Kathy
Well-known member
Toxicol Appl Pharmacol. 2005 Sep 1;207(2):112-24.
Chlorpyrifos exerts opposing effects on axonal and dendritic growth in primary neuronal cultures.
Howard AS, Bucelli R, Jett DA, Bruun D, Yang D, Lein PJ.
Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Evidence that children are widely exposed to organophosphorus pesticides (OPs) and that OPs cause developmental neurotoxicity in animal models raises significant concerns about the risks these compounds pose to the developing human nervous system. Critical to assessing this risk is identifying specific neurodevelopmental events targeted by OPs. Observations that OPs alter brain morphometry in developing rodents and inhibit neurite outgrowth in neural cell lines suggest that OPs perturb neuronal morphogenesis. However, an important question yet to be answered is whether the dysmorphogenic effect of OPs reflects perturbation of axonal or dendritic growth. We addressed this question by quantifying axonal and dendritic growth in primary cultures of embryonic rat sympathetic neurons derived from superior cervical ganglia (SCG) following in vitro exposure to chlorpyrifos (CPF) or its metabolites CPF-oxon (CPFO) and trichloropyridinol (TCP). Axon outgrowth was significantly inhibited by CPF or CPFO, but not TCP, at concentrations > or =0.001 microM or 0.001 nM, respectively. In contrast, all three compounds enhanced BMP-induced dendritic growth. Acetylcholinesterase was inhibited only by the highest concentrations of CPF (> or =1 microM) and CPFO (> or =1 nM); TCP had no effect on this parameter. In summary, these compounds perturb neuronal morphogenesis via opposing effects on axonal and dendritic growth, and both effects are independent of acetylcholinesterase inhibition. These findings have important implications for current risk assessment practices of using acetylcholinesterase inhibition as a biomarker of OP neurotoxicity and suggest that OPs may disrupt normal patterns of neuronal connectivity in the developing nervous system.
PMID: 16102564 [PubMed - indexed for MEDLINE]
ie: measurement of acetylcholinesterase inhibition is not identifying all the methods by which OPs affect the nervous system, yet it is the current biomarker for OP toxicity. Not good enough!
At an Autism conference in Calgary on January 19/07 (with many good speakers), one speaker was bold enough to mention the damaging neurotoxic effects of organophophates (OPs).
During a private conversation with this doctor, from Phoenix, AZ, she revealed to me that many of her autistic patients do no show heavy loads of mercury in their chelate profiles. They do, however, show heavy loads of uranium. She has always wondered where these patients could have possibly come into contact with uranium (they do not live near any mines). Sadly, it is probably the case that these children are being exposed to the uranium via any one, or combination of the following:
-uranium fallout from atmospheric testing (much of which took place next door in Nevada.
-uranium fallout from manufacture or testing of Depleted Uranium weapons, and other nuclear weapons.
-parents working at facilities that process uranium, store nuclear waste, or military bases where weapons are kept.
She also stated that the majority of certain types of OPs used in the USA, are used in-side households to kill bugs. The developing fetus and young brain, she stated, is particularly susceptible to the neurotoxic effects of OPs.
Are we to blindly ignore the neurotoxic effects to livestock? The methods of neurotoxicity of OPs are not limited to inhibition of acetylcholinesterase, as the first study demonstrated. Multi-factoral disease processes all depend on exposure to what, when and how much, and via which exposure route(s) (inhalation, ingestion, absorption).
The co-inciding use of OPs, at rates never used before (ie: extremely high concentrations) for the UK warble eradication program STARTING in 1982 cannot be ignored in its relationship to their massive BSE cases. Other european countries also used OPs at high concentrations during this time frame.
OPs are used to spray crops which deer and other wildlife freely wander through. While exposure alone (of a healthy animal), is not enough to cause CWD, it is a contributing factor which can push a weakened animal over the top, creating all kinds of neurotoxic damage and oxidative stress.
OPs are also used to spray fruit crops which are often located near communities. Spray drift is another method of exposure to OPs and other chemicals.
One mother at the Autism symposium who lives on an acreage stated she won't grow her own garden because she is surrounded by crop land which the farmer sprays several times a year. She is concerned the veggies in a garden would be contaminated. She should also be concerned that they are inhaling these chemicals.
I met some very interesting and hard working people at this conference. There was alot of hope for treatment of Autism with various therapies, they included: injections of methyl cobalamine (Vitamin B12), digestive enzymes and acidophilus (re-establishing the good bacteria in the gut).
When it comes down to the nitty gritty, human biology is not all that different from other mammals. Toxicity of any substance is enhanced when the proper mechanisms to deal with the chemicals, metals, oxidative stress are lacking or completely gone.
Chlorpyrifos exerts opposing effects on axonal and dendritic growth in primary neuronal cultures.
Howard AS, Bucelli R, Jett DA, Bruun D, Yang D, Lein PJ.
Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Evidence that children are widely exposed to organophosphorus pesticides (OPs) and that OPs cause developmental neurotoxicity in animal models raises significant concerns about the risks these compounds pose to the developing human nervous system. Critical to assessing this risk is identifying specific neurodevelopmental events targeted by OPs. Observations that OPs alter brain morphometry in developing rodents and inhibit neurite outgrowth in neural cell lines suggest that OPs perturb neuronal morphogenesis. However, an important question yet to be answered is whether the dysmorphogenic effect of OPs reflects perturbation of axonal or dendritic growth. We addressed this question by quantifying axonal and dendritic growth in primary cultures of embryonic rat sympathetic neurons derived from superior cervical ganglia (SCG) following in vitro exposure to chlorpyrifos (CPF) or its metabolites CPF-oxon (CPFO) and trichloropyridinol (TCP). Axon outgrowth was significantly inhibited by CPF or CPFO, but not TCP, at concentrations > or =0.001 microM or 0.001 nM, respectively. In contrast, all three compounds enhanced BMP-induced dendritic growth. Acetylcholinesterase was inhibited only by the highest concentrations of CPF (> or =1 microM) and CPFO (> or =1 nM); TCP had no effect on this parameter. In summary, these compounds perturb neuronal morphogenesis via opposing effects on axonal and dendritic growth, and both effects are independent of acetylcholinesterase inhibition. These findings have important implications for current risk assessment practices of using acetylcholinesterase inhibition as a biomarker of OP neurotoxicity and suggest that OPs may disrupt normal patterns of neuronal connectivity in the developing nervous system.
PMID: 16102564 [PubMed - indexed for MEDLINE]
ie: measurement of acetylcholinesterase inhibition is not identifying all the methods by which OPs affect the nervous system, yet it is the current biomarker for OP toxicity. Not good enough!
At an Autism conference in Calgary on January 19/07 (with many good speakers), one speaker was bold enough to mention the damaging neurotoxic effects of organophophates (OPs).
During a private conversation with this doctor, from Phoenix, AZ, she revealed to me that many of her autistic patients do no show heavy loads of mercury in their chelate profiles. They do, however, show heavy loads of uranium. She has always wondered where these patients could have possibly come into contact with uranium (they do not live near any mines). Sadly, it is probably the case that these children are being exposed to the uranium via any one, or combination of the following:
-uranium fallout from atmospheric testing (much of which took place next door in Nevada.
-uranium fallout from manufacture or testing of Depleted Uranium weapons, and other nuclear weapons.
-parents working at facilities that process uranium, store nuclear waste, or military bases where weapons are kept.
She also stated that the majority of certain types of OPs used in the USA, are used in-side households to kill bugs. The developing fetus and young brain, she stated, is particularly susceptible to the neurotoxic effects of OPs.
Are we to blindly ignore the neurotoxic effects to livestock? The methods of neurotoxicity of OPs are not limited to inhibition of acetylcholinesterase, as the first study demonstrated. Multi-factoral disease processes all depend on exposure to what, when and how much, and via which exposure route(s) (inhalation, ingestion, absorption).
The co-inciding use of OPs, at rates never used before (ie: extremely high concentrations) for the UK warble eradication program STARTING in 1982 cannot be ignored in its relationship to their massive BSE cases. Other european countries also used OPs at high concentrations during this time frame.
OPs are used to spray crops which deer and other wildlife freely wander through. While exposure alone (of a healthy animal), is not enough to cause CWD, it is a contributing factor which can push a weakened animal over the top, creating all kinds of neurotoxic damage and oxidative stress.
OPs are also used to spray fruit crops which are often located near communities. Spray drift is another method of exposure to OPs and other chemicals.
One mother at the Autism symposium who lives on an acreage stated she won't grow her own garden because she is surrounded by crop land which the farmer sprays several times a year. She is concerned the veggies in a garden would be contaminated. She should also be concerned that they are inhaling these chemicals.
I met some very interesting and hard working people at this conference. There was alot of hope for treatment of Autism with various therapies, they included: injections of methyl cobalamine (Vitamin B12), digestive enzymes and acidophilus (re-establishing the good bacteria in the gut).
When it comes down to the nitty gritty, human biology is not all that different from other mammals. Toxicity of any substance is enhanced when the proper mechanisms to deal with the chemicals, metals, oxidative stress are lacking or completely gone.
