==================================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