UAB Magazine Weekly - Features on Research
Epigenetics Shapes the Future of Health
By Matt Windsor and Emily Delzell | Illustrations by Ron Gamble
Trygve Tollefsbol believes you can change your destiny—with broccoli. The UAB biologist, a pioneer in the booming field of epigenetics, has the data to make his case. In a widely publicized review paper published this spring in the journal Clinical Epigenetics, Tollefsbol and colleagues at UAB explained how a diet rich in broccoli, green tea, grapes, and other key ingredients can fight off cancer and other aging-related diseases.
UAB scientists are hardly the first experts to tout the health benefits of “superfoods” like leafy vegetables and wine. But epigeneticists like Tollefsbol explain how they help on a genetic level. Their investigations offer new insights on ways to slow the aging process, reduce cancer risk, and more.
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Tollefsbol, who holds doctorates in molecular biology and osteopathic medicine, has published eight books on epigenetics, with more on the way. He is a leader in a discipline that contains a heartening message of biochemical empowerment. Epigenetics is the study of factors that affect your genes without changing the underlying DNA code. To put it another way, epigeneticists try to understand how the genetic instructions contained in our DNA are carried out in the real world.
UAB Geologist Analyzes Alabama’s Faults
By Grant Martin
Scott Brande demonstrates how rock layers react under the stress created by movement of the earth's crust.
In January, 2010, a 7.0 magnitude earthquake devastated Haiti. On March 11, 2011, an 8.9 magnitude earthquake off the coast of Japan—the most powerful in the nation’s recorded history—generated a massive tsunami that killed thousands and has triggered a nuclear crisis. And on August 23, 2011, a 5.8 magnitude earthquake with an epicenter in northern Virginia rattled houses and nerves from Florida to Maine, damaging the Washington Monument and other historic structures (see East Coast, West Coast).
These events, plus a host of other, less well-chronicled earthquakes in Chile, China, Pakistan, and Argentina, lead to two questions: Are we seeing an unusual pattern of major quakes? And could one hit home in Alabama?
Predicting the Mega-Quakes
The spate of earthquakes seen in the past two years doesn’t likely represent a trend so much as an unfortunate coincidence, says UAB geologist Scott Brande, Ph.D. “The number of earthquakes that occur in the world larger than about 6 to 6.5 on the magnitude scale is about 120 or 130 per year—and a magnitude 6 earthquake can do significant damage in a populated area,” Brande says. “The number of quakes larger than 7 might be 10 or 15, and the number larger than 8 might be one or two per year. So these larger quakes actually occur fairly often.”
New Views Inside the Eye
By Tyler Greer
Fifteen years ago, Yuhua Zhang, Ph.D., was learning to design cameras, telescopes, and microscopes in his native China. Then his mother-in-law developed sudden, severe bleeding in her left eye, and his focus changed. After learning that doctors did not have the equipment to produce high-resolution images of the retina, he devoted his career to ocular imaging. Now, Zhang, a UAB assistant professor of ophthalmology, has developed a high-resolution imaging instrument that provides an unequaled view of the human eye.
“This is, to our knowledge, the fastest practical adaptive optics for the living human eye,” Zhang says. “The development of this instrument has positioned UAB at the forefront of this emerging technology—available at only five other centers worldwide.”
Adaptive optics is technology that was originally created to help high-powered telescopes see clearly through the turbulent atmosphere in deep space. Applied to vision, adaptive optics enables retinal imaging systems to compensate for the optical defects of the human eye’s cornea and lens, offering the ability to visualize living cells within the eye.
UAB’s adaptive-optics scanning-laser ophthalmoscope (AOSLO) will help ophthalmologists detect age-related macular degeneration, diabetic retinopathy, and glaucoma, allowing them to treat the diseases earlier and slow their progression.
Answers from a Headache Expert
By Matt Windsor | Illustrations by Ron Gamble
1. Migraine Doesn’t Fit the Stereotypes
“Migraine is not just one type of headache,” says neurologist John F. Rothrock, M.D., director of the UAB Headache Treatment and Research Program. “It implies a spectrum of headache. A migraine attack may involve visual aura only, without any head pain, or it can involve what everyone thinks of as ‘migraine’—a throbbing, sickening, and very, very severe headache. Or it can be anything along the spectrum between those two extremes—including a relatively mild headache that precisely resembles a tension-type headache. Besides that, in individual patients the migraine follows its own particular path as the months and years pass. At some point some patients find their headache disorder may “transform” from episodic migraine to chronic migraine. Of these, some spontaneously may remit back to episodic migraine. It’s a dynamic disorder that changes its clinical pattern over the person’s lifetime.”
2. Migraine Is the Result of a Hypersensitive Brain
Most physicians—including experts in headache medicine—used to believe that migraine was caused by cranial blood vessels expanding and contracting, Rothrock says. “It was thought that migraine-associated constriction of blood vessels reduced blood flow to the eye or brain, producing aura, and that a compensatory dilation of the blood vessels caused the throbbing, sickening head pain.”
But it turns out that migraine is actually “a genetic condition that, as with epilepsy, produces a hypersensitive brain,” Rothrock says. He notes that researchers at Harvard recently reported evidence indicating that electrical events originating in the brain itself may provoke activation of the receptors for head pain that are located “downstream,” within the meninges that cover the brain.
“It appears that a migraine attack may originate within the visual cortex of the brain,” Rothrock says, “with activity generated at that site serving to promote the trigeminal nerve to release neuropeptides that in turn induce blood vessels located in the meninges to leak pro-inflammatory proteins, which activate and further sensitize head pain receptors, which consequently send a message back to the brain that ‘there’s pain out here.’ This to-and-fro, self-reinforcing process—brain to meninges/meninges to brain—builds and builds until finally it wears itself out, or one administers a therapy that blocks the signaling of head pain.”
3. Know Your Triggers
Because people who experience migraine have hypersensitive brains, they are susceptible to changes in their internal and external environments, including shifts in hormone levels, stress or sudden release from stress, over/undersleeping and weather changes—all of which are known migraine triggers.
Although there are certain triggers commonly reported by patients with migraine, no single trigger will cause migraine in all patients, Rothrock notes. Even for a given individual, a proven trigger doesn’t necessarily cause an attack of migraine every time it’s encountered.
“Events that occur in a person’s life may have an enormous influence on how much or little that person’s genetic predisposition to migraine is expressed clinically,” says Rothrock. “We recently published a paper on the topic of migraine triggers, and from the studies that generated that paper we found that no matter what the race, ethnicity, culture, or country involved, the most common trigger of an acute migraine attack is stress. It seems logical to assume that for chronic migraine the same is true: Stress promotes and reinforces the tendency for episodic migraine to turn chronic.” Rothrock suggests that the converse is likely to be true as well: Stress reduction may make a significant contribution towards improving one’s migraine.
4. Caffeine Has Its Place
Although caffeine is commonly reported as a migraine trigger, and chronic overuse of caffeine may promote migraine “chronification,” caffeine can help in the treatment of acute migraine, Rothrock notes. During an acute migraine attack, drugs may pass more slowly from the stomach to the small intestine, where they are absorbed. Drinking a caffeinated beverage can get the stomach moving again, increasing the likelihood of a positive treatment response, says Rothrock.
5. Education Is Key
While he was working at the University of South Alabama, Rothrock and colleagues there conducted a study to determine whether adding patient education to regular medical management could help migraine sufferers. One hundred clinic patients received either standard treatment or standard treatment plus a three-class course in migraine causes and management. After six months, the patients who took the classes reported fewer and less painful headaches, used less medication, and made fewer unscheduled visits for acute headache treatment than their peers who received standard treatment alone. “At least from these results, it appears that migraine patients benefit greatly from being educated about their disorder,” Rothrock says.
Learn more about migraine causes and treatment here.
Learn more about the UAB Headache Research and Treatment Program.
Treating Chronic Migraine with Botox
By Matt Windsor
You’ve probably already heard about the latest migraine treatment—in a slightly different context. In October 2010, the U.S. Food and Drug Administration (FDA) approved the use of Allergan’s anti-wrinkle drug Botox-A—properly known as onabotulinumtoxin-A—for the prevention of chronic migraine. As opposed to the more familiar episodic form, chronic migraine implies that the afflicted individual has experienced at least 15 days of headache per month for at least three consecutive months. That makes Botox-A the only FDA-approved treatment for a condition that affects as many as 6 million Americans and is the most common reason for referral to a specialized headache clinic, says neurologist John F. Rothrock, M.D., director of the UAB Headache Treatment and Research Program.
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In this video, UAB neurologist John Rothrock explains how Botox injections can treat migraine—and two of his patients discuss their experiences. Watch larger version of video.
In studies conducted while he was on the faculty at the University of South Alabama and now at UAB, Rothrock helped to demonstrate the safety and efficacy of Botox-A as a preventive therapy for chronic migraine. This effort complements his work performed more than two decades ago, when he assisted in the development of self-administered injectable sumatriptan (marketed commercially as Imitrex, Sumavel, or their generic equivalent). Injectable sumatriptan is a safe and highly effective therapy for acute, severe migraine headache, Rothrock says, and its introduction has empowered millions of individuals with migraine to terminate migraine attacks that otherwise would have required a visit to an emergency room (ER) or simply “suffering in silence” at home.