PURPOSE: To clarify the morphologic and quantitative changes of mechanoreceptors of the human ACL with degenerative arthritis. MATERIALS AND METHODS: Eleven fresh specimens of anterior cruciate ligament (ACL) were obtained from patients with degenerative arthritis during TKA. As a control, two fresh specimens were taken from healthy men at the time of a traumatic above knee amputation. The whole ligaments were serially frozen and sectioned at a thickness of 40 mum. After immunohistochemical staining, the mechanoreceptors were observed under a light microscope. The ratios of sections showing mechanoreceptors were calculated. Statistical analyses were performed using the chi-square test. RESULTS: In the two control specimens, nineteen mechanoreceptors were found, evenly distributed at the femoral and tibial ends. However, the average number of mechanoreceptors was 1.4 (total 15) in the arthritic ligaments (p<0.05), and these were located near the femoral side rather than the tibial end. The percentage of sections showing mechanorecptors was 8.3% in the arthritic group and 40.2% in the control group (p<0.05). All receptors were round or fusiform shaped Ruffini corpuscles; Pacinian corpuscles could not be found in either group. Nine of 15 mechanoreceptors in the arthritic groups were "necrotic" in shape. CONCLUSION: Mechanoreceptors in arthritic ACL were significantly reduced in number and mainly necrotic in shape. Our findings suggest that the numerical and morphological changes of mechanoreceptors are closely related with reduced proprioception in degenerative arthritis.
Amputation ; Anterior Cruciate Ligament* ; Humans ; Knee ; Ligaments ; Male ; Mechanoreceptors* ; Osteoarthritis* ; Pacinian Corpuscles ; Proprioception

PURPOSE: To identify sensory nerve endings in the human hip joint capsule and in the pseudocapsule after total hip replacement. MATERIALS AND METHODS: Ten hip joint capsules from patients undergoing bipolar hip replacement for acute femoral neck fracture, and six pseudocapsules from patients undergoing revision hip surgery for failed total hip replacement were harvested and stained in bulk using a modified gold-chloride method. Sensory nerve endings were identified using the criteria described by Freeman and Wyke. RESULTS: Three morphologically distinct types of nerve endings were identified in the normal human hip joint capsules; type I Ruffini corpuscles, type II Pacinian corpuscles and type IV free nerve endings. In contrast, no proprioceptive nerve endings (type I and II receptors) were observed in pseudocapsular tissues. A small number of type IV receptors were noted in the pseudocapsule, but these were significantly fewer in number than in normal hip capsular tissue. CONCLUSION: The pseudocapsule that forms after hip replacement surgery may protect joint stability through a mechanical check-rein effect rather than through a proprioceptive feedback mechanism.
Arthroplasty, Replacement, Hip* ; Capsules ; Feedback, Sensory ; Femoral Neck Fractures ; Hip Joint* ; Hip* ; Humans* ; Joints ; Mechanoreceptors ; Nerve Endings ; Pacinian Corpuscles ; Sensory Receptor Cells

The cochlear auditory epithelium contains two types of sound receptors, inner hair cells (IHCs) and outer hair cells (OHCs). Mouse models for labelling juvenile and adult IHCs or OHCs exist; however, labelling for embryonic and perinatal IHCs or OHCs are lacking. Here, we generated a new knock-in Fgf8^P2A-3×GFP/+ (Fgf8^GFP/+) strain, in which the expression of a series of three GFP fragments is controlled by endogenous Fgf8 cis-regulatory elements. After confirming that GFP expression accurately reflects the expression of Fgf8, we successfully obtained both embryonic and neonatal IHCs with high purity, highlighting the power of Fgf8^GFP/+. Furthermore, our fate-mapping analysis revealed, unexpectedly, that IHCs are also derived from inner ear progenitors expressing Insm1, which is currently regarded as an OHC marker. Thus, besides serving as a highly favorable tool for sorting early IHCs, Fgf8^GFP/+ will facilitate the isolation of pure early OHCs by excluding IHCs from the entire hair cell pool.
Animals ; Mice ; Hair Cells, Auditory, Inner ; Cochlea/metabolism* ; Hair Cells, Auditory, Outer/metabolism* ; Disease Models, Animal ; Fibroblast Growth Factor 8/metabolism*

Breathing is critically depending on a variety of sensory feedbacks from multiple sources for its optimal performance. The sensory information from the lung and airways probably provides one of the most important feedbacks to adjust the respiratory controller to generate optimal breathing movements. Since Breuer and Hering made the seminal report regarding role of the vagus nerve in control of breathing in 1868, airway sensory receptors have been a subject for intensive and extensive studies. After more than a century investigation, our knowledge accumulates immensely, however, our understanding of the nature of these sensory receptors is still far from complete. This brief review provides an overview on this topic.
Humans ; Lung ; innervation ; physiology ; Mechanoreceptors ; physiology ; Neuroepithelial Bodies ; physiology ; Pulmonary Stretch Receptors ; physiology ; Reflex ; physiology ; Respiratory System ; innervation ; Vagus Nerve ; physiology

Cochlear sensory hair cells (HCs) are crucial for hearing as mechanoreceptors of the auditory systems. Clarification of transcriptional regulation for the cochlear sensory HC development is crucial for the improvement of cell replacement therapies for hearing loss. Transcription factor Atoh1 is the key player during HC development and regeneration. In this review, we will focus on Atoh1 and its related signaling pathways (Notch, fibroblast growth factor, and Wnt/β-catenin signaling) involved in the development of cochlear sensory HCs. We will also discuss the potential applicability of these signals for the induction of HC regeneration.
Cochlea ; Fibroblast Growth Factors ; Hair Cells, Auditory ; Hair ; Hearing ; Hearing Loss ; Mechanoreceptors ; Regeneration ; Transcription Factors

BACKGROUND AND OBJECTIVES: Locacorten Vioform (Novartis UK) is frequently prescribed for otomycosis. Its component, Clioquinol, also has anti-bacterial properties. Up to this point, its ototoxic potential has not been evaluated. Our objective aims to evaluate Locacorten Vioform’s potential ototoxicity when applied directly to the middle ear cavity. MATERIALS AND METHODS: We performed an experimental prospective animal study in our animal research center with 20 Hartley guinea pigs divided into 2 groups. The first group (experimental) was treated with Locacorten Vioform in one ear and with a physiologic saline solution in the other. The second group (positive control) was treated with concentrated gentamycin in one ear and physiologic saline in the other. Auditory brainstem response measurements were obtained before and after three sets of injections. Statistics were analyzed using a variance analysis with repeated measures. The histological state of cochlear outer hair cells was compared between the two groups using scanning electron microscopy. RESULTS: Average hearing loss in ears treated with Locacorten Vioform was 32.1 dB, compared with a 2.5 dB average loss in the saline-treated ears. Ears treated with gentamycin lost an average of 33.0 dB. There were clinically and statistically significant differences between the two ears of the guinea pigs in both groups (p < 0.001). Scanning electron microscopy revealed severe pericochlear and cochlear inflammation and ossification in the Locacorten Vioform-treated ears. Gentamycin caused significant destruction of outer hair cell architecture. CONCLUSIONS: Locacorten Vioform induces a hearing loss similar to that caused by gentamycin when applied directly to the middle ear of a guinea pig model. Electron microscopy indicates a pericochlear and cochlear inflammatory reaction with ossification.
Animal Experimentation ; Animals ; Clioquinol ; Ear ; Ear, Middle ; Evoked Potentials, Auditory, Brain Stem ; Gentamicins ; Guinea Pigs ; Guinea ; Hair ; Hair Cells, Auditory, Inner ; Hair Cells, Auditory, Outer ; Hearing Loss ; Inflammation ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Otomycosis ; Prospective Studies ; Sodium Chloride

OBJECTIVE: To detect the expression variation of microRNA-183 family in cochlea of animal model characterized by noise-induced deafness at various time points, and to explore the mechanisms responsible for noise-induced deafness. METHOD: Fifty mice were randomly divided into 5 groups. In the experimental group, 40 mice were exposed to 2-4 kHz narrow band noise at 100 dB SPL 6h per day for 3 consecutive days. The rest 10 mice served as the control group without receiving any noise. Auditory brainsterm response (ABR) were examined at the 1st, 7th, 14th and 28th day compaired with the ABR before the experiment,to confirm noise lead to the permanent threshold shift. The pathological damage processes of hair cell were detected by the basilar membrane stretched techniques. Real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) was apply to quantify the expression of microRNA183 family members. Statistical analysis was performed by the SPSS 17.0 software. RESULT: The hearing of mice in the experimental group was significantly less than that in the control group. In the experimental group, the hearing of mice exposed to noise were markedly less when compared with the one exposure to null-noise. The hearing in the 1st day group was least among experimental groups, and the followed one was mice in the 7th day group. No statistical difference were observed between the 14th and 28th day groups (P > 0.05). The results of surface preparation showed that the outer hair cells were chaotic, deformational, and their number decreased is time-dependent. The missing of the outer hair cells occurred mainly in the first and second rows, while the inner hair cells were not pronouncedly missing. The qRT-PCR showed that the expressions of the three genes (miR-183/96/182)in the 1st day and 7th day group with exposure to noise were less than in the control group (P < 0.01), while no significant difference was found between 1st day and 7th day group (P > 0.05). The expressions rised in the 14th day experimental groups, whereas the 28th day group's expressions of the three genes decreased markedly which were more than that in the 1st day and 7th day group (P < 0.01). CONCLUSION After noise exposure for some time, the expressions of miRNA-183 family members have significant changes in animal model with noise-induced deafness, which indicated that the miRNA183 family members may play important roles in the pathogenesis and development of noise-induced deafness.
Animals ; Disease Models, Animal ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hair Cells, Auditory, Inner ; pathology ; Hair Cells, Auditory, Outer ; pathology ; Hearing Loss, Noise-Induced ; metabolism ; pathology ; Male ; Mice ; MicroRNAs ; metabolism

BACKGROUND AND OBJECTIVES: The antioxidant ebselen will be able to limit or prevent the ototoxicity arising from 2-hydroxypropyl-β-cyclodextrin (HPβCD). Niemann-Pick Type C (NPC) disease is a disorder of lysosomal storage manifested in sphingolipidosis. Recently, it was noted that experimental use of HPβCD could partially resolve the symptoms in both animals and human patients. Despite its desirable effect, HPβCD can induce hearing loss, which is the only major side effect noted to date. Understanding of the pathophysiology of hearing impairment after administration of HPβCD and further development of preventive methods are essential to reduce the ototoxic side effect. The mechanisms of HPβCD-induced ototoxicity remain unknown, but the resulting pathology bears some resemblance to other ototoxic agents, which involves oxidative stress pathways. To indirectly determine the involvement of oxidative stress in HPβCD-induced ototoxicity, we tested the efficacy of an antioxidant reagent, ebselen, on the extent of inner ear side effects caused by HPβCD. MATERIALS AND METHODS: Ebselen was applied prior to administration of HPβCD in mice. Auditory brainstem response thresholds and otopathology were assessed one week later. Bilateral effects of the drug treatments also were examined. RESULTS: HPβCD-alone resulted in bilateral, severe, and selective loss of outer hair cells from base to apex with an abrupt transition between lesions and intact areas. Ebselen co-treatment did not ameliorate HPβCD-induced hearing loss or alter the resulting histopathology. CONCLUSIONS: The results indirectly suggest that cochlear damage by HPβCD is unrelated to reactive oxygen species formation. However, further research into the mechanism(s) of HPβCD otopathology is necessary.
Animals ; Ear, Inner ; Evoked Potentials, Auditory, Brain Stem ; Hair Cells, Auditory, Outer ; Hearing Loss ; Hearing ; Humans ; Mice ; Oxidative Stress ; Pathology ; Reactive Oxygen Species ; Sphingolipidoses ; Tight Junctions

Ouabain, a Na(+)/K(+)-ATPase inhibitor, induces slowly adapting pulmonary stretch receptors (SARs) to discharge paradoxically. Paradoxical discharge is characterized by increased SAR activity during lung deflation coupled with silence during lung inflation. We hypothesized that over-excitation silences the SARs. Accordingly, if cyclic inflation pressure was reduced so as to lower SAR stimulation, paradoxical discharge would be prevented. In the present study, single-unit activity of SARs was recorded in anesthetized, open-chest and mechanically ventilated rabbits with positive-end-expiratory pressure (PEEP). After microinjection of ouabain into the receptive field, SAR activity initially increased and then gradually became paradoxical. During paradoxical cycling, SAR activity started and stopped abruptly, oscillating between high frequency discharge during lung deflation and silence during peak inflation. Removing PEEP reduced basal cyclic stimulation and returned the discharge pattern to normal, that is, SAR activity was highest at peak inflation pressure but silent during deflation. It is speculated that stretching SARs causes Na(+) influx, producing generator potential (GP). Normally, GP recovers by Na(+) extrusion via Na(+)/K(+)-ATPase. Ouabain inhibits the ATPase, which limits Na(+) extrusion, and thus sustains the GP. Therefore, after ouabain microinjection, lung inflation will further increase GP, causing over-excitation to silence the SARs.
Action Potentials ; physiology ; Adaptation, Physiological ; drug effects ; Animals ; Lung ; drug effects ; physiology ; Male ; Mechanoreceptors ; physiology ; Ouabain ; pharmacology ; Pulmonary Stretch Receptors ; drug effects ; physiology ; Pulmonary Ventilation ; drug effects ; physiology ; Rabbits ; Sodium-Potassium-Exchanging ATPase ; antagonists & inhibitors ; physiology ; Vagus Nerve ; physiology

OBJECTIVETo study the effects of Erlong Zuoci Pill (, ELZCP) and its disassembled: prescriptions on gentamicin (GM)-induced ototoxicity model in vitro.

METHODSAfter the spiral organ of cochleae: of newborn mice (postnatal days: 2-3) cultured for 24 h, GM alone or combined with water extracting-alcohol precipitating solution of ELZCP or with its disassembled prescriptions was added. Hair cells were observed under a fluorescence microscope after TRITC-phalloidin staining, and the cochlear hair cell loss rate was calculated by counting the whole cochlear hair cells and analyzed by whole cochlear hair cells analyzing software.

RESULTSGM induced cochlear outer hair cells (OHCs) and inner hair cells (IHCs) injuries in a dose-dependent manner, and they were significantly different as compared with those in the normal control group (P<0.05, P<0.01). ELZCP at the concentration of 0.003-3 mg/mL could decrease the hair cells loss induced by the 0.3 mmol/L GM (P<0.05, P<0.01), the effects was in a dose-dependent manner, and the concentration of 0.3 mg/mL showed the optimal protective effect. For the ELZCP disassembled prescriptions, Liuwei-Dihuang could decrease OHC loss rate than that in the 0.3 mmol/L GM model group (P<0.05), but the OHC loss rate was still higher than that in the ELZCP group (P<0.01), which indicated that the protective effect of hair cells by Liuwei-Dihuang was not better than that of ELZCP. Poria decreased OHC loss rate from 72.1 % +/-3.7 % to 58.8 %+/- 8.2 % (P<0.05).

CONCLUSIONSELZCP could play a role in antagonizing the injury of cochlear hair cells induced by GM ototoxicity,: and its disassembled prescriptions, Liuwei-Dihuang was the main component to protect the cochlear hair cells from GM-induced ototoxicity, and Magnetitum combined with Radix Bupleurui could strengthen the action of the whole prescription; Poria could reduce GM-induced OHC loss.

Animals ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Gentamicins ; toxicity ; Hair Cells, Auditory, Inner ; drug effects ; pathology ; Hair Cells, Auditory, Outer ; drug effects ; pathology ; Mice ; Organ of Corti ; drug effects ; pathology ; Prescriptions ; Tablets