Biomedical subjects

M Anniko

Publications and source records attributed to M Anniko.

At least 217 records · Page 12Linked to original sources

PubMedDate not supplied

Cisplatin: evaluation of its ototoxic potential.

The ototoxic potential of cisplatin was analyzed in an organ culture model exposing the hair cells and other inner ear structures to cisplatin doses from 0.1 to 10 micrograms/ml. Selective hair cell degeneration was obvious at concentrations of 0.1 microgram/ml. Incubation with 1 microgram/ml caused morphologic damage in the supporting cells in both the cochlear and vestibular parts of the labyrinth. Exposure to 10 micrograms/ml during five days caused a total collapse of the membranous labyrinth. The morphologic degeneration pattern at the ultrastructural level is nonspecific, except that nuclear chromatin was either swollen and disintegrated or considerably condensed. Based on inner ear concentrations equivalent to aminoglycoside antibiotics in the range of 0.1 to 10 micrograms/ml, cisplatin is, in the in vitro model used in this study, the most ototoxic drug known. However, because of its single dose administration and long intervals between administration, clinical ototoxicity is less pronounced than that from aminoglycoside antibiotics.

Animals↗

PubMedDate not supplied

Ethacrynic acid effects on the isolated inner ear: evaluation of the ototoxic potential in an organ culture system.

The ototoxic potential of ethacrynic acid, defined as causing morphologic damage to hair cells or adjacent supporting structures, was analyzed in an organ culture model exposing inner ear structures to concentrations attainable during clinical conditions (0.1 to 10 micrograms/ml). In low doses more) ethacrynic acid caused generalized toxic effects on the tissue morphology of many types of inner ear tissues and an arrest of tissue differentiation. Although by definition ethacrynic acid is an ototoxic agent, there is, at least in the in vitro system, a very narrow dose range between the selective hair cell damaging concentration and that causing generalized toxic effects.

Animals↗

PubMedDate not supplied

The round window as access route for agents injurious to the inner ear.

The ototoxicity of 50% propylene glycol, 70% isopropyl alcohol, 2% acetic acid, Otic Domeboro solution (Miles Pharmaceuticals, West Haven, CT), 1% Gentian violet (Purepac Pharmaceutical, Elizabeth, NJ), Vosol Otic solution (Wallace Laboratories, Cranbury, NJ), Genoptic Ophthalmic solution (Allergan Pharmaceuticals, Irvine, CA), Cortisporin Otic suspension (Burroughs Wellcome, Greenville, NC), Coly-Mycin S Otic (Parke-Davis, Rochester, MI), and Pyocidin Otic (Berlex Laboratories, Cedar Knolls, NJ) was studied in rats according to their effect on the latencies of the second peak of the auditory brainstem responses (ABR) at different sound pressure levels. The substances were instilled into the round window (RW) niches of rats, and the ABR to 1-kHz and 6-kHz tonebursts were obtained, 30 minutes, two hours, and 1 week after exposure. For all substances except isopropyl alcohol and propylene glycol, which evidently quickly penetrated the RW, approximately two hours of exposure were required before inner ear function was affected. The ototoxic effect of the antibiotic drugs was to some degree reversed with time, whereas the recorded potentials for antiseptics such as 1% Gentian violet, 2% acetic acid, and Otic Domeboro indicate that they caused severe damage to inner ear function. Some increases in latencies were also noted after exposure to propylene glycol and isopropyl alcohol, except when the latter was quickly withdrawn from the RW niche.

Animals↗

PubMedDate not supplied

Staphylococcus aureus exotoxin has limited and transient effects on cochlear electrophysiology.

Seven ears of Sprague-Dawley rats were exposed to 20 microliters Staphylococcus aureus exotoxin suspension by injection via the tympanic membrane into the round window niche. Another 6 ears were exposed to 20 microliters broth as controls. ABR was performed in the interval 2-31.5 kHz immediately before and 1, 2, 5, 7 and 10 days after the exposure. Although threshold changes could be found in the toxin-exposed group but not the control group in the frequency range 10-20 kHz, there were only statistically significant threshold changes--at 31.5 kHz--on the 1st, 2nd, 5th, and 7th days after the exotoxin injection. S. aureus exotoxin has minor transient but reversible effects on the inner ear, causing chiefly high-frequency threshold and latency changes.

Animals↗

PubMedDate not supplied

Localization of nitric oxide synthase isoforms (NOS I, II and III) in the vestibular end organs of the guinea pig.

The localization of nitric oxide (NO) synthase (NOS) isoforms was investigated in the vestibular organ of the pigmented guinea pig by indirect immunohistochemistry. The cytoplasm of both type I and type II vestibular sensory cells as well as vestibular ganglion cells showed both NOS I and III immunoreactivity, whereas there was no reactivity in their nuclei and sensory hairs. The afferent nerve chalices were usually not stained. NOS III staining was also observed in the nerve fibers contacting type II cells and in the subepithelial tissue. The endothelial lining of the blood vessels displayed reactivity for NOS III. The cytoplasm of fluid transporting cells showed weak staining for NOS I and moderate staining for NOS III. Immunostaining for NOS II did not display any reactivity in general. These findings may suggest that NO is a mediator of neurotransmission in the vestibular system in sensory cells and ganglia. NO in the fluid transporting cells may play an important role for maintaining the endolymph and ion homeostasis, and NOS III in vascular endothelial cells implies regulatory effects of NO on vascular wall tonus and vestibular blood supply.

Animals↗

PubMedDate not supplied

Interleukin 8 can affect inner ear function.

The chemokine interleukin 8 (IL-8) was instilled into the round window niche of rats through a small perforation in the tympanic membrane in order to study its effect on inner ear function by electrophysiological and morphological techniques. The frequency-specific auditory brainstem response (ABR) was recorded at the frequencies 4, 8, 10, 12, 16 and 20 kHz just before and 1, 2, 5 and 14 days after instilling IL-8 to ascertain the hearing level during each interval. Morphological examination by light microscopy was performed during the same interval following the instillation of IL-8. On day 1, the rise in ABR threshold was within 5 dB SPL (non-significant elevation). However, a significant threshold elevation (above 5 dB SPL) occurred in high-frequency areas (16 and 20 kHz) on day 2, and in middle frequency areas (10 and 12 kHz) on day 5 with sensorineural hearing loss type intensity-latency curves. By day 14, the elevated thresholds had returned to pre-instillation levels. In the lowest areas (4 and 8 kHz), no significant threshold elevation was detected at any time during the observation period. By light microscopy, on day 1, clusters of inflammatory cells (predominantly neutrophils) were observed just outside the round window membrane (RWM), while only a few neutrophils were detected in the cochlea. These cells were still present outside the RWM on day 2. The neutrophils had disappeared by day 5 and only macrophages were present on the middle ear side of the RWM. However, throughout the observation period, the organ of Corti and stria vascularis appeared to be intact. These results suggest that IL-8 in the middle ear cavity is able to influence inner ear function.

Animals↗

PubMedDate not supplied

Possible involvement of free radicals in lipopolysaccharide-induced labyrinthitis in the guinea pig: a morphological and functional investigation.

Intratympanic injection of bacterial lipopolysaccharide impaired caloric responses and caused severe and widespread morphological damage to vestibular end organs and the endolymphatic sac in the guinea pig. These effects could be blocked with N-nitro-L-arginine methylester, a competitive inhibitor of nitric oxide synthase, with superoxide dismutase, an O2 scavenger, with dexamethasone, and with ebselen, a scavenger of peroxynitrite. These observations indicate that enhanced nitric oxide and superoxide production, resulting in formation of peroxynitrite, is probably an important factor responsible for the pathological damage to vestibuli. If this is so, we may have found a way to study vestibular pathogenesis in inner ear disease.

Animals↗

PubMedDate not supplied

Lipopolysaccharide-induced expression of reactive oxygen species and peroxynitrite in the guinea pig vestibular organ.

The purpose of this study was to investigate the occurrence of reactive oxygen species and peroxynitrite in the vestibular organ of the guinea pig following inoculation with bacterial lipopolysaccharide (LPS). The animals were injected transtympanically with 1 mg of LPS 24 h after the intraperitoneal injection of 0.1 mg LPS. Forty-eight hours after the inoculation, varying degrees of degeneration of the vestibular end organs were observed. Immunohistochemical study revealed immunoreactivity to xanthine oxidase (which generates O-2) in the vestibular organ after inoculation with LPS. Immunohistochemical investigation with a specific antinitrotyrosine antibody also showed intense staining of sensory epithelium, fluid transporting cells and the endolymphatic sac, suggesting formation of peroxynitrite in the vestibular organ through the reaction of NO with O-2. On the basis of these data, it can be concluded that NO together with O-2, which form more reactive peroxynitrite, may be the most important pathogenic agents in LPS-induced labyrinthitis in the guinea pig.

Animals↗

PubMedDate not supplied

Programmed cell death in the mouse cochleovestibular ganglion during development.

Programmed cell death (PCD) is as essential to development as is cell proliferation. Our objective was to elucidate the spatiotemporal occurrence of PCD during the development of the cochleovestibular ganglion. We performed a time-sequence study on the distribution of in situ PCD, apoptosis, during the development of the mouse cochleovestibular ganglion by using the TUNEL method to detect apoptosis histochemically. Apoptosis in the cochleovestibular ganglion was observed from the 11.5th gestational day (GD) to the 18. 5th GD. Apoptosis was seen most extensively in the vestibular ganglion cells at the 13.5th GD, while in the spiral ganglion cells apoptosis was maximal between the 15.5th and 16.5th GD. Because these times of peak apoptotic activity almost exactly corresponded to the events of innervation and terminal mitosis of the cochleovestibular ganglion cells, we infer that PCD is involved in the innervation and modulates the number of cochleovestibular ganglion cells overproduced by terminal mitosis.

Animals↗

PubMedDate not supplied

Interleukin-2 affects cochlear function gradually but reversibly.

Interleukin-2 (IL-2), one of the chemical mediators produced by helper T cells, activates its target cells via its receptor and induces inflammatory reactions indirectly. In this study, IL-2 was instilled into the round window niche of rats and the electrophysiological effects of inflammation on the inner ear were evaluated by a frequency-specific auditory brainstem response (ABR) technique. ABR threshold curves and intensity-latency (I-L) curves were investigated. In most cases, moderate sensorineural hearing loss (SNHL) was observed in the high-frequency areas (16-31.5 kHz). In the time course investigation of I-L curves, the responses of SNHL type appeared only 1 day after instillation (day 1) gradually becoming more prominent, to become most pronounced on days 5-7. The electrophysiological impairment was reversible within 2 weeks. Differing degrees of responsiveness of effusion production were observed following the instillation of IL-2, varying from pronounced middle ear effusion causing rather severe mixed hearing loss, to complete lack of effusion. Inflammation induced by IL-2 affects cochlear function gradually but reversibly.

Animals↗

PubMedDate not supplied

Free radicals in the guinea pig inner ear following gentamicin exposure.

The purpose of this study was to investigate the occurrence of free radicals, nitric oxide (NO), superoxide (O-2) and peroxynitrite, in the inner ear of the guinea pig following intratympanic injection with 5 mg of gentamicin (GM). Forty-eight hours after GM injection, varying degrees of degeneration of the inner ear were observed. Immunohistochemical study revealed immunoreactivity to NO synthase II (which generates NO) and to xanthine oxidase (which generates O-2) in both the vestibular organ and the organ of Corti. Immunohistochemical investigation, using a specific antinitrotyrosine antibody, also showed intense staining, suggesting formation of peroxynitrite in the inner ear through the reaction of NO with O-2. Scanning electron-microscopic study showed that the ototoxic effects could be blocked with N-nitro-L-arginine methylester, a competitive inhibitor of NO synthase, with superoxide dismutase, an O-2 scavenger, and with ebselen, a scavenger of peroxynitrite. On the basis of these findings, it can be concluded that NO together with O-2, which form more reactive peroxynitrite, play an important role in GM ototoxicity in the guinea pig.

Animals↗

PubMedDate not supplied

Hearing loss in relation to round window membrane morphology in experimental chronic otitis media.

The present study was performed to test the effect of single and repeated Pseudomonas aeruginosa exotoxin A (PaExoA) instillations in the middle ear of the rat. The hearing level was examined by the ABR technique, round window membrane (RWM) thickness was measured and morphology was studied by light microscopy. The results showed both reversible and permanent hearing loss (HL). In animals that received a single dose of PaExoA, the RWM thickness doubled initially and remained thickened during the observation period. When PaExoA was instilled on several occasions, RWM thickness doubled, before decreasing to near-control levels. This study confirms the toxicity of PaExoA and the partially reversible HL occurring after a single application of the toxin. The diminished effect of repeated toxin instillations--despite the decreasing thickness of the RWM--is discussed.

ADP Ribose Transferases↗

PubMedDate not supplied

Distribution of alpha-ANP in the cochlea and the vestibular organs.

The distribution of rat alpha-atrial natriuretic polypeptide (ANP) was studied in the adult inner ear of the Sprague-Dawley rat using immunohistochemical methods. Immunostaining, in particular of the subepithelial stroma cells of the spiral ligament, the spiral prominence and below neuroepithelial areas of all five vestibular organs, was identified. We hypothesize that alpha-ANP is involved in perilymphatic dynamics rather than generating endolymph. The strong staining for alpha-ANP of outer hair cells indicates specific mechanisms for volume control as compared with inner hair cells and vestibular hair cells which all lack this immunostaining. The functional significance of the specific staining of nerve calyces in only the three cristae ampullaris but not in the two maculae remains to be clarified. The positivity of epithelial cells in the endolymphatic sac supports a previous hypothesis which looks upon this organ as a pressure regulation system in the inner ear.

Animals↗

PubMedDate not supplied

Cytoskeletal basis for contractility of outer hair cells in the normal adult human organ of Corti: comparisons with vestibular hair cells.

The present study is the first consecutive analysis of the adult normal human organ of Corti and vestibular hair cells with regard to the expression of F-actin, actin-associated proteins (alpha-actinin, alpha- and beta-spectrins, vinculin and tropomyosin), beta-tubulin and the calcium-binding protein synaptophysin. The expression of these cytoskeletal and their associated proteins in man is largely similar to, although not identical with, that previously described for several other mammalian species. However, a few very unusual staining patterns were found. In several long outer hair cells a rod of F-actin extended from the infracuticular area to the cell nucleus. Fluorescence for tropomyosin occurred both in the cuticular plates of the outer and inner hair cells, and in the area of close apposition between the base of the outer hair cell and the apical part of Deiter's cell. In contrast, the vestibular hair cells showed immunoreactivity for tropomyosin only in the cuticular plates.

Actinin↗

PubMedDate not supplied

The human spiral ganglion.

The adult normal human spiral ganglion (SG) was analyzed with regard to ultrastructure and immunohistochemistry. The cytoskeleton of the SG cells was found to comprise F-actin, intermediate filaments (IFs) and microtubules (MTs). The IF subgroups (cytokeratins, Cks; neurofilaments, NFs, vimentin, glial fibrillary acidic proteins, GFAP; desmin) displayed characteristic staining patterns. Ck No. 8 was found in all SG cells, whereas vimentin was lacking. GFAP stained only a small subpopulation of SG cells (type 2?). The light (68 kD) and medium-sized chains of NFs occurred in all SG cells and axons, whereas the 200-kD NF subunit was only found in the axonal hillock of (type 2?) SG cells, but in no other part of the cytoplasm, and regionally in nerve fibres. MAP-1 and MAP-2 occurred in all SG cells but only MAP-1 was found in the nerve fibres. The calcium-binding protein synaptophysin (SY) was expressed only in SG cells, in contrast to the S-100 which occurred more generally in the labyrinth. The neuropeptides VIP and substance P were identified in all SG cells, in contrast to NPY which was expressed in a small subpopulation of SG cell (type 2?). Staining for neuron-specific enolase (NSE) identified most (type 1?) but not all SG cells. The cell surface glycoprotein Thy-1 was expressed in SG cells in a way similar to that described for neurons in the CNS. The SG cells express a high degree of cytoskeletal complexity, allowing one to distinguish between type 1 and type 2 cells. The cell bodies and their adjacent nerve fibres show characteristic features of calcium-binding proteins, surface membrane glycoproteins, NSE and neuropeptides but the basic pattern is still similar to neurons in the CNS.

Actins↗

PubMedDate not supplied

Microtubule-associated proteins in adult human sensory organs.

The distribution of microtubule-associated proteins MAP-1 and MAP-2 was analysed with immunomorphological techniques in the serially sectioned adult human membranous labyrinth. In the organ of Corti, monoclonal antibodies to MAP-1 did not stain. Positivity for MAP-2 occurred in the entire outer hair cell cytoplasm, in the inner hair cells (?), in the nerve fibres and in the cytoplasm of epithelial cells of the spiral prominence. In addition, staining for MAP-2 was identified in many (but not all) cells or Reissner's membrane. Immunofluorescence for MAP-1 occurred in the supporting cells of the cristae and maculae interpreted to be localized in the apical region adjacent to the sensory cells. Thus, the distribution of MAP-1 and MAP-2 in the adult human membranous labyrinth was the same as described for several animal species with regard to the cochlea. In contrast to such a pattern, both MAP-1 and MAP-2 were identified in the human vestibular organs, thus identifying a subpopulation of centrally located nerve calyces and possibly also the apical portion of vestibular hair cells.

Acoustic Maculae↗

PubMedDate not supplied

Hyaluronic acid as a molecular filter and friction-reducing lubricant in the human inner ear.

Immunofluorescence for hyaluronic acid occurred intracellularly in morphologically highly specialized areas in the adult human inner ear, for instance in the cuticular plates of all types of hair cells, at the apposition between outer hair cells and Deiter's cell bodies and in the near-surface area of Hensen's cells. The cytoskeletal organization in these regions is characterized by tightly packed filamentous proteins. Under physiological stimulus these regions undergo micromechanical change, either actively moving (force generation) or passively vibrating with changes in elasticity. Hyaluronic acid might therefore act as a friction-reducing molecular lubricant. In the lateral wall of the cochlea an accumulation of hyaluronic acid occurred in the loose connective tissue of the spiral ligament, in particular close to the stria vascularis. Due to its complex molecular network, hyaluronic acid offers considerable resistance to bulk flow of water and may exclude molecules. The basal cell region of the stria vascularis is thus given additional support to minimize (seal?) the stria vascularis towards all other areas except the endolymphatic space. Here, hyaluronic acid could act as a molecular filter.

Adolescent↗

PubMedDate not supplied

Comparative cytoskeletal analyses of the inner ear in man and the squirrel monkey.

Serially sectioned human and squirrel monkey labyrinths were analyzed with high-resolution light microscopy after using 25 different monoclonal antibodies (mAbs) identifying all three main classes of cytoskeletal proteins. A high degree of similarity was found in labyrinths from man and squirrel monkey. Only 1 of 25 mAbs stained differently between the two species. In the squirrel monkey but not in the human the mAbs identifying S-100 proteins stained subpopulations of type I vestibular hair cells in the striola of the two macula and the summit of the cristae as compared to the same type of hair cells in the periphery of vestibular organs. Such an establishment of subpopulations of hair cells with the same ultrastructure has previously not been described in higher vertebrates. In contrast to the species differences in the distribution of neuroactive substances, the cytoskeletal architecture seems to be relatively unchanged and stable during evolution. Since each species has its own hearing and equilibrium function, neurotransmitters (neuropeptides, amino acids, etc.) could contribute to such species-specific functions.

Acoustic Maculae↗