Agroterrorism - University of Georgia College of Veterinary Medicine

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Companion AnimalsCompanion animals reside in 55 million U.S. homes. These animalsinclude an estimated 66 million cats, 58 million dogs, 88 million fish, 40million birds, 13 million small animals (rabbits, hamsters, and gerbils),and 8 million reptiles. The increasing recognition of the close bondbetween people and their pets has maginfied the importance of insuringthe qualityof our pets’ lives. Because of medical advances, companionanimals are living longer than their predecessors. Longer life, however,means more age-related diseases and ailments, such as cancer, neural degeneration,kidney dysfunction, poor circulation, and decreased respiratory andcardiac capacity.However, unlike other research areas, there are no federal funds andonly limited state funds to support projects specifically forcompanion animals. The VMES has been useful in assisting new clinicalfaculty in their initial research projects, but the vast majority of funding has come from foundationsand private industry. Industrial monies have been awarded based upon the potentialknowledge gained from studying companion animals with diseases comparable to diseasesfound in humans. Examples of externally funded projects include urinary incontinence, diabetesmellitus, renal disease, pain relief for arthritis, transdermal fentanyl patches for pain relief,feline baronellosis and herpes virus, and minimally invasive surgery.Efficacy of recombinant feline omega interferonon feline herpesvirus 1 (FHV-1) replication invitroThe use of high dose recombinant human alphainterferon for the treatment of ocular herpessimplex keratitis (HSV-1) in humans is consideredan effective topical treatment, if alpha interferonsare given in adequate doses before or shortly afterinfection.The objectives of this study are to evaluate the efficacyof feline recombinant omega interferon (rFeIFN-ω)on feline herpesvirus 1 (FHV-1)-replication in cellculture and to determine the optimal concentrationof this drug that could be eventually used for thetreatment of ocular herpesvirus infection in cats.FHV-1 (strain C-27) will be grown on Crandell-Reese feline kidney cells and virus titers establishedafter multiple passages. Virulence and homogeneityof FHV-1 will be verified by transmission electronmicroscopy, indirect immunofluorescent antibodytesting and a plaque forming assay. Five differentdilutions of rFeIFN-ω will be dissolved in culturemedium. 10-fold concentrations ranging from 1x10 2to 1x10 6 U/ml will be used. Antiviral assay will beconducted as a plaque reduction test, and run intriplicates to test the reproducibility of the assay.Feline omega interferon will be added to the cellculture before and after virus challenge and culturedin maintenance medium for 2-3 days. Plaques will becounted and expressed in percent of counts obtainedfrom untreated control cultures.FHV-1-induced ocular disease is widespread amongthe cat population. Antiviral treatment is onlyeffective during virus shedding in the active phaseof infection; the latent stage of the disease cannot beinfluenced by conventional antiviral therapy. Interferonsmight be used for prophylaxis and therapy ofFHV-1-related ocular infections in cats.The following steps of this research project have beencompleted since start time in April 2003:• Crandell-Reese feline kidney cells were propagatedand cultivated in cell culture medium. Theseventh passage was harvested and stored andwill serve as our working cell stock.• FHV-1 virus was grown in cell culture from theoriginally established virus stock and cytopathogeniceffect on cell culture monolayer was readilyobserved. Virus was verified by electron microscopy.Virus titration for TCDI 50 was started in4 x 24 well plates.• We are currently working on a plaque assay inorder to determine virus infectivity. Mean viraltiters will be expressed as plaque forming units(PFU)/0.1 ml.• Antiviral assay using recombinant feline interferonomega will be performed from mid to endof September 2003. First results of this assayshould be expected by the end of September/beginning of October 2003.PI: Dr. Ursula Dietrich (dietrich@vet.uga.edu)Co-PI: Dr. N. Siebeck, Dr. M. Garcia, andDr. C. Greene16Veterinary Medical Experiment Station
Comparative biomedicine investigates how a particular disease affects one species versus another;that is, how a disease manifests itself for example in a mouse versus a human or cow. Researcherscan compare diseases between species because different species oftenshare substantial genetic information. Scientists studydata such as symptoms, disease progression, treatments,mortality, and so on. Thus, one species servesas a disease model for another. And interestingly, bothspecies may benefit. For example, researchers studycardiomyopathy in dogs and humans and both havebenefited in the short- and long-term.Evaluation of Chalcone Derivatives in a MurineModel of Canine NeoplasiaTherapeutic inhibition of angiogenesis as a treatmentfor cancer has gained much interest in thelast 30 years because of the potential for broad-spectrumefficacy, lack of acquired resistance, and lowincidence of associated adverse effects. Chalconeis a biologically active flavonoid compound that iswidely distributed in edible plants. Chalcone and itsderivatives have been identified as anti-proliferativeagents and their anti-angiogenic activity has beendemonstrated in vitro. The purpose of this studywas to evaluate chalcone derivities in vivo, using amouse model of canine cancer, the anti-angiogenic,anti-tumor, and anti-metastatic activity of syntheticchalcone derivatives designed and synthesized by theUniversity of Georgia, Department of Chemistry.One goal of this study was to standardize our productionof reliable, predictably behaving models of bothcanine prostatic carcinoma and osteosarcoma. UsingBALB/c-nu/nu (athymic) mice. In the first year ofthe study, we developed the ability to reliably producetransplanted canine prostatic carcinomas with aggressive,metastatic behavior. The canine osteosarcomacell line was not reliably tumorigenic in the athymicmice so this cell line was not included in the study.In preliminary studies, we encountered difficultyin solubilizing the test compounds into a formthat would be safe and reliable for administration.Although we were able to administer the compoundsorally, poor water solubility and the potential for ineffectivedrug delivery was a concern. The Departmentof Chemistry then developed several water-solublechalcone derivatives that could be safely administeredsubcutaneously. Based on in vitro testing ofanti-angiogenic activity at Emory University, themost effective water-soluble agent was selected forevaluation in our murine model of prostatic cancer.Unfortunately, this agent was uniformly hepatotoxic,resulting in the death of the mice, even when reformulatedand dosed at ½ and ¼ of the original dose.It is unclear why a compound that should be safewas so toxic. Consequently, further development ofchalcone derivatives has been put on hold pendingrecruitment of a pharmacologist to this collaborativeeffort.Using the expertise in creating mouse models ofcancer that was acquired in this study, we haverecently initiated a novel study to investigate molecularmechanisms controlling the biologic behavior ofinjection site sarcomas in cats. This is a particularlyaggressive type of cancer that is very invasive locallyand will metastasize in approximately 25% of cats.Understanding the mechanisms responsible forthe behavior of injection site sarcomas will help topredict the behavior of this tumor in individual catsand allow the development of more specific targetedtherapies to prevent or control this cancer.PI: Dr. Nicole Northrup (northrup@vet.uga.edu)Co-PI: Dr. Karen Cornell and Dr. Nancy StedmanComparative BiomedicineVeterinary Medical Experiment Station 17
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Agroterrorism - University of Georgia College of Veterinary Medicine

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