In a study with important consequences for studies on the effects of chemicals on steroid responses in humans, a team of French and American scientists, including Michael E. Baker, PhD, professor in UC San Diego’s Department of Medicine, Division of Nephrology-Hypertension, have found that – contrary to earlier assumptions – enzymes used for the synthesis of steroids in insects, snails, octopuses and corals are unrelated to those used in humans. 

The research, led by a team at the Université de Lyon, ENS Lyon, provides insight into the evolution of steroid hormone signaling and the relationship of steroid synthesis to enzymes that detoxify harmful chemicals in the environment. Their findings will be published the week of June 29, 2009 in the advance online publication of the Proceedings of the National Academy of Sciences (PNAS.) 

“The toxic effects of chemicals on snails and corals remain a major area of environmental concern,” said Vincent Laudet, professor in the Institute of Functional Genomics of Lyon, Division of Molecular Zoology. “For a long time, it has been thought that many invertebrate animals share with humans the same steroid hormones and enzymes that synthesize steroids. However, our research indicates that the method by which toxic chemicals effect the steroid hormone signaling of snails, corals, insects and other invertebrates can’t be extrapolated to human disease.” 

Steroids hormones are key to many vital physiological responses in humans, ranging from anti-inflammatory agents to regulating events during pregnancy. They are also the target of many chemical pollutants, known as endocrine disruptors. As part of a program to understand the evolution of steroid hormone signaling, Laudet – along with Gabriel Markov, a student in the Institute of Functional Genomics, initially trained by Raquel Tavares at Université de Lyon, characterized the evolutionary relationships between proteins that synthesize steroids in animals. They traced the origin of such enzymes from vertebrates, insects, snails and jelly fish and interpreted these results through extensive discussions with Baker, Chantal Dauphin-Villemant at Université Paris 6, and Barbara Demeneix from the National Museum of Natural History in Paris. 

Through an analysis of several invertebrate genomes, the scientists discovered that snails and insects utilize steroid-synthesizing enzymes that are not vertebrate–related, but instead belong in an invertebrate family. Moreover, these invertebrate steroidogenic enzymes have a strong evolutionary connection to enzymes that detoxify chemicals (called xenobiotics). 

This unexpected finding led them to hypothesize that these steroid-synthesizing enzymes arose independently from specific pathways used by snails and worms for detoxifying environmental chemicals. 

“This finding shows that, if we want to really understand the effects of environmental chemicals on steroid synthesis in snails, worms, octopuses and such animals, we must switch from a human-centered viewpoint to snail-centered viewpoint. This is the best way to accumulate knowledge that could be useful to human health,” said Laudet, adding that this emphasizes the need for more cross-disciplinary studies between toxicologists, endocrinologists and zoologists.  

Reference: University of California – San Diego, PR Toxic chemicals affect steroid hormones differently in humans and invertebrates, June 29, 2009

Hope for Patients with environmental illnesses? Bill to Fund Neuroendocrine Immune Disorder Center of Excellence in New Jersey 

The New Jersey Assembly has unanimously passed Assembly Resolution 202 to fund a Center of Excellence in New Jersey for Chronic Neuroendocrine Immune Disorders – which include CFS, FM, MCS and related illnesses. The bill is now going to the New Jersey House as Senate Resolution 133. 

The Research Center would be dedicated to ME/CFS, Fibromyalgia, Gulf War Illness, Lyme disease, Multiple Chemical sensitivity and other environmental illnesses 

SENATE RESOLUTION No. 133

STATE OF NEW JERSEY

213th LEGISLATURE

INTRODUCED JUNE 22, 2009

Sponsored by: 

Senator CHRISTOPHER “KIP” BATEMAN

District 16 (Morris and Somerset)

Senator LORETTA WEINBERG

District 37 (Bergen)

SYNOPSIS

Urges Governor and memorializes Congress to encourage establishment of research center in New Jersey dedicated to chronic neuroendocrine immune disorders.  

CURRENT VERSION OF TEXT

As introduced. 

A Senate Resolution urging the Governor and memorializing Congress to encourage the establishment of a research center in New Jersey dedicated to chronic neuroendocrine immune disorders. 

Whereas, Neuroendocrine immune disorders (NEIDs) currently include Chronic Fatigue Syndrome/Myalgic Encephalopathy, Fibromyalgia, Gulf War illness, Lyme disease, Multiple Chemical Sensitivity Syndrome, and other environmental illnesses; and 

Whereas, Chronic Fatigue Syndrome/Myalgic Encephalopathy, Fibromyalgia, Gulf War illness, Lyme disease, and Multiple Chemical Sensitivity Syndrome have been characterized as being as disabling as Chronic Obstructive Pulmonary disease, End-stage Renal failure, and Rheumatoid Arthritis; and as life-impairing as Multiple Sclerosis, AIDS, and cancer chemotherapy treatments; and 

Whereas, The mechanisms of transmission of NEIDs include parasite-borne infections; and 

Whereas, The similarity of symptoms of NEIDs imply a common pathophysiology of these illnesses; therefore, discoveries and advances made in the etiology and treatment of any one of these illnesses will be applicable and beneficial to the other NEIDs because of their common pathophysiology; and 

Whereas, An estimated 20 million American adults and children suffer with NEIDs; and 

Whereas, The time from illness onset to diagnosis of NEIDs is approximately three to seven years, except for Lyme disease which may take decades to diagnose; and

Whereas, There is mounting evidence of similarities of presentation and origins of NEIDs with Autism, Alzheimer’s disease, Multiple Sclerosis, Lupus, Parkinson’s and other autoimmune diseases; and   

Whereas, Having a research center in this State is essential to: promoting research into the etiology of, and therapeutic interventions for, NEIDs; establishing treatment protocols and providing patient care for all individuals in the State of New Jersey afflicted with NEIDs; serving as a repository for NEIDs research data, patient data and research publications; serving as a resource for NEIDs researchers by sponsoring scientific meetings and encouraging discourse among researchers; serving as a tertiary resource for both physicians and patients in their efforts to manage NEIDs; and advancing both NEIDs research and patient care by disseminating the most recent advances in NEIDs research, diagnostics and treatment protocols; now, therefore,

Be It Resolved by the Senate of the State of New Jersey:

1.    This House urges the Governor to encourage the establishment of a research center in this State dedicated to chronic neuroendocrine immune disorders. 

2.    This House respectfully memorializes Congress to encourage the establishment of a research center in this State dedicated to chronic neuroendocrine immune disorders. 

3.    Duly authenticated copies of this resolution, signed by the President of the Senate and attested by the Secretary thereof, shall be transmitted to: 

a.     Governor Corzine and the Commissioner of Health and Senior Services; and

b.    The Majority and Minority Leaders of the United States Senate, the Speaker and

Minority Leader of the United States House of Representatives, and to every member of the United States Congress from this State.

STATEMENT

This resolution urges the Governor and respectfully memorializes Congress to encourage the establishment of a research center in New Jersey dedicated to understanding and treating chronic neuroendocrine immune illnesses (NEIDs) such as Chronic Fatigue Syndrome/Myalgic Encephalopathy (CFS/ME), Fibromyalgia, Gulf War illness, Lyme disease and Multiple Chemical Sensitivity Syndrome. 

It is estimated by the Centers for Disease Control and Prevention (CDC) that CFS/ME affects between one and four million Americans and that 85% of individuals suffering with this debilitating and disabling illness have not been properly diagnosed.  The economic impact and loss of worker productivity in the United States due to CFS/ME, alone, is estimated to be over $9 billion per year.  Census data, and the incidence rate of CFS in the United States, projects that an estimated 28,000 to 30,000 citizens of New Jersey will suffer from CFS/ME.  The symptoms of CFS/ME include flu-like symptoms (sore throat, fever, chills, tender neck and armpit lymph nodes, unrefreshing or non-restorative sleep, headaches, and post-exertional malaise lasting more than 24 hours), as well as body-wide muscle and joint pain, cognitive impairment, and short term memory loss. 

The CDC reports that Fibromyalgia (FM) affects five million women, men, and children in the United States.  FM is a condition characterized by body-wide muscle pain, tender points, sleep disturbance, cognitive impairment (“fibro-fog” or “brain fog”), overwhelming fatigue, swelling, joint pain, non-restorative sleep and migraine headaches. 

According to the Research Advisory Committee on Gulf War Veterans’ Illnesses, Gulf War illness (GWI) is estimated to affect between 175,000 to 200,000 U.S. veterans, some of whom have been suffering for over 17 years.  GWI is characterized by multiple, diverse symptoms that include a combination of memory and concentration problems, chronic headache, unexplained fatigue, widespread pain, chronic digestive problems, respiratory symptoms, and skin rashes. 

The CDC has announced that Lyme disease is the fastest-spreading infectious disease in the United States, and that New Jersey ranks third in the nation for reported cases of Lyme disease. Yet, Lyme disease is seriously underreported in the United States.  Current literature suggests that co-infections associated with Lyme disease play a major role in precipitating chronic illness with symptoms that include flu-like symptoms, extreme fatigue, skin rashes, unexplained weight gain or loss, other endocrine disorders, urinary problems, sexual and reproductive dysfunction, gastrointestinal dysfunction, heart problems, joint pain or swelling, muscle twitching and muscle pain, peripheral neuropathy, vision and/or hearing problems, disorientation, psychiatric disorders, cognitive dysfunction, disturbed sleep, and poor balance. 

Multiple Chemical Sensitivity Syndrome and other environmental illnesses are estimated to affect 10% of the American population.  These illnesses have a variable, and overlapping presentation with other NEIDs, and have symptoms that include any combination of extreme fatigue/lethargy, muscle/joint pain, sleep disturbances, headaches/migraine headaches, sensitivity to light and noise, dizziness/vertigo, poor memory/poor concentration, nausea/digestive problems, sore throat, constant coughing, wheezing, skin rashes or burning/stinging eyes.

Many parents worry about their child’s exposure to phthalates, the chemical compounds used as plasticizers in a wide variety of personal care products, children’s toys, and medical devices. Phthalate exposure can begin in the womb and has been associated with negative changes in endocrine function. A new study soon to be published in the Journal of Pediatrics examines the possibility that in utero phthalate exposure contributes to low birth weight in infants. Low birth weight is the leading cause of death in children under 5 years of age and increases the risk of cardiovascular and metabolic disease in adulthood.  

To investigate the associations between in utero phthalate exposure and low birth weight, Dr. Renshan Ge of the Population Council and colleagues from Fudan University and Second Military Medical University in Shanghai studied 201 pairs of newborns and their mothers between 2005 and 2006. Of the 201 infants studied, 88 were born with low birth weight. The researchers analyzed samples of the infants’ meconium, the first bowel movement that occurs after birth, and cord blood to determine phthalate levels.  

They found quantifiable levels of phthalate and phthalate metabolites in more than 70% of the samples. Infants with low birth weight had consistently higher levels of phthalates. According to Dr. Ge, “The results showed that phthalate exposure was ubiquitous in these newborns, and that prenatal phthalate exposure might be an environmental risk factor for low birth weight in infants.” Although these associations are not conclusive, this study supports the accelerating efforts to minimize phthalate exposure. 

Reference: The study, reported in “Phthalate Levels and Low Birth Weight: A Nested Case-Control Study of Chinese Newborns” by Zhang Y, PhD, Lin L, MD, Cao Y, PhD, Chen B, MD, Zheng L, MSC, Ge R, MD, appears in the Journal of Pediatrics, DOI 10.1016/j.jpeds.2009.04.007, published by Elsevier. EurekAlert, June 25, 2009.

Just like Germany, Austria is now classifying Chemical Sensitivity / MCS – Multiple Chemical Sensitivity as a physical disease under the code T78.4 of the ICD-10 (the register of diseases). The news comes from a recent letter by the Department of Health of the Austrian Government.

MCS in the ICD-10 in Germany

In a letter dated September 4, 2008 the DIMDI, the Cooperation Partner for Germany of the WHO, wrote that MCS – Multiple Chemical Sensitivity was classified in the register ICD-10 GM which is valid in Germany:

MCS – Multiple Chemical Sensitivity

T78.4…Allergy, not otherwise specified;

Chapter 19 (Injuries, Intoxication and certain other outcomes), Article T66-T78 (Other and unspecified injuries caused by external causes).

MCS in Austria recognized as physical disease

With a letter dated June 24, 2009 regarding “Chemical Sensitivity / MCS – Multiple Chemical Sensitivity (T78.4)”, the Department of Health of the Austrian Government declares that:

In response to your letter dated 4/14/2009 to the Minister of Health Mr. Stoerger, we inform you that the WHO ICD-10 Code modified for Germany from DIMDI is used in Austria as well.

Also in Austria MCS is not a psychological disease

It should be emphasized that the German Institute for Medical Documentation and Information (DIMDI) declared explicitly that there is not any allocation of MCS in Chapter 5 (Mental and behavioural disorders) of the ICD-10-GM. Thus, the debate about MCS as mental illness is at an end.

In Germany doctors who document the diagnosis and the hospital administrations work under the Social Security Code V, which states that the diagnoses have to be made according to the systematic list of ICD-10-GM. Thus, the ICD-10 classification is legally binding.

The Department of Health of the Austrian Government refers in the letter that MCS – Multiple Chemical Sensitivity is recognized in Austria as a physical disease, because also there it will have the code T78.4 in the ICD-10.

Author: Silvia K. Müller, CSN – Chemical Sensitivity Network, 26. June 2009

References:

Bundesministerium für Gesundheit, Chemikalien-Sensitivität / MCS – Multiple Chemical Sensitivity (ICD-10 T78.4), 24.06.2009, Wien, Österreich.

DIMDI Letter to CSN, MCS ICD-10, 04.09.2008

DIMDI Letter, 04.09.2008

Manufactured nanoparticles can be toxic via interactions with proteins and enzymes. Acetylcholinesterase (AChE) is a key enzyme present in the brain, blood and nervous system. Therefore, adsorption and inhibition of AChE by eight nanoparticles, SiO(2), TiO(2), Al(2)O(3), Al, Cu, Cu-C (carbon-coated copper), multi-walled carbon nanotubes (MWCNT) and single-walled carbon nanotubes (SWCNT), were examined.

A modified Ellman assay was used to measure AChE activity because nanoparticles could adsorb the yellowish product, 5′-mercapto-2′-nitrobenzoic acid (5-MNBA) during the color development. Adsorption and inhibition rates by nanoparticles were estimated by decrease of AChE activities compared to controls.

Carbon nanotubes had high affinity for AChE adsorption, the highest being SWCNT (94%). Nano SiO(2) and Al(2)O(3) showed the lowest adsorption. Inhibition by the tested nanoparticles was primarily caused by adsorption.

However, Cu(2+) release in Cu and Cu-C nanoparticle suspensions caused 40% and 45% of AChE activity reduction, respectively. AChE inhibition by bulk Cu and activated carbon particles was also measured for comparison, showing that the inhibition by bulk particles was lower than their counterpart nanoparticles. For bulk Cu particles, AChE inhibition was primarily caused by dissolved ions, but mainly by adsorption for activated carbon.

AChE inhibition by Cu, Cu-C, MWCNT and SWCNT had dose-response relationships, and their median inhibitory concentrations (IC(50)) were 4, 17, 156 and 96mgL(-1), respectively, showing that these nanoparticles may have neurotoxicity and AChE may have potential to be used as a biomarker for nanoparticles.

Reference: Wang Z, Zhao J, Li F, Gao D, Xing B., Adsorption and inhibition of acetylcholinesterase by different nanoparticles, College of Environmental Science and Engineering, Ocean University of China, Qingdao 266100, China, Chemosphere. 2009 Jun 18.