Medical citations on
aluminium
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Medical citations
[2008] Song Y, Xue Y, Liu X, Wang P, Liu L. Effects of acute exposure to aluminum on blood-brain barrier and the protection of zinc Our present studies suggest that aluminum increases the permeability of BBB by changing its ultrastructure and the expression of occludin and F-actin
[pdf 2006/7]
ALUMINUM ADJUVANT LINKED TO GULF WAR SYNDROME INDUCES
MOTOR NEURON DEATH IN MICE M.S. Petrik1,2,
M.C. Wong1,2, R.C. Tabata1, R.F. Garry5 and C.A. Shaw1,3,4
ABSTRACT: Gulf War Syndrome (GWS) affects a high percentage of
veterans of the 1991 conflict, but its origins
remain unknown. One neurological complication of GWS is an increased
incidence of amyotrophic lateral sclerosis (ALS). While many
environmental factors have been linked to GWS, the
role of the anthrax vaccine administered to deployed
troops has come under increasing scrutiny. Among the vaccine’s
potentially toxic components are the adjuvant
aluminum hydroxide and squalene. To examine whether
these materials might contribute to neurologic toxicity, we injected
young male colony CD-1 mice with these adjuvants
at doses equivalent to those given to service personnel.
Mice were subjected to a battery of motor and cognitive behavioral
tests over a six month period. Following
sacrifice, CNS tissue was examined using immunohistochemistry for
evidence of neural death. Behavioral testing showed both motor and
cognitive functions were impacted by the tested
adjuvants to differing degrees. Apoptotic neurons were
identified in lumbar spinal cord and motor cortex in the groups
receiving the adjuvants. Aluminum injected
animals also showed a significant increase of astrocytes in the lumbar
spinal cord. Our findings suggest a possible role for either or both
compounds in some neurological features associated
with GWS.
Bishop NJ, Morley R, Day JP, Lucas A.
Aluminum neurotoxicity in preterm infants receiving intravenous-feeding
solutions. N Engl J Med. 1997 May
29;336(22):1557-61. Comment in:
N Engl J Med. 1997 Oct 9;337(15):1090-1 PMID: 9324646
Medical Research Council (MRC) Dunn Nutrition Unit, Cambridge, United
Kingdom.
BACKGROUND: Aluminum, a contaminant of commercial intravenous-feeding solutions,
is potentially neurotoxic. We investigated the effect of perinatal exposure to
intravenous aluminum on the neurologic development of infants born prematurely.
METHODS: We randomly assigned 227 premature infants with gestational ages of
less than 34 weeks and birth weights of less than 1850 g who required
intravenous feeding before they could begin enteral feeding to receive either
standard or specially constituted, aluminum-depleted intravenous-feeding
solutions. The neurologic development of the 182 surviving infants who could be
tested was assessed by using the Bayley Scales of Infant Development at 18
months of age. RESULTS: The 90 infants who received the standard feeding
solutions had a mean (+/-SD) Bayley Mental Development Index of 95+/-22, as
compared with 98+/-20 for the 92 infants who received the aluminum-depleted
solutions (P=0.39). In a planned subgroup analysis of infants in whom the
duration of intravenous feeding exceeded the median and who did not have
neuromotor impairment, the mean values for the Bayley Mental Development Index
for the 39 infants who received the standard solutions and the 41 infants who
received the aluminum-depleted solutions were 92+/-20 and 102+/-17, respectively
(P=0.02). The former were significantly more likely (39 percent, vs. 17 percent
of the latter group; P=0.03) to have a Mental Development Index of less than 85,
increasing their risk of subsequent educational problems. For all 157 infants
without neuromotor impairment, increasing aluminum exposure was associated with
a reduction in the Mental Development Index (P=0.03), with an adjusted loss of
one point per day of intravenous feeding for infants receiving the standard
solutions. CONCLUSIONS: In preterm infants, prolonged intravenous feeding with
solutions containing aluminum is associated with impaired neurologic
development.
Canales JJ, et al. Aluminium
impairs the glutamate-nitric oxide-cGMP pathway in cultured neurons and in rat
brain in vivo: molecular mechanisms and implications for neuropathology.
J Inorg Biochem. 2001 Nov;87(1-2):63-9.
Aluminium (Al) is a neurotoxicant and appears as a possible etiological factor
in Alzheimer's disease and other neurological disorders. The mechanisms of Al
neurotoxicity are presently unclear but evidence has emerged suggesting that Al
accumulation in the brain can alter neuronal signal transduction pathways
associated with glutamate receptors. In cerebellar neurons in culture, long
term-exposure to Al added 'in vitro' impaired the glutamate-nitric oxide
(NO)-cyclic GMP (cGMP) pathway, reducing glutamate-induced activation of NO
synthase and NO-induced activation of the cGMP generating enzyme, guanylate
cyclase. Prenatal exposure to Al also affected strongly the function of the
glutamate-NO-cGMP pathway. In cultured neurons from rats prenatally exposed to
Al, we found reduced content of NO synthase and of guanylate cyclase, and a
dramatic decrease in the ability of glutamate to increase cGMP formation.
Activation of the glutamate-NO-cGMP pathway was also strongly impaired in
cerebellum of rats chronically treated with Al, as assessed by in vivo brain
microdialysis in freely moving rats. These findings suggest that the impairment
of the Glu-NO-cGMP pathway in the brain may be responsible for some of the
neurological alterations induced by Al.
Carpenter DO. Effects of metals on the
nervous system of humans and animals. Int J Occup
Med Environ Health. 2001;14(3):209-18. School of
Public Health University at Albany Rensselaer, NY 12144, USA.
Several metals have toxic actions on nerve cells and neurobehavorial
functioning. These toxic actions can be expressed either as developmental
effects or as an increased risk of neurodegenerative diseases in old age. The
major metals causing neurobehavioral effects after developmental exposure are
lead and methylmercury. Lead exposure in young children results in a permanent
loss of IQ of approximately 5 to 7 IQ points, and also results in a shortened
attention span and expression of anti-social behaviors. There is a critical time
period (<2 years of age) for development of these effects, after which the
effects do not appear to be reversible even if blood lead levels are lowered
with chelation. Methylmercury has also been found to have effects on cognition
at low doses, and prenatal exposure at higher levels can disrupt brain
development. Metals have also been implicated in neurodegenerative diseases,
although it is unlikely that they are the sole cause for any of them. Elevated
aluminum levels in blood, usually resulting from kidney dialysis at home with
well water containing high aluminum, result in dementia that is similar to but
probably different from that of Alzheimer's disease. However, there is some
epidemiological evidence for elevated risk of Alzheimer's in areas where there
is high concentration of aluminum in drinking water. Other metals, especially
lead, mercury, manganese and copper, have been implicated in amvotrophic lateral
sclerosis and Parkinson's disease.
Erasmus RT, Savory J, Wills MR, Herman MM.
Aluminum neurotoxicity in experimental animals.
Ther Drug Monit. 1993 Dec;15(6):588-92. Department of
Pathology, University of Virginia Health Sciences Center, Charlottesville 22908.
Neurotoxic effects of aluminum (Al) were recognized > 100 years ago, but have
only recently been studied in detail. By far, the most dramatic effect of Al is
that of producing intraneuronal perikaryal neurofilamentous aggregates, which
consist of phosphorylated neurofilaments. Several species have been used to
demonstrate this effect, rabbit being most common; the effect also is seen in in
vitro systems. Besides its role in producing neurofibrillary pathology, Al
appears to modify the blood-brain barrier and exert cholinergic and
noradrenergic effects. Possible mechanisms of Al neurotoxicity could be related
to cell damage via free radical production, impairment of glucose metabolism,
and effects on signal transduction.
Gupta
RK, Relyveld EH. Adverse reactions after injection of adsorbed
diphtheria-pertussis-tetanus (DPT) vaccine are not due only to pertussis organisms or
pertussis components in the vaccine. Vaccine. 1991 Oct;9(10):699-702. Review.PMID: 1759487; UI: 92101590
Aluminium compounds such as aluminium phosphate and aluminium hydroxide are the most
commonly used adjuvants with vaccines for human use. Due to the increasing concern about
the toxicity of aluminium, other adjuvants like calcium phosphate may be evaluated as an
alternative to aluminium adjuvants. To minimize reactions after immunization with DPT
vaccine due to impurities in the toxoids, the use of toxoided purified toxins is
suggested.
Gherardi, R. K.
et al. Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived
aluminium hydroxide in muscle http://brain.oupjournals.org/cgi/content/abstract/124/9/1821
(WHALE: a/al2.html)
Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause, detected in
patients with diffuse arthromyalgias and fatigue, and characterized by muscle infiltration
by granular periodic acid–Schiff's reagent-positive macrophages and lymphocytes.
Intracytoplasmic inclusions have been observed in macrophages of some patients. To assess
their significance, electron microscopy was performed in 40 consecutive cases and chemical
analysis was done by microanalysis and atomic absorption spectrometry. Inclusions were
constantly detected and corresponded to aluminium hydroxide, an immunostimulatory compound
frequently used as a vaccine adjuvant. A lymphocytic component was constantly observed in
MMF lesions. Serological tests were compatible with exposure to aluminium
hydroxide-containing vaccines. History analysis revealed that 50 out of 50 patients had
received vaccines against hepatitis B virus (86%), hepatitis A virus (19%) or tetanus
toxoid (58%), 3–96 months (median 36 months) before biopsy. Diffuse myalgias were
more frequent in patients with than without an MMF lesion at deltoid muscle biopsy (P <
0.0001). Myalgia onset was subsequent to the vaccination (median 11 months) in 94% of
patients. MMF lesion was experimentally reproduced in rats. We conclude that the MMF
lesion is secondary to intramuscular injection of aluminium hydroxide-containing vaccines,
shows both long-term persistence of aluminium hydroxide and an ongoing local immune
reaction, and is detected in patients with systemic symptoms which appeared subsequently
to vaccination.
Nayak P, Chatterjee AK. Effects of
aluminium exposure on brain glutamate and GABA systems: an experimental study in
rats. Food Chem Toxicol. 2001 Dec;39(12):1285-9.
It has been postulated that the neurotoxic effects of aluminium could be
mediated through glutamate, an excitatory amino acid. Hence the effects of
aluminium administration (at a dose of 4.2mg/kg body weight daily as aluminium
chloride, hexahydrate, intraperitoneally, for 4 weeks) on glutamate and
gamma-amino butyrate (GABA), an inhibitory amino acid, and related enzyme
activities in different regions of the brain were studied in albino rats. The
glutamate level increased significantly in the cerebrum, thalamic area,
midbrain-hippocampal region and cerebellum in response to in vivo aluminium
exposure. The aluminium insult also caused significant increases in glutamate
alpha-decarboxylase activity in all the brain regions. However, on aluminium
insult, the GABA content was not significantly changed except in the thalamic
area, where it was elevated. On the contrary, the GABA-T activities of all the
regions were reduced significantly in all regions except the midbrain-hippocampal
region. However, the succinic semi-aldehyde content of all brain regions
increased, often significantly. The aluminium-induced modification of the enzyme
activities may be either due to the direct impact of aluminium or due to
aluminium-induced changes in the cellular environment. The aluminium-induced
differential regional accumulation of glutamate or other alterations in enzymes
of the glutamate-GABA system may be one of the causes of aluminium-induced
neurotoxicity.
Skowron F, et al. Persistent nodules at sites of hepatitis B vaccination due to aluminium sensitization. Contact Dermatitis. 1998 Sep;39(3):135-6. No abstract available.PMID: 9771990; UI: 98442988
Aluminium is widely used as an adjuvant in human vaccines, and children can often receive up to 3.75 mg of parenteral aluminium during the first six months of life. We show that intraperitoneal injection of aluminium adsorbed vaccines into mice causes a transient rise in brain tissue aluminium levels peaking around the second and third day after injection. This rise is not seen in the saline control group of animals or with vaccine not containing aluminium. It is likely that aluminium is transported to the brain by the iron-binding protein transferrin and enters the brain via specific transferrin receptors.
Rob PM, Niederstadt C, Reusche E.
Dementia in patients undergoing long-term dialysis: aetiology, differential
diagnoses, epidemiology and management. CNS Drugs.
2001;15(9):691-9. Nephrologisches Zentrum am Klinikum
Süd, Kalhlhorststrasse 31, D-23552 Lübeck, Germany.
prof-rob@gmx.de
Dementia in patients undergoing long-term dialysis has not been clearly defined;
however, four different entities have been described. Uraemic encephalopathy is
a complication of uraemia and responds well to dialysis. Dialysis encephalopathy
syndrome, the result of acute intoxication of aluminium caused by the use of an
aluminium-containing dialysate, was a common occurrence prior to 1980. However,
using modern techniques of water purification, such acute intoxication can now
be avoided. Dialysis-associated encephalopathy/dementia (DAE) is always
associated with elevated serum aluminium levels. Pathognomonic morphological
changes in the brain have been described, but the mechanism for the entry of
aluminium into the CNS is incompletely understood. The mechanisms involved in
the pathogenesis of the neurotoxicity associated with aluminium are numerous.
Although only a very small fraction of ingested aluminium is absorbed, the
continuous oral aluminium intake from aluminium-based phosphate binders, and
also of dietary or environmental origin, is responsible for aluminium overload
in dialysis patients. Age-related dementia, especially vascular dementia, occurs
in patients undergoing long-term dialysis as frequently as it does in the
general population. The differential diagnoses of dialysis-associated dementias
should include investigation for metabolic encephalopathies, heavy metal or
trace element intoxications, and distinct structural neurological lesions such
as subdural haematoma, normal pressure hydrocephalus, stroke and, particularly,
hypertensive encephalopathy and multi-infarct dementia. To prevent DAE, dietary
training programmes should aim to achieve the lowest phosphate intake and
pharmacological tools should be used to keep serum phosphate levels below 2 mmol/L.
To prevent vascular dementia, lifestyle modification should be undertaken,
including optimal physical activity and fat intake, nicotine abstinence, and
targeting optimal blood glucose, cholesterol and triglyceride levels, and blood
pressure, to those outlined in current recommendations.
Szutowicz A. Aluminum, NO, and nerve
growth factor neurotoxicity in cholinergic neurons.
J Neurosci Res. 2001 Dec 1;66(5):1009-18.
Several neurotoxic compounds, including Al, NO, and beta-amyloid may contribute
to the impairment or loss of brain cholinergic neurons in the course of various
neurodegenerative diseases. Genotype and phenotypic modifications of cholinergic
neurons may determine their variable functional competency and susceptibility to
reported neurotoxic insults. Hybrid, immortalized SN56 cholinergic cells from
mouse septum may serve as a model for in vitro cholinotoxicity studies.
Differentiation by various combinations of cAMP, retinoic acid, and nerve growth
factor may provide cells of different morphologic maturity as well as activities
of acetylcholine and acetyl-CoA metabolism. In general, differentiated cells
appear to be more susceptible to neurotoxic signals than the non-differentiated
ones, as evidenced by loss of sprouting and connectivity, decreases in choline
acetyltransferase and pyruvate dehydrogenase activities, disturbances in acetyl-CoA
compartmentation and metabolism, insufficient or excessive acetylcholine
release, as well as increased expression of apoptosis markers. Each neurotoxin
impaired both acetylcholine and acetyl-CoA metabolism of these cells. Activation
of p75 or trkA receptors made either acetyl-CoA or cholinergic metabolism more
susceptible to neurotoxic influences, respectively. Neurotoxins aggravated
detrimental effects of each other, particularly in differentiated cells. Thus
brain cholinergic neurons might display a differential susceptibility to Al and
other neurotoxins depending on their genotype or phenotype-dependent variability
of the cholinergic and acetyl-CoA metabolism.
Yokel RA. The toxicology of aluminum in
the brain: a review. Neurotoxicology. 2000
Oct;21(5):813-28. College of Pharmacy and Graduate
Center for Toxicology, University of Kentucky Medical Center, Lexington, USA.
ryokel1@pop.uky.edu
Aluminum is environmentally ubiquitous, providing human exposure. Usual human
exposure is primarily dietary. The potential for significant Al absorption from
the nasal cavity and direct distribution into the brain should be further
investigated. Decreased renal function increases human risk of Al-induced
accumulation and toxicity. Brain Al entry from blood may involve transferrin-receptor
mediated endocytosis and a more rapid process transporting small molecular
weight Al species. There appears to be Al efflux from the brain, probably as Al
citrate. There is prolonged retention of a fraction of Al that enters the brain,
suggesting the potential for accumulation with repeated exposure. Al is a
neurotoxicant in animals and humans. It has been implicated in the etiology of
sporadic Alzheimer's disease (AD) and other neurodegenerative disorders,
although this is highly controversial. This controversy has not been resolved by
epidemiological studies, as only some found a small association between
increased incidence of dementia and drinking water Al concentration. Studies of
brain Al in AD have not produced consistent findings and have not resolved the
controversy. Injections of Al to animals produce behavioral, neuropathological
and neurochemical changes that partially model AD. Aluminum has the ability to
produce neurotoxicity by many mechanisms. Excess, insoluble amyloid beta protein
(A beta) contributes to AD. Aluminum promotes formation and accumulation of
insoluble A beta and hyperphosphorylated tau. To some extent, Al mimics the
deficit of cortical cholinergic neurotransmission seen in AD. Al increases
Fe-induced oxidative injury. The toxicity of Al to plants, aquatic life and
humans may share common mechanisms, including disruption of the inositol
phosphate system and Ca regulation. Facilitation of Fe-induced oxidative injury
and disruption of basic cell processes may mediate primary molecular mechanisms
of Al-induced neurotoxicity. Avoidance of Al exposure, when practical, seems
prudent.
Zheng W. Neurotoxicology of the brain
barrier system: new implications. J Toxicol Clin
Toxicol. 2001;39(7):711-9.
The concept of a barrier system in the brain has existed for nearly a century.
The barrier that separates the blood from the cerebral interstitial fluid is
defined as the blood-brain barrier, while the one that discontinues the
circulation between the blood and cerebrospinal fluid is named the
blood-cerebrospinal fluid barrier. Evidence in the past decades suggests that
brain barriers are subject to toxic insults from neurotoxic chemicals
circulating in blood. The aging process and some disease states render barriers
more vulnerable to insults arising inside and outside the barriers. The
implication of brain barriers in certain neurodegenerative diseases is
compelling, although the contribution of chemical-induced barrier dysfunction in
the etiology of any of these disorders remains poorly understood. This review
examines what is currently understood about brain barrier systems in central
nervous system disorders by focusing on chemical-induced neurotoxicities
including those associated with nitrobenzenes, N-methyl-D-aspartate, cyclosporin
A, pyridostigmine bromide, aluminum, lead, manganese,
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and 3-nitropropionic acid.
Contemporary research questions arising from this growing understanding show
enormous promises for brain researchers, toxicologists, and clinicians.
Medical citations (links) on vaccination originally compiled by Sebastiana Pienaar: http://www.geocities.com/alebencal/index.html
Neurotoxic effect of enteral aluminium
Aluminium phosphate but not calcium phosphate stimulates the specific IgE
response in guinea pigs to tetanus toxoid.
Long-term effects of aluminium on the fetal mouse brain.
Effect of aluminium hydroxide administration on normal mice
Occupational asthma caused by aluminium welding.
Acute and long-term airway hyperreactivity in aluminium-salt
Aluminum as an adjuvant in vaccines and post-vaccine reactions
Aluminium-adjuvanted vaccines transiently increase aluminium levels
Aluminum in enteral nutrition formulas and parenteral solutions.
Aluminum content of vaccines used in Turkey.
The health effects of aluminium--a review.
Aluminium increases permeability of the blood-brain barrier
Central nervous system disease in patients with macrophagic myofasciitis.
Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived
aluminium hydroxide in muscle.
Characterization of aluminium-containing adjuvants.
Analysis of aluminum hydroxyphosphate vaccine adjuvants by (27)Al MAS NMR.
Public health. Aluminum is put on trial as a vaccine booster. No abstract