Mixed oddities in the chemistry of autism

  

 

This suggest how the advanced glycation endpoints (AGEs) interact with the receptors (RAGE) and this has various effects inside the cells e.g. the production of reactive oxygen species (ROS), angiotensin II etc.  All this will depend on the cell type that is the recipient.

 

Mixed oddities

They may well not be as odd as you think in that many findings simply have not been followed up or their significance indicated by other work. Often the work has not been fully published (e.g. the EGOT work here) but its also it is commonly extremely difficult for some authors to get findings published in major journals.  As a result scientists will commonly find that, as they will not get much credit anyway, the work is not encouraging.

 

Also, scientists generally require funding and, if official sources would either much rather the findings were not found, or if the opposite was found then the funding will go towards that end (this is not a good viewpoint for anyone outside the field!).

 

The findings of the changes in RAGE are very interesting and discussions of these must be take place.

 

 

 

 

 

 

 

 

Mixed oddities

In a way these are important to publish in that it is always difficult in science to move forward and it is essential that even minor findings do come forward.  What it does mean, however, is that they need to be repeated. 

 

Low EGOT (aspartate transferase) in 82% and all 12 subjects low in 4 amino acids (tyrosine, carnosine, lysine, hydroxylysine). Dietary analysis revealed below-RDA intakes in Zinc (12 of 12 subjects, Calcium (8 of 12), Vitamin D (9 of 12), Vitamin E (6 of 12) and Vitamin A (6 of 12) (G. Kotsanis, DAN Conf., Sept, 1996)

 

Tierney E, Bukelis I, Thompson RE, Ahmed K, Aneja A, Kratz L, Kelley RI. Abnormalities of cholesterol metabolism in autism spectrum disorders. Am J Med Genet B Neuropsychiatr Genet. 2006 Sep 5;141(6):666-8.  (They tested samples, with no specific association with symptoms apart from ‘autism’ with the levels of various cholesterols and derivatives in blood.  They found 19% to be extremely low and the reason for this was not followed.)

 

Goldberg M, Hattab J, Meir D, Ebstein RP, Belmaker RH. Plasma cyclic AMP and cyclic GMP in childhood-onset psychoses. J Autism Dev Disord. 1984 Jun;14(2):159-64.  (levels of cyclic AMP were found to be over 100% higher in the autistic group of 18 patients.  The reason was uncertain).

 

Boso M, Emanuele E, Minoretti P, Arra M, Politi P, Ucelli di Nemi S, Barale F. Alterations of circulating endogenous secretory RAGE and S100A9 levels indicating dysfunction of the AGE-RAGE axis in autism. Neurosci Lett. 2006 Dec 27;410(3):169-73. (excess accumulation of advanced glycation end products – AGEs – in autistic brains.  This article reports a significantly reduced peripheral level of their receptors (RAGE) coupled with an elevated s100A9 – its proinflammatory ligand – point to a subtle but definite dysfunction of the AGE/RAGE axis in autism.  The authors do not say why whey feel this should be involved with autism but that the changes did indeed appear to be associated with the level of the autism rating scale.  The mechanism was also not clear).  The literature on AGEs and RAGEs are exceptionally complex but most of the work has appeared due to the appearance of AGEs in diabetics and the possibility that these glycations of proteins may be a cause of pathology.  In fact this can be inhibited (although not pharmaceutically, currently).  The findings here suggest that the glycated proteins no longer adequately interact with the receptors of them in such a way that particular factors may take place (e.g. involvement with immunity).

 

Junaid MA, Kowal D, Barua M, Pullarkat PS, Sklower Brooks S, Pullarkat RK.  Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor.  Am J Med Genet A. 2004 Nov 15;131(1):11-7.  (they found an excess of certain nucletide formats for glyoxylase 1 in half the 8 patients with autism that they tested.  They also found by Western blot analysis an accumulation of advanced glycation end products (AGE's) in autism brains, which they thought might be due to a genetic modification in autistic cases).

 

Factors that would need to be replicated before considered acceptable:

i)        diminished platelet function, increased baseline CSF homovanillic acid,

ii)      decreased nerve cell adhesion molecule serum fragment,

iii)    blunted prolactin response to fenfluramine.

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