Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic circulatory, neurological, hematological, gastrointestinal, reproductive and immunological pathologies.  

The mechanism of lead induced toxity is not fully understood. The prime targets to lead toxicity are the heme synthesis enzymes, thiol-containing antioxidants and enzymes (superoxide dismutase, catalase, glutathione peroxidase, glucose 6-phosphate dehydrogenase and antioxidant molecules like GSH). The low blood lead levels are sufficient to inhibit the activity of these enzymes and induce generation of reactive oxygen species and intensification oxidative stress.  

Oxidative stress plays important role in pathogenesis of lead-induced toxity and pathogenesis of coupled disease. The primary target of lead toxicity is the central nervous system. There are different cellular, intracellular and molecular mechanisms of lead neurotoxicity: such as induction of oxidative stress, intensification of apoptosis of neurocites, interfering with Ca(2+) dependent enzyme like nitric oxide synthase.  

Population studies have demonstrated a link between lead exposure and subsequent development of hypertension and cardiovascular disease. The vascular endothelium is now regarded as the main target organ for the toxic effect of lead. Lead affects the vasoactive function of endothelium through the increased production of reactive oxygen species, inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species, leading to a limiting nitric oxide availability, impairing nitric oxide signaling.  

This review summarizes recent findings of the mechanism of the lead-induced toxity and possibilities of its prevention. 

Reference:  Nemsadze K, Sanikidze T, Ratiani L, Gabunia L, Sharashenidze T., Mechanisms of lead-induced poisoning, Tbilisi State Medical University; National Center of child development, Georgian Med News. 2009 Jul-Aug;(172-173):92-6.

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.

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.

Tobacco is an important cash crop of Pakistan. Pesticides are commonly used to increase the crop yield, but their health impact has not been studied yet.  

The objectives of the study were to determine the frequency of pesticide poisoning and to explore the knowledge, attitudes and practices (KAP) towards safety measures among the tobacco farmers in Swabi, Pakistan.  

One hundred and five tobacco farmers involved in pesticide application were randomly selected from two villages of district Swabi. A structured questionnaire was used for clinical and KAP information. Plasma cholinesterase (PChE) levels were measured by Ellman’s method by using GD Italy kits. All tobacco farmers were males with a mean (SD) age of 26 (9) years.  

The majority of the farmers reported multiple symptoms headache, dizziness, vomiting, shortness of breath, muscle weakness and skin rash correlate with the clinically significant depression of PChE levels. 

Out of 105 pesticide applicators, 58 (55%) had post-exposure reduction in PChE levels <20% from baseline, 35 (33%) had mild poisoning (20-40% reduction) and 12 (11%) had moderate poisoning (>40% reduction).  

Most of the farmers did not use any personal protective equipment during pesticide handling. Only a few used shoes (31%), masks (14%) and gloves (9%) during pesticide spray.  

In conclusion, the tobacco farmers had mild to moderate pesticide poisoning, which was correlated with depression in PChE levels. Moreover, most farmers had little knowledge about the safety measures, casual attitude and unsatisfactory safety practices with regard to the use of basic protective equipments during pesticide applications on the tobacco crop. 

Reference: Khan DA, Shabbir S, Majid M, Naqvi TA, Khan FA., Risk assessment of pesticide exposure on health of Pakistani tobacco farmers, aDepartment of Pathology, Army Medical College, NUST, Rawalpindi, Pakistan, Journal of Exposure Science and Environmental Epidemiology advance online publication, 17 June 2009; doi:10.1038/jes.2009.13.

The chemical bisphenol A, commonly found in many plastic household items, has been linked to yet another health problem in animals—an increased frequency of arrhythmias, or , a new study found. The results, seen only in females, will be presented Saturday at The Endocrine Society’s 91st Annual Meeting in Washington, D.C.

Past animal studies show that bisphenol A, or BPA, can have harmful effects on the reproductive, nervous and immune systems. Also, a study in humans reported last year found an increased prevalence of cardiovascular disease in people with high levels of BPA in the urine.

However, the effects of BPA on the heart are unknown, said study co-author Scott Belcher, PhD, associate professor in the University of Cincinnati’s Department of Pharmacology and Cell Biophysics.

In the new study, funded by the National Institutes of Health, the University of Cincinnati researchers found that low-dose BPA and estrogen can act alone or in combination to increase harmful arrhythmias in female rats and mice. Because BPA has properties similar to the main female hormone estrogen, it is considered an “environmental estrogen.”

Mice and rats in the study had normal heart rhythms at baseline, before administration of BPA or estrogen (estradiol), Belcher said. The investigators studied heart rhythms in both the working heart and in cultured heart muscle cells. In both models, exposure to BPA increased the frequency of arrhythmias, compared to baseline, in females but not in male animals, the authors found. Administration of estrogen alone also increased the frequency of arrhythmias in females.

Arrhythmias were most frequent in the female rats and mice when they received both BPA and estrogen, at levels normally found in female humans.

“We have identified a new possible risk for female heart health, caused by increased levels of estrogens in the body and exposure to the environmental estrogen BPA,” Belcher said.

BPA is found in polycarbonate-plastic baby bottles, refillable water bottles and food containers as well as the linings of metal food cans. Last year the U.S. Food and Drug Administration said more research on the safety of BPA is needed.

Arrhythmias occur when the heart beats too slowly or too fast or when it skips heartbeats. These heart rhythm irregularities can cause fatigue, lightheadedness, fainting or sudden cardiac death. If a fast heart rate affects the heart’s ability to pump, it can cause a heart attack.

The study’s lead author, Hong-Sheng Wang, PhD, assistant professor at the University of Cincinnati, will present the results.

Reference: The Endocrine Society, Bisphenol A exposure increases risk of abnormal heart rhythms in female rodents, 10-Jun-2009