LE Magazine February 2003
Eye Health
Use of vitamin supplements
and cataract: the Blue Mountains Eye Study.
PURPOSE: To investigate
relationships between use of vitamin supplements and the three
principal cataract types in a population-based sample.
METHODS: We studied 2873 of the 3654 participants (79%) aged
49 to 97 years attending the cross-sectional Blue Mountains
Eye Study who completed a detailed food frequency
questionnaire, which included type, dose and duration of
vitamin supplement use. Masked grading of nuclear, cortical
and posterior subcapsular opacities from lens photographs was
performed, using the Wisconsin method. RESULTS: Use of
multivitamin supplements was associated with reduced
prevalence of nuclear cataract, odds ratio 0.6, 95% confidence
interval 0.4 to 1.0, P =.05. For both nuclear and cortical
cataract, longer duration of multivitamin use was associated
with reduced cataract prevalence (nuclear cataract, trend P
=.02; cortical cataract, trend P =.03). Use of thiamin
supplements was associated with reduced prevalence of nuclear
(odds ratio 0.6, confidence interval 0.4 to 1.0, P =.03, dose
trend P =.03) and cortical cataract (odds ratio 0.7,
confidence interval 0.5 to 0.9, P =.01, dose trend P =.02).
Riboflavin (odds ratio 0.8, confidence interval 0.6 to 1.0, P
=.05) and niacin (odds ratio 0.7, confidence interval 0.6 to
1.0, P =.04) supplements exerted a weaker protective influence
on cortical cataract. Vitamin A supplements were protective
against nuclear cataract (odds ratio 0.4, confidence interval
0.2 to 0.8, P =.01, dose trend P =.01). Folate (odds ratio
0.4, confidence interval 0.2 to 0.9, P =.03) appeared
protective for nuclear cataract, whereas both folate (odds
ratio 0.6, confidence interval 0.3 to 0.9, P =.01, dose trend
P =.04) and vitamin B12 supplements (odds ratio 0.7,
confidence interval 0.5 to 1.0, P =.03, dose trend P =.02)
were strongly protective against cortical cataract.
CONCLUSIONS: Long-term use of multivitamins, B group and
vitamin A supplements was associated with reduced prevalence
of either nuclear or cortical cataract. A strong protective
influence on cortical cataract, from use of folate or vitamin
B12 supplements, is a new finding.
Am J Ophthalmol 2001
Jul;132(1):19-26
Serum status of carotenoids and
tocopherols in patients with age-related cataracts: a
case-control study.
BACKGROUND: Cataract is an important
health problem that increase with age, causes decreased visual
acuity and constitute a major cause of disability in the
elderly. Epidemiological studies have shown that elevated
serum levels and/or intake of several antioxidants, such as
carotenoids, vitamin E and ascorbic acid, are associated with
a diminished risk for cataracts. OBJECTIVE: To assess the
serum fat-soluble antioxidant status in patients with
cataracts and its relationship with visual function. METHODS:
One hundred thirty eight patients with senile cataracts,
classified according to visual acuity, and 110 age and
sex-matched controls were studied for individual carotenoids
and tocopherols in serum by a quality-controlled HPLC method.
One-way ANOVA analysis and logistic regression analysis were
applied. RESULTS: Higher serum levels of lutein and zeaxanthin
were associated as risk factors for cataract while
b-cryptoxanthin and g-tocopherol appeared as protective
variables. Higher levels of zeaxanthin and lower
concentrations of b-cryptoxanthin were associated with
cataracts in people < 61y whereas only lower levels of
g-tocopherol were shown in subjects > 61y. No significant
correlations (adjusted for sex and age) were found between
visual acuity and serum concentrations of carotenoids or
tocopherols. CONCLUSION: Although the relation between
carotenoids and cataracts is biologically plausible, serum
carotenoid levels are highly dependent on dietary intake and
thus may not be clinically relevant biomakers for cataracts
risk.
J Nutr Health
Aging 2002;6(1):66-8
Antioxidant systems in rat lens as a
function of age: effect of chronic administration of vitamin E
and ascorbate.
Oxidative damage occurring in the lenses
of patients with senile cataract may be due to partially
reduced forms of oxygen. We assayed the activities of
superoxide dismutase (SOD), glutathione peroxidase (GSH-Px),
glutathione reductase (GSH-Red), and glucose-6-phosphate
dehydrogenase (G6PD) in rat lenses at different ages (1, 4 and
24 months), and also evaluated lens glutathione (GSH) levels
and the effects of chronic administration of vitamin E and
sodium ascorbate. We observed a significant age-related
decrease in GSH-Px, GSH-Red and G6PD activities, but no
age-related change in SOD activity. Chronic treatment with
both vitamin E and sodium ascorbate failed to restore
enzymatic activities to the levels of younger rats. An
age-related reduction in GSH content was also observed;
however, chronic administration of vitamin E, but not of
sodium ascorbate, restored GSH levels to those of younger
rats.
Aging (Milano) 1999
Feb;11(1):39-43
Experimental evidence for interactive
effects of chronic UV irradiation and nutritional deficiencies
in the lens.
The eye lens is subjected to many risk
factors over time, which contribute to changes in its
transparency, finally leading in combination to cataract
development. Ultra violet (UV) radiation is regarded as one of
the widespread risk factors contributing to cataract
formation, for example in combination with nutritional
deficiencies. Both factors possibly contribute to the high
number of cataracts in the sunbelt region of the world. In
this study, two essential nutritional factors were
investigated in Brown Norway rats, zinc and vitamin E
deficiencies, alone and in combination with UV-A and UV-B
irradiation. Young female Brown Norway rats were put on a
special diet for 10 weeks, either highly deficient in zinc or
in vitamin E. The diet was otherwise identical to the control
diet. Two weeks after putting the animals on the diet, UV
irradiation was started in some of the groups with mydriatic
pupils with three irradiation sessions per week (UV-A 1 J/cm2;
UV-B 0.2 J/cm2). Irradiation was continued until the end of
the diet treatment period. Body weight and food consumption
were established at weekly intervals, as well as slitlamp
microscopy to monitor changes in anterior eye segment
morphology. In addition changes in transparency of the cornea
and lens have been monitored and evaluated with a Scheimpflug
camera (Topcon SL-45) at baseline, and after four and eight
weeks of irradiation. After sacrifice of the animals, the lens
wet weight as well as the activity of superoxide dismutase
(SOD) were determined. Zinc deficiency alone led to an almost
complete arrest of body weight increase. In the cornea, UV-A
in combination with zinc or vitamin E deficiency did not have
any interactive effects. The combination of UV-B and zinc
deficiency showed subtractive instead of additive effects on
corneal transparency and neovascularization. In the lens both
deficiencies positively interacted with UV-A and UV-B by
increasing the density of the capsular and cortical layers.
The lens fresh weight was significantly lower in
zinc-deficient animals additionally irradiated with UV-A or
UV-B. The activity of SOD was significantly lower in the
lenses of zinc- or vitamin E-deficient animals additionally
irradiated with UV-B. The experiments presented clearly
demonstrate that dietary zinc and vitamin E deficiencies do
interact with UV radiation damage in the cornea and lens of
Brown Norway rats.
Dev Ophthalmol 2002;35:113-24
CoQ10/Parkinson's
Ubiquinone (coenzyme q10) and
mitochondria in oxidative stress of Parkinson's disease.
Parkinson's disease is the second most
common neurodegenerative disorder after Alzheimer's disease
affecting approximately 1% of the population older than 50
years. There is a worldwide increase in disease prevalence due
to the increasing age of human populations. A definitive
neuropathological diagnosis of Parkinson's disease requires
loss of dopaminergic neurons in the substantia nigra and
related brain stem nuclei, and the presence of Lewy bodies in
remaining nerve cells. The contribution of genetic factors to
the pathogenesis of Parkinson's disease is increasingly being
recognized. A point mutation which is sufficient to cause a
rare autosomal dominant form of the disorder has been recently
identified in the alpha-synuclein gene on chromosome 4 in the
much more common sporadic, or 'idiopathic' form of Parkinson's
disease, and a defect of complex I of the mitochondrial
respiratory chain was confirmed at the biochemical level.
Disease specificity of this defect has been demonstrated for
the parkinsonian substantia nigra. These findings and the
observation that the neurotoxin 1-methyl-4-phenyl-1,2,3,
6-tetrahydropyridine (MPTP), which causes a Parkinson-like
syndrome in humans, acts via inhibition of complex I have
triggered research interest in the mitochondrial genetics of
Parkinson's disease. Oxidative phosphorylation consists of
five protein-lipid enzyme complexes located in the
mitochondrial inner membrane that contain flavins (FMN, FAD),
quinoid compounds (coenzyme Q10, CoQ10) and transition metal
compounds (iron-sulfur clusters, hemes, protein-bound copper).
These enzymes are designated complex I (NADH:ubiquinone
oxidoreductase, EC 1.6. 5.3), complex II (succinate:ubiquinone
oxidoreductase, EC 1.3.5.1), complex III
(ubiquinol:ferrocytochrome c oxidoreductase, EC 1.10.2.2),
complex IV (ferrocytochrome c:oxygen oxidoreductase or
cytochrome c oxidase, EC 1.9.3.1), and complex V (ATP
synthase, EC 3.6.1.34). A defect in mitochondrial oxidative
phosphorylation, in terms of a reduction in the activity of
NADH CoQ reductase (complex I) has been reported in the
striatum of patients with Parkinson's disease. The reduction
in the activity of complex I is found in the substantia nigra,
but not in other areas of the brain, such as globus pallidus
or cerebral cortex. Therefore, the specificity of
mitochondrial impairment may play a role in the degeneration
of nigrostriatal dopaminergic neurons. This view is supported
by the fact that MPTP generating 1-methyl-4-phenylpyridine
(MPP(+)) destroys dopaminergic neurons in the substantia
nigra. Although the serum levels of CoQ10 is normal in
patients with Parkinson's disease, CoQ10 is able to attenuate
the MPTP-induced loss of striatal dopaminergic neurons.
Biol Signals Recept 2001
May-Aug;10(3-4):224-53
Age-related changes in the lipid
compositions of rat and human tissues.
The levels of cholesterol, ubiquinone,
dolichol, dolichyl-P, and total phospholipids in human lung,
heart, spleen, liver, kidney, pancreas and adrenal from
individuals from one-day-old to 81 years of age were
investigated and compared with the corresponding organs from
two to 300 day-old rats. The amount of cholesterol in human
tissues did not change significantly during aging, but the
level of this lipid in the rat was moderately elevated in the
organs of the oldest animals. In human pancreas and adrenal
the ubiquinone content was highest at one year of age, whereas
in other organs the corresponding peak value was at 20 years
of age, and was followed by a continuous decrease upon further
aging. A similar pattern was observed in the rats, with the
highest concentration of ubiquinone being observed at 30 days
of age. Dolichol levels in human tissues increase with aging,
but they increase to very different extents. In the lungs this
increase is seven-fold, and in the pancreas it is 150-fold.
The elevation in the dolichol contents of rat tissues ranges
from 20 to 30-fold in our material. In contrast, the levels of
the phosphorylated derivative of dolichol increased to a more
limited extent, i.e., two to six-fold in human tissues and
even less in the rat. These results demonstrate that the
levels of a number of lipids in human and rat organs are
modified in a characteristic manner during the life span. This
is in contrast to phospholipids, which constitute the bulk of
the cellular lipid mass.
Lipids 1989 Jul;24(7):579-84
Age-related decline in dopamine
transporters: analysis of striatal subregions, nonlinear
effects and hemispheric asymmetries.
Neuroimaging studies have documented an
age-related decline in striatal dopamine transporters (DATs)
as a marker of dopaminergic neurodegeneration. The authors
further elucidated the effects on this neural system in
healthy aging, in contrast to Parkinson disease (PD). The
effects of age on striatal DAT availability were examined in a
large, healthy subject sample (N=126) with
[123I]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
([123I]beta-CIT) and single photon emission computed
tomography (SPECT). Striatal DAT availability (V3") showed a
significant inverse correlation with age, declining in a
nearly linear manner by 46% over the age range 18 to 88 years,
or 6.6% per decade. Rates of decline were comparable for
caudate (48%) and putamen (45%), with only minimal increase in
left-right asymmetry with age. Hemispheric asymmetries were
unrelated to the handedness of subjects. These results
demonstrate that aging is associated with a relatively
symmetric loss of DATs in the caudate and putamen in both
hemispheres. These findings have implications not only for
healthy aging but also for neurodegenerative disorders such as
PD.
Am J Geriatr Psychiatry 2002
Jan-Feb;10(1):36-43
Dopamine neurons derived from
embryonic stem cells function in an animal model of
Parkinson's disease.
Parkinson's disease is a widespread
condition caused by the loss of midbrain neurons that
synthesize the neurotransmitter dopamine. Cells derived from
the fetal midbrain can modify the course of the disease, but
they are an inadequate source of dopamine-synthesizing neurons
because their ability to generate these neurons is unstable.
In contrast, embryonic stem (ES) cells proliferate extensively
and can generate dopamine neurons. If ES cells are to become
the basis for cell therapies, we must develop methods of
enriching for the cell of interest and demonstrate that these
cells show functions that will assist in treating the disease.
Here we show that a highly enriched population of midbrain
neural stem cells can be derived from mouse ES cells. The
dopamine neurons generated by these stem cells show
electrophysiological and behavioural properties expected of
neurons from the midbrain. Our results encourage the use of ES
cells in cell-replacement therapy for Parkinson's disease.
Nature 2002 Jul 4;418(6893):50-6
Results of chronic subthalamic nucleus
stimulation for Parkinson's disease: a 1-year follow-up
study.
BACKGROUND: Deep brain stimulation (DBS)
has been established as an alternative approach for the
treatment of advanced Parkinson's disease (PD). Recently, the
subthalamic nucleus (STN) has been identified as the optimal
target for DBS. METHODS: Thirty-eight patients have undergone
surgery for advanced PD since 1996. They include 12 females
and 26 males with a mean age of 55.6 years. The mean stage on
the Hoehn and Yahr Scale was 3.5 (off condition). Electrodes
(Medtronic DBS 31389) were stereotactically implanted into the
STN bilaterally. Targeting was performed using computerized
tomography (CT) scans and ventriculography (VG). After four
days of external stimulation, permanent neurostimulators were
implanted. Patients were evaluated preoperatively and 1, 6 and
12 months postoperatively. Evaluations were performed in
defined on and off states using the Unified Parkinson's
Disease Rating Scale (UPDRS) as well as the Hoehn and Yahr
Scale, the dyskinesia scale, and the Activities of Daily
Living (ADL) Scale. RESULTS: Significant improvement of all
motor symptoms was found in all patients (UPDRS motor score
32/48 preoperatively versus 15/30 at 12-month follow-up, p
< 0.001). Daily off-times were reduced by 35%. Dyskinesias
also improved markedly (UPDRS IV: 3.2/3.1 [on/off] vs. 0.9/1.3
at 12 months follow-up). Postoperative L-dopa medication was
adjusted (mean reduction: 53%). Complications occurred in two
patients (5%) who developed infections, leading to system
removal. Systems were replaced after six months. Two patients
(5%) had a permanent worsening of a previously known
depressive state and developed progressive dementia.
CONCLUSIONS: TN stimulation is a relatively safe procedure for
treating advanced PD. The possibility of readjusting the
stimulation parameters postoperatively improves the
therapeutic outcome and reduces side effects in comparison to
ablative methods.
Surg Neurol 2002 May;57(5):306-11;
discussion 311-3
Novel physical treatments for the
management of neuropsychiatric disorders.
OBJECTIVE: To briefly describe the novel
non-drug physical interventions currently in use in the
investigation and treatment of neuropsychiatric disorders
regarding their efficacy and potential future applications.
METHODS: A systematic review of the literature concerning
transcranial magnetic stimulation (TMS), deep brain
stimulation (DBS), vagus nerve stimulation (VNS) and
neurosurgery for mental disorders (NMD) was conducted using
Medline and literature known to the authors. RESULTS: A
summary of each procedure is provided giving a succinct
overview of efficacy, current applications and possible future
indications. CONCLUSION: Novel and innovative physical
interventions are currently being used to study brain function
in health and disease. In particular, TMS has quickly
established itself as a useful investigational tool and is
emerging as a possible antidepressant therapy. Similarly, VNS
has been applied successfully in the management of intractable
epilepsy and is undergoing evaluation in the management of
patients with treatment-resistant depression. DBS has shown
significant promise in the treatment of Parkinson's disease
and may have use in the management of obsessive-compulsive
disorder. Finally, neurosurgical procedures for the treatment
of mental disorders have been sufficiently refined to stage a
comeback, although rigorous scientific study of their efficacy
and indications is still necessary.
J Psychosom Res 2002
Aug;53(2):709-19
Subthalamic GAD gene therapy in a
Parkinson's disease rat model.
The motor abnormalities of Parkinson's
disease (PD) are caused by alterations in basal ganglia
network activity, including disinhibition of the subthalamic
nucleus (STN), and excessive activity of the major output
nuclei. Using adeno-associated viral vector-mediated somatic
cell gene transfer, we expressed glutamic acid decarboxylase
(GAD), the enzyme that catalyzes synthesis of the
neurotransmitter GABA, in excitatory glutamatergic neurons of
the STN in rats. The transduced neurons, when driven by
electrical stimulation, produced mixed inhibitory responses
associated with GABA release. This phenotypic shift resulted
in strong neuroprotection of nigral dopamine neurons and
rescue of the parkinsonian behavioral phenotype. This strategy
suggests that there is plasticity between excitatory and
inhibitory neurotransmission in the mammalian brain that could
be exploited for therapeutic benefit.
Science 2002 Oct
11;298(5592):425-9
Distribution of coenzyme Q homologues
in brain.
Ubiquinone (coenzyme Q10), in addition to
its function as an electron and proton carrier in
mitochondrial electron transport coupled to ATP synthesis,
acts in its reduced form (ubiquinol) as an antioxidant,
inhibiting lipid peroxidation in biological membranes and
protecting mitochondrial inner-membrane proteins and DNA
against oxidative damage accompanying lipid peroxidation.
Tissue ubiquinone levels are subject to regulation by
physiological factors that are related to the oxidative
activity of the organism: they increase under the influence of
oxidative stress, e.g. physical exercise, cold adaptation,
thyroid hormone treatment, and decrease during aging. In the
present study, coenzyme Q homologues were separated and
quantified in the brains of mice, rats, rabbits and chickens
using high-performance liquid chromatography. In addition, the
coenzyme Q homologues were measured in cells such as NG-108,
PC-12, rat fetal brain cells and human SHSY-5Y and monocytes.
In general, Q1 content was the lowest among the coenzyme
homologues quantified in the brain. Q9 was not detectable in
the brains of chickens and rabbits, but was present in the
brains of rats and mice. Q9 was also not detected in human
cell lines SHSY-5Y and monocytes. Q10 was detected in the
brains of mice, rats, rabbits, and chickens and in cell lines.
Since both coenzyme Q and vitamin E are antioxidants, and
coenzyme Q recycles vitamins E and C, vitamin E was also
quantified in mice brain using HPLC-electrochemical detector
(ECD). The quantity of vitamin E was lowest in the substantia
nigra compared with the other brain regions. This finding is
crucial in elucidating ubiquinone function in bioenergetics;
in preventing free radical generation, lipid peroxidation, and
apoptosis in the brain; and as a potential compound in
treating various neurodegenerative disorders.
Neurochem Res 2002
May;27(5):359-68
Effects of coenzyme Q10 in early
Parkinson disease: evidence of slowing of the functional
decline.
BACKGROUND: Parkinson disease (PD) is a
degenerative neurological disorder for which no treatment has
been shown to slow the progression. OBJECTIVE: To determine
whether a range of dosages of coenzyme Q10 is safe and well
tolerated and could slow the functional decline in PD. DESIGN:
Multicenter, randomized, parallel-group, placebo-controlled,
double-blind, dosage-ranging trial. SETTING: Academic movement
disorders clinics. PATIENTS: Eighty subjects with early PD who
did not require treatment for their disability. INTERVENTIONS:
Random assignment to placebo or coenzyme Q10 at dosages of
300, 600, or 1200 mg/d. MAIN OUTCOME MEASURE: The subjects
underwent evaluation with the Unified Parkinson Disease Rating
Scale (UPDRS) at the screening, baseline, and 1-, 4-, 8-, 12-
and 16-month visits. They were followed up for 16 months or
until disability requiring treatment with levodopa had
developed. The primary response variable was the change in the
total score on the UPDRS from baseline to the last visit.
RESULTS: The adjusted mean total UPDRS changes were +11.99 for
the placebo group, +8.81 for the 300-mg/d group, +10.82 for
the 600-mg/d group, and +6.69 for the 1200-mg/d group. The P
value for the primary analysis, a test for a linear trend
between the dosage and the mean change in the total UPDRS
score, was.09, which met our prespecified criteria for a
positive trend for the trial. A prespecified, secondary
analysis was the comparison of each treatment group with the
placebo group, and the difference between the 1200-mg/d and
placebo groups was significant (P =.04). CONCLUSIONS: Coenzyme
Q10 was safe and well tolerated at dosages of up to 1200 mg/d.
Less disability developed in subjects assigned to coenzyme Q10
than in those assigned to placebo, and the benefit was
greatest in subjects receiving the highest dosage. Coenzyme
Q10 appears to slow the progressive deterioration of function
in PD, but these results need to be confirmed in a larger
study.
Arch Neurol 2002
Oct;59(10):1541-50
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