Polluted Air Leads to Disease by Promoting Widespread Inflammation

ScienceDaily (Apr. 14, 2011) — Chronic inhalation of polluted air appears to activate a protein that triggers the release of white blood cells, setting off events that lead to widespread inflammation, according to new research in an animal model.

Chronic inhalation of polluted air appears to activate a protein that triggers the release of white blood cells, setting off events that lead to widespread inflammation, according to new research.

This finding narrows the gap in researchers' understanding of how prolonged exposure to pollution can increase the risk for cardiovascular problems and other diseases.

The research group, led by Ohio State University scientists, has described studies in mice suggesting that chronic exposure to very fine particulate matter triggers events that allow white blood cells to escape from bone marrow and work their way into the bloodstream. Their presence in and around blood vessels alters the integrity of vessel walls and they also collect in fat tissue, where they release chemicals that cause inflammation.

The cellular activity resembles an immune response that has spiraled out of control. A normal immune response to a pathogen or other foreign body requires some inflammation, but when inflammation is excessive and has no protective or healing role, the condition can lead to an increased risk for cardiovascular diseases, diabetes and obesity, as well as other disorders.

Though many questions about the beginning of this process remain unanswered, the scientists predict that the damage may originate in fluid that lines the lung. Tiny molecules in this fluid change structure after being exposed to polluted air, and that change appears to set off this cascade of damaging white blood cell behavior by activating a receptor called "toll-like receptor 4."

The job of toll-like receptor 4, or TLR4, is to recognize specific characteristics of pathogens and then send out signals to activate other players in the immune system. Mice that lack this molecule don't produce as much inflammation after exposure to pollution as do normal mice, suggesting that TLR4 has a prominent role in the body's response to chronic exposure to particulate matter.

"Our main hypothesis is that particulate matter stimulates inflammation in the lung, and products of that inflammation spill over into the body's circulation, traveling to fat tissue to promote inflammation and causing vascular dysfunction," said Sanjay Rajagopalan, professor of cardiovascular medicine at Ohio State and senior author of the study. "We haven't identified the entire mechanism, but we have evidence now that activation of TLR4 influences this response."

The research is published in a recent issue of the journalCirculation Research.

Many of these researchers already have documented the link between chronic exposure to polluted air and high blood pressure, diabetes and obesity. They now aim to pinpoint how and where the earliest damage occurs.

For this study, the scientists exposed different groups of mice to either filtered air or air containing between eight and 10 times more fine particulates than the ambient air in an urban environment -- an average of approximately 111 micrograms per cubic meter. The mice were exposed for six hours per day for five days per week for at least 20 weeks.

The polluted air contained fine particulates that are so tiny -- 2.5 micrometers or smaller in diameter, or about 1/30th of the average width of a human hair -- that they can reach deep areas of the lungs and other organs in the body.

For most of the experiments, the effects of exposure to pollution were compared in normal mice and mice deficient in TLR4.

After exposure to polluted air, the normal mice showed higher levels of white blood cells known as inflammatory monocytes in their spleens and circulating in their bloodstream than did mice breathing filtered air. Deficiency of TLR4 diminished this effect in mice breathing dirty air. That suggested that if the receptor is not active, the monocytes will not be released.

Other findings implicated yet another potential compound involved in the damage. The increase in monocytes was accompanied by an increase in superoxides in the blood vessels. These compounds are designed to kill pathogens, but they are toxic if they have no bug to fight. They are produced by an enzyme called NADPH oxidase -- and NADPH oxidase is found inside monocytes.

In an experiment comparing normal mice and mice lacking a component of the NADPH oxidase enzyme, the mice without the enzyme produced fewer oxygen free radicals in response to polluted air than did normal mice.

"The free radicals can have a high impact on vascular function," explained Thomas Kampfrath, a postdoctoral researcher in Ohio State's Davis Heart and Lung Research Institute and first author of the study. Indeed, an examination of the aortas of these mice showed that vessels in animals exposed to polluted air exhibited exaggerated responsiveness to stressors -- a sign of incipient hypertension, or high blood pressure, Kampfrath said.

Yet another model of mice genetically altered so their monocytes express yellow fluorescent protein allowed the researchers to observe exactly where the monocytes traveled in segments of mouse muscles and fat tissue. In mice breathing polluted air, the monocytes began to stick to blood vessel walls and fat cells.

"This is a sign that the monocytes are responding to inflammatory stimuli -- which in our case is particulate matter -- and then in turn they can cause more inflammation because they release inflammatory factors," said Rajagopalan, who is also the associate director for vascular research at the Davis Heart and Lung Research Institute.

Those factors include what are called proinflammatory cytokines, including TNFa (tumor necrosis factor alpha), MCP-1 (monocyte chemoattractant protein) and IL-12 (interleukin-12). These are chemical messengers that cause inflammation, most often to fight infection or repair injury. When they circulate without an infection to fight, the body experiences excess inflammation.

Mice breathing polluted air showed higher levels of these cytokines in their blood than did mice breathing filtered air. And the mice deficient in the TLR4 receptor showed dramatically lower levels of the cytokines.

"Most of our experiments initially assessed global inflammation. The monocytes are virtually everywhere in the body," Rajagopalan said. "And then we asked the question, how does it happen, and where does it come from?"

Kampfrath in particular is focused on the lung's role in this process. Those same cytokines were also significantly elevated in the lungs of mice that had experienced prolonged exposure to polluted air, and the lack of TLR4 activation lowered this effect.

Protective fluid in the lung contains molecules called phospholipids, and this research showed that those molecules become oxidized -- meaning a chemical reaction changes their shape and function -- after they are exposed to polluted air. That much is determined.

And a series of experiments in different types of white blood cells demonstrated that when the cells are treated with oxidized phospholipids, they will release those proinflammatory cytokines. The lack of TLR4 in those cells diminishes these effects.

These experiments confirmed that these activities in the lung could trigger inflammation seen throughout the rest of the body in mice exposed to polluted air. The question that remains unanswered, however, is the process by which phospholipids become oxidized after chronic lung exposure to dirty air, Kampfrath said.

"After exposure, there is an increase in oxidized phospholipids in the lung fluid. We know it happens, but we don't know how," he said. "What we do know is that the increase in oxidized phospholipids in turn promotes inflammation."

In an editorial in the same issue of Circulation Research, Daniel Conklin of the University of Louisville wrote, "Is the mystery solved regarding the mechanism how inhaled [fine particulate matter] exposure stimulates vascular inflammation and injury? Well, probably not completely, but the present scenario laid out … connects findings from their study with many disparate human and animal epidemiological/exposure studies into a plausible story."

This research was supported by grants from the National Institutes of Health and DFG (German Research Foundation).

Co-authors include Andrei Maiseyeu, Zhekang Ying, Zubair Shah, Jeffrey Deiuliis, Nisharahmed Kherada, Sampath Parthasarathy, Susan Moffatt-Bruce and Qinghua Sun of the Davis Heart and Lung Research Institute; Xiaohua Xu of the Division of Environmental Health Sciences; and Kongara Reddy and Nitin Padture of the Department of Materials Science and Engineering, all at Ohio State; Robert Brook of the University of Michigan; Lung Chi Chen of New York University; and Henning Morawietz of the University of Technology in Dresden, Germany.

What Sea Squirts Can Teach Us About the Heart

ScienceDaily (Apr. 11, 2011) — Each year in the U.S., approximately 40,000 babies are born with a heart defect. Without the proper diagnosis and treatment, many of these babies would die before their first birthday, according to Dr. Scott Klewer, a cardiologist at the UA's College of Medicine.

Ciona allows scientists to study in detail how cells interact to build complex organs. In this microscopic image, two of the cells that will form the heart were stained with a green fluorescent marker and can be seen in the lower portion of the tadpole-like Ciona embryo.

"We still don't know much about the causes of many of these defects. Some have been linked to certain genes but the picture is still sketchy," he says. "At this point, we can't predict how children will respond to current methods, but if we had genetic indicators we could use them to personalize treatments."

Dr. Ricardo Samson, who heads the pediatric cardiology section at the College of Medicine, adds that "some heart defects can be difficult to diagnose because they don't present the typical signs such as a heart murmur or blueness of the skin."

"Fortunately, prenatal ultrasound allows obstetricians to identify many babies with specific forms of severe heart defects before they are born," he says. "But because of the way the heart develops in a fetus, some severe defects go undetected and don't cause problems until the baby has gone home from the nursery."

Samson and Klewer both are members of the UA's Steele Children's Research Center and the UA's Sarver Heart Center's heart development research group, which is internationally recognized for its discoveries expanding the understanding of molecular elements that cause congenital heart defects.

In studying heart-specifying genes, less is more

Studying the genetic underpinnings of heart defects is complicated by the fact that humans, like all other vertebrates, have multiple and slightly different copies of each gene. This redundancy makes it difficult if not impossible to tease apart the functions associated with a particular gene, because disrupting its function in model organisms such as mice to figure out its role does not always result in an obvious effect.

In their quest to better understand and help clinicians develop better diagnostics and treatments for congenital heart defects, scientists at the UA's department of molecular and cell biology have turned to a creature most people -- with the possible exception of scuba divers -- would not consider a familiar sight: a sea squirt in the genus Ciona.

Lacking a head, appendages and eyes, sea squirts resemble strange-looking, leathery sacks more than animals. Up to 6 inches long, with two conspicuous openings, Ciona spends its life attached to submerged rocks or piers, pumping sea water through its body and straining out food particles, much like clams do. Its simple body structure, however, belies the sea squirts' biological kinship, which places them closer to the vertebrate lineage than any other invertebrate. Most importantly, Ciona's genetic blueprint is almost the same as that of vertebrates.

"We want to understand the basic processes by which embryonic cells make the decision to become heart cells," says Brad Davidson, an assistant professor in the UA's department of molecular and cellular biology and a member of the Sarver Heart Center. "Early steps of heart formation are very similar in Ciona, mice and humans."

Except -- and for a scientist studying heart development, this is huge -- each of Ciona's genes is represented only once because the genome has not been duplicated as in vertebrates. Therefore, Ciona has only one copy of the major genes involved in heart development.

One of the genes vital for heart development is GATA, a so-called transcription factor or master gene that controls other heart-specific genes and plays a key role in heart development. Human babies with GATA mutations have congenital heart defects. If the gene's function is disrupted, both the heart and the gut are deformed.

"But it's not clear where the problem is," Davidson says. "Is it because the heart doesn't form properly or because the gut doesn't form properly? Ciona allows us to break it apart."

IMAGE: This is Katerina Ragkousi, the first author of the research report, with principal investigator Brad Davidson.

Click here for more information.

A heart needs a gut

"We tend to think of cells building an organ as an isolated process but that is never true in an embryo," he says. "Anything that is being built has to be made alongside all the other organs, and there are a lot of complications in terms of the instructions."

Katerina Ragkousi, a postdoctoral fellow in Davidson's lab, just published the results of a study shedding light on this process in the journal Developmental Biology. The editors deemed her work important enough to feature it on the cover of the magazine.

"We know that in vertebrates, GATA has to be activated not only in the future heart cells, but in the neighboring gut cells, too," Ragkousi says. "In this study, we show that this is the same in Ciona, justifying even more the value of this model organism in studying heart development."

"Vertebrates have three GATA factors that are both in the developing gut and in the heart, so it has been really difficult to tease apart what's going on with these factors in each tissue."

When Ragkousi and her team experimentally disrupted GATA in heart precursor cells, the cells lost their identity.

"They don't express the right genes and stay in a state of limbo instead of moving on with their development," Davidson said.

"When we disturb GATA function independently in the developing gut, we see that heart cell identity is not perturbed, at least not at this stage," Ragkousi says. "However, we find that GATA in the gut plays an indirect role in heart formation in that it is necessary for heart precursors to be properly positioned in the developing embryo."

In addition to its genetic similarity to vertebrates, Ciona comes with several other benefits. It is easy to keep in the lab, and, unlike vertebrate embryos, a Ciona embryo consists of a mere few hundred cells. The embryos develop in only 24 hours and are translucent, allowing scientists to literally watch as the heart forms from only four cells.

"It is this simplicity that we are hoping to be able to exploit," Davidson says. "That we can not only see vaguely and in general how the cells build a heart, but very specifically how each cell is acting as they come together to make the heart."

In their natural habitat, Ciona embryos drift along with the ocean currents until they hatch as tiny, tadpole-like larvae.

"They need to develop rapidly because until they hatch, they're floating around as food," Davidson says. "Sometimes it can take days for them to settle. They can stay alive for five or six days. In the right kind of current, they can go pretty far."

Once the larvae come to rest on the seafloor, a rock or a pier, they undergo one of the most dramatic metamorphoses found in the natural world. Giving their body a total makeover, they morph from a free-swimming larva with a brain, primitive eyes and a tail into the sponge-like sack that spends remainder of its life attached to the very place it settled down.

"With Ciona, we can introduce genes into the early embryo and as it develops, we can study where the genes are expressed," Ragkousi says. "We also can locate the cells relative to each other. We are looking at the cellular interactions that happen during the early stages heart formation. It has been almost impossible to address this at such a high resolution and study the behavior of individual cells in more complex organisms."

Bench-to-bedside medicine, or from the water tank to the hospital

"Basic research with model organisms like Ciona allows us to identify the genes involved in heart development and recognize who the players are," says Klewer. "We can then look at these factors in patients to determine the best approach for treatment that would benefit that particular patient. It also gives us an opportunity to refine our approaches based on the genetic background. I am hopeful that we can soon integrate that knowledge in our clinical practice."

Researchers studying heart development put high hopes in Ciona not only to improve diagnostic tests through a better understanding of the genetic mechanisms underlying heart development, but also to develop better therapeutics for failing hearts.

"Many people are going to have a heart attack at some point in their lives," says Davidson. "And since the heart can't regenerate damaged tissue, what do you do to manage that? There is a big push to see if we can reprogram cells to build heart tissue. Progress is being made, but there are a lot of stumbling blocks to figuring out how to do that right. One of the keys is to make sure the cells that doctors put into a damaged heart behave like heart cells and not like cancer cells and don't do the wrong things."

Klewer adds: "In the future, clinicians will have more options for successfully performing surgery on a fetus. But they can't do that unless they know there is a problem. This approach holds the promise of correcting a heart problem early, and allow for more normal heart growth and function during development, which might save an affected child from a lot of complicated procedures that otherwise would be needed after birth."

Vision Loss in Eye Disease Slowed Using Novel Encapsulated Cell Therapy

ScienceDaily (Apr. 11, 2011) — A phase 2 clinical trial for the treatment of a severe form of age-related macular degeneration called geographic atrophy (GA) has become the first study to show the benefit of a therapy to slow the progression of vision loss for this disease. The results highlight the benefit of the use of a neurotrophic factor to treat GA and provide hope to nearly one million Americans suffering from GA.

Image showing geographic atrophy (GA).

The multi-center research team, including Kang Zhang, MD, PhD, of the University of California, San Diego, Shiley Eye Center, the lead author of the paper and one of the leading investigators in the study, found that long-term delivery of ciliary neurotrophic factor (CNTF) served to re-nourish the retina and stop or slow the loss of visual acuity caused by the disorder. The results were recently published online in theProceedings of National Academy of Sciences (PNAS).

According to Zhang -- professor of ophthalmology and human genetics at the UCSD School of Medicine and director of UCSD's Institute of Genomic Medicine -- there is currently no effective treatment for dry AMD or GA, though there is a very big need. "This could open the door to long-term treatment of dry AMD, using a simple surgical procedure."

Age-related macular degeneration, or AMD, is a leading cause of vision loss in Americans age 60 and older. It is a disease that causes cells in the macula -- the part of the eye that allows us to see in fine detail -- to die. There are two forms of the disorder, wet and dry AMD. GA is considered the end stage of dry AMD, where central vision is lost.

According to the National Eye Institute, wet AMD occurs when abnormal blood vessels behind the retina start to grow under the macula. These new blood vessels tend to be very fragile and often leak blood and fluid. The blood and fluid raise the macula from its normal place at the back of the eye, resulting in rapid loss of central version. There is currently a very effective therapy for wet AMD. Dry AMD occurs when the light-sensitive cells in the macula slowly break down, gradually blurring central vision in the affected eye.

In the trial, high-dose CNTF was delivered to 27 GA patients using encapsulated cell therapy (ECT). Another 24 patients received either a sham surgery (12) or a low-dose of CNTF (12). CNTF affects survival and differentiation of cells in the nervous system, including retinal cells. CNTF has been shown to retard the loss of photoreceptor cells in many animal models of retinal degeneration.

The ECT utilized a capsule that contains genetically engineered cells to continuously produce CNTF over a 12-month period. The CNTF-secreting capsule was implanted in the back of the study subject's eye. The implant allows the CNTF molecules to diffuse into the eye tissue, while keeping out antibodies and immune cells that would attack and destroy the CNTF-producing cells.

There was a statistically significant difference in the change of the total macular volume in the eyes of study participants at the 12-month point, versus baseline in the high-dose group, according to Zhang. "In addition, all but one of the patients in the high dose group, or 96.3 percent, maintained stabilized vision, compared to only 75% of the patients in the sham-treatment group."

The patients treated with a high dose of CNTF also showed an increase in retinal thickness as early as four months after implant, an increase that correlated to the stabilization of vision.

Additional contributors to the study included Jill J. Hopkins, Retina-Vitreous Associates Medical Group, Los Angeles; Jeffrey S. Heier, Ophthalmic Consultants of Boston; David G. Birch, Retina Foundation of the Southwest, Dallas; Lawrence S. Halperin, Retina Group of Florida, Ft. Lauderdale; Thomas A. Albini, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine; David M. Brown, Retina Consultants of Houston, Houston; Glenn J. Jaffe, Duke University Eye Center; Weng Tao, Neurotech USA, Lincoln, RI; and George A. Williams, Beaumont Eye Institute, Royale Oak, MI.

Zhang's research is supported by the National Eye Institute, National Institutes of Health; the Macula Vision Research Foundation; Burroughs Wellcome Fund; Research to Prevent Blindness, Lew Wasserman Merit Award and Senior Investigator Award; and the Chinese National 985 Project to Sichuan University and West China Hospital.

E. Coli Enzyme Must Move to Function

ScienceDaily (Apr. 7, 2011) — Slight oscillations lasting just milliseconds have a huge impact on an enzyme's function, according to a new study by Scripps Research Institute scientists. Blocking these movements, without changing the enzyme's overall structure or any of its other properties, renders the enzyme defective in carrying out chemical reactions.

A team led by Scripps Research Institute Professor Peter Wright used a mutant of E. coli dihydrofolate reductase to demonstrate that motions in the dihydrofolate reductase enzyme are essential for efficient catalysis. The hydride transfer reaction is shown at the center.

The study, published in April 8, 2011 issue of the journal Science, adds to a growing body of evidence pointing to the importance of movement in the ability of enzymes and other types of proteins to do their job. The findings may also help scientists design more specific and effective drugs targeting enzymes.

"Ever since the first X-ray structures of proteins emerged, scientists have been talking about proteins as though their structures were fixed in space," said Peter Wright, chair of the Department of Molecular Biology and member of the Skaggs Institute for Chemical Biology at Scripps Research who was senior author of the study, "but that is not how proteins work. They are like the machines we build. They have moving parts and they need motion to work."

A Model Enzyme

The new study examined the enzyme dihydrofolate reductase (DHFR) from the common bacterium Escherichia coli, which the Wright group has been using as a model for understanding how enzymes catalyze (cause or accelerate) chemical reactions. Most strains of E. coli are harmless, but some can cause serious food poisoning.

Bacterial cells cannot live without DHFR, thus this enzyme is the target for many antibiotics. Human cells, and in particular rapidly dividing cells, also use DHFR; drugs that target human DHFR, such as methotrexate, are often used in cancer chemotherapy.

DHFR spurs the conversion of a compound called dihydrofolate (DHF) to a different form, tetrahydrofolate (THF), which is needed by cells for synthesis of DNA. In its chemical reaction, DHFR uses a helper or co-factor, called NADPH. It catalyzes the transfer of a hydride (a negative hydrogen ion) from NADPH to DHF to produce THF. Previous studies by Wright and others have shown that the loops surrounding the active site are flexible, and that one of the loops in particular, called the Met20 loop can adopt two different conformations during the catalytic cycle.

Until now, however, the significance of these motions remained obscure.

Linking Motion to Function

Wright, graduate student Gira Bhabha, and colleagues from both Scripps Research and Pennsylvania State University decided to investigate.

For the new study, the scientists turned to an imaging technique known as nuclear magnetic resonance (NMR) spectroscopy, in combination with X-ray crystallography. Unlike X-ray crystallography, a technique used to determine the structure of proteins in crystals, recently developed NMR methods allow scientists to visualize the motions of proteins in solution. The technique can capture protein motions "in a time scale that is relevant to biology, from microseconds to milliseconds to seconds," said Wright.

To determine the importance of the oscillations, the team set out to make a mutation in the DHFR enzyme that prevented the flexible Met20 loop from moving. To know which amino acids to change, the scientists compared the bacterial DHFR protein sequence to that of the human enzyme, since in the human enzyme the Met20 loop is more rigid.

Using this approach, the scientists successfully produced a rigidified mutatant E. coli DHFR. When the scientists examined it using X-ray crystallography, they could see the mutant enzyme's structure was almost identical to the wild type enzyme. However, NMR analysis revealed that the Met20 loop and other parts of the active site were no longer flexible in the mutant.

Significantly, the mutated E. coli enzyme transferred hydride at a rate that was 16 fold slower than that of the wild type enzyme -- a substantial loss in enzyme function.

"We demonstrated that locking down the motion in the active site prevents catalysis," said Wright.

While previous work had indicated that enzymes can exist in different shapes and forms and that changes in enzyme shape enable enzymes to bind to their substrates and co-factors or release the products, "this is the first demonstration that motions play a role in the actual chemistry of a reaction," said Wright.

Clamping Down on the Active Site

The scientists reason that, when the E. coli DHFR carries out its chemical reaction, motions in the active site assist in pushing NADPH and DHF closer to one another. This proximity makes the transfer of the hydride from NAPDH to DHF more efficient. If the active site can't move, the molecules are not sufficiently close to one another for the chemical reaction to occur. "We think that the mutations prevent the enzyme from clamping down on the hydride donor and acceptor, so they can no longer get as close to each other as is necessary for efficient catalysis," explained Bhabha.

Taking motion into account when designing drugs to either inhibit or increase enzyme function could result in more effective or more specific drugs. For example, because the motions in the bacterial DHFR differ from those in the human enzyme, this difference might be exploited to design drugs that are specific for the bacterial enzyme. "It might help reduce the serious side effects of drugs that target DHFR," said Wright.

"The idea is to harness these motions in drug design," added Bhabha. "It's a difficult and challenging problem, but it could have huge impact."

In addition to Wright and Bhabha, co-authors for the paper "A dynamic knockout reveals that conformational fluctuations influence the chemical step of enzyme catalysis," include Damian C. Ekiert, Ian A. Wilson, and H. Jane Dyson at Scripps Research, and Jeeyeon Lee, Jongsik Gam, and Stephen J. Benkovic at Pennsylvania State University.

The research was supported by the National Institutes of Health and the Skaggs Institute for Chemical Biology.

Vehicle Pollution Significantly Damages Mouse Brain

ScienceDaily (Apr. 7, 2011) — If mice commuted, their brains might find it progressively harder to navigate the maze of Los Angeles freeways. A new study reveals that after short-term exposure to vehicle pollution, mice showed significant brain damage -- including signs associated with memory loss and Alzheimer's disease.

If mice commuted, their brains might find it progressively harder to navigate the maze of Los Angeles freeways. A new study reveals that after short-term exposure to vehicle pollution, mice showed significant brain damage -- including signs associated with memory loss and Alzheimer's disease. 

The mind-numbing toxin is not an exhaust gas, but a mix of tiny particles from burning of fossil fuel and weathering of car parts and pavement, according to the study to be published April 7 in the journalEnvironmental Health Perspectives.

Many studies have drawn a link between vehicle pollution and health problems. This is the first to explore the physical effect of freeway pollution on brain cells.

The authors found a way to recreate air laden with freeway particulate matter inside the laboratory. Whether in a test tube or in live mice, brain cells showed similar responses:

Neurons involved in learning and memory showed significant damage,

The brain showed signs of inflammation associated with premature aging and Alzheimer's disease,

Neurons from developing mice did not grow as well.

The freeway particles measured between a few dozen to 200 nanometers -- roughly one-thousandth the width of a human hair, and too small for car filtration systems to trap.

"You can't see them, but they are inhaled and have an effect on brain neurons that raises the possibility of long-term brain health consequences of freeway air," said senior author Caleb Finch, an expert in the effects of inflammation and holder of the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging.

Co-author Constantinos Sioutas, of the USC Viterbi School of Engineering, developed the unique technology for collecting freeway particulates in a liquid suspension and recreating polluted air in the laboratory. This made it possible to conduct a controlled study on cultured brain cells and live animals.

Exposure lasted a total of 150 hours, spread over 10 weeks, in three sessions per week lasting five hours each.

"Of course this leads to the question, 'How can we protect urban dwellers from this type of toxicity?' And that's a huge unknown," Finch said.

• The authors hope to conduct follow-up studies on issues such as:
• Memory functions in animals exposed to freeway particulates,
• Effects on development of mice exposed prenatally,
• Lifespan of exposed animals,
• Interaction of particulates with other components of smog, such as heat and ozone,
• Potential for recovery between periods of exposure,
• Comparison of effects from artificially and naturally occurring nanoparticles,
• Chemical interactions between freeway particulates and brain cells.

If further studies confirm that freeway particulates pose a human health hazard, solutions will be hard to find.

Even an all-electric car culture would not solve the problem on its own, Finch said.

"It would certainly sharply decrease the local concentration of nanoparticles, but then at present electrical generation still depends upon other combustion processes -- coal -- that in a larger environment contribute nanoparticles anyway.

"It's a long-term global project to reduce the amount of nanoparticles around the world. Whether we clean up our cars, we still have to clean up our power generation."

Fatty Liver: How a Serious Problem Arises

ScienceDaily (Apr. 6, 2011) — Excess fat around the hips and belly may not really be compatible with current beauty ideals, but, to a certain degree, it is a normal, even vital energy store of our body. However, it is a different matter if the organism stores fat in organs such as the liver, pancreas or muscles. This is a clear sign of a metabolic disorder.

3D-illustration of a human liver with blood vessels (red and blue) and bile duct (green). 

Up to 80 percent of obese people develop fatty liver disease, which is regarded a typical characteristic of the dangerous metabolic syndrome. Deposition of fat in the liver may lead to chronic liver inflammation and even to liver cancer. In addition, fatty liver is considered to be an independent risk factor for coronary heart disease and atherosclerosis.

The great medical relevance of fatty liver as a severe condition accompanying insulin resistance and type II diabetes caused the research group headed by Dr. Stephan Herzig of the Division of Molecular Metabolic Control to investigate how this syndrome arises. Which molecular switches are turned on or off in a cell when food delivers too much energy-rich fat molecules, or triglycerides?

To this end, the investigators determined the level of particular proteins involved in specific gene activation in the liver tissue of mice. These proteins, which are known as transcriptional co-activators, regulate which proteins are read and transcribed into messenger RNA molecules in a cell. In overweight mice, the researchers observed that a high triglyceride level in the liver was always associated with reduced production of a co-activator called TBL1. This was found both in animals that developed fatty liver for hereditary reasons and in those animals that received calorie-rich food.

TBL1 was originally discovered in connection with a rare hereditary hearing disorder. In the liver, but not in other tissues, an oversupply of fat reduces the production of TBL1. As a result, fat burning in the liver is reduced so that more fat molecules are deposited in liver cells. "This, in turn, may lead to a further reduction of TBL1," says Stephan Herzig.

Not only in mice is TBL1 linked to the liver fat (lipid) metabolism. The group found the same pattern in human liver tissue samples: the higher their triglyceride levels, the lower their TBL1 levels.

Stephan Herzig expects a practical use of these results. "We might be able in the future to use TBL1 levels for identifying those obese persons who have a special risk of developing fatty liver. We could then give specific dietary recommendations to counteract this."

Chemical Engineers Have Designed Molecular Probe to Study Disease

ScienceDaily (Apr. 6, 2011) — (Santa Barbara, Calif.) -- Chemical engineers at UC Santa Barbara expect that their new process to create molecular probes may eventually result in the development of new drugs to treat cancer and other illnesses.

This shows enhanced detection of endogenous protease activity. 

Their work, reported in the journalChemistry & Biology, describes a new strategy to build molecular probes to visualize, measure, and learn about the activities of enzymes, called proteases, on the surface of cancer cells.

Patrick Daugherty, senior author and professor of chemical engineering at UCSB, explained that the probes are effective at understanding proteases involved in tumor metastasis.

"Tumor metastasis is widely regarded as the cause of death for cancer patients," said Daugherty. "It's not usually the primary tumor that causes death. Metastasis is mediated by proteases, like the one we are studying here. These proteases can enable tumor cells to separate and degrade surrounding tissue, and then migrate to sites distant from the primary tumor. The tumor doesn't just fall apart. There are many events that must occur for a tumor to release cancerous cells into the blood stream that can circulate and end up in other tissues such as liver or bone."

The probes allowed the researchers, for the first time, to measure directly the activity of a protease involved in metastasis. They did this by adding their probe into a dish of tumor cells. They then measured the activity of this protease that breaks down collagen -- the single most abundant protein (by mass) in the human body.

"We have immediate plans to use similar probes to effectively distinguish metastatic HER2 positive tumors, one of the most commonly used biomarkers of breast cancer," said Daugherty. "A significant fraction of patients have HER2 positive tumors but we don't know which of those tumors is going to metastasize yet. But our ability to make these probes can allow us to identify which of those HER2 positive tumors have the ability to break down that surrounding tissue, to detach from the primary tumor, and to establish a separate tumor somewhere else in the body."

The authors designed the molecular probe to be recognized by a single protease rather than by the many proteases that are present in human tissues. That is half of the probe. The other half of the probe involves an optical technique used to measure activity. This approach relies upon the use of two engineered fluorescent proteins, derived from marine organisms, that absorb and emit light in a process called FRET, or Forster resonance energy transfer.

To prepare the probes, the researchers introduced a gene that encodes the probe into the bacteria E. coli. Then they produced and purified significant quantities of the probe. All of the information needed for the probe is encoded by a DNA sequence. The probes are easy and inexpensive to produce, as well as easily shared with other researchers.

In addition to studying cancer, similarly constructed probes have ramifications for studying Alzheimer's disease, arthritis and connective tissue diseases, bacterial infections, viruses, and many other diseases.

"The fact that you can generalize the concept, and the way you make these probes, to many systems, makes it attractive," said Daugherty. "We happen to study the activity of this protease and a certain type of tumor cells that are derived from cancer patients. But you could apply this to hundreds of molecules and really develop a working understanding of how groups of proteases function together in cell biology."

In individuals with rheumatoid arthritis, for example, there is increased production of proteases, including the one studied by Daugherty's team. This protease mediates collagen breakdown and joint destruction. "If you've got an enzyme that can chew up collagen and you've got lots of collagen in your joints, then you would expect that you would see more rapid degradation of the joint by those proteases," said Daugherty.

Daugherty's research group has created approximately 25 probes analogous to the one presented in the paper. They are building a panel of about 100 probes and will use this panel to characterize how different proteases function. This investigation could lead to new drug therapies for a variety of diseases.

The first author on the paper is Daugherty's former graduate student, Abeer Jabaiah, who is applying a similar process to another protease involved in tumor metastasis as a postdoctoral fellow in Daugherty's lab. Funding for this work was provided by the National Institutes of Health through the National Cancer Institute's Center of Cancer Nanotechnology Excellence and the National Heart, Lung, and Blood Institute's Program of Excellence in Nanotechnology.

Scientists Develop New Technology for Stroke Rehabilitation

ScienceDaily (Apr. 6, 2011) — Devices which could be used to rehabilitate the arms and hands of people who have experienced a stroke have been developed by researchers at the University of Southampton.

The new technologies will help patient rehabilitation. 

In a paper to be presented this week (6 April) at the Institution of Engineering and Technology (IET) Assisted Living Conference, Dr Geoff Merrett, a lecturer in electronic systems and devices, will describe the design and evaluation of three technologies which could help people who are affected by stroke to regain movement in their hand and arm.

Dr Merrett worked with Dr Sara Demain, a lecturer in physiotherapy and Dr Cheryl Metcalf, a researcher in electronic systems and devices, to develop three 'tactile' devices which generate a realistic 'sense of touch' and sensation -- mimicking those involved in everyday activities.

Dr Demain says: "Most stroke rehabilitation systems ignore the role of sensation and they only allow people repetitive movement. Our aim is to develop technology which provides people with a sense of holding something or of feeling something, like, for example, holding a hot cup of tea, and we want to integrate this with improving motor function."

Three tactile devices were developed and tested on patients who had had a stroke and on healthy participants. The devices were: a 'vibration' tactile device, which users felt provided a good indication of touch but did not really feel as if they were holding anything; a 'motor-driven squeezer' device, which users said felt like they were holding something, a bit like catching a ball; and a 'shape memory alloy' device which has thermal properties and creates a sensation like picking up a cup of tea.

Dr Merrett adds: "We now have a number of technologies, which we can use to develop sensation. This technology can be used on its own as a stand-alone system to help with sensory rehabilitation or it could be used alongside existing health technologies such as rehabilitation robots or gaming technologies which help patient rehabilitation."

Hotspots of Genetic Rearrangement: Findings in Mice Could Aid Understanding of How Mammals Genetically Adapt

ScienceDaily (Apr. 5, 2011) — Researchers have zoomed in on mouse chromosomes to map hotspots of genetic recombination -- sites where DNA breaks and reforms to shuffle genes. The findings of the scientists at the National Institutes of Health and Uniformed Services University of Health Sciences (USU) have the potential to improve the detection of genes linked to disease and to help understand the root causes of genetic abnormalities.

In this image, hundredfold magnification of a single sperm precursor cell shows the chromosomes -- in green -- and the places where these chromosomes are most likely to break apart and re-form, called genetic recombination hotspots -- in red. Genetic rearrangements at these hotspots have the potential to shuffle maternal and paternal chromosomes, the end results of which ensure that the genetic information in every sperm cell is unique.

The research, published online April 3 in Nature, moves scientists one step closer to understanding how mammals evolve and respond to their environments.

In this image, hundredfold magnification of a single sperm precursor cell shows the chromosomes -- in green -- and the places where these chromosomes are most likely to break apart and re-form, called genetic recombination hotspots -- in red. Genetic rearrangements at these hotspots have the potential to shuffle maternal and paternal chromosomes, the end results of which ensure that the genetic information in every sperm cell is unique. Source: Fatima Smagulova, Ph.D., USU, and Kevin Brick, Ph.D., NIDDK, NIH.Genetic recombination occurs at hotspots in cells that form sperm and eggs. At these sites, rearrangements ensure that the combination of genes passed on to every sperm and egg cell is unique. By studying precursors of mouse sperm cells during the early stages of genetic recombination, the scientists have created a precise, first-of-its-kind map of recombination hotspots in a multi-celled organism.

With this map, researchers also hope to pinpoint where, how and why abnormalities in the number of chromosomes can occur. Such abnormalities -- for instance, the extra copy of chromosome 21 that gives rise to Down syndrome -- are the leading known cause of miscarriages, congenital birth defects, and mental retardation in the United States.

"We wanted to figure out how recombination varied across the genome," said R. Daniel Camerini-Otero, M.D., Ph.D., one of the senior authors on the paper and a researcher at the NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). "Hotspots are the starting point for the process that ensures that every person is unique. These hotspots facilitate the adaptation of populations to environmental influences through evolution. Our findings will allow us to explore things like how environment and genetic background affect the recombination landscape."

"Now that we have mapped recombination hotspots genome-wide, we can actually carry out studies on the whole mouse genome. This will be very beneficial in extending our knowledge to organisms as complex as humans," said Galina Petukhova, Ph.D., assistant professor in the USU Department of Biology and one of the paper's senior authors. "Faulty recombination can lead to infertility or birth defects, and this work brings us closer to our ultimate goal of helping to prevent these health issues."

Camerini-Otero compared the map's new level of precision to the difference between being able to zoom in to see a city block to being able to zoom in to see each building on the block. "What we were looking for was resolution that was much higher than ever seen before," said Camerini-Otero. "Now that we can actually see these individual events of genetic recombination, we can begin to understand their molecular structure."

The researchers -- including lead authors Fatima Smagulova, Ph.D., of USU, and Ivan V. Gregoretti, Ph.D., of NIDDK -- used cutting-edge DNA sequencing technology and lots of computational power to take a snapshot of all the individual pieces of DNA that were taking part in recombination at a given moment in living cells. They then used this snapshot of short DNA pieces to draw a map of where chromosomes have an increased potential to be broken and to come back together in new ways.

Mice were used as subjects for this study because the researchers needed a population that could be created with a specific and identical genetic background. With this initial study a success, they hope to apply the same techniques to study recombination in people in the near future.

The end result is a catalog of about 10,000 hotspots and resembles a detailed map of where diversity can arise in the genome and of sites where such processes may go awry. The researchers next plan to apply what they've seen and learned with this new map to further understand chromosomal abnormalities, genetic recombination, genome stability and evolution.

The NIH's National Institute of General Medical Sciences and the March of Dimes Foundation helped fund this research through grants to Petukhova.

Autism: Exceptional Visual Abilities Explained

ScienceDaily (Apr. 5, 2011) — Researchers directed by Dr. Laurent Mottron at the University of Montreal's Centre for Excellence in Pervasive Development Disorders (CETEDUM) have determined that people with autism concentrate more brain resources in the areas associated with visual detection and identification, and conversely, have less activity in the areas used to plan and control thoughts and actions. This might explain their outstanding capacities in visual tasks.

This is the spatial distribution of regions showing more task-related activity in autistics than non-autistics for the three processing domains: "faces" in red, "objects" in green, and "words" in blue. 

The team published their findings inHuman Brain Mapping on April 4, 2011.

Aiming to understand why autistic individuals have strong abilities in terms of processing visual information, the researchers collated 15 years of data that covered the ways autistic brain works when interpreting faces, objects and written words. The data came from 26 independent brain imaging studies that looked at a total of 357 autistic and 370 non-autistic individuals. "Through this meta-analysis, we were able to observe that autistics exhibit more activity in the temporal and occipital regions and less activity in frontal cortex than non-autistics. The identified temporal and occipital regions are typically involved in perceiving and recognizing patterns and objects. The reported frontal areas subserve higher cognitive functions such as decision making, cognitive control, planning and execution,'' explained first author Fabienne Samson, who is also affiliated with the CETEDUM.

"This stronger engagement of the visual processing brain areas in autism is consistent with the well documented enhanced visuo-spatial abilities in this population," Samson said. The current findings suggest a general functional reorganization of the brain in favor of perception processes -- the processes by which information is recorded the brain. This allows autistic individuals to successfully perform, albeit in their own way, higher-level cognitive tasks that would usually require a strong involvement of frontal areas in typical individuals. These are tasks that require reasoning -- for example, a research participant would be asked if a statement is true or false, or to categorize a range of objects into groups.

"We synthesized the results of neuroimaging studies using visual stimuli from across the world. The results are strong enough to remain true despite the variability between the research designs, samples and tasks, making the perceptual account of autistic cognition currently the most validated model," Mottron said. "The stronger engagement of the visual system, whatever the task, represents the first physiological confirmation that enhanced perceptual processing is a core feature of neural organization in this population. We now have a very strong statement about autism functioning which may be ground for cognitive accounts of autistic perception, learning, memory and reasoning." This finding shows that the autistic brain successfully adapt by reallocating brain areas to visual perception, and offers many new lines of enquiry with regards to developmental brain plasticity and visual expertise in autistics.

Dr. Isabelle Soulières of the CETEDUM and the Neural Systems Group at the Massachusetts General Hospital (NSGMGH) and Dr.Thomas Zeffiro of the NSGMGH, also contributed to the findings. The CETEDUM is based at the University of Montreal affiliated Rivière-des-Prairies Hospital and is part of the Fernand-Seguin Research Centre. It is officially known as Centre d'Excellence en Troubles Envahissants du Développement de l'Université de Montréal. The research was financed in part by grants from Autism Speaks, the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes for Health Research and the Fonds de la Recherche en Santé du Québec.

New Technology Capable of Detection of 150 Genetic Syndromes from an Amniocentesis

ScienceDaily (Apr. 5, 2011) — Genetadi Biotech has presented to the scientific community -- meeting at the XXVI National Congress on Human Genetics held in Murcia -- a prenatal diagnostic device based on amniocentesis. More concretely, it is based on microarray technology (genomic hybridisation genetic chips) and with a diagnostic resolution 100 times greater than the common cytogenetic techniques.

The new device, known as Amniochip, is able to detect 150 genetic syndromes. "This involves currently validated genetic syndromes, including malformations and idiopathic mental deficiency not detected with a conventional kariotype," explained Ms Silvia Ávila, co-director of Genetadi.

The scientists pointed out that one of the advantages of this innovative technique is the fact that "a cell culture is not necessary." Thus, "the waiting time for the results with the new device drops to 48 hours, in contrast to the three weeks it currently takes through conventional kariotype technique."

Nevertheless, from a clinical perspective, the procedure for the diagnosis does not change, starting with a standard amniocentesis undertaken by the specialist gynaecologist. "The sample of amniotic liquid does not differ at all from the current amniocentesis procedure," explained doctor Ávila. "With the Amniochip only 8 or 10 ml of amniotic liquid are necessary in a tube, and which is sent to a laboratory via messenger, exactly as with the usual genetic trials."

The application of this new technology, through a prescription from the specialist in gynaecology and obstetrics, is especially suitable for all those pregnant women who require a conventional genetic study (kariotype or FISH). That is, those suspected from ecographs of having malformations, or with positive triple marker, or the over 35s. It is also suitable for couples with a history of miscarriage, or with a family history of genetic syndromes.

In those cases in which the research using this new technology found a result with doubtful clinical significance, "the DNA of the two progenitors were also analysed; in order to discard any family polymorphic alterations," explained Dr Ávila.

The new device for enhanced prenatal diagnosis, developed by Genetadi "is based on Comparative Genomic Hybridisation" (aCGH) microarray technology. Using this technique, "the sample to study and a reference are marked with different fluorochromes. These DNA hybridise on a crystal which contains thousands of different segments of human DNA. The regions selected on the Amniochip belong to regions of the human genome involved in more than 150 already known syndromes. Subsequently, computer software is used to identify the areas of differential hybridisation between the patient and the DNA control, thus indicating the existence of an alteration in its dosage (microdeletion or microduplication)."

Protein Found to Be the Link Missing Between HPV Infection and Cervical Cancer Development

ScienceDaily (Apr. 5, 2011) — Most women are infected with human papillomavirus (HPV), which can cause cervical cancer -- yet few develop the cancer. Now researchers at Georgetown Lombardi Comprehensive Cancer Center, a part of Georgetown University Medical Center, believe they have found the missing link explaining why: activation of the beta-catenin oncogene.

At the American Association for Cancer Research (AACR) 102nd Annual Meeting 2011, the researchers say that a new mouse model they developed demonstrates that switching the oncogene on in the cervix of HPV infected mice promoted development of aggressive cervical cancer.

These early findings suggest clinical implications that are both preventive and therapeutic, says the study's senior investigator, Aykut Üren, M.D., an associate professor of oncology at Lombardi

"We can potentially develop a screening method to check for HPV and beta-catenin activation in pap smears," he says. "That will identify individuals at a higher risk of developing cancer compared to ones who are only HPV positive. Then they can be more closely followed for cancer development."

Secondly, Üren points out that there are new drugs being developed to target the Wnt pathway that includes the beta-catenin protein. "Activation of this pathway is very common in colon cancer and is found in a dozen other cancers, so these same novel drugs might be useful in treating advanced stage cervical cancer patients," he says.

Üren points out that while cervical cancer has been kept in check in the U.S. and other developed nations due to use of Pap smears and, of late, the HPV vaccine that protects uninfected females, cervical cancer is the second leading cause of cancer deaths in women worldwide. "New international approaches to control and treat cervical cancer are desperately needed," he says.

Their novel mouse model was created by cross-breeding two other strains of transgenic mice -- one that expresses HPV genes in the cervix and the other that forces the beta catenin/Wnt pathway to be constantly activated, also in the cervix. While the HPV infected mice are programmed to develop cervical cancer, the tumors that grew in the double transgenic mice were larger and more aggressive.

The study was funded by the National Cancer Institute. Gülay Bulut, Ph.D., a postdoctoral researcher in Üren's laboratory, will present the results at a poster session.

The authors report having no personal financial interests related to the study.

Toward a Solution to Nerve Agent Exposure: Chemist Uses Supercomputers to Test Reagents for New Treatments

ScienceDaily (Apr. 5, 2011) — Scientists are working to develop a new drug that will regenerate a critical enzyme in the human body that "ages" after a person is exposed to deadly chemical warfare agents.

Preliminary simulations conducted by Ohio State Professor Christopher Hadad identify catalytic amino acid residues and other critical binding residues in the active site of AChE.

Christopher Hadad, Ph.D., professor of chemistry at The Ohio State University (OSU), is leveraging Ohio Supercomputer Center (OSC) resources to help develop a more effective antidote to lethal chemicals called organophosphorus (OP) nerve agents.

"This project is a combination of synthetic and computational organic chemistry conducted through OSC at Ohio State, and biochemical studies conducted by colleagues at the U.S. Army Medical Research Institute of Chemical Defense at Aberdeen Proving Ground in Maryland," said Hadad.

OP nerve agents inhibit the ability of an enzyme called acetylcholinesterase (AChE) to turn off the messages being delivered by acetylcholine (ACh), a neurotransmitter, to activate various muscles, glands and organs throughout the body. After exposure to OP agents, AChE undergoes a series of reactions, culminating in an "aging" process that inactivates AChE from performing its critical biological function. Without the application of an effective antidote, neurosynaptic communication continues unabated, resulting in uncontrolled secretions from the mouth, eyes and nose, as well as severe muscle spasms, which, if untreated, result in death.

Conventional antidotes to OP nerve agents block the activity of the nerve agent by introducing oxime compounds, which have been the focus of a number of studies. These compounds attach to the phosphorus atom of the nerve agent, after the OP is bound to AChE, and then split it away from the AChE enzyme, allowing the AChE to engage with receptors and finally relax the tissues.

However, in some cases, the combined nerve agent/AChE molecule undergo a process called aging, in which groups of single-bonded carbon and hydrogen atoms called alkyl groups are removed from the molecule and a phosphonate residue is left behind in the AChE active site. Relatively unstudied in nerve agents, this process, called dealkylation, makes the nerve agent/AChE molecule unreceptive to oximes -- an unfortunate situation, considering that certain nerve agents (e.g., soman) can undergo aging within minutes of exposure to AChE.

Hadad's study is focused on the identification of compounds that would return an appropriate alkyl group to the aged nerve agent/AChE molecule, thus allowing treatment with oximes to provide for complete recovery. The project is investigating common OP nerve agents Tabun, VX, VR, Sarin, Soman, Cyclosarin and Paraoxon, all of which take on a similar molecular structure upon aging.

"Computational studies of the interaction of the alkylating compounds with AChE were used to provide insight for the design of selective reagents," Hadad explained. "Ligand-receptor docking, followed by molecular dynamics simulations of the interactions of alkylating compounds with aged OP-AChE, was carried out in conjunction with experimental studies to investigate the binding of alkylating compounds to AChE. These results were then used to suggest interactions that aided in the orientation of alkylating compounds for maximal efficacy."

Throughout the project, Hadad employed computational studies to guide the progress of each objective, as well as to rationalize the observed experimental results.

"Dr. Hadad's work on this project has made use of a range of the tools of electronic structure theory, molecular docking, molecular dynamics and hybrid quantum mechanical/molecular mechanical methods," said Ashok Krishnamurthy, interim co-executive director of OSC. "It was by design that OSC's flagship system, the Glenn IBM 1350 Opteron cluster, was developed to meet the needs of the bioscience research investigators, such as Dr. Hadad."

Hadad's investigations of nerve agent antidotes are funded by the Defense Threat Reduction Agency (W81XWH-10-2-0044) and supported by the award of an OSC Discovery Account.

Agrotóxicos ameaçam saúde humana e meio ambiente

Perigos dos defensivos agrícolas

Os defensivos agrícolas precisam ser substituídos por produtos de menor toxicidade.

Além disso, deve-se dar toda a atenção para o perigo do uso de agrotóxicos contrabandeados.

Estes foram os principais alertas feitos por especialistas que participaram de mesa-redonda promovida pela Rádio Nacional de Brasília para debater o uso inadequado de agrotóxicos nas lavouras.

Contaminação dos produtos agrícolas

Os debatedores observaram que é preocupante a contaminação dos produtos agrícolas e de origem animal que pode afetar a saúde humana.

O professor da Universidade Federal do Rio de Janeiro e ex-presidente da Comissão Nacional de Energia Nuclear, José Luiz Santana, ponderou que o uso de defensivos acaba sendo necessário para que a produção agrícola mundial se situe no patamar anual de 2 bilhões de toneladas de grãos.

Por isso, segundo ele, "é preciso que a própria sociedade cobre o emprego correto desses produtos de forma que os efeitos negativos para a saúde do consumidor sejam reduzidos".

Contaminação do leite materno

O médico e doutor em toxicologia da Universidade Federal de Mato Grosso Wanderlei Pignatti afirmou que, em 2009, foram utilizados, no Brasil, 720 milhões de litros de agrotóxicos. Só em Mato Grosso, foram consumidos 105 mil litros do produto.

Ele indaga "onde vai parar todo esse volume" e defende a reciclagem das embalagens vazias a fim de não contaminarem o meio ambiente. A chuva e os ventos favorecem a contaminação dos lençóis freáticos.

Entre os defensivos agrícolas mais perigosos, ele cita os clorados, que estão proibidos em todo o mundo e ainda são utilizados largamente no Brasil. São defensivos que causam problemas hormonais e que podem afetar a formação de fetos, segundo o médico.

O professor relatou que, nos locais onde o uso de agrotóxicos não é feito com critério, encontram-se casos de contaminação do próprio leite materno, "o alimento mais puro que existe", o que ocorre pela ingestão do leite de vaca. "A mulher vai ter todo o seu organismo afetado quando o seu leite não estiver puro e os efeitos tóxicos podem ficar armazenados nas camadas de gordura do corpo".

Ele lembrou ainda que há uma resolução do Ministério da Agricultura que proíbe a pulverização de agrotóxicos num raio de 500 metros onde haja habitação e instalações para abrigar animais, distância que tem que ser observada também em relação às nascentes.

Alertas e alarmes

O professor Mauro Banderali, especialista em instrumentação ambiental na área de aterros sanitários, reconhece que, apesar da cultura de separação do lixo tóxico em aterros que há existe no país, ainda não se sabe exatamente o potencial dos agrotóxicos para contaminar o solo e a água e, consequentemente, os seres humanos pelo consumo de alimentos cultivados em áreas pulverizadas.

"A preparação do campo para o plantio é, frequentemente, feita sem se saber se vai vir chuva. Quando o tempo traz surpresas, ocorre a contaminação das nascentes em lugares onde a aplicação foi demasiada," disse Banderali.

O professor José Luiz Santana ressalva que existem propriedades muito bem administradas onde há a preocupação de manter práticas sustentáveis. Mas ele denunciou que há agricultores que usam marcas tidas como ultrapassadas na área dos químicos e que podem ser substituídas por alternativas de produtos mais evoluídos, disponíveis no mercado.

Para ele, apesar da seriedade do assunto, "não se deve assustar as pessoas quanto ao consumo de alimentos", já que as áreas do governo que cuidam do tema têm o dever de trabalhar pelo bom uso dos agrotóxicos e, além disso, conforme ressaltou, a agricultura conta com um "trabalho de apoio importante por parte de organizações não-governamentais que procuram difundir o uso correto dos defensivos agrícolas.