Inflammatory and immune responses in the cochlea: potential therapeutic targets for sensorineural hearing loss

The inner ear was previously assumed to be an immune-privileged organ due to the existence of its tight junction-based blood-labyrinth barrier. However, studies performed during the past decade revealed that the mesenchymal region of the cochlea, including its lateral wall, is a common site of inflammation. Neutrophils do not enter this region, which is consistent with the old dogma; however, bone marrow-derived resident macrophages are always present in the spiral ligament of the lateral wall and are activated in response to various types of insults, including noise exposure, ischemia, mitochondrial damage and surgical stress. Recent studies have also revealed another type of immune cell, called perivascular melanocyte-like macrophages (PVM/Ms), in the stria vascularis. These dedicated antigen-presenting cells also control vascular contraction and permeability. This review discusses a series of reports regarding inflammatory/immune cells in the cochlear lateral wall, the pathways involved in cochlear damage and their potential as therapeutic targets

Management of deep neck infection by a transnasal approach: a case report

<p>Abstract</p> <p>Introduction</p> <p>Deep neck infection is a life-threatening condition, and intravenous antibiotic therapy is preferable in the early stages of the disease. However, in the advanced stages, surgical drainage should be performed. Although several surgical treatment strategies are available, it is necessary to standardize treatment according to the patient's general condition and history.</p> <p>Case presentation</p> <p>We report the case of a 68-year-old man with a deep neck abscess and with severe diabetes mellitus and inflammation. Computed tomography identified a deep neck infection extending from the level of the epipharynx to that of the hyoid bone. We performed surgical drainage by transnasal endoscopy. The patient exhibited no evidence of either recurrent disease or post-surgical complications within 30 months of follow-up.</p> <p>Conclusions</p> <p>This case report provides evidence that transnasal endoscopic drainage should be recommended as a standard approach in patients with a deep neck abscess and with a severe general condition, diabetes mellitus, and inflammation.</p

Receptor-mediated release of inositol phosphates in the cochlear and vestibular sensory epithelia of the rat

Various neurotransmitters, hormones and other modulators involved in intercellular communication exert their biological action at receptors coupled to phospholipase C (PLC). This enzyme catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) to inositol 1,4,5-trisphosphate (InsP3) and 1,2-diacylglycerol (DG) which act as second messengers. In the organ of Corti of the guinea pig, the InsP3 second messenger system is linked to muscarinic cholinergic and P2y purinergic receptors. However, nothing is known about the the InsP3 second messenger system in the vestibule. In this study, the receptor-mediated release of inositol phosphates (InsPs) in the vestibular sensory epithelia was compared to that in the cochlear sensory epithelia of Fischer-344 rats. After preincubation of the isolated intact tissues with myo-[3H] in-ositol, stimulation with the cholinergic agonist carbamylcholine or the P2 purinergic agonist ATP-[gamma]-S resulted in a concentration-dependent increase in the formation of [3H]InsPs in both epithelia. Similarly, the muscarinic cholinergic agonist muscarine enhanced InsPs release in both organs, while the nicotinic cholinergic agonist dimethylphenylpiperadinium (DMPP) was ineffective. The muscarinic cholinergic antagonist atropine completely suppressed the InsPs release induced by carbamylcholine, while the nicotinic cholinergic antagonist mecamylamine was ineffective. Potassium depolarization did not alter unstimulated or carbamylcholine-stimulated release of InsPs in either organ. In both tissues, the P2 purinergic agonist [alpha],[beta]-methylene ATP also increased InsPs release, but the P1 purinergic agonist adenosine did not. These results extend our previous observations in the organ of Corti of the guinea pig to the rat and suggest a similar control of the InsP3 second messenger system in the vestibular sensory epithelia. In contrast to the cochlear sensory epithelia, atropine also significantly suppressed unstimulated InsPs release in the vestibular sensory epithelia. This suggests that the physiological mechanisms of the efferent nervous systems involving InsP3 second messenger system might be different in vestibular versus cochlear sensory epithelia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30596/1/0000233.pd

Where did the super-small sized large bowel advanced cancer come from?

Our study suggested that the super-small sized (less than 15 mm in maximum diameter) large bowel advanced cancers, which were sometimes found, were derived from the superficial depressed-type or flat elevation-type of the colorectal early cancers, not polyp-type of those

Bcl-2 genes regulate noise-induced hearing loss

Proteins of the Bcl-2 family have been implicated in control of apoptotic pathways modulating neuronal cell death, including noise-induced hearing loss. In this study, we assessed the expressions of anti- and proapoptotic Bcl-2 genes, represented by Bcl-xL and Bak following noise exposures, which yielded temporary threshold shift (TTS) or permanent threshold shift (PTS). Auditory brainstem responses (ABRs) were assessed at 4, 8, and 16 kHz before exposure and on days 1, 3, 7, and 10 following exposure to 100 dB SPL, 4 kHz OBN, 1 hr (TTS) or 120 dB SPL, 4 kHz OBN, 5 hr (PTS). On day 10, subjects were euthanized. ABR thresholds increased following both exposures, fully recovered following the TTS exposure, and showed a 22.6 dB (4 kHz), 42.5 dB (8 kHz), and 44.9 dB (16 kHz) mean shift on day 10 following the PTS exposure. PTS was accompanied by outer hair cell loss progressing epically and basally from the 4-kHz region. Additional animals were euthanized for immunohistochemical assessment. BcL-xL was robustly expressed in outer hair cells following TTS exposure, whereas Bak was expressed following PTS exposure. These results indicate an important role of the Bcl-2 family proteins in regulating sensory cell survival or death following intense noise. Bcl-xL plays an essential role in prevention of sensory cell death following TTS levels of noise, and PTS exposure provokes the expression of Bak and, with that, cell death. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58028/1/21533_ftp.pd

Severity of Tinnitus Distress Negatively Impacts Quality of Life in Patients With Vestibular Schwannoma and Mimics Primary Tinnitus

Objective: Quality of life (QoL) and subjective symptoms are predominantly used to evaluate treatment outcome of patients with vestibular schwannoma (VS). However, for patients undergoing conservative treatment—the most frequently used intervention—the association between QoL and subjective symptoms is unclear. Moreover, it is unknown whether VS-related tinnitus could be associated with the audiological and psychological status of the patient. Our overall aim is to provide objective evidence of this association to better guide treatment of VS.Methods: In a prospective study, we analyzed factors that influence VS-related tinnitus and QoL in 72 patients receiving conservative management of unilateral sporadic VS. This was done through questionnaires that assessed QoL, anxiety, depression, and audiological examinations. We used the SF-36 Short Form to assess QoL; the Tinnitus Handicap Inventory, Dizziness Handicap Inventory, Facial Clinimetric Evaluation Scale, Visual Analog Scale for hearing impairment to assess symptoms subjectively; and pure tone audiometry, the speech discrimination for hearing measurements. For psychological status, we used the Hospital Anxiety and Depression Scale. For analyses, we used Pearson correlation analysis and multiple regression between variables and QoL.Results: Correlation and regression analyses revealed that the severity of tinnitus distress had the largest negative impact on QoL in all domains of SF-36. The severity of tinnitus was significantly associated with subjective hearing impairment and the degree of depression and anxiety. Hearing thresholds had no statistical association with severity of tinnitus.Conclusions: To our knowledge, this is the first study to investigate VS-related tinnitus with respect to both patients' hearing status and psychological condition. Our results suggest that tinnitus distress strongly affects VS patients' QoL and that its characteristics are similar to primary tinnitus. An intervention for VS-related tinnitus, therefore, should assess to what extent tinnitus bothers patients, and it should reduce any unpleasant emotions that may exacerbate symptoms. This approach should improve their QoL

Multicascade-linked synthetic wavelength digital holography using an optical-comb-referenced frequency synthesizer

Digital holography (DH) is a promising method for non-contact surface topography because the reconstructed phase image can visualize the nanometer unevenness in a sample. However, the axial range of this method is limited to the range of the optical wavelength due to the phase wrapping ambiguity. Although the use of two different wavelengths of light and the resulting synthetic wavelength, i.e., synthetic wavelength DH, can expand the axial range up to a few tens of microns, this method is still insufficient for practical applications. In this article, a tunable external cavity laser diode phase-locked to an optical frequency comb, namely, an optical-comb-referenced frequency synthesizer, is effectively used for multiple synthetic wavelengths within the range of 32 um to 1.20 m. A multiple cascade link of the phase images among an optical wavelength (= 1.520 um) and 5 different synthetic wavelengths (= 32.39 um, 99.98 um, 400.0 um, 1003 um, and 4021 um) enables the shape measurement of a reflective millimeter-sized stepped surface with the axial resolution of 34 nm. The axial dynamic range, defined as the ratio of the maximum axial range (= 0.60 m) to the axial resolution (= 34 nm), achieves 1.7*10^8, which is much larger than that of previous synthetic wavelength DH. Such a wide axial dynamic range capability will further expand the application field of DH for large objects with meter dimensions.Comment: 19 pages, 7 figure