Biomedical subjects

Evelyne Ferrary

Publications and source records attributed to Evelyne Ferrary.

14 recordsLinked to original sources

PubMed2006

What's new in ion transports in the cochlea?

Recent advances in the field of the physiology of inner ear fluids permitted the characterization of the molecular mechanisms involved in critical processes such as the absorption of K(+) through cochlear sensory hair cells (mechanoelectrical transduction) or the secretion of K(+) by marginal cells of the stria vascularis. In addition, new pathways for ion circulations were evidenced. Mutations of transporters involved in some of these pathways, especially in K(+) recycling through gap junction systems, and in local pH regulation, are among the most frequent etiologies of genetic deafness in humans.

Acid-Base Equilibrium↗

PubMed2006

Functional IsK/KvLQT1 potassium channel in a new corticosteroid-sensitive cell line derived from the inner ear.

Endolymph, a high K(+)/low Na(+) fluid, participates in mechanoelectrical transduction in inner ear. Molecular mechanisms controlling endolymph ion homeostasis remain elusive, hampered by the lack of appropriate cellular models. We established an inner ear cell line by targeted oncogenesis. The expression of SV40 T antigen was driven by the proximal promoter of the human mineralocorticoid receptor (MR) gene, a receptor expressed in the inner ear. The EC5v cell line, microdissected from the semicircular canal, grew as a monolayer of immortalized epithelial cells forming domes. EC5v cells exhibited on filters of high transepithelial resistance and promoted K(+) secretion and Na(+) absorption. Functional MR and the 11beta-hydroxysteroid dehydrogenase type 2, a key enzyme responsible for MR selectivity were identified. Expression of the epithelial sodium channel and serum glucocorticoid-regulated kinase 1 was shown to be up-regulated by aldosterone, indicating that EC5v represents a novel corticosteroid-sensitive cell line. Ionic measurements and (86)Rb transport assays revealed an apical secretion of K(+) at least in part through the I(sK)/KvLQT1 potassium channel under standard culture conditions. However, when cells were exposed to high apically K(+)/low Na(+) fluid, mimicking endolymph exposure, I(sK)/KvLQT1 actually functioned as a strict apical to basolateral K(+) channel inhibited by clofilium. Quantitative reverse transcriptase-PCR further demonstrated that expression of KvLQT1 but not of I(sK) was down-regulated by high K(+) concentration. This first vestibular cellular model thus constitutes a valuable system to further investigate the molecular mechanisms controlling ionic transports in the inner ear and the pathophysiological consequences of their dysfunctions in vertigo and hearing loss.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2006

[Effects of noise on inner ear].

The effects of noise on health depend both on individual factors and characteristics of sound exposure. In case of acoustic trauma, reversible or irreversible lesions of inner ear components are possible. Most often there is immediately an acute tinnitus and hearing loss. Audiometric tests demonstrate hearing loss on the high frequency, generally focused on 4 kHz. Immediate treatment is recommended even there is no currently indicator of the ability to restore hearing. New perspectives on treatment are directed to local treatment and/or using new procedure as antioxidative treatment. Occupational and leisure are the two conditions in which chronic exposure to noise is found. Detection and prevention of noise-induced hearing loss is easier in case of industrial workers than in case of noise exposition for musicians and other sounds and stage technicians or concert managers, and of course non-professional with exposure to amplified music.

Ear, Inner↗

PubMed2006

Glucocorticoids inhibit diastrophic dysplasia sulfate transporter activity in otosclerosis by interleukin-6.

HYPOTHESIS/OBJECTIVE: Otosclerosis is a bone remodeling disorder localized to the otic capsule and associated with inflammation. In vitro, increased activity of the diastrophic dysplasia sulfate transporter (DTDST), which is implicated in bone metabolism, has been reported. Because glucocorticoids modulate the bone turnover and inhibit inflammatory processes, we investigated the effect of dexamethasone (Dex) on interleukin-6 and DTDST in otosclerosis. STUDY DESIGN: The authors conducted a prospective, case-control study. MATERIALS AND METHODS: Primary cell cultures were obtained from stapes and external auditory canals in otosclerosis (n = 21) and control patients (n = 18). Assays with [H]Dex evaluated specific binding sites in otosclerotic and control stapes. The effects of Dex (10 to 10 M) and RU486 (10 M), a glucocorticoid antagonist, were studied on DTDST activity by sulfate uptake. IL-6 secretion was measured in culture media before and after Dex (10 M, 24 hours). The effect of IL-6 (10 M, 24 hours) was assessed on DTDST activity in control stapes. RESULTS: : The number of specific Dex-binding sites was similar in all stapedial cultures. Dex inhibited DTDST activity (19.4 +/- 1.02 vs. 29.4 +/- 3.94 pmol/microg prot/5 minutes) only in otosclerotic stapes. This effect was dose-dependent, antagonized by RU 486 and only observed 24 hours after Dex exposure. Interleukin (IL)-6 stimulated DTDST activity in normal stapes, whereas Dex inhibited IL-6 production only in otosclerotic stapes. CONCLUSION: Dex inhibits the DTDST activity, at least in part, through a reduction of IL-6 secretion only in otosclerotic cells. This effect is mediated through the glucocorticoid receptors and may lead to the reduction of bone turnover.

Analysis of Variance↗

PubMed2005

Detection of labyrinthine fistulas in human temporal bone by virtual endoscopy and density threshold variation on computed tomographic scan.

OBJECTIVE: To assess the sensitivity of the routine computed tomographic (CT) scan of the temporal bone coupled to a virtual endoscopy, with density threshold variation, in detecting small fistulas in human temporal bone specimens. DESIGN: Single-blind, before-after trial. SETTING: This study was carried out in a research laboratory in collaboration with a radiology department. PATIENTS: Five human adult temporal bone specimens were included. INTERVENTIONS: The fistulas were created with calibrated burrs (0.3, 0.5, and 0.8 mm) in the 3 semicircular canals and in the promontory of 3 temporal bones. Two other temporal bones served as controls. All bones underwent CT scan (1-mm section thickness) before and after dissection. Three-dimensional images were obtained from CT scan native axial views at different density reconstruction thresholds. The virtual endoscope was placed in the middle ear cavity looking to the inner ear wall. The threshold at which a bony defect appeared on virtual endoscopic images (opening threshold in Hounsfield units [H]) was noted for each location. MAIN OUTCOME MEASURES: Opening thresholds before and after dissection. RESULTS: On standard axial views, fistulas smaller than 0.5 mm were not visualized. By virtual endoscopy, all fistulas could be visualized. The opening threshold decreased after fistula creation in the semicircular canals (1244 +/- 50.5 H [n = 36] vs 778 +/- 52.4 H [n = 34]; P<.001; 1-way analysis of variance and Dunnett multiple comparisons posttest) and in the promontory (1541 +/- 37.8 H [n = 12] vs 1334 +/- 35.1 H [n = 8]; P<.001). The opening thresholds in the control specimens remained unchanged after dissection. CONCLUSION: Virtual endoscopy with variation of reconstruction threshold allows the detection of small labyrinthine fistulas with diameters of 0.3 mm or smaller.

Adult↗

PubMed2005

[Auditory rehabilitation].

Auditory rehabilitation depends of the cause and the severity of the hearing loss (or deafness). Hearing losses dues to middle ear pathologies can beneficiate of medical or surgical treatments, by ossicular prostheses, if it is necessary to restore the function of the ossicles chain. In the sensorineural hearing losses, with inner ear pathology, the use of auditory aid is immediately considered. In the cases for which they are insufficient because of severity of the hearing loss or not suitable because of local non-tolerance, it is possible to use middle ear implant or cochlear implant. The indications of the auditory brainstern implants remain at this day limited to the total bilateral hearing losses due to a complete destruction of cochleae and auditory nerves. These therapeutic orientations are selected after a multidisciplinary evaluation of the deaf person, evaluation that allows the characterization of the hearing loss and its repercussion. In all the cases, the restoration of a bilateral hearing has to be done if possible, making an improvement of the speech comprehension, mainly in the noisy situations, as well as the localization of the sound sources.

Cochlear Implants↗

PubMed2005

Conservative management versus surgery for small vestibular schwannomas.

A high rate of deterioration in hearing function and the loss of patient compliance during conservative management should be taken into account when considering hearing preservation strategies for patients with vestibular schwannoma (VS). To compare conservative management with surgery for solitary small VS. Among 693 patients followed up for VS between 1991 and 2002, 114 (16%) intracanalicular VSs (stage 1) and 302 (44%) VSs measuring <15 mm in the cerebellopontine angle (stage 2) were included in this study. Initially, surgery was performed in 305 (73%) cases (50 stage 1, 255 stage 2) and 111 (27%) were managed conservatively (64 stage 1, 54 stage 2) by means of annual MRI scans and audiometry. Conservative management was chosen in patients aged >60 years and in those who refused surgery. In this subgroup, the mean follow-up period was 33 months (range 6-111 months). In the conservative management group, 47% of VSs showed significant growth, 47% were stable and 6% showed regression. Seventeen patients (15%) were operated on secondarily for tumour growth and 1 (1%) was irradiated for tumour growth and because surgery was contraindicated. Deterioration of hearing function by > or =1 class was observed in 56% of cases, 34% of patients were initially in hearing class D and only 10% showed stable hearing function. Of the conservative management group, 17% were lost during follow-up. After surgery, grade 1 or 2 facial function was obtained in 86% of cases. Following hearing preservation attempts (n=137), 54% of patients were in hearing classes A-C.

Adolescent↗

PubMed2004

[The endolymphatic sac: its roles in the inner ear].

The endolymphatic sac is a non-sensory organ of the inner ear. It is connected to the endolymphatic compartment that is filled with endolymph, a potassium-rich fluid that bathes the apical side of inner ear sensory cells. The main functions ascribed to the endolymphatic sac are the regulation of the volume and pressure of endolymph, the immune response of the inner ear, and the elimination of endolymphatic waste products by phagocytosis. Functional alteration of these functions, leading to deficient endolymph homeostasis and/or altered inner ear immune response, may participate to the pathophysiology of Ménière's disease, an inner ear pathology that causes episodes of vertigo, sensorineural hearing loss and tinnitus, and is characterized by an increase in volume of the cochleo-vestibular endolymph (endolymphatic hydrops).

Endolymph↗

PubMed2004

Aquaporin-2 in the human endolymphatic sac.

OBJECTIVE: To detect and localize aquaporin-2 (AQP-2), a water channel regulated by the antidiuretic hormone, in human endolymphatic sac. MATERIAL AND METHODS: Human endolymphatic sacs were sampled during removal of vestibular schwannomas via a translabyrinthine approach. Samples were immediately fixed in 10% formalin (24 h) and embedded in paraffin; in situ hybridization and immunohistochemistry were performed with an AQP-2-specific probe and a polyclonal antibody. RESULTS: Both AQP-2 mRNA and protein were detected in the epithelium of the endolymphatic sac. AQP-2 immunostaining was mainly cytoplasmic, suggesting that most AQP-2 was located in intracellular pools. CONCLUSIONS: In the endolymphatic sac, AQP-2 probably participates in the homeostasis of endolymph; the possibility of reducing the volume of endolymph by inhibiting its expression and membranous insertion using an antidiuretic hormone inhibitor represents a new therapeutic approach for the treatment of Ménière's disease.

Aquaporin 2↗

PubMed2004

Effect of 17 beta-estradiol on diastrophic dysplasia sulfate transporter activity in otosclerotic bone cell cultures and SaOS-2 cells.

OBJECTIVE: Diastrophic dysplasia sulfate transporter (DTDST) is involved in the regulation of bone turnover, and its activity in otosclerosis has been shown to be abnormally high. Taking into account the role of estrogens in the progression of otosclerosis, the possible effect of estrogens on DTDST was investigated in otosclerotic bone cell cultures and in SaOS-2, a human osteoblastic cell line. MATERIAL AND METHODS: Primary bone cell cultures of stapes and external auditory canal (EAC) bone were obtained from 33 patients with otosclerosis and 18 control patients undergoing cerebellopontine angle tumor surgery. These cultures were assessed in parallel with SaOS-2 cells. Estrogen receptors (ERs) were detected using reverse transcriptase polymerase chain reaction. DTDST activity was assessed by sulfate uptake at baseline and after 24 h of incubation with 17 beta-estradiol at concentrations ranging from 10(-12) to 10(-6) M. RESULTS: Stapes and EAC cultures predominantly expressed mRNA of ER alpha, while ER beta expression was predominant in SaOS-2 cells. In stapes and EAC cultures no modification of DTDST activity was observed with 10(-8) M 17 beta-estradiol. In SaOS-2 cells, DTDST activity was inhibited by 17 beta-estradiol (93.5+/-9.21 vs 83.6+/-8.83 pmol/mg protein/5 min, n=29; mean of differences=10.0+/-3.22, paired t-test, p<0.01). CONCLUSION: DTDST activity is regulated by estrogens in SaOS-2 cells, but not in primary cell cultures from stapes and EAC. This difference in the regulation mechanisms may be related to the type of estrogen receptor expressed.

Adult↗

PubMed2003

Clinical and Histologic Parameters Correlated with Facial Nerve Function After Vestibular Schwannoma Surgery.

This study was conducted to identify clinical and histologic factors that would influence, independently of tumor staging, postoperative facial function after removal of a vestibular schwannoma. A prospective study was performed on 35 consecutive patients with vestibular schwannomas who underwent the translabyrinthine approach. Facial function was assessed before and 1 year after surgery. The factors that influenced the postoperative outcome of the facial function independently of tumor staging were the absence or the desynchronization of homolateral auditory brainstem responses and tumor edema. Other factors (audiovestibular signs of brainstem compression, tumor inflammation, positive p53 protein immunostaining) were predictive of postoperative facial function but also correlated with tumor staging. Besides the well-known prognostic value of tumor staging for postoperative facial outcome, clinical (auditory brainstem responses) and histologic (tumor edema) factors correlated with postoperative facial function.

Journal Article↗

PubMed2003

High variability of perilymphatic entry of neutral molecules through the round window.

OBJECTIVE: To improve the efficacy of intratympanic therapy using perilymphatic entry through the round window membrane. MATERIAL AND METHODS: The perilymphatic entry characteristics of 2 neutral molecules, mannitol (182.2 Da) and inulin (7,000 Da), were studied. A polyethylene catheter was placed in contact with the guinea pig round window membrane and sealed with cyanoacrylate glue. This catheter was linked to an osmotic minipump that delivered 100 microl portions of 3H-mannitol or 3H-inulin solutions over a 7-day period at a constant rate (0.5 microl/h). Perilymph in the scala vestibuli and scala tympani, cerebrospinal fluid (CSF) and plasma were sampled after 4-7 days of delivery. RESULTS: Despite the constant rate of infusion, perilymphatic radioactivity varied widely from one animal to the other, probably as a function of the position of the microcatheter within the round window niche and/or the permeability of the round window. Even a large molecule such as inulin entered the perilymphatic space. Seven days after the beginning of 3H-mannitol administration, the radioactivity was higher in the perilymph of the scala tympani than in that of the scala vestibuli. The perilymphatic radioactivity on Day 7 was approximately 50% lower than that measured on Day 4 (p = NS). Finally, round window membrane delivery did not preclude distant spread of the molecules into the blood and CSF. CONCLUSIONS: Using round window membrane delivery, the perilymphatic entry of mannitol and inulin depended on their molecular weight. Intratympanic delivery induced a high inter-individual heterogeneity of the drug concentration within the inner ear, with subsequent variability of the therapeutic effects.

Administration, Topical↗

PubMed2003

Increased activity of the diastrophic dysplasia sulfate transporter in otosclerosis and its inhibition by sodium fluoride.

HYPOTHESIS: This study investigates the function of the diastrophic dysplasia sulfate transporter (DTDST) in otosclerotic bone and the effect on it of sodium fluoride (NaF). BACKGROUND: Otosclerosis is a localized bone dystrophy with increased bone turnover. DTDST is implicated in the regulation of the bone turnover. MATERIALS AND METHODS: Primary cultures of cells were obtained from the stapes and external auditory canal (EAC) of 26 patients with otosclerosis and from nine control patients. Sulfate uptake was quantified under basal conditions and with NaF. The NaF signaling pathways were investigated using forskolin and verapamil. RESULTS: The relative initial rates of sulfate uptake and the apparent Vmax values were: otosclerotic stapes > EAC > control stapes = control EAC. The sulfate uptake by the otosclerotic stapes was correlated with the loss of sensorineural hearing. The amounts of DTDST mRNA (RNase protection assay) in the four subgroups did not differ. NaF (10(-6)M, 1 hr) inhibited sulfate uptake by the otosclerotic stapes and EAC cells but not by control samples. CONCLUSION: The authors believe that whether the increased DTDST activity is a cause or an effect of otosclerosis, it appears to be a specific target for NaF treatment.

Adult↗

PubMed2002

In vivo absorption of water and electrolytes in mouse intestine. Application to villin -/- mice.

This study was done to establish and validate a single-pass perfusion method for measuring the absorption of water and electrolytes by the mouse small intestine. The method was then used to study intestinal absorption in mice whose villin gene had been invalidated (v-/-). The single-pass perfusion of the jejunum measures the absorption of water, Cl(-), Na(+), K(+), HCO, and glucose in anesthetized wild-type and v-/- mice in vivo. We measured absorption under basal and stimulated conditions (carbachol, vasoactive intestinal polypeptide, intralumen PGE(2)). Basal absorption and stimulated secretions were similar to those previously obtained in rats. There was no difference between wild-type and v-/- mice in animals with mixed genetic background or in pure C57BL6 mice. We conclude that this in vivo perfusion method is suitable for studying the absorption/secretion of electrolytes in the mouse intestine and that a lack of villin does not significantly alter basal and secretagogue-stimulated electrolyte movements across the epithelium of the mouse jejunum in vivo.

Animals↗