Endotoxins

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Toxic byproducts of bacteria or metabolism

Dr. Stratton Cautions on Protecting the Liver

In recent correspondence, Dr. Stratton has been discussing reports in the medical literature that certain antibiotic agents can cause liver damage or failure. Noting that these agents are typically the most potent anti-chlamydials, he has drawn some important hypotheses from this that anyone on an antibiotic protocol should know about.

His cautionary note is that use of some of the new, powerful agents against Cpni must be carefully monitored, and that a more gradual treatment for many is advisable. His observations also affirm the importance of supplementsi in their liver-protective role.

Dr. Stratton notes:
"A recent report of Ketek causing liver failure has crystallized some thoughts that I have had for some time. Cpn can infect the liver and the kidney, but in particular the liver is a target due to the Kupfer cells. Any drug that acts against Cpn (including statins) will therefore in some patients cause hepatic damage or even hepatic failure. The better the activity against Cpn of the agent (or combination of agents), the more likely the liver damage. Even penicillamine can cause liver damage, as does Augmentin.

Another reason to take melatonin

As we know, Cpni binding endotoxini uses up melatonin and supplementation has been helpful to a lot of us. In addition it's an excellent antioxidanti. The study below adds even another reason to supplement it:

J Pineal Res. 2005 Oct;39(3):266-75.

Melatonini neutralizes neurotoxicity induced by quinolinic acid in brain tissue culture.

Cpn Treatment Information

The links below will take you to pages with specific information involved in the treatment of Cpni.

Diagnostic Testing For Cpn<
Information on serological testing and the problems of this in Cpn.
Combination Antibiotic Treatment Protocols for Cpn<
Links to pages on the current versions of Vanderbilt/Stratton and Wheldon Protocols for treating Cpn infectionsi in various diseasesi.
Experts Comments<

Commentary and interviews  with various experts in treating Cpn which help guide and inform about various facets of treatment.
Treatment Reactions<
Information on some of the kinds and sources of treatment reactions one can expect on combination antibiotic protocols in treating Cpn, including cytokinei reactions, endotoxini reactions, secondary porphyriai and other reactions. These are often lumped under the term "herx," an inaccurate term and not as useful as really understanding what's going on.

 

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-->

The Basics Page

Hello and Welcome!

This site is focused on treatment of chronic disease like Multiple Sclerosis (MSi) Chronic Fatigue Syndromei (CFSi) and Fibromyalgia (FMSi) an many other diseasesi with antibioticsi. Recent research indicates that Chlamydia Pneumoniae (CPni) plays a role in these diseases.

Here are the basics that make it easier for people new to the site to get going (if your brain isn't ready for even this much right now-- we've all been there-- read Cpn Simple< first):

Is this a sexually transmitted disease? No. this is chlamydia pneumoniae, a bacteria that can cause pneumonia. It may soon be called chlamydiophilia (meaning in the family of).

Is chlamydia pneumoniae (CPn) rare?

-Chemical, biological, and immunochemical properties of the Chlamydia psittaci

Infect Immun. 1986 Nov;54(2):568-74. Related Articles, Links

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

Brade L, Schramek S, Schade U, Brade H.

The lipopolysaccharide (LPSi) 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.

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.

Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production

Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production< HD Danenberg, G Alpert, S Lustig and D Ben-Nathan Department of Virology, Israel Institute for Biological Research, Ness- Ziona.

Recent reports have demonstrated an immunomodulating activity of dehydroepiandrosterone (DHEAi) different from that described for glucocorticoids. The present study was designed to test DHEA's activity in endotoxic shock and to investigate its effect on endotoxin-induced production of tumor necrosis factor (TNF). Mortality of CD-1 mice exposed to a lethal dose of lipopolysaccharidei (LPSi; 800 micrograms per mouse) was reduced from 95 to 24% by treatment with a single dose of DHEA, given 5 min before LPS. LPS administration resulted in high levels of TNF, a response that was significantly blocked by DHEA, both in vivo and in vitro. DHEA treatment also reduced LPS-induced increments in serum corticosterone levels, a parameter considered not to be mediated by TNF. In another experimental model, mice sensitized with D-galactosamine, followed by administration of recombinant human TNF, were subjected to 89% mortality rate, which was reduced to 55% in DHEA-treated mice. These data show that DHEA protects mice from endotoxin lethality. The protective effect is probably mediated by reduction of TNF production as well as by effecting both TNF-induced and non-TNF-induced phenomena.

Protective Effects of Vitamin C, Alone or in Combination with Vitamin A, on Endotoxin-Induced Oxidative Renal Tissue Damage in R

Protective Effects of Vitamin C, Alone or in Combination with Vitamin A, on Endotoxin-Induced Oxidative Renal Tissue Damage in Rats< MEHMET KANTER, OMER COSKUN, FERAH ARMUTCU,1 YESIM HULYA UZ and GULNUR KIZILAY Tohoku J. Exp. Med., 2005, 206(2) Department of Histology-Embryology, Faculty of Medicine, Trakya University, Edirne, and 1Department of Biochemistry, Faculty of Medicine, Zonguldak Karaelmas University, Zonguldak, Turkey This study was designed to investigate the protective effects of vitamin C and vitamin A on oxidative renal tissue damage. Male Wistar rats were given an intraperitoneal injection of 0.5 ml saline (control) or 0.5 ml solution of lipopolysaccharide (10 mg/kg), which caused endotoxemia.

Endotoxin depletes ascorbate...Protective effects of vitamins C and E against oxidative stress.

Endotoxin depletes ascorbate in the guinea pig heart. Protective effects of vitamins C and E against oxidative stress.< Rojas C, Cadenas S, Herrero A, Mendez J, Barja G. Department of Animal Biology-II (Animal Physiology), Faculty of Biology Complutense University, Madrid, Spain. The effect of acute endotoxin-induced septic shock on myocardium oxidative stress after low or high vitamin C and/or E dietary supplementation was studied in guinea pigs, laboratory animals which, like human, do not have capacity for ascorbate synthesis. Neither the antioxidanti enzymes or GSH were modified by endotoxin and vitamin treatments. Vitamin E showed a strong capacity to protect the myocardium against both enzymatic and non-enzymatic lipid peroxidation even in the presence of endotoxin. Vitamin C supplementation increased heart ascorbate whereas endotoxic shock totally depleted the heart ascorbate of vitamin C supplemented animals without changing vitamin E. Endotoxin significantly increased myocardium uric acid, a marker of ischemia induced oxidative stress, in animals fed with low vitamin C levels. This increase was totally prevented in vitamin C supplemented, but not in vitamin E supplemented animals. Strongly depressed levels of plasma vitamin C have been recently described in sepsis in human patients. The results suggest that ascorbate is a primary antioxidant target in the heart of endotoxin treated mammals lacking the capacity to synthesize ascorbate and that ascorbate can have a protective value against endotoxin-induced free radical damage in the myocardium. Implications of these results for the possible preventive role of vitamin C in humans during sepsis are discussed.

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

Use of Vitamin C to bind bacterial endotoxins.

Useful information on use of Vitamin C to bind bacterial endotoxins. Endotoxin and Vitamin C: Part I - Sepsis, Endotoxin and Vitamin C< Archie Kalokerinos, MBBS, FACNEM Ian Dettman, PhD, BSc (Hons), ND, MACNEM Cliff Meakin, ND, BHSc, AACNEM

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

Reactions to Treatment: Endotoxins, cytokines, porphyria, etc.

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

These are often casually 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 endotoxini which is released as a matter of course during infection and is partially responsible for the on-going symptoms of the infection. When these bacterial are killed en masse they release larger amounts of endotoxin causing significant symptoms during initial phases of treatment. If the amount of endotoxin exceeds the body's ability to get rid of it, these toxic effects can be life threatening. Even in less threatening amounts, the endotoxins and the resulting reactions can cause oxidative stress and damage to body organs.

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