Front Cover
 Table of Contents
 Research highlights
 Keeping tick-borne diseases at...
 Racing to determine causes of greyhound...
 Helping frail foals survive
 Seeking solutions to cat overpopulation...
 Troubleshooting West Nile...
 Foamy viruses show gene therapy...
 Charting new territory with immunodeficiency...
 Changing standards of care while...
 Advancing animal reproductive...
 Studying the cough mechanism
 Focusing on breathing awareness...
 Evaluating treatments for...
 Mycoplasmas play key role in disease...
 Advancing health of wildlife, endangered...
 Mapping the brain's possibilit...
 Assessing risks to animal, human...
 Giving opportunities
 Contact information
 Back Cover

Title: Research
Full Citation
Permanent Link: http://ufdc.ufl.edu/UF00088919/00001
 Material Information
Title: Research
Physical Description: Book
Language: English
Creator: College of Veterinary Medicine, University of Florida
Publisher: College of Veterinary Medicine, University of Florida
Publication Date: 2008
Subject: University of Florida.   ( lcsh )
Spatial Coverage: North America -- United States of America -- Florida
 Record Information
Bibliographic ID: UF00088919
Volume ID: VID00001
Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: All rights reserved, Board of Trustees of the University of Florida


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Table of Contents
    Front Cover
        Page 1
    Table of Contents
        Page 2
        Page 3
        Page 4
    Research highlights
        Page 5
    Keeping tick-borne diseases at bay
        Page 6
        Page 7
    Racing to determine causes of greyhound deaths
        Page 8
        Page 9
    Helping frail foals survive
        Page 10
        Page 11
    Seeking solutions to cat overpopulation problems
        Page 12
        Page 13
    Troubleshooting West Nile Virus
        Page 14
        Page 15
    Foamy viruses show gene therapy potential
        Page 16
        Page 17
    Charting new territory with immunodeficiency virus research
        Page 18
        Page 19
    Changing standards of care while improving sight
        Page 20
        Page 21
    Advancing animal reproductive health
        Page 22
        Page 23
    Studying the cough mechanism
        Page 24
        Page 25
    Focusing on breathing awareness and disease
        Page 26
        Page 27
    Evaluating treatments for osteoporosis
        Page 28
        Page 29
    Mycoplasmas play key role in disease of humans, animals
        Page 30
        Page 31
    Advancing health of wildlife, endangered species
        Page 32
        Page 33
    Mapping the brain's possibilities
        Page 34
        Page 35
    Assessing risks to animal, human and environmental health
        Page 36
        Page 37
    Giving opportunities
        Page 38
    Contact information
        Page 39
    Back Cover
        Page 40
Full Text


University of Florida Research
College of Veterinary Medicine

Introduction ............ ......... ..... .............. .1-2
Research Highlights .......... ............. ............... .3
Keeping Tick-borne Diseases at Bay ...................................... .4
Racing to Determine Causes of Greyhound Deaths ......................6
Helping Frail Foals Survive ............. .... ............. ........ 8
Seeking Solutions to Cat Overpopulation Problems .................... 10
Troubleshooting West Nile Virus ............ ..... ............. 12
Foamy Viruses Show Gene Therapy Potential .............................14
Charting New Territory With Immunodeficiency Virus Research ..............16
Changing Standards of Care While Improving Sight .............. ........18
Advancing Animal Reproductive Health ........... .................20
Studying the Cough Mechanism ............. ..................22
Focusing on Breathing Awareness and Respiratory Disease ...................24
Evaluating Treatments for Osteoporosis ............ ............... 26
Mycoplasmas Play Key Role in Disease of Humans, Animals ................28
Advancing Health of Wildlife, Endangered Species ........................30
Mapping the Brain's Possibilities ............ ..................32
Assessing Risks to Animal, Human and Environmental Health ................34
Giving Opportunities ............. ......... .. .............. 36
Contact Information ............. .. .............. .Inside Back Cover

* Infectious Diseases 0 Clinical Physiology Environment General


0Universit oiaCOg of V

W Whether developing new
ways to restore sight and
sense, pinpointing levels of toxicity
in the environment, or investigating
microscopic organisms and viruses
to protect against disease,
researchers at the University of
Florida College of Veterinary
Medicine are in the forefront of
advancing animal, human and
environmental health.

Improving quality of life for
you, your pets, food animals
and the world's endangered species
is our primary goal, and our
objectives for doing this unfold in
multifaceted ways every day at the
UF veterinary college.

We hope this document will
enhance your awareness of what
we do here at the college and how
our multiple approaches to disease
diagnosis and prevention come
together to make up the whole of
who we are as an institution and
how we serve the public. Basic
biomedical research aimed at
improving human health, clinical
research to improve domestic animal
health and productivity, and
conservation medicine and biology
to improve the health and well-
being of wildlife and our
environment are all part of our
overall college research program.

In this brochure, we've put faces to
some of the individuals who make
up these programs, and the stories
you will read here offer unique
insights into not only who's doing
what, and why, but also food for
thought as to why research makes
a difference in our everyday lives.

Some of our individual
researchers and their
programs are better known
than others. Many readers
may know already that a
vaccine against Feline
Immunodeficiency Virus
(Feline AIDS) was
developed and patented
by a UF researcher whose
work into relationships
between FIV and human
AIDS is ongoing. Others
familiar with the college's
history may recall that one
of the cornerstones of our
research program was the
infectious disease group
focusing on devastating
tick-borne diseases such
as heartwater in livestock.
This group's role in
keeping such diseases at
bay in sub-Saharan Africa
and preventing them from
taking root in the U.S. has
received international
recognition through
continued funding from
agencies such as the U.S.
Agency for International
Development. As a result
of our team's dedication,
a vaccine against
heartwater is believed to
be close at hand.

Introduction, continued on page 2

Dr Joseph A. DiPietro, dean, and Dr. Charles H. Courtney,
associate dean for research and graduate studies

www vetmed ufl edu



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Introduction, continued from page 1

The preferred animal model for the
study of osteoporosis in women
was developed by one of our faculty
members in the mid 1980s. That
same individual has helped evaluate
several osteoporosis treatments now
on the market. Mice that were part
of his related studies involving bone
loss and its relationship to
weightlessness have flown on the
Space Shuttle.

More recently, UF veterinary
researchers made headlines when
they reported in conjunction with
the Centers for Disease Control
that equine influenza virus had
jumped species into dogs and was
the likely cause of several racing
greyhound deaths in Jacksonville.
Mysterious greyhound deaths
continue in Florida and elsewhere
from respiratory illness,
and so does our investigators'
research into the cause.

Another of our researchers is well
known locally and internationally
for her advocacy of homeless cats
and her studies of how to improve
cat population control.

When West Nile virus began
grabbing media attention a few
years ago, another of our researchers
soon became the point person for
monitoring the incidence of


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outbreaks affecting horses at our
Veterinary Medical Center and
elsewhere in Florida. With funding
from state and federal sources, she
has helped to build a database that
will help both horse owners and
veterinary professionals better
understand the potential for
infection as well as how to better
track West Nile disease spread.

In spite of all the public
acknowledgments our researchers
have received, much work continues
without headlines or fanfare. In this
collection of stories, a meaningful
cross-section of research taking
place here at the college, we
celebrate all of these individuals
and their commitment to keeping
animals, humans and the
environment healthy. We hope
you will as well.

Best Regards,

Joseph A. DiPietro, D.V.M. M.S.
Dean, UF College of
Veterinary Medicine

Charles H. Courtney, D.V.M. Ph.D.
Associate Dean for Research and
Graduate Studies


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Research HiglIghts_

T The College of Veterinary
Medicine at the University
of Florida, the state's only veterinary
college, offers comprehensive service
to the public through a fourfold
mission: teaching, research,
extension, and patient care.
Following graduation of its first
class in 1980, the college has built
on the university's reputation for
excellence and is consistently
ranked in the top 10 of all U.S.
veterinary colleges by U.S. News
and World Report.

The college is unique in that it
is administered jointly by UF's
Institute of Food and Agricultural
Sciences and the Health Science
Center, with the Dean of
Veterinary Medicine answering to
both the Vice President for
Agriculture and Natural Resources
and the Vice President for Health
Affairs. Over half of college faculty
hold both IFAS and Health
Science Center faculty
appointments. Organizationally,
the college is divided into four
academic departments.

The department of large animal
clinical sciences is responsible for
teaching, clinical service and
research involving diseases of
livestock, poultry and fish. Major
programs include animal
reproduction, food animal
production medicine, equine colic
and equine performance medicine.

The department of pathobiology
is responsible for teaching, clinical
service and research involving
pathology, molecular biology,
microbiology and parasitology
of animal diseases. Major programs
include tick-borne diseases,
EPM in horses, the AIDS viruses
of animals and mycoplasmal

diseases. The department also
hosts the college's comparative
clinical immunology program.

The department of physiological
sciences is responsible for teaching,
clinical service and research
involving basic physiology and
toxicology. Major programs include
environmental toxicology, forensic
toxicology, the neuroscience, and
respiratory and cardiac physiology.

The department of small animal
clinical sciences is primarily
responsible for teaching, clinical
service, and research involving
diseases of pets and zoo animals,
but some work is done with
livestock, primarily in the field
of ophthalmology.

In addition to the above four
departments, the college also is host
to the Center for Environmental and
Human Toxicology. Included within
this center are the analytical core
toxicology laboratory, the aquatic
toxicology facility and the
University of Florida Racing
Laboratory. The racing laboratory,
one of only five such internationally
certified laboratories in the United
States, is responsible for conducting
drug screens on all horses and
greyhounds raced at tracks
throughout Florida.

The college also hosts the
university's marine mammal
program jointly with the
Whitney Laboratory. This
interdisciplinary program
supports research and training in
the care of marine mammals with
emphasis on manatees.


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Keeping Tick-born Dise at

many emerging diseases today are
tick-borne. While heartwater affects
cattle, sheep, goats and deer
not people -tick-borne afflictions
like Lyme disease and African tick
bite fever do affect humans.
Studying bont ticks may help in
controlling other disease-carrying
ticks, he notes.

Burridge has been horrified by
the ease with which exotic ticks
travel. In 1997, an injured tortoise
from a reptile breeding facility in
Central Florida was brought to
UF's veterinary hospital for
treatment and, almost by accident,
found to be carrying exotic ticks.
With the United States responsible
for more than 80 percent of world
trade in live reptiles in the 1990s, the
threat of importing ticks via reptiles
is very real.

The tropical bont tick also could
jump borders by hitching a ride
from the Caribbean to Florida on
a migratory bird, like a cattle egret.
Southern climates are ideal for the
ticks which, with wild deer as a
host, would be impossible to
eradicate once they arrive.

The UF team has focused much of
its research offshore. UF scientist
Suman Mahan oversees the program
in southern Africa, where much of
the research has been successfully

On campus in Gainesville,
pathobiology professor Anthony
Barbet, who has had breakthroughs
in the study of the tick-borne disease
anaplasmosis, brings biotechnology
and its advances to the heartwater
team. With Mahan and Burridge,
Barbet has helped develop technology
for a conventional vaccine that is on
the verge of being marketed.

His focus now is on using genetic
engineering to produce a recombinant
DNA vaccine. Laboratory results
have been promising, and the new
vaccine would be the best tool yet
in fighting heartwater.

Biotechnology also has yielded
more advanced diagnostic tests for
heartwater. Previously, diagnosing
heartwater required a difficult and
costly brain biopsy. In a huge
advance, the UF heartwater team
has developed two blood tests for
detecting the disease.

Another breakthrough has been in
tick control. Burridge and colleagues
invented a bont tick decoy, which
can be attached to the ear or tail or
worn in a collar around an animal's
neck. The small, plastic tag attracts
ticks with pheromones then delivers
a tickicide. The decoy lasts three
months and eliminates the need for
ranchers to dip or spray whole
herds, which releases toxic
chemicals into the environment.

For tick control in wild animals,
Burridge and his colleagues
developed the AppliGatorM, which

can be attached to a feeding trough
and applies pesticide passively as
deer brush against it.

Both the decoy and the AppliGator
are inexpensive and easy to use and
the AppliGator is stress-free both
for animals and the people who need
to treat them, Burridge said.

Intervet International of the
Netherlands, the world's largest
manufacturer of large animal
veterinary vaccines, is working
with the UF heartwater team
to commercialize the vaccine.

The Heartwater Research
Program has spawned more than
a dozen patents and attracted
more than $16 million in funding
from the U.S. Agency for
International Development alone.

Burridge says he is perhaps most
gratified by the scope and
completeness of the project.

"What we've done with this
heartwater project is unique in
the world. We've taken a disease
and we've gone from the very
basic science of understanding it
at the cellular level and moved on
to applied science and then on to
commercialization of useful
products," Burridge said. "I don't
know of another project that has
gone from the subcellular level to
commercialization of products in
the field in quite the same way."

If -or when -the tropical bont
tick jumps the U.S. border, the
UF Heartwater Research Team
will be ready.

Photo left: Dr Suman Mahan, left, and
Dr Michael Burridge are shown with wild African
buffalo during a recent visit to South Africa.

Infectious Diseases www vetmed ufl edu

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on developing a diagnostic assay to
identify infected dogs in hopes of
catching the disease earlier.

Crawford said respiratory disease
outbreaks are the top cause of
illness in racing greyhounds, but
the severity and duration of these
outbreaks led her to suspect a
novel infectious agent.

"In the past, these outbreaks
would shut down greyhound
racing every five years or so,"
Crawford said. "But they started
occurring annually and lasted for
several weeks."

Influenza is highly contagious,
especially for dogs kenneled in
close quarters. It causes fever,
coughing, nasal discharges and
pneumonia, and can be fatal.
Greyhounds have been dear to
Crawford since her days as a
student in the UF veterinary
college. "I adopted my first
greyhound here," said Crawford,
who now owns three.

The College of Veterinary
Medicine has particular expertise
in racehorses and racing
greyhounds through its Center for
Veterinary Sports Medicine and is
the only veterinary college with its
own greyhound racing track.

During 10 years of private veterinary
practice, Crawford ran a greyhound
adoption group for retired racers in
Tallahassee. Veterinary medical
research beckoned, however, so she
gave up private practice and
returned to her alma mater. Her first
posting was in a laboratory for
feline immunodeficiency virus
research and her work in that area
continues today.

Lately, Crawford and UF researcher
Julie Levy have been working to
identify a diagnostic test that
accurately detects feline
immunodeficiency virus, or FIV,
in cats. Cats infected with FIV are
usually diagnosed by the presence of
antibodies to the virus in their
bloodstream, and the tests available
for detection of these antibodies are

accurate. However, the introduction
in 2002 of a vaccine for protection of
cats against FIV infection has
created a problem for diagnosis.

When a cat whose history is
unknown shows up at a veterinary
clinic or animal shelter and tests

or vaccination.

"We now have a diagnostic
dilemma," Crawford said. "The
antibodies the cat makes when it is
vaccinated are indistinguishable
from the antibodies the cat makes
when it is infected with FIV."

It is important to identify the
infection because it is contagious
and lifelong. FIV-infected cats
need to be segregated from other
cats to avoid spreading the virus,
a procedure particularly
important in shelter cat
populations. Shelter cats also face
euthanasia -instead of adoption
if they test positive for FIV,
making an accurate diagnostic
test a life or death issue.

After three years, Crawford
said, a test to differentiate
between vaccinated and infected
cats is no closer, but the work
will continue.

Crawford also directs the blood
donor program at the UF
veterinary teaching hospital,
which provides blood products
for transfusion of their dog
and cat patients. Her research
is supported by grants from the
Winn Feline Foundation, Morris
Trust Fund, Alachua County
Department of Health and the
Division of Pari-mutuel Wagering.

"I very much enjoy what I do.
Every veterinary researcher's big
dream is to contribute something
that improves animal health and
welfare," Crawford said. "That's also
my big dream."

Photo left: Dr Cynda Crawford and her
colleagues concluded in 2004 that equine
influenza virus had jumped the species
barrier from horses to dogs.

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Helping Frail Foals Survive

focused on an anomaly that makes
newborn horses highly susceptible
to Rhodococcus, which causes
pneumonia, while adult horses
largely are immune to it.

"With Rhodococcus, we are trying
to discover why only the babies get
it, not adults. What is different in
the immune system of the babies?"
Giguere said.

Rhodococcus is the leading
cause of illness and death in foals
in the United States and the
leading cause of pneumonia in
foals from 3 weeks to 5 months
of age. It is financially devastating
for horse breeders, who sometimes
see 40 percent of their foal crop
contract the disease. Foals that
do recover are much less likely
to race as adults.

Giguere says a long-term goal is to
develop a vaccine to protect foals
from Rhodococcus. But first, he
needs to find the reason for foals'
peculiar susceptibility to the
infection. Preliminary results show
that the immune systems of adult
horses rapidly dispatch
Rhodococcus infections. Foals'
immune cells, however, fail to
react, allowing Rhodococcus to
cause pneumonia.

"Rhodococcus lives in the
environment, so it's very difficult to
get rid of. Oftentimes, foals don't
show clinical signs till the disease is
too advanced," Giguere said. "I want
to try to find better ways to identify
the disease earlier so we can start
treating it sooner. One day maybe
we can prevent it, possibly with a
vaccine. It's a big challenge. Since
the infection occurs so close to
birth, there is a small window to
build an immune response."

In his work in UF clinics, Giguere
found himself faced with a need to
measure blood pressure and cardiac
output in critically ill foals, but with
few well-standardized, non-invasive
ways to perform those tests. So he
embarked on studies to find more
precise and less invasive ways to
take the measurements.

In one study, he looked at the
accuracy of blood pressure monitors
and foals and he evaluated the effect
of the site of cuff placement on the
accuracy of the measurements.
He found that most blood pressure
monitors commonly used worked
well but found that the best
placement for the cuffs was on a
foal's tail. The non-invasive monitors
are portable and easily used on the
farm or in a veterinary office.

To improve methods to measure
cardiac output in critically ill foals,

Giguere decided to evaluate many
non-invasive methods. He found
that ultrasound examination of
the heart was very accurate in
measuring cardiac output and
easily used without causing distress
to the sick foals.

Giguere also evaluated kits
commonly used on horse farms
to measure concentrations of
antibodies in newborn foals.
He found the kits varied widely
in accuracy and made his results
available to veterinarians and
farm managers. Giguere also has
been studying multiple
antibiotics for use in foals in an
attempt to improve treatment
of bacterial infections. Systemic
bacterial infection is the leading
cause of mortality in foals.

Giguere's work has been
funded by Morris Animal
Foundation and Florida's Pari-
Mutuel Trust Fund as well as
the Florida Thoroughbred
Breeders' and Owners'
Association. In fact, support from
the association allowed the
college to establish a breeding
herd of 17 mares that provide
foals each year for research.
Once the research is completed,
the foals are adopted, Giguere said.

"With access to the foals, we can
answer more questions so the
breeding herd is very important,"
Giguere said. "These projects are
practical for the horse owner.

"We can change the way we
practice, discover better therapies,"
Giguere said. "I see my mission as
improving equine health."

Photo left: Dr Steeve Giguere and
veterinary care technician Maria Gore
monitor a foal using ultrasound technology.

Infectious Diseases www vetmed ufl edu


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and Levy says much work still
needs to be done. Her research
group currently is conducting
studies on another vaccine that
looks more promising. Questions
that need to be answered with
contraceptive vaccines include how
soon they work and how long they
provide contraception.

If a high percentage of feral cats in
a colony can be sterilized -either
surgically or with a vaccination
that will bring down the birth rate
and eventually the population.

"With feral cats, you may only get
to see them once in their life," Levy
said. "So what we're looking for is
herd immunity. And it will be
important to have a product that
works on both males and females.

"It's a population that is breeding
continuously so somehow we need
to increase our capacity to sterilize,"
Levy said.

Levy said few things spark a
controversy in a community the way
feral cats do. On one side
are cat-lovers seeking a humane way
to bring the population under
control. On the other side are
wildlife advocates who say that
feral cats harm native animals like
birds by hunting. In between is a
lot of misinformation.

For example, one community's
debate on feral cats centered on
the notion that feral cats spread
rabies. Not so, says Levy. Wild
animals are the reservoir for rabies,
and cats and dogs are incidentally
infected during encounters with
wildlife. To decrease the risk of
rabid cats further, Levy recommends
vaccinating all cats that are
sterilized in TNR programs.


Levy also does research on feline
infectious diseases and says feral
cats serve as a sentinel animal and
a window on what pet cats might
face. So far, for example, surveys
of cats exposed to West Nile virus,
a mosquito-borne disease, show that
cats are commonly exposed to the
virus but seem to survive the
infection. Levy's research also
showed that, contrary to a common
misconception, feral cats are not more
likely than pet cats allowed outdoors
to be infected with feline leukce in.i
feline immunodeficiency virus nd
other common feline diseases

"Feral cats are a very poorly
understood population in term
of infectious diseases, system
infections, diseases that are a
threat to other species or humans,"
Levy said.

The alternative to trap-neuter-
return programs is euthanasia, a
policy that does not work, Levy
says. Even if a community wanted to

remove all its feral cats, who
would do it and who would pay
for it, Levy asks. And studies
show that as cats are removed
from an environment, other cats
take their place.

Levy's work on overpopulation
of unwanted pets is so well-
known that she was asked to
join a team that went to the
Galapagos for a wide-scale cat
and dog sterilization program in
2004. In the past, the Galapagos
had used euthanasia for animal
control. In 2004, the islanders
and the Park Service agreed to
try neutering the animals.

"In a lot of ways it was the
perfect place to do this, with no
animals coming in from
somewhere else to fill the void,"
Levy said.

After 15 years of working on the feral
cat issue, Levy said she is beginning
to notice more communities talking
about the issue.

"It's a hugely controversial topic,
but people are finally starting to do
something about it," Levy said.
"Veterinary schools are an important
connection for training veterinary
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a database to more complicated
questions such as why one horse
dies and another survives. Long and
her colleagues have investigated
testing procedures for the Florida
Department of Agriculture and
Consumer Services. All cases of
West Nile in horses in Florida also
are entered into a database of
information obtained from a two-
page questionnaire filled out at the
time of testing.

The U.S. Department of
Agriculture heard about the
UF work and funded a follow-up
questionnaire, which has become
the foundation for research into
the types of horses, husbandry
and management practices that
may affect a horse's chances of
becoming infected with
West Nile and other mosquito-
borne viruses in Florida. The
information collected -breed, age,
vaccination history, clinical signs,
location of the horse -is a valuable
tool in tracking West Nile's
spread, Long said.

The collected information also
revealed that the horses that
become sick are not vaccinated
or not vaccinated often enough,
leading to new recommendations,
Long said.

Other research investigates the
effectiveness of vaccines.

"Currently marketed are the first-
generation vaccines for West Nile
and Eastern Equine Encephalitis,"
said Long, referring to another
mosquito-borne disease. "What we
need now is a better class of
vaccines for enhanced protection.

"We need to explore questions like
what makes a protected horse, why

the virus goes to the brain, whether
we can breed for immunity," Long
said. "Another question is which
mosquitoes like horses compared
to birds and which mosquitoes
also share a taste for humans.
Which mosquitoes are the biggest
threat? We don't even know that
basic information. A grant funded
by the charity of the Florida Derby
Gala is assisting in research that
consists of vacuuming mosquitoes
directly off horses.

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"Horses get the same diseases
we do," Long said, "so this is
an excellent model of a
human/animal disease."

Long said the West Nile outbreak
was exciting because of the
opportunities it offered to go
deeper into basic science and
research and to collaborate with
other UF experts on emerging

diseases, like virologist Paul Gibbs.
But in the clinics, the disease only
brought sadness.

"During the first couple of years,
I had vets with 30 and 40 years of
experience calling from all over the
country, extremely upset over the
devastation they were seeing," said
Long, who has owned horses since
she was 5 years old. "There is no
treatment, so it was really hard on
everybody. I felt very powerless
when people asked me if their
horse would get better."

As West Nile has spread, other
veterinary colleges and research
institutions have turned to Long
and her UF colleagues for advice
on how to set up high-
containment research facilities to
study newly emerging diseases.

"Every veterinary school and
every region of the country
was touched by this
outbreak," Long said. "It was
a phenomenal outbreak."

Although the emergency has
passed -there were only a
handful of West Nile cases in
2004 -Long says Floridians
should be braced for the next

"We're stuck with the threat
of new viruses in Florida because of
our subtropical climate," Long said.
"We're at risk of outbreaks from our
common diseases on a cyclical basis
every five to 10 years. Because we are
an important import state we are also
constantly at risk for new infectious
diseases that threaten our animals,
whether pets or production animals."

Photo left: Dr Maureen Long has
helped UF to become a leader
in West Nile virus research in horses.

Infectious Diseases www vetmed ufl edu

' "* *- *


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A Ayalew Mergia has spent the
last 10 years working on a way
to use the foamy virus as a delivery
vehicle (vector) for gene therapy, the
ultimate goal being gene therapy for
HIV patients. In gene therapy,
desirable genetic traits are delivered
to a patient's cells, which then
replicate the desirable traits and
strengthen the body's defense
against disease.

"The foamy virus may turn out to be
an ideal model for delivering gene
therapy, precisely because it does
not cause disease," Mergia said.

Mergia points out that some virus
vectors now being studied for gene
therapy have problems with
efficiently delivering genes to target
cells. Others deliver genes but pose
potential safety problems for use in
human gene therapy. The ideal
delivery system is a virus vector that
doesn't cause any of its own
problems as it delivers the benefits
of gene therapy to a patient's cells.

"With every vector you use,
there could be some kind of
problem. Remember, these vectors
are derived from viruses, and viruses
can cause disease in humans,"
Mergia said. "So maybe this is
where the foamy virus may have
an advantage. It appears to be safe
and effective."

Already, researchers have studied
humans who have contracted the
foamy virus accidentally from
animals. These include hunters and
animal caretakers, whose cells show
the presence of the virus without
any ill effects. There are no known
instances of human-to-human
transmission of the virus, Mergia
said, thus a gene therapy treatment
that uses a foamy virus vector

should not spread unintentionally
from the patient to other people.
And animals that have the virus
show no ill effects, either.

"There are many monkeys in
primate centers that are infected
with the foamy virus, and they're
healthy," Mergia said. "Nothing
happens to them."

So far in trials with mice, Mergia
has used the foamy virus to deliver
marker genes, which tell a scientist
where the virus travels and which
cells the virus enters. The ultimate
goal of Mergia's research is to use
the foamy virus in gene therapy for
HIV patients.

Mergia's work has been funded by
the National Institutes of Health
since 1995.

"We still have a significant amount
of basic research we have to
accomplish for the next five years
to make the foamy virus vector an
efficient gene delivery system.
Furthermore, we need to be careful.
What if there is something the
foamy virus is doing that we haven't
discovered?" Mergia said. "Gene
therapy is a promising novel
approach, and with an efficient and
safe gene delivery system will help
cure many diseases."

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Photo top left: Dr Ayalew Mergia, shown with
post-doctoral associate Dr Nadja Matvienko,
has focused on research that may one day
lead to advances in gene therapy.

Photo above: 293T Cells infected
with Foamy Virus Vector containing
Green Fluorescent Protein gene.

Photo bottom: Higher magnification of top image.


U University of Florida
immunologist Janet Yamamoto
says the feline immunodeficiency
virus, or FIV, has biological
similarities to human
immunodeficiency virus, or HIV,
and those similarities could yield
advances in efforts to develop an
HIV vaccine.

Yamamoto says she has "always
liked viruses." In the early 1980s, she
worked on the virus that causes
feline leukemia and in 1986, she and
a colleague discovered FIV, the virus
that causes AIDS in cats. Her work
during the 1990s culminated in an
FIV vaccine that became
commercially available in 2002.

Yamamoto found her work on FIV
often intersected with research on
HIV. There are points in the
structures of both viruses, in fact,
where the two are so similar that
research into one virus may help in
research into the other.

"We are working on a new
generation of feline vaccines that
actually are made with HIV
proteins," said Yamamoto, who
directs the Laboratory of
Comparative Immunology and
Retrovirology at UF's College of
Veterinary Medicine. "We've found
that HIV proteins are closely related
to FIV proteins and are useful in
developing an FIV vaccine, so that
leads us to ask whether FIV proteins
can help humans."

Immunodeficiency viruses have "a
good side and a bad side,"
Yamamoto said. People are familiar
with the bad, which leads to AIDS, a
disease that has killed 22 million
people worldwide since it was
identified in 1981, according to
United Nations estimates.

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Yamamoto said the virus likes to
hide its "good" side, which provides
protection against disease, making it
very difficult to isolate it. But in
people -and cats -who have an
immunodeficiency virus for years
without getting ill, the virus' good
side is at work. These people and
cats are called long-term
nonprogressors and the strains they
carry may provide a key to
prevention, therapy or even a cure
for the disease.

The work is painstaking. Imagine
that FIV and HIV are long ribbons.
One section of the ribbon may
contain elements that cause disease
or accelerate it. But the flip side of
that section of ribbon may be "good"
and hold elements that provide
protection against disease or retard
the disease. Then imagine five FIV
ribbons and two HIV ribbons.

Researchers have found five distinct
subtypes of FIV, each with its own
characteristics that had to be
understood and studied before
moving forward on a vaccine. The
protective properties in the
subtypes had to be combined in
numerous ways to bring out the
most protective combination while
suppressing the harmful properties.

"We were about to give up on an
FIV vaccine when we combined
subtype A and subtype D,"
Yamamoto said. "The overlap of
those two gave us the protection we
were seeking."

Cats can't get HIV infection, so
Yamamoto now is researching ways
to use the protective elements of
HIV in a feline vaccine. Her research
found a protective section of HIV
that provides better immunity for
cats than the protective sections of

FIV. This section of HIV is so
similar to FIV that it is usable in a
feline vaccine. And since cats can't
get infected with HIV, the HIV
proteins that promote disease in
humans do nothing to cats.

Since the reverse is also true
humans can't get FIV -she would
like to continue her work by looking
for FIV strands that trigger an
immune response in humans
without promoting the disease.

"It was important to find out that
HIV proteins are so closely related
to FIV proteins," Yamamoto said.
"Hopefully, I can contribute to the
human vaccine with my model."

Selecting the right strains to trigger
immunity in cats is much easier than
doing so with humans. As
Yamamoto said, "In cats, we could
immunize and watch. But there are
no laboratory humans."

Yamamoto believes that tests with
people who already have HIV would
show whether a vaccine developed
from FIV could be useful as therapy
and perhaps eventually useful in a
human vaccine.

"We have identified, so far, three
regions of FIV that are similar to
HIV-1, and these FIV regions
could be tested with immune cells
from people who have HIV,"
Yamamoto said. "If these regions
are recognized by the immune cells
from people with HIV, it would
suggest that those regions may be
useful as components for HIV
vaccines for non-infected humans.
However, more studies are needed
not only in cats but also in monkeys
to determine the significance of
these FIV regions as components
for HIV vaccines."

Yamamoto spent much of 2004 and
will spend more time in 2005
collaborating with colleagues at the
University of California at San
Francisco and the University of
Pittsburgh, as part of her strong
belief that teamwork will be the key
to further breakthroughs on
immunodeficiency viruses. Her
vaccine work has been funded with
more than $3.4 million in grants
from the National Institutes of
Health since 1989. She also has
funded her research with more than
$1 million in royalties from her
patents, including the patent on the
Fel-O-Vax FIV'T, which is marketed
by Fort Dodge Animal Health, a
division of Wyeth pharmaceuticals.

Yamamoto said she uses her patent
money to explore ideas. When an
idea bears fruit, she seeks grants.
"NIH funding is taxpayer money, so
we need to repay it with discovery."

She personally repays some of
her laboratory cats, veterans of
bone marrow transplants, by
providing a home for them. But she
would like to see her feline studies
pay off for people.

"Seeing animals and people live
longer, that's why we do this work,"
Yamamoto said. "I enjoy seeing my
concept and products help. It's
applied research. I believe the cats
can benefit not only cats, but
people, too."

Photo left: Dr Janet Yamamoto's work on FIV
often intersects with research on HIV

Infectious Diseases www vetmed ufl edu


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"It took him a minute or two, but the
baby figured out the huge animal in
front of him was his mother," Brooks
said. "It's a big high to restore sight."

Brooks has spent a career working
toward such success stories. He has
performed cataract surgery on a
Bengal tiger and used laser surgery
to treat glaucoma in horses and
dogs. At UF, Brooks and his
colleagues have performed more
cornea transplants on horses than
anywhere else in the world.

While some pet and horse owners
may focus on more routine veterinary
care, vision problems are the fourth
most common health problem for
horses, and dogs are second only to
humans in incidence of glaucoma,
making the need for veterinary
ophthalmology research easy to see.

Brooks has not only personally
saved sight for many animals, his
research has changed the standard
of care other veterinarians provide
for equine eye problems.

"We're right here in the middle of
Florida's horse industry, and in the
early 1980s we started seeing a lot of
horses with eye problems at a time
when no one was successful with
horse eye problems. Horse eye
problems scared people," Brooks said.
"So we started working harder to
figure out why the horse eye healed so
poorly, how we could help it heal."

Eye problems in horses typically are
worse than eye problems in other
species, including humans. Brooks
and his colleagues figured any
advances in treating equine eyes
might eventually benefit other
animals and people. The researchers
studied tears collected from horses'
damaged eyes and found high levels

of enzymes. The enzymes, in effect,
were causing the eyes to begin
digesting themselves.

"The horse eye is so destructive,"
Brooks said. "But once we knew the
enzyme level was up, we could
figure out how to reduce the enzyme
level and allow the eye to heal."

The research was published in
January 2005 and resulted in
changes in the legal standard of
veterinary medical care for horse eye
problems. A veterinarian now must
address the enzyme level in a horse
with a damaged eye, and failure to
address it amounts to a failure to
meet the new standard of care.

"We've changed the legal standard
of care for these animals, and I'm
pretty proud of that," Brooks said.

Brooks' research began with
glaucoma in dogs. He was the first
to start examining how the blood
flow and blood pressure in the eye
affects the optic nerve and currently
is in the midst of a large grant
project to examine electrical
changes in the eye.

"It requires a very large team of
people to make contributions in this
area," Brooks said. "I'll be studying
glaucoma my whole career. It's a big
puzzle, and what I'm trying to do is
put some of the pieces together. I'm
hoping someone comes along one
day and puts all the pieces together."

When Brooks' career brought him to
UF, he found himself in the midst of
horse country and facing some of the
most intransigent eye problems
around. Not every horse's eyesight
could be saved, but Brooks has
found inspiration among the blind
animals as well.

One inspiration, a plucky Palm
Beach County thoroughbred named
Valiant, competes in dressage
although he is blind. Brooks tried in
vain to save Valiant's sight and says
he has been impressed by what
Valiant and his owner have
accomplished without sight.
"A horse with no eyes can do
better than you think," Brooks said.

The Valiant Equine Ophthalmology
Research and Development Center
is named after the horse and helps to
fund Brooks' research.

"These animals can live without
seeing, but they want to see,"
Brooks said. "When you can give
them sight, their personalities
change big-time."

Brooks holds a veterinary medicine
degree and a doctorate, making him
part doctor and part scientist. He
teaches as well and has written a
text called "Equine Ophthalmology."
He praises his graduate students
and the university environment.

"The graduate students make you
better," Brooks said. "If I worked
all by myself, without colleagues
or students, I would not be doing
nearly as well as I am in working
at a university."

While Brooks' work appears
specialized -only about 10
veterinarians worldwide share his
expertise -he says he doesn't think
he has narrowed his focus at all.

"I've opened a door to a whole
universe of knowledge," Brooks
said. "It will keep me busy my
whole career."

Photo left: Dr Dennis Brooks combines
scientific aptitude with clinical knowledge
in veterinary ophthalmology.

Clincal www vetmed ufi edu

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ChangSing Standards of CareWhile Improving Sight

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Advancing Animal ReproduIctive Healt

Troedsson came to UF in 2002,
attracted by the synergy between
the college's clinical and research
facilities. Being able to treat equine
patients and conduct research into
their reproductive health issues, too,
was a key for him. He is one of five
veterinarian-researchers, three
working on equine reproductive
issues and two on small animal
reproductive issues. The staff is
international: Troedsson grew up
in Sweden, and recently
researchers from Poland and
Belgium have joined the staff.

"UF is one of the main veterinary
colleges when it comes to both
equine research and clinics,"
Troedsson said. "The proximity of
the horse-breeding center in Ocala
helps, too."

Troedsson's research has focused
on equine endometritis, a leading
cause of fertility problems in
mares. In fact, uterine
inflammation affects about 15
percent of mares, a high rate of
incidence for any disease.

Troedsson started out looking for the
part of the uterine defense mechanism
that was breaking down. He found
that mares susceptible to endometritis
don't contract the uterus in the same
way non-susceptible mares do.
Susceptible mares were responding to
an inflammation that caused them to
fail reproductively.

At first, Troedsson thought bacteria
caused the inflammation. But he
found that sperm cells trigger a
normal inflammatory response, too.
In a normal mare, semen causes
an inflammation that flushes out
excess sperm cells from the uterus.
The inflammation is modulated,
however, by seminal plasma, ensuring

a healthy environment when a fertilized
egg descends into the uterus.

In a susceptible mare, the inflammation
process continued, causing the embryo
to be lost. Troedsson currently is trying
to identify proteins in seminal plasma
that protect sperm cells.

The work could lead to better
management of mares who are
susceptible to endometritis.

"In the past, we believed that seminal
plasma was just a vehicle," Troedsson
said. "Now we recognize its importance."

Troedsson also is in the early stages of
research into genetic testing of embryos
to improve the health of future crops
of horses.

Nearly all horse breeds suffer from a
disease unique to that breed. Quarter
horses have a debilitating muscle
condition. American paint horses suffer
from a genetic disease that kills foals just
days after their birth. The roots of the
diseases are genetic, and the key to curing
them may lie in disrupting the genetic
link from generation to generation.

Troedsson has started a project to do
molecular genetic testing on embryos
before they are implanted. The
research calls for removing single cells
from a five- or six-day-old embryo
and testing the cells for genetic
diseases. Only healthy, disease-free
embryos would then be implanted in
mares, leading to fewer genetic
diseases in future generations.

"We can sort out the bad genes
and save the good genetics,"
Troedsson said. "There are so
many diseases. So we have to
make a decision: What can they
live with; what are the genetic
traits that are so desired?"

Troedsson has collaborated with
obstetricians and gynecologists at
UFs College of Medicine and
researchers in the Department of
Animal Sciences, as well as with
veterinary colleagues who study
fertility issues in stallions.
Although there are few major
grants for equine research each year,
he says the Reproduction Service has
been able to conduct research with a
range of smaller grants from
organizations like the American
Quarter Horse Association, the
GraysonJockey Club Foundation and
internal funding from the university.

"It's very difficult to get funding in
equine research, with only a handful
of national grants each year,"
Troedsson said. "But I like
specializing in equine reproduction
because it has great potential to
apply basic research findings to
clinical advances through assisted
reproduction. It's a very results-

oriented science."

Photo left: Dr Mats Troedsson's research
has focused on equine endometritis,
a leading cause of fertility problems in mares.

Clincal www vetmed uft edu

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Studying the Cough Mechanism

"When I first started working
on this issue, I was amazed at how
little information existed, how
much fundamental information
is not known about cough and
how cough-suppressant drugs
work," Bolser said. "It seems
almost any experiment I devise
will yield important and
fundamental information."

Bolser is among the relatively few
scientists working on understanding
how and why we cough and
whether our treatments for cough
do what we think they do.

"Codeine, for example, is one of the
most widely prescribed drugs in the
world, yet we know relatively little
about what it actually does," Bolser
said. "It doesn't work on everyone,
and when it does work, no one
knows exactly how it's working."

The issue, Bolser said, is finding out
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conducted research from both sides
of the issue, working in
pharmaceutical testing and
development at Schering-Plough
and moving to UF to study the
science and physiology of cough.

Breathing is controlled in the
brainstem, and scientists long have
thought that the mechanism that
controls cough originates there, too.

However, drugs that suppress cough
have no effect on breathing, so
something more is at work. Bolser
calls it a hidden regulatory element
in the control system for cough.

"What is the nature of that
element?" Bolser asks. "We have a
lot of knowledge about breathing
and the brainstem, and we know
that the neural elements that govern
cough are restricted to the
brainstem, but there are profound
regulatory differences between
cough and breathing."

In one model Bolser has proposed,
he theorizes that there may be
previously unidentified neurons
that are active only during a cough.
These neurons may have remained
unidentified because they are
located in a region of the brain not
thought to be related to breathing I I
that turns out to be true, it present
researchers with a challenge both i
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Cough suppressants like codeine
and dextromethorphan act on
the brainstem, but how they
suppress cough -when they do
-is not known.

Bolser is designing an experiment to
inject codeine into the brainstem of
laboratory animals to see where the
codeine goes to work. Making the
laboratory animals cough and then
figuring out how to control the
cough will yield new information
that may eventually help in studying
cough in humans, Bolser said.

Pharmaceutical companies recently
have turned their attention from
asthma medications to cough
medications, Bolser said.

"Another medicine was not needed
for asthma," Bolser said. "So they
started looking at cough. Our
current array of medicines is
inadequate, even codeine, the one
thought to be the gold standard."

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while powerful, don't always work.
This is an emerging issue."
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fundamentals, how cough is
produced in humans and why drugs,
while powerful, don't always work.
This is an emerging issue."

Photo left: Dr Donald Bolser,
shown with scientist Melanie Rose,
is among the relatively few scientists
working on understanding
how and why we cough.

Physiology www vetmed ufl edu

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work, regulating respiration. For
some asthmatic children, those
signals from the brain are faulty.

"If a patient can't sense a problem
with their breathing, they can't
compensate for it," said Davenport, a
professor in UF's College of
Veterinary Medicine since 1981.

So Davenport and colleagues in the
UF College of Medicine developed
the Respiratory Related Evoked
Potential test in 1986. During the
test, a patient's breathing is
increasingly impeded with a
mechanical device as scientists
measure brain wave activity and
breathing responses. The test helps
identify children who lack the
ability to sense difficulty breathing,
so they can be monitored and avoid
a life-threatening asthma attack.

Asthma is the top chronic disease
of childhood, and 60 percent of the
children who have life-threatening
asthma have a reduced ability to
tell the difference between a mild
obstruction to their breathing and a
severe obstruction, Davenport said.
People who have had a double lung
transplant or spinal cord injuries
also have trouble sensing difficulties
with their breathing.
"For most people, if you stop
breathing for 2/10 of a second, it
elicits a reaction," Davenport said.

"Most people can feel a chest
tightness and treat themselves."

The reverse issue patients who are
too aware of their breathing, which
leads to anxiety and overuse of
medication -also is a topic of
research for Davenport.

"One group can't perceive breathing
problems, the other group is

hyperperceptive about breathing
problems," Davenport said. "So we
want to understand the physiology of
breathing. If you can't breathe,
nothing else matters."

In the hyperperceptive group of asthma
patients, the anticipation of a future
breathing problem leads to anxiety. In
effect, they prompt a respiratory event
with their anxiety and panic and end up
relying heavily on medication.

"Nothing bothers you more than the
sense of suffocation," Davenport said.
"So these patients end up reaching for
their inhaler at the slightest sign of
tightening in their chests and end up
taking in more medication than they
need to regulate their asthma.

"We're wandering into a brand new
area," Davenport said.

Davenport also has explored ways to
strengthen respiratory muscles and
has invented a device that amounts to
a barbell for the lungs. The device can
be used for healthy people, like tuba
players in a high school marching
band, and by people who have
suffered a loss of respiratory capacity,
such as people on ventilators or
victims of spinal cord injuries. In fact,

Davenport worked with actor
Christopher Reeve and U.S. Navy
divers in testing the device.

One advantage of the device is that
it does not involve a drug; it's
mechanical, so it can be used by just
about anyone.

"We need to change the way we
look at ventilation," Davenport said.
"We don't want to just make a
patient comfortable on a
breathing machine, we want to
rehab because it is possible to do
respiratory rehabilitation."

Patients on ventilators have been
anesthetized and immobilized
and lose some of their respiratory
capacity. That leads to fear when
it's time for them to breathe on
their own. But with therapy to
strengthen their respiratory
muscles, 90 percent of the
patients who initially fail to wean
from a breathing machine can
come off ventilation.

Although he's a physiologist, not
a veterinarian, Davenport is one
of the few researchers in the
college working on both humans
and animals.

"There are some questions we
can only address in humans and
some questions we can only
address in animals," Davenport said.
"We can't answer all the questions
in one species."

In addition to his research grants
from the National Institutes of
Health and the American Lung
Association, Davenport also has won
the Merck National Creativity in
Teaching Award. He used the
$25,000 grant to fund seminars on
creative teaching strategies.

Physiology www vetmed ufl edu


'*- --'.' L

Focusig on Beathig AwarnessadDisase
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Evaluaing Treat t fr Os leeo

D During the last 15 minutes of
the bone lecture in his
musculoskeletal course, University
of Florida Professor Thomas
Wronski talks about a topic he
hopes will save his students' health
decades ahead. He lectures the
women to get plenty of calcium and
hopes the men will help the women
they love do the same.

"Women develop their peak bone
mass at 25 to 35 years of age," said
Wronski, a researcher in UF's
College of Veterinary Medicine.
"So to avoid getting osteoporosis
during menopause, they need to be
very aware of getting calcium while
they're young.

"I feel it's just to take 15 minutes
to educate them," Wronski said.
"If that little talk prevents just a
couple of them from getting post-
menopausal osteoporosis, that's
more important than what I do
with the rats."

That's saying a lot, since what
Wronski has done with the rats
is groundbreaking.

Wronski has established an animal
model with ovariectomized rats that
allows for the evaluation of
osteoporosis treatments for humans.
He has won awards for his work
and sent an experiment into orbit on
the space shuttle.

In his work, Wronski has shown
that ovariectomized rats become
estrogen deficient just as women do
at menopause and, like menopausal
women, the estrogen deficiency
contributes to loss of bone density.
The ovariectomized rats have
proven to be such a good animal
model in bone density studies that
the Food and Drug Administration
now requires new osteoporosis

treatments to be tested first in
ovariectomized rats before being
used in women.

Wronski has played a key role
in validating the animal model
and helping evaluate several
osteoporosis treatments now on
the market.

"In the mid-1970s, bone loss was not
well understood, and people had a
hard time believing the
ovariectomized rat could be a good
model to use in osteoporosis
research," Wronski said. "In my
work since the mid-1980s, I've been
able to show that it is a good model.

"Once the model was established, it
could be used to evaluate
treatments. Several drugs approved
by the FDA for osteoporosis were
evaluated in our studies here, so
we've been able to make a
contribution, and it's been a nice
application of our research,"
Wronski said.

Wronski's work with rats attracted
attention from NASA in 1996, when
he won a grant to send an
experiment up on the space shuttle
to evaluate the causes of bone loss in
space. NASA doctors had noted that
astronauts returned from space with
decreased bone mass and wanted to

know if it was due to stress
hormones, which inhibit bone
growth, or lack of gravity, since
bones need to bear weight to remain

"It had always been thought that
stress increases levels of
corticosteroids, which inhibits bone
formation and leads to bone loss,"
Wronski said. "So I decided to
test that theory."

In Wronski's experiment, six rats
had their adrenal glands removed
to eliminate the source of
corticosteroids and six kept their
adrenal glands. Their bone mass
was evaluated upon their return.
Based on the experiment,
Wronski said it appears that
bone changes in space are caused
by a lack of mechanical forces
rather than increased stress
hormone levels.

The National Institutes of Health
has continuously funded Wronski's
work since 1986, and his current
grant runs through 2008.

The NIH also awarded him its
prestigious MERIT (Method to
Extend Research in Time) award,
which goes to fewer than 1 percent
of investigators, for his sustained
contribution to research on aging. In
making the award, the NIH noted
that Wronski's work "represents a
splendid example of how beautifully
simple good science can be when
the investigator has the ability to
ask the right questions and do the
right experiments."

Photo left: Dr Tom Wronski, shown with laboratory
technician Mercy Rivera, established an animal
model with ovariectomized rats that allows for the
evaluation of osteoporosis treatments for humans.
Photo above: Laboratory technician
Melissa Rodriguez

Physiology www vetmed ufl edu



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It's no wonder that pathobiologist "Only a few hundred of us "There are so many interesting hosts
Mary Brown is one of the top- worldwide work on these in veterinary medicine,
funded researchers in the University of microbes," Brown said. "We try to encompassing animal and human
Florida's College of Veterinary Medicine. advance the basic science, and I health as well as conservation
Her specialty microscopic organisms always find there are so many issues," Brown said. "With this
called mycoplasmas show up just questions to ask but so little time." research we can not only help the
about everywhere. animals but help humans, too."
Mycoplasmas are the smallest free-
Over the past 20 years, Brown has living bacteria. They need intimate Most recently, Brown has been
studied infections in creatures from contact with a host, for instance in studying the role of mycoplasmas
alligators to humans. She has studied the respiratory or urogenital tract, in a respiratory infection that has
the role of mycoplasma in the premature and establish a chronic disease that spread rapidly among Florida gopher
birth of babies and in a respiratory usually is not fatal because they tortoises, a species of special concern.
ailment of tortoises. Mycoplasmas are need the host in order to survive. The gopher tortoise population has
at work in urinary tract infections in The bacteria spread through direct declined in part because of loss of
women and in economically important contact, and "walking pneumonia" is habitat. The habitat loss also means
diseases of dairy calves. one example of a mycoplasmal gopher tortoises live in closer
disease in people. Few could love proximity to each other, a condition
Mycoplasmas are busy, and they keep mycoplasmas, but they have yielded that likely allows infections to spread
Brown busy, too. a lifetime of research for Brown. more easily.


W Research University of Florida College of Veterinary Medicine

Li M y Play Key Rmle iieof .um

Well-meaning citizens have
compounded the problem, Brown
said. In one study site in Duval
County, people were releasing
tortoises displaced by development
of a subdivision. The newcomer
tortoises were sick with
respiratory mycoplasmosis, which
swept quickly through the existing
gopher tortoise population.

"This was a prime example of what
happens when an acute disease
comes through a population,"
Brown said. "We are seeing very
sick animals and increased deaths.
Some females also appear not to be
producing eggs. Loss of
reproductive-age adults, decreased
reproductive rates and the low
survival rate of young tortoise
hatchlings combine to make it very
hard for a tortoise population to
recover from a population crash."

Brown and her team worked with
regulatory agencies, state parks and
water management districts to do a
statewide survey of habitat status
and changes in the gopher tortoise
population. She and the team also
developed a diagnostic test for the
presence of mycoplasma.

Her work with the threatened species
attracted a $2.2 million grant from
the National Science Foundation to
support further investigation.

"We're just beginning to understand
the diseases in wildlife that are
caused by mycoplasma," Brown said.
"It's a very adaptive organism."

On the human side, women stand to
benefit from Brown's research.
Mycoplasma can take up residence
in the urogenital tract, causing a
variety of problems.

Brown has been awarded a National
Institutes of Health grant to study
the role of mycoplasma in recurrent
urinary tract infections in women.
Her research is centered on finding
the factors that dispose some
women to recurrent infections as
opposed to one-time infection and
whether mycoplasma plays a role in
an exaggerated inflammatory
response to an infection. She is also
studying whether there are genetic
factors in a woman's susceptibility
to urinary infections.

Women also could gain from a study
on mycoplasma infections in thib
genital tract and their role in
pregnancy loss and premature I-.. tLh

In that study, Brown is questioning
whether loss of pregnancy is tih
body's response to the infection. Her
eventual goal is to develop a method
to screen women for pregnancy loss.
In the meantime, she is working on
an animal model using rats infected
with mycoplasma.

"Once we establish the model, we
can ask and answer a lot of
questions," Brown said. "Some
strains of rats are more
susceptible to adverse pregnancy
outcome, so we will look into
which genes are turned on in the
placenta of those rats and when
they are turned on and turned off"

"The data would help humans
and animals, and that makes it a
win-win," Brown said.

The U.S. Department of
Agriculture has funded yet
another study of mycoplasmal
disease in food and fiber animals.
In dairy cows, for instance, the
bacteria cause mastitis. In young
calves, a mycoplasmal infection can
lead to severe disease and sometimes
even death, and is an important herd
cost for dairy farmers.

"There are as many different
species of mycoplasma as there are
hosts," Brown said. "All these
projects require large teams, a real
team approach. Science is not done
in a vacuum."

Brown likes to share her success at
getting grants by helping graduate
students and other young
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He is the go-to guy for Unlike veterinarians who treat the project with the Archie Carr
people who want to help better-known domestic animals, Center for Sea Turtle Research and
ailing reptiles, including endangered wildlife veterinarians often have the St. Lucie Power Plant. "This
turtles at sea and tortoises on land. little of even the most basic will become more and more
The plight of these mild-mannered information, and that is where important as we try to help these
creatures has taken University Jacobson's work begins. animals survive."
of Florida wildlife and zoological
medicine Professor ElliottJacobson "For many wildlife species we don't Jacobson and his colleagues began
from the Florida Keys to the have reference values," Jacobson working on fibropapillomatosis in
Mojave Desert. said. "So we need to establish a sea turtles in the mid-1980s when
normal database in order to turtles with the bizarre growths
Jacobson has seen sea turtles determine what is not normal for began showing up at a hospital in
with fibropapillomatosis these animals. Marathon. A single turtle can have
grotesque tumors that are benign more than 50 lesions, some as large
in themselves but kill when they "We're in the process of building a as 12 inches across, on both soft
cover the eyes or mouth or interfere database on blood values for sea body tissue and the shell. Sea turtles
with the motion of flippers. turtles in Florida and around the are endangered and reproduce
In tortoises, both in the Mojave world, so we will know what's in slowly, so a disease like
Desert and Florida, he has studied their blood, the biochemical fibropapillomatosis, which affects
deadly respiratory ailments that components of their blood," said more than 50 percent of some turtle
can spread quickly. Jacobson, who is collaborating on populations, can be devastating.


W Research University of Florida College of Veterinary Medicine

Advmnci HeatI io Widie End ngred eies

Jacobson and a graduate student
discovered herpes virus in the
tumors. The student is now the
head of Laboratory Animal Medicine
at Albert Einstein College of
Medicine in New York and is
investigating a link between the
virus and the tumors.

More recently, Jacobson has
begun work on ways to improve
diagnosis of maladies in wildlife. In
November, he published the results
of a study of the usefulness of
magnetic resonance imaging and
radiography in determining the
presence of internal fibropapillomas
in sea turtles.

At the turtle hospital in Marathon,
veterinarians have been able to
remove the exterior tumors from sea
turtles and return them to the
ocean. However, the possibility
existed that the animals would go
on to suffer and die from internal
tumors. Most turtles with internal
tumors need to be euthanized
because the tumors interfere with
the operation of organs and severely
damage surrounding tissue.

Jacobson's study found
radiography's benefits limited
because internal views were
somewhat obscured by the shell.
However, MRI scans were not
affected by the shell and
provided detailed views of the
turtle's organs and internal tissue,
easily revealing the presence or
absence of the tumors.

There are both practical and
emotional reasons to do this work,
Jacobson said.

"Sea turtles are important to Florida.
We have the largest nesting beaches
in the United States and more dead

turtles wash up here than
elsewhere," Jacobson said. "It's a
federally listed, charismatic animal.
You see a sea turtle laying eggs and
people are fascinated by them. They
are benign, long-lived animals."

Jacobson and a graduate student
also have begun work on another
problem plaguing sea turtles.
Somewhere on their round-trip
between Florida and the
Mediterranean, the animals are
picking up deadly parasites.

"Sea turtles have the most unique
migration pattern of any animal
on the planet," Jacobson said.
"They travel from here to the
Mediterranean and back, and
sometimes it takes 10 to 20 years
to complete that migration. These
parasites don't exist in the Canary
Islands, so that's an important part
of this puzzle. They're picking them
up when they come back."

Necropsies have shown clusters
of parasites in the brain, but
Jacobson and veterinary pathologist
Brian Stacy are just beginning
research to find out where the
parasites come from.

On land, Jacobson's work with
tortoises began in 1989 with an
urgent call from a Californin
preservation group worri., .Ih-'uIL .
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Soon after, the problem cropped iup
closer to home w lin I '1 rIl.l, ..-'l.he r
tortoises began ,.'n1L I'. Li LI. h
respiratory ailment. i he research

used in the desert tortoise studies
was applied to the gopher tortoises
and the presence of the mycoplasma
was detected.

While scientists continue to study
the disease in tortoises, which are
species of concern due to sharp
declines in their populations,
Jacobson says some common sense
guidelines would help control
spread of the disease. For example,
in high-growth areas it is common
for well-meaning people to relocate
the displaced animals to another
wild area. What they don't realize,
Jacobson said, is that they may be
relocating a sick animal and
spreading the disease.

With 260 species of turtles and
tortoises, most in decline, more
research and collaboration is
needed,Jacboson said.

"We're seeing an extreme loss of
tortoises and habitat," Jacobson
said. "As populations dwindle, those
populations will need to be more
intensely managed. One of the most
important outcomes of our work is
to bring attention to these issues
and educate people."

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Mapping the Br*ain' Psi

the antibodies encouraged neurons
in the damaged regions of the rats'
brains to sprout. Over time, in some
rats, the new neurons appeared to
take over the work the damaged
tissue used to do and restored
normal behavior.

"By investigating mechanisms of
neural repair in rats, there's hope for
developing a therapy to promote
recovery in humans," Reep said.

"Our question is what kinds of
changes can the brain make to
compensate for injury from stroke?
Are there parts of the brain that
can be repaired?"

For the 700,000 Americans who
have a stroke each year, the
answers will be vital.

Florida conservationists, too,
have reason to pay attention to
Reep's research. Reep also studies
evolution of the brain and recently
has focused on the manatee brain,
in hopes of developing insights that
can help in conservation of the
protected animals.

"I guess you could say I lead two
research lives," Reep said. "I'm a
Florida native, and because of that
and my own sensibilities, I want to
preserve what I can of the natural
domain of Florida, and that includes
the animals."

Reep says the order Sirenia, to
which manatees belong, evolved
independently from other lines that
led to elephants and hyraxes,
beginning about 50 million years
ago. There are striking differences
between manatee brains and the
brains of animals of similar size.
Every brain even a third as large as a
manatee brain becomes convoluted,

with folds of matter. Manatee brains
are smooth and their brains are
smaller relative to their body size.

"It's not so much that their brains
are small but their bodies have
become large because of the need to
eat large amounts of plants per day,
and to conserve heat," Reep said.

In recent years, researchers also have
discovered that manatees use tactile
hair -a sense of touch -to detect
underwater currents and vibrations.
Reep and his colleagues at Mote
Marine Laboratory are currently
using behavioral testing to
determine the capacities of this
system to detect significant water
movement, such as the approach of
other animals from behind.

Reep's group also works closely
with the state marine mammal
pathology laboratory and
Sea World so that the scientists can
examine manatee brains quickly
following a manatee death. The
postmortem examinations show
that manatees have specific clumps
of cells on the cerebral cortex that
deal with tactile information
transmitted from the hairs.

"What we have is an indication that
manatees have an elaborate system

to process tactile information,"
Reep said. "It's a neurobiological
solution for living in the world.
By understanding more about the
kind of information the animal has
to work with, we can more
effectively design protective habitat
and alter our behavior in a way that
is meaningful to them."

The research could have
implications for regulators who
Shave designed no-wake zones to
protect manatees, Reep said.
Scientists are asking whether
manatees can sense fast-moving
boats better than they sense
slower boats.

The common thread in Reep's
work is the brain and using basic
science to understand it. The
National Institutes of Health is a
major source of funding for his
research, which has been published
in the journal Brain Research.

"Purely as science, this is
fascinating," Reep said. Of his work
with spatial neglect, he added, "As
the population ages, more people
will get this, and we will need to
learn more about the higher order
regions of the brain. In a person
with stroke, we have an opportunity
to learn from the nature of their

Photo left: Dr Roger Reep has focused
on the manatee brain in hopes of
developing insights that can help in
conservation of the protected animals.

Environment www vetmed ufl edu

.~ a
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Protecting the health of "We have a lot of strength in environment remain in the hands of
Florida's people and toxicology across the campus, so the policy makers.
environment is a huge task, and center's role is to take those
policy makers often lack the strengths and foster research, A case in point involved a
expertise to tackle scientific questions. education and service," said center controversy in 2001 over pressure-
Director Stephen Roberts. "We treated lumber used in playgrounds.
How much of a chemical is harmful draw from the health science center, The lumber was treated with
and how much is acceptable? Does engineering, agriculture and others. chromated copper arsenate, or CCA,
the hazard posed by a toxin change We're the go-to point for human a pesticide that contains arsenic,
depending on whether it is present and environmental toxicology." which can cause neurological
in water or in soil? How does the problems, cardiovascular disease
cost to clean up a hazardous waste The center has contracts with the and even cancer.
site balance with the likelihood of Florida Department of
public exposure? Environmental Protection to provide The state asked the center to
advice on risks posed by investigate the issue and evaluate
Environmental policy makers on the environmental contaminants and is risk assessments that had been
state and national level place such involved in the evaluation of conducted on exposure to arsenic
issues in the hands of scientists at virtually all major contaminated from pressure-treated wood,
the University of Florida's Center sites in the state. Roberts stresses particularly exposure of children
for Environmental and Human that the center's role is using wooden play structures. The
Toxicolo an interdisciplinary informational and advisory- the center found that a critical
center housed in the College of decisions on how to manage the weakness in the assessments was
Veterinary Medicine. risks posed by chemicals in the the absence of data regarding how
36 Research University of Florida College of Veterinary Medicine


AssessigRikt Anml HuaadB j ilv5roa H

much arsenic children actually
receive from contacting CCA-
treated wood. Estimates of exposure
and risk varied widely, making it
unclear the extent to which the
wood posed a health problem.

The U.S. Environmental Protection
Agency decided to conduct its
own assessment of risks to children
from pressure-treated wood.
Roberts provided technical advice
to the agency on how to perform the
assessment through his role
as a member of the EPA's Scientific
Advisory Panel. Ultimately, amid
mounting concern, the
pressure-treated wood industry
voluntarily agreed to withdraw
CCA-treated wood from the
market for most uses.

"Our role is to provide sound,
objective technical advice. Most of
the time we're out of the limelight,"
Roberts said. "We don't want to be
portrayed as a crusader."

The issue of arsenic contamination
in Florida doesn't stop at
playgrounds. Roberts said the state
has thousands of agricultural sites
contaminated with arsenic, dating
back to an era when cattle tick fever
was treated by dipping cattle in vats
of arsenic. Golf courses, too, can be
contaminated with arsenic. The
fodder for toxicologists is endless.

"If arsenic is in drinking water, we
know its toxicity," Roberts said.
"But if it's in soil, is it as toxic? Does
the soil bind it? We're doing studies
to find out what is an acceptable
level for arsenic in soil. And the
results could mean the difference of
millions in cleanup costs."

The work of the center extends well
beyond arsenic. A health department
official might ask for help explaining
the hazards of benzene in drinking

water. An environmental manager
overseeing cleanup of a
contaminated site might ask for
guidelines on chemical
concentrations in soil (the center
has issued guidelines for 500
chemicals). A military installation
might need help evaluating the risks
from unexploded ordnance on old
training fields. In between, Roberts
travels to Washington, D.C., every
six weeks or so for meetings of the
EPA Scientific Advisory Panel.

"Our role is science advice, not
policy," Roberts said. "We want to
understand what chemical
substances do from the level of
molecules up to entire populations
of individuals. We give regulators
the science to decide whether
there's a health problem."

Among the newest research
initiatives for the center is
nanotechnology. The center
collaborated with the College of
Engineering last fall to put on UF's
first seminar on nanotoxicology.

Nanotechnology is the science of
creating materials on an extremely
small, molecular scale, called
nanoscale. The size of the molecules
is measured in nanometers, or one
billionth of a meter. Nanotechnology
can be used to create computer
chips, for example, that are

thousands of times smaller than
current methods allow.

"The federal government is spending
billions on nanotechnology," said
Roberts, "but there's been almost no
research on the environmental
effects of nanotechnology."

Roberts said nanotechnology is a big
concern for the EPA and U.S. Food
and Drug Administration because
eventually materials, chemicals and
foods produced with
nanotechnology will get into the
environment. Already, sports
equipment and fabrics are being
produced with nanotechnology.

UF is uniquely positioned to
contribute to the science of
nanotoxicology because the
center can draw together the
resources of the health science
center and UF's strength in
particle engineering. The center is
using Department of Defense
grants to conduct pilot studies on
penetration of nanoscale particles
through the skin and inhalation of
the particles.

"What do we know? It's a basic
question," Roberts said. "When you
produce something on a nanoscale,
the properties of matter change. Do
biological properties change, too?
And if so, does our conventional
wisdom about what's toxic and
what's not change, too?"

"It's a brand new, emerging field,"
Roberts said, "and it's exciting for
UF to be a main player."

Photo left: Dr Steve Roberts and scientists at
UF's Center for Environmental and Human
Toxicology are key players on the state and national
scene when it comes to environmental policy

Environment www vetmed ufl edu


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Gift Opportunit
The Colleg of Veterinary Medicine recognizes the need to advance animal

and human health through researchIprogram s erate new knowledge,

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intumna 0n shddn lih*ntemytre.fbthaianhmndsae

Its major strengths include both an~ima n ua elhifciu ies

For more information about the University of Florida

College of Veterinary Medicine, please contact:

Office of the Dean ............ ............. .. ..............(352) 392-4700, Ext. 5000

Office of Development and Alumni Affairs ................ .................... (352) 392-4700, Ext. 5200

Office of Public Relations/Publications ............. ................(352) 392-4700, Ext. 5206

Associate Dean for Research and Graduate Studies ............. .............(352) 392-4700, Ext. 5100

Associate Dean for Students and Instructions ............................... (352) 392-4700, Ext. 5300

Department of Small Animal Clinical Sciences ................ .............. (352) 392-4700, Ext. 5700

Department of Large Animal Clinical Sciences ................................ (352) 392-4700, Ext. 5600

Department of Pathobiology .............. ...... ...............(352) 392-4700, Ext. 5800

Department of Physiological Sciences ............ ................. (352) 392-4700, Ext. 3800



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