Borrelia neurotoxin circulation

[stf]

Dr Burrascano writes:

It has been said that the longer one is ill with Lyme, the more neurotoxin is present in the body. It probably is stored in fatty tissues, and once present, persists for a very long time. This may be because of enterohepatic circulation, where the toxin is excreted via the bile into the intestinal tract, but then is reabsorbed from the intestinal tract back into the blood stream. This forms the basis for treatment.

(see: http://ilads.org/burrascano_0905.html)

Could anyone explain to me why is that toxin reabsorbed? It isn't the usual way for toxins and other s*it to be handled by humans, is it? I would guess that the whole deal with liver and the bile is to do only this first step: excrete the toxin via the bile into the intestinal tract.

STF

[cave76]

Note these words in Burrascano's text:

It has been said

probably

may

See my post at:

viewtopic.php?f=7&t=1700

[Fin24]

explanation physiology

the body DOES put toxins and byproducts from liver into the gut where it is expected that most of it binds with gut materials and stool/feces and then poops out BUT as the lining of the gut is such that it absorbs well ( for nutirents) it follows that this isnt a perfect system and that some can and will be reabsorbed back

its one of biology's oxymorons thats for now the best system anyway--putting stuff you want taken out with the garbage into a place designed to absorb--like using a paper bag you need to keep to carry smelly messy garbage to the trash--you know SOME of that garbage will be absorbed by the bag but most will be dumped so you live with it

this is the basis for the binders like Questran-or clays--ingest it and it sits there waiting for the toxins and grabs them to eliminate

the theory does actually work...better for some than others...be aware of the side effects and long vs short term gains and losses--like with all else

[Claudia]

I much more agree with LymeMD's take on this possible therapeutic effect, than I do with Burrascano's and Shoemaker's:

LymeMD.blog wrote:

Welchol, Questran and neurotoxins?

This one is a bit technical. You can skip to the bottom.
Neuroborreliosis the most common and dreaded syndrome I see in patients with disseminated Lyme disease is amongst the most challenging clinical problems seen.
Some mechanisms of CNS dysfunction have been fairly well demonstrated. Bb can cross the blood brain barrier. The pathogens are greeted by local immune cells including: monocytes, macrophages and dendritic cells. An inflammatory reaction medicated by cytokines and chemokines is initiated. Antibody producing B cells appear in the CSF(spinal fluid) in unexpectedly high numbers. The Bb bacteria seem to enter glial cells(supporting cells) rather than brain neurons. A proliferation of killer T cell(clones) has been shown. The damage to nerve cells seems to be due to cytotoxic(cell killing)side effects of this process. Autoimmune processes via the production of autoantibodies and molecular mimicry have been established in animal models. The third purported cause of Lyme/brain disease involves "neurotoxins." From what I can gather, this seems to be a theoretical idea; there is not much science to support it.

The most frequently mentioned neurotoxin is quinolinic acid. High levels of this toxin have been measured in the spinal fluid of patients with various chronic neurological diseases. There is experimental evidence that macrophages incubated with Bb produce quinolinic acid. Scientific evidence, from my review of the literature, does not support the accumulation of quinolinic acid in the brains, spinal fluid or bile of Lyme patients. If such evidence exists please post it here.

The neurotoxin theory, as it relates to bile acid sequestrants is:
Lipid soluble toxins are postulated to be processed through the liver, then end up in bile, which is recirculated. These toxins are then able to egress back into the blood stream, find their way past the blood brain barrier and cause neurological dysfunction. These toxins have not been identified. Bile binding resins remove these toxins causing an improvement in neurolgical dysfunction.

These ideas stem from theories described by Dr. Shoemaker in Maryland. And have been repeated by Dr. Burasccano in his guidelines.

Standing back, the theory seems dubious at the very least.

In my clinical practice I have tried these drugs: they work! How?

It turns out that Welchol lowers CRP- C-reactive protein, a primary marker for inflammation or immune activation. CRP is a circulating protein which initiates the complement cascade. This a major "effector" mechanism of the immune system.

Rather than removing neurotoxins, Welchol may be removing inflammatory byproducts of the immune response to Lyme infection. This dovetails with my observation that this drug frequently reduces not only brain inflammation, but can frequently improve other immune mediated symptoms like joint pain.

Bottom line: Welchol and Questran help. They remove "something" that is bound to bile, or by some other mechanism. They lower inflammation based on studies which show a reduction in CRP.

Food for thought: Statin drugs like Lipitor also lower CRP. This mechanism in the prevention of heart disease may be more important than the cholesterol lowering effect. Some studies have shown that patients on statins have a lower rate of Alzheimer's disease. Anti-inflammatory effect? "Neuroprotective" effect?

Better news. Coffee is the new wonder drug. It lowers the risk of Parkinson's, Alzheimer's, liver disease and more. It apparently reduces brain inflammation.


http://lymemd.blogspot.com/2008_12_01_archive.html

[Martian]

Some doctors try to remove a hypothetical neurotoxin allegedly produced by Bb from the body. Some talk about it as if it's a fact that this happens and that this treatment helps removing those toxins.

From Burrascano's guidelines 2005, page 13:

BORRELIA NEUROTOXIN (With thanks to Dr. Shoemaker)
Two groups have reported evidence that Borrelia, like several other bacteria, produce neurotoxins. These compounds reportedly can cause many of the symptoms of encephalopathy, cause an ongoing inflammatory reaction manifested as some of the virus-like symptoms common in late Lyme, and also potentially interfere with hormone action by blocking hormone receptors. At this time, there is no assay available to detect whether this compound is present, nor can the amount of toxin be quantified. Indirect measures are currently employed, such as measures of cytokine activation and hormone resistance. A visual contrast sensitivity test (VCS test) reportedly is quite useful in documenting CNS effects of the neurotoxin, and to follow effects of treatment. This test is available at some centers and on the internet.

No reference is given as to what groups reported that evidence. The limited evidence that I have seen about this does not tell us if Bb indeed produces neurotoxins. The VCS test comes from Dr. Shoemaker. He writes about it at his website. It all looks quite dubious to me:

Source: http://www.chronicneurotoxins.com/

How We Can Help You
Standard medical diagnostic tests are usually normal in patients who have these biotoxin-induced illnesses, which makes it difficult to diagnose and treat. We have a simple tool that assists in diagnosis by showing evidence of a neurological deficit. That screening tool is the visual contrast sensitivity test (VCS). A positive VCS test, in the presence of biotoxin exposure potential, and a symptom complex involving multiple systems, and in the absence of other historical, medical or treatment conditions that likely explain the symptoms, provide a basis for making a diagnosis of Probable Biotoxin-Mediated Illness. Users of this website can take a screening version of the VCS test and complete questionnaires on exposure potential, symptoms and medical history. When biotoxins are suspected, users can purchase a package that includes the treatment protocol and three additional vision tests that can be used to monitor recovery during treatment. Patients can request treatment by taking the protocol and the associated research articles to their local physician or to Dr. Shoemaker.

How the VCS Test Works
The visual system includes a complex neurological network that involves the retina, optic nerve, brain nuclei and the visual cortex. One of the main outputs of the visual system is pattern vision. The VCS tests is an indicator of ability to detect visual patterns. The test measures the least amount of contrast between light and dark bars (sinusoidal grating) that is needed for the viewer to detect the bars. VCS is measured at five different bar sizes (spatial frequencies) because perception of different bar sizes is mediated by different physiological components, and these components are differentially susceptible to effects from different toxic substances (10-17). The largest effects of biotoxins are at the mid-size bars (1-8). To measure VCS, viewers are presented a series of bar patterns at each of the five bar sizes. Viewers respond by indicating that the bars are tilted to the left, tilted to the right, are straight up and down, or that they cannot see any bars. The pattern with the lowest contrast that is correctly identified is the measure of VCS for that bar size. Upon completing the VCS test, viewers receive a message indicating that biotoxins are (positive) or are not (negative) likely to be involved in their illness. The criteria for getting a "positive" VCS result is set high to avoid false positive results. This occasionally results in a false negative result; some cases of chronic-biotoxin induced illness may pass the VCS test a some times. VCS can be measured during treatment to monitor recovery.

[Martian]

Also check the video of Burrascano discussing Lyme toxins and the Shoemaker Protocol, taken from a Hope to Heal Lyme conference. (original title: Neurotoxins & Lyme disease - Joseph J. Burrascano, MD)

Lyme Disease and Biotoxins: http://nl.youtube.com/watch?v=DFwHXy99M2o

Dr. Joseph J. Burrascano discusses the biotoxin work of Dr. Ritchie Shoemaker

[BlueSky]

[*]

[Claudia]

A couple of studies (thanks, Joe Ham) that support LymeMD's more likely theory as to the possible therapeutic effect of these binders, as opposed to Burrascano and Shoemaker's:

From the thread Borrelia and the Brain: ( posting.php?mode=quote&f=5&p=15533#postingbox)

Am J Pathol. 2008 Nov;173(5):1415-27. Epub 2008 Oct 2.
Interaction of the Lyme disease spirochete Borrelia burgdorferi with brain parenchyma elicits inflammatory mediators from glial cells as well as glial and neuronal apoptosis.
http://www.ncbi.nlm.nih.gov/pubmed/18832582

Ramesh G, Borda JT, Dufour J, Kaushal D, Ramamoorthy R, Lackner AA, Philipp MT.
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University, Covington, LA 70433, USA.

Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, often manifests by causing neurocognitive deficits. As a possible mechanism for Lyme neuroborreliosis, we hypothesized that B. burgdorferi induces the production of inflammatory mediators in the central nervous system with concomitant neuronal and/or glial apoptosis.

To test our hypothesis, we constructed an ex vivo model that consisted of freshly collected slices from brain cortex of a rhesus macaque and allowed live B. burgdorferi to penetrate the tissue. Numerous transcripts of genes that regulate inflammation as well as oligodendrocyte and neuronal apoptosis were significantly altered as assessed by DNA microarray analysis. Transcription level increases of 7.43-fold (P = 0.005) for the cytokine tumor necrosis factor-alpha and 2.31-fold (P = 0.016) for the chemokine interleukin (IL)-8 were also detected by real-time-polymerase chain reaction array analysis. The immune mediators IL-6, IL-8, IL-1beta, COX-2, and CXCL13 were visualized in glial cells in situ by immunofluorescence staining and confocal microscopy.

Concomitantly, significant proportions of both oligodendrocytes and neurons undergoing apoptosis were present in spirochete-stimulated tissues. IL-6 production by astrocytes in addition to oligodendrocyte apoptosis were also detected, albeit at lower levels, in rhesus macaques that had received in vivo intraparenchymal stereotaxic inoculations of live B. burgdorferi.

These results provide proof of concept for our hypothesis that B. burgdorferi produces inflammatory mediators in the central nervous system, accompanied by glial and neuronal apoptosis.

PMID: 18832582 [PubMed - indexed for MEDLINE]

Mol Med. 2008 Mar–Apr; 14(3-4): 205–212.

The Pathogenesis of Lyme Neuroborreliosis: From Infection to Inflammation

Tobias A Rupprecht, et al
Department of Neurology, Ludwig-Maximilians University, Munich, Germany
http://www.pubmedcentral.nih.gov/articl ... l14_3p0205
...
Major clinical findings of the neurological manifestation of acute Lyme neuroborreliosis (LNB) include painful meningoradiculitis with inflammation of the nerve roots and lancinating, radicular pain (Bannwarth’s syndrome), lymphocytic meningitis, and various forms of cranial or peripheral neuritis (5). ...

The clinical picture of painful meningoradiculitis was first described in 1922 (6), but the etiology was unknown till the description of the causative spirochetes by Burgdorfer et al. in 1982 (7) and the isolation of spirochetes from the CSF of a patient with Bannwarth’s syndrome in 1984 (8). ...

One reason for our incomplete understanding of the mechanisms that lead to LNB is the limited availability of an adequate animal model. The only induction of reliable, clinically manifest LNB in an animal model so far was in a primate model involving the rhesus macaque, where for example, spirochetes could be demonstrated at the nerve roots (9). ...

The borrelia possess several mechanisms that enable them to escape (Figure 1) including (1) downregulation of immunogenic surface proteins, (2) inactivation of effector mechanisms, or (3) hiding in less accessible compartments like the extracellular matrix. ...

The most prominent clinical manifestation of Bannwarth’s syndrome is lancinating radicular pain (5), whereas patients with meningitis suffer mainly from headache and facial nerve palsy (2,95). Besides these symptoms, focal abnormalities like paresis or paresthesias are frequently observed in patients with polyradiculoneuritis or cranial neuritis (5). These symptoms are the result of a focal or diffuse neural dysfunction, but the pathophysiology is far from clear. ...

Borrelia adhere to neuronal cells. ... The adherent borrelia can be cytotoxic for the neural cells (97), and OspA induces apoptosis and astrogliosis (99). ...

On the other hand, secreted substances could injure the neural cells. Although B.b. do not possess any known endotoxin (100), cells of the host could secret neurotoxic products in response to the spirochetes. ...

Although B.b. do not possess any known endotoxin (100), cells of the host could secret neurotoxic products in response to the spirochetes. Schwann cells, for example, appear to produce nitric oxide (NO) in the rhesus monkey model of LNB (101) ...

[hv808ct]

Fascinating…….but for the fact that B. burgdorferi does not produce any toxins.

No neurotoxins. No cytotoxins. No hemolysins. No enterotoxins. No endotoxins. No exotoxins. No exfoliative toxins.

No classical bacterial toxin. Period.

The closest anyone has come to seeing any toxin activity with B. burgdorferi was some test tube hemolysis back in 1992. And that turned out to be wrong as two guys at Wesleyan showed in 2000 (J Bacteriol. 2000 Dec;182(23):6791-7).

But why believe an online stranger. Ask Burrsanaco or Shoemaker. Ask them a couple of very fundamental questions such as….

What’s the molecular weight of this toxin?
Is it plasmid-encoded?
If it’s plasmid-encoded do all strains carry this plasmid and produce a toxin?
Is it a protein or a glycoprotein?
What’s its receptor?
Is it released or membrane-bound?
Has anyone produced commercial antibody to it?
Has it been sequenced (like the burgdorferi genome) and can I look it up in GenBank?
If it plays a role in pathogenesis, why hasn’t it been attenuated for use as a vaccine candidate?

And finally, “Are you an idiot or just a liar?”

Please let us know how either one of them responses to this last important question.

[Claudia]

Fascinating…….but for the fact that B. burgdorferi does not produce any toxins.

No neurotoxins. No cytotoxins. No hemolysins. No enterotoxins. No endotoxins. No exotoxins. No exfoliative toxins.

No classical bacterial toxin. Period.

The closest anyone has come to seeing any toxin activity with B. burgdorferi was some test tube hemolysis back in 1992. And that turned out to be wrong as two guys at Wesleyan showed in 2000 (J Bacteriol. 2000 Dec;182(23):6791-7).

Thank you. This bears out why I could never find any medical science information from a peer-reviewed source on these alleged "Lyme 'bug' toxins" that patients must "detoxify" from (as if that was even possible).

If anybody has any peer-reviewed information stating otherwise, please post it.