WF10(4) Systemic Reaction during Inflammation
Following papers will link this to known evidence about WF10... the problem, for many of us, is tying the "micro" analysis of WF10 (heme, signalling, macrophages, chemical reactions) to the "macro" (or whole-body, systemic) picture.
So perhaps it's best to take a step back for a minute, and take a look at the body as a whole. When we do, we can see the possible places where WF10 is interacting with macro processes - and we can see reasons for Dr. Pugen's results - and the potential in the WF10 P3.
So, there 's something to look for, here - because we know one of the primary places HAART has an adverse effect is on the liver. As I've posted before, people are no longer dying of AIDS - they're dying from HAART. Life is prolonged, and AIDS-defining events are reduced - but the liver suffers from the long-term consequences of HAART usage.
And this is one of the many areas where WF10 shows promise, because the literature already shows that WF10 downregulates inflammatory cytokines, and can be expected to mitigate the development of fibrosis, and other effects of chronic liver inflammation.
That's the connection, and that's the genius of the P3 design - if the trials data clinically confirms existing data on WF10 gene regulation - then it will be demonstrated that WF10 is an ideal adjunct to HAART, to minimize its damaging effects on the liver.
This paper deal with the body's immediate response to a challenge - not the chronic response. But it deals with the subject of ACUTE-PHASE PROTEINS so well, that I thought I'd use it to start.
bentham.org
"The response to infection and injuries usually involves a large number of changes both local and distant from the site of inflammation. This physiological condition takes place at the very beginning of the inflammatory process and lasts for 1-2 days. After that, the host returns to normal functions. The systemic response can also be prolonged, if acute inflammation becomes too chronic [1]. These events lead to a wide-ranging systemic response that is also called acute-phase.
The purpose of acute-phase reaction is to counteract the underlying challenge in order to restore the homeostasis as soon as possible. This result is accomplished by isolating and destroying the infective organisms, or removing the harmful molecules, and activating the repair process. Acute-phase reaction includes a wide range of neuroendocrine, hematopoietic, metabolic and hepatic changes, summarized in Table 1.
One of the most interesting features of the acute-phase is the change in the concentrations of many plasma proteins, known as the acute-phase proteins. An acute-phase protein (APP) has been defined as one whose plasma concentration increases (positive acute-phase proteins) or decreases (negative acute-phaseproteins) by at least 25 percent during inflammatory disorders [2]. The very first APP to be described, C-reactive protein (CRP), was discovered in 1930 [3] in the plasma of patients during the acute phase of pneumococcal infection. In some pathologies, CRP may increase more than 1000 times."
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The following links take the subject further, to CHRONIC inflammation... and give a sense of how it all works together:
mcb.berkeley.edu
kumc.edu
nic.sav.sk
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In future, we can look at the linkage between heme and chronic inflammation - and what that information suggests, particularly as it applies to the liver - with its implications for the P3, and for Greg Pugen's work.
Jim |
