Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Dr. S said,"Until recently, no tests could show if a patient had living Lyme spirochetes. Our paper, sent last month to the New England Journal of Medicine on use of C4a, may be a breakthrough."
When C4A is present, there's a LOT inflammation going on.
If a person was missing the gene to make this, it is very likely they would die of many diseases since inflammation is, and always has been, a part of the healing process.
In 1989:
Hack CE, et al. Elevated plasma levels of the
anaphylatoxins C3a and C4a are associated
with a fatal outcome in sepsis.
Am J Med 1989;86:20-26.
(Don't freak...we make an inactivator.!)
The following was presented at a conference in May, 2006 in Malta. The conference was called: Cellular and Molecular Targets in Allergy and Clinical Immunology
C3a and C4a: Complement Split Products Identify Patients with Acute Lyme disease
R. Shoemaker1, P. Giclas2, A. Barbour3, D. House1 and M.M. Glovsky4 1Center for Research on Biotoxin Associated Illnesses, Pocomoke, MD 2National Jewish Research and Medical Center, Denver, CO 3UC Irvine, Irvine, CA 4Quest Diagnostics, Department of Immunology, San Juan Capistrano, CA
Background: Lyme disease, caused in the USA by infection with the tickborne spirochete Borrelia burgdorferi, is an increasingly prevalent infectious disease.
Immune mediated inflammatory responses, both innate and acquired, are important in the eradication of the spirochete.
Innate immune responses, especially complement, could serve as a marker for illness in patients seen shortly after a tick bite. No test is currently available to diagnose acute Lyme disease.
Conclusions: C3a and C4a anaphylatoxins were significantly higher (p<.001) in the acute Lyme patients compared with the tick bite controls and normal patients. Measuring C3a and C4a should be helpful in differentiating acute Lyme disease from non-Lyme disease patients.
"Immune mediated inflammatory responses, both innate and acquired, are important in the eradication of the spirochete."
Not quite. In order to make healthy antibodies to eradicate Bb, we need Mg and Ca. If Mg levels drop, the antibodies are damaged, or a part of them called the "fab" portion, and they don't work. Up goes TNF alpha because ONE of its jobs is to rid damaged antibodies.
The anti-AChR (anti-acetylcholine receptor)antibodies are believed to damage the post-synaptic membrane and thus create these abnormalities through the complement pathway (Zweiman & Levinson, 1992). The binding of an antibody to its target may trigger the classical complement pathway (Janeway et al., 1999).
(Stay with me.)
The small peptide fragments C3a, C4a, and C5a that are released during complement activation bind to specific receptors and
*produce local inflammatory responses.*
This inflammation, which will be chronic because the pathway triggering AChR/anti-AChR antibody binding will occur repeatedly, is believed to damage the post-synaptic membrane of the muscle fiber over time (Novella, 1998).
That is logical. If an infection is STILL PRESENT and if that infection is triggering too much acetylcholine (but we need some), one would assume the body would turn this pathway on and off to try to clear the infection (Bb is after our choline), yet at the same time, provide enough to keep us functioning.
The anaphylatoxins have powerful effects on blood vessel walls, causing contraction of smooth muscle and an increase in vascular permeability.
These effects show specific tachyphylaxis (i.e. repeated stimulation induces diminishing responses) and can be blocked by antihistamines; they are probably mediated indirectly via release of histamine from mast cells and basophils.
C5a is the most powerful, approximately 100 times more effective than C3a, and 1000 times more effective than C4a. The smooth muscle contraction in the lungs is primarily mediated by LTC and LTD . This activity decrease in the following order:
C5a >histamine > acetylcholine > C3a > C4a
Note:
"Complement C3 contributes to ethanol-induced liver steatosis in mice."
Lyme patients are not alone when it comes to C4A:
Complement activation in a model of chronic fatigue syndrome.
B Sorevsen et al. Journal of Allergy and Clinical Immunology, August 2003; 112; pages 397-403.
This study looked at post-exercise immune changes. A significant increase in the split complement protein C4a was detected in the CFS group six hours post exercise, correlating with post-exercise symptom reports.
In healthy subjects, C4a generation is only stimulated at much higher exercise levels than those involved in this study, and levels return to normal within three hours.
The authors note that the exercise challenge allowed them to study CFS subjects in an exacerbated state of illness, as the patients subsequently showed significant increases in symptoms."
During exercise, we make lactic acid. Our system becomes more acidic. We also make CoQ10 (need Mg and B6) which carries hydrogen INTO the cells when we exercise and increases the need for more oxygen.
C4A has been "discussed" with regards to Alzheimer's too:
"C4A is a component of the blood-borne complement cascade. Its allelic variation has drawn some attention, and disparate papers have conflicted on its phenotype in AD vs control patients."
During surgery, when certain drugs are given:
Recent clinical studies following cardiopulmonary bypass reported that the plasma levels of C3a and C4a are increased immediately after protamine administration for heparin neutralization,7-8 thereby confirming in humans the occurrence of nonimmunological complement activation by heparin-protamine interaction.
Several human studies have demonstrated complement activation by protamine neutralization of heparin with an increase of plasma C3a and C4a (but not C5a), indicating classical pathway complement activation. 5-7-8
Whether or not C4A gene deficiency plays a part in lupus is controversial. Here is one that says no:
Our results argue against a specific role for C4A gene deficiency in determining disease susceptibility among patients with SLE that are C4-deficient. [References: 37]
You're going to be quizzed on it later, so commit it to memory. (Just kidding!)
"Carboxypeptidase B catalyzes the hydrolysis (a chemical reaction that uses water to break down a compound) of the peptide bonds involving basic amino acids lysine, arginine and ornithine. This hydrolysis occurs at the C-terminal bond in these polypeptides."
What's so special about this - where is it made, what does it do?
It comes from the pancreas and it binds zinc.
Basics...Bb follows the glycolysis pathway. This bugger is a sugar lover. When blood levels of sugar (glucose) rise, acidic insulin (from the pancreas beta cells) counters the alkaline sugar. When the blood sugar is back to normal, the pancreas alpha cells releases another acid to downregulate insulin. It is called glucagon. Glucagon is the ONLY thing that will INactivate PFK2. PFK1 and 2 are "rate limiting" enzymes for the glycolysis (sugar to make ATP) route. Bb is "PFK dependent". Several things INactivate PFK1 (Mg is one), and insulin ACTIVATES it.
Now, when sugar is broken down, one thing that results is ethanol (alcohol) which is damaging to many organs, so it should come as no surprise that protective measures kick in.
This should come as no surprise:
"Active carboxypeptidase B is present in free form in serum from patients with acute pancreatitis."
"Indeed, it has been shown in in vitro experiments that pCPB (pancreatic carboxypeptidase B) inhibits Plg (plasminogen ) activation and prolongs fibrinolysis..."
The pancreatic carboxypeptidase B enzyme is released. Why? I'll get to that in a minute.
Zinc. In our neutrophils (most abundant white blood cell) is something called calprotectin which binds zinc. Isn't it curious from a timing standpoint that the neutrophils regenerate about every 3 weeks. That appears to coincide with herx cycles. And it has been reported that indeed calprotectin can "cure" lyme.
PMID: 12874352
I have to pull a very old file for some "basic" material:
"Metalloproteases, on the other hand, seem to be a common feature in most bacterial pathogens."
Now, what is happens when calprotectin or carboxypeptidase B deplete zinc?
This is IMPORTANT:
In addition to calcium, other physiologically important divalent cations
(magnesium and zinc)
are known to influence fibrin formation and structure.
We have studied the effect of different concentrations (0-20 micromol/l) of zinc ions (Zn2+) in the absence and presence of calcium on the gel structure formed in purified fibrinogen-enzyme systems.
For that purpose, we used turbidity measurement, liquid permeation and confocal three-dimensional microscopy of the gel as well as sodium dodecyl sulphate (SDS)-gel electrophoresis. The results of turbidity measurements indicated that the clotting time decreased with increasing concentrations of Zn2+.
The fiber mass: length ratio (mu) values showed that the porosity of the gels increased in a concentration-dependent manner, i.e. at higher concentrations of Zn2+, larger pores with thicker fibrin fibers were formed. Three-dimensional microscopy data of the gels were in good agreement with the mu data. On SDS-gel electrophores of reduced fibrin, no cross-linking was observed in the presence of zinc ions only (without the addition of calcium ions), nor were D-D dimer bands observed in non-reduced plasmin digested fibrin samples in the presence of zinc ions only.
The above results show that zinc changes the fibrin gel structure and that this effect appears to be independent of calcium.
PMID: 9863712
acute zinc depletion impairs platelet aggregation and prolongs bleeding time.
In addition, Zinc supplements have been shown in some studies to decrease Cu/Zn-superoxide dismutase activity, primarily due to the antagonistic relationship between high zinc intakes and copper absorption.
Journal of the American College of Nutrition, Vol. 25, No. 4, 285-291 (2006)
Cu/Zn superoxide dismutase is an ANTIOXIDANT enzyme. These minerals need to be in balance.
So...by depleting zinc, we "thin" the blood and change the fibrin "cloak" preventing the locking on/shielding.
But...did you happen to catch the mention of Mg as working the same?
In conclusion, these results indicate that the antiplatelet activity of magnesium sulfate may be involved in the following two pathways:
(1) Magnesium sulfate may inhibit the activation of protein kinase C, followed by inhibition of phosphoinositide breakdown and intracellular Ca+2 mobilization, thereby leading to inhibition of the phosphorylation of P47.
(2) On the other hand, magnesium sulfate inhibits the Na+/H+ exchanger, leading to reduced intracellular Ca+2 mobilization, and ultimately to inhibition of platelet aggregation and the ATP-release reaction.
PMID: 14730206
Borrelia burgdorferi isolate B31 expressed a 47 kDa (P47) fibronectin-binding protein that was localized to the outer envelope based on susceptibility to proteinase K.
PMID: 9988477
"An activity series is a list of substances ranked in order of relative reactivity.
For example, magnesium metal can knock hydrogen ions out of solution, so it is considered more reactive than elemental hydrogen:
Mg(s) + 2 H+(aq) H2(g) + Mg2+(aq)
Zinc can also displace hydrogen ions from solution:
Zn(s) + 2 H+(aq) H2(g) + Zn2+(aq) so zinc is also more active than hydrogen.
***But magnesium metal can remove zinc ions from solution: Mg(s) + Zn2+(aq) Zn(s) + Mg2+(aq)***
The reverse reaction does occur- a very tiny amount of zinc placed in a solution of magnesium ions will dissolve."
So, dear Dr. S...while C4A may indicate ongoing inflammation, if you really want to halt this disease, look very closely at Mg pyrophosphate and B6.
In other words...Dr. Valletta's U.S. patent titled: Magnesium for autoimmune.
Mg is attached to ATP (phosphate)and works in concert with B6.
Mg can displace zinc. Mg (and Ca) are needed to make healthy antibodies. Mg INactivates PFK Mg INactivates HMG CoA reductase halting the cholesterol pathway which follows Mg is needed to make ALL proteins...hormones, enzymes besides the antibodies Mg, and ONLY Mg is attached to our energy carrier...ATP Mg is an anti-inflammatory Mg is an anti-histamine Mg stimulates DNA REPAIR
Researchers are right now trying to figure out how to monitor Mg levels and give it to our astronauts who suffer the "oxidative stress" problems when in space and return with PFK problem levels and anemia.
We are also very aware of the medical abstract from a CANCER hospital in Romania titled:
"Lyme disease and magnesium deficiency"
And the very "significant" drop at the outset.
Other "alternative" therapies (besides nutrition) seem to work in other ways, but can do the job too.
Like you, Dr. S...I prefer to stick to the facts.
[ 22. September 2006, 08:22 AM: Message edited by: Marnie ]
Posts: 9481 | From Sunshine State | Registered: Mar 2001
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northstar
Frequent Contributor (1K+ posts)
Member # 7911
posted
Hi Marnie,
That was a good response......am still working on understanding the middle! Did I ever mention I had 8 o'clock lectures for chemistry......snore.......and it was why I transferred out of biology major! And where can I get a carboxy pill! As a person with lyme, I am always looking for the magic solution!
Anyway, the use of c4 as a marker for lyme seems kind of generic to me; sort of like a fever is a generic marker for illness.
Genetic lack may predispose to a certain way of responding to infection, and affect resolution, but it is not a direct indicator of a specific infection, nor true across all populations.
Northstar
Posts: 1331 | From hither and yonder | Registered: Sep 2005
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She would probably write, but me thinks she's a woman ahead of her time. Her understanding and research would undermine exactly what the "good ol' boys" have been given credit for many years.
Science and academia is where she was sentenced, because if she wrote an abstract, it wouldn't be submitted and she would be referred to teach chemistry at some college so that she wouldn't take the thunder away from "the guys at Yale".
Is that how it panned out for you Marnie? You are so passionate about healing the sick. You are very much admired.
-------------------- Lymester Posts: 519 | From CT | Registered: Jun 2004
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northstar
Frequent Contributor (1K+ posts)
Member # 7911
posted
My 2 cents, if she wrote:
He is on his C4 pillar, and will not see anything else.....what group of researchers does that sound like? Microscopic vision.....
Also, Marnie's contribution will probably be "lifted" by another researcher. Has happened many times before.
Northstar
Posts: 1331 | From hither and yonder | Registered: Sep 2005
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Tincup
Honored Contributor (10K+ posts)
Member # 5829
posted
uh oh!
Someone is in BIG trouble now.
For some VERY strange reason I ALMOST understood all that! That's a first!
Thanks for the explanation Marnie. As usual.. excellent work! And I really did follow most of it! Wow! I KNOW you are proud of me!
Hope you won't mind if I share this with a few good docs? Do let me know!
Oh.. and the questions I have...
The title of the abstract you shared was.. "C3a and C4a: Complement Split Products Identify Patients with Acute Lyme disease"
Not to sound stupid.. but do we really need a TEST to identify "acute Lyme"? Seems that is a pretty obvious/simple thing after we've been doing it for 25 years now.
Plus.. do we .. those who have experience first hand... REALLY believe ANY Lyme test will be 100 percent accurate after all the garbage going on in the past... and still going on?
Do YOU want to trust YOUR life.. or the life of YOUR family members... to the results of another Lyme test?
Which brings up another problem.
Notice the co-authors on the abstract... specifically, "A. Barbour3". That caught my eye.
Now.. From what I recall, A. Barbour is connected ... and has been for years... to patents for "stuff" used in Lyme tests. (The Barbour medium.. ring a bell?)
The old "tests" (which have been critized by everyone from the FDA, CDC, IDSA, to my dog Spot) were tested for their ability to accurately determine if people with Lyme actually had Lyme. (Hopkins study, Oct. 2005)
From what I recall... keeping in mind this is simply from memory sitting here late at night... and I am just yaking as usual...
Hopkins researchers (one of many groups who have spoken out) determined NONE of the Lyme tests (Barbour medium was mentioned) were able to accurately diagnose Lyme disease in the majority of patients proven to have Lyme disease. Even when using several types of tests together.. the failure rate was significant.
Actually, the accuracy rates using the current Lyme tests was pitiful, at best. I believe the word Hopkins used to describe the tests was "unreliable".
Now.. if everyone KNOWS those tests have sucked for so many years... why is anyone associating with A. Barbour.... or possibly using anything connected to A. Barbour's "stuff".... to make new tests? Why is A. Barbour even involved in MORE tests at this point?
Another patent perhaps? Hmmmmmmmmmmm??? I don't know. It would be interesting to check out though.
Or... Could these tests be in the making because the old tests, that have been largely responsible for missing so many in the past, will most likely be discontinued once that big law suit gets rolling?
Do I hear that familiar $$ sound?
Cha-ching??
I also noted "Quest Lab" is listed on the abstract. Shame shame, everybody knows your name.
True.. in our survey here they didn't rate as low as Labcorp's tests for Lyme.. or did they?
Yes.. I do believe they tied for last place now that I think about it.... or Quest came in slightly above Labcorp... by a frog's hair.
My guess is.. unfortunately... that I won't be able to sleep tonight worrying about why anyone is using Barbour's past reputation ... along with his "stuff".. to make a test to TRY to diagnose "acute" Lyme.
Especially when the CDC has been saying for years you don't NEED a positive test...
CAUSE IT'S A CLINICAL DIAGNOSIS!
Don't we already know that acute Lyme and a number of other tick borne diseases can be prevented ... and/or treated in most cases in the the very early stages... for less than $30.00 worth of doxycycline.
Isn't it better to treat those folks with acute fevers, history of tick bite in an endemic area, rash, etc. than to play around and depend on another "test" to determine a persons future?
Have we learned NOTHING?
Why should people be wasting money... and VALUABLE TIME... making an appointment with a doctor (or duck), getting a lab slip.. having blood drawn.. waiting for results.. waiting for a prescription to be written and arguements with their insurance.. and going to pick up the prescription...
When the bacterial infection causing the symptoms will need to be treated anyway.. Lyme or NOT?
What was that figure? They found Lyme was detected in the spinal fluid in as little as FOUR hours?
OR.. do I see in my crystal ball.. a plan to use any NEW tests developed for an upcoming vaccine trial... or it's distribution?
With over 1.4 million LymeRix vaccines sold during it's short lifespan.. not counting the Lyme vaccine trials... even at $10.00 a pop for the "stuff"...
HOLY COW Batman! We are looking at over 12 MILLION dollars!
Be still my heart!
It must be bed time for Bonzo. No more opinions tonight from meeeeeee.
But I would like to know YOUR thoughts and opinions on the matter.
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