Dopamine Theory Aberrant Behavior.
ironj...@aol.com
such as severe alcoholism,cocaine, heroin, marijuana and nicotine use,
glucose bingeing, pathological gambling, sex addiction, ADHD,
Tourette's Syndrome,
autism, chronic violence, posttraumatic stress disorder,
schizoid/avoidant cluster, conduct disorder and antisocial
behavior."
This article clearly shows in the plant .. maltol a sugar .. is
ESSENTIAL for the breakdown of dopamine .. it keeps the dopamine
THERE .. / prevents the breakdown.
Effect of maltol on the oxidation of DL-DOPA, dopamine, N-
acetyldopamine (NADA), and norepinephrine by mushroom tyrosinase.
Pigment Cell Res. 1997 Jun;10(3):139-49.
Kahn V, Ben-Shalom N.
Department of Food Science, Agricultural Research Organization,
Volcani Center, Bet Dagan, Israel.
Maltol (3-hydroxy-2-methyl-4H-pyran-4-one) appears to inhibit the rate
of oxidation of DL-DOPA, dopamine, NADA and epinephrine by tyrosinase
when assayed spectrophotometrically but not when assayed
polarographically.
Maltol has an effect on the spectrum of product(s) formed when each
catecholamine was oxidized by tyrosinase showing that maltol hastens
the disappearance of the quinones, possibly by conjugating with them.
Indeed, at relatively high concentrations, maltol prevented the
conversion of DL-DOPA, dopamine, and norepinephrine to their
corresponding melanins via tyrosinase.
PMID: : 9266600
---------------------------------------------------------
'Dopamine theory' states it might be
useful to attempt to DO what the successful drugs
have been shown to do.
Raise dopamine levels in the brain?
Or utilize the dopamine we produce .. or both?
---------------------------------------------------------
Dopamine Extinguishes Smoking
Drug dulls desire for cigarettes, study finds
WEDNESDAY, Sept 4 (HealthScoutNews) -- Medicine that mimics increased
levels of the brain chemical dopamine could help extinguish a smoker's
desire for cigarettes.
That's the finding of a study, appearing in the September issue of
Nicotine and Tobacco Research, that focused on 20 heavy smokers.
They were given drugs that either increased or decreased their
brain's dopamine levels. Dopamine is a neurotransmitter that affects
motor function and is believed to affect emotion.
Animal studies show nicotine causes dopamine release in brain areas
linked to feelings of pleasure.
This new study found that when the smokers were given the dopamine-
mimicking drug bromocriptine, they smoked less than when given a drug
that impedes the effects of dopamine.
Bromocriptine is used to treat Parkinson's disease, some tumors and
menstrual problems.
"Overall, these results imply that smoking behavior can be
manipulated within the same subjects in opposite directions by
alternately stimulating and blocking dopamine, which strongly
suggests the importance of dopamine in reinforcement from cigarette
smoking," says lead researcher Nicholas H. Caskey, of the Veterans
Affairs Greater Los Angeles Healthcare System and the
Neuropsychiatric
Institute at UCLA's David Geffen School of Medicine.
--------------------------------------------------------
http://www.pslgroup.com/dg/13e79a.htm
DG DISPATCH - AACAP: Nicotine Patches Improve Adult AD/HD Symptoms
------------------------------------------------------
So anything which raises your dopamine seems to be in order?
Phytol / inositol / sugar or .. maltol / sugar.
In India they have shown a very high rate of cure of opiate addiction
with simple vegetable lecithin and in extreme cases sugar added.
The phytol / inositol / sugar / iron chelator in THAT / vegetable
lecithin treatment ..
As opposed to maltol / sugar / iron chelator shown to raise dopamine
in man .. ?
One might wonder whether phytol has been shown to raise dopamine in
the mind.
These sugars phytol and maltol are found in any health food store and
also plants .. fruits and vegetables.
IP6 / phytol / inositol is a natural iron chelating sugar found in
any
health food store or from food 'bran' and in vegetable lecithin .
Maltol is an iron chelating sugar found in any health food store or
your food ..
This article shows what happens when iron is involved in the mouse
brain.
Maltol is a hydroxypyridone a sugar natural iron binder.
"Hydroxypyridone influenced dopamine metabolism"
"Causes significant variations in dopamine turnover"
Brain iron in the ferrocene-loaded rat: its chelation and influence
on dopamine metabolism.
Biochem Pharmacol 1995 Jun 16;49(12):1821-6
Ward RJ, Dexter D, Florence A, Aouad F, Hider R, Jenner P, Crichton
RR.
Department of Clinical Biochemistry, Kings College, London, U.K.
After administration of the ferrocene derivative 3,5,5-trimethyl
hexanoyl ferrocene to rats for 4 weeks various brain regions
including substantia nigra, cerebellum and cerebral cortex showed
up to 50% increase in iron content.
Subsequent administration of one of the hydroxypyridones CP20, CP24
and CP94, or the siderophore desferrioxamine caused a significant
decrease in the iron content of these various brain regions.
Each of the hydroxypyridones and the siderophore influenced
dopamine metabolism by causing significant variations in both
homovanillic acid and dopamine turnover.
PMID: 7598744
----------------------------------------------------------
Reward deficiency syndrome: a biogenetic model for the diagnosis and
treatment of impulsive, addictive, and compulsive behaviors.
J Psychoactive Drugs 2000 Nov;32 Suppl:i-iv, 1-112
Blum K, Braverman ER, Holder JM, Lubar JF, Monastra VJ, Miller D,
Lubar JO, Chen TJ, Comings DE
Department of Biological Sciences, University of North Texas,
Denton, Texas, USA.
The dopaminergic system, and in particular the dopamine D2
receptor, has been implicated in reward mechanisms.
The net effect of neurotransmitter interaction at the mesolimbic
brain region induces "reward" when dopamine (DA) is released
from the neuron at the nucleus accumbens and interacts with
a dopamine D2 receptor.
"The reward cascade" involves the release of serotonin, which
in turn at the hypothalmus stimulates enkephalin, which in turn
inhibits GABA at the substania nigra, which in turn fine tunes the
amount of DA released at the nucleus accumbens or "reward site."
It is well known that under normal conditions in the reward site DA
works to maintain our normal drives.
In fact, DA has become to be known as the "pleasure molecule"
and/or the "antistress molecule."
When DA is released into the synapse, it stimulates a number a DA
receptors (D1-D5) which results in increased feelings of well-being
and stress reduction.
A consensus of the literature suggests that when there is a
dysfunction in the brain reward cascade, which could be caused by
certain genetic variants (polygenic), especially in the DA system
causing a hypodopaminergic trait, the brain of that person requires a
DA fix to feel good.
This trait leads to multiple drug-seeking behavior.
This is so because alcohol, cocaine, heroin, marijuana, nicotine,
and glucose all cause activation and neuronal release of brain DA,
which could heal the abnormal cravings.
Certainly after ten years of study we could say with confidence that
carriers of the DAD2 receptor A1 allele have compromised D2
receptors.
Therefore lack of D2 receptors causes individuals to have a high risk
for multiple addictive, impulsive and compulsive behavioral
propensities, such as severe alcoholism, cocaine,heroin,marijuana and
nicotine use, glucose bingeing, pathological gambling, sex addiction,
ADHD, Tourette's Syndrome, autism, chronic violence, posttraumatic
stress disorder, schizoid/avoidant cluster, conduct disorder and
antisocial behavior.
In order to explain the breakdown of the reward cascade due to
both multiple genes and environmental stimuli (pleiotropism) and
resultant aberrant behaviors, Blum united this hypodopaminergic trait
under the rubric of a reward deficiency syndrome.
PMID: 11280926, UI: 21177392
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
David
of antipsychotic one more antidepressant and a mood stabalizer. if you are
being offended then tell someone and quit trying to helping humanity.
<ironj...@aol.com> wrote in message
news:848edb4b-764a-422f...@z28g2000prd.googlegroups.com...
ironj...@aol.com
usually antidepressants are helpful for most behaviors, with a small
amount
of antipsychotic one more antidepressant and a mood stabalizer. if
you are
being offended then tell someone and quit trying to helping humanity.
<<
Maybe you can afford anti-depressants .. and anti-psychotica and mood
stablizers .. but there are a few people who would PREFER not to have
to smoke and drink and dooo drugs and cut themselves ..
I believe only YOU and a few other may ENJOY the prospect of the
above ..
Since you DO enjoy the prospect OF the above .. you shouldn't be on my
threads .. there .. Dave .. like you've been TOLD .. dave ..
You are not contributory .. and looks like you may be a bit ..
tetched ..
Tetched don't cut it on my threads ..
Remember Dave what I said about BEING .. tetched and what I said
about .. YOU .. ?
Don't post to my threads ..
Use your .. Doctor .. as your method of expression ..
He is your drug supplier .. make your case with him ..
Because I don't deal with .. cases ..
Head .. cases ..
Heh .. heh ..
%
ironj...@aol.com
Maltol <<
"Maltol inhibited iron-mediated lipid peroxidation"
Maltol as an antioxidant : Inhibition of lipid peroxidation and
protection of NADP- isocitrate dehydrogenase from the iron-mediated
inactivation
MURAKAMI Keiko ; ITO Masae ; TANEMURA Yasuko ; YOSHINO Masataka ;
Maltol (3-hydroxy-2-methyl-4-pyrone) inhibited iron-mediated lipid
peroxidation, determined as the formation of thiobarbituric acid-
reactive substances, but dimethylpyrone, an analogue of maltol showed
no effect on the formation of lipid peroxides.
NADP-isocitrate dehydrogenase, a principal enzyme generating reduced
NADP, was protected by maltol but not by dimethylpyrone from the
ferrous ion-mediated inactivation.
Protection of NADP-isocitrate dehydrogenase can enhance the supply of
NADPH required for the regeneration of reduced glutathione for
scavenging reactive oxygen species.
Antioxidant properties of maltol were closely related to the enhanced
oxidation of ferrous ion as a prooxidant, and can be explained by the
electron-deficient nature of 3-hydroxypyrone ring.
Revue / Journal Title
Biomedical research ISSN 0388-6107 CODEN BRESD5
Source / Source
2001, vol. 22, no4, pp. 183-186 [4 page(s) (article)]
Biomedical Research Foundation, Tokyo, JAPON (1980) (Revue)
INIST-CNRS, Cote INIST : 19053, 35400010016716.0010
Copyright 2008 INIST-CNRS. All rights reserved
Toute reproduction ou diffusion même partielle, par quelque procédé
ou
sur tout support que ce soit, ne pourra être faite sans l'accord
préalable écrit de l'INIST-CNRS.
No part of these records may be reproduced of distributed, in any
form
or by any means, without the prior written permission of INIST-CNRS.
Nº notice refdoc (ud4) : 13468314
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/634q5a
ironj...@aol.com
"Maltol inhibited iron-mediated lipid peroxidation"<<
Maltol in soybeans, mung beans, kidney beans, and azuki beans
Inhibitory effects of volatile antioxidants found in various beans on
malonaldehyde formation in horse blood plasma.
Food Chem Toxicol. 2005 Apr;43(4):515-20.
Lee SJ, Lee KG.
Korea Food Research Institute, San 46-1, Backhyun, Bundang-gu,
Sungnam,
Kyonggi-do 463-746, Korea.
The inhibitory effect of aroma extracts isolated from dried soybeans,
mung beans, kidney beans, and azuki beans on malonaldehyde (MA)
formation from horse blood plasma oxidized with Fenton's reagent was
determined by gas chromatography (GC) coupled with nitrogen-
phosphorus
detector (NPD).
Aroma chemicals such as maltol, eugenol, benzyl alcohol, 1-octen-3-ol,
butyrolactone, and 1-methyl-2-pyrrolidone, found in the aroma
extracts
of beans, were also examined for their inhibitory effect on the same
system.
Among the four aroma extracts tested, the aroma extract of soybeans
exhibited the strongest antioxidant activity.
Extracts of soybeans, mung beans, azuki beans, and kidney beans
inhibited MA formation by 58%, 47%, 40%, and 23%, respectively, at
the
level of 400mug/mL, whereas, alpha-tocopherol and BHT inhibited MA
formation by 52% and 70%, respectively, at the same level.
Among the tested aroma chemicals, the antioxidant activity decreased
in the
following order: eugenol>maltol>1-octen-3-ol>benzyl
alcohol>butyrolactone>1-methyl-2-pyrrolidone.
PMID: 15721197
%
samuel_ant...@yahoo.com
belies the use of antipsychotics tp "treat" someones "abherant
behavior". This information reveals that antipsychotics rather then
relieving stress will actually cause stress. I have been telling
people this for years. Please read my report written in 1997 at
http://tinyurl.com/7tnv3
http://www.angelfire.com/az3/love_will_rule_soon/The_Horrible_Truth_About_Psychiatric_Drugs.htm
If the tiny URL link did not work then use the link above........
samuel_ant...@yahoo.com
http://www.angelfire.com/az3/love_will_rule_soon/The_Horrible_Truth_About_Psychiatric_Drugs.htm
If the tiny URL link did not work then use the link above........
On Jan 17, 8:06 am, "David" <dd2...@spamex.com> wrote:
> usually antidepressants are helpful for most behaviors, with a small amount
> of antipsychotic one more antidepressant and a mood stabalizer. if you are
> being offended then tell someone and quit trying to helping humanity.
>
> <ironjust...@aol.com> wrote in message
> >http://tinyurl.com/zk9fk- Hide quoted text -
>
> - Show quoted text -
ironj...@aol.com
amount
of antipsychotic <<
"Called to end unnecessary and prolonged prescribing of antipsychotics
among Alzheimer’s and dementia patients."
Alzheimer's: Antipsychotics double risk of death
Published on Saturday, January 17, 2009
by Healthy News Service
Powerful antipsychotic drugs can double the risk of death in
Alzheimer’s patients, according to one of the first independent
studies not paid for by a drug company.
The drugs are routinely given to Alzheimer’s and dementia patients
while in hospital or nursing homes as a quick way to sedate them –
even though they are not supposed to be used for this purpose.
While the drugs, known as atypical antipsychotics, can help calm the
patient in the immediate term, symptoms such as chest infections,
decline in brain function, stroke – and even death – start to appear
within weeks.
According to a new study from King’s College, London, only half the
patients taking an antipsychotic were still alive compared to those
given a placebo, and the margin widened by the third year by which
time just 30 per cent of those taking antipsychotics were living
compared to 59 per cent on the placebo.
Lead researcher Dr Clive Ballard has called for an immediate end to
"unnecessary and prolonged prescribing" of antipsychotics among
Alzheimer’s and dementia patients.
(Source: The Lancet Neurology, 2009; doi: 10.1016/51474-4422(08)
70295-3).
Provided by What Doctors Don't Tell You on 1/17/2009
%
hi
ironjustice
"Multiple addictive, impulsive and compulsive behavioral
propensities,
such as severe alcoholism,cocaine, heroin, marijuana and nicotine
use,
glucose bingeing, pathological gambling, sex addiction,ADHD,
Tourette's Syndrome, autism, chronic violence, posttraumatic stress
disorder,
schizoid/avoidant cluster, conduct disorder and antisocialbehavior."
<<
Risk-Takers May Lack Ability to Limit Brain Chemical
Finding might lead to new treatments for a variety of addictions,
researchers say
HealthDay
Tuesday, December 30, 2008
TUESDAY, Dec. 30 (HealthDay News) -- Just in time for New Year's Eve
comes research suggesting that "thrill-seeking" behaviors may be hard-
wired into the brain.
Specifically, the study suggests that risk-takers -- those people who
often engage in impulsive, rule-breaking entanglements with food,
drink, drugs, sex, money and the like -- have fewer so-called dopamine
"auto-receptors." These auto-receptors are designed to limit the
release of the brain chemical dopamine. As a result, exciting
activities typically associated with "feel good" dopamine stimulation
trigger higher levels of dopamine release than normal -- essentially
rewarding and encouraging thrill-seeking behavior, the researchers
said.
"It starts to suggest that these auto-receptors might be an
appropriate target for drug abuse," said lead author David H. Zald, an
associate professor of psychology at Vanderbilt University in
Nashville, Tenn. "Of course, we do not yet have good drugs to target
these auto-receptors alone, and until there's a proven way to
intervene pharmacologically, I would say this is all still
hypothetical. But if you can understand the basic risk factors, you
may ultimately be able to both reduce the risk for drug abuse or, more
probably, readily treat people during the withdrawal stage of drug
abuse."
Zald went on to say that "if you took away the novelty-seekers, we
would be a very boring society. So, I would be very hesitant to
describe this type of spontaneous personality as an entirely negative
thing. But it is a style that does put people at greater risk for
developing troubling drug-abuse problems. And now, we've been able to
link this specific personality type with a specific aspect of the
dopamine neurotransmitter system."
Zald and his colleagues reported on their work, funded by the U.S.
National Institute on Drug Abuse, in the Dec. 31 issue of The Journal
of Neuroscience.
Building on prior studies with rodents, the researchers examined
differences in the neural structure of human risk-takers by analyzing
personality-trait questionnaires completed by 34 healthy adults -- 18
men and 16 women, with an average age of about 24.
The participants answered questions about their novelty-seeking
tendencies, spontaneity, decision-making speed, and rule-breaking
inclinations. The researchers then compared the responses to brain
scans of the same participants.
The results: Those who displayed risk-taking traits possessed a
smaller number of dopamine auto-receptors in their brains, giving them
a relatively weakened ability to control and inhibit dopamine release.
Dr. Adam Bisaga, an addiction psychiatrist at the New York State
Psychiatric Institute, agreed that the findings could help lead to
improved addiction treatment.
"The importance of this research is that, hopefully, in the future,
we'll be able to treat patients better, because we can do some
genotyping and target treatment better depending on a patient's
genetic make-up," Bisaga said. "Probably, dopamine receptor
variability is not going to explain all the differences in behavior.
It's a little more complicated than that. But this work now gives us
at least some biological basis for understanding temperament and other
personality characteristics."
HealthDay
Copyright (c) 2008 ScoutNews, LLC. All rights reserved.
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
> "Multiple addictive, impulsive and compulsive behavioral propensities,
> such as severe alcoholism,cocaine, heroin, marijuana and nicotine use,
> glucose bingeing, pathological gambling, sex addiction, ADHD,
> Tourette's Syndrome,
> autism, chronic violence, posttraumatic stress disorder,
> schizoid/avoidant cluster, conduct disorder and antisocialbehavior."
>
> This article clearly shows in the plant .. maltol a sugar .. is
> ESSENTIAL for the breakdown ofdopamine.. it keeps thedopamine
> THERE .. / prevents the breakdown.
>
> Effect of maltol on the oxidation of DL-DOPA,dopamine, N-
> acetyldopamine (NADA), and norepinephrine by mushroom tyrosinase.
> Pigment Cell Res. 1997 Jun;10(3):139-49.
> Kahn V, Ben-Shalom N.
> Department of Food Science, Agricultural Research Organization,
> Volcani Center, Bet Dagan, Israel.
>
> Maltol (3-hydroxy-2-methyl-4H-pyran-4-one) appears to inhibit the rate
> of oxidation of DL-DOPA,dopamine, NADA and epinephrine by tyrosinase
> when assayed spectrophotometrically but not when assayed
> polarographically.
> Maltol has an effect on the spectrum of product(s) formed when each
> catecholamine was oxidized by tyrosinase showing that maltol hastens
> the disappearance of the quinones, possibly by conjugating with them.
> Indeed, at relatively high concentrations, maltol prevented the
> conversion of DL-DOPA,dopamine, and norepinephrine to their
> corresponding melanins via tyrosinase.
>
> PMID: : 9266600
>
> ---------------------------------------------------------
> 'Dopaminetheory' states it might be
> useful to attempt to DO what the successful drugs
> have been shown to do.
> Raisedopaminelevels in the brain?
> Or utilize thedopaminewe produce .. or both?
> ---------------------------------------------------------
>
> DopamineExtinguishes Smoking
>
> Drug dulls desire for cigarettes, study finds
>
> WEDNESDAY, Sept 4 (HealthScoutNews) -- Medicine that mimics increased
> levels of the brain chemicaldopaminecould help extinguish a smoker's
> desire for cigarettes.
> That's the finding of a study, appearing in the September issue of
> Nicotine and Tobacco Research, that focused on 20 heavy smokers.
> They were given drugs that either increased or decreased their
> brain'sdopaminelevels.Dopamineis a neurotransmitter that affects
> motor function and is believed to affect emotion.
>
> Animal studies show nicotine causesdopaminerelease in brain areas
> linked to feelings of pleasure.
>
> This new study found that when the smokers were given thedopamine-
> mimicking drug bromocriptine, they smoked less than when given a drug
> that impedes the effects ofdopamine.
>
> Bromocriptine is used to treat Parkinson's disease, some tumors and
> menstrual problems.
>
> "Overall, these results imply that smokingbehaviorcan be
> manipulated within the same subjects in opposite directions by
> alternately stimulating and blockingdopamine, which strongly
> suggests the importance ofdopaminein reinforcement from cigarette
> smoking," says lead researcher Nicholas H. Caskey, of the Veterans
> Affairs Greater Los Angeles Healthcare System and the
> Neuropsychiatric
> Institute at UCLA's David Geffen School of Medicine.
>
> --------------------------------------------------------
>
> http://www.pslgroup.com/dg/13e79a.htm
>
> DG DISPATCH - AACAP: Nicotine Patches Improve Adult AD/HD Symptoms
>
> ------------------------------------------------------
>
> So anything which raises yourdopamineseems to be in order?
> Each of the hydroxypyridones and the siderophore influenceddopaminemetabolism by causing significant variations in both
> homovanillic acid anddopamineturnover.
>
> PMID: 7598744
>
> ----------------------------------------------------------
>
> Reward deficiency syndrome: a biogenetic model for the diagnosis and
> treatment of impulsive, addictive, and compulsive behaviors.
> J Psychoactive Drugs 2000 Nov;32 Suppl:i-iv, 1-112
> Blum K, Braverman ER, Holder JM, Lubar JF, Monastra VJ, Miller D,
> Lubar JO, Chen TJ, Comings DE
> Department of Biological Sciences, University of North Texas,
> Denton, Texas, USA.
>
> The dopaminergic system, and in particular thedopamineD2
> receptor, has been implicated in reward mechanisms.
> The net effect of neurotransmitter interaction at the mesolimbic
> brain region induces "reward" whendopamine(DA) is released
> from the neuron at the nucleus accumbens and interacts with
> adopamineD2 receptor.
> resultantaberrantbehaviors, Blum united this hypodopaminergic trait
> under the rubric of a reward deficiency syndrome.
>
> PMID: 11280926, UI: 21177392
>
> Who loves ya.
> Tom
>
mya...@gmail.com
> comes research suggesting that "thrill-seeking" behaviors may be hard-
> wired into the brain.
I was a thrill-seeker when I was 20 yrs. old, as I got into my 30's &
40's, much less so...
so is it really hard-wired, or do the dopamine auto-receptors decline
in some people as we age ?
Andrew Heenan
1. I'd not put too much credence on one research study (no reference
supplied!)
2. It didn't mention age (at least, if it did, you didn't share that)
3. Age effects most everything - except the quality of research, perhaps
4. There may be other factors (which also amy be 'hard wired') taking
priority. EG disease.
5. How much of a thrill seeker are you now *compared to others your age*?
6. Why have you crossposted to all these groups, NONE of which is likely to
have the expertise you seek?
Please don't cross-post ironjustice's threads to other groups - he thinks he
owns usenet, and gets very upset if you do anything without his permission.
And he's not been taking his tablets lately, so he may be dangerous.
You have been warned.
ironjustice
so is it really hard-wired, or do the dopamine auto-receptors decline
in some people as we age ?<<
Studies seem to show the receptors can be induced by choline to rise
or lower ..
sooo .. it is not hardwired .. in some at least ..
"Through either increased expression of D2 receptors or increased
dopamine release"
Effect of antidepressant drugs on dopamine D1 and D2 receptor
expression and dopamine release in the nucleus accumbens of the rat
byAinsworth K, Smith SE, Zetterstrom TS, Pei Q, Franklin M, Sharp T
University of Oxford,
Department of Clinical Pharmacology,
Radcliffe Infirmary, UK.
Psychopharmacology (Berl) 1998 Dec; 140(4):470-7
ABSTRACT
This study examined the effect of repeated treatment with the
antidepressant drugs, fluoxetine, desipramine and tranylcypromine, on
dopamine receptor expression (mRNA and binding site density) in sub-
regions of the nucleus accumbens and striatum of the rat. The effect
of these treatments on extracellular levels of dopamine in the
nucleus
accumbens was also measured. Experiments using in situ hybridisation
showed that the antidepressants caused a region-specific increase in
D2 mRNA, this effect being most prominent in the nucleus accumbens
shell. In contrast, none of the treatments increased D1 mRNA in any
of
the regions examined. Measurement of D2-like binding by receptor
autoradiography, using the ligand [3H]YM-09151-2, revealed that both
fluoxetine and desipramine increased D2-like binding in the nucleus
accumbens shell; fluoxetine had a similar effect in the nucleus
accumbens core. Tranylcypromine, however, had no effect on D2-like
binding in the nucleus accumbens but decreased binding in the
striatum. In micro-dialysis experiments, our data showed that levels
of extracellular dopamine in the nucleus accumbens were not altered
in
rats treated with either fluoxetine or desipramine, but increased by
tranylcypromine. From our findings, we propose that the
antidepressant
drugs tested enhance dopamine function in the nucleus accumbens
through either increased expression of post-synaptic D2 receptors
(fluoxetine and desipramine) or increased dopamine release
(tranylcypromine).
----------------------
"Antinociceptive effect of choline"
http://www.uludag.edu.tr/english/deptofmedpharm.htm
3) Pain and Analgesia: Antinociceptive effect of centrally and
peripherally administered drugs (such as choline and choline
derivatives), opioid tolerance, withdrawal, addiction and physical
dependence (effect of Gly-Gn on morphine tolerance, withdrawal,
addiction and physical dependence).
--------------
http://www.delano.com/ReferenceArticles/CDPc-aGPC-Sharpe.html
Another useful property shared by alpha GPC and CDP-choline is that
oral administration of either one increases the release of the
neurotransmitter dopamine in the brain.
ironjustice
it is not hardwired .. in some at least .. <<
"Other closely related, untreatable neurological disorders have now
been recognized as variants of tardive dyskinesia.
Tardive akathisia involves painful feelings of inner
tension and anxiety and a compulsive drive to move the body.
In the extreme, the individual undergoes internal torture and can
no longer sit still.
Tardive akathisia often develops in children who have been treated
for "hyperactivity", ironically and tragically subjecting them to
permanent
inner torture.
Tardive dystonia involves muscle spasms, frequently of the face, neck
and
shoulders, and it too can be disfiguring, disabling and agonizing. "
-------------------------
This study shows specifically the use of neuroleptics increases the
degree of
iron in the brain .. and is related to the development of tardive ..
Isr J Med Sci 1993 Sep;29(9):587-92
Iron modulates neuroleptic-induced effects related to the dopaminergic
system.
Ben-Shachar D, Livne E, Spanier I, Zuk R, Youdim MB
Department of Pharmacology, B. Rappaport Faculty of Medicine, Technion
Haifa,
Israel.
Long-term neuroleptic medication to schizophrenic patients is often
associated
with extrapyramidal side effects, of which tardive dyskinesia is the
most
severe.
The mechanism by which neuroleptics induce these side effects is
unclear.
The dopaminergic system is the main target with which the
neuroleptics
interact in the brain.
Intact dopaminergic function is dependent on normal iron metabolism.
Thus, the relationship between iron and the neuroleptics may
elucidate some new aspects of their mechanism of action.
Indeed, peripheral iron status plays a crucial role in
neuroleptic-induced dopamine supersensitivity.
Moreover, neuroleptics such as haloperidol and chlorpromazine,
alter the blood brain barrier (BBB) of the rat and enhance the
normally restricted iron transport into the brain.
Increased brain iron levels may be related to the toxic effects of
these drugs since clozapine, an atypical neuroleptic with a low
incidence of extrapyramidal side effects, prohibits iron uptake into
the brain but causes sedimentation of iron in brain blood vessels.
The demonstration that peripheral iron concentrations affect
neuroleptic-induced dopamine receptor supersensitivity as well as
iron
transport into the brain may have therapeutic significance.
In addition, the different potentials of typical and atypical
neuroleptics
to increase iron transport into the brain may be related to the
severity
of the side effects they induce and to the pathophysiology of tardive
dyskinesia.
Publication Types:
Review
Review, tutorial
PMID: 7901181, UI: 94042034
------------------------
This compilation of articles .. speaks to phosphatidylcholine ..
lecithin ..
simply lecithin ... which is a PREMIERE iron binder / chelator.
Clinical Trials and Studies
Treatment of tardive dyskinesia with lecithin.
Source Am J Psychiatry 1979 Nov;136(11):1458-60
Jackson IV, Nuttall EA,
Ibe IO, Perez-Cruet J.
Six patients with moderate or severe tardive dyskinesia participated
in a
14-day double-blind crossover comparison of placebo with 50 g/day of
lecithin.
There were no side effects, and Abnormal Involuntary Movement Scale
(AIMS)
ratings of videotaped examinations indicated significant improvement
in the
dyskinesias of all subjects during the lecithin trial, even with
concomitant
administration of a constant dose of neuroleptic medication to five
patients.
-----------------------
Choline and lecithin in the treatment of tardive dyskinesia:
preliminary
results from a pilot study.
Source Am J Psychiatry 1979 Jun;136(6):772-6
Gelenberg AJ, Doller-Wojcik JC, Growdon JH.
Tardive dyskinesia is thought to reflect increased dopaminergic
activity of the
central nervous system.
To compensate for this by increasing CNS cholinergic tone, the
authors administered oral choline and its natural dietary source,
lecithin, to 5 men
with mild to severe tardive dyskinesia in a nonblind trial.
Both choline and lecithin increased serum choline levels and improved
abnormal
movements in all patients.
Lecithin had fewer adverse effects.
---------------
Lecithin consumption raises serum-free-choline levels.
Source Lancet 1977 Jul 9;2(8028):68-9
Wurtman RJ, Hirsch
MJ, Growdon JH.
Consumption of choline by rats sequentially increases serum-choline,
brain-choline, and brain-acetylcholine concentrations.
In man consumption of choline increases in levels in the serum and
cerebrospinal fluid; its administration is an effective way of
treating tardive dyskinesia.
We found that oral lecithin is considerably more effective
in raising human serum-choline levels than an equivalent quantity of
choline chloride.
30 minutes after ingestion of choline chloride (2-3 g free base),
serum-choline levels rose by 86% and returned to normal values
within 4 hours; 1 hour after lecithin ingestion, these
levels rose by 265% and remained significantly raised for 12 hours.
Lecithin may therefore be the method of choice for accelerating
acetylcholine
synthesis by increasing the availability of choline, its precursor in
the blood.
---------------------
The use of cholinergic precursors in neuropsychiatric diseases.
Source Am J Clin Nutr 1982 Oct;36(4):709-20
Rosenberg GS, Davis KL.
Preclinical data suggest that cholinergic precursors such as choline
or
lecithin, increase levels of acetylcholine in specific brain
structures, and
under certain conditions may enhance cholinergic neurotransmission.
A variety of neuropsychiatric diseases including tardive dyskinesia.
Huntington's chorea, ataxias, Tourette's syndrome, schizophrenia,
affective illness, and senile dementia of the Alzheimer type, has
been
implicated with a general underactivity of central cholinergic
mechanisms.
Recent studies have investigated the possibility that cholinergic
precursor
loading strategies may provide viable treatments for these disorders
of presumed
cholinergic underactivity.
Extensive data demonstrate that the symptoms of tardive dyskinesia can
be reduced
by choline or lecithin, whereas investigations in other disorders have
met with mild
success, at best, or are still in preliminary stages.
Further controlled studies with choline or lecithin using broader dose
ranges, longer
durations of treatment, and concomitant administration of agents which
may increase
the release of acetylcholine are warranted.
---------------------------------
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
>
> "Through either increased expression of D2 receptors or increaseddopaminerelease"
>
> Effect of antidepressant drugs ondopamineD1 and D2 receptor
> expression anddopaminerelease in the nucleus accumbens of the rat
> byAinsworth K, Smith SE, Zetterstrom TS, Pei Q, Franklin M, Sharp T
> University of Oxford,
> Department of Clinical Pharmacology,
> Radcliffe Infirmary, UK.
> Psychopharmacology (Berl) 1998 Dec; 140(4):470-7
>
> ABSTRACT
> This study examined the effect of repeated treatment with the
> antidepressant drugs, fluoxetine, desipramine and tranylcypromine, ondopaminereceptor expression (mRNA and binding site density) in sub-
> regions of the nucleus accumbens and striatum of the rat. The effect
> of these treatments on extracellular levels ofdopaminein the
> nucleus
> accumbens was also measured. Experiments using in situ hybridisation
> showed that the antidepressants caused a region-specific increase in
> D2 mRNA, this effect being most prominent in the nucleus accumbens
> shell. In contrast, none of the treatments increased D1 mRNA in any
> of
> the regions examined. Measurement of D2-like binding by receptor
> autoradiography, using the ligand [3H]YM-09151-2, revealed that both
> fluoxetine and desipramine increased D2-like binding in the nucleus
> accumbens shell; fluoxetine had a similar effect in the nucleus
> accumbens core. Tranylcypromine, however, had no effect on D2-like
> binding in the nucleus accumbens but decreased binding in the
> striatum. In micro-dialysis experiments, our data showed that levels
> of extracellulardopaminein the nucleus accumbens were not altered
> in
> rats treated with either fluoxetine or desipramine, but increased by
> tranylcypromine. From our findings, we propose that the
> antidepressant
> drugs tested enhancedopaminefunction in the nucleus accumbens
> through either increased expression of post-synaptic D2 receptors
> (fluoxetine and desipramine) or increaseddopaminerelease
> (tranylcypromine).
> ----------------------
>
> "Antinociceptive effect of choline"
>
> http://www.uludag.edu.tr/english/deptofmedpharm.htm
>
> 3) Pain and Analgesia: Antinociceptive effect of centrally and
> peripherally administered drugs (such as choline and choline
> derivatives), opioid tolerance, withdrawal, addiction and physical
> dependence (effect of Gly-Gn on morphine tolerance, withdrawal,
> addiction and physical dependence).
> --------------
>
> http://www.delano.com/ReferenceArticles/CDPc-aGPC-Sharpe.html
>
> Another useful property shared by alpha GPC and CDP-choline is that
> oral administration of either one increases the release of the
> neurotransmitterdopaminein the brain.
>
> Who loves ya.
> Tom
>
ironjustice
dyskinesia <<
This could be what one might call a .. human model of iron induced
degeneration of the brain.
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=neuroferritin
Neuroferritinopathy
[Ferritin-Related Neurodegeneration, Hereditary Ferritinopathy]
Patrick F Chinnery, MBBS, PhD, MRCP
Department of Neurology
University of Newcastle upon Tyne Medical School
08082007neuroferritin
Initial Posting: April 25, 2005.
Last Update: August 8, 2007.
Summary
Disease characteristics. Neuroferritinopathy typically presents with
progressive adult-onset chorea or dystonia and subtle cognitive
deficits. The movement disorder involves additional limbs within five
to ten years and becomes more generalized within 20 years. When
present, asymmetry remains throughout the course of the disorder. The
majority of individuals develop a characteristic orofacial action-
specific dystonia related to speech that leads to dysarthrophonia.
Frontalis overactivity and orolingual dyskinesia are common. Cognitive
deficits, behavioral issues, and dysphagia become major problems with
time.
Diagnosis/testing. The diagnosis of neuroferritinopathy is based on
clinical findings including adult-onset chorea or dystonia and MRI or
CT showing excess iron storage or cystic degeneration. FTL is the only
gene currently known to be associated with neuroferritinopathy.
Molecular genetic testing is available clinically on a limited basis.
Management. Treatment of Manifestations: standard doses of levodopa,
tetrabenazine, benzhexol, sulpiride, diazepam, clonazepam, and deanol
for the movement disorder; botulinum toxin for painful focal dystonia.
Prevention of secondary complications: adequate caloric intake;
physiotherapy to maintain mobility and prevent contractures. Agents/
circumstances to avoid: Iron supplements are not recommended.
Genetic counseling. Neuroferritinopathy is inherited in an autosomal
dominant manner. Most individuals diagnosed with neuroferritinopathy
have an affected parent; the proportion of cases caused by de novo
mutations is unknown. Each child of an individual with
neuroferritinopathy has a 50% chance of inheriting the mutation.
Prenatal testing for pregnancies at increased risk may be available
through laboratories offering custom prenatal testing if the disease-
causing mutation in the family is known.
Diagnosis
Clinical Diagnosis
Neuroferritinopathy is suspected in individuals with the following:
Adult-onset progressive movement disorder (either chorea or dystonia)
Family history consistent with autosomal dominant transmission
Figure 1
a. Non-contrast brain CT symmetrical (more...)
Figure 1
a. Non-contrast brain CT symmetrical low signal in the putamina
b. T2-weighted MRI image showing cystic change involving the putamina
and globus pallidi and with increased signal in the heads of the
caudate nuclei
[Crompton et al 2005]
Evidence of excess iron storage on brain MRI, and in advanced cases,
cystic degeneration apparent on MRI and CT (see Figure 1)
Pathologic diagnosis. Neuroferritinopathy may be diagnosed post-mortem
based upon the characteristic basal ganglia cavitation, iron
deposition, and ferritin deposition accompanying neuronal loss.
Clinical Description
Natural History
Neuroferritinopathy typically presents in adult life (mean age 40
years), although onset in early teenage years and in the sixth decade
has been reported. The two presenting phenotypes are typically chorea
or dystonia, although one individual presented with late-onset
parkinsonism [Curtis et al 2001, Burn & Chinnery 2006, Chinnery et al
2007] and one family with cerebellar features [Vidal et al 2004]. The
movement disorder is progressive, involving additional limbs in five
to ten years and becoming more generalized within 20 years [Crompton
et al 2005]. Some individuals have striking asymmetry, which remains
throughout the course of the disorder. The majority of individuals
develop a characteristic orofacial action-specific dystonia related to
speech and leading to dysarthrophonia. Frontalis overactivity is
common, as is orolingual dyskinesia [Crompton et al 2005]. Eye
movements are well preserved throughout the disease course.
Subtle cognitive deficits are apparent in most individuals from the
outset [Crompton et al 2005]. Formal neuropsychometry reveals frontal/
subcortical deficits [Wills et al 2002] that are not as prominent as
those seen in Huntington disease. The cognitive and behavioral
component eventually becomes a major problem, as does dysphagia (see
Table 2).
Table 2. Clinical Findings in Individuals with Neuroferritinopathy
Presenting Phenotype Number Percent
Chorea 20/40 50%
Dystonia 17/40 42.5%
Parkinsonsim 3/40 7.5%
Asymmetry 25/40 62.5%
Speech and swallowing
Dysarthria 31/40 77.5%
Dysphonia 19/40 47.5%
Orolingual dyskinesia 26/40 65%
Dysphagia 16/40 40%
Eyes
Abnormal EOM 3/40 7.5%
Abnormal fundi 0/40 0%
Motor
Bradykinesia 14/40 35.5%
Tremor 0/40 0%
Dystonia 33/40 82.5%
Chorea 28/40 70%
Spasticity 0/40 0%
Normal power in nondystonic limbs 40/40 100%
Increased tendon reflexes 7/40 17.5%
Babinski reflex 0/40 0%
Ataxia 0/40 0%
Chinnery et al [2007]
Neuroimaging. From the outset, all affected individuals have evidence
of excess brain iron accumulation on MRI. Later stages are associated
with high signal on T2-MRI in the caudate, globus pallidus, putamen,
substantia nigra, and red nuclei, followed by cystic degeneration in
the caudate and putamen.
Histopathologic examination of three individuals confirmed evidence of
abnormal iron accumulation throughout the brain and particularly in
the basal ganglia [Hautot et al 2007]. Affected regions contain iron
and ferritin-positive spherical inclusions, often colocalizing with
microglia, oligodendrocytes, and neurons. Axonal swellings
(neuroaxonal spheroids) that were immunoreactive to ubiquitin, tau,
and neurofilaments were also present. Mancuso et al [2005] report
neuropathology in a person with C insertion at nt646-647 in FTL.
Serum ferritin. Serum ferritin concentrations were low (<20 µg/L) in
the majority of males and postmenopausal females but within normal
limits for premenopausal females [Chinnery et al 2007].
Genotype-Phenotype Correlations
A male with a 2-bp insertion in exon 4 of FTL (498InsTC) presented at
age 20 years with tremor followed by cerebellar signs at age 47 years
(dysarthria and ataxia, but no nystagmus), frontal/subcortical
cognitive impairment, dyskinesia (described as involuntary movement of
the face, resembling tardive dyskinesia, evolving into dystonic
posturing and buccolingual dyskinesia), brisk tendon reflexes, and
Babinski signs [Vidal et al 2004].
The 646InsC mutation was identified in a 63-year-old man presenting
with chorea, limb ataxia, areflexia, and bilateral extensor plantar
responses [Mancuso et al 2005].
The 474G>A (p.Ala96Thr) mutation was found in a man with mild non-
progressive mental retardation who developed a gait disturbance at age
13 years, followed by episodes of psychosis, which was treated with
neuroleptics. He subsequently developed an akinetic-rigid syndrome,
ataxia, and pyramidal signs. His 40-year-old mother also had the same
missense mutation and was asymptomatic [Maciel et al 2005].
With the exception of the reported cerebellar signs, the clinical
presentation of the persons with the 498InsTC and 646InsC mutations
fall within the spectrum seen in individuals with the 460InsA mutation
[Chinnery et al 2007]. The clinical picture was different in the
individual with a missense mutation, raising the possibility that
missense mutations cause a different phenotype, although neuroleptic
medication may have complicated the picture.
Prominent psychiatric features were noted in one individual with the
460InsA mutation [Wills et al 2002].
Despite the clinical differences, the neuroimaging was similar accross
cases involving the four different FTL mutations.
In simplex cases (i.e., only one affected individual in a family) and
in individuals with a family history consistent with autosomal
dominant inheritance, Huntington disease and spinocerebellar ataxia
type 17 should be considered; however, neither has the characteristic
findings on neuroimaging.
The phenotype in some individuals with neuroferrinopathy is strikingly
similar to that seen in early-onset primary dystonia (DYT1),
idiopathic torsion dystonia caused by the DYT1 GAG deletion [Crompton
et al 2005].
The orofacial dyskinesia seen in neuroferritinopathy resembles that
seen in choreoacanthocytosis and McLeod neuroacanthocytosis syndrome;
however, in contrast to these two disorders, the reflexes are
preserved in neuroferritinopathy.
Other dominantly inherited spinocerebellar ataxias with extrapyramidal
features, including SCA2 and SCA3, should also be considered.
In simplex and autosomal recessive cases, early-onset movement
disorders including Parkin-type of juvenile-onset Parkinson disease,
aceruloplasminemia, and Neimann-Pick type C should be considered.
These disorders do not show the characteristic neuroimaging of
neuroferrinopathy, but very similar MRI findings are found in
pantothenate kinase-associated neurodegeneration (PKAN, formerly known
as Hallervorden-Spatz disease, and also known as neurodegeneration
with brain iron accumulation type 2). Individuals with
neuroferritinopathy also show the "eye of the tiger" sign.
Basal ganglia abnormalities on MRI are also seen in mitochondrial
disorders, which should thus be considered in the differential
diagnosis (see Mitochondrial Disease Overview).
Management
Evaluations Following Initial Diagnosis
To establish the extent of disease in an individual diagnosed with
neuroferritinopathy, the following evaluations are recommended:
Treatment of Manifestations
The movement disorder is particularly resistant to conventional
therapy, but some response has been recorded with levodopa,
tetrabenazine, benzhexol, sulpiride, diazepam, clonazepam, and deanol
in standard doses [Crompton et al 2005].
Botulinum toxin is helpful for painful focal dystonia.
1 September 2004 (pfc) Original submission
-------------------------
http://focus.psychiatryonline.org/cgi/content/full/5/3/354
A Review of Antipsychotics in the Treatment of Obsessive Compulsive
Disorder
Naomi A. Fineberg, Tim M. Gale, and Thanusha Sivakumaran
Journal of Psychopharmacology 2006; 20(1):97–103
--------------------
Involvement of Activation of Dopamineraic Neuronal System in Learning
and Memory Deficits Associated with Experimental Mild Traumatic Brain
Injury
European Journal of Neuroscience
Ya-Ping Tang 1 , Yukihiro Noda 1 Toshitaka Nabeshima 1
1 Department of Neuropsychopharmacology and Hospital Pharmacy,
Nagoya University School of Medicine, Nagoya 466, Japan
ABSTRACT
Much evidence has indicated that a disturbance in dopamine
neurotransmission following mild to moderate traumatic brain injury is
involved in the development of post traumatic memory deficits. In the
present study we examined the effects of a dopamine receptor agonist
and some antagonists on latent learning and memory deficits associated
with a concussive traumatic brain injury in mice. Anaesthetized
animals were subjected to mild traumatic brain injury by dropping a
weight onto the head, and a single-dose injection of apomorphine (0.3–
3.0 mg/kg) or haloperidol (0.3–3.0 mg/kg) was made i.p. 15 min after
the trauma. One week later, a water-finding task consisting of an
acquisition trial, a retention test and a retest was employed to
assess learning and memory functions. Mice that had received a
traumatic brain injury were impaired in task performance, with
prolonged latencies for finding and drinking in the retention test and
retest. Administration of haloperidol but not of apomorphine
significantly shortened the prolonged latency in both of the tests,
indicating that antagonism of dopamine receptors is beneficial for the
recovery of post traumatic memory deficits. In order to evaluate which
receptor subtype plays the major role in this model, we examined the
effects of SCH-23390 (0.03–0.3 mg/kg), a D1 receptor antagonist, and
sulpiride (3.0–30 mg/kg), a D2 receptor antagonist, in the same
experimental paradigm. The results showed that administration of
sulpiride but not of SCH-23390 significantly improved the deficits in
task performance, indicating that D2 receptors are the major site of
action. However, combined treatment with SCH-23390 (0.03–0.3 mg/kg)
and sulpiride (3.0 mg/kg) at doses that had no effect when the
antagonists were given alone exerted a significant additive effect in
improving these deficits, indicating that interaction between D1 and
D2 receptors is involved in these processes. The present results
suggest that a dopaminergic mechanism contributes to the memory
dysfunction associated with traumatic brain injury.
KEYWORDS
D1 receptor • D2 receptor • dopamine • latent learning • traumatic
brain injury
Correspondence to Toshitaka Nabeshima, as above
Copyright 1997 European Neuroscience Association
Received 16 July 1996, revised 9 December 1996, accepted 14 March 1997
European Journal of Neuroscience
Volume 9 Issue 8, Pages 1720 - 1727
Published Online: 7 Apr 2006
Journal compilation © 2009 Federation of European Neuroscience
Societies and Blackwell Publishing Ltd
DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1460-9568.1997.tb01529.x About DOI
ironjustice
Tardive dyskinesia <<
Research article summary (published 29 Sep 2007):
Protective effect of rutin, a polyphenolic flavonoid against
haloperidol-induced orofacial dyskinesia and
associated behavioural, biochemical and neurochemical changes.
Full Abstract
The occurrence and irreversibility of tardive dyskinesia (TD), a motor
disorder of the orofacial region,
resulting from chronic neuroleptic treatment has been considered a
major clinical issue in the treatment of schizophrenia.
The molecular mechanism underlying the pathophysiology of TD is not
completely known.
Several animal studies have demonstrated an enhancement of oxidative
damage and increased glutamatergic transmission
after chronic administration of neuroleptics.
The present study investigated the effect of rutin, an antioxidant in
haloperidol-induced orofacial dyskinesia by using different
behavioural (orofacial dyskinetic movements, stereotypic rearing,
locomotor activity, percent retention), biochemical
[lipid peroxidation, reduced glutathione levels, antioxidant enzyme
levels (SOD and catalase)] and neurochemical
(neurotransmitter levels) parameters.
Chronic administration of haloperidol (1 mg/kg i.p. for 21 days)
significantly increased vacuous chewing movements,
tongue protrusions and facial jerking in rats, which were
significantly inhibited by rutin.
Chronic administration of haloperidol also resulted in dopamine
receptor sensitivity as evident by a well-shaped response
(initial decrease followed by increase) in locomotor activity and
stereotypic rearing and also decreased percent retention time
on elevated plus maze paradigm. Pretreatment with rutin reversed these
behavioural changes.
Besides, haloperidol also induced oxidative damage in all regions of
brain which was prevented by rutin, especially in the subcortical
region containing striatum.
Although turnover of dopamine and noradrenaline decreased in both
cortical and subcortical regions after chronic administration of
haloperidol, it was significantly reversed by high-dose rutin
treatment.
The findings of the present study suggested the involvement of free
radicals in the development of neuroleptic-induced orofacial
dyskinesia, a putative model of TD, and rutin as a possible
therapeutic option to treat this hyperkinetic movement disorder.
Bishnoi, Mahendra (M); Chopra, Kanwaljit (K); Kulkarni, Shrinivas K
(SK);
Centre with Potential for Excellence in Biomedical Sciences, Panjab
University, Chandigarh - 160 014, India.
Fundamental & clinical pharmacology (Fundam Clin Pharmacol)
Reference: 2007-Oct; vol 21 (issue 5) : pp 521-9
PMID: 17868205
---------------------------------
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
>
> This could be what one might call a .. human model of iron induced
> degeneration of the brain.
>
> http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=neurofer...
> the face, resemblingtardivedyskinesia, evolving into dystonic
> tetrabenazine, benzhexol, sulpiride, diazepam, ...
>
> read more »
ironjustice
wrote:"Multiple addictive, impulsive and compulsive behavioral
propensities,
such as severe alcoholism,cocaine, heroin, marijuana and nicotine
use,
glucose bingeing, pathological gambling, sex addiction,ADHD,
Tourette's Syndrome, autism, chronic violence, posttraumatic stress
disorder,
schizoid/avoidant cluster, conduct disorder and antisocialbehavior."
<<
Anti Dementia Drugs Could Aid in Binge Eating Prevention
View Votes
Submitted by staff on Tue, 09/02/2008 - 12:51pm.
From Reuters Health comes the news that binge eaters who have no
control over their binging may in fact be helped by the Alzheimers
drugs menantine, which will not apparently help to reduce the weight
of the patient, but will reduce their binging in both frequency and
severity.
McLean Hospital in Belmont Mass.,told Reuters that the study chief, Dr
Brian Brennan and his team had originally hypothesized that memantine
would reduce the binging and were not suprised by the study's results.
They were however surprised that the drug was not helpful in body
weight reduction.
A study previously done using memantine in just five people showed
that it did reduce both binging as well as body weight.
The binge eater very often will eat massive amounts of food,
completely losing control over their eating, but do not, like the
bulimia patient purge afterwards.
In this study, 16 binge eater took the memantine for twelve weeks and
found that their average number of binges decreased from about five to
one per week, which is a significant decrease.
There was however no effect on the weight,or anxiety or depression.
International Journal of Eating Disorders, September 2008.
ironjustice
"Multiple addictive, impulsive and compulsive behavioral
propensities, such as severe alcoholism,cocaine, heroin, marijuana
and nicotine use, glucose bingeing, pathological gambling, sex
addiction,ADHD, Tourette's Syndrome, autism, chronic violence,
posttraumatic stress
disorder, schizoid/avoidant cluster, conduct disorder and
antisocialbehavior." <<
FDA Approves Humanitarian Device Exemption For Deep Brain Stimulator
For Severe Obsessive-Compulsive Disorder
Main Category: Psychology / Psychiatry
Also Included In: Mental Health; Regulatory Affairs / Drug Approvals
Article Date: 21 Feb 2009 - 1:00 PST
The U.S. Food and Drug Administration approved a humanitarian device
exemption for the first implantable device that delivers intermittent
electrical therapy deep within the brain to suppress the symptoms
associated with severe obsessive-compulsive disorder (OCD).
The U.S. Food and Drug Administration today approved a humanitarian
device exemption for the first implantable device that delivers
intermittent electrical therapy deep within the brain to suppress the
symptoms associated with severe obsessive-compulsive disorder (OCD).
The Reclaim system uses a small electrical generator known as a pulse
generator to create electrical stimulation that blocks abnormal nerve
signals in the brain. This small battery-powered device is implanted
near the abdomen or the collar bone and connected to four electrodes
implanted in the brain through an insulated electric wire known as the
lead. Two device systems may be implanted to stimulate both sides of
the brain or one device may be implanted with two lead outputs.
Human device exemptions facilitate the development of medical devices
intended to treat or diagnose a disease or condition affecting fewer
than 4,000 people per year in the United States. To receive approval,
a company must demonstrate the safety and probable benefit of the
device.
"Deep brain stimulation using the Reclaim system may provide some
relief to certain patients with severe obsessive compulsive disorder
who have not responded to conventional therapy," said Daniel Schultz,
M.D., director, Center for Devices and Radiological Health. "However,
Reclaim is not a cure for OCD. Individual results will vary and
patients implanted with the device are likely to continue to have some
mild to moderate impairment in functioning and continue to require
medications."
OCD is an anxiety disorder and is characterized by recurrent, unwanted
thoughts (obsessions) and/or repetitive behaviors (compulsions).
Repetitive behaviors such as handwashing, counting, checking, or
cleaning are often performed with the hope of preventing obsessive
thoughts or making them go away. Performing these actions provides
only temporary relief, but not performing them markedly increases
anxiety.
The approval of the human device exemption was based on a review of
data from 26 patients with severe treatment resistant OCD who were
treated with the device at four sites. On average, patients had a 40
percent reduction in their symptoms after 12 months of therapy. While
all patients reported adverse events, the majority of these events
ended after an adjustment was made in the amount of electrical
stimulation.
Patients who require electroconvulsive shock therapy should not be
implanted with the Reclaim device. Other patients who should not use
the device include persons who will undergo magnetic resonance imaging
(MRI) or deep tissue heat treatment known as diathermy.
U.S. Food and Drug Administration
--------
Who loves ya.
Tom
ironjustice
"Multiple addictive, impulsive and compulsive behavioral
propensities, such as severe alcoholism,cocaine, heroin, marijuana
and nicotine use, glucose bingeing, pathological gambling, sex
addiction,ADHD, Tourette's Syndrome, autism, chronic violence,
posttraumatic stress
disorder, schizoid/avoidant cluster, conduct disorder and
antisocialbehavior." <<
'Anti-phobia pill' breaks link between memory and fear
18:00 15 February 2009 by Linda Geddes
Phobias and post-traumatic stress could be banished for good by taking
a commonly prescribed drug for blood pressure.
Previous studies had suggested that people who experienced traumatic
events such as rape and car crashes showed fewer signs of stress when
recalling the event if they had first been injected with the beta
blocker propranolol, but it was unclear whether the effect would be
permanent or not. Fearful memories often return, even after people
have been treated for them.
To investigate whether propranolol could stop fear returning in the
longer term, Merel Kindt and her colleagues at the University of
Amsterdam, the Netherlands, conditioned 60 healthy students to
associate a picture of a spider with an electric shock, so that they
would eventually be startled by the picture even in the absence of a
shock.
However, if the conditioned students were given oral propranolol
before seeing the picture, their startle response was eliminated.
What's more, it didn't return when the students were put through a
second round of conditioning that should have reinstated their fear -
suggesting that the association may have been permanently broken.
Shock tactics
Those given a placebo pill could eventually be trained not to be
startled by the spider picture, by repeatedly showing it to them in
the absence of a shock.
A similar technique is often used in phobia clinics - exposing people
with arachnophobia to spiders in a safe and calm environment, for
example. However, "even after successful treatment of anxiety
disorders many fears and phobias come back," says Kindt.
When those in the placebo group were given a series of electric
shocks, their fear of the spider also returned, while those in the
propranolol group continued to react calmly to the spider picture,
suggesting that the association may have been permanently erased, or
at least negated to such a point that it has no effect.
When people experience traumatic events, the body releases adrenaline
- also called epinephrine - which affects an area of the brain
involved in emotional processing called the amygdala, and makes an
emotional connection to the memory.
Recurrence fear
Reliving the memory triggers further release of adrenaline,
reinforcing the memory still further. Since propranolol blocks
adrenaline receptors in the amygdala, Kindt believes it may also block
this reinforcement process and break fear association.
"We can't prove that the memory has gone away, but it is at least
weakened so much that we can't find it anymore," says Kindt.
However, Chris Brewin, a memory expert at University College London,
UK, says the findings are interesting, but cautions that Kindt's group
only tested the volunteers over the course of three days.
"The fear might come back if they tested them several weeks later," he
says.
Also, Kindt only looked at the degree to which the volunteers were
startled - but conditions like post traumatic stress disorder often
involve other emotions such as anger and shame, and we don't know how
propranolol would affect them, he says.
Journal reference: Nature Neuroscience (DOI: 10.1038/nn.2271)
--------
Who loves ya.
Tom
> > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk- Hide quoted text -
%
i'm glad all these studies were done in the US ,
that way they don't apply to the rest of the world
ironjustice
investigate whether propranolol could stop fear returning in the
longer term <<
D-Propranolol Attenuates Lysosomal Iron Accumulation and
Oxidative Injury in Endothelial Cells
Journal of Pharmacology And Experimental Therapeutics
I. Tong Mak, Joanna J. Chmielinska, Lucie Nedelec, Armida Torres,
and William B. Weglicki
Departments of Biochemistry and Molecular Biology and Medicine,
Division of Experimental Medicine, George Washington University
Medical Center, Washington DC
The influence of selected -receptor blockers on iron overload and
oxidative stress in endothelial cells (ECs) was assessed.
Confluent bovine ECs were loaded with iron dextran (15 µM) for 24 h
and then exposed to dihydroxyfumarate (DHF), a source of reactive
oxygen species, for up to 2 h. Intracellular oxidant formation,
monitored
by fluorescence of 2',7'-dichlorofluorescin (DCF; 30 µM), increased
and
peaked at 30 min; total glutathione decreased by 52 ± 5% (p < 0.01)
at 60 min.
When the ECs were pretreated 30 min before iron loading with 1.25 to
10 µM D-propranolol, glutathione losses were attenuated 15 to 80%,
with EC50 = 3.1 µM.
D-Propranolol partially inhibited the DCF intensity increase, but
atenolol
up to 10 µM was ineffective.
At 2 h, caspase 3 activity was elevated 3.2 ± 0.3-fold (p < 0.01) in
the
iron-loaded and DHF-treated ECs, and cell survival, determined 24 h
later,
decreased 47 ± 6% (p < 0.01).
Ten micromoles of D-propranolol suppressed the caspase 3 activation
by 63% (p < 0.05) and preserved cell survival back to 88% of control
(p < 0.01).
In separate experiments, 24-h iron loading resulted in a 3.6 ± 0.8-
fold
increase in total EC iron determined by atomic absorption
spectroscopy;
D-propranolol at 5 µM reduced this increase to 1.5 ± 0.4-fold (p <
0.01)
of controls.
Microscopic observation by Perls' staining revealed that the
excessive
iron accumulated in vesicular endosomal/lysosomal structures, which
were substantially diminished by D-propranolol.
We previously showed that propranolol could readily concentrate into
the
lysosomes and raise the intralysosomal pH; it is suggested that the
lysosomotropic properties of D-propranolol retarded the EC iron
accumulation
and thereby conferred the protective effects against iron load-
mediated
cytotoxicity.
Received October 26, 2005; accepted February 1, 2006.
Address correspondence to: Dr. I. Tong Mak, Dept. of Biochemistry and
Molecular Biology, Division of Experimental Medicine, George
Washington University Medical Center, 2300 Eye Street, N.W. Ross Hall,
Rm 443, Washington DC 20037. E-mail: it...@gwu.edu
--------------------------
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Tom
> > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk-Hide quoted text -
>
> > - Show quoted text -- Hide quoted text -
ironjustice
investigate whether propranolol could stop fear returning in the
longer term D-Propranolol Attenuates Lysosomal Iron Accumulation and
Oxidative Injury in Endothelial Cells <<
This would give evidence of iron being involved due to the iron being
targeted from the blood spilled in the stroke.
Page last updated at 01:05 GMT, Wednesday, 25 February 2009
Stroke post-traumatic stress risk
Peter Chapman experienced PTSD after a brain haemorrhage
Many stroke sufferers are left with post-traumatic stress disorder
(PTSD), a British study suggests.
More than a third of 105 brain haemorrhage survivors tested positive
for the disorder, with flashbacks and painful memories of their
bleed.
This is a similar level to that found in soldiers returning from war
zones and amongst victims of sexual assault, Neurosurgery journal
reports.
The authors of the study say diagnosing and treating PTSD will aid
recovery.
Subarachnoid haemorrhage affects about 8,000 people in the UK each
year and is a sudden leak of blood over the surface of the brain.
Doctors do realise this type of stroke is stressful for the patient,
but they do not always ask the patient about anxiety and depression.
Someone needs to
Professor Allan House of the Stroke Association
Although emotional distress following this type of stroke is common,
it is under-recognised, they say, partly because clinicians tend to
focus on physical recovery.
The team from Durham University, the James Cook University Hospital in
Middlesbrough and the Newcastle General Hospital assessed the patients
at three months and again at 13 months after their subarachnoid
haemorrhage using a simple questionnaire.
At both stages, the answers given suggested 37% of the patients had
PTSD.
Traumatic event
The authors say their findings are not surprising, given the nature of
this type of stroke - its sudden, often unexpected and painful onset
in relatively young people, requiring emergency invasive
investigations and surgery.
Add to this having to deal with the fact that they have had a life-
threatening illness, it is understandable why many patients experience
emotional reactions, they say.
Adam Noble and his team say it is relatively easy to spot which stroke
patients are at greatest risk of PTSD by looking for signs of "poor"
coping, such as denial and self-blame.
These patients could be offered pre-emptive treatment, they say.
Mr Noble suggested tailored treatment such as group therapy "and,
where possible, prevention through teaching patients more appropriate
stress-coping strategies after they suffer a stroke".
Professor Allan House of the Stroke Association said: "Doctors do
realise this type of stroke is stressful for the patient, but they do
not always ask the patient about anxiety and depression. Someone needs
to.
"Some patients undoubtedly have PTSD, while others might have
depression or anxiety after a subarachnoid haemorrhage and it is
understandable why."
Peter Chapman, from Hartlepool, suffered a subarachnoid brain
haemorrhage at the age of 45 in 2001.
His PTSD was not picked up until two years after his stroke.
He said: "The first six months were the worst. I was so worried that
it might happen again and I have never shed so many tears in my life.
"If I had been tested and treated for PTSD right from the beginning,
my life would have been 500% better than what it has been, and would
have made the world of difference to my recovery."
-----------------
http://www.dragonsmedicalbulletin.com/b_clinical.html#6
Intracerebral Hemorrhage Patients Might Benefit From Iron Chelation
Treatment?
Abstract: Iron accumulates in the brain and contributes to brain
injury after intracerebral hemorrhage (ICH). The c-Jun-N-terminal
kinase (JNK) signaling pathway mediates cell death after ischemic
stroke, however, the involvement of JNK in ICH is not well known.
This study investigated whether the JNK signaling pathway is
activated
by iron after ICH. Male Sprague-Dawley rats received an infusion of
autologous whole blood (as a model of ICH) or ferrous iron into the
right basal ganglia and control rats had an infusion of saline. Some
ICH rats were treated with either deferoxamine (DFX), an iron
chelator, or vehicle.
Activation of JNK was measured by Western blot analysis and
immunohistochemistry. Free iron in cerebrospinal fluid (CSF) and
behavioral outcomes following ICH were also examined. We found that
activated JNK in the brain were increased after ICH, and an
intracerebral infusion of ferrous iron also upregulated brain
activated JNK. Free iron accumulated in CSF and systemic
administration of DFX after ICH reduces free iron contents in CSF,
suppresses JNK activation and improves ICH-induced neurological
deficits.
Our results demonstrated that the JNK signaling pathway is activated
after ICH and iron may contribute to this activation. DFX reduces
free
iron levels and attenuates activation of JNK suggesting iron
chelation
may be useful therapy for ICH patients.
Wan S, et al. Activation of c-Jun-N-terminal kinase in a rat model of
intracerebral hemorrhage: The role of iron. Neurosci Res. 2009;63(2):
100-5.
David
"ironjustice" <teamt...@hotmail.com> wrote in message
news:7be41765-4860-4782...@c36g2000yqn.googlegroups.com...
ironjustice
in some people as we age ? <<
This seems to show if the iron increases it seem to lower the
receptors and when
TARGETED with iron specific substances the D2 receptors CAN be ..
resurrected ..
"Rescued dopaminergic neurons in iron excess condition"
Neuroprotective Effect of Green Tea Polyphenol, EGCG in
Animal Model of Parkinson’s Disease
Manju B Reddy1, Qi Xu2, Ying Zhou1 and
Anumantha G Kanthasamy2
1 Food Science Human Nutrition,
2 Biomedical Sciences, Iowa State University, Ames, IA
ABSTRACT
Disrupted iron metabolism leading to excessive iron can promote
oxidative stress and subsequently induce neurodegeneration in
Parkinson’s disease (PD).
Major green tea polyphenol, (-)-epigallocatechin gallate (EGCG),
has both antioxidant and iron chelating properties.
In the present study, we determined the prevention and
neurorescue potential of EGCG (25mg/kg, oral administration)
against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP, 25 or 20 mg /kg , IP) induced neurotoxicity in
iron-overloaded mice (2.5% carbonyl iron for 7d). EGCG (7d)
prevented MPTP induced neurotoxicity by increasing the
locomotor activity (p<0.0001), the number of tyrosine hydroxylase
(TH) positive neurons (p<0.01), and striatal dopamine (DA)
concentrations (p<0.05).
Neurorescue effect was also seen in striatal DA with EGCG
(10d) administration after MPTP treatment.
In vitro studies with mice brain sections showed reduction
in TH activity with iron, in a dose dependent manner (10–100 µM)
and EGCG (100 µM) partially reversed the effect which may be
due to its iron binding capability.
Collectively, our results demonstrated that EGCG not only
prevented MPTP induced neurodegeneration, but also rescued
dopaminergic neurons after MPTP treatment in iron excess
condition.
Supported by Center for Designing Foods to Improve Nutrition,
Iowa State University.
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
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ironjustice
Disrupted iron metabolism leading to excessive iron can promote
oxidative stress and subsequently induce neurodegeneration in
Parkinson’s disease (PD). <<
Neuroprotective effect of the natural iron chelator, phytic acid in a
cell culture model of Parkinson's disease
Toxicology, Volume 245, Issues 1-2, 12 March 2008, Pages 101-108
Qi Xu, Anumantha G. Kanthasamy, Manju B. Reddy
Abstract
Disrupted iron metabolism and excess iron accumulation has been
reported in the brains of Parkinson's disease (PD) patients.
Because excessive iron can induce oxidative stress subsequently
causing degradation of nigral dopaminergic neurons in PD, we
determined the protective effect of a naturally occurring iron
chelator,
phytic acid (IP6), on 1-methyl-4-phenylpyridinium (MPP+)-induced
cell death in immortalized rat mesencephalic/dopaminergic cells.
Cell death was induced with MPP+ in normal and iron-excess
conditions and cytotoxicity was measured by thiazolyl blue
tetrazolium bromide (MTT assay) and trypan blue staining.
Apoptotic cell death was also measured with caspase-3
activity, DNA fragmentation, and Hoechst nuclear staining.
Compared to MPP+ treatment, IP6 (30 ìmol/L) increased cell
viability by 19% (P < 0.05) and decreased cell death by 22%
(P < 0.05).
A threefold increase in caspase-3 activity (P < 0.001) and a
twofold increase in DNA fragmentation (P < 0.05) with MPP+
treatment was decreased by 55% (P < 0.01) and 52%
(P < 0.05), respectively with IP6.
Cell survival was increased by 18% (P < 0.05) and 42%
(P < 0.001) with 30 and 100 ìmol/L of IP6, respectively
in iron-excess conditions.
A 40% and 52% (P < 0.001) protection was observed in
caspase-3 activity with 30 and 100 ìmol/L IP6, respectively
in iron-excess condition.
Similarly, a 45% reduction (P < 0.001) in DNA fragmentation
was found with 100 ìmol/L IP6.
In addition, Hoechst nuclear staining results confirmed
the protective effect of IP6 against apoptosis.
Similar protection was also observed with the differentiated
cells.
Collectively, our results demonstrate a significant
neuroprotective effect of phytate in a cell culture model
of PD.
----------------------------------------------------------------------------------
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Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
> On Feb 4, 7:14 am, myan...@gmail.com wrote:
> Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh
>
> Man Is A Herbivore!http://tinyurl.com/a3cc3
>
> DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk
ironjustice
wrote:dopamine <<
"Increasing iron might be responsible for dopamine oxidation"
Effect of dietary iron overload in rat brain: oxidative stress,
neurotransmitter level and serum metal ion in relation to
neurodegenerative disorders.
Elseweidy MM, Abd El-Baky AE
Indian J Exp Biol 2008 Dec; 46(12):855-8.
Excess iron causes cell injury by reacting with superoxide anions
(O2*) and hydrogen peroxide (H2O2) and producing hydroxyl radical
(OH*) and reactive oxygen species (ROS).
In the present study, albino rats were fed with biscuits enriched
with ferrous sulphate (0.3% w/w) for 10 weeks to have overload iron
conditions and observed a significant decrease in serum chromium,
brain serotonin and dopamine, while iron and zinc increased
significantly in serum.
Increasing iron level might be responsible for accelerated dopamine
oxidation with subsequent quinone formation.
Indian journal of experimental biology [Indian J Exp Biol]
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
> On Feb 28, 5:02 pm, ironjustice <teamtan...@hotmail.com> wrote:
> Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh
>
> Man Is A Herbivore!http://tinyurl.com/4rq595
>
> DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk
> > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk- Hide quoted text -
ironjustice
neurotransmitter <<
1 drug may help people both lay down the drink and put out the
cigarette
Published: Monday, March 2, 2009 - 12:32 in Health & Medicine
A popular smoking cessation drug dramatically reduced the amount a
heavy drinker will consume, a new Yale School of Medicine study has
found. Heavy-drinking smokers in a laboratory setting were much less
likely to drink after taking the drug varenicline compared to those
taking a placebo, according to a study published online in the journal
Biological Psychiatry. The group taking varenicline, sold as a stop-
smoking aid under the name Chantix, reported feeling fewer cravings
for alcohol and less intoxicated when they did drink. They were also
much more likely to remain abstinent after being offered drinks than
those who received a placebo, the study found.
Additionally, there were no adverse effects associated with combining
varenicline with alcohol in the doses studied. When combined with low
doses of alcohol, varenicline did not change blood pressure or heart
rate, nor did it seem to induce nausea or dizziness.
"We anticipate that the results of this preliminary study will trigger
clinical trials of varenicline as a primary treatment for alcohol use
disorders, and as a potential dual treatment for alcohol and tobacco
use disorders," said Sherry McKee, associate professor of psychiatry
at the Yale School of Medicine and lead author of the study.
Smokers are more likely to drink alcohol and to consume greater
quantities of alcohol, and they are four times more likely to meet
criteria for alcohol use disorders. Diseases related to tobacco use
are the leading causes of death in alcoholics.
"A medication such as varenicline, which may target shared biological
systems in alcohol and nicotine use, holds promise as a treatment for
individuals with both disorders" according to McKee.
McKee said that 80% of participants receiving varenicline did not take
a drink at all, compared to 30% of the placebo group. The findings
suggest that varenicline has the potential to be at least as effective
in reducing drinking as naltrexone, another drug found to reduce
alcohol consumption in heavy drinkers. Unlike naltrexone, varenicline
is not metabolized by the liver and may be safe to use by those with
impaired liver function, a frequent consequence of heavy alcohol use,
McKee said.
Source: Yale University
Who loves ya.
Tom
> Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh
>
> Man Is A Herbivore!http://tinyurl.com/a3cc3
>
> DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk
> > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk-Hide quoted text -
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> > - Show quoted text -- Hide quoted text -
ironjustice
addictive, impulsive and compulsive behavioral
propensities, such as severe alcoholism,cocaine, heroin,
marijuana and nicotine use, glucose bingeing, pathological
chronic violence, posttraumatic stress disorder, schizoid/avoidant
cluster, conduct disorder and antisocialbehavior." <<
Cognitive enhancement drug may also cause addiction
Modafinil's effect on the brain suggests it could be addictive for
some.
Heidi Ledford
A drug used to treat narcolepsy — and often taken to increase
alertness and improve cognitive performance — may have the potential
to become addictive, a small pilot study has shown.
Brain-imaging studies performed on ten men before and after taking the
drug, called modafinil (Provigil), showed that it boosts levels of a
chemical called dopamine, which influences the brain's reward system1.
Drugs of abuse, from tobacco to heroin, also impact dopamine levels,
particularly in an area of the brain called the nucleus accumbens. In
the new study, published on 17 March by the Journal of the American
Medical Association, modafinil also increased dopamine in that
region.
The effect of cognitive-enhancement drugs on the brain is not well
known.GettyIt is an indirect measure of the propensity to trigger
addiction, and patients rarely become dependent upon modafinil, notes
Martha Farah, director of the Center for Cognitive Neuroscience at the
University of Pennsylvania in Philadelphia, who was not involved with
the study. "However, we know that drug dependence is a result of
drugs' effects on the brain's reward system," she says, "and so
finding that modafinil affects this system is also relevant and should
prompt us to look more carefully at the risks of dependence for this
drug."
Use and abuse
Meanwhile, the results should not prompt those who take modafinil for
medical conditions to discontinue the drug, says study author Nora
Volkow, director of the National Institute on Drug Abuse in Bethesda,
Maryland. Physicians, however, should be aware that addiction is a
possibility and can tell their patients to watch for signs of
dependency, she says.
The US Food and Drug Administration has approved modafinil to treat
narcolepsy and some other sleep disorders, and doctors will sometimes
prescribe the drug off label to treat attention-deficit disorder and
schizophrenia. In recent years, the drug has joined the ranks of
methylphenidate (Ritalin) and amphetamines — drugs which are misused ,
often by students, to improve cognitive function. A recent survey by
Nature found that of those who use drugs to improve focus, 44% have
tried modafinil.
Addiction is a familiar consequence of taking stimulants such as
amphetamines or cocaine and has been found among those who take
methylphenidate as well, although generally only when abnormally high
doses of the drug are taken, or when the drug is administered by
injection rather than orally. But researchers thought modafinil acted
via a different mechanism — one that did not affect the dopamine
system.
"People were saying, 'With Provigil, we don't have to worry'," says
Volkow. "Unfortunately, that is not the case. As of now, all of the
medications that are being used with the expectation of improving
cognitive performance have the potential to produce addiction."
Addictive qualities
Modafinil was thought to promote wakefulness by increasing responses
to brain hormones called orexins. But animal studies showed that
rodents that lack dopamine receptors are unresponsive to the drug, and
in 2006, researchers found that modafinil affects dopamine levels in
the brains of rhesus macaques2.
The animals in these studies were often given high doses of the drug
by injection, whereas humans would take the drug orally and at lower
doses. So Volkow, along with Joanna Fowler of Brookhaven National
Laboratory in Upton, New York, and their colleagues, decided the
effects needed to be analyzed directly in humans.
Volkow and her team administered labelled compounds that bound to free
dopamine receptors and dopamine transporters to ten paid volunteers
before and after the volunteers took modafinil. By imaging these
compounds, the team was able to estimate how many receptors and
transporters in the brain were bound to dopamine after taking the
drug. They found that modafinil blocked dopamine transporters in the
brain, resulting in an increase in dopamine concentration.
The study was performed in only ten subjects, but that is not unusual
for labour-intensive brain-imaging studies, notes Michael Minzenberg,
who studies neurochemical systems at the University of California,
Davis Health System Imaging Research Center. Pilot studies such as
this may not capture the full variation in how individuals within a
population will respond to the drug, he says, but the impact on the
dopamine system is clear.
Still, that dopamine connection may not tell the full story, says
Bertha Madras, professor of psychobiology at Harvard Medical School in
Southborough, Massachusetts. For example, some drugs increase dopamine
levels but have other properties that make them aversive rather than
addictive. "The full spectrum of the pharmacology of the drug is what
drives the abuse potential," she says.
References
Volkow, N. D. et al. JAMA 301, 1148-1154 (2009).
Madras, B. K. et al. J. Pharmacol. Exp. Therapeutics 319, 561-569
(2006).
Published online 17 March 2009 | Nature | doi:10.1038/news.2009.170
Who loves ya.
Tom
> Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh
>
> Man Is A Herbivore!http://tinyurl.com/a3cc3
>
> DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk
>
>
>
> > On Feb 28, 5:37 pm, ironjustice <teamtan...@hotmail.com>
> > wrote:dopamine<<
>
> > "Increasing iron might be responsible fordopamineoxidation"
>
> > Effect of dietary iron overload in rat brain: oxidative stress,
> > neurotransmitter level and serum metal ion in relation to
> > neurodegenerative disorders.
> > Elseweidy MM, Abd El-Baky AE
> > Indian J Exp Biol 2008 Dec; 46(12):855-8.
>
> > Excess iron causes cell injury by reacting with superoxide anions
> > (O2*) and hydrogen peroxide (H2O2) and producing hydroxyl radical
> > (OH*) and reactive oxygen species (ROS).
> > In the present study, albino rats were fed with biscuits enriched
> > with ferrous sulphate (0.3% w/w) for 10 weeks to have overload iron
> > conditions and observed a significant decrease in serum chromium,
> > brain serotonin anddopamine, while iron and zinc increased
> > > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk-Hidequoted text -
%
so
ironjustice
"Multiple addictive, impulsive and compulsive behavioral
propensities, such as severe alcoholism,cocaine, heroin,
marijuana and nicotine use, glucose bingeing, pathological
gambling, sex addiction, ADHD, Tourette's Syndrome, autism,
chronic violence, posttraumatic stress disorder, schizoid/avoidant
cluster, conduct disorder and antisocialbehavior." <<
Choline ..
"Anterior cingulate functioning in attention deficit hyperactivity
disorder (ADHD)"
"Role of Anterior Cingulate Cortex in Parkinson's Disease"
"Fewer D2 receptors in the anterior cingulate cortex in patients with
schizophrenia"
"The anterior cingulate cortex in bipolar disorder "
Brain Abnormality Found in Boys with Attention Deficit Hyperactivity
Disorder
18 March 2009
Researchers trying to uncover the mechanisms that cause attention
deficit hyperactivity disorder (ADHD) and conduct disorder have found
an abnormality in the brains of adolescent boys suffering from the
conditions, but not where they expected to find it.
Boys with either or both of these disorders exhibited a different
pattern of brain activity than normally developing boys when they
played a simple game that sometimes gave them a monetary reward for
correct answers, according to a new study by a University of
Washington research team.
The research focused on two brain areas, the striatum and anterior
cingulate cortex. The striatal region is a network of structures in
the mid brain that motivates people to engage in pleasurable or
rewarding behavior. The anterior cingulate is higher in the brain and
normally activates when an expected reward stops. However, this
process, called extinction, doesn't occur, at least as quickly, in
boys with attention deficit hyperactivity or conduct disorders.
Instead, the striatal region continues to be activated, said Theodore
Beauchaine, a UW associate professor of psychology and senior author
of the paper.
"When children engage in impulsive behavior they are looking to
stimulate themselves and have fun. Children with attention deficit
hyperactivity disorder are always looking to have fun and that is what
gets them in trouble," he said. "A behavior should stop when the
reward stops. When you stop the reward for children with these
disorders, they continue to focus on the reward long afterward and the
anterior cingulate does not appear to become activated."
Attention deficit hyperactivity disorder (ADHD) is one of the most
common mental disorders among children, affecting between 3 and 5
percent of school-age youngsters, or an estimated 2 million.
The researchers used functional magnetic resonance imaging (fMRI) to
compare brain activity in 19 boys with either or both disorders and 11
normally developing boys. The adolescents ranged in age from 12 to 16.
Their brains were scanned while they played the game. The boys looked
at a screen and there was a button under each of their thumbs. When a
light flashed on the left or right side of the screen they were
instructed to press the button on that side. The screen lit up very
fast, up to 100 times a minute. The boys received five cents for each
correct response and could win up to $50. They were not penalized for
wrong answers and their accumulated winnings showed up on the screen.
Each boy had four five-minute blocks of trials. The first and third
trials involved opportunities to earn money. The second and fourth
trials did not involve winning money, but the boys were told to keep
playing the game because the game would change at some point.
Beauchaine said there was no difference in the accuracy or speed – the
behavioral response – between the two groups. But there was a
difference in brain activation. When the non-reward blocks came up the
anterior cingulate lit up for normally developing boys, but those with
either of the disorders, which frequently co-occur, continued to only
show activation in the striatum.
"This shows there is an abnormality, but not in the place we expected
to find it. We expected to find a difference in the way the striatum
functions, but instead found it in anterior cingulate functioning,"
said Beauchaine.
Source: EurekAlert
----------
Decreased dopamine D2 receptor binding in the anterior cingulate
cortex in schizophrenia.
Arch Gen Psychiatry. 2002 Jan;59(1):25-30.Related Articles, Links
Comment in:
Arch Gen Psychiatry. 2002 Jan;59(1):31-4.
Suhara T, Okubo Y, Yasuno F, Sudo Y, Inoue M, Ichimiya T,
Nakashima Y, Nakayama K, Tanada S, Suzuki K, Halldin C, Farde L.
Division of Advanced Technology for Medical Imaging,
National Institute of Radiological Sciences, 9-1,
Anagawa 4-Chome, Inage-ku, Chiba-shi,
263-8555 Japan. suh...@nirs.go.jp
BACKGROUND:
The clinical efficacy of dopamine D2 receptor antagonism on the
psychotic symptoms of schizophrenia has been widely demonstrated.
However, most in vivo imaging studies have not been able to detect
significant changes in striatal D2 receptors in schizophrenia.
On the other hand, a number of studies have reported abnormalities
in the cerebral cortex of schizophrenia.
The aim of this study was to examine the extrastriatal D2 receptors
of patients with schizophrenia.
METHODS:
Eleven drug-naive male patients with schizophrenia were examined
with positron emission tomography using carbon 11-labeled FLB 457.
Symptoms were assessed using the Brief Psychiatric Rating Scale.
Eighteen healthy controls were used for comparison.
Region-of-interest analysis was performed using the reference tissue
method, and binding potential (BP) was used for the index of dopamine
D2 receptor binding. RESULTS: The BP value was significantly lower,
by about 12.5%, in the anterior cingulate cortex in drug-naive
patients
with schizophrenia than in healthy controls.
A significant negative correlation was observed between BP in the
anterior cingulate cortex and the positive symptom score on Brief
Psychiatric Rating Scale.
CONCLUSIONS:
The lower BP values indicate fewer D2 receptors in the anterior
cingulate cortex in patients with schizophrenia.
Alterations in D2 receptor function in the extrastriatal region may
underlie the positive symptoms of schizophrenia.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
PMID: 11779278
Cerebral Cortex 1992; 2:513-525
© Oxford University Press 1992
--------------------------------------------------------------------------------
Attention and Sentence Processing Deficits in Parkinson's
Disease: The Role of Anterior Cingulate Cortex
Murray Grossman, Peter Crino, Martin Reivich,
Matthew B. Stem and Howard I. Hurtig
Department of Neurology, University of Pennsylvania School
of Medicine, and The Graduate Hospital Philadelphia,
Pennsylvania 19104-4283
Correspondence should be addressed to Murray Grossman,
Cognitive Neurology Section, Department of Neurology,
Hospital of the University of Pennsylvania,
3400 Spruce Street, Philadelphia, PA 19104-4283
Parkinson's disease (PD) is a complex neurodegenerative condition
involving a motor disorder that is related to reduced dopaminergic
input to the striatum.
Intellectual deficits are also seen in PD, but the pathophysiology
of these difficulties is poorly understood.
Regional cerebral blood flow (rCBF) was studied in neurologically
intact subjects during the performance of attention-demanding,
sentence processing tasks using positron emission tomography
(PET). T
he results demonstrated significantly increased rCBF in a distributed
set of cerebral regions during the detection of an adjective or a
particular agent in a sentence, including anterior cingulate cortex,
left inferior and middle frontal cortex, left inferior temporo-
occipital
cortex, posterolateral temporal cortex, left caudate, and left
thalamus.
We identified defects in this cerebral network by studying PD
patients
with two PET techniques.
Resting PET studies revealed a significant correlation between
regional cerebral glucose metabolism in anterior cingulate cortex
and deficits in attending to subtle grammatical aspects of sentences.
Studies of PD patients with the PET activation technique revealed
little
change in anterior cingulate and left frontal CBF during performance
of
the adjective detection or agent detection tasks.
These data suggest that a defect in anterior cingulate cortex
contributes
to the cognitive impairments observed in PD.
---------------
Choline, myo-inositol and mood in bipolar disorder: a proton magnetic
resonance spectroscopic imaging study of the anterior cingulate
cortex.
Moore CM, Breeze JL, Gruber SA, Babb SM, Frederick BB,
Villafuerte RA, Stoll AL, Hennen J, Yurgelun-Todd DA, Cohen BM,
Renshaw PF.
Bipolar Disord 2000 Sep;2(3 Pt 2):207-16
OBJECTIVES:
Alterations in choline and myo-inositol metabolism have been noted
in bipolar disorder, and the therapeutic efficacy of lithium in mania
may be
related to these effects.
We wished to determine the relationship between anterior cingulate
cortex
choline and myo-inositol levels, assessed using proton magnetic
resonance
spectroscopic imaging (MRSI), and mood state in subjects with bipolar
disorder.
METHODS:
Serial assessments of anterior cingulate cortex choline and myo-
inositol
metabolism were performed in nine subjects with bipolar disorder,
taking
either lithium or valproate, and 14 controls.
Each bipolar subject was examined between one and four times (3.1 +/-
1.3).
On the occasion of each examination, standardized ratings of both
depression
and mania were recorded.
RESULTS:
In the left cingulate cortex, the bipolar subjects' depression ratings
correlated
positively with MRSI measures of Cho/Cr-PCr.
In the right cingulate cortex, the Cho/Cr-PCr ratio was significantly
higher in
subjects with bipolar disorder compared with control subjects.
In addition, bipolar subjects not taking antidepressants had a
significantly
higher right cingulate cortex Cho/Cr-PCr ratio compared with patients
taking
antidepressants or controls.
No clinical or drug-related changes were observed for the Ino/Cr-PCr
ratio.
CONCLUSIONS:
The results of this study suggest that bipolar disorder is associated
with
alterations in the metabolism of cytosolic, choline-containing
compounds in
the anterior cingulate cortex.
As this resonance arises primarily from phosphocholine and
glycerophosphocholine, both of which are metabolites of
phosphatidylcholine,
these results are consistent with impaired intraneuronal signaling
mechanisms.
%
so
Ken
>
> read more »
ironjustice
Shteater ..
Take it to alt.kook.mutated.shteating.freaks .. like you been told ..
Choline ..
Source: EurekAlert
----------
PMID: 11779278
--------------------------------------------------------------------------------
---------------
%
so
Ken
(~)
ironjustice
%
take it on a tuna boat
Ken
(~)
ironjustice
snip <<
Shteater .. I told you ain't allowed ..
But you continue in the charade that you are someone to "be
contended with" ..
Well shteater .. you are .. **nuts** .. understand ..
Assylum .. bound ..
Juba
> wrote:
>
>> I(O O)I
>> (~)
Gigglz wrote:
> <pardon interruption>
>
> what a childish, moronic buffoon you are.
> is this really ALL you have in your life? how pathetic.
Apparently so.
>
> call me whatever you wish, because i could hardly care what someone of
> your maturity level and caliber thinks of me.
>
> i just can't believe that you don't have anything better to do with
> your time/life. hospitals and nursing homes need volunteers...sick
> people need help...homeless shelters need volunteers.
>
> good luck with your unproductive life!
Well, he is a "winner" in one respect. His Kook Faq is still rising in
the Google search results. :o)
#4 for "Ken Kellogg"
#1 for "Flakey714"
http://www.google.com/search?hl=en&safe=off&rlz=1B3GGGL_enUS177US229&num=30&q=flakey714&btnG=Search
#2 for "811 Billings St"
--
Juba
Read The Ken Kellogg Kook Faq
http://kook.us/ken-kellogg.htm
ironjustice
snip <<
Shteaters congregating again ..
I told you shteaters you ain't allowed ..
Take it to alt.kook.mutated.shteating.freaks .. like you been TOLD ..
Screwball mutated shteating freaks ..
Ken
(~)
%
> I(O O)I
> (~)
what fantastic talent ,
and to think you pay ,
a service provider to the that
Ken
More of a drawing but thank ya anyhows...K
ironjustice
No shteating mutated screwballs .. allowed ..
Take it to alt.kook.mutated.shteating.freaks .. like you been TOLD ..
Screwball mutated shteating freak ..
%
Ken
(~)
%
> I(O O)I
> (~)
canuck puts it right back again ,
and says you pay a service provider to do that ,
talk about BS , what a cartoon
( * | * )
*
Ken
You're rather easily entertained
%
you're rather easily used
ironjustice
%
get to sit there mouth shut and read it
ironjustice
i do what i like and you , get to sit there mouth shut and read it <<
You actually think I read the stuff from shteaters .. ?
Take some advice ..
Don't read what shteaters .. post ..
It is sorta like puke for the brain ..
THAT is just like it sounds ..
Choline ..
Source: EurekAlert
----------
PMID: 11779278
--------------------------------------------------------------------------------
Ken
I(O O)I
(~)
ironjustice
snip <<
Stay out of the groups there .. shteater ..
%
Ken
>
> read more »
%
Juba
> what
>
Please don't stalk the stalker who is stalking the Ironman troll.
--
Juba
www.masterjuba.com
ironjustice
Ken
(~)
ironjustice
snip <<
WHAT did I say about .. lily livered screwball shteating freaks ..
shteater .. ?
Take it to
alt.kook.lily.livered.screwball.mutated.shteating.freaks ..
Ken
-~-
ironjustice
Ken
(-)
%
> I(O O)I
> (-)
hi everybody
( O|O )
*
ironjustice
Michael B
about stuff he didn't understand, except for it being about young boys.
ironjustice
<<
Shteater .. you've been told to stay off my threads ..
You .. DOOO .. it ..
Understand .. creepo .. ?
Ken
(~)
%
ironjustice
screwball .. freaks .. again ..
Michael B
break your copraphagia habit, you need to make sure your
magnesium and iron levels are adequate. Might also want
to take Vitamin C for better iron absorption. Gotta correct
those deficiencies of yours one way or another. You could
be more socially acceptable if you would get rid of your
poop-breath.
And how about your absorption with adolescent boys? You
probably need to get out of your mother's basement and go
join the YMCA. You could learn to sing with the boys.
Well, Tom, enough for now. Hope this helps you realize that
your personal problems that you have shared with us are
completely understandable and we don't hate you for them.
But you really need to get some help. You could get some
nasty pathogens from eating all that fecal matter. Even if it's
your own. But you realize that already.
ironjustice
I told YOU **specifically** .. screwball shteating .. freak ..
Stay OFF my threads ..
Understand .. freak ..?
Go eat some sht somewhere ..
This thread seems again to be inundated by mutated shteating
screwball .. freaks .. again ..
"Multiple addictive, impulsive and compulsive behavioral
Ken
%
Ken
%
news:CbOdnaIjV5HY2FPU...@giganews.com:
> hi
>
>
>
i sure am a pathetic cunt
somebody should follow me around
and make my life hell
i wonder if it will be me
Michael B
{;-Þ
ironjustice
allowed .. do you shteaters fail to understand .. ?
Take your shteating to
alt.kook.lily.livered.screwball.mutated.shteating.freaks ..
Michael B
of the stuff you plagiarise, you need to be able to at least be
understanding SOMETHING you post. So we give you an
opportunity to talk about some of your personal issues. Like
your fondness of adolescent boys, your devotion to feces
consumption, your overall inability to articulate your need to
get a real job and leave your mom's basement.
You don't even understand the rudimentary physiology of iron
absorption, and can't even respond to basic questions on the
other topics you post about, either. So you must feel pretty
useless. The only time you see some self-worth is when you're
complaining about people getting onto ....'your threads'. Which
is obviously (obvious to others than yourself) a stupid stance
to take.
Anyone with a keyboard can post to any subject. That means
even you, Tom. But for your sake, it would be better if you
didn't make it so apparent that you are so astonishingly stupid.
Ken
> Just doing you a favor, Tom. Since you have no understanding
> of the stuff you plagiarise, you need to be able to at least be
> understanding SOMETHING you post. So we give you an
> opportunity to talk about some of your personal issues. Like
> your fondness of adolescent boys, your devotion to feces
> consumption, your overall inability to articulate your need to
> get a real job and leave your mom's basement.
>
> You don't even understand the rudimentary physiology of iron
> absorption, and can't even respond to basic questions on the
> other topics you post about, either. So you must feel pretty
> useless. The only time you see some self-worth is when you're
> complaining about people getting onto ....'your threads'. Which
> is obviously (obvious to others than yourself) a stupid stance
> to take.
>
> Anyone with a keyboard can post to any subject. That means
> even you, Tom. But for your sake, it would be better if you
> didn't make it so apparent that you are so astonishingly stupid.
Exactly
ironjustice
You screwball shteating freaks .. are NOT allowed on my threads ..
Ken
%
Ken
ironjustice
NO screwball shteating freaks .. are NOT allowed on my threads ..
You find English hard to understand .. shteater .. ?
Michael B
the only one qualified to post on one with that name.
At least, according to you.
But you're welcome to stay there, we'll leave you alone.
Alone.
That's you.
ironjustice
<<
You find English hard to understand .. shteater .. ?
Screwball shteating disease ridden freaks .. are NOT allowed on my
threads ..
You were TOLD to take your shteating to
alt.kook.lily.livered.disease.ridden.screwball.mutated.shteating.freaks ..
Or something that sounds like that ..
Michael B
of your house? (Actually, your mother's house, but same idea).
Do you swing your arms and jump around when you are telling
someone that you demand that they park elsewhere? Must be
quite a show, obviously ineffective on your part. Kinda like your
trying to tell everybody else to stay off 'your threads'.
It must be terribly annoying to you, maybe like parents being
concerned about your paying attention to their adolescent sons.
But you need to get over it. Get a real job, like working at the
Salvation Army. Get away from your mom's basement, try new
things in life.
Does it seem that I have trouble understanding English? Ever
consider that it might be you that doesn't understand? You
might want to glance at some of those empty plastic
containers laying around, you may be needing to renew
some prescriptions.
ironjustice
<<
English hard for you to understand .. shteater .. ?
Write this down ...
YOU .. screwball shteating disease ridden freaks .. are NOT allowed on
my
threads ..
You've been TOLD numerous times to take your shteating to
alt.kook.lily.livered.disease.ridden.screwball.mutated.shteating.freaks ..
You think normal people don't care if you try to interact with them ..
Well .. you are wrong shteater ..
Take your shteating ways .. elsewhere .. creepy ..
Take your shteating to
alt.kook.lily.livered.disease.ridden.screwball.mutated.shteating.freaks ..
Or something that sounds like that ..
Ken
accompanying delusions
%
> Seek professional help for your obsessive compulsive behavior and
> accompanying delusions
would you like an apple pie with that
ironjustice
<<
Shteater .. should .. write this down ...
Screwball shteating disease ridden freaks .. are NOT allowed on
my threads ..
Screwball shteating disease ridden freaks have been TOLD numerous
times to
take shteating to
alt.kook.lily.livered.disease.ridden.screwball.mutated.shteating.freaks ..
Normal people don't care to interact with you ..
Shteaters .. are abnormal .. that's why ..
Take your screwball shteating ways .. elsewhere .. creepy ..
Take your shteating to
alt.kook.lily.livered.disease.ridden.screwball.mutated.shteating.freaks ..
%
Ken
> hi
Ironhead is definately a mental case suffering from obsessive
compulsive behavior, probably on the public dole, and not getting help
for his delusions