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

Mary Ann Liebert, Inc. - Antioxidants & Redox Signaling - 0(0):: "Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders"

Study Points To Genetic Driver Of Severe Asthma

Study Points To Genetic Driver Of Severe Asthma: "Scientists have identified a genetic basis for determining the severity of allergic asthma in experimental models of the disease."

Study Points To Genetic Driver Of Severe Asthma

Study Points To Genetic Driver Of Severe Asthma: "Scientists have identified a genetic basis for determining the severity of allergic asthma in experimental models of the disease."

Cell signaling mediated by nitrated cyclic guanine nucleotide.

"8-Nitro-cGMP activated the Nrf2 signaling pathway by triggering dissociation of Keap1, via S-guanylation of its highly nucleophilic cysteine sulfhydryls. We also determined that S-guanylation of Keap1 was involved in cytoprotective actions of NO and 8-nitro-cGMP by inducing oxidative stress response genes such as heme oxygenase-1"


Read more: CiteULike: Cell signaling mediated by nitrated cyclic guanine nucleotide.:

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
 
 

Water Intrusion, Mold and Sensitivity!

Water Intrusion, Mold and Sensitivity!

Fertilizer chemicals linked to animal developmental woes

Fertilizer chemicals linked to animal developmental woes

Sphingosine-1-phosphate phosphohydrolase-1 regulates ER stress-induced autophagy

Sphingosine-1-phosphate phosphohydrolase-1 regulates ER stress-induced autophagy

Association of dopamine DA-D2 receptor in rotenone-induced cytotoxicity in PC12 cells

Association of dopamine DA-D2 receptor in rotenone-induced cytotoxicity in PC12 cells

Association of dopamine DA-D2 receptor in rotenone-induced cytotoxicity in PC12 cells

Association of dopamine DA-D2 receptor in rotenone-induced cytotoxicity in PC12 cells

Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury

Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury

PFOS Significantly Elevates Inflammatory Cytokines From LPS Stimulation.

CiteULike: Subchronic effects of perfluorooctanesulfonate exposure on inflammation in adult male C57BL/6 mice.: "Dong, G.-H. H., Zhang, Y.-H. H., Zheng, L., Liang, Z.-F. F., Jin, Y.-H. H., and He, Q.-C. C. (2010). Subchronic effects of perfluorooctanesulfonate exposure on inflammation in adult male c57bl/6 mice. Environmental toxicology."

Metals, oxidative stress and neurodegenerative disorders.

"Jomova, K., Vondrakova, D., Lawson, M., and Valko, M. (2010). Metals, oxidative stress and neurodegenerative disorders. Molecular and cellular biochemistry."

Abstract link: CiteULike: Metals, oxidative stress and neurodegenerative disorders.:

Positive correlation between PPAR{gamma}/PGC-1{alp... [Acta Biochim Biophys Sin (Shanghai). 2010] - PubMed result

Comment: Recent studies suggest Nrf2 may regulate to PPAR-gamma to a degree.

"activation of the PPARgamma/PGC-1alpha pathway may protect against COPD progression by upregulating gamma-GCS and relieving oxidative stress."

Read more: Positive correlation between PPAR{gamma}/PGC-1{alp... [Acta Biochim Biophys Sin (Shanghai). 2010] - PubMed result:

AMPK agonist downregulates innate and adaptive immune responses in TNBS-induced murine acute and relapsing colitis.

"AICAR-initiated AMPK activation may act as a central downregulator in ongoing innate and adaptive immune responses of murine colitis, providing a novel therapeutic approach in the treatment of IBD."

Read more: CiteULike: AMPK agonist downregulates innate and adaptive immune responses in TNBS-induced murine acute and relapsing colitis.:

For further reading: AMPK

Endotoxin tolerance attenuates airway allergic inflammation in model mice by suppression of the T-cell stimulatory effect of dendritic cells

Endotoxin tolerance attenuates airway allergic inflammation in model mice by suppression of the T-cell stimulatory effect of dendritic cells

Respiration-dependent H2O2 Removal in Brain Mitochondria via the Thioredoxin/Peroxiredoxin System — JBC

Respiration-dependent H2O2 Removal in Brain Mitochondria via the Thioredoxin/Peroxiredoxin System — JBC: "respiration- and thioredoxin-dependent ROS removal as a potentially important mitochondrial function that may contribute to physiological and pathological processes in the brain."

Respiration-dependent H2O2 Removal in Brain Mitochondria via the Thioredoxin/Peroxiredoxin System [Molecular Bases Of Disease]

Respiration-dependent H2O2 Removal in Brain Mitochondria via the Thioredoxin/Peroxiredoxin System [Molecular Bases Of Disease]

CiteULike: Nrf2 is closely related to allergic airway inflammatory responses induced by low-dose diesel exhaust particles in mice.

CiteULike: Nrf2 is closely related to allergic airway inflammatory responses induced by low-dose diesel exhaust particles in mice.: "Li, Y. J. J., Takizawa, H., Azuma, A., Kohyama, T., Yamauchi, Y., Takahashi, S., Yamamoto, M., Kawada, T., Kudoh, S., and Sugawara, I. (2010). Nrf2 is closely related to allergic airway inflammatory responses induced by low-dose diesel exhaust particles in mice. Clinical immunology (Orlando, Fla.)."

Black Women With Lupus Develop CVD at Younger Age

Black Women With Lupus Develop CVD at Younger Age

Hand-held sniffer picks out grave sites

Hand-held sniffer picks out grave sites

Scientists find link in humans between nerve cell production and memory

"Production of new nerve cells in the human brain is linked to learning and memory, according to a new study from the University of Florida."

Read more:Scientists find link in humans between nerve cell producti... ( Production of new nerve cells in the...):

Polyphenol antioxidants inhibit iron absorption

Polyphenol antioxidants inhibit iron absorption: "University Park, Pa. — Health benefits from polyphenol antioxidants — substances found in many fruits and vegetables — may come at a cost to some people. Penn State nutritional scientists found that eating certain polyphenols decreased the amount of iron the body absorbs, which can increase the risk of developing an iron deficiency."

Study suggests oxytocin makes people trusting, but not gullible

"Oxytocin (OT) is a hormone that plays an important role in social behavior—it has even been nicknamed 'the love hormone' and 'liquid trust.' Increased levels of OT have been associated with greater caring, generosity, and trust. But does OT increase people's trust in just anybody or does it act more selectively?"

Read more: Study suggests oxytocin makes people trusting, but not gullible:

Men's Health: BPA and testosterone levels

BPA and testosterone levels: "An international group of researchers led by the Peninsula Medical School and the University of Exeter have for the first time identified changes in sex hormones associated with BPA exposure in men, in a large population study. The study results are published in the latest issue of Environmental Health Perspectives."

Vitamin D may treat and prevent allergic reaction to mold in cystic fibrosis patients

Comment: The following study helps support the HEIRS and others' hypothesis that MCS and other environmental illnesses are a "loss of tolerance" which involves impaired Treg production.


"PITTSBURGH, Aug. 25 – Vitamin D may be an effective therapy to treat and even prevent allergy to a common mold that can cause severe complications for patients with cystic fibrosis and asthma, according to researchers from Children's Hospital of Pittsburgh of UPMC, the University of Pittsburgh School of Medicine and Louisiana State University School of Medicine."

Read more: Vitamin D may treat and prevent allergic reaction to mold in cystic fibrosis patients:

For further reading: Tregs, loss of tolerance, FoxP3
     **********You can also search the HEIRS Citation database for related citations.


Duan, W., So, T., and Croft, M. (2008). Antagonism of airway tolerance by endotoxin/lipopolysaccharide through promoting ox40l and suppressing antigen-specific foxp3+ t regulatory cells. Journal of immunology (Baltimore, Md. : 1950), 181(12):8650-8659.   http://www.citeulike.org/user/HEIRS/article/3752381

Transcription factor Nrf2 activation by deltamethrin in PC12 cells : Involvement of ROS

Transcription factor Nrf2 activation by deltamethrin in PC12 cells : Involvement of ROS: "Transcription factor Nrf2 activation by deltamethrin in PC12 cells : Involvement of ROS"

Monocrotophos toxicity and bioenergetics of muscle... [Toxicology. 2010] - PubMed result

Monocrotophos toxicity and bioenergetics of muscle... [Toxicology. 2010] - PubMed result: "Monocrotophos toxicity and bioenergetics of muscle weakness in the rat."

Nrf2 is a key transcription factor that regulates ... [J Immunol. 2004] - PubMed result

Nrf2 is a key transcription factor that regulates ... [J Immunol. 2004] - PubMed result: "This pathway is sensitive to pro-oxidative and electrophilic DEP chemicals and is also activated by ambient ultrafine particles. We propose that Nrf2-mediated phase II enzyme expression protects against the proinflammatory effects of particulate pollutants in the setting of allergic inflammation and asthma."

Methylation Matters: Interaction Between Methylation Density and Serotonin Transporter Genotype Predicts Unresolved Loss or Trauma

Methylation Matters: Interaction Between Methylation Density and Serotonin Transporter Genotype Predicts Unresolved Loss or Trauma: "5HTTLPR polymorphisms and psychological problems are significantly altered by environmentally induced methylation patterns. Methylation may serve as the interface between adverse environment and the developing organism."

Health Problems for Deepwater Workers - MedicineNet - Health and Medical Information Produced by Doctors

Health Problems for Deepwater Workers - MedicineNet - Health and Medical Information Produced by Doctors: "The fate of fishermen involved in cleaning up a massive oil spill off the northwest coast of Spain in 2002 could shed light on potential health problems facing workers involved in the recent Deepwater disaster in the Gulf of Mexico."

Dietary olive oil effect on antioxidant status and fatty acid profile in the erythrocyte of 2,4-D- exposed rats

Dietary olive oil effect on antioxidant status and fatty acid profile in the erythrocyte of 2,4-D- exposed rats

Impaired Redox Signaling and Antioxidant Gene Expression in Endothelial Cells in Diabetes: Role for Mitochondria & Nrf2~!

"We hypothesize that diminished Nrf2/ARE activity contributes to increased oxidative stress and mitochondrial dysfunction in the vasculature leading to endothelial dysfunction, insulin resistance, and abnormal angiogenesis observed in diabetes. Sustained hyperglycemia further exacerbates redox dysregulation, thereby providing a positive feedback loop for severe diabetic complications"Mary Ann Liebert, Inc. - Antioxidants & Redox Signaling - 0(0)::

Disruption of Nrf2 Enhances the Upregulation of Nuclear Factor-kappaB Activity, Tumor Necrosis Factor-α, and Matrix Metalloproteinase-9 after Spinal Cord Injury in Mice

Disruption of Nrf2 Enhances the Upregulation of Nuclear Factor-kappaB Activity, Tumor Necrosis Factor-α, and Matrix Metalloproteinase-9 after Spinal Cord Injury in Mice: "Disruption of Nrf2 Enhances the Upregulation of Nuclear Factor-kappaB Activity, Tumor Necrosis Factor-α, and Matrix Metalloproteinase-9 after Spinal Cord Injury in Mice"

Inflammatory Effects of Ex Vivo Human Th17 Cells A... [J Immunol. 2010] - PubMed result

Inflammatory Effects of Ex Vivo Human Th17 Cells A... [J Immunol. 2010] - PubMed result: "Inflammatory Effects of Ex Vivo Human Th17 Cells Are Suppressed by Regulatory T Cells."

Study Identifies Genetic Variation Linked To Lupus In Asian Men

Study Identifies Genetic Variation Linked To Lupus In Asian Men

Vitamin D Linked To Autoimmune And Cancer Disease Genes, Underscoring Risks Of Deficiency

Vitamin D Linked To Autoimmune And Cancer Disease Genes, Underscoring Risks Of Deficiency: "Vitamin D insufficiency is a risk factor for a number of diseases and thus, is a growing concern worldwide, as approximately one billion people may be vitamin D deficient."

Resveratrol differentially modulates inflam responses of microglia & astrocytes

Comment: An extremely useful read for those interested in this kind of stuff. Full text available.

"the first report of a difference between microglial cell and astrocyte in response to LPS, and of a difference in the capacity of resveratrol to protect microglia and astrocytes from inflammatory insults."


Lu, X., Ma, L., Ruan, L., Kong, Y., Mou, H., Zhang, Z., Wang, Z., Wang, J. M., and Le, Y. (2010). Resveratrol differentially modulates inflammatory responses of microglia and astrocytes. Journal of Neuroinflammation, 7(1):46+.  http://www.citeulike.org/user/HEIRS/article/7694580

Nair, S., Barve, A., Khor, T.-O. O., Shen, G.-X. X., Lin, W., Chan, J. Y., Cai, L., and Kong, A.-N. N. (2010). Regulation of nrf2- and ap-1-mediated gene expression by epigallocatechin-3-gallate and sulforaphane in prostate of nrf2-knockout or c57bl/6j mice and pc-3 ap-1 human prostate cancer cells. Acta pharmacologica Sinica. http://www.citeulike.org/user/HEIRS/article/7694509

CiteULike: Regulation of Nrf2- and AP-1-mediated gene expression by epigallocatechin-3-gallate and sulforaphane in prostate of Nrf2-knockout or C57BL/6J mice and PC-3 AP-1 human prostate cancer cells.

CiteULike: Regulation of Nrf2- and AP-1-mediated gene expression by epigallocatechin-3-gallate and sulforaphane in prostate of Nrf2-knockout or C57BL/6J mice and PC-3 AP-1 human prostate cancer cells.: "gene expression changes induced by dietary phytochemicals SFN and EGCG in Nrf2-deficient mice and in PC-3 cells in vitro demonstrates that the effects of SFN+EGCG could be mediated via concerted modulation of Nrf2 and AP-1 pathways in the prostate."


Nair, S., Barve, A., Khor, T.-O. O., Shen, G.-X. X., Lin, W., Chan, J. Y., Cai, L., and Kong, A.-N. N. (2010). Regulation of nrf2- and ap-1-mediated gene expression by epigallocatechin-3-gallate and sulforaphane in prostate of nrf2-knockout or c57bl/6j mice and pc-3 ap-1 human prostate cancer cells. Acta pharmacologica Sinica.  http://www.citeulike.org/user/HEIRS/article/7694509

Dogs, Rodents May Prevent Future Epidemics : Discovery News

Dogs, Rodents May Prevent Future Epidemics : Discovery News: "Disease-detecting dogs and mice may be trained to sniff out bird influenza and other deadly illnesses before they spread, suggests new research reported today at the National Meeting of the American Chemical Society."

Mice with gene disruption of both endothelial and neuronal nitric oxide synthase exhibit insulin resistance.

CiteULike: Mice with gene disruption of both endothelial and neuronal nitric oxide synthase exhibit insulin resistance.: "NO plays a role in modulating insulin sensitivity and carbohydrate metabolism and that the eNOS isoform may play a dominant role relative to nNOS"

Omega-3 Fatty Acids May Help to Keep Arteries Soft & Supple | Trusted.MD Network

Omega-3 Fatty Acids May Help to Keep Arteries Soft & Supple Trusted.MD Network: "A study done in the UK found that increased intakes of omega-3 fatty acids could help to make blood vessels less stiff following a meal, adding to a strong body of research linking long chain omega-3 fats with improved heart health"

2,3,7,8-Tetrachlorodibenzo-P-Dioxin Impairs Stable Establishment of Oral Tolerance in Mice

2,3,7,8-Tetrachlorodibenzo-P-Dioxin Impairs Stable Establishment of Oral Tolerance in Mice

New molecular signaling cascade increases glucose uptake

New molecular signaling cascade increases glucose uptake: "Skeletal muscles combust both lipids and carbohydrates during exercise. The carbohydrates consist of both glycogen stored in the muscles as well as glucose extracted from the blood. Being a major sink for glucose disposal, skeletal muscle represents an important model tissue for studying the intracellular signaling pathways leading to increased glucose transport."

Eating berries may activate the brain's natural housekeeper for healthy aging

Eating berries may activate the brain's natural housekeeper for healthy aging: "Scientists today reported the first evidence that eating blueberries, strawberries, and acai berries may help the aging brain stay healthy in a crucial but previously unrecognized way."

Disasters especially tough on people with disabilities, mental disorders

Disasters especially tough on people with disabilities, mental disorders

Inflammation-Induced Anhedonia: Endotoxin Reduces ... [Biol Psychiatry. 2010] - PubMed result

Inflammation-Induced Anhedonia: Endotoxin Reduces ... [Biol Psychiatry. 2010] - PubMed result: "Inflammation-Induced Anhedonia: Endotoxin Reduces Ventral Striatum Responses to Reward."

Inflammation-Induced Anhedonia: Endotoxin Reduces ... [Biol Psychiatry. 2010] - PubMed result

Inflammation-Induced Anhedonia: Endotoxin Reduces ... [Biol Psychiatry. 2010] - PubMed result: "Inflammation-Induced Anhedonia: Endotoxin Reduces Ventral Striatum Responses to Reward."

Low vitamin B12 and folate common in Crohn’s disease patients

Low vitamin B12 and folate common in Crohn’s disease patients

Dietary Broccoli Sprouts Protect Against Myocardia... [Plant Foods Hum Nutr. 2010] - PubMed result

We love broccoli!

Dietary Broccoli Sprouts Protect Against Myocardia... [Plant Foods Hum Nutr. 2010] - PubMed result: "results show that a relatively short dietary treatment with broccoli sprouts can strongly protect the heart against oxidative stress and cell death caused by ischemia-reperfusion."

S-nitroso-N-acetylcysteine ameliorates ischemia-reperfusion injury in the steatotic liver

S-nitroso-N-acetylcysteine ameliorates ischemia-reperfusion injury in the steatotic liver

Gene's Action May Help Explain Why Restricting Diet Lengthens Life In Animals

"A team of University of Michigan scientists has found that suppressing a newly discovered gene lengthens the lifespan of roundworms."

Gene's Action May Help Explain Why Restricting Diet Lengthens Life In Animals:

Study Suggests CFS, IBS and Fibro May Be Related To Uninary Problems!

CiteULike: Interstitial Cystitis/Painful Bladder Syndrome and Associated Medical Conditions With an Emphasis on Irritable Bowel Syndrome, Fibromyalgia and Chronic Fatigue Syndrome.: "Irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome are more prevalent in patients with interstitial cystitis/painful bladder syndrome than in asymptomatic control subjects, and result in significant impact."

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

WOW! I think studies have demonstrated that NRF-1 is important in its regulation with PGC-1a for mitochondrial biogenesis and regulated by Nrf2. This further supports the importance of Nrf2 in environmental disease especially those that have been associated with folate deficiency! We noted another study that broccoli has a role in regulating folate which supports the need for proper Nrf2 function.


CiteULike: The obligatory intestinal folate transporter PCFT (SLC46A1) is regulated by nuclear respiratory factor 1 (NRF-1).: "identify NRF-1 as a major inducible transcriptional regulator of PCFT gene expression. The implications of this linkage between folate transport and metabolism with mitochondria biogenesis and respiration are discussed"

Steatosis in Mice Is Associated with Gender, Folate Intake, and Expression of Genes of One-Carbon Metabolism.

CiteULike: Steatosis in Mice Is Associated with Gender, Folate Intake, and Expression of Genes of One-Carbon Metabolism.: "Our work demonstrates that chronic folate insufficiency leads to steatosis in mice. Increased utilization of betaine for Hcy remethylation in males and in both genders during folate deficiency may lead to steatosis by disrupting choline metabolism."

Broccoli has protective effects against oxidant-induced strand breaks~!

"broccoli intake was associated with increased protection against H(2)O(2)-induced DNA strand breaks and lower levels of oxidised DNA bases in PBMCs from smokers. This protective effect could be related to an overall improved antioxidant status."

Read more: CiteULike: DNA damage and repair activity after broccoli intake in young healthy smokers.:

Low-intensity exercise enhances expression of markers of alternative activation in circulating leukocytes: Roles of PPARgamma and Th2 cytokines.

CiteULike: Low-intensity exercise enhances expression of markers of alternative activation in circulating leukocytes: Roles of PPARgamma and Th2 cytokines.: "we propose that exercise-induced PPARgamma/PGC-1(alpha/beta)-mediated M2 polarisation may constitute a novel anti-inflammatory benefit of low-intensity exercise."

CiteULike: Valproate induces DNA demethylation in nuclear extracts from adult mouse brain.

CiteULike: Valproate induces DNA demethylation in nuclear extracts from adult mouse brain.: "Dong, E., Chen, Y., Gavin, D. P., Grayson, D. R., and Guidotti, A. (2010). Valproate induces dna demethylation in nuclear extracts from adult mouse brain. Epigenetics, 5(8)."

Epigenetic reprogramming of host genes in viral and microbial pathogenesis.

CiteULike: Epigenetic reprogramming of host genes in viral and microbial pathogenesis.: "Paschos, K. and Allday, M. J. (2010). Epigenetic reprogramming of host genes in viral and microbial pathogenesis. Trends in microbiology."

National CFIDS Foundation Announces Link between CFS and Low Level Radiation

Radon exposure is probably the most prevalent source of low level radiation while far infrared therapy may be another source.

"The National CFIDS Foundation Inc., of Needham Mass, has announced its formal disease model for Chronic Fatigue Syndrome (CFS) also known as Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) as well as Myalgic Encephalomyelitis (ME). According to the NCF, a subgroup of patients with CFS fit a unique disease profile based on a model for a radioactive toxin"

Read more: National CFIDS Foundation (NCF) Announces Link between Chronic Fatigue Syndrome and Low Level... -- NEEDHAM, Mass., Aug. 20 /PRNewswire-USNewswire/ --:

Essential role of ER-alpha-dependent NO production... [Am J Physiol Heart Circ Physiol. 2010] - PubMed result

Well....well!  More evidence of sexual dimorphism.....????


Essential role of ER-alpha-dependent NO production... [Am J Physiol Heart Circ Physiol. 2010] - PubMed result: "These data thus suggest that RESV inhibits vascular proliferative responses after injury, predominately through an ER-alpha-dependent increase in NO production."

In vivo and in vitro inhibition of mice thioredoxi... [Biometals. 2010] - PubMed result

In vivo and in vitro inhibition of mice thioredoxi... [Biometals. 2010] - PubMed result: "In vivo and in vitro inhibition of mice thioredoxin reductase by methylmercury"

Oxytocin Attenuates Amygdala Reactivity to Fear in Generalized Social Anxiety Disorder

"OXT has a specific effect on fear-related amygdala activity, particularly when the amygdala is hyperactive, such as in GSAD, thereby providing a brain-based mechanism of the impact of OXT in modulating the exaggerated processing of social signals of threat in patients with pathological anxiety"

Read more:CiteULike: Oxytocin Attenuates Amygdala Reactivity to Fear in Generalized Social Anxiety Disorder:

NHS Evidence - Gastroenterology and liver diseases - Meta-analysis: antioxidant supplements for liver diseases - the Cochrane Hepato-Biliary Group

NHS Evidence - Gastroenterology and liver diseases - Meta-analysis: antioxidant supplements for liver diseases - the Cochrane Hepato-Biliary Group: "Meta-analysis: antioxidant supplements for liver diseases - the Cochrane Hepato-Biliary Group"

Prenatal Pesticide Exposures Linked to Attention Disorders in Preschool Children

"Exposure to organophosphate (OP) pesticides before birth can increase susceptibility to attention disorders such as attention deficit/hyperactivity disorder (ADHD), according to new research published in the journal Environmental Health Perspectives (EHP)."

Read more: Prenatal Pesticide Exposures Linked to Attention Disorders in Preschool Children:

PPAR-gamma Protects Against Pathogenic Strains of Influenza~!

Considering the evidence from this study and others, chemical pollutants, drugs and environmental conditions that positively or negative regulate PPAR-gamma should be an important consideration when evaluating an individual for different environmental illnesses and alterations in cellular homeostasis. In addition, the recent studies that PPAR-gamma is regulated by Nrf2 also puts more emphasis as an important target for environmentally-induced disease.

 

"preliminary evidence that two classes of drugs, peroxisome proliferator-activated receptor-gamma agonists and AMP-activated protein kinase agonists, provide protection in mice infected with highly pathogenic and pandemic strains of influenza virus."

Read more: CiteULike: Moseley, C. E., Webster, R. G., and Aldridge, J. R. (2010). Peroxisome proliferator-activated receptor and amp-activated protein kinase agonists protect against lethal influenza virus challenge in mice. Influenza and other respiratory viruses, 4(5):307-311. http://www.citeulike.org/user/HEIRS/article/7679239


For Further Reading: Nrf2, PPAR-gamma
 
 
 

TLRs Interaction W/ Pathogens Can Increase Resistance From Host Immune Defense.

"A special set of sugars found on some disease-causing pathogens helps those pathogens fight the body's natural defenses as well as vaccines, say two Iowa State University researchers"

Read more: Cause Of Immune System Avoidance Of Certain Pathogens: Discovery By ISU Researchers:

SEPSIS AND GLUCOCORTICOIDS DOWNREGULATE THE EXPRESSION OF THE NUCLEAR COFACTOR PGC-1beta IN SKELETAL MUSCLE.

"sepsis- and glucocorticoid-induced muscle wasting may, at least in part, be regulated by decreased expression of the nuclear corepressor PGC-1beta."

CiteULike: SEPSIS AND GLUCOCORTICOIDS DOWNREGULATE THE EXPRESSION OF THE NUCLEAR COFACTOR PGC-1beta IN SKELETAL MUSCLE.:

Dysfunctional Nrf2-Keap1 redox signalling in skeletal muscle of sedentary old.

"an active lifestyle is an important determinant of cellular redox status. We propose that the metabolic induction of Nrf2-Keap1 redox signalling promises to be a viable therapy for attenuating oxidative stress-mediated damage in skeletal muscle associated with physical inactivity."

Read more: CiteULike: Dysfunctional Nrf2-Keap1 redox signalling in skeletal muscle of sedentary old.:

Anti-diabetic Effects of Sage May Be Mediated via PPAR-gamma~!

"Salvia officinalis were able to activate PPARgamma and hence, the anti-diabetic activity of this plant could in part be mediated through this nuclear receptor."

CiteULike: Activation of the nuclear receptor PPARgamma by metabolites isolated from sage (Salvia officinalis L.).:

New Findings Involving Enxymes that Promote Protective Effects of Hydrogen Sulfide.

Background: It has been suggested that individuals with chemical sensitivity are more susceptible to the effects of hydrogen sulfide even though hydrogen sulfide has beneficial effects at low endogenous or exogenous levels. It has been shown that some of the benefits of H2S are regulated through Nrf2 and HO-1. In Nrf2 knock-outs, H2S fails to elicit the strong antioxidant HO-1 and reduces tissue resistance to oxidative stress.

H2S protects tissue and " is an endogenously produced gaseous signaling molecule with a diverse physiological profile. Its production in mammalian systems has been attributed to 2 key enzymes in the cysteine biosynthesis pathway, cystathionine β-synthase (CBS) and cystathionine -lyase (CGL). A new study provides evidence that animals lacking either CBS or CGL may be more suceptible to oxidative stress but have slightly different presentations diagnostically. The latter may require supplementation with cysteine in deficiency.  In either case, the inability to synthesize or utilize H2S may contribute to environmental illnesses.


Calvert, J. W., Jha, S., Gundewar, S., Elrod, J. W., Ramachandran, A., Pattillo, C. B., Kevil, C. G., and Lefer, D. J. (2009). Hydrogen sulfide mediates cardioprotection through nrf2 signaling. Circ Res, 105(4):365-374. http://www.citeulike.org/user/HEIRS/article/5211207?show_msg=already_posted
Ishii, I., Akahoshi, N., Yamada, H., Nakano, S., Izumi, T., and Suematsu, M. (2010). Cystathionine γ-lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. Journal of Biological Chemistry, 285(34):26358-26368. http://www.citeulike.org/user/HEIRS/article/7657999

Cystathionine γ-Lyase-deficient Mice Require Dietary Cysteine to Protect against Acute Lethal Myopathy and Oxidative Injury

"These results reveal novel roles of trans-sulfuration previously unrecognized in mice lacking another trans-sulfuration enzyme cystathionine β-synthase (Cbs−/−). Because Cbs−/− mice display hyperhomocysteinemia and hypermethioninemia, our results raise questions against the homocysteine-based etiology of CBS deficiency and the current newborn screening for homocysteinemia using Guthrie's method, which detects hypermethioninemia."

Read abstract: CiteULike: Cystathionine γ-Lyase-deficient Mice Require Dietary Cysteine to Protect against Acute Lethal Myopathy and Oxidative Injury:

Childhood abuse, adversity may shorten life, weaken immune response among the elderly

Childhood abuse, adversity may shorten life, weaken immune response among the elderly

Gut Inflammation and Changes in Intestinal Function From Loss of NO Neurons~!

In a recent study the author writes "enteric neurons are supported by glial cells, the ENS counterparts of astrocytes of the CNS, that can modulate enteric neuron function. Enteric neurons are known to control virtually all GI functions, including motility, secretion, blood flow, mucosal growth and aspects of the local immune system. Consequently, permanent or even transient structural alterations in the ENS, as occur in IBD, disrupt normal GI function. Structural changes in the ENS are predictive of disease evolution suggesting that neuroprotection would decrease disease severity and may play a role in recurrence in CD." Further he continues that under conditions of experimental trichinosis infection in the murine "that in this animal model of colitis, there was a significant loss of nitric oxide synthase- (NOS-) immunoreactive neurons in the myenteric plexus of infected rats. Moreover, the selective loss of NOS-positive neurons appears to underlie changes in motility." (Lakhan) Recent reports also suggest that hormones such as serotonin influences gut regulation and may activate inflammatory cytokines in the intestine leading to alterations in gut function. (Khan) Inflammatory activity such as Tnf-a in the periphery such as the gut may influence production of cytokines and changes in gene expression in the brain that change behavior and have other unexpected health effects.




Khan, W. I. and Ghia, J. E. (2010). Gut hormones: emerging role in immune activation and inflammation. Clinical and experimental immunology, 161(1):19-27.
http://www.citeulike.org/user/HEIRS/article/7323747

Lakhan, S. E. and Kirchgessner, A. (2010). Neuroinflammation in inflammatory bowel disease. Journal of neuroinflammation, 7:37+.
http://www.citeulike.org/user/HEIRS/article/7471133

Antioxidant System Deficiency Increases Allergic Immune Response~!

Background: Nrf2 expression can be influenced by a number of factors including diet and age and may influence or be influenced by the expression of other proteins.

Rangasamy demonstrates that immune reactions from ragweed are more severe in Nrf2-deficiency. The author's findings suggest that "defect in Nrf2 mediated signaling mechanisms alters the response of DC to a common environmental allergen, which may contribute to the susceptibility to allergic diseases." Importantly, one must also note that other studies have suggest endotoxin reduces the threshold for allergic reactions and EGCG, the compound found in green tea, has a suppressive influence on histamine producing cells. More and more studies are providing evidence that EGCG acts through the Nrf2 antioxidant system and therefore should warrant further study as therapeutic for allergic-type reactions.


Rangasamy, T., Williams, M. A., Bauer, S., Trush, M. A., Emo, J., Georas, S. N., and Biswal, S. (2009). Nrf2 inhibits the maturation of murine dendritic cells by ragweed extract. American Journal of Respiratory Cell and Molecular Biology.
http://www.citeulike.org/user/HEIRS/article/7652681
Melgarejo, E., Medina, M. A. A., Sánchez-Jiménez, F., and Urdiales, J. L. L. (2010). Targeting of histamine producing cells by egcg: a green dart against inflammation? Journal of physiology and biochemistry, 66(3):265-270.
http://www.citeulike.org/user/HEIRS/article/7652686

Safer, longer-lasting regulatory T cells with -catenin

"investigators suggest that the activation of the canonical Wnt pathway is essential in Treg cell homeostasis and may have a key role in anergy induction in matured T cells2." http://www.nature.com/nm/journal/v14/n2/full/nm0208-118.html




HEIRS Health Research Blog: Activation of {beta}-Catenin in Dendritic Cells Regulates Immunity Versus Tolerance in the Intestine

Green Tea Compound, Hypermethylation and Tregs In Allergy and Chemical Sensitivity!

Recent studies propose that environmental illnesses are caused from "loss of tolerance" and that alterations in T regulatory cells (Tregs) may be a important factor. A number of studies demonstrate health benefits from epigallocatechin gallate (EGCG) which is a compound found in green tea. Yun shows EGCG can enhance Tregs production and enhance expression of histone deacetylases while decreasing expression of NF-kappaB. It also has been shown to reactivate genes that have been silenced by hypermethylation and prevent these changes to subsequent passage to daughter cells by DNA methyltransferases. (Fang) Interestingly, CCL18 is a chemokine that is elevated in allergic patients and may contribute to the "loss of tolerance" because in normal patients it promotes the generation of normal normal Tregs but in allergic patients it does not and may
an increased prevalence for symptoms that are common with chemical sensitivity in allergic patients. In addition, other factors including the proper expression of the Nrf2 system and other pathways for antioxidant expression may mitigate the effects while impairments may exacerbate them. EGCG has been shown to act through Nrf2, although this may not be its only mode of action. In any event, EGCG may provide some therapeutic effects for these kinds of conditions.


Yun, J.-M. and Jialal, I. Effects of epigallocatechin gallate on regulatory t cell number and function in obese versus lean volunteers. FASEB.http://www.citeulike.org/user/HEIRS/article/7651808
Fang, M. Z. Z., Wang, Y., Ai, N., Hou, Z., Sun, Y., Lu, H., Welsh, W., and Yang, C. S. (2003). Tea polyphenol (-)-epigallocatechin-3-gallate inhibits dna methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer research, 63(22):7563-7570.
http://www.citeulike.org/user/HEIRS/article/3326104
Chang, Y., de Nadai, P., Azzaoui, I., Morales, O., Delhem, N., Vorng, H., Tomavo, S., Ait Yahia, S., Zhang, G., Wallaert, B., Chenivesse, C., and Tsicopoulos, A. (2010). The chemokine ccl18 generates adaptive regulatory t cells from memory cd4+ t cells of healthy but not allergic subjects. The FASEB journal. http://www.citeulike.org/user/HEIRS/article/7651843

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."

Endotoxin tolerance and cross-tolerance in mast cells involves TLR4, TLR2 and FcepsilonR1 interactions and SOCS expression: perspectives on immunomodulation in infectious and allergic diseases

Endotoxin tolerance and cross-tolerance in mast cells involves TLR4, TLR2 and FcepsilonR1 interactions and SOCS expression: perspectives on immunomodulation in infectious and allergic diseases

Heat Shock Protein Can Restore Nerve Damage In Diabetic Mice

Heat Shock Protein Can Restore Nerve Damage In Diabetic Mice: "Researchers have been able to use a common chaperone protein, Hsp70, to reverse the loss of function in the nerves of mice with diabetes."

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.:

Mechanisms, diagnosis and management of hepatic encephalopathy.

CiteULike: Mechanisms, diagnosis and management of hepatic encephalopathy.: "therapy for HE is largely based on the principle of reducing the production and absorption of ammonia in the gut through administration of pharmacological agents such as rifaximin and lactulose, which are approved by the FDA for the treatment of HE."

Severe dyslipidaemia, atherosclerosis, and sudden cardiac death in mice lacking all NO synthases fed a high-fat diet — Cardiovasc Res

Severe dyslipidaemia, atherosclerosis, and sudden cardiac death in mice lacking all NO synthases fed a high-fat diet — Cardiovasc Res: "Severe dyslipidaemia, atherosclerosis, and sudden cardiac death in mice lacking all NO synthases fed a high-fat diet"

Neuroprotective and Anti-inflammatory Activities of Ketogenic Diet on MPTP-induced Neurotoxicity.

Comments: I believe the results of this study are indicative of the fact that a keen understanding of the patients environmental illness and the factors that lead to it are crucial for the best holistic treatment and management of it. It is obvious that a one size fits treatment plan is probably not in the best interest of most patients.

"The change of dopamine was very similar to dopaminergic neurons in the SN. KD inhibited the activation of microglia induced by MPTP in the SN. The levels of proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) in the SN were also decreased and induced by MPTP. So, we concluded that KD was neuroprotective and anti-inflammatory against MPTP-neurotoxicity."

Read more: CiteULike: Neuroprotective and Anti-inflammatory Activities of Ketogenic Diet on MPTP-induced Neurotoxicity.:

Chronic exposure to low levels of inorganic arsenic causes alterations in locomotor activity and in the expression of dopaminergic and antioxidant systems in the albino rat.

CiteULike: Chronic exposure to low levels of inorganic arsenic causes alterations in locomotor activity and in the expression of dopaminergic and antioxidant systems in the albino rat.: "Rodríguez, V. M. M., Limón-Pacheco, J. H. H., Carrizales, L., Mendoza-Trejo, M. S. S., and Giordano, M. (2010). Chronic exposure to low levels of inorganic arsenic causes alterations in locomotor activity and in the expression of dopaminergic and antioxidant systems in the albino rat. Neurotoxicology and teratology."

Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals.

"suppresses the proinflammatory transcription factors nuclear factor-kappa B, signal transducer and activators of transcription-3, and Wnt/beta-catenin, and it activates peroxisome proliferator-activated receptor-gamma and Nrf2 cell-signaling pathways, thus leading to the downregulation of adipokines, including tumor necrosis factor, interleukin-6, resistin, leptin, and monocyte chemotactic protein-1, and the upregulation of adiponectin and other gene products."

Read more: CiteULike: Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals.:

Hope For A Cure For Tinnitus - 'Ringing In The Ears'

"The NIH has granted a University of Texas at Dallas researcher and a university-affiliated biomedical firm $1.7 million to investigate whether nerve stimulation offers a long-term cure for tinnitus."

Read more: Hope For A Cure For Tinnitus - 'Ringing In The Ears':

Laboratory Investigation - Abstract of article: Cytokines induce small intestine and liver injury after renal ischemia or nephrectomy

Laboratory Investigation - Abstract of article: Cytokines induce small intestine and liver injury after renal ischemia or nephrectomy: "Cytokines induce small intestine and liver injury after renal ischemia or nephrectomy"

Food Molds: Does Impairment of PGC-1a Contribute to Their Toxicity?

Background: PGC-1a is an important regulator of metabolism in different tissues including the muscle and liver and its expression may be of important significance in a variety of diseases including neurodegenerative diseases and diabetes and influences circadian rythyms.  In addition, its activities are directly influenced by a number of other proteins including AMPK and SIRT1.

Vomitoxin, also known as deoxynivalenol (DON) is a  mycotoxin found in different types of foodstuffs and can be associated with mycotoxicosis in both animals and humans.While its negative health effects are generally milder than other mycotoxins susceptible populations could be more at risk. Generally, this class of mycotoxins are proteins inhibitors and may alter expression of neurotransmitters such as serotonin which can lead to weight loss because of the anorexic effects of elevations of serotonin.  These changes may also influence normal activity of the respiratory tract. (Wipedia) According to a recent study and in-line with the DON's ability to negative influence protein expression, DON has been demonstrated to upregulate a known of repressor of PGC-1a in addition to other proteins.  This could explain why individuals ( or animals) with impaired antioxidant and immune systems, metabolic dysfunctions, or the aged may show more health effcts upon mold exposure. 


Osman, A. M., Pennings, J. L., Blokland, M., Peijnenburg, A., and van Loveren, H. (2010). Protein expression profiling of mouse thymoma cells upon exposure to the trichothecene deoxynivalenol (don): implications for its mechanism of action. Journal of immunotoxicology, 7(3):147-156. http://www.citeulike.org/user/HEIRS/article/7607619




Leone, T. C., Lehman, J. J., Finck, B. N., Schaeffer, P. J., Wende, A. R., Boudina, S., Courtois, M., Wozniak, D. F., Sambandam, N., Bernal-Mizrachi, C., Chen, Z., Holloszy, Medeiros, D. M., Schmidt, R. E., Saffitz, J. E., Abel, E. D., Semenkovich, C. F., and Kelly, D. P. (2005). Pgc-1α deficiency causes multi-system energy metabolic derangements: Muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol, 3(4):e101+.  http://www.citeulike.org/user/HEIRS/article/2909101?show_msg=already_posted

Reports on How Stress gets under our skin

Stress gets under our skin ( Everyone experiences social stress w...): "In a new report, UCLA researchers have discovered that how your brain responds to social stressors can influence the body's immune system in ways that may negatively affect health"

The effect of pre- and probiotics on the colonic ammonia metabolism in humans as measured by lactose-[lsqb]15N2[rsqb]ureide

Hmmmm. I thought so....

"The prebiotic intake of FP and WPS lowered the colonic generation and the renal excretion of toxic 15NH3, respectively, when using 15N-LU as a xenobiotic marker."

Read more: European Journal of Clinical Nutrition - Abstract of article: The effect of pre- and probiotics on the colonic ammonia metabolism in humans as measured by lactose-[lsqb]15N2[rsqb]ureide:

Study reveals top functional cherry types

Study reveals top functional cherry types: "A new study investigating the bioactivity of cherry compounds has identified polyphenol-rich varieties that could be ‘promising functional foods’"

Brain's Link Between Sounds, Smells and Memory Revealed | Anxiety Disorders | LiveScience

"Sights, sounds and smells can all evoke emotionally charged memories. A new study in rats suggests why: The same part of the brain that's in charge of processing our senses is also responsible, at least in part, for storing emotional memories."

Read more: Brain's Link Between Sounds, Smells and Memory Revealed Anxiety Disorders LiveScience:

AKT/GSK-3beta/beta-catenin signalling within hippocampus and amygdala reflects genetically determined differences in posttraumatic stress disorder like symptoms.

"Taken together our study identifies lasting changes in the AKT/GSK-3beta/beta-catenin cascade within the hippocampus and amygdala as molecular correlates of genetically determined differences in the severity of PTSD-like symptoms."

CiteULike: AKT/GSK-3beta/beta-catenin signalling within hippocampus and amygdala reflects genetically determined differences in posttraumatic stress disorder like symptoms.:

Supplemental: Resveratrols, a compound found in wine and grapes exert their protective effects against neuronal damage and death are mediated throught this same pathway.

Fukui, M., Choi, H. J. J., and Zhu, B. T. T. (2010). Mechanism for the protective effect of resveratrol against oxidative stress-induced neuronal death. Free radical biology & medicine, 49(5):800-813. http://www.citeulike.org/user/HEIRS/article/7301406
Xi, J., Wang, H., Mueller, R. A., Norfleet, E. A., and Xu, Z. (2009). Mechanism for resveratrol-induced cardioprotection against reperfusion injury involves glycogen synthase kinase 3beta and mitochondrial permeability transition pore. European journal of pharmacology, 604(1-3):111-116. http://www.citeulike.org/user/HEIRS/article/7588469

Endotoxin and Loss of Tolerance via Reduced HO-1: Potential Mechanism in CFS and MCS?

It has been suggested that chemical sensitivity and possibly other environmental illness conditions can be the result of a "loss of tolerance".  Notably, this "loss of tolerance" may be the result of altered signaling of the immune response and contrbuting factors may include the presence of endotoxin which can 1) activate inflammatory responses, 2) reduce the threshold of reactions to allergens and 3) alter gene expression from ROS and alterations in methylation. In addition, endotoxin through activtion of GSK3b provides a mechanism to "deactivate" the antioxidant system, Nrf2. High fat diets and hyperglycemia may also promote the translocation of bacteria in the respiratory and intestinal tract. This may further increase inflammation and promote neuroinflammation in the brain as a consequence of cytokine activity in the intestinal tract and liver. At some point, the break down of the blood brain barrier may increase the likelihood of brain inflammation and changes in behavior and neurotransmission.

A recent study provides support for the hypothesis of "loss of tolerance" in environmental illness because of the role of Nrf2 as a master regulator of detoxification.  Heme oxygease is an antioxidant that is regulated by Nrf2. Naidu explains that past research has demonstrated that HO-1 deficient animals are highly susceptable to toxicity from endotoxin. Further " the potential significance of HO-1 in the adaptive immune system has been implied by a recent report, in which genetic deficiency of HO-1 decreased the suppressive activity of regulatory T cells (8)." This loss of supression could suggest a possible explanation of some symptoms related to environmental illness, especially chemical sensitivity and to some extent chronic fatigue syndrome.  There is debate on the benefits and potential harmful effects of  exercise on the latter and there are now a number of reports that demonstrate that exercise elevates HO-1 expression. On the other hand, it also can lead to an increase of translocation of bacteria that are alway present in the gut, even though the balance of gut may be different at one point vs another. In any event, the effect of exercise on bacteria translocation and HO-1 levels offer an explanation why some patients improve with exercise while others do not. As Naidu explains, there may be multiple pathways for the expession of HO-1 and may be species specific. Interestingly, he does point out that inhibition of the P38 pathway contributes to HO-1 expression at least in this study and this expression occurs via regulation by Nrf2 and reactive species are involved with this activation. This supports other research that blockade of the P38 pathway increases the expression of NO by endotoxin.


Naidu, S., Vijayan, V., Santoso, S., Kietzmann, T., and Immenschuh, S. (2009). Inhibition and genetic deficiency of p38 mapk up-rregulates heme oxygenase-1 gene expression via nrf2. Journal of Immunology, 182:7048-7057.  http://www.citeulike.org/user/HEIRS/article/7586285