Author: Admin (---.gtecablemodem.com)
Date: 03-26-02 06:53
Ken,
This is an easy-to-read reference but it needs explanation.
IMO it is wrong to focus on the formation of granuloma by macrophages and forget to ask why they become fibrotic in a sarc patients body yet they they are re-assimilated into the body of a 'normal' individual. Marcrophages have a specific job to do, in everybody, and they perform that job well. It is to clean up damaged or dying cells. Everybody has macrophages.
A sarc patient should not focus on the macrophages and granuloma, IMO, but on the formation of the inflammatory cytokines, kinins and the other chemicals, both within the macrophages and from other sources. Once the granuloma have become "old", especially if they have become fibrotic, they no longer affect our immune system. Our body becomes tolerant of them. The old granuloma themselves are no longer part of 'the inflammation'.
In response to an new immune challenge, the T-lymphocytes go into action. T-lymphocytes cause monocytes to produce ACE, ACE catalyses some amino acids into Angiotensin II, which in turn creates many of the inflammatory chemicals that allow macrophages (which are actually groups of monocytes) to break down the diseased tissue. We now have some new safe drugs that can stop the Angiotensin II from releasing those inflammatory chemicals.
It seems to me to be more useful to protect the tissue from inflammation so that it doesn't die - and the macrophages don't have to clean it up - and the macrophages don't then agglomerate into granuloma - than to focus on the granuloma themselves. Granuloma are only the end-product of an inflammation process that can be stopped at its source, at least substantially stopped, using relatively innocuous new drugs.
Angiotensin II also acts at other sites in the body to help the regeneration (apoptosis) of new tissue. This is an emerging field of research, and much of the published data on tissue regeneration is being obtained from animal experiments with relation to heart failure. But you might find these following references interesting. All of them relate to the beneficial effects on inflammed and diseased tissue resulting from Angiotensin II blockade using one of the new 'sartan' drugs such as Diovan (Valsartan). Particularly note the reversal of renal fibrosis and delaying of diabetic nephropathy in the references below. There is no fundamental reason the sartans should not have similar effects in sarcoidosis.
But any sarc patient contemplating the use of these drugs needs to show their doctor a copy of our manuscript on the psychotic effects of valsartan in sarc patients - Angiotensin II therapy, although very safe, affects sarcoid patients profoundly (as you would expect). It affects the brain as well as the inflammed tissue. With proper dosing can the psychotic effects be extremely beneficial. Write me for a copy (click on the "Trevor" link at the very bottom of this page).
"Angiotensin II and renal fibrosis"
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11566946&dopt=Abstract
"Role of angiotensin II in tubulointerstitial injury"
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11709803&dopt=Abstract
"Good news for patients with type 2 diabetes: angiotensin receptor blocker treatment delays progression of diabetic nephropathy"
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11856909&dopt=Abstract
"Retinal Neovascularization (retinopathy) Is Prevented by Blockade of the Renin-Angiotensin System"
http://hyper.ahajournals.org/cgi/content/full/36/6/1099
".. angiotensin II type 1 receptor blockade with valsartan in the improvement of inflammation-induced vascular injury"
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11723025&dopt=Abstract
Please email me if you want a full copy (31 pages) of the following reference:
"The role of angiotensin II in cognition and behaviour"
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11906704&dopt=Abstract
..Trevor..
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