Some Germs Are Good for You: Surface Bacteria Maintain Skin's Healthy Balance

On the skin's surface, bacteria are abundant, diverse and constant, but inflammation is undesirable. Research at the University of California, San Diego School of Medicine now shows that the normal bacteria living on the skin surface trigger a pathway that prevents excessive inflammation after injury.

"These germs are actually good for us," said Richard L. Gallo, MD, PhD, professor of medicine and pediatrics, chief of UCSD's Division of Dermatology and the Dermatology section of the Veterans Affairs San Diego Healthcare System.

The study, to be published in the advance on-line edition of Nature Medicine on November 22, was done in mice and in human cell cultures, primarily performed by post-doctoral fellow Yu Ping Lai .

"The exciting implications of Dr. Lai's work is that it provides a molecular basis to understand the 'hygiene hypothesis' and has uncovered elements of the wound repair response that were previously unknown. This may help us devise new therapeutic approaches for inflammatory skin diseases," said Gallo.

The so-called "hygiene hypothesis," first introduced in the late 1980s, suggests that a lack of early childhood exposure to infectious agents and microorganisms increases an individuals susceptibility to disease by changing how the immune system reacts to such "bacterial invaders." The hypothesis was first developed to explain why allergies like hay fever and eczema were less common in children from large families, who were presumably exposed to more infectious agents than others. It is also used to explain the higher incidence of allergic diseases in industrialized countries.

The skin's normal microflora -- the microscopic and usually harmless bacteria that live on the skin -- includes certain staphylococcal bacterial species that will induce an inflammatory response when they are introduced below the skin's surface, but do not initiate inflammation when present on the epidermis, or outer layer of skin.

In this study, Lai, Gallo and colleagues reveal a previously unknown mechanism by which a product of staphylococci inhibits skin inflammation. Such inhibition is mediated by a molecule called staphylococcal lipoteichoic acid (LTA) which acts on keratinocytes -- the primary cell types found on the epidermis.

The researchers also found that Toll-like receptor 3 (TLR3) activation is required for normal inflammation after skin injury.

"Keratinocytes require TLR3 to mount a normal inflammatory response to injury, and this response is kept from becoming too aggressive by staphylococcal LTA," said Gallo. "To our knowledge, these findings show for the first time that the skin epithelium requires TLR3 for normal inflammation after wounding and that the microflora helps to modulate this response."

Additional contributors to the paper include Yuping Lai, Anna Di Nardo, Teruaki Nakatsuji, Anna L Cogen, Chun-Ming Huang and Katherine A. Radek, UCSD Division of Dermatology and the VA San Diego Healthcare System; Anke Leichtle and Allen F. Ryan, UCSD Department of Surgery/Otolaryngology and the VA San Diego Healthcare System; Yan Yang and Zi-Rong Wu, School of Life Science, East China Normal University, Shanghai; Lora V Hooper, Howard Hughes Medical Institute and University of Texas Southwestern Medical Center, Dallas; and Richard R Schmidt and Sonja von Aulock, University of Konstanz, Germany.

The study was funded by grants from the National Institutes of Health, and a US Veterans Administration Merit Award.

Courtesy: ScienceDaily

Can Meditation Curb Heart Attacks?

When Julia Banks was almost 70, she took up transcendental meditation. She had clogged arteries, high blood pressure and too much weight around the middle, and she enrolled in a clinical trial testing the benefits of meditation.

Now Mrs. Banks, 79, of Milwaukee, meditates twice a day, every day, for 20 minutes each time, setting aside what she calls “a little time for myself.”

“You never think you’ve got that time to spare, but you take that time for yourself and you get the relaxation you need,” said Mrs. Banks, who survived a major heart attack and a lengthy hospitalization after coronary artery bypass surgery six years ago.

“You have things on your mind, but you just blot it out and do the meditation, and you find yourself being more graceful in your own life,” she said. “You find out problems you thought you had don’t exist — they were just things you focused on.”

Could the mental relaxation have real physiological benefits? For Mrs. Banks, the study suggests, it may have. She has gotten her blood pressure under control, though she still takes medication for it, and has lost about 75 pounds.

Findings from the study were presented this week at an American Heart Association meeting in Orlando, Fla. They suggest that transcendental meditation may have real therapeutic value for high-risk people, like Mrs. Banks, with established coronary artery disease.

After following about 200 patients for an average of five years, researchers said, the high-risk patients who meditated cut their risk of heart attacks, strokes and deaths from all causes roughly in half compared with a group of similar patients who were given more conventional education about healthy diet and lifestyle.

Among the roughly 100 patients who meditated, there were 20 heart attacks, strokes and deaths; in the comparison group, there were 32. The meditators tended to remain disease-free longer and also reduced their systolic blood pressure by five millimeters of mercury, on average.

“We found reduced blood pressure that was significant – that was probably one important mediator,” said Dr. Robert Schneider, director of the Institute for Natural Medicine and Prevention, a research institute based at the Maharishi University of Management in Fairfield, Iowa, who presented the findings. The study was conducted at the Medical College of Wisconsin in Milwaukee, in collaboration with the institute.

An earlier study of high-risk Milwaukee residents, many of them overweight or obese, also found transcendental meditation, along with conventional medications, could help reduce blood pressure. Most of those in the study had only high-school educations or less, about 40 percent smoked and roughly half had incomes of less than $10,000 a year.

The participants found transcendental meditation easy to learn and practice, Dr. Schneider said.

“Fortunately, it does not require any particular education and doesn’t conflict with lifestyle philosophy or beliefs; it’s a straightforward technique for getting deep rest to the mind and body,” he said, adding that he believes the technique “helps to reset the body’s own self-repair and homeostatic mechanism.”

Dr. Schneider said other benefits of meditation might follow from stress reduction, which could cause changes in the brain that cut stress hormones like cortisol and dampen the inflammatory processes associated with atherosclerosis.

“What is it about stress that causes cardiovascular disease?” said Dr. Theodore Kotchen, associate dean for clinical research at the Medical College of Wisconsin. “Hormones, neural hormones, cortisol, catecholamines — all tend to be elevated in stress. Could they in some way be contributing to cardiovascular disease? Could a reduction in these hormones with meditation be contributing to reduction in disease? We can only speculate.”

Another recent study focusing on transcendental meditation, published in The American Journal of Hypertension, focused on a young healthy population. It found that stressed-out college students improved their mood through T.M., and those at risk for hypertension were able to reduce their blood pressure. Dr. Schneider was also involved in that study, which was carried out at American University in Washington and included 298 students randomly assigned to either a meditation group or a waiting list.

Students who were at risk of hypertension and practiced meditation reduced systolic blood pressure by 6.3 millimeters of mercury and their diastolic pressure by 4 millimeters of mercury on average.

Courtesy:Newyork times

Termites Create Sustainable Monoculture Fungus Farming

Food production of modern human societies is mostly based on large-scale monoculture crops, but it now appears that advanced insect societies have the same practice. Our societies took just ten thousand years of (mainly cultural) evolution to adopt this habit and we are far from convinced that it is sustainable. Farming ants and termites had tens of millions of years to evolve their fungus farming systems and here monocultures are apparently evolutionary stable.

In a study published in the journal Science, researchers from the Laboratory of Genetics of Wageningen University and the Centre for Social Evolution at the University of Copenhagen take significant steps to resolve this puzzle.

The fungus-growing termites of the old-world tropics build impressive mounds consisting of thousands of workers and soldiers. These societies domesticated African Termitomyces mushrooms more than 30 million years ago and became obligatorily dependent on farming their own fungal food in their often gigantic nest mounds. The termite fungus-farming symbiosis had a single African rain-forest origin and now comprises ca 330 species. It is of major ecological importance for decomposition and mineralcycling.

A colony-founding termite queen and king normally do not acquire their first garden until they have raised the first workers. These helpers collect Termitomyces spores while foraging, together with the plant material that they defecate in the nest to establish a garden substrate. These spores are amply available because the fungus gardens produce large mushrooms once a year on top of the termite mounds.

However, this farming practice offers a paradox: Evolutionary theory predicts that symbioses with multiple lineages per colony should be unstable, because these genotypes can be expected to compete for making mushrooms rather than collaborate to serve the termite farmers.

The new study shows that a very special mechanism is in place to prevent this from happening. All colonies from which multiple fungal samples were genetically analyzed contained only a single fungal genotype in spite of gardens having been initiated from at least two and probably many more genetically different spores.

Duur Aanen, Koos Boomsma and their respective colleagues in Wageningen and Copenhagen show that genotypes that happen to be common in a garden, become even more common at the expense of rarer genotypes. This happens not because common genotypes are better direct competitors, but because they have a higher chance of having an identical genotype as neighbor. Every time this happens, such genetically identical mycelia merge, which enhances the efficiency by which they produce asexual spores that the termites eat and deposit in new garden material of the colony. This process of positive reinforcement makes every colony end up with a life-time commitment to a single fungal symbiont in spite of the population at large having many fungal genotypes.

Shifting Vaccine for Flu to Elderly

Federal health officials are trying to shift supplies of the seasonal flu vaccine away from chain pharmacies and supermarkets to nursing homes, hoping to counter a shortage that threatens to cause a wave of deaths this winter among the nation’s most vulnerable population.

The extent of the shortage is still unclear, but Janice Zalen, director of special programs for the American Health Care Association, which represents 11,000 nursing homes and assisted-living facilities, called it “a very big problem.”

Ms. Zalen said that of 1,000 nursing home managers who responded to a survey of the association’s 11,000 members, 800 reported they could not get enough vaccine.

Dr. Carol Friedman, head of adult immunization at the Centers for Disease Control and Prevention, said she did not have a figure for the size of the shortage, but added, “It’s a problem, and it’s all over the country.”

Mary Hahn, who manages six Ohio nursing homes with 800 beds, said she could not get vaccine for any of her patients.

“It’s just so disheartening, because we’re having to leave people unprotected,” she said. “You see people get flus and get sent to the hospital because they really can’t fight it off.”

A nationwide shortage of the seasonal flu vaccine has been reported for several weeks, but nursing homes and their suppliers have grown more alarmed in recent days. Of the 36,000 Americans who die of seasonal flu in the average year, more than 90 percent are 65 or older, and nursing home outbreaks are particularly deadly. By contrast, the swine flu epidemic has been most deadly among younger people.

The nursing homes’ predicament has been caused by a confluence of factors. Because of the swine flu pandemic, far more people than usual are seeking vaccination, Dr. Friedman said — even though the seasonal vaccine does not protect against swine flu.

The five companies licensed to make flu shots for the United States originally planned to make only slightly more than the 118 million they made in 2008. Then, production problems caused GlaxoSmithKline to cut its run by half; Novartis’s shrank by 10 percent. Then all five companies had to switch over early to making swine flu vaccine.

So the total supply of vaccine is about 114 million doses, of which about 95 million have been shipped.

At the same time, reports of price gouging have grown more frequent. That also happened in 2004, when sterility problems at a British plant cut the American flu vaccine supply in half; prices shot up as high as $90 a dose, from the normal level of $8 to $9.

Gouging is illegal in about half the states, but each state varies in how big a price increase constitutes gouging and as to whether an emergency must have been declared for the law to kick in.

“To pursue a case, we need to show it’s not just a couple of dollars but is very significant,” said Attorney General Richard Blumenthal of Connecticut, who has opened an investigation.

Criminal charges are less likely than a civil suit, Mr. Blumenthal said. But he added that if distributors were “masquerading or fraudulently claiming to have vaccine,” that could end in a criminal charge. While he had suspicions, he said, “we don’t have hard evidence yet.”

Dr. Friedman said that once the agency became aware of the shortage at nursing homes, “we began working with the manufacturers to see if they could redirect some of their vaccine.”

“Several big-box retailers and pharmacies volunteered to go into the long-term-care facilities and set up flu clinics,” she said.

Dr. Friedman said she knew of one major supplier to nursing homes that received 100,000 fewer doses from the vaccine makers than it had ordered. Her agency began acting as a broker among the homes, vaccine distributors and other customers. Since then, she said, that supplier has found about 50,000 more doses.

“That’s definitely not going to close the gap,” she said, “but it will help.”

Also, both she and Ms. Zalen said, pharmacy and supermarket chains like Walgreen’s and Safeway that bought millions of doses to sell for $25 to $30 have offered to give shots in nursing homes. They do not charge but get Medicare reimbursements, which vary by state but run up to $25.

By contrast, Bob McKay, chief of sales for PharMerica, one of the two largest wholesale pharmacies supplying nursing homes, said he had received 95 percent of the 300,000 doses he ordered and “the voids are getting filled in” at the nursing homes he supplies.

“We’re not hearing rage and craziness out there,” Mr. McKay said. “If a lot of homes were still short, they’d be beating our doors down.”

But he said he had asked some not to buy shots for their staffs. Flu experts say that in nursing homes, vaccination of staff members is just as important as patient vaccination.

Prices offered to PharMerica for the extra doses they needed were “in the $15-$16 range,” Mr. McKay said. “That’s more than we’d normally pay, but not price-gouging.”

Jim Mathews, an executive at Hometown Pharmacy, a smaller wholesale pharmaceutical company supplying Michigan nursing homes, said that late last month he found himself 3,000 doses short; his usual supplier, which charges $6.75 per dose, was out of stock. He called the C.D.C. for advice, was directed to a Web page listing other suppliers and contacted all 10. Only one had vaccine, and it sent him a fax in broken English asking for $57 to $59 per dose.

Mr. Mathews said he reported that to local law enforcement officials, but he is more worried about the patients who will not get shots.

“When I first recognized the potential death toll from this shortage, there was time to prioritize the remaining supply for the most vulnerable elderly,” he said. “Now I’m afraid it’s too late. From what I see, the seasonal flu vaccine shortage is going to cost more lives than the H1N1 shortage is.”

Dr. Friedman, of the C.D.C., said she had heard of “about 15” price-gouging complaints.

Dr. Lillian Overman, an internist in East Hartford, Conn., was one of the first to alert Mr. Blumenthal, the state’s attorney general, about gouging accusations. On Oct. 26, her office manager began looking for vaccine, for which she normally pays $8.50 a dose. A saleswoman at ABO Pharmaceuticals in San Diego wanted $60 per dose, she said.

“That’s just prohibitive,” a frustrated Dr. Overman said. “If I’d known there would be a shortage, I would have called in my most vulnerable patients first.”

Mark Nemeth, an ABO sales manager, denied that anyone there had asked for $60.

“I can guarantee you without a shadow of a doubt, we would never have offered it at that price,” he said; the company is asking “in the ballpark of $12 to $14” for its remaining supplies.

Courtesy: Newyorktimes

New Synthetic Molecules Trigger Immune Response To HIV And Prostate Cancer

Researchers at Yale University have developed synthetic molecules capable of enhancing the body's immune response to HIV and HIV-infected cells, as well as to prostate cancer cells. Their findings, published online in theJournal of the American Chemical Society, could lead to novel therapeutic approaches for these diseases.

The molecules -- called "antibody-recruiting molecule targeting HIV" (ARM-H) and "antibody-recruiting molecule targeting prostate cancer" (ARM-P) -- work by binding simultaneously to an antibody already present in the bloodstream and to proteins on HIV, HIV-infected cells or cancer cells. By coating these pathogens in antibodies, the molecules flag them as a threat and trigger the body's own immune response. In the case of ARM-H, by binding to proteins on the outside of the virus, they also prevent healthy human cells from being infected.

"Instead of trying to kill the pathogens directly, these molecules manipulate our immune system to do something it wouldn't ordinarily do," said David Spiegel, Ph.D., M.D., assistant professor of chemistry and the corresponding author of both papers.

Because both HIV and cancer have methods for evading the body's immune system, treatments and vaccinations for the two diseases have proven difficult. Current treatment options for HIV and prostate cancer -- including antiviral drugs, radiation and chemotherapy -- involve severe side effects and are often ineffective against advanced cases. While there are some antibody drugs available, they are difficult to produce in large quantities and are costly. They also must be injected and are accompanied by severe side effects of their own.

By contrast, the ARM-H and ARM-P molecules, which the team has begun testing in mice, are structurally simple, inexpensive to produce, and could in theory be taken in pill form, Spiegel said. And because they are unlikely to target essential biological processes in the body, the side effects could be smaller, he noted.

"This is an entirely new approach to treating these two diseases, which are extraordinarily important in terms of their impact on human health," Spiegel said.

HIV is a global pandemic that affects 33 million people worldwide, while prostate cancer is the second leading cause of cancer-related death among American men, with one out of every six American men expected to develop the disease.

Funding for this research was provided by the National Institutes of Health.

Courtesy: ScienceDaily

Seafloor Fossils Provide Clues To Climate Change

Deep under the sea, a fossil the size of a sand grain is nestled among a billion of its closest dead relatives. Known as foraminifera, these complex little shells of calcium carbonate can tell you the sea level, temperature, and ocean conditions of Earth millions of years ago. That is, if you know what to look for.

Assistant Professor of Earth and Environmental Sciences at Rensselaer Polytechnic Institute Miriam Katz has spent the past two decades studying these ancient, deep-sea fossils to reconstruct the climates of Earth up to 250 million years ago. Through ice ages and greenhouse climates, Katz has been able to piece together oxygen, carbon, and faunal data to paint a portrait of how, when, and why our climate has changed so drastically over geologic history. In addition, her investigations into the deep past of Earth have important implications for understanding and tracking the potential drastic repercussions of modern, human-induced climate change.

"There is a saying among scientists in my field that 'the past is a window on the future,' " Katz said. "By reconstructing the climates of the past, particularly those where we see massive and rapid changes in the climate, we can provide a science-based means to explore or predict possible system responses to the current climate change."

While her work requires a lot of time in the laboratory, Katz has spent nearly two years at sea on seven different ocean voyages around the world to drill for foraminifera as part of the Integrated Ocean Drilling Program (IODP), an international marine research effort that explores the Earth's history and structure by looking at seafloor sediments and rocks. During each two-month IODP excursion, Katz and the other scientists on board never set foot on land and spend hours poking through the millions of layers of sediment, trapped gases, fossils, and trace elements found in huge cores drilled from deep under the seafloor.

Just a few inches in diameter, each core is painstakingly drilled and removed from the seafloor. From top to bottom, the core provides a reverse chronology of the various organisms, sediments, and elements that were found on Earth throughout history. Unlike cores from sedimentary layers from the continents that are quickly destroyed by the forces of plate tectonics, wind, and water, these rarely disturbed ocean sediment cores can provide records up to 180 million years ago as new layers of sediment bury and preserve those of the past.

Katz is most interested in the foraminifera found in the cores. The foraminifera she studies live on or just below the seafloor. When they die, their hard shells are incorporated in the surrounding sediments and buried over time in a nearly uniform layer.

The assemblages of foraminifera in each layer can provide valuable information on the climate of that time. "Some species are only found in certain environments, such as in warm water or in shallow, tidal areas," Katz said. "By piecing together the species assemblages that are found in a given area during the given time period, we can reconstruct the sea level and ocean and climate conditions of that period based on our knowledge of each foraminiferal species."

In addition to the specific type of foraminifera seen in each layer, valuable information can also be gathered by looking at variations in the chemical structure of the fossilized calcium carbonate (CaCO3) shell seen in the various layers. During their life, the foraminiferal shells are formed from the elements found in the seas that they lived in. The ratios of various isotopes of the elements carbon and oxygen found in foraminiferal shells at different times in Earth's history provide important information needed to reconstruct the climate and ocean waters that surrounded them during their short lives millions of years ago.

In the case of oxygen (O), the ratio between isotopes 18O and 16O tells scientists how much water is trapped in glacial ice, providing important clues about temperature and the size of the ancient continental ice sheets. Carbon (C) in the shells can be analyzed for either 12C or 13C isotopes. Plants prefer to incorporate lighter 12C during photosynthesis, increasing the ratio of 13C to 12C in foraminifera when plant and algae production is high. This carbon data provides clues on the types and amounts of vegetation at various times as well as ocean circulation, according to Katz.

Gathering this information from cores has allowed Katz to develop important theories on one of the most recent and dramatic climate change events that has occurred in recent geologic history -- the transition from the greenhouse climate of the Eocene epoch to the "icehouse" or glacial conditions of the Oligocene epoch approximately 33.5 million years ago.

"The boundary between the late Eocene to the early Oligocene is a striking example of rapid climate change that we can look to in Earth's past," Katz said. "Information from this period can provide us with important information on how rapid changes in temperature can significantly impact ice volume, sea level, and the evolution of life on Earth."

Katz has used oxygen and carbon isotopes as well as the ratio of magnesium to calcium within foraminifera from this period to reconstruct the changes that occurred as the climate rapidly cooled. Along with her research colleagues, she has shown that ice sheets at the end of the transition were approximately 25 percent larger than today, causing a decrease in sea level of approximately 105 meters.

Her research also reaches even further back to reconstruct conditions earlier in Earth's history. In particular, she took part in a study of atmospheric oxygen and carbon dioxide concentrations since the Jurassic period 205 million years ago. The group has found that oxygen levels doubled in the short period of time from the Jurassic period to the Eocene epoch (~150 million years ago), providing a climate with just enough oxygen for placental mammals to develop.

Scientists make cells that form eggs and sperm in lab

U.S. researchers have found a way to coax human embryonic stem cells to turn into the types of cells that make eggs and sperm, shedding light on a stage of early human development that has not been fully understood.

The findings could lead to new understanding of inherited diseases and transform treatments for infertility, they said.

"We are really trying to look at the origins of normal and abnormal human development by going to the source," said Dr. Renee Riejo Pera of Stanford University in California, whose study appears in the journal Nature.

"For years and years, we haven't had the ability to look at how germ cells -- the cells that give rise to eggs and sperm -- how they are made -- what genes are required, what pathways are active," Pera said in a telephone interview.

This part of the human reproductive cycle cannot be studied in animals because the genes involved are unique to humans.

"Germ cells in humans normally develop between day 12 after fertilization through the first trimester. That is a place we can't look. We can't see because obviously it is in utero," Pera said.

She said the findings will finally allow researchers to begin to study the earliest stages of human development, and gather new clues about inherited diseases and infertility.

"The potential is enormous," Darren Griffin, a professor of Genetics at the Britain's University of Kent, said in a statement.

He said the work could make it possible to study a range of genetic and environmental effects on fertility, including pollution.

GREEN LIGHT

Dr. Kehkooi Kee, a researcher in Pera's lab, devised a way to isolate the germ cells from embryonic stem cells by adding a gene that makes green glowing proteins when germ cells are active.

"A green light comes on when a germ cell has been formed. It raises its hand," Pera said.

Once they were convinced they had germ cells, they began turning on and off several genes -- called DAZ, DAZL and BOULE -- they believed were important in converting stem cells to immature germ cells.

One of these genes, DAZL, was key to transforming embryonic stem cells into germ cells. When turned off, half as many germ cells formed.

The other two genes, DAZ and BOULE, played a role in getting cells to cut the number of chromosomes in half, a process called meiosis that must take place before fertilization.

Some of the sperm cells went all the way through meiosis. "It means we really did hit the nail on the head. We got where we wanted to go if we see meiosis in the dish," Pera said.

She said these cells formed a round spermatid, an immature sperm cell that contains just one copy of the chromosomes that would be suitable for use in an in vitro fertilization clinic.

Producing too few germ cells or poor quality germ cells is a major cause of infertility in humans.

"We think if there's immature germ cells that are available in a person, we might be able to use this system to mature them and push them forward into development," she said.

Pera hopes to try the same approach with so-called induced pluripotent stem cells, which are adult cells that have been reprogrammed to behave like embryonic stem cells.

The idea is to take cells from people with infertility problems, produce germ cells and study them to see what caused the infertility.

The study was funded in part by the National Institutes of Health.

Courtesy: ScienceDaily

Pig DNA mapped: may help with vaccines

An international team of researchers said Monday it had mapped the DNA of a domestic pig, work they say could help lead to better breeding techniques as well as improve vaccines against diseases such as swine flu.

They plan to look for genes useful in pork production and immunity in pigs, which are similar in size to humans. And, like humans, they catch influenza very easily.

"Understanding the swine genome will lead to health advancements in the swine population and accelerate the development of vaccinations for pigs," said Roger Beachy, Director of the U.S. Department of Agriculture's National Institute of Food and Agriculture.

"This new insight into the genetic makeup of the swine population can help reduce disease and enable medical advancements in both pigs and humans," Beachy said in a statement.

"The pig is a unique animal that is important for food and that is used as an animal model for human disease," added Larry Schook of the University of Illinois in Champaign, who helped direct the project.

"And because the native wild animals are still in existence, it is a really exciting animal to look at to learn about the genomic effects of domestication."

The pandemic H1N1 swine flu virus originated in pigs and evidence suggests it can be passed from humans to pigs and back again. Pigs are also susceptible to many other strains of influenza.

Courtesy: ScienceDaily

Common Pain Relievers May Dilute Power Of Flu Shots

With flu vaccination season in full swing, research from the University of Rochester Medical Center cautions that use of many common pain killers -- Advil, Tylenol, aspirin -- at the time of injection may blunt the effect of the shot and have a negative effect on the immune system.

Richard P. Phipps, Ph.D., professor of Environmental Medicine, Microbiology and Immunology, and of Pediatrics, has been studying this issue for years and recently presented his latest findings to an international conference on inflammatory diseases.

"What we've been saying all along, and continue to stress, is that it's probably not a good idea to take common, over-the-counter pain relievers for minor discomfort associated with vaccination," Phipps said. "We have studied this question using virus particles, live virus, and different kinds of pain relievers, in human blood samples and in mice -- and all of our research shows that pain relievers interfere with the effect of the vaccine."

A study by researchers in the Czech Republic reported similar findings in the Oct. 17, 2009, edition of The Lancet. They found that giving acetaminophen, the active ingredient in Tylenol, to infants weakens the immune response to vaccines.

Phipps' research has tested whether production of antibodies using a cell culture system was blunted by over-the-counter pain relievers. He found that a variety of pain relievers -- even though Tylenol and Advil have different ingredients -- seemed to dilute the production of necessary antibodies to protect against illness.

Many of the pain relievers in question are classified as NSAIDs or nonsteroidal anti-inflammatory drugs, which act in part by blocking the cyclooxygenase-2 (cox-2) enzyme. Blocking the cox-2 enzyme is not a good idea in the context of vaccination, however, because the cox-2 enzyme is necessary for the optimal production of B-lymphocytes.

Therefore, when a person takes a medication to reduce pain and fever, he or she might also inadvertently reduce the ability of B cells to make antibodies.

Phipps and colleagues also demonstrated that timing of the administration of pain relievers is important as well, according to the study published earlier this year in the journal Cellular Immunology

They exposed human cells and mice to ibuprofen, Tylenol, aspirin and naproxen (Aleve) in amounts comparable to doses commonly used by millions of Americans every day to prevent or treat pain and fever, or arthritis, or to prevent heart attack and stroke.

Treatment during the earliest stages of inflammation -- or when the first signs of pain, swelling, redness or fever would occur -- had the most detrimental effects on the immune system, the study noted.

The connection between NSAIDs and antibody production is still being actively pursued. Phipps said researchers believe ibuprofen, in particular, affects lymphocytes' ability to produce antibodies.

Meanwhile, until a full clinical trial provides a clearer picture, Phipps urges regular users of NSAIDs to be aware of the risks.

"NSAIDs are one of the most commonly used drugs; they are recommended for all age categories, are prescribed for relieving transient pain or in cases of serious inflammatory diseases," Phipps said. "By decreasing antibody synthesis, NSAIDs also have the ability to weaken the immune system which can have serious consequences for children, the elderly and the immune-compromised patients."

The U.S. Public Health Service has funded Phipps' studies.

URMC co-investigators on the study in Cellular Immunology include: David Topham, Ph.D., an expert in the immune response to influenza and a principal investigator in the David H. Smith Center for Vaccine Biology and Immunology, and Simona Bancos and Matthew P. Bernard, of the Department of Environmental Medicine, Lung Biology and Disease Program.

Courtesy: ScienceDaily

Stem Cell 'Daughters' Lead To Breast Cancer

Walter and Eliza Hall Institute scientists have found that a population of breast cells called luminal progenitor cells are likely to be responsible for breast cancers that develop in women carrying mutations in the gene BRCA1.

BRCA1 gene mutations are found in 10-20 per cent of women with hereditary breast cancer. Women with BRCA1 mutations often develop 'basal-like' breast cancer, which is a particularly aggressive form of the disease.

A team led by Associate Professors Jane Visvader and Geoff Lindeman from the institute's Victorian Breast Cancer Research Consortium Laboratory have discovered that luminal progenitor cells – the 'daughters' of breast stem cells – are the likely source of basal-like breast tumours. Their finding, published in today's issue of the international journal Nature Medicine, represents a major shift in the way scientists think breast cancer develops.

Dr Visvader said it had been thought in recent years that breast stem cells gave rise to BRCA1 tumours. "However, research carried out at the institute by Drs Elgene Lim and François Vaillant has shown that breast tissue from women with BRCA1 mutations has unexpectedly high numbers of luminal progenitor cells," she said.

"Further, our gene expression studies have revealed that BRCA1 breast tissue and basal breast tumors are more similar to normal luminal progenitor cells than any other cell type in the breast. This places the spotlight on errant luminal progenitors, rather than breast stem cells."

Dr Lindeman, who also heads the Familial Cancer Centre at the Royal Melbourne Hospital, said that now the importance of luminal progenitor cells in breast cancer was known it opened the way for the development of new drugs or therapies to treat breast cancer, one of the biggest causes of premature death in women.

"BRCA1 women have approximately a 65 per cent lifetime chance of developing breast cancer. Following surgery, treatment options available to these women are often limited to chemotherapy and radiotherapy, so identifying new treatment and prevention strategies is a priority for us," he said.

Luminal progenitor cells in women with BRCA1 mutations have 'forgotten' how to behave, Dr Lindeman said. "Usually, luminal progenitor cells multiply rapidly in the presence of certain growth factors. In BRCA1 women these cells don't even require growth factors to proliferate – they misbehave from the outset.

"We also know that the BRCA1 gene is required for normal DNA repair. There may therefore be a triple whammy effect – faulty growth control, faulty DNA repair and expanded luminal progenitor cell numbers –ultimately resulting in breast cancer in some BRCA1 mutation carriers."

Dr Visvader said in the long-term, breast biopsies might be able to reveal misbehaving luminal progenitor cells. What's more, certain 'markers' might one day help guide diagnosis and treatment. "For example, c-KIT is a key marker of the luminal progenitor cell and I expect we will see an increase in pathologists routinely using this as a diagnostic marker for basal-like tumours," she said. "It may even be possible to develop new drugs that target c-KIT, since drugs are already available that target different forms of this marker."

Dr Lindeman said the identification of stem cells, luminal progenitor cells and other cell types in the breast was now beginning to reveal a breast cancer roadmap - highlighting cancer-prone cell types and key genetic pathways. "Hopefully this will lead to new, tailored therapies for the next generation of women."

Dr Visvader said the research had only been possible through the generous donation of breast tissue by women undergoing breast surgery, together with the support of their surgeons and pathologists. The study was facilitated by the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer.

The research was supported by the Victorian Breast Cancer Research Consortium, the Susan G. Komen Foundation, the National Breast Cancer Foundation, the National Health and Medical Research Council, the Australian Stem Cell Centre, the US Department of Defense and the Australian Cancer Research Foundation.

Courtesy: ScienceDaily

Medical Imaging May Help Researchers Understand Pathogenesis Of H1N1 Virus

Researchers at the National Institutes of Health (NIH) have found that imaging can now be used as a tool for identifying severe cases of H1N1 and may play a key role in understanding the pathogenesis of the virus, possibly leading to earlier diagnoses of severe cases in the future, according to a study published online today in the American Journal of Roentgenology.

The study will be published in the December issue of AJR.

Imaging revealed a severe case of H1N1 after a patient had tested negative using a nasal swab rapid antigen test. Radiography (standard X-ray) showed peripheral lung opacities, and computed tomography (CT) revealed peripheral ground-glass opacities. Both findings raised suspicion of H1N1 and reports revealed that the patient later died from a severe case of H1N1.

"The role of radiologic imaging in epidemic detection and response is evolving, with imaging being used as a tool for identifying severe cases," said Daniel J. Mollura, M.D., lead author of the study. "At the Center for Infectious Disease Imaging (CIDI) at the NIH, the study of influenza is a priority with a focus on achieving early diagnosis and understanding its pathogenesis," he said.

"Early CT may help clinicians recognize cases of severe influenza and monitor response to treatment. More cases will certainly need to be analyzed and compared in the future, but this is a promising early result," said Dr. Mollura.

Reference:

Mollura et al. Imaging Findings in a Fatal Case of Pandemic Swine-Origin Influenza A (H1N1). American Journal of Roentgenology, December 2009 (in press)

TV Exposure May Be Associated With Aggressive Behavior In Young Children

Three-year-old children who are exposed to more TV appear to be at an increased risk for exhibiting aggressive behavior, according to a report in the November issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

"Early childhood aggression can be problematic for parents, teachers and childhood peers and sometimes is predictive of more serious behavior problems to come, such as juvenile delinquency, adulthood violence and criminal behavior," according to background information in the article. Various predictive factors for childhood aggression have been studied. These include parents' discipline style, neighborhood safety and media exposure. "After music, television is the medium children aged 0 to 3 years are exposed to the most." Although the American Academy of Pediatrics recommends no screen media for children younger than age 2, studies have found consistent use of television in that age group.

Jennifer A. Manganello, Ph.D., M.P.H., of University at Albany, State University of New York, Rensselaer, and Catherine A. Taylor, Ph.D., M.S.W., M.P.H., of Tulane University School of Public Health and Tropical Medicine, New Orleans, analyzed data from 3,128 mothers of children born from 1998 to 2000 in 20 large U.S. cities to examine associations of child television exposure and household television use with aggressive behavior in children. Parents were interviewed at the time of the child's birth and at one and three years. At three years, they were asked to report time the child spent watching TV directly as well as household TV use on a typical day. Aggression also was assessed at 3 years of age using a 15-item aggressive subscale for 2- and 3-year-old children. Demographic information and other risk factors for aggression were also noted.

About two-thirds (65 percent) of mothers reported that their 3-year-old child watched more than two hours of television per day. On average, children were exposed to an additional 5.2 hours of household TV use per day.

Direct child TV exposure and household TV use were both significantly associated with childhood aggression, after accounting for other factors such as parent, family, neighborhood and demographic characteristics. "One explanation that could link both child and household TV measures with aggression involves the parenting environment," the authors write. Households with higher rates of TV use may have fewer restrictions on children's viewing habits such as exposure to unregulated television content. Increased household television use may also affect daily routines such as eating and communication patterns and may decrease time spent on other activities.

"Current American Academy of Pediatrics recommendations mainly suggest limitations for direct child exposure to TV and other media; however, our findings suggest that additional household TV use may also be an important predictor of negative childhood outcomes, such as early childhood aggression," the authors conclude. "Future research in this area should consider inclusion of both of these TV variables along with additional parent-child interaction assessments, observational assessments when possible, quality and/or content of TV programs and longitudinal analyses."

Reference:

Jennifer A. Manganello; Catherine A. Taylor. Television Exposure as a Risk Factor for Aggressive Behavior Among 3-Year-Old Children. Archives of Pediatrics and Adolescent Medicine, 2009; 163 (11): 1037 DOI: 10.1001/archpediatrics.2009.193