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Noise-induced hypertension and magnesium in rats: relationship to microcirculation and calcium.
Altura BM, Altura BT, Gebrewold A, Ising H, Gunther T. Department of Physiology, State University of New York, Brooklyn 11203.
J Appl Physiol 1992 Jan;72(1):194-202
It has been demonstrated that audiogenic stress (AS) can induce elevation of arterial blood pressure (ABP) in animals and humans and that noise-induced hearing loss may be associated with alterations in Mg metabolism. Experiments were designed to determine whether 1) there is a causal relationship among environmental noise stress, serum and vascular tissue (aortas and portal veins) Mg contents, and development of hypertension and 2) such noise-induced hypertension has a microcirculatory basis and what the mechanism may be. Rats maintained on normal Mg-containing diets for 12 wk (plasma [Mg] = 0.96 +/- 0.02 mM) and subjected to AS (85 dB(A), 12 h/day for 8 wk; 95 dB(A), 16 h/day for 4 wk) demonstrated significant elevation in systolic and diastolic ABP; plasma [Mg] showed a 15% deficit, whereas aortic and portal vein muscle exhibited slight reductions in Mg content and elevation in Ca. Moderate and more severely Mg-deficient animals not subjected to AS also exhibited significant elevations in systolic and diastolic ABP; vascular tissue Mg content decreased, whereas Ca content rose. Animals subjected to combined Mg deficiency and AS for 12 wk exhibited the greatest deficits in plasma and vascular muscle Mg and the greatest elevations in systolic and diastolic ABP; vascular tissue Ca contents also showed the greatest increases. In situ measurements of mesenteric arterioles, venules, and precapillary sphincters in the various subgroups revealed that the lower the plasma [Mg], the more constricted the microvessels, and the higher the ABP, the lower the plasma [Mg]. Capillary blood flow velocities were decreased in relation to the degree of plasma Mg deficit.(ABSTRACT TRUNCATED AT 250 WORDS)
NG-methyl-L-arginine protects the guinea pig cochlea from the cytotoxic effects of pneumolysin.
Amaee FR, Comis SD, Osborne MP. Department of Physiology, Medical School, University of Birmingham, England.
Acta Otolaryngol 1995 May;115(3):386-91
Sensorineural hearing loss is a major sequela of the bacterial meningitis associated in particular with Streptococcus pneumoniae. Recent studies have shown pneumolysin, a toxin elaborated by S. pneumoniae, to be cytotoxic to the guinea pig cochlea. The mechanisms of this cytotoxicity are, however, not fully understood. In the present study this deleterious action of pneumolysin has been shown to be blocked by pretreating the cochlea with NG-methyl-L-arginine, a known inhibitor of nitric oxide synthesis. Furthermore, pretreatment of the cochlea with MK-801, an NMDA receptor antagonist, was also found to confer marked protection from the action of pneumolysin. This latter finding is consistent with previous reports that excess stimulation of NMDA receptors within the cochlea, an event known to lead to excess nitric oxide release, have similar effects on the cochlea as pneumolysin perfusion. It would therefore appear that nitric oxide may represent a significant link in the chain of events leading to the deafness of bacterial meningitis.
The consequences of untreated hearing loss in older persons.
Anon.
ORL Head Neck Nurs. 2000 Winter; 18(1): 12-6.
No abstract available.
Vitamin E and lipoic acid, but not vitamin C improve blood oxygenation after high-energy IMPULSE noise (BLAST) exposure.
Armstrong KL, Cooper MF, Williams MT, Elsayed NM Department of Respiratory Research, Walter Reed Army Institute of Research, Washington, DC 20307, USA. MAJ_KARYN_ARMSTRONG@WRSMTP-CCMAIL.ARMY.MIL
Biochem Biophys Res Commun 1998 Dec 9;253(1):114-8
Exposure to high energy impulse noise (BLAST) caused by explosions, result in structural and functional damage to the hollow organs, especially to the respiratory and auditory systems. Lung damage includes alveolar wall rupture, edema and hemorrhage, and may be fatal. Previous observations at the molecular level using the rat model, suggested that secondary free radical-mediated oxidative stress occurs post exposure resulting in antioxidant depletion and hemoglobin (Hb) oxidation. This study examined whether a short period of pre-exposure supplementation with antioxidants would protect Hb from the effects of BLAST exposure. Six groups of male Sprague-Dawley rats (8/group) were gavaged with 800 IU vitamin E (VE) in 2 ml corn oil, 1000 mg vitamin C (VC) in 2 ml distilled water or 25 mg or (-lipoic acid (LA) in 2 ml corn oil for 3 days. Matched control groups were gavaged with the respective vehicles. On day 4, rats were deeply anesthetized and exposed to a simulated BLAST wave with an average peak pressure of 62 +/- 2 kPa. Rats were euthanized one hour post exposure and blood samples were obtained by cardiac puncture and analyzed using a hemoximeter. Post exposure oxygenation states (HbO2, O2 saturation, and O2 content) were markedly decreased, while reduced-Hb was increased. Supplementation with VE and LA reversed the trend and increased Hb oxygenation, but VC did not. This suggests that a brief dietary loading with pharmacological doses of VE or LA, but not VC shortly before BLAST exposure may be beneficial. Moreover, measurement of blood oxygenation may function as a simple semi-invasive biomarker of BLAST-induced injury applicable to humans.
Oral magnesium intake reduces permanent hearing loss induced by noise exposure.
Attias J, Weisz G, Almog S, Shahar A, Wiener M, Joachims Z, Netzer A, Ising H, Rebentisch E, Guenther T. Institute of Noise Hazards Research, I.D.F. Medical Corps, Haifa, Israel.
Am J Otolaryngol 1994 Jan-Feb;15(1):26-32
INTRODUCTION: Following animal experiments where correlations were observed between serum magnesium level and noise-induced permanent hearing threshold shifts (NIPTS), we tested the prophylactic effect of magnesium in human subjects exposed to hazardous noise. METHODS: Subjects were 300 young, healthy, and normal-hearing recruits who underwent 2 months of basic military training. This training necessarily included repeated exposures to high levels of impulse noises while using ear plugs. During this placebo-controlled, double-blind study, each subject received daily an additional drink containing either 6.7 mmol (167 mg) magnesium aspartate or a similar quantity of placebo (Na-aspartate). RESULTS: NIPTS was significantly more frequent and more severe in the placebo group than in the magnesium group, especially in bilateral damages. NIPTS was negatively correlated to the magnesium content of blood red cells but especially to the magnesium mononuclear cells. Long-term additional intake of a small dose of oral magnesium was not accompanied by any notable side effect. CONCLUSION: This study may introduce a significant natural agent for the reduction of hearing damages in noise-exposed population.
Hearing loss.
Bertoni, J.M. et al.
In Professional Guide to Signs & Symptoms, Third Edition 2001, pp. 286, 370-5. Springhouse, PA: Springhouse.
[Vitamin A and the ear. Review of the literature.] [Article in German]
Biesalski HK.
Z Ernahrungswiss 1984 Jun;23(2):104-12
Since the first characterization and description of vitamin A this is used in otolaryngologic therapy for different forms of hearing disorders, and its relation to the inner ear is subject of investigation. Animal experiments and clinical studies were done to clarify the significance of vitamin A for the function of hearing. Besides this there were a lot of observations describing correlations between vitamin A metabolism and hearing loss. Recent investigations showed that vitamin A is present in high concentrations in the inner ear and stored there. Morphological experiments revealed different and in some way contradictory results, but they showed that vitamin A seems to be essential for inner-ear morphogenesis.
Vitamin A deficiency increases noise susceptibility in guinea pigs.
Biesalski HK, Wellner U, Weiser H. Department of Physiological Chemistry, University of Mainz, West Germany.
J Nutr 1990 Jul;120(7):726-37
The effect of vitamin A deficiency in guinea pigs on noise-induced temporary threshold shift (TTS) was evaluated after short (15 min) acoustic overstimulation with a moderate (90 dB) broad-band white noise. Some guinea pigs were fed ad libitum a purified diet deficient in vitamin A (VAD group) until biochemical signs of deficiency occurred. A second, control group (VA group) received the same diet as well as 100 IU vitamin A daily by pharyngeal tube. Cochlear potentials were recorded by special computerized equipment using implanted electrodes. Before acoustic stimulation, a baseline value was determined with a test stimulus [90 dBA (A-filter according to usual DIN instructions)] corresponding to that for TTS measurements. Noise-induced changes were determined by calculating the changes in latency and amplitude of the N1-signal of the compound action potential (CAP) at various times (1, 3, 5, 7, 11 min) after termination of acoustic stimulation in comparison with baseline values. Statistical analysis of the CAP data showed that the VAD group had significantly smaller amplitudes and increased latency of the N1-potential after acoustic stimulation and that the VA group did not show a significant change in amplitude or latency. The reduction in N1-amplitude and N1-latency in the VAD group reflects changes in inner ear hair cell activity. We conclude that vitamin A deficiency increases the sensitivity of the inner ear to noise and that this increased sensitivity increases the probability of noise-induced hearing loss.
Effect of ascorbic acid on the numerical hair cell loss in noise exposed guinea pigs.
Branis M, Burda H. Institute of Experimental Medicine, Czechoslovak Academy of Sciences, Prague.
Hear Res 1988 May;33(2):137-40
Two groups of guinea pigs were exposed to 1/3 octave band noise centered at 4 kHz, 113-118 dB SPL, for 2 h. The animals of the first group were treated with ascorbic acid (AA), 0.5 mg per 1 g of body mass injected intraperitoneally before noise exposure. The second group (control) was exposed without being treated. By means of the surface specimen method and consequent assessment of numerical atrophy of cochlear hair cells it was found that application of ascorbic acid before the noise exposure resulted in a lower or no loss of hair cells especially within the respective frequency segment of the basilar membrane. Possible protective effect of AA and/or the negative effect of hypovitaminosis "C" are discussed.
Biotin-responsive encephalopathy with myoclonus, ataxia, and seizures.
Bressman S, Fahn S, Eisenberg M, Brin M, Maltese W.
Adv Neurol 1986;43:119-25
Prominent neurological abnormalities, including myoclonus, seizures, ataxia, and hearing loss, have been noted in juvenile-onset biotin-responsive MCD. The underlying defect in many of these patients, who generally present in the first year of life, appears to be a deficiency of biotinidase. We have presented a young woman with adult-onset myoclonus, ataxia, hearing loss, seizures, hemianopia, and hemiparesis who responded to pharmacologic dosages of biotin. Although she displayed many of the clinical and biochemical features of juvenile-onset MCD, she did not have a biotinidase deficiency, and the underlying defect remains to be determined. Because of her response to biotin, we have advocated that other patients with unexplained myoclonus syndromes be evaluated for biotin-dependent carboxylase deficiencies and undergo a therapeutic trial with biotin.
Vitamin D deficiency--a new cause of cochlear deafness.
Brookes GB.
J Laryngol Otol 1983 May;97(5):405-20
Ten patients are reported with bilateral cochlear deafness which was associated with vitamin D deficiency. The features of these cases are discussed following an overview of the clinical aspects and diagnosis of vitamin D deficiency. The most likely pathogenesis is localized demineralization of the cochlea resulting in secondary morphological changes. Replacement therapy resulted in unilateral hearing improvement in two of the four patients in whom the response to treatment could be assessed. This suggests a previously unrecognized causal correlation between vitamin D deficiency and cochlear deafness. Impaired vitamin D activity may be important in the aetiology of otosclerosis, presbyacusis and the deafness associated with chronic renal failure. Vitamin D deficiency should be considered in the differential diagnosis of unexplained bilateral cochlear deafness. It is important, as this 'new' metabolic type of sensorineural deafness may be reversible, and may also lead to the diagnosis of early osteomalacia before more serious generalized skeletal symptoms can occur.
Vitamin D deficiency and deafness: 1984 update.
Brookes GB.
Am J Otol 1985 Jan;6(1):102-7
Vitamin D deficiency has been diagnosed in 27 patients with bilateral deafness in a period of just over 3 years. It should be considered in the differential diagnosis of unexplained bilateral cochlear deafness and may be important in the origin of some cases of otosclerosis, presbyacusis, and the deafness associated with chronic renal failure. Treatment should prevent progressive hearing loss, which may occasionally be partly reversible, and the development of clinical osteomalacia with more generalized skeletal symptoms.
Vitamin D deficiency and otosclerosis.
Brookes GB.
Otolaryngol Head Neck Surg 1985 Jun;93(3):313-21
A prospective study of 47 patients with otosclerosis was undertaken to investigate the possible etiologic role of vitamin D undernutrition. The population comprised 27 women and 20 men, with a mean age of 46.4 years (range 21 to 79). The disease was bilateral in 43 patients, and cochlear involvement was present in 84.4%. The mean duration of symptoms was 17.1 years. Vitamin D status was evaluated by measuring the plasma 25-hydroxy vitamin D3 (25-OHD), which is the main storage metabolite. Abnormally low 25-OHD levels were found in 10 patients (21.7%) and borderline low levels in another two. Raised serum alkaline phosphatase levels were present in 32.6%, calcium in 6.5%, and inorganic phosphate in 4.3%. Calcium and vitamin D replacement therapy resulted in significant hearing improvement in 3 of 16 patients; these data support a causal correlation. Vitamin D deficiency is probably a factor in the etiology of some cases of otosclerosis and is important, since the deafness resulting from cochlear involvement may be reversible.
D-methionine provides excellent protection from cisplatin ototoxicity in the rat.
Campbell KC, Rybak LP, Meech RP, Hughes L. Department of Surgery, SIU School of Medicine, Springfield, IL 62794-1618, USA.
Hear Res 1996 Dec 1;102(1-2):90-8
Cisplatin (CDDP) is a widely used chemotherapeutic agent. Unfortunately, CDDP is highly ototoxic. We tested D-methionine (D-Met), a sulfur containing compound, as an otoprotectant in male Wistar rats. Complete data sets were obtained for five groups of five animals each, including a treated control group (16 mg/kg CDDP), an untreated control group (administered an equivalent volume of saline) and three groups that received either 75, 150, or 300 mg/kg D-Met 30 min prior to the 16 mg/kg CDDP dosing. Auditory brainstem response (ABR) thresholds were obtained in response to clicks, and 1 kHz, 4 kHz, 8 kHz, and 14 kHz toneburst stimuli, before and 3 days after drug administration. Scanning electron microscopy (SEM) was used to examine the outer hair cells of the apical, middle and basal turns of the cochlea. Animal weight was measured on the first and final day. D-Met provided excellent otoprotection even at the lowest level with complete otoprotection obtained for the 300 mg/kg dosing as measured by both ABR and SEM. D-Met also markedly reduced weight loss and mortality. All animals receiving D-Met (15/15) survived to the end of the study period as opposed to only 5/10 of the treated controls.
Influence of dietary magnesium on the amplitude of wave V of the auditory brainstem response.
Cevette MJ, Franz KB, Brey RH, Robinette MS. Mayo Clinic-Scottsdale, Brigham Young University, Scottsdale, AZ 85259.
Otolaryngol Head Neck Surg 1989 Nov;101(5):537-41
Thirty-six weanling guinea pigs were fed either a low (600 ppm) or normal (3000 ppm) diet of magnesium for 8 weeks. One half of each diet group received intramuscular injections of magnesium-depleting drugs, furosemide and gentamicin. The other half were controls and received equal intramuscular injections of saline. Auditory brainstem responses were obtained from all animals before and after 8 weeks of treatment of diet and drugs to examine the effects of treatment upon hearing and auditory brainstem function. A three-way analysis of variance of dietary magnesium, by drug and by sex, showed no significant differences in auditory brainstem wave V thresholds, wave V latencies, or interpeak wave I-V latencies between the control and experimental groups. The low magnesium diet group, which received drugs, had significantly greater wave V auditory brainstem response amplitudes. Results can be explained on the basis of magnesium influencing the uptake of calcium into both the hair cells and associated brainstem pathways.
The role of taurine in infant nutrition.
Chesney RW, Helms RA, Christensen M, Budreau AM, Han X, Sturman JA. University of Tennessee College of Medicine, Memphis, USA.
Adv Exp Med Biol 1998;442:463-76
The importance of taurine in the diet of pre-term and term infants has not always been clearly understood and is a topic of interest to students of infant nutrition. Recent evidence indicates that it should be considered one of the "conditionally essential" amino acids in infant nutrition. Plasma values for taurine will fall if infants are fed a taurine-free formula or do not have taurine provided in the TPN solution. Urine taurine values also fall, which is indicative of an attempt by the kidney to conserve taurine. The very-low-birth-weight infant, for a variety of reasons involving the maturation of tubular transport function, cannot maximally conserve taurine by enhancing renal reabsorption and, hence, is potentially at greater risk for taurine depletion than larger pre-term or term infants, and certainly more than older children who have taurine in their diet. Taurine has an important role in fat absorption in pre-term and possibly term infants and in children with cystic fibrosis. Because taurine-conjugated bile acids are better emulsifiers of fat than glycine-conjugated bile acids, the dietary (or TPN) intake has a direct influence on absorption of lipids. Taurine supplementation of formulas or TPN solutions could potentially serve to minimize the brain phospholipid fatty acid composition differences between formula-fed and human milk-fed infants. Taurine appears to have a role in infants, children, and even adults receiving most (> 75%) of their calories from TPN solutions in the prevention of granulation of the retina and electroencephalographic changes. Taurine has also been reported to improve maturation of auditory-evoked responses in pre-term infants, although this point is not fully established. Clearly, taurine is an important osmolyte in the brain and the renal medulla. At these locations, it is a primary factor in the cell volume regulatory process, in which brain or renal cells swell or shrink in response to osmolar changes, but return to their previous volume according to the uptake or release of taurine. While there is a dearth of clinical studies in man concerning this volume regulatory response, studies in cats, rats, and dog kidney cells indicate the protective role of taurine in hyperosmolar stress. The infant depleted of taurine may not be able to respond to hyper- or hyponatremic stress without massive changes in neuronal volume, which has obvious clinical significance. The fact that the brain content of taurine is very high at birth and falls with maturation may be a protective feature, or compensation for renal immaturity Defining an amino acid as "conditionally essential" requires that deficiency result in a clinical consequence or consequences which can be reversed by supplementation. In pre-term and term infants, taurine insufficiency results in impaired fat absorption, bile acid secretion, retinal function, and hepatic function, all of which can be reversed by taurine supplementation. Therefore, this small beta-amino acid, taurine, is indeed conditionally essential.
Experimental studies on the role of vitamin A in the inner ear.
Chole RA.
Otolaryngology 1978 Jul-Aug;86(4 Pt 1):ORL-595-620
With the sole exception of the hair cells of the inner ear, where information is lacking, all special somatic afferent receptor cells have been shown to be dependent upon vitamin A for normal function. In view of the paucity of information on the role of vitamin A in the inner ear, three experiments were performed to examine this relationship. Temporal bone histopathology was studied in rats deprived of vitamin A. In a second experiment, vitamin A-deficient rats were maintained with vitamin A acid and the histopathology was studied under the light microscope. In the third experiment, a microfluorometric estimate of the content of vitamin A in the guinea pig cochlea was performed. A fluorescent compound with the exact spectral characteristics of vitamin A was found in the guinea pig cochlea at a concentration of 21.2 micrograms/gm, which is ten times the vitamin A concentration found in most other tissues.
Temporal bone histopathology in experimental hypovitaminosis A.
Chole RA, Quick CA.
Laryngoscope 1976 Mar;86(3):445-53
Twenty-five years ago hearing loss was observed in some subjects during a comprehensive study of the effects of hypovitaminosis A on human volunteers. Experimental studies documenting histopathological changes in the temporal bone due to hypovitaminosis A are conflicting. Even the recent textbooks of otolaryngology and physiology make no mention of a role of vitamin A in the ear. To explore the role of vitamin A in the ear adult and weanling rats maintained on a diet totally lacking vitamin A were sacrificed at intervals. Their temporal bones were examined with the light microscope. After six weeks on a vitamin A free diet weanling rats showed hypertrophy of the periostial portions of the otic capsule. At 16 weeks a narrowing of the internal auditory canal due to bony exostoses was present. The neuroepithelia of the cochlea and the vestibular apparatus were histologically normal even in the longest surfiving animals. Adult rats maintained on a vitamin A free diet showed minimal thickening of the bone adjacent to the internal auditory meatus. The cochlea and the vestibular appartus in these animals remained normal throughout the 28-week experiment. Although we have demonstrated marked abnormalities of the otic capsule in hypovitaminosis A, our results do not support those of some earlier investigators who reported that atrophy of the cochlear and vestibular neuroepithelium occurred in the absence of dietary vitamin A.
Hearing aids.
Clayman, C.B.
In The American Medical Association Encyclopedia of Medicine 1989, p. 511.
New York: Random House.
Attenuation of neomycin ototoxicity by iron chelation.
Conlon BJ, Perry BP, Smith DW. Division of Otolaryngology-Head and Neck Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Laryngoscope 1998 Feb;108(2):284-7
Increasing evidence suggests that aminoglycoside ototoxicity is mediated by the formation of an aminoglycoside-iron complex and that the creation of this complex is a preliminary step in generation of free radical species and subsequent hair cell death. In this study we have assessed the ability of the iron chelator deferoxamine to attenuate the hearing loss induced by an ototoxic dose of the aminoglycoside neomycin (100 mg/kg per day for 14 days). Experiments were carried out on pigmented guinea pigs weighing 250 to 300 g. Changes in auditory sensitivity were characterized by monitoring shifts in compound action potential (CAP) thresholds, recorded through indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results show that animals receiving neomycin alone suffered a mean threshold shift exceeding 35 dB at all test frequencies (2.0, 4.0, and 8.0 kHz) 30 days after initiation of treatment. In comparison, all animals receiving cotherapy of neomycin and deferoxamine (150 mg/kg twice daily for 14 days) maintained their CAP threshold, suggesting significant protection from neomycin ototoxicity. A statistical comparison of treatment groups showed that in the animals receiving cotherapy with neomycin and deferoxamine, deferoxamine produced a significant protective effect against neomycin-induced ototoxicity (P < 0.001). These results provide further evidence of the intrinsic role of iron in aminoglycoside ototoxicity and suggest that deferoxamine may have a therapeutic role in attenuating the cytotoxic action of aminoglycoside antibiotics.
Attenuation of aminoglycoside-induced cochlear damage with the metabolic antioxidant alpha-lipoic acid.
Conlon BJ; Aran JM; Erre JP; Smith DW The Hearing Research Laboratories, Division of Otolaryngology-Head and Neck Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Hear Res (Netherlands) Feb 1999, 128 (1-2) p40-4
Free radical generation is increasingly implicated in a variety of pathological processes, including drug toxicity. Recently, a number of studies have demonstrated the ability of gentamicin to facilitate the generation of radical species both in vivo and in vitro, which suggests that this process plays an important role in aminoglycoside-induced ototoxicity. Free radical scavengers are compounds capable of inactivating free radicals, thereby attenuating their tissue damaging capacity. In this study we have determined the ability of the powerful free radical scavenger alpha-lipoic acid (100 mg/kg/day) to attenuate the cochlear damage induced by a highly ototoxic regimen of the aminoglycoside amikacin (450 mg/kg/day, i.m.). Experiments were carried out on pigmented guinea pigs initially weighing 200-250 g. Changes in cochlear function were characterized as shifts in compound action potential (CAP) thresholds, estimated every 5 days, by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results showed that animals receiving alpha- lipoic acid in combination with amikacin demonstrated a significantly less severe elevation in CAP thresholds compared with animals receiving amikacin alone (P < 0.001; t-test). These results provide further evidence of the recently reported intrinsic role of free radical generation in aminoglycoside ototoxicity, and highlight a potential clinical therapeutic use of alpha-lipoic acid in the management of patients undergoing aminoglycoside treatment.
Iodine deficiency disorders in Europe.
Delange F, Burgi H.
Bull World Health Organ 1989;67(3):317-25
Recent data on iodine excretion in the urine of adults, adolescents and newborns and on the iodine content of breast milk indicate a high prevalence of iodine deficiency (moderate in many cases and severe in a few) in many European countries. These cases may manifest as subclinical hypothyroidism in neonates and as goitre in adolescents and adults. Lack of iodine causes not only goitre, but also mental deficiency, hearing loss and other neurological impairments, and short stature due to thyroid insufficiency during fetal development and childhood. Although iodinated salt is available theoretically in most countries where it is needed, its quality and share of the market are often unsatisfactory. In many countries where only household salt is iodinated the iodine content has been set too low owing to an overestimation of household salt consumption. Governments are therefore urged to pass legislation and provide means for efficient iodination of salt wherever this is necessary.
Effects of nutrition on brain development in humans.
DeLong GR. Division of Pediatric Neurology, Duke University Medical Center, Durham, NC 27710.
Am J Clin Nutr 1993 Feb;57(2 Suppl):286S-290S
Brain development in humans is remarkably resistant to permanent damage from protein-energy malnutrition. However, specific nutrients have crucial roles. Iodine deficiency is the most important and widespread nutrient deficiency; it causes endemic cretinism, associated with deaf-mutism and cerebral palsy. Iodine deficiency during pregnancy causes both maternal and fetal hypothyroxinemia, resulting in irreversible impairment of brain development at a critical stage. Neuropathological data place this after 14 wk, perhaps continuing through the third trimester. Gross brain structure, including the gyral pattern of the cerebral cortex, develops normally; the insult affects neuron and dendrite growth. Recent magnetic-resonance-imaging (MRI) images of neurological cretin brains show remarkably normal appearance except for gliotic lesions of the globus pallidus, correlating with the proximal motor rigidity seen clinically. Myxedematous cretinism is paradoxical in showing more severe hypothyroidism and growth failure, yet better intellectual, motor, and hearing function; these observations implicate a second independent factor in its pathogenesis.
Effects of dietary taurine on auditory function in full-term infants.
Dhillon SK, Davies WE, Hopkins PC, Rose SJ. Hearing Services Centre City Hospital, Birmingham, England.
Adv Exp Med Biol 1998;442:507-14
Three groups of neonates fed taurine supplemented infant formula, non-supplemented infant formula or breast milk, respectively, were studied from birth to 12 weeks of age. In addition to the measurement of whole blood taurine content, auditory function was monitored using auditory brainstem responses (ABRs) and transient evoked otoacoustic emissions (TEOAEs). The results showed a significant reduction in whole blood taurine concentration in the non-supplemented formula group. In addition, there was a significant drop in whole blood taurine levels in all 3 groups over the first four weeks of life. ABR wave latencies were significantly shorter in the non-supplemented group, with wave V showing the greatest reductions. Falling taurine levels after full-term birth may aid synaptic maturation/efficiency within the auditory system. TEOAE responses were significantly larger over the low to mid frequencies in the breast fed group suggesting improved middle ear function.
[Therapeutic trial in acute cochlear deafness. A comparative study of Ginkgo biloba extract and nicergoline]
Dubreuil C
Presse Med (France) Sep 25 1986, 15 (31) p1559-61
Ischemia and the metabolic disorder it entails would seem to be the pathogenic mechanism behind acute cochlear deafness, irrespective of the triggering process. The prognosis is entirely dependent on the rapid initiation of an effective treatment. At the end of a double-blind therapeutic trial comparing Ginkgo biloba extract and a standard alpha blocker (nicergoline), a significant recovery was observed in both therapeutic groups, but improvement was distinctly better in the Ginkgo biloba group.
Effect of copper-deficient diet on metabolism in rat auditory structures.
Farms WB, Godfrey DA, Askari A. Department of Otolaryngology, Medical College of Ohio, Toledo 43699-0008.
Hear Res 1993 May;67(1-2):45-50
Copper is a trace element known to be critical for normal brain function, and abnormal copper metabolism has been associated with some disorders involving the auditory system. We examined effects of copper deficiency on metabolism in major structures of the auditory system. Homogenates of cochlea, cochlear nucleus and inferior colliculus of rats, as well as whole brain, were assayed for activities of enzymes of oxidative and glycolytic energy metabolism--malate and lactate dehydrogenase, enzymes of acetylcholine metabolism--choline acetyltransferase and acetylcholinesterase, and concentrations of amino acids. Whole brain was also assayed for activity of superoxide dismutase, a copper-containing enzyme, and concentrations of minerals. For these chemicals and tissues, the only significant differences between copper-deficient and copper-adequate rats were: (1) decreased copper and magnesium and increased potassium concentrations in whole brain of copper-deficient rats and (2) an elevation of glutamine concentration in inferior colliculus and whole brain of copper-deficient rats. The elevated glutamine could not be related to any change in activity of glutamine synthetase or glutaminase, major enzymes of glutamine metabolism. It is speculated that the increase in glutamine might result from a net increase in ammonia accumulation in the brains of copper-deficient rats.
Sudden hypoacusis treated with hyperbaric oxygen therapy: a controlled study.
Fattori B, Berrettini S, Casani A, Nacci A, De Vito A, De Iaco G. ENT Clinic, Department of Neurosciences, University of Pisa, Via Savi no. 10, 56100 Pisa, Italy. bfattori@ent.med.unipi.it
Ear Nose Throat J. 2001b Sep;80(9):655-60.
The term sudden hypoacusis describes a hearing loss of rapid onset and unknown origin that can progress to severe deafness. Of the many therapeutic protocols that have been proposed for treating sudden hypoacusis, hyperbaric oxygen therapy (HOT) plays a leading role. We studied 50 patients who had been referred to our ENT unit within 48 hours of the onset of sudden hypoacusis. We randomly assigned 30 of these patients to undergo once-daily administration of HOT for 10 days; the other 20 patients were treated for 10 days with an intravenous vasodilator. Response to therapy in all patients was evaluated by calculating the mean hearing threshold at frequencies between 500 and 4,000 Hz and by assessing liminal tonal audiometry results recorded at baseline and 10 days after the cessation of treatment. These results, plus the findings of other audiologic and otoneurologic examinations, revealed that the patients in the HOT group experienced a significantly greater response to treatment than did those in the vasodilator group, regardless of age and sex variables. Significantly more patients in the HOT group experienced a good or significant response. In both groups, patients with pantonal hypoacusis responded significantly better than did those with a milder condition. Based on our findings, coupled with the fact that oxygen therapy is well tolerated and produces no side effects, we conclude that HOT should be considered the preferred treatment for patients with sudden hypoacusis.
[Oxygen therapy in the long term treatment of Meniere's disease] [Article in Italian]
Fattori B, Nacci A, Casani A, Donati C, De Iaco G. Dipartimento di Neuroscienze, Clinica ORL, Universita di Pisa.
Acta Otorhinolaryngol Ital. 2001a Feb;21(1):1-9.
Endolymphatic hydrops is the hystopathological substrate characteristic of Meniere's disease. Besides the classical treatment with diuretics and/or osmotic drugs for some time, now treatment in a "pressure chamber" (OTI) has also been applied. The oxygen administered in the hyperbaric chamber can reduce the hydrops both by increasing the hydrostatic pressure and by mechanically stimulating the flow of endolymph toward the duct and endolymphatic sac. In addition, an increase is seen in the amount of O2 dissolved in the labyrinthine fluids and this contributes to recovering cell metabolism and restoring normal cochlear electrophysiological functions. Between 1992 and 1996 40 patients with monolateral Meniere's disease were studied: 15 underwent oxygen therapy at a constant pressure (2.2 ATA) (HOT), 25 with a continuous variation in pressure (from 1.7 to 2.2 ATA) (Alternobaric therapy, AOT). During the acute phase the patients underwent daily OTI treatment for 15 days in a row. The maintenance treatment called for one treatment cycle (one session a day for 5 days in a row) a month for 1 year, followed by for one treatment cycle (one session a day for 5 days in a row) every three months during the 2nd, 3rd and 4th years. The controls consisted of a group of 18 patients treated with 10% glycerol i.v. (during the acute phase) and betahystine (8 mg x 3/die) between episodes. A comparison was made of the average hearing threshold for the frequencies 500-3000 Hz (PTA), how frequently episodes of dizziness arose and extent of hearing loss in the three groups after the initial 15 days of treatment and at the end of the 4-year follow-up, in compliance with the criteria laid down by the Committee on Hearing and Equilibrium in 1995. At the end of the first 15 days of treatment, there were no statistically significant differences between the three groups. At the end of the follow-up, on the other hand, hyperbaric treatment, and in particular alternobaric therapy, enabled a significant reduction in the episodes of dizziness as compared to the control group. PTA and deafness also improved significantly in the patients who had undergone hyperbaric treatment. The results of the present work show that HOT, and in particular AOT, offer a valid alternative to drugs in the treatment of Meniere's disease.
Protection of both auditory hair cells and auditory neurons from cisplatin induced damage.
Gabaizadeh R, Staecker H, Liu W, Kopke R, Malgrange B, Lefebvre PP, Van de Water TR. Department of Otolaryngology, Albert Einstein College of Medicine Bronx, New York, USA.
Acta Otolaryngol 1997 Mar;117(2):232-8
Cisplatin is an effective anti-neoplastic agent used in the treatment of squamous cell cancer of the head and neck, but with serious side effects. One serious side effect is damage to both the auditory hair cells and the auditory neurons. The damage to the neurons has been shown to be a direct effect and not due to the loss of the neurotrophic support provided by the hair cells. Several neurotrophins have been shown to lessen the extent of cisplatin induced damage of auditory neurons in vitro, but these neurotrophins have had no effect on the extent of damage to the hair cells. D-methionine (D-met) has been demonstrated to provide protection against cisplatin's nephrotoxicity in vivo and ototoxicity in vitro. In this study the combination of brain derived neurotrophic factor (BDNF) with D-met has shown that both auditory neurons and auditory hair cells can be protected from cisplatin induced damage in vitro. These results demonstrate that this type of combination therapy (i.e. a neurotrophin combined with a free radical scavenger) can provide more complete protection for the auditory receptor against cisplatin toxicity than either of these agents alone. Because both BDNF and D-met have been shown to have trophic activity in vitro we proposed that the combination of these agents will also provide effective protection against cisplatin induced ototoxicity and neurotoxicity of the auditory receptor in vivo.
Taurine in pediatric nutrition: review and update.
Gaull GE. Department of Pediatrics, Northwestern University School of Medicine, Chicago.
Pediatrics 1989 Mar;83(3):433-42
Taurine was long considered an end product of the metabolism of the sulfur-containing amino acids, methionine and cyst(e)ine. Its only clearly recognized biochemical role had been as a substrate in the conjugation of bile acids. Taurine is found free in millimolar concentrations in animal tissues, particularly those that are excitable, rich in membranes, and generate oxidants. Various lines of evidence suggest one major nutritional role as protecting cell membranes by attenuating toxic substances and/or by acting as an osmoregulator. The totality of evidence suggests that taurine is nonessential in the rodent, it is an essential amino acid in the cat, and it is conditionally essential in man and monkey. Absence from the diet of a conditionally essential nutrient does not produce immediate deficiency disease but, in the long term, can cause problems. Taurine is now added to many infant formulas as a measure of prudence to provide improved nourishment with the same margin of safety for its newly identified physiologic functions as that found in human milk. Such supplementation can be justified by the finding of improved fat absorption in preterm infants and in children with cystic fibrosis, as well as by salutary effects on auditory brainstem-evoked responses in preterm infants. Experimental findings in animal models and in human cell models provide further justification for taurine supplementation of infant formulas.
Biochemical mechanisms affecting susceptibility to noise-induced hearing loss.
Gunther T, Ising H, Joachims Z. Institut fur Molekularbiologie und Biochemie, Freie Universitat Berlin, West Germany.
Am J Otol 1989 Jan;10(1):36-41
In magnesium (Mg)-deficient rats and guinea pigs, noise-induced hearing loss (NIHL) was found to be correlated to the decrease of Mg in serum and perilymph. Also, in noise-exposed humans, NIHL increased with decreasing serum Mg. During the process of mechanoelectrical transduction within the hair cells in the inner ear, membrane permeability of K+ and Ca2+ will transiently increase. Mg deficiency may additionally increase membrane permeability and, therefore, energy-dependent K+ and Ca2+ turnover. The increased release of catecholamines in Mg deficiency may affect the hair cells, either directly by increasing the intracellular concentration of free Ca2+ and/or indirectly by reducing the blood flow. Also, thromboxane A2, which is increased in Mg deficiency, may reduce the blood flow in the inner ear. By these mechanisms, Mg deficiency may cause energy depletion and irreversible damage to the hair cells.
[Mitochondrial neurogastrointestinal encephalomyopathy presenting with protein-losing gastroenteropathy and serum copper deficiency: a case report.] [Article in Japanese]
Hamano H, Ohta T, Takekawa Y, Kouda K, Shinohara Y. Department of Neurology, Tokai University School of Medicine.
Rinsho Shinkeigaku 1997 Oct;37(10):917-22
We report a 56-year old female with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), presenting with protein-losing gastroenteropathy and serum copper deficiency. There was no neuromuscular disease in her family members. Three years prior to admission, she developed severe gastrointestinal symptoms including diarrhea, nausea, vomiting and ascites, and was diagnosed as having protein-losing gastroenteropathy based on alpha(1)-antitrypsin clearance and other tests. She was referred to our department when neurological symptoms were apparent. Neurological examinations revealed bilateral ptosis, ophthalmoplegia, hearing loss, facial and limb muscle weakness, mild sensory deficit of vibration on her feet and hypoactive deep tendon reflexes. Pigmentary retinopathy, cerebellar ataxia and heart block were not seen. Serum copper level was decreased to 45 micrograms/dl (normal: 83-155). Chronic intestinal pseudo-obstruction was proven by X-ray studies, and diffuse leukoencephalopathy demonstrated on brain MRI. On EMG, motor nerve conduction velocities were prolonged with temporal dispersion. Her muscle biopsy from biceps brachii muscle showed both neuropathic and myopathic changes, scattered ragged-red fibers and focal cytochrome c oxidase deficiency. Southern blot and polymerase chain reaction analysis on mitochondrial DNA showed no deletions nor point mutations. The clinical and pathologic findings of the present patient fulfilled the diagnostic criteria of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) proposed by Hirano et al. There are few reported patients with MNGIE in Japan, but none presented with protein-losing gastroenteropathy and serum copper deficiency. Since the copper is a cofactor of cytochrome c oxidase, decreased serum copper level may aggravate the respiratory chain enzyme metabolism in mitochondria. Therefore, treatment for gastrointestinal tract disturbance and copper administration may be necessary to prevent disease progression.
[Ginkgo extract EGb 761 (tenobin)/HAES versus naftidrofuryl A randomized study of therapy of sudden deafness]
Hoffmann F; Beck C; Schutz A; Offermann P Universitats-HNO-Klinik Freiburg im Breisgau.
Laryngorhinootologie (Germany) Mar 1994, 73 (3) p149-52
80 patients with idiopathic sudden hearing loss existing no longer than 10 days were included in a randomised reference-controlled study. The therapeutic value of Ginkgo EGb 761 (Tebonin) + HAES was compared to that of Naftidrofuryl (Dusodril)+HAES. The main mechanisms of action of EGb 761 are a vasoregulating activity (increased blood flow), the platelet activating factor antagonism and a prevention of membrane damage caused by free radicals. Naftidrofuryl has antiserotonergic and therefore vasodilatory properties. The statistical analysis of the audiometric data was performed in measuring the relative hearing gain as described by Eibach 1979. After one week of observation, 40% of the patients in each group showed a complete remission of hearing loss. This was also observed by other authors who had compared other drugs. Therefore, in these cases, it is most likely that spontaneous recovery is the most important factor. After two and three weeks of observation, measuring the relative hearing gain, there was a significant borderline benefit of EGb 761 (p = 0.06) without any side effects. Some patients of the reference group developed side effects such as orthostatic dysregulation or headache or sleep disturbances. Minimising side effects should be one of the most important goals in therapy of sudden hearing loss until the efficiency of infusion therapy is proved.
[Ginkgo special extract EGb 761 in tinnitus therapy. An overview of results of completed clinical trials]. [Article in German]
Holstein N. Facharzt fur Hals-Nasen-Ohrenheilkunde, Allergologie, Chirotherapie, Stimm- und Sprachstorungen, Neuensteinstrasse 14, D-76227 Karlsruhe.
Fortschr Med 2001 Jan 11;118(4):157-64
In a systematic search of the literature 19 clinical trials investigating the effects of tinnitus treatment with Ginkgo biloba special extract EGb 761 were identified and evaluated. The results of eight controlled studies on tinnitus due to cerebrovascular insufficiency or labyrinthine disorders of varying genesis for the most part show a statistically significant superiority of treatment with the Ginkgo biloba special extract EGb 761 as compared with placebo or reference drugs applied of periods of one to three months. Open studies, too, some involving large numbers of patients, revealed appreciable improvements under ginkgo treatment. Therapeutic success was not directly correlated with either the genesis or the duration of tinnitus. However, investigations of prognostic factors revealed that short-standing disorders have a better prognosis, so that better results can be expected from early-onset treatment. The tolerability of Ginkgo biloba special extract EGb 761 was excellent, and in this respect the controlled clinical trials revealed little difference between drug-treated and control groups.
Age-related hearing loss, vitamin B-12, and folate in elderly women.
Houston DK, Johnson MA, Nozza RJ, Gunter EW, Shea KJ, Cutler GM, Edmonds JT. Department of Foods and Nutrition, The University of Georgia, Athens 30602, USA.
Am J Clin Nutr 1999 Mar;69(3):564-71
BACKGROUND: Hearing impairment is 1 of the 4 most prevalent chronic conditions in the elderly. However, the biological basis of age-related hearing loss is unknown. OBJECTIVE: The objective was to test the hypothesis that age-related hearing loss may be associated with poor vitamin B-12 and folate status. DESIGN: A thorough audiometric assessment was conducted in 55 healthy women aged 60-71 y. Hearing function was determined by the average of pure-tone air conduction thresholds at 0.5, 1, 2, and 4 kHz and was categorized into 2 groups for logistic regression analyses: normal hearing (<20 dB hearing level; n = 44) and impaired hearing (> or = 20 dB hearing level; n = 11). RESULTS: Mean age was the same (65 y) for the normal hearing and impaired hearing groups. Pure-tone averages were inversely correlated with serum vitamin B-12 (r = -0.58, P = 0.0001) and red cell folate (r = -0.37, P = 0.01). Women with impaired hearing had 38% lower serum vitamin B-12 (236 compared with 380 pmol/L, respectively, P = 0.008) and 31% lower red cell folate (425 compared with 619 nmol/L, respectively, P = 0.02) than women with normal hearing. Among participants who did not take supplements containing vitamin B-12 or folate, women with impaired hearing had 48% lower serum vitamin B-12 (156 compared with 302 pmol/L, respectively, P = 0.0007) and 43% lower red cell folate (288 compared with 502 nmol/L, respectively, P = 0.001) than women with normal hearing. CONCLUSION: Poor vitamin B-12 and folate status may be associated with age-related auditory dysfunction.
Evaluation of vitamin D metabolism in patients with bilateral sensorineural hearing loss.
Ikeda K, Kobayashi T, Itoh Z, Kusakari J, Takasaka T. Department of Otolaryngology, Tohoku University School of Medicine, Sendai, Japan.
Am J Otol 1989 Jan;10(1):11-3
The possible role of vitamin D in hearing impairment was investigated by the measurement of three metabolites of vitamin D in 28 patients with bilateral sensorineural hearing loss (BSNHL). Twenty-three of 28 patients showed a significantly decreased level of 1,25-dihydroxyvitamin D3, with a normal value of 25-hydroxyvitamin D3. In addition to experimental and clinical reports regarding vitamin D deficiency, the present study suggests that vitamin D deficiency is one of the etiologies of BSNHL, through the calcium metabolism and microcirculation in the cochlea.
Increased noise trauma in guinea pigs through magnesium deficiency.
Ising H, Handrock M, Gunther T, Fischer R, Dombrowski M.
Arch Otorhinolaryngol 1982;236(2):139-46
Mg-deficient guinea pigs developed significantly increased hearing loss during 4 weeks of noise exposure [95 dB(A)] as compared to animals fed a Mg-rich diet. The hearing loss was negatively correlated to the Mg content of the perilymph (r = -0.86). Besides this auditory effect, there was a decrease of intracellular Mg and an increase of collagen in the myocardium, both of which were correlated to the hearing loss and caused by Mg deficiency and noise stress.
[Hydergine in pathology of the inner ear] [Article in Spanish]
Jimenez-Cervantes Nicolas J; Amoros Rodriguez LM
An Otorrinolaringol Ibero Am (Spain) 1990, 17 (1) p85-98
There have been treated a total of 20 patients with troubles on the cochlear compartment and/or vestibular level which have been clinically expressed by a perceptive hypoacusia, tinnitus and rotatory vertigo. The final evaluation is referred to 17 patients, since three patients do not appear for control. All patients were treated only with Hydergine, on doses of 30 drops thrice daily, which is the equivalent to 4.5 mg/day of active substance. This treatment remained unaltered till the end of the last control. Controls have been effected after 30, 60 and 90 days of starting the treatment. In each control there was evaluated the subjective improvement of vertigo, tinnitus and hypoacusia when effecting to all patients by means of liminar- supraliminar- and automaticaudiometry, impedancimetry, T one-decay-test and electrooculonistagmography. The most meliorated symptomatology was vertigo, with a global improvement of 93.7 per cent on the treated patients. Tinnitus improve by 57.1 per cent and hypoacusia by 20 per cent. There is a total correspondence between the subjective data furnished by the patients and the objective tests carried out in the successive controls.
[Prevention of noise-induced hearing loss.] [Article in Hebrew]
Joachims HZ, Ising H, Gunther T. Otolaryngology Dept., Rambam Medical Center, Haifa.
Harefuah 1989 Sep;117(5-6):133-5
Noise-induced hearing loss appears to result from energy depletion in the hair cells. Cell membrane permeability is increased in hypomagnesemia, causing Na+ and Ca++ influx, with subsequent increase in energy-dependent ion-pumping. Energy exhaustion is further enhanced by hypomagnesemia-induced vasoconstriction. Dietary supplementation with magnesium was shown to lessen hearing loss in noise-exposed rats. It is postulated that the same mechanisms may act in man and the possible benefit of magnesium supplementation for noise-exposed workers should be investigated.
Dependence of noise-induced hearing loss upon perilymph magnesium concentration.
Joachims Z, Babisch W, Ising H, Gunther T, Handrock M.
J Acoust Soc Am 1983 Jul;74(1):104-8
Noise-induced hearing loss (NIHL) is significantly greater in rats fed a magnesium-deficient diet than in rats on a magnesium-rich diet. The hearing loss was found to be negatively correlated with the magnesium concentration of the perilymph. It is suggested that also in man, the magnesium concentration in the perilymph may be of importance in determining susceptibility to NIHL.
Oral magnesium supplementation as prophylaxis for noise-induced hearing loss: results of a double blind field study. (Article in German).
Joachims Z, Netzer A, Ising H, Rebentisch E, Attias J, Weisz G, Gunther T.
Schriftenr Ver Wasser Boden Lufthyg 1993;88:503-16
The effect of oral Mg-supplementation as prophylaxis against noise-induced hearing loss was tested in a placebo-controlled double blind study involving 320 voluntary subjects during a 2-month period of military training. The hearing thresholds of all subjects were checked and only persons with normal hearing were accepted. Before and after the 2-month training, blood samples were collected and Mg was analysed in serum, erythrocytes and lymphocytes. Seven days after the last exposure to firearm noise, the audiograms of all test subjects were checked and permanent threshold shifts (PTS) were determined. The total group received a drink containing either 4g Mg granulate verum (6.7 mmol Mg aspartate) or placebo every working day during the 2-month training period. The primary source of noise exposure were firearms: 420 shots per person, mean peak level 164 dB(A). The recruits used ear plugs with a mean insertion loss of 25 dB. In both groups Mg-concentration in serum and in erythrocytes increased with time. Lymphocyte Mg increased in the Mg group only. In the placebo group the percentages of ears with PTS > 25 dB at 4 kHz/6 kHz and/or 8 kHz after exposure to firearm noise were twice as high as in the Mg group.
Effects of Ginkgo biloba extract on the cochlear damage induced by local gentamicin installation in guinea pigs.
Jung HW; Chang SO; Kim CS; Rhee CS; Lim DH Department of Otorhinolaryngology - Head & Neck Surgery, Seoul National University College of Medicine, Korea.
J Korean Med Sci (Korea) Oct 1998, 13 (5) p525-8
Investigations evaluating the protective effect of Ginkgo biloba extract (EGb) on gentamicin (GM) ototoxicity were undertaken. Guinea pigs treated with 5 mg/kg gentamicin sulfate on the round window niche (RWN) showed acute changes on electrocochleogram and hair cell or microvilli damage on scanning electron microscopy (SEM). There was accumulation of GM in the whole cochlea, especially in the organ of Corti, stria vascularis, and type III fibrocyte on immunohistochemical study. However, the guinea pigs pretreated with local or systemic EGb revealed no significant changes by local GM installation. From these results, we concluded that EGb has a protective effect on the development of GM ototoxicity in the cochlea.
Glutathione protection against gentamicin ototoxicity depends on nutritional status.
Lautermann J, McLaren J, Schacht J. Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506, USA.
Hear Res 1995 Jun;86(1-2):15-24
This study demonstrates that gentamicin ototoxicity depends on dietary factors and correlates with tissue glutathione levels. After 15 days of gentamicin injections (100 mg/kg/day s.c.) guinea pigs on a regular protein diet (18.5% protein) had an average hearing loss of 9 dB at 3 kHz, 31 dB at 8 kHz and 42 dB at 18 kHz. Guinea pigs on a 7% protein diet showed an increased hearing loss of 52 dB at 3 kHz, 63 dB at 8 kHz and 74 dB at 18 kHz. Supplementing the low protein diet with either essential or sulfur-containing amino acids did not protect against gentamicin ototoxicity. Glutathione levels in the cochlear sensory epithelium were decreased in animals on a low protein diet and could be restored to normal by oral administration of glutathione monoethyl ester (1.2 g/kg/day) in combination with vitamin C (100 mg/kg/day). Glutathione supplementation significantly reduced the magnitude of hearing loss in the low protein diet group at all frequencies (43 dB reduction at 3 kHz, 27 dB reduction at 8 kHz and 21 dB reduction at 18 kHz). In animals on a full protein diet, dietary glutathione neither increased cochlear glutathione levels nor attenuated hearing loss. Serum gentamicin levels did not differ between animals on the various diets with or without glutathione supplement. These results suggest that gentamicin toxicity and detoxifying mechanisms are affected by the metabolic state of the animal and the glutathione content of the tissue. Thus, compounds that could potentially protect against gentamicin ototoxicity may be more correctly assessed in animal models of deficient nutritional states in which endogenous detoxifying mechanisms are compromised. This animal model might also be more realistically related to the clinical situation of a critically ill patient receiving gentamicin treatment.
The influence of chronic vitamin A deficiency on human and animal ears.
Lohle E.
Arch Otorhinolaryngol 1982;234(2):167-73
After feeding young rats a diet deficient in vitamin A, we examined the inner ear with the electron microscope. There were changes in the cuticle of the outer and inner hair cells. Furthermore, there were changes in the reticular system of the intermediate zone and massive degenerative changes in the ganglion cells of the VIII nerve. In a second experiment with older animals we found no significant changes in the sensory cells, though there was new bone formation in Rosenthal's canal and damage to the ganglion cells, of a lesser extent than was evident in the first experiment, however. In a further clinical study, we carefully chose human subjects suffering from alcoholic liver disease who also had a negative history of ear infection, noise exposure, head injury and use of streptomycin. Normal auditory function in the family was also a criterion. A decreased auditory function associated with low vitamin A levels was found in these patients. Those with liver disease showed not only a significant auditory dysfunction in the higher frequencies, but as well a poorer performance in the tone decay test. They were compared to a control group with normal hepatic, renal and thyroid status.
Age-related cochlear hair cell loss is enhanced in mice lacking copper/zinc superoxide dismutase.
McFadden SL, Ding D, Reaume AG, Flood DG, Salvi RJ. Center for Hearing and Deafness, State University of New York at Buffalo, 14214, USA. mcfadden@acsu.buffalo.edu
Neurobiol Aging 1999 Jan-Feb;20(1):1-8
Age-related hearing loss in humans and many strains of mice is associated with a base-to-apex gradient of cochlear hair cell loss. To determine if copper/zinc superoxide dismutase (Cu/Zn SOD) deficiency influences age-related cochlear pathology, we compared hair cell losses in cochleas obtained from 2-, 7-, and 17- to 19-month-old wild type (WT) mice with normal levels of Cu/Zn SOD and mutant knockout (KO) mice with a targeted deletion of Sod1, the gene that codes for Cu/Zn SOD. WT and KO mice exhibited similar patterns of hair cell loss with age, i.e., a baso-apical progression of hair cell loss, with greater loss of outer hair cells than inner hair cells. Within each age group, the magnitude of loss was much greater in KO mice compared to WT mice. The results indicate that Cu/Zn SOD deficiency potentiates cochlear hair cell degeneration, presumably through metabolic pathways involving the superoxide radical.
Cu/Zn SOD deficiency potentiates hearing loss and cochlear pathology in aged 129,CD-1 mice.
McFadden SL, Ding D, Burkard RF, Jiang H, Reaume AG, Flood DG, Salvi RJ. Center for Hearing and Deafness, State University of New York, Buffalo, New York 14214, USA. mcgadden@acsu.buffallo.edu
J Comp Neurol 1999 Oct 11;413(1):101-12
Copper/zinc superoxide dismutase (Cu/Zn SOD) is a first-line defense against free radical damage in the cochlea and other tissues. To determine whether deficiencies in Cu/Zn SOD increase age-related hearing loss and cochlear pathology, we collected auditory brainstem responses (ABRs) and determined cochlear hair cell loss in 13-month-old 129/CD-1 mice with (a) no measurable Cu/Zn SOD activity (homozygous knockout mice), (b) 50% reduction of Cu/Zn SOD (heterozygous knockout mice), and (c) normal levels of Cu/Zn SOD (wild-type mice). ABRs were obtained by using 4-, 8-, 16-, and 32-kHz tone bursts. Cochleas were harvested immediately after testing, and separate counts were made of inner and outer hair cells. Compared with wild-type mice, homozygous and heterozygous knockout mice exhibited significant threshold elevations and greater hair cell loss. Phenotypic variability was higher among heterozygous knockout mice than among wild-type or homozygous knockout mice. Separate groups of wild-type and homozygous knockout mice were examined for loss of spiral ganglion cells and eighth nerve fibers. At 13 months of age, both wild-type and knockout mice had significantly fewer nerve fibers than did 2-month-old wild-type mice, with significantly greater loss in aged knockout mice than in aged wild-type mice. Thirteen-month-old knockout mice also had a significant loss of spiral ganglion cells compared with 2-month-old wild-type mice. The results indicate that Cu/Zn SOD deficiencies increase the vulnerability of the cochlea to damage associated with normal aging, presumably through metabolic pathways involving the superoxide radical. Copyright 1999 Wiley-Liss, Inc.
Hypothyroidism and the ear: electrophysiological, morphological, and chemical considerations.
Meyerhoff WL.
Laryngoscope 1979 Oct;89(10 Pt 2 Suppl 19):1-25
There is both clinical and laboratory evidence that hearing loss can result from congenital and acquired hypothyroidism. The reversibility of this process, however, and its incidence and pathophysiology are not universally agreed upon. Laboratory animals rendered hypothyroid with radioactive iodine 131 or propylthiouracil demonstrated normal perilymph sodium and potassium levels but increased auditory thresholds for N1N2 response and brain stem evoked audiometry as well as a crystallized consistency of the bone of the bullae and cochleae, ossicular abnormalities, obliteration of the oval and round window, large dark staining lipid accumulations in Hensen's cells, large intercellular spaces in the stria vascularis with degeneration of the marginal and intermediate cells, inner and outer hair cell degeneration, debris in the cochlear duct, and tectorial membrane irregularity. Otic capsule biochemical alterations were identified which may account for the osseous changes observed morphologically. The morphological, biochemical, and electrophysiological findings in this study support the hypothesis that the cochlea is a site of lesion for sensorineural hearing loss in hypothyroidism. Middle ear changes identified could be responsible for the conductive component. |