Marnie
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Most of this not linked because I linked it in another post re: the other protein, P8, that Bb acquires on "his" way out of the tick.
1. Bb expresses an outer surface protein, OspC on �his� way out of the tick and into us.
2. Bb picks up from the tick saliva, SALP 15 -a glycoprotein that contains 2 sugars: mannose and galactose.
3. But Bb ***also*** picks up another protein from the tick�s saliva called, P8 which prevents mannose (a sugar) binding lectin (a protein). That is a very �bad� protein.
4. This mannose binding lectin inhibitor (P8) blocks a pathway called the lectin pathway that is absolutely critical to eliminate Bb.
5. P8 was renamed the tick salivary lectin pathway inhibitor (TSLPI), but I will continue to use P8 to simplify.
6. So along comes Bb with mannose (and another sugar - galactose) plus a protein to prevent mannose binding lectin (MBL).
7. Bb needs mannose, that sugar, which is why �he� carries it along and prevents the binding of mannose (MBL).
8. Our dendrite cells (think of them as soldier scouts and the first to encounter the enemy, Bb) have a type II C-type lectin (protein) that is supposed to bind to SALP15.
10. That situation interferes with total phagocytosis (internalization of Bb into our defense cells to help start �his� destruction). It is critical for destruction of Bb that the lectin pathway is activated. Bb prevents that from happening thanks to P8.
11. During the journey from the tick to us, Bb is ***stressed*** and expresses RpoS which in turn, looks to upregulate OspC which binds the tick saliva proteins, SALP15 and P8.
12. OspC with the SALP15 protein and P8 protein attached helps Bb invade by interfering with our immune responders� �job� and thus alters our immune response.
13. OspC also looks to ***downregulate OspA.***
14. This is likely why the vaccine to Bb (designed based on OspA) did not work. Our first encounter with Bb involves OspC with SALP15 and P8 attached, not OspA.
15. Furthermore, our own antibody made in response to Bb�s OspB protein is damaged (although Mg can restore the health of that antibody IF it is available).
16. Along comes a cell signal called GLUT4 which is normally INSIDE the cell and only rarely goes to the cell surface.
17. GLUT4 helps deliver to the cell surface the insulin growth factor II � mannose 6 phosphate receptor i.e. IGF-II/Man-6-P receptor.Remember Bb loves and needs mannose (which is attached to a protein).
18. That receptor (IGF II-Man-6-P) is a substrate for type V transforming growth factor-beta ***receptor*** i.e., TGF beta receptor.
19. Normally TGF beta is excreted by many cells, including the macrophages.
20. Some cells that secrete TGF-β also have receptors for TGF-β.
21. TGF-β induces apoptosis in numerous cell types.
22. So�the IGFII-Man-6 P receptor (if GLUT4 was able to bring that receptor to the surface), would act as a substrate for the TGF beta receptor and when TGF beta locks onto its receptor this triggers cell death.
23.TGF-β blocks advance through the G1 phase of the cycle. In doing so, TGF-β ***suppresses*** expression of c-myc, a gene which is involved in G1 cell cycle progression. C-myc is regulator gene that codes for a transcription factor. A recent study demonstrated that ***temporary inhibition of Myc*** selectively kills mouse lung cancer cells, making it a potential cancer drug target. (Wikipedia).
24. TGF-β is believed to be important in regulation of the immune system by Foxp3+ Regulatory T cell and the differentiation of both Foxp3+ Regulatory T cell and Th17 cells. TGF-β appears to block the activation of lymphocytes and monocyte derived phagocytes. They are highly inflammatory and excessive amounts of the Th 17 cells are thought to play a key role in autoimmune disease such as multiple sclerosis (which was previously thought to be caused by Th1 cells), but also psoriasis, autoimmune uveitis, juvenile diabetes, rheumatoid arthritis, and Crohn's disease.) See how berberine helps those with MS here:
25. TGF-β also converts effector T-cells, which normally attack cancer with an inflammatory (immune) reaction, into regulatory (suppressor) T-cells, which ***turn off the inflammatory reaction.***
26. One animal study suggests that cholesterol suppresses the responsiveness of cardiovascular cells to TGF-β and ***its protective qualities,*** thus allowing atherosclerosis and heart disease to develop,*** while statins, drugs that lower cholesterol levels, may enhance the responsiveness of cardiovascular cells to the protective actions of TGF-beta. Wikipedia. (Note berberine and magnesium like statin drugs inhibit HMG CoA reductase and halt ***the cholesterol pathway*** that Bb takes to build �his� cell walls.
27. Higher concentrations of TGF-β are found in the blood and cerebrospinal fluid of patients with Alzheimer's Disease as compared to control subjects, suggesting a possible role in the neurodegenerative cascade leading to Alzheimer's Disease symptoms and pathology. (Wikipedia). However, are the RECEPTORS �available�? Remember, the receptor (IGF II-Man-6-P) is a substrate for type V transforming growth factor-beta receptor.
Doesn�t do a lot of good to have TGF beta and no receptor to lock onto!
28. Now I have to tell you more about P8, the MBL (mannose binding lectin) inhibitor. IF, I repeat IF, that protein is actually AKT8, this maybe a very dangerous situation because AKT8 (a retrovirus) contains viral and nonviral components. Obviously, I�m concerned about the viral component.
Akt is an oncogene (potentially causes cancer) - transduced (transferred) by an acute transforming retrovirus (Akt-8). Akt is an oncogene transduced by an acute transforming retrovirus (Akt-8) encodes a serine/threonine protein kinase (transfer phosphates).
Akt is also known as protein kinase B or simplified, PKB. In other words, it appears PKB/Akt comes from Akt8. Akt is also known as Akt1 as well as PKB. It blocks cell death i.e., it inhibts the apoptotic (cell death) processes.
29. Now we have Akt/Akt1/PKB�and along comes Akt2. Akt2 is an important signaling molecule in the Insulin signaling pathway. ***It is required to induce glucose transport.*** In a mouse which is null for Akt1 but normal for Akt2, glucose homeostasis is unperturbed, but the animals are smaller, consistent with a role for Akt1 in growth.
In contrast, mice which do not have Akt2, but have normal Akt1, have mild growth deficiency and display a diabetic phenotype (insulin resistance), again consistent with the idea that Akt2 is more specific for the insulin receptor signaling pathway. Wikipedia.
Thus Akt1/Akt/PKB may cause insulin resistance. Insulin, as many of you already know, helps transport glucose into the cells. When cells become �insulin resistant� this -> diabetes. It is not uncommon for lyme patients to have/develop insulin resistance -> diabetes. This impacts the transport of glucose into the cells.
30. You may say (rightly) that Bb needs glucose/the sugar mannose and you are correct. Bb needs the carbons. But our own cells need glucose too (and our brain cells need a LOT of glucose ongoing�.the amt. is quite amazing).
Without glucose/blocking the uptake which Bb needs, what is Bb going to do? In a situation where Bb has not enough glucose this upregulates Bb�s stress response. The same stress response may also happen if Bb is starved of amino acids (protein building blocks).
31. In serum starvation, B. burgdorferi responds by inducing a starvation response that results in changes in protein expression and eventually in the transformation of motile helical vegetative cells into nonmotile spherical starvation-stress forms.
32. Since IL1b (interleukin 1 beta) is upregulated (produced by the infected macrophages) this causes insulin resistance. PMID: 16865359 . With preventing glucose entry, this would starve/stress Bb and cause Bb to transform into a cyst form.
33. Proinflammatory IL1b (also called catabolin), instigates joint damage in rheumatoid arthritis. Il1b causes the induction of COX2 which contributes to inflammatory pain hypersensitivity.
34. Not only that but we now know The interleukin 1 beta (IL1B) gene is associated with failure to achieve remission and impaired emotion processing in major depression. PMID: 20044070
35. Berberine suppresses inflammatory agents-induced interleukin-1beta and tumor necrosis factor-alpha productions via the inhibition of IkappaB degradation in human lung cells. (Lung inflammation is not good.) PMID: 17681786
36.Berberine hydrochloride inhibited the expression of IL-1beta and TNF-alpha in periodontal tissues in rats periodontitis model and promoted the regeneration of the periodontal tissues. This study suggested that berberine hydrochloride may have potential clinical application. PMID: 18357892
37.Berberine (BER), the major alkaloidal component of Rhizoma coptidis, has multiple pharmacological effects including inhibition of acetylcholinesterase, reduction of cholesterol and glucose levels, anti-inflammatory, neuroprotective and neurotrophic effects.
It has also been demonstrated that BER can reduce the production of beta-amyloid40/42, which plays a critical and primary role in the pathogenesis of Alzheimer's disease. http://www.biomedcentral.com/1471-2202/12/125/ (Acetylcholinesterase is the enzyme that BREAKS down the neurotransmitter, acetylcholine.)
38.Treatment of hyperhomocysteinemic rats with berberine for 5 days ***inhibited HMG-CoA reductase*** activity and reduced hepatic cholesterol content.
Bb follows the �cholesterol pathway� to build �his� cell walls. It is important to block this i.e., to inhibit HMG CoA �reductase. Or take a look at this:
39. Though some researchers say it does not inhibit HMG CoA reductase in the liver, but works a different way i.e., enhances LDL (low density lipoprotein) RECEPTOR protein and mRNA levels in liver cells to control serum cholesterol levels without the side effects attributed to statin drugs.
40. The most important link re: berberine involves its impact on SPIROCHETES.
�In addition to its traditional and pharmacological use as an alterative, current pharmacological models of herbal medicine note berberine (one of the main active alkaloids in Berberis) to be a specific for 25 strains of bacteria, as well as fungal, protozoal and spirochetal infections (Zhang, 2007; Chen, 2004; Mills & Bone, 2000).
Berberine was comparable to quinine in vitro against two clones of human malaria (Mills & Bone, 2000). Another berberine containing plant, Huang Lian (Coptis chinensis) has been used as an antispirochetal, where it is thought to be most commonly used herbal antimicrobial agent in China (Zhang, 2007;Chen, 2004). http://lymepoland.com/pliki/LD-%20zio%C3%85%C2%82a.pdf
Enough for now...but, yes I have more - all linked (documented). Anyone want more? Or do you want me to jump to the conclusion?
We needed a Th2 response (not Th1 or Th17 response) because Bb grabs ahold of a NEUROTOXIN on his way out of the tick.
[ 06-28-2012, 09:39 PM: Message edited by: Marnie ]
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surprise
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Sorry- don't mean to be dense-
I am assuming when you talk about Berberine, it is Golden Seal supplement/ herb.
My daughter had the metametrix stool test, done with DNA, and gives a list of both pharmacuetical antibiotics, and natural herbs,
which will effectively fight/kill that particular persons bacteria and fungal infections.
Golden Seal/Berberine was the only one listed as not going to have any impact for her.
I was also on another health board for years for her, and it was recommended there not to use Golden Seal/Berberine for more than 2 weeks at a time.
Just a different experience.
-------------------- Lyme positive PCR blood, and positive Bartonella henselae Igenex, 2011. low positive Fry biofilm test, 2012. Update 7/16- After extensive treatments, doing okay! Posts: 2518 | From USA | Registered: Nov 2011
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Razzle
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According to Buhner, we get a Th1 response upon Lyme infection initially, but this eventually turns into a chronic Th2 response in chronic Lyme...thus the connection with increased allergies and other Th2 dominant illnesses (Lupus, etc.).
-------------------- -Razzle Lyme IgM IGeneX Pos. 18+++, 23-25+, 30++, 31+, 34++, 39 IND, 83-93 IND; IgG IGeneX Neg. 30+, 39 IND; Mayo/CDC Pos. IgM 23+, 39+; IgG Mayo/CDC Neg. band 41+; Bart. (clinical dx; Fry Labs neg. for all coinfections), sx >30 yrs. Posts: 4166 | From WA | Registered: Feb 2011
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Razzle
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Berberine is actually a constituent in a number of herbs, not just goldenseal... Some of these herbs include Oregon Grape, Barberry, Coptis, Goldenseal, etc...
-------------------- -Razzle Lyme IgM IGeneX Pos. 18+++, 23-25+, 30++, 31+, 34++, 39 IND, 83-93 IND; IgG IGeneX Neg. 30+, 39 IND; Mayo/CDC Pos. IgM 23+, 39+; IgG Mayo/CDC Neg. band 41+; Bart. (clinical dx; Fry Labs neg. for all coinfections), sx >30 yrs. Posts: 4166 | From WA | Registered: Feb 2011
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surprise
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Actually, I just looked at her test, and it was labeled together:
Berberine- Golden Seal
-------------------- Lyme positive PCR blood, and positive Bartonella henselae Igenex, 2011. low positive Fry biofilm test, 2012. Update 7/16- After extensive treatments, doing okay! Posts: 2518 | From USA | Registered: Nov 2011
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Razzle
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posted
Maybe she needs a different berberine containing herb than the goldenseal? Or maybe berberine wasn't the right thing for her at the time of the testing (but this may change at some future date)...?
-------------------- -Razzle Lyme IgM IGeneX Pos. 18+++, 23-25+, 30++, 31+, 34++, 39 IND, 83-93 IND; IgG IGeneX Neg. 30+, 39 IND; Mayo/CDC Pos. IgM 23+, 39+; IgG Mayo/CDC Neg. band 41+; Bart. (clinical dx; Fry Labs neg. for all coinfections), sx >30 yrs. Posts: 4166 | From WA | Registered: Feb 2011
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posted
What is the recommended dosage of berberine?
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surprise
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Thank you Razzle- I've just never used it with her, as there are so many other herbs to choose from (and we've done antibiotics) and this came back a no go.
Maybe my point is Berberine might not be for everyone, and it is still recommended for no more than 2 weeks at a time (Golden Seal)
-------------------- Lyme positive PCR blood, and positive Bartonella henselae Igenex, 2011. low positive Fry biofilm test, 2012. Update 7/16- After extensive treatments, doing okay! Posts: 2518 | From USA | Registered: Nov 2011
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Marnie
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posted
Berberine ***Chloride (HCL)*** 250mg Three times a day
***15 minutes PRIOR to a carb. rich diet (meals)***
appears to be the type of berberine (NOT berberine sulfate)/dosage/timing in trials i.e., "safe".
That translates to 3 good meals a day with Berberine chloride, 250 i.e., GlycoX 250, 15 minutes prior to your 3 meals. GlycoX 500 is also available, but I think the 250 TID (3x/day) is sufficient and safe. I am concerned about SAFE dosages.
That is GlycoX 250. Avail. on Amazon. Not expensive - relatively.
If you "cheat" and take in carbs./glucose "snacks" it it likely you will prevent the desired outcome.
Repeat that!!! NO carb. snacking. NO CHEATING.
I think it is important to use the (already) open chloride channels.
Keep in mind...IV MgCl was given...utilizing the chloride channels.
I understand that Tamoxifen (for breast cancer) and Frontline (to protect our dogs from lyme transmission - by blocking the chloride channels IN THE TICK) works by BLOCKING the chloride channels.
It is important -esp. for gals - that you know, Tamoxifen doesn't always work...alone. The cells are "resistant" to dying.
Keep this in your heads...ongoing inflammation IS a cancer trigger.
Google the words, "Tamoxifen EPA". EPA (OmegaBrite) reduces inflammation.
It is KEY that we reduce inflammation AND hit Bb.
Believe me...the Th1 response to Bb is up and fully active...ongoing. TNF alpha, IL-1 B, etc.
I don't care if you attribute the toxin component to P8/AKT8 (which contains nonviral and ***viral protein*** components) or Bbtox1 (a neuroTOXIN)
Does ANYONE want the additional information with links?
I'm trying hard to contact lyme-literate persons with this very very important information...which IS very "RECENT"!!!
Knowing about P8 (a lectin pathway inhibitor via inhibiting mannose bindin lectin(MBL)that Bb picks up (in addition to the SALP15 protein) impacts our ability from the get-go...to eliminate Bb -> ONGOING infection. Researchers first discovered this protein and published their findings in August of 2011.
[ 06-28-2012, 09:44 PM: Message edited by: Marnie ]
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Lymeorsomething
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Tamoxifen is also useful for guys (can boost T) but is rendered not too practical by its clot causing potential.
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Marnie
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blood-thinning properties of EPA(Omega 3)...
Or just good old ASA...a child dose...once a day - to prevent clots.
Tamoxifen is a man-made PKC inhibtor. I thought PKC required calcium and some forms of PKC do, but others don't.
It was my understanding that C stood for calcium, P stood for protein and K stood for "kinase" = help transfer phosphates...
Calcium activated phosphate transfer onto a protein...so I thought...wrongly.
"Members of the Protein Kinase C (PKC) family are serine/threonine protein kinases that play a key regulatory role in a number of cellular functions including cell growth and differentiation, hormone secretion, and gene expression.
Multiple genes and alternative splicing result in three subfamilies, which differ in their co-factor requirements:
conventional PKC isoforms (alpha, beta 1, beta 2, and gamma) which *require calcium* and phosphatidylserine (PS), diacylglycerol (DAG) or phorbol esters for activation;
novel isoforms (delta, epsilon, eta, and theta), which are *calcium-independent* but are still regulated by PS, DAG, or phorbol esters; and
atypical isoforms (iota/lambda and zeta), which are *calcium-independent* and do not require PS, DAG, or phorbol esters for activation."
Phosphatidylserine impacts the HPA axis...beneficially.
The hypothalamic-pituitary-adrenal...
Google this: Phosphatidylserine HPA axis
Bb's proteins: "B. burgdorferi contained only phosphatidylglycerol and phosphatidylcholine" (a component in lecithin)
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Marnie
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Looking for Bb's DNA in stool?
Try looking for Bb's DNA in URINE. Betcha it is like this:
Which is why your daughter's stool spec. did not indicate she really really could us berberine chloride!
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