|Deadly rugby virus spreads in sumo wrestlers
Rugby players may get more than just the ball out of a scrum – herpes virus can cause a skin disease called "scrumpox" and it spreads through physical contact. Researchers have studied the spread of the disease among sumo wrestlers in Japan and have discovered that a new strain of the virus could be even more pathogenic, according to an article published in the October issue of the Journal of General Virology.
"Scrumpox", or herpes gladiatorum, is a skin infection caused by the herpes virus, which can cause coldsores. It is spread through direct skin-to-skin contact so it is common among rugby players and wrestlers. Symptoms can start with a sore throat and swollen glands and the telltale blisters appear on the face, neck, arms or legs. The disease is highly infectious, so players who are infected are often taken out of competition to stop the virus from spreading.
"Scientists in Japan believe that a strain of herpes virus called BgKL has replaced the strain BgOL as one of the most common and pathogenic, causing a skin disease in sumo wrestlers," said Dr Kazuo Yanagi from the National Institute of Infectious Diseases in Tokyo, Japan. "We wanted to see if this is the case, so we studied the spread of the disease in sumo wrestlers in Tokyo."
The researchers looked at samples taken from 39 wrestlers diagnosed with herpes gladiatorum, who were living in 8 different sumo stables in Tokyo between 1989 and 1994. Tests showed that some of the cases were primary infections, being the first time the wrestlers had been infected. However, in some cases the disease had recurred several times.
"Herpes virus can hide in nerve cells for long periods of time and symptoms can reappear later," said Dr Yanagi. "Our research showed that the BgKL strain of herpes is reactivated, spreads more efficiently and causes more severe symptoms than BgOL and other strains. This is the first study to suggest that the recurrence of herpes gladiatorum symptoms in humans may depend on the strain of virus."
Professional sumo wrestlers live and train together in a stable called a heya. This makes studying the spread of herpes virus easier. Their living arrangement suggests that the source of primary herpes infections among sumo wrestlers in each stable was their fellow wrestlers.
"Two of the wrestlers died as a result of their infections, so cases like this do need to be investigated," said Dr Yanagi. "This research will aid future studies on herpes and may help identify herpes genes that are involved in recurrence and spread of the disease. We hope it will also contribute to the development of medicines to stop the disease from spreading and recurring in infected patients."
New study proves that pain is not a symptom of arthritis, pain causes arthritis
New treatments will seek to interrupt 'crosstalk' between joints and the spinal cord
Pain is more than a symptom of osteoarthritis, it is an inherent and damaging part of the disease itself, according to a study published today in journal Arthritis and Rheumatism. More specifically, the study revealed that pain signals originating in arthritic joints, and the biochemical processing of those signals as they reach the spinal cord, worsen and expand arthritis. In addition, researchers found that nerve pathways carrying pain signals transfer inflammation from arthritic joints to the spine and back again, causing disease at both ends.
Technically, pain is a patient's conscious realization of discomfort. Before that can happen, however, information must be carried along nerve cell pathways from say an injured knee to the pain processing centers in dorsal horns of the spinal cord, a process called nociception. The current study provides strong evidence that two-way, nociceptive "crosstalk" may first enable joint arthritis to transmit inflammation into the spinal cord and brain, and then to spread through the central nervous system (CNS) from one joint to another.
Furthermore, if joint arthritis can cause neuro-inflammation, it could have a role in conditions like Alzheimer's disease, dementia and multiple sclerosis. Armed with the results, researchers have identified likely drug targets that could interfere with key inflammatory receptors on sensory nerve cells as a new way to treat osteoarthritis (OA), which destroys joint cartilage in 21 million Americans. The most common form of arthritis, OA eventually brings deformity and severe pain as patients loose the protective cushion between bones in weight-bearing joints like knees and hips.
"Until relatively recently, osteoarthritis was believed to be due solely to wear and tear, and inevitable part of aging," said Stephanos Kyrkanides, D.D.S., Ph.D., associate professor of Dentistry at the University of Rochester Medical Center. "Recent studies have revealed, however, that specific biochemical changes contribute to the disease, changes that might be reversed by precision-designed drugs. Our study provides the first solid proof that some of those changes are related to pain processing, and suggests the mechanisms behind the effect," said Kyrkanides, whose work on genetics in dentistry led to broader applications. The common ground between arthritis and dentistry: the jaw joint is a common site of arthritic pain.
Past studies have shown that specific nerve pathways along which pain signals travel repeatedly become more sensitive to pain signals with each use. This may be a part of ancient survival skill (if that hurt once, don't do it again). Secondly, pain has long been associated with inflammation (swelling and fever).
In fact, past research has shown that the same chemicals that cause inflammation also cause the sensation of pain and hyper-sensitivity to pain if injected. Kyrkanides' work centers around one such pro-inflammatory, signaling chemical called Interleukin 1-beta (IL-1β), which helps to ramp up the bodies attack on an infection.
Specifically, Kyrkanides' team genetically engineered a mouse where they could turn up on command the production of IL-1β in the jaw joint, a common site of arthritis. Experiments showed for the first time that turning up IL-1β in a peripheral joint caused higher levels of IL-1β to be produced in the dorsal horns of the spinal cord as well.
Using a second, even more elaborately engineered mouse model, the team also demonstrated for the first time that creating higher levels of IL-1β in cells called astrocytes in the spinal cord caused more osteoarthritic symptoms in joints. Past studies had shown astrocytes, non-nerve cells (glia) in the central nervous system that provide support for the spinal cord and brain, also serve as the immune cells of CNS organs. Among other things, they release cytokines like IL-1β to fight disease when triggered. The same cytokines released from CNS glia may also be released from neurons in joints, possibly explaining how crosstalk carries pain, inflammation and hyper-sensitivity back and forth.
In both mouse models, experimental techniques that shut down IL-1β signaling reversed the crosstalk effects. Specifically, researchers used a molecule, IL-1RA, known to inhibit the ability of IL-1β to link up with its receptors on nerve cells. Existing drugs (e.g. Kineret® (anakinra), made by Amgen and indicated for rheumatoid arthritis) act like IL-1RA to block the ability IL-1β to send a pain signal through its specific nerve cell receptor, and Kyrkanides' group is exploring a new use for them as osteoarthritis treatment.
The implications of this process go further, however, because the cells surrounding sensory nerve cell pathways too can be affected by crosstalk. If 10 astrocytes secrete IL-1β in response to a pain impulse, Kyrkanides said, perhaps 1,000 adjacent cells will be affected, greatly expanding the field of inflammation. Spinal cord astrocytes are surrounded by sensory nerve cells that connect to other areas of the periphery, further expanding the effect. According to Kyrkanides' model, increased inflammation by in the central nervous system can then send signals back down the nerve pathways to the joints, causing the release of inflammatory factors there.
Among the proposed, inflammatory factors is calcitonin gene related peptide (CGRP). The team observed higher levels calcitonin-gene related peptide (CGRP) production in primary sensory fibers in the same regions where IL-1β levels rose, and the release of IL-1β by sensory neurons may cause the release of CGRP in joints. Past studies in Kyrkanides reveal that CGRP can also cause cartilage-producing cells (chondrocytes) to mature too quickly and die, a hallmark of osteoarthritis.
Joining Kyrkanides in the publication from the University of Rochester School of Medicine and Dentistry were co-authors M. Kerry O'Banion, M.D., Ph.D., Ross Tallents, D.D.S., J. Edward Puzas, Ph.D. and Sabine M. Brouxhon, M.D. Paolo Fiorentino was a student contributor and Jennie Miller was involved as Kyrkanides' technical associate. Maria Piancino, led a collaborative effort at the University of Torino, Italy. This work was supported in part by grants from the National Institutes of Health.
"Our study results confirm that joints can export inflammation in the form of higher IL-1β along sensory nerve pathways to the spinal cord, and that higher IL-1β inflammation in the spinal cord is sufficient in itself to create osteoarthritis in peripheral joints," Kyrkanides said. "We believe this to be a vitally important process contributing to orthopaedic and neurological diseases in which inflammation is a factor."
Meat-eating dinosaur from Argentina had bird-like breathing system
ANN ARBOR, Mich.--The remains of a 30-foot-long predatory dinosaur discovered along the banks of Argentina's Rio Colorado is helping to unravel how birds evolved their unusual breathing system.
University of Michigan paleontologist Jeffrey Wilson was part of the team that made the discovery, to be published Sept. 29 in the online journal Public Library of Science ONE and announced at a news conference in Mendoza, Argentina.
The discovery of this dinosaur builds on decades of paleontological research indicating that birds evolved from dinosaurs.
Birds have a breathing system that is unique among land animals. Instead of lungs that expand, birds have a system of bellows, or air sacs, which help pump air through the lungs. This novel feature is the reason birds can fly higher and faster than bats, which, like all mammals, expand their lungs in a less efficient breathing process.
Wilson was a University of Chicago graduate student working with noted dinosaur authority Paul Sereno on the 1996 expedition during which the dinosaur, named Aerosteon riocoloradensis ("air bones from the Rio Colorado") was found. Although the researchers were excited to find such a complete skeleton, it took on even more importance as they began to understand that its bones preserved hallmark features of a bird-like respiratory system.
Arriving at that understanding took some time. Laboratory technicians spent years cleaning and CT-scanning the bones, which were embedded in hard rock, to finally reveal the evidence of air sacs within Aerosteon's body cavity. Previously, paleontologists had found only tantalizing evidence in the backbone, outside the cavity with the lungs.
Wilson worked with Sereno and the rest of the team to scientifically describe and interpret the find. The vertebrae, clavicles, and hip bones bear small openings that lead into large, hollow spaces that would have been lined with a thin layer of soft tissue and filled with air in life. These chambers result from a process called pneumatization, in which outpocketings of the lungs (air sacs) invade the bones. Air-filled bones are the hallmark of the bellows system of breathing in birds and also are found in sauropods, the long-necked, long-tailed, plant-eating dinosaurs that Wilson studies.
"In sauropods, pneumaticity was key to the evolution of large body size and long necks; in birds it was key to the evolution of a light skeleton and flight," Wilson said. "The ancient history and evolutionary path of this feature is full of surprising turns, the explanations for which must account for their presence in a huge predator like Aerosteon and herbivores like Diplodocus, as well as in a chicken."
In the PLoS ONE paper, the team proposes three possible explanations for the evolution of air sacs in dinosaurs: development of a more efficient lung; reduction of upper body mass in tipsy two-legged runners; and release of excess body heat.
Sereno, a National Geographic Explorer-in-Residence, said he is especially intrigued by heat loss, given that Aerosteon was likely a high-energy predator with feathers but without the sweat glands that birds possess. At approximately 30 feet in length and weighing as much as an elephant, Aerosteon might well have used an air system under the skin to rid itself of unwanted heat.
In addition to Sereno and Wilson, coauthors of the PLoS ONE article include Ricardo Martinez and Oscar Alcober of the Universidad Nacional de San Juan, Argentina, David Varricchio of Montana State University and Hans Larsson of McGill University. The expedition that led to the discovery was supported by the National Geographic Society and The David and Lucille Packard Foundation.
For more information: Jeffrey Wilson--- http://www.ns.umich.edu/htdocs/public/experts/ExpDisplay.php?ExpID=1007
http://www-personal.umich.edu/~wilsonja/JAW/Home.html National Geographic Society: http://www.nationalgeographic.com/
MS patients have higher spinal fluid levels of suspicious immune molecule
St. Louis, Sept. 29, 2008 — A protein that helps keep immune cells quiet is more abundant in the spinal fluid of patients with multiple sclerosis (MS), further boosting suspicion that the protein, TREM-2, may be an important contributor to the disease.
More of an immune-control protein might seem like a boon to MS sufferers, whose symptoms are caused by misdirected immune attacks on the protective lining that coats nerve cell branches. But researchers at Washington University School of Medicine in St. Louis found the extra TREM-2 was not in the right place to reduce aggression in immune cells, a revelation that could eventually lead scientists to new pharmaceutical targets for MS prevention.
"Previously, TREM-2 had only been seen on the surface of immune cells; in the new study, we found it floating freely in spinal fluid," says lead author Laura Piccio, M.D., Ph.D., postdoctoral fellow. "This is only speculation for now, but these 'free agent' copies of TREM-2 could be making it harder for the TREM-2 that is attached to immune cells to keep the cells' aggressiveness under control."
Piccio explains that TREM-2 is a receptor protein, which means that another molecule activates it. Scientists don't currently know what that other molecule is, but the "free agent" TREM-2 in the spinal fluid could be binding to the molecule, reducing the chances that it will bind to and activate TREM-2 attached to immune cells. If Piccio and her colleagues can confirm their theory, the TREM-2 in the spinal fluid or its unknown partner could become targets for new MS treatments. The findings appear in the journal Brain.
Epidemiologists estimate that 400,000 people in the United States have MS. Symptoms, which often strike in episodic bursts, include bladder and bowel dysfunction, memory problems, fatigue, dizziness, depression, difficulty walking, numbness, pain and vision problems. The disease is more common among Caucasians than any other group and affects two to three times as many women as men.
TREM-2 first came to MS researchers' attention because of Nasu-Hakola disease, a rare genetic disorder that involves a mutation in the gene for TREM-2. Among other symptoms, Nasu-Hakola causes loss of the same protective sheath around nerve cell branches that is damaged by MS.
One place where the TREM-2 protein commonly appears is the macrophage, an immune cell that performs a variety of functions, including cleaning up debris and emitting inflammatory signals that escalate immune attacks. Macrophages come in two classes: one that promotes inflammation and one that suppresses it. TREM-2 is present only on the anti-inflammatory macrophages.
Prior experiments had shown that activation of the TREM-2 receptor can help reduce immune inflammation and promote phagocytosis, a process that lets cells consume things. In the context of the central nervous system, researchers think this allows macrophages to consume dying nerve cells and to perform "housekeeping functions," such as shutting down inflammatory processes.
"The main thing we knew about MS and the function of TREM-2 before this study was that blocking TREM-2 in a mouse model of MS made their conditions worse," says senior author Anne Cross, M.D., professor of neurology and head of the neuroimmunology section.
After Piccio identified TREM-2 in the spinal fluid, she compared that form of the protein in patients with various types of MS, patients with other inflammatory diseases of the central nervous system, and patients with non-inflammatory central nervous system diseases. To ensure that the soluble TREM-2 wasn't seeping into the patients' spinal fluid from the bloodstream, they also analyzed TREM-2 levels in blood.
While there were no differences in blood levels, the soluble form of TREM-2 was significantly higher in the spinal fluid of MS patients.
Scientists are trying to develop a mouse line where the TREM-2 gene has been disabled to learn more about the protein's contributions to the immune system.
Piccio L, Buonsanti C, Cella M, Tassi I, Schmidt RE, Rinker II J, Naismith RT, Panina-Bordignon P, Passini N, Fenoglio C, Galimberti D, Scarpini E, Colonna M, Cross AH. Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation. Brain, September 13, 2008
Supplements no better than placebo in slowing cartilage loss in knees of osteoarthritis patients
SALT LAKE CITY – In a two-year multicenter study led by University of Utah doctors, the dietary supplements glucosamine and chondroitin sulfate performed no better than placebo in slowing the rate of cartilage loss in the knees of osteoarthritis patients.
This was an ancillary study concurrently conducted on a subset of the patients who were enrolled in the prospective, randomized GAIT (Glucosamine/chondroitin Arthritis Intervention Trial). The primary objective of this ancillary study was to investigate whether these dietary supplements could diminish the structural damage of osteoarthritis. The results, published in the October issue of Arthritis & Rheumatism, show none of the agents had a clinically significant effect on slowing the rate of joint space width loss —the distance between the ends of joint bones as shown by X-ray.
However, in line with other recent studies, the researchers observed that all the study's participants had a slower rate of joint space width loss than expected, making it more difficult to detect the effects of the dietary supplements and other agents used in the study.
Rheumatologist Allen D. Sawitzke, M.D., associate professor of internal medicine at the University of Utah School of Medicine, was lead investigator. "At two years, no treatment achieved what was predefined to be a clinically important reduction in joint space width loss," Sawitzke said. "While we found a trend toward improvement among those with moderate osteoarthritis of the knee in those taking glucosamine, we were not able to draw any definitive conclusions."
More than 21 million Americans have osteoarthritis, with many taking glucosamine and chondroitin sulfate, separately or in combination, to relieve pain. The original GAIT, led by University of Utah rheumatologist Daniel O. Clegg, M.D., professor of internal medicine, was a multicenter, randomized, national clinical trial that studied whether these dietary supplements provided significant pain relief to people with osteoarthritis in the knees. GAIT found that the supplements produced no more pain relief than placebo (New England Journal of Medicine, February 2006), although a subset of the original GAIT participants with moderate to severe osteoarthritis knee pain appeared to receive significant pain relief when they took a combination of glucosamine and chondroitin sulfate.
In this ancillary study, GAIT patients were offered the opportunity to continue their original study treatment for an additional 18 months, for a total of two years. Participants remained on their originally assigned GAIT treatment: 500 mg of glucosamine three times a day; or 400 mg of chondroitin sulfate three times a day; or a combination of the two supplements; or 200 mg of celecoxib daily; or a placebo.
X-rays were obtained at study entry and again at one and two years. Joint space width was measured on 581 knees from 357 patients. None of the trial groups showed significant improvement. The group taking glucosamine had the least change in joint space width, followed by the groups taking chondroitin sulfate, celecoxib, placebo and the combination of both dietary supplements.
The total joint space width loss over two years for each group was:
* 0.013mm (glucosamine)
* 0.107mm (chondroitin sulfate)
* 0.111mm (celecoxib)
* 0.166mm (placebo)
* 0.194mm (glucosamine and chondroitin sulfate)
The interpretation of the results was problematic because the placebo group's joint space width loss was much less at two years than the 0.4mm the researchers' expected. Based on other large studies published in scientific journals, the researchers hypothesized that a loss of 0.2mm or less at two years would mean a slowed rate of cartilage loss. However, because the reduction in rate of joint space loss for all the groups was under the 0.2mm threshold, the researchers concluded none of the agents significantly slowed the loss of joint space width.
Josephine P. Briggs, M.D., director of the National Center for Complementary and Alternative Medicine, one of the study's funders, said although no definitive conclusions can be drawn about the two dietary supplements yet, "the results of the study provide important insights for future research."
Clegg said the trial shed light on osteoarthritis progression, techniques that can more reliably measure joint space width loss, possible effects of glucosamine and chondroitin sulfate, and on identifying patients who may respond best as further studies are pursued.
The other centers in the study were: The Arthritis Research and Clinical Centers, Wichita, Kan.; University of Arizona, Tucson; Case Western Reserve University, Cleveland; Cedars-Sinai Medical Center; Los Angeles; Indiana University, Indianapolis; University of California, Los Angeles; University of California, San Francisco; University of Pittsburgh.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases also funded the study. Both it and the National Center for Complementary and Alternative Medicine are part of the National Institutes of Health.
In the language of love, money talks
* 11:36 29 September 2008
* NewScientist.com news service
* Ewen Callaway
Money can't buy love, but it seems to earn you more babies. Rich men sire more children than paupers, according to a new study of thousands of middle-aged British men.
Women are more likely to marry men who can provide for them and their children than penniless men, says Daniel Nettle, a behavioural scientist at Newcastle University, UK, who led the new study.
"It's not that if you're richer you'll have more children – if you're richer you're less likely to be childless," he says.
For much of civilization, females have tended to mate with better providers, but many sociologists argue that the industrial and sexual revolutions have immunised people in developed countries such evolutionary pressures.
Census surveys have suggested that wealthier men have fewer kids, says Rosemary Hopcroft, a sociologist at the University of North Carolina in Charlotte, who is not affiliated with the study.