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Archive for the ‘Autism & Alzheimer’s’ Category

The Man Working To Reverse-Engineer Your Brain – February 29, 2012 NPR
http://www.npr.org/2012/02/29/147190092/the-man-working-to-reverse-engineer-your-brain

Our brains are filled with billions of neurons, entangled like a dense canopy of tropical forest branches. When we think of a concept or a memory — or have a perception or feeling — our brain’s neurons quickly fire and talk to each other across connections called synapses.

How these neurons interact with each other — and what the wiring is like between them — is key to understanding our identity, says Sebastian Seung, a professor of computational neuroscience at MIT.

Seung’s new book, Connectome: How the Brain’s Wiring Makes Us Who We Are, explains how mapping out our neural connections in our brains might be the key to understanding the basis of things like personality, memory, perception and ideas, as well as illnesses that happen in the brain, like autism and schizophrenia.

“These kinds of disorders have been a puzzle for a long time,” says Seung. “We can look at other brain diseases, like Alzheimer’s disease and Parkinson’s disease, and see clear evidence that there is something wrong in the brain.”

But with schizophrenia and autism, there’s no clear abnormality during autopsy dissections, says Seung.

“We believe these are brain disorders because of lots of indirect evidence, but we can’t look at the brain directly and see something is wrong,” he says. “So the hypothesis is that the neurons are healthy, but they are simply connected together or organized in an abnormal way.”

One current theory, says Seung, is that there’s a connection between the wiring that develops between neurons during early infancy and developmental disorders like schizophrenia and autism.

“In autism, the development of the brain is hypothesized to go awry sometime before age 2, maybe in the womb,” he says. “In schizophrenia, no one knows for sure when the development is going off course. We know that schizophrenia tends to emerge in early adulthood, so many people believe that something abnormal is happening during adolescence. Or it could be that something is happening much earlier and it’s not revealed until you become an adult.”

What scientists do know, he says, is that the wiring of the brain in the first three years is critical for development. Infants born with cataracts in poor countries that don’t have the resources to restore their eyesight remain blind even after surgery is performed on them later in life.

“No matter how much they practice seeing, they can never really see,” says Seung. “They recover some visual function, but they are still blind by comparison to you and me. And one hypothesis is that the brain didn’t wire up properly when they were babies, so by the time they become adults, there’s no way for the brain to learn how to see properly.”

At birth, he says, you are born with all of the neurons you will ever have in life, except for neurons that exist in two specific areas of the brain: the dentate gyrus of the hippocampus, which is thought to help new memories form, and the olfactory bulb, which is involved in your sense of smell.

“The obvious hypothesis [is] that these two areas need to be highly plastic and need to learn more than other regions, and that’s why new neurons have to be created — to give these regions more potential for learning,” says Seung. “But we don’t really have any proof of that hypothesis.”

But not everything is set in stone from birth. The complex synaptic connections that allow neurons to communicate with one another develop after babies have left the womb.

“As far as we know, this is happening throughout your life,” he says. “Part of the reason that we are lifelong learners — that no matter how old you get, you can still learn something new — may be due to the fact that synapse creation and elimination are both continuing into adulthood.”

Connectomes: Reverse-Engineering The Brain

Only one organism has had its full connectome — or neural map — mapped out by neuroscientists. It’s a tiny worm no bigger than a millimeter, but it took scientists more than a dozen years to map out its 7,000 neural connections. They started out by using the world’s most powerful knife and slicing the worm into slices a thousand times thinner than a human hair. They then put each slice in an electron microscope and created a 3-D image of the worm’s nervous system. That’s when the true labor started, says Seung.

“That’s when [neuroscientists had to] go through all these images and trace out the paths taken by all of the branches of the neurons and find the synapses, and compile all that information to create the connectome,” he says.

Each of the worm’s 300 neurons had between 20 and 30 connections. In comparison, humans have 10,000 connections of neurons — and billions of neurons. And scientists still aren’t sure what the various pathways in a worm’s nervous system mean.

“We’re still far away from understanding the worm,” says Seung. He says that scientists would like to eventually map a 1-millimeter cube of a human brain or a mouse brain, which contains 100,000 neurons and a billion connections.

“The imaging of all of those slices of brain can be automated and made much more reliable,” he says. “And now we have computers that are getting better at seeing.”

So far, though, neuroscientists have only mapped the neural connections of a piece of a mouse retina, which is very thin.

“What we know in the retina is a catalog of the types of neurons,” he says. “The next challenge is to figure out what are the rules of connection between these types of neurons. And that’s where we still don’t know a whole lot.”

Mapping more of these connections, he says, will tell us a lot about brain function and possible pathways that can be treated.

“I don’t want to promise too much, and my goal right now is simply to see what is wrong,” he says. “That’s not in itself a cure. But obviously it’s a step toward finding better treatments. The analogy I make is the study of infectious diseases before the microscope. You could see the symptoms, but you couldn’t see the microbes — the bacteria that caused disease. We’re in an analogous stage with mental disorders. We see the symptoms, but we don’t have a clear thing we can look at in the brain and say, ‘This is what’s wrong.’ ”

http://www.npr.org/2012/02/29/147190092/the-man-working-to-reverse-engineer-your-brain

Bernard Weiss
http://www2.envmed.rochester.edu/envmed/tox/faculty/weiss.html

Neurobiology and Behavior

Our brains, the ultimate product of millions of years of evolution, are what make us human. But over the past few decades, scientists have discovered that many chemicals in our environment threaten the integrity of our brains. Thousands more have never been studied for their effects. We know some of the outcomes: reduced intelligence and cognitive function, increased antisocial tendencies, impaired senory and motor function, and elevated risks of neurodegenerative disorders such as Parkinson’s disease.

Most of these chemicals are ubiquitous and persistent. We are exposed throughout our lifetimes. But some periods of life are more vulnerable than others. Early development is an especially perilous time for exposure to toxic chemicals. The brain is exquisitely sensitive during this period because of the many paths by which it expands and differentiates on the path to maturity. Cells divide and proliferate; they migrate to specific target areas; they grow connections to other cells to form massive neural networks; neurotransmitter systems take root. All these processes are candidates for interference by toxic chemicals. All are reflected in neurobehavioral outcomes that can be measured when organisms mature to a stage at which they can be tested by procedures that are sensitive to such interference. Late in life, we enter another period of enhanced vulnerability. We are not as able as during earlier periods to compensate for toxic processes and many of our organ systems operate at diminished capacity. It is also a period when these reduced capacities may begin to reflect the damage inflicted earlier in life.

My own research aims to relate behavioral measures to neurotoxicant exposure. Behavioral research occupies a special role in safety assessment because it offers the ability to trace changes in function as organisms mature and age. Among the endpoints of salient interest to regulatory agencies such as EPA and to chemical and pharmaceutical manufacturers are learning capacity, other aspects of cognitive capacity, motor and sensory performance, and differences between males and females.

My efforts have spanned a variety of agents: metals such as mercury and manganese; solvents such as toluene and methanol; air pollutants such as ozone; adventitious contaminants such as dioxin; and endocrine disruptors, which include common ingredients in consumer products such as phthalates.

For more on Bernard Weiss and his research see below.

School of Medicine & Dentistry
Molecular Toxicology & Environmental Medicine Cluster
Ph.D. Program in Toxicology

Bernard Weiss
Professor of Environmental Medicine
and Pediatrics;
Environmental Health Sciences Center,
and Center for Reproductive Epidemiology.
B.A. 1949 (New York University)
Ph.D. 1953 (University of Rochester)

http://www2.envmed.rochester.edu/envmed/tox/faculty/weiss.html

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I have stumbled upon one factor that has been overlooked in Autism research and infant and children’s health. Pediatricians often recommend giving infants and children Tylenol and Mortin (for infants over 6 months) for pain management prior or just after they’ve received a vaccine. What public and health care professionals do not know is that there is an excipient in the infant and children Tylenol and some of the Motrin formulations that contains a chlorocarbon (or organochloride) utilized as the sweetening agent.


To access Children’s Tylenol ingredient list click here.

Sucralose or what is commonly known as Splenda is the organochloride or chlorocarbon utilized in the suspension fluids. The invention of sucralose or Splenda was documented in the New Yorker article, “The Search For Sweet,” by Burkhard Bilger – May 22, 2006.

The substance in the flask seemed to have all the makings of an excellent insecticide. It was a fine crystaline powder and its molecules were full of chlorine atoms, like DDT. ..by taking an eye-dropper full of sulfuryl chloride – a highly toxic chemical – and adding it to a sugar solution, one drop at a time. In the violent reaction that followed, a wholly new compound was born: 1′, 4,6,6′-tetrachloro-1′,4,6,6′-tetra-deoxygalactosucrose. “It isn’t of any use as an insecticide,” Hough told me recently, “That was tested.” But it has proven useful as a food. In its pure form, it is known as sucralose. When mixed with fillers and sold in bright yellow sachets, it’s known as Splenda, the best-selling artificial sweetener in America.”

Sucralose was declared safe by the Food and Drug Administration in 1998, but most of the taste researchers I talked to won’t eat it. “I look at that structure and I have an irrational fear of it,” one of them said.

To access this article view on the link below. The New Yorker does charge a small fee to access this archived issue.


The Search For Sweet by Burkhard Bilger for The New Yorker – May 22, 2006


THE LETHAL SCIENCE OF SPLENDA, A POISONOUS CHLOROCARBON by James Bowen, M.D.

James Bowen explains the impacts of Splenda (sucralose).

“Splenda/sucralose is simply chlorinated sugar; a chlorocarbon. Common chlorocarbons include carbon tetrachloride, trichlorethelene and methylene chloride, all deadly. Chlorine is nature’s Doberman attack dog, a highly excitable, ferocious atomic element employed as a biocide in bleach, disinfectants, insecticide, WWI poison gas and hydrochloric acid.

“Sucralose is a molecule of sugar chemically manipulated to surrender three hydroxyl groups (hydrogen + oxygen) and replace them with three chlorine atoms. Natural sugar is a hydrocarbon built around 12 carbon atoms. When turned into Splenda it becomes a chlorocarbon, in the family of Chlorodane, Lindane and DDT.

“It is logical to ask why table salt, which also contains chlorine, is safe while Splenda/sucralose is toxic? Because salt isn’t a chlorocarbon. When molecular chemistry binds sodium to chlorine to make salt carbon isn’t included. Sucralose and salt are as different as oil and water.

“Unlike sodium chloride, chlorocarbons are never nutritionally compatible with our metabolic processes and are wholly incompatible with normal human metabolic functioning. When chlorine is chemically reacted into carbon-structured organic compounds to make chlorocarbons, the carbon and chlorine atoms bind to each other by mutually sharing electrons in their outer shells. This arrangement adversely affects human metabolism because our mitochondrial and cellular enzyme systems are designed to completely utilize organic molecules containing carbon, hydrogen, oxygen, nitrogen, and other compatible nutritional elements.

“By this process chlorocarbons such as sucralose deliver chlorine directly into our cells through normal metabolization. This makes them effective insecticides and preservatives. Preservatives must kill anything alive to prevent bacterial decomposition.”

Dr. Bowen believes ingested chlorocarbon damage continues with the formation of other toxins: “Any chlorocarbons not directly excreted from the body intact can cause immense damage to the processes of human metabolism and, eventually, our internal organs. The liver is a detoxification organ which deals with ingested poisons. Chlorocarbons damage the hepatocytes, the liver’s metabolic cells, and destroy them.

In test animals Splenda produced swollen livers, as do all chlorocarbon poisons, and also calcified the kidneys of test animals in toxicity studies. The brain and nervous system are highly subject to metabolic toxicities and solvency damages by these chemicals. Their high solvency attacks the human nervous system and many other body systems including genetics and the immune function. Thus, chlorocarbon poisoning can cause cancer, birth defects, and immune system destruction. These are well known effects of Dioxin and PCBs which are known deadly chlorocarbons.”

Dr. Bowen continues: “Just like aspartame, which achieved marketplace approval by the Food and Drug Administration when animal studies clearly demonstrated its toxicity, sucralose also failed in clinical trials with animals. Aspartame created brain tumors in rats. Sucralose has been found to shrink thymus glands (the biological seat of immunity) and produce liver inflammation in rats and mice.

“In the coming months we can expect to see a river of media hype expounding the virtues of Splenda/sucralose. We should not be fooled again into accepting the safety of a toxic chemical on the blessing of the FDA and saturation advertising. In terms of potential long-term human toxicity we should regard sucralose with its chemical cousin DDT, the insecticide now outlawed because of its horrendous long term toxicities at even minute trace levels in human, avian, and mammalian tissues.

Researchers have known for a long time that chlorinated compounds impact liver functionality. Rachel Carson discussed chlorinated compounds in Silent Spring. She also discusses Methoxychlor, another organochlorine once used as an insecticide, and it’s toxicity when combined with other chlorinated compounds like DDT.

One of the most significant facts about the chlorinated hydrocarbon insecticides is their effect on the liver. Of all the organs in the body the liver is most extraordinary. In its versatility and in the indispensable nature of its functions it has no equal. It presides over so many vital activities that even the slightest damage is fraught with serious consequences. Not only does it provide bile for the digestion of fats, but because of its location and the special circulatory pathways that converge upon it the liver receives blood directly from the digestive tract and is deeply involved in the metabolism of all the principal foodstuffs. It stores sugar in the form of glycogen and releases it as glucose in carefully measured quantities to keep the blood sugar at a normal level. It builds body proteins, including some essential elements of blood plasma concerned with blood-clotting. It maintains cholesterol at its proper level in the blood plasma, and inactivates the male and female hormones when they reach excessive levels. It is a storehouse of many vitamins, some of which in turn contribute to its own proper functioning.

Without a normally functioning liver the body would be disarmed–defenseless against the great variety of poisons that continually invade it. Some of these are normal by-products of metabolism, which the liver swiftly and efficiently makes harmless by withdrawing their nitrogen. But poisons that have no normal place in the body may also be detoxified. The “harmless” insecticides malathion and methoxychlor are less poisonous than their relatives only because a liver enzyme deals with them, altering their molecules in such a way that their capacity for harm is lessened. In similar ways the liver deals with the majority of the toxic materials to which we are exposed.

Our line of defense against invading poisons or poisons from within is now weakened and crumbling. A liver damaged by pesticides in not only incapable of protecting us from poisons, the whole range of its activities may be interfered with. Not only are the consequences far-reaching, but because of their variety and the fact that they may not immediately appear they may not be attributed to their true cause…..

The effect of a chemical of supposedly innocuous nature can be drastically changed by the action of another; one of the best examples is a close relative of DDT called methoxychlor (Actually, methoxychlor may not be as free from dangerous qualities as it is generally said to be, for recent work on experimental animals shows a direct action on the uterus and a blocking effect on some of the powerful pituitary hormones–reminding us again that these are chemicals with enormous biological effect. Other work shows that methoxychlor has a potential ability to damage the kidneys.) Because it is not stored to any great extent when given alone, we are told that methoxychlor is a safe chemical. But this is not necessarily true. If the liver has been damaged by another agent, methoxychlor is stored in the body at 100 times its normal rate, and will then imitate the effects of DDT with long-lasting effects on the nervous system. Yet the liver damage that brings this about might be so slight as to pass unnoticed. It might have been the result of any number of commonplace situations–using another insecticide, using a cleaning fluid containing carbon tetrachloride, or taking one of the so-called tranquilizing drugs, a number (but not all) of which are chlorinated hydrocarbons and possess power to damage the liver.

This raises very serious questions. Infant and children’s pharmaceutical excipients, inactives, or inerts (Take your pick on the term) need serious review. The Johnson & Johnson McNeil Fort Washington Facility is now closed. The FDA inspection review showed chronic failures in quality and consistency of the oral suspension formulations. This is the same facility where they make sucralose and utilized it in their infant and children’s Tylenol and Motrin formulations. Johnson & Johnson’s McNeil failed to understand the potential implications of utilizing a chlorocarbon (or organochloride) as a sweetener in infant and children’s pharmaceuticals. Parents give their infants and children Tylenol and Motrin products to help relieve their pain and suffering not knowing that something in that product may have serious long term health consequences. Has Splenda or sucralose ever been tested for its synergistic properties? Could sucralose impair liver functionality and cause other poisons or toxins to be absorbed at an accelerated rate? Those are the questions that need immediate answers.

The FDA inspection report is deeply disturbing in light of this information.

Observation 3
Control procedures fail to include adequacy of mixing to assure uniformity and homogeneity.

Control procedures used did not validate the manufacturing processes that caused variability in the characteristics of the drug product. For examples, the agitation speeds and time to reach [Blacked out] in the hold tank during processing of the [blacked out] super potent batches that failed APAP (end of run) assays, [blacked out] released batches, and the demonstration batch. The firm did not demonstrate the adequacy of mixing to assure uniformity and homogeneity for Infant’s Dye-Free Tylenol Suspension Drops, Formula [blacked out] using a [blacked out] batch in a [blacked out] hold tank. Agitation and tank levels with [blacked out] the amount of liquid) in a [blacked out] hold tank were evaluated with one demonstration bulk batch, lot ]blacked out] packaged as lot [blacked out] The [blacked out] batches into [blacked out] hold tanks used [blacked out] and the agitator was shut off at [blacked out] using the weight of [blacked out] for the [blacked out] batch in a [blacked out] hold tank. With the [blacked out] super potent batches, APAP concentrated at the end run when the agitator was shut off at [blacked out] in the tank).

To review the complete inspection report click on the link below to review the PDF.


Food & Drug Administration Facility Inspection Results for McNeil Consumer Healthcare, Division of McNeil-PPC, Inc.

The inspection results are also available here at this site.
https://renchemista.wordpress.com/2010/07/13/fda-facility-inspection-results-for-mcneil-ppc-fort-washington-pa-4192010-4302010-childrens-tylenol-motrin-recalls/

J Toxicol Environ Health A. 2008;71(21):1415-29. doi: 10.1080/15287390802328630.
Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats.
Abou-Donia MB1, El-Masry EM, Abdel-Rahman AA, McLendon RE, Schiffman SS.
Author information

Abstract
Splenda is comprised of the high-potency artificial sweetener sucralose (1.1%) and the fillers maltodextrin and glucose. Splenda was administered by oral gavage at 100, 300, 500, or 1000 mg/kg to male Sprague-Dawley rats for 12-wk, during which fecal samples were collected weekly for bacterial analysis and measurement of fecal pH. After 12-wk, half of the animals from each treatment group were sacrificed to determine the intestinal expression of the membrane efflux transporter P-glycoprotein (P-gp) and the cytochrome P-450 (CYP) metabolism system by Western blot. The remaining animals were allowed to recover for an additional 12-wk, and further assessments of fecal microflora, fecal pH, and expression of P-gp and CYP were determined. At the end of the 12-wk treatment period, the numbers of total anaerobes, bifidobacteria, lactobacilli, Bacteroides, clostridia, and total aerobic bacteria were significantly decreased; however, there was no significant treatment effect on enterobacteria. Splenda also increased fecal pH and enhanced the expression of P-gp by 2.43-fold, CYP3A4 by 2.51-fold, and CYP2D1 by 3.49-fold. Following the 12-wk recovery period, only the total anaerobes and bifidobacteria remained significantly depressed, whereas pH values, P-gp, and CYP3A4 and CYP2D1 remained elevated. These changes occurred at Splenda dosages that contained sucralose at 1.1-11 mg/kg (the US FDA Acceptable Daily Intake for sucralose is 5 mg/kg). Evidence indicates that a 12-wk administration of Splenda exerted numerous adverse effects, including (1) reduction in beneficial fecal microflora, (2) increased fecal pH, and (3) enhanced expression levels of P-gp, CYP3A4, and CYP2D1, which are known to limit the bioavailability of orally administered drugs.

http://www.ncbi.nlm.nih.gov/pubmed/18800291

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Autism & Alzheimer’s

I watched the Nova Program called, “Ghost in Your Genes,” from HHMI – well four times. I keep thinking about the studies on identical twins where one twin has severe autism and the other does not have any symptoms (Identical twins discordant for autism). This means that it is not genetics itself or both twins would have developed autism. I was reading how twins are more likely to both have autism but that would make sense because most twins have the same environmental exposures. The studies on twins discordant for autism are critically important. Walter Kaufmann was the researcher. I wanted to review his findings.

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