Biomedical subjects

E Ferrary

Publications and source records attributed to E Ferrary.

At least 19 recordsLinked to original sources

PubMed2006

[Performances and complications of cochlear implant in 134 adult patients implanted since 1990].

OBJECTIVE: The aim of this study was to analyse performance of cochlear implants in a retrospective series of adults with postlingually in order to search for predictive factors and identify complications. METHODS: Between 1990 and 2003, 134 adult patients were implanted: 129 patients on one side and 5 patients on both sides. Hearing benefit at 6, 12, 24 and 36 months and performance at 12 months were analyzed as function of the etiology, age at implantation, lipreading and speech coding strategy. RESULTS: Compared to performances before implantation, cochlear implants provided significant and rapid improvement at 6 months (p<0.0001). The results were not correlated with age at implantation, etiology or lipreading ability before implantation. Performances were worse in patients with meningitis (p<0.01), but the percentage of improvement was similar between the different etiologies. Major complications were rare: one case of regressive postoperative facial nerve weakness. CONCLUSION: Cochlear implants provide significant and rapid improvement, with low morbidity. Results are not correlated with age at implantation, etiology or lipreading ability.

Adolescent↗

PubMed2004

[Beneficial effect of cochlear implants in the elderly].

OBJECTIVE: To evaluate the benefit of cochlear implantation in older adults aged 60 Years and over. METHODS: Fifty-six profoundly or totally hearing-impaired patients, aged 60 Years and over, were studied retrospectively. At the end of the preoperative evaluation, 28 patients received a cochlear implant. The mean age was 66 Years and the median follow-up was 22.5 Months. Speech perception scores before and after implantation were analyzed in order to evaluate the benefit of cochlear implantation. The speech perception score before implantation was compared to that of the non-implanted patients. RESULTS: There was a significant improvement of the dissyllabic words and sentences scores after implantation. The patients who are over 70 Years performed as well as those who are younger (between 60 and 70 Years). One patient developed a postoperative vertigo due a perilymphatic fistula. There was no flap-related problems. In the non-implanted group (mean age: 68 Years), 18 patients declined the cochlear device because they thought the subjective benefit of their hearing aid was sufficient and 5 patients declined because of surgical risk. The mean age, the cause and the duration of the deafness, and the speech perception scores were similar between implanted and non-implanted patients. CONCLUSION: This study demonstrates the beneficial effect of cochlear implantation in the elderly. These results suggest that a similar benefit could have been obtained in the patients who declined surgery. An early implantation could reduce the duration of the deafness and preserve binaural sound perception allowing increased performance in older people.

Aged↗

PubMed2004

Temporal bone density measurements using CT in otosclerosis.

OBJECTIVE: To assess the bone density around the bony labyrinth in otosclerosis patients and to compare it to that of a control population. MATERIAL AND METHODS: This was a prospective case-control study. Ten patients with otosclerosis (mean age 42 years; range 24-55 years) and 33 control patients with vestibular schwannoma (mean age 46 years; range 20-71 years) were included. All patients underwent a clinical examination, audiometry and a CT scan comprising axial and coronal views of both temporal bones. In the otosclerosis group, audiometry showed unilateral involvement in six patients and bilateral hearing loss in four. The bone density was measured at the fissula ante fenestram (FAF) and at five other anatomical points on the bony labyrinth. RESULTS: In the control group, the bone density was similar at the six anatomical points. In the otosclerosis patients, the mean bone density at the FAF was lower than that in control patients (1649+/-99.1 vs 2049+/-13.4 HU; p < 0.01). For patients with FAF bone densities < 2000 HU, a correlation was observed between hearing threshold and FAF bone density. CONCLUSION: FAF bone density appears to be a good indicator of disease progression, and could serve as a follow-up and prognostic parameter.

Adult↗

PubMed2002

Local administration of antioxidants to the inner ear. Kinetics and distribution(1).

Round window (r.w.) administration of drugs involves the delivery of medication directly into the inner ear via the r.w. membrane, avoiding a systemic effect of the therapy. Earlier experimental studies suggest that a number of antioxidants and scavengers hold promise for ameliorating the tissue damaging capacity of reactive oxygen species in some acquired cochlear disorders. D-Methionine and thiourea are two small sulfur-containing molecules with an antioxidative and scavenging effect. The passage through the r.w. of radioactive D-methionine and thiourea administered by 1 h infusion to the r.w. was studied in a rat model. Levels of the tracers were measured in scala tympani perilymph (PLT) 17-254 min after r.w. administration. Both tracers pass the r.w. membrane readily. Peak levels were found in the earliest taken samples after the administration. The radioactivity in PLT of the basal turn reached a peak to about 1.5-1.9% of the irrigating medium radioactivity. Following the r.w. administration, the concentration of radioactive D-methionine and thiourea declined with a terminal half-life of 0.57 and 0.77 h, respectively. The distribution of the tracers at the cellular level was analyzed by autoradiography. The most intense expression was found in the lateral wall of the cochlea. It can be postulated that local delivery to the cochlea of D-methionine and thiourea via the r.w. gives high local concentrations of the substances in PLT in the basal turn.

Animals↗

PubMed2002

[Na transport in the cochlea of mammals].

Endolymph, the fluid that bathes the apical side of the inner ear sensory cells, is a K-rich and Na-poor fluid. In the cochlea, various epithelial transport systems involved in the transport of Na from the apical endolymphatic to the basolateral perilymphatic compartments have been identified: basolateral Na+, K(+)-ATPase, apical non selective cationic channels, Na+/H+ exchanger, and ENaC epithelial Na channel. These transporters may be involved in physiological and pathological processes in which endolymph Na concentration is high.

Animals↗

PubMed2001

Effects of acute and chronic hypertension on the labyrinthine barriers in rat.

Hearing loss, vertigo, and tinnitus have been related to arterial hypertension. The aim of the present work was to study the permeability of the blood-perilymph and of the labyrinthine barrier, between endolymph and perilymph, to small molecules during chronic and acute hypertension. Experiments were performed in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Acute hypertension was induced by phenylephrine. Perilymph was sampled from the first turn of the scala vestibuli and the Na, K, urea, and radioactive concentrations ((14)C-urea and (3)H-mannitol) were measured. In another experimental set, the endocochlear potential was recorded from the basal turn of scala media, before and after phenylephrine injection. The composition of the perilymph and the kinetic constants for (14)C-urea and (3)H-mannitol were similar in WKY and SHR, and not modified after acute hypertension. In endolymph, the endocochlear potential in SHR (+80+/-2.7 mV, n=24) was lower (P<0.001) than in WKY (+98+/-1.5 mV, n=29). The endocochlear potential was decreased by 40 mV during acute hypertensive peak in seven out of 19 WKY but not in SHR rats (n=13). In conclusion, chronic or acute hypertension did not severely alter the permeability to small molecules of the blood-perilymph barrier. The relationship between the low endocochlear potential and hypertension in SHR remains to be evaluated. After acute hypertensive peak, the presence of vascular protective mechanisms in the cochlea could account for the stable endocochlear potential recorded in SHR and 60% of normotensive rats.

Acute Disease↗

PubMed2001

Influence of trimetazidine on the synthesis of complex lipids in the heart and other target organs.

Trimetazidine exerts antianginal properties at the cellular level, without haemodynamic effect in clinical and experimental conditions. This cytoprotection was attributed to a decreased utilization of fatty acids for energy production, balanced by an increased incorporation in structural lipids. This study evaluated the influence of Trimetazidine on complex lipid synthesis from [2-(3)H] glycerol, in ventricular myocytes, isolated rat hearts and in vivo in the myocardium and several other tissues. In cardiomyocytes, Trimetazidine increased the synthesis of phosphatidyl-choline (+ 80%), phosphatidyl-ethanolamine (+ 210%), phosphatidyl-inositol (+ 250%) and cardiolipid (+ 100%). The common precursor diacylglycerol was also increased (+ 40%) whereas triacylglycerol was decreased (-70%). Similar results were obtained in isolated hearts with 10 microm Trimetazidine (phosphatidyl-choline + 60%, phosphatidyl-ethanolamine + 60%, phosphatidyl-inositol + 100% and cardiolipid + 50%), the last two phospholipids containing 85% of the radioactivity. At 1 microm, Trimetazidine still stimulated the phospholipid synthesis although the difference was found significant only in phosphatidyl-inositol and cardiolipid. In vivo studies (10 mg/kg per day for 7 days and 5 mg/kg, i.p. before the experiment) revealed significant changes in the intracellular lipid biosynthesis, with increased labelling of phospholipids and reduced incorporation of glycerol in nonphosphorous lipids. Trimetazidine increased the glycerol uptake from plasma to the other tissues (liver, cochlea, retina), resulting in an altered lipid synthesis. The anti-anginal properties of Trimetazidine involve a reorganisation of the glycerol-based lipid synthesis balance in cardiomyocytes, associated with an increased uptake of plasma glycerol that may contribute to explain the pharmacological properties reported in other organs.

Animals↗

PubMed2001

H+,K+-ATPase is not involved in endolymph pH homeostasis.

In endolymph, the calculated electrochemical gradients suggest the presence of active transport of H+ and K+. The presence of H+,K+-ATPase, an active transporter that mediates the exchange of intracellular H+ for extracellular K+, was investigated using reverse transcription-polymerase chain reaction on rat microdissected inner ear tissues. Distal colon and kidney were used as positive controls. The two H+,K+-ATPase colonic or gastric isoforms were not detected in the rat cochlea and endolymphatic sac. This result suggests that H+,K+-ATPase is not involved in H+ and K+ endolymph homeostasis.

Acid-Base Equilibrium↗

PubMed2001

Purine and pyrimidine nucleotide-sensitive phospholipase A(2) in ampulla from frog semicircular canal.

This study was attempted to characterize pharmacologically the P2Y receptors triggering phospholipase A(2) (PLA(2)) activation in ampulla from frog semicircular canal. A microassay was developed to screen the abilities of UTP analogs to stimulate [(3)H]arachidonic acid release by labeled ampullas. At 26 degrees C UTP induced a dose-dependent and saturable increase of PLA(2) activity (apparent activation constant 1.3 +/- 0.4 microM, Hill coefficient 0.9 +/- 0.2, maximal stimulating factor 2.0 +/- 0.1). The rank order of potency of agonists for PLA(2) activation was UTP > or = UDP > adenosine 5'-O-(2-thiodiphosphate) = adenosine 5'-O-(3-thiotriphosphate) > or = ATP = 2-methylthio-ATP > or = ADP = diadenosine tetraphosphate > or = alpha,beta-methylene-ATP = CTP > 2' and 3'-O-(4-benzoylbenzoyl)-ATP > or = AMP = UMP >> uridine and adenosine. UTP- and 2-methylthio-ATP-induced PLA(2) activations were inhibited by U-73122, GF-109203X, and methyl arachidonyl fluorophosphate. Basal activity was stimulated by phorbol ester and epinephrine and reduced by vasotocin, isoproterenol, prostaglandin E(2), cAMP, and forskolin. H-89 restored the cAMP- and forskolin-inhibited PLA(2) activities. Results indicate that P2Y receptor-mediated PLA(2) stimulation requires phopholipase C and protein kinase C activations and basal activity is inhibited by agonist-stimulated cAMP-dependent mechanisms.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2001

Location and function of the epithelial Na channel in the cochlea.

In the cochlea, endolymph is a K-rich and Na-poor fluid. The purpose of the present study was to check the presence and to assess the role of epithelial Na channel (ENaC) in this organ. alpha-, beta-, and gamma-ENaC subunit mRNA, and proteins were detected in rat cochlea by RT-PCR and Western blot. alpha-ENaC subunit mRNA was localized by in situ hybridization in both epithelial (stria vascularis, spiral prominence, spiral limbus) and nonepithelial structures (spiral ligament, spiral ganglion). The alpha-ENaC-positive tissues were also positive for beta-subunit mRNA (except spiral ganglion) or for gamma-subunit mRNA (spiral limbus, spiral ligament, and spiral ganglion), but the signals of beta- and gamma-subunits were weaker than those observed for alpha-subunit. In vivo, the endocochlear potential was recorded in guinea pigs under normoxic and hypoxic conditions after endolymphatic perfusion of ENaC inhibitors (amiloride, benzamil) dissolved either in K-rich or Na-rich solutions. ENaC inhibitors altered the endocochlear potential when Na-rich but not when K-rich solutions were perfused. In conclusion, ENaC subunits are expressed in epithelial and nonepithelial cochlear structures. One of its functions is probably to maintain the low concentration of Na in endolymph.

Action Potentials↗

PubMed2000

Identification of uridine 5'-triphosphate receptor mRNA in rat cochlear tissues.

Previous investigations have reported the presence of uridine 5'-triphosphate (UTP) and adenosine 5'-triphosphate (ATP) receptors triggering phospholipase C (PLC) activation in the frog semicircular canal. The aim of this work was to characterize the molecular subtypes of these nucleotide receptors. Due to the lack of molecular tools for purinoceptors in amphibia, this study was performed on the rat. The stria vascularis, organ of Corti and spiral ligament were microdissected from Long Evans rat cochlea. RNA was extracted from four cochleas and polymerase chain reaction (PCR) was performed after reverse transcription (RT) using oligonucleotides for sequences of P2Y1, P2Y2, P2Y4 and P2Y6 receptors. Various tissues were used as negative controls (testis for P2Y1 and P2Y6 receptors, brain for P2Y2 and P2Y4 receptors and liver for P2Y4 receptors). Data show the expression of the four transcripts in the stria vascularis, organ of Corti and spiral ligament. When results were normalized to the signal obtained with S14 mRNA, a ribosomal protein used as an internal standard, expressions were similar in the three structures. In conclusion, these results demonstrate the mRNA expression of the three UTP receptors (P2Y2, P2Y4 and P2Y6) and of the P2Y1 ATP receptor in both sensory and secretory structures of the rat inner ear. Their functional roles remain to be defined.

Animals↗

PubMed2000

Blood-perilymph barrier and ototoxicity: an in vivo study in the rat.

Cisplatin and gentamicin are two ototoxicants that are supposed to be transported by the paracellar route, i.e. via cellular junctions, to the perilymphatic compartment. This study was initiated to test the hypothesis that susceptive variation of individuals to ototoxic drugs may be explained by variability in transport properties. The transport of radioactive mannitol through the blood-perilymph barrier was correlated in vivo with the acute effect of cisplatin and gentamicin on auditory function. Transport of radioactive mannitol across the blood-perilymph barrier was monitored by sampling of scala vestibuli perilymph at 60 and 120 min after an intravenous infusion of the tracer to nephrectomized Long Evans rats. Counting of hair cell loss was performed in the animals receiving 16 mg/kg body weight cisplatin. The transport of radioactive mannitol across the blood-perilymph barrier did not correlate with the ototoxic effect of cisplatin, evaluated as changes in the auditory-evoked brainstem response thresholds or loss of outer hair cells. The results provide evidence that the barrier function is not involved in the interindividual variability of the ototoxic effect of cisplatin. Furthermore, it can be postulated that neither cisplatin nor gentamicin induce a disruption of endothelial cell junction stability in the inner ear.

Animals↗

PubMed2000

No evidence of measles virus in stapes samples from patients with otosclerosis.

Otosclerosis is a localized bone dystrophy of unknown etiology mainly involving the stapes. The hypothesis of a persistent infection by the measles virus was based on the inconstant detection of the virus by various methods, including reverse transcription-PCR (RT-PCR) of patients' stapes samples. The aim of this work was to investigate the presence of the measles virus in stapedial otosclerosis foci by different sensitive methods. Pathologic stapes samples were obtained from 35 patients suffering from otosclerosis. Measles virus detection was performed by (i) cocultures of Vero cells and primary cell cultures of bone samples (n = 7), (ii) immunofluorescence study of these cocultures (n = 3), and (iii) RT-PCR on RNA directly obtained from fresh frozen samples (n = 28) and on RNA extracted from the primary cell cultures (n = 2). Viral genomic regions coding for N (nucleoprotein) and M (matrix) proteins were separately amplified. PCR sensitivity was optimized on the measles virus Edmonston strain. Glyceraldehyde-3-phosphate dehydrogenase mRNA was used as a marker of total RNA recovery. PCR products were tested by Southern blot hybridization technique to improve sensitivity and specificity. PCRs amplifying the M and the N protein genes were able to detect the control measles virus RNA at titers as low as 0.1 and 0.01 50% tissue culture infective dose, respectively. With these highly sensitive methods, we could not evidence the presence of the measles virus in any of our bone samples or primary bone cell cultures. Our results do not confirm the hypothesis of persistent measles virus infection in otosclerosis.

Adult↗

PubMed2000

UTP binding and phosphoinositidase C activation in ampulla from frog semicircular canal.

Pyrimidine nucleotide-sensitive phosphoinositidase C activity (PLC), previously identified in frog semicircular canal ampulla, was pharmacologically characterized. Binding of [(3)H]UTP and abilities of unlabeled nucleotide analogs to inhibit binding and to stimulate PLC in myo-[(3)H]inositol-loaded ampullas were determined. Specific [(3)H]UTP binding was competitively inhibited by UTP [apparent dissociation binding constant = 0.8 microM; Hill coefficient = 0.7]. Scatchard analysis revealed a minor class of high-affinity binding sites [45 fmol UTP bound/microgram protein; dissociation constant (K(D1)) = 0.4 microM] and a major class of moderate-affinity binding sites (365 fmol UTP bound/microgram protein; K(D2) = 10 microM). The stereospecificity pattern for UTP analog recognition was UMP > UDP >/= ADP = UTP = dTTP > adenosine 5'-O-(3-thiotriphosphate) = ATP = CTP = 2'-and 3'-O-4-(benzoylbenzoyl)-ATP (Bz-ATP) >/= AMP >/= 2-methylthio-ATP = alpha,beta-methylene-ATP > uridine = diadenosine tetraphosphate (Ap(4)A); cAMP and adenosine were inactive. Antagonist recognition pattern was DIDS = pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) = reactive blue 2 > suramin. The rank order of potencies for agonist-induced PLC activation was UDP >/= UTP >/= Ap(4)A >/= UMP = Bz-ATP; uridine was inactive. UTP-stimulated PLC activity was inhibited by DIDS = reactive blue 2 = PPADS > suramin. These results suggest that the population of [(3)H]UTP-labeled binding sites is heterogeneous, with a low number of high-affinity UTP receptors whose function(s) need to be determined and a large number of moderate-affinity receptors triggering PLC activation.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2000

Effect of locally applied drugs on the pH of luminal fluid in the endolymphatic sac of guinea pig.

The aim of the present work was to assess the effect of various drugs applied locally on the pH of the luminal fluid (pH(lum)) in guinea pig endolymphatic sac. pH(lum) and transepithelial potential, when measured in vivo by means of double-barrelled pH-sensitive microelectrodes, were 7.06 +/- 0.08 and +6.1 +/- 0.34 mV (mean +/- SE; n = 84), respectively, which is consistent with a net acid secretion in the luminal fluid of the endolymphatic sac. Bafilomycin and acetazolamide increased and decreased, respectively, pH(lum). Amiloride, ethylisopropylamiloride, ouabain, and Schering 28080 had no effect on pH(lum). Results obtained with inhibitors of anionic transport systems were inconclusive; e.g., DIDS reduced pH(lum), whereas neither SITS nor triflocin had any effect. We conclude that bafilomycin-sensitive H(+)-ATPase activity accounts for the transepithelial acid gradient measured in the endolymphatic sac and that intracellular and membrane-bound carbonic anhydrase probably participates in regulating endolymphatic sac pH(lum). The relationship between acid pH, endolymph volume, and Ménière's disease remains to be further investigated.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1999

In vivo, villin is required for Ca(2+)-dependent F-actin disruption in intestinal brush borders.

Villin is an actin-binding protein localized in intestinal and kidney brush borders. In vitro, villin has been demonstrated to bundle and sever F-actin in a Ca(2+)-dependent manner. We generated knockout mice to study the role of villin in vivo. In villin-null mice, no noticeable changes were observed in the ultrastructure of the microvilli or in the localization and expression of the actin-binding and membrane proteins of the intestine. Interestingly, the response to elevated intracellular Ca(2+) differed significantly between mutant and normal mice. In wild-type animals, isolated brush borders were disrupted by the addition of Ca(2+), whereas Ca(2+) had no effect in villin-null isolates. Moreover, increase in intracellular Ca(2+) by serosal carbachol or mucosal Ca(2+) ionophore A23187 application abolished the F-actin labeling only in the brush border of wild-type animals. This F-actin disruption was also observed in physiological fasting/refeeding experiments. Oral administration of dextran sulfate sodium, an agent that causes colonic epithelial injury, induced large mucosal lesions resulting in a higher death probability in mice lacking villin, 36 +/- 9.6%, compared with wild-type mice, 70 +/- 8.8%, at day 13. These results suggest that in vivo, villin is not necessary for the bundling of F-actin microfilaments, whereas it is necessary for the reorganization elicited by various signals. We postulate that this property might be involved in cellular plasticity related to cell injury.

Actin Cytoskeleton↗

PubMed1999

Evidence for apical K conductance and Na-K-2Cl cotransport in the endolymphatic sac of guinea pig.

The transepithelial potential in the endolymphatic sac (ESP) was recorded up to 60 min after apical injection of ouabain, bumetanide, quinine, barium, tetraethylammonium, and 4-aminopyridine. After control injection, ESP decreased by 74% and completely recovered at 30 min. After ouabain, barium, or quinine injection, the ESP time course was similar to that in the control group. After bumetanide, tetraethylammonium, or 4-aminopyridine injection, complete recovery was only observed at 60 min. These results suggest that apical K+ conductance and Na-K-2Cl cotransporter could be involved in the genesis of ESP.

Animals↗

PubMed1999

In vivo study of the electrochemical composition of luminal fluid in the guinea pig endolymphatic sac.

The aim of this study was to investigate the ionic composition (sodium, potassium) of the luminal fluid in the endolymphatic sac and to correlate it with the transepithelial potential. Experiments were performed in guinea pigs using either an intradural posterior fossa approach or a translabyrinthine approach. The endolymphatic sac transepithelial potential (ESP) was measured and the luminal fluid was sampled. The sodium, potassium and protein concentrations were determined. The results were: i) the luminal fluid in the endolymphatic sac differs in composition from perilymph, on the one hand, and from both cochlear and vestibular endolymph, on the other hand, indicating that the endolymphatic sac maintains chemical (sodium, potassium) and electrical (ESP) gradients; ii) the calculated osmolarity (Na + K) x 2 was about 230 mosm/l; iii) no correlation was observed between sodium and potassium concentrations; iv) large interindividual variations exist from one animal to another, suggesting physiological variations in the functional status of the endolymphatic sac. In conclusion, the variation in composition of the endolymphatic sac luminal fluid reflected variations in ion transport by the epithelium and thus a possible adaptation of the ion transport to different physiopathological conditions.

Animals↗