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Evaluation of
tinnitus patients by peroral multi-drug treatment.
Ohsaki K, Ueno M, Zheng HX, Wang QC, Nishizaki K, Nobuto
Y, Fujimura T.
Division of Clinical Otology, University Hospital,
University of Tokushima, School of Medicine, Japan.
Auris Nasus Larynx 1998 May;25(2):149-54
To evaluate patients complaining of subjective tinnitus,
this study examined their response to peroral betahistine
mesilate, vitamin B complex and diazepam in combination.
Because three drugs were used together, it remains to be
seen whether a single drug or a combination of drugs was
effective. We issued questionnaires to 67 patients with
tinnitus associated with sensorineural hearing loss of
unknown etiology or tinnitus, despite normal hearing in
pure tone audiometry and lack of distinct systemic
disorders. Our original questionnaire contained seven items
and allotted points for each item to facilitate evaluation.
After prescribing the above drugs and observing patients'
progress for 5 weeks, 50 of the 67 subjects were evaluated
again by the same questionnaire. The present study
evaluates tinnitus of patients as an example of clinical
applications; this was not a controlled double blind study.
It was found that, after patients took the prescribed
medication, the total number of points were significantly
reduced (paired t-test, P < 0.001). After
medication, cases of bilateral tinnitus were significantly
reduced from 27 to 14, and cases of two types of tinnitus
sound, were significantly decreased from 22 to 11 (chi
2-test, P < 0.05). After 5 weeks of administration,
54% of patients felt treatment had been effective.
Preliminary results suggest this peroral multi-drug
treatment may provide relief for some patients with
subjective tinnitus. However, long-term efficacy of the
treatment was not investigated.
Pediatric and Geriatric
Tinnitus.
Podoshin L, Ben-David J, Teszler CB.
Otolaryngology, Head & Neck Surgery
Department, Bnai-Zion Medical Center, and Technion-B.
Rappaport Faculty of Medicine, Haifa, Israel.
Int Tinnitus J 1997;3(2):101-103
The subject of tinnitus in the population
extremes-children and the elderly-is ignored by the
literature, probably because children do not complain of
tinnitus spontaneously, whereas it is only one challenge
among other major health problems in the elderly. A short
review of the literature on this subject is presented.
Presbytinnitus, defined as tinnitus that accompanies the
progressive hearing loss of presbycusis is classified as:
type 1 (normal aging affecting the cochlea), and type II
(preexistent sensorineural hearing loss accompanied by
multiple systemic complaints, especially of sensory ones).
The incidence of tinnitus in presbycusis is 11%. Like in
other age groups, there is no significant gender
predilection in the prevalence of tinnitus, but a
correlation was demonstrated between the severity of
tinnitus and exposure to noise. Hypertension was associated
with a lower incidence of tinnitus, as compared to
normotension and hypotension. Several treatment modalities
of geriatric tinnitus are reviewed: the superiority of the
band-noise masker in patients with presbycusis, as compared
to electrical promontory stimulation; amino-oxyacetic in
presbycusis and Meniere's disease; zinc supplementation in
marginally zinc-deficient elderly patients in improving
sensorineural hearing loss and tinnitus; aeration of the
middle ear in presbycusis caused by secretory otitis media.
Pediatric tinnitus has an incidence of 13% in children who
passed an audiometric screening test, and 23-60% in those
with hearing loss, 44% in secretory otitis media, but only
3% complain spontaneously because that the child considers
tinnitus to be a normal event. There is no significant
difference between children with tinnitus and those without
in terms of hearing level, age, gender, or etiology of the
deafness. Despite the fact that often children do not
mention it, tinnitus may incite behavioral problems.
Auditory startle response
is diminished in rats after recovery from perinatal copper
deficiency.
Prohaska JR, Hoffman RG.
Department of Biochemistry, University of Minnesota,
Duluth, USA.
J Nutr 1996 Mar;126(3):618-27
Recovery from perinatal copper deficiency was studied in
female and male Sprague Dawley rats for 6 mo. Month-old
offspring reared by dams on copper-deficient treatment
starting d 7 of pregnancy had up to 80% reductions in
regional brain copper concentrations compared with
offspring from copper-supplemented dams. Liver copper
concentrations and plasma ceruloplasmin diamine oxidase
activities of copper-deficient rats were restored to
control levels within 1 mo of nutritional repletion with
dietary copper. However, brain copper concentrations, with
the exception of the hypothalamus and medulla, remain lower
than in controls even after 5 mo of treatment. Rats were
screened for startle responses and foot splay after 1, 3
and 5 mo of repletion. Diminished auditory startle was
evident in rats of both sexes at all repletion times
tested, whereas tactile startle and preimpulse inhibition
of tactile startle were not influenced by prior copper
deficiency, suggesting auditory sensory perception
abnormalities. In a separate study, postweaning male rats
deprived of dietary copper for 5 wk exhibited clear signs
of copper deficiency but normal acoustic startle responses
and foot splay. Long-term neurochemical and behavioral
abnormalities persist in rats after perinatal copper
deficiency.
L- and D- methionine
provide equivalent long term protection against
CDDP-induced ototoxicity in vivo, with partial in vitro and
in vivo retention of antineoplastic activity.
Reser D, Rho M, Dewan D, Herbst L, Li G, Stupak H, Zur
K, Romaine J, Frenz D,
Goldbloom L, Kopke R, Arezzo J, Van De Water T.
Department of Neuroscience, Albert Einstein College of
Medicine, Bronx, NY 10461, USA.
Neurotoxicology 1999 Oct;20(5):731-48
Treatment of metastatic tumors with ionic platinum
compounds is hampered by the potent nephrotoxic, ototoxic
and neurotoxic properties of these drugs. Recent studies
have shown that sulfur-containing antioxidants relieve the
dose limiting side effects of cis-diamminedichloroplatinum
(CDDP), the most commonly used ionic platinum therapy. Here
we report that both isomers of the sulfur-containing
antioxidant methionine (MET) completely block the in vivo
ototoxic and nephrotoxic effects of CDDP, and the duration
of MET otoprotection is longer than has been previously
reported. Rats treated with either L- or D-MET in addition
to CDDP exhibited no signs of auditory system damage after
7 days, as evaluated by the auditory brainstem response and
scanning electron microscopic examination of the organ of
Corti, while CDDP-treated rats exhibited pronounced
evidence of ototoxic damage after only 3 days. Microscopic
examination of kidney tissue revealed moderate to severe
nephrotoxic damage to CDDP-treated rats after 5 days, while
rats co-treated with either MET isomer showed no evidence
of kidney damage. Mortality among CDDP-treated subjects
increased steadily over the period of the study, while all
of the MET-protected rats survived. Finally, the efficacy
of CDDP in the presence of L- or D-MET was evaluated in
vitro using cultures of MTLN-3 breast tumor cell lines, and
in vivo using implanted MTLN-3 tumors. Both L- and D-MET
reduced the ability of CDDP to kill tumor cells in vitro
and in vivo, however, our data suggest that a higher
proportion of the antineoplastic activity of CDDP is
retained in the presence of L- MET.
An epidemic in Cuba of
optic neuropathy, sensorineural deafness, peripheral
sensory neuropathy and dorsolateral
myeloneuropathy.
Roman GC.
Neuroepidemiology Branch, National Institute of
Neurological Disorders and Stroke, National Institutes of
Health, Bethesda, MD.
J Neurol Sci 1994 Dec 1;127(1):11-28
An epidemic outbreak of peripheral neuropathy affected
Cuba in 1992-93 resulting in 50,862 cases (national
cumulative incidence rate (CIR) 461.4 per 100,000).
Clinical forms included retrobulbar optic neuropathy,
sensory and dysautonomic peripheral neuropathy,
dorsolateral myeloneuropathy, sensorineural deafness,
dysphonia and dysphagia, spastic paraparesis, and mixed
forms. For epidemiological purposes, cases were classified
as optic forms (CIR 242.39) or peripheral forms (CIR
219.25). Increased risk was found among smokers (odds ratio
(OR) 4.9), those with history of missing meals (OR 4.7)
resulting in lower intake of animal protein, fat, and foods
that contain B-vitamins, combined drinking and smoking (OR
3.5), weight loss (OR 2.8), excessive sugar consumption (OR
2.7) and heavy drinking (OR 2.3). Optic neuropathy was
characterized by decreased vision, bilateral and symmetric
central or cecocentral scotomata, and loss of color vision
due to selective lesion of the maculopapillary bundles.
Peripheral neuropathy was a distal axonopathy lesion
affecting predominantly large myelinated axons. Deafness
produced selective high frequency (4-8 kHz) hearing loss.
Myelopathy lesions combined dorsal column deficits and
pyramidal involvement of lower limbs with spastic bladder.
Clinical features were those of Strachan syndrome and
beriberi. Intensive search for neurotoxic agents, in
particular organophosphorus esters, chronic cyanide, and
trichloroethylene intoxication, yielded negative results.
Treatment of patients with B-group vitamins and folate
produced rewarding results. Most patients improved
significantly and less than 0.1% of them remained with
sequelae; there were no fatal cases. Supplementation of
multivitamins to the entire Cuban population resulted in
curbing of the epidemic. Overt malnutrition was not
present, but a deficit of micronutrients, in particular
thiamine, cobalamine, folate and sulfur amino acids appears
to have been a primary determinant of this epidemic.
The therapeutic effect of
vitamins A and E in neurosensory hearing loss.
Romeo G.
Acta Vitaminol Enzymol 1985;7 Suppl:85-92
After an anatomical and physiological outline of the
organ of Corti, the pathology of the cochlea related to the
sensorineural deafness is described. The role of Vitamin A
on cochlear function and the effects of Vitamin E in man
are then emphasized, on the base of some experimental
results. Clinical and therapeutic efficacy of the
combination of Vitamin A + E is shown by a number of
papers, pointing out a 5-15 decibel improvement of the
pure-tone threshold in patients with sensorineural
hearing-loss particularly when the auditory troubles are
due to presbyaccusis.
Chemical anatomy of
excitatory endings in the dorsal cochlear nucleus of the
rat: differential synaptic distribution of aspartate
aminotransferase, glutamate, and vesicular
zinc.
Rubio ME, Juiz JM.
Instituto de Neurociencias, Universidad Miguel Hernandez,
Alicante, Spain.
lrubio@pop.nidcd.nih.gov
J Comp Neurol 1998 Sep 28;399(3):341-58
In order to identify cytochemical traits relevant to
understanding excitatory neurotransmission in brainstem
auditory nuclei, we have analyzed in the dorsal cochlear
nucleus the synaptic distribution of aspartate
aminotransferase, glutamate, and vesicular zinc, three
molecules probably involved in different steps of
excitatory glutamatergic signaling. High levels of
glutamate immunolabeling were found in three classes of
synaptic endings in the dorsal cochlear nucleus, as
determined by quantitation of immunogold labeling. The
first type included auditory nerve endings, the second were
granule cell endings in the molecular layer, and the third
very large endings, better described as "mossy." This
finding points to a neurotransmitter role for glutamate in
at least three synaptic populations in the dorsal cochlear
nucleus. The same three types of endings enriched in
glutamate immunoreactivity also contained histochemically
detectable levels of aspartate aminotransferase activity,
suggesting that this enzyme may be involved in the synaptic
handling of glutamate in excitatory endings in the dorsal
cochlear nucleus. There was also extrasynaptic localization
of the enzyme. Zinc ions were localized exclusively in
granule cell endings, as determined by a Danscher-selenite
method, suggesting that this ion is involved in the
operation of granule cell synapses in the dorsal cochlear
nucleus.
Dose dependent protection
by lipoic acid against cisplatin-induced ototoxicity in
rats: antioxidant defense system.
Rybak LP, Husain K, Whitworth C, Somani SM.
Department of Pharmacology, Southern Illinois University,
School of Medicine,
Springfield 62794, USA.
Toxicol Sci. 1999 Feb;47(2):195-202.
This study investigated the alterations that occur in
auditory brainstem-evoked responses (ABRs) concurrent with
changes in cochlear concentrations of glutathione (GSH),
lipid peroxidation, and antioxidant enzyme activity in
cisplatin-induced ototoxicity and in dose-dependent
otoprotection by an antioxidant lipoate. Male Wistar rats
were divided into different groups and were treated as
follows, with: (1) vehicle (saline) control; (2) cisplatin
(16 mg/kg, i.p.); (3) lipoate (100 mg/kg, i.p.) plus
saline; (4) cisplatin plus lipoate (25 mg/kg); (5)
cisplatin plus lipoate (50 mg/kg), and (6) cisplatin plus
lipoate (100 mg/kg). Post-treatment ABRs were evaluated
after three days, the rats were sacrificed, and cochleae
were harvested and analyzed. The cisplatin-injected rats
showed ABR threshold elevations above the pre-treatment
thresholds. Rats treated with lipoate plus cisplatin did
not show significant elevation of hearing thresholds.
Cisplatin administration resulted in a depletion of
cochlear GSH concentration (69% of control), whereas,
cisplatin-plus-lipoate treatment increased GSH
concentration close to control value. Cisplatin-treated
rats showed a decrease in cochlear superoxide dismutase
(SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and
glutathione reductase (GR) activities (57, 78, 59, and 58%
of control, respectively), and an increase in
malondialdehyde (MDA) concentration (196% of control).
Cochlear SOD, CAT, GSH-Px, and GR activities and MDA
concentrations were restored in the rats injected with
cisplatin plus graded doses of lipoate than those with
cisplatin alone. It is concluded that cisplatin-induced
ototoxicity is related to impairment of the cochlear
antioxidant defense system, and the dose-dependent
otoprotection conferred by an antioxidant lipoate against
cisplatin ototoxicity is associated with sparing of the
cochlear antioxidant defense system.
Application of
antioxidants and other agents to prevent cisplatin
ototoxicity.
Rybak LP, Whitworth C, Somani S.
Department of Surgery, Southern Illinois University,
School of Medicine,
Springfield 62794-9638, USA.
Laryngoscope. 1999 Nov;109(11):1740-4.
OBJECTIVE/HYPOTHESIS: To review the recent data from
experiments performed in this laboratory to test the
hypothesis that cisplatin ototoxicity is related to
depletion of glutathione and antioxidant enzymes in the
cochlea and that the use of antioxidants or protective
agents would protect the cochlea against cisplatin damage
and prevent hearing loss.
STUDY DESIGN/METHODS: Data were reviewed from
experiments performed in this laboratory. Control rats were
treated intraperitoneally with cisplatin 16 mg/kg.
Experimental rats were given cisplatin in combination with
one of the following protective agents:
diethyldithiocarbamate, 4-methylthiobenzoic acid, ebselen,
or lipoic acid.
Animals in each group underwent auditory brainstem
response (ABR) threshold
testing before and 3 days after treatment. Cochleae were
removed after final ABR testing and analyzed for
glutathione and activities of the enzymes superoxide
dismutase, catalase, glutathione peroxidase, glutathione
reductase, and malondialdehyde.
RESULTS: Rats in the control group receiving cisplatin
were found to have significant ABR threshold shifts. This
was accompanied by a reduction of glutathione and the
activity of antioxidant enzymes (superoxide dismutase,
glutathione peroxidase, catalase, and glutathione
reductase) and an elevation of malondialdehyde.
Experimental animals had preservation of ABR thresholds and
levels of glutathione, antioxidant enzyme activity,
and
malondialdehyde that were similar to untreated
animals.
CONCLUSION: Cisplatin ototoxicity appears to be
initiated by fee-radical production, which causes depletion
of glutathione and antioxidant enzymes in the cochlea, and
lipid peroxidation, manifested by an increase in
malondialdehyde. These effects were blocked by each of a
series of antioxidant compounds given in combination with
cisplatin. A mechanism for cisplatin ototoxicity is
elaborated with a proposed plan of chemoprevention using
agents with different mechanisms of action. These
substances could be used alone or in combination to reduce
the severity of cisplatin ototoxicity in patients.
Ototoxicity.
Amelioration by protective agents.
Rybak LP, Somani S.
Department of Surgery, Southern Illinois University,
School of Medicine,
Springfield 62794-9638, USA.
Ann N Y Acad Sci. 1999 Nov 28;884:143-51.
The findings of studies from this laboratory are
summarized to compare the efficacy of four chemoprotective
agents against the effects of cisplatin-induced hearing
loss and biochemical damage in the rat cochlea. A number of
studies have shown that cisplatin is ototoxic, resulting in
hearing loss, morphologic damage, and biochemical changes
in the cochlea. These studies used Wistar rats, which
underwent pre- and posttreatment ABR testing using clicks
and tonebursts stimuli at 8, 16, and 32 kHz. Controls
received i.p. saline injection. Cisplatin-treated rats were
given 16 mg/kg cisplatin i.p. Animals received protective
agents in the following dosage: DDTC protected rats
received 600 mg/kg subcutaneously an hour after cisplatin.
MTBA-protected animals were given 250 mg/kg i.p. 30 minutes
before cisplatin. Animals protected with ebselen received
16 mg/kg i.p. an hour before cisplatin. One hundred mg/kg
of alpha-lipoic acid was injected i.p. 30 minutes before
cisplatin. Rats were sacrificed three days after treatment
and the cochleae were harvested and frozen in liquid
nitrogen and stored at -80 degrees C until analysis of
glutathione (GSH), the activity of antioxidant enzymes
(superoxide dismutase, catalase, glutathione peroxidase,
and glutathione reductase) and malondialdehyde was
performed. Cisplatin-treated rats were found to have ABR
threshold shifts of 27-40 dB, and rats treated with
chemoprotective agents plus cisplatin all had ABR
thresholds shifts of less than 10 dB. Significant depletion
of glutathione and decrease of the activities of the
antioxidant enzymes were observed in cisplatin-treated
rats. These changes were accompanied by a marked elevation
of malondialdehyde. These changes were almost completely
prevented by the use of the chemoprotective agents. These
findings suggest that cisplatin ototoxicity is related to
lipid peroxidation and that the use of protective agents
prevents hearing loss and lipid peroxidation by sparing the
antioxidant defense system in the cochlea.
[Hearing recovery in
sudden deafness with profound hearing loss.]
[Article in Japanese]
Sano H, Okamoto M, Hirayama M, Ono Y, Nitta M.
Department of Otolaryngology, School of Medicine, Kitasato
University, Sagamihara.
Nippon Jibiinkoka Gakkai Kaiho 1998
Jun;101(6):836-40
We investigated the hearing recovery in 51 patients with
sudden deafness with the initial averaged five-frequency
hearing levels worse than or equal to 100 dB. Twenty-two
patients were treated in an outpatient setting with a
peri-oral steroid, vasodilator, metabolic activator, and
vitamin B. The remaining 29 patients were treated in the
hospital with additional hyperbaric oxygenation therapy
and/or Satellite ganglion block. The results were as
follows. 1) The ultimate averaged five-frequency hearing
levels were mainly distributed from 55 to 80 dB. Only seven
patients showed ultimate hearing levels worse than 100 dB.
Two patients achieved complete recovery better than 20 dB.
2) There was no significant difference in the hearing
recovery between the patients treated in an outpatient
setting and in the hospital. 3) The time interval until the
hearing recovery began was distributed broadly between 2
and 28 days from the onset. While most of the patients who
began to recover within 14 days from the onset showed
ultimate hearing levels better than 80 dB, the patients who
recovered after 14 days had worse hearing levels.
Pharmacokinetics of
coenzyme Q10 in recovery of acute sensorineural hearing
loss due to hypoxia.
Sato K.
Department of Otolaryngology, Kanazawa Medical University,
Japan.
Acta Otolaryngol Suppl 1988;458:95-102
Coenzyme Q10 (CoQ10) has already been favorably
evaluated in the clinical treatment of heart disease. In
the otolaryngological field, it has been reported that
CoQ10 is effective in promoting recovery from acute sudden
deafness. However, the pharmakinetics of CoQ10 in the inner
ear is not yet clarified. The present study focuses upon
the pharmacokinetics of CoQ10 using guinea pigs with acute
sensorineural hearing loss artificially induced by hypoxia
conditions. The respiration of the animals was controlled
in an artificial respirator while the ABR, ECG and blood
pressure were monitored. Repeated hypoxia caused a gradual
disappearance of the ABR. After the experiments, the
animals were sacrificed and brain and inner ear were
examined by histological and histochemical methods as well
as by SEM and TEM. The results indicated that CoQ10 is
effective in promoting recovery from damage in auditory
hairs as well as preventing respiratory metabolic
impairment of hair cell due to hypoxia.
Preventive effect of
magnesium supplement on noise-induced hearing loss in the
guinea pig.
Scheibe F, Haupt H, Ising H.
Department of Otorhinolaryngology, Charite Hospital,
Humboldt University, Schumannstrasse 20-21, 10117 Berlin,
Germany. fred.scheibe@charite.de
Eur Arch Otorhinolaryngol 2000;257(1):10-6
The effect of magnesium (Mg) on noise-induced hearing
loss was investigated in two groups of adult pigmented
guinea pigs maintained either on optimal or suboptimal
(physiologically high or low) Mg produced by different
diets. The total Mg concentrations of the perilymph (PL),
cerebrospinal fluid, blood plasma and red blood cells were
measured by atomic absorption spectrometry and were found
to differ significantly between the two groups (P <
0.01). One ear of each animal was exposed to either a
single shooting impulse at a peak pressure level of 187 dB
or two impulse noise series at a rate of 1/s and peak
pressure levels of 150 dB (1,000 impulses) and 167 dB
(2,280 impulses), respectively. Temporary (TTS) and
permanent (PTS) hearing threshold shifts in anesthetized
animals were measured 2 h and 1 week after the noise
exposure, using auditory brain stem response (ABR)
audiometry at a frequency range from 3.75 to 30 kHz.
Exposure to the single noise impulse resulted in a mean TTS
that was significantly lower in the high Mg group than that
in the low Mg group (P < 0.05), although no
substantial PTS was observed in either group. In the
animals exposed to 150 dB noise, the TTS showed a tendency
towards an Mg-related reduction at the higher frequencies.
A small difference in PTS was found between the low Mg and
high Mg groups, but was not significant. Exposure to the
167-dB noise series caused a considerable TTS, which was
significantly lower in the high Mg group at 7.5 and 15 kHz
than in the low Mg group (P < 0.05). The mean PTS
showed a significant difference between the two Mg groups
over the whole frequency range (P < 0.05) and was
found to correlate negatively with the total Mg
concentrations of both PL and plasma (P < 0.05).
Moreover, the high Mg group showed a faster recovery from
the hearing threshold shift than the low Mg group. The
present findings show that preventive oral Mg supplements
can significantly reduce the rate of acoustic trauma caused
by high-level impulse noise exposure in the guinea pig.
Preventive magnesium
supplement reduces ischemia-induced hearing loss and blood
viscosity in the guinea pig.
Scheibe F, Haupt H, Vlastos GA.
Department of Otorhinolaryngology, Charite Hospital,
Humboldt University, Berlin, Germany.
fred.scheibe@charite.de
Eur Arch Otorhinolaryngol 2000;257(7):355-61
The effect of magnesium (Mg) on ischemia-induced hearing
loss was investigated in two groups of adult pigmented
guinea pigs of either an optimal or suboptimal
(physiologically high or low) Mg status maintained by
different diets. Total Mg concentrations of the perilymph,
cerebrospinal fluid, blood plasma and red blood cells were
found to differ significantly between the two groups, as
tested in a previous study. Local vascular impairment was
produced by unilateral ferromagnetic thrombosis of cochlear
blood vessels. Cochlear blood flow (CBF) and hearing
function were measured using laser Doppler flowmetry and
auditory brain-stem response audiometry, respectively.
Ferromagnetic thrombosis resulted in significant reductions
of the mean apical CBF in both experimental groups and of
the mean basal CBF in the low Mg group compared to the
contralateral ears. In the high Mg group, the basal CBF was
not decreased. However, the laser Doppler signals revealed
considerable interindividual variations and the differences
found between the two experimental groups were not
significant. In contrast, the hearing loss in the low Mg
group was significantly higher than that in the high Mg
group. A correlation was found to exist between the
vascular impairment and the hearing threshold shift. In a
separate series, we also tested the effect of Mg on
hemorheology and found both the blood viscosity and blood
viscoelasticity to be significantly lower in the high Mg
group than in the low Mg group, depending on the shear
rates tested. The present findings show that a preventive
oral Mg supplement can significantly reduce the rate of
ischemia-induced hearing loss and improve blood viscosity
in the guinea pig.
Biologic activity of
mitochondrial metabolites on aging and age-related hearing
loss.
Seidman MD, Khan MJ, Bai U, Shirwany N, Quirk WS.
Department of Otolaryngology Head & Neck Surgery,
Henry Ford Health System,
Detroit, Michigan 48323, USA.
Am J Otol. 2000 Mar;21(2):161-7.
HYPOTHESIS: Compounds that upregulate mitochondrial
function in an aging model will improve hearing and reduce
some of the effects of aging.
BACKGROUND: Reactive oxygen metabolites (ROM) are known
products of oxidative metabolism and are continuously
generated in vivo. More than 100 human clinical conditions
have been associated with ROM, including atherosclerosis,
arthritis, autoimmune diseases, cancers, heart disease,
cerebrovascular accidents, and aging. The ROM are extremely
reactive and cause extensive DNA, cellular, and tissue
damage. Specific deletions within the mitochondrial DNA
(mtDNA) occur with increasing frequency in age and
presbyacusis. These deletions are the result of chronic
exposure to ROM. When enough mtDNA damage accrues, the cell
becomes bioenergetically deficient. This mechanism is the
basis of the mitochondrial clock theory of aging, also
known as the membrane hypothesis of aging. Nutritional
compounds have been identified that enhance mitochondrial
function and reverse several age-related processes. It is
the purpose of this article to describe the effects of two
mitochondrial metabolites, alpha-lipoic acid and acetyl
L-carnitine, on the preservation of age-related hearing
loss.
METHODS: Twenty-one Fischer rats, aged 24 months, were
divided into three groups: acetyl-1-carnitine, alpha-lipoic
acid, and control. The subjects were orally supplemented
with either a placebo or one of the two nutritional
compounds for 6 weeks. Auditory brainstem response testing
was used to obtain baseline and posttreatment hearing
thresholds. Cochlear, brain, and skeletal muscle tissues
were obtained to assess for mtDNA mutations.
RESULTS: The control group demonstrated an expected
age-associated threshold deterioration of 3 to 7 dB in the
6-week study. The treated subjects experienced a delay in
progression of hearing loss. Acetyl-1-carnitine improved
auditory thresholds during the same time period
(p<0.05). The mtDNA deletions associated with aging
and presbyacusis were reduced in the treated groups in
comparison with controls.
CONCLUSIONS: These results indicate that in the proposed
decline in mitochondrial function with age, senescence may
be delayed by treatment with mitochondrial metabolites.
Acetyl-1-carnitine and alpha-lipoic acid reduce
age-associated deterioration in auditory sensitivity and
improve cochlear function. This effect appears to be
related to the mitochondrial metabolite ability to protect
and repair age-induced cochlear mtDNA damage, thereby
upregulating mitochondrial function and improving
energy-producing capabilities.
Salicylate attenuates
gentamicin-induced ototoxicity.
Sha SH, Schacht J.
Kresge Hearing Research Institute, Department of
Otolaryngology, University of Michigan, Ann Arbor
48109-0506, USA.
Lab Invest 1999 Jul;79(7):807-13
Aminoglycosides, primarily gentamicin, are the most
commonly used antibiotics worldwide despite their toxicity
to the kidney and the inner ear. A preventive therapy
against these side effects should combine safety and
efficacy with low cost because aminoglycoside-induced
deafness is most prevalent in developing countries. We have
previously shown that aminoglycosides catalyze the
formation of free radicals in an iron-dependent reaction
and have delineated the structure of an iron-gentamicin
complex. Here we demonstrate that 2-hydroxybenzoate
(salicylate), which can act as an iron chelator and
antioxidant, effectively protects against
gentamicin-induced hearing loss in guinea pigs. Co-therapy
with salicylate reduced a profound gentamicin-induced
auditory threshold shift of more than 60 dB to less than 20
dB. Morphological assessment of the inner ear confirmed
protection of auditory sensory cells. Salicylate altered
neither serum levels of gentamicin nor its antibacterial
efficacy. Because the required salicylate levels correspond
to anti-inflammatory levels in humans, this treatment holds
promise for clinical application.
Antioxidants attenuate
gentamicin-induced free radical formation in vitro and
ototoxicity in vivo: D-methionine is a potential
protectant.
Sha SH, Schacht J.
Kresge Hearing Research Institute, Department of
Otolaryngology, University of Michigan, 1301 East Ann
Street, Ann Arbor, MI, USA.
Hear Res 2000 Apr;142(1-2):34-40
We have recently suggested antioxidant therapy against
aminoglycoside-induced hearing loss based on the hypothesis
of a redox-active aminoglycoside-iron complex causing
ototoxicity. The present study compares seven antioxidants
and iron chelators for their ability to attenuate
gentamicin-induced free radical generation in vitro and
ototoxicity in guinea pig in vivo.Free radical formation by
gentamicin was measured by chemiluminescence detection both
in a non-enzymatic system in vitro and in cell culture.
Deferoxamine, 2,3-dihydroxybenzoate, or salicylic acid
suppressed gentamicin-induced luminescence in both tests.
This indicated the usefulness of the assay as a screen for
potential protectants since these agents had previously
been shown to attenuate gentamicin-induced ototoxicity in
vivo. Histidine and D-methionine, amino acids with
chelating and antioxidant properties, also suppressed
gentamicin-mediated luminosity both in vitro and in cell
culture. In contrast, the metal chelators succimer (2,
3-dimercaptosuccinic acid (DMSA)) and trientine (N,
N'-bis[2-aminoethyl]-1,2 ethanediamine) promoted free
radical formation and were excluded from further studies.
Histidine and D-methionine were then administered to guinea
pigs receiving concurrent treatment with gentamicin (120
mg/kgx19 days). Threshold shifts induced by gentamicin were
significantly attenuated by twice-daily injections of
D-methionine. Once-daily injections of histidine or
D-methionine were less effective, pointing to the
importance of pharmacokinetics in antioxidant protection in
vivo.The study presents a simple screening system for
agents with the potential to attenuate gentamicin-induced
hearing loss. It also supports the hypothesis of free
radical formation as an underlying cause of gentamicin
ototoxicity.
Zinc: the neglected
nutrient.
Shambaugh GE Jr.
Shambaugh Hearing and Allergy, Hinsdale, IL 60521.
Am J Otol 1989 Mar;10(2):156-60
Zinc was first recognized as essential for animals at
the University of Illinois School of Agriculture in 1916,
when it was found that zinc-deficient baby pigs were runty,
developed dermatitis on their legs, and were sterile. Zinc
deficiency was first recognized in man by Dr. Ananda Prasad
of Detroit 26 years ago when he measured serum and hair
zinc levels in young male Egyptian dwarfs who had failed to
mature and were small in stature. By simply adding zinc to
their regular diet, they grew in height and became sexually
mature. It is now recognized that dwarfism in males is
frequent around the Mediterranean, where wheat is the
staple of life and has been grown for 4,000 years on the
same soil, thereby resulting in the depletion of zinc.
Professor Robert Henkin first suggested that zinc
deficiency might cause hearing-nerve impairment. Assay of
the soft tissues of the cochlea and vestibule revealed a
zinc level higher than that of any other part of the body.
Previously, the eye was considered to have the highest
level of zinc of any organ. To diagnose zinc deficiency
clinically, we use serum zinc assays made at the Mayo
Clinic Trace Element Laboratory. With zinc supplementation
in patients who are marginally zinc deficient, there has
been improvement in tinnitus and sensorineural hearing loss
in about one-third of elderly adults. We believe zinc
deficiency is one causation of presbycusis; by recognizing
and correcting it, a progressive hearing loss can be
arrested.
Vitamin B12 deficiency
in patients with chronic-tinnitus and noise-induced hearing
loss.
Shemesh Z, Attias J, Ornan M, Shapira N, Shahar A.
Institute of Noise Hazards Research and Evoked Potentials
Laboratory, IDF, Chaim-Sheba Medical Center, Ramat-Gan,
Israel.
Am J Otolaryngol 1993 Mar-Apr;14(2):94-9
INTRODUCTION: This study examines the incidence of
vitamin B12 deficiency in three groups of noise-exposed
subjects: patients with chronic tinnitus and noise-induced
hearing loss (NIHL), patients with NIHL only, and subjects
demonstrating normal hearing. MATERIALS AND METHODS: A
group of 113 army personnel exposed to military noise was
studied. The mean age was 39 years. Chronic tinnitus and
NIHL existed in 57 subjects. NIHL alone was observed in 29
subjects, and 27 subjects had normal audiograms. All
subjects were queried about noise exposure and dietary
habits. Vitamin B12 serum levels were measured. RESULTS:
Patients with tinnitus and NIHL exhibited vitamin B12
deficiency in 47% of cases (blood levels < or = 250
pg/mL). This was significantly more (P < .023)
compared with NIHL and normal subjects who exhibited
vitamin B12 deficiency in 27% and 19%, respectively.
CONCLUSION: These observations suggest a relationship
between vitamin B12 deficiency and dysfunction of the
auditory pathway. Some improvement in tinnitus and
associated complaints were observed in 12 patients
following vitamin B12 replacement therapy. The authors
recommend that routine vitamin B12 serum levels be
determined when evaluating patients for chronic
tinnitus.
Delayed auditory
brainstem response in thiamin-deficient rats.
Shigematsu Y, Nakai A, Kuriyama M, Kikawa Y, Konishi I,
Sudo M, Itokawa Y.
Department of Pediatrics, Fukui Medical School, Japan.
J Nutr Sci Vitaminol (Tokyo) 1990 Jun;36(3):209-15
We recorded the auditory brainstem responses of rats fed
a thiamin-deficient diet. The interpeak latencies between
waves I and III, as well as those between waves I and IV,
were significantly prolonged from day 24, while the latency
of wave I was prolonged on day 26 of the thiamin-deficient
diet. These delayed responses were corrected in 2 to 4 days
after the initiation of daily intraperitoneal thiamin
injections from day 32. The rats that were fed the
thiamin-deficient diet, and then sacrificed on day 32,
showed a decrease of total thiamin levels in the brain (26%
of the level in control rat brains). Based on these
results, we emphasize the value of the auditory brainstem
response to detect thiamin deficiency.
Clinical improvement of
memory and other cognitive functions by Ginkgo biloba:
review of relevant literature.
Soholm B.
Sano-Pharm A/S, Vedbaek, Denmark.
Adv Ther 1998 Jan-Feb;15(1):54-65
Ginkgo biloba is a plant extract used to alleviate
symptoms associated with cognitive deficits, e.g.,
decreased memory performance, lack of concentration,
decreased alertness, tinnitus, and dizziness. Pharmacologic
studies have shown that the therapeutic effect of ginkgo is
based on several active constituents with vasoactive and
free radical-scavenging properties. The use of ginkgo
extract in either dementias of the Alzheimer or
multi-infarct type or in the case of cerebral
insufficiency, a symptom complex related to
age-dependent
impairment of cerebral circulation, is based mainly on
positive results from good-quality placebo-controlled
studies that enrolled approximately 1,200 patients with
criteria established by International Classification of
Diseases (9th and 10th revisions, ICD-9 and ICD-10) or the
3rd revision of the Diagnostic and Statistical Manual
(DSM-III-R) (uncomplicated dementia). Effect on cognitive
symptoms was within the range of a 25% reduction. Memory,
concentration, and alertness were the first symptoms to be
relieved, with tinnitus and dizziness improving somewhat
later. A minimum of 4 to 6 weeks were needed before a
pronounced effect could be expected. The pharmacologic
advantage of ginkgo seems to be a very tolerable
side-effect profile, with a side-effect frequency at
the
placebo level.
Protection from
gentamicin ototoxicity by iron chelators in guinea pig in
vivo.
Song BB, Anderson DJ, Schacht J.
Kresge Hearing Research Institute, University of Michigan,
Ann Arbor 48109-0506, USA.
J Pharmacol Exp Ther 1997 Jul;282(1):369-77
This study details the prevention of gentamicin-induced
hearing loss in guinea pig in vivo. The approach is based
on our recent demonstrations of a redox-active
gentamicin-iron complex in vitro and partial attenuation of
gentamicin-induced hearing loss by the iron chelators
deferoxamine and 2,3-dihydroxybenzoate. In our study,
guinea pigs receiving injections of gentamicin (120 mg/kg
body weight daily x 19 days) developed a progressive
threshold shift reaching 50 to 70 dB at 18 kHz. Concurrent
treatment with different doses of 2,3-dihydroxybenzoate
(30-300 mg/kg/day) reduced the threshold shift to 25 to 15
dB. Coinjection of gentamicin with dihydroxybenzoate (100
mg/kg/day) plus mannitol (15 mg/kg/day) yielded complete
functional and morphological protection from gentamicin
ototoxicity although partial protection was observed with
combinations of dihydroxybenzoate and deferoxamine.
Dihydroxybenzoate also attenuated gentamicin-induced
vestibular toxicity. The iron chelators and radical
scavengers affected neither serum levels nor the
antimicrobial efficacy of gentamicin against Escherichia
coli. These results confirm that iron and free radicals
play a crucial role in the toxic side effects of
gentamicin. Furthermore, they suggest that iron chelators,
which are well-established drugs in clinical therapy, may
be promising therapeutic agents to reduce aminoglycoside
ototoxicity.
Variable efficacy of
radical scavengers and iron chelators to attenuate
gentamicin ototoxicity in guinea pig in vivo.
Song BB, Schacht J.
Kresge Hearing Research Institute, University of Michigan,
Ann Arbor 48109-0506, USA.
Hear Res 1996 May;94(1-2):87-93
Recent studies from our laboratory have suggested that
the ototoxic side effects of gentamicin are caused by a
metabolized or 'activated' from the drug. Furthermore, we
have postulated that the activation proceeds via the
formation of an iron-gentamicin complex and that this
complex produces free radicals. The present study assessed
the protection effects of free radical scavengers and iron
chelators on gentamicin-induced ototoxicity in guinea pigs
in vivo. Gentamicin (120 mg/kg per day for 19 days) caused
progressive threshold shifts reaching 50-65 dB at 18 kHz.
Co-therapy with different radical scavengers yielded
results ranging from no protection (with allopurinol,
dimethyl sulfoxide, benzoate, lazaroid U74389G) to a
moderate attenuation of hearing loss (with mannitol,
4-methylthiobenzoate, WR-2721). This finding agrees well
with previous reports of inconsistent effects of scavengers
on aminoglycoside-induced ototoxicity although it should be
cautioned that only a single dose and route of application
was tested. Two iron chelators, deferoxamine and
2,3-dihydroxybenzoate, significantly reduced the
gentamicin-induced threshold shifts to about 10 dB or less.
Iron chelators markedly decreased total serum iron levels
while gentamicin treatment alone had no influence. There
were no differences in serum gentamicin levels among all
treated groups. This study confirms that iron plays a
critical role in gentamicin ototoxicity and suggests that
iron chelators, which are well-established drugs in
clinical therapy, may be promising therapeutic agents to
reduce aminoglycoside ototoxicity.
Iron chelators protect
from aminoglycoside-induced cochleo- and
vestibulo-toxicity.
Song BB, Sha SH, Schacht J.
Kresge Hearing Research Institute, University of Michigan,
Ann Arbor 48109-0506, USA.
Free Radic Biol Med 1998 Jul 15;25(2):189-95
The attenuation of gentamicin-induced hearing loss by
iron chelators and radical scavengers has recently been
demonstrated in guinea pig in vivo. The present study
investigated whether this protective treatment is effective
against hearing loss and vestibular damage caused by other
aminoglycosides. In a direct comparison, dihydroxybenzoate
was chosen over deferoxamine because of its more effective
action against gentamicin-induced hearing loss. Guinea pigs
received daily injections of kanamycin (250 mg/kg/d) or
streptomycin (300 mg/kg/d) for 23 d to induce severe
cochlear or vestibular toxicity, respectively. Kanamycin
injections resulted in a progressive threshold shift of 60
to 80 dB at 18 kHz, while streptomycin injections induced
only a small threshold shift. In contrast, streptomycin
abolished almost all vestibular responses. Coinjection
of
aminoglycosides with a mixture of dihydroxybenzoate (100
mg/kg/d) and mannitol (30 mg/kg/d) significantly attenuated
kanamycin-induced hearing loss and protected against
streptomycin-induced vestibulotoxicity. DHB/mannitol did
not affect serum levels or the antibacterial efficacy of
either aminoglycoside. This study supports the idea that
iron and free radicals play a critical role in the toxic
side effects of aminoglycoside antibiotics. Furthermore,
the previously proposed therapeutic protection is not
limited to gentamicin but applicable to other
aminoglycosides as well.
[The effect of
polikatan on the ototoxic action of kanamycin.]
[Article in Russian]
Spasov AA, Lobzov MS, Sanzharovskaia NK, Kozhevnikova
EV, Kuzubova EA.
Volgograd State Medical Academy, Russia.
Eksp Klin Farmakol 1999 Jul-Aug;62(4):65-6
Experiments on guinea pigs demonstrated that preliminary
injection of polycatan (standardized magnesium solution
containing the mineral bischofite) into the parotid region
by means of electrophoresis reduces the ototoxic effect of
the aminoglycoside antibiotic kanamycin. Polycatan prevents
kanamycin-induced degenerative changes of the hair cells
found in the labyrinth of the internal ear and improves the
local blood flow.
[Noise from a car
airbag as a cause of acute acoustic trauma]
[Article in Polish]
Stankiewicz C, Przewozny T, Kozlowski J.
Katedra i Klinika Chorob Uszu, Nosa, Gardla i Krtani AM w
Gdansku.
Otolaryngol Pol. 2000;54(6):775-81.
A case of acute acoustic trauma in 32 year male, caused
by a noise from car airbag, was described. The symptoms
occurring directly after the airbag shot were tinnitus and
hearing loss in right ear. Patient was admitted to ENT
Clinic in Gdansk just after 5 months after an accident.
Treatment--vasodilatators and oxygen hyperbaric
therapy--was ineffective. Review of literature, concerning
the side effects of car airbag shot, was made. A mechanism
of airbag action was presented as a source of short time
noise.
Iron deficiency and
hearing loss. Experimental study in growing
rats.
Sun AH, Xiao SZ, Li BS, Li ZJ, Wang TY, Zhang YS.
ORL J Otorhinolaryngol Relat Spec 1987;49(3):118-22
Cochlear changes were studied in 141 growing rats raised
on a basic iron-deficient diet for 7-100 days; 130 rats
served as normal or chronic anemia controls.
Electrophysiological findings showed that the incidence of
an auditory threshold elevation of more than 15 dB was
31.85% in the iron-deficient rats, but it was unchanged in
all the control animals. The main cochlear
histopathological changes induced by iron deficiency were
strial atrophy and reduction of spiral ganglion cells. It
is concluded that the observed anomalies may be attributed
solely to iron deficiency of the cochlear tissue.
Changes in the cochlear
iron enzymes and adenosine triphosphatase in experimental
iron deficiency.
Sun AH, Li JY, Xiao SZ, Li ZJ, Wang TY.
Otolaryngological Laboratories, Changhai Hospital,
Shanghai, People's Republic of China.
Ann Otol Rhinol Laryngol 1990 Dec;99(12):988-92
The influences of iron deficiency on the cochlear iron
enzymes and adenosine triphosphatase were studied in 68
iron-deficient rats and 68 control rats (normal and with
chronic anemia). A disorderly or topographic distribution
and reduction or disappearance of the cochlear succinic
dehydrogenase and peroxidase reaction products were found
in 37.8% of the rats fed on a basic iron-deficient diet for
14 to 100 days. The activity of cochlear
sodium-potassium-dependent adenosine triphosphatase in
iron-deficient rats was slightly increased, compared to
that in normal controls. These results suggest that iron
deficiency would produce significant abnormalities of
succinic dehydrogenase and peroxidase activity, which in
turn would disturb cell respiration and initiate
peroxidative damage to the inner ear cells, result in
sensorineural hearing loss, or provide a pathologic basis
for cochlear deafness.
Noise-induced hearing
loss in iron-deficient rats.
Sun AH, Wang ZM, Xiao SZ, Li ZJ, Lin DY, Liang ZF, Hu
ZY, Wang GY, Ye XT.
Otolaryngological Laboratories, Changhai Hospital,
Shanghai, China.
Acta Otolaryngol 1991;111(4):684-90
The role of iron deficiency in noise-induced hearing
loss (NIHL) was evaluated in 64 rats of four different
experimental groups. Iron-deficient rats (ID-rats) and
normal rats (N-rats) were simultaneously exposed to a
steady state white noise (20-10,000 Hz) at 110 dB SPL for
30 min. Unexposed ID- and N-rats served as controls. In
N-rats the temporary threshold shifts (TTS) would have
completely disappeared if the animals were allowed to
survive for 72 h. No permanent threshold shift (PTS) was
seen in any of the N-rats. The ultrastructural correlates
in N-rats are stereocilia disarray and mitochondria
swelling in outer hair cells (OHCs). The TTS in ID-rats
were larger than those in the N-rats, and most ID-rats with
larger threshold shifts showed varying degrees of PTSs at
11 days post-exposure. The ultrastructural correlates of
NIHL in ID-rats are obvious pathology of the stereocilia,
such as segmental coalescence of stereocilia of many
continuous OHCs and fusion of the tips of stereocilia of
OHCs, and a significant reduction of mitochondria as well
as slight degeneration of nucleus in the OHCs. It is
concluded that iron deficiency can provide a pathological
basis for NIHL.
The effects of coenzyme
Q10 treatment on maternally inherited diabetes mellitus and
deafness, and mitochondrial DNA 3243 (A to G)
mutation.
Suzuki S, Hinokio Y, Ohtomo M, Hirai M, Hirai A, Chiba
M, Kasuga S, Satoh Y, Akai H, Toyota T.
Third Department of Internal Medicine, Tohoku University
School of Medicine, Sendai, Japan.
Diabetologia 1998 May;41(5):584-8
The characteristic clinical features of diabetes
mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation
are progressive insulin secretory defect, neurosensory
deafness and maternal inheritance, referred to as
maternally inherited diabetes mellitus and deafness (MIDD).
A treatment for MIDD to improve insulin secretory defects
and reduce deafness has not been established. The effects
of coenzyme Q10 (CoQ10) treatment on insulin secretory
response, hearing capacity and clinical symptoms of MIDD
were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant
subjects with impaired glucose tolerance (IGT), and 15
mutant subjects with normal glucose tolerance (NGT) were
treated daily with oral administration of 150 mg of CoQ10
for 3 years. Insulin secretory response, blood lactate
after exercise, hearing capacity and other laboratory
examinations were investigated every year. In the same way
we evaluated 16 MIDD patients (control-DM), 5 mutant IGT
and 5 mutant NGT subjects in yearly examinations. The
insulin secretory response assessed by glucagon-induced
C-peptide secretion and 24 h urinary C-peptide excretion
after 3 years in the CoQ10-DM group was significantly
higher than that in the control-DM group. CoQ10 therapy
prevented progressive hearing loss and improved blood
lactate after exercise in the MIDD patients. CoQ10
treatment did not affect the diabetic complications or
other clinical symptoms of MIDD patients. CoQ10 treatment
did not affect the insulin secretory capacity of the mutant
IGT and NGT subjects. There were no side effects during
therapy. This is the first report demonstrating the
therapeutic usefulness of CoQ10 on MIDD.
Long-term auditory and
visual complications of biotinidase
deficiency.
Taitz LS, Leonard JV, Bartlett K.
Early Hum Dev 1985 Sep;11(3-4):325-31
The biochemical, dermatological and neurological motor
disorders of biotinidase deficiency (multiple carboxylase
deficiency) show a dramatic response to pharmacological
doses of biotin. This condition is characterised by the
accumulation of biocytin and depletion of biotin.
Neuromuscular function returns to normal with the reversal
of the characteristic organic acidaemia. It would appear
that the optic and auditory nerves or their related
neurological structures may suffer damage from the excess
biocytin and deficient biotin. Despite reversal of the
dermatological and psychomotor abnormalities children are
likely to be left with auditory and/or visual handicaps if
diagnosis and treatment is delayed beyond the first year of
life. Treatment with biotin was commenced 6, 18, and 13
months after onset of symptoms. Two children subsequently
were found to have visual impairment (acquired retinal
dysplasia) and two had sensori-neural deafness. In one
patient both defects were present.
Randomized trial of
taurine supplementation for infants less than or equal to
1,300-gram birth weight: effect on auditory
brainstem-evoked responses.
Tyson JE, Lasky R, Flood D, Mize C, Picone T, Paule
CL.
Department of Pediatrics, University of Texas Southwestern
Medical Center, Dallas 75235.
Pediatrics 1989 Mar;83(3):406-15
Taurine may be important to the developing eye and brain
of the small preterm infant. A blinded randomized trial was
conducted to determine whether taurine supplementation of
healthy infants of less than or equal to 1,300 g birth
weight until their discharge from the hospital increases
their growth rate, neurobehavioral development,
electroretinographic development, or maturation of auditory
brainstem-evoked responses. Infants were fed with Similac
Special Care as desired, which was prepared to contain less
than 5 mg/L of taurine or 45 mg/L of taurine, a
concentration similar to that of human milk. Infants who
did not receive taurine supplementation (n = 19) and those
who did (n = 18) were similar with respect to condition at
study entry, caloric intake, and growth rates throughout
the study, and electroretinographic findings and scores on
the Brazelton Behavioral Assessment Scale at 37 weeks'
postmenstrual age. Infants who received taurine
supplementation had greater overall plasma taurine
concentrations. The group receiving taurine supplementation
also had more mature auditory-evoked responses at 37 weeks'
postmenstrual age with a modest (0.2 to 0.5 ms) but
consistent reduction (P less than .05) in the interval
between stimulus and response at two different stimulation
rates. Although further study is needed, taurine intake
appears to influence auditory system maturation of preterm
infants.
Iodine intakes assessed
by urinary iodine concentrations in healthy children aged
ten months, two years, and four years.
Valeix P, Preziosi P, Rossignol C, Farnier MA, Hercberg
S.
Institut Scientifique et Technique de la Nutrition et de
l'Alimentation, CNAM, Paris.
Biol Trace Elem Res 1992 Jan-Mar;32:259-66
Urinary iodine excretion was assessed in 642 healthy
children aged 10 mo (n = 243), 2 yr (n = 183), and 4 yr (n
= 216) living in the Paris area and originating from
continental France (60.3%), North Africa (13.8%), the West
Indies (9.1%), West Africa (8.3%), Southeast Asia (4.8%),
and southern Europe (3.8%). Mild impairment of neurological
(reflexes, tone, audiometry) and intellectual development
(Brunet-Lezine scale) was assessed in relation to iodine
status. Iodine excretions (median values) were 18.4, 11.9,
and 10.9 micrograms/100 mL at 10 mo, 2 yr, and 4 yr,
respectively, and risk of mild iodine deficiency (5-10
micrograms/100 mL) was 18.1%, 34.8%, and 38.3% for the same
age groups. No relationship was found between
anthropometry, global development quotient, and iodine
status. High hearing thresholds were more commonly
associated with lower iodine excretion, suggesting mild
hearing defects. In spite of iodine prophylaxis, the risk
of mild to moderate iodine deficiency still exists in
France and in a number of European countries. Evaluation of
neurological sequels of borderline iodine status is a major
public health problem in European communities.
Relationship between
urinary iodine concentration and hearing capacity in
children.
Valeix P, Preziosi P, Rossignol C, Farnier MA, Hercberg
S.
Institut Scientifique et Technique de la Nutrition et de
l'Alimentation, CNAM, France.
Eur J Clin Nutr 1994 Jan;48(1):54-9
Urinary iodine excretion was assessed in 1222 healthy
children aged 10 months (n = 456), 2 years (n = 368) and 4
years (n = 398) living in the Paris area and originating
from continental France (55.2%), North Africa (15.7%), the
West Indies (9.7%), West Africa (8.2%), Southeast Asia
(5.5%), and southern Europe (5.7%). Iodine excretions
(median values) were, respectively, 18.1, 13.4 and 11.6
micrograms/100 ml at 10 months, 2 years and 4 years, and
risk of mild to moderate iodine deficiency (< 10
micrograms/100 ml) was 18.0%, 32.3% and 37.2% for the same
age groups. Urinary iodine excretion was highest among
Southeast Asian children, and lowest among West Africans.
Hearing acuity was measured either by conventional
mono-aural pure-tone audiometry or by binaural free field
testing depending on the child's age. Hearing loss at 4000
Hz and average hearing impairment at speech frequencies
(500, 1000 and 2000 Hz) were more severe among children at
risk of mild to moderate iodine deficiency (less than 10
micrograms/100 ml) compared with those with urinary
excretion above 10 micrograms/100 ml.
Comparison of the
developmental changes of the brainstem auditory evoked
response (BAER) in taurine-supplemented and
taurine-deficient kittens.
Vallecalle-Sandoval MH, Heaney G, Sersen E, Sturman
JA.
Department of Developmental Biochemistry, Institute for
Basic Research in Developmental Disabilities, Staten
Island, NY 10314.
Int J Dev Neurosci 1991;9(6):571-9
A similar development of the brainstem auditory evoked
response is present in taurine-supplemented and
taurine-deficient kittens between the second postnatal week
and the third month of life. Between birth and the second
postnatal week kittens from mothers fed the 1% taurine diet
showed earlier maturation of the brainstem auditory evoked
response as indicated by lower threshold, shorter P1
latency and shorter central conduction time when compared
to the kittens from mothers fed the 0.05% taurine diet.
These results suggest an important role of taurine in the
anatomical and functional development of the auditory
system.
Biotinidase deficiency:
presymptomatic treatment.
Wallace SJ.
Arch Dis Child. 1985 Jun;60(6):574-5.
Biotinidase deficiency presents with clinical signs of
biotin deficiency at the age of 3 months, or soon after. In
an infant in whom the diagnosis was made on cord blood,
vision and hearing were normal before presymptomatic
treatment with biotin. Physical and mental development are
good at 14 months.
Improvement in hearing
among otherwise normal schoolchildren in iodine-deficient
areas of Guizhou, China, following use of iodized
salt.
Wang YY, Yang SH.
Lancet 1985 Sep 7;2(8454):518-20
According to a survey in Guizhou province of China, the
average hearing level of otherwise normal schoolchildren in
an area of endemic iodine-deficient goitre and cretinism
was significantly poorer than in a non-endemic control
area. After iodine prophylaxis for three years, audiometric
tests showed that the average hearing level had improved
and approached that of the non-endemic controls. In
addition, mean values for thyroid function tests were
restored to within the normal range. It is suggested that
the most likely cause of the poorer hearing level among the
ostensibly normal schoolchildren in endemic areas is
subclinical hypothyroidism due to prolonged severe iodine
deficiency.
Biotinidase deficiency:
a survey of 10 cases.
Wastell HJ, Bartlett K, Dale G, Shein A.
Department of Clinical Biochemistry, Newcastle General
Hospital, Newcastle upon Tyne.
Arch Dis Child 1988 Oct;63(10):1244-9
Ten patients with biotinidase deficiency were studied.
Clinical findings at presentation varied with
dermatological signs (dermatitis and alopecia),
neurological abnormalities (fits, hypotonia, and ataxia),
and recurrent infections being the most common features,
although none of these occurred in every case.
Biochemically the disease is characterised by metabolic
acidosis and organic aciduria. Treatment with biotin
results in pronounced, rapid, clinical and biochemical
improvement, but some patients have residual neurological
damage comprising neurosensory hearing loss, visual pathway
defects, ataxia, and mental retardation. The cause of this
permanent damage remains obscure and it is not clear if the
early introduction of treatment will prevent it.
[Results of multistep
oxygen therapy in the treatment of sudden hearing
loss.] [Article in German]
Wolf O, Hanson J.
Abteilung fur Hor- und Gleichgewichtsstorungen, Stadt.
Klinikums, Dessau.
Laryngorhinootologie 1991 Sep;70(9):475-8
Oxygen multistep therapy (von Ardenne) was applied in 28
patients suffering from an idiopathic sudden hearing loss.
The oxygen therapy consisted of a multistep short
procedure, each of which lasted for 15 minutes. The results
of our study were evaluated by means of standardised
statistics confirming the effectiveness and even the
superiority of the oxygen multistep therapy in comparison
with any other treatment, and also in view of the
spontaneous remission rate in cases of sudden hearing
loss.
Role of glutathione in
protection against noise-induced hearing loss.
Yamasoba T, Nuttall AL, Harris C, Raphael Y, Miller
JM.
Kresge Hearing Research Institute, The University of
Michigan, 1301 East Ann Street, Ann Arbor, MI 48109-0506,
USA.
Brain Res 1998 Feb 16;784(1-2):82-90
A potential mechanism of hearing loss due to acoustic
overstimulation is the generation of reactive oxygen
species (ROS). ROS not removed by antioxidant defenses
could be expected to cause significant damage to the
sensory cells of the cochlea. We studied the influence of
the antioxidant glutathione (GSH) on noise-induced hearing
loss by using l-buthionine-[S,R]-sulfoximine (BSO), an
inhibitor of GSH synthesis, and
2-oxothiazolidine-4-carboxylate (OTC), a cysteine prodrug,
which promotes rapid restoration of GSH when GSH is acutely
depleted. Pigmented female guinea pigs were exposed to
broadband noise (102 dB SPL, 3 h/day, 5 days) while
receiving daily injections of BSO, OTC, or saline. By weeks
2 and 3 after noise exposure, BSO-treated animals showed
significantly greater threshold shifts above 12 kHz than
saline-treated subjects, whereas OTC-treated animals showed
significantly smaller threshold shifts at 12 kHz than
controls. Histologically assessed noise-induced damage to
the organ of Corti, predominantly basal turn row 1 outer
hair cells, was most pronounced in BSO-treated animals.
High performance liquid chromatographic analysis showed
that OTC significantly increased cysteine levels, but not
GSH levels, in the cochlea. These findings show that GSH
inhibition increases the susceptibility of the cochlea to
noise-induced damage and that replenishing GSH, presumably
by enhancing availability of cysteine, attenuates
noise-induced cochlear damage. Copyright 1997 Elsevier
Science B.V.
Influence of intense
sound exposure on glutathione synthesis in the
cochlea.
Yamasoba T, Harris C, Shoji F, Lee RJ, Nuttall AL,
Miller JM.
Kresge Hearing Research Institute, The University of
Michigan, 1301 East Ann Street, Ann Arbor, MI 48109-0506,
USA.
Brain Res 1998 Aug 31;804(1):72-8
Previous studies have shown that depletion of endogenous
glutathione (GSH) potentiates noise-induced hearing loss
(NIHL), whereas replenishment of GSH attenuates NIHL
(Yamasoba et al., Brain Res. 784 (1998) 82-90). Since these
findings indicate an important role of GSH in protection
from NIHL, we assessed the influence of intense sound
exposure (broadband noise, 105 dB SPL, 5 h) on GSH and
cysteine levels in the guinea pig cochlea using high
performance liquid chromatography. GSH levels were
significantly increased in the lateral wall 2 and 4 h
post-exposure and returned to normal 6 h post-exposure. GSH
levels in the sensory epithelium and modiolus did not show
significant changes following noise. Cysteine levels were
unchanged in any of the cochlear segments. For the cochlea
as a whole, intense sound exposure did not significantly
change GSH or cysteine levels throughout the 6-h
measurement period post-exposure. These results indicate
that GSH synthesis is markedly upregulated selectively in
the lateral wall by noise exposure, presumably in response
to the robust consumption of GSH, as it is utilized in
scavenging reactive oxygen species. Copyright 1998 Elsevier
Science B.V.
L-carnitine treatment
improves brain stem auditory evoked potentials in diabetic
rats.
Yildiz O, Ozata M, Ozkardes A, Corakci A, Gundogan N,
Gundogan MA.
Department of Pharmacology, Gulhane School of Medicine,
Ankara, Turkey.
Neuroreport 1996 Nov 25;7(18):2957-9
The effect of L-carnitine (LC) on brain stem auditory
evoked potentials (BAEP), was examined in alloxan-diabetic
rats. LC (200 mg kg-1, i.p., once daily) was given to
diabetic rats starting from the third week after the
induction of diabetes, lasting for 4 weeks. Age-matched
non-diabetic rats served as controls. The latency of wave I
and interpeak latency I-IV were measured once weekly.
Diabetes-induced deficits in BAEP latencies (p <
0.05, diabetics vs non-diabetic controls) were improved
after LC treatment (p < 0.05, LC-treated diabetic
rats vs non-diabetic controls). Weight and glucose levels
were not influenced by LC treatment. Our results suggest
that LC had beneficial effects on diabetic central
neuropathy but these effects are not associated with the
regulation of glycaemia in alloxan-diabetic rats.
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