*******************************************************

http://groups.yahoo.com/group/aspartameNM/message/1279
all three aspartame metabolites harm human erythrocyte [red blood cell]
membrane enzyme activity, KH Schulpis et al, two studies in 2005,
Athens, Greece, 2005.12.14: 2004 research review, RL Blaylock:
Murray 2006.01.14

"High or abuse concentrations of ASP hydrolysis products significantly
decreased the membrane enzyme activity,
which was completely or partially prevented by L-cysteine
or reduced GSH."

[ Definition of Erythrocyte
Erythrocyte:
A cell that contains hemoglobin and can carry oxygen to the body.
Also called a red blood cell (RBC).
The reddish color is due to the hemoglobin.
Erythrocytes are biconcave in shape,
which increases the cell's surface area
and facilitates the diffusion of oxygen and carbon dioxide.
This shape is maintained by a cytoskeleton
composed of several proteins.
Erythrocytes are very flexible
and change shape when flowing through capillaries.
Immature erythrocytes, called reticulocytes,
normally account for 1-2 percent of red cells in the blood. ]


Eur J Clin Nutr. 2005 Dec 14; [Epub ahead of print]
The effect of L-cysteine and glutathione on inhibition of
Na(+), K(+)-ATPase activity by aspartame metabolites
in human erythrocyte [red blood cell] membrane.
Schulpis KH,   Kleopatra H. Schulpis, MD, PhD.
Institute of Child Health, Aghia Sophia Children's Hospital,
GR-11527 Athens (Greece) +30 1 7708291, Fax +30 1 7700111 
inchildh@otenet.gr;
Papassotiriou I,   biochem@paidon-agiasofia.gr;
Parthimos T,
Tsakiris T,
Tsakiris S.      Stylianos Tsakiris.   stsakir@cc.uoa.gr;
1 Institute of Child Health, Research Center,
'Aghia Sophia' Children's Hospital, Athens, Greece.
 ggbriass@med.uoc.gr;  ersi_voskaridou@yahoo.com;
 mmoschov@med.uoa.gr;  siahanidou@hotmail.com;


Background:
Reports have implicated Aspartame
(N-L-a-aspartyl-L-phenylalanine methyl ester, ASP)
in neurological problems.

Aim:
To evaluate Na(+), K(+)-ATPase activities in human erythrocyte
[red blood cell] membranes
after incubation with the ASP metabolites,
phenylalanine (Phe),
methanol (MeOH) and
aspartic acid (Asp).

Methods:
Erythrocyte [red blood cell] membranes
were obtained from 12 healthy individuals and
were incubated at 37 degrees C for 1 h
with the sum or each of the ASP metabolites separately,
which are commonly measured in blood after ASP ingestion.

Na(+), K(+)-ATPase and Mg(2+)-ATPase activities were measured
spectrophotometrically.

Results:
Membrane Mg(2+)-ATPase activity was not altered.

The sum of ASP metabolite concentrations corresponding
to 34, 150 or 200 mg/kg of the sweetener ingestion
resulted in an inhibition of the membrane
Na(+), K(+)-ATPase by -30, -40, -48%, respectively.

MeOH concentrations of 0.14, 0.60 or 0.80 mM
decreased the enzyme activity by -25, -38, -43%, respectively.

Asp concentrations of 2.80, 7.60 or 10.0 mM
inhibited membrane Na(+), K(+)-ATPase by -26, -40, -46%,
respectively.

Phe concentrations of 0.14, 0.35 or 0.50 mM
reduced the enzyme activity by -24, -44, -48%, respectively.

Preincubation with L-cysteine or reduced glutathione (GSH)
completely or partially restored
the inhibited membrane Na(+), K(+)-ATPase activity
by high or toxic ASP metabolite concentrations.

Conclusions:
Low concentrations of ASP metabolites had no effect
on Na(+), K(+)-ATPase activity.

High or abuse concentrations of ASP hydrolysis products significantly
decreased the membrane enzyme activity,
which was completely or partially prevented by L-cysteine
or reduced GSH. [reduced glutathione]

European Journal of Clinical Nutrition advance online publication,
14 December 2005; doi:10.1038/sj.ejcn.1602355. PMID: 16391576
*******************************************************

http://groups.yahoo.com/group/aspartameNM/message/1213
aspartame (methanol, phenylalanine, aspartic acid) effects, detailed
expert studies in 2005 Aug and 1998 July, Tsakiris S, Schulpis KH,
Karikas GA, Kokotos G, Reclos RJ, et al, Aghia Sophia Children's
Hospital, Athens, Greece: Murray 2005.09.09

Rich Murray, MA  Room For All  rmforall@comcast.net
505-501-2298  1943 Otowi Road   Santa Fe, New Mexico 87505
http://groups.yahoo.com/group/aspartameNM/messages
group with 148 members, 1,213 posts in a public, searchable archive

[ The lowest dose level tested, 34 mg aspartame per kg body weight,
well below the FDA daily human limit of 50 mg/kg, 16 12-oz cans,
caused enzyme activity reduction by -33% in human red blood cell
membranes. ]

However, a missed opportunity in both studies is that the inevitable,
extremely and cumulatively toxic products of methanol in the human
body, formaldehyde and formic acid, which are responsible for the
toxicity of methanol, were not independently tested.

" It is concluded that low concentrations of ASP metabolites had no
effect on the [human red blood cell] membrane enzyme activity,
whereas high or toxic concentrations partially or remarkably decreased
the [human red blood cell] membrane AChE activity, respectively.
Additionally, neurological symptoms, including learning and memory
processes, may be related to the high or toxic concentrations of the
sweetener metabolites. " ]

Pharmacol Res. 2005 Aug 26; [Epub ahead of print]
The effect of aspartame metabolites on human [red blood cell]
erythrocyte membrane acetylcholinesterase activity.
Tsakiris S,
Giannoulia-Karantana A,
Simintzi I,
Schulpis KH.
Department of Experimental Physiology, Medical School,
University of Athens, P.O. Box 65257, GR-154 01 Athens, Greece.

Stylianos Tsakiris.   stsakir@cc.uoa.gr;

Giannoulia-Karantana A.  First Department of Pediatrics,
Aghia Sophia Children's Hospital, University of Athens, Greece.

Kleopatra H. Schulpis, MD, PhD. Institute of Child Health,
Aghia Sophia Children's Hospital,  GR-11527 Athens (Greece)
Tel. +30 1 7708291, Fax +30 1 7700111   inchildh@otenet.gr;

[ Papoutsakis T.      tina.papoutsakis@hua.gr;

Papadopoulos G.  Department of Biochemistry and Biotechnology,
University of Thessaly, Ploutonos 26, 41221 Larisa, Greece
papg@chem.auth.gr;  ]

Abstract:

Studies have implicated aspartame (ASP) with neurological problems.
The aim of this study was to evaluate acetylcholinesterase (AChE)
activity in human erythrocyte [red blood cell] membranes
after incubation with the sum of ASP metabolites,
phenylalanine (Phe),
methanol (met) and
aspartic acid (aspt),
or with each one separately.

Erythrocyte [human red blood cell] membranes were obtained from
12 healthy individuals and were incubated with ASP hydrolysis
products for 1h at 37 degrees C.
AChE was measured spectrophotometrically.

Incubation of membranes with ASP metabolites corresponding
with 34 mg/kg, 150 mg/kg or 200 mg/kg of ASP consumption
resulted in an enzyme activity reduction by -33%, -41%, and -57%,
respectively.

Met concentrations 0.14 mM, 0.60 mM, and 0.80 mM decreased
the enzyme activity by -20%, -32% or -40%, respectively.

Aspt concentrations 2.80 mM, 7.60 mM or 10.0 mM inhibited
membrane AChE acitivity by -20%, -35%, and -47%, respectively.

Phe concentrations 0.14 mM, 0.35 mM or 0.50 mM reduced the
enzyme activity by -11%, -33%, and -35%, respectively.

Aspt or Phe concentrations 0.82 mM or 0.07 mM, respectively,
did not alter the membrane AChE activity.

It is concluded that low concentrations of ASP metabolites had
no effect on the membrane enzyme activity,
whereas high or toxic concentrations partially or remarkably
decreased the membrane AChE activity, respectively.
Additionally, neurological symptoms, including learning and memory
processes, may be related to the high or toxic concentrations of the
sweetener metabolites.  PMID: 16129618
******************************************************

http://groups.yahoo.com/group/aspartameNM/message/1213
aspartame (methanol, phenylalanine, aspartic acid) effects, detailed
expert studies in 2005 Aug and 1998 July, Tsakiris S, Schulpis KH,
Karikas GA, Kokotos G, Reclos RJ, et al, Aghia Sophia Children's
Hospital, Athens, Greece: Murray 2005.09.09

http://groups.yahoo.com/group/aspartameNM/message/939
aspartame (aspartic acid, phenylalanine) binding to DNA:
Karikas July 1998: Murray 2003.01.05 rmforall
Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
Measurement of molecular interaction of aspartame and
its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
Dept. of Chemistry, University of Athens, Greece
http://www.chem.uoa.gr gkokotos@atlas.uoa.gr
K.H. Schulpis inchildh@otenet.gr G.J. Reclos reklos@otenet.gr


http://groups.yahoo.com/group/aspartameNM/message/1277
50% UK baby food is now organic -- aspartame or MSG
with food dyes harm nerve cells, CV Howard 3 year study
funded by Lizzy Vann, CEO, Organix Brands,
Children's Food Advisory Service: Murray 2006.01.13
*******************************************************

http://groups.yahoo.com/group/aspartameNM/message/1090
aspartame, MSG, excitotoxins, NMDA glutamate receptors, multiple
sclerosis: Blaylock: Martini: Murray 2004.06.09 rmforall

[ Rich Murray:  I have corrected typos and spelling, and added spacing
to improve readability.  I found abstracts for 7 of the 9 references, and
added more abstracts that show a vigorous scientific advance, with
scores of scientists and studies.   These studies may well be relevant
to very recent research that aspartame hurts memory in rats:

http://groups.yahoo.com/group/aspartameNM/message/1088
Murray, full plain text & critique:
chronic aspartame in rats affects memory, brain cholinergic receptors,
and brain chemistry, Christian B, McConnaughey M et al, 2004 May:
2004.06.05 rmforall    ]

http://www.rense.com/general53/ms.htm
The connection between MS and aspartame
Russell L. Blaylock, M.D. Neurosurgeon  2004.06.07
http://www.russellblaylockmd.com

Recently, much controversy has surrounded a claim that aspartame
may produce an MS-like syndrome.
A current review of recent peer-reviewed scientific studies have
disclosed a pathophysiological mechanism to explain this connection.

As far back as 1996 it was shown  that the lesions produced in the
myelin sheath of axons in cases of multiple sclerosis were related to
excitatory receptors on the primary cells involved, called
oligodendroglia.
Recent studies have now confirmed what was suspected back then.
The loss of myelin sheath on the nerve fibers characteristic of the
disease are due to the death of these oligodendroglial cells at the site
of  the lesions (called plaques). Further, these studies have shown
that the death of these important cells is as a result of excessive
exposure to excitotoxins at the site of the lesions.

Normally, most of these excitotoxins are secreted from microglial
immune cells in the central nervous system.
This not only destroys these myelin-producing cells,  it also breaks
down the blood-brain barrier (BBB), allowing excitotoxins in the
blood stream to enter the site of damage.

Aspartame contains the excitotoxin aspartate as 40% of its
molecular structure. Numerous studies have shown that consuming
aspartame can significantly elevate the excitotoxin level in the blood.

[  Rich Murray:  A Searle Laboratories team in 1976 reported that
in 4 monkeys fed aspartame, by 12 hours:  "...the major fraction
(70%) of the [aspartate] label appeared in the expired air (Fig.6)...
Urinary and fecal 14C [ aspartate derived ] amounted to 4--6%
of the administered  [ aspartate ] label."
This gives a total of a maximum 76% excreted aspartate
from the aspartame, indicating that 24% of this excitotoxin
was retained in the body.
It is reasonable to conclude that daily use of aspartame must lead to
substantial accumulation of this excitotoxin, aspartate, in body tissues.

Their 1979 review said: "Aspartame... is hydrolyzed in the gut to yield
aspartic acid, phenylalanine, and methanol....
Aspartate may also be incorporated into body constitutents such as
other amino acids, proteins, pyrimidines, asparagine, and
N-acetylaspartic acid."

J Environ Pathol Toxicol. 1979 Mar-Apr; 2(4): 979-85.
A review of the metabolism of the aspartyl moiety of aspartame in
experimental animals and man.
Ranney RE, Oppermann JA.
Department of Drug Metabolism and Radiochemistry,
Searle Laboratories, Skokie, Illinois.

Aspartame (3-amino-N-(alpha-carboxyphenethyl) succinamic acid,
methyl ester; the methyl ester of aspartylphenylalanine, SC-18862)
is hydrolyzed in the gut to yield aspartic acid, phenylalanine,
and methanol.
This review of the literature describes the metabolic paths
followed by aspartate in its conversion to CO2
or its incorporation into body constituents.
About 70 percent of 14C from [asp-14C]-aspartame is
converted in the monkey to 14CO2.
Some of the aspartate is converted at the intestinal mucosal level to
alanine by decarboxylation.
This amino acid may be oxidized to CO2 by entering the
tricarboxylic acid cycle via pyruvate and acetyl CoA.
In addition, transamination of aspartate to oxaloacetate
permits this product also to enter the tricarboxylic acid cycle.
Aspartate may also be incorporated into body constitutents such as
other amino acids, proteins, pyrimidines, asparagine,
and N-acetylaspartic acid.
It is concluded that the aspartate moiety of aspartame
is metabolized in a manner similar to that of dietary aspartic acid.
Publication Types: Review  PMID: 376770 ]

There is a  common situation during which the excitotoxin
exposure is even greater.
When aspartate (as aspartame) is combined in the diet with
monosodium glutamate  (MSG) blood levels are several fold higher
than normal.
With the BBB damaged, as in MS, these excitotoxins can freely enter
the site of injury, greatly magnifying the damage.
So, we see that dietary excitotoxins, such as aspartame and MSG,
can greatly magnify the damage produced in multiple sclerosis.
Likewise, excitotoxins have been shown to breakdown the BBB as well.

Of equal concern is observation that we know that about 10% of the
population (based on autopsy studies of elderly) have MS lesions without 
ever developing the full blown disease,
a condition called benign MS.

A diet high  in excitotoxins, such as aspartame, can convert this benign,
subclinical condition into full-blown clinical MS.
The amount of  excitotoxins consumed in the average American diet is
considerable, as shown by several studies.

In addition, the toxin methanol is also in the aspartame molecule.
Methanol is an axon poison.
Combined toxicity of the aspartate and the methanol adds up to
considerable brain toxicity, and can convert benign, subclinical MS
into full-blown MS.
Once the MS becomes full-blown, further consumption of
excitotoxins magnifies the toxicity,  increasing disability and death.

Recent studies have also shown that even single exposures to these
food-based excitotoxins can produce prolonged worsening of
neurological lesions.

In addition, it has been demonstrated that autoimmune reactions
(as occurs with MS) greatly magnifies the toxicity of aspartate
and glutamate (the excitotoxins).

We also know  liquid forms of excitotoxins are significantly more
toxic because of rapid absorption and higher blood levels.

In the face of this connection between excitotoxicity and the
pathophysiology of MS, it would be ludicrous to allow further use
of this excitotoxin containing sweetener.

TREATMENT FOR MS:
It is now known the cause for the destruction of the myelin in the
lesions is overactivation of the microglia in the region of the myelin.
An enzyme that converts glutamine to glutamate, called glutaminase,
increases tremendously, thereby greatly increasing excitotoxicity.

Mercury also activates microglia, even in subtoxic doses.

Any dietary excitotoxin can activate the microglia, thereby greatly
aggravating the injury.
This includes the aspartate in aspartame.
The methanol adds to this toxicity as well.

Now, the secret to treatment appears to be shutting down, or at least
calming down, the microglia.
It has been found  that the antibiotic minocycline powerfully shuts
down the microglia.
I tried this treatment on a friend of mine who just came down with
fulmanant MS.
He was confined to a wheelchair.
I had him placed on minocycline and now, just a few weeks later,
he is walking.

The good news is that other things also calm the microglia --
the most potent are: silymarin, curcumin and ibuprophen.
Phosphatidylcholine helps re-myelinate the nerve sheaths that are
damaged, as does B12, B6, B1, vitamin D, folate, vitamin C,
natural vitamin E (mixed tocopherols) and L-carnitine.

DHA plays a major role in repairing the myelin sheath.

Vitamin D may even prevent MS, but it acts as an immune modulator,
preventing further damage -- the dose is 2000 IU a day.

Magnesium, as magnesium malate, is needed
in a dose of 500 mg 2X a day.

They must avoid all excitotoxins, even natural ones in foods --
such as  soy, red meats, nuts, mushrooms and tomatoes.

Avoid all fluoride and especially all vaccinations, since these
either inhibit antioxidant enzymes or trigger harmful immune reactions.

( Dr. Blaylock is a recently retired board-certified neurosurgeon
with more than twenty six years experience.  He is a recently retired
Clinical Assistant Professor of Neurosurgery at the Medical University
of Mississippi.   Author of thirty scientific papers on various medical
subjects, chapters in three medical textbooks and a booklet on multiple
sclerosis, he recently completed a booklet on bioterrorism and is the
author of "Excitotoxins: The Taste That Kills",
"Health & Nutrition Secrets  to Save Your Life", and
"Natural Strategies for Cancer Patients".
http://www.russellblaylockmd.com/
He serves on the editorial staff of The Journal of American Physicians
and Surgeons,  the Journal of the American Nutraceutical Association,
and acts as a medical advisor to the American Nutraceutical Association.
His excellent newsletter can be gotten at
http://www.blaylockreport.com/
He lives in Ridgeland, Mississippi.)

References and additional abstracts:

1.  Neurobiol Dis. 1999 Dec; 6(6): 475-85.
AMPA and kainate receptors each mediate excitotoxicity in
oligodendroglial cultures.
Sanchez-Gomez MV, Matute C.
Departamento de Neurociencias, Universidad del Pais Vasco,
Leioa, Vizcaya, 48940, Spain.
[ Sanchez-Gomez MV has 11 abstracts in PubMed since 1992
on this line of research, while Matute C has 63 abstracts since 1985.
Carlos Matute Almau +34-946-012-865  onpmaalc@lg.ehu.es;   ]

Recent studies indicate that oligodendrocytes are vulnerable to
excitotoxic insults mediated by glutamate receptors.
The present study was carried out to characterize the type of glutamate
receptors triggering cell death in optic nerve oligodendrocyte cultures.
Acute activation of either AMPA or kainate receptors was toxic to
oligodendrocytes, an effect that was prevented by CNQX.
However, exposure to agonists of the NMDA and metabotropic
glutamate receptors did not impair cell viability.
Dose-response curves showed that toxicity was mediated
by three distinct populations of receptors:
an AMPA-type receptor and high- and low-affinity kainate-type
receptors.
Expression and immunocytochemical studies suggested that the
glutamate receptor subunits give rise to the native receptors
in each population.
In all instances, Ca(2+) entry was a major determinant
of glutamate receptor excitotoxicity.
However, its influence varied for each receptor subtype.
These results indicate that aberrantly enhanced activation of
AMPA and/or kainate receptors may be involved
in demyelinating diseases.
Copyright 1999 Academic Press.  PMID: 10600403

J Neurosci. 2003 Oct 22; 23(29): 9519-28.
Caspase-dependent and caspase-independent oligodendrocyte
death mediated by AMPA and kainate receptors.
Sanchez-Gomez MV, Alberdi E, Ibarretxe G, Torre I, Matute C.
Departamento de Neurociencias, Universidad del Pais Vasco,
E-48940 Leioa, Vizcaya, Spain.
[  Department of Neurosciences, Faculty of Medicine and Dentistry,
University of the Basque Country, Leioa, Vizcaya, Spain
Carlos Matute Almau +34-946-012-865  onpmaalc@lg.ehu.es;  ]

Oligodendrocytes are vulnerable to excitotoxic signals mediated
by AMPA receptors and by high- and low-affinity kainate receptors.
Here we investigated the nature of the cell death triggered by activation
of these receptors in primary cultures of oligodendrocytes
from the rat optic nerve.
Activation of AMPA receptors at both submaximal and maximal
concentrations of the agonist induced massive calcium entry,
mitochondrial depolarization, and a rise in the level of reactive oxygen
species that correlated with a decrease in the levels of reduced 
glutathione.
In addition, excitotoxicity initiated by submaximal, but not maximal,
activation of AMPA receptors was prevented by caspase-3 blockade
and by the concomitant blockade of caspases 8 and 9.
In turn, maximal activation of high- or low-affinity kainate receptors
induced mitochondrial events and toxicity levels similar to those observed
with submaximal activation of AMPA receptors.
In contrast to AMPA receptor-mediated insults, calcineurin inhibition
or caspase-9 blockade was sufficient to prevent cell death triggered
by both types of kainate receptors.
Consistent with these results, prolonged glutamate receptor activation in
freshly isolated optic nerves caused selective activation of caspase-3
and chromatin condensation in oligodendrocytes.
Overall, the evidence presented here indicates that oligodendrocyte
death by excitotoxicity is mediated
by caspase-dependent and -independent mechanisms.  PMID: 14573531

free full text  http://www.ehu.es/ingles/paginas/prin_i.htm
Glia. 2002 Sep; 39(3): 304-13.
Multiple angiotensin receptor subtypes in normal and tumor astrocytes in
vitro.
Fogarty DJ, Sanchez-Gomez MV, Matute C.
Department of Neurosciences, Faculty of Medicine and Dentistry,
University of the Basque Country, Leioa, Vizcaya, Spain.
Carlos Matute Almau +34-946-012-865  onpmaalc@lg.ehu.es;

A role for neuropeptide receptors in glial tumorigenesis has recently
been proposed.
Although angiotensin receptors are known to mediate proliferative
effects in many cell types, including brain astrocytes, the possible
participation of these receptors in glial tumorigenesis remains unknown.
In the present study, we have examined the expression of the molecularly
defined angiotensin receptor subtypes AT(1a), AT(1b), and AT(2) in
normal perinatal rat astrocytes and in a panel of tumor adult astrocytoma
cells,
using the reverse transcriptase-polymerase chain reaction (RT-PCR).
Subsequently, we compared the mitogenic effect of the angiotensins
A(1-8), A(2-8), A(3-8) and the heptapeptide "metabolite" A(1-7),
on both normal and tumor astrocytes,
measured in terms of the incorporation of tritiated thymidine.
Our results indicate that AT(1a), AT(1b), and AT(2) angiotensin
receptor mRNA is commonly expressed by many of these cells.
Of notable exception is the astrocytoma U373 which was not found
to express AT(1) or AT(2) mRNA.
Chronic (24-h) incubation of cells with A(1-8) and A(1-7) lead to the
induction of mitogenesis, even in the AT(1) and AT(2) mRNA negative
astrocytoma cell line U373.
Moreover, pharmacological analysis indicated that the observed
mitogenic effects are not mediated by the AT(1) or AT(2) type
receptors, but rather by a novel, specific A((1-7)) angiotensin
receptor, since mitogenesis was shown
to be partially blocked by the A(1-7) analogue D-Ala(7)A(1-7)
and by the protease inhibitor orthophenanthroline (100 microM).
Using Fura-2 spectrophotometry, we found that activation of this
receptor does not alter intracellular calcium levels;
however, preincubation with the protein kinase kinase inhibitor
U0126 (10 microM) was found to inhibit these mitogenic effects
partially.
Overall, these results which demonstrate that normal and tumor
astrocytes express a greater variety of angiotensin receptor subtypes
than previously thought,
support the idea that A(1-7) and its receptor signaling system may
play an important role in shaping the astrocyte population during
development.
Moreover, the untimely expression of this A((1-7)) receptor
may represent an important etiological component in the development
of brain astrocytomas.
Copyright 2002 Wiley-Liss, Inc.  PMID: 12203396

free full text  http://www.ehu.es/ingles/paginas/prin_i.htm
Carlos Matute, Elena Alberdi, Gaskon Ibarretxe,
Maria Victoria Sanchz-Gomez.
Excitotoxicity in glial cells.
European J. Pharmacology 2002; 447: 239-246.
Carlos Matute Almau +34-946-012-865  onpmaalc@lg.ehu.es;

Excitotoxicity results from prolonged activation of glutamate receptors
expressed by cells in the central nervous system (CNS).
This cell death mechanism was first discovered in retinal ganglion cells
and subsequently in brain neurons.
In addition, it has been recently observed that CNS glial cells can also
undergo excitotoxicity.
Among them, oligodendrocytes are highly vulnerable to glutamate signals
and alterations in glutamate homeostasis may contribute to demyelinating
disorders.
We review here the available information on excitotoxity in CNS glial
cells and its putative relevance to glio-pathologies.  PMID: 12151015

Trends Neurosci. 2001 Apr; 24(4): 224-30.
The link between excitotoxic oligodendroglial death and demyelinating
diseases.
Matute C, Alberdi E, Domercq M, Perez-Cerda F, Perez-Samartin A,
Sanchez-Gomez MV.
Departamento de Neurociencias, Universidad del Pais Vasco,
48940 Leioa, Spain.       Carlos Matute Almau +34-946-012-865 
onpmaalc@lg.ehu.es;

Oligodendrocytes, the myelinating cells of CNS axons, are highly
vulnerable to excitotoxic signals mediated by glutamate receptors of the
AMPA and kainate classes.
Receptors in these cells are commonly activated by glutamate that is
released from axons and glial cells.
In addition, oligodendrocytes contribute to the control of extracellular
glutamate levels by means of their own transporters.
However, acute and chronic alterations in glutamate homeostasis
can result in overactivation of AMPA and kainate receptors
and subsequent excitotoxic oligodendroglial death.
Furthermore, demyelinating lesions caused by excitotoxins
can be similar to those observed in multiple sclerosis.
This, together with the effect of AMPA and kainate receptor
antagonists in ameliorating the neurological score of animals with
experimental autoimmune encephalomyelitis
(an animal model of multiple sclerosis), indicates that
oligodendrocyte excitotoxicity could be involved in the pathogenesis of
demyelinating disorders.  Publication Types: Review Review Literature
PMID: 11250007

Adv Exp Med Biol. 1999; 468: 97-107.
On how altered glutamate homeostasis may contribute to demyelinating
diseases of the CNS.
Matute C, Domercq M, Fogarty DJ, Pascual de Zulueta M,
Sanchez-Gomez MV.
Departamento de Neurociencias Universidad del Pais Vasco,
Vizcaya, Spain.
Carlos Matute Almau +34-946-012-865  onpmaalc@lg.ehu.es;

Glial cells communicate reciprocally with neurons in multiple ways,
both in synaptic and non-synaptic regions of the central nervous system.
In the latter, neuron to glial and glial to glial signals can be mediated by
neurotransmitters.
Here, we review the presence and some of the functional properties of
glutamate transporters and receptors in oligodendrocytes.
In addition, we present data illustrating that alterations in glutamate
homeostasis can be excitotoxic to oligodendroglia and that the tissue
lesions caused by overactivation of glutamate receptors resemble those
observed in demyelinating diseases such as multiple sclerosis.
Overall, this information indicates that aberrant glutamate signaling may
contribute to the development of some white matter pathologies.
Publication Types: Review Review, Tutorial    PMID: 10635022

2.  J Neurosci Res. 1996 Nov 15; 46(4): 427-37.
Pathophysiology of oligodendroglial excitotoxicity.
Yoshioka A, Bacskai BJ, Pleasure DE.
Division of Neurology, Children's Hospital of Philadelphia, PA 19104, USA.
DAVID E PLEASURE  pleasure@email.chop.edu;  215-590-2090

Oligodendrocyte-like cells (OLD) derived from the rat oligodendroglial
precursor line, CG-4, express Ca(2+)-permeable non-methyl-D-aspartate
glutamate receptor channels (GluR).
Exposure to kainate, an L-glutamate analogue, markedly elevates OLC Ca2+
influx and cytosolic [Ca2+], and results in damage to both OLC plasma
membrane and OLC nuclear DNA.
Two observations indicate that kainate-induced OLC internucleosomal DNA
nicking is not simply a delayed consequence of cell necrosis:
1) there is no temporal lag between onset of plasma membrane injury and of 
DNA nicking; and
2) aurintricarboxylic acid, an endonuclease inhibitor, blocks
kainate-induced damage to the plasma membrane.
N-acetyl-L-cysteine also inhibits OLC kainate injury, suggesting that
reactive oxygen species participate in OLC excitotoxicity.
Kainate-induced OLC Ca2+ influx and excitotoxicity are blocked by
alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), indicating 
that these kainate effects are mediated by AMPA-GluR.
AMPA and L-glutamate
fail to elicit OLC damage unless cyclothiazide, an AMPA-GluR desensitization 
blocker, is present.
OLC express both the "flip" and "flop" forms of GluR2,
GluR3, and GluR4 mRNAs, but neither flip nor flop GluR1 mRNA.
These data, together with the restriction of the desensitization-blocking
activity of cyclothiazide to GluR containing flip-encoded GluR subunits, and 
the sharply diminished Ca2+ permeability of GluR containing edited GluR2, 
suggest OLC excitotoxicity is mediated by AMPA-GluR that contain flip GluR3 
and/or flip GluR4 protein subunits,
but neither flip nor flop GluR2 protein subunits.
Rapid desensitization of these GluR is likely to be important in protecting
cells of the oligodendroglial lineage from excitotoxicity.   PMID: 8950702

J Biol Chem. 1997 Jan 3; 272(1): 647-56.
N-methyl-D-aspartate receptors expressed in a nonneuronal cell line mediate
subunit-specific increases in free intracellular calcium.
Grant ER, Bacskai BJ, Pleasure DE, Pritchett DB, Gallagher MJ, Kendrick SJ,
Kricka LJ, Lynch DR.
[  for free full text     http://www.jbc.org/cgi/content/full/272/1/647
Elfrida R. Grant , Brian J. Bacskai §, David E. Pleasure §¶, Dolan B.
Pritchett ¶, Michael J. Gallagher , Shelley J. Kendrick , Larry J. Kricka
and David R. Lynch §¶**      73 references ]

From the Departments of  Pharmacology, § Neurology, ¶ Pediatrics,
Pathology and Laboratory Medicine, University of Pennsylvania School
of Medicine, Children's Seashore House,
Philadelphia, Pennsylvania 19104
DAVID E PLEASURE  pleasure@email.chop.edu  215-590-2090 ]

N-methyl-D-aspartate (NMDA) receptors can mediate cell death
in neurons and in non-neuronal cells that express recombinant NMDA
receptors.
In neurons, increases in intracellular calcium correlate with NMDA
receptor-mediated death, supporting a key role for loss of cellular
calcium homeostasis in excitotoxic cell death.
In the present study, free intracellular calcium concentrations were
examined in response to activation of recombinant NMDA receptors
expressed in human embryonic kidney 293 cells.
Intracellular calcium was measured in transfected cell populations by
cotransfection with the calcium-sensitive, bioluminescent protein aequorin
and by single cell imaging with the fluorescent calcium indicator fluo-3.
Agonist application to NR1/2A or NR1/2B-transfected cells elicited
robust rises in intracellular calcium.
NR1/2A responses were inhibited by the noncompetitive antagonists
MK-801 and dextromethorphan and were dependent on extracellular
calcium but not on intracellular calcium stores.
In contrast, no detectable intracellular calcium responses were observed
in NR1/2C-transfected cells.
These findings indicate that NMDA receptors in the absence of other
neuron-specific factors can mediate increases in intracellular calcium with
subunit specificity and extracellular calcium dependence.
PMID: 8995308

http://jpet.aspetjournals.org/cgi/content/full/300/3/717  free full text
Pharmacology and Experimental Therapeutics.
March 2002; 300 (3): 717-723.
Excitotoxicity: Perspectives Based on N-Methyl-D-Aspartate
Receptor Subtypes
David R. Lynch and Rodney P. Guttmann
Departments of Neurology (D.R.L.), Pediatrics (D.R.L.),
and Pharmacology (R.P.G.), University of Pennsylvania and
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
lynch@pharm.med.upenn.edu;  215-590-2242
rodneyg@email.uky.edu;         (859) 257-1412 x275

Since excitotoxicity has been implicated in a variety of neuropathological
conditions, understanding the pathways involved in this type of cell death
is of critical importance to the future clinical treatment of many diseases.
The N-methyl-D-aspartate (NMDA) receptor has become a primary
focus of excitotoxic research because early studies demonstrated that
antagonism of this receptor subtype was neuroprotective.
However, initial pharmacological agents were not clinically useful due to
the adverse effects of complete NMDA receptor blockade.
Understanding the biochemical properties of the multitude of NMDA
receptor subtypes offers the possibility of developing more effective and
clinically useful drugs. With the discovery of the basis of heterogeneity
of NMDA receptors through molecular biological approaches,
many new potential therapeutic targets have been uncovered,
and several model systems have been developed for the study of
NMDA receptor-mediated cell death.
This review discusses these models and the current understanding
of the relationship between NMDA receptor subtypes and excitotoxicity.

3.  Mol Cell Biochem. 2003 Jan; 243(1-2): 139-45.
Prolonged glutamate excitotoxicity: effects on mitochondrial antioxidants
and antioxidant enzymes.  [ strong toxicity of MSG in rat brains ]
Singh P, Mann KA, Mangat HK, Kaur G.
Neurochemistry and Neuroendocrinology Laboratory, Department of
Biotechnology, Guru Nanak Dev University, Amritsar, India.

Glutamate, a major excitatory amino acid neurotransmitter is also an
endogenous excitotoxin.
The present study examined the prolonged and delayed effects of
glutamate excitotoxicity on mitochondrial lipid peroxidation and
antioxidant parameters in different brain regions, namely,
cerebral hemisphere, cerebellum, brain stem and diencephalon.
Wistar rats (male) were exposed to monosodium glutamate (MSG)
(4 mg x g body wt(-1), i.p.) for 6 consecutive days and sacrificed
on 30th and 45th day after last MSG dose.
MSG treatment markedly decreased the mitochondrial manganese
superoxide-dismutase (Mn-SOD), catalase
and reduced glutathione (GSH) content,
and increased the lipid peroxidation (LPx), uric acid and
glutathione peroxidase (GPx) activity.
These results indicate that oxidative stress produced by glutamate in
vulnerable brain regions may persist for longer periods and mitochondrial
function impairment is an important mechanism of excitatory amino acid
mediated neurotoxicity in chronic neurodegeneration.  PMID: 12619899

4.  Neurobiol Dis. 2003 Dec; 14(3): 336-48.
AMPA receptors are the major mediators of excitotoxic death in mature
oligodendrocytes.
Leuchtmann EA, Ratner AE, Vijitruth R, Qu Y, McDonald JW.
Center for the Study of Nervous System Injury, Washington University
School of Medicine, Box 8518, St. Louis, MO 63108, USA.
John Wood McDonald     JMcDonald@WUSTL.EDU;
+1 314 454-7825    fax: +1 314 454-5300

Myelination of axons is important for central nervous system function,
but oligodendrocytes, which constitute CNS myelin, are vulnerable
to excitotoxic injury and death.
Although mature oligodendrocytes express functional
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA)
and kainate-type glutamate receptors, the relative roles of these
subtypes in excitotoxicity are not well understood.
Using recently developed selective antagonists for subtypes of
ionotropic non-NMDA receptors, we addressed this issue.
By examining the pharmacological, biochemical, and morphologic
features of kainite-induced excitotoxic death, we also determined
whether it occurs by apoptosis, necrosis, or both.
We conclude that when mature oligodendrocytes die after exposure
to kainate:
(1) AMPA receptors are the most important mediators,
(2) kainate receptors play a smaller role, and
(3) death occurs predominantly by necrosis, not apoptosis.
PMID: 14678751

5. Annals of Neurology. 2003 May; 53 5); 588 - 595.
Interleukin-1 promotes oligodendrocyte death through glutamate
excitotoxicity.
Jennifer L. Takahashi, MD 1, Fabrizio Giuliani, MD 1,
Christopher Power, MD 1, Yoshinori Imai, MD 2,
V. Wee Yong, PhD 1 3 *
1 Department of Clinical Neurosciences, University of Calgary,
Calgary, Alberta, Canada
2 National Institute of Neuroscience, Kodaira, Tokyo, Japan
3 Department of Oncology, University of Calgary, Calgary,
Alberta, Canada   email: V. Wee Yong  vyong@ucalgary.ca;
*Correspondence to V. Wee Yong, Neuroscience Research Group,
University of Calgary, 3330 Hospital Drive,
Calgary, Alberta T2N 4N1, Canada
Funded by: Multiple Sclerosis Society of Canada
Canadian Institutes of Health Research; Grant Number: MT H246

Glutamate excitotoxicity is implicated in the progressive loss of
oligodendrocytes in multiple sclerosis, but how glutamate metabolism
is dysregulated in the disease remains unclear.
Because there is microglia activation in all stages of multiple sclerosis,
we determined whether a microglia product, interleukin-1,
could provide the mechanism for glutamate excitotoxicity.
We found that whereas interleukin-1 did not kill oligodendrocytes
in pure culture, it produced apoptosis of oligodendrocytes in coculture
with astrocytes and microglia.
This requirement for a mixed glia environment suggests that interleukin-1
impairs the well-described glutamate-buffering capacity of astrocytes.
In support, antagonists at AMPA/kainate glutamate receptors,
NBQX and CNQX,
blocked the interleukin-1 toxicity to oligodendrocytes.
Another microglia/macrophage cytokine, tumor necrosis factor-,
also evoked apoptosis of oligodendrocytes in a mixed glia environment
in an NBQX-blockable manner.
These results provide a mechanistic link between the persistent and
insidious microglia activation that is evident in all stages of multiple
sclerosis, with the recent appreciation that glutamate excitotoxicity leads
to the destruction of oligodendrocytes in the disease.

6.  Neurology. 2003 Oct 28; 61(8): 1113-20.
Glutamate uptake by oligodendrocytes: Implications for excitotoxicity in
multiple sclerosis.
Pitt DF, Nagelmeier IE, Wilson HC, Raine CS.  dfpitt@yahoo.com;
Department of Neurology, Albert Einstein College of Medicine,
Bronx, NY, USA.        Cedric S.  Raine  jni@aecom.yu.edu;

BACKGROUND:
Excitotoxic damage is a common pathologic event in a number of
neurologic diseases occurring after accumulation of excess extracellular
glutamate in the CNS and subsequent overstimulation
of glutamate receptors.
In gray matter, astrocytes take up synaptically released glutamate
and are thus key cells in maintaining glutamate homeostasis.
In white matter, oligodendrocytes have been shown to express
glutamate transporters, but their role in extracellular glutamate
removal is unclear.
OBJECTIVE:
To investigate whether cultured human fetal oligodendrocytes
functionally express the main glutamate transporters
EAAT-1 and EAAT-2.
METHODS:
Cultures of fetal human oligodendrocytes were examined by
immunocytochemistry and [3H]glutamate uptake, and the findings were
correlated with glutamate transporter expression in normal and multiple
sclerosis (MS) CNS tissue.
RESULTS:
Both EAAT-1 and EAAT-2 were expressed
by human oligodendrocytes in vitro.
Incubation of oligodendrocytes with the proinflammatory cytokine
tumor necrosis factor-alpha (TNFalpha) reduced EAAT-1 expression
and inhibited glutamate uptake by >75%.
Furthermore, in normal human white matter, oligodendrocytes
were found to be the predominant cells to express
EAAT-1 and EAAT-2, both at the mRNA and at the protein level.
A small number of astrocytes in white matter expressed these receptors,
more so EAAT-1 than EAAT-2.
In MS white matter, oligodendrocytes lost expression of
EAAT-1 and EAAT-2 receptors in the lesion vicinity.
CONCLUSIONS:
Oligodendrocytes appear to be predominant cells for glutamate
clearance in human white matter.
Glutamate receptor expression and glutamate removal were defective
in MS white matter, possibly mediated by TNFalpha, changes that
might underlie high extracellular glutamate and an increased risk for
glutamate excitotoxicity. PMID: 1458167

7.  Neuroscience. 2004; 123(2): 441-9.
Excitotoxic insults to the optic nerve alter visual evoked potentials.
Soto A, Perez-Samartin AL, Etxebarria E, Matute C.
Departamento de Neurociencias, Universidad del Pais Vasco,
E-48940 Leioa, Vizcaya, Spain.
Carlos Matute Almau +34-946-012-865  onpmaalc@lg.ehu.es;

Excitotoxic oligodendroglial death is one of the mechanisms which
has been proposed to underlie demyelinating diseases of the CNS.
We describe here functional consequences of excitotoxic lesions to the
rabbit optic nerve by studying the visual evoked potentials (VEPs)
measured in the visual cortex.
Nerves were slowly infused with the excitotoxin kainate a
subcutaneously implanted osmotic pump which delivered the
toxin through a cannula onto the optic nerve.
Records of VEPs were obtained before pump implantation and at
1, 3 and 7 days post-implantation, and weekly evaluated thereafter
for up to 4 months.
We observed that the VEPs generated by light stimuli progressively
changed in both amplitude and profile after the lesion as well as in
comparison to those generated in control animals infused with vehicle.
Histological examination of the damage caused by the excitotoxic insult
showed that large areas of the optic nerve were demyelinated and their
axons distorted.
These observations were confirmed and extended by
immunohistochemical analyses using markers to neurofilaments,
myelin basic protein and the oligodendrocyte marker APC.
The results of the present paper indicate that the consequences of
excitotoxicity in the optic nerve share functional and morphological
alterations which are found in demyelinating disorders.
In addition, this experimental paradigm may be useful to evaluate the
functional recovery of demyelinated optic nerves following various
repair strategies.  PMID: 14698751

http://www.ehu.es/ingles/paginas/prin_i.htm
Neurobiol Dis. 2002 Mar;9(2):234-43.
Ca(2+) influx through AMPA or kainate receptors alone is sufficient to
initiate excitotoxicity in cultured oligodendrocytes.
Alberdi E, Sanchez-Gomez MV, Marino A, Matute C.
Departamento de Neurociencias, Universidad del Pais Vasco,
Leioa, Vizcaya, Spain.

8. Blaylock RL.
Interactions of cytokines, excitotoxins and reactive  nitrogen and oxygen
species in autism spectrum disorders.
Journal of  American Nutraceutical Association 6: 21-35, 2003.
[ Not in PubMed ]

9. Blaylock RL.
Chronic microglial activation and excitotoxicity secondary to excessive
immune stimulation: possible factors in Gulf War Syndrome and autism.
Journal American Physicians and Surgeons, Summer, 2004.
[ Not in PubMed ]
*******************************************************

http://groups.yahoo.com/group/aspartameNM/message/97
Lancet website aspartame letter 1999.07.29:
Excitotoxins 1999 Part 1/3 Blaylock: Murray 2000.01.14 rmforall
The Medical Sentinel Journal  1999 Fall; (95 references)
http://www.dorway.com/blayenn.html

Russell L. Blaylock, MD  601-982-1175  Madison, Mississippi
"Excitotoxins: The Taste that Kills", 1977, 298 p., 493 references.
"Health and Nutrition Secrets that can save your life", 2002, 459 p.,
558 + 30 references, $ 30   http://www.russellblaylockmd.com/

http://www.truthinlabeling.org/    Truth in Labeling Campaign [MSG]
Adrienne Samuels, PhD   The toxicity/safety of processed
free glutamic acid (MSG): a study in suppression of information.
Accountability in Research 1999;  6:  259-310.  52-page review
P.O. Box 2532 Darien, Illinois 60561
858-481-9333   adandjack@aol.com
*******************************************************

January 14, 2006

Any unsuspected source of methanol, which the body always quickly
and largely turns into formaldehyde and then formic acid, must be
monitored, especially for high responsibility occupations, often with
night shifts, such as pilots and nuclear reactor operators.

In particular, the next review gives many recent mainstream
peer-reviewed studies that show formaldehyde,
always inevitably derived in the body from any methanol source,
including aspartame, causes endothelial injury,
ie, diabetic neuropathy -- among the most serious and complex
complications of diabetes.

http://groups.yahoo.com/group/aspartameNM/message/1263
many studies on endothelial injury (diabetic neuropathy) by adducts of
formaldehyde derived from methylamine from many of the same sources
as also supply methanol (formaldehyde), including aspartame:
PH Yu et al: DJ Conklin et al: Murray 2005.12.04

http://groups.yahoo.com/group/aspartameNM/message/1237
ubiquitous potent uncontrolled co-factors in nutrition research are
formaldehyde from wood and tobacco smoke and many sources,
including from methanol in dark wines and liquors, in pectins
in fruits and vegetables, and in aspartame: Murray 2006.01.13

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text Trocho & Alemany 1998.06.26
Universitat Autònoma de Barcelona : Murray 2002.12.22

http://groups.yahoo.com/group/aspartameNM/message/1250
aspartame causes cancer in rats at levels approved for humans,
Morando Soffritti et al, Ramazzini Foundation, Italy &
National Toxicology Program
of National Institute of Environmental Health Sciences
2005.11.17 Env. Health Pers. 35 pages: Murray

http://groups.yahoo.com/group/aspartameNM/message/1271
combining aspartame and quinoline yellow, or MSG and brilliant blue,
harms nerve cells, eminent C. Vyvyan Howard et al, 2005
education.guardian.co.uk, Felicity Lawrence: Murray 2005.12.21

http://groups.yahoo.com/group/aspartameNM/message/1274
harm to fetus from formaldehyde from methanol from aspartame,
Woodrow C. Monte: Murray 2006.01.02

http://groups.yahoo.com/group/aspartameNM/message/1279
all three aspartame metabolites harm human erythrocyte [red blood cell]
membrane enzyme activity, KH Schulpis et al, two studies in 2005,
Athens, Greece, 2005.12.14: 2004 research review, RL Blaylock:
Murray 2006.01.14

As a medical layman, I suggest that evidence mandates immediate
exploration of the role of these ubiquitious, potent formaldehyde
sources as co-factors in epidemiology, research, diagnosis,
and treatment in a wide variety of disorders.

Folic acid, from fruits and vegetables, plays a role by powerfully
protecting against methanol (formaldehyde) toxicity.

Many common drugs, such as aspirin, interfere with folic acid,
as do some mutations in relevant enzymes.

The majority of aspartame reactors are female.

In mutual service, Rich Murray
*******************************************************

"Of course, everyone chooses, as a natural priority,
to actively find, quickly share, and act upon the facts
about healthy and safe food, drink, and environment."

Rich Murray, MA  Room For All  rmforall@comcast.net
505-501-2298  1943 Otowi Road   Santa Fe, New Mexico 87505

http://groups.yahoo.com/group/aspartameNM/messages
group with 149 members, 1,280 posts in a public, searchable archive
http://RoomForAll.blogspot.com  http://AspartameNM.blogspot.com

Dark wines and liquors, as well as aspartame, provide
similar levels of methanol, above 100 mg daily, for
long-term heavy users, 2 L daily, about 6 cans.

Methanol is inevitably largely turned into formaldehyde,
and thence largely into formic acid.
It is the major cause of the dreaded symptoms of "next
morning" hangover.

Fully 11% of aspartame is methanol -- 1,120 mg aspartame
in 2 L diet soda, almost six 12-oz cans, gives 123 mg
methanol (wood alcohol). If 30% of the methanol is turned
into formaldehyde, the amount of formaldehyde, 37 mg,
is 18.5 times the USA EPA limit for daily formaldehyde in
drinking water, 2.0 mg in 2 L average daily drinking water.

http://groups.yahoo.com/group/aspartameNM/message/1108
faults in 1999 July EPA 468-page formaldehyde profile:
Elzbieta Skrzydlewska PhD, Assc. Prof., Medical U. of
Bialystok, Poland, abstracts -- ethanol, methanol,
formaldehyde, formic acid, acetaldehyde, lipid peroxidation,
green tea, aging: Murray 2004.08.08 2005.07.11

http://groups.yahoo.com/group/aspartameNM/message/835
ATSDR: EPA limit 1 ppm formaldehyde in drinking water July
1999: Murray 2002.05.30 rmforall

Aspartame is made of phenylalanine (50% by weight) and
aspartic acid (39%), both ordinary amino acids, bound
loosely together by methanol (wood alcohol, 11%).
The readily released methanol from aspartame is within hours
turned by the liver into formaldehyde and then formic acid,
both potent, cumulative toxins.

http://groups.yahoo.com/group/aspartameNM/message/1141
Nurses Health Study can quickly reveal the extent of aspartame
(methanol, formaldehyde, formic acid) toxicity: Murray 2004.11.21
[ Any scientist can get access to this data for free by submitting a proper
research proposal.
No one has admitted mining the extensive data on diet soda use
and many symptoms for decades for about 100,000 nurses. ]

http://groups.yahoo.com/group/aspartameNM/message/1213
aspartame (methanol, phenylalanine, aspartic acid) effects, detailed
expert studies in 2005 Aug and 1998 July, Tsakiris S, Schulpis KH,
Karikas GA, Kokotos G, Reclos RJ, et al,
Aghia Sophia Children's Hospital, Athens, Greece: Murray 2005.09.09

http://groups.yahoo.com/group/aspartameNM/message/939
aspartame (aspartic acid, phenylalanine) binding to DNA:
Karikas July 1998: Murray 2003.01.05 rmforall
Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
Measurement of molecular interaction of aspartame and
its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
Dept. of Chemistry, University of Athens, Greece
http://www.chem.uoa.gr gkokotos@atlas.uoa.gr
K.H. Schulpis inchildh@otenet.gr G.J. Reclos reklos@otenet.gr

http://groups.yahoo.com/group/aspartameNM/message/1088
Murray, full plain text & critique: chronic aspartame in rats affects
memory, brain cholinergic receptors, and brain chemistry, Christian B,
McConnaughey M et al, 2004 May: 2004.06.05

http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame,
AM Hill & DV Belsito, Nov 2003: Murray 2004.03.30

Thrasher (2001): "The major difference is that the Japanese
demonstrated the incorporation of FA and its metabolites into the
placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [ Ref. 14-16 ]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH. toxicology@drthrasher.org
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html full text

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds
methanol 98 mg/L [ becomes formaldehyde in body ]: EU Scientific
Committee on Foods 2001.07.12: Murray 2004.01.22

http://groups.yahoo.com/group/aspartameNM/message/1131
genotoxicity of aspartame in human lymphocytes 2004.07.29
full plain text, Rencuzogullari E et al, Cukurova University,
Adana, Turkey 2004 Aug: Murray 2004.11.06

http://groups.yahoo.com/group/aspartameNM/message/1237
ubiquitous potent uncontrolled co-factors in nutrition research are
formaldehyde from wood and tobacco smoke and many sources,
including from methanol in dark wines and liquors, in pectins
in fruits and vegetables, and in aspartame: Murray 2006.01.13

http://groups.yahoo.com/group/aspartameNM/message/1264
fructose in rats increases uric acid, obesity, insulin resistance,
endothelial damage -- RJ Johnson et al, U. Florida: Murray 2005.12.07
*******************************************************

http://groups.yahoo.com/group/aspartameNM/message/1106
hangover research relevant to toxicity of 11% methanol in
aspartame (formaldehyde, formic acid): Calder I (full text):
Jones AW: Murray 2004.08.05 2005.09.28

Since no adaquate data has ever been published on the exact
disposition of toxic metabolites in specific tissues in
humans of the 11% methanol component of aspartame, the many
studies on morning-after hangover from the methanol impurity
in alcohol drinks are the main available resource to date.

Jones AW (1987) found next-morning hangover from red wine
with 100 to 150 mg methanol (9.5% w/v ethanol, 100 mg/L
methanol, 0.01%, one part in ten thousand).

http://groups.yahoo.com/group/aspartameNM/message/1182
Joining together: short review: research on aspartame
methanol, formaldehyde, formic acid) toxicity: Murray
2005.07.08 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1071
research on aspartame (methanol, formaldehyde, formic acid)
toxicity: Murray2004.04.29 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1250
aspartame causes cancer in rats at levels approved for humans,
Morando Soffritti et al, Ramazzini Foundation, Italy &
National Toxicology Program
of National Institute of Environmental Health Sciences
2005.11.17 Env. Health Pers. 35 pages: Murray

http://groups.yahoo.com/group/aspartameNM/message/1226
USA National Institutes of Health National Toxicology
Program aids eminent Ramazzini Foundation, Bologna, Italy,
in more results on cancers in rats from lifetime low levels
of aspartame (methanol, formaldehyde), Felicity Lawrence,
www.guardian.co.uk: Murray 2005.09.30

http://groups.yahoo.com/group/aspartameNM/message/1186
aspartame induces lymphomas and leukaemias in rats, full plain text,
M Soffritti, F Belpoggi, DD Esposti, L Lambertini: Ramazzini
Foundation study 2005.07.14: main results agree with their previous
methanol and formaldehyde studies: Murray 2005.09.03

http://groups.yahoo.com/group/aspartameNM/message/1189
Michael F Jacobson of CSPI now and in 1985 re aspartame
toxicity, letter to FDA Commissioner Lester Crawford;
California OEHHA aspartame critique 2004.03.12; Center for
Consumer Freedom denounces CSPI: Murray 2005.07.27

http://groups.yahoo.com/group/aspartameNM/message/1143
methanol (formaldehyde, formic acid) disposition: Bouchard M
et al, full plain text, 2001: substantial sources are
degradation of fruit pectins, liquors, aspartame, smoke:
Murray 2005.04.02
*******************************************************

http://groups.yahoo.com/group/aspartameNM/message/1070
critique of aspartame review, French Food Safety Agency AFSSA
2002.05.07 aspartamgb.pdf (18 pages, in English), Martin Hirsch:
Murray 2004.04.13

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF,
EU Scientific Committee on Food, a whitewash; Murray 2003.01.12

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references

http://www.HolisticMed.com/aspartame    mgold@holisticmed.com
Aspartame Toxicity Information Center    Mark D. Gold
12 East Side Drive #2-18 Concord, NH 03301     603-225-2100
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

Gold points out that industry methanol assays were too insensitive to
properly measure blood methanol levels.  ]

http://www.eatright.org/Nutritive(1).pdf
J Am Diet Assoc. 2004 Feb; 104(2): 255-75.
Position of the American Dietetic Association: use of nutritive and
nonnutritive sweeteners. American Dietetic Association.

http://groups.yahoo.com/group/aspartameNM/message/1068
critique of aspartame review by American Dietetic Association
Feb 2004, Valerie B. Duffy & Madeleine J. Sigman-Grant:
Murray 2004.05.14

"Survey of aspartame studies: correlation of outcome and funding
sources," 1998, unpublished:   http://www.dorway.com/peerrev.html
Walton found 166 separate published studies in the peer reviewed
medical literature, which had relevance for questions of human safety.
The 74 studies funded by industry all (100%) attested to aspartame's
safety, whereas of the 92 non-industry funded studies, 84 (91%)
identified a problem. Six of the seven non-industry funded studies
that were favorable to aspartame safety were from the FDA, which
has a public record that shows a strong pro-industry bias.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio
Universities, College of Medicine, Dept. of Psychiatry, Youngstown,
OH 44501, Chairman, The Center for Behavioral Medicine,
Northside Medical Center, 500 Gypsy Lane, P.O. Box 240
Youngstown, OH 44501    330-740-3621    rwalton193@aol.com
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

http://groups.yahoo.com/group/aspartameNM/message/857
www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research: Murray 2002.07.31

http://groups.yahoo.com/group/aspartameNM/message/858
Samuels: Strong: Roberts: Gold:  flaws in double-blind studies re
aspartame and MSG toxicity: Murray 2002.08.01

http://www.truthinlabeling.org/    Truth in Labeling Campaign [MSG]
Adrienne Samuels, PhD   The toxicity/safety of processed
free glutamic acid (MSG): a study in suppression of information.
Accountability in Research 1999;  6:  259-310.  52-page review
P.O. Box 2532 Darien, Illinois 60561
858-481-9333   adandjack@aol.com

http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3:
Gregory Gordon, UPI reporter: Murray 2000.07.10

http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 1999.11.06

http://groups.yahoo.com/group/aspartameNM/message/928
revolving door, Monsanto, FDA, EPA: NGIN: Murray 2002.12.23

http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA
approval: Turner: Murray 2002.12.23 rmforall
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http://groups.yahoo.com/group/aspartameNM/message/1280
Aspartame: Bill would ban food containing sweetener [in New Mexico]:
Diana Heil, The New Mexican: Murray 2006.01.14

http://groups.yahoo.com/group/aspartameNM/message/1276
NM EIB votes 7-0 to delay 5-day aspartame hearing until Jan 2007,
Diana Heil, The New Mexican: comment by Stephen Fox:
Murray 2006.01.04

http://groups.yahoo.com/group/aspartameNM/message/1273
citizens against aspartame (methanol, formaldehyde), made by
Ajinomoto, at Jan 3 hearing of NM EIB in Santa Fe: Lehrman:
Murray 2006.01.01

http://groups.yahoo.com/group/aspartameNM/message/1272
New Mexico Gov. Bill Richardson endorses Nutrition Council,
mercury ban, aspartame hearings: Lehrman, Fox, Stoller:
Murray 2005.12.27

http://groups.yahoo.com/group/aspartameNM/message/1248
Aspartame and Thimerosal getting banned in New Mexico
by the Pharmacy Board? with notes by Rich Murray: 2005.11.15

http://groups.yahoo.com/group/aspartameNM/message/1247
Aspartame quagmire quickly deepens, methanol (formaldehyde, formic
acid) toxicity facts spreading at the grassroots level,
3 items in The New Mexican,
and long article in Vanity Fair by Rich Cohen: Murray 2005.11.15

http://groups.yahoo.com/group/aspartameNM/message/1245
Fox, Stoller, Murray to give Citizen's Petition
to ban aspartame (methanol, formaldehyde) and mercury
in children's medicines and vitamins: New Mexico Board of Pharmacy,
2:45-3:45 pm Monday Nov. 14, Albuquerque: Murray 2005.11.13

http://groups.yahoo.com/group/aspartameNM/message/1228
NM EIB votes 4-2 for 5-day aspartame toxicity hearing July,
2006, requesting a Hearing Officer and a medical expert from
Environmental Dept. and legal advice from NM Attorney
General: Murray 2005.10.04
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