==================================BSR11==================================
11. Aluminum intoxication: central nervous system, peripheral nervous
system.
Axonal flow- aluminum intoxication.
Congo Red Staining Neurofibrillary Tangles - advantages/disadvantages
in comparison with silver staining.
1
UI - 87093071
AU - Margolin RA ; Ban TA
TI - Neuroimaging and psychopharmacology in the diagnosis and treatment of
dementia.
AB - Contributions of noninvasive brain imaging technologies to the diagnosis
of organic dementias with special reference to Alzheimer's disease are
reviewed. Included among the different techniques are: a. computed
tomography b. magnetic resonance imaging c. positron emission tomography.
Biochemical hypotheses with possible relevance to the pathogenesis of
Alzheimer's disease are presented and their therapeutic implications are
discussed. Included among the different hypotheses are: a. interference
with protein synthesis b. acetylcholine deficiency c. aluminum
deposition. Present status of the pharmacotherapy of Alzheimer's disease
is outlined.
MH - Acetylcholine/DEFICIENCY ; Aluminum/TOXICITY ; Brain/METABOLISM/
*PATHOLOGY ; Dementia, Senile/*DIAGNOSIS/DRUG THERAPY/ETIOLOGY ; Human ;
Nuclear Magnetic Resonance ; Proteins/BIOSYNTHESIS ; Review ; Tomography,
Emission Computed ; Tomography, X-Ray Computed
SO - Prog Neuropsychopharmacol Biol Psychiatry 1986;10(3-5):493-500
2
UI - 87093063
AU - De Estable-Puig RF ; Estable-Puig JF ; Ven Murthy MR ; Radouco-Thomas S ;
Chawla S ; Radouco-Thomas M ; Radouco-Thomas C
TI - On the pathogenesis and therapy of dementia of the Alzheimer type: some
neuropathological, biochemical, genetic and pharmacotherapeutic
considerations.
AB - The extensive literature on dementia of Alzheimer type (DAT) testifies to
the enormous progress achieved in the clinical and biochemical
delineation of this disease. Newly developed laboratory and imaging
techniques are also being applied to the diagnosis of DAT. Nevertheless,
unequivoval diagnosis still relies primarily on morphological data from
biopsy or autopsy. An overview is presented of major morphological
changes occurring at different levels of organization in the central
nervous system (CNS) in DAT. Currently formulated etiopathogenic
hypotheses of DAT are reviewed and discussed in the context of
morphological alterations. Some of the recombinant DNA methods, that are
currently available for gene analysis, are described. Some approaches for
studying Alzheimer specific genes using the above methods have been
suggested. Finally, a critical overview of the current
pharmacotherapeutic armamentarium used in DAT and senile dementia is
presented. The efficacy, side effects, and the main mechanisms of action
of the two categories of drug therapy -supposed etiopathogenic and
symptomatic- are presented.
MH - Aluminum/TOXICITY ; Alzheimer's Disease/DRUG THERAPY/*ETIOLOGY/FAMILIAL &
GENETIC ; Atrophy ; Base Sequence ; Brain/PATHOLOGY ; Down's Syndrome/
COMPLICATIONS ; DNA/ANALYSIS ; Human ; Neuroregulators/PHYSIOLOGY ;
Oncogenes ; Polymorphism (Genetics) ; Review
SO - Prog Neuropsychopharmacol Biol Psychiatry 1986;10(3-5):355-90
3
UI - 87093062
AU - Ebstein RP ; Oppenheim G ; Ebstein BS ; Amiri Z ; Stessman J
TI - The cyclic AMP second messenger system in man: the effects of heredity,
hormones, drugs, aluminum, age and disease on signal amplification.
AB - The intracellular effects of a number of hormonal signals are mediated by
the cyclic AMP second messenger system in man and the ubiquitous
distribution of hormone-stimulated adenylate cyclase suggests the
importance of this enzyme complex in normal aging and pathophysiological
states. Various vectors including heredity, endogenous catecholamines,
steroid hormones, and drugs affect the activity of hormone-stimulated
adenylate cyclase in man. The effect of heredity was studied using
lymphocytes obtained from monozygotic twin pairs and age and sex-matched
sib pairs. Only for forskolin-stimulated activity is a significant
proportion of individual variance attributable to heredity, suggesting
the relative stability of the catalytic subunit. Beta-adrenergic and
prostaglandin E-1 activity are "state: characteristics and their
activities are controlled by environmental parameters. A significant
reduction in isoproterenol-stimulated cyclic AMP accumulation between the
menses and luteal phase of the menstrual cycle is observed in lymphocytes
obtained from 11 female subjects. The lowest level of beta-adrenergic
receptor activity is associated with the highest levels of progesterone
and estradiol hormone levels in blood. Lithium at therapeutic
concentrations markedly inhibits adenylate cyclase activity in platelet
membranes. Moreover, marked individual differences are observed in
sensitivity to lithium as determined by Dixon plot derived Ki values for
9 normal, healthy subjects. Human adenylate cyclase obtained from
platelets and lymphocytes is activated by micromolar amounts of aluminum
in the presence of NaF. Irreversible activation of adenylate cyclase by
aluminum is suggested as a possible mechanism of this metal's
neurotoxicity. The biochemical basis for the age-associated decline in
beta-adrenergic responsiveness in man is discussed. Several
investigations suggest a deficit at two levels in the adenylate cyclase
complex: an impaired coupling of the receptor/N protein subunits and an
additional lesion distal to the receptor at the level of N/C coupling.
Perfusion studies with salbutamol suggest that the decline in
beta-adrenergic sensitivity is general and not restricted to lymphocytes.
Possible abnormalities in cyclic AMP signal amplification and recognition
in various disease states is discussed. Increased prostaglandin
E-1-stimulated cyclic AMP accumulation is observed in lymphocytes
obtained from patients with Alzheimer's disease compared to age-matched
controls and correlated with severity of the disease state.(ABSTRACT
TRUNCATED AT 400 WORDS)
MH - Adenosine Cyclic Monophosphate/*PHYSIOLOGY ; Adenyl Cyclase/ANALYSIS ;
*Aging ; Aluminum/*TOXICITY ; Alzheimer's Disease/ETIOLOGY ; Female ;
Genetics ; Homeostasis ; Hormones/*PHYSIOLOGY ; Human ; Lithium/
PHARMACODYNAMICS ; Lymphocytes/ENZYMOLOGY ; Male ; Receptors, Adrenergic,
Beta/DRUG EFFECTS ; Review ; Support, Non-U.S. Gov't
SO - Prog Neuropsychopharmacol Biol Psychiatry 1986;10(3-5):323-53
4
UI - 87077665
AU - Perl DP ; Pendlebury WW
TI - Aluminum neurotoxicity--potential role in the pathogenesis of
neurofibrillary tangle formation.
AB - Alzheimer's disease is a progressive neurodegenerative disease
characterized neuropathologically by the development of large numbers of
neurofibrillary tangles in certain neuronal populations of affected
brains. This paper presents a review of the available evidence which
suggests that aluminum is associated with Alzheimer's disease and
specifically with the development of the neurofibrillary tangle. Aluminum
salts inoculated into experimental animals produce neurofilamentous
lesions which are similar, though not identical, to the neurofibrillary
tangle of man. Although a few reports have suggested evidence of
increased amounts of aluminum in the brains of Alzheimer's disease
victims, such bulk analysis studies have been difficult to replicate.
Using scanning electron microscopy with x-ray spectrometry, we have
identified accumulations of aluminum in neurofibrillary tangle-bearing
neurons of Alzheimer's disease. Similar accumulations have been
identified in the neurofibrillary tangle-bearing neurons found in the
brains of indigenous natives of Guam who suffer from parkinsonism with
dementia and amyotrophic lateral sclerosis. This ongoing research still
cannot ascribe a causal role of aluminum in the pathogenesis of
neurofibrillary tangle formation; however, it does suggest that
environmental factors may play an important part in the formation of this
abnormality.
MH - Aluminum/METABOLISM/*TOXICITY ; Alzheimer's Disease/METABOLISM/PATHOLOGY
; Animal ; Brain/METABOLISM ; Dementia/ETIOLOGY ; Guam ; Human ;
Intracellular Membranes/METABOLISM ; Lasers/DIAGNOSTIC USE ; Nervous
System/*DRUG EFFECTS ; Neurofibrils/*DRUG EFFECTS/PATHOLOGY ; Parkinson
Disease/COMPLICATIONS/PATHOLOGY ; Support, Non-U.S. Gov't ; Support, U.S.
Gov't, P.H.S.
SO - Can J Neurol Sci 1986 Nov;13(4 Suppl):441-5
5
UI - 87044993
AU - Bizzi A ; Gambetti P
TI - Phosphorylation of neurofilaments is altered in aluminium intoxication.
AB - A series of monoclonal antibodies that distinguish phosphorylated and
nonphosphorylated neurofilament (NF) epitopes was used to immunostain
brain stem neurons from control rabbits and from rabbits chronically
intoxicated with Aluminium (Al). In controls, none of the monoclonal
antibodies to phosphorylated NF stained the perikaryon of neurons. In
contrast, in animals treated with Al, all neuronal perikarya containing
Al-induced neurofilament bundles (NB) and some lacking well-formed NB
immunoreacted with two of the five antibodies to phosphorylated NF. Axons
were stained by all five antibodies to phosphorylated NF in both control
and Al-treated animals. A broadly reacting monoclonal antibody to a
nonphosphorylated NF epitopes immunoreacted with neuronal cell bodies,
dendrites and axons in control and Al-intoxicated animals regardless of
the presence of Al-induced NB. Staining of Al-induced NB with one of the
antibodies to phosphorylated NF was greatly diminished after treatment of
sections with trypsin and phosphatase. It is concluded that NF which
compose the Al-induced NB have different immunocytochemical
characteristics from those of the NF present in the perikaryon of normal
neurons. It is likely that, contrary to normal perikaryal NF, NF of
Al-induced NB are phosphorylated. Moreover, phosphorylation of NF of
Al-induced NB is probably abnormal, since NF of Al-induced NB have
immunostaining characteristics different from NF of normal axons.
Al-induced NB may result from abnormal phosphorylation of NF in the
perikaryon, preventing normal axonal transport of these structures.
MH - Aluminum/*TOXICITY ; Animal ; Axoplasmic Flow ; Brain Stem/*METABOLISM ;
Hypoglossal Nerve/*METABOLISM ; Immunoenzyme Technics ; Intermediate
Filament Proteins/*METABOLISM ; Phosphorylation ; Rabbits ; Support, U.S.
Gov't, P.H.S.
SO - Acta Neuropathol (Berl) 1986;71(1-2):154-8
6
UI - 86308089
AU - Du Val G ; Grubb BR ; Bentley PJ
TI - Tissue distribution of subcutaneously administered aluminum chloride in
weanling rabbits.
AB - The purpose of our investigation was to determine blood and tissue levels
of aluminum (Al) in normal young rabbits. Furthermore, we wished to
determine tissue distribution and accumulation of Al as related to its
blood concentration in Al-dosed rabbits. The levels of Al accumulated
were determined in different tissues of growing rabbits after continuous
subcutaneous administration of Al chloride (3.78 mg/d) for 28 d. No signs
of toxicity were apparent from comparisons of hematocrit or weight gain
between control and Al-dosed rabbits. The largest concentration of the Al
was observed in bone, which was also found to have the highest levels in
the control rabbit tissues. Following bone, the experimental animals
showed the greatest increase of Al levels in kidney cortex, kidney
medulla, liver, testes, skeletal muscle, heart, brain white matter, and
brain hippocampus, in that order. No significant difference was found in
brain grey matter between control and experimental animals. As the brain
tissue of the Al-treated animals had the lowest Al level of the tissues
measured, it appears that there is a partial blood-brain barrier to entry
of Al.
MH - Aluminum/*METABOLISM/TOXICITY ; Animal ; Brain/METABOLISM ; Injections,
Subcutaneous ; Male ; Rabbits ; Support, U.S. Gov't, P.H.S. ; Tissue
Distribution ; Weaning
SO - J Toxicol Environ Health 1986;19(1):97-104
7
UI - 86299902
AU - Edwardson JA ; Klinowski J ; Oakley AE ; Perry RH ; Candy JM
TI - Aluminosilicates and the ageing brain: implications for the pathogenesis
of Alzheimer's disease.
AB - Senile plaques are a neuropathological feature of the ageing brain and
consist of abnormal neuritic and glial processes surrounding an
extracellular core of material with fibrillary ultrastructure. Present at
low densities in the cerebral cortex of most aged individuals, they occur
in large numbers in Alzheimer's disease, the major form of senile
dementia. Energy-dispersive X-ray microprobe analysis of isolated cores
and plaques in situ from patients with Alzheimer's disease or Down's
syndrome and from normal controls has shown co-localization of high
concentrations of aluminium (4-19%) and silicon (6-24%) at the centre of
the core. The presence of these elements as aluminosilicates has been
confirmed using solid-state 27Al nuclear magnetic resonance. These
findings provide a link with the other major neuropathological feature of
Alzheimer's disease, the neurofibrillary tangle-bearing neurons, where
high intracellular levels of Al and Si have also been reported. The focal
deposition of these elements may be an early and essential factor in the
pathogenesis of Alzheimer-type changes, reflecting an increased exposure
to aluminium.
MH - Aged ; Aging ; Aluminum/TOXICITY ; Aluminum Silicates/*ANALYSIS ;
Alzheimer's Disease/*ETIOLOGY/PATHOLOGY ; Brain/*GROWTH & DEVELOPMENT/
PATHOLOGY/ULTRASTRUCTURE ; Human ; Microscopy, Electron ; Microscopy,
Electron, Scanning
SO - Ciba Found Symp 1986;121:160-79
8
UI - 86220026
AU - Ganrot PO
TI - Metabolism and possible health effects of aluminum.
AB - Literature regarding the biochemistry of aluminum and eight similar ions
is reviewed. Close and hitherto unknown similarities were found. A
hypothetical model is presented for the metabolism, based on documented
direct observations of Al3+ and analogies from other ions. Main
characteristics are low intestinal absorption, rapid urinary excretion,
and slow tissue uptake, mostly in skeleton and reticuloendothelial cells.
Intracellular Al3+ is probably first confined in the lysosomes but then
slowly accumulates in the cell nucleus and chromatin. Large, long-lived
cells, e.g., neurons, may be the most liable to this accumulation. In
heterochromatin, Al3+ levels can be found comparable to those used in
leather tannage. It is proposed that an accumulation may take place at a
subcellular level without any significant increase in the corresponding
tissue concentration. The possible effects of this accumulation are
discussed. As Al3+ is neurotoxic, the brain metabolism is most
interesting. The normal and the lethally toxic brain levels of Al3+ are
well documented and differ only by a factor of 3-10. The normal brain
uptake of Al3+ is estimated from data on intestinal uptake of Al3+ and
brain uptake of radionuclides of similar ions administered intravenously.
The uptake is very slow, 1 mg in 36 years, and is consistent with an
assumption that Al3+ taken up by the brain cannot be eliminated and is
therefore accumulated. The possibility that Al3+ may cause or contribute
to some specific diseases, most of them related to aging, is discussed
with the proposed metabolic picture in mind.
MH - Aluminum/*METABOLISM/PHARMACODYNAMICS/TOXICITY ; Alzheimer's Disease/
ETIOLOGY ; Amyotrophic Lateral Sclerosis/ETIOLOGY ; Aneuploidy ; Animal ;
Autoimmune Diseases/IMMUNOLOGY ; Beryllium/METABOLISM ; Biological
Transport ; Bone and Bones/METABOLISM ; Brain/METABOLISM ; Cations ; Cell
Division ; Cells/METABOLISM ; Chromium/METABOLISM ; Connective Tissue/
METABOLISM ; Cytoplasm/METABOLISM ; Down's Syndrome/ETIOLOGY ; DNA/
METABOLISM ; Encephalitis/ETIOLOGY ; Erythrocytes/METABOLISM ; Feces/
METABOLISM ; Gallium/PHARMACODYNAMICS ; Hemodialysis/ADVERSE EFFECTS ;
Human ; Hypersensitivity/IMMUNOLOGY ; Immunity, Cellular ; Indium/
METABOLISM ; Intestinal Absorption ; Intestinal Mucosa/METABOLISM ; Lung/
METABOLISM ; Membrane Lipids/METABOLISM ; Microfilaments/DRUG EFFECTS ;
Microtubules/DRUG EFFECTS ; Muscular Dystrophy/ETIOLOGY ; Nondisjunction,
Genetic/DRUG EFFECTS ; Osteomalacia/ETIOLOGY ; Parkinson Disease/ETIOLOGY
; Review ; Scandium/METABOLISM ; Support, Non-U.S. Gov't ; Tissue
Distribution ; Transferrin/METABOLISM ; Yttrium/METABOLISM ; Zirconium/
METABOLISM
SO - Environ Health Perspect 1986 Mar;65:363-441