Lipopolysaccharide endotoxin

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Lipopolysaccharide endotoxin

Finally a Break and a Visit to the Eye Doctor

Finally a break in the unrelenting parade of toxic nastiness.Twelve days of burning skin, feeling groaty and shaky,muscle pains and headache,head ringing,sore eyes, chills and night sweats finally gave way yesterday. I was able to get out in the fresh air and sunshine and go to lunch feeling much better. I ran my juicer for a few days and think all the anti-oxidants I consumed must have helped.Today I feel a little tired but still better.I am back to sleeping well.

Help I am so confused

I am still trying to get a grasp on Chlamydia Pneumoniae, I just found out on 4-11-07.  But I have been sick for awhile  Cry.  I am just starting Antibioticsi again......eeeeek Foot in mouth.  My symptoms have been sinus infectionsi and uppper respitory infections , Phlaringitis, Broncotitis, Asthmai.  In and out of the Dr. office the month of April, and my throat swelled shut I could go on and on.  I ended up at an Infetious disease Dr.

LPS antagonism

I was wondering if there was any research being done on endotoxini antagonists. Low and behold, here's an interesting slide show about some research into the topic.

http://www.molecularsurgeon.org/presentations/dunn/presentation_text.html

Most is way above my head but might be interesting to some of our med/science members.

Raven

CAPi since 8-05 for Cpni and Mycoplasma P. for MSi and/or CFSi. USA

Five Ways of Feeling Lousy

 Dr. David Wheldoni's succinct summary of the different reactions to Cpni and its treatment helps in sorting out the different responses and what to do about them. I've moved this from his comment in another members blog post to a page of it's own here in the Cpn Treatment Handbook.

Jim K (Editor in Chief) 

Five Ways of Feeling Lousy

I am inclined to think that there are five major mechanisms behind those unpleasant side effects of chronic large-load infection with C pneumoniae which worsen in the short-term with antichlamydial treatment.

a) Lipid peroxidation may likely get worse in the short-term as bacterial products are released both by breaking down EBs and by apoptosisi< of infected cells. Antioxidantsi<i< and B vitaminsi< (including B12) may help with this. I find melatonin">i<i< at night helpful.

endotoxin, cortisol, melatonin

Researchers T.S. Wiley and Bent Formby believe that overeating fat and a lack of exercise do not cause obesity, heart diseasei, diabetes, and cancer. They base their conclusions on more than a decade of research at the National Institutes of Health in Washington D.C. They believe the problems of overweight and cancer can be helped with a solution as cheap as turning off a light bulb. "Lights Out: Sleep, Sugar, and Survival" by T.S.Wiley and Bent Formby, Simon & Schuster Inc., NY 2000 Up to about 1900 when the sun set, it got dark. If people stayed up late it was to the dim red glow of fire or candles. When it got dark people went to bed and slept. In the winter people spent up to 14 hours a day in the dark. The abdominal fat pad common in insulin-resistant, high cholesteroli and Type II diabetes patients would have kept internal organs warm and served as an energy store for famine season of winter. The liver dumps sugar into cholesterol production to lower the freezing temperature of cell membranes. Chronic high insulin leads to insulin resistance. Blood sugar cannot enter muscles cells, so all sugar goes to fat cells for storage or gets turned into cholesterol. This makes insulation and antifreeze to prepare the body for the winter famine that never comes for many in the modern world.

Stress is increasing the endotoxin-induced inflammation in the brain

Stress increases vulnerability to inflammationi in the rat prefrontal cortex.
de Pablos RM, Villaran RF, Arguelles S, Herrera AJ, Venero JL, Ayala A, Cano J,
Machado A.
Journal of Neuroscience 2006 May 24;26(21):5709-19. 

Inflammation could be involved in some neurodegenerative disorders that
accompany signs of inflammation. However, because sensitivity to inflammation is
not equal in all brain structures, a direct relationship is not clear. Our aim
was to test whether some physiological circumstances, such as stress, could
enhance susceptibility to inflammation in the prefrontal cortex (PFC), which
shows a relative resistance to inflammation. PFC is important in many brain
functions and is a target for some neurodegenerative diseasesi. We induced an
inflammatory process by a single intracortical injection of 2 microg of
lipopolysaccharidei (LPSi), a potent proinflammogen, in nonstressed and stressed
rats. We evaluated the effect of our treatment on inflammatory markers, neuronal
populations, BDNF expression, and behavior of several mitogen-activated protein
(MAP) kinases and the transcription factor cAMP response element-binding
protein. Stress strengthens the changes induced by LPS injection: microglial
activation and proliferation with an increase in the levels of the
proinflammatory cytokinei tumor necrosisi factor-alpha; loss of cells such as
astroglia, seen as loss of glial fibrillary acidic protein immunoreactivity, and
neurons, studied by neuronal-specific nuclear protein immunohistochemistry and
GAD67 and NMDA receptor 1A mRNAs expression by in situ hybridization. A
significant increase in the BDNF mRNA expression and modifications in the levels
of MAP kinase phosphorylation were also found. In addition, we observed a
protective effect from RU486 [mifepristone
(11beta-[p-(dimethylamino)phenyl]-17beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3
-one)], a potent inhibitor of the glucocorticoid receptor activation. All of
these data show a synergistic effect between inflammation and stress, which
could explain the relationship described between stress and some
neurodegenerative pathologies.

End of Day One Fred

I first posted this in response to Paul's comments on another thread, so I'm just repeating it here so it's part of my "Fred" blog. Here's how I've learned to sort my reactions out in terms of my own experience, correctly or not!

  1. Endotoxini reactions seem to typically include feeling chilled, cold, cold hands and feet, and so on. Dr. Powell had a great biochemical explanation as to why this is so, for the life of me I can't recall what it was. I just remember it as typified by chill, cold extremities and peripheral vasoconstriction.
  2. Cytokinei (immunei) reactions are typified by inflammationi, consequent pain, swelling or congestion of tissues, and cascade of other responses like histimine release and so on.
  3. Porphyric reactions seem typified by a feeling of loggyness, depression or anxiety, nausea, disorientation, discoordination (when not caused by loss of muscle control function, see below) bowel disturbance, fatigue, hypersensitivity to light, sound and other stimuli. You note, Paul, that the porphyrins also bind to nerve receptors, especially GABA receptors, and thus interfere with the modulating functions the correct neuroransmitter would perform, hence increased pain sensitivity and anxiety and depression (both modulated by GABA). But increased pain sensitivity is not the same as pain-causing, and I know inflammatory pain feels quite different from hypersensitivity.
  4. Cell deathi seems typified by loss of baseline function (eg worsening of hand function in MS), pain, and so on followed by slower recovery and then improvement above baseline. 

 I see this in my reactions to the Fred pulse. When the dose hit a couple hours after taking it, I started to feel increased chill and cold despite all the things Dr. Powell has me on to counter endotoxin which usually do well to counter these symptoms. Then I had a rather rapid porphyric response (over the next hour or so) where my coordination, mental focus, disorientation really increased. Mac noted how visible my typing problems were on the chat. What they didn't see was how many times I had to type and retype a word before I could complete a sentence, and that poorly spelled and error laden even so.

Reactions to CAP Treatment: That "Kissed by a Dementor" kind of feeling*

Bacterial Endotoxini reactions, Cytokinei (immunei) reactions and inflammationi<

These are often casually. but inaccurately, referred to as “herx” reactions, or scientifically as “herxheimer-like” alluding to the Jarisch-Herxheimer reaction to bacterial toxins specifically from syphilis. All gram-negative bacteria, of which Cpni is one, have contain Lipopolysaccharide endotoxinsi as well as HSPi's (heat shock proteins) which are released as a matter of course during infection and are in part responsible for the on-going symptoms of the infection.

When these bacterial are killed en masse during treatment, they release relatively large amounts of endotoxin, causing significant symptoms especially during initial phases of treatment, as well as when an additional antibiotic agent is added to the protocol. If the amount of endotoxin exceeds the body's ability to get rid of it, these toxic effects can be life threatening. But even in less threatening amounts, the endotoxins and the resulting reactions can cause oxidative stress and damage to body organs.

IL-17 and LPS

Well I am going to venure into editorial again. Please forgive me. IL-17 has been noted to be high in MSi. One researcher speculated that peraps this was finally "it". Knock out the IL-17 and bingo! A novel approach to stopping MS. Being curious I looked into Il-17 and CPn. There was not much expressly in that arena but IL-17 and LPS and we have something important. Here< we have a paper that describes putting LPS in lung tissue to observe IL-17. Sure enough the lps induced upregulation of IL-17 a pro-inflammatory factor.

This kind of thing is interesting because it points out that while some people still buy the autoimmune model and point to things like higher than usual levels of proinflammartory cytokines as proof, it is not the only explanation for why any particular chemokine might be present in MS brains. IL-17: a factor raised in LPS damage and another smoking gun for CPn, not proof of autoimmunity.

Persistent chlamydial envelope antigens in antibiotic-exposed infected cells

J Infect Dis. 1999 Apr;179(4):954-66. 

 

Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis.

Wyrick PB, Knight ST, Paul TR, Rank RG, Barbier CS.

Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7290, USA. pbwyrick@med.unc.edu

An in vitro coculture model system was used to explore conditions that trigger neutrophil chemotaxis to Chlamydia trachomatis infected human epithelial cells (HEC-1B). Polarized HEC-1B monolayers growing on extracellular matrix (ECM) were infected with C. trachomatis serovar E. By 36 h, coincident with the secretion of chlamydial lipopolysaccharidei and major outer membrane protein to the surfaces of infected cells, human polymorphonuclear neutrophils (PMNL) loaded with azithromycin migrated through the ECM and infiltrated the HEC-1B monolayer. Bioreactive azithromycin was delivered by the chemotactic PMNL to infected epithelial cells in concentrations sufficient to kill intracellulari chlamydiae. However, residual chlamydial envelopes persisted for 4 weeks, and PMNL chemotaxis was triggered to epithelial cells containing residual envelopes. Infected endometrial cells demonstrated up-regulation of ENA-78 and GCP-2 chemokine mRNA. Thus, despite appropriate antimicrobial therapy, residual chlamydial envelope antigens may persist in infected tissues of culture-negative women and provide one source for sustained inflammationi.<!--break-->

Persistent Chlamydial Enveolpe Antigens

J Infect Dis. 1999 Apr;179(4):954-66.
†
Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis.
Wyrick PB, Knight ST, Paul TR, Rank RG, Barbier CS.
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7290, USA. pbwyrick@med.unc.edu
An in vitro coculture model system was used to explore conditions that trigger neutrophil chemotaxis to Chlamydia trachomatis infected human epithelial cells (HEC-1B). Polarized HEC-1B monolayers growing on extracellular matrix (ECM) were infected with C. trachomatis serovar E. By 36 h, coincident with the secretion of chlamydial lipopolysaccharidei and major outer membrane protein to the surfaces of infected cells, human polymorphonuclear neutrophils (PMNL) loaded with azithromycin migrated through the ECM and infiltrated the HEC-1B monolayer. Bioreactive azithromycin was delivered by the chemotactic PMNL to infected epithelial cells in concentrations sufficient to kill intracellulari chlamydiae. However, residual chlamydial envelopes persisted for 4 weeks, and PMNL chemotaxis was triggered to epithelial cells containing residual envelopes. Infected endometrial cells demonstrated up-regulation of ENA-78 and GCP-2 chemokine mRNA. Thus, despite appropriate antimicrobial therapy, residual chlamydial envelope antigens may persist in infected tissues of culture-negative women and provide one source for sustained inflammation.

Chemical, biological, and immunochemical properties of the Chlamydia psittaci lipopolysaccharide.

Infect Immun. 1986 Nov;54(2):568-74.

Brade L, Schramek S, Schade U, Brade H.
The lipopolysaccharidei (LPS) of Chlamydia psittaci was extracted from yolk sac-grown elementary bodies, purified, and characterized chemically, immunochemically, and biologically. The LPS contained D-galactosamine, D-glucosamine, phosphorus, long-chain fatty acids, and 3-deoxy-D-manno-2-octulosonic acid in the molar ratio of approximately 1:2:2:6:5. The antigenic properties of the isolated LPS were compared with those of the LPS from Chlamydia trachomatis and Salmonella minnesota Re by the passive hemolysis and passive hemolysis inhibition tests, absorption, hydrolysis kinetics, and Western blot analysis with rabbit polyclonal antisera against chlamydiae and with a mouse monoclonal antibody recognizing a genus-specific epitope of chlamydial LPS. Two antigenic determinants were identified, one of which was chlamydia specific and the other of which was cross-reactive with Re LPS. Both determinants were destroyed during acid hydrolysis, whereby a third antigen specificity was exposed which was indistinguishable from the lipid A antigenicity. In rabbit polyclonal antisera prepared against Formalin-killed elementary bodies or detergent-solubilized membranes, two antibody specificities were differentiated. One of these was chlamydia specific, and the other was cross-reactive with Re LPS. The LPS of C. psittaci was inactive within typical endotoxini parameters (lethal toxicity, pyrogenicity, local Shwartzman reactivity); it was, however, active in some in vitro assays, such as those testing for mouse B-cell mitogenicity and the induction of prostaglandin E2 in mouse peritoneal macrophages.

Chlamydial lipopolysaccharide.

Biochim Biophys Acta. 1999 Oct 8;1455(2-3):387-402. Related Articles, Links

Chlamydial lipopolysaccharidei.
Kosma P.
Universitat fur Bodenkultur Wien, Institute of Chemistry, Vienna, Austria. pkosma@edv2.boku.ac.at
Chlamydiae are obligatory intracellulari parasites which are responsible for various acute and chronic diseases in animals and humans. The outer membrane of the chlamydial cell wall contains a truncated lipopolysaccharide (LPS) antigen, which harbors a group-specific epitope being composed of a trisaccharide of 3-deoxy-D-manno-oct-2-ulosonic (Kdo) residues of the sequence alpha-Kdo-(2-->8)-alpha-Kdo-(2-->4)-alpha-Kdo. The chemical structure was established using LPS of recombinant Escherichia coli and Salmonella enterica strains after transformation with a plasmid carrying the gene encoding the multifunctional chlamydial Kdo transferase. Oligosaccharides containing the Kdo region attached to the glucosamine backbone of the lipid A domain have been isolated or prepared by chemical synthesis, converted into neoglycoproteins and their antigenic properties with respect to the definition of cross-reactive and chlamydia-specific epitopes have been determined. The low endotoxic activity of chlamydial LPS is related to the unique structural features of the lipid A, which is highly hydrophobic due to the presence of unusual, long-chain fatty acids.

David Wheldon Comments on endotoxins & reactions

Cpni endotoxini is about 100 times less powerful than Neisserial endotoxin, but there must be a lot of it released, particularly with the active killing by metronidazolei. Hence the need for caution at this stage of treatment. The long-term damaging effect of far more potent endotoxins on the CNSi is vividly illustrated by this story: http://www.endotoxin.gmxhome.de/ which resulted in a letter in the BMJ: http://oem.bmjjournals.com/cgi/content/full/60/5/378

One quite common side effect of Cpn treatment is vestibular disturbance. A number of other medics who treat CFSi with antibiotics have noticed this. It can go on for months, tends to have a diurnal rhythm and can be quite incapacitating. Its severity seems to be linked to bacterial load. The diurnal pattern suggests that it may be of host origin, perhaps cytokinei. Here's a link to a webpage which notes the association between vestibular disturbance and cognitive deficits. http://www.backgroundfacts.com/menieres/COGDIS.htm

Cholesterol levels, bacterial endotoxin, and inflammation

Acute inflammation and infection maintain circulating phospholipid levels and enhance lipopolysaccharide binding to plasma lipoproteins< Richard L. Kitchens1,*, Patricia A. Thompson*, Robert S. Munford*, and Grant E. O'Keefe,** * Departments of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9113 Microbiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9113 Surgery, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9113 ** Department of Surgery, University of Washington, Harborview Medical Center, Seattle, WA 98104-2499 To whom correspondence should be addressed. e-mail: richard.kitchens@utsouthwestern.edu
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