Acute inflammatory response to contrast agent aspiration and its mechanisms in the rat lung.

Objectives/hypothesisContrast agent (CA) aspiration is an established complication of upper gastrointestinal and videofluoroscopic swallow studies. The underlying molecular biological mechanisms of acute response to CA aspiration in the respiratory organs remain unclear. The aims of this study were to elucidate the histological and biological influences of three kinds of CAs on the lung and to clarify the differences in acute responses.Study designAnimal model.MethodsEight-week-old male Sprague Dawley rats were divided into five groups (n = 6 in each group). Three groups underwent tracheal instillation of one of three different CAs: barium (Ba) sulfate, nonionic contrast agents (NICAs), and ionic contrast agents (ICAs). A control group was instilled with saline and a sham group was instilled with air. All animals were euthanized on day 2 after treatment and histological and gene analysis was performed.ResultsNo animal died after CA or control/sham aspiration. Ba caused severe histopathologic changes and more prominent inflammatory cell infiltration in the lungs compared with the two other iodinated contrast agents. Increases in expressions of inflammatory cytokines (tumor necrosis factor [Tnf], interleukin-1β [Il1b], and interferon-γ [Ifng]) were observed in Ba aspiration rats, and upregulation of Il1b was seen in ICA aspiration rats. NICA did not cause obvious histologic changes or expressions of inflammatory cytokines and fibrosis-related genes in the lungs.ConclusionsBa caused significantly more acute lung inflammation in a rodent model than did ioinic and nonionic iodinated CAs. Nonionic contrast did not cause any discernible inflammatory response in the lungs, suggesting that it may be the safest contrast for videofluoroscopic swallow studies.Level of evidenceNA Laryngoscope, 129:1533-1538, 2019

The Relationship between the Efficacy of Tonsillectomy and Renal Pathology in the Patients with IgA Nephropathy

Objective. The aim of this study was to evaluate the effects of tonsillectomy as a treatment for IgA nephropathy in relation to renal pathological findings. Methods. This is a retrospective analysis of 13 patients having IgA nephropathy treated by tonsillectomy. Results. UP/UCre levels decreased from 820.8 to 585.4 one month postsurgery and then showed slight worsening to 637.3 at the most recent follow-up. There was no significant difference in the improvement rate between pathological grades I–III and IV. There was positive correlation between Pre-UP/UCre level and the reduction rate of UP/UCre, which was statistically significant (R = 0.667, R2 = 0.445, and P=0.01). Conclusions. Reduction of UP/UCre at one month postsurgery is considered to be an overall prognostic factor, and tonsillectomy is considered to be an effective therapy for IgA patients regardless of the grade of renal pathology

Dose-Dependent Effects of Insulin-Like Growth Factor 1 in the Aged Olfactory Epithelium

Background: Olfaction is known to be impaired by aging. We hypothesized that insulin-like growth factor-1 (IGF-1) administered at an appropriate dose could prevent age-induced negative effects on olfactory receptor neurons (ORNs). We explored the effects of low- and high-dose administration of IGF-1 on the ORN cell system in aged mice and investigated the involvement of the cellular mechanisms of IGF-1 in the regeneration of ORNs in aged mice.Methods: We subcutaneously administered recombinant human IGF-1 (rhIGF-1) to 16-month-old male mice over 56 days, and then examined the histological effects of rhGF-1 on cellular composition, cell proliferation, and cell death in the aged olfactory epithelium (OE), by comparing among saline-treated and low- and high-dose rhIGF-1-treated mice.Results: Low-dose rhIGF-1 administration increased the numbers of olfactory progenitors, immature ORNs, and mature ORNs in the OE, despite an increase in Cas3+ apoptotic cells. Notably, high-dose rhIGF-1 administration increased the numbers of only immature ORNs, not olfactory progenitors and mature ORNs, with a concurrent increase in apoptotic cells.Conclusion: Our data suggest that in aged mice, IGF-1 administered at an appropriate dose could increase the number of mature ORNs and further human studies may contribute to the development of treatments for aging-related olfactory impairment

Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers.

Although promoter-associated CpG islands have been established as targets of DNA methylation changes in cancer, previous studies suggest that epigenetic dysregulation outside the promoter region may be more closely associated with transcriptional changes. Here we examine DNA methylation, chromatin marks, and transcriptional alterations to define the relationship between transcriptional modulation and spatial changes in chromatin structure. Using human papillomavirus-related oropharyngeal carcinoma as a model, we show aberrant enrichment of repressive H3K9me3 at the transcriptional start site (TSS) with methylation-associated, tumor-specific gene silencing. Further analysis identifies a hypermethylated subtype which shows a functional convergence on MYC targets and association with CREBBP/EP300 mutation. The tumor-specific shift to transcriptional repression associated with DNA methylation at TSSs was confirmed in multiple tumor types. Our data may show a common underlying epigenetic dysregulation in cancer associated with broad enrichment of repressive chromatin marks and aberrant DNA hypermethylation at TSSs in combination with MYC network activation

Morphological and physiological effects of long duration infusion of strychnine into the organ of Corti

Acute strychnine administration has long been used as a method to eliminate the effects of efferent activity. It has been shown that long after termination of chronic strychnine infusion into the cochlea, the ear becomes more susceptible to acoustic trauma suggesting that chronic strychnine infusion results in long lasting or permanent disruption of efferent function. Much research has been directed towards the functional significance of the olivocochlear system. However, there is little information concerning the effect of long duration inactivation of the medial olivocochlear system in an awake behaving animal. This study was designed to determine the structural and functional consequences of inactivation of the efferents by chronic infusion of strychnine into the cochlear perilymph of guinea pigs for two weeks via an osmotic pump. Physiological evaluations showed that the strychnine infusion eliminated the efferent induced reduction of the cochlear whole-nerve action potential three weeks after cessation of strychnine infusion. Contralateral efferent function remained unaltered. Histological evaluation at the light and electron microscopic levels revealed disoriented efferent synapses under the outer hair cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47459/1/11068_2004_Article_241027.pd

Activation of the PGE2–EP2 pathway as a potential drug target for treating eosinophilic rhinosinusitis

Current treatments of eosinophilic chronic rhinosinusitis (ECRS) involve corticosteroids with various adverse effects and costly therapies such as dupilumab, highlighting the need for improved treatments. However, because of the lack of a proper mouse ECRS model that recapitulates human ECRS, molecular mechanisms underlying this disease are incompletely understood. ECRS is often associated with aspirin-induced asthma, suggesting that dysregulation of lipid mediators in the nasal mucosa may underlie ECRS pathology. We herein found that the expression of microsomal PGE synthase-1 (encoded by PTGES) was significantly lower in the nasal mucosa of ECRS patients than that of non-ECRS subjects. Histological, transcriptional, and lipidomics analyses of Ptges-deficient mice revealed that defective PGE2 biosynthesis facilitated eosinophil recruitment into the nasal mucosa, elevated expression of type-2 cytokines and chemokines, and increased pro-allergic and decreased anti-allergic lipid mediators following challenges with Aspergillus protease and ovalbumin. A nasal spray containing agonists for the PGE2 receptor EP2 or EP4, including omidenepag isopropyl that has been clinically used for treatment of glaucoma, markedly reduced intranasal eosinophil infiltration in Ptges-deficient mice. These results suggest that the present model using Ptges-deficient mice is more relevant to human ECRS than are previously reported models and that eosinophilic inflammation in the nasal mucosa can be efficiently blocked by activation of the PGE2-EP2 pathway. Furthermore, our findings suggest that drug repositioning of omidenepag isopropyl may be useful for treatment of patients with ECRS

The Hearing Outcomes of Cochlear Implantation in Waardenburg Syndrome

Objectives. This study aimed to determine the feasibility of cochlear implantation for sensorineural hearing loss in patients with Waardenburg syndrome. Method. A retrospective chart review was performed on patients who underwent cochlear implantation at the University of Tokyo Hospital. Clinical classification, genetic mutation, clinical course, preoperative hearing threshold, highresolution computed tomography of the temporal bone, and postoperative hearing outcome were assessed. Result. Five children with Waardenburg syndrome underwent cochlear implantation. The average age at implantation was 2 years 11 months (ranging from 1 year 9 months to 6 years 3 months). Four patients had congenital profound hearing loss and one patient had progressive hearing loss. Two patients had an inner ear malformation of cochlear incomplete partition type 2. No surgical complication or difficulty was seen in any patient. All patients showed good hearing outcome postoperatively. Conclusion. Cochlear implantation could be a good treatment option for Waardenburg syndrome

Mucus extravasation and retention phenomena: a 24-year study

<p>Abstract</p> <p>Background</p> <p>Mucoceles are benign lesions related to the minor salivary glands and their respective ducts frequently affecting oral structures which are generally asymptomatic. Mucoceles are generally characterized by swollen nodular lesions preferentially located on the lower lip and differ from the so-called ranulas, which are lesions located on the floor of the mouth and related to the sublingual or submandibular glands.</p> <p>Methods</p> <p>The objective of the present study was to analyze data such as age, gender, race and site of the lesion of 173 mucocele cases diagnosed at the Discipline of Stomatology, São José dos Campos Dental School, UNESP, over a period of 24 years (April 1980 to February 2003).</p> <p>Results</p> <p>Of the 173 cases analyzed, 104 (60.12%) were females and 69 (39.88%) were males. Age ranged from 4 to 70 years (mean ± SD: 17 ± 9.53) and most patients were in the second decade of life (n = 86, 49.42%); white (n = 124, 71.68%). The lower lip was the site most frequently affected by the lesions (n = 135, 78.03%), whereas the lowest prevalence was observed for the soft palate, buccal mucosa, and lingual frenum.</p> <p>Conclusion</p> <p>In this study, mucoceles predominated in white female subjects in the second decade of life, with the lower lip being the most frequently affected site.</p