Attention all US citizens! Your landscaper, condominium association, apartment maintenance crew or even your neighbor next door may be poisoning you! (read below for new study results)

Although this chemical is allowed for only licensed use, what about the possible cross-contamination????

UA research on fruit flies finds mutations, toxic exposure linked to disease Wednesday, March 07, 2007
DAVE PARKS
News staff writer

Researchers at the University of Alabama have demonstrated with fruit flies that Parkinson's disease can be triggered by a combination of gene mutation and exposure to a common herbicide, according to an article being published today in the Journal of Neuroscience.

The study supports a long-standing belief that Parkinson's disease is caused by a combination of genetic and environmental factors. In addition, the UA study provides scientific evidence that some genetic mutations may make some people more susceptible to very low levels of toxic exposures, and other genetic mutations may actually protect people from toxic exposures.
. . .
Janis O'Donnell, a co-author of the study and a professor of biology at UA, said it was surprisingly simple to find varying levels of toxic susceptibility linked to the genetic makeup of fruit flies.
. . . . . .

The finding could lead to tests for toxins that cause Parkinson's and help pinpoint human genetic variations that are susceptible to the disease. The research also could help scientists design new drugs, she said.

The experiments leading to the discovery were performed at Tuscaloosa over the past few years using fruit flies and the herbicide paraquat, which has been linked to Parkinson's disease through epidemiological studies. The Centers for Disease Control reports that paraquat is one of the most commonly used herbicides in the world. In the United States, paraquat is available for use only by commercially licensed users because of its toxicity.

O'Donnell said researchers first created a lab model in which fruit flies were exposed to the toxin to the point that they essentially developed Parkinson's disease, a condition marked by the death of neurons that produce the neurotransmitter dopamine.

"We developed techniques that gave us specific loss of those neurons," O'Donnell said. "Amazingly, the flies ended up with symptoms that seemed to very accurately replicate those of a Parkinson patient."

The flies developed tremors, difficulty walking and gradually began to lose their balance, she said.
. . . .

Then researchers used the model to test a hypothesis - specific genetic mutations would differ in susceptibility to toxic exposures.

The fruit fly provided a good model for the test because it is neurologically similar to a human, and earlier research identified genes that lead to the production of dopamine.
. . . . .

But genetic makeup made a big difference when the flies were exposed to paraquat. Flies with one type of genetic mutation developed symptoms of Parkinson's at a low level of exposure; flies with no genetic mutation developed symptoms at a higher level of exposure, and flies with another type of genetic mutation developed symptoms at a still higher level of exposure.
. . .

Parkinson's disease is still largely a mystery, she said. Scientists know the cause of only about 10 percent of cases. This experiment provides some insight into why some people may develop the disease while others don't. . . .

It's not much of a scientific leap to say that the research shows that some people are more susceptible to toxic exposures than others.
. . .

For example, men are about twice as likely to develop Parkinson's disease than women, O'Donnell said. "We were amazed to find that we see exactly the same effect in male fruit flies," she said. "The male fruit flies showed symptoms earlier and died more rapidly than the females did - which means, perhaps, that we can exploit this system to help us understand why this discrepancy is there. It's an interesting corollary that surprised us. We didn't expect that degree of parallel."

The experiments raise more concerns about the long-term impact of low-level toxic exposure, she said.

"An individual may have a change in one of these genes that is not normally detectable in family history, in their health, in their behavior, in their overall life span," she said. "But it might be sitting there creating subtle differences in the neurons that alter how they respond to a toxic exposure ... just those subtle daily chemical exposures that we have in our food, in our agricultural products, in our drinking water."

E-mail: dparks@bhamnews.com

http://www.al.com/news/birminghamnew...age=__._,_.___

Also, I find this info from the CDC alarming:

In the United States, paraquat is available primarily as a liquid in various
strengths. It is classified as “restricted use,” which means that it can be used only by people who are licensed applicators.

Because paraquat is highly poisonous, the form of it that is marketed in the United States has a blue dye to keep it from being confused with beverages such as coffee, a sharp odor to serve as a warning, and an added agent to cause vomiting if someone drinks it. Paraquat from outside the United States may not have these safeguards added
source: http://www.bt.cdc.gov/agent/paraquat/basics/facts.asp

Safeguards?????
Peggy

http://www.urmc.rochester.edu/pr/news/archive/park.html

Which one or combination will be next?

Any organic gardeners out there using rotenone? This is a prime example of the "multiple hits" hypothesis that I have been mentioning in a subtle attempt to change the world....<Parkie Personality Alert!> The following is probably one of the most important abstracts we are going to see.

1: Exp Neurol. 2004 Dec;190(2):373-83.

Rotenone potentiates dopamine neuron loss in animals exposed to
lipopolysaccharide prenatally.

Ling Z, Chang QA, Tong CW, Leurgans SE, Lipton JW, Carvey PM.

Department of Pharmacology, Rush University Medical Center, Chicago, IL 60612,
USA. zling@rush.edu

We previously demonstrated that treating gravid female rats with the
bacteriotoxin lipopolysaccharide (LPS) led to the birth of offspring with fewer
than normal dopamine (DA) neurons. This DA neuron loss was long-lived and
associated with permanent increases in the pro-inflammatory cytokine tumor
necrosis factor alpha (TNFalpha). Because of this pro-inflammatory state, we
hypothesized that these animals would be more susceptible to subsequent exposure
of DA neurotoxins. We tested this hypothesis by treating female Sprague-Dawley
rats exposed to LPS or saline prenatally with a subtoxic dose of the DA
neurotoxin rotenone (1.25 mg/kg per day) or vehicle for 14 days when they were
16 months old. After another 14 days, the animals were sacrificed. Tyrosine
hydroxylase-immunoreactive (THir) cell counts were used as an index of DA neuron
survival. Animals exposed to LPS prenatally or rotenone postnatally exhibited a
22% and 3%, respectively, decrease in THir cell counts relative to controls. The
combined effects of prenatal LPS and postnatal rotenone exposure produced a
synergistic 39% THir cell loss relative to controls. This loss was associated
with decreased striatal DA and increased striatal DA activity ([HVA]/[DA]) and
TNFalpha. Animals exposed to LPS prenatally exhibited a marked increase in the
number of reactive microglia that was further increased by rotenone exposure.
Prenatal LPS exposure also led to increased levels of oxidized proteins and the
formation of alpha-Synuclein and eosin positive inclusions resembling Lewy
bodies. These results suggest that exposure to low doses of an environmental
neurotoxin like rotenone can produce synergistic DA neuron losses in animals
with a preexisting pro-inflammatory state. This supports the notion that
Parkinson's disease (PD) may be caused by multiple factors and the result of
"multiple hits" from environmental toxins.

PMID: 15530876 [PubMed - indexed for MEDLINE]

Genes Linked to Parkinson’s Risk Identified in Animal Models

Source: University of Alabama
Released: Tue 06-Mar-2007, 17:25 ET
http://www.newswise.com/articles/view/527921/?sc=rssn

Researchers are offering clues as to why some people appear to have a higher risk of developing Parkinson’s disease following exposure to a widely used chemical weed killer. The research pinpoints three genes within animal models which influence how susceptible they are to developing a Parkinson’s disease-like movement disorder.


Newswise — Researchers at The University of Alabama are offering clues as to why some people appear to have a higher risk of developing Parkinson’s disease following exposure to a widely used chemical weed killer.

The research, publishing in the March 7 edition of the Journal of Neuroscience, pinpoints three genes within animal models which influence how susceptible they are to developing a Parkinson’s disease-like movement disorder, said Dr. Janis O’Donnell, a co-author of the research and a professor of biological sciences at The University of Alabama.

“We found these genes do affect how susceptible these individuals are,” O’Donnell said. “Our hope is we can use this observation to discover other genes that might be influencing how these models, or human beings, might be more or less susceptible to these toxic agents.”

The research focused on select genes that influence dopamine synthesis and the release of dopamine from brain cells. The genes identified include those that regulate tetrahydrobiopterin, a compound that is required to make dopamine, as well as those involved directly in dopamine synthesis.

O’Donnell, and current and former students and post-doctoral researchers working in a UA laboratory with her, studied these genes following the animal model’s exposure to the chemical paraquat, an herbicide commonly used throughout the world.

Previous studies have shown elevated Parkinson’s rates within particular agricultural communities. “It was thought that paraquat might be the causative agent,” O’Donnell said, “because the chemical structure of paraquat looks a lot like dopamine, and perhaps it might confuse the cells. But not everybody that lives in these communities gets Parkinson’s. What is it that’s different about different individuals that would alter their susceptibility?”

The answer now appears, at least in part, to lie within these genes identified by the UA researchers.

O’Donnell and her colleagues use fruit flies, known in biological circles by their scientific name, Drosophila melanogaster, in their research. Flies share with humans, and other mammals, many biochemical similarities, particularly in regard to chemicals produced within their brain cells.

Within the fly’s brain is a distinct type of neurotransmitter, dopamine. Each fly has about 200 neurons within its brain that produce dopamine. The human brain, by contrast, has billions of neurons. The simplicity of the fly’s brain lends itself to manageable tracing of experimental impacts on specific neurons. Yet, there are enough similarities in these animals to make them an acceptable model for studying human disease.

“The flies have dopamine neurons, and these dopamine neurons function much like they do in higher organisms,” O’Donnell said. “Dopamine controls your movement, and it controls the fly’s movement. One of the reasons we study the dopamine pathways in the flies is because the genes involved in this process, the proteins involved, the enzymes that make these chemicals, are virtually identical in human beings and in fruit flies.”

In Parkinson’s disease, a movement disorder affecting some 1 million Americans, neurons in the brain that make dopamine die. Recently, genes associated with some cases of Parkinson’s have been identified, but the root cause of most Parkinson’s disease is not understood. The disease is characterized by rigid and tremoring limbs, difficulty in movement, and impaired reflexes.

Using a specialized microscope, the UA researchers analyzed the flies’ brains after the models had ingested low concentrations of paraquat. Within 12 hours, dopamine neurons within particular regions of the brain began dying. Within 24 hours, many of the dopamine neurons were gone.

“Part of our study was to show that it seems to be, initially at least, specifically those neurons that paraquat impacts and not that it’s just a generic cell killer. Later, all kinds of cells are impacted.”

Visual observations of the flies also revealed paraquat’s impact. After ingesting paraquat, the flies, as video evidence shows, began to tremor. They moved slowly, if at all. “These animals are developing symptoms that almost precisely parallel most of the symptoms that doctors find in Parkinson’s patients.”

That wasn’t the only parallel. “Men seem to be about twice as susceptible to Parkinson’s disease, as women are,” O’Donnell said. “We were amazed to find that we see exactly the same effect in male fruit flies. The male fruit flies show symptoms earlier and die more rapidly than the females did—which means, perhaps, that we can exploit this system to help us understand why this discrepancy is there. It’s an interesting corollary that surprised us. We didn’t expect that degree of parallel.”

Another surprising find came in how mutating genes impacted the experiment’s results. “Under certain conditions, dopamine can react to the extent where it becomes damaging to some of the cell structures. We think of these dopamine neurons as being more susceptible to this kind of damage, called oxidative damage, because they have more dopamine.”

However, in the study, flies with a mutated gene that made too little dopamine became very susceptible to paraquat while mutants who made too much dopamine were resistant.

In some cases, flies with a particular mutated gene showed no neuron damage despite ingesting the paraquat.

“That’s exciting because it tells us that perhaps there are ways to exploit this, to identify different ways that people could be treated to help slow down the progress of this disease. By the time you discover a person has Parkinson’s disease, they have lost so many neurons, it’s almost impossible to reverse the trend. If you could predict it in advance, perhaps there would be some sort of therapy that could be applied to help protect those individuals.”

The lead author of the study, parts of which were initially funded by NASA and the National Institutes of Health, is Dr. Anathbandhu “Andy” Chaudhuri, a former post-doctoral researcher at UA. Current UA graduate students Kevin Bowling, Hakeem Lawal and Arati Inamdar are co-authors, as are UA graduates Christopher Funderburk and Zhe Wang.

“The importance to me,” O’Donnell said of the study, “is that it is setting the stage for a more detailed study of how all these genes interact together. There is so much that we don’t know yet about how the genes are functioning in particular parts of the brain and how they interact with the environment. We’re interested to know if there are other important genes that are helping to regulate this, and, if there are, those would be possible targets that human geneticists would be interested in investigating.”

http://www.ourtoxicearth.com/warning.htm

I'd better go see if all my links still work.

michael b.

I have seen this info. a few times in the past. I find it interesting in light of my history with PD. My father was a farmer in the Midwest and was dx with PD around 1976. He died in 1991. I can recall vividly when Paraquat was in the news and my dad took me to the barn to show me the sacks of it he had and was using. I don't know if he used maneb. He grew mainly corn and soybeans.

I was dx in 1998. I think my PD was caused by a combination of things, two of which are the exposure to chemicals and the genetic link. I know of two farmers within twenty miles of our farm who developed PD. I haven't lived on the farm full time since 1963, but would spend summers there and worked in the fields quite a bit.

To complicate this a bit---in 1994, I was dx with NHLymphoma and received 8 rounds of chemo. I relapsed in 2002 and had Rituxan (monoclonal antibody) and in a couple years was back in remission. My take on this is I think I would have developed PD anyway, and the chemo, etc. just sort of "jump-started" it all. Both my PD and lymphoma are the slow growing type, so I'm lucky with that.
mari-mari

Is agricultural dust, particularly seed dust from corn, wheat, etc. It has an unusually high amount of LPS toxin in it which triggers inflammation and opens the BBB PLUS it synergizes with the chemicals much of the time.

1: Occup Environ Med. 2006 Jan;63(1):59-67.

Agricultural seed dust as a potential cause of organic dust toxic syndrome.

Smit LA, Wouters IM, Hobo MM, Eduard W, Doekes G, Heederik D.

Institute for Risk Assessment Sciences, Division of Environmental and
Occupational Health, Utrecht University, Utrecht, The Netherlands.
L.Smit@iras.uu.nl

AIMS: Episodes of serious work related health problems resembling organic dust
toxic syndrome (ODTS) in workers of a grass seed quality inspection laboratory
prompted the authors to study personal endotoxin exposure levels in this
facility and in the agricultural seed processing industry. In addition,
microbial and inflammatory characteristics of agricultural seeds were studied.
METHODS: The authors assessed inhalable dust and endotoxin levels in 101 samples
from 57 workers in grass, cereal, and vegetable seed plants who were handling
mainly grass seeds as bulk product, and horticulture seeds in smaller
quantities. Additionally, real-time dust exposure was measured using a DataRAM
monitor in 12 grass seed workers to obtain more information on exposure patterns
during specific tasks. Endotoxin concentrations in seed extracts were determined
by LAL assay and seed samples were analysed by scanning electron microscopy.
Release of inflammatory cytokines was measured in supernatants of whole blood
samples stimulated with lipopolysaccharide (LPS) or agricultural seed extracts
in a human whole blood assay (WBA). RESULTS: Endotoxin concentrations in
personal samples were high (geometric mean 1800 EU/m3), particularly in the
grass seed quality inspection lab where endotoxin levels up to 274 000 EU/m3
were measured. The recommended health based endotoxin exposure limit of 50 EU/m3
was amply exceeded in almost all personal samples. Job tasks dumping and mixing
were associated with highest dust and endotoxin exposures, which was confirmed
by real-time measurements. Microbial infestation was found in almost all seed
samples. WBA results showed that most seed extracts were capable of inducing a
pronounced dose dependent cytokine release. CONCLUSIONS: Workers handling grass,
cereal, or vegetable seeds are at risk of exposure to high levels of endotoxin
containing seed dust. Occupational exposure to inhalable agricultural seed dust
can induce inflammatory responses, and is a potential cause of ODTS.

PMID: 16361407 [PubMed - indexed for MEDLINE]

Neurology, august, 2006, report concerning a genetic variation for coding 3 specific detoxifying enzymes that are directly responsible for metabolizing statin drugs and other pharmeceutical agents and for detoxifying both pesticides and nerve gases.
exposure to these environmental factors--statins, nerve gas and pesticides--in individuals with these genetic variations may be a risk factor for developing the neuromuscular diseases associated with PON gene cluster variants.

http://www.sciencedaily.com/releases...0705185155.htm

Source: Northwestern University
Date: July 6, 2006

Variations In Detoxifying Genes Linked To Lou Gehrig's Disease
Genetic variations in three enzymes that detoxify insecticides and nerve gas agents as well as metabolize cholesterol-lowering statin drugs may be a risk factor for developing sporadic amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), and possibly responsible for a reported twofold increased risk of ALS in Gulf War veterans.

These findings, from a study led Teepu Siddique, M.D., and colleagues at Northwestern University, open the door to investigating gene-environment interactions as a cause of ALS and other illnesses and to the development of molecular targets for specific treatments. The study was published in the August 22 online issue (available now) of the journal Neurology.

Siddique is Les Turner ALS Foundation/Herbert C. Wenske Professor, Davee Department of Neurology and Clinical Neurosciences, professor of cell and molecular biology and director of the Neuromuscular Disorders Program at Northwestern University Feinberg School of Medicine.

ALS is a complex neurodegenerative disorder of the motor neurons that results in muscle weakness, difficulty speaking, swallowing and breathing and eventual total paralysis and death generally within five years.

In 1993 Siddique and collaborators determined that mutations in a gene known as SOD1 account for 20 percent of familial, or inherited, ALS (2 percent of all cases of ALS). However, the cause of sporadic ALS is still unknown.

In earlier research Siddique and other researchers hypothesized that sporadic ALS is modulated by variations in multiple genes interacting with each other and environmental exposures.

The genes for human paraoxanases (PON 1, PON 2 and PON 3), which are located on chromosome 7q21.3, code for the production of detoxifying enzymes involved in the metabolism of a variety of drugs, organophosphate insecticides, such as parathion, diazinon and chlorpyrifos, and nerve gas agents such as sarin.

Previous research described a possible twofold increased risk for developing ALS in veterans of the Gulf War, indicating a war-related environmental exposure to organophosphates and sarin in genetically susceptible individuals as a possible cause.



PON gene cluster variants have previously been associated with other neurodegenerative and vascular disorders, including Alzheimer's disease, Parkinson's disease, coronary artery disease and stroke.



Although the Northwestern DNA study samples were not analyzed for inclusion of Gulf War veterans, Siddique and co-researchers found significant evidence that gene variations (polymorphisms) on the chromosome region encompassing PON2-PON3 were strongly associated with sporadic ALS.

“Thus, single nucleotide polymorphism genotyping in the intergenic regions of the PON gene cluster, and replication, gene expression, gene-gene interaction and PON serum/enzymatic studies may help elucidate the complexity of PON cluster association with ALS,” Siddique said.

Siddique hopes to study DNA samples from Gulf War veterans with increased incidence of sporadic ALS and has applied for their DNA from the Veterans Administration collection.

Collaborating with Siddique on this research were Mohammad Saeed, M.D.; Nailah Siddique; Wu-Yen Hung; Elena Usacheva; Erdong Liu, M.D.; Robert L. Sufit, M.D.; Scott L. Heller, M.D., Northwestern University Feinberg School of Medicine; Jonathan L. Haines, Vanderbilt University Medical Center; and Margaret Pericak-Vance, Duke University Medical Center.

This study was supported by grants from the National Institute of Neurological Disorders and Stroke; Les Turner ALS Foundation; V. E. Schaff ALS Research Trust; Wenske Foundation; Harold Post Professorship; Les Turner ALS Foundation/Herbert C. Wenske Foundation Professorship; Falk Foundation Fund; and The David C. Asselin M.D., Memorial Fund.

It seems that Paraquat has another chemical in the same family. It is Diquat. Here is what pub med says about it:

It seems to me that chemicals in the same family should have similar effects Since Rotenone's mode of action is Oxidation Phosphorylation Inhibitor, while Paraquat and Diquat perform by destroying the integrity of the cell membrane, we could begin to identify toxins with similar structure and mode of action and test those first to see if Parkinson's develops.

OR maybe we should just start eating fruit healthy flies in order to obtain their genetic information



michael b.

one of the questions a neurologist whom we consulted was if we live on a golf course (we do not) or if my husband plays golf--which he does on a regular basis during golf season if either or both of our sons wish to play. she advised they not play the day the course is "sprayed" and to find out the pesticides used to determine if they are the ones implicated in PD, suggesting the product could be changed if needed. I had forgotten all about this "to do" task until this thread prompted my memory (In our case, having a caretaker along, listening to what the physician has to say does not necessarily mean someone will retain the information!)