Long-term air pollution exposure and risk factors for Cardiovascular Disease

Long-term air pollution exposure and risk factors ... [Occup Environ Med. 2010] - PubMed result: "Changes in blood pressure, blood lipids, blood sugar and haematological markers of inflammation are associated with long-term exposure to ambient air pollutants. This might provide a link between air pollution and atherosclerotic cardiovascular diseases"

A formal analysis of cytokine networks in chronic ... [Brain Behav Immun. 2010] - PubMed result

A formal analysis of cytokine networks in chronic ... [Brain Behav Immun. 2010] - PubMed result: "A formal analysis of cytokine networks in chronic fatigue syndrome."

CiteULike: Neuromotor deficits and mercury concentrations in rats exposed to methyl mercury and fish oil.

CiteULike: Neuromotor deficits and mercury concentrations in rats exposed to methyl mercury and fish oil.: "Day, J. J., Reed, M. N., and Newland, M. C. (2005). Neuromotor deficits and mercury concentrations in rats exposed to methyl mercury and fish oil. Neurotoxicology and teratology, 27(4):629-641."

Induction of regulatory T cells by macrophages is ... [Proc Natl Acad Sci U S A. 2010] - PubMed result

Induction of regulatory T cells by macrophages is ... [Proc Natl Acad Sci U S A. 2010] - PubMed result: "Induction of regulatory T cells by macrophages is dependent on production of reactive oxygen species"

Homocysteine impairs coronary artery endothelial function by inhibiting tetrahydrobiopterin in patients with hyperhomocysteinemia.

Hmm...seems like this is right in line with why some therapies for MCS and autism.  Note: Nrf2 is involved with maintaining coupling of NO and BH4.

Homocysteine impairs coronary artery endothelial function by inhibiting tetrahydrobiopterin in patients with hyperhomocysteinemia.

Two unrelated Chinese patients with hyperinsulinis... [J Pediatr Endocrinol Metab. 2010] - PubMed result

Two unrelated Chinese patients with hyperinsulinis... [J Pediatr Endocrinol Metab. 2010] - PubMed result: "Two unrelated Chinese patients with hyperinsulinism /hyperammonemia (HI/HA) syndrome due to mutations in glutamate dehydrogenase gene"

PGC-1 alpha regulates expression of myocardial mit... [Antioxid Redox Signal. 2010] - PubMed result

PGC-1 alpha regulates expression of myocardial mit... [Antioxid Redox Signal. 2010] - PubMed result: "PGC-1 alpha regulates expression of myocardial mitochondrial antioxidants and myocardial oxidative stress after chronic systolic overload"

Postnatal development of lipopolysaccharide-induce... [Inflamm Res. 2010] - PubMed result

Postnatal development of lipopolysaccharide-induce... [Inflamm Res. 2010] - PubMed result: "TLR-4-mediated innate immunity in the brain was significantly delayed in P1 animals, and underwent significant development during the early postnatal period"

LPS-induced dissociation of multidrug resistance-a... [Biochem Pharmacol. 2010] - PubMed result

LPS-induced dissociation of multidrug resistance-a... [Biochem Pharmacol. 2010] - PubMed result: "LPS-induced dissociation of multidrug resistance-associated protein 2 (Mrp2) and radixin is associated with Mrp2 selective internalization in rats."

Tea tree oil attenuates experimental contact dermatitis

Tea tree oil attenuates experimental contact dermatitis

Pollution and Its Impact on Wild Animals: A Meta-Analysis on Oxidative Stress

"main findings of this meta-analysis reveal that, as predicted, there is an overall increase in oxidative stress when exposed to pollution. This is mainly due to a weak overall increase of oxidative damages, although there is some variation across taxa. The reduced form of glutathione (GSH) and its associated enzymes are the most reliable biomarkers."

Read more: CiteULike: Pollution and Its Impact on Wild Animals: A Meta-Analysis on Oxidative Stress:

Stress can control our genes, researchers find

Stress can control our genes, researchers find: "Stress has become one of the major disease states in the developed world. But what is stress? It depends on from where you look."

Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues

"our study suggests that PM2.5 exposure differentially activates the UPR branches, leading to ER stress-induced apoptosis through the PERK-eIF2alpha-CHOP UPR branch. This work provides novel insights into the cellular and molecular basis by which ambient PM2.5 exposure elicits its cytotoxic effects that may be related to air pollution-associated pathogenesis"

Read more: CiteULike: Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues:

Endoplasmic reticulum stressed by pollution. Focus on "Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues"

Endoplasmic reticulum stressed by pollution. Focus on "Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues"

Characteristics of heavy metals in airborne particulate matter on misty and clear days.

"Lee, B.-K. K. and Park, G.-H. H. (2010). Characteristics of heavy metals in airborne particulate matter on misty and clear days. Journal of hazardous materials."

Read more: CiteULike: Characteristics of heavy metals in airborne particulate matter on misty and clear days.:

Oxidative stress, inflammation and DNA damage in rats after intratracheal instillation or oral exposure to ambient air and wood smoke particulate matter.

CiteULike: Oxidative stress, inflammation and DNA damage in rats after intratracheal instillation or oral exposure to ambient air and wood smoke particulate matter.: "Danielsen, P. H. H., Loft, S., Jacobsen, N. R. R., Jensen, K. A. A., Autrup, H., Ravanat, J.-L. L., Wallin, H., and Møller, P. (2010). Oxidative stress, inflammation and dna damage in rats after intratracheal instillation or oral exposure to ambient air and wood smoke particulate matter. Toxicological sciences : an official journal of the Society of Toxicology."

Mycotoxin Downregulates Nrf2 -Causes Brain Oxidative Stress

CiteULike: Brain oxidative stress after dermal and subcutaneous exposure of T-2 toxin in mice.: "T-2 toxin exposure resulted in down regulation of transcription factor Nrf2 and its downstream target genes of phase II detoxifying enzymes NQO1, Gclc, Gclm and hemeoxygenase-1. Results of our study show that percutaneously and subcutaneously applied T-2 toxin can cause brain oxidative damage possibly after crossing blood-brain barrier by altering its permeability."

Canada: Mould thriving after damp Alberta summer

Mould thriving after damp Alberta summer

Breast cancer tied to hormone use: study

Breast cancer tied to hormone use: study

CiteULike: Mechanisms of Diesel-Induced Endothelial Nitric Oxide Synthase Dysfunction in Coronary Arterioles

CiteULike: Mechanisms of Diesel-Induced Endothelial Nitric Oxide Synthase Dysfunction in Coronary Arterioles: "Cherng, T. W., Paffett, M. L., Jackson-Weaver, O., Campen, M. J., Walker, B. R., and Kanagy, N. L. (2010). Mechanisms of diesel-induced endothelial nitric oxide synthase dysfunction in coronary arterioles. Environmental Health Perspectives."

MedWire News - Bone Health - Oxidative stress linked to osteoporosis

MedWire News - Bone Health - Oxidative stress linked to osteoporosis: "Oxidative stress is associated with increased bone resorption and decreased bone mass in otherwise healthy postmenopausal women, Korean researchers report."

State Fire Marshal Urges Safety While Using Generators Install at least one carbon monoxide detector in every home

State Fire Marshal Urges Safety While Using Generators Install at least one carbon monoxide detector in every home

Research Commentary on Protection of Radio-Collared Bears in St. Louis County, MN -Respect The Research and Protect Radio-collared Bears!

This is a research commentary in response to “reactions” and “no action” from public officials

to a request by Dr. Lynn Roger for protection for WRI collared- with-ribbons research bears from being

hunted in St. Louis County,MN. These bears have a higher incidence of mortality because it is legal to hunt

radio-collared animals in the state of Minnesota. Statistically and for this issue I am speaking of thirteen animals out of an estimated 11,000 or more black bears in Minnesota.  Dr. Garshelis, leading bear biologist for the DNR in 2008 explained in a report “the rate of mortality of collared-bears is “not sustainable” population-wide and has documented a high harvest rate of collared bears since 2003”. For this report, I believe he speaks generally of radio-collared bears in MN and includes those collared by the DNR. This report, Ecology and Population Dynamics of Black Bears in Minnesota, is available to the public and is posted on the Internet and is public information. For a number of years, the DNR has repeatedly (verbally and in published documents) discouraged the “harvesting” of radio-collared bears. Unfortunately, these attempts and verbal recommendations to prevent the harvesting of these animals have proved inadequate. For a number of reasons stated in the paragraphs below, immediate and enforceable legal steps with sanctions need to be implemented to ensure the health and safety of the bears and all the people involved with these important research animals.

The recent death of Dr. Rogers’ Sarah Bear has brought to light an issue that has needed to be addressed for a long time. It is an issue that has motivated a significant amount of unjust negative criticism for this kind of research and sheds a negative light on the WRI research in general which unnecessarily makes the grant application and permit process more difficult. Unfortunately, certain public officials and local media companies in Minnesota are adding fuel to this fire by openly criticizing Dr. Rogers’ methods. When all is said and done, the kind of observational study method of research Dr. Rogers’ uses provides a substantial amount of data and important information to a variety of audiences including ethologist, ecologists, wildlife biologists, veterinarians, educators and a host of different scientifically-based fields related to animals, in addition to those that study human and animal interaction. Probably, the two most famous researchers that have or have had similar research methods include Jane Goodall with a resume that touts 50 years of study of chimpanzees and the late Dian Fossy and her study of mountain gorillas. In the distant and recent past, state officials have made comments to the media which are biased, only half true or just plain laughable just to sway public opinion in their favor. What is dismissed or ignored is the fact there are numerous supporters both of the research and for protection of these bears in St. Louis County, MN. Plus, both Dr. Rogers’ who is an accomplished and prolific writer with numerous publications, and Sue Mansfield are both highly respected by their peers.

Unfortunately, parallel to biased comments by public officials, “critics” from the general public are speaking out against Dr. Rogers and the research in the press and the Internet. Many commenters have been downright “ugly” and vehement in voicing their disdain; they are also misinforming readers by misrepresenting the research while doing their best to discredit the value of the information and the reputations of both researchers. It is apparent from the present Internet buzz, a number of individuals had made a conscious plan and carried out the “hunting” and death of Sarah bear. One person went so far as to say, “the shooting of this bear was to send a message....”and there is a similar tone of “style” that includes “harsh language and untruths” meant to inflame and bully on several websites across the Internet. Most of the rhetoric shows anger directed towards specific individuals and/or the entire group of “donors” and “volunteer fundraisers and supporters” in the Lily community. In recent weeks, these comments have been directed at their “good deeds” including helping to secure a “sizable” grant for a State Park in Ely, MN and promoting companies important to the state and locals economies such as Coca Cola, General Mills and Pepsi. So at this point, one needs to ask, why the negativity from state officials and why do they insist on antagonizing the public by making false statements that only serve to increase the level of these types of harrassments?

To find a reasonable answer to this question, one only needs to review a little history about recent politics in Minnesota and provide a little background of the “mining industry” which is making attempts to get a stronger foothold in the Ely area. In recent years, just like many rural towns, the  economy downturn has had a negative impact on jobs and quality of life in this hurting community. It is estimated that an increase in industrial non-ferrous mining will bring a substantial increase in the amount of revenue and jobs to the state overall and an influx to the local economies as well. On the other hand, this kind of mining causes environmental damage with significant environmental costs that may be felt more at the local level and may include rising health care expenditures and secondary costs that are unpredictable, are unknown or under-estimated and may entail possible heavy financial penalties. Admittedly, the companies’ development plans include reimbursement for environmental damage if they can remain financially solvent which if history repeats itself in Minnesota, they may not! In the event of a hazardous spill, damage  reimbursement dollars can never replace the impacts such as damages to the environment that may take  decades or never recover and will never adequately address emotional or physical suffering from potential  serious permanent injury or death or the loss of recreational areas or the disruptions in habitats that will be  permanent or last longer than most peoples’ lifetime. So far, there have been few positive and mostly  discouraging reports that mine damages can be contained at a level that is “minimal”. Recently, the EPA sent  a “damming” report to developers of a planned mine south of Ely that says there is “no proof” “no proof” that the project will not result in water contamination. Critics argue that important factors were left out of this  report, but the general consensus amongst experts is that water contamination from the PolyMet and other proposed mines is inevitable. All of these events have occurred under the governance and leadership of Tim Pawlenty who had aspirations for the vice-presidency bid in the last presidential election and is currently trying to secure a Republican bid for the next presidential election. Of course, there are substantial benefits of public endorsements from “larger industries” because they have large memberships with lots of voters and  financial backing and therefore, lobbying power. Also under Pawlenty, there has been evidence of  governmental mismanagement and poor supervision including a spending scandal in the Department of Natural Resources and a supposed purposeful one-year delay in the release of data that shows a doubling of the incidence rate of cancer in taconite Iron Range miners from 1997 to 2005 compared to the report for the previous nine years. Reportedly, many that understand Minnesota politics believe this “suppression” of information was a political move.

So what does this all have to do with the bears you ask? Simple, it all comes down to the health and safety of the environment and in the end, who has “motivation” to advocate a specific political agenda that will have economic benefits but at substantial costs to public health and the health of the environment. There is a lot of history in relation to these study bears and the community that makes up part of their territory. A few years back, there were issues with a bear named Solo that eventually was “removed as a nuisance” from the Eagle’s Nest community to Michigan where she eventually died. In my personal opinion, there is merit in what Sue Mansfield said at the time, “something had changed at the Eagle’s Nest Isthmus to attract the animal.” Generally, animals do not acutely change their behaviors unless “lured” to do so and in this case, it is obvious that something motivated the bear to do so. The level and lack of cooperation from public officials on this issue and others and some of the media and certain members of the community who were so outspoken about it, leads one to suspect there is a perceived benefit from these “bear removals” and the negative publicity. Lately, I expect these perceived “benefits” have taken a “big hit” with the influx of “oneness and support” for bear education, the WRI and the NABC by the “Lily Community” and may reflect some of the most recent elevations in “ugly”chatter and the death of Sarah bear!

Mining operations utilize a significant amount of resources including water in many cases, produce a

significant amount of wastes even before the real operations begin and as noted above, there is a very high

risk for water contamination that may kill fish and fauna. Unfortunately, this poses a potential problem for  mining developers because Dr. Rogers will be the first to become aware of potential public health and environmental hazards from pollution. Importantly, this is a consequence of the specific nature of his research methods which includes bio-monitoring and the ability for the researchers to “walk with” and “follow the bears for long distances” in their natural habitat or “over hill and over dale” as I like to say! Any environmental or biological scientist can tell you the first signs of environmental damages are often first observed in effected wildlife, flora and fauna. From mining operations, specific pollutants that are expected include contamination from heavy metals and “noxious” odors. Studies have demonstrated exposures and both can lead to changes in behavior from neuro-inflammatory responses that effect cognition and instinct and in animals these changes may impact navigation and possibly increase or decrease expressions of fear and aggression. These same pollutants from mine sites which contaminate the purity of the natural food and water supply are known to potentially lead to epigenetic changes that can be passed to offspring for generations.

Animal studies in both bears and wolves demonstrate their superior sense of smell, intelligence and an “olfactory range” of several miles. Some reports say the bear’s olfactory capability has up to a 20 mile range and therefore their “bear scent sense” would include most of the area of mining interests near Ely. (This is at least as the crow flies and starting at different points.) For more background health information taken from polar bears studies for example, it says that “the insidious danger to many species comes incrementally, through the food web. Levels of mercury, other heavy metals and persistent organic pollutants (POPs) generated by industrial processes in southern latitudes are turning up in tissue samples of most arctic species, including polar bears. They are particularly vulnerable because of their reproductive biology and their place at the top of the arctic food web. On the other hand, adult females are able to offload some of these high concentrations of toxins to their offspring,“thereby, reducing their risks from exposures but increasing the risks in their cubs.” This problem of course would cause worry for the black bear researcher. Another problem is mining pollution would be comparable for metals but different because, as far as I am aware, there would be little or no contamination from persistent chemicals (POPS). However, it is also impossible to know what pollutants are already “lurking” in those environments. The same author from the resource above explains, “contaminants enter the web through precipitation tainted by winds blowing from the industrialized south” and this would closely mimic the particulate dust from waste blowing around and the settling of metal dust on drying beds and plants from these industrial sites. In the polar region, “the chemicals are first ingested by the smallest organisms on the tundra and in the water, and then passed to successively higher trophic levels.” (Hrynyshyn)

Both wolves and bears are near the tops of their food chain and have shared scavenging activities and therefore, they have an elevated risk for effects of exposure from mining waste particulates and volatile odors. Ammonia, a common waste pollutant from mining interacts well with other airborne gases, especially sulfates and nitrates, to produce particulate matter and can have a number of irritating effects including exciting chronic immune responses. (Unknown) In humans, exposure to particulate matter (PM) has been associated with a variety of health conditions including chronic inflammation and respiratory diseases such as allergies and asthma and more recently, implicated in diabetes and autoimmune-type diseases. Veterinarians have  identified many commonly known chronic environmentally-induced diseases in domestic animals but research  of their existence and prevalence data is very limited in wild animals for a number of different reasons.  Chronic exposure to irritants like ammonia, sulfur and other volatiles from hazard sites like mines and their  waste sites may modulate and precipitate unwanted behaviors in the different species including the lynx, the  bears, the raptors and the wolf populations that inhabit the area. Curiously, this was not addressed in a report  of the impact of these mines on wildlife which I read that was posted on the Internet. Generally, the  combination of the health effects of metals and volatiles augment one another and the effects of the will be  greater compared to the effects of each individually. Improper and unorganized feeding also may incite important and unsafe changes of behavior in a similar physiological manner. From most accounts, it is impossible to predict the extent of these kinds of environmental influences on genetic change because knowledge of specific epigenetic changes are limited for all species and even more so for wildlife. It also appears, there are a number of factors that influence epigenetic change and these may not be the same in similar or different environments and are more than likely, species specific.

Now I turn my attention away from the environmental aspects for a need to protect these bears to the recent comments made by state officials published in an online article from TwinCities.com. In this article, DNR Commissioner Holsten was quoted as saying he doubted he would rule for a “protection order for Rogers’s bears because it is not the type of research they protect because it involves social interactions between bears and humans.” Similarly, his description at this time, of the depth of research performed by Dr. Rogers and Sue Mansfield was very short-sighted and therefore, inaccurate. I am sure many of Dr. Rogers and Sue Mansfield’s peers would argue the Commissioner made an extremely simple and very limited assessment of both the kinds of information and data that is collected and their “professional” activities and accomplishments. Actually, the research of both Dr. Rogers and Sue Mansfield is quite involved, is labor, expense and time intensive and includes activities generally performed by biologists, animal ecologists and animal behaviorists. Their job description includes participating in the active scientific study of everything animals do and try to determine the biological and psychological motivations and significance for doing them. This involves investigating the relationship of animals to their environment, as well as to other organisms and not just humans and includes, but is not limited to how animals find and defend resources, avoid predators, choose mates and reproduce and care for their young. On the WRI website there is a complete list of research areas which Dr. Rogers and Ms. Mansfield are currently engaged in. 

In his statement, the DNR Commissioner explains the DNR is not motivated to “offer protection because the research is limited to social research between bears and humans” because they are not all inclusive and do not reflect the interests of the sportsman (ie. hunters). Technically, there is only one area that provides details about the research of the interactions of bears and humans on the WRI research activities list. All the other areas mentioned are bear related and include land tenure and social systems of bears, bear communication, daily and seasonal travel patterns, food and weight, reproduction, hibernation, care and development of cubs, play behavior, morphology and physiology of bears, bear signs, habitat, responses to environmental factors, and factors that effect research methods including the benefits of using different technology for collecting data. These are all necessary for bear education and for the understanding of it by the general public, wildlife-career oriented students and the sportsman. To restate, Holsten argues the DNR does not “protect social research on human and bear interaction.” In response, this could partly explain the escalating numbers of conflicts between people and bears in Minnesota because the DNR is not adequately addressing or educating the public about “bear preventive” measures. From his own comments and with further explanation on the WRI website, the DNR Commissioner explains he does not support their role in areas of the research which includes “educating the public so they better understand bear behavior, doesn’t support researching elements that may increase conflict between humans and bears or research that analyzes, describes and provides data into the human behaviors and cultural factors that increase “nuisance” behaviors, and doesn’t support research on factors that contribute to bear attacks, garbage and odor containment, etc.” (Rogers) All I have to got to say to this is, WHY NOT!? Obviously, he really doesn’t understand much of what Rogers’ research is about even though he is critical of it in public statements or maybe he does understand it and if he does, maybe he needs to publicly define what “ is the DNR’s role is in terms of bear education and then maybe redefine it!” I could place a bet, the majority of the public are open to more education, if it will reduce property loss and risk of injury and mortality! It is quite clear, there is very little representation for public concerns, at least in these concerns with the DNR. If he is a pubic representative, then why isn’t he addressing the needs of his public?

In the same article, DNR Biologist, Dr. Garshelis made several interesting comments including “he doesn’t think Rogers’ bears should get special protection. Further, he says, “by giving them (meaning Dr. Rogers’ bears) legal protection and not ours, it gives the perception that those bears are more important. Lynn (Dr. Rogers) might think that and people might believe that, but I do not think that.” From my perspective, I don’t believe Dr. Rogers ever meant to exclude other radio-collared bears, but does have a right as a business manager to focus his attentions and resources on “WRI” collared-with-ribbons research bears. Whatever regulations the DNR puts in place for their own collared bears, it really up to them anyway! All in all and from this latest interview with DNR representatives, it appears this interview like so many others in the past, sets the stage for the public and media to receive more incorrect information and misrepresentation of the research. Unfortunately, a lot of it the public is getting directly from DNR officials which only adds to the “half-truths” that are popping up in the media! So what is the intent behind all of this misinformation? Is it political, most definitely! Personally I feel the level at which the DNR is criticizing Dr. Rogers’ work and putting his bears in the middle , is NOT RIGHT and NOT FAIR! In this case, public officials should let the research explain the data and leave it at that.... and stop using the bears as political scapegoats and turning them into “objects” to force a political agenda!

The critical question here is why the DNR obviously supports mining development in the Ely area and ignores the potential and obvious benefits of Dr. Rogers research. Those bears, just by being bears, are “instruments” to monitor the health of areas that may be negatively affected by environmental damage. This is true, even with the bad data the mining operations are providing and bad environmental reports they have been receiving from the EPA. This is in addition to the fact that the mining industry carries a very high risk for injury and disability. In any case, with allowance and no interference for continued study and research of these bears, there is opportunity for Dr. Rogers to offer a relatively good and cost-effective mechanism for habitat surveillance and in the case of an “mine event” he may be the first to identify early the environmental impact. Importantly, there is no doubt in my mind, both researchers would report anything that didn’t seem quite right!

In conclusion, it is important to consider taking immediate steps and legislation to see these animals are kept

safe and at this point, it is not just the animals that are now in harms way. I hope the preceeding paragraphs has made it more clear about what really underlies the ridicule and reservations about this valuable research

and the real issue needs more consideration by a number of people in different agencies in Minnesota government. I hope I have expressed the point that the “real” issues here have nothing to do with preventing

the right to hunt, nor is it just about the bears but mostly about whether the safety of people and their pets, the environment and wildlife is more important than the games public officials’ play with their politics.

HEIRS Research

Independent Health and Environmental Researcher

www.heirs-online.com/  http://bear-research.heirs-online.com/

Research Citation Library: HEIRS Library

My bio is available through a link at my website at www.heirs-online.com under About HEIRS! For further reading, I encourage you to browse my citation library that will help in the understanding of this document. Tags to search include methylation, heavy metals, particulate matter, air pollution and specific names of heavy metals like copper and other environmental factors related to what is mentioned in this document including, endotoxin, inflammation, epigenetics, mining, etc. Specific documents are also filed by groups including heavy metals and genetics, mining, etc. You can also access my research blogs on the right corner at http://www.heirsresearch.blogspot.com/ http://bear-research.heirs-online.com and Facebook. Please feel free to email me at heirs_health@heirs-online.com for more information or clarifications.

The original of this document is available here at Research Commentary . The sources used in this document are also located here.

Triclosan Persists at Low-Levels in the Environment for Long Periods of Time

Triclosan Persists at Low-Levels in the Environment for Long Periods of Time

One of My Mentors -- Dr. Ward, Bioanthropology

What a great professor he is....I must say congratulations on your appointment!

http://newscenter.iupui.edu/4774/IUPUI-Names-Richard-Ward-as-Interim-Dean-of-University-College-

nNOS and eNOS modulate cGMP formation and vascular response in contracting fast-twitch skeletal muscle -- LAU et al. 2 (1): 21 -- Physiological Genomics

nNOS and eNOS modulate cGMP formation and vascular response in contracting fast-twitch skeletal muscle -- LAU et al. 2 (1): 21 -- Physiological Genomics: "increases in cGMP and NO-dependent vascular relaxation in contracting fast-twitch skeletal muscle may require both nNOS and eNOS"

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."

A case of methamphetamine use disorder treated wit... [Gen Hosp Psychiatry. 2010 Sep-Oct] - PubMed result

Well, DUH!


A case of methamphetamine use disorder treated wit... [Gen Hosp Psychiatry. 2010 Sep-Oct] - PubMed result: "case of methamphetamine use disorder treated with the antibiotic drug minocycline."

Running exercise protects the substantia nigra dop... [Brain Behav Immun. 2010] - PubMed result

Running exercise protects the substantia nigra dop... [Brain Behav Immun. 2010] - PubMed result: "Running exercise protects the substantia nigra dopaminergic neurons against inflammation-induced degeneration via the activation of BDNF signaling pathway."

SKN-1/Nrf2 inhibits dopamine neuron degeneration i... [Toxicol Sci. 2010] - PubMed result

SKN-1/Nrf2 inhibits dopamine neuron degeneration i... [Toxicol Sci. 2010] - PubMed result: "SKN-1/Nrf2 inhibits dopamine neuron degeneration in a Caenorhabditis elegans model of methylmercury toxicity."

Oxytocin Reduces Background Anxiety in a Fear-Pote... [Neuropsychopharmacology. 2010] - PubMed result

Oxytocin Reduces Background Anxiety in a Fear-Pote... [Neuropsychopharmacology. 2010] - PubMed result: "Oxytocin may have antianxiety properties that are particularly germane to the hypervigilance and exaggerated startle typically seen in PTSD patients"

Methylmercury Toxicity and Nrf2-dependent Detoxification in Astrocytes

CiteULike: Methylmercury Toxicity and Nrf2-dependent Detoxification in Astrocytes: "Wang, L., Jiang, H., Yin, Z., Aschner, M., and Cai, J. (2008). Methylmercury toxicity and nrf2-dependent detoxification in astrocytes. Toxicological Sciences."

Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis

Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis: "summary, we have demonstrated the differential ability of NO and NO-related species to induce apoptosis in human MDMϕ, and have established that ONOO-, but not NO radical, is pro-apoptotic in this cell type (figure ​(figure5).5). Furthermore, our results demonstrate the presence of a cGMP-dependent pre-conditioning mechanism to limit ONOO--induced apoptosis in human macrophages."

Cyclic GMP protects human macrophages against pero... [J Inflamm (Lond). 2009] - PubMed result

Cyclic GMP protects human macrophages against pero... [J Inflamm (Lond). 2009] - PubMed result: "Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis"

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm

Chronic Stress May Cause Long-Lasting Epigenetic Changes

"Long-term exposure to a common stress hormone may leave a lasting mark on the genome and influence how genes that control mood and behavior are expressed, a mouse study led by Johns Hopkins researchers suggests."

Read more: Chronic Stress May Cause Long-Lasting Epigenetic Changes:

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.

Altered glial-neuronal crosstalk: cornerstone in t... [Neurochem Int. 2010] - PubMed result

Altered glial-neuronal crosstalk: cornerstone in t... [Neurochem Int. 2010] - PubMed result: "Altered glial-neuronal crosstalk: cornerstone in the pathogenesis of hepatic encephalopathy."

Increased Na, K-ATPase alpha2 isoform gene express... [Neurochem Int. 2010] - PubMed result

Increased Na, K-ATPase alpha2 isoform gene express... [Neurochem Int. 2010] - PubMed result: "Increased Na, K-ATPase alpha2 isoform gene expression by ammonia in astrocytes and in brain in vivo."

Nrf2 and DJ1 are consistently upregulated in inflammation in MS

Nrf2 and DJ1 are consistently upregulated in infla... [Free Radic Biol Med. 2010] - PubMed result: "our findings suggest that persistent Nrf2-mediated transcription occurs in active MS lesions, but that this endogenous response is insufficient to prevent ROS-induced cellular damage, which is abundant in inflammatory MS lesions."

Bacillus Anthracis Endospores Regulate Ornithine D... [Curr Microbiol. 2010] - PubMed result

Bacillus Anthracis Endospores Regulate Ornithine D... [Curr Microbiol. 2010] - PubMed result: "Bacillus Anthracis Endospores Regulate Ornithine Decarboxylase and Inducible Nitric Oxide Synthase Through ERK1/2 and p38 Mitogen-Activated Protein Kinases."

Effect of glutamine synthesis inhibition with meth... [Neurochem Res. 2008] - PubMed result

Effect of glutamine synthesis inhibition with meth... [Neurochem Res. 2008] - PubMed result: "Effect of glutamine synthesis inhibition with methionine sulfoximine on the nitric oxide-cyclic GMP pathway in the rat striatum treated acutely with ammonia: a microdialysis study"

Glutamine as a mediator of ammonia neurotoxicity: ... [Biochem Pharmacol. 2010] - PubMed result

Glutamine as a mediator of ammonia neurotoxicity: ... [Biochem Pharmacol. 2010] - PubMed result: "Glutamine as a mediator of ammonia neurotoxicity: A critical appraisal."

Inflammation and tissue damage in mouse lung by si... [Inhal Toxicol. 2010] - PubMed result

Inflammation and tissue damage in mouse lung by si... [Inhal Toxicol. 2010] - PubMed result: "The constituents with major contributions to the inflammatory responses were oxidized organic compounds and transition metals in PM(2.5-0.2) samples, Cu and soil minerals in PM(10-2.5) samples, and Zn in both size ranges. In contrast, poor biomass and coal combustion were associated with elevated levels of polycyclic aromatic hydrocarbons (PAHs) and a consistent inhibitory effect on the inflammatory activity of PM(2.5-0.2) samples."

Nrf2 Involved in Fatty Acid Suppression of LPS Inflammation

"our study clearly shows for the first time that, DHA/EPA would induce Nrf2 signaling pathway and that Nrf2 plays a role in DHA/EPA suppression of LPS-induced inflammation."

Read asrac: CiteULike: Role of Nrf2 in Suppressing LPS-induced Inflammation in Mouse Peritoneal Macrophages by Polyunsaturated Fatty Acids Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA).:

Misfolded neural proteins linked to autism disorders

Misfolded neural proteins linked to autism disorders

The Effect of Small Changes in Hematocrit on Nitric Oxide Transport in Arterioles

Question: So does anemia cause the opposite...Just askin?

"Our analysis reveals that small increases in Hct may raise NO availability in the vascular wall."

Read abstract:Mary Ann Liebert, Inc. - Antioxidants & Redox Signaling - 0(0)::

Several Inflammatory Factors Induced By Bacterial Infection May Be Reduced By Insulin

Several Inflammatory Factors Induced By Bacterial Infection May Be Reduced By Insulin

Hypoxia-Inducible Factor-1alpha Is Involved in the... [Biol Pharm Bull. 2010] - PubMed result

Hypoxia-Inducible Factor-1alpha Is Involved in the... [Biol Pharm Bull. 2010] - PubMed result: "Hypoxia-Inducible Factor-1alpha Is Involved in the Pro-angiogenic Effect of Hydrogen Sulfide under Hypoxic Stress."

Effects of glutamine and curcumin on bacterial translocation in jaundiced rats.

CiteULike: Effects of glutamine and curcumin on bacterial translocation in jaundiced rats.: "On the basis of these findings, both curcumin and glutamine are thought to be effective in preventing or reducing bacterial translocation and oxidative damage in obstructive jaundice."

Association between endothelial dysfunction and hyperuricaemia

Association between endothelial dysfunction and hyperuricaemia

Plant-based Compounds Induction of Antioxidants ~1

Comment: This provides evidence that a diet that contains food with antioxidant-inducing properties are probably more effective than supplementation.

"plant-based foods contain compounds that can be absorbed and induce the antioxidant defence in a living organism in an organ-specific manner."

CiteULike: Coffee, broccoli and spices are strong inducers of electrophile response element-dependent transcription in vitro and in vivo - Studies in electrophile response element transgenic mice.:

CiteULike: NF-kappaB Links CO2 Sensing to Innate Immunity and Inflammation in Mammalian Cells.

The suggests existence of a molecular CO(2) sensor in mammalian cells that is linked to the regulation of genes involved in innate immunity and inflammation.

CiteULike: NF-kappaB Links CO2 Sensing to Innate Immunity and Inflammation in Mammalian Cells.: "Cummins, E. P., Oliver, K. M., Lenihan, C. R., Fitzpatrick, S. F., Bruning, U., Scholz, C. C., Slattery, C., Leonard, M. O., McLoughlin, P., and Taylor, C. T. (2010). Nf-kappab links co2 sensing to innate immunity and inflammation in mammalian cells. Journal of immunology (Baltimore, Md. : 1950)."

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

Inhibition of ornithine decarboxylase potentiates nitric oxide production in LPS-activated J774 cells.

These results show that DFMO potentiates LPS-induced nitrite production in the murine macrophage cell line J774. Since the only known mechanism of action of DFMO is inhibition of ODC, and thus polyamine biosynthesis, we conclude that expression of iNOS can be critically regulated by endogenous polyamines.

CiteULike: Inhibition of ornithine decarboxylase potentiates nitric oxide production in LPS-activated J774 cells.: "Baydoun, A. R. and Morgan, D. M. (1998). Inhibition of ornithine decarboxylase potentiates nitric oxide production in lps-activated j774 cells. British journal of pharmacology, 125(7):1511-1516."

Ghrelin suppresses insulin secretion in healthy nondiabetics

Ghrelin suppresses insulin secretion in healthy nondiabetics

Hemin inhibits NO production by IL-1beta-stimulated human astrocytes through induction of heme oxygenase-1 and reduction of p38 MAPK activation

Seems to me that the findings from this author are pretty important....:)

"up-regulation of HO-1 in astrocytes is associated with down-regulation of iNOS expression and thereby NO production, an effect that involves the p38 MAPK signaling pathway, which suggests that this glial cell response could play an important protective role against oxidative stress in the brain."

"Sheng, W., Hu, S., Nettles, A., Lokensgard, J., Vercellotti, G., and Rock, R. (2010). Hemin inhibits no production by il-1beta-stimulated human astrocytes through induction of heme oxygenase-1 and reduction of p38 mapk activation. Journal of Neuroinflammation, 7(1):51+."

Read more: CiteULike: Hemin inhibits NO production by IL-1beta-stimulated human astrocytes through induction of heme oxygenase-1 and reduction of p38 MAPK activation:

Long term administration of green tea polyphenols and pentoxifylline to mdx5Cv dystrophic mice: differential effects on muscle function and kyphosis

P3.43 Long term administration of green tea polyphenols and pentoxifylline to mdx5Cv dystrophic mice: differential effects on muscle function and kyphosis

P3.44 Green tea polyphenols enhance the motor performance of the mdx5Cv dystrophic mouse and normalize calcium influx in muscle fibres

P3.44 Green tea polyphenols enhance the motor performance of the mdx5Cv dystrophic mouse and normalize calcium influx in muscle fibres

P3.40 Potential role of sirtuin-1 as druggable target in muscular dystrophy: effect of a chronic resveratrol treatment on in vivo and ex vivo pathological signs of dystrophic mdx mouse

P3.40 Potential role of sirtuin-1 as druggable target in muscular dystrophy: effect of a chronic resveratrol treatment on in vivo and ex vivo pathological signs of dystrophic mdx mouse

A new role for insulin in cell survival, cell metabolism and stress response

A new role for insulin in cell survival, cell metabolism and stress response

Nrf2-ARE stress response mechanism: A control poin... [Free Radic Res. 2010] - PubMed result

Nrf2-ARE stress response mechanism: A control poin... [Free Radic Res. 2010] - PubMed result: "Nrf2-ARE stress response mechanism: A control point in oxidative stress-mediated dysfunctions and chronic inflammatory diseases."

Protective effect of combination of sulforaphane a... [Biol Pharm Bull. 2010] - PubMed result

Protective effect of combination of sulforaphane a... [Biol Pharm Bull. 2010] - PubMed result: "Protective effect of combination of sulforaphane and riluzole on glutamate-mediated excitotoxicity"

Inhibition of Repair of Oxidized Base Damage in Human Genome by Copper and Iron — JBC

Specific Inhibition of NEIL-initiated Repair of Oxidized Base Damage in Human Genome by Copper and Iron — JBC: "Inhibition of NEIL-initiated Repair of Oxidized Base Damage in Human Genome by Copper and Iron"

Regulatory T cells activity is potentiated by glycogen synthase kinase 3beta inhibition.

Comment: It has been suggested that chemical sensitivity and other conditions related to other environmentally-induced syndromes are a consequence of "loss of tolerance" which may be attributed to a reduction in the production of regulatory T cells that can suppress autoimmune responses and also may help in glucose homeostatic regulation. GSK-3b is similar to the on/off switch for the antioxidant system and is upregulated in inflammatory conditions.  Insulin and exercise have been shown to inhibit GSK-3b and other studies report that inhibiting GSK-3b may also reduce Il-6.

"Inhibition of GSK-3beta leads to increased suppression activity by Tregs."

CiteULike: Suppressive Treg cell activity is potentiated by glycogen synthase kinase 3beta inhibition.:

Related: GSK-3b

Contaminants in Air Pollution Including Endotoxin and Dioxin May Increase Insulin Resistance~!

Complications associated with insulin resistance may play a significant role in environmental diseases including obesity, sleep apneas and potentially Gulf War Syndrome and chemical sensitivity just for examples. Other studies show that sustained endotoxin, a potential consideration in CFS and other environmental illnesses, is a common component of particulate matter and environmental pollutants may alter insuling signalling in muscle especially under sustained stress such as malnutrition. These conditions may potentiate one another if they occur at the same time.....


"TCDD stimulates expression and secretion of TNF-alpha in adipocytes through activation of AhR, ERK1/2, and JNK, and the secreted TNF-alpha causes the downregulation of IRbeta, IRS1, and GLUT4 through TNFR1, resulting in insulin resistance."

Read more: CiteULike: 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs an insulin signaling pathway through the induction of tumor necrosis factor-alpha in adipocytes.:


For further understanding: IRS-1

McCowen, K. C., Ling, P. R., Ciccarone, A., Mao, Y., Chow, J. C., Bistrian, B. R., and Smith, R. J. (2001). Sustained endotoxemia leads to marked down-regulation of early steps in the insulin-signaling cascade. Critical care medicine, 29(4):839-846. http://www.citeulike.org/user/HEIRS/article/7782376

Polymorphism in the reduced folate carrier and hypomethylation in mothers of children with autism.

A functional polymorphism in the reduced folate ca... [Am J Med Genet B Neuropsychiatr Genet. 2010] - PubMed result: "A functional polymorphism in the reduced folate carrier gene and DNA hypomethylation in mothers of children with autism."

Control of Redox State and Redox Signaling by Neur... [Antioxid Redox Signal. 2010] - PubMed result

Control of Redox State and Redox Signaling by Neur... [Antioxid Redox Signal. 2010] - PubMed result: "Control of Redox State and Redox Signaling by Neural Antioxidant Systems"

Il-6 impairs endothelium-dependent NO-cGMP-mediated relaxation and enhances contraction in systemic vessels of pregnant rats

"Orshal, J. M. and Khalil, R. A. (2004). Interleukin-6 impairs endothelium-dependent no-cgmp-mediated relaxation and enhances contraction in systemic vessels of pregnant rats. Am J Physiol Regul Integr Comp Physiol, 286(6):R1013-1023."


Read more: CiteULike: Interleukin-6 impairs endothelium-dependent NO-cGMP-mediated relaxation and enhances contraction in systemic vessels of pregnant rats:

Folic Acid Mitigated Cardiac Dysfunction by Normal... [Am J Physiol Heart Circ Physiol. 2010] - PubMed result

Folic Acid Mitigated Cardiac Dysfunction by Normal... [Am J Physiol Heart Circ Physiol. 2010] - PubMed result: "folic acid administered post-MI significantly improved cardiac ejection fraction and induced TIMP, CBS, CSE, and 5-MTHFR. We showed that folic acid supplementation resulted in significant improvement of myocardial function after MI. The study eluted the importance of homocysteine metabolism and folic acid supplementation for cardiovascular health in humans."


Further reading: The obligatory intestinal folate transporter PCFT (SLC46A1) is regulated by nuclear respiratory factor 1 (NRF-1).

Pivotal study finds link between PTSD and dementia

Pivotal study finds link between PTSD and dementia: "Results of a study reported in the September issue of the Journal of the American Geriatrics Society suggest that Veterans with post-traumatic stress disorder (PTSD) have a greater risk for dementia than Veterans without PTSD, even those who suffered traumatic injuries during combat."

DIVERSITY IN ANTIOXIDANT RESPONSE ENZYMES IN PROGR... [Drug Metab Dispos. 2010] - PubMed result

DIVERSITY IN ANTIOXIDANT RESPONSE ENZYMES IN PROGR... [Drug Metab Dispos. 2010] - PubMed result: "DIVERSITY IN ANTIOXIDANT RESPONSE ENZYMES IN PROGRESSIVE STAGES OF HUMAN NON-ALCOHOLIC FATTY LIVER DISEASE."

DIVERSITY IN ANTIOXIDANT RESPONSE ENZYMES IN PROGR... [Drug Metab Dispos. 2010] - PubMed result

"Nrf2 activation occurs in response to disease progression followed by induction of specific Nrf2 targets, while functionality of specific antioxidant defense enzymes appear to be impaired as NAFLD progresses."


Read more: DIVERSITY IN ANTIOXIDANT RESPONSE ENZYMES IN PROGR... [Drug Metab Dispos. 2010] - PubMed result:

Effects of Exposure to Decabromodiphenyl Ether on the Development of the Immune System in Rats

Postnatal Day 77, levels of Tregs were decreased. This says to me that in animal exposed at an early age to DBPE may have reduced tolerance to environmental exposures as they age. So my question is...if there is a another point of elevated neural development such as would occur after injury does this kind of sensitivity also occur?

CiteULike: Effects of Exposure to Decabromodiphenyl Ether on the Development of the Immune System in Rats: "Teshima, R., Nakamura, R., Nakamura, R., Hachisuka, A., Sawada, J.-i., and Shibutani, M. (2008). Effects of exposure to decabromodiphenyl ether on the development of the immune system in rats. Journal of Health Science, 54(4):382-389."

Gulf War Syndrome, Chemical Sensitivity and Why Benefits of CPAP!

It has only been in the not-to-distant past that officials and medical experts have come out and admitted that Gulf War Syndrome is an actual disease and while many that have tried to find the cause the "true cause" is not yet known. In previous blogs, I have discussed how Gulf War Syndrome shares many of the same symptoms as other environmental conditions and are often co-morbid and include chronic fatigue syndrome, fibromyalgia and multiple chemical sensitivity and other environmental factors may contribute to fascilitate the condition that is commonly regarded as Gulf War Syndrome. One well-respected research blogger, Dr. Art Ayers, explains that CFS, MCS and fibromyalgia "can be induced by organophosphate pesticide exposure. In GWS, two insults seem to be needed: acetylcholine signal disruption and inflammation. He says that in the effected individuals the acetylcholine mimetics (pesticides, pyridostigmine) disrupted the nervous system and numerous immunological, infectious, chemical and emotional stresses generated a high level of chronic inflammation. The vaccine against anthrax and exposure to burning oil wells may have contributed to inflammation." Without a clear understanding of what causes GWS, physicians and health experts are mostly at a loss on how to treat it and clearly, most of the research is now focused on providing effective therapies until a cure is found for it.

In recent weeks, two interesting studies have been released that show CPAP (continuous positive airway pressure) may be beneficial in treating symptoms of Gulf War Syndrome with sleep disordered breathing. In the pilot study, findings demonstrated improvements in many symptoms including pain, fatigue, cognitive function, sleep quality, physical and mental health. The researchers' concluded from this experiment that CPAP can greatly improve overall health in GW patients with sleep disordered breathing which may be a distinguishing factor in veterans with GWI compared to veterans without Gulf War Illness. (Amin)  While this research is preliminary it provides interesting insight into GWS. Admittedly, there are reported side-effects associated with CPAP use and the pros and cons of it should be addressed fully with a qualified physician even if CPAP is taken out of the research lab and used as therapy for GWS.

To date, even with these published findings, the reader is left with the question why CPAP may be effective for treating some symptoms of GWS. The author only makes the comment that GWS experience a "frequency of arousals related to apneas, hypopneas, and mild inspiratory airflow limitation."  Taking a more holistic systematic approach to understanding the nature of GWS ; one can draw some conclusions that provide at least a reasonable explanation of what may be occurring in GW patients with sleep apneas and why CPAP may provide at least "some" relief. CPAP has been used for quite some time to  treat sleep apneas and more recently has been used for a variety of other medical respiratory conditions. Budhiraja explains that sleep disordered breathing is often associated with hypertension and that "sleep apnea, hypocapneas and hypoxemia contribute to alterations in sympathetic activity, changes in the renin-angiotensin pathway, impede xanthine oxireductase production, cause endothelial dysfunction and lower levels of eNOS."  If you are a consistent reader of my feeds, chronic low-level inflammation contributes to endothelial dysfunction and higher risk for cardiovascular disease in many environmentally-induced health conditions.

Recently, it has been suggested that sickness syndrome contributes to symptoms in GWS and may explain  fatigue, pain and other behavioral changes as well. Sickness syndrome is in associated with elevated levels of cytokines including Il-1b and Il-6 and these inflammatory cytokines may also be associated with PTSD and CFS and are activated during the general response to stress which can lead to changes in genetic expression. Two researchers, Burioka and Steiropoulis found significant changes in Il-6 and Tnf-a, uric acid and immune complexes after CPAP. These findings suggest intermittent hypoxia contibutes significantly to inflammation and noted positive changes in patients that use regularly CPAP .  We have suggested that insulin resistance may be a critical factor in environmental illness and obesity and dietary influences may influence the severity of many environmental diseases including sickness syndrome, PTSD, MCS, CFS and fibromyalgia. To some extent, this can be explained by the fact that inflammatory cytokines and adipokines such as leptin and adiponectin can produce systemic changes. Patients with OSA have a higher prevalence of insulin resistance both in the obese and non-obese. (Lam)

In severa studies, agents such as pesticides, particulates and compounds emitted from fires and other environmental conditions that GW veterans may have been exposed too, exert an inhibitory and/or negative influence on cell function. (Gulati) For example, the metabolites of many toxic chemicals consistent with these types of exposures bio-accumulate in adipose tissue and contribute to inflammation and insulin resistance. (Nov) More specifically, it is proposed immune-mediate macrophages in adipose tissue contribute to insulin resistance and Tregs dampen this response and their reduction may contribute to insulin resistance. (Winer) Also, smaller particulates that bind to metals and hydrocarbons and contain endotoxin may infiltrate deeply into body tissues and through a complex process, end up in vessels and contribute to inflammation that leads to vascular disease.  (Li) An August 2010 study of Gulf War patients demonstrate high prevalence of problems with hypercoagulation which are also common in sleep apnea patients and can potentially be reversed by use of CPAP in some individuals. (Guardiola, Nichols)

Sleep apnea often accompanies obesity and for years, it has been assumed that inflammation is an important consequence of obesity. However, many experts now believe endothelial inflammation probably precedes obesity. Whatever the case may be, CPAP has demonstrated therapeutic effects on inflammation in obesity and this inflammatory process is similar in other environmentally-induced diseases. This leads one to assume its benefits may be achieved in the same way for GWS patients. Budhiraja and others have shown,  "CPAP therapy improves endothelial function, decreases the abnormally increased levels of circulating apoptotic endothelial cells, attenuates free radical production from neutrophils and monocytes, reduces the levels of C-reactive protein (CRP), a marker of vascular inflammation, increases vasodilator levels and mediates a decline in vasoconstrictor levels  in patients with sleep apnea altering blood flow. In the future, more studies may demonstrate CPAP may be of benefit for other "somatic" environmental illnesses as well.  (Gold, El Soth) In CPAP studies in obese patients, CPAP therapy has shown to reduce oxidative stress as well as, raise levels of SOD and alter nitrate and nitrite levels. Other changes that are reflected during CPAP adjustments also may have positive influences on physiology in a so-far unknown way. (Calero)

I have agreed with a few health experts and proposed due to my own experiences with several environmental diseases, severe reactions of MCS may be caused by the "lack of tolerance" to environmental conditions. Reactions develops to conditions that were considered normal and therefore, is more like an autoimmune disease and inflammatory cytokines and epigenetic changes in gene expression are contributory to this disruption. This "loss of tolerance" could explain why MCS patients develop extreme sensitivity to very low levels of pollutants such as those found in perfumes and detergents. Chemical sensitivity is also common in Gulf War veterans but the research disagrees with the Treg theory at least in part. Interestingly, a recent study demonstrated that post-natal exposure to flame retardents in animals leads to inhibitory functions on the AhR and a reduction of Tregs (Wahl)  and supports that the AhR modulates Treg production (Mezrich) and they may  be a factor at least in some types of reactions to certain toxins.  It would be interesting to examine different Treg ratios and to compare them with patients with MCS that are not GW patients and also compare this to other factors. Specifically, one example would be extenuating circumstances that dramatically effect stress response regulation. From my own experience, I would suggest actual stress and anxiety levels may alter certain markers because my own reactions are significantly different in different environments.

As far as chemical sensitivity, the idea of "loss of tolerance" is relatively new and may involve a better understanding of a "bridge" that links the immune system and metabolic homeostasis.  Because glucose and metabolic dysregulation seems to be concurrent with many environmental illnesses, one must consider metabolic syndrome as a risk factor for any environmental illness and there is little doubt some may contribute to GWS.  Hersoug hypothesizes that diseases like atopy, asthma and autoimmune diseases which are more common with obesity are the result of changes in adipokines including leptin, adiponectin, Il-6 and tumor necrosis factor (Tnf-a) secreted by white adipose tissue.  He adds that body weight contributes to an increase of these inflammatory mediators which in turn down-regulate regulatory T cells which in turn results in a reduction of the anti-inflammatory Il-10. He proposes that this process forms the basis of the idea of "loss of tolerance" and this author believes the loss of "Tregs" contributes significantly to chemical and environmental pollutant sensitivity. Other factors such as endotoxin and loss by genetics or environmental depression of Nrf2 and aberrant AhR signalling may augment the inflammation and allergic and non-allergic reactions and responses and may explain some of the sensitivity to "oil fires".  This may partially be explained by the fact that crude oil and coal dust contain significant amounts of polyaromatic hydrocarbons (PAH) and are ligands for the AhR. (Neff)  They are present in high amounts in diesel exhaust and disruption of the Nrf2 raises allergic airway inflammatory reactions to oxidative stress at much lower levels of diesel exhaust exposure. This may be true and does not dismis some reactions may be a consequence of diesel hydrocarbon content. (Li) Quinatana concludes the AhR, depending on the ligand, is able to modulate both Tregs and Il-17 which is often upregulated in inflammatory autoimmune diseases. It is easy to gather from all of this, that there is probably no simple answer to resolution of environmental disease except to prevent and limit exposures to the "activating" agents.

Of course, one needs to consider the initial "trigger" and the resulting inflammatory immune response may be different through time and be altered through interaction with other other chronic environmental and behavioral factors such as exercise, diet and other noxious "agents" of exposure in one's environment.  The AhR may provide a clue or two because of its role in activation from dioxins and its aberrant signals could be enough to initiate inflammatory responses that may be important in GWS and chemical sensitivity. I have proposed that some of this is due to the communication channel between the Nrf2 and the AhR. Jensen explains that exposure to PAH AhR ligands suppress B cell production and suppress Il-6 and makes an important comment that any alteration in Il-6 can lead to assorted pathologies including autoimmune disease, vitiligo, lupus and multple sclerosis.  Under normal conditions, elevations in Il-6 increase significantly through time in response to endotoxin but when cells are exposed to dioxin or another AhR ligand, cells presented with much lower levels of Il-6. Jensen concludes, "Any environmental chemical capable of compromising this response has the potential to disrupt the regulation of many important stromal cell functions, including generation of inflammatory responses in general and the elaboration of several cytokines, including IL-6, to regulate blood cell development in particular."  In addition, Jensen's research shows that exposures of different AhR ligands including PAH which are prevalent both in indoor and outdoor environments may be different depending on the tissue and may lead to elevations in other inflammatory cytokines such as Tnf-a. Considering that these influences are common in the environment, they can serve to augment responses in GWS or any environmental disease for that matter. (Jensen) One potential consideration is that if alterations in cytokines contribute to blood abnormalities that contribute to hypoxic conditions,
improvements observed with CPAP may reflect improvements in blood parameters of one sort or another. (Incidentally, after my last chemical injury obvious symptoms could have been explained by blood abnormalities like these. Unfortunately, they were not diagnosed because of improper medical care by a licensed practitioner and brings up concerns about access to properly trained practioners for environmental disease which I have discussed at length in other blogs.)

Foster shows that impaired regulation to hypoxic condition in sleep apnea patients and CPAP increases blood flow to normal levels. Another study demonstrates "hypoxia and dioxin response pathways can compete for limiting cellular factor(s) and cross-talk that occur between the hypoxia and dioxin signal transduction pathways and identify Epo as an AHR-regulated gene." (Chan)  This suggests signal dysfunction may influence a battery of physiological and toxicological responses. Most recently in fish, there is evidence that hypoxia reduces the response of the AhR. (Matson) This brings to light two important concerns in light of the discussion here. One is that there is direct interaction between the AhR and the Nrf2 antioxidant system and two, the AhR is an activator of Tregs regulation. In this context, dysfunction could certainly lead to apneas and chronic inflammation. It also may lead to other impairments in the antioxidant system and possibly to chemical sensitivities with a lower Treg production and a "loss of tolerance". It is also worth pondering the extent of effects of blood cell production in relation to circadian rhythm and influence on the positive effects of CPAP (Burioka).

An alternative example of aberrant levels of Il-6 demonstrates the complexity of environmental disease in relation to inflammatory mediators. Curiously, a recent report shows how different factors may be instrumental and  suggest that stress and the effect of pyridostigmine bromide (PB) may be a plausible cause of GWS. Mauck says that his research shows that while stress normally upregulates muscarinic receptor density, the application of  pyridostigmine bromide or physostigmine reduces them. One of the muscarinic targets is the Nrf2 and may suggest a reduction in these receptors may also reduce or prevent the activation of Nrf2. In addition, GSK-3b inhibition also augments muscarinic signals and Treg expression. Thus, conditions where GSK-3b is upregulated may have a negative influence on both chemical sensitivity in GWS and also other types of chemical sensitivity.  The other part of the puzzle in these conditions may be explained and supported by evidence that shows pesticides may contribute to insulin resistance and diabetes and may negatively influence how the body reacts to infection. This could alter inflammatory mediator production and in turn, contribute to the neuroinflammatory process as shown through reductions of Il-6 by GSk-3b inhibition.(Beurel) Dioxins on the other hand, seem to contribute to insulin resistance independant of the AhR. (Hsu)

I have often said in other blogs that environmental illnesses seem more like a failure to adapt and the concept of down-regulation of Tregs provides a viable mechanism for "maladaptation" at least in multiple chemical sensitivity. It may end up that taking genetic expression and immune regulators into account could be what differentiates the forms of chemical sensitivity in autism and MCS from GWS. If Amin is correct and the presence of apneas can be a predictor of  GW syndrome, then one can presume dysregulation of glucose metabolism similar to that that would occur with obesity and the development of chronic inflammation even though GW patients may not be overweight may contribute to GWS. Obesity is a problem in all age groups and classes and is associated with Western diets and GSK-3b may also play its part. It is worth considering that Gulf War veterans that are overweight and eat a typical Western diet will be more at risk for more severe GWI symptoms and those with conditions that depress Nrf2 (which are often diet, exposure and epigenetic influences related) will be even more so!  One may suggest that a lifestyle that promotes healthy eating and low-inflammatory menu like a Mediterranean diet may provide some healthy benefits.





Amin, M. M., Belisova, Z., Hossain, S., Gold, M. S., Broderick, J. E., and Gold, A. R. (2010). Inspiratory airflow dynamics during sleep in veterans with gulf war illness: a controlled study. Sleep & breathing = Schlaf & Atmung. http://www.citeulike.org/user/HEIRS/article/7756111
Gold, A. R., Dipalo, F., Gold, M. S., and Broderick, J. (2004). Inspiratory airflow dynamics during sleep in women with fibromyalgia. Sleep, 27(3):459-466. http://www.citeulike.org/user/HEIRS/article/7756324
Omurtag, G. Z., Tozan, A., Sehirli, A. O. O., and Sener, G. (2008). Melatonin protects against endosulfan-induced oxidative tissue damage in rats. Journal of pineal research, 44(4):432-438.  http://www.citeulike.org/user/HEIRS/article/2674835
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CiteULike: Vitamin D inhibits CEACAM1 to promote insulin/IGF-I receptor signaling without compromising anti-proliferative action.

CiteULike: Vitamin D inhibits CEACAM1 to promote insulin/IGF-I receptor signaling without compromising anti-proliferative action.: "Liu, W., Guo, M., Ezzat, S., and Asa, S. L. (2010). Vitamin d inhibits ceacam1 to promote insulin/igf-i receptor signaling without compromising anti-proliferative action. Laboratory investigation; a journal of technical methods and pathology."

Melatonin protects against endosulfan-induced oxidative tissue damage in rats.

"Omurtag, G. Z., Tozan, A., Sehirli, A. O. O., and Sener, G. (2008). Melatonin protects against endosulfan-induced oxidative tissue damage in rats. Journal of pineal research, 44(4):432-438."

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Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression.

"Jager, J., Grémeaux, T., Cormont, M., Le Marchand-Brustel, Y., and Tanti, J.-F. F. (2007). Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology, 148(1):241-251."

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Endotoxin (LPS) induced activation of the immune system in control rats and rats chronically exposed to a low level of the insecticide, acephate

"chronic low-level Ace exposure may impair the lineage commitment in lymphocytes, possibly by altering cytokine signaling in the brain."

"Singh, A. K. and Jiang, Y. Lipopolysaccharide (lps) induced activation of the immune system in control rats and rats chronically exposed to a low level of the organothiophosphate insecticide, acephate. Toxicology and Industrial Health, 19(2-6):93-108."

Read more: CiteULike: Lipopolysaccharide (LPS) induced activation of the immune system in control rats and rats chronically exposed to a low level of the organothiophosphate insecticide, acephate: