NPR-C Attenuates Accumulation of ROS and NOS In Ammonia-Treated Astrocytes!

STIMULATION OF NATRIURETIC PEPTIDE RECEPTOR C (NPR... [J Neurochem. 2010] - PubMed result: "STIMULATION OF NATRIURETIC PEPTIDE RECEPTOR C (NPR-C) ATTENUATES ACCUMULATION OF REACTIVE OXYGEN SPECIES AND NITRIC OXIDE SYNTHESIS IN AMMONIA-TREATED ASTROCYTES."

Ammonia Upregulates Membrane Channel Associated with Autoimmune Conditions in Astrocytes~!

"Ammonium chloride induced upregulation of aquaporin-4 in astrocytes is regulated by the p38 mitogen-activated protein kinase pathway. Inhibiting p38 activation prevented ammonium chloride induced aquaporin-4 protein upregulation." It has been suggested that aquaporins are responsible for autoimmune-type conditions including MS and past studies show it upregulates the inflammatory cytokine that initiates the inflammatory cascade that increases oxidative stress via NO.

CiteULike: Ammonia induces upregulation of aquaporin-4 in neocortical astrocytes of rats through the p38 mitogen-activated protein kinase pathway.:


Reference: (2005). Aquaporin-4, water channel protein implicated in a disorder similar to multiple sclerosis. http://www.citeulike.org/user/HEIRS/article/7859740
Sinke, A. P., Jayakumar, A. R., Panickar, K. S., Moriyama, M., Reddy, P. V., and Norenberg, M. D. (2008). Nfkappab in the mechanism of ammonia-induced astrocyte swelling in culture. Journal of neurochemistry, 106(6):2302-2311.

Comments: Sulphoraphane, Ammonia and ALS Drug....

I find this interesting ................................... As we have already established there is potential for the Nrf2 to protect astrocytes from damage. Excitotoxicity from glutamate has been implicated in a number of neurodegenerative conditions. As a new report suggests, sulphoraphane and riluzole,a ALS drug, may be more effective combined that each alone to  minimize excitotoxicity.  The former has been shown to act through Nrf2 while the latter is is presumed at least to improve transport by regulating glutamate transporters. The former I get but as to the latter I do not have a lot of information here....Is caveolin responsible for urea and ammonia leakiness? Do conditions that elevate ammonia...alter proteins that coregulate that influence muscle weakness? Can this be a factor in weakness associated with old age or other illness where excitoxity becomes a factor.? Is this drug, only used for ALS? Just askin? Understanding animal behavior sometimes is alot easier...and wonder why is it that this stuff fascinates me.....? Even if it hard to understand when I do not have a lot to go on.....! Too much to learn, so little time and too little time before I will forget...or not!


 Geng Chang, Yansu Guo, Yaqiong Jia, Weisong Duan, Bin Li, Jixu Yu and Chunyan Li, “Protective Effect of Combination of Sulforaphane and Riluzole on Glutamate-Mediated Excitotoxicity”, Biol. Pharm. Bull., Vol. 33, 1477-1483 (2010) .  http://www.ncbi.nlm.nih.gov/pubmed/20823560

Mark J Hernandez, Tina M Roberts and Christopher D Hardin. Caveolin-1 and the Organization of Glycolysis in Astrocytes: Modulation by Ammonia. FASEB Journal 2007. 21:748.9   http://www.fasebj.org/cgi/content/meeting_abstract/21/6/A872-c

Meth Labs, Wood Treatments, Pesticides and Ammonia Toxicity on Astrocytes~!

Astrocytes: (astroglia) : are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical support of endothelial cells which form the blood-brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, and a principal role in the repair and scarring process of the brain and spinal cord following traumatic injuries. (Wipedia: Astrocytes)

This study would suggest that any condition that impairs the antioxidant system which has a primary role in protecting astrocytes against damage (ie Nrf2)  would augment the toxicity of ammonia whether it be produced endogenously or from exogenous exposures. Young children, the elderly and those with impaired immune systems would also be more at risk. Products that contain ammonia or have it as an "inert" ingredient or exposures from hazardous environments such as methamphetamine labs pose an elevated risk for the above populations because they would be more susceptible to ammonia toxicity.

"This study demonstrated that in rats with HA or HE ammonia specifically promote GSH synthesis and export from astrocytes and increase its extracellular degradation, which may improve the availability of precursors for GSH synthesis in neurons and their resistance to ammonia toxicity."

Hilgier, W., Wegrzynowicz, M., Ruszkiewicz, J., Oja, S. S., Saransaari, P., and Albrecht, J. (2010). Direct exposure to ammonia and hyperammonemia increase the extracellular accumulation and degradation of astroglia-derived glutathione in the rat prefrontal cortex. Toxicological sciences : an official journal of the Society of Toxicology, 117(1):163-168. http://www.citeulike.org/user/HEIRS/article/7292948?show_msg=already_posted
 
 

Activation of {beta}-Catenin in Dendritic Cells Regulates Immunity Versus Tolerance in the Intestine

Background: It has been suggested that environmental illnesses such as chemical sensitivity entails a "loss of tolerance". Interestingly, it has also been proposed that the condition also be associated with inflammation in the gut and supports claims that it often develops after infection. Endotoxin activates the protein GSK-3b which has been shown to negatively influence the activities of beta-catenin and also the Nrf2. A new study by Manicassamy et al supports the necessity for beta-catenin in the development of tolerogenic dendritic cells. Another important note is the role of DISC1 which has been implicated in a number of mental disorders and subset of chronic fatigue syndrome inhibits GSK-3b activity. The beta-catenin pathway is also responsible for toxin removal of ammonia.


Activation of {beta}-Catenin in Dendritic Cells Re... [Science. 2010] - PubMed result: "Activation of {beta}-Catenin in Dendritic Cells Regulates Immunity Versus Tolerance in the Intestine."

Colon luminal content and epithelial cell morphology are markedly modified in rats fed with a high protein diet.

"basal oxygen consumption of colonocytes was similar in the NP and HP groups, but ammonia was found to provoke a dose-dependent decrease of oxygen consumption in the isolated absorbing colonocytes. The activity of glutamine synthetase (which condenses ammonia and glutamate) was found to be much higher in colonocytes than in small intestine enterocytes and was 1.6-fold higher (p=0.0304) in colonocytes isolated from HP animals than NP. Glutaminase activity remained unchanged."

Read more: CiteULike: Colon luminal content and epithelial cell morphology are markedly modified in rats fed with a high protein diet.:

Adaptative increase of ornithine production and decrease of ammonia metabolism in rat colonocytes after hyperproteic diet ingestion.

This would be an interesting explanation at the hypothesis that the failure to adapt leads to environmental illess. Of course, the failure of the Nrf2 antioxidant system to work effectively is also maladaptive...and there has been studies that suggest that Nrf2 may regulate this pathway to some extent. Lowering protein levels may be an additional way to reduce some EI symptoms and deserves much further study!

". In response to increased NH(4)(+)/NH(3) concentration in the colon, the increased capacity of the colonocytes to synthesize l-ornithine is likely to correspond to an elevated l-ornithine requirement for the elimination of excessive blood ammonia in the liver urea cycle"

Read more: CiteULike: Adaptative increase of ornithine production and decrease of ammonia metabolism in rat colonocytes after hyperproteic diet ingestion.:

Ammonia and Hyperammonemia Increase the Extracellular Accumulation/ Degradation of Astroglia-Derived Glutathione.

These results suggest that in rats with HA or HE ammonia specifically promotes GSH synthesis and export from astrocytes and increases its extracellular degradation, which may improve the availability of precursors for GSH synthesis in neurons and their resistance to ammonia toxicity.

CiteULike: Direct Exposure to Ammonia and Hyperammonemia Increase the Extracellular Accumulation and Degradation of Astroglia-Derived Glutathione in the Rat Prefrontal Cortex: "Hilgier, W., Wegrzynowicz, M., Ruszkiewicz, J., Oja, S. S., Saransaari, P., and Albrecht, J. (2010). Direct exposure to ammonia and hyperammonemia increase the extracellular accumulation and degradation of astroglia-derived glutathione in the rat prefrontal cortex. Toxicol. Sci., pages kfq171+."

Glutamine Synthetase, PFOS and Neurotransmission

PFC are chemicals that are ubiquitous in the environmental and can or could be found in products including building materials, fabrics, packaging, clothing, protective gear etc. Recent studies show that these chemicals have the capacity to regulate or impair gene expression including those that regulate the excretion of toxic waste products that may result in alterations of neurotransmission and contribute to their toxicity. In addition, genetic problems may aggravate this inhibition and augment the physical consequences of exposure. Glutamine synthetase is one enzyme that is important for regulation of toxins such as ammonia in the brain as well as production of glutathione. In addition, certain conditions, such as in endotoxemia and implicated as a causal factor is CFS, the activity of this enzyme is further reduced. Nrf2 is protective against PFOS through the generation of HO-1 and reductions in its production may augment oxidative stress damage from PFOS.


Yang, X., Wang, L., Sun, W., and Xue, Z. (2009). [effects of perfluorooctane sulfonate on amino acid neurotransmitters and glutamine synthetase in rats]. Wei sheng yan jiu = Journal of hygiene research, 38(1):19-21. http://www.citeulike.org/user/HEIRS/article/6999108
Häussinger, D. and Schliess, F. (2007). Glutamine metabolism and signaling in the liver. Frontiers in Bioscience, 12:371-391.
http://www.citeulike.org/user/HEIRS/article/7208003
Shi, X. and Zhou, B. (2010). The role of nrf2 and mapk pathways in pfos-induced oxidative stress in zebrafish embryos. Toxicol. Sci., 115(2):391-400.
http://www.citeulike.org/user/HEIRS/article/6761678

Ammonia and Urea in Acidosis

"Ammonia is excreted only as a defense against an acidosis condition because the neutralization of acid by ammonia has the effect of conserving bases in the blood."

Urea Cycle:

Lactic acidosis from Heavy Metal Poisoning.

"Heavy metal toxicity, including poisoning with arsenic, can raise lactate levels and lead to generalized metabolic acidosis"

Lactic acidosis - Wikipedia, the free encyclopedia:

Ammonia, Smoking,Insulin Resistance and Protein Dysfunction in MCS

Background: Manufacturers of cigarettes have admitted to adding ammonia since the 1960s to make them more addictive by boosting the absorption of nicotine significantly. This may make cigarette smoke more toxic to some including people that are more vulnerable such as young children with immature immune systems, the elderly or other individuals that have urinary impairments or genetic factors that alter excretory metabolism. Below are some examples of why adding ammonia to cigarettes may be indirectly responsible, at least in part, for the rise in cardiovascular and other diseases from smoking because of its toxic effects on genes and different tissues in the body.

In cells, chemical toxins effect metabolic pathways which may run parallel, are independant and/or interact, potentiate or possibly minimize the effects of each another.   For this reason, it is difficult to predict the severity and the consequences of them on the health of an organism. Exposure to cigarette smoke is no different and has been shown to act differently in different people and on more than one molecular pathway at the same time. Through the years, hundreds of studies have demonstrated the health hazards associated with the toxic effects of smoking and one of these effects includes the dysregulation of metabolism including altering blood sugar homeostasis. Personally, I have suspected this to be the case for some time. Over the past several years, scientists have discovered smoking not only increases the risk for diabetes which includes higher glucose levels, higher insulin levels and increased blood pressure it may also contribute to episodes of hypoglycemia in diabetes. As one article state, "this may be due to an effect of smoking on insulin clearance, leading to hyperinsulinemia, increasing hypoglycemia, and worsening metabolic control. In addition, smoking has been shown to increase the secretion of hormones (i.e., growth hormone, vasopressin, and cortisol) that counteract insulin action, leading to an increased insulin requirement. Smokers have been found to require more insulin than nonsmokers to achieve the same level of glycemic control in some, but not all, studies." (Hirai)

In addition to ammonia making cigarettes more addictive, ammonia can act on the cortico-releasing factor (CRF) system which regulates behavior including feeding and increases serotonin and dopamine levels. As a consequence, it can influence mood and alter homeostasis leading the conditions like the weight loss and weight gain from smoking and cessation, respectively.  Activation of this pathway, in fact, mediates  psychological effects of nicotine withdrawal.  (Grunberg) I recently mentioned that because ammonia activates the CRF pathway that regulates neuroendocrine, drug abuse responses and aversion one could relate MCS behaviors to a scewed form of addictive behavior. (Kreibich, Sahuque) More simply, its activation leads to changes in hormone production and alter behaviors, it is possible that abherrant signaling in this system may be responsible for some of the symptoms of MCS and similar to those from chemical withdrawal but modified into aversive response. It is also possible the addictive nature of smoking from ammonia or other volatiles on the CRF from smoke exposure could be a sensitizing factor, stimulate the immune system and also initiate a "loss of tolerance" which has been suggested as an explanation of multiple chemical sensitivity and sensitivities in autism. An interesting research study could be designed to determine wether a potential correlation of MCS sensitization and smoking could exist.

To support this idea further, researchers have demonstrated the addictive nature of smoking involves a cellular pathway called CREB that involves the relationship of reward to smoking behaviors and their association with environmental cues.  Also, recent research findings show a strong association of CREB and CRF in stress-induced drug reward behavior. It is not beyond reason to suggest that alterations in signals that lead to physical and psychological symptoms of drug withdrawal may also influence physical and emotional aversive behaviors of MCS and argues against the notion of that symptoms of MCS are "psychosomatic".  The high levels of cadmium may further disrupt the CREB pathway and normal cell functions.  Both of these discoveries provide an important mechanism to explain activation of MCS by environmental cues and suggests that insulin resistance may play a part in some of its reactions. "Previously,it has been shown the CREB pathway keeps blood sugar in balance under certain metabolic conditions and excessive CREB activity in diabetes contributes to high blood sugar and insulin resistance. New findings show CREB encourages insulin resistance by lowering adiponectin and the insulin-sensitive glucose transporter 4 (GLUT4)." (US Health News) CREB is a mediator of inflammation and both of these findings demonstrate that overactive CREB may contribute to endothelial dysfunction and impair cognitive function by mediating inflammation and insulin resistance. (Ishiki)  On the other hand, downregulation of the cGMP/NO/CREB by amyloid or hyperammonemia may contribute to neurodegenerative diseases and Alzheimer's. (Copper Mountain, CO, Puzzo) This has important implications not only for cigarette smoke but persistent organic pollutants considering they both may contribute to diabetes complications.Other environmental factors such as other exposures to heavy metals implicated in contributing to diabetes and altered methylation may also contribute to these conditions. (Pozharny)

Along those same lines, cigarette smoking also contributes to weight loss through activation of the aryl hydrocarbon and endoplasmic reticulum stress. In other blogs, I have suggested this process also is involved in MCS. A recent study agrees with findings that cigarette smoke and dioxin does lower adiponectin but also demonstrated that PPAR-gamma and c/EPB were also decreased. In another study, ornithine impairments in c/EPB knock-outs from hypoglycemia presented with significantly higher levels of ammonia. Further, it has been shown ornithine enzymes interact with C/EPB and is important for ammonia detoxification. Without it, you get impaired excretion of urea and gluconeogenesis. As one can see, metabolically cigarette smoke may cause severe alterations in metabolism. This may include alterations of ammonia which may potentially sensitize an individual towards development and contribute to multiple chemical sensitivity.




Citations and other documents available here.

The Ammonia Hypothesis - A Science and Protocal of Spiritual Alchemy

The following ties together much of what I have written on the possible physiology of kundalini so far and is the most speculative piece in this book. I am pretty sure that convulsive/seizure/kindling can actually produce ammonia, as well as be caused by ammonia. If so this could be one of the main causes of people running into extended periods of difficulty with kundalini.

CiteULike: The Ammonia Hypothesis - A Science and Protocal of Spiritual Alchemy: "The ammonia hypothesis - a science and protocal of spiritual alchemy."

Thought for the Day: Hyperammonemia and Environmental Illness...

Does anyone see these as being familiar symptoms? To me, they seem like some common symptoms in CFS or exposures????

The symptoms and blood ammonia values of mild to moderate chronic hyperammemia (CH) are similar to those observed during physical exhaustion with ‘exercise-induced hyperammonemia’ (EIH). These include confusion, hyperventilation, and muscular dysfunction.....Treatments for lowering CH and EIH are similar, and include: 1) restriction of dietary
protein, 2) increasing carbohydrate (%) intake, 3) administration of amino acids (AA’s)that enhance ammonia clearance into (the less toxic) urea, and 4) correction of the underlying metabolic etiology

HEIRS Library Tags: Hyperammonemia
Blog Tags: Hyperammonemia, ammonia

Edwards, W. ARM CRANK POWER AND HYPERAMMONEMIA IN RESPONSE TO L-ASPARTIC ACID SUPPLEMENTATION. PhD thesis, Louisiana State University.
http://www.citeulike.org/user/HEIRS/article/7111333

Toxicology: Cells Deficient in Ornithine Decarboxylase Activity Induced by Ethyl Methane Sulfonate.

"one null mutant, which was induced with ethyl methane sulfonate and which makes ODC mRNA but no active enzyme, is nevertheless revertible with 5-azacytidine."

CiteULike: Chinese hamster cells deficient in ornithine decarboxylase activity: reversion by gene amplification and by azacytidine treatment.:

Chronic Elevated Ammonia Contributes to Neuroinflammation, Cognitive and Motor Dysfunction.

CiteULike: Hyperammonemia Induces Neuroinflammation that Contributes to Cognitive Impairment in Rats with Hepatic Encephalopathy.: "Chronic moderate hyperammonemia or BDL activated the microglia, especially in cerebellum; increased iNOS, IL-1beta, and prostaglandin E2 levels; and impaired cognitive and motor function, compared with controls"

Chronic hyperammonemia alters the circadian rhythm... [J Neurosci Res. 2010] - PubMed result

Chronic hyperammonemia alters the circadian rhythm... [J Neurosci Res. 2010] - PubMed result: "Chronic hyperammonemia alters the circadian rhythms of corticosteroid hormone levels and of motor activity in rats."

Dysfunction of Methylation and Nrf2 in Environmental Illness - Is This A Better Explanation than NO/ONOO- ?

One of the most important themes of my research is that accumulation of ammonia may play a causal role in including in conditions such MCS and autism through alterations in the methionine and glutamine synthetase pathway and elevations of ammonia in general which may change the expression of a variety of genes that regulate cell function. Of course, this has been suggested by a number of experts. Further, I also have proposed that the dysfunction in Nrf2 and related genes contribute to the severity and elicits autoimmune-type responses and chemicals such as PFOS may influence it or "trigger" it in addition to other chemicals that are more commonly considered as more toxic. In support, in support it has been suggested that hyperammonemia may alter that nitric-oxide-cGMP pathway (Hermenegildo) and as a result this could alter NO funtioning and contribute to conditions such as fibrosis in some tissuesand endothelial dysfunction. Alterations in the ornithine pathway may contribute to this but it is worth mentioning that NO may alter this pathway on it own. (Bauer) Interestingly, recently it has been reported that one of the benefits of fish oil may be mediated through the eNOS-cGMP pathway. (Lopez)  Nrf2 also has an important role in regulating NO and CO through its interaction with the antioxidant HO-1 and plays a substantial neuroprotective role against diseases such as Parkinson's disease. The deficiency or lack of Nrf2 expression offers one explanation of why individuals with MCS are so sensitive to carbon monoxide, nitrous oxide and other greenhouse gases. Mainly, because of the dysregulation of their regulator HO-1 by Nrf2. Tinnitus is common with MCS and can be associated with over-exposure to nitrous oxide which may also indicate problems associated with vitamin B and methylation. (Wipedia) Genetic polymorphisms in HO-1 and metal toxicity may also contribute to this problem. (You can see how lead, mercury and aluminum alter function in different steps in the cycle....here but you have to look closely.) Other Nrf2 interactions include modulation of Il-6 which is elevated in neuroinflammatory responses in the brain and Il-10 which is an anti-inflammatory that modulates sickness syndrome. According to a new report, sickness syndrome may be implicated in causing some of the symptoms of Gulf War Syndrome.


In addition, conditions such as elevations of ammonia activate the CRF pathway in animals that display hyperanxious behavior and recently this pathway has been shown to regulate both anxiety and depression as a consequence of stress. (Biomedicine) Interestingly, the glutamine pathway is also altered during depression and as a result, one may suggest this pathway may be dysregulated from exposure to chemicals such as PFOS and cause mood changes such as depression and anxiety and endogenous elevations of ammonia may induce mood changes even more. In addition, dysfunction of Nrf2 may lead to neurotoxicity and other consequences including augmenting ammonia accumulation. Chemical sensitivity has been implied as important in autism and ammonia may contribute to this which is produced endogenously and exogenously and many therapies used for MCS have also been used to reduce ammonia levels in autism. An interesting suggestion is that in some form through the dysfunction of Nrf2, deficits in the ornithine pathway contribute to the cellular toxicity experienced in MCS and autism. Of course, there are a number of other genetic defects that may alter the urea-cycle, including minor ones that may not appear until adulthood or later because of compensation from other pathways lost with ageing. Ammonia production is higher correlated with inflammatory markers in liver injury and has a profound effect on the permeability of the blood-brain-barrier, providing access of more toxic agents to brain tissue. (Jalan)

Alterations in the methionine pathway have also been suggested to play an important role in autism and we suggest here, MCS and relies on the notion of abherrant methylation "tagging" that potentiate the problems or vice versa. Q10 and vitamin B12 has been used as a therapy for MCS but is also used to assist mitochondrial function and support the methionine cycle and reduce ammonia, respectively. In methyl cycle disfunction, BH4 is drained in ammonia detoxification (Yasko ?) in addition in contrast to its role for NOS production and peroxynitrite which is part of the NO/ONOO- hypothesis. (Pall) Here we see the dichotomy between the Methyl Pathway and the NO/ONOO- hypothesis where BH4 is concerned. In one BH4-dependant process, NOS is converted to nitric oxide and on the other hand it assists in ammonia detoxification in the methylation cycle. If you put alterations in Nrf2 function, which is activated by ONOO- into the mix it can alter expression of genes important for these processes. ONOO- is not the only pro-oxidant that activates the Nrf2, it has been suggested that H2O2 is a much stronger activator and numerous other conditions normally upregulate Nrf2 in normal circumstances. Marzec recently demonstrated that SNPs that exist in the Nrf2 may make on more or less susceptible to oxidative stress and therefore cellular injury and disfunction. The inheritability hypothesis of epigenetics also relies on methylation and helps to explain why environmental illnesses largely run in families and the relationships between gene expression help to explain why gender plays an important role too! Unfortunately, alterations in methylation and consequently, alteration of function has been demonstrated in Nrf2 and several other genes implicated in environmental illness including autism. (To get an idea of how complicated genetics in environmental illness is --click here. ) In addition, alterations in Nrf2 and PGC-1a may contribute to diabetes and insulin resistance and are associated with POP exposures. In addition, GSK-3b involvement from reduced expression of PGC-1a, elevations in dopamine and exposures to bacteria (endotoxin) are a few additional factors that may hamper Nrf2 detoxification system which can lead to more elevations of neuroinflammatory processes, mood changes and significantly increase the likelihood of more neurodegeneration; all associated with environmental illness. GSK-3b signalling also may involve alterations in dopamine-regulated behaviors such as twitching (Tourette's) and ADHD that are often co-morbid with environmental illnesses after exposure injury. Incidentally, a number of behavioral responses to drugs (ie cocaine) can be reduced by GSK-3b inhibitors.

Currently, the NO/ONOO- cycle hypothesis which implicates elevation in ONOO as an important cause for responses in the conditions and proposed by Martin Pall, PhD is one of the most commonly accepted hypothesis to explain many of the symptoms in many environmental illnesses including MCS, chronic fatigue syndrome, fibromyalgia and PTSD. While this hypothesis is an important one, I can not say that it accurately describes the multi-inflammatory processes that occur in all of these illnesses and fails to adequately describe the metabolic processes that lead to these conditions. For one, obesity and insulin resistance and diabetes are important in environmental disease and the complications of ageing augment most of these and others as well. Recent evidence is highly suggestive these conditions may influence the development of the more commonly accept EI conditions and for this reason, I have to include them under that umbrella as well. In addition, there is no mention of methylation or how dysregulation of the antioxidant system Nrf2 negatively impacts the expression of NO, CO, HO-1, Il-10 as well as, modulates inflammatory cytokine expression. HO-1 (again with interaction from Nrf2) and vitamin D are involved in the suppressive function of regulatory Tcells. Their absence has been implicated in autoimmune disease that provides an explanation for why environmental illnesses like CFS and GWS and others including diabetes have autoimmune-type behavior. A recent study has presented the hypothesis that exposure to environmental pollutants and high ammonia levels directly alters Treg behavior. In would suggest the inability of oxidants including peroxynitrite and H2O2 to activate Nrf2 is one explanation for failure of the Nrf2 antioxidant system in addition to impairments in activation and regulation of Keap1 and genetic expression of the many genes that regulate the system in different ways. Not only does Nrf2 regulate NO but so does SIRT1 through AMPK, all of which are indirectly or directly involved in activating PGC-1a upregulated by exercise which prevents activation of GSK-3b that turns off the antioxidant system which provide upregulation of nuclear factors including NRF1. In further support, pharmaceutical therapies such as those that elevate PGC-1a and reduce ammonia levels, electroacupuncture, food therapies that elevate Nrf2 through sauna or Waon therapy and nutrition and antioxidant support to reduce mitochondrial dysfunction may be a valuable "tool kit" for the treatment of MCS, autism, provide some relief in CFS and PTSD and help prevent endothelial damage that may be instrumental in causing a number of conditions in many of them.

HEIRS Tags: ammonia, hyperammonemia, homocitrulline, diabetes, insulin resistance, GSK-3b, HO-1, Nrf2, PGC-1a, SIRT1, AMPK, NO/ONOO-, H2O2, dopamine, DAR, cocaine, encephelopathy, Il-6, neuropathy, B12, methionine


HEIRS Tags: ammonia, hyperammonemia, homocitrulline, diabetes, insulin resistance, GSK-3b, HO-1, Nrf2, PGC-1a, SIRT1, AMPK, NO/ONOO-, H2O2,

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Original Article and Citations:

Toxic Chemicals In Upholstery May Increase Susceptibility to Infection.

Background: I have suggested that PFOA plays a part in MCS by altering the genes in the methionine cycle that could influence ammonia detoxification. Other new studies demonstrate that effects of methionine metabolism may be exacerbated by deficiencies in the Nrf2 which is neuroprotective through numerous mechanisms including regulating transferases, ornithine proteins and modulating cobalamin upregulation.

Findings of a new study on the toxicity of PFOA chemicals in carpets, upholstery, etc. may alter the function of immune cells called lysozymes. Wipedia explains these cells are responsible for providing protection from damage from invading bacteria and are found in secretions from membranes such as tears and mucus. Infants lacking these enzymes have elevations in diarrheal disease; potentially because they fight against infection of bacteria such as Salmonella, E. coli and Pseudomonas.

Question: Why on earth do they still use this stuff?

Further Reading: PFOA alters liver gene expression.(CHEMICAL EXPOSURES): An article from: Environmental Health Perspectives

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Wu, L.-L. L., Chen, L., Song, C., Liu, X.-W. W., Deng, H.-P. P., Gao, N.-Y. Y., and Gao, H.-W. W. (2010). Potential enzyme toxicity of perfluorooctanoic acid. Amino acids, 38(1):113-120. http://www.citeulike.org/user/HEIRS/article/3746495

Ammonia, Hyperglycemia and Metabolism in Ferrets

Interesting statement: Hyperglycemia has also been reported in near-adult cats fed arginine-free diet. Hyperglycemia is usually associated with high ammonia levels and is probably due to release of glucagon by the action of ammonia.

CiteULike: Effect of Arginine-Free Diet on Ammonia Metabolism in Young and Adult Ferrets12: "Thomas, P. E. and Deshmukh, A. R. (1986). Effect of arginine-free diet on ammonia metabolism in young and adult ferrets12. The Journal of Nutrition, 116:545-551."