Practical guide for the diagnosis and management of primary ciliary dyskinesia.

OBJECTIVE: Primary ciliary dyskinesia (PCD) is a relatively rare genetic disorder that affects approximately 1 in 20,000 people. Approximately 50 genes are currently known to cause PCD. In light of differences in causative genes and the medical system in Japan compared with other countries, a practical guide was needed for the diagnosis and management of Japanese PCD patients. METHODS: An ad hoc academic committee was organized under the Japanese Rhinologic Society to produce a practical guide, with participation by committee members from several academic societies in Japan. The practical guide including diagnostic criteria for PCD was approved by the Japanese Rhinologic Society, Japanese Society of Otolaryngology-Head and Neck Surgery, Japanese Respiratory Society, and Japanese Society of Pediatric Pulmonology. RESULTS: The diagnostic criteria for PCD consist of six clinical features, six laboratory findings, differential diagnosis, and genetic testing. The diagnosis of PCD is categorized as definite, probable, or possible PCD based on a combination of the four items above. Diagnosis of definite PCD requires exclusion of cystic fibrosis and primary immunodeficiency, at least one of the six clinical features, and a positive result for at least one of the following: (1) Class 1 defect on electron microscopy of cilia, (2) pathogenic or likely pathogenic variants in a PCD-related gene, or (3) impairment of ciliary motility that can be repaired by correcting the causative gene variants in iPS cells established from the patient's peripheral blood cells. CONCLUSION: This practical guide provides clinicians with useful information for the diagnosis and management of PCD in Japan.

Effect of intranasal administration of concentrated growth factors on regeneration of the olfactory epithelium in an olfactory dysfunction-induced rat model.

OBJECTIVE: The development of treatments that promote the regenerative capacity of the olfactory epithelium (OE) is desirable. This study aimed to evaluate the effects of intranasal administration of concentrated growth factors (CGFs) in a rat model of olfactory dysfunction. STUDY DESIGN: Animal study. METHODS: Nineteen male rats were used. Fourteen olfactory dysfunction models were created by intraperitoneal administration of 3-methylindole. We randomly divided the rats from the olfactory dysfunction model after 1 week into the CGF or saline group; CGFs were administered to seven animals and saline to seven animals. Behavioral assessments using the avoidance test were conducted until day 28 after CGF/saline administration. On day 28, histological evaluation was conducted to determine olfactory epithelial thickness and the olfactory marker protein (OMP)-positive cell count. Five animals were intraperitoneally injected with saline as the control group. RESULTS: The avoidance rate remained decreased until 28 days after CGF/saline administration, and there was no significant difference between the two groups. Olfactory epithelial thicknesses on day 28 were 38.64 ± 3.17 µm and 32.84 ± 4.50 µm in the CGF and saline groups, respectively. OE thickness was significantly thicker in the CGF group than in the saline group (P = 0.013). The numbers of OMP-positive cells were 40.29 ± 9.77/1.0 × 104 µm2 and 31.00 ± 3.69/1.0 × 104 µm2 in the CGF and saline groups, respectively. The number of OMP+ cells in the CGF group was significantly increased compared with that in the saline group (P = 0.009). Both groups showed no improvement compared with the control group (OE thickness: 54.08 ± 3.36 µm; OMP+ cell count: 56.90 ± 9.91/1.0 × 104 µm2). CONCLUSIONS: The CGF group showed improved olfactory epithelial thickness and OMP-positive cell numbers compared with that in the saline group.

Clinical utility of new bone imaging using zero-echo-time sequence in neurosurgical procedures: Can zero-echo-time be used in clinical practice in neurosurgery?

PURPOSE: The purpose of this study was to evaluate the clinical usefulness of zero-echo-time (ZTE)-based magnetic resonance imaging (MRI) in planning the optimum surgical approach and applying ZTE for anatomical guidance during transcranial surgery. METHODS: Eleven of 26 patients who underwent transcranial surgery and carotid endarterectomy and in whom ZTE-based MRI and magnetic resonance angiography (MRA) data were obtained were analyzed by creating ZTE/MRA fusion images and 3D ZTE-based MRI models. We examined whether these images and models can be substituted for computed tomography imaging for neurosurgical procedures. Furthermore, the clinical usability of the 3D ZTE-based MRI models was evaluated by comparing them with actual surgical views. RESULTS: Zero-echo-time/MRA fusion images and 3D ZTE-based MRI models clearly illustrated the cranial and intracranial morphology without radiation exposure or the use of iodinated contrast medium. The models allowed determination of the optimum surgical approach to cerebral aneurysms, brain tumors near the brain surface, and cervical internal carotid artery stenosis by visualizing the relationship of lesions with adjacent bone structures. However, ZTE-based MRI did not provide useful information for surgery for skull base lesions such as vestibular schwannoma because bone structures of the skull base often include air components, which cause signal disturbance in MRI. CONCLUSIONS: Zero-echo-time sequences on MRI allowed distinct visualization of not only bone but also vital structures around the lesion. This technology has low invasiveness for patients and was useful for preoperative planning and guidance of the optimum approach during surgery in a subset of neurosurgical diseases.

Development of a proficiency-based training curriculum for beginners in endoscopic endonasal surgery.

OBJECTIVE: Precise endoscopic skills are critical for endoscopic endonasal surgery (EES) to ensure patient safety, as well as to succeed as a surgeon. Among these skills, basic skills such as hand-eye coordination and bimanual dexterity are the most important skills for novice surgeons. However, there is no proficiency-based training for the basic skills in EES. In this study, we aimed to develop a proficiency-based training curriculum for beginners in EES using tractable tasks and to assess the curriculum's validity and educational benefits. METHODS: Training tasks for basic surgical skills of EES were created by experts, using a low-cost and simple simulator. Subsequently, a proficiency-based training curriculum was developed through a preliminary study. The face and content validity of the curriculum was evaluated by expert surgeons. The construct validity was confirmed by comparing the scores of the medical students with those of the experts. In addition, the educational benefits of the curriculum were assessed by comparing the scores of the medical students before and after the implementation of the curriculum. RESULTS: A proficiency-based training curriculum using six tractable tasks was developed in the preliminary study. Replication of real surgical situation, camera navigation, and instrument operability under endoscopy were all highly appreciated (4.6, 4.6, and 4.8 out of 5 points, respectively), which indicates face validity. The content validity of the curriculum was demonstrated by the results of the questionnaire (4.4 out of 5 points). The curriculum was implemented by 12 medical students. The initial student scores were significantly lower than the expert scores (mean score: 61.9 vs. 100.0, p < 0.001), and each coefficient of variation of the student scores was higher than that of the expert scores (p < 0.01), supporting the construct validity of the curriculum. The mean student composite scores were statistically improved after the training (61.9 vs. 93.3, p < 0.0001). In addition, improvement of five other medical students' EES skills through this training curriculum was confirmed in cadaver dissection (1.7 vs. 3.7, p < 0.0001). CONCLUSION: The validity of the proficiency-based training curriculum developed through the preliminary study was established based on the questionnaire of experts and the difference between student and expert scores. In addition, the educational benefits were demonstrated by the students' learning curves. The low-cost and simple simulator seems appropriate as an entry model for beginners in EES, and this curriculum can provide rapid intervention and objective assessment of basic skills in EES.

Simultaneous combined endoscopic endonasal and transcranial surgery for giant pituitary adenomas: Tips and traps in operative indication and procedure.

OBJECTIVES: This retrospective analysis of patients treated with endoscopic endonasal transsphenoidal surgery (ETSS) alone or simultaneous combined surgery investigated imaging features suitable for surgical methods and pitfalls in simultaneous combined surgery for giant pituitary adenoma. PATIENTS AND METHODS: Ten patients with giant pituitary adenoma treated by ETSS alone or simultaneous combined endoscopic endonasal and transcranial surgery were enrolled. By analyzing tumor imaging features on magnetic resonance imaging (MRI), operative findings and clinical outcomes, we examined types of imaging features suitable for each surgical method. RESULTS: Four patients received ETSS alone and six patients underwent simultaneous combined endonasal and transcranial surgery. Four patients treated by ETSS alone and three patients treated by combined surgery had high resection rates and good outcomes. The remaining three patients with combined surgery achieved partial resection and visual deterioration in one patient. MRI features suitable for ETSS included an enlarged sella, upward tumor extension, and round surface, whereas those for combined surgery included normal/enlarged sella, anterior and/or unilateral tumor extension, and a multilobulated surface. Tumors extending extensively bilaterally or upward and encasing neurovascular structures could not be effectively resected even under combined surgery. CONCLUSION: Both ETSS alone and simultaneous combined endonasal and transcranial surgery showed good results for giant pituitary adenoma when the surgical methods matched suitable imaging features. Tumors with unilateral or anterior extension and a multilobulated surface were maximally resected without neurological deficit by combined surgery, but tumors showing extensive multi-directional extension and full encasement of neurovascular structures were not effectively resected even with combined surgery.

Exteriorization of Petrous Bone Cholesteatoma by Endonasal Endoscopic Approach: A Case Report.

A 61-year-old woman presented with diplopia and headache. The patient had a longstanding history of petrous bone cholesteatoma (PBC) on the left side and had undergone multiple surgeries to address it. Computed tomography (CT) revealed a radiolucent lesion with bony destruction in the left petrous apex. Magnetic resonance imaging of the lesion revealed a hypointense area on T1-weighted images and a hyperintense area on T2-weighted and abnormal diffusion-weighted images. A diagnosis of recurrent petrous apex cholesteatoma was made. The patient was treated by exteriorization using an endoscopic endonasal approach. The patient is in remission and doing well. The ideal treatment of PBC is complete excision, though exteriorization using an endoscopic endonasal approach is considered a second option when excision is not possible.

Tricks and traps of ICG endoscopy for effectively applying endoscopic transsphenoidal surgery to pituitary adenoma.

Differentiating tumor from normal pituitary gland is very important for achieving complete resection without complications in endoscopic endonasal transsphenoidal surgery (ETSS) for pituitary adenoma. To facilitate such surgery, we investigated the utility of indocyanine green (ICG) fluorescence endoscopy as a tool in ETSS. Twenty-four patients with pituitary adenoma were enrolled in the study and underwent ETSS using ICG endoscopy. After administering 12.5 mg of ICG twice an operation with an interval > 30 min, times from ICG administration to appearance of fluorescence on vital structures besides the tumor were measured. ICG endoscopy identified vital structures by the phasic appearance of fluorescent signals emitted at specific consecutive elapsed times. Elapsed times for internal carotid arteries did not differ according to tumor size. Conversely, as tumor size increased, elapsed times for normal pituitary gland were prolonged but those for the tumor were reduced. ICG endoscopy revealed a clear boundary between tumors and normal pituitary gland and enabled confirmation of no more tumor. ICG endoscopy could provide a useful tool for differentiating tumor from normal pituitary gland by evaluating elapsed times to fluorescence in each structure. This method enabled identification of the boundary between tumor and normal pituitary gland under conditions of a low-fluorescence background, resulting in complete tumor resection with ETSS. ICG endoscopy will contribute to improve the resection rate while preserving endocrinological functions in ETSS for pituitary adenoma.

Clinical features and endoscopic findings of granular cell tumor of the sellar region: A case report and review of the literature.

BACKGROUND: Granular cell tumor (GCT) of the sellar region is a rare tumor of the sellar and suprasellar regions that originate from the neurohypophysis. This tumor is very difficult to differentiate from other pituitary neoplasms, such as pituitary adenoma, pituicytoma, and spindle cell oncocytoma. We report a rare case of GCT arising from the posterior pituitary of the sellar region and suggest a useful indicator for accurate diagnosis and pitfalls for surgical procedures. CASE DESCRIPTION: A 42-year-old woman was admitted to our hospital with bitemporal hemianopsia. Neuroimaging showed a large pituitary tumor in the sellar and suprasellar regions with a hypointense part on T2-weighted magnetic resonance imaging, and the enhanced anterior pituitary gland was displaced anteriorly. Laboratory findings showed mild hyperprolactinemia. Subtotal resection of the tumor was achieved using an endoscopic endonasal transsphenoidal approach. Histological findings showed round or polygonal cells with abundant granular eosinophilic cytoplasm staining strongly for thyroid transcription factor 1. The tumor was, therefore, diagnosed as a GCT of the sellar region, belonging to tumors of the posterior pituitary. After surgery, visual impairment and anterior pituitary function were improved. Follow-up neuroimaging after 1 year showed no signs of recurrence. CONCLUSION: GCT of the sellar region is difficult to diagnose on routine neuroimaging. Therefore, accurate diagnosis requires careful identification of clinical signs, magnetic resonance imaging including hypointensity on T2-weighted imaging, and analysis of combined morphological and immunohistochemical studies.

Clinical utility of new three-dimensional model using a zero-echo-time sequence in endoscopic endonasal transsphenoidal surgery.

OBJECTIVES: Recognizing the anatomical orientation surrounding the sellar floor is crucial in endoscopic endonasal transsphenoidal surgery (ETSS). Zero-echo-time (ZTE) sequences were recently suggested for a new bone identification technique on magnetic resonance imaging (MRI). This study aimed to evaluate the clinical usefulness of three-dimensional (3D)-ZTE-based MRI models in providing anatomical guidance for ETSS. PATIENTS AND METHODS: ZTE-based MRI and magnetic resonance angiography (MRA) data from 15 consecutive patients with pituitary tumor treated between September 2018 and May 2019 were used to create 3D-MRI models. From these, the architecture surrounding the sellar floor, particularly anatomical relationships between tumors and internal carotid arteries (ICAs), was visualized to preoperatively plan surgical procedures. In addition, 3D-ZTE-based MRI models were compared to actual surgical views during ETSS to evaluate model applicability. RESULTS: These 3D-ZTE-based MRI models clearly demonstrated the morphology of the sellar floor and matched well with intraoperative views, including pituitary tumor, by successively eliminating sphenoidal structures. The models also permitted determination of the maximum marginal line of the opening of the sellar floor by presenting vital structures such as ICAs and tumors. With such 3D-MRI models, the surgeon could access the intracranial area through the sellar floor more safely, and resect the pituitary tumor maximally without complications. CONCLUSION: Our 3D-MRI models based on ZTE sequences allowed distinct visualization of vital structures and pituitary tumor around the sellar floor. This new method using 3D-ZTE-based MRI models showed low invasiveness for patients and was useful in preoperative planning for ETSS, facilitating maximum tumor resection without complications.

A transnasal foreign body penetrating the spinal cord from the nasopharynx.

OBJECTIVE AND IMPORTANCE: This is the first article regarding a transnasal Foreign bodies (FB) penetrating the spinal cord. We tried to remove it safely with a bilateral approach by performing a nasal endoscopy and partial laminectomy. CLINICAL PRESENTATION: During logging work, a tree hit the occipital region of a 47-year-old man, producing unconsciousness with left paresis. Although he did not remember his injuries due to traumatic amnesia, a computed tomography (CT) scan showed a metal rod lodged from the left side wall of the nasopharynx to the spinal column at the cranial-cervical transition. INTERVENTION: A C1 laminectomy, partial occipital bone resection, and endoscopic intranasal extirpation were done jointly by an otolaryngologist and neurosurgeon under general anesthesia to safely remove the FB. All procedures were performed in the right lateral decubitus position so we could approach both the nasopharynx and occipital sides. The otolaryngologist withdrew the FB from the nasal cavity using an endoscope while the neurosurgeon monitored the occipital bone side. The FB was safely removed. CONCLUSION: The site of penetration at the nasopharynx contracted gradually to a scar with no cerebrospinal fluid (CSF) leak. The patient was finally discharged 39 days after surgery with no motor/sensory paralysis.

Humeral Head Morphometry Can Predict the Presence of Subacromial Spurs: Measurements of Dried Bones from Human Shoulder Girdles.

OBJECTIVE: To clarify the relationship between the morphological characteristics of the bones of the shoulder girdle and the presence of subacromial spurs (SS). METHODS: The bones of 36 cadaveric shoulder girdles were measured. After dividing the bone specimens into SS present and absent groups, various bone parameters between the two groups were statistically compared. Logistic regression analysis was conducted to assess the significance of each parameter as a predictor of SS formation. A receiver operating characteristic curve analysis was used to determine the cut-off point and to assess the sensitivity and specificity of the parameters showing significant differences. RESULTS: SS were found in 16 scapulae. The values for five parameters of the examined shoulder girdles were significantly different between the two groups. The presence of SS depended on the humeral head ratio, which was calculated by dividing the length of the greater tubercle of the humerus by the length of the lesser tubercle. A cut-off value of 1.97 was suitable for discriminating between the presence and absence of SS (sensitivity, 75%; specificity, 80%). CONCLUSION: The presence of SS is related to several morphological characteristics of the shoulder girdle and, the presence of SS can be predicted using humeral head morphometry.

Effect of forward head posture on thoracic shape and respiratory function.

[Purpose] This study investigated the effect of forward head posture on upper and lower thoracic shape in adults to better understand the relationship between a forward head posture and respiratory function. [Participants and Methods] Fifteen healthy males were recruited after obtaining informed consent from all participants. All participants were instructed to respire in both the forward and neutral head postures while seated. Respiratory function was assessed using spirometry. Thoracic shape during respiration was assessed using 23 markers on both the upper and the lower thorax and compared between the 2 postures. [Results] Forced vital capacity, expiratory and inspiratory reserve volumes, forced expiratory volume at 1 second, and the peak flow rate observed with the forward head posture were significantly lower than that with the neutral head posture. The upper thorax showed a greater forward shift and the lower thorax showed a greater forward and inward shift with the forward head posture than with the neutral head posture. No significant difference in upper thoracic mobility was observed during respiration between the forward head posture and the neutral head posture. However, mobility of the lower thorax during respiration was significantly reduced with the forward head posture. [Conclusion] The forward head posture causes expansion of the upper thorax and contraction of the lower thorax, and these morphological changes cause decreased respiratory function.

Instantaneous changes in respiratory function induced by passive pelvic suspension in the supine position in relation to increased diaphragm excursion.

[Purpose] This study aimed to introduce an approach of pelvic suspension (PS) using sling cords and to obtain evidence for changes in respiratory function of healthy subjects. [Subjects and Methods] Subjects were 25 healthy men. In the supine position, with hip and knee joints flexed at 90°, the subjects' pelvises were suspended with sling belts. Diaphragm excursion, respiratory function, and respiratory comfort in these postures were measured using ultrasonography, respirometry, and visual analog scale (VAS), respectively. [Results] When the pelvis was passively suspended with sling cords, the diaphragm moved 5 mm cranially and diaphragm excursion showed an instantaneous increase compared with the control. The tidal volume (VT) showed an increase and the respiration rate (RR) showed a decrease. The extent of diaphragm excursion was correlated with changes in VT under the control and PS conditions. Independent measurements of pulmonary function revealed that PS reduced the expiratory reserve volume, being correlated positively and negatively to increases in vital and inspiratory capacities, respectively. Furthermore, VAS values for respiratory ease were greater with PS than with the control. [Conclusion] These results suggest that PS effectively changed diaphragm excursion and respiratory function, leading to ease of breathing (i.e., deep and slow respiration).

Single electron transfer-induced coupling of alkynylzinc reagents with aryl and alkenyl iodides.

Alkynylzinc reagents were found to undergo coupling with aryl and alkenyl iodides to give arylalkynes and alkenylalkynes without the aid of transition metals. The coupling reaction proceeds through a single electron transfer mechanism, where a substoichiometric amount of a phosphine works as an indispensable activator.

Efficacy of chlorophyll c2 for seasonal allergic rhinitis: single-center double-blind randomized control trial.

Chlorophyll c2 extracted from Sargassum horneri improved allergic symptoms in an animal model of allergic rhinitis. In the present study, we explored the efficacy of chlorophyll c2 in patients with seasonal allergic rhinitis. This was a single-center, randomized, double-blind placebo-controlled trial. Sixty-six patients aged 20-43 years, each with a 2-year history of seasonal allergic rhinitis, were randomly assigned to receive either a single daily dose (0.7 mg) of chlorophyll c2 or placebo for 12 weeks. The use of medications including H1-antihistamines and topical nasal steroids was recorded by rescue medication scores (RMSs) noted after 4, 8, and 12 weeks of treatment. Disease-specific quality of life was measured using the Japan Rhinitis Quality of Life Questionnaire (JRQLQ) both before and after 4, 8, and 12 weeks of treatment. The RMS at 8 weeks was significantly better in the chlorophyll c2 than the placebo group (mean RMS difference = -3.09; 95 % confidence interval = -5.96 to -0.22); the mean RMS at 4 weeks was only slightly better in the chlorophyll c2 group. The JRQLQ scores did not differ significantly between the two groups. Chlorophyll c2 would have a potential to be an alternative treatment for allergic rhinitis.

Role of Denosumab in Endoscopic Endonasal Treatment for Juvenile Clival Giant Cell Tumor: A Case Report and Review of the Literature.

BACKGROUND: Giant cell tumors (GCTs) are histologically benign bone neoplasms with a locally aggressive nature that primarily occur in the epiphyses of the long bones. A small proportion of these tumors, however, occur in the pelvis, spine, or skull bones. Among these, GCTs of the skull base cannot be completely resected and require adjuvant therapy. We report a juvenile case of clival GCT that was successfully treated by endoscopic endonasal transsphenoidal surgery and subsequent adjuvant therapy with denosumab, a monoclonal antibody to receptor activator of nuclear factor-κB ligand. CASE DESCRIPTION: A 16-year-old boy was admitted to our hospital with progressively intolerable headache and right oculomotor nerve palsy. Computed tomography and magnetic resonance imaging showed a large tumor mass in the sphenoid sinus with extensive erosion of the clivus and compression of the right cavernous sinus. The tumor was resected by endonasal transsphenoidal surgery and histologically diagnosed as GCT. The giant cells showed positive immunostaining for CD68 and Mib-1 labeling index was less than 1.0%. Postoperative course was uneventful and the oculomotor disturbance was markedly improved. However, magnetic resonance imaging 2 weeks after surgery revealed marked enlargement of the tumor. Adjuvant therapy with denosumab was therefore initiated, resulting in marked reductions in tumor size. CONCLUSIONS: This is the first report to describe beneficial effects of denosumab in the treatment of GCT of the skull base.

Usefulness of an Image Fusion Model Using Three-Dimensional CT and MRI with Indocyanine Green Fluorescence Endoscopy as a Multimodal Assistant System in Endoscopic Transsphenoidal Surgery.

Purpose. We investigate the usefulness of multimodal assistant systems using a fusion model of preoperative three-dimensional (3D) computed tomography (CT) and magnetic resonance imaging (MRI) along with endoscopy with indocyanine green (ICG) fluorescence in establishing endoscopic endonasal transsphenoidal surgery (ETSS) as a more effective treatment procedure. Methods. Thirty-five consecutive patients undergoing ETSS in our hospital between April 2014 and March 2015 were enrolled in the study. In all patients, fusion models of 3D-CT and MRI were created by reconstructing preoperative images. In addition, in 10 patients, 12.5 mg of ICG was intravenously administered, allowing visualization of surrounding structures. We evaluated the accuracy and utility of these combined modalities in ETSS. Results. The fusion model of 3D-CT and MRI clearly demonstrated the complicated structures in the sphenoidal sinus and the position of the internal carotid arteries (ICAs), even with extensive tumor infiltration. ICG endoscopy enabled us to visualize the surrounding structures by the phasic appearance of fluorescent signals emitted at specific consecutive elapsed times. Conclusions. Preoperative 3D-CT and MRI fusion models with intraoperative ICG endoscopy allowed distinct visualization of vital structures in cases where tumors had extensively infiltrated the sphenoidal sinus. Additionally, the ICG endoscope was a useful real-time monitoring tool for ETSS.

Preventive effects of bortezomib on denervation-induced atrophy of the intrinsic laryngeal muscles: an experimental study in the rat.

CONCLUSION: Bortezomib was effective in attenuating atrophy of the posterior cricoarytenoid (PCA) muscle, but not the thyroarytenoid (TA) muscle. This was probably due to differences in the fiber composition of the two muscles. The PCA muscle is composed of a combination of fast- and slow-twitch fibers, and therefore is more resistant to atrophy than the TA muscle, which is composed solely of fast-twitch fibers. OBJECTIVES: To investigate the preventive effects of bortezomib on denervation-induced atrophy of the TA and PCA muscles in the rat. METHODS: Following transection of the left recurrent laryngeal nerve, bortezomib (100 µg/kg) was administered subcutaneously on post-denervation days 1 and 4, followed by a 10-day rest period every 14 days; each 2-week period constituted a single treatment cycle. In controls, saline was administered instead. Animals were killed for histological examination at 4 (n = 6), 8 (n = 7), and 12 (n = 7) weeks post-denervation. Muscle atrophy was assessed using three indices: wet muscle weight, muscle fiber cross-sectional area, and the number of muscle fibers/mm(2). The effects of bortezomib were evaluated by comparing the left (L) and right (R) muscles, with sequential changes in the L/R ratio assessed. RESULTS: In saline-administered animals, atrophy of the left-sided TA and PCA muscles progressed rapidly during the first 4 weeks post-denervation, following which progression slowed. Atrophy was greater in the TA compared with the PCA muscle, although this difference was not statistically significant. In bortezomib-administered animals, atrophy of the PCA muscle was attenuated significantly at post-denervation weeks 8 and 12; no such reduction in atrophy was observed for the TA muscle.

Expression of atrophy-related transcription factors in the process of intrinsic laryngeal muscle atrophy after denervation.

We examined changes in the expressions of three atrophy-related transcription factors (FOXO3a, P-FOXO3a, and PGC-1α) in the process of intrinsic laryngeal muscle atrophy after denervation. In total, 51 Wistar rats were used. After transection of the unilateral recurrent laryngeal nerve, the thyroarytenoid (TA) muscle and the posterior cricoarytenoid (PCA) muscle were excised and subjected to histological and Western blot studies. Relationships between the expressions of transcription factors during atrophy of the intrinsic laryngeal muscles were investigated by comparing the results of the treated side (T) with those of the untreated side (U), and sequential changes in the T/U ratio after denervation were assessed. Loss of wet muscle weight, together with a decrease in muscle fiber cross-sectional area and increase in the number of muscle fibers/mm(2), occurred more quickly in TA muscle than in PCA muscle. Muscle atrophy progressed rapidly between 7 and 28 days after denervation, while expression of FOXO3a was maximal on day 7, in both TA and PCA muscles. By contrast, P-FOXO3a expression decreased gradually after denervation. Expression of PGC-1α increased slowly until day 7, and then it declined. Denervation-induced atrophy of the intrinsic laryngeal muscles was closely linked with the expression of FOXO3a and PGC-1α, suggesting that atrophy of these muscles may involve the actions of these transcription factors. In addition, muscle atrophy progressed faster in TA muscle than in PCA muscle, due mainly to differences in muscle fiber composition.