College of Veterinary Medicine University of Florida Research

ResearchUniversity of FloridaCollege of Veterinary Medicine

Advancing Human, Animal and Environmental Health

www.vetmed.ufl.edu

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University of Florida College of Veterinary Medicine Introduction

Whether developing new ways to restore sight and

sense, pinpointing levels of toxicityin the environment, or investigatingmicroscopic organisms and virusesto protect against disease,researchers at the University ofFlorida College of VeterinaryMedicine are in the forefront ofadvancing animal, human andenvironmental health.

Improving quality of life for you, your pets, food animals and the world’s endangered speciesis our primary goal, and ourobjectives for doing this unfold inmultifaceted ways every day at theUF veterinary college.

We hope this document willenhance your awareness of what we do here at the college and howour multiple approaches to diseasediagnosis and prevention cometogether to make up the whole ofwho we are as an institution andhow we serve the public. Basicbiomedical research aimed atimproving human health, clinicalresearch to improve domestic animalhealth and productivity, andconservation medicine and biologyto improve the health and well-being of wildlife and ourenvironment are all part of ouroverall college research program.

In this brochure, we’ve put faces tosome of the individuals who makeup these programs, and the storiesyou will read here offer uniqueinsights into not only who’s doingwhat, and why, but also food forthought as to why research makes a difference in our everyday lives.

Some of our individualresearchers and theirprograms are better knownthan others. Many readersmay know already that avaccine against FelineImmunodeficiency Virus(Feline AIDS) wasdeveloped and patented by a UF researcher whosework into relationshipsbetween FIV and humanAIDS is ongoing. Othersfamiliar with the college’shistory may recall that oneof the cornerstones of ourresearch program was theinfectious disease groupfocusing on devastatingtick-borne diseases such as heartwater in livestock.This group’s role inkeeping such diseases atbay in sub-Saharan Africaand preventing them fromtaking root in the U.S. hasreceived internationalrecognition throughcontinued funding fromagencies such as the U.S.Agency for InternationalDevelopment. As a result of our team’s dedication,a vaccine againstheartwater is believed tobe close at hand.

W

Introduction, continued on page 2Dr. Joseph A. DiPietro, dean, and Dr. Charles H. Courtney,

associate dean for research and graduate studies

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 Clinical Physiology Environment General

ResearchUniversity of Florida

College of Veterinary Medicine

In the 10 years from 1994 to 2004, the

dollar amount of grants and contracts

awarded annually to UF College of Veterinary

Medicine faculty nearly doubled, from

$5,221,642 in 1994 to $9,616,498 in

2004 despite an overall decline in state-

supported faculty numbers.

Most of the increase was a result of a 2.5-fold

increase in federal funding, a 3-fold increase

in corporate funding and a 3.5-fold increase in

funding from charitable foundations, whereas

research grant funding by the state of Florida

declined to 80 percent of 1994 levels.

www.vetmed.ufl.edu•

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54Research • University of Florida College of Veterinary Medicine

Research Highlights

The College of VeterinaryMedicine at the University

of Florida, the state’s only veterinarycollege, offers comprehensive serviceto the public through a fourfoldmission: teaching, research,extension, and patient care.Following graduation of its firstclass in 1980, the college has built on the university’s reputation forexcellence and is consistentlyranked 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’sInstitute of Food and AgriculturalSciences and the Health ScienceCenter, with the Dean of Veterinary Medicine answering toboth the Vice President forAgriculture and Natural Resourcesand the Vice President for HealthAffairs. Over half of college facultyhold both IFAS and Health Science Center facultyappointments. Organizationally, the college is divided into fouracademic departments.

The department of large animalclinical sciences is responsible forteaching, clinical service andresearch involving diseases oflivestock, poultry and fish. Majorprograms include animalreproduction, food animalproduction medicine, equine colicand equine performance medicine.

The department of pathobiology is responsible for teaching, clinicalservice and research involvingpathology, molecular biology,microbiology and parasitology of animal diseases. Major programsinclude tick-borne diseases, EPM in horses, the AIDS viruses of animals and mycoplasmal

diseases. The department also hosts the college’s comparativeclinical immunology program.

The department of physiologicalsciences is responsible for teaching,clinical service and researchinvolving basic physiology andtoxicology. Major programs includeenvironmental toxicology, forensictoxicology, the neurosciences, andrespiratory and cardiac physiology.

The department of small animalclinical sciences is primarilyresponsible for teaching, clinicalservice, and research involvingdiseases of pets and zoo animals, but some work is done withlivestock, primarily in the field of ophthalmology.

In addition to the above fourdepartments, the college also is hostto the Center for Environmental andHuman Toxicology. Included withinthis center are the analytical coretoxicology laboratory, the aquatictoxicology facility and theUniversity of Florida RacingLaboratory. The racing laboratory,one of only five such internationallycertified laboratories in the UnitedStates, is responsible for conductingdrug screens on all horses andgreyhounds raced at tracksthroughout Florida.

The college also hosts theuniversity’s marine mammalprogram jointly with the Whitney Laboratory. Thisinterdisciplinary program supports research and training inthe care of marine mammals withemphasis on manatees.

The preferred animal model for thestudy of osteoporosis in women was developed by one of our facultymembers in the mid 1980s. Thatsame individual has helped evaluateseveral osteoporosis treatments nowon the market. Mice that were partof his related studies involving boneloss and its relationship toweightlessness have flown on theSpace Shuttle.

More recently, UF veterinaryresearchers made headlines whenthey reported in conjunction withthe Centers for Disease Control that equine influenza virus hadjumped species into dogs and wasthe likely cause of several racinggreyhound deaths in Jacksonville.Mysterious greyhound deathscontinue in Florida and elsewherefrom respiratory illness, and so does our investigators’research into the cause.

Another of our researchers is wellknown locally and internationallyfor her advocacy of homeless catsand her studies of how to improvecat population control.

When West Nile virus begangrabbing media attention a fewyears ago, another of our researcherssoon became the point person formonitoring the incidence of

outbreaks affecting horses at ourVeterinary Medical Center andelsewhere in Florida. With fundingfrom state and federal sources, shehas helped to build a database thatwill help both horse owners andveterinary professionals betterunderstand the potential forinfection as well as how to bettertrack West Nile disease spread.

In spite of all the publicacknowledgments our researchershave received, much work continueswithout headlines or fanfare. In thiscollection of stories, a meaningfulcross-section of research takingplace here at the college, wecelebrate all of these individuals and their commitment to keepinganimals, humans and theenvironment 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 andGraduate Studies

TIntroduction, continued from page 1

Infectious Diseases • www.vetmed.ufl.edu•

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Keeping the ticks that carrydeadly heartwater disease

from jumping U.S. borders andinfecting livestock and wildlifemight seem like an impossible task,the kind that would take a giantfence around the country.

But a research team at theUniversity of Florida’s College ofVeterinary Medicine thinks a goodvaccine to prevent heartwaterwould be better – and more effective– than any fence.

And after two decades of workingwith heartwater disease, the team ison the verge of marketing aconventional vaccine even as itworks to develop an even bettervaccine with genetic engineering.

Heartwater is spread to livestockand wildlife by the bont tick, anative of Africa. The transoceanictropical bont tick has shown up inthe Caribbean, lurking just offFlorida’s shores and making itsarrival in the United States possibleif not likely.

The UF Heartwater ResearchProject, led by pathobiologyProfessor Michael Burridge, hasbeen in a 20-year race against timeto understand the disease, developbetter methods to diagnose it,control the ticks that carry it andinvent a vaccine to protect against itif – or when – it arrives.

Heartwater can kill up to 90 percentof the animals it infects, decimating

an entire herd. The disease damagesthe lining of blood vessels, allowingfluid to accumulate in the lungs andbody cavities, causing an agonizingdeath for the infected animal. Thetropical bont tick also is associatedwith acute dermatophilosis, adisease that causes the skin of cattleliterally to peel off. Burridge said itis impossible to underestimate thethreat to U.S. wildlife and livestockfrom the tropical bont tick.

“Heartwater is a potentialbioterrorism or agriterrorism agent,”Burridge said. “It’s a disease wedefinitely need to keep out of theUnited States.”

Burridge, a parasitologist andepidemiologist, points out that

Keeping Tick-borne Diseases at Bay

many emerging diseases today aretick-borne. While heartwater affectscattle, sheep, goats and deer – not people – tick-borne afflictionslike Lyme disease and African tickbite fever do affect humans.Studying bont ticks may help incontrolling other disease-carryingticks, he notes.

Burridge has been horrified by the ease with which exotic tickstravel. In 1997, an injured tortoisefrom a reptile breeding facility inCentral Florida was brought to UF’s veterinary hospital fortreatment and, almost by accident,found to be carrying exotic ticks.With the United States responsiblefor more than 80 percent of worldtrade in live reptiles in the 1990s, thethreat of importing ticks via reptilesis very real.

The tropical bont tick also couldjump borders by hitching a ridefrom the Caribbean to Florida on a migratory bird, like a cattle egret.Southern climates are ideal for theticks which, with wild deer as ahost, would be impossible toeradicate once they arrive.

The UF team has focused much ofits research offshore. UF scientistSuman Mahan oversees the programin southern Africa, where much ofthe research has been successfullyfield-tested.

On campus in Gainesville,pathobiology professor AnthonyBarbet, who has had breakthroughsin the study of the tick-borne diseaseanaplasmosis, brings biotechnologyand its advances to the heartwaterteam. With Mahan and Burridge,Barbet has helped develop technologyfor a conventional vaccine that is onthe verge of being marketed.

His focus now is on using geneticengineering to produce a recombinantDNA vaccine. Laboratory resultshave been promising, and the newvaccine would be the best tool yet in fighting heartwater.

Biotechnology also has yieldedmore advanced diagnostic tests forheartwater. Previously, diagnosingheartwater required a difficult andcostly brain biopsy. In a hugeadvance, the UF heartwater teamhas developed two blood tests fordetecting the disease.

Another breakthrough has been intick control. Burridge and colleaguesinvented a bont tick decoy, whichcan be attached to the ear or tail orworn in a collar around an animal’sneck. The small, plastic tag attractsticks with pheromones then deliversa tickicide. The decoy lasts threemonths and eliminates the need forranchers to dip or spray wholeherds, which releases toxicchemicals into the environment.

For tick control in wild animals,Burridge and his colleaguesdeveloped the AppliGator™, which

can be attached to a feeding troughand applies pesticide passively asdeer brush against it.

Both the decoy and the AppliGatorare inexpensive and easy to use andthe AppliGator is stress-free bothfor animals and the people who needto treat them, Burridge said. .Intervet International of theNetherlands, the world’s largestmanufacturer of large animalveterinary vaccines, is working with the UF heartwater team

to commercialize the vaccine.

The Heartwater ResearchProgram has spawned more thana dozen patents and attractedmore than $16 million in fundingfrom the U.S. Agency forInternational Development alone.

Burridge says he is perhaps mostgratified by the scope andcompleteness of the project.

“What we’ve done with thisheartwater project is unique inthe world. We’ve taken a diseaseand we’ve gone from the verybasic science of understanding itat the cellular level and moved on

to applied science and then on tocommercialization of usefulproducts,” Burridge said. “I don’tknow of another project that hasgone from the subcellular level tocommercialization of products inthe 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.

“Heartwater

is a potential

bioterrorism or

agriterrorism

agent.”K

Photo left: Dr. Suman Mahan, left, and

Dr. Michael Burridge are shown with wild African

buffalo during a recent visit to South Africa.

Dr. Michael Burridge


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At first, Florida greyhoundowners thought they had a

particularly tough case of kennelcough on their hands. Thengreyhounds started dying from themysterious respiratory ailment.

For answers, the dog owners turnedto University of Florida immunologyand infectious disease specialistCynda Crawford.

When Crawford beganinvestigating, she found an epidemicof nationwide proportions. By June2004, racetracks and kennels acrossthe country were reportinghundreds of sick greyhounds,causing quarantines and putting ahalt to racing in some locations.

No one liked what came next.Crawford’s conclusion: equineinfluenza virus had jumped thespecies barrier from horses to dogs.

“In the veterinary profession, we hadnot identified influenza as a cause ofrespiratory disease in dogs before,”said Crawford, a researcher in UF’sCollege of Veterinary Medicine. “Infact, it has not been described indomestic species other than horses,pigs, and poultry. But our DNAanalysis of the virus genome showedthat this virus actually jumped fromhorses to dogs.

“When the influenza virus crosses a species barrier, it’s a big dealbecause you don’t know which

species will be next down the line,” Crawford said. “Are peoplesubject to acquiring influenza fromdogs now?”

Despite the surprising discovery, thediagnosis gave veterinarians a target.With the culprit identified,Crawford is now pursuing researchon a vaccine for prevention ofinfection and use of antiviral drugsfor treatment of sick dogs.Crawford works with a team thatincludes UF veterinary researchersPaul Gibbs, William Castleman andRichard Hill as well as researchersat the Cornell University College ofVeterinary Medicine and thenational Centers for Disease Controland Prevention. She is also working

Racing to Determine Causes of Greyhound Deaths

on developing a diagnostic assay toidentify infected dogs in hopes ofcatching the disease earlier.

Crawford said respiratory diseaseoutbreaks are the top cause ofillness in racing greyhounds, but the severity and duration of theseoutbreaks 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 startedoccurring annually and lasted forseveral weeks.”

Influenza is highly contagious,especially for dogs kenneled inclose quarters. It causes fever,coughing, nasal discharges andpneumonia, and can be fatal. Greyhounds have been dear toCrawford since her days as astudent in the UF veterinarycollege. “I adopted my firstgreyhound here,” said Crawford,who now owns three.

The College of Veterinary Medicine has particular expertisein racehorses and racinggreyhounds through its Center forVeterinary Sports Medicine and isthe only veterinary college with itsown greyhound racing track.

During 10 years of private veterinarypractice, Crawford ran a greyhoundadoption group for retired racers inTallahassee. Veterinary medicalresearch beckoned, however, so shegave up private practice andreturned to her alma mater. Her first posting was in a laboratory for feline immunodeficiency virusresearch and her work in that areacontinues today.

Lately, Crawford and UF researcherJulie Levy have been working toidentify a diagnostic test thataccurately detects felineimmunodeficiency virus, or FIV, in cats. Cats infected with FIV areusually diagnosed by the presence ofantibodies to the virus in theirbloodstream, and the tests availablefor detection of these antibodies are

accurate. However, the introductionin 2002 of a vaccine for protection ofcats against FIV infection hascreated a problem for diagnosis.

When a cat whose history isunknown shows up at a veterinaryclinic or animal shelter and testspositive for FIV antibodies during aroutine health screening, there is noother test available to verify whetherthe antibodies are due to infectionor vaccination.

“We now have a diagnosticdilemma,” Crawford said. “Theantibodies the cat makes when it isvaccinated are indistinguishablefrom the antibodies the cat makeswhen it is infected with FIV.”

It is important to identify theinfection because it is contagiousand lifelong. FIV-infected cats

need to be segregated from othercats to avoid spreading the virus,a procedure particularlyimportant in shelter catpopulations. Shelter cats also faceeuthanasia – instead of adoption– if they test positive for FIV,making an accurate diagnostictest a life or death issue.

After three years, Crawford said, a test to differentiatebetween vaccinated and infectedcats is no closer, but the workwill continue.

Crawford also directs the blooddonor program at the UFveterinary teaching hospital, which provides blood productsfor transfusion of their dog and cat patients. Her research is supported by grants from theWinn Feline Foundation, MorrisTrust Fund, Alachua County

Department of Health and theDivision of Pari-mutuel Wagering.

“I very much enjoy what I do. Every veterinary researcher’s bigdream is to contribute somethingthat improves animal health andwelfare,” Crawford said. “That’s alsomy big dream.”

“When the influenza

virus crosses

a species barrier, it’s a

big deal because you

don’t know which

species will be next

down the line.” A

Photo left: Dr. Cynda Crawford and her

colleagues concluded in 2004 that equine

influenza virus had jumped the species

barrier from horses to dogs.

Dr. Cynda Crawford


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When he was a boy, the formula seemed simple

to University of Florida researcher Steeve Giguère: become a veterinarian, own a horse, keep riding.

Today, his research into equineneonatology brings him into contact with plenty of horses,although he doesn’t own them orride them. But that’s OK withGiguère, who says he has found a new mission in helping frail foalssurvive. And he likes knowing hiswork makes a difference.

“If you do clinics, you deal withhorses and their problems everyday,” Giguère said. “That way youknow what kinds of research really

will help, as opposed to somethingthat is interesting fundamentally butnot really helpful clinically.”

Since the mid-1980s, Giguère said,the UF College of VeterinaryMedicine has built up itsneonatology program, publishingthe first equine neonatal text in1990. The university long has been atop referral center for clinical care ofneonates and is playing a key role inequine neonatology research.

“The discipline of equineneonatology started here,” Giguèresaid. “Every project helps inunderstanding better ways to treatequine neonatal diseases.”

A big part of Giguère’s research is

Helping Frail Foals Survive

focused on an anomaly that makesnewborn horses highly susceptibleto Rhodococcus, which causespneumonia, while adult horseslargely are immune to it.

“With Rhodococcus, we are tryingto discover why only the babies getit, not adults. What is different inthe immune system of the babies?”Giguère said.

Rhodococcus is the leading cause of illness and death in foalsin the United States and theleading cause of pneumonia in foals from 3 weeks to 5 months of age. It is financially devastatingfor horse breeders, who sometimessee 40 percent of their foal cropcontract the disease. Foals thatdo recover are much less likely to race as adults.

Giguère says a long-term goal is todevelop a vaccine to protect foalsfrom Rhodococcus. But first, heneeds to find the reason for foals’peculiar susceptibility to theinfection. Preliminary results showthat the immune systems of adulthorses rapidly dispatchRhodococcus infections. Foals’immune cells, however, fail toreact, allowing Rhodococcus tocause pneumonia.

“Rhodococcus lives in theenvironment, so it’s very difficult toget rid of. Oftentimes, foals don’tshow clinical signs till the disease istoo advanced,” Giguère said. “I wantto try to find better ways to identifythe disease earlier so we can starttreating it sooner. One day maybewe can prevent it, possibly with avaccine. It’s a big challenge. Sincethe infection occurs so close tobirth, there is a small window tobuild an immune response.”

In his work in UF clinics, Giguèrefound himself faced with a need tomeasure blood pressure and cardiacoutput in critically ill foals, but withfew well-standardized, non-invasiveways to perform those tests. So heembarked on studies to find moreprecise and less invasive ways totake the measurements.

In one study, he looked at theaccuracy of blood pressure monitorsand foals and he evaluated the effectof the site of cuff placement on theaccuracy of the measurements.He found that most blood pressuremonitors commonly used workedwell but found that the bestplacement for the cuffs was on afoal’s tail. The non-invasive monitorsare portable and easily used on thefarm or in a veterinary office.

To improve methods to measurecardiac output in critically ill foals,

Giguère decided to evaluate manynon-invasive methods. He foundthat ultrasound examination of the heart was very accurate inmeasuring cardiac output and easily used without causing distressto the sick foals.

Giguère also evaluated kitscommonly used on horse farms to measure concentrations ofantibodies in newborn foals. He found the kits varied widelyin accuracy and made his resultsavailable to veterinarians andfarm managers. Giguère also hasbeen studying multipleantibiotics for use in foals in anattempt to improve treatment of bacterial infections. Systemicbacterial infection is the leadingcause of mortality in foals.

Giguère’s work has been funded by Morris AnimalFoundation and Florida’s Pari-Mutuel Trust Fund as well as the Florida ThoroughbredBreeders’ and Owners’Association. In fact, support fromthe association allowed thecollege to establish a breedingherd of 17 mares that providefoals each year for research. Once the research is completed,

the foals are adopted, Giguère said.

“With access to the foals, we cananswer more questions so thebreeding herd is very important,”Giguère said. “These projects arepractical for the horse owner.

“We can change the way wepractice, discover better therapies,”Giguère said. “I see my mission asimproving equine health.”

“I see my mission

as improving

equine health.”

W

Photo left: Dr. Steeve Giguère and

veterinary care technician Maria Gore

monitor a foal using ultrasound technology.

Dr. Steeve Giguère


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University of Floridaresearcher Julie Levy has her

eye on the big picture, a future inwhich there are no homeless catsbecause the cat overpopulationproblem has been solved.

On her way to that future, Levyfocuses on today, sterilizing andvaccinating feral cats at monthlyclinics at UF’s College of Veterinary Medicine. OperationCatnip sterilizes and providesveterinary care each year for about2,000 cats, which are trapped,neutered and returned to theirenvironment. The low-costoperation – Levy and otherveterinarians, veterinary techniciansand students donate their time andthe college provides the facilities –

is an attempt to make a dent in aproblem of almost staggeringproportions.

Since 1994, Operation Catnip’s threechapters have sterilized more than20,000 cats, yet estimates put thenumber of homeless cats nationwideat about 70 million.

“There is a huge cat overpopulationproblem,” Levy said. “A largenumber of strays are fed by peoplebut receive no veterinary care. Thesepeople are trying to make a situationbetter that they had nothing to dowith creating.

“We can help by providing freeveterinary care for the cats. We’re the machine that makes it all

work,” Levy said. “Our clinics arefull every month.”

Operation Catnip in Gainesville ismodeled on a trap-neuter-return, or TNR, program Levy started while in graduate school at NorthCarolina State University. Similarclinics are scattered across thecountry and she concedes thatsurgical sterilization alone won’tend the overpopulation problem.

But her outreach program has fueledher research. Levy evaluatescontraceptive vaccines for use inferal cats. A successful vaccinewould work by triggering antibodiesthat suppress fertility. One suchvaccine that had been used onwildlife did not work in feral cats,

Seeking Solutions to Cat Overpopulation Problems

and Levy says much work still needs to be done. Her researchgroup currently is conductingstudies on another vaccine thatlooks more promising. Questionsthat need to be answered withcontraceptive vaccines include howsoon they work and how long theyprovide contraception.

If a high percentage of feral cats ina colony can be sterilized – eithersurgically or with a vaccination –that will bring down the birth rateand eventually the population.

“With feral cats, you may only getto see them once in their life,” Levysaid. “So what we’re looking for isherd immunity. And it will beimportant to have a product thatworks on both males and females.

“It’s a population that is breedingcontinuously so somehow we needto increase our capacity to sterilize,”Levy said.

Levy said few things spark acontroversy in a community the wayferal cats do. On one side are cat-lovers seeking a humane wayto bring the population undercontrol. On the other side arewildlife advocates who say that feral cats harm native animals likebirds by hunting. In between is a lot of misinformation.

For example, one community’sdebate on feral cats centered on the notion that feral cats spreadrabies. Not so, says Levy. Wildanimals are the reservoir for rabies,and cats and dogs are incidentallyinfected during encounters withwildlife. To decrease the risk ofrabid cats further, Levy recommendsvaccinating all cats that aresterilized in TNR programs.

Levy also does research on felineinfectious diseases and says feralcats serve as a sentinel animal and a window on what pet cats mightface. So far, for example, surveys of cats exposed to West Nile virus, a mosquito-borne disease, show thatcats are commonly exposed to thevirus but seem to survive theinfection. Levy’s research alsoshowed that, contrary to a commonmisconception, feral cats are not morelikely than pet cats allowed outdoorsto be infected with feline leukemia,feline immunodeficiency virus and other common feline diseases.

“Feral cats are a very poorlyunderstood population in terms of infectious diseases, systemicinfections, diseases that are a threat to other species or humans,”Levy said.

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

remove all its feral cats, whowould do it and who would payfor it, Levy asks. And studiesshow that as cats are removedfrom an environment, other catstake their place.

Levy’s work on overpopulation of unwanted pets is so well-known that she was asked tojoin a team that went to theGalapagos for a wide-scale catand dog sterilization program in2004. In the past, the Galapagoshad used euthanasia for animalcontrol. In 2004, the islandersand the Park Service agreed to try neutering the animals.

“In a lot of ways it was theperfect place to do this, with noanimals coming in from

somewhere else to fill the void,”Levy said.

After 15 years of working on the feralcat issue, Levy said she is beginningto notice more communities talkingabout the issue.

“It’s a hugely controversial topic,but people are finally starting to dosomething about it,” Levy said.“Veterinary schools are an importantconnection for training veterinarystudents how to work safely withferal cats and how to contribute topet overpopulation solutions.

“It is society’s problem; OperationCatnip is one solution,” Levy said.“Trap-neuter-return is an example ofthe really wonderful altruisticinstincts of human beings.

“It’s the human-animal bond,” Levysaid. “We protect that.”

U

Photo above: Dr. Julie Levy’s outreach program,

Operation Catnip, has fueled her research.


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In 2001, University of Floridaveterinarian Maureen Long

became an expert on West Nilevirus almost by accident.

That year, in clinics at UF’s Collegeof Veterinary Medicine, Long andother large animal medicineclinicians saw an increase in thenumber of horses coming in withthe mosquito-borne disease. Prior toits arrival in Florida, there had beenfewer than 100 cases of the diseasediagnosed in the United States.

Intrigued, Long and her colleaguesput together a proposal that wasfunded by the Pari-mutuelWagering Trust Fund in Florida tostudy the disease outbreak. Thetiming could not have been better.

The next year, 14,000 cases of the dreaded equine disease werediagnosed and the demand forLong’s expertise kept hercrisscrossing the country, makingher a national expert by the end of the year.

Today, Long runs biosafety level 2and level 3 laboratories and is able to study the disease in horsesunder high-containment conditions. In just a few short years, UF hasbecome a leader in West Nileresearch in horses.

“We became the go-to point by theaccident of seeing a lot of cases in2001 in our clinics,” Long said.“Now, we’re one of two places in thecountry to be able to house horses in

a facility with special air flow andwaste decontamination, and withtwo labs that offer the proper labworker protection.”

West Nile virus causes encephalitis,both in horses and people, adding ahuman component to Long’sresearch. In horses, it has a 30percent mortality rate and there isno treatment. The virus affects thecentral nervous system andsymptoms can range from fever toparalysis to death. The level ofinfection in horses is important, too,because it’s an indication of whatpeople might face with the virus.

Long’s research has spanned allaspects of the disease fromsomething as standard as building

Troubleshooting West Nile Virus

a database to more complicatedquestions such as why one horsedies and another survives. Long andher colleagues have investigatedtesting procedures for the FloridaDepartment of Agriculture andConsumer Services. All cases ofWest Nile in horses in Florida alsoare entered into a database ofinformation obtained from a two-page questionnaire filled out at thetime of testing.

The U.S. Department ofAgriculture heard about the UF work and funded a follow-upquestionnaire, which has becomethe foundation for research into the types of horses, husbandry and management practices thatmay affect a horse’s chances ofbecoming infected with West Nile and other mosquito-borne viruses in Florida. Theinformation collected – breed, age,vaccination history, clinical signs,location of the horse – is a valuabletool in tracking West Nile’sspread, Long said.

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

Other research investigates theeffectiveness of vaccines.

“Currently marketed are the first-generation vaccines for West Nileand Eastern Equine Encephalitis,”said Long, referring to anothermosquito-borne disease. “What weneed now is a better class ofvaccines for enhanced protection.

“We need to explore questions likewhat makes a protected horse, why

the virus goes to the brain, whetherwe can breed for immunity,” Longsaid. “Another question is whichmosquitoes like horses compared to birds and which mosquitoes also share a taste for humans.Which mosquitoes are the biggestthreat? We don’t even know thatbasic information. A grant funded by the charity of the Florida DerbyGala is assisting in research thatconsists of vacuuming mosquitoesdirectly off horses.

“Horses get the same diseases we do,” Long said, “so this is an excellent model of ahuman/animal disease.”

Long said the West Nile outbreakwas exciting because of theopportunities it offered to go deeper into basic science andresearch and to collaborate withother UF experts on emerging

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

“During the first couple of years, I had vets with 30 and 40 years ofexperience calling from all over thecountry, extremely upset over thedevastation they were seeing,” saidLong, who has owned horses sinceshe was 5 years old. “There is notreatment, so it was really hard oneverybody. I felt very powerless

when people asked me if their horse would get better.”

As West Nile has spread, otherveterinary colleges and researchinstitutions have turned to Longand her UF colleagues for adviceon how to set up high-containment research facilities tostudy newly emerging diseases.

“Every veterinary school andevery region of the country was touched by this outbreak,” Long said. “It was a phenomenal outbreak.”

Although the emergency haspassed – there were only ahandful of West Nile cases in2004 – Long says Floridiansshould be braced for the nextoutbreak.

“We’re stuck with the threat of new viruses in Florida because ofour subtropical climate,” Long said.“We’re at risk of outbreaks from ourcommon diseases on a cyclical basisevery five to 10 years. Because we arean important import state we are alsoconstantly at risk for new infectiousdiseases that threaten our animals,whether pets or production animals.”

“Horses get the

same diseases we

do, so this is an

excellent model of a

human/animal

disease.”

I

Photo left: Dr. Maureen Long has

helped UF to become a leader

in West Nile virus research in horses.

Dr. Maureen Long

When University of Floridaresearcher Ayalew Mergia was agraduate student in the late 1980s,he became intrigued by foamyviruses.

“There was some interest in foamyviruses in the 1960s and early 1970s.However, since these viruses are notassociated with any disease,research into foamy viruses did notgain momentum,” said Mergia, aprofessor in the pathobiologydepartment of UF’s College ofVeterinary Medicine. “None of uswere quite sure what to do with thisgroup of viruses.”

So what do you do with a virus thatdoesn’t cause disease? Perhaps,Mergia answers, use it as atreatment for diseases.


•


Foamy Viruses Show Gene Therapy Potential

Ayalew Mergia has spent thelast 10 years working on a way

to use the foamy virus as a deliveryvehicle (vector) for gene therapy, theultimate goal being gene therapy forHIV patients. In gene therapy,desirable genetic traits are deliveredto a patient’s cells, which thenreplicate the desirable traits andstrengthen the body’s defenseagainst disease.

“The foamy virus may turn out to bean ideal model for delivering genetherapy, precisely because it doesnot cause disease,” Mergia said.

Mergia points out that some virusvectors now being studied for genetherapy have problems withefficiently delivering genes to targetcells. Others deliver genes but posepotential safety problems for use inhuman gene therapy. The idealdelivery system is a virus vector thatdoesn’t cause any of its ownproblems as it delivers the benefitsof gene therapy to a patient’s cells.

“With every vector you use, there could be some kind ofproblem. Remember, these vectorsare derived from viruses, and virusescan cause disease in humans,”Mergia said. “So maybe this is where the foamy virus may have an advantage. It appears to be safeand effective.”

Already, researchers have studiedhumans who have contracted thefoamy virus accidentally fromanimals. These include hunters andanimal caretakers, whose cells showthe presence of the virus withoutany ill effects. There are no knowninstances of human-to-humantransmission of the virus, Mergiasaid, thus a gene therapy treatmentthat uses a foamy virus vector

should not spread unintentionallyfrom the patient to other people.And animals that have the virusshow no ill effects, either.

“There are many monkeys in primate centers that are infectedwith the foamy virus, and they’rehealthy,” Mergia said. “Nothinghappens to them.”

So far in trials with mice, Mergia has used the foamy virus to delivermarker genes, which tell a scientistwhere the virus travels and whichcells the virus enters. The ultimategoal of Mergia’s research is to usethe foamy virus in gene therapy forHIV patients.

Mergia’s work has been funded bythe National Institutes of Healthsince 1995.

“We still have a significant amountof basic research we have toaccomplish for the next five years to make the foamy virus vector anefficient gene delivery system.Furthermore, we need to be careful.What if there is something thefoamy virus is doing that we haven’tdiscovered?” Mergia said. “Genetherapy is a promising novelapproach, and with an efficient andsafe gene delivery system will helpcure many diseases.”

“The foamy virus may turn out

to be an ideal model

for delivering gene therapy,

precisely because it

does not cause disease.”

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.

A

Dr. Ayalew Mergia


•


Charting New Territory With Immunodeficiency Virus Research

University of Floridaimmunologist Janet Yamamoto

says the feline immunodeficiencyvirus, or FIV, has biologicalsimilarities to humanimmunodeficiency virus, or HIV,and those similarities could yieldadvances in efforts to develop anHIV vaccine.

Yamamoto says she has “alwaysliked viruses.” In the early 1980s, sheworked on the virus that causesfeline leukemia and in 1986, she anda colleague discovered FIV, the virusthat causes AIDS in cats. Her workduring the 1990s culminated in anFIV vaccine that becamecommercially available in 2002.

Yamamoto found her work on FIVoften intersected with research onHIV. There are points in thestructures of both viruses, in fact,where the two are so similar thatresearch into one virus may help inresearch into the other.

“We are working on a newgeneration of feline vaccines thatactually are made with HIVproteins,” said Yamamoto, whodirects the Laboratory ofComparative Immunology andRetrovirology at UF’s College ofVeterinary Medicine. “We’ve foundthat HIV proteins are closely relatedto FIV proteins and are useful indeveloping an FIV vaccine, so thatleads us to ask whether FIV proteinscan help humans.”

Immunodeficiency viruses have “agood side and a bad side,”Yamamoto said. People are familiarwith the bad, which leads to AIDS, adisease that has killed 22 millionpeople worldwide since it wasidentified in 1981, according toUnited Nations estimates.

Yamamoto said the virus likes tohide its “good” side, which providesprotection against disease, making itvery difficult to isolate it. But inpeople – and cats – who have animmunodeficiency virus for yearswithout getting ill, the virus’ goodside is at work. These people andcats are called long-termnonprogressors and the strains theycarry may provide a key toprevention, therapy or even a curefor the disease.

The work is painstaking. Imaginethat FIV and HIV are long ribbons.One section of the ribbon maycontain elements that cause diseaseor accelerate it. But the flip side ofthat section of ribbon may be “good”and hold elements that provideprotection against disease or retardthe disease. Then imagine five FIVribbons and two HIV ribbons.

Researchers have found five distinctsubtypes of FIV, each with its owncharacteristics that had to beunderstood and studied beforemoving forward on a vaccine. Theprotective properties in thesubtypes had to be combined innumerous ways to bring out themost protective combination whilesuppressing the harmful properties.

“We were about to give up on anFIV vaccine when we combinedsubtype A and subtype D,”Yamamoto said. “The overlap ofthose two gave us the protection wewere seeking.”

Cats can’t get HIV infection, soYamamoto now is researching waysto use the protective elements ofHIV in a feline vaccine. Her researchfound a protective section of HIVthat provides better immunity forcats than the protective sections of

FIV. This section of HIV is sosimilar to FIV that it is usable in afeline vaccine. And since cats can’tget infected with HIV, the HIVproteins that promote disease inhumans do nothing to cats.

Since the reverse is also true –humans can’t get FIV – she wouldlike to continue her work by lookingfor FIV strands that trigger animmune response in humanswithout promoting the disease.

“It was important to find out thatHIV proteins are so closely relatedto FIV proteins,” Yamamoto said.“Hopefully, I can contribute to thehuman vaccine with my model.”

Selecting the right strains to triggerimmunity in cats is much easier thandoing so with humans. AsYamamoto said, “In cats, we couldimmunize and watch. But there areno laboratory humans.”

Yamamoto believes that tests withpeople who already have HIV wouldshow whether a vaccine developedfrom FIV could be useful as therapyand perhaps eventually useful in ahuman vaccine.

“We have identified, so far, threeregions of FIV that are similar toHIV-1, and these FIV regions could be tested with immune cellsfrom people who have HIV,”Yamamoto said. “If these regions are recognized by the immune cellsfrom people with HIV, it wouldsuggest that those regions may beuseful as components for HIVvaccines for non-infected humans.However, more studies are needednot only in cats but also in monkeysto determine the significance ofthese FIV regions as components for HIV vaccines.”

Could cats,

rather than dogs,

be man’s best friend?

When it comes

to AIDS research,

the answer might be yes.

Yamamoto spent much of 2004 andwill spend more time in 2005collaborating with colleagues at theUniversity of California at SanFrancisco and the University ofPittsburgh, as part of her strongbelief that teamwork will be the keyto further breakthroughs onimmunodeficiency viruses. Hervaccine work has been funded withmore than $3.4 million in grantsfrom the National Institutes ofHealth since 1989. She also hasfunded her research with more than$1 million in royalties from herpatents, including the patent on theFel-O-Vax FIV™, which is marketedby Fort Dodge Animal Health, adivision of Wyeth pharmaceuticals.

Yamamoto said she uses her patentmoney to explore ideas. When anidea bears fruit, she seeks grants.“NIH funding is taxpayer money, sowe need to repay it with discovery.”

She personally repays some of her laboratory cats, veterans of bone marrow transplants, byproviding a home for them. But shewould like to see her feline studiespay off for people.

“Seeing animals and people livelonger, that’s why we do this work,”Yamamoto said. “I enjoy seeing myconcept and products help. It’sapplied research. I believe the catscan benefit not only cats, butpeople, too.”

U

18

Photo left: Dr. Janet Yamamoto’s work on FIV

often intersects with research on HIV.

Clincal • www.vetmed.ufl.edu•

•


Veterinary ophthalmologistDennis Brooks has fond

memories of some of his patients,such as a blind foal that ended up inhis University of Florida clinic a fewyears ago for an eye operation.

“We were taking the baby back tothe mare, and when the baby got 10to 15 feet from the mare, the babydug in his hooves, just stopped, andwould not go any closer,” Brooksrecalled. “We were trying to pushthe baby gently toward the marewhen a student figured out theproblem. The baby had never seenhis mother.

Changing Standards of Care While Improving Sight

“It took him a minute or two, but thebaby figured out the huge animal infront of him was his mother,” Brookssaid. “It’s a big high to restore sight.”

Brooks has spent a career workingtoward such success stories. He hasperformed cataract surgery on aBengal tiger and used laser surgeryto treat glaucoma in horses anddogs. At UF, Brooks and hiscolleagues have performed morecornea transplants on horses thananywhere else in the world.

While some pet and horse ownersmay focus on more routine veterinarycare, vision problems are the fourthmost common health problem forhorses, and dogs are second only tohumans in incidence of glaucoma,making the need for veterinaryophthalmology research easy to see.

Brooks has not only personallysaved sight for many animals, hisresearch has changed the standardof care other veterinarians providefor equine eye problems.

“We’re right here in the middle ofFlorida’s horse industry, and in theearly 1980s we started seeing a lot ofhorses with eye problems at a timewhen no one was successful withhorse eye problems. Horse eyeproblems scared people,” Brooks said.“So we started working harder tofigure out why the horse eye healed sopoorly, how we could help it heal.”

Eye problems in horses typically areworse than eye problems in otherspecies, including humans. Brooksand his colleagues figured anyadvances in treating equine eyesmight eventually benefit otheranimals and people. The researchersstudied tears collected from horses’damaged eyes and found high levels

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

“The horse eye is so destructive,”Brooks said. “But once we knew theenzyme level was up, we couldfigure out how to reduce the enzymelevel and allow the eye to heal.”

The research was published inJanuary 2005 and resulted inchanges in the legal standard ofveterinary medical care for horse eyeproblems. A veterinarian now mustaddress the enzyme level in a horsewith a damaged eye, and failure toaddress it amounts to a failure tomeet the new standard of care.

“We’ve changed the legal standardof care for these animals, and I’mpretty proud of that,” Brooks said.

Brooks’ research began withglaucoma in dogs. He was the firstto start examining how the bloodflow and blood pressure in the eyeaffects the optic nerve and currentlyis in the midst of a large grantproject to examine electricalchanges in the eye.

“It requires a very large team ofpeople to make contributions in thisarea,” Brooks said. “I’ll be studyingglaucoma my whole career. It’s a bigpuzzle, and what I’m trying to do isput some of the pieces together. I’mhoping someone comes along oneday and puts all the pieces together.”

When Brooks’ career brought him toUF, he found himself in the midst ofhorse country and facing some of themost intransigent eye problemsaround. Not every horse’s eyesightcould be saved, but Brooks hasfound inspiration among the blindanimals as well.

One inspiration, a plucky PalmBeach County thoroughbred namedValiant, competes in dressagealthough he is blind. Brooks tried invain to save Valiant’s sight and sayshe has been impressed by whatValiant and his owner haveaccomplished without sight. “A horse with no eyes can do better than you think,” Brooks said.

The Valiant Equine OphthalmologyResearch and Development Centeris named after the horse and helps tofund Brooks’ research.

“These animals can live withoutseeing, but they want to see,” Brooks said. “When you can givethem sight, their personalitieschange big-time.”

Brooks holds a veterinary medicinedegree and a doctorate, making himpart doctor and part scientist. Heteaches as well and has written atext called “Equine Ophthalmology.”He praises his graduate studentsand the university environment.

“The graduate students make youbetter,” Brooks said. “If I worked all by myself, without colleagues or students, I would not be doingnearly as well as I am in working at a university.”

While Brooks’ work appearsspecialized – only about 10veterinarians worldwide share hisexpertise – he says he doesn’t thinkhe has narrowed his focus at all.

“I’ve opened a door to a wholeuniverse of knowledge,” Brooks said. “It will keep me busy my whole career.”

“These animals can live without seeing,

but they want to see.

When you can give them sight,

their personalities change big-time.”

V

Photo left: Dr. Dennis Brooks combines

scientific aptitude with clinical knowledge

in veterinary ophthalmology.

Dr. Dennis Brooks

Clincal • www.vetmed.ufl.edu•

•


Advances in animalreproductive health have

mirrored advances in humanreproductive health. Horses, forexample, get in vitro fertilizationand have ultrasound examinationsof unborn babies, just like people do.

While horse owners come to theUniversity of Florida’s ReproductionService in the College of VeterinaryMedicine for such procedures, someare now offered by veterinarianscloser to home. Where does thatleave UF’s Reproduction Service?Poised to take the next step into the future, says service chief Mats Troedsson.

UF has done its job when itpopularizes health care technologyfor animals, Troedsson said. Thepoint of developing new treatmentsis to get the advances into the handsof veterinarians.

“People don’t need to come here forultrasound anymore,” Troedssonsaid, although they can, if they like.“So we will develop new assistedreproduction technologies.

“And when those technologies arerefined enough to go into the field,we will be one step ahead, workingon the next technology.”

Advancing Animal Reproductive Health

Troedsson came to UF in 2002,attracted by the synergy betweenthe college’s clinical and researchfacilities. Being able to treat equinepatients and conduct research intotheir reproductive health issues, too,was a key for him. He is one of fiveveterinarian-researchers, threeworking on equine reproductiveissues and two on small animalreproductive issues. The staff isinternational: Troedsson grew upin Sweden, and recentlyresearchers from Poland andBelgium have joined the staff.

“UF is one of the main veterinarycolleges when it comes to bothequine research and clinics,”Troedsson said. “The proximity ofthe horse-breeding center in Ocalahelps, too.”

Troedsson’s research has focusedon equine endometritis, a leadingcause of fertility problems inmares. In fact, uterineinflammation affects about 15percent of mares, a high rate ofincidence for any disease.

Troedsson started out looking for thepart of the uterine defense mechanismthat was breaking down. He foundthat mares susceptible to endometritisdon’t contract the uterus in the sameway non-susceptible mares do.Susceptible mares were responding toan inflammation that caused them tofail reproductively.

At first, Troedsson thought bacteriacaused the inflammation. But hefound that sperm cells trigger anormal inflammatory response, too.In a normal mare, semen causes an inflammation that flushes outexcess sperm cells from the uterus.The inflammation is modulated,however, by seminal plasma, ensuring

a healthy environment when a fertilizedegg descends into the uterus.

In a susceptible mare, the inflammationprocess continued, causing the embryoto be lost. Troedsson currently is tryingto identify proteins in seminal plasmathat protect sperm cells.

The work could lead to bettermanagement of mares who aresusceptible to endometritis.

“In the past, we believed that seminalplasma was just a vehicle,” Troedssonsaid. “Now we recognize its importance.”

Troedsson also is in the early stages ofresearch into genetic testing of embryosto improve the health of future crops of horses.

Nearly all horse breeds suffer from adisease unique to that breed. Quarterhorses have a debilitating musclecondition. American paint horses sufferfrom a genetic disease that kills foals justdays after their birth. The roots of thediseases are genetic, and the key to curingthem may lie in disrupting the geneticlink from generation to generation.

Troedsson has started a project to domolecular genetic testing on embryosbefore they are implanted. Theresearch calls for removing single cellsfrom a five- or six-day-old embryoand testing the cells for geneticdiseases. Only healthy, disease-freeembryos would then be implanted inmares, leading to fewer genetic

diseases in future generations.

“We can sort out the bad genesand save the good genetics,”Troedsson said. “There are somany diseases. So we have tomake a decision: What can theylive with; what are the genetictraits that are so desired?”

Troedsson has collaborated withobstetricians and gynecologists atUF’s College of Medicine andresearchers in the Department ofAnimal Sciences, as well as withveterinary colleagues who studyfertility issues in stallions.Although there are few major

grants for equine research each year,he says the Reproduction Service hasbeen able to conduct research with arange of smaller grants fromorganizations like the AmericanQuarter Horse Association, theGrayson Jockey Club Foundation andinternal funding from the university.

“It’s very difficult to get funding inequine research, with only a handfulof national grants each year,”Troedsson said. “But I likespecializing in equine reproductionbecause it has great potential toapply basic research findings toclinical advances through assistedreproduction. It’s a very results-oriented science.”

“We can sort out

the bad genes

and save

the good genetics.”

Photo left: Dr. Mats Troedsson’s research

has focused on equine endometritis,

a leading cause of fertility problems in mares.

A

Dr. Mats Troedsson

•

•


“There are profound

regulatory differences

between cough

and breathing.”

Physiology • www.vetmed.ufl.edu

It’s a nagging, hacking,wheezing, gasping problem,

and it’s the second most commonreason people in the United Statessee doctors, according to theCenters for Disease Control and Prevention.

It’s the cough, a common problemthat is uncommonly complex, saysUniversity of Florida physiologistDonald Bolser.

“It’s a difficult problem to deal withclinically,” said Bolser, a professorand researcher in UF’s College ofVeterinary Medicine. “Just because apatient is coughing doesn’t mean weknow why.

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

Bolser is among the relatively fewscientists working on understandinghow and why we cough andwhether our treatments for coughdo what we think they do.

“Codeine, for example, is one of themost widely prescribed drugs in theworld, yet we know relatively littleabout what it actually does,” Bolsersaid. “It doesn’t work on everyone,and when it does work, no oneknows exactly how it’s working.”

The issue, Bolser said, is finding outwhich areas of the brain triggercough, then deciphering how theyfunction and react to drugs. He hasconducted research from both sidesof the issue, working inpharmaceutical testing anddevelopment at Schering-Ploughand moving to UF to study thescience and physiology of cough.

Breathing is controlled in thebrainstem, and scientists long havethought that the mechanism thatcontrols cough originates there, too.

However, drugs that suppress coughhave no effect on breathing, sosomething more is at work. Bolsercalls it a hidden regulatory elementin the control system for cough.

“What is the nature of thatelement?” Bolser asks. “We have alot of knowledge about breathingand the brainstem, and we knowthat the neural elements that governcough are restricted to thebrainstem, but there are profoundregulatory differences betweencough and breathing.”

In one model Bolser has proposed,he theorizes that there may bepreviously unidentified neuronsthat are active only during a cough.These neurons may have remainedunidentified because they arelocated in a region of the brain notthought to be related to breathing. Ifthat turns out to be true, it presentsresearchers with a challenge both inunderstanding cough and treating it.The challenge is magnified furtherbecause different coughs – forexample, a laryngeal cough asopposed to a cough from theairways farther into the lungs – maywell be controlled differently by thebrain.

Cough suppressants like codeineand dextromethorphan act on the brainstem, but how theysuppress cough – when they do – is not known.

I

Studying the Cough Mechanism

Bolser is designing an experiment toinject codeine into the brainstem oflaboratory animals to see where thecodeine goes to work. Making thelaboratory animals cough and thenfiguring out how to control thecough will yield new informationthat may eventually help in studyingcough in humans, Bolser said.

Pharmaceutical companies recentlyhave turned their attention fromasthma medications to coughmedications, Bolser said.

“Another medicine was not neededfor asthma,” Bolser said. “So theystarted looking at cough. Ourcurrent array of medicines isinadequate, even codeine, the onethought to be the gold standard.”

Bolser collaborates with otherresearchers and UF’s own BrainInstitute. He said medical researchfunding organizations, such as theNational Institutes of Health, arereceptive to research proposals oncough, partly because they recognizehow unique the work is.

“When you see someone cough,what are they actually doing?”Bolser asks. “We have to explore thefundamentals, how cough isproduced 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.

Dr. Don Bolser

Physiology • www.vetmed.ufl.edu•

•


Focusing on Breathing Awareness and Disease

It’s a common description, that something is as natural as breathing.

But for some children with severeasthma, breathing isn’t natural at all.In fact, these children can’t sensewhen they struggle with breathingand often end up in the emergencyroom on the verge of respiratoryfailure, said University of FloridaProfessor Paul Davenport.

For years, Davenport has beenstudying something most peopletake for granted: How youconsciously know you are breathing.For healthy people, it seemsautomatic, but the brain is still at

work, regulating respiration. Forsome asthmatic children, thosesignals from the brain are faulty.

“If a patient can’t sense a problemwith their breathing, they can’tcompensate for it,” said Davenport, aprofessor in UF’s College ofVeterinary Medicine since 1981.

So Davenport and colleagues in theUF College of Medicine developedthe Respiratory Related EvokedPotential test in 1986. During thetest, a patient’s breathing isincreasingly impeded with amechanical device as scientistsmeasure brain wave activity andbreathing responses. The test helpsidentify children who lack theability to sense difficulty breathing,so they can be monitored and avoida life-threatening asthma attack.

Asthma is the top chronic diseaseof childhood, and 60 percent of thechildren who have life-threateningasthma have a reduced ability totell the difference between a mildobstruction to their breathing and asevere obstruction, Davenport said.People who have had a double lungtransplant or spinal cord injuriesalso have trouble sensing difficultieswith their breathing.“For most people, if you stopbreathing for 2/10 of a second, itelicits a reaction,” Davenport said.

“Most people can feel a chesttightness and treat themselves.”

The reverse issue - patients who aretoo aware of their breathing, whichleads to anxiety and overuse ofmedication – also is a topic ofresearch for Davenport.

“One group can’t perceive breathingproblems, the other group is

hyperperceptive about breathingproblems,” Davenport said. “So wewant to understand the physiology ofbreathing. If you can’t breathe,nothing else matters.”

In the hyperperceptive group of asthmapatients, the anticipation of a futurebreathing problem leads to anxiety. Ineffect, they prompt a respiratory eventwith their anxiety and panic and end uprelying heavily on medication.

“Nothing bothers you more than thesense of suffocation,” Davenport said.“So these patients end up reaching fortheir inhaler at the slightest sign oftightening in their chests and end uptaking in more medication than theyneed to regulate their asthma.

“We’re wandering into a brand newarea,” Davenport said.

Davenport also has explored ways tostrengthen respiratory muscles andhas invented a device that amounts toa barbell for the lungs. The device canbe used for healthy people, like tubaplayers in a high school marchingband, and by people who havesuffered a loss of respiratory capacity,such as people on ventilators orvictims of spinal cord injuries. In fact,

Davenport worked with actorChristopher Reeve and U.S. Navydivers in testing the device.

One advantage of the device is thatit does not involve a drug; it’smechanical, so it can be used by justabout anyone.

“We need to change the way welook at ventilation,” Davenport said.“We don’t want to just make a

patient comfortable on abreathing machine, we want torehab because it is possible to dorespiratory rehabilitation.”

Patients on ventilators have beenanesthetized and immobilizedand lose some of their respiratorycapacity. That leads to fear whenit’s time for them to breathe ontheir own. But with therapy tostrengthen their respiratorymuscles, 90 percent of thepatients who initially fail to weanfrom a breathing machine cancome off ventilation.

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

“There are some questions we can only address in humans andsome questions we can only address in animals,” Davenport said.“We can’t answer all the questionsin one species.”

In addition to his research grantsfrom the National Institutes ofHealth and the American LungAssociation, Davenport also has wonthe Merck National Creativity inTeaching Award. He used the$25,000 grant to fund seminars oncreative teaching strategies.

“If you can’t

breathe,

nothing else

matters.”

Photo top: Dr. Paul Davenport, shown in his lab with graduate student Sarah

Peiying Chan, is one of the few researchers in the college working on both

humans and animals. Photo below demonstrates the use of a breathing device.

I

Dr. Paul Davenport

Physiology • www.vetmed.ufl.edu•

•


Evaluating Treatments for Osteoporosis

During the last 15 minutes ofthe bone lecture in his

musculoskeletal course, Universityof Florida Professor ThomasWronski talks about a topic hehopes will save his students’ healthdecades ahead. He lectures thewomen to get plenty of calcium andhopes the men will help the womenthey love do the same.

“Women develop their peak bonemass at 25 to 35 years of age,” saidWronski, a researcher in UF’sCollege of Veterinary Medicine. “So to avoid getting osteoporosisduring menopause, they need to bevery aware of getting calcium whilethey’re young.

“I feel it’s just to take 15 minutes to educate them,” Wronski said. “If that little talk prevents just acouple of them from getting post-menopausal osteoporosis, that’smore important than what I do with the rats.”

That’s saying a lot, since whatWronski has done with the rats is groundbreaking.

Wronski has established an animalmodel with ovariectomized rats thatallows for the evaluation ofosteoporosis treatments for humans.He has won awards for his workand sent an experiment into orbit onthe space shuttle.

In his work, Wronski has shownthat ovariectomized rats becomeestrogen deficient just as women doat menopause and, like menopausalwomen, the estrogen deficiencycontributes to loss of bone density.The ovariectomized rats haveproven to be such a good animalmodel in bone density studies thatthe Food and Drug Administrationnow requires new osteoporosis

treatments to be tested first inovariectomized rats before beingused in women.

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

“In the mid-1970s, bone loss was notwell understood, and people had ahard time believing theovariectomized rat could be a goodmodel to use in osteoporosisresearch,” Wronski said. “In mywork since the mid-1980s, I’ve beenable to show that it is a good model.

“Once the model was established, itcould be used to evaluatetreatments. Several drugs approvedby the FDA for osteoporosis wereevaluated in our studies here, sowe’ve been able to make acontribution, and it’s been a niceapplication of our research,”Wronski said.

Wronski’s work with rats attractedattention from NASA in 1996, whenhe won a grant to send anexperiment up on the space shuttleto evaluate the causes of bone loss inspace. NASA doctors had noted thatastronauts returned from space withdecreased bone mass and wanted to

know if it was due to stresshormones, which inhibit bonegrowth, or lack of gravity, sincebones need to bear weight to remainhealthy.

“It had always been thought thatstress increases levels ofcorticosteroids, which inhibits bone

formation and leads to bone loss,”Wronski said. “So I decided totest that theory.”

In Wronski’s experiment, six ratshad their adrenal glands removedto eliminate the source ofcorticosteroids and six kept theiradrenal glands. Their bone masswas evaluated upon their return.Based on the experiment,Wronski said it appears thatbone changes in space are causedby a lack of mechanical forces

rather than increased stresshormone levels.

The National Institutes of Healthhas continuously funded Wronski’swork since 1986, and his currentgrant runs through 2008.

The NIH also awarded him itsprestigious MERIT (Method toExtend Research in Time) award,which goes to fewer than 1 percentof investigators, for his sustainedcontribution to research on aging. Inmaking the award, the NIH notedthat Wronski’s work “represents asplendid example of how beautifullysimple good science can be whenthe investigator has the ability toask the right questions and do theright experiments.”

What Wronski has done

with the rats to further

osteoporosis research

is groundbreaking.

D

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

Environment • www.vetmed.ufl.edu•

•


It’s no wonder that pathobiologistMary Brown is one of the top-

funded researchers in the University ofFlorida’s College of Veterinary Medicine.Her specialty – microscopic organismscalled mycoplasmas – show up justabout everywhere.

Over the past 20 years, Brown hasstudied infections in creatures fromalligators to humans. She has studied the role of mycoplasma in the prematurebirth of babies and in a respiratoryailment of tortoises. Mycoplasmas are at work in urinary tract infections inwomen and in economically importantdiseases of dairy calves.

Mycoplasmas are busy, and they keepBrown busy, too.

“Only a few hundred of usworldwide work on thesemicrobes,” Brown said. “We try toadvance the basic science, and Ialways find there are so manyquestions to ask but so little time.”

Mycoplasmas are the smallest free-living bacteria. They need intimatecontact with a host, for instance inthe respiratory or urogenital tract,and establish a chronic disease thatusually is not fatal because theyneed the host in order to survive.The bacteria spread through directcontact, and “walking pneumonia” isone example of a mycoplasmaldisease in people. Few could lovemycoplasmas, but they have yieldeda lifetime of research for Brown.

“There are so many interesting hostsin veterinary medicine,encompassing animal and humanhealth as well as conservationissues,” Brown said. “With thisresearch we can not only help theanimals but help humans, too.”

Most recently, Brown has beenstudying the role of mycoplasmas in a respiratory infection that hasspread rapidly among Florida gophertortoises, a species of special concern.The gopher tortoise population hasdeclined in part because of loss ofhabitat. The habitat loss also meansgopher tortoises live in closerproximity to each other, a conditionthat likely allows infections to spreadmore easily.

Mycoplasmas Play Key Role in Disease of Humans, Animals

Well-meaning citizens havecompounded the problem, Brownsaid. In one study site in DuvalCounty, people were releasingtortoises displaced by developmentof a subdivision. The newcomertortoises were sick withrespiratory mycoplasmosis, whichswept quickly through the existinggopher tortoise population.

“This was a prime example of whathappens when an acute diseasecomes through a population,”Brown said. “We are seeing verysick animals and increased deaths.Some females also appear not to beproducing eggs. Loss ofreproductive-age adults, decreasedreproductive rates and the lowsurvival rate of young tortoisehatchlings combine to make it veryhard for a tortoise population torecover from a population crash.”

Brown and her team worked withregulatory agencies, state parks andwater management districts to do astatewide survey of habitat statusand changes in the gopher tortoisepopulation. She and the team alsodeveloped a diagnostic test for thepresence of mycoplasma.

Her work with the threatened speciesattracted a $2.2 million grant fromthe National Science Foundation tosupport further investigation.

“We’re just beginning to understandthe diseases in wildlife that arecaused by mycoplasma,” Brown said.“It’s a very adaptive organism.”

On the human side, women stand tobenefit from Brown’s research.Mycoplasma can take up residencein the urogenital tract, causing avariety of problems.

Brown has been awarded a NationalInstitutes of Health grant to studythe role of mycoplasma in recurrenturinary tract infections in women.Her research is centered on findingthe factors that dispose somewomen to recurrent infections asopposed to one-time infection andwhether mycoplasma plays a role inan exaggerated inflammatoryresponse to an infection. She is alsostudying whether there are geneticfactors in a woman’s susceptibilityto urinary infections.

Women also could gain from a studyon mycoplasma infections in thegenital tract and their role inpregnancy loss and premature birth.

In that study, Brown is questioningwhether loss of pregnancy is thebody’s response to the infection. Hereventual goal is to develop a methodto screen women for pregnancy loss.In the meantime, she is working onan animal model using rats infectedwith mycoplasma.

“Once we establish the model, wecan ask and answer a lot ofquestions,” Brown said. “Somestrains of rats are moresusceptible to adverse pregnancyoutcome, so we will look intowhich genes are turned on in theplacenta of those rats and whenthey are turned on and turned off.”

“The data would help humansand animals, and that makes it awin-win,” Brown said.

The U.S. Department ofAgriculture has funded yetanother study of mycoplasmaldisease in food and fiber animals.In dairy cows, for instance, thebacteria cause mastitis. In young

calves, a mycoplasmal infection canlead to severe disease and sometimeseven death, and is an important herdcost for dairy farmers.

“There are as many different species of mycoplasma as there arehosts,” Brown said. “All theseprojects require large teams, a realteam approach. Science is not donein a vacuum.”

Brown likes to share her success atgetting grants by helping graduatestudents and other youngresearchers obtain grants of theirown. For her, that’s as rewarding asthe basic science.

“When I watch the development ofthese young scientists,” Brown said,“I can’t imagine having a better job.”

I

30

Photo left: Dr. Mary Brown, shown with scientist

Dr. Lori Wendland, has been studying the role

of mycoplasmas in a respiratory infection

that has spread rapidly among Florida gopher

tortoises, a species of special concern.


•


He is the go-to guy for people who want to help

ailing reptiles, including endangeredturtles at sea and tortoises on land.The plight of these mild-manneredcreatures has taken Universityof Florida wildlife and zoological

medicine Professor Elliott Jacobsonfrom the Florida Keys to the Mojave Desert.

Jacobson has seen sea turtles with fibropapillomatosis –grotesque tumors that are benign in themselves but kill when theycover the eyes or mouth or interferewith the motion of flippers. In tortoises, both in the Mojave Desert and Florida, he has studieddeadly respiratory ailments that can spread quickly.

Unlike veterinarians who treatbetter-known domestic animals,wildlife veterinarians often havelittle of even the most basicinformation, and that is whereJacobson’s work begins.

“For many wildlife species we don’thave reference values,” Jacobsonsaid. “So we need to establish anormal database in order todetermine what is not normal forthese animals.

“We’re in the process of building adatabase on blood values for seaturtles in Florida and around theworld, so we will know what’s intheir blood, the biochemicalcomponents of their blood,” saidJacobson, who is collaborating on

the project with the Archie CarrCenter for Sea Turtle Research andthe St. Lucie Power Plant. “This will become more and moreimportant as we try to help theseanimals survive.”

Jacobson and his colleagues beganworking on fibropapillomatosis insea turtles in the mid-1980s whenturtles with the bizarre growthsbegan showing up at a hospital inMarathon. A single turtle can havemore than 50 lesions, some as largeas 12 inches across, on both softbody tissue and the shell. Sea turtlesare endangered and reproduceslowly, so a disease likefibropapillomatosis, which affectsmore than 50 percent of some turtlepopulations, can be devastating.

Advancing Health of Wildlife, Endangered Species

Jacobson and a graduate studentdiscovered herpes virus in thetumors. The student is now thehead of Laboratory Animal Medicineat Albert Einstein College ofMedicine in New York and isinvestigating a link between thevirus and the tumors.

More recently, Jacobson hasbegun work on ways to improvediagnosis of maladies in wildlife. InNovember, he published the resultsof a study of the usefulness ofmagnetic resonance imaging andradiography in determining thepresence of internal fibropapillomasin sea turtles.

At the turtle hospital in Marathon,veterinarians have been able toremove the exterior tumors from seaturtles and return them to theocean. However, the possibilityexisted that the animals would goon to suffer and die from internaltumors. Most turtles with internaltumors need to be euthanizedbecause the tumors interfere withthe operation of organs and severelydamage surrounding tissue.

Jacobson’s study foundradiography’s benefits limitedbecause internal views weresomewhat obscured by the shell.However, MRI scans were notaffected by the shell and provided detailed views of theturtle’s organs and internal tissue,easily revealing the presence orabsence of the tumors.

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

“Sea turtles are important to Florida.We have the largest nesting beachesin the United States and more dead

turtles wash up here than elsewhere,” Jacobson said. “It’s afederally listed, charismatic animal.You see a sea turtle laying eggs andpeople are fascinated by them. Theyare benign, long-lived animals.”

Jacobson and a graduate studentalso have begun work on anotherproblem plaguing sea turtles.Somewhere on their round-tripbetween Florida and theMediterranean, the animals arepicking up deadly parasites.

“Sea turtles have the most uniquemigration pattern of any animal on the planet,” Jacobson said. “They travel from here to theMediterranean and back, andsometimes it takes 10 to 20 years to complete that migration. Theseparasites don’t exist in the CanaryIslands, so that’s an important partof this puzzle. They’re picking themup when they come back.”

Necropsies have shown clustersof parasites in the brain, butJacobson and veterinary pathologistBrian Stacy are just beginningresearch to find out where theparasites come from.

On land, Jacobson’s work withtortoises began in 1989 with anurgent call from a Californiapreservation group worried about astrange upper respiratory tractdisease that was causing a die-off oftortoises in the Mojave Desert.Jacobson put together a researchteam that discovered a microbeknown as mycoplasma wasresponsible for the infections.

Soon after, the problem cropped upcloser to home when Florida gophertortoises began contracting the respiratory ailment. The research

used in the desert tortoise studieswas applied to the gopher tortoisesand the presence of the mycoplasmawas detected.

While scientists continue to studythe disease in tortoises, which arespecies of concern due to sharpdeclines in their populations,Jacobson says some common senseguidelines would help controlspread of the disease. For example,in high-growth areas it is commonfor well-meaning people to relocatethe displaced animals to anotherwild area. What they don’t realize,Jacobson said, is that they may berelocating a sick animal andspreading the disease.

With 260 species of turtles andtortoises, most in decline, moreresearch and collaboration isneeded, Jacboson said.

“We’re seeing an extreme loss oftortoises and habitat,” Jacobsonsaid. “As populations dwindle, thosepopulations will need to be moreintensely managed. One of the mostimportant outcomes of our work isto bring attention to these issuesand educate people.”

H

Photo left: Dr. Elliott Jacobson shown

with a sea turtle that received rehabilitation

after being drawn into a canal near the

Port St. Lucie Power Plant. Jacobson works

with many sea turtles, snakes and other

reptiles both clinically and in his research.


•


Every 45 seconds, someone inthe United States has a stroke

– and a reason to be interested inthe research of University of Floridaphysiologist Roger Reep.

Reep studies spatial neglect, asyndrome that robs stroke victims ofthe awareness of half of their world.A stroke on the right side of thebrain, for example, takes away thevictims’ awareness of everything ontheir left. The problem isn’t visual –their eyesight is fine – but they arenot aware of the left side unless theyturn around.

“Under normal circumstances,whether you pass on my right or myleft, I will say hello,” said Reep, aprofessor in UF’s College of

Veterinary Medicine and aresearcher in UF’s McKnight BrainInstitute. “If I’ve had a stroke in theright hemisphere of my brain, I’llneglect to say hello to you if youpass on my left.

“The interesting thing is that peoplewith neglect don’t even realizethey’re missing half the world, andsince they’re unaware of theproblem, they aren’t motivated toseek therapy.”

Filmmaker Federico Fellini, whosuffered a stroke at 73, posted noteseverywhere as reminders to “lookleft.” Artists with spatial neglectshow a strong bias toward the rightside of a painting or sculpture. Butfor the bulk of stroke victims,

mostly the elderly, it’s the everydaymanifestations of spatial neglectthat alter their lives: Stroke victimsin nursing homes, for instance, mayeat only the right half of a meal untila worker turns the plate around.

During 20 years of research, Reepand his colleagues developed andused a model in rats that allows forthe study of spatial neglectsyndrome. The researchers located aregion of the brain in rats that issimilar to the region of the humanbrain affected by spatial neglectsyndrome. They induced damage tothis region in the rats, thenadministered monoclonalantibodies, which override a proteinthat prevents neuron growth. Theirpreliminary findings indicate that

Mapping the Brain's Possibilities

the antibodies encouraged neuronsin the damaged regions of the rats’brains to sprout. Over time, in somerats, the new neurons appeared totake over the work the damagedtissue used to do and restorednormal behavior.

“By investigating mechanisms ofneural repair in rats, there’s hope fordeveloping a therapy to promoterecovery in humans,” Reep said.

“Our question is what kinds ofchanges can the brain make tocompensate for injury from stroke?Are there parts of the brain thatcan be repaired?”

For the 700,000 Americans whohave a stroke each year, theanswers will be vital.

Florida conservationists, too, have reason to pay attention toReep’s research. Reep also studiesevolution of the brain and recentlyhas focused on the manatee brain, in hopes of developing insights thatcan help in conservation of theprotected animals.

“I guess you could say I lead tworesearch lives,” Reep said. “I’m aFlorida native, and because of thatand my own sensibilities, I want topreserve what I can of the naturaldomain of Florida, and that includesthe animals.”

Reep says the order Sirenia, towhich manatees belong, evolvedindependently from other lines thatled to elephants and hyraxes,beginning about 50 million yearsago. There are striking differencesbetween manatee brains and thebrains of animals of similar size.Every brain even a third as large as amanatee brain becomes convoluted,

with folds of matter. Manatee brainsare smooth and their brains aresmaller relative to their body size.

“It’s not so much that their brainsare small but their bodies havebecome large because of the need toeat large amounts of plants per day,and to conserve heat,” Reep said.

In recent years, researchers also havediscovered that manatees use tactilehair – a sense of touch – to detectunderwater currents and vibrations.Reep and his colleagues at MoteMarine Laboratory are currentlyusing behavioral testing todetermine the capacities of thissystem to detect significant watermovement, such as the approach ofother animals from behind.

Reep’s group also works closelywith the state marine mammalpathology laboratory and Sea World so that the scientists canexamine manatee brains quicklyfollowing a manatee death. Thepostmortem examinations showthat manatees have specific clumpsof cells on the cerebral cortex thatdeal with tactile informationtransmitted from the hairs.

“What we have is an indication thatmanatees have an elaborate system

to process tactile information,” Reep said. “It’s a neurobiologicalsolution for living in the world. By understanding more about thekind of information the animal hasto work with, we can moreeffectively design protective habitatand alter our behavior in a way thatis meaningful to them.”

The research could haveimplications for regulators whohave designed no-wake zones toprotect manatees, Reep said.Scientists are asking whethermanatees can sense fast-movingboats better than they senseslower boats.

The common thread in Reep’swork is the brain and using basicscience to understand it. TheNational Institutes of Health is amajor source of funding for his

research, which has been publishedin the journal Brain Research.

“Purely as science, this isfascinating,” Reep said. Of his workwith spatial neglect, he added, “Asthe population ages, more peoplewill get this, and we will need tolearn more about the higher orderregions of the brain. In a personwith stroke, we have an opportunityto learn from the nature of theirdeficits.”

“Are there

parts of

the brain

that can

be repaired?”

E

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.

Dr. Roger Reep


•


Protecting the health ofFlorida’s people and

environment is a huge task, andpolicy makers often lack theexpertise to tackle scientific questions.

How much of a chemical is harmfuland how much is acceptable? Doesthe hazard posed by a toxin changedepending on whether it is presentin water or in soil? How does thecost to clean up a hazardous wastesite balance with the likelihood ofpublic exposure?

Environmental policy makers on thestate and national level place suchissues in the hands of scientists atthe University of Florida’s Centerfor Environmental and HumanToxicology, an interdisciplinarycenter housed in the College ofVeterinary Medicine.

“We have a lot of strength intoxicology across the campus, so thecenter’s role is to take thosestrengths and foster research,education and service,” said centerDirector Stephen Roberts. “Wedraw from the health science center,engineering, agriculture and others.We’re the go-to point for humanand environmental toxicology.”

The center has contracts with theFlorida Department ofEnvironmental Protection to provideadvice on risks posed byenvironmental contaminants and isinvolved in the evaluation ofvirtually all major contaminatedsites in the state. Roberts stressesthat the center’s role isinformational and advisory; thedecisions on how to manage therisks posed by chemicals in the

environment remain in the hands ofpolicy makers.

A case in point involved acontroversy in 2001 over pressure-treated lumber used in playgrounds.The lumber was treated withchromated copper arsenate, or CCA,a pesticide that contains arsenic,which can cause neurologicalproblems, cardiovascular diseaseand even cancer.

The state asked the center toinvestigate the issue and evaluaterisk assessments that had beenconducted on exposure to arsenicfrom pressure-treated wood,particularly exposure of childrenusing wooden play structures. Thecenter found that a criticalweakness in the assessments wasthe absence of data regarding how

Assessing Risks to Animal, Human and Environmental Health

much arsenic children actuallyreceive from contacting CCA-treated wood. Estimates of exposureand risk varied widely, making itunclear the extent to which thewood posed a health problem.

The U.S. Environmental ProtectionAgency decided to conduct its own assessment of risks to childrenfrom pressure-treated wood.Roberts provided technical advice to the agency on how to perform theassessment through his role as a member of the EPA’s ScientificAdvisory Panel. Ultimately, amidmounting concern, the pressure-treated wood industryvoluntarily agreed to withdrawCCA-treated wood from themarket for most uses.

“Our role is to provide sound,objective technical advice. Most ofthe time we’re out of the limelight,”Roberts said. “We don’t want to beportrayed as a crusader.”

The issue of arsenic contaminationin Florida doesn’t stop atplaygrounds. Roberts said the statehas thousands of agricultural sitescontaminated with arsenic, datingback to an era when cattle tick feverwas treated by dipping cattle in vatsof arsenic. Golf courses, too, can becontaminated with arsenic. Thefodder for toxicologists is endless.

“If arsenic is in drinking water, weknow its toxicity,” Roberts said.“But if it’s in soil, is it as toxic? Doesthe soil bind it? We’re doing studiesto find out what is an acceptablelevel for arsenic in soil. And theresults could mean the difference ofmillions in cleanup costs.”

The work of the center extends wellbeyond arsenic. A health departmentofficial might ask for help explainingthe hazards of benzene in drinking

water. An environmental manageroverseeing cleanup of acontaminated site might ask forguidelines on chemicalconcentrations in soil (the centerhas issued guidelines for 500chemicals). A military installationmight need help evaluating the risksfrom unexploded ordnance on oldtraining fields. In between, Robertstravels to Washington, D.C., everysix weeks or so for meetings of theEPA Scientific Advisory Panel.

“Our role is science advice, notpolicy,” Roberts said. “We want tounderstand what chemicalsubstances do from the level ofmolecules up to entire populationsof individuals. We give regulatorsthe science to decide whetherthere’s a health problem.”

Among the newest researchinitiatives for the center isnanotechnology. The centercollaborated with the College ofEngineering last fall to put on UF’sfirst seminar on nanotoxicology.

Nanotechnology is the science ofcreating materials on an extremelysmall, molecular scale, callednanoscale. The size of the moleculesis measured in nanometers, or onebillionth of a meter. Nanotechnologycan be used to create computerchips, for example, that are

thousands of times smaller thancurrent methods allow.

“The federal government is spendingbillions on nanotechnology,” saidRoberts, “but there’s been almost noresearch on the environmentaleffects of nanotechnology.”

Roberts said nanotechnology is a bigconcern for the EPA and U.S. Foodand Drug Administration becauseeventually materials, chemicals and

foods produced withnanotechnology will get into theenvironment. Already, sportsequipment and fabrics are beingproduced with nanotechnology.

UF is uniquely positioned tocontribute to the science ofnanotoxicology because thecenter can draw together theresources of the health sciencecenter and UF’s strength inparticle engineering. The center isusing Department of Defense

grants to conduct pilot studies onpenetration of nanoscale particlesthrough the skin and inhalation ofthe particles.

“What do we know? It’s a basicquestion,” Roberts said. “When youproduce something on a nanoscale,the properties of matter change. Dobiological properties change, too?And if so, does our conventionalwisdom about what’s toxic andwhat’s not change, too?”

“It’s a brand new, emerging field,”Roberts said, “and it’s exciting forUF to be a main player.”

“It’s exciting for UF

to be a main player.”

P

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.

Dr. Stephen Roberts

•38Research • University of Florida College of Veterinary Medicine

The College of Veterinary Medicine recognizes the need to advance animaland human health through research programs that generate new knowledge,both basic and applied. Because of the similarity in physiology betweenhumans and animals, the college has conducted comparative studies that areinstrumental in shedding light on the mysteries of both animal and human disease.

Its major strengths include both animal and human health infectious diseaseresearch, gene therapy approaches, vaccine development, basic and appliedfood safety research, research on comparative medicine, and the commitmentto support the nation’s need to advance the career development ofveterinarians and graduate students who wish to pursue clinical and/or basicresearch as a career aspiration.

To further these efforts, support from the private sector is always welcome.

Ways you can helpOutright Gifts: Most charitable gifts are made when you write a check tofulfill a pledge, be it a one-time gift or a pledge paid over a period of years.Other types of outright gifts include gifts of stock, bonds or real estate, someof which may have important tax advantages for you, the donor.

Bequest Gifts: You may want to consider including a provision in your willfor the benefit of the College of Veterinary Medicine.

How to make a giftIf you are interested in more information about endowment funds, estate giftsor other methods of giving, please contact:

Zoë HaynesSenior Director of DevelopmentUF College of Veterinary MedicineP.O. Box 100125Gainesville, FL 32610-0125(352) 392-4700, Ext. 5212

Karen HickokDirector of Development and Alumni AffairsUF College of Veterinary MedicineP.O. Box 100125Gainesville, FL 32610-0125(352) 392-4700, Ext. 5213

Or visit our Web site at www.vetmed.ufl.edu.

Gift Opportunities 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

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

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

Editor:Director of Public RelationsSarah Carey, M.A., A.P.R.

Photography:Kristen Bartlett and Ray Carson,UF News and Public AffairsJan Botha, South AfricaSarah Carey, M.A., A.P.R.Laurel Canty-Ehrich, NOAA

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