Neuroscience
Month
August 2, 2012
New tools have confirmed high rates of misdiagnosis of patients with chronic disorders of consciousness, such as the vegetative state. An increasing number of patients’ families wish to use these novel techniques for diagnosis, prognosis, and treatment. An international team of researchers, including Dr. Éric Racine, researcher at the IRCM, analyzed the clinical, social and ethical issues that clinicians are now facing. Their article is published in the August edition of The Lancet Neurology, a renowned journal in the field of clinical neurology.
"Patients with disorders of consciousness have traditionally been regarded as unaware by definition, but findings from recent clinical studies have revealed astounding cases of awareness despite clinical unresponsiveness," explains Dr. Racine, a Montréal neuroethics specialist.
Severe brain injury can leave patients with chronic disorders of consciousness, which are medical conditions that inhibit consciousness. Patients thus have severe motor and cognitive impairments, remain fully dependent on others for all activities of daily living, and have no or very limited means to functionally communicate their thoughts or wishes, depending on their state.
Even with a careful neurological assessment of these types of disorders, some signs of awareness can elude the clinician because the clinical diagnosis relies on the observation of motor signs of awareness, which can be very subtle and fluctuate over time.
New technological developments can now measure brain function both in resting states and in response to simple commands, independent of muscle function, which could help establish a more accurate diagnosis. As a result, diagnostic classifications have been revised and prognostic knowledge is improving. For the first time, therapeutic studies have recently shown the effects of treatment on the improvement of patient responsiveness.
"The medical decision to stop or continue rehabilitation, or to transfer a patient to a long-term care facility can be hard to accept for the family, but one of the most difficult treatment decisions by family members remains whether to continue life-sustaining therapy or to discontinue it and only provide palliative care," says Dr. Racine.
Media coverage of disorders of consciousness has increased and information on the subject is increasingly available to the public. Clinicians such as neurologists, rehabilitation specialists, family doctors, and nurses must answer more requests from patients’ family members for novel diagnostic and therapeutic procedures.
"Clinicians therefore need to be prepared to discuss disorders of consciousness with ethical sensitivity, especially considering that the new procedures remain investigational," adds Dr. Racine. "They must be aware of the level of evidence supporting them and of the unavoidable ethical and social issues involved in responding to requests from patients’ family members."
Provided by Institut de recherches cliniques de Montreal
Source: medicalxpress.com
Have you ever gone on a trip and unexpectedly found yourself in need of medical care? What if your condition could have been predicted? Better yet, what if you already had the medicine needed to treat that condition in your luggage?
The Hierarchical Association Rule Model (HARM), which I co-developed with Tyler McCormick of the University of Washington and David Madigan of Columbia University, can help patients be better prepared by warning them (and their doctors) about the conditions they may likely experience next. The predictive modeling tool checks data about an individual patient against other patients in the database with similar situations to help determine future conditions. It also alerts patients about any higher risks they may have for certain types of conditions.
ScienceDaily (Aug. 1, 2012) — Scientists have known for some time that throwing off the body’s circadian rhythm can negatively affect body chemistry. In fact, workers whose sleep-wake cycles are disrupted by night shifts are more susceptible to chronic inflammatory diseases such as diabetes, obesity and cancer.
Researchers at the Salk Institute for Biological Studies have now found a possible molecular link between circadian rhythm disturbances and an increased inflammatory response. In a study published July 9 in Proceedings of the National Academy of Sciences, the Salk team found that the absence of a key circadian clock component called cryptochrome (CRY) leads to the activation of a signaling system that elevates levels of inflammatory molecules in the body.
"There is compelling evidence that low-grade, constant inflammation could be the underlying cause of chronic diseases such as diabetes, obesity and cancer," says senior author Inder Verma, a professor in Salk’s Laboratory of Genetics and the Irwin and Joan Jacobs Chair in Exemplary Life Science. "Our results strongly indicate that an arrhythmic clock system, induced by the absence of CRY proteins, alone is sufficient to increase the stress level of cells, leading to the constant expression of inflammatory proteins and causing low-grade, chronic inflammation."
Cryptochrome serves as a break to slow the circadian clock’s activity, signaling our biological systems to wind down each evening. In the morning, CRY stops inhibiting the clock’s activity, helping our physiology ramp up for the coming day.
To gain insight into the role of circadian clock components on immune function, the Salk scientists measured the expression of inflammatory mediators in the hypothalamus (the area of the brain responsible for sleep-wake cycle regulation) of mice with deleted CRY genes. Through a variety of tests, these knockout mice showed a significant increase in the expression of certain inflammatory proteins known as cytokines, including interleukin-6 and tumor necrosis factor-α, compared to mice with CRY genes.
"Our findings demonstrate that a lack of cryptochrome activates these proinflammatory molecules, indicating a potential role for cryptochrome in the regulation of inflammatory cytokine expression," says Satchidananda Panda, an associate professor in Salk’s Regulatory Biology Laboratory and one of the senior authors of the study.
In addition, the researchers found that a lack of CRY activated the NF-kB pathway, a molecular signaling conduit that controls many genes involved in inflammation. NF-kB is a protein complex in a cell’s cytoplasm, “just happily doing nothing,” says Verma. In response to stimuli, it is transferred to the cell’s nucleus, where it binds to inflammation genes and turns them on. The regulation of these genes is tightly controlled, but NF-kB does not completely shut off their expression. This lingering expression causes inflammation.
"Every time this pathway is turned on, there is a residual amount of inflammation left in the body," says Rajesh Narasimamurthy, a research associate in Verma’s laboratory and the paper’s first author. "That adds up over time, contributing to inflammation-related diseases like obesity and diabetes."
Previous research has shown that suppressing the activity of the NF-kB pathway might be a suitable therapy for some diseases. For example, NF-kB is activated automatically in cancer cells of multiple myeloma, which affects infection-fighting plasma cells in the bone marrow and allows the cells to proliferate. Drugs that inhibit this activity might be able to degrade NF-kB to the point that it may kill off the disease.
The researchers say the goal now is to find out how to suppress NF-kB activation in the short term to treat diseases like diabetes. They caution that any long-term suppression of the pathway could lead to chronic infection. “We would like to find molecules that modify this activity and focus on those small-molecule inhibitors to treat disease,” Verma adds.
Source: Science Daily
August 1, 2012
(Medical Xpress) — In work that may revolutionise rehabilitation for stroke patients, researchers from The University of Auckland and the Auckland District Health Board have shown it is possible to predict an individual’s potential for recovery of hand and arm function after a stroke.
The new approach can be used to personalise rehabilitation so that patients and therapists set realistic goals for recovery. It may also improve outcomes of trials that evaluate new therapies, by identifying patients who are most likely to respond to specific treatments.
“One in six people worldwide will have a stroke in their lifetime,” says principal investigator Professor Winston Byblow. “After stroke, impairment of the arm and hand is very common and has a major impact on independence and quality of life.
“Until now it has only been possible to group patients together according to their broad similarity to others who have already gone through upper limb rehabilitation, but this information cannot inform an individual patient’s rehabilitation plan. We have developed the first clinical algorithm to actually predict the individual patient’s potential for recovery based on information gathered before rehabilitation begins.”
The lead author of the study, Dr Cathy Stinear explains: “The algorithm begins with a bedside test within three days of stroke. The test takes only a few minutes and requires no special equipment. This is sufficient to provide a prediction for many patients, but for others an additional test is required to measure the integrity of neural pathways from the brain to the arm. If this test gives no definitive result, an MRI assessment can be performed to better determine whether the pathways in the stroke-damaged side of the brain remain viable.”
The research team have trialled the process in patients and followed their recovery. “When the tests are combined in our stepwise algorithm they accurately predict each patient’s recovery at 12 weeks, which is around the time that therapy normally ends,” says Dr Stinear.
Neurologist Professor Alan Barber, a member of the research team and Head of the Auckland Hospital Stroke Service, says that the findings are very significant. “This is the first study to predict an individual’s potential for motor recovery using measures obtained from that patient in the initial days after stroke. This information can be used to tailor rehabilitation before it begins.”
The team is now involved in a three-year trial of the algorithm within the hospital. The results will show whether the algorithm leads to improved outcomes for patients and increases the efficiency of rehabilitation services.
Provided by University of Auckland
Source: medicalxpress.com
ScienceDaily (July 31, 2012) — Research just published by scientists at Cold Spring Harbor Laboratory (CSHL) links gene mutations found in some patients with Meier-Gorlin syndrome (MGS) with specific cellular dysfunctions that are thought to give rise to a particularly extreme version of dwarfism, small brain size, and other manifestations of abnormal growth which generally characterize that rare condition.
Although only 53 cases of Meier-Gorlin syndrome have been reported in the medical literature since the first patient was described in 1959, it is a malady whose mechanisms are bringing to light new functions for some of the cellular processes common to all life. Pathology related to MGS is traced in the new research to one of these, the fundamental process called mitosis in which cells replicate their genetic material and prepare to divide into two identical “daughter” cells.
CSHL President and Professor Bruce Stillman, Ph.D., a cancer biologist who has made seminal discoveries over three decades that have helped reveal the exquisite choreography of how chromosomes are duplicated in cells, led the new research, which suggests how, during mitosis, mutant versions of a protein called Orc1 contribute in two distinct ways to severe MGS pathology. The research is published online ahead of print in Genes & Development.
ScienceDaily (July 31, 2012) — New research demonstrates that blocking the delta opioid receptor in mice created resistance to weight gain and stimulated gene expression promoting non-shivering thermogenesis.
Imagine eating all of the sugar and fat that you want without gaining a pound. Thanks to new research published in The FASEB Journal, the day may come when this is not too far from reality. That’s because researchers from the United States and Europe have found that blocking one of three opioid receptors in your body could turn your penchant for sweets and fried treats into a weight loss strategy that actually works. By blocking the delta opioid receptor, or DOR, mice reduced their body weight despite being fed a diet high in fat and sugar. The scientists believe that the deletion of the DOR gene in mice stimulated the expression of other genes in brown adipose tissue that promoted thermogenesis.
"Our study provided further evidence that opioid receptors can control the metabolic response to diets high in fat and sugar, and raise the possibility that these gene products (or their respective pathways) can be targeted specifically to treat excess weight and obesity," said Traci A. Czyzyk, Ph.D., a researcher involved in the work from the Department of Physiology at the Mayo Clinic in Scottsdale, Arizona.
Scientists studied mice lacking the delta opioid receptor (DOR KO) and wild type (WT) control mice who were fed an energy dense diet (HED), high in fat and sugar, for three months. They found that DOR KO mice had a lean phenotype specifically when they were fed the HED. While WT mice gained significant weight and fat mass on this diet, DOR KO mice remained lean even though they consumed more food. Researchers then sought to determine how DOR might regulate energy balance and found that DOR KO mice were able to maintain their energy expenditure levels, in part, due to an increase in non-shivering thermogenesis. This was evidenced by an increase in thermogenesis-promoting genes in brown adipose tissue, an increase in body surface temperature near major brown adipose tissue depots, and the ability of DOR KO mice to maintain higher core body temperatures in response to being in a cold environment.
"Don’t reach for the ice cream and doughnuts just yet," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “We don’t know how all this works in humans, and of course, a diet of junk food causes other health problems. This exciting research identifies genes that activate brown adipose tissue to increase our burning of calories from any source. It may lead to a safe diet pill in the future.”
Source: Science Daily
July 31, 2012
Wayne State University School of Medicine researchers, working with colleagues in Canada, have found that one or more substances produced by a type of immune cell in people with multiple sclerosis (MS) may play a role in the disease’s progression. The finding could lead to new targeted therapies for MS treatment.
B cells, said Robert Lisak, M.D., professor of neurology at Wayne State and lead author of the study, are a subset of lymphocytes (a type of circulating white blood cell) that mature to become plasma cells and produce immunoglobulins, proteins that serve as antibodies. The B cells appear to have other functions, including helping to regulate other lymphocytes, particularly T cells, and helping maintain normal immune function when healthy.
In patients with MS, the B cells appear to attack the brain and spinal cord, possibly because there are substances produced in the nervous system and the meninges — the covering of the brain and spinal cord — that attract them. Once within the meninges or central nervous system, Lisak said, the activated B cells secrete one or more substances that do not seem to be immunoglobulins but that damage oligodendrocytes, the cells that produce a protective substance called myelin.
The B cells appear to be more active in patients with MS, which may explain why they produce these toxic substances and, in part, why they are attracted to the meninges and the nervous system.
The brain, for the most part, can be divided into gray and white areas. Neurons are located in the gray area, and the white parts are where neurons send their axons — similar to electrical cables carrying messages — to communicate with other neurons and bring messages from the brain to the muscles. The white parts of the brain are white because oligodendrocytes make myelin, a cholesterol-rich membrane that coats the axons. The myelin’s function is to insulate the axons, akin to the plastic coating on an electrical cable. In addition, the myelin speeds communication along axons and makes that communication more reliable. When the myelin coating is attacked and degraded, impulses — messages from the brain to other parts of the body — can “leak” and be derailed from their target. Oligodendrocytes also seem to engage in other activities important to nerve cells and their axons.
The researchers took B cells from the blood of seven patients with relapsing-remitting MS and from four healthy patients. They grew the cells in a medium, and after removing the cells from the culture collected material produced by the cells. After adding the material produced by the B cells, including the cells that produce myelin, to the brain cells of animal models, the scientists found significantly more oligodendrocytes from the MS group died when compared to material produced by the B cells from the healthy control group. The team also found differences in other brain cells that interact with oligodendrocytes in the brain.
"We think this is a very significant finding, particularly for the damage to the cerebral cortex seen in patients with MS, because those areas seem to be damaged by material spreading into the brain from the meninges, which are rich in B cells adjacent to the areas of brain damage," Lisak said.
The team is now applying for grants from several sources to conduct further studies to identify the toxic factor or factors produced by B cells responsible for killing oligodendrocytes. Identification of the substance could lead to new therapeutic methods that could switch off the oligodendrocyte-killing capabilities of B cells, which, in turn, would help protect myelin from attacks.
Provided by Wayne State University
Source: medicalxpress.com
July 31, 2012
(HealthDay) — For patients with dementia with Lewy bodies (DLB), treatment with 5 or 10 mg/day donepezil is associated with significant cognitive, behavioral, and global function improvements, according to research published in the July issue of the Annals of Neurology.
Etsuro Mori, M.D., Ph.D., of the Tohoku University Graduate School of Medicine in Sendai, Japan, and colleagues conducted a randomized, double-blind, placebo-controlled trial involving 140 patients with DLB who received either placebo or 3, 5, or 10 mg of donepezil hydrochloride per day for 12 weeks (35, 35, 33, and 37 patients, respectively). Cognitive function was measured using the Mini-Mental State Examination (MMSE); behavioral changes were measured using the Neuropsychiatric Inventory; global function was evaluated using the Clinician’s Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus); and caregiver burden was also assessed.
The researchers found that, compared with placebo treatment, the MMSE scores were significantly better with donepezil 5 mg (mean difference, 3.8) and 10 mg (mean difference, 2.4), but the 3 mg/day dose was not significantly better than placebo (P = 0.017). Donepezil at doses of 3, 5, and 10 mg/day correlated with significant improvements versus placebo on CIBIC-plus. Both the 5 and 10 mg doses of donepezil resulted in significant improvements in behavioral measures. Caregiver burden also improved, but only with the 10 mg/day dose. The safety results were similar among the groups and were consistent with the known profile.
"Donepezil at 5 and 10 mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose," the authors write. Several authors disclosed financial ties to pharmaceutical companies, including Eisai Co., which funded the study and manufactures donepezil.
Source: medicalxpress.com
Jul 31, 2012 by Laura Bailey
Concussions and even lesser head impacts may speed up the brain’s natural aging process by causing signaling pathways in the brain to break down more quickly than they would in someone who has never suffered a brain injury or concussion.
The photos compare images of two brains, one with and without head injury. The red areas indicates electrical activity in response to the task researchers asked study participants to perform, and non-injured brains show more red, thus more electrical activity during the task. Image courtesy of Steven Broglio
Researchers from the University of Michigan School of Kinesiology and the U-M Health System looked at college students with and without a history of concussion and found changes in gait, balance and in the brain’s electrical activity, specifically attention and impulse control, said Steven Broglio, assistant professor of kinesiology and director of the Neurotrauma Research Laboratory.
The declines were present in the brain injury group up to six years after injury, though the differences between the study groups were very subtle, and outwardly all of the participants looked and acted the same.
Broglio, who is also affiliated with Michigan NeuroSport, stressed that the studies lay out a hypothesis where concussions and head impacts accelerate the brain’s natural aging process.
The study, “Cognitive decline and aging: The role of concussive and subconcussive impacts,” appears in the July issue of journal Exercise and Sport Sciences Reviews.
"The last thing we want is for people to panic. Just because you’ve had a concussion does not mean your brain will age more quickly or you’ll get Alzheimer’s," Broglio said. "We are only proposing how being hit in the head may lead to these other conditions, but we don’t know how it all goes together just yet."
Broglio stressed that other factors, such as lifestyle choices, smoking, alcohol consumption, physical exercise, family history and whether or not you “exercise” your brain also impact the brain’s aging process. Concussion may only be one small factor.
To begin to understand how concussions might impact brain activity and its signaling pathways, researchers asked the participants to perform certain tasks in front of a computer, and took images of their brains. The brains of the nonconcussed group showed a greater area of electrical activation than the participants with a history of brain injury.
The signaling pathways in our brains are analogous to a five-lane highway. On a new highway, traffic runs smoothly and quickly as all lanes are in top shape. However, during normal aging, the asphalt deteriorates and lanes might become bumpy or even unusable. Traffic slows.
Similarly, our brains start with all pathways clear to transfer electrical signals rapidly. As we age, the brain’s pathways break down and can’t transfer the information as quickly. Concussive and other impacts to the head may result in a ‘pothole’ on the brain’s highway, causing varying degrees of damage and speeding the pathway’s natural deterioration.
"What we don’t know is if you had a single concussion in high school, does that mean you will get dementia at age 50?" Broglio said. "Clinically, we don’t see that. What we think is it will be a dose response.
"So, if you played soccer and sustained some head impacts and maybe one concussion, then you may have a little risk. If you went on and played in college and took more head balls and sustained two more concussions, you’re probably at a little bigger risk. Then if you play professionally for a few years, and take more hits to the head, you increase the risk even more. We believe it’s a cumulative effect."
In the next phase of study, researchers will look at people in their 20s, 40s and 60s who did and did not sustain concussions during high school sports. They hope to learn if there is an increasing effect of concussion as the study subjects age. If interested in participating in the study, email neurotraumalab.umich@gmail.com.
Researchers from the departments of Physical Medicine and Rehabilitation, and Neurology, and the Michigan Alzheimer’s Disease Center also participated in the study.
Source: University of Michigan
July 31, 2012
The presence of specific autoantibodies of the immune system is associated with blood vessel damage in the brain. These findings were made by Marion Bimmler, a graduate engineer of medical laboratory diagnostics at the Max Delbrück Center for Molecular Medicine Berlin-Buch and Dr. Peter Karczewski of the biotech company E.R.D.E.-AAK-Diagnostik GmbH in studies on a rat model. The researchers’ results suggest that autoimmune mechanisms play a significant role in the pathogenesis and progression of Alzheimer’s and vascular dementia.
(MR Angiography/Copyright: MDC)
Antibodies are the defense molecules of the body’s immune system against foreign invaders. If the antibodies cease to distinguish between “foreign” and “self”, they attack the cells of the own body, and are thus referred to as autoantibodies. These can trigger autoimmune diseases. Using MR angiography and other methods, Marion Bimmler and her colleagues have now shown that the autoantibodies bind to specific surface proteins (alpha1 andrenergic receptors) of vascular cells and thereby damage the blood vessels of the brain. The reason: The autoantibodies generate a continual stimulation of the receptor and at the same time trigger an increase in intracellular calcium ion levels. As a result, the blood vessel walls thicken, and blood flow to the brain is disturbed.
First Encouraging Results after Removal of Autoantibodies by Immunoadsorption
In earlier studies, Marion Bimmler and her research team examined blood samples of patients with Alzheimer’s or vascular dementia and showed that half of them had comparable autoantibodies. A first clinical trial together with Charité – Universitätsmedizin Berlin is currently ongoing with a collective of patients with Alzheimer’s or vascular dementia. The patients were divided into two groups – a small group whose autoantibodies were removed from the blood via immunoadsorption and a control group that did not receive this treatment. Until now, over an observation period of 6 and subsequently 12 months, the patient group who had undergone immunoadsorption improved in their memory performance and in their ability to cope with their everyday lives. In contrast, the condition of the patients who did not receive immunoadsorption treatment and continued to have autoantibodies in their blood deteriorated dramatically. Now the researchers are planning further clinical trials with larger numbers of patients.
Provided by Helmholtz Association of German Research Centres
Source: medicalxpress.com
Tuesday, July 31, 2012
TAU researchers develop bioactive coating to “camouflage” neutral electrodes
Brain-computer interfaces are at the cutting edge for treatment of neurological and psychological disorder, including Parkinson’s, epilepsy, and depression. Among the most promising advance is deep brain stimulation (DBS) — a method in which a silicon chip implanted under the skin ejects high frequency currents that are transferred to the brain through implanted electrodes that transmit and receive the signals. These technologies require a seamless interaction between the brain and the hardware.
But there’s a catch. Identified as foreign bodies by the immune system, the brain attacks the electrodes and forms a barrier to the brain tissue, making it impossible for the electrodes to communicate with brain activity. So while the initial implantation can diminish symptoms, after a few short years or even months, the efficacy of this therapy begins to wane.
Now Aryeh Taub of Tel Aviv University's School of Psychological Sciences, along with Prof. Matti Mintz, Roni Hogri and Ari Magal of TAU’s School of Psychological Sciences and Prof. Yosi Shacham-Diamand of TAU’s School of Electrical Engineering, has developed a bioactive coating which not only “camouflages” the electrodes in the brain tissue, but actively suppresses the brain’s immune response. By using a protein called an “interleukin (IL)-1 receptor antagonist” to coat the electrodes, the multi-disciplinary team of researchers has found a potential resolution to turn a method for short-term relief into a long-term solution. This development was reported in the Journal of Biomedical Materials Research.
Limiting the immune response
To overcome the creation of the barrier between the tissue and the electrode, the researchers sought to develop a method for placing the electrode in the brain tissue while hiding the electrode from the brain’s immune defenses. Previous research groups have coated the electrodes with various proteins, says Taub, but the TAU team decided to take a different approach by using a protein that is active within the brain itself, thereby suppressing the immune reaction against the electrodes.
In the brain, the IL-1 receptor antagonist is crucial for maintaining physical stability by localizing brain damage, Taub explains. For example, if a person is hit on the head, this protein works to create scarring in specific areas instead of allowing global brain scarring. In other words, it stops the immune system from overreacting. The team’s coating, the first to be developed from this particular protein, not only integrates the electrodes into the brain tissue, but allows them to contribute to normal brain functioning.
In pre-clinical studies with animal models, the researchers found that their coated electrodes perform better than both non-coated and “naïve protein”-coated electrodes that had previously been examined. Measuring the number of damaged cells at the site of implantation, researchers found no apparent difference between the site of electrode implantation and healthy brain tissue elsewhere, Taub says. In addition, evidence suggests that the coated electrodes will be able to function for long periods of time, providing a more stable and long-term treatment option.
Restoring brain function
Approximately 30,000 people worldwide are currently using deep brain stimulation (DBS) to treat neurological or psychological conditions. And DBS is only the beginning. Taub believes that, in the future, an interface with the ability to restore behavioral or motor function lost due to tissue damage is achievable — especially with the help of their new electrode coating.
"We duplicate the function of brain tissue onto a silicon chip and transfer it back to the brain," Taub says, explaining that the electrodes will pick up brain waves and transfer these directly to the chip. "The chip then does the computation that would have been done in the damaged tissue, and feeds the information back into the brain — prompting functions that would have otherwise gotten lost."
Source: Tel Aviv University
July 30, 2012
In the first human study of its kind, researchers found that using stem cells to re-grow craniofacial tissues—mainly bone—proved quicker, more effective and less invasive than traditional bone regeneration treatments.
Researchers from the University of Michigan School of Dentistry and the Michigan Center for Oral Health Research partnered with Ann Arbor-based Aastrom Biosciences Inc. in the clinical trial, which involved 24 patients who required jawbone reconstruction after tooth removal.
Patients either received experimental tissue repair cells or traditional guided bone regeneration therapy. The tissue repair cells, called ixmyelocel-T, are under development at Aastrom, which is a U-M spinout company.
"In patients with jawbone deficiencies who also have missing teeth, it is very difficult to replace the missing teeth so that they look and function naturally," said Darnell Kaigler, principal investigator and assistant professor at the U-M School of Dentistry. "This technology and approach could potentially be used to restore areas of bone loss so that missing teeth can be replaced with dental implants."
William Giannobile, director of the Michigan Center for Oral Health Research and chair of the U-M Department of Periodontics and Oral Medicine, is co-principal investigator on the project.
The treatment is best suited for large defects such as those resulting from trauma, diseases or birth defects, Kaigler said. These defects are very complex because they involve several different tissue types—bone, skin, gum tissue—and are very challenging to treat.
The main advantage to the stem cell therapy is that it uses the patient’s own cells to regenerate tissues, rather than introducing man-made, foreign materials, Kaigler said.
The results were promising. At six and 12 weeks following the experimental cell therapy treatment, patients in the study received dental implants. Patients who received tissue repair cells had greater bone density and quicker bone repair than those who received traditional guided bone regeneration therapy.
In addition, the experimental group needed less secondary bone grafting when getting their implants.
The cells used for the therapy were originally extracted from bone marrow taken from the patient’s hip. The bone marrow was processed using Aastrom’s proprietary system, which allows many different cells to grow, including stem cells. These stem cells were then placed in different areas of the mouth and jaw.
Stem cell therapies are still probably 5-10 years away from being used regularly to treat oral and facial injuries and defects, Kaigler said. The next step is to perform more clinical trials that involve larger craniofacial defects in a larger number of patients.
The study, “Stem cell therapy for craniofacial bone repair: A randomized, controlled clinical trial,” appears this month in the journal Cell Transplantation.
See the video here
Source: University of Michigan
July 30, 2012
UC Irvine scientists have discovered intriguing differences in the brains and mental processes of an extraordinary group of people who can effortlessly recall every moment of their lives since about age 10.
The phenomenon of highly superior autobiographical memory – first documented in 2006 by UCI neurobiologist James McGaugh and colleagues in a woman identified as “AJ” – has been profiled on CBS’s “60 Minutes” and in hundreds of other media outlets. But a new paper in the peer-reviewed journal Neurobiology of Learning & Memory’s July issue offers the first scientific findings about nearly a dozen people with this uncanny ability.
All had variations in nine structures of their brains compared to those of control subjects, including more robust white matter linking the middle and front parts. Most of the differences were in areas known to be linked to autobiographical memory, “so we’re getting a descriptive, coherent story of what’s going on,” said lead author Aurora LePort, a doctoral candidate at UCI’s Center for the Neurobiology of Learning & Memory.
Surprisingly, the people with stellar autobiographical memory did not score higher on routine laboratory memory tests or when asked to use rote memory aids. Yet when it came to public or private events that occurred after age 10½, “they were remarkably better at recalling the details of their lives,” said McGaugh, senior author on the new work.
"These are not memory experts across the board. They’re 180 degrees different from the usual memory champions who can memorize pi to a large degree or other long strings of numbers," LePort noted. "It makes the project that much more interesting; it really shows we are homing in on a specific form of memory."
She said interviewing the subjects was “baffling. You give them a date, and their response is immediate. The day of the week just comes out of their minds; they don’t even think about it. They can do this for so many dates, and they’re 99 percent accurate. It never gets old.”
The study also found statistically significant evidence of obsessive-compulsive tendencies among the group, but the authors do not yet know if or how this aids recollection. Many of the individuals have large, minutely catalogued collections of some sort, such as magazines, videos, shoes, stamps or postcards.
UCI researchers and staff have assessed more than 500 people who thought they might possess highly superior autobiographical memory and have confirmed 33 to date, including the 11 in the paper. Another 37 are strong candidates who will be further tested.
"The next step is that we want to understand the mechanisms behind the memory," LePort said. "Is it just the brain and the way its different structures are communicating? Maybe it’s genetic; maybe it’s molecular."
McGaugh added: “We’re Sherlock Holmeses here. We’re searching for clues in a very new area of research.”
Provided by University of California, Irvine
Source: medicalxpress.com
30 July 2012
Researchers from The University of Queensland’s Institute for Molecular Bioscience have discovered a potential new approach to treating chronic inflammatory diseases such as arthritis.
Professor David Fairlie and his colleagues have developed an experimental treatment that has proven effective at reducing symptoms and stopping the progression of the disease in models of arthritis.
“Human enzymes called proteases stimulate the secretion of immune cells that, when the correct amount is released, play important roles in digestion, fighting infections and healing wounds,” Professor Fairlie said.
“But in chronic inflammatory diseases such as arthritis, these enzymes continuously stimulate the release of immune cells, which cause inflammation when present at high levels. This leads to ongoing tissue damage.”
Professor Fairlie and his team have developed experimental compounds that block this stimulation and successfully reduce chronic inflammatory arthritis in experimental models.
If the treatment could be transferred to humans, it has the potential to reduce both the health and economic impacts of chronic inflammatory diseases.
Almost four million Australians suffer from chronic joint pain and disability caused by various forms of arthritis, including osteoarthritis, rheumatoid arthritis and gout.
Related healthcare and loss of employment cost Australia over $20 billion per year, an amount that is expected to increase dramatically as our population ages.
These promising new findings are published in the current hard-copy edition of The Federation of American Societies For Experimental Biology Journal, the world’s most cited scientific journal in biology.
Journal subscribers can access the paper at this address: http://bit.ly/Pg8lgk
Source: The University of Queensland
July 30, 2012
Is attention-deficit/hyperactivity disorder (ADHD) due to a delay in brain development or the result of complete deviation from typical development? In the current issue of Biological Psychiatry, Dr. Philip Shaw and colleagues present evidence for delay based on a study by the National Institutes of Health.
The cerebral cortex is the folded gray tissue that makes up the outermost portion of the brain, covering the brain’s inner structures. This tissue has left and right hemispheres and is divided into lobes. Each lobe performs specific and vitally important functions, including attention, thought, language, and sensory processing.
Two dimensions of this structure are cortical thickness and cortical surface area, both of which mature during childhood as part of the normal developmental process. This group of scientists had previously found that the thickening process is delayed in children diagnosed with ADHD. So in this study, they set out to measure whether surface area development is similarly delayed.
They recruited 234 children with ADHD and 231 typically developing children and scanned each up to 4 times. The first scan was taken at about age 10, and the final scan was around age 17. Using advanced neuroimaging technology, they were able to map the trajectories of surface area development at over 80,000 points across the brain.
They found that the development of the cortical surface is delayed in frontal brain regions in children with ADHD. For example, the typically developing children attained 50% peak area in the right prefrontal cortex at a mean age of 12.7 years, whereas the ADHD children didn’t reach this peak until 14.6 years of age.
"As other components of cortical development are also delayed, this suggests there is a global delay in ADHD in brain regions important for the control of action and attention," said Dr. Shaw, a clinician studying ADHD at the National Institute of Mental Health and first author of this study.
"These data highlight the importance of longitudinal approaches to brain structure," commented Dr. John Krystal, Editor of Biological Psychiatry. "Seeing a lag in brain development, we now need to try to understand the causes of this developmental delay in ADHD."
Dr Shaw agrees, adding that this finding “guides us to search for genes that control the timing of brain development in the disorder, opening up new targets for treatment.”
Additional work expanding these measures into adulthood will also be important. Such data would help determine whether or when a degree of normalization occurs, or if these delays translate into long-lasting cortical deficits.
Provided by Elsevier
Source: medicalxpress.com