar and central incisor of both the upper and lower arches. After OA use, two measurement sessions (short- and long-term) were performed. Results. Compressive strain on the labial surface was significantly larger than the stretching strain on the lingual surface on U1. On L1, the stretching strain on the labial surface was significantly larger than the compressive strain on the lingual surface. Comparing the upper and lower teeth, the stretching strain was significantly greater on L1 than on U1 in both test sessions. Moreover, the stretching strain was significantly larger on U6 than on L6. Conclusion. OA side effects, such as forcing on the incisors, might be repeated every night. In this way, permanent occlusal changes, such as labial tipping of L1, may occur, followed by lingual tipping of U1 and buccal and lingual movements of the U6 and L6, respectively.

Antihypertensive effects and endothelial progenitor cell activation by intake of chicken collagen hydrolysate in pre- and mild-hypertension.

Chicken collagen hydrolysate was given to 15 mildly hypertensive subjects for 4 weeks. Blood pressure was significantly decreased by 11.8 mmHg (P<0.01). A reduction in plasma renin activity was observed in blood test after intake. A colony assay of endothelial progenitor cells in blood samples from non-smokers revealed an approximately 30% increase in the number of colonies.

Effect of Prolyl-hydroxyproline (Pro-Hyp), a food-derived collagen peptide in human blood, on growth of fibroblasts from mouse skin.

We examined the effect of prolyl-hydroxyproline (Pro-Hyp), which occurs in human peripheral blood after ingestion of collagen peptide, on the migration and growth of mouse skin fibroblasts. Mouse skin discs were cultured on a 24-well plastic plate in a fetal bovine serum (FBS)-free medium. Addition of Pro-Hyp (200 nmol/mL) significantly increased the number of fibroblasts migrating from the skin to the plate after incubation for 72 h. This effect of Pro-Hyp was abolished by the addition of mitomycin C. The fibroblasts that had migrated from the mouse skin were collected and cultured on collagen gel. The growth of fibroblasts on the collagen gel was suppressed even in the presence of FBS, while rapid fibroblast growth was observed on the plastic plate. Addition of Pro-Hyp (0-1000 nmol/mL) to the medium containing 10% FBS enhanced the growth of fibroblasts on the collagen gel in a dose-dependent manner. These results suggest that Pro-Hyp might stimulate the growth of fibroblasts in the skin and consequently increase the number of fibroblasts migrating from the skin.

Angiotensin I-converting enzyme-inhibitory peptides obtained from chicken collagen hydrolysate.

In this study, collagen extracted from chicken legs (which are the yellow keratin parts containing a nail) was hydrolyzed with various enzymes, and the angiotensin I-converting enzyme (ACE)-inhibitory activity of each hydrolysate was determined. The hydrolysate by treatment with an Aspergillus species-derived enzyme had the highest activity (IC 50 = 260 microg/mL). The fraction of this hydrolysate obtained by ultrafiltration with a molecular-weight cutoff of 3000 Da (low fraction) had a stronger activity (IC 50 = 130 microg/mL) than the fractionated one. This fraction was further fractionated by HPLC, and the peptides in the fraction with high ACE-inhibitory activity were identified. The amino acid sequences of the four peptides were identified using a protein sequencer. These peptides were synthesized to confirm their ACE-inhibitory activities; this showed that peptides with a Gly-Ala-Hyp-Gly-Leu-Hyp-Gly-Pro sequence had the highest activity (IC 50 = 29 microM). When the low fraction was administered to spontaneous hypertensive rats, a decrease in their blood pressure was observed after 2 h of administration, and a significant decrease in blood pressure (-50 mmHg) was observed after 6 h. Moreover, long-term administration studies indicated that the low fraction showed a significant suppression of increased blood pressure.

Identification of food-derived bioactive peptides in blood and other biological samples.

Recent studies have demonstrated the presence of food-derived peptides in human blood after ingestion of enzymatic hydrolysates of food proteins, while most peptides in food are degraded into amino acids during digestion and absorption. To capture and clarify the food-derived peptides in blood, solid-phase extraction (SPE) using a mini-spin column packed with a strong cation exchanger was developed. This technique allows the use of a nonvolatile acid such as trichloroacetic acid, a strong protein denaturant, for the deproteinizing procedure. To improve resolution of hydrophilic peptide and increase specificity and sensitivity in the detection of peptide by reversed-phase high-performance liquid chromatography (RP-HPLC) after subfractionation by size-exclusion chromatography (SEC), peptides are derivatized with phenyl isothiocyanate. The resultant phenyl thiocarbamyl (PTC)-peptides can be resolved with high resolution and sensitivity by RP-HPLC. By comparing chromatograms of PTC derivatives from blood before and after ingestion of a peptide sample, food-derived peptide can be detected. The isolated PTC-peptide can be applied to a peptide sequencer based on the Edman degradation reaction.

Royal jelly peptides inhibit lipid peroxidation in vitro and in vivo.

Royal jelly peptides (RJPx) isolated from hydrolysates of water-soluble royal jelly proteins prepared with protease P exhibited significantly stronger hydroxyl radical-scavenging activity (p<0.001), and antioxidant activity against lipid peroxidation (LPO, p<0.001), than did water-soluble royal jelly protein (WSRJP) in vitro. We also investigated the in vivo antioxidant activity of RJPx against ferric nitrilotriacetate (Fe-NTA)-induced LPO. Male Wistar rats were divided into a control group (Group C), an Fe-NTA group (Group Fe), and an Fe-NTA with RJPx group (Group Fe+R). Rats in Group Fe+R were fed RJPx (2 g/kg body weight) daily for 5 wk. Fe-NTA (8 mg Fe/kg body weight) was then intraperitoneally injected, and serum lipid levels were examined 2 h later. Serum total cholesterol (TC) levels were lower (p<0.05) while low-density lipoprotein (LDL) and LPO were significantly higher (p<0.01) in Group Fe than in Group C. TC (p<0.05) and LPO levels (p<0.01) were lower in Group Fe+R than in Group Fe. Our data suggest that RJPx may inhibit LPO both in vitro and in vivo.

Granular cell tumor of hypopharynx: report of a rare case.

Granular cell tumor is a rare tumor, probably of Schwann cell origin. The head and neck are most frequently affected, but hypopharyngeal lesion is extremely rare. We report the seventh case of hypopharyngeal granular cell tumor. Immunohistochemical staining for S100 protein is helpful for the correct diagnosis. There is some possibility of malignancy despite absence of histological evidence, thus the treatment is exclusively surgical resection. The microlaryngoscopic approach is feasible for hypopharyngeal lesions in most cases. Recurrence can occur even after appropriate resection.

Comparison of quantity and structures of hydroxyproline-containing peptides in human blood after oral ingestion of gelatin hydrolysates from different sources.

We compared quantity and structures of food-derived gelatin hydrolysates in human blood from three sources of type I collagen in a single blind crossover study. Five healthy male volunteers ingested type I gelatin hydrolysates from fish scale, fish skin, or porcine skin after 12 h of fasting. Amounts of free form Hyp and Hyp-containing peptide were measured over a 24-h period. Hyp-containing peptides comprised approximately 30% of all detected Hyp. The total area under the concentration-time curve of the fish scale group was significantly higher than that of the porcine skin group. Pro-Hyp was a major constituent of Hyp-containing peptides. Ala-Hyp, Leu-Hyp, Ile-Hyp, Phe-Hyp, and Pro-Hyp-Gly were detected only with fish scale or fish skin gelatin hydrolysates. Ala-Hyp-Gly and Ser-Hyp-Gly were detected only with fish scale gelatin hydrolysate. The quantity and structure of Hyp-containing peptides in human blood after oral administration of gelatin hydrolysate depends on the gelatin source.

Improvement in isolation and identification of food-derived peptides in human plasma based on precolumn derivatization of peptides with phenyl isothiocyanate.

For the isolation and detection of food-derived peptides in blood, an approach based on the derivatization of peptides with phenyl isothiocyanate (PITC) was developed. This approach allows hydrophilic peptides to be resolved and specifically detected by reversed-phase (RP) HPLC. For the rapid capturing and clarification of peptides in human plasma, solid-phase extraction by using a mini spin column (5 mmx5 mm) packed with a strong cation exchanger was used. The clarified peptide fraction was further fractionated by size-exclusion chromatography (SEC). The peptides in the SEC fractions were derivatized with PITC, and the derivatives were resolved by RP-HPLC by using an ammonium acetate buffer or a trifluoroacetic acid system. An automatic peptide sequencer based on Edman degradation with a modified program can directly analyze the resolved derivatives. Some synthetic peptides and food-derived peptides in human plasma were successfully isolated and identified by this approach.

Cochlear protection by local insulin-like growth factor-1 application using biodegradable hydrogel.

OBJECTIVE: The aim of this experimental study was to examine the potential of local recombinant human insulin-like growth factor-1 (rhIGF-1) application through a biodegradable hydrogel for the treatment of cochleae. METHODS: A hydrogel immersed with rhIGF-1 was placed on the round window membrane of Sprague-Dawley rats while a hydrogel immersed with physiological saline was applied to control animals. On day 3 after drug application, the animals were exposed to white noise at 120 dB sound pressure level (SPL) for 2 hours. Cochlear function was monitored using measurements of auditory brain stem responses (ABRs) at frequencies of 8, 16, and 32 kHz. The temporal bones were collected 7 or 30 days after noise exposure and the loss of hair cells was quantitatively analyzed. RESULTS: Local rhIGF-1 treatment significantly reduced the elevation of ABR thresholds on days 7 and 30 after noise exposure. Histologic analysis revealed that local rhIGF-1 treatment significantly prohibited the loss of outer hair cells. CONCLUSIONS: These findings demonstrate that local IGF-1 application through the biodegradable hydrogel has the potential for protection of cochleae from noise trauma.

Novel strategy for treatment of inner ears using a biodegradable gel.

OBJECTIVE: The present study aimed to evaluate the efficacy of a biodegradable hydrogel as a drug-delivery medium for the inner ear. Brain-derived neurotrophic factor (BDNF) was chosen as the agent to be administered. METHOD: First, we used an enzyme-linked immunosorbent assay to measure BDNF concentrations in the cochlear fluid after placing a hydrogel containing this agent onto the round-window membrane of the ear. Second, the functional and histologic protection of the auditory primary neurons (spiral ganglion neurons [SGNs]) by BDNF applied through the hydrogel was examined using an animal model of SGN degeneration. RESULTS: The results revealed sustained delivery of BDNF into the cochlear fluid by way of the hydrogel. Second, the functional and histologic protection of the auditory primary neurons (SGNs) by BDNF applied through the hydrogel was examined using an animal model of SGN degeneration. The measurement of electrically evoked auditory-brainstem responses demonstrated that BDNF delivered by way of the hydrogel significantly reduced the threshold elevation. Immunohistochemistry for neurofilament 200 kD demonstrated increased survival of SGNs because of BDNF application through the hydrogel. CONCLUSION: These findings indicate that biodegradable hydrogels can be used for drug delivery to the inner ear.

Identification of food-derived collagen peptides in human blood after oral ingestion of gelatin hydrolysates.

In the present study, we identified several food-derived collagen peptides in human blood after oral ingestion of some gelatin hydrolysates. Healthy human volunteers ingested the gelatin hydrolysates (9.4-23 g) from porcine skin, chicken feet, and cartilage after 12 h of fasting. Negligible amounts of the peptide form of hydroxyproline (Hyp) were observed in human blood before the ingestion. After the oral ingestion, the peptide form of Hyp significantly increased and reached a maximum level (20-60 nmol/mL of plasma) after 1-2 h and then decreased to half of the maximum level at 4 h after the ingestion. Major constituents of food-derived collagen peptides in human serum and plasma were identified as Pro-Hyp. In addition, small but significant amounts of Ala-Hyp, Ala-Hyp-Gly, Pro-Hyp-Gly, Leu-Hyp, Ile-Hyp, and Phe-Hyp were contained.

Serofendic acid promotes survival of auditory hair cells and neurons of mice.

Serofendic acid is a newly discovered neuroprotective substance derived from fetal calf serum. It has previously been shown to protect cortical neurons from the cytotoxicity of nitric oxide, glutamate and oxygen species. In the present study, we examined the protective effects of serofendic acid on auditory hair cells exposed to aminoglycoside toxicity using explant cultures of mouse auditory epithelia. We also determined the effect of serofendic acid on auditory neurons experiencing neurotrophin deprivation using primary cultures of mouse spiral ganglion neurons. Supplementation with serofendic acid significantly promoted the survival of auditory hair cells and neurons, and its protective effects were stronger than those of the caspase inhibitor z-VAD-fmk. These findings demonstrate the great potential of serofendic acid for protection of the auditory system.

Nestin expression in the developing rat cochlea sensory epithelia.

An intermediate filament (IF), nestin, is used as an immature cell marker because nestin occurs in neural progenitors during early development. Recent cell culture studies have indicated that proliferating otic progenitor cells express nestin in vitro. However, localization of nestin in the developing inner ear has not yet been clarified. In this study, the ontogenetical expression of nestin epitopes in the rat cochlea was examined immunohistochemically. Sensory epithelial cells in the rat Corti organ (e.g. hair cells and support cells) transiently demonstrated immunoreactivity for nestin during the late embryonic period. After birth, nestin expression in the sensory epithelia disappeared gradually. The findings of this study indicate that the expression of nestin epitopes in the developing cochlea is linked with the plasticities of sensory epithelial cells, such as proliferation or differentiation.

Penetrating injury to the pharynx by a toothbrush in a pediatric patient: a case report.

Penetrating injury of the pharynx is rare, but it can cause serious sequelae in children. A 12-month-old boy was impaled with a toothbrush in the retropharyngeal space after falling from a baby-bed. The point of the toothbrush was embedded beside the carotid artery and was removed by endoscopic surgical technique. The patient was discharged without neurological complication or abscess formation. We present a rare case of a penetrating injury by a toothbrush and discuss such injuries.