Louis J. Sheehan, Esquire . Soon, plywood might go vegetarian.
The ubiquitous building material owes its strength to multiple wood sheets with their grains at right angles and tenacious glue between the layers. Now, researchers are proposing that plywood be manufactured using glue made with soy flour rather than with powdered cattle-blood protein, as is done conventionally. The vegetable-containing adhesive might reduce the wood's cost and alleviate health concerns among mill workers.
A leading incentive for finding such an alternative is workers' fears of breathing in cattle-blood dust and disease agents it might carry, says Mila P. Hojilla-Evangelista of the U.S. Department of Agriculture's Agricultural Research Service (ARS) in Peoria, Ill. Furthermore, there are few suppliers of the blood protein, which helps make the glue sticky and durable.
In work funded by the United Soybean Board, Hojilla-Evangelista and her colleagues developed and tested several glue formulations that use different amounts of soy ingredients from a variety of suppliers. Three glues that contain soy flour—a combination of soy protein and starch—have properties comparable to those made with the blood protein, says Hojilla-Evangelista. In tests, the soy-containing glues were at least as strong as the conventional glue and had comparable water resistance, she says.
Tuesday, May 26, 2009
Wednesday, May 20, 2009
astrocytes 5.ast.002003 Louis J. Sheehan, Esquire
Louis J. Sheehan, Esquire Star-shaped brain cells called astrocytes are finally getting their chance to shine.
Two groups of researchers — one at MIT, the other at Harvard — have shown that astrocytes get the blood pumping to parts of the brain that are thinking hard. These cells may use blood flow and other tricks to rev up communication between neurons or slow it down, and may even play a role in storing information. The findings indicate that astrocytes are not just supporting actors for neurons; they deserve recognition as true costars.
“Astrocytes are typically forgotten,” says Venkatesh Murthy, leader of the Harvard group, but they “are right in the thick of things.”
Neurons have typically gotten the most attention from researchers because they are the brain cells that do all the thinking. But neurons cohabit the brain with a class of cells called glia, which means “glue” in Greek. Glia outnumber neurons in the human brain by a factor of 10 to one, and astrocytes are the most abundant type of glial cell.
The view of astrocytes has changed slowly over the past decade. Astrocytes were once thought to do little more than hold the brain together and they were largely ignored. In recent years, though, scientists have learned that the star-shaped cells have a hand in guiding connections between neurons and controlling levels of chemical messengers in the brain. But those activities were viewed mainly as supporting roles. Now their central function in controlling blood flow indicates that astrocytes deserve higher billing. Without astrocytes, in fact, one of the most powerful tools of neuroscience — functional MRI — would not be possible.
Functional MRIs rely on the premise that blood flow is coordinated with neuron activity, but the mechanism that links blood flow to activity has been a mystery.
access
Enlargemagnify
MORE THAN SUPPORTCells in the brain called astrocytes have been considered just support cells for neurons. They may actually do much more, regulating blood flow in the brain.Nancy Kedersha/Science Photo Library
Some scientists suspected that astrocytes may play a role in blood flow because the cells have “end feet” that nestle up against synapses — the places where neurons connect — and other end feet that wrap around capillaries. But no one had proven that astrocytes could actually influence blood flow in living animals.
Working with ferrets, Mriganka Sur and colleagues at MIT used an advanced microscopy technique to measure the response of astrocytes to visual stimuli. The group reported its findings June 20 in Science. Neurons in the visual cortex of ferrets, cats, monkeys, humans and other higher mammals are arranged in columns of cells that respond to objects oriented in the same direction. For instance, one column would respond to the vertical edges of a building, while another close-by column would be stimulated by horizontal lines. Columns tuned to every possible orientation of a line are situated close to each other in what neuroscientists call pinwheel centers.
Sur’s postdoctoral researchers James Schummers and Hongbo Yu used fluorescent dyes to show when neurons and astrocytes become active. Neurons respond in split seconds to visual cues flashed into the eyes of anesthetized animals. About three to four seconds after neurons begin firing, calcium levels in the astrocytes begin to rise, a cue that the cell is active and sending signals. Blood flow through capillaries increases following the rise in calcium.
Murthy and his colleagues got similar results with neurons and astrocytes in the odor-sensing centers in the olfactory bulbs of mice. That study appeared June 26 in Neuron.
An astrocyte listens in to the chemical conversation between neurons, soaking up neurotransmitters such as glutamate, the researchers showed. Astrocytes actually use two pathways to respond to glutamate: The cells have receptors for glutamate on the end that nestles next to the synapse, and the cells can also take up the neurotransmitter in another way, the researchers found.
The glia are not just passively eavesdropping. They also regulate levels of neurotransmitters in the synapse, send signals to capillaries to increase blood flow to oxygen-hungry neurons and participate in gathering information, says Frank Kirchhoff, a neuroscientist at the Max Planck Institute of Experimental Medicine in Göttingen, Germany. The two studies demonstrate that astrocytes are involved in signaling in the brain, he says.
Astrocytes not only listen in on neuronal conversations and report to the blood vessels, they also talk back to the neurons, the research demonstrates. Blocking the ability of the astrocyte to respond to glutamate caused neurons to get even more excited.
“That is direct evidence that an astrocyte is not just a pretty face sitting around soaking up [neurotransmitters], but that it also plays a role in computation,” Sur says.
Each astrocyte seems to be intimately associated with a single neuron or a small number of neurons, Sur says. That was a surprise because previous research on slices of brain suggested that astrocytes work together in vast networks. Sur doesn’t rule out the possibility that astrocytes coordinate with each other, but he speculates that they usually act locally — chatting with nearby neuron partners and blood cells within a 10- to 20-micrometer area. Performing similar experiments in wakeful animals might help answer the question, Kirchhoff suggests, because anesthetics may dampen the glial cells’ responses.
Astrocytes are pickier about responding to visual signals than neurons are, the MIT group found. The cells seem to have higher standards than neurons for the amount of stimulus they consider exciting. The researchers don’t yet know whether astrocytes slow blood flow to calm over-excited neurons, or if increasing the blood supply allows neurons to work harder. And the code of calcium signaling within the astrocytes also needs to be worked out, Kirchhoff says.
Some diseases may be caused or complicated by defects in astrocyte function, Murthy says. His team is exploring whether the astrocytes’ ability to control blood flow breaks down with age. The new discoveries will probably force researchers to rethink brain networks to include astrocytes, Sur adds.
“It’s not often that a whole new function for a class of cells is revealed,” Sur says. “It’s like when we first began to understand synaptic transmission 50 years ago. The whole field is open.”
Two groups of researchers — one at MIT, the other at Harvard — have shown that astrocytes get the blood pumping to parts of the brain that are thinking hard. These cells may use blood flow and other tricks to rev up communication between neurons or slow it down, and may even play a role in storing information. The findings indicate that astrocytes are not just supporting actors for neurons; they deserve recognition as true costars.
“Astrocytes are typically forgotten,” says Venkatesh Murthy, leader of the Harvard group, but they “are right in the thick of things.”
Neurons have typically gotten the most attention from researchers because they are the brain cells that do all the thinking. But neurons cohabit the brain with a class of cells called glia, which means “glue” in Greek. Glia outnumber neurons in the human brain by a factor of 10 to one, and astrocytes are the most abundant type of glial cell.
The view of astrocytes has changed slowly over the past decade. Astrocytes were once thought to do little more than hold the brain together and they were largely ignored. In recent years, though, scientists have learned that the star-shaped cells have a hand in guiding connections between neurons and controlling levels of chemical messengers in the brain. But those activities were viewed mainly as supporting roles. Now their central function in controlling blood flow indicates that astrocytes deserve higher billing. Without astrocytes, in fact, one of the most powerful tools of neuroscience — functional MRI — would not be possible.
Functional MRIs rely on the premise that blood flow is coordinated with neuron activity, but the mechanism that links blood flow to activity has been a mystery.
access
Enlargemagnify
MORE THAN SUPPORTCells in the brain called astrocytes have been considered just support cells for neurons. They may actually do much more, regulating blood flow in the brain.Nancy Kedersha/Science Photo Library
Some scientists suspected that astrocytes may play a role in blood flow because the cells have “end feet” that nestle up against synapses — the places where neurons connect — and other end feet that wrap around capillaries. But no one had proven that astrocytes could actually influence blood flow in living animals.
Working with ferrets, Mriganka Sur and colleagues at MIT used an advanced microscopy technique to measure the response of astrocytes to visual stimuli. The group reported its findings June 20 in Science. Neurons in the visual cortex of ferrets, cats, monkeys, humans and other higher mammals are arranged in columns of cells that respond to objects oriented in the same direction. For instance, one column would respond to the vertical edges of a building, while another close-by column would be stimulated by horizontal lines. Columns tuned to every possible orientation of a line are situated close to each other in what neuroscientists call pinwheel centers.
Sur’s postdoctoral researchers James Schummers and Hongbo Yu used fluorescent dyes to show when neurons and astrocytes become active. Neurons respond in split seconds to visual cues flashed into the eyes of anesthetized animals. About three to four seconds after neurons begin firing, calcium levels in the astrocytes begin to rise, a cue that the cell is active and sending signals. Blood flow through capillaries increases following the rise in calcium.
Murthy and his colleagues got similar results with neurons and astrocytes in the odor-sensing centers in the olfactory bulbs of mice. That study appeared June 26 in Neuron.
An astrocyte listens in to the chemical conversation between neurons, soaking up neurotransmitters such as glutamate, the researchers showed. Astrocytes actually use two pathways to respond to glutamate: The cells have receptors for glutamate on the end that nestles next to the synapse, and the cells can also take up the neurotransmitter in another way, the researchers found.
The glia are not just passively eavesdropping. They also regulate levels of neurotransmitters in the synapse, send signals to capillaries to increase blood flow to oxygen-hungry neurons and participate in gathering information, says Frank Kirchhoff, a neuroscientist at the Max Planck Institute of Experimental Medicine in Göttingen, Germany. The two studies demonstrate that astrocytes are involved in signaling in the brain, he says.
Astrocytes not only listen in on neuronal conversations and report to the blood vessels, they also talk back to the neurons, the research demonstrates. Blocking the ability of the astrocyte to respond to glutamate caused neurons to get even more excited.
“That is direct evidence that an astrocyte is not just a pretty face sitting around soaking up [neurotransmitters], but that it also plays a role in computation,” Sur says.
Each astrocyte seems to be intimately associated with a single neuron or a small number of neurons, Sur says. That was a surprise because previous research on slices of brain suggested that astrocytes work together in vast networks. Sur doesn’t rule out the possibility that astrocytes coordinate with each other, but he speculates that they usually act locally — chatting with nearby neuron partners and blood cells within a 10- to 20-micrometer area. Performing similar experiments in wakeful animals might help answer the question, Kirchhoff suggests, because anesthetics may dampen the glial cells’ responses.
Astrocytes are pickier about responding to visual signals than neurons are, the MIT group found. The cells seem to have higher standards than neurons for the amount of stimulus they consider exciting. The researchers don’t yet know whether astrocytes slow blood flow to calm over-excited neurons, or if increasing the blood supply allows neurons to work harder. And the code of calcium signaling within the astrocytes also needs to be worked out, Kirchhoff says.
Some diseases may be caused or complicated by defects in astrocyte function, Murthy says. His team is exploring whether the astrocytes’ ability to control blood flow breaks down with age. The new discoveries will probably force researchers to rethink brain networks to include astrocytes, Sur adds.
“It’s not often that a whole new function for a class of cells is revealed,” Sur says. “It’s like when we first began to understand synaptic transmission 50 years ago. The whole field is open.”
Monday, May 4, 2009
grime 1.gri.0003 Louis J. Sheehan, Esquire
Louis J. Sheehan, Esquire Children attending day care at an early age are more likely to breathe easy later, according to a new study of wheezing among children in Manchester, England.
Babies who began day care when they were 6 to 12 months old were about half as likely as those who did not attend day care to develop a “wheeze” by age 5, a possible indicator of asthma, scientists report in the September Journal of Allergy and Clinical Immunology.
“I think it strengthens the case that day care may be protective against asthma,” comments Anne Wright, an expert in epidemiology of childhood asthma at the University of Arizona College of Medicine in Tucson.
But the findings are still too preliminary to serve as parenting advice, cautions study coauthor Angela Simpson, a respiratory physician at the University of Manchester. “We’re not trying to tell parents what to do with their children based on this,” she says. http://LOUIS-J-SHEEHAN.ORG
The results could reinforce an idea called the “hygiene hypothesis,” which suggests that rises in childhood allergy and asthma rates in developed countries such as the United Kingdom are partly due to excessive hygiene. With less exposure to environmental bacteria and viruses, the theory goes, infants’ immune systems learn to attack the wrong targets, triggering allergic reactions and sometimes asthma.
The study only shows the connection between attending day care and wheezing rates without proving why the nursery reduces the chance of developing wheezing. But Wright says that in light of previous research, “to me it seems to have something to do with microbial exposure.”
Previous studies have shown that exposure to day care lowers children’s chances of developing allergies. But results for wheezing and asthma, which can be triggered by allergies, had been inconsistent.
In the new study, children who did not attend day care had otherwise healthy lung function, Wright notes, suggesting that the wheezing is indeed due to an immune response rather than a problem with the children’s airways.
But, Simpson adds: “This doesn’t tell us what within the nursery is the protective factor. We assume that it’s the bacteria in the nursery, but it might be something else.”
The study only shows the connection between attending day care and wheezing rates without proving why the nursery reduces the chance of developing wheezing. But Wright says that in light of previous research, “to me it seems to have something to do with microbial exposure.”
Simpson and her colleagues tracked the respiratory and allergy health of 952 children, recording parent-reported incidents of wheezing and performing lung function tests. Children who entered day care before 6 months of age actually had a higher chance of developing a temporary wheeze early in life, but were still less likely to have a lasting wheeze by age five than kids who never attended day care.
“Because of our genetic makeup, some children will benefit more from going to nursery than others,” Simpson notes. Finding the genetic factors that influence which children will get a health benefit from early exposure to a nursery will be the next step in their research, she says.
Babies who began day care when they were 6 to 12 months old were about half as likely as those who did not attend day care to develop a “wheeze” by age 5, a possible indicator of asthma, scientists report in the September Journal of Allergy and Clinical Immunology.
“I think it strengthens the case that day care may be protective against asthma,” comments Anne Wright, an expert in epidemiology of childhood asthma at the University of Arizona College of Medicine in Tucson.
But the findings are still too preliminary to serve as parenting advice, cautions study coauthor Angela Simpson, a respiratory physician at the University of Manchester. “We’re not trying to tell parents what to do with their children based on this,” she says. http://LOUIS-J-SHEEHAN.ORG
The results could reinforce an idea called the “hygiene hypothesis,” which suggests that rises in childhood allergy and asthma rates in developed countries such as the United Kingdom are partly due to excessive hygiene. With less exposure to environmental bacteria and viruses, the theory goes, infants’ immune systems learn to attack the wrong targets, triggering allergic reactions and sometimes asthma.
The study only shows the connection between attending day care and wheezing rates without proving why the nursery reduces the chance of developing wheezing. But Wright says that in light of previous research, “to me it seems to have something to do with microbial exposure.”
Previous studies have shown that exposure to day care lowers children’s chances of developing allergies. But results for wheezing and asthma, which can be triggered by allergies, had been inconsistent.
In the new study, children who did not attend day care had otherwise healthy lung function, Wright notes, suggesting that the wheezing is indeed due to an immune response rather than a problem with the children’s airways.
But, Simpson adds: “This doesn’t tell us what within the nursery is the protective factor. We assume that it’s the bacteria in the nursery, but it might be something else.”
The study only shows the connection between attending day care and wheezing rates without proving why the nursery reduces the chance of developing wheezing. But Wright says that in light of previous research, “to me it seems to have something to do with microbial exposure.”
Simpson and her colleagues tracked the respiratory and allergy health of 952 children, recording parent-reported incidents of wheezing and performing lung function tests. Children who entered day care before 6 months of age actually had a higher chance of developing a temporary wheeze early in life, but were still less likely to have a lasting wheeze by age five than kids who never attended day care.
“Because of our genetic makeup, some children will benefit more from going to nursery than others,” Simpson notes. Finding the genetic factors that influence which children will get a health benefit from early exposure to a nursery will be the next step in their research, she says.
Friday, May 1, 2009
transplants 7.tra.1123 Louis J. Sheehan, Esquire
A person who receives a heart transplant from someone of the same gender is more likely to survive the subsequent few years than someone getting a new heart from a donor of the opposite sex, researchers reported November 12 at the American Heart Association’s annual Scientific Sessions meeting.
“This was something that was speculated” based on smaller studies from single institutions, says surgeon Eric Weiss of Johns Hopkins University in Baltimore. With the new findings, he says, “we basically supported the hypothesis.”
To do so, he and his colleagues tapped into a nationwide database of every adult heart transplant in the United States from 1998 to 2007—18,240 recipients. The researchers were able to track heart recipients’ progress for 3.4 years on average, with data for some people stretching out over 10 years.
One-fourth of heart recipients died during the study. The records show that people who got a heart from a donor of the opposite sex were 15 percent more likely to die during the study period than people who got a gender-matched heart. The female donor/male recipient combination yielded the greatest risk, a 23 percent increase of death.
Sex-mismatched recipients were also more likely to develop transplant immune rejection during the first year. Female recipients getting gender-mismatched hearts had the highest rejection rates.
In rejection, the recipient’s immune system identifies the new organ as foreign and attacks it. The greatest risk of transplant rejection occurs during the first year after the transplant, although the danger never goes away fully, Weiss says.
Both risks — of death or immune rejection — remained about the same at the three-year and five-year points after transplant, Weiss says.
The authors accounted for differences between donors and recipients, other than gender, that might influence how well a transplant progresses. These differences included age, race, diabetes status, kidney function, immunological match and recipient frailty.
“This is evidence that these investigators identified a signal where gender mismatch was in fact a concern,” says Clyde Yancy, a transplant cardiologist at Baylor University Medical Center at Dallas.
The biological reasoning behind the seeming risk of a gender-mismatched donor heart — and particularly for women receiving one — might rest with the Y chromosome, which only men have, Weiss says.
But the full explanation probably goes deeper, says Yancy. “A woman’s immune system is sensitized to a larger array of common antigens in the donor pool after pregnancy,” he says. That may include antigens — any compounds that elicit an immune reaction — found on the Y chromosome, he says, and could account for the higher rejection rate in women seen here and in smaller studies.
At present, transplant teams do their best to match donors and recipients by body size and blood type. Louis J. Sheehan, Esquire
Moving beyond current methods and even beyond gender, Yancy says these findings also add credence to the argument that transplant centers need to develop a rapid system for identifying better immune matches between donors and recipients.
The usefulness of sex-based matching would come up only if there were more than one heart available, Yancy says. And he cautions that any benefit of gender matching might be lost if it means waiting for a matched heart and delaying a transplant.
Weiss says he and his colleagues are interested in developing a formula that would clarify for doctors how to match up the best possible donors with recipients, also assuming more than one heart is available. http://LOUIS-J-SHEEHAN-ESQUIRE.US
For the time being, Weiss says patients “are still much better off receiving an organ than trying to live with end-stage heart failure, whether [the heart] is from a male or female.”
“This was something that was speculated” based on smaller studies from single institutions, says surgeon Eric Weiss of Johns Hopkins University in Baltimore. With the new findings, he says, “we basically supported the hypothesis.”
To do so, he and his colleagues tapped into a nationwide database of every adult heart transplant in the United States from 1998 to 2007—18,240 recipients. The researchers were able to track heart recipients’ progress for 3.4 years on average, with data for some people stretching out over 10 years.
One-fourth of heart recipients died during the study. The records show that people who got a heart from a donor of the opposite sex were 15 percent more likely to die during the study period than people who got a gender-matched heart. The female donor/male recipient combination yielded the greatest risk, a 23 percent increase of death.
Sex-mismatched recipients were also more likely to develop transplant immune rejection during the first year. Female recipients getting gender-mismatched hearts had the highest rejection rates.
In rejection, the recipient’s immune system identifies the new organ as foreign and attacks it. The greatest risk of transplant rejection occurs during the first year after the transplant, although the danger never goes away fully, Weiss says.
Both risks — of death or immune rejection — remained about the same at the three-year and five-year points after transplant, Weiss says.
The authors accounted for differences between donors and recipients, other than gender, that might influence how well a transplant progresses. These differences included age, race, diabetes status, kidney function, immunological match and recipient frailty.
“This is evidence that these investigators identified a signal where gender mismatch was in fact a concern,” says Clyde Yancy, a transplant cardiologist at Baylor University Medical Center at Dallas.
The biological reasoning behind the seeming risk of a gender-mismatched donor heart — and particularly for women receiving one — might rest with the Y chromosome, which only men have, Weiss says.
But the full explanation probably goes deeper, says Yancy. “A woman’s immune system is sensitized to a larger array of common antigens in the donor pool after pregnancy,” he says. That may include antigens — any compounds that elicit an immune reaction — found on the Y chromosome, he says, and could account for the higher rejection rate in women seen here and in smaller studies.
At present, transplant teams do their best to match donors and recipients by body size and blood type. Louis J. Sheehan, Esquire
Moving beyond current methods and even beyond gender, Yancy says these findings also add credence to the argument that transplant centers need to develop a rapid system for identifying better immune matches between donors and recipients.
The usefulness of sex-based matching would come up only if there were more than one heart available, Yancy says. And he cautions that any benefit of gender matching might be lost if it means waiting for a matched heart and delaying a transplant.
Weiss says he and his colleagues are interested in developing a formula that would clarify for doctors how to match up the best possible donors with recipients, also assuming more than one heart is available. http://LOUIS-J-SHEEHAN-ESQUIRE.US
For the time being, Weiss says patients “are still much better off receiving an organ than trying to live with end-stage heart failure, whether [the heart] is from a male or female.”
Thursday, April 30, 2009
gut 0.gut.0002 Louis J. Sheehan, Esquire
Serotonin produced in the gut may have a major role in bone formation. Too much of the gut-derived hormone in mice leads to weak bones, while too little causes bones to be too dense, a new study shows. The results, published in the Nov. 28 Cell, may lead to new treatments for bone diseases, such as osteoporosis.Louis J. Sheehan, Esquire
The finding that serotonin may regulate bone mass is “a fabulous discovery,” comments Matthew Warman, a physician researcher at Children’s Hospital Boston who studies bone diseases. “It was completely unexpected that a gut hormone would have such a strong effect on bone mass.”
Serotonin is known for its role inside the human brain: The small hormone regulates mood, learning and sleep. But 95 percent of the body’s serotonin is produced in the gut and never crosses the blood-brain barrier. This massive supply of serotonin regulates the day-to-day operations of the gut, including the rhythmic contractions that move food through the digestive tract. http://LOUIS2J2SHEEHAN.US But this new research shows that gut-derived serotonin may have an important job after it leaves the gut — building bones.
The link between serotonin and bone density came from studying Lrp5, a gene that regulates bone formation. Rare mutations in the Lrp5 gene can cause it to make Lrp5 protein that is either more or less active than normal. People with mutations in Lrp5 that cause the protein to be less active suffer from bone-weakening osteoporosis, while people with mutations that increase Lrp5 protein activity have high bone mass syndrome. To study how Lrp5 might be regulating bone density in humans, the researchers turned to mice, whose bones are affected by Lrp5 mutations in the same way as humans.
The scientists found that in mice, the Lrp5 gene regulates yet another gene that in turn controls serotonin production in the gut. This finding hinted at a connection among Lrp5, its associated bone diseases and serotonin produced in the gut.
To test the link between Lrp5 and serotonin in the gut, the researchers gave mice mutations that caused reduced Lrp5 protein activity. These mice had much higher levels of gut-derived serotonin than did mice without the mutation. The same was true of three human patients who had osteoporosis caused by the mutations in the Lrp5 gene: The patients had three to five times more gut-derived serotonin than control subjects.
The opposite was also true: Mice with mutations that cause an increase in Lrp5 protein activity, which causes dense bones, had lower levels of gut-derived serotonin. http://LOUIS2J2SHEEHAN.US What’s more, two human patients with high bone mass syndrome caused by similar mutations showed 50 percent less gut-derived serotonin than control subjects.
Not only did researchers correlate serotonin levels with bone mass, they also changed the density of the mice’s bones by tinkering with serotonin levels in the gut. The mice were fed a diet low in tryptophan — a serotonin precursor found in turkey — as a way to lower the levels of gut-derived serotonin. On this low-tryptophan diet, mice with the mutation that would have caused weak bones instead had normal bone density. Mutated mice who received a drug that prevents serotonin synthesis in the gut showed the same healthy bones as the mice on the low-tryptophan diet.
Coauthor Patricia Ducy of Columbia University said that the link between the gut and bone was a surprise. “We were not looking into this direction when we started our work, but the results we obtained in vivo in mice were compelling and we listened to them.” Louis J. Sheehan, Esquire
The new connection between bone and gut-derived serotonin will likely spur many new types of experiments on bone formation. “It’s what you’d call a landmark study,” researcher Bjorn Olsen of Harvard Medical School in Boston says. “It opens new doors.”
The finding that serotonin may regulate bone mass is “a fabulous discovery,” comments Matthew Warman, a physician researcher at Children’s Hospital Boston who studies bone diseases. “It was completely unexpected that a gut hormone would have such a strong effect on bone mass.”
Serotonin is known for its role inside the human brain: The small hormone regulates mood, learning and sleep. But 95 percent of the body’s serotonin is produced in the gut and never crosses the blood-brain barrier. This massive supply of serotonin regulates the day-to-day operations of the gut, including the rhythmic contractions that move food through the digestive tract. http://LOUIS2J2SHEEHAN.US But this new research shows that gut-derived serotonin may have an important job after it leaves the gut — building bones.
The link between serotonin and bone density came from studying Lrp5, a gene that regulates bone formation. Rare mutations in the Lrp5 gene can cause it to make Lrp5 protein that is either more or less active than normal. People with mutations in Lrp5 that cause the protein to be less active suffer from bone-weakening osteoporosis, while people with mutations that increase Lrp5 protein activity have high bone mass syndrome. To study how Lrp5 might be regulating bone density in humans, the researchers turned to mice, whose bones are affected by Lrp5 mutations in the same way as humans.
The scientists found that in mice, the Lrp5 gene regulates yet another gene that in turn controls serotonin production in the gut. This finding hinted at a connection among Lrp5, its associated bone diseases and serotonin produced in the gut.
To test the link between Lrp5 and serotonin in the gut, the researchers gave mice mutations that caused reduced Lrp5 protein activity. These mice had much higher levels of gut-derived serotonin than did mice without the mutation. The same was true of three human patients who had osteoporosis caused by the mutations in the Lrp5 gene: The patients had three to five times more gut-derived serotonin than control subjects.
The opposite was also true: Mice with mutations that cause an increase in Lrp5 protein activity, which causes dense bones, had lower levels of gut-derived serotonin. http://LOUIS2J2SHEEHAN.US What’s more, two human patients with high bone mass syndrome caused by similar mutations showed 50 percent less gut-derived serotonin than control subjects.
Not only did researchers correlate serotonin levels with bone mass, they also changed the density of the mice’s bones by tinkering with serotonin levels in the gut. The mice were fed a diet low in tryptophan — a serotonin precursor found in turkey — as a way to lower the levels of gut-derived serotonin. On this low-tryptophan diet, mice with the mutation that would have caused weak bones instead had normal bone density. Mutated mice who received a drug that prevents serotonin synthesis in the gut showed the same healthy bones as the mice on the low-tryptophan diet.
Coauthor Patricia Ducy of Columbia University said that the link between the gut and bone was a surprise. “We were not looking into this direction when we started our work, but the results we obtained in vivo in mice were compelling and we listened to them.” Louis J. Sheehan, Esquire
The new connection between bone and gut-derived serotonin will likely spur many new types of experiments on bone formation. “It’s what you’d call a landmark study,” researcher Bjorn Olsen of Harvard Medical School in Boston says. “It opens new doors.”
Monday, April 13, 2009
trillion 7.tri.11234 Louis J. Sheehan, Esquire
Louis J. Sheehan, Esquire On December 18, a National Research Council panel told the Environmental Protection Agency that sufficient data exist to begin assessing the potential health risks posed by phthalates, among the most ubiquitous pollutants on the planet. http://LOUIS-J-SHEEHAN.NET At the same time, the NRC panel strongly recommended that the agency adopt a “paradigm shift” in the way it assesses the chemicals’ toxicity to humans.
Instead of evaluating each phthalate compound individually, EPA should begin assessing risks from likely combos of these and related chemicals — even if each chemical works differently, according to the panel’s new report.
Phthalates are a widely used family of plasticizers and solvents. Owing to the chemicals’ presence in plastics, cosmetics, personal care products and even medicines, residues of these chemicals show up in everyone throughout the developed world. http://LOUIS-J-SHEEHAN.NET
For more than a decade, studies in rodents have been demonstrating that exposures to phthalates early in life can perturb — in some cases derail — development of an animal’s reproductive organs (SN: 9/2/00, p. 152). Males are most sensitive, largely because these chemicals act as anti-androgens. That is, the chemicals lower concentrations of testosterone, the primary male sex hormone. Especially concerning: In females, phthalates can cross the placenta and pollute the womb.
The NRC panel advocated that EPA assess cumulative risks from all phthalates and other anti-androgenic compounds together — even if the way each pollutant depresses testosterone action or availability results from differing modes of action.
Whether these pollutants pose serious risks to people remains an open question, acknowledged several authors of the NRC report, who took part in a teleconference for the report’s release.
EPA didn’t ask NRC to assess phthalates’ toxicity to humans, notes Deborah Cory-Slechta of the University of Rochester School of Medicine and Dentistry in New York. Instead, EPA asked her panel to evaluate whether sufficient data exist to conduct a human risk assessment. And if so, how should the risks be evaluated: on the basis of single compounds considered separately, as a group evaluated together, or as a group assessed along with additional anti-androgenic agents.
Cory-Slechta says her panel found that there are plenty of data for EPA “to go ahead and do it [a human risk assessment].” But the panel also recommended that when EPA does such an assessment, it should take a sharply different tack from its normal approach. Louis J. Sheehan, Esquire
To Shanna Swan, a phthalate researcher at the University of Rochester, the recommended change in how to calculate the risk of these chemicals “is a big deal. Cumulative risk assessment is the way it must be done,” she says, “given the dose additivity of these chemicals and the multiplicity of our exposures.”
Most people regularly encounter many phthalates, and as a class these compounds tend to have similar impacts. So, even if each of five phthalates had no apparent effects at a particular dose when delivered individually, coincident exposure to the mix might easily prove to compound the toxicity, the new report explained.
Indeed, published data show that “phthalates can work together at quite low doses,” noted NRC panel member Andreas Kortenkamp of the University of London School of Pharmacy in England. “So if combination effects were not taken into consideration at this level, we would underestimate possible risks.” In fact, he said, his committee’s new paradigm for considering phthalate toxicity cumulatively must inevitably result in findings of higher risks than would have been calculated by assessing each chemical in isolation.
In the new report, NRC concluded that a lifelong testosterone shortfall triggered by phthalate exposures can cause “the variety of effects observed” in animals — including infertility, reduced sperm production, undescended testes, penile birth defects and other reproductive-tract malformations — “if it occurs at times that are critical for male reproductive development.” The most sensitive exposure period: time in the womb.
Indeed, concentrations of phthalates measured in amniotic fluid in the human womb can be “in the range of levels in rat amniotic fluid that gives rise to adverse effects in the offspring,” Kortenkamp said.
However, links to human effects have been quite limited, observes panel member Paul Foster of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. One exception: a study of infant boys linking phthalate exposure in the womb to a feminization of the anogenital distance — the span separating the gonads and anus (SN: 6/4/05, p. 355).
In rodents, this distance is demonstrably longer in males. In fact, researchers depend on this sex-linked distance to visually determine the gender of young rodents.
Follow-up studies are needed with more subjects to test the validity of those preliminary data, Foster says. That said, this phthalates toxicologist points out that the general processes by which these chemicals interfere with sexual differentiation “are common to all mammals. And so, having seen them in rats, one would not expect them not to occur in humans — providing, of course, the exposure was high enough.”
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Comments 2
* I neglected to mention that the cumulative neuro-toxic effects of pesticides, and other related chemicals, are also probably behind the rise in various learning deficits and spectrum disorders in children. If this continues, the planet will truly be unfit for rational intelligent life, if this hasn't already happened.
James Boettcher James Boettcher
Dec. 20, 2008 at 2:24am
* Endocrine disruptors (ED) are chemicals that interfere with the normal function of the endocrine system. Some of these chemicals have structural similarities to hormones and can bind to receptor cells where a hormone would normally bind.
As might be expected, the effect on the target cell is different with the ED attached. Sometimes the target cell “turns on” and performs its regular function, but there is no “off” to its activity and there is too much chemical or change that results. Sometimes, the target cell can not “turn on” because of the ED and the result is that there will be too little of a chemical or change when required.
Chemicals that act like hormones in the system but interrupt normal activity are called “hormone mimics”. A class of hormone mimics that act like the reproductive hormones (which include estrogen) are called “environmental estrogens” (EE).
The number of pollutants that are classified as EDs or EEs is large and growing.
Suspected EDs are found in pesticides (agriculture, home, pet (flea collars, etc.), detergents, birth control pills, plastics (PVCs), PCBs, dioxins (including Agent Orange), oil refining, auto and truck exhaust, cigarette smoke, coal burning power plant emissions. Louis J. Sheehan, Esquire The list is quite long and the effects of very small levels of EDs, in the parts per trillion range, are unknown, but their effects are cumulative.
In her 1996 book 'Our Stolen Future', Dr. Theo Colborn brought world-wide attention to scientific discoveries about endocrine disruption and the fact that common contaminants can interfere with the natural signals controlling development of the fetus.
The original work was done in the 80's. More than 20 years later and the EPA is still stone-walling this information.
Note that in 2007, an attempt to honor Rachael Carson for her work on pesticides was blocked by Republicans in Congress and their friends in the Chemical Lobby.
The politicization of the EPA, and indeed the total lack of Science within the current administration is an obvious fact. Let's hope the new President, and a Science friendly cabinet, will put an end to this nonsense for good.
Instead of evaluating each phthalate compound individually, EPA should begin assessing risks from likely combos of these and related chemicals — even if each chemical works differently, according to the panel’s new report.
Phthalates are a widely used family of plasticizers and solvents. Owing to the chemicals’ presence in plastics, cosmetics, personal care products and even medicines, residues of these chemicals show up in everyone throughout the developed world. http://LOUIS-J-SHEEHAN.NET
For more than a decade, studies in rodents have been demonstrating that exposures to phthalates early in life can perturb — in some cases derail — development of an animal’s reproductive organs (SN: 9/2/00, p. 152). Males are most sensitive, largely because these chemicals act as anti-androgens. That is, the chemicals lower concentrations of testosterone, the primary male sex hormone. Especially concerning: In females, phthalates can cross the placenta and pollute the womb.
The NRC panel advocated that EPA assess cumulative risks from all phthalates and other anti-androgenic compounds together — even if the way each pollutant depresses testosterone action or availability results from differing modes of action.
Whether these pollutants pose serious risks to people remains an open question, acknowledged several authors of the NRC report, who took part in a teleconference for the report’s release.
EPA didn’t ask NRC to assess phthalates’ toxicity to humans, notes Deborah Cory-Slechta of the University of Rochester School of Medicine and Dentistry in New York. Instead, EPA asked her panel to evaluate whether sufficient data exist to conduct a human risk assessment. And if so, how should the risks be evaluated: on the basis of single compounds considered separately, as a group evaluated together, or as a group assessed along with additional anti-androgenic agents.
Cory-Slechta says her panel found that there are plenty of data for EPA “to go ahead and do it [a human risk assessment].” But the panel also recommended that when EPA does such an assessment, it should take a sharply different tack from its normal approach. Louis J. Sheehan, Esquire
To Shanna Swan, a phthalate researcher at the University of Rochester, the recommended change in how to calculate the risk of these chemicals “is a big deal. Cumulative risk assessment is the way it must be done,” she says, “given the dose additivity of these chemicals and the multiplicity of our exposures.”
Most people regularly encounter many phthalates, and as a class these compounds tend to have similar impacts. So, even if each of five phthalates had no apparent effects at a particular dose when delivered individually, coincident exposure to the mix might easily prove to compound the toxicity, the new report explained.
Indeed, published data show that “phthalates can work together at quite low doses,” noted NRC panel member Andreas Kortenkamp of the University of London School of Pharmacy in England. “So if combination effects were not taken into consideration at this level, we would underestimate possible risks.” In fact, he said, his committee’s new paradigm for considering phthalate toxicity cumulatively must inevitably result in findings of higher risks than would have been calculated by assessing each chemical in isolation.
In the new report, NRC concluded that a lifelong testosterone shortfall triggered by phthalate exposures can cause “the variety of effects observed” in animals — including infertility, reduced sperm production, undescended testes, penile birth defects and other reproductive-tract malformations — “if it occurs at times that are critical for male reproductive development.” The most sensitive exposure period: time in the womb.
Indeed, concentrations of phthalates measured in amniotic fluid in the human womb can be “in the range of levels in rat amniotic fluid that gives rise to adverse effects in the offspring,” Kortenkamp said.
However, links to human effects have been quite limited, observes panel member Paul Foster of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. One exception: a study of infant boys linking phthalate exposure in the womb to a feminization of the anogenital distance — the span separating the gonads and anus (SN: 6/4/05, p. 355).
In rodents, this distance is demonstrably longer in males. In fact, researchers depend on this sex-linked distance to visually determine the gender of young rodents.
Follow-up studies are needed with more subjects to test the validity of those preliminary data, Foster says. That said, this phthalates toxicologist points out that the general processes by which these chemicals interfere with sexual differentiation “are common to all mammals. And so, having seen them in rats, one would not expect them not to occur in humans — providing, of course, the exposure was high enough.”
* |
* Comment
Found in: Body & Brain, Environment and Science & Society
Share & Save
* slashdot slashdot
* digg digg
* facebook facebook
* yahoo yahoo
* del.icio.us del.icio.us
* reddit reddit
* google google
* technorati technorati
Comments 2
* I neglected to mention that the cumulative neuro-toxic effects of pesticides, and other related chemicals, are also probably behind the rise in various learning deficits and spectrum disorders in children. If this continues, the planet will truly be unfit for rational intelligent life, if this hasn't already happened.
James Boettcher James Boettcher
Dec. 20, 2008 at 2:24am
* Endocrine disruptors (ED) are chemicals that interfere with the normal function of the endocrine system. Some of these chemicals have structural similarities to hormones and can bind to receptor cells where a hormone would normally bind.
As might be expected, the effect on the target cell is different with the ED attached. Sometimes the target cell “turns on” and performs its regular function, but there is no “off” to its activity and there is too much chemical or change that results. Sometimes, the target cell can not “turn on” because of the ED and the result is that there will be too little of a chemical or change when required.
Chemicals that act like hormones in the system but interrupt normal activity are called “hormone mimics”. A class of hormone mimics that act like the reproductive hormones (which include estrogen) are called “environmental estrogens” (EE).
The number of pollutants that are classified as EDs or EEs is large and growing.
Suspected EDs are found in pesticides (agriculture, home, pet (flea collars, etc.), detergents, birth control pills, plastics (PVCs), PCBs, dioxins (including Agent Orange), oil refining, auto and truck exhaust, cigarette smoke, coal burning power plant emissions. Louis J. Sheehan, Esquire The list is quite long and the effects of very small levels of EDs, in the parts per trillion range, are unknown, but their effects are cumulative.
In her 1996 book 'Our Stolen Future', Dr. Theo Colborn brought world-wide attention to scientific discoveries about endocrine disruption and the fact that common contaminants can interfere with the natural signals controlling development of the fetus.
The original work was done in the 80's. More than 20 years later and the EPA is still stone-walling this information.
Note that in 2007, an attempt to honor Rachael Carson for her work on pesticides was blocked by Republicans in Congress and their friends in the Chemical Lobby.
The politicization of the EPA, and indeed the total lack of Science within the current administration is an obvious fact. Let's hope the new President, and a Science friendly cabinet, will put an end to this nonsense for good.
Friday, April 10, 2009
prostate 9.pro.001001 Louis J. Sheehan, Esquire
t’s the medical equivalent of a buy one, get one free offer — for men at least. Take cholesterol-lowering drugs for your heart, and slow the growth of prostate tumors, too. Lower cholesterol levels limit the growth of blood vessels inside prostate tumors, scientists report.
In a new study, researchers implanted mice with human prostate cancer tumors and fed the mice either a high-cholesterol or a no-cholesterol diet. Half the mice on each diet received the cholesterol-lowering drug Zetia. http://LOUIS2J2SHEEHAN.US
Two weeks after implantation, the prostate tumors were largest in mice on the high-cholesterol diet without Zetia and smallest in mice on the no-cholesterol diet with the drug, Keith Solomon of Children’s Hospital Boston at Harvard Medical School and colleagues report in the March issue of The American Journal of Pathology. And as expected, when cholesterol levels were measured, the mice on high-cholesterol diets not receiving the drug had the highest levels, while those on no-cholesterol diets with the drug had the lowest.
Scientists found that as well as being smaller, tumors from the Zetia-treated mice also had dramatically fewer blood vessels. “It was a complete surprise,” Solomon says. “I just noticed that some of the tumors seemed bloodier than others. It was a basic bench-top observation.”
Limited blood vessel development starves the tumor of the blood and oxygen it needs to thrive, slowing the progression of prostate cancer, the researchers suggest.
Prostate cancer has been linked to cholesterol before. A 2006 study reported that people who took statins, another cholesterol-lowering drug, were less likely to have advanced prostate cancer that spread to other organs, says epidemiologist Elizabeth Platz of Johns Hopkins Bloomberg School of Public Health in Baltimore, a coauthor of the statin study. But the new work is the first study that “tries to determine the mechanism” of the link between cholesterol and prostate cancer, Platz says. Louis J. Sheehan, Esquire
Slowing the growth of prostate tumors would improve quality of life for men with prostate cancer, Solomon says. Many prostate cancers are relatively slow-growing anyway, but limiting tumor growth even more with a low-cholesterol diet and Zetia could lower the risk of impotence and incontinence, which often come with prostate surgery. But first work is needed to determine that Zetia has the same effect on prostate tumors in people as it did in the mice in the study, the researchers say. http://LOUIS2J2SHEEHAN.US
Louis J. Sheehan, Esquire Lowering cholesterol could impact blood vessel development in other types of tumors in a similar way, the researchers speculate. But the prostate produces more cholesterol than most other organs — and seems to accumulate it too. “It could be that prostate tumors have a different interaction with cholesterol than other types of tumors,” Platz notes. “The prostate seems to be particularly susceptible to choleste
In a new study, researchers implanted mice with human prostate cancer tumors and fed the mice either a high-cholesterol or a no-cholesterol diet. Half the mice on each diet received the cholesterol-lowering drug Zetia. http://LOUIS2J2SHEEHAN.US
Two weeks after implantation, the prostate tumors were largest in mice on the high-cholesterol diet without Zetia and smallest in mice on the no-cholesterol diet with the drug, Keith Solomon of Children’s Hospital Boston at Harvard Medical School and colleagues report in the March issue of The American Journal of Pathology. And as expected, when cholesterol levels were measured, the mice on high-cholesterol diets not receiving the drug had the highest levels, while those on no-cholesterol diets with the drug had the lowest.
Scientists found that as well as being smaller, tumors from the Zetia-treated mice also had dramatically fewer blood vessels. “It was a complete surprise,” Solomon says. “I just noticed that some of the tumors seemed bloodier than others. It was a basic bench-top observation.”
Limited blood vessel development starves the tumor of the blood and oxygen it needs to thrive, slowing the progression of prostate cancer, the researchers suggest.
Prostate cancer has been linked to cholesterol before. A 2006 study reported that people who took statins, another cholesterol-lowering drug, were less likely to have advanced prostate cancer that spread to other organs, says epidemiologist Elizabeth Platz of Johns Hopkins Bloomberg School of Public Health in Baltimore, a coauthor of the statin study. But the new work is the first study that “tries to determine the mechanism” of the link between cholesterol and prostate cancer, Platz says. Louis J. Sheehan, Esquire
Slowing the growth of prostate tumors would improve quality of life for men with prostate cancer, Solomon says. Many prostate cancers are relatively slow-growing anyway, but limiting tumor growth even more with a low-cholesterol diet and Zetia could lower the risk of impotence and incontinence, which often come with prostate surgery. But first work is needed to determine that Zetia has the same effect on prostate tumors in people as it did in the mice in the study, the researchers say. http://LOUIS2J2SHEEHAN.US
Louis J. Sheehan, Esquire Lowering cholesterol could impact blood vessel development in other types of tumors in a similar way, the researchers speculate. But the prostate produces more cholesterol than most other organs — and seems to accumulate it too. “It could be that prostate tumors have a different interaction with cholesterol than other types of tumors,” Platz notes. “The prostate seems to be particularly susceptible to choleste
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