Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) are two major cytokines that rise to relatively high levels during systemic inflammation and the endothelial cell response to these cytokines may explain some of the dysfunction that occurs.
To better understand the cytokine-induced responses of endothelial cells at gene expression level, human umbilical vein endothelial cells (HUVEC) were exposed to IL-1β or TNF-α for various times and subjected to cDNA microarray analyses for the alterations of their mRNA expression.
Of ~ 4,000 genes on the microarray, the expression levels of 33 genes appeared to be affected by IL-1β treatment and 58 by TNF-α.
Twenty-five of these genes responded to both treatments.
These results suggest the effects of IL-1β and TNF-α on endothelial cells are redundant and it may be necessary to suppress both at the same time to ameliorate the systemic response.
( I broke up the paragraph to make it easier to read.)
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northstar
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Member # 7911
posted
I would think it would be important to determine if the cytokine response is from infection, or from the euphemous "auto-immune"?
Would not finding root cause determine whether or not to treat symptomatically or treating infection, or both?
Northstar
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Marnie
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Member # 773
posted
That immune response is exactly what Bb needs to happen.
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northstar
Frequent Contributor (1K+ posts)
Member # 7911
posted
The cytokine response is also found in bartonella and babesiosis. Makes bb realllllly happy, then.
So, do you want to suppress the response?
What benefit is it for the body to have a cytokine response?
What is downside of suppressing cytokines?
(ok, let me guess....."happy medium"! So, check crp levels.....and what else?)
How do you suppress both tnf and il?
Northstar
p.s. I am working with Tom Kenyon's healing cd's....White Gold Alchemy, Immunity, and Hathors. If your sister meditates, etc., they can be quite powerful.
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Inactivate NFkB.
Normally glutathione and other nutrients can do this, but as you know...glutathione is kapoot because Bb has the hungries for 2 of the 3 nutrients that make up glutathione.
Use the other things that can INactivate NFkB.
I've listed them...curcumin is my top choice. Take with coconut oil. We don't know therapeutic doses...I personally would try it and ramp up as tolerated. It works synergistically with other things too...like green tea (do NOT add milk).
I love my Soloflex machine. Oscillations also inactivate NFkB (pubmed abstract).
Inflammation is always a part of healing. It is when this stage doesn't shut off that the problems accumulate.
I'm sure you've read that constant inflammation is thought to be cancer-causing, right?
Some of this has to do with IFG-1 and IFGBP-3...insulin growth factor and insulin growth factor binding protein.
Transferrin is one of the IGFBP-3 proteins. Bb loves to transport transferrin OUT...no iron please.
'Cause lactoferrin and transferrin (bind and transfer iron respectively) can damage the cell walls of most gram negative pathogens.
There is another...yes, another imbalance in between IGF-1 (calcium related) and IGFBP-3 (magnesium related). No surprise that in "autoimmune", it looks like IGF-1 is up and IGFBP-3 is down.
Chronic estridol (one of 3 forms of estrogen) or Tamoxifen inhibit IFGBP-3.
Tamoxifen is a man-made PFK inhibitor to kill breast cancer cells.
Bb has a PFK inhibitor. It looks to be PKC delta.
Energy malnutrition is characterized by the important decreases in the leptin, insulin, IGF-1 AND IGFBP-3 levels.
These data are compatible with the hypothesis that premenopausal women with a relatively high circulating concentration of IGF-I and low IGFBP-3 are at an increased risk of developing breast cancer.
Open cancer resection, unlike its minimally invasive alternative, induces a dramatic decrease in concentration of intact IGFBP-3, which may have important implications with regard to colon cancer recurrence.
Recent epidemiologic studies have established a correlation between high levels of circulating insulin-like growth factor (IGF) and low levels of IGF binding protein 3 [?] (IGFBP-3 [?]), and relative risk of developing colon, breast, prostate, and lung cancer, which are known to produce MMP-7...
Calprotectin, a 36 kDa protein present in neutrophil (most abundant WBC) cytoplasm, has antimicrobial and apoptosis (cell killing) inducing activities,
which are reversed by the addition of zinc.
Matrix metalloproteinases (MMPs), a family of zinc dependent enzymes, are important in many normal biological processes including embryonic development, angiogenesis, and wound healing, but also pathological processes such as inflammation, cancer, and tissue destruction.
The aim of this study was to investigate whether calprotectin can inhibit MMP activity, and whether such inhibition could be overcome by the addition of zinc.
All MMPs except MMP-1 were active against gelatin,
whereas MMP-7 was the only enzyme active against -casein. (More on that later!)
The addition of calprotectin inhibited the activity of all the MMPs, but different concentrations of the protein, from 0.3�M to > 11�M, were necessary to produce a 50% inhibition of the MMPs. Inhibition by calprotectin was largely overcome by the addition of zinc.
Conclusions--The findings suggest that calprotectin inhibits MMPs by sequestration of zinc. The data also suggest that MMPs have different affinities for zinc and that calprotectin has a lower zinc affinity than the MMPs.
Translation: calprotectin in our neutrophils (major WBC produced about every 3 weeks) binds zinc. Bb would not like that.
Zinc dependent metalloproteinases are important in most aspects of life, from ovulation, embryonic development, and parturition to the development of malignant disease and death.1
Even lower organisms, such as Gram positive and negative bacteria, produce similar enzymes, which can cause tissue destruction directly via activation of our own matrix metalloproteinases (MMPs),
or release of membrane anchored cytokines or cytokine receptors .
Casein (from Latin caseus "cheese") is the most predominant phosphoprotein found in milk and cheese.
Also mentioned is the incidence of higher cancer rates in countries that consume more dairy products, specifically cheese, which has more than 10 times the casein density of milk.
Casein has been documented to break down in the stomach to produce the peptide casomorphin, an opioid that appears to act primarily as a histamine releaser.
As it exists in milk, it is a salt of calcium.
Casein is not coagulated by heat. It is precipitated by acids and by rennet enzymes, a proteolytic enzyme typically obtained from the stomachs of calves. The enzyme trypsin can hydrolyze off a phosphate-containing peptone.
It is commonly used by bodybuilders as a slow-digesting source of amino acids as opposed to the fast-digesting whey protein, and also as an extremely high source of glutamine (post-workout).
A study found that children with Autism placed on a casein-free diet for eight weeks showed significant behavior improvements.
It is well known that casein (from human or cow milk) will break down in the stomach to produce a peptide known as casomorphin which, as the name implies, will have opioid activities.
Similar effects are noted with gluten from wheat and some other cereals in which case the compounds formed are gluteomorphins.
If this opioid excess hypothesis is correct, there are a number of strategies which can be adopted. Firstly the anti-opioid drug Naltrexone could be considered, and promising initial results have been reported.
To date, we have identified N-acetylneuraminic acid, D-galactose and 2-acetamido-2-deoxy-D galactose on the glycopeptides.
These sugars are the same as those identified in K-casein
(Alais &Jolles, 1961) and for the first time demonstrate that the 2-amino-2-deoxy-D-galactose is present as the N-acetyl derivative.
the casein is precipitated by warming the powdered milk and adding dilute acetic acid .
Humm...remember my chemistry mathematical no-no about curcumin?
Curcumin comes in 3 forms as curcuminoids...
C21H20O6 - C20H18O5 - C19H16O4
Chemists will hate me for doing this (!), but...mathematically if we take C21H20O6 (curcumin) minus C19H16O4 (warfarin..there is ``H16'' marker for blood vessel damage) = C2H4O2 = acetic acid ! ODD...very odd.
Casein free diet + curcumin + coconut oil???
IL 1 beta upregulates PKC delta...
In The Key of Healing is a great "healing" CD.
Meditation downregulates the upregulated sympathetic system.
We're in sync.
When paying bills, to de-stress ;-) I listen to Italian music. Oh, how I want to return to Capri!
Posts: 9481 | From Sunshine State | Registered: Mar 2001
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quote:Originally posted by Marnie: That immune response is exactly what Bb needs to happen.
I agree we need an immune response to eradicate Bb. I become concerned when that immune response grows so large that tissue/organ damage occurs due to chronic excess inflammation. At that point, we lymies need something that damps down the inflammation without turning off the immune system's work against Bb.
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Vermont_Lymie
Frequent Contributor (1K+ posts)
Member # 9780
posted
Bb has a tendency to disable the immune system. For example, my blood tests show that the immediate immune response (do not recall whether that is Ig or Im) is below normal limits. My llmd says that is something seen often in folks with long-term untreated lyme.
Wouldn't that effect also dampen down inflammation?
I have a bit of herx-lyme brain today, so Marnie's post seems more difficult than usual to grok. Any translating appreciated!
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kelmo
Frequent Contributor (1K+ posts)
Member # 8797
posted
Dguy...that's what I've been wrestling with lately. My daughter has a positive autoimmune titer. It has been as high as 1:640 and as low as 1:116.
Lately, the babesia treatment has hit muscle tissue. She has been in so much pain that she had to back off. Her LLMD was concerned that her autoimmune response was killing too many good cells.
That's where the dilemma comes in. Some say don't back off on mepron, you have to gut it out. But, when two vicodin doesn't touch the pain, it's really hard to tough it.
Sorry Marnie, usually I don't have the patience to read and sort the information in the long posts. I'm glad they are there, for reference purposes, but could you summarize them?
Take care.
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
"To test the hypothesis that fluid flow alters NF-kappaB activation and expression of cell adhesion molecules in osteoblastic cells, we examined the effect of
oscillating fluid flow (OFF)
on tumor necrosis factor (TNF)-alpha-induced NF-kappaB activation in rat osteoblast-like UMR106 cells.
We found that OFF inhibits NF-kappaB-DNA binding activities, especially TNF-alpha -induced p50-p65 heterodimer NF-kappaB activation and TNF-alpha -induced intercellular adhesion molecule-1 mRNA expression.
The inhibitory effects of OFF on both TNF-alpha -induced NF-kappaB activation and intercellular adhesion molecule-1 mRNA expression were shear stress-dependent and also increased with OFF exposure duration, indicating that OFF has potent effects on mechanotransduction pathways.
OFF also inhibited TNF-alpha -induced IkappaBalpha degradation and TNF-alpha -induced IkappaB kinase (IKK) activity in a shear stress-dependent manner.
These results demonstrate that IKK is an initial target molecule for OFF effects on osteoblastic cells.
Thus, OFF inhibits TNF-alpha -induced IKK activation, leading to a decrease in phosphorylation and degradation of inhibitory IkappaBalpha , which in turn results in the decrease of TNF-alpha -induced NF-kappaB activation and potentially the transcription of target genes. J. Biol. Chem. (2001)
PMID: 11096064
Basically, we are stimulating circulation.
Want news articles on this?
Bb triggers the wrong immune response (for us), but the right one for Bb to survive.
That's kind of obvious.
[ 16. July 2007, 04:06 AM: Message edited by: Marnie ]
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