Contact: Angela Babb
American Academy of Neurology
ST. PAUL, Minn. – People taking cholesterol-lowering drugs such as atorvastatin after a stroke may be at an increased risk of hemorrhagic stroke, or bleeding in the brain, a risk not found in patients taking statins who have never had a stroke. But researchers caution the risk must be balanced against the much larger overall benefit of the statin in reducing the total risk of a second stroke and other cardiovascular events when making treatment decisions. The research is published in the December 12, 2007, online issue of Neurology®, the medical journal of the American Academy of Neurology.
For the study, researchers conducted a secondary analysis of the results of the Stroke Prevention with Aggressive Reduction in Cholesterol Levels (SPARCL) clinical trial. The trial enrolled 4,731 people who were within one to six months of having had a stroke or transient ischemic attack, or mini-stroke, and with no history of heart disease. Half of the participants received atorvastatin and half received a placebo. The participants were then followed for an average of four and a half years.
Overall, treatment was associated with a 16-percent reduction in total stroke, the study’s primary endpoint, as well as significant reductions in coronary heart events. However, secondary analysis found that the overall reduction in stroke included an increase in the risk of brain hemorrhage. Of those people randomized to atorvastatin, the study found 2.3 percent experienced a hemorrhagic stroke during the study compared to 1.4 percent of those taking placebo. The study also found there was a 21-percent reduction in ischemic stroke, a more common type of stroke involving a block in the blood supply to the brain, among people taking atorvastatin.
Other factors were also found to increase the risk of brain hemorrhage. For example, those who had experienced a hemorrhagic stroke prior to the study were more than five times as likely to suffer a second stroke of this kind. Men were also nearly twice as likely as women to suffer a hemorrhagic stroke. People with severe high blood pressure at their last doctor’s visit prior to the hemorrhagic stroke had over six times the risk of those with normal blood pressure.
“Although treatment of patients with a stroke or transient ischemic attack was clearly associated with an overall reduction in a second stroke, hemorrhagic stroke was more frequent in people treated with atorvastatin, in those with a prior hemorrhagic stroke, in men and in those with uncontrolled hypertension,” according to study author Larry B. Goldstein, MD, with Duke University Medical Center in Durham, North Carolina, and Fellow of the American Academy of Neurology. “This risk of hemorrhagic stroke also increased with age.”
“Treatment with atorvastatin did not disproportionately increase the frequency of brain hemorrhage associated with these other factors. The risk of hemorrhage in patients who have had a transient ischemic attack or stroke must be balanced against the benefits of cholesterol-lowering drugs in reducing the overall risk of a second stroke, as well as other cardiovascular events,” said Goldstein.
The SPARCL trial was funded by Pfizer, the maker of atorvastatin.
The American Academy of Neurology, an association of more than 20,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer’s disease, epilepsy, Parkinson disease, and multiple sclerosis.
For more information about the American Academy of Neurology, visit http://www.aan.com.
by Jeanne Hambleton © 2007
NFA Leader Against Pain – Advocate
Maybe I should mention that you just might need some kleenex tissues before you start this story but please read it anyway, if only in the spirit of Goodwill to All Children. The men are big enough to look after themselves.
As folks in the UK were getting ready this morning to do some Christmas shopping an email arrived on my desktop with a warning, which said, “This email needs to circulate forever.”
How could I pass up this invitation to inquire within? The email also stated, “This is a real eye opener. A real tear jerker No prerequisites (commitments). Simply, because everyone should be reminded.“
This was sent to me by a lady from Montevideo, Uruguay called Marta. Where the pictures, shown in the email, were taken, it does not say, but I am sure it conveys a worldwide message, especially within the African continent.
Picture 1. shows European students sat at computers working, with the caption, “Does studying annoy you?”
Picture 2. reveals children, possibly from Africa, without shoes, sat on a bench and drawing their lessons in the dirt with their fingers. The caption says, “ Not them!”
Picture 3. is a happy family picture of a father with his daughter enjoying a beef burger roll with the words, “Hate veggies?”
Picture 4. is a picture of a long line of native mothers and starved children, clothed, in rags and waiting in line with a bowl for some food handouts. This caption says, “They starve from hunger!”
Picture 5. reveals the back view of a jolly obese child having fun, with a caption which reads, “On a diet?”
Picture 6. gives a close-up of a painfully thin starved child with a tape measure around the child’s matchstick thin arm. The caption referring to diet says, “They die from it!” Or the lack of any kind of diet.
Picture 7. shows a baby being cuddled by a parent revealing the lovely cuddly cheeks of a child’s bottom. This reads, “Does your parent’s care tire you?”
Picture 8. shows a sibling cuddling a child with the last bone in the baby’s spine clearly visible as she rests in sister’s arms for comfort. This caption tells us these children have no parents to grow tired of. “They don’t have any!”
Picture 9. reveals youngsters sat at a games console and states, “Bored with the same game?”
Picture 10. Shows a young unclothed child playing in the dirt with a bit of stick, next to the human skull of someone who had probably died from starvation. The caption reads, “They have no option!”
Picture 11. shows a smart new trainer with a caption which reads, “Someone got you Adidas instead of Nike?”
Picture 12. pictures the feet of a child with half of a plastic bottle cut to make the sole of a pair of sandals. The picture clearly reveals the screw top of the plastic bottle on the footwear, which is tied onto the foot with rag. This caption states, “They only have one brand?” Maybe it is cola?????
Picture 13. is of a sweet little girl in clean pyjamas snuggled up in her cosy bed. This caption reads, “Aren’t you thankful for a bed to sleep in?”
Picture 14. The final contrast picture shows a child laying in the dirt, half covered with a piece of old rag, trying to sleep, with a caption that reads, “They’d wish not to wake up!”
The closing slide asks, “Are you still complaining? Observe around you and be thankful for all that you have in this transitory lifetime…. We are fortunate to have much more than what we need to be content. Let us try not to feed this endless cycle of consumerism and immortality in which this ‘modern and advanced’ society forgets and ignores the other two thirds of our brothers and sisters. Send this information without any obligation or expectation in receiving good luck. Don’t keep it! Send it and it won’t be in vain. Let us complain less and give more!”
I imagine you feel as I do. I work hard for my dollar and I do not believe in sharing my hard earned cash with large charities who have magnificent offices, managing directors, hundreds of paid staff and devote just a fraction of their donations to their ‘good’ works. You can call me the woman with the long pockets if you like, but I want to know my money is going where it will doing some good and helping those would really need it. How to be confident about that I am not sure? In true Scorpion fashion I hate to be misled or deceived.
Quite how we can help these starving children is the burning question. I have had masses of appeals for all sorts of charities drop on my doormat in recent weeks. At least these ends up in the local hospice waste paper recycling skip and help them a little along with our papers and magazines. I looked on the Internet at our UK BBC Children in Need but could not see children in a similar situation.
SAVE THE CHILDREN
The UK Save the Children organisation has produced a Christmas shopping catalogue, on line, so should you decide to buy Christmas gifts from them you are indirectly donating while shopping, just how much remains to be seen! Perhaps this might be more acceptable – buying and giving at the same time. It is easy to look at this site to see the work they are doing and possibly shop with them. Every Christmas I seem to receive more and more cards printed by charities and sent by to me by friends.
However I should mention that if you telephone their UK number – 0844 557 5425 – instead of ordering on line, it could cost you 40p a minute as you give your details and make your mind up. Some of that money will be going to the charity.
Our doctors’ surgery is using this 0844 prefix number and getting a rake off which is a bit vexing considering how much our GPs are reported to be earning – but that is another story.
No – I am not a sales rep for any charity – just a concerned parent. No, this is not a commercial for children’s charities – it is a wake up call.
The American Save the Children website also appears to have a programme for under privileged children in developing countries, who are suffering from hunger and poverty. It seems you can also purchase festive gifts from them indirectly helping the cause.
What you decide to do is between you and your conscience. I would however like to leave you with these thoughts.
These pictures and words certainly do bring you down to earth especially when you consider the wastage by governments the world over. I am just sorry I could not reproduce the pictures but I am sure you know the kind of scenes I mean – you must have seen them on TV from time to time. Send me your email address with the request for these pictures if you would like them forwarding.
Just consider the money all of the worldwide governments squander… it is time someone added the total figure and gave us some home truths.
These starving children, if they live, may be our next generation – our future leaders. Do you think if they survive they could be future terrorists? I am sure they will have a grudge against the world – surely they will feel the world owes them a living. This is all very sad and really makes you think. Whatever happened to the innocence of childhood?
Just imagine what we spend on consumerism not to mention what we will spend on our own children this Christmas 2007. I wonder what our children would think if we put these pictures under the Christmas tree on Dec.25 instead of a new bike, a new game toy and all the other things children of our modern world expect to receive from their parents aka Father Christmas?
What would it be like if children all over the world went without just one toy from their festive gifts in aid of the starving and poverty stricken children. It would take a lot of organizing to gather in that money and it is a huge task but it could be done – all it needs is a good website supported by reliable well known people…. even if it took until Easter to collect the money – the children would still be starving.
Where are you Bob Geldorf? Can you help us with this? Does someone know his email address? My mind is boggling at the power of the people…… How about Skinny Kids for a campaign title – that rather sums it up!
Just a thought – maybe if that £5 we would be spending on a nonsense stocking gift for someone who has everything, was replaced with a warm note telling them Christmas is for children – starving children in particular – and they would be receiving his gift money with a tax gift aid. Sorry but this has been sent to starving “Skinny Kids” who have nothing.
I would hope we would get a really warm hug for this initiative. This friend really did not need an air freshener toy for his car or a key ring. If we did not get a big hug that receiver is a Christmas Meanie…. Take it from me. We will cross him off our Christmas list in future – so there.
Sorry to be a party pooper – but someone has to do it. I will make up for it and send you some happier stories in the near future.
Take care. Jeanne.
Contact: Beth Bukata
American Society for Therapeutic Radiology and Oncology
Internet resources and access remain scarce
Although Spanish-speaking cancer patients are rapidly increasing their search for patient education resources on the Internet, there are very few Spanish-language Web sites available to provide this information, according to a study presented October 28, 2007, at the American Society for Therapeutic Radiology and Oncology’s 49th Annual Meeting in Los Angeles.
Spanish-speaking cancer patients were also shown to have more limited access to the Internet compared to English-speaking users of cancer information Web sites, based on the user patterns of the two groups.
“There is an urgent need for more Web-based information to be more available to Spanish-speaking patients with cancer, and Internet access needs to be more widely available,” said Charles Simone II, M.D., lead author of the study and a radiation oncologist at the Hospital of the University of Pennsylvania in Philadelphia. “The increased knowledge gained among these patients will help to eliminate healthcare disparities and lead to improved medical outcomes.”
The Spanish-language cancer information Web site, OncoLink en español, quadrupled their number of unique visitors last year, from 7,000 visitors per month in January 2006 to nearly 29,000 monthly visitors by the end of the year. More than 200,000 users visited the Web site in 2006.
In contrast, the English-language version of the site, OncoLink, had nearly 2 million visitors last year, although their number of unique visitors did not increase throughout the year. OncoLink en espanõl was launched in 2005 by OncoLink, one of the oldest and largest Internet-based cancer information resources. Both sites are managed by the University of Pennsylvania.
The study shows that OncoLink en español users were less likely to browse the Internet during weekends and morning hours, compared to the users who browsed OncoLink, suggesting that they are accessing the Internet more through work or specialized services.
In addition to when they accessed the Internet, OncoLink en español users also differed on the types of cancers they searched for, as well as the timing and method of their Internet search patterns.
“Awareness of these differences can assist cancer education Web sites to tailor their content to best meet the needs of their Spanish-speaking users,” said Dr. Simone.
The study was carried out using AWStats, a Web-data analyzing program, to collect and compare statistical data from the secure servers of both language versions of OncoLink.
For more information on radiation therapy in English and in Spanish, visit http://www.rtanswers.org.
The abstract, “The Utilization of Radiation Oncology Web-based Resources in Spanish-speaking Oncology Patients,” will be presented for poster viewing starting at 10:00 a.m, Sunday, October 28, 2007. To speak to the study author, Charles Simone, II, M.D, please call Beth Bukata or Nicole Napoli October 28-31, 2007, in the ASTRO Press Room at the Los Angeles Convention Center at 213-743-6222 or 213-743-6223. You may also e-mail them at email@example.com or firstname.lastname@example.org.
Contact: Yivsam Azgad
Weizmann Institute of Science
A group of Israeli scientists from the Technion – Israel Institute of Technology, the Weizmann Institute of Science and Teva Pharmaceutical Industries have recently identified genes responsible for the positive response of many multiple sclerosis patients to the drug Copaxone®. These findings may contribute to the development of personalized medicine for multiple sclerosis sufferers.
Copaxone® was the first original Israeli drug to be approved by the U.S. Food and Drug Administration (FDA), and is today marketed in over 40 countries worldwide, including the U.S.A., Europe, Australia, Latin America and Israel.
The drug molecule was the fruit of research by Prof. Michael Sela, Prof. Ruth Arnon and Dr. Dvora Teitelbaum of the Weizmann Institute’s Immunology Department. It was developed for the treatment of multiple sclerosis (MS) by Teva, which produces and markets Copaxone® today.
‘Until now, medical treatments for all kinds of diseases have relied on trial and error methods to determine dosage and treatment protocols,’ says Prof. Ariel Miller of the Ruth and Bruce Rappaport Faculty of Medicine at the Technion, and Head of the Multiple Sclerosis and Brain Research Center, Carmel Medical Center, Haifa. ‘But the process of fixing the correct dosage affects the efficacy of the treatment and can lead to complications in some cases.’ In the past few years, it has been shown that many drugs are not equally effective for every patient, and this variability is due, at least in part, to genetic differences. Finding medications and doses to suit the genetic make-up of each individual patient is likely to be more successful and to cause fewer side effects.
The new research, which deals with the genetic components of the response to Copaxone®, was recently published in the journal Pharmacogenetics and Genomics. It represents a significant step toward realizing this medical vision. In the collaborative study, Teva supplied DNA samples from drug-treated patients, and the genetic tests were performed at the Crown Human Genome Center of the Weizmann Institute, headed by Prof. Doron Lancet of the Institute’s Department of Molecular Genetics. The scientists used state-of-the-art equipment – the first of its kind in Israel –which allows for the rapid and accurate scanning of variations in the human genome. The scientists then examined the links between the genetic markers they found and the response of MS patients to Copaxone®. They identified several genes that are tied to a positive response to the drug. ‘We analyzed the DNA sequences in 27 candidate genes from each patient participating in the trial,’ said Lancet, ‘and we identified two genes with a high potential for determining the response to Copaxone®. In the future, it may be possible to use this method to scan the genome of MS sufferers, to predict the response levels in advance, and to optimize the dosage and treatment protocol to suit each patient personally.’
Also participating in the research were Prof. Jacques Beckmann (formerly at the Weizmann Institute); Drs. Liat Hayardeny and Dan Goldstaub of Teva; and Iris Grossman, a joint research student at the Technion and the Weizmann Institute.
Copaxone® – Interface between Past and Future
In the 1950’s, Prof. Efraim Katzir of the Weizmann Institute of Science, later fourth president of the State of Israel, commenced research on the properties of proteins – the building blocks of all biological systems. This research led to the design of simple synthetic models of proteins, called ‘polyamino acids.’ His research student at the time, Prof. Michael Sela (who later became President of the Weizmann Institute and was the recipient of, among many honors, the Israel Prize), decided to test the influence of these synthetic molecules on the immune system. This research led him to the conclusion that it might be possible to use these synthetic substances to curb symptoms of multiple sclerosis – an autoimmune disease in which the body’s immune system attacks proteins in the fatty layer surrounding nerve fibers, preventing the conductance of electrical signals through them. Sela, together with his student at the time, Prof. Ruth Arnon (recipient of the Israel Prize and past Vice President of the Weizmann Institute and Vice President of the Association of Academies of Sciences in Asia), and Dr. Dvora Teitelbaum, conducted a long series of experiments. These experiments eventually led to the development of Copaxone®, and clinical trials carried out by Teva showed its efficacy in treating MS. At the end of the process, in 1996, Copaxone® became the first original Israeli drug to be approved by the FDA. Today, following ten years of active sales in the U.S. and 40 countries around the world, Copaxone® has made a significant contribution to the Israeli economy.
Prof. Doron Lancet’s research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Crown Human Genome Center; and the Laub Fund for Oncogene Research. Prof. Lancet is the incumbent of the Ralph and Lois Silver Professorial Chair in Human Genomics.
The Weizmann Institute of Science in Rehovot, Israel, is one of the world’s top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.
Weizmann Institute news releases are posted on the World Wide Web at http://wis-wander.weizmann.ac.il.
Contact: Amelyn Reyes
ROCHESTER, Minn. — Mayo Clinic researchers have found that a human antibody administered in a single low dose in laboratory mouse models can repair myelin, the insulating covering of nerves that when damaged can lead to multiple sclerosis and other disorders of the central nervous system.
The study will be presented on Oct. 9 at the American Neurological Association meeting in Washington, D.C.
“The repair of chronic spinal cord injury is seldom modeled in laboratory studies, but it is an important reality for the treatment of humans. The concept of using natural human antibodies to treat disease of this kind has not yet been tested in humans, but these research findings are very promising,” says Moses Rodriguez, M.D., a Mayo Clinic neurologist and the study’s corresponding author. “The findings could eventually lead to new treatments that could limit permanent disability,” states Arthur Warrington, Ph.D., a Mayo Clinic scientist and study author.
Myelin repair normally occurs spontaneously, but in multiple sclerosis and other disorders of the central nervous system, the myelin repair process occurs very slowly or fails altogether. Researchers are trying to determine how to speed up the myelin healing process, which they hope will eventually lead to new treatments for patients.
The antibody, which was genetically engineered from a single cell, binds to myelin and the surface of cells in the brain and spinal cord, then it triggers the cells to begin the repair process called remyelination. This antibody is the first known reagent designed to induce repair by acting within the central nervous system at the damage sites on cells responsible for myelin synthesis.
The study uses laboratory mouse models of chronic progressive multiple sclerosis in humans. The severity of the disease and also success of the treatment were largely defined by how naturally active the mice were, particularly during the night because mice are nocturnal and are especially active at this time. They received a single dose of the antibody. A minimum of 25 mcg/kg was needed to trigger remyelination, which is equivalent to about 2 mg in the average adult, considered a very low dose. The myelin repair plateaued after five weeks in the mice models.
In addition, when combined with daily methylprednisolone, (an immune modulating steroid) the antibody still promotes remyelination in mouse models. This is an important fact because the first multiple sclerosis patients treated with the antibody will have been treated first with methylprednisolone.
As a naturally occurring protein of the immune system, antibodies do not appear to carry any side effects, nor are they toxic — even when administered at 4,000 times the minimal effective dose — though the concept has not yet been tested in humans, the researchers say.
In summary, this antibody:
Promotes remyelination with a single dose as low as 25 mcg/kg in mice models
The remyelination plateaus at five weeks after a single dose
Converts a model of chronic immune mediated demyelination to one that repairs with the speed of a toxin induced model of demyelination
In terms of replicating the findings in humans, the researchers have already produced the antibody through genetic engineering and conducted preliminary toxicology experiments in mice showing that 1,000 times the therapeutic dose is not toxic. The study continues to be explored in animal models and eventually, in clinical trials.
In short, the critical finding is that when combined with methylprednisolone, the antibody still effectively promotes remyelination and does not make the mice worse, Dr. Warrington states.
About Multiple Sclerosis:
Multiple sclerosis (MS) is a chronic, potentially debilitating disease that affects the central nervous system, which is made up of the brain and spinal cord. Multiple sclerosis is widely believed to be an autoimmune disease, a condition in which the immune system attacks components of the body as if they’re foreign.
Multiple sclerosis affects an estimated 300,000 people in the United States and probably more than 1 million people around the world — including twice as many women as men. Most people experience their first signs or symptoms between ages 20 and 40.
Collaboration and Support
The study was funded by the National Institutes of Health, the National Multiple Sclerosis Society, Multiple Sclerosis Society of Canada, the Hilton Foundation and Mr. and Mrs. Eugene Applebaum.
To obtain the latest news releases from Mayo Clinic, go to http://www.mayoclinic.org/news. MayoClinic.com (www.mayoclinic.com) is available as a resource for your health stories. For more on Mayo Clinic research, go to http://www.mayo.edu.
Contact: Richard Merritt
Duke University Medical Center
DURHAM, N.C. – Long denigrated as vestigial or useless, the appendix now appears to have a reason to be – as a “safe house” for the beneficial bacteria living in the human gut.
Drawing upon a series of observations and experiments, Duke University Medical Center investigators postulate that the beneficial bacteria in the appendix that aid digestion can ride out a bout of diarrhea that completely evacuates the intestines and emerge afterwards to repopulate the gut. Their theory appears online in the Journal of Theoretical Biology.
“While there is no smoking gun, the abundance of circumstantial evidence makes a strong case for the role of the appendix as a place where the good bacteria can live safe and undisturbed until they are needed,” said William Parker, Ph.D., assistant professor of experimental surgery, who conducted the analysis in collaboration with R. Randal Bollinger, M.D., Ph.D., Duke professor emeritus in general surgery.
The appendix is a slender two- to four-inch pouch located near the juncture of the large and small intestines. While its exact function in humans has been debated by physicians, it is known that there is immune system tissue in the appendix.
The gut is populated with different microbes that help the digestive system break down the foods we eat. In return, the gut provides nourishment and safety to the bacteria. Parker now believes that the immune system cells found in the appendix are there to protect, rather than harm, the good bacteria.
For the past ten years, Parker has been studying the interplay of these bacteria in the bowels, and in the process has documented the existence in the bowel of what is known as a biofilm. This thin and delicate layer is an amalgamation of microbes, mucous and immune system molecules living together atop of the lining the intestines.
“Our studies have indicated that the immune system protects and nourishes the colonies of microbes living in the biofilm,” Parkers explained. “By protecting these good microbes, the harmful microbes have no place to locate. We have also shown that biofilms are most pronounced in the appendix and their prevalence decreases moving away from it.”
This new function of the appendix might be envisioned if conditions in the absence of modern health care and sanitation are considered, Parker said.
“Diseases causing severe diarrhea are endemic in countries without modern health and sanitation practices, which often results in the entire contents of the bowels, including the biofilms, being flushed from the body,” Parker said. He added that the appendix’s location and position is such that it is expected to be relatively difficult for anything to enter it as the contents of the bowels are emptied.
“Once the bowel contents have left the body, the good bacteria hidden away in the appendix can emerge and repopulate the lining of the intestine before more harmful bacteria can take up residence,” Parker continued. “In industrialized societies with modern medical care and sanitation practices, the maintenance of a reserve of beneficial bacteria may not be necessary. This is consistent with the observation that removing the appendix in modern societies has no discernable negative effects.”
Several decades ago, scientists suggested that people in industrialized societies might have such a high rate of appendicitis because of the so-called “hygiene hypothesis,” Parker said. This hypothesis posits that people in “hygienic” societies have higher rates of allergy and perhaps autoimmune disease because they — and hence their immune systems — have not been as challenged during everyday life by the host of parasites or other disease-causing organisms commonly found in the environment. So when these immune systems are challenged, they can over-react.
“This over-reactive immune system may lead to the inflammation associated with appendicitis and could lead to the obstruction of the intestines that causes acute appendicitis,” Parker said. “Thus, our modern health care and sanitation practices may account not only for the lack of a need for an appendix in our society, but also for much of the problems caused by the appendix in our society.”
Parker conducted a deductive study because direct examination the appendix’s function would be difficult. Other than humans, the only mammals known to have appendices are rabbits, opossums and wombats, and their appendices are markedly different than the human appendix.
Parker’s overall research into the existence and function of biofilms is supported by the National Institutes of Health. Other Duke members of the team were Andrew Barbas, Errol Bush, and Shu Lin.
Mouse experiments reveal ‘flight or fight’ hormone’s role
Contact: Nick Zagorski
Johns Hopkins Medical Institutions
Both extensive psychological research and personal experiences confirm that events that happen during heightened states of emotion such as fear, anger and joy are far more memorable than less dramatic occurrences. In a report this week in Cell, Johns Hopkins researchers and their collaborators at Cold Spring Harbor and New York University have identified the likely biological basis for this: a hormone released during emotional arousal “primes” nerve cells to remember events by increasing their chemical sensitivity at sites where nerves rewire to form new memory circuits.
Describing the brain as a big circuit board in which each new experience creates a new circuit, Hopkins neuroscience professor Richard Huganir, Ph.D. says that he and his team found that during emotional peaks, the hormone norepinephrine dramatically sensitizes synapses – the site where nerve cells make an electro-chemical connection – to enhance the sculpting of a memory into the big board.
Image showing phosphorylated GluR1 receptors congregating around sites of neuronal synapses.
Norepinephrine, more widely known as a “fight or flight” hormone, energizes the process by adding phosphate molecules to a nerve cell receptor called GluR1. The phosphates help guide the receptors to insert themselves adjacent to a synapse. “Now when the brain needs to form a memory, the nerves have plenty of available receptors to quickly adjust the strength of the connection and lock that memory into place,” Huganir says.
Huganir and his team suspected that GluR1might be a target of norepinephrine since disruptions in this receptor cause spatial memory defects in mice. They tested the idea by either injecting healthy mice with adrenaline or exposing them to fox urine, both of which increase norepinephrine levels in brain. Analyzing brain slices of the mice, the researchers saw increased phosphates on the GluR1 receptors and an increased ability of these receptors to be recruited to synapses.
When the researchers put mice in a cage, gave a mild shock, took them out of that cage and put them back in it the next day, mice who had received adrenaline or fox urine tended to “freeze” in fear – an indicator they associated the cage as the site of a shock – more frequently, suggestive of enhanced memory.
However, in a similar experiment with mice genetically engineered to have a defective GluR1 receptor that phosphates cannot attach to, adrenaline injections had no effect on mouse memory, further evidence of the “priming” effect of the receptor in response to norepinephrine.
The researchers plan on continuing their work by going in the opposite direction and engineering another mouse strain that has a permanently phosphorylated or “primed” receptor. “We’re curious to see how these mice will behave,” Huganir says. “We suspect that they’ll be pretty smart, but at the same time constantly anxious.”
The research was funded by the National Institutes of Health, Damon Runyon Postdoctoral Fellowship, NARSAD, and the Ale Davis and Maxine Harrison Foundation
Authors on the paper are Hailan Hu, Eleonore Real, and Roberto Malinow of Cold Spring Harbor Laboratory; Joe LeDoux of New York University; and Kogo Takamiya, Myoung-Goo Kang, and Huganir of Johns Hopkins
Contact: Alyssa Kneller
Harvard Medical School
BOSTON, Mass. (Oct. 3, 2007)—Imagine an epidural or a shot of Novocain that doesn’t paralyze your legs or make you numb, yet totally blocks your pain. This type of pain management is now within reach. As a result, childbirth, surgery and trips to the dentist might be less traumatic in the future, thanks to researchers at Massachusetts General Hospital (MGH) and Harvard Medical School, who have succeeded in selectively blocking pain-sensing neurons in rats without interfering with other types of neurons.
The pint-sized subjects received injections near their sciatic nerves, which run down their hind limbs, and subsequently lost the ability to feel pain in their paws. But they continued to move normally and react to touch. The injections contained QX-314, a normally inactive derivative of the local anesthetic lidocaine, and capsaicin, the active ingredient in hot peppers. In combination, these chemicals targeted only pain-sensing neurons, preventing them from sending signals to the brain.
“We’ve introduced a local anesthetic selectively into specific populations of neurons,” explains Harvard Medical School Professor Bruce Bean, an author on the paper, which appears in Nature on Oct. 4. “Now we can block the activity of pain-sensing neurons without disrupting other kinds of neurons that control movements or non-painful sensations.”
“We’re optimistic that this method will eventually be applied to humans and change our experience during procedures ranging from knee surgery to tooth extractions,” adds Professor Clifford Woolf of Massachusetts General Hospital, who is senior author on the study.
Despite enormous investments by industry, surgical pain management has changed little since the first successful demonstration of ether general anesthesia at MGH in 1846. General and local anesthetics work by interfering with the excitability of all neurons, not just pain-sensing ones. Thus, these drugs produce dramatic side effects, such as loss of consciousness in the case of general anesthetics or temporary paralysis for local anesthetics.
“We’re offering a targeted approach to pain management that avoids these problems,” says Woolf.
The new work builds on research done since the 1970’s showing how electrical signaling in the nervous system depends on the properties of ion channels, that is, proteins that make pores in the membranes of neurons.
“This project is a perfect illustration of how research trying to understand very basic biological principles can have practical applications,” says Bean.
The new method exploits a membrane-spanning protein called TRPV1, which is unique to pain-sensing neurons. TRPV1 forms a large channel, where molecules can enter and exit the cell. But a “gate” typically blocks this opening. The gate opens when cells are exposed to heat or the chili-pepper ingredient capsaicin. Thus, bathing pain-sensing neurons in capsaicin leaves these channels open, but non-pain sensing neurons are unaffected because they do not possess TRPV1.
The new method then takes advantage of a special property of the lidocaine derivative QX-314. Unlike most local anesthetics, QX-314 can’t penetrate cell membranes to block the excitability of the cell, so it typically lingers outside neurons where it can’t affect them. For this reason it is not used clinically.
When pain-sensing neurons are exposed to capsaicin, however, and the gates guarding the TRPV1 channels disappear, QX-314 can enter the cells and shut them down. But the drug remains outside other types of neurons that do not contain these channels. As a result, these cells fully retain their ability to send and receive signals.
The team first tested their method in the Petri dish. Alexander Binshtok, a postdoctoral researcher in Woolf’s lab, applied capsaicin and QX-314 (separately and in combination) to isolated pain-sensing and other neurons and measured their responses. Indeed, the combination of capsaicin and QX-314 selectively blocked the excitability of pain-sensing neurons, leaving the others unaffected.
Next, Binshtok injected these chemicals into the paws of rats and measured their ability to sense pain by placing them on an uncomfortable heat source. The critters tolerated much more heat than usual. He then injected the chemicals near the sciatic nerve of the animals and pricked their paws with stiff nylon probes. The animals ignored the provocation. Although the rats seemed immune to pain, they continued to move normally and respond to other stimuli, indicating that QX-314 failed to penetrate their motor neurons.
The team must overcome several hurdles before this method can be applied to humans. They must figure out how to open the TRPV1 channels without producing even a transient burning pain before QX-314 enters and blocks the neurons, and they must tinker with the formulation to prolong the effects of the drugs. Both Bean and Woolf are confident they’ll succeed.
“Eventually this method could completely transform surgical and post-surgical analgesia, allowing patients to remain fully alert without experiencing pain or paralysis,” says Woolf. “In fact, the possibilities seem endless. I could even imagine using this method to treat itch, as itch-sensitive neurons fall into the same group as pain-sensing ones.”
Research in the Woolf lab is supported by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Dental and Craniofacial Research. Research in the Bean lab is supported by NINDS and the National Institute of General Medical Sciences.
Harvard and MGH have filed patents on this technology platform.
Contact: Janet Rettig Emanuel
Links (in order of appearance in the text) to have active are: Anthony Leiserowitz Yale Project on Climate Change
New Haven, Conn. — A growing number of Americans consider global warming an important threat that calls for drastic action, and 40% say that a presidential candidate’s position on the issue will strongly influence how they vote, according to a national survey conducted by Yale University, Gallup and the ClearVision Institute.
“One of the most surprising findings was the growing sense of urgency,” said Anthony Leiserowitz, director of the Yale Project on Climate Change and the study’s principal investigator. “Nearly half of Americans now believe that global warming is either already having dangerous impacts on people around the world or will in the next 10 years—a 20-percentage-point increase since 2004. These results indicate a sea change in public opinion.”
The survey’s findings include:
Sixty-two percent of respondents believe that life on earth will continue without major disruptions only if society takes immediate and drastic action to reduce global warming.
Sixty-eight percent of Americans support a new international treaty requiring the United States to cut its emissions of carbon dioxide 90 percent by the year 2050. Yet, Leiserowitz notes, the United States has yet to sign the Kyoto Protocol, an international treaty that would require the United States to cut its emissions 7 percent by the year 2012.
A surprising 40 percent of respondents say a presidential candidate’s position on global warming will be either extremely important (16 percent) or very important (24 percent) when casting their ballots. “With the presidential primaries and general election near,” Leiserowitz said, “candidates should recognize that global warming has become an important issue for the electorate.”
Eight-five percent of those polled support requiring automakers to increase the fuel efficiency of cars, trucks and SUVs to 35 miles per gallon, even if it meant a new car would cost up to $500 more; and 82 percent support requiring electric utilities to produce at least 20 percent of their electricity from renewable energy sources, even if it cost the average household an extra $100 a year.
Majorities of Americans, however, continue to oppose carbon taxes as a way to address global warming — either in the form of gasoline (67 percent against) or electricity taxes (71 percent against). —.
Finally, 50 percent of respondents say they are personally worried —15 percent say a “great deal”— about global warming. “Many Americans, however, believe that global warming is a very serious threat to other species, people and places far away,” said Leiserowitz, “but not so serious of a threat to themselves, their own families or local communities. Nonetheless, they do strongly support a number of national and international policies to address this problem.”
The survey was conducted July 23-26, 2007, using telephone interviews with 1,011 adults, aged 18-plus. Respondents came from Gallup’s household panel, which was originally recruited through random selection methods. The final sample is consideredto be representative of U.S. adults nationwide, with a margin of error of ±4 percentage points. Survey results are available online: http://environment.yale.edu/news/5305-american-opinions-on-global-warming/.
The Yale Project on Climate Change at the Yale School of Forestry & Environmental Studies supports public discourse and engagement with climate-change solutions.
Gallup, Inc., headquartered in Washington, D.C., is one of the world’s leading research companies focusing on studying human nature and behavior. The Gallup Poll has been monitoring U.S. public opinion since 1935, and Gallup now tracks public opinion in over 100 countries worldwide on an ongoing basis.
The ClearVision Institute is a nonprofit organization dedicated to applying entertainment education as a social-change strategy to address climate change through U.S. commercial television.
Contact: Amy Molnar
John Wiley & Sons, Inc.
A new study examined the possible associations between occupation and the risk of dying from systemic autoimmune diseases and found that occupational exposures in farming and industry may be linked to higher death rates from these diseases.
More than 8 million Americans suffer from autoimmune diseases, in which the immune system attacks the body’s own tissues and several occupational exposures have been linked to systemic autoimmune diseases, which affect multiple organs. A new study published in the October issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis) examined the possible associations between occupation and the risk of dying from systemic autoimmune diseases and found that occupational exposures in farming and industry may be linked to higher death rates from these diseases.
Led by L.S. Gold and A.J. De Roos, of the Fred Hutchinson Cancer Research Center in Seattle, WA, researchers examined death certificate data from 26 states from 1984 to 1998. Any cases that listed a systemic autoimmune disease (for example, rheumatoid arthritis) as a cause of death, were included, as were disease types with a suspected systemic autoimmune disease origin (such as unspecified connective tissue disorder). Five control subjects matched by age, sex, race, year of death and geographic region were also selected. The researchers established each person’s longest-held occupation from the “usual occupation” listed on the death certificate. In addition, they examined specific exposures based on occupation and industry. These included asbestos, solvents, benzene, pesticides and other substances. Occupations involving significant exposure to the public (such as teachers, and waiters/waitresses) or animals were also tracked.
The results showed that some occupations involving exposure to the public (such as nurses and teachers) were associated with an increased risk of dying from a systemic autoimmune disease but this was not the case with all jobs involving public exposure (for example food service jobs). Farmers showed increased risk of death from systemic autoimmune disease, particularly for those who worked with crops versus livestock. In addition, several industrial occupations such as mining and textile machine operators, as well as timber cutting and logging had an increased risk of death from this group of diseases.
Further analysis showed that the same occupations and exposures were present in those who were older than the typical retirement age when they died, “implying that the occupational exposures were involved in a chronic pathogenic process leading to either disease incidence or slow progression of existing autoimmunity,” according to the authors. They suggest that the higher risk associated with jobs involving public contact may be due to exposure to multiple infectious agents leading to an autoimmune response.
The authors note that autoimmune diseases tend to be underreported on death certificates, and that the increased risk seen with certain occupations, such as teachers, may be due to the fact that these individuals have extensive health benefits even after retirement, and therefore better access to care. This would also help explain why other occupations that involve public contact but lower health insurance coverage, such as waiter/waitress, seemed to have a lower risk of death from autoimmune disease. However, not all the occupational associations they found are expected to be affected by insurance status.
“The size of our study allowed us to estimate associations between specific occupations and death from autoimmune diseases and to generate hypotheses that will be useful as starting points for future studies in this area,” the authors conclude. They note that future studies should focus on obtaining more detailed occupational histories from the groups found to be at increased risk.
Article: “Systemic Autoimmune Disease Mortality and Occupational Exposures,” L.S. Gold, M.H. Ward, M. Dosemeci, A.J. De Roos, Arthritis & Rheumatism, October 2007; (DOI: 10.1002/art.22880).
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