Unwanted consequence of dental disease and other infections: Dramatically increased potential for mold hypersensitization and illness.

[Guest guest]

I am wondering, when the " experts " who calculate risk/benefit

analysis, do their examinations of the effects of single mycotoxins on

lab animals to come up with their declarations that all is well, do

they take papers like these into account?

But bacterial exposure, is common, especially for poor people. It can

come from dental issues, infections of any kind, brownwater residue in

one's environment, etc.

Please read these papers:

I am trying to make the connection between endotoxin exposure (I'm

using the example of dental disease here, but many other diseases also

involve endotoxins)

and dramatically increase likelihood of mold illness obvious..

Two of MANY articles on lipopolysaccharides and endotoxins in dental

infections.. (many poor people have chronic dental issues because they

cannot afford adequate dental care)

Fogorv Sz. 2008 Jun;101(3):101-5.

Related Articles, Links

[Associations between oral infections and cardiovascular disease]

[Article in Hungarian]

Martos R, Márton I.

Debreceni Egyetem Orvos és Egészségtudományi Centrum

Fogorvostudományi Kar, Debrecen.

The potential role of periodontal disease, gingivitis and other

dental infections as a possible chronic source of infection and

inflammation represents a continuous challange to the host organism.

The high number of oral pathogenes, lipopolysaccharides and soluble

mediators are related to the pathogenesis of the local inflammation

and the initiation of systemic inflammation process, which may impair

the systemic health. In the last decades, studies suggesed that there

could be a connection between the local oral infections and several

systemic conditions such as the diabetes, cardiovascular disease, low

birth weight and the chronic obstructive pulmonary disease.

Cardiovascular disease is the number one cause of death in the last

century. The primary contributing factor in the majority of

cardiovascular diseases is atherosclerosis. The role of infection is

believed to provide a critical inflammatory stimulus that contributes

to atherogenesis. The present review is a short summary of studies of

the last years about the possible pathogenic role of local oral

infections as a contributing factor in the initiation and progression

of cardiovascular disease.

Publication Types:

* English Abstract

PMID: 18756845 [PubMed - in process]

Innate Immun. 2008 Apr;14(2):99-107.

Related Articles, Links

Click here to read

Lipopolysaccharide (LPS) of Porphyromonas gingivalis induces

IL-1beta, TNF-alpha and IL-6 production by THP-1 cells in a way

different from that of Escherichia coli LPS.

Diya Zhang , Lili Chen , Shenglai Li , Zhiyuan Gu , Jie Yan .

Department of Stomatology, The Second Afiliated Hospital, School

of Medicine, Zhejiang University, Hangzhou, China.

Lipopolysaccharide (LPS) derived from the periodontal pathogen

Porphyromonas gingivalis has been shown to differ from enterobacterial

LPS in structure and function; therefore, the Toll-like receptors

(TLRs) and the intracellular inflammatory signaling pathways are

accordingly different. To elucidate the signal transduction pathway of

P. gingivalis, LPS-induced pro-inflammatory cytokine production in the

human monocytic cell line THP-1 was measured by ELISA, and the TLRs

were determined by the blocking test using anti-TLRs antibodies. In

addition, specific inhibitors as well as Phospho-ELISA kits were used

to analyze the intracellular signaling pathways. Escherichia coli LPS

was used as the control. In this study, P. gingivalis LPS showed the

ability to induce cytokine production in THP-1 cells and its induction

was significantly (P < 0.05) suppressed by anti-TLR2 antibody or JNK

inhibitor, and the phosphorylation level of JNK was significantly

increased (P < 0.05). These results indicate that TLR2-JNK is the main

signaling pathway of P. gingivalis LPS-induced cytokine production,

while the cytokine induction by E. coli LPS was mainly via

TLR4-NF-kappaB and TLR4-p38MAPK. This suggests that P. gingivalis LPS

differs from E. coli LPS in its signaling pathway in THP-1 cells, and

that the TLR2-JNK pathway might play a significant role in P.

gingivalis LPS-induced chronic inflammatory periodontal disease.

Publication Types:

* Research Support, Non-U.S. Gov't

PMID: 18713726 [PubMed - in process]

Now for a VERY few of the MANY papers on inflammatory priming and MYCOTOXINS

http://www.ncbi.nlm.nih.gov/pubmed/17483119

or free full text at:

http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051 & itool=AbstractPlus-\

def & uid=17483119 & db=pubmed & url=http://toxsci.oxfordjournals.org/cgi/pmidlookup?v\

iew=long & pmid=17483119

Toxicol Sci. 2007 Aug;98(2):526-41. Epub 2007 May 4.

Neurotoxicity and inflammation in the nasal airways of mice exposed to

the macrocyclic trichothecene mycotoxin roridin a: kinetics and

potentiation by bacterial lipopolysaccharide coexposure.

Islam Z, Amuzie CJ, Harkema JR, Pestka JJ.

Department of Food Science and Human Nutrition, Michigan State

University, East Lansing, Michigan 48824, USA.

Macrocyclic trichothecene mycotoxins produced by indoor air molds

potentially contribute to symptoms associated with damp building

illnesses. The purpose of this investigation was to determine (1) the

kinetics of nasal inflammation and neurotoxicity after a single

intranasal instillation of roridin A (RA), a representative

macrocyclic trichothecene; and (2) the capacity of lipopolysaccharide

(LPS) to modulate RA's effects. C57Bl/6 female mice were intranasally

instilled once with 50 mul of RA (500 mug/kg body weight [bw]) in

saline or saline only and then nose and brain tissues were collected

over 72 h and processed for histopathologic and messenger RNA (mRNA)

analysis. RA-induced apoptosis specifically in olfactory sensory

neurons (OSNs) after 24 h postinstillation (PI) causing marked atrophy

of olfactory epithelium (OE) that was maximal at 72 h PI.

Concurrently, there was marked bilateral atrophy of olfactory nerve

layer of the olfactory bulbs (OBs) of the brain. In the ethmoid

turbinates, upregulated messenger RNA (mRNA) expression of the

proapoptotic gene FAS and the proinflammatory cytokines tumor necrosis

factor-alpha, interleukin (IL)-6, IL-1, and macrophage inhibitory

protein-2 was observed from 6 to 24 h PI, whereas expression of

several other proapoptotic genes (PKR, p53, Bax, and caspase-activated

DNAse) was detectable only at 24 h PI. Simultaneous exposure to LPS

(500 ng/kg bw) and a lower dose of RA (250 mug/kg bw) magnified

RA-induced proinflammatory gene expression, apoptosis, and

inflammation in the nasal tract. Taken together, the results suggest

that RA markedly induced FAS and proinflammatory cytokine expression

prior to evoking OSN apoptosis and OE atrophy and that RA's effects

were augmented by LPS.

PMID: 17483119 [PubMed - indexed for MEDLINE]

J Toxicol Environ Health A. 1999 May 28;57(2):115-36.Links

Amplified proinflammatory cytokine expression and toxicity in mice

coexposed to lipopolysaccharide and the trichothecene vomitoxin

(deoxynivalenol).

Zhou HR, Harkema JR, Yan D, Pestka JJ.

Department of Food Science and Human Nutrition, Michigan State

University, East Lansing 48824, USA.

A single oral exposure to the trichothecene vomitoxin (VT) has

been previously shown in the mouse to increase splenic mRNA levels for

several cytokines in as little as 2 h. Since one underlying mechanism

for these effects likely involves superinduction of transiently

expressed cytokine genes, VT may also potentially amplify cytokine

responses to inflammatory stimuli. To test this possibility, the

effects of oral VT exposure on tumor necrosis factor-alpha

(TNF-alpha), interleukin-6 (IL-6), and IL-1beta expression were

measured in mice that were intraperitoneally injected with

lipopolysaccharide (LPS), a prototypic inflammatory agent. As

anticipated, VT alone at 1, 5, and 25 mg/kg body weight increased

splenic mRNA expression of all three cytokines after 3 h in a

dose-response fashion. LPS injection at 1 and 5 mg/kg body weight also

induced proinflammatory cytokine mRNA expression. There was a

synergistic increase in TNF-alpha splenic mRNA levels in mice treated

with both VT and LPS as compared to mice treated with either toxin

alone, whereas the effects were additive for IL-6 and IL-1beta mRNA

expression. When relative mRNA levels were examined over a 12-h period

in mice given LPS (1 mg/kg) and/or VT (5 mg/kg), significant

enhancement was observed up to 6, 12, and 3 h for TNF-alpha, IL-6, and

IL-1beta, respectively. When plasma cytokine concentrations were

measured, TNF-alpha was found to peak at 1 h and was significantly

increased at 1, 3, and 6 h if mice were given LPS and VT, whereas LPS

or VT alone caused much smaller increases in plasma TNF-alpha Plasma

IL-6 peaked at 3 h in LPS, VT, and LPS/VT groups, with the combined

toxin group exhibiting additive effects. Plasma IL-1beta was not

detectable. The potential for VT and LPS to enhance toxicity was

examined in a subsequent study. Mortality was not observed up to 72 h

in mice exposed to a single oral dose of VT at 25 mg/kg body weight or

to an intraperitoneal dose of LPS at 1 or 5 mg/kg body weight;

however, all mice receiving VT and either LPS dose became moribund in

less than 40 h. The principal histologic lesions in the moribund mice

treated with VT and LPS were marked cell death and loss in thymus,

Peyer's patches, spleen, and bone marrow. In all of these lymphoid

tissues, treatment-induced cell death had characteristic histologic

features of apoptosis causing lymphoid atrophy. These results suggest

that LPS exposure may markedly increase the toxicity of trichothecenes

and that the immune system was a primary target of these interactive

effects.

PMID: 10344227 [PubMed - indexed for MEDLINE]

Toxicol Appl Pharmacol. 2006 Feb 15;211(1):53-63. Epub 2005 Jul 11.

Related Articles, Links

Click here to read

LPS priming potentiates and prolongs proinflammatory cytokine

response to the trichothecene deoxynivalenol in the mouse.

Islam Z, Pestka JJ.

Department of Microbiology and Molecular Genetics, Michigan State

University, East Lansing, MI 48824, USA.

Simultaneous exposure to lipopolysaccharide (LPS) markedly

amplifies induction of proinflammatory cytokine expression as well as

IL-1-driven lymphocyte apoptosis by trichothecene deoxynivalenol (DON)

in the mouse. The purpose of this research was to test the hypothesis

that LPS priming will sensitize a host to DON-induced proinflammatory

cytokine induction and apoptosis. In mice primed with LPS (1 mg/kg bw)

ip. and treated 8 h later with DON po., the minimum DON doses for

inducing IL-1alpha, IL-1beta, IL-6 and TNF-alpha serum proteins and

splenic mRNAs were significantly lower than the DON doses required for

vehicle-primed mice. LPS priming also decreased onset time and

dramatically increased magnitude and duration of cytokine responses.

LPS-primed mice maintained heightened sensitivity to DON for up to 24

h. LPS priming doses as low as 50 microg/kg bw evoked sensitization.

DNA fragmentation analysis and flow cytometry also revealed that mice

primed with LPS (1 mg/kg) for 8 h and exposed to DON (12.5 mg/kg)

exhibited massive thymocyte loss by apoptosis 12 h later compared to

mice exposed to DON or LPS alone. LPS priming decreased DON-induced

p38 and ERK 1/2 phosphorylation suggesting that enhanced

mitogen-activated protein kinase activation was not involved in

increased cytokine responses. Taken together, exposure to LPS rendered

mice highly susceptible to DON induction of cytokine expression and

this correlated with increased apoptosis in the thymus.

Publication Types:

* Comparative Study

* Research Support, N.I.H., Extramural

PMID: 16009389 [PubMed - indexed for MEDLINE]

Note: it appears that all trichothecenes are similar in this respect..

satratoxin G and H, roridin A, etc. - Apoptopsis thresholds are

increased by LPS, are subject to priming by LPS.