Candida's quorum sensing, farsenol, and Addison's disease

Microbes talk to each other by secreting compounds to each other.  These compounds have the ability to interfere with the host within whom the infection lives.  Candida secretes farnesol which is known to inhibit P450 enzymes.  This could explain the correlation of addison's disease and candida infections.

Polyglandular Autoimmune syndrome type one strongly associated with candida infections
http://emedicine.medscape.com/article/124183-clinical

Autoimmune thyroid and candida
http://www.ncbi.nlm.nih.gov/pubmed/9039290

Addison's disease has antibodies to 21-hydroxylase

21-hydroxylase is a p450 enzyme
https://en.wikipedia.org/wiki/21-Hydroxylase

Farnesol inhibits cytochromeP450
https://libres.uncg.edu/ir/uncg/f/G_Raner_Farnesol_2002.pdf

liver disease in PAI
http://www.ncbi.nlm.nih.gov/pubmed/9025859

Cytochrome p450 is a hepatic autoantigen in PAI
http://www.ncbi.nlm.nih.gov/pubmed/9141515

P450 antibodies different in PAI and idopathic addison's disease
http://www.jci.org/articles/view/116843

Farnesol is a quorum haulting Candida growth and is secreted by candida
http://aem.asm.org/content/68/11/5459.abstract
http://www.ncbi.nlm.nih.gov/pubmed/16420349

Lymphocytic colitis and polyglandular syndrome one in a patient
http://www.ncbi.nlm.nih.gov/pubmed/?term=microscopic+colitis+polyglandular

Lymphocytic colitis is associated with Candida
http://www.ncbi.nlm.nih.gov/pubmed/23314667

Polyglandular syndrome type two, more commonly found in adults has a strong association with 21-hydroxylase antibodies but not candida?

Could type 2 be different types of fungal infections that also use farnesol for quorum? Is it saccharomyces in the GI tract or candida in the vagina?

The idopathic addison's is associated with PAII
http://www.ncbi.nlm.nih.gov/pubmed/2333733

adult idopathic addison's major antibody is 21-hydroxylase
http://www.ncbi.nlm.nih.gov/pubmed/1511745
http://www.ncbi.nlm.nih.gov/pubmed/8959085

Microscopic colitis, addison's, and skin pigmentation
http://www.ncbi.nlm.nih.gov/pubmed/?term=microscopic+colitis+addison%27s

Patient with ?ulcerative colitis?, vitilgo, addison's (vitilgo is a  hypopigmentation skin disease)
http://www.ncbi.nlm.nih.gov/pubmed/25148815

Hyperpigmentation and PAII
http://www.ncbi.nlm.nih.gov/pubmed/25148815

Hypopigmentation is caused by malassezia (tinea vesicolor)
http://www.ncbi.nlm.nih.gov/pubmed/24320140

Microscopic colitis in woman has been found to have increased autoantibodies and anti-saccharomyces
http://www.ncbi.nlm.nih.gov/pubmed/23776613

note that saccharomyces is currently being used as a probiotic for c.diff
http://iai.asm.org/content/67/1/302.full

Collagenous colitis and addison's disease
http://www.ncbi.nlm.nih.gov/pubmed/9881910
http://www.ncbi.nlm.nih.gov/pubmed/2801683
https://www.jstage.jst.go.jp/article/endocrj1993/45/4/45_4_581/_article


Raynaud's is a mysterious vasodilation issue where when exposed to the cold the person has the opposite response to cold: instead of dilating the vessels of the fingers the blood vessels contract first in a vasospasm

p450 and vasodilation
http://www.ncbi.nlm.nih.gov/pubmed/17572144

Nitric oxide normally inhibits P450
http://www.ncbi.nlm.nih.gov/pubmed/9400024

When the body is exposed to cold temperatures nitric oxide triggers the blood vessels to contract.

What would happen if farsenal is constantly inhibiting p450 ?

Sclerodema and raynaud's
All scleroderma patients have secondary raynaud's....but not all raynaud's have scleroderma

Scloerodema and p450
http://www.ncbi.nlm.nih.gov/pubmed/11263781

How often is raynaud's with addison's disease?

Asthma and p450
http://www.ncbi.nlm.nih.gov/pubmed/15066132

Mesothelioma and co-carcinogenesis

Francis Peyton Rous' Co-carcinogenesis hypothesis: that a virus and a carcinogen together cause cancer. (1966 Nobel prize for HPV work)  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135410/

What I surmise from his hypothesis:

A virus enters a cell through a receptor, opens up and alters host DNA telomeres. The carcinogen  inhibits the virus' polymerase because viral polymerases have stronger binding affinities than the host's.

Cancer cells can make unlimited copies because of the telomere modifications done by the virus. 

There are DNA polymerases and RNA polymerases. Think of DNA as the cookbook and RNA as recipes...one polymerase copies the entire cookbook, one makes repairs, and one polymerase copies just a recipe.

If the viral polymerases are inhibited by the carcinogen instead of the host's polymerase then the cancer "stem" cell could be created.  The host's polymerases have access to and can make unlimited copies.

In mesothelioma the carcinogen that has been linked is asbestos and the virus which has been linked is sv40.

Gangliosides are receptors to sv40
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC202381/

Ganglioside GM2 is increased in Mesothelioma 
http://www.ncbi.nlm.nih.gov/pubmed/25421609

sv40 induces mesothelioma
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1886912/

asbestos and mesothelioma
http://www.ncbi.nlm.nih.gov/pubmed/18671157

Asbestos inhibiting polymerases
http://www.ncbi.nlm.nih.gov/pubmed/21543585

Hashimoto's thyroid disease: cross-targeting of Candida and a flavivirus?

Autoimmune cross-targeting hypothesis: a virus marks the inside of a cell while a larger infection marks the outside and the combination triggers autoimmune disease.  The immune system is instructed to destroy both the inside and the outside of the target.

For Hashimoto's does a flavivirus mark the inside while candida marks the outside?

Hashimoto's and viral infections

http://www.ncbi.nlm.nih.gov/pubmed/20625285

Hepatitis C (flavivirus)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350409/

note the the flavivirus dengue has been linked to the thyroid too

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482561/

HPV B19

http://www.ncbi.nlm.nih.gov/pubmed/21190433

Family with genetic disorder linking Hashimoto's and Candida infections

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226065/

Sjogren's with Hashimoto's  thyroid
http://www.ncbi.nlm.nih.gov/pubmed/23884987
http://www.ncbi.nlm.nih.gov/pubmed/16984944
http://www.ncbi.nlm.nih.gov/pubmed/8422556
http://www.ncbi.nlm.nih.gov/pubmed/9010968

Candida and Sjogren's
http://www.ncbi.nlm.nih.gov/pubmed/9343767
http://www.ncbi.nlm.nih.gov/pubmed/10200720

could other fungal infections do the same? aspergillus?

what about flaviviruses as the culprit for melanoma and parkinson's?

could Hashimoto's encephalitis be flavivirus in the brain?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091936/



west nile sympotms
http://www.kansan.com/news/west-nile-virus-hits-kansas-leaves-patients-with-long-term/article_0920f8a4-1df3-11e5-bbc2-1f39b26d461c.html

Depression's SSRIs, the flu, and autism...can cross-targeting explain why only 50% get autism?

Autoimmune cross-targeting hypothesis: a virus marks the inside of a cell while a larger infection marks the outside and the combination triggers autoimmune disease.  The immune system is instructed to destroy both the inside and the outside of the target.

Low serotonin causes depression

Autism increased by 50% when antidepressant drugs are taken during pregnancy: Selective serotonin reuptake inhibitors specifically
http://www.sciencedaily.com/releases/2015/12/151214130227.htm

SSRIs bound to the outside of the frontal lobe nerves at the serotonin transporters

Testosterone increases the number of serotonin transporters
http://www.sciencedaily.com/releases/2015/01/150126083816.htm

This means more bound to the outside of the frontal lobe nerves increasing the change of the immune system attacking.

If we say that autism is an autoimmune disease caused by cross-targeting.

Autism and autoimmune antibodies to fetal brain
https://spectrumnews.org/news/researchers-flag-targets-of-autism-linked-antibodies/

 The flu virus which infects inside the frontal lobe nerves and RA which causes antibodies against the outside of frontal lobe nerves had been considered as the cause of birth autism on this blog.

Flu and autism
http://www.webmd.com/brain/autism/news/20121109/flu-pregnancy-autism

Frontal lobe and the flu
http://www.sciencedirect.com/science/article/pii/S0887899499001502

RA in mothers and autism
https://spectrumnews.org/news/large-study-links-autism-to-autoimmune-disease-in-mothers/

 (the vaccine triggered form of autism occurs on different parts of the brain according to this blog)

 However the amount of RA diagnosed has been decreasing and the amount of antidepressants prescribed has been increasing.

Could it be that SSRIs replace the outer infections of RA (mycoplasmas)? Did these babies born with autism from mothers taking SSRI get exposed to the flu? Is that why it is only 50% and not all?

Note that penicillin triggers autoimmune hemolytic anemia much the same way by coating the outside of the red blood cells.

Not just the flu but flaviviruses and heptachlor could trigger Parkinson's through cross-targeting

Cross-targeting hypothesis suggests that simultaneous infections on one target triggers autoimmunity.  One infection on the outside of the target cell and one infection, like a virus, on the inside of the target.  

Target: substantia nigra neurons
Inside: swine flu, flavivirus, heptachlor
Outside: mycobacteras

parkinson's and melanoma
http://cebp.aacrjournals.org/content/16/6/1081.full
http://www.ncbi.nlm.nih.gov/pubmed/16718266?dopt=Abstract

Is this a shared virus between melanoma and parkinson's? Flaviviruses?

melanoma and flaviviruses
http://angelabiggs.blogspot.com/2015/09/skin-cancer-melanoma-and-melanocortin.html

Note that they are currently creating parkinson's disease mouse models with flaviviruses
http://www.ncbi.nlm.nih.gov/pubmed/17447419

prostate cancer, melanoma and parkinson's seem linked
http://www.neurologyreviews.com/specialty-focus/parkinson-s-disease/article/parkinson-s-disease-may-increase-risk-of-melanoma-or-prostate-cancer/87b6d2451e0f60eab67b5671d4128c70.html

chikyngunya virus and prostate cancer
http://www.hindawi.com/journals/criu/2015/120535/

hepatitis C which is a flavivirus has also been linked to risk of parkinson's
http://www.ncbi.nlm.nih.gov/pubmed/25608223

swine flu and parkinson's
http://www.ncbi.nlm.nih.gov/pubmed/23271861
http://www.ncbi.nlm.nih.gov/pubmed/21655265

Note that it only takes one virus to mark the inside.

Can heptachlor replace the virus in some cases? thus explaining the milk and parkinson's disease connection since milk has been found to be contaminated with heptachlor.  The inside of the cell has been marked as foreign and non self...a chemical instead of a virus.

Breast cancer and melamona cancers are increased in parkinson's patients
http://www.ncbi.nlm.nih.gov/pubmed/22278152

Does too much heptachlor leaves deposits in the breast and brain?

Heptachlor also deposits in the breast where it acts like a carcinogen with the  viruses: hpv or epstein barr

Bullous pemphigoid with breast cancer, psoriasis and parkinson's
 http://www.ncbi.nlm.nih.gov/pubmed/24791209

psoriasis and parkinon's connection

mycobacteria connections

ischemic stroke connected to high cholesterol and parkinson's

(evidence that mycobacterias are there)

Up until now I have said that cancer is caused by a carcinogen which inhibits a polymerase and a virus.  Obviously heptachlor and viruses can exist together in the substantia nigra neurons.  The reason these neurons die and do not become cancerous is because neurons cannot go through cell division because they lack centrioles. 

Mycobacterias possible connection to Type 2 diabetes and nonalcoholic fatty liver disease.

Title:
Mycobacterias possible connection to Type 2 diabetes and nonalcoholic fatty liver disease.

Abstract:
 Mycobacterias could cause disease when the cGMP they produce for quorum sensing interferes with the host's normal cGMP cellular systems.

https://www.researchgate.net/publication/270164235_Quorum_Sensing_and_Biofilm_Formation_in_Mycobacteria_Role_of_c-di-GMP_and_Methods_to_Study_This_Second_Messenger

Introduction:

Chron's, psoriasis, psoriatic arthritis, and parkinon's disease have all been associated with mycobacterias.  All 4 have also been associated with fatty acid liver disease and type 2 diabetes.

 The chemical reactions for type 2 diabetes and fatty acid liver disease are basically the same involving NO increasing cGMP levels.

Type 2 diabetes is when the pancreas makes insulin but the body's cells do not respond to insulin, a state called insulin resistance.  Normally when cells see insulin they produce NO which activates cGMP at the plasma membrane which stimulates the glucose transporter to import glucose into the cell.  The glucose transporter might be overloaded if mycobacterias are present and as a result shut down.

The same sort of NO/cGMP system functions in the liver for the break down of fatty acids.
http://www.ncbi.nlm.nih.gov/pubmed/12632570  If cGMP levels are constantly high this could cause the fatty acid liver disease.

Note that Nitric oxides role has been considered but that the reason for a disfunction at this step has not been found. http://www.ncbi.nlm.nih.gov/pubmed/24878261

Mycobacterias use cGMP for quorum sensing to communicate about the growth of the biofilm mycobacteria colony size.  It seems logical that a mycobacteria infection would cause cGMP pathways to become disrupted. This hypothesis paper analyzes mycobacterias cause as a possible cause of  cGMP linked diseases including type2 diabetes and fatty liver disease.

Hypothesis
Mycobacterias cause type 2 diabetes and nonalcoholic fatty liver disease by secreting cGMP into the bloodsteam of the host.

Evaluation of Hypothesis

Tuberculosis has a long history of association with type 2 diabetes and has recently been discovered to be linked to non alcoholic fatty liver disease.  Both type 2 diabetes and non alcoholic fatty liver disease can be connected to cGMP in their pathways of normal function.   Mycobacterias like tuberculosis use quorum sensing to communicate and the molecule they use is a type of cGMP. The hypothesis is that the cGMP made by the mycobacteria disrupts the normal cGMP processes of the host causing high cholesterol through fatty liver disease and insulin resistance by disrupting the glucose transporter.

Resveratrol, which has been shown to activate cGMP, has also been shown to decrease the amount of fat in the liver in cases of non alcoholic fatty liver disease.  Does the normal cGMP inside the cell down regulate if the mycobacteria has flooded the bloodstream with cGMP? Does fatty liver disease cause high cholesterol?

The glucose transporter of all of our cells has a plasma membrane cGMP stimulation that occurs after insulin raises NO levels in cells.  Is there less internal cGMP to turn the transporter on if bloodstream cGMP is high? Is this state what causes the insulin resistance of type 2 diabetes?

Both type 2 diabetes and nonalcoholic fatty liver disease has been connected to obesity.
However, Type 2 diabetes is not always associated with obesity because for obesity to be caused by the mycobacteria the immune system must be engaged and producing TNF-alpha.

 THF-alpha is part of the immune response against mycobacterial infections and separately TNF-alpha is how the host's body maintains the proper about of adipose tissue. If the immune system is over engaged for too long against mycobacterias the body would have unusually high leptin levels favoring more adipose tissue....obesity.

 If the host's immune system has chosen to calm down or doesn't fight the mycobacterias then high cholesterol and type 2 diabetes could exist without obesity because these are caused not by TNF-alpha but by the cGMP.  The cGMP from the mycobacteria can cause the fatty liver disease and type 2 diabetes in a person who would appear healthy and not obese.

The finding of high levels of alpha-synuclein in the blood of type 2 diabetes patients, parkinson's patients brains, and some Crohn's patients guts connect it to cGMP too. In fact cGMP was found to increase the levels of alpha-synuclein.

High cGMP could prevent the normal stimulation of glucose transport of cells and the breakdown of fatty acids while simultaneously dumping synuclein where the mycobacterias are growing because of the same cGMP.

Bipolar disorder has a strong association with type 2 diabetes too.  Could bipolar disorder be a cGMP disorder too? The SERT transporter which moves serotonin has been shown to be altered by cGMP levels. Or is bipolar a separate autoimmune disease triggered by the combination of mycobacterias and cmv virus?

Also note that Testosterone levels appear to be altered.
http://www.ncbi.nlm.nih.gov/pubmed/23797822?dopt=Abstract&holding=f1000,f1000m,isrctn

Heterocyclic Amines, cancer, and fire fighters...a co-carcinogenesis hypothesis

Firefighters are probably exposed the most to polycyclic aromatic hydrocarbon compounds.
http://www.ncbi.nlm.nih.gov/pubmed/24512044

Heterocyclic amines are from meat cooked at high temperatures.
Polycyclic aromatic hydrocarbons are from plant matter cooked at high temperatures.

Polycyclic aromatic hydrocarbon compound:
A compound built from two or more benzene rings. Sources of PAHs include fossil fuels and incomplete combustion of organic matter (in auto engines, incinerators, and even forest fires)." - National Research Council, 1994

Benzenes are carcinogens and inhibit polymerases.

https://books.google.com/books?id=sPgEDYgjlKAC&pg=PA203&lpg=PA203&dq=benzene+inhibits+polymerases&source=bl&ots=HQcY8V1E-H&sig=y7R938yWNDKgUc9xj91eIlUnDgQ&hl=en&sa=X&ved=0ahUKEwjLw5vjkb7JAhWCdx4KHRGoBOEQ6AEIPzAF#v=onepage&q=benzene%20inhibits%20polymerases&f=false

Lung cancer and leukemia from PAH
http://www.ncbi.nlm.nih.gov/pubmed/11293301
http://www.ncbi.nlm.nih.gov/pubmed/15833386

PAH has caused cancer in animals' lung, stomach, and skin.
Benzene goes into lung cells and migrates to the bone marrow. PAH is probably similar.

Francis Peyton Rous' Co-carcinogenesis hypothesis: that a virus and a carcinogen together cause cancer. (1966 nobel prize)

What I surmise from his hypothesis:

A virus enters a cell through a receptor, opens up and alters host DNA telomeres. The carcinogen with a benzene ring inhibits the virus' polymerase because viral polymerases have stronger binding affinities than the host's.

Cancer cells can make unlimited copies because of the telomere modifications. Co-carcinogenesis requires a virus and a carcinogen to start the cancer. The cancer tumor wears the entry receptor on the surface.

So what viruses infects bone marrow or lung tissue?

Respiratory syncytial virus infects lung, blood, and bone marrow....so does flaviviruses
We need a vaccine for these viruses to protect our firefighters.

The conundrum of high cholesterol, type2 diabetes, low testosterone, and fatty liver: is it from a mycobacteria's quorum cGMP?

Type 2 diabetes : the pancreas makes insulin but the body's cells do not respond to the insulin. 

Normally insulin from the pancreas stimulates the body's cells to produce NO which then activates cGMP which stimulates the glucose transporter to import glucose.  

Mycobacterias use cGMP for quorum sensing, communicating the growth of the biofilm mycobacteria colony.

If the body is infected with mycobacterias could the cGMP released by them disrupt the host's system causing the cells not to respond to insulin? cGMP does control the glucose transporter. Normally insulin raises NO which then triggers cGMP to turn on and import glucose at the transporter.

 High cholesterol tends to exist with Type 2 diabetes too.  Could cGMP be upsetting the liver which makes the cholesterol? Does high plasma cGMP cause nonalcoholic fatty liver disease? not the other way around? Fatty liver disease has been found statistically high with tuberculosis patients. 

Resveratrol has been shown to decrease fat deposits in the liver. Resveratrol has been shown to activate cGMP in cells. Has intracellular cGMP been suppressed because of the high plasma cGMP from mycobacterias?

Testosterone is made from cholesterol in the body. Why would testosterone be low when cholesterol is high? 

Testosterone is made in the testicles. The level of cGMP is critical for the proper function of males. Cholesterol is made into testosterone then the testosterone triggers cGMP.  cGMP is raised for reaction but then must go down. If cGMP is abnormally high it would make sense that the body would suppress testosterone production to keep internal cGMP lower?

Note that psoriasis has been associated with mycobacterias.  Psoriasis alone has been associated with a risk of fatty liver disease.

 Chron's has also been associated with fatty liver disease

http://www.ncbi.nlm.nih.gov/pubmed/16514570

Earlier post about mycobacterias:

http://angelabiggs.blogspot.com/2013/06/mycobacteria-diseases-psoriasis-chrons.html

References: 

mycobacteria's use and require cholesterol

http://nopr.niscair.res.in/bitstream/123456789/4363/1/IJEB%2047(6)%20407-411.pdf

Nat Rev Endocrinol. 2013 Aug;9(8):479-93. doi: 10.1038/nrendo.2013.122. Epub 2013 Jun 25.

Testosterone and insulin resistance in the metabolic syndrome and T2DM in men.

Rao PM1, Kelly DM, Jones TH.

http://www.ncbi.nlm.nih.gov/pubmed/23797822?dopt=Abstract&holding=f1000,f1000m,isrctn

Mycobacteria in host macrophage uses cholesterol
http://www.sciencedirect.com/science/article/pii/S1074552112000099

Quorum sensing and biofilm formation in mycobacteria: role of c-di-GMP and methods to study this second messenger.

Sharma IM1, Petchiappan A, Chatterji D.

Testosterone protects against type 2 diabetes in men

http://www.ncbi.nlm.nih.gov/pubmed/20126841

Testosterone and its precursors and metabolites enhance guanylate cyclase activity (progesterone/5a-dihydrotestosterone/pregnenolone/cyclic GMP) DAVID L. VESELY
http://www.pnas.org/content/76/7/3491.full.pdf

Insulin stimulates cGMP pathway in smooth muscle

http://www.ncbi.nlm.nih.gov/pubmed/14615391

non alcoholic fatty liver disease with type 2 diabetes...70% of those with type 2

http://www.ncbi.nlm.nih.gov/pubmed/19262374
http://care.diabetesjournals.org/content/30/6/e56.full

Fatty liver disease with TB

http://archinte.jamanetwork.com/article.aspx?articleid=550748

mycobacteria and metabolic syndrome

http://www.ncbi.nlm.nih.gov/pubmed/18448263

TB and type 2 diabetes
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887603/

Fatty liver disease and psoriasis
https://www.psoriasis.org/advance/psoriasis-alone-raises-risk-for-nonalcoholic-liver-disease

Resveratrol activates cGMP
http://www.readcube.com/articles/10.1211%2F146080800128735917?r3_referer=wol&tracking_action=preview_click&show_checkout=1&purchase_referrer=onlinelibrary.wiley.com&purchase_site_license=LICENSE_DENIED_NO_CUSTOMER

Resveratrol decreased Fat deposits
http://www.biomedcentral.com/1471-230X/8/40

testosterone, crohn's
http://www.ncbi.nlm.nih.gov/pubmed/26020563

metabolic syndrome and urine secretion of cGMP
http://www.sciencedirect.com/science/article/pii/S0021915006000761

mycobacteria and type 2 Diabetes: hypothesis
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-3156.2010.02632.x/pdf
http://www.ncbi.nlm.nih.gov/pubmed/15967589