Newborn Possibilities Fund Awards Grant to Georgia Health Sciences University Foundation to Support Groundbreaking Pediatric Research

/PRNewswire/ -- The Newborn Possibilities Fund, a grantmaking program established by Cord Blood Registry (CBR), today announced it will provide its first-ever grant to the Georgia Health Sciences University Foundation. The university's medical center is conducting the first FDA-regulated clinical trial evaluating cord blood stem cells as a medical intervention for cerebral palsy. The grant will provide financial support to help curb travel and other expenses for families with a child participating in the trial.

The study will include 40 children, ages 1 to 12 and will begin with a neurological exam. Then, half of the study participants will receive an infusion of their own cord blood while the other half receives a placebo. Three months later, the children will be evaluated without physicians knowing which group received the stem cell infusion. Afterward, children who didn't get their cord blood initially will receive an infusion. Children in the study will return three and six months later for evaluation, where researchers will assess their motor skills and neurological development.

"This is a very well-designed clinical study that will provide new insights into the potential of cord blood stem cells to help children recover from nerve tissue damage to the brain," said Heather Brown, vice president of scientific and medical affairs at CBR. "However, the study design requires a family to make trips at their own expense to the study center. The goal of The Newborn Possibilities Fund is to remove financial barriers that may prevent eligible children from participating in this cutting-edge research and receiving investigational treatments that may improve their quality of life."

The Newborn Possibilities Fund (NPF) was created to help advance clinical research investigating the use of a child's own cord blood stem cells as a treatment for conditions like cerebral palsy and traumatic brain injury. The NPF directs financial grants to non-profit organizations to help cover the cost of travel for families who have the chance to participate in FDA-regulated trials. The Fund is administered by Tides, a public charity, on behalf of CBR.

Patients who meet the inclusion criteria and are enrolled in the trial at Georgia Health Sciences University will be notified of the Newborn Possibilities Fund and have the opportunity to receive funds to use toward the cost of travel to Augusta, Georgia for the cord blood infusion procedure and required follow up visits.

"The hope for stem cells, really from the beginning, is that they might serve as some type of replacement for cells in the nervous system that have been destroyed or never developed properly," said Dr. James Carroll, professor and chief of pediatric neurology at Georgia Health Sciences University and principal investigator on the study. "The main goal of our research is to try to help improve the lives of children with cerebral palsy and find out if the method we're using is going to help these children in the future."

A growing body of research in animals has shown that infused stem cells help to initiate repair and induce healing in the brain. While the Georgia Health Sciences University is the first controlled clinical trial to be conducted, anecdotal reports from previous studies have shown marked improvement in children with cerebral palsy about three months after an initial infusion of cord blood, which led Dr. Carroll to design his trial.

Through generous donations, the Newborn Possibilities Fund hopes to provide financial support for additional trials already underway at leading research universities across the country. For more information on the program or to donate, please visit www.newbornpossibilities.com/donate.asp

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City Leaders Launch Medicare Diabetes Screening Project in Augusta

/PRNewswire/ -- Senator Ed Tarver (D - District 22), Jeanette Cummings, Director, Central Savannah River Area Regional Development Center (CSRA RDC) Area Agency on Aging (AAA), and other city and community leaders today urged all Augusta area seniors to learn more about their personal risk for diabetes, as they launched the Medicare Diabetes Screening Project (MDSP) in Augusta before a crowd gathered at the Henry H. Brigham Senior Center on Golden Camp Road. On a national level, the MDSP is co-chaired by the American Diabetes Association, the Health Care Leadership Council, and Novo Nordisk, and is supported by more than 20 organizations representing the interests of seniors and health care providers.

"Today, I am proud to announce the start of the Medicare Diabetes Screening Project in Augusta," said Sen. Tarver. "When diabetes is undiagnosed and untreated, it can be devastating, and new government statistics show that our senior citizens are especially vulnerable."

According to a study in the February 2009 issue of Diabetes Care, 32% of adults ages 65 and older have diabetes. What's more, almost half (46%) of those seniors with diabetes don't know they have it - they have not been diagnosed. In addition to those with diabetes, another 40% of adults ages 65 and older have pre-diabetes, putting them at very high risk of developing diabetes and heart disease, and it is likely that most of them are unaware of their status. When these statistics are applied to Richmond County, it is estimated that approximately 3,400 seniors ages 65 and older have undiagnosed diabetes, and an additional 9,300 seniors ages 65 and older have pre-diabetes.

"These statistics show why it is crucial that we create awareness of the benefits that Medicare offers for diabetes screening, and motivate our seniors to ask their health care providers about being tested for diabetes," said CSRA AAA Director, Jeanette Cummings.

Since 2005, Medicare has offered benefits for diabetes screening, but usage of these benefits has been minimal. For people who are ages 65 and older and have one risk factor for diabetes, Medicare offers a free diabetes-screening test in a health care provider's office, with no deductible and no co-pay. If seniors are found to have pre-diabetes, they are eligible for another free screening in six months.

To encourage use of these benefits, the Medicare Diabetes Screening Project was conceived and launched in 2007 in Columbus, Georgia. City and community leaders in Columbus developed a model for public awareness and outreach, and that model is being adapted for implementation here in Augusta.

"Augusta elected officials and other leaders from the community immediately saw the need for the Project," said Commissioner Jerry Brigham, "and they have quickly developed ideas and networks for reaching out to seniors and their health care providers with messages of what Medicare offers for diabetes screening. This type of collaboration represents the best of Augusta."

The MDSP will reach out to Augusta-area primary care physicians and their office managers via a letter signed by diabetes specialist Dr. Charles Shaefer of University Primary Care. "To complement public awareness activities, it is important that we directly inform physicians and their staff about the MDSP and the screening benefits that Medicare offers their patients," said Dr. Shaefer.

Also planned are a series of educational seminars at local senior centers, to be coordinated and implemented by the CSRA Area Agency on Aging. And according to Rev. Robert Ramsey, Pastor of the Gospel Water Branch Baptist Church, seniors and their family members will also hear about the MDSP and Medicare diabetes screening via the faith-based community. "Communicating health information to our congregants is not only possible, it's been proven successful," said Rev. Ramsey, who recently participated in a diabetes prevention faith-based program as part of a research study funded by the National Institutes of Health (NIH).

The most currently-available estimates from the Centers for Disease Control and Prevention (CDC) show that the prevalence of diabetes is 25% higher in the state of Georgia as compared to the national average (10% versus 8%, respectively). The CDC also estimates that 10.3% of all adults ages 20 and older in Richmond County have diabetes.

The Medicare Diabetes Screening Project in Augusta is a community-based effort to reach and motivate seniors who have undiagnosed diabetes or pre-diabetes, and encourage them to see their doctors or other health care providers, and take advantage of the free diabetes screening benefits offered by Medicare. To learn more, visit www.screenfordiabetes.org.

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Agent Orange exposure increases veterans' risk of aggressive recurrence of prostate cancer

Veterans exposed to Agent Orange are at increased risk of aggressive recurrence of prostate cancer, researchers report.

A study of 1,495 veterans who underwent radical prostatectomy to remove their cancerous prostates showed that the 206 exposed to Agent Orange had nearly a 50 percent increased risk of their cancer recurring despite the fact that their cancer seemed relatively nonaggressive at the time of surgery. And, their cancer came back with a vengeance: the time it took the prostate specific antigen, or PSA, level to double – an indicator of aggressiveness – was eight months versus more than 18 months in non-exposed veterans.

"There is something about the biology of these cancers that are associated with prior Agent Orange exposure that is causing them to be more aggressive. We need to get the word out," says Dr. Martha Terris, chief of urology at the Charlie Norwood VA Medical Center in Augusta and professor of urology at the Medical College of Georgia School of Medicine.

Dr. Terris, corresponding author on the study published in the May issue of British Journal of Urology International, says she wants her colleagues following prostate cancer patients with Agent Orange exposure to know those patients may need more meticulous scrutiny and so-called salvage therapy quickly if their prostate cancer returns. "Not only are their recurrence rates higher but their cancers are coming back and growing much faster when they do come back," the Georgia Cancer Coalition Distinguished Scholar says.

The PSA of prostate cancer patients is typically measured every three months for two years after surgery then every six months for life. After surgery to remove the diseased prostate, the PSA should be zero, but any prostate cancer cells left behind continue to make PSA, a red flag of recurrence, Dr. Terris says. The PSA often "percolates along" so physicians tend to watch it for a while to determine if additional therapy is needed. However in patients with Agent Orange exposure, radiation or hormone therapy to kill remaining cells may need to be done sooner rather than later, she says.

Increasing evidence is emerging that exposure to Agent Orange, a herbicide and defoliant used during the Vietnam War, increases risk for a variety of health problems, including prostate cancer, although the exact mechanism is unclear. Dioxin, its known carcinogen, also is found in herbicides and pesticides used by U.S. farmers, forestry and chemical plant workers who studies have shown to have an increased cancer risk. Scientists suspect dioxin activates regulatory regions of genes to enable the uncontrolled cell division that is a cancer hallmark.

Dr. Terris led a separate study of 1,653 veterans at VA medical centers in five cities between 1990 and 2006 that also showed recurrence rates were higher and recurring cancers were more aggressive with Agent Orange exposure. Dr. Sagar R. Shah, MCG urology resident, presented the findings at the 2007 annual meeting of the American Urological Association.

This new study – which includes the VA Medical Center in Augusta, Veterans Affairs Greater Los Angeles Healthcare System, Veterans Affairs Palo Alto Healthcare System and six affiliated medical schools – included new patients as well as longer follow up on many of the original study patients. As with the previous study, prostate cancer seemed to have a similar course in blacks and whites, but Agent Orange exposure was more common in blacks, who were more likely to be ground troops in Vietnam.

Plenty of questions remain, such as what happens to patients whose primary treatment is standard radiation or brachytherapy, where rice-size radiation pellets are implanted in the prostate, rather than surgery, Dr. Terris says.

She also wants to know whether the veterans' degree of exposure is related to the severity of their cancer. Everyone has some dioxin exposure; "Even if you never set foot in Vietnam or outside the United States," she says. So she is now measuring levels in the body fat – which is like a repository for what the body has been exposed to – to determine how levels correlate to their cancer severity.

Prostate cancer is the most common cancer in men and trails lung cancer as the second leading cause of cancer death.

The study was funded by the Department of Veterans Affairs, the National Institutes of Health, the Georgia Cancer Coalition, the Department of Defense Prostate Cancer Research Program and the American Urological Association/Astellas Rising Star in Urology Award.

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Male impotence drugs may deserve a second look in women

New studies indicate the three drugs used to treat male impotence also appear to work in females, albeit a little differently, and should give the scientific community pause to take a second look at their potential in the 40 percent of women who report sexual dysfunction, researchers say.

In one of the first studies of the effect of phosphodiesterase Type 5 inhibitors - Viagra®, Levitra® and Cialis® - on the pudendal arteries that supply the penis, vagina and clitoris the blood needed to produce a satisfying sexual experience, Medical College of Georgia researchers showed the drugs relax the artery in male and female rats.

"It shows the drugs need to be investigated more for women and small alterations could make these compounds more effective for women living with these disorders," says Dr. Kyan J. Allahdadi, postdoctoral fellow in physiology at MCG. He's presenting the findings during the 122nd Annual Meeting of the American Physiological Society held in New Orleans April 18-22 as part of the Experimental Biology 2009 scientific conference.

Although there was talk years ago of a pink pill for women to parallel the blue Viagra for men, early clinical trials found essentially no response in women.

MCG researchers decided to look again, first giving a drug to constrict the internal pudendal arteries in male and female rats – as they would be in a non-erect state – then giving doses of each impotency drug to see the impact. The arteries from male rats displayed a relatively standard concentration-dependent relaxation – the more drug they got, the more they relaxed - while in females arteries, there was an initial relaxation then an odd oscillation between relaxation and contraction with subsequent dosing.

While they don't fully understand the swing, the unique female response likely provides more evidence that sexual function is more complex in females, says Dr. R. Clinton Webb, chair of the MCG Department of Physiology and a study author. Scientists define female sexual dysfunction as a multifaceted disorder that includes anatomical, psychological, physiological and social-interpersonal aspects.

MCG researchers have shown part of that complexity may be the smooth muscle cells in the internal pudendal arteries of females communicate, agreeing to contract and relax, while male smooth muscle cells make independent decisions to just relax.

They found one other distinction: females were more sensitive to Viagra®, or sildenafil, while males were most sensitive to Levitra®, or vardenafil.

Previous studies on the effectiveness of these drugs focused on the cavernosal tissue, or penis. The internal pudendal artery actually feeds the penile artery which is buried deep in the penis where numerous caverns enable it to be flaccid when not engorged with blood. Physical stimulation of the area causes the tissue, endothelial cells and nerves to release nitric oxide, a powerful dilator of blood vessels. The system works pretty much the same way in the vagina and clitoris.

"If you have too much constriction or not enough relaxation to allow blood to go through the internal pudendal artery, you are not going to get the net effect of an erection," Dr. Allahdadi says. "That is why we wanted to begin to characterize what was going on in this blood vessel."

Perhaps as importantly, the MCG scientists and others are beginning to believe sexual dysfunction provides an early, or at least visible, clue of vascular disease. Vascular problems, that can result from diabetes, hypertension, high cholesterol and the like, are a major cause of sexual dysfunction in men and women. "You don't feel atherosclerosis but you know darn well if you are not getting an erection," Dr. Webb says. In fact, the MCG scientists are beginning to look at animal models of disease states, such as diabetes, to see what it does to these internal pudendal arteries.

"What we have seen preliminarily is there is big difference in responsiveness in these arteries. The diabetic pudendal arteries are much more sensitive to contraction," Dr. Allahdadi says. They will look at how drugs like Viagra impact that contraction in the days ahead.

In fact MCG scientists suspect one reason that many of the women participants in previous studies of Viagra did not seem to respond is because they did not have vascular problems that could have been circumvented by a drug that relaxes arteries so blood can enter. In men with a healthy vasculature, the drugs likely would still produce a longer erection.

Dr. Rita C. Tostes, associate professor in the MCG Department of Physiology, is a co-author who contributed to the design and analysis of the study.

Toni Baker
Medical College of Georgia

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Taking Control of Your Diabetes Conference Heads to Augusta to Bring Answers, Advocacy and Hope - February 28, 2009

/PRNewswire/ -- Taking Control of Your Diabetes (TCOYD) conference and health fair will be held February 28, 2009 at the Augusta Marriott Hotel, bringing national and local medical experts in diabetes care to people with all types of diabetes, those at risk for diabetes, and their loved ones for a day of highly informative and motivational programs.

Leading specialist will discuss practical advice and developments in the treatment of diabetes, the complications of the disease, psychological barriers to controlling diabetes, prevention, nutritional issues and much more. Health professionals from the Medical College of Georgia, University Primary Care, University Hospital, Augusta Foot and Ankle, Veterans Administration Medical Center, University Medical Associates, and a host of other diabetes specialists have partnered with Taking Control of Your Diabetes to hold this premier conference and health fair.

TCOYD participants can hear lectures, participate in screenings, and speak one-on-one with diabetes specialists including physicians, pharmacists, dieticians, certified diabetes educators and podiatrists.

A health fair with 35 informational exhibits from national and local diabetes-related companies and organizations will be open throughout the day. A banquet lunch is included and will feature special guest speaker All-Star Hawks player Dominique Wilkins who will share his inspiring story, living well with diabetes.

"With the increase in obesity, more and more Georgians are being diagnosed every day with diabetes. This conference and health fair is a great way to learn as much as you possibly can in one day and in one location from a variety of diabetes experts. We want to help individuals and families living with diabetes to be educated, motivated and empowered to take control of their diabetes," says Charles Shaefer, Jr., MD, conference co-director.

Pre-registration is recommended and financial aid is available for those who need assistance. Early registration fees are $15 per person. Registration fees include breakfast, lunch, all conference activities and materials. FINANCIAL ASSISTANCE IS AVAILABLE BY CALLING TCOYD. Onsite registration begins at 9 a.m. and costs $20. The conference is from 10:00 a.m. to 4:00 p.m. To register or get more information, call 800-998-2693 or visit www.tcoyd.org, or www.AugustaDiabetes.org.

TCOYD founder and director Steven Edelman, MD, an internationally recognized leader in diabetes treatment, research and education, who has lived with diabetes for 37 years, says, "Diabetes is demanding and people's daily decisions have an immediate impact on their health. At the same time, information about living with diabetes is complex. Education is critical to staying on top of this disease."

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Prevalence of Disordered Eating Behaviors in Diabetics Probed

Children with diabetes are at an increased risk for developing eating disorders and researchers want to know if it's their disease or treatment that's to blame.

"Diabetes treatment prescribes obsessive food behavior, such as carbohydrate restriction," said Dr. Deborah Young-Hyman, pediatric psychologist in the Medical College of Georgia's Georgia Prevention Institute. "We want to know if those prescribed behaviors contribute to disordered eating and/or whether there are physiological mechanisms which prevent children with diabetes from controlling their eating behavior. For example, treatment with insulin makes you hungry and can cause you to gain weight."

There is some unfortunate synergy: diabetes makes it difficult to control blood glucose and disordered eating behavior does as well, Dr. Young-Hyman said.

Over the next three years, with funding from the American Diabetes Association, she and researchers at Emory and Harvard universities will study 90 children age 10-17 newly-diagnosed with diabetes or transitioning to an insulin pump. They will monitor treatment patterns, weight, psychological adjustment and attitudes about weight and eating. They'll also look at changes in eating patterns and blood sugar levels in response to insulin.

Children and their parents will answer computer-based questionnaires about eating behaviors and psychological adjustment - in the context of their disease and its treatment.

These include questions about parental attitudes, family factors, personality of the child and parents and perceived societal attitudes.

"As they are diagnosed and are adjusting to diabetes treatment, children are already dealing with all sorts of issues that put them at an increased risk for eating disorders. The psychological issues that come with the diagnosis can add to that risk," she said. "There is also the existing drive for thinness that exists in our society, dealing with the diagnosis and management of a long-term illness and the psychological adjustment that comes with that."

Even the insulin the children must take may be a factor. "Large doses can lead to uncontrolled hunger, which can be mislabeled as disordered eating behavior. Patients with type 1 diabetes also lose amylin production - a hormone responsible for gastric emptying and associated with feelings of fullness - that can also lead to increased feelings of hunger," Dr. Young-Hyman said.

Study findings could support a different treatment approach.

"We might come to understand that putting a child or adolescent on an insulin pump sooner rather than later and providing them with a more flexible nutrition regimen could decrease their insulin needs and prevent excess hunger," she said. "If we don't approach weight control as dieting, place less emphasis on food restriction and focus on healthy nutrition and usual eating patterns, we can help patients gain more control over their eating behaviors and their treatment without adoption of maladaptive weight management strategies. Studies indicate that feeling in control of your illness is one of the keys to successful treatment and good psychological adjustment."

Jennifer Hilliard
Medical College of Georgia

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Exercise Helps Overweight Children Reduce Anger Expression

Regular exercise seems to reduce anger expression in overweight but otherwise healthy children, researchers said.

The first published study on the topic looked at 208 typically sedentary 7- to 11-year-olds who participated in a 10-15 week afterschool aerobic exercise program or maintained their usual inactive routine. The Pediatric Anger Expression Scale, used to gauge common anger expressions such as slamming doors and hitting, was given before and after the program.

"Exercise had a significant impact on anger expression in children," said Dr. Catherine Davis, clinical health psychologist in the Medical College of Georgia School of Medicine. "This finding indicates that aerobic exercise may be an effective strategy to help overweight kids reduce anger expression and aggressive behavior."

The finding fits with evidence that exercise reduces depression and anxiety in children and with what's considered common knowledge that exercise helps adults manage anger, she said.

It also gives parents and other caregivers another reason to get and keep children moving. "I think it's reasonable to encourage children to exercise for a lot of good reasons," said Dr. Davis whose research on overweight children has shown regular physical activity not only reduces fatness but improves cognition and reduces insulin resistance – which can lead to diabetes.

"I think if teachers could see that exercise helps kids control their behavior and get along, they would be the top proponents of physical activity for kids," said Dr. Davis, noting that other studies suggests overweight children are more likely to be bullies and to be bullied. High levels of anger and hostility have been associated with delinquency in children, cardiovascular disease in adults and metabolic syndrome - which can lead to heart attack, stroke and diabetes - in adolescents.

The new finding, published in the November issue of Pediatric Exercise Science, appears to apply to overweight children generally, regardless of factors such as race, gender, socioeconomic status or even fitness or fatness levels, the researchers wrote. In fact, even though all participants in the exercise portion lost a significant amount of weight, they remained overweight at the study's conclusion.

With help from a five-year $3.6 million grant from the National Heart, Lung and Blood Institute, Dr. Davis already is looking to see if the finding holds in a similar group of children, who are part of a study on the impact of exercise on cognition. The goal is to determine if it was the exercise or participation in an after-school program that made the difference.

Extra attention from adults and time away from usual routines that could include disagreements with siblings and watching violence on television definitely could have a psychological impact. "With a psychological outcome like cognition or anger control, positive interaction with adults can make a big difference," Dr. Davis said.

In the published study, only the exercising children came to MCG's Georgia Prevention Institute after school. In the new study, both groups are coming to the institute, with non-exercisers enjoying arts, crafts and games. "We are trying to make it so the only difference is exercise," said Dr. Davis.

By Toni Baker
Medical College of Georgia

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MCG Receives $100,000 Grand Challenges Explorations Grant for Innovative Global Health Research by Dr. Koni

The Medical College of Georgia announced November 5th that it has received a $100,000 Grand Challenges Explorations grant from the Bill & Melinda Gates Foundation. The grant will support an innovative global health research project conducted by Dr. Pandelakis A. Koni titled “Antibody-Dependent Cellular Cytotoxicity Targeted Against HIV-1 Env Glycans.”

Dr. Koni’s project is one of 104 grants recently announced by the Gates Foundation for the first funding round of Grand Challenges Explorations, an initiative to help scientists around the world explore bold, new solutions for health challenges in developing countries. The grants were provided to all levels of scientists in 22 countries and five continents.

To receive funding, Dr. Koni showed in a two-page application how his idea falls outside current scientific paradigms and could lead to significant advances in global health if successful.

His goal is to develop a vaccine against HIV, a virus that is notoriously slippery, constantly mutating itself to avoid being targeted by the immune system. In fact, the dynamic of this virus is one reason vaccines to date have failed, Dr. Koni said. But he thinks there may be chinks in the armor. Like many cells in the body, HIV and HIV-infected cells are sugar-coated. In fact, one role of this complex carbohydrate shield is believed to be protecting HIV from attack. However there are some consistencies in the sugar coating which Dr. Koni believes are critical to the virus and may be good vaccine targets.

As a first step, the immunologist is working to develop antibodies to these segments of the sugar coating with the idea that they are sites of potential vulnerability for the durable virus. "My idea is that these areas are always conserved and are consistent for a reason," said Dr. Koni. While his goal is to develop a protective vaccine, Dr. Koni said if he's successful in his pursuit, the antibodies may provide new targeted treatment strategies as well.

“I congratulate each individual who took the initiative to share their idea with us to help fight the world’s most serious diseases,” said Dr. Tachi Yamada, president of the Gates Foundation’s Global Health Program. “The number of creative approaches we received exceeded our highest aspirations. Projects from this initial pool of grants have the potential to transform health in developing countries, and I will be rooting for their success.”

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Green Tea May Delay Onset of Type 1 Diabetes

A powerful antioxidant in green tea may prevent or delay the onset of type 1 diabetes, Medical College of Georgia researchers say.

Researchers were testing EGCG, green tea's predominant antioxidant, in a laboratory mouse with type 1 diabetes and primary Sjogren's syndrome, which damages moisture-producing glands, causing dry mouth and eyes.

"Our study focused on Sjogren's syndrome, so learning that EGCG also can prevent and delay insulin-dependent type 1 diabetes was a big surprise," says Dr. Stephen Hsu, molecular/cell biologist in the School of Dentistry.

They found it also worked well in their original disease focus.

In the mouse, EGCG reduced the severity and delayed onset of salivary gland damage associated with Sjogren's syndrome, which has no known cure.

"EGCG modulates several important genes, so it suppresses the abnormality at the molecular level in the salivary gland. It also significantly lowered the serum autoantibodies, reducing the severity of Sjogren's syndrome-like symptoms," Dr. Hsu says. Autoantibodies are antibodies the body makes against itself.

Both type 1 diabetes and Sjogren's syndrome are autoimmune diseases, which cause the body to attack itself. Autoimmune disorders are the third most common group of diseases in the United States and affect about 8 percent of the population, says Dr. Hsu. Sjogren's syndrome can occur alone or secondary to another autoimmune disease, such as lupus, rheumatoid arthritis or type 1 diabetes.

The study, published in the Oct. 24 issue of Life Sciences, supports earlier research showing EGCG's impact on helping prevent autoimmune disease.

Researchers treated a control group of mice with water and a test group with a purified form of EGCG dissolved in the drinking water. At 16 weeks, the EGCG-fed mice were 6.1 times more likely to be diabetes-free than the water-fed group, and 4.2 times more likely at 22 weeks.

"Previous studies used another animal model that developed type 1 diabetes only after an injected chemical killed the insulin-producing cells. That may not accurately resemble disease development in humans, because type 1 diabetes is a genetic disease," says Dr. Hsu, the study's corresponding author.

"Our study is significant because we used a mouse model with the genetic defects that cause symptoms similar to human type 1 diabetes and Sjogren's syndrome, so the immune cells attack the pancreas and salivary glands until they are no longer functional."

Another related finding was that even when salivary cells were under attack, they seemed to be rapidly reproducing in the control group. The proliferation was suppressed in the EGCG-fed group.

"It's kind of counterintuitive – why would there be proliferation of the glandular cells occurring when the present cells are not secreting saliva?" says Dr. Kevin Gillespie, first author of the study he conducted for his master's research project at MCG.

The proliferation phenomenon also can be observed in psoriasis, an autoimmune disease affecting the skin and joints, says Dr. Hsu. "Normal skin cells turn over every 30 days or so, but skin cells with psoriasis turn over every two or three days." Dr. Hsu's group previously found that green tea polyphenols, including EGCG, inhibited rapid proliferation in an animal model for human psoriasis.

"We never thought proliferation was going on to this extent in the salivary gland, but we now believe it is tightly associated with Sjogren's syndrome," he says.

The next step is to observe Sjogren's syndrome in human salivary gland samples to determine whether the study findings hold up in humans.

"If the abnormal expression of these genes is the same in humans as in the animal model, then the second stage will be intervention and treatment with a pure form of EGCG," says Dr. Hsu.

"The benefit of using green tea in preventing or slowing these autoimmune diseases is that it's natural and not known to harm the body," says Dr. Gillespie, periodontics chief resident at Fort Gordon's Tingay Dental Clinic. "EGCG doesn't have the negative side-effects that can be associated with steroids or other medications that could otherwise be prescribed."

By Paula Hinely
Medical College of Georgia

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Memories Selectively, Safely Erased in Mice

New and old memories have been selectively and safely removed from mice by scientists.

"While memories are great teachers and obviously crucial for survival and adaptation, selectively removing incapacitating memories, such as traumatic war memories or an unwanted fear, could help many people live better lives," says Dr. Joe Z. Tsien, brain scientist and co-director of the Brain & Behavior Discovery Institute at the Medical College of Georgia School of Medicine.

"Our work reveals a molecular mechanism of how that can be done quickly and without doing damage to brain cells," says the Georgia Research Alliance Eminent Scholar in Cognitive and Systems Neurobiology.

Dr. Tsien's research team, in collaboration with scientists at East China Normal University in Shanghai, were able to eliminate new and old memories alike by over-expressing a protein critical to brain cell communication just as the memory was recalled, according to research featured on the cover of the Oct. 23 issue of Neuron.

Dr. Tsien had already created a mouse that couldn't form memories by eliminating the NMDA receptor, which receives messages from other neurons. He then garnered international acclaim by making "Doogie," a smart mouse in which a subunit of the NMDA receptor is over-expressed. Younger brains have higher amounts of this NR2B subunit which leaves communication channels between brain cells open longer. That is why young people can learn faster than older adults.

This time he was examining downstream cascades of the NMDA receptor to learn more about memory formation. An abundant protein found only in the brain, called αCaMKII, was a logical place to look because it's a major signaling molecule for the NMDA receptor. He found that when he over-expressed αCaMKII while a memory was being recalled, that single memory was eliminated.

Receptors such as the NMDA receptor are like front doors to cells, providing an opening for signaling molecules such as calcium. Synapses are the point of communication between two cells, and NMDA receptors are on the receiving end of the message. Like people, neurons change with the signals they receive. "Learning changes the way cells connect to each other," says Dr. Tsien. To form a memory, the NMDA receptor is activated, which results in the insertion of AMPA receptors into those synapses and subsequent strengthening of the synaptic connections among hundreds of thousands of neurons. Scientists believe that αCaMKII plays an important role in the insertion of AMPA receptors into synapses during learning and subsequent strengthening of connections between neurons to create a memory.

Memory has four distinct stages: learning, consolidation, storage and recall. It has been difficult to dissect the molecular mechanisms of these stages because researchers lacked techniques to manipulate proteins quickly. For example, when researchers disable a gene suspected to play a role in the memory process, the deletion typically occurred throughout the entire period so it was impossible to tell which parts of processes were impaired. Previous technology would take several days to switch off a protein, which is the product of a gene.

So Dr. Tsien’s team developed a powerful chemical-genetic method that allows him to use a pharmacologic inhibitor to instantly turn αCaMKII off and on in a mouse that he genetically engineered to over express this signaling molecule. That enabled him to study exactly what happened if he threw off the natural balance during the retrieval stage.

Much as a war veteran remembers a fateful patrol when he was fired upon, mice can establish a very long-lasting emotional memory about a place if, for example, they receive a mild shock to the paws while there. The researchers showed if they over-expressed αCaMKII, this powerful memory was rapidly erased as the animals tried to retrieve them while other memories remained intact.

A similar approach was taken with object recognition memory, giving mice a couple of toys to play with then erasing their memory of one of them. "You will feel like every time, it's a new toy," says Dr. Tsien.

While the ability to rapidly erase a selective memory is exciting, he cautions that its translation to humans would be difficult at this stage. “We are barely at the foot of a huge mountain,” says Dr. Tsien. A possible strategy for humans would be a drug that mimics the αCaMKII over expression that researchers accomplished through genetic manipulation. Or, further downstream substrates that αCaMKII acts upon could become possible drug targets.

The research was funded by the National Institute of Mental Health, the National Institute on Aging and the Georgia Research Alliance.

By Toni Baker

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Online Course Gives Physicians Useful Info about Community-Associated MRSA

A new bacterial infection is running rampant in communities because of antibiotic abuse, but ironically it is often misdiagnosed and treated with the wrong antibiotics, says a physician working to stop it.

Physicians regularly mistake the abscesses, or pockets of pus, caused by community-associated MRSA, or CA-MRSA, for spider bites and treat them as such, say Dr. Jim Wilde, pediatric emergency medicine and infectious disease physician at the Medical College of Georgia.

"Don't be fooled into thinking it's a spider bite," he says. "Think MRSA if you see a sore like that on somebody's hand or arm. The problem is that doctors are choosing the wrong oral antibiotics or are just not recognizing it at all."

Now they can log on to a new online lecture through the MCG Division of Continuing Education to learn more about this leading cause of skin and soft-tissue infections in the state.

It's part of a statewide educational campaign sponsored by Georgia United against Antibiotic Resistant Disease, or GUARD, to raise awareness about CA-MRSA.

Doctors and the general public can access the lecture at www.mcg.edu/ce/Online/mrsaonline. Physicians can receive continuing medical education credits for participating.

"The lecture, which is the first online continuing medical education course at MCG, is an excellent opportunity to learn more about this epidemic," says Caro Cassels, director of the continuing education division.

"There is a lot of misinformation and misunderstanding about MRSA, even among practicing physicians," says Dr. Wilde, who directs GUARD. "And we see dozens of cases of CA-MRSA in the emergency room every week here. It is a different type of MRSA than what we've known for the last 40 years and is spreading all over the country very rapidly."

MRSA, or methicillin resistant Staph aureus, cannot be killed by methicillin, a type of penicillin. It is spread by physical contact, not by breathing the same air or coughing. It lives on the skin and can survive on others surfaces for at least 24 hours. Hospital-associated MRSA (HA-MRSA) has been rampant inside hospitals since the early 1960s but was rare among healthy people in the community. CA-MRSA popped up around 2003 and quickly spread nationwide, causing infections primarily in healthy people outside hospitals. Infections caused by either form of MRSA can be treated, but HA-MRSA is much more dangerous. Both are resistant to all beta-lactam antibiotics, which are the most widely used class of antibiotics available.

"And yet, despite the fact that most skin and soft-tissue infections now are caused by CA-MRSA, there are still many doctors who are prescribing these antibiotics," Dr. Wilde says. "We're trying to do is get the word out to everyone in the state to stop using beta-lactams for skin infections."

In addition to the online course, 9,700 primary care physicians received educational packets from GUARD. Each packet contains a CA-MRSA fact sheet, an informational poster, a two-page synopsis of Centers for Disease Control and Prevention recommendations for treating CA-MRSA and a fill-in-the-blank discharge sheet. Dr. Wilde also coordinates a speakers' bureau on CA-MRSA with more than 30 members available to deliver lectures anywhere in the state.

GUARD is the Georgia chapter of the CDC's Get Smart about Antibiotic Use Program. The coalition seeks to reduce antibiotic-resistant disease by decreasing inappropriate antibiotic use. The educational campaign also is sponsored by the Georgia Department of Human Resources.

For more information about the online course and coalition, visit www.ga-guard.org.

By Amy Connell
Medical College of Georgia

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Breast cancer Cells Recycle to Escape Death by Hormonal Therapy

Many breast cancer cells facing potentially lethal antiestrogen therapy recycle to survive, researchers say.

About 70 percent of breast cancer cells have receptors for the hormone estrogen, which acts as a nutrient and stimulates their growth. Patients typically get an antiestrogen such as tamoxifen for five years to try to starve them to death, says Dr. Patricia V. Schoenlein, cancer researcher in the Medical College of Georgia Schools of Medicine and Graduate Studies.

"About 50 to 60 percent of these women really benefit from hormonal therapy," says Dr. Schoenlein. Why others don't has been asked for at least two decades.

One reason may be breast cancer cells switch into a survival mode that normal cells also use when faced with starvation, according to research published in the September issue of Molecular Cancer Therapeutics. Dr. Schoenlein also is reporting on the research during the 2nd World Conference on Magic Bullets (Ehrlich II) Oct. 3-5 in Nürenberg, Germany.

It's called macroautophagy – autophagy means "self eating" – and within a week, breast cancer cells can reorganize component parts, degrade non-essentials and live in this state until antiestrogen therapy is stopped or the cells mutate and resume proliferation in the presence of tamoxifen. "It's like taking your foot off of the gas pedal of your car," says Dr. Schoenlein, corresponding author on the study. "The cancer cell is in idle, unable to grow or replicate. But the cell is smart enough to use component parts generated by macroautophagy for the most necessary things required for survival." She notes that macroautophagy can't be maintained indefinitely; cells can actually self-digest. "This is a time-buying strategy."

Chemotherapeutic drugs are more direct killers but also kill healthy cells and can be tolerated by patients only for relatively short periods. Antiestrogen therapy is more specific, targeting breast cancer cells that express estrogen receptors.

In the laboratory, 20-25 percent of breast cancer cells died when Dr. Schoenlein and colleagues gave antiestrogen continuously over time – similar to how patients get it. More typically, the cells expressed increasing levels of macroautophagy and survived. "They don't grow, but they survive the therapy. They will grow if you take away the therapy." Adding a macroautophagy inhibitor promoted robust cell death.

"We believe targeting the autophagosome function will significantly improve the efficacy of hormonal treatment for estrogen-positive breast cancer," says the researcher. She recently received a three-year, $1.1 million National Cancer Institute grant to pursue that strategy.

She'll now look for ways to block macroautophagy in an animal model, including using chloroquine, a drug used to treat malaria. "We know patients can take it with few side effects," she says. If it works in animals, the drug, in combination with an antiestrogen, could move relatively quickly into human testing.

During autophagy, the internal pH for the recycling center of the reorganized cell gets acidic and chloroquine increases pH. "If you add this particular inhibitor of the recycling center, you alter the pH and block its ability to do what it is supposed to do," says Dr. Schoenlein.

A University of Pennsylvania team led by Dr. Craig Thompson reported in 2007 in The Journal of Clinical Investigation that chloroquine increased death of suicide-resistant lymphoma cells being treated with chemotherapy. Dr. Schoenlein will give chloroquine along with an antiestrogen and measure cell death.

"Most cancers probably use autophagy as a survival mechanism. You can either block the autophagosome with your therapy or you can make the cell eat itself to the point of no return and the cell self-destructs. You have to push it either way," she says. Although there are no known compounds in clinical use to induce self-destruction by autophagy, there is some evidence arsenic trioxide, a compound used in China to treat some aggressive cancers, prompts cancer cells to die from self digestion, she says. That and other compounds will no doubt be studied further, she says.

Dr. Schoenlein believes breast cancer survival during macroautophagy requires high activity of the tumor suppressor protein Rb and low levels of the lipid ceramide. Ceramide is vital but causes cell death at high levels. MCG researcher Erhard Bieberich and colleague Dr. Brian G. Condie at the University of Georgia showed in 2003 that high levels of ceramide kill cells that are unnecessary to the developing brain. The new studies will further explore the roles of Rb and ceramide in breast cancer survival during macroautophagy and determine if chloroquine can change their balance.

By Toni Baker
Medical College of Georgia

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Indian Spice Reduces Size of Hemorrhagic Stroke

By: Amy Connell
Medical College of Georgia
2008 September 22

You might want to make curcumin part of your daily diet.

This active ingredient of the Indian curry spice, turmeric, not only lowers your chances of getting cancer and Alzheimer's disease, but may reduce the size of a hemorrhagic stroke, say Medical College of Georgia researchers.

Second-year medical student Jay McCracken is working with Dr. Krishnan Dhandapani, neuroscientist in the MCG School of Medicine, using animal models to study curcumin's effect on intracerebral hemorrhages, bleeding in the brain caused by ruptured vessels.

Patients with this type of stroke are often treated for symptoms – such as headache and nausea – with medications, but not the stroke itself. Invasive surgery to remove the clot is usually needed, but some patients may not be good candidates, says Mr. McCracken. About 17 percent of strokes are hemorrhagic, according to the American Stroke Association, and usually occur in people with high blood pressure.

"We found that curcumin significantly decreases the size of a blood clot, but we're not sure why it happens," says the Alpharetta native. He thinks it may be because curcumin is a potent anti-inflammatory and antioxidant. For the study, he dissolved the yellow powder, which gives turmeric its color, in corn oil and injected it into the abdomen of an animal model of hemorrhagic stroke three times over three hours. He suspects less may work and is trying to establish the optimal dose and timing.

Timing is critical for patients who often don't know they have had a stroke and may not be seen by a physician for several hours. "Usually, patients can experience other symptoms like seizures, vision or cognitive problems, so they come to the (emergency room) fairly quickly under most circumstances," says Dr. Dhandapani. "Many patients also arrive due to head trauma and are seen within an hour or so. However, treating these injuries, even after an hour, can be tricky."

Patients likely will need to get curcumin intravenously. The researchers believe it may also help prevent strokes; they intend to pursue this line of study with the idea of also making it available in a concentrated tablet form for those at-risk.

Mr. McCracken has worked on this project since May as part of the School of Medicine Dean's Summer Research Fellowship, which enables rising sophomore students to design and participate in cutting-edge basic and/or clinical research. He is among 25 students presenting their findings today from noon to 1 p.m. in the lobby of the Carl T. Sanders Research and Education Building. School of Medicine Dean D. Douglas Miller will recognize students for their work and talk about the importance and role of research.

Mr. McCracken will continue his research through the year. "I like the research, and I think it's good preparation for residency," he says. He hopes to pursue a neurosurgery residency after graduation.

A graduate of the University of Georgia, where he received biochemistry and microbiology degrees, it was a high school football injury that inspired Mr. McCracken to pursue medicine.

"I snapped my ankle, and when I met the orthopedic surgeon, I thought he was so nice and interesting," says Mr. McCracken. "And then, for an anatomy class, we had to interview someone in science or health care, and I chose my surgeon. He let me shadow him, and I thought it was the best thing in the world."

During his first year at MCG, Mr. McCracken found he really enjoyed anatomy, especially neuroanatomy.

"I think it's interesting and challenging," he says. "I've seen patients come in who have terrible tumors or hemorrhages, and neurosurgeons can change their life in a matter of hours. Patients come in expecting three months to live, and surgeons give them years to live. It's amazing."

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