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| | From: Johann (Original Message) | Sent: 6/4/2007 9:14 PM |
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Did you read the Alzheimer's and oxidative stress thread? Take a look at that if not. Nobody can say what causes it in any one individual, but the evidence suggests that having arachidonic acid in one's brain cells makes one much more susceptible. For example:
Jpn J Pharmacol. 2000 Feb;82(2):85-94.
"New anti-inflammatory treatment strategy in Alzheimer's disease."
Numerous reports have indicated that patients suffering from inflammatory diseases (e.g., arthritis) who take anti-inflammatory medication have a reduced risk of developing Alzheimer's disease (AD). Thus, the first generation of anti-inflammatory cyclooxygenase (COX) inhibitors, such as aspirin and indomethacin, have been tested as potential therapeutics in AD. Because the inhibition of COX-1 is also known to cause tissue damage in the gastrointestinal system from the resultant reduced cytoprotection, selective COX-2 inhibitors are being investigated and tested clinically as potentially better therapeutics for AD patients. However, such drugs may also trigger unwanted effects; for example, the COX-2 inhibitors, which reduce the production of one type of eicosanoids, the prostaglandins, may increase the production of other eicosanoids; i.e., the leukotriene B4 (LTB4), which is one of the most potent endogenous chemotactic/inflammatory factors. LTB4 production is initiated by the enzyme 5-lipoxygenase (5-LOX). The expression of the 5-LOX gene is upregulated during neurodegeneration and with aging. In spite of the fact that 5-LOX and leukotrienes are major players in the inflammation cascade, their role in AD pathobiology/therapy has not been extensively investigated. We propose that the 5-LOX inflammatory cascade may take part in the process of aging-associated neurodegenerative diseases, and we point to the role of 5-LOX in neurodegeneration and discuss its relevance for anti-inflammatory therapy of AD.
And:
Dement Geriatr Cogn Disord. 2007 Apr 23;23(6):423-431 [Epub ahead of print].
"Altered Expression of COX-2 in Subdivisions of the Hippocampus during Aging and in Alzheimer's Disease: The Hisayama Study."
Background: It has been reported that nonsteroidal anti-inflammatory drugs may delay the onset of Alzheimer's disease (AD). Since nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase (COX), COX-2, an inducible form of COX, may be involved in the pathology of AD in association with the arachidonic acid cascade. In addition, it has been suggested that alterations in the balance of polyunsaturated fatty acids are associated with brain dysfunctions such as neurodegerative pathologies of the aging brain. Method: To explore COX-2 expression in the hippocampus, we analyzed 45 consecutive autopsy subjects without dementia and 25 AD patients derived from the town of Hisayama, Japan. Results: The neuronal expression of COX-2 in the CA3 subdivision of the hippocampus, subiculum, entorhinal cortex and transentorhinal cortex were consistently observed in both nondemented and AD brains, and COX-2 immunoreactivity correlated with age in nondemented brains. In AD patients, neurons of CA1 exhibited increased COX-2 immunoreactivity which correlated with the severity of AD pathology. This correlation was not apparent in nondemented subjects. Conclusion: These results suggest that COX-2 expression may be differentially regulated among subdivisions of the hippocampus and that elevated COX-2 expression in the CA1 of AD brains may be associated with AD pathology and thus cognitive dysfunction. Copyright (c) 2007 S. Karger AG, Basel.
You can go to www.pubmed.com and do your own searches, for example, arachidonic Alzheimer's or Alzheimer's LTB4. Also, whenever you read about "inflammtion," that is basically the effect of the arachidonic acid metabolites. |
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| | From: Johann | Sent: 6/5/2007 12:17 AM |
What role do you think metals (too much aluminum, loose copper ions, etc) play in this? I ask because I have been taking the amino acid L-Carnosine every now and then and I notice that I on the days that I take it, I have a tremendous increase in clarity and I was wondering if this is because of its chelating. |
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My guess is that the carnosine is stopping the arachidonic acid metabolites for doing damage. On my present diet, I am able to concentrate better and think clearer. Too much of certain metals can be a problem, but it seems as though this is especially pronounced if there is too much lipid peroxidation going on. An iron and PUFA-rich diet seems especially bad. A scientist named Spiteller described the process: QUOTE: Apparently nature uses the unique sensitivity of polyunsaturated fatty acids (PUFAs) versus oxygen to generate chemical signals if the surface of a cell is influenced by an outside or inside event; for instance the attack of microorganisms, proliferation, aging or by treatment of isolated cells with surfactants. It seems that mammalian and plant cells respond equally to such changes in their structures by transformation of polyunsaturated fatty acids localized in the phospholipid layer of the cell wall to lipidhydroperoxides (LOOHs). These lipid peroxidation (LPO) processes involve all PUFAs, not only arachidonic acid.Slight physiological changes of the cell wall for instance by proliferation seem to activate enzymes, e.g., phospholipases and lipoxygenases (LOX). When an outside impact (for instance by attack of microorganisms) exceeds a certain level LOX commit suicide and liberate iron ions. These start a nonenzymatic LPO. Enzymatic and nonenzymatic LPO distinguish fundamentally which has not been recognized in the past. In the enzymatic LPO processes peroxyl radicals generated as intermediates cannot leave the enzyme complex. In contrast in a nonenzymatic LPO process peroxyl radicals are not trapped. They attack nearly any kind of biological molecules, for instance proteins. Thus only the amount of an outside impact decides if proliferation, apoptosis, or necrosis is started.Some evidence indicates that cancer might be the consequence of a low response of cells to induce apoptotic LPO processes. In contrast to high level of LPO processes induces diseases combined with inflammation, for instance rheumatic arthritis. After consumption of food rich in linoleic acid its LPO products become increased in low density lipoprotein (LDL). This LDL is able to enter endothelial cells and damage cells from inside, long before an inflammatory response is detectable. UNQUOTE. |
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