Does anyone have acces to Epilepsia?

[Dutch mom]

I'd like to read this article but there is no free acces. Not even an abstract on Pubmed.

The ketogenic diet and epilepsy: Is adenosine the missing link?



Authors: Masino, Susan A.1; Geiger, Jonathan D.2
Source: Epilepsia, Volume 50, Number 2, February 2009 , pp. 332-333(2)
Publisher: Blackwell Publishing

[Bernard]

ABSTRACT
Despite over 80 years of use, the ketogenic diet (KD) has never been tested in a blinded manner. Twenty children with intractable Lennox-Gastaut syndrome (Lennox-Gastaut Syndrome) were fasted 36 h and then randomized to receive the classic KD in conjunction with a solution containing either 60 g/day of glucose or saccharin. Parents and physicians were blinded to both the solution composition and level of ketosis. A crossover to the KD with the alternate solution occurred following the sixth day and a repeat fast. A 24-h electroencephalography (EEG) was obtained at baseline and after each arm. After administration of the solution, there was moderate evidence of a reduction in parent-reported seizures between the glucose and saccharin arms, with a median difference of 1.5 seizures per day (p = 0.07). There was no reduction in the number of EEG-identified events, with a median reduction of 7 events per day (p = 0.33). Ketosis was not completely eliminated in the glucose-added arm.

http://www3.interscience.wiley.com/j...83970/abstract

[Dutch mom]

Thanx Bernard. This is another (but also interesting) article. Indeed I 've never read aboud a blind study before.

But the article I'm looking for is the one about adenosine (Epilepsia 50,2 Feb. '09)

[Nakamova]

Can't access the one you want, but below is an abstract of a related article. The gist is that ketosis via the ketogenic diet increases the presence of adenosine in the brain. Increased adenosine = higher seizure threshold.

The anticonvulsive effect of a ketogenic diet was investigated using mice fed on a ketogenic milk powder which contained medium-chain triglycerides (MCT). Electroconvulsive shocking and determination of adenosine nucleotides in mice brain were performed on three mice groups, (1) a control group; free access to a commercially available diet, (2) a fasted group; fasted for two days, and (3) a ketotic group; fasted for two days and then fed on the ketogenic milk powder for two weeks. The maximal electroconvulsive threshold of the ketotic group was significantly higher than that of the fasted group (p less than 0.001). The maximal electroconvulsive threshold of the fasted group was significantly higher than that of the control group (p less than 0.05). The contents of adenosine triphosphate (ATP) in the brain of the ketotic group was significantly higher than that of the control group (p less than 0.01). These results suggest that chronic ketosis with the ketogenic diet increases the contents of ATP in the brain and this increase in ATP probably accounts for the neuronal stability.

[Bernard]

But the article I'm looking for is the one about adenosine (Epilepsia 50,2 Feb. '09)

D'oh! Clicked the wrong link. Here's the page for the article/study you wanted:

http://www3.interscience.wiley.com/j...63746/abstract

but it simply says, "No Abstract".

[paolomainardi]

I'm waiting to have a pdf of the recent paper of Masino, but this is the abstract of a previous work:

Masino SA, Geiger JD. Are purines mediators of the anticonvulsant/neuroprotective effects of ketogenic diets? Trends Neurosci. 2008 Jun;31(6):273-8. Epub 2008 May 9.

Neuroscience Program/Psychology Department, Trinity College, Life Sciences
Center, 300 Summit Street, Hartford, CT 06106, USA. susan.masino@trincoll.edu

Abnormal neuronal signaling caused by metabolic changes characterizes several
neurological disorders, and in some instances metabolic interventions provide
therapeutic benefits. Indeed, altering metabolism either by fasting or by
maintaining a low-carbohydrate (ketogenic) diet might reduce epileptic seizures
and offer neuroprotection in part because the diet increases mitochondrial
biogenesis and brain energy levels. Here we focus on a novel hypothesis that a
ketogenic diet-induced change in energy metabolism increases levels of ATP and
adenosine, purines that are critically involved in neuron-glia interactions,
neuromodulation and synaptic plasticity. Enhancing brain bioenergetics (ATP) and
increasing levels of adenosine, an endogenous anticonvulsant and neuroprotective
molecule, might help with understanding and treating a variety of neurological
disorders.

It's interesting to link this hypothesis to the increase in metabolism due to stressor.
ATP levels increase toghether NPY and noradrenalin levels showing a response of our body to an emergency. Then the neuroendocrine system play an important role.

SInce 1986 it's know the anticonvulsive effect of adenosine.

M. Dragunow, Adenosine: the brain's natural anticonvulsant?, Trends Pharmacol. Sci. 7 (1986), pp. 128–130
D. Boison, Adenosine kinase, epilepsy and stroke: mechanisms and therapies, Trends Pharmacol. Sci. 27 (2006), pp. 652–658

More recently the anticonvulsive effect of NPY and noradrenalin was shown, too.
NPY is named "endogenous anticonvulsant".

The stimuli to obtain this neuroendocrine response are: fasting, intestinal nutrients as: fats, medium chain triglycerids, tryptophan and serotonin.

The authors report KD increase ATP, then increase Krebs cycle,then peptide synthesis.

Neuropeptides are linked to neurogenesis and synapthogenesis, in this way they increase neuroprotective effects. In agreement with Jobe's theory (J neurochem 2005), neurogenesis and synapthogenesis allow to the brain to keep isolated bad function neurons, in this way there is not pathological manifestations.

Do you know KD carry out good clinical results in other pathologies than epilepsy?
I link the anticonvulsive effect of antidepressant SSRIs to the intestinal increasing of serotonin. It's reported for many anti-epileptic drugs carry out an intestinal increase in tryptophan and/or serotonin. The anticonvulsive effect showed by alpha-lactalbumin (ALAC) is due to intestinal tryptophan increase.

This paper suggest in our body there are endogenous systems to control brain. The acute phase reaction to an emergency start these systems. The basal mechanism of trasformation the food in energy are involved, i.e Krebs cycle, ATP, neuropeptide syntehesis. To study these systems could be very important to solve many pathologies.

Not only, the pathogenetic mechanisms of many diseases could be linked to nutritional aspects. In fact, ketogenic diet, MCT diet, ALAC diet are all diets. Can a diet to be more effective than drugs? Food better than drugs.
A too permeable intestinal membrane could be responsible of neurotoxic compunds in the blood. Surely it's responsible of an uncorrected metabolism of proteins, amino acids being decarbossiled to dangerous amine. For example tryptohan carry out to scatole and indole. In autism there is the theory of excess of opioid compunds...

A lot of studies have to be performed. Unfortunately multipharms are not interested to them.

Paolo Mainardi

[brain]

Okay just to clarify some confusions here:

Blackwell-Synergy, Wiley - have merged;
and what used to be three separate entities
are now a trio band of one.

However - there is another website I strongly
recommend you to sub-up - it is free and you
can control the subscriptions as well - and it
DOES include Epilepsia in there for FREE PDF
downloads - so I do enroll via the emails and
this website has become the hottest website
since it's come out - if you can't find or access
it anywhere else ---> HEAD HERE because
the chances are ... you just might find it opened
here:

Nature.com

YES - it is free, but they also have freebies once
in awhile, tons of abstracts, and a whole bunch of
stuff and more ...

As implied - you can CONTROL everything you want
specifically - and WHEN you want it, you do not even
have to opt for the emails, but I do.

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

GET THIS: 'BEFORE PUBLICATIONS' gets in there
quickly! You can get the news before the news makes
the news! It really does happen, and I've had people
wondering how in the world did "I" know this before it
was even published?



Got to love it - but now many folks have joined and
there is no further need for me to "post such" anymore.
You will see why "Nature" is so hot and hot and HOT!

I've had Surgeons to Professors thanking me for that
website when it first came out; to those who wonders
how in the world did I learn of this? Easily, my former
College Classmate who is now a Professor, had his
preliminary posted in Nature's 2nd Edition (so it just
came out on the web and at that time was very limited,
today - it's so broad and vast - it's truly amazing!) and
emailed me about it with the link! Since then, I've been
a member - and there is NO COST (IT is FREE!) to join,
however - some articles, publications, etc - they do charge
but if you "wait" patiently, eventually it will become "free"
via PDF - so I check TWICE A MONTH - in that site for
free PDF files ---> especially in Epilepsia!

But of course you did not hear or read that last part
from me - *laughing* - that was a "ghost post"!

[paolomainardi]

I have the pdf of the last paper of Masino, I can send it to personal emails.

[Dutch mom]

Yes please, I'd like to have the article. I'll send you my e-mail adress by PM. Thank so much you for the offer.