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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.

Objectives: The purpose of this study was to perform a three-dimensional analysis on the pharyngeal airway of supine patients who have undergone mandibular setback surgery, using multislice computed tomography (MSCT). We also measured the respiratory disturbance index pre- and post-surgery, using a portable sleep monitor. Materials and Methods: The subjects included two males and nine females who were diagnosed with mandibular prognathism at Hiroshima University Hospital and were scheduled to undergo the bilateral sagittal split osteotomy. Using a CT scanner, baseline MSCT images were obtained from the subjects before surgery for morphological analysis, and then the two further scans were obtained after mandibular setback surgery. All patients were provided with at-hoeme sleep monitor to use it both at baseline and approximately 1 year after surgery. Results: Middle and epiglottis pharyngeal space and cross-sectional area were significantly decreased immediately after setback surgery, but did not change further over the 1-year period. Mandibular setback was not associated with the development of sleep breathing disorder (SBD) during the 1-year follow-up period. Conclusion: We found no evidence that the reduction in the pharyngeal airway space immediately after mandibular setback surgery recovered significantly during the follow-up period, although mandibular setback was not associated with development of SBD.

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.

Introduction: 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 athome 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

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.

降圧作用を有する鶏コラーゲン加水分解物（C-COP）を健常人に摂取させ，C-COPの血中動態およびアンジオテンシン変換酵素（ACE）阻害活性との関連性について検討した．体重60kgあたり25gのC-COPをヒトに単回摂取させた場合，血中に遊離ヒドロキプロリン（Hyp）とともに，ペプチド型のHypも確認された．血中のペプチド型Hyp量は，2時間後（91.1μmol/L）に最大となった．摂取2時間後の血中からPro-Hyp, Leu-Hyp, Pro-Hyp-Gly, Phe-Hyp, Ala-Hyp, Hyp-Gly, Glu-Hyp-Gly, Ala-Hyp-Gly, Ser-Hyp-GlyのHyp含むペプチドが確認された．血中ペプチドは，ACEに対する阻害活性を有しており，Ala-Hyp（IC50 : 0.177mmol/L）の活性がもっとも高かった．以上より，C-COPの降圧作用は，血中ペプチドによるACE阻害が作用機序であると考えられた．

本研究では，鶏コラーゲンペプチド中に含まれ，強いACE阻害活性を有するオクタペプチドのSHRへの血圧降下作用および消化酵素による分解性について検討した．（1） オクタペプチドをSHRに4.5mg/kg体重で単回投与した結果，SHRの収縮期血圧値を有意に低下させた．（2） 試験管レベルでオクタペプチドは，ペプシンおよび，トリプシン/キモトリプシン，小腸上皮酵素に対して難消化性を示し，そのACE阻害活性は維持されていた．以上の結果から，鶏コラーゲンペプチドに含まれるオクタペプチドは，in vitroでのACE阻害活性を持つだけでなく，SHRの血圧降下作用を示すことが確認された．

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.

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.

最近5年間に当科で初治療を行った下咽頭癌49例のうち食道癌との重複例16例について検討した。食道癌治療後に下咽頭癌が見つかった9例中6例は当院で経過観察されており，そのほとんどは早期癌で発見され喉頭保存治療が可能であった。3年累積生存率は62%で，死亡例5例中3例が食道癌死であった。下咽頭癌による死亡例はなかった。生存者11例中，発声機能が喪失したもの7例，気管カニューレ装着中1例，重篤な嚥下障害が残ったもの6例であった。予後には食道癌の治療が最も関与し，両癌の治療で嚥下障害が増大する傾向が示された。

患側の声門上部を広範に合併切除する咽喉頭部分切除において, 有茎の骨筋弁と遊離前腕皮弁で声門上部と下咽頭を再建する手術を考案した。胸骨舌骨筋を茎とした舌骨半部で喉頭蓋の部分欠損を再建するとともにその有茎筋弁で披裂部の隆起を形成した後に, 前腕皮弁を用いて声門上部を被覆し下咽頭腔を再建するという方法である。これまでに下咽頭癌5例に行い, 術後の喉頭機能を評価した。全例が気切口を閉鎖でき音声が温存された。5例中4例はほぼ正常な声であった。嚥下機能は2例がほぼ正常, 2例が軽度障害, 1例が高度障害であり, 両側頸部郭清や下咽頭腔の全周切除を要さず, 術前に通過障害がないT2梨状陥凹癌例が良好な嚥下機能を示した。以上より, 咽喉頭部分切除における声門上部再建術は喉頭機能を温存するのに有用な手術方法であると考えられた。

We report two cases of thyroid hemiagenesis. The first case was a 49-year-old female with hemiagenesis of the left thyroid lobe and the second case was 75-year-old female with goiter in the right thyroid lobe and a defect of the left lobe. In both patients the thyroid function tests were euthyroid, and US, CT and 99mTcO4-scintigraphy were useful for the diagnosis of thyriod hemiagenesis Both patients are being conservatively managed without surgery.

Chicken collagen hydrolysate was given to 15 mildly hypertensive subjects for 4 weeks. Blood pressure was significantly decreased by 11.8 mmHg (P

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.

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.

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.

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.

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.

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 mm x 5 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.

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.

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 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.

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.