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Bench to Bedside
Life after a severe burn injury can be extremely difficult.
Burn patients —many of them young children —are often left with
severe scarring and other physical impairments. Significant muscle and
bone loss is one of the most frustrating consequences slowing recovery
from a severe burn injury. Researchers have long known that a badly burned
body breaks down its own muscle and bone, presumably in an effort to heal
itself. This breakdown process, called "catabolism," can significantly
impact time to recovery. NIGMS-supported burn surgeon David N. Herndon
of the University of Texas Medical Branch in Galveston has come up
with a promising medical treatment to thwart this devastating muscle and
bone loss. Herndon and his colleagues performed a small clinical study
on 25 badly burned children, who had experienced burns covering more than
40 percent of their bodies. Half of the burn patients received a 2-week
course of a standard heart rate-lowering drug called a "beta-blocker."
After the study was complete, Herndon discovered that the children who
received the beta-blocker (which lowers the body's heart rate and overall
metabolism) gained muscle and protein, as measured by levels of hormones
and electrolytes in body fluids and X-ray analysis of muscle and bone
mass. In contrast, the control subjects (who received no beta-blocker
treatment) lost muscle and protein mass.
 Photo credit: Jay Hirsh |
To many people, fruit flies are the annoying consequence of buying too
many on-sale bananas. Yet these tiny red-eyed creatures— known to
scientists as the insect species Drosophila melanogaster— hold
a secret key to curing human diseases. Fruit flies first jumped into the
research fray 100 years ago, when a biologist named T. H. Morgan noticed
a fly on the wall of his lab that had white eyes instead of the usual
red ones. Years later, scientists discovered that this particular strain
of fruit fly had white eyes because one of the fly's genes hadn't worked
properly. Today, Drosophila is one of the most valuable research
tools available to scientists who study the relationship between genes
and health. For example, one recent study performed by NIGMS-supported
scientist Ethan Bier of the University of California, San Diego
unearthed 548 fly genes that are so similar to genes involved in 714 different
human genetic disorders that the likelihood of the similarity occurring
by chance alone is 1 in 10 billion. What this means is that scientists
can look for causes and treatments for blindness, cancer, Parkinson's
disease, diabetes, and other disorders using lab fruit flies that are
inexpensive and can be bred very quickly. Bier predicts that a few hundred
fly "disease" genes will make proteins that are indistinguishable from
their human counterparts. Ultimately, Bier says, fly genes can play an
important role in the study of at least 1,000 of the 5,000 known genetic
diseases in people. Pretty impressive for an insect!
Swallowing certain medicines with a glass of grapefruit juice can provide
an unwanted surprise. For 10 years now, scientists have known that a natural
chemical in grapefruit juice can boost the blood levels of a variety
of medicines in some people. Researchers figured out that grapefruits
do this by knocking back the activity of a drug-chewing intestinal enzyme
called cytochrome P4503A4, or CYP3A4. Doctors have observed this "grapefruit
juice effect" with more than 20 different medicines, including drugs used
to treat allergies, heart disease, and infections. NIGMS-supported researcher
Paul B. Watkins has now discovered that Seville (sour) orange juice—
but not regular orange juice— has the same effect on the body's handling
of these medicines. Watkins and his coworkers at the University of North
Carolina at Chapel Hill assembled 10 people who volunteered to participate
in the juice-medicine study. Each person took a standard dose of felodipine
(a drug commonly used to treat high blood pressure) diluted in grapefruit
juice, sour orange juice, or plain orange juice. The researchers measured
blood levels of the medicine at various times afterward. The team observed
that grapefruit juice and sour orange juice led to the same increase in
felodipine levels in the blood while regular orange juice had no effect.
Since both juices contain a chemical called dihydroxybergamottin, the
scientists suspect that this chemical may be the molecular culprit accounting
for the grapefruit juice effect, although further lab tests are needed
to confirm this suspicion. Who drinks sour orange juice? While not a typical
breakfast choice, Seville oranges are often ingredients in food products
such as marmalade. However, further studies will need to confirm whether
the amount of dihydroxybergamottin in such food products is enough to
affect the body's processing of medicines.
 Photo credit: Paul Keim |
Biologists play a key role in sleuthing bioterrorism cases. Last fall,
when potentially deadly anthrax bacteria showed up in letters addressed
to Senate Majority Leader Thomas A. Daschle (D-S. D.) and NBC News anchor
Tom Brokaw, biologists went to work to identify the source of the bacteria,
which also infected and killed photographer Bob Stevens of American Media,
Inc. in southern Florida and four others. Just as a criminal can be identified
by a unique fingerprint pattern, a bacterial strain can be pinpointed
through analysis of its genetic fingerprint (DNA). Samples of DNA from
bacteria that evolved from the same microbial ancestor have DNA with a
nearly identical sequence of genetic "letters"— building blocks called
nucleotides. NIGMS-supported evolutionary biologist Paul Keim of
Northern Arizona University developed the molecular technique used by
authori-ties to identify the anthrax strains used in bioterrorist attacks
in the fall of 2001. Keim has also used his DNA fingerprinting tech-nique
recently to analyze the strain of anthrax bacteria released in 1993 by
the Japanese cult Aum Shinrikyo. His analysis showed that the attack failed
because the cult members used a veterinary vaccine strain of anthrax that
is not dangerous to humans.
The use of herbal therapies is on the rise in the United States.
While millions of people take herbs routinely to treat various health
problems, many herbal concoctions can be harmful and some have proven
to be deadly. Unlike many prescription (or even over-the-counter) medicines,
herbs contain many, many different ingredients— sometimes thousands
of them— and researchers do not know in the majority of cases how
herbs work inside the human body. Because herbs are natural prod-ucts,
they are not regulated by the U. S. Food and Drug Administration. Scientists
have not performed careful studies to evaluate the usefulness and safety
of most herbs. Certain herbs, however, are showing medical promise. For
example, a handful of controlled scientific studies in people have hinted
that the herb feverfew is effective in combating migraine headaches. Scientists
have suspected that this herb, which is also known by its plant name "bachelor's
button," exerts its effects by halting inflammation, a standard immune
system response that is one of the body's most basic defense mechanisms.
Recently, NIGMS-supported chemist Craig Crews of Yale University
discovered how an inflammation-fighting ingredient in feverfew may work
inside the cells of the body. Crews used chemistry and biology experiments
to show that the ingredient, called parthenolide, disables a key cellular
process involved in kickstarting inflammation.
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