I've been meaning to post about the gluten schizophrenia paper in Nutrition and Metabolism, prompted by the paper itself, a forward from Bloggeier and now a reminder on the THINCS formum by Bogdan. But it turned in to an epic with lots of threads to interweave so, while I get it sorted, here's a quick one liner on the joys of a gluten based diet that I can fit in over a coffee break now I've run out of filler and floor board timber.
Take one adult established schizophrenic with recent onset diarrhoea and weight loss. For some reason do a SPECT scan to look at the blood flow within their brain and note that it is abnormal in the left frontal lobe.
Place on gluten free diet.
Re-scan a little while later and re-biopsy the gut.
All cured, including the "schizophrenic" disorder.
You don't have to be mad to eat bread, but you might end up that way!
Peter
BTW it's possible to speculate whether the blood flow is a vascular phenomenon due to the gluten affecting the arteries in the brain or a hypoperfusion due to abnormal brain metabolism, ie a direct neural effect. I'd never really considered that the gluten effects on the brain might be vascular...
Tuesday, June 30, 2009
Saturday, June 27, 2009
Alzheimers and BSE: Prions are not Tau
While sniffing around BSE research in the aftermath of the Tau protein paper find I came upon this quite interesting review. A quick pubmed of the author suggests that BSE is, in her book, a viral infection by a currently uncharacterised virus about 25nm across. I'm not experienced enough at looking at electron micrographs to tell how convincing her pictures are, but they certainly look OK to me.
If she is correct then Prof Ebringer is wrong on this one, as he feels that the TSEs are auto immune attacks comparable to MS.
The biggest problem with the virus hypothesis is the effect of converting the virus to ash and still having it retain its infectivity. I'm a bit puzzled as to how formalin fixation might enhance the virulence of a virus too. This is not typical behaviour of virus particles. Where as sticking ash or formalin fixed gunk in to a brain may do enough of the right sort of damage to trigger an auto immune attack.
On top of this there is the fact that SCID (severe combined immunodeficient) mice are extremely resistant to BSE. How many viral problems are blunted by having a crippled immune system?
The problem here for the auto immune hypothesis is that while SCID mice are very resistant to BSE, they are not completely so. This is less of a problem to me as even SCID mice have some residual functional immune tissue and auto immune attack does not seem to be wholly dependent on antibodies, it probably uses all sorts of cells.
But ultimately it is becoming clearer that the prion hypothesis is probably wrong because the better the purification of putative infectious prion proteins, the lower the infectivity. I would guess that synthetic prion proteins will prove to be fully harmless unless their injection in to a mouse's brain does as much damage as injecting ash.
Add to this the limited ability of the brain to produce disease specific pathologies (ie most end stage diseases look similar!). CJD looks VERY like MS to a histopathologist and simply injecting TNFalpha in to the eye produces lesions indistinguishable from CJD in the optic nerve!
I think the jury is definitely out on this one but it will be interesting to watch the progress of the prion hypothesis and whether prions turn out to be neurotoxic at all.
Peter
If she is correct then Prof Ebringer is wrong on this one, as he feels that the TSEs are auto immune attacks comparable to MS.
The biggest problem with the virus hypothesis is the effect of converting the virus to ash and still having it retain its infectivity. I'm a bit puzzled as to how formalin fixation might enhance the virulence of a virus too. This is not typical behaviour of virus particles. Where as sticking ash or formalin fixed gunk in to a brain may do enough of the right sort of damage to trigger an auto immune attack.
On top of this there is the fact that SCID (severe combined immunodeficient) mice are extremely resistant to BSE. How many viral problems are blunted by having a crippled immune system?
The problem here for the auto immune hypothesis is that while SCID mice are very resistant to BSE, they are not completely so. This is less of a problem to me as even SCID mice have some residual functional immune tissue and auto immune attack does not seem to be wholly dependent on antibodies, it probably uses all sorts of cells.
But ultimately it is becoming clearer that the prion hypothesis is probably wrong because the better the purification of putative infectious prion proteins, the lower the infectivity. I would guess that synthetic prion proteins will prove to be fully harmless unless their injection in to a mouse's brain does as much damage as injecting ash.
Add to this the limited ability of the brain to produce disease specific pathologies (ie most end stage diseases look similar!). CJD looks VERY like MS to a histopathologist and simply injecting TNFalpha in to the eye produces lesions indistinguishable from CJD in the optic nerve!
I think the jury is definitely out on this one but it will be interesting to watch the progress of the prion hypothesis and whether prions turn out to be neurotoxic at all.
Peter
Thursday, June 25, 2009
Alzheimers and Tau proteins
This report on the "spreadable" nature of Alzheimers within the brain is in New Scientist and came to me via Glyn Wainwright on the THINCS forum. It's interesting in it's own right but I rather liked the related paper it linked to about the "contagious" nature of misfolded Tau proteins.
I think it would be reasonable to summarise the abstract as claiming that Tau proteins are non pathogenic structural proteins present inside, and essential to, normal nerve cells. Tau protein aggregates, which are abnormal products, "are observed" outside cells. My assumption is that, as healthy Tau are normally intracellular proteins, they have to be either excreted or exocytosed. Or the cell has to die to released them, before they can be found outside cells. The latter seems the more believable option.
Placing healthy monomer Tau proteins outside neuronal cells in culture does nothing. Placing Tau aggregates outside cells promotes endocytosis of those aggregates and, once endocytosed, the aggregates are directly toxic ("induce fibrillization") to the normal intracellular structural Tau. When this cell then dies it too will release it's abnormal Tau aggregates, which will go on to kill further recipient cells.
OMG its a locally contagious protein! Except it's not, it's a toxic substance which triggers the production of the same toxic substance from healthy tissue on contact.
Where do the original Tau aggregates come from? I suspect that Blaylock would argue they are shrapnel from the death of a neurone killed by catastrophic energy failure, induced by excitotoxins hitting glutamate-receptor sporting cells. This will no doubt involve hyperphosphorylation of Tau and all of the other exciting co factors for Alzheimers. Oh, and might be avoidable by supplying alternative energy molecules such as ketones. The shrapnel is itself neurotoxic and the product of its damage is more of the same neurotoxic shrapnel. This is a chain reaction and Alzheimers then becomes the neurological equivalent of Hiroshima. At this point Blaylock must be feeling quite justified in his views.
The obvious comparison, which is made in the abstract, is to prion proteins as featured in BSE.
If misfolded prion proteins are endocytosed, as Tau proteins are, and are themselves toxic to normal prion proteins, you then have the mirage of a contagious protein.
BSE can be induced in the brain of almost any recipient species by injecting a slurrry from the brain of a BSE case, which contains misfolded prion protein. But what is the trigger for the initial misfolding?
If I was prof Ebringer I might strongly suggest that the original trigger for prion misfolding is an autoimmune attack on myelin basic protein, or a similar structural protein, in the brain. We're not thinking neat and tidy apoptosis here, more like sudden death and spill your contents. Once the misfolding chain reaction is started the progression to BSE via more misfolding and cell death might then follow on, exactly as the Tau aggregates spread.
There is then no need for a contagious protein. In fact, it is easy to "spread" BSE by injecting the ash from incinerated BSE brain (600 deg C in the presence of oxygen. This means incinerated!!!). All you need is for the ash to damage the recipient brain enough to trigger protein misfolding and you have "transmitted" BSE using ash. Thoroughly formalin fixed brain tissue does the job rather better than fresh brain tissue too!
You really have to wonder what is going on here and the Tau "transmission" abstract makes Prof Ebringer and Russell Blaylock look pretty good as proposers of the correct triggers for the respective diseases to me.
Fascinating stuff.
Peter
I think it would be reasonable to summarise the abstract as claiming that Tau proteins are non pathogenic structural proteins present inside, and essential to, normal nerve cells. Tau protein aggregates, which are abnormal products, "are observed" outside cells. My assumption is that, as healthy Tau are normally intracellular proteins, they have to be either excreted or exocytosed. Or the cell has to die to released them, before they can be found outside cells. The latter seems the more believable option.
Placing healthy monomer Tau proteins outside neuronal cells in culture does nothing. Placing Tau aggregates outside cells promotes endocytosis of those aggregates and, once endocytosed, the aggregates are directly toxic ("induce fibrillization") to the normal intracellular structural Tau. When this cell then dies it too will release it's abnormal Tau aggregates, which will go on to kill further recipient cells.
OMG its a locally contagious protein! Except it's not, it's a toxic substance which triggers the production of the same toxic substance from healthy tissue on contact.
Where do the original Tau aggregates come from? I suspect that Blaylock would argue they are shrapnel from the death of a neurone killed by catastrophic energy failure, induced by excitotoxins hitting glutamate-receptor sporting cells. This will no doubt involve hyperphosphorylation of Tau and all of the other exciting co factors for Alzheimers. Oh, and might be avoidable by supplying alternative energy molecules such as ketones. The shrapnel is itself neurotoxic and the product of its damage is more of the same neurotoxic shrapnel. This is a chain reaction and Alzheimers then becomes the neurological equivalent of Hiroshima. At this point Blaylock must be feeling quite justified in his views.
The obvious comparison, which is made in the abstract, is to prion proteins as featured in BSE.
If misfolded prion proteins are endocytosed, as Tau proteins are, and are themselves toxic to normal prion proteins, you then have the mirage of a contagious protein.
BSE can be induced in the brain of almost any recipient species by injecting a slurrry from the brain of a BSE case, which contains misfolded prion protein. But what is the trigger for the initial misfolding?
If I was prof Ebringer I might strongly suggest that the original trigger for prion misfolding is an autoimmune attack on myelin basic protein, or a similar structural protein, in the brain. We're not thinking neat and tidy apoptosis here, more like sudden death and spill your contents. Once the misfolding chain reaction is started the progression to BSE via more misfolding and cell death might then follow on, exactly as the Tau aggregates spread.
There is then no need for a contagious protein. In fact, it is easy to "spread" BSE by injecting the ash from incinerated BSE brain (600 deg C in the presence of oxygen. This means incinerated!!!). All you need is for the ash to damage the recipient brain enough to trigger protein misfolding and you have "transmitted" BSE using ash. Thoroughly formalin fixed brain tissue does the job rather better than fresh brain tissue too!
You really have to wonder what is going on here and the Tau "transmission" abstract makes Prof Ebringer and Russell Blaylock look pretty good as proposers of the correct triggers for the respective diseases to me.
Fascinating stuff.
Peter
Sunday, June 14, 2009
Bob Michell on meta-analysis
Quote of the century, from Bob Michell (taught me applied physiology many moons ago at the RVC and is a seriously bright guy).
"Meta-analysis of dross remains dross"
Ahhhhh that's good.
Peter
Edit: It's possibly as good as Malcolm Kendrick's definition of meta-analysis: one, two, skip a few, 99, one hundred.
"Meta-analysis of dross remains dross"
Ahhhhh that's good.
Peter
Edit: It's possibly as good as Malcolm Kendrick's definition of meta-analysis: one, two, skip a few, 99, one hundred.
Tuesday, June 02, 2009
Gluten: The NICE guidelines for UK diagnosis
For UK readers who want to go the mainstream route here are the NICE guidelines as supplied by Ali in the comments after the Gluten and MS post.
This is part of her comment:
"I am sure you will be pleased to note that the care pathway now includes the referral to a gastroenterologist of those with negative tests but persisting coeliac symptoms."
Yes, too right. I'd personally still go LC as part of my gluten free approach but not everyone wants to go that way. I suppose I went gluten free without anything other than reading the literature! But being armed with the information you are positively coeliac is an opportunity to avoid so many auto immune diseases. If you need a positive test to make the change, these guidelines will help you.
Thanks Ali.
Peter
This is part of her comment:
"I am sure you will be pleased to note that the care pathway now includes the referral to a gastroenterologist of those with negative tests but persisting coeliac symptoms."
Yes, too right. I'd personally still go LC as part of my gluten free approach but not everyone wants to go that way. I suppose I went gluten free without anything other than reading the literature! But being armed with the information you are positively coeliac is an opportunity to avoid so many auto immune diseases. If you need a positive test to make the change, these guidelines will help you.
Thanks Ali.
Peter
Monday, June 01, 2009
Gluten, coeliac and multiple sclerosis
These are a set of MRI images taken from a paper in Spanish entitled "Sustained clinical remission in a patient with remittent-recurrent multiple sclerosis and celiac disease gluten-free diet for 6 years". Something seems to have gotten lost in translation, but you get the gist. Pictures A are before gluten free eating and B after six years gluten free, I think.
Even on the relatively poor reproduction here you can see the white plaques typical of MS lesions on the left and their absence on the right is equally notable. Click to enlarge. That's as far as my Spanish (which is non existent) will take me with the paper.
Of course this may just be a complete fluke, MS does do remission. But I doubt it and anyone with MS or related problems can take note and realise that it is not necessarily a one way ticket, remission is possible, six years is a good start and eating gluten is probably your key to progression of the disease. It becomes debatable whether eating low carbohydrate is needed but, if nothing else, going low carb makes the avoidance of gluten about a million times easier than deciding whether to trust the labelling for complete freedom from gluten. No gluten in a home cooked steak.
For those who do have MS but don't have coeliac disease, I stumbled on this paper as a link related to the Spanish paper. It is almost impossible to describe how utterly, totally and completely cr*p the antibody tests for coelaic disease are. In the UK you will not get an intestinal biopsy unless you are antibody positive. You can have flat intestinal villi with a negative antibody titre. You can also have flat villi in large areas of your gut and the guy driving the endoscope might just biopsy the last six minute patches of normal mucosa you had left. Leaving you with no normal gut lining, a negative diagnosis and a label of over vivid imagination about gut pain. Conclusion: A deficiency of Prozac. The hydrogen breath test seems a lot better than serology, if you can get one done.
There is no need to believe you are coeliac negative. If you have MS it seems very unlikely you would be coeliac negative. Risking MS progression for toast is a pretty amazing trade off! There are no adverse reactions to a gluten free diet. Oh, once you are through the withdrawal syndrome that is, about 4-6 weeks.
Peter
Even on the relatively poor reproduction here you can see the white plaques typical of MS lesions on the left and their absence on the right is equally notable. Click to enlarge. That's as far as my Spanish (which is non existent) will take me with the paper.
Of course this may just be a complete fluke, MS does do remission. But I doubt it and anyone with MS or related problems can take note and realise that it is not necessarily a one way ticket, remission is possible, six years is a good start and eating gluten is probably your key to progression of the disease. It becomes debatable whether eating low carbohydrate is needed but, if nothing else, going low carb makes the avoidance of gluten about a million times easier than deciding whether to trust the labelling for complete freedom from gluten. No gluten in a home cooked steak.
For those who do have MS but don't have coeliac disease, I stumbled on this paper as a link related to the Spanish paper. It is almost impossible to describe how utterly, totally and completely cr*p the antibody tests for coelaic disease are. In the UK you will not get an intestinal biopsy unless you are antibody positive. You can have flat intestinal villi with a negative antibody titre. You can also have flat villi in large areas of your gut and the guy driving the endoscope might just biopsy the last six minute patches of normal mucosa you had left. Leaving you with no normal gut lining, a negative diagnosis and a label of over vivid imagination about gut pain. Conclusion: A deficiency of Prozac. The hydrogen breath test seems a lot better than serology, if you can get one done.
There is no need to believe you are coeliac negative. If you have MS it seems very unlikely you would be coeliac negative. Risking MS progression for toast is a pretty amazing trade off! There are no adverse reactions to a gluten free diet. Oh, once you are through the withdrawal syndrome that is, about 4-6 weeks.
Peter
Subscribe to:
Posts (Atom)
