Theses and Dissertations

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Open Access
Epidemiology of reported scrapie in the United States: 1947-1991
(Colorado State University. Libraries, 1993) Wineland, Nora E., author; Salman, M., advisor; Kimberling, Cleon V., committee member; Gould, Daniel H., committee member; Weber, Stephen, committee member
Data collected in support of the United States Department of Agriculture (USDA) scrapie eradication program between 1947 and September 30, 1991 were evaluated to determine the presence of trends or patterns which might help further the understanding of natural sheep scrapie. The USDA records from 957 confirmed positive cases of natural scrapie in 581 flocks from 39 states were reviewed and compiled into a database. Possible host and management risk factors for scrapie such as age at death, within-flock mortality, breed, sex, sire and dam disease status, flock size, and location were examined. There were several significant findings from the study. The proportion of reported positive flocks in those states reporting positive cases showed a steady increase between 1965 and 1991. In addition, the average flock mortality showed a slight increase between 1947 and 1991. These increases did not seem to be directly related to any changes in the USDA eradication program. The average age at death for confirmed cases was 43.6 months. Rams died of scrapie an average of five months younger than did the ewes. This difference was statistically significant, but likely due to the small numbers of rams included in the study. There were insufficient numbers of twins (26 pairs) to allow any significant conclusions to be drawn. There were no statistically significant differences between age at death for the eight geographical regions or the various sheep breeds affected. The Suffolk breed comprised 88% of the reported cases, and Hampshire sheep accounted for 6% of the cases. Attempts were made to further define the role of vertical transmission in natural scrapie. The scrapie disease status of the sire had no appreciable effect on the age of death of positive offspring. The scrapie disease status of the dam had a detectable effect with positive offspring from positive dams diagnosed at a significantly younger age than positive offspring from other dams. Unfortunately it was not possible to determine when a positive dam might begin shedding the scrapie agent and consequently present a threat to her offspring. All of the positive dams in the study gave birth to their positive offspring in flocks where there were other active cases of scrapie which might have been the source of infection for the offspring. The source of infection could not be determined for over half of the reported cases. Several possible explanations for this situation were presented. Failure to detect the sources of infection may in part be responsible for the apparent increase in the magnitude of the scrapie problem in the United States. Data quality and consistency was a major issue for this study. The records available from the technical program staff of USDA contained varying amounts of information about each of the positive animals and flocks. In addition to variation in the records, the eradication program itself went through several phases during the study period. These different phases may have had multiple effects on the levels of disease reported to USDA. Unfortunately these effects could not be measured or corrected for in the analysis.
Open Access
Gene expression in phenotypically homogeneous chondrocytes from different articular cartilage layers of equine osteoarthritic and control joints: method validation and gene array analysis
(Colorado State University. Libraries, 2007) Düsterdieck, Katja Friederike, author; Frisbie, David D., advisor
Osteoarthritis remains a common and debilitating disease in horses, despite advances in diagnosis and treatment. Cartilage is commonly considered to play a central role in the pathophysiology of osteoarthritis. The investigation of differences in gene expression in cells from osteoarthritic and control cartilage is expected to yield genes possibly playing a role in the pathophysiology of osteoarthritis, representing new targets for treatment of the disease. The goals of this investigation were to develop a methodology to isolate RNA from phenotypically homogeneous cells of various cartilage layers for gene array analysis and to determine differentially expressed genes in these cells in osteoarthritic and control cartilage. A methodology to isolate phenotypically homogeneous chondrocytes from frozen sections of adult equine articular cartilage was developed using laser capture microdissection, RNA isolation, amplification and qrt-PCR. Expression levels of candidate genes were compared to those in conventionally isolated RNA from paired cartilage samples. The methodology was adequate to produce sufficient amounts of RNA for gene array analysis. Gene expression was found to be altered, but in a consistent fashion. The validated methodology, followed by gene array analysis was utilized to compare expression patterns in chondrocytes from tangential and radial layers of experimentally induced osteoarthritic and control cartilage. 154 genes were differentially expressed between tangential and radial cartilage layers and 17 genes were differentially expressed between osteoarthritic and control cartilage. The gene expression pattern of the tangential layer reflected support of cell proliferation, suppression of apoptosis and several genes involved in cell-matrix interactions or inflammatory processes. In contrast, the gene expression pattern of the radial layer was dominated by genes supporting the synthesis of proteins and proteoglycans. The gene expression pattern from osteoarthritic cartilage suggested an active response to oxidative stress, activation of the NF-κB pathway, decreased anti-apoptotic ability and downregulation of proteoglycan synthesis and glycolysis. This study was the first to determine gene expression patterns between two different layers of articular cartilage, improving our understanding of cartilage homeostasis in health and disease.
Open Access
Surveillance and diagnosis of transmissible spongiform encephalopathies in the United States
(Colorado State University. Libraries, 2007) Dennis, Michelle Marie, author; Salman, Mo, advisor
Since limited knowledge of transmissible spongiform encephalopathies (TSEs) restricts treatment and successful control interventions, and since some may cause fatal food-borne disease in humans, the United States (U.S.) has established TSE surveillance programs to support control efforts and to protect agriculture-based economy. The enhanced BSE surveillance system was conducted to characterize the extent of the presence of BSE in the U.S. cattle population in order to reassure consumers and trading partners of the U.S. BSE status. Given the level of importance and the cost of the enhanced BSE surveillance program, surveillance system evaluation was conducted to provide feedback for improving future surveillance and to determine the extent to which the system had met its objectives. Recommendations were made to improve efficiency and quality of future BSE surveillance systems. The enhanced BSE surveillance certainly met its stated objectives. Surveillance interests in the U.S. were subsequently re-directed towards efficiently assuring that BSE control measures remain effective, and to maintain assurance of trading partners of the U.S. BSE status. A plan for ongoing BSE surveillance was constructed using the standards and guidelines for animal health surveillance established by the National Surveillance Unit (NSU). Results derived from the enhanced BSE surveillance system and its evaluation prompted appriopriate adaptations for maintenance surveillance methods. Conditions which naturally degrade prions need to be elucidated to facilitate disposal of prion-contaminated biowastes. In order to determine whether long-term heating could destroy prions, the immunodetection of protease-resistant, disease-associated prion protein (PrPres) was evaluated in brain from chronic wasting disease (CWD)-affected elk. Using 3 diagnostic assays for CWD, progressive loss of PrPres immunodetectability, which increased with incubation temperature, was demonstrated when brain homogenates were incubated at 37, 55, and 80° C over a period of 200 days. Disposal systems which use heat over time may effectively degrade prions. Furthermore, the validity of test results derived from tissues which have been exposed to such conditions is questionable. In the U.S., scrapie surveillance uses PrPres immunohistochemistry (IHC) applied to tissues collected postmortem. The only live animal test available, PrPres IHC applied to third eyelid biopsy, is limited by comparatively lower sensitivity, high frequency of inconclusive test results, and the limited amount of tissue available for repeat testing. A study evaluated PrP res IHC applied to recto-anal mucosa associated lymphoid tissue (RAMALT) biopsy for scrapie diagnosis in live sheep. Biopsy-related complications were rare. The sensitivity of RAMALT biopsy PrPres IHC ranged from 87.5-89.3%, and approximated or exceeding that applied to third eyelid biopsy. The use of PrPres IHC applied to RAMALT biopsies for scrapie diagnosis in live high-risk sheep is expected to improve the surveillance activities that support the success of the U.S. National Scrapie Eradication Program.
Open Access
Immunoproteomic identification of bovine pericardium xenoantigens
(Colorado State University. Libraries, 2008) Griffiths, Leigh G., author; Orton, E. Christopher, advisor; Reardon, Kenneth F., advisor
Bovine pericardium (BP) is an important biomaterial used in the production of gluteraldehyde-fixed heart valves and tissue engineering applications. The ability to perform proteomic analysis on BP is potentially useful for several reasons including investigation of immune rejection after implantation. The importance of humoral and cell mediated rejection responses towards such xenogeneic tissues are becoming increasingly apparent. I have applied a novel immunoproteomic approach to survey the antigenic determinants of BP. Proteomic analysis of fibrous tissues like BP is challenging due to their relative low cellularity and abundance of extracellular matrix. A variety of methods for tissue homogenization, protein extraction, and fractionation were investigated with the aim of producing high quality 2-DE gels for both water- and lipid-soluble BP proteins. MALDI-TOF/TOF MS protein identifications were performed to confirm bovine origin and appropriate subcellular fractionation of resolved proteins. Sixteen unique predominantly cytoplasmic bovine proteins were identified from the water-soluble gels. Twenty-two unique predominantly membrane bovine proteins were identified from the lipid-soluble gels. These results demonstrate that the final 2-DE protocol produced high quality proteomic data from BP for both cytoplasmic and membrane proteins. Duplicate 2-DE gels were used to generate western blots from both water- and lipid-soluble gels. Western blots were probed with pre- and post-exposure anti-BP rabbit serum, with detection of immune complexes limited to the IgG subtype. Western blots were compared to duplicate 2-DE gels and spots matched using Delta 2D image analysis software. Protein identifications of matched spots were performed using either MALDI-TOF/TOF MS or ESI MS/MS. This approach identified 31 putative antigens, capable of stimulating an IgG humoral rejection response. To the best of my knowledge, this study was the first to apply an immunoproteomic approach for identification of antigenic targets in xenotransplanted tissues. The results provide important information for understanding and possibly mitigating the immune response to fixed and unfixed BP xenografts.
Open Access
Peri-slaughter ecology of Escherichia coli O157 and Salmonella enterica in feedlot beef cattle
(Colorado State University. Libraries, 2008) Dewell, Grant Alan, author; Salman, Mo, advisor
Risk factors for prevalence of E. coli O157 prior to slaughter and the genotypic relationship between feedlot and slaughter isolates were investigated. The odds of E. coli O157 positive fecal samples from cattle fed brewers grains were 6 times that for cattle not fed brewers grains. The odds of E. coli O157 positive fecal samples from cattle from Central Nebraska was 9 times that for cattle from Eastern Colorado. Within the sampled pens, 64% of the hide samples at the abattoir corresponded to a feedlot isolate. For carcass samples, 59% of isolates had a corresponding feedlot isolate. Transportation of cattle from the feedlot to the slaughter plant could influence hide contamination of Escherichia coli O157 or Salmonella enterica. Cattle held in E. coli O157 positive lairage pens had eight times greater relative risk of having E. coli O157 positive hide samples compared to cattle held in culture-negative pens. Cattle that were held in lairage pens contaminated with feces had three times greater relative risk for E. coli O157 positive hide samples and twice the relative risk for S. enterica positive hide samples compared to cattle held in clean pens. Cattle that were transported for long distances (> 160.9 km) had twice the relative risk of having E. coli O157 positive hide samples and twice the relative risk of having S. enterica positive hide samples compared to cattle transported shorter distances. Cattle with positive Salmonella enterica hide samples at the feedlot had almost twice the relative risk of having S. enterica positive hide samples compared to cattle without S. enterica positive feedlot hide samples. Cattle transported in trailers with positive S. enterica samples had over twice the relative risk of having S. enterica positive hide samples compared to cattle transported in culture negative trailers. Cattle held off feed longer than 18 hours before loading had a greater relative risk of having S. enterica positive hide samples compared to cattle held off feed for shorter times. Cattle that were agitated during loading had twice the relative risk of having S. enterica positive hide samples compared to cattle that were calm.
Open Access
Valve interstitial cell phenotypes and signaling pathways involved with canine myxomatous degenerative mitral valve disease
(Colorado State University. Libraries, 2008) Disatian, Sirilak, author; Orton, E. Christopher, advisor
Myxomatous mitral valve disease is a common heart disease of dogs that is similar to myxomatous mitral valve disease in humans. The first hypothesis of this dissertation is that interstitial cell phenotype transformation described in human myxomatous valves also occurs in dogs with myxomatous mitral valves and correlates with disease severity. Normal and early-, intermediate-, and late-stage myxomatous canine mitral valves were examined by immunohistochemistry for cytoskeletal (vimentin, desmin, smooth muscle α-actin, smooth muscle myosin, and non-muscle myosin), collagenolytic (MMP-1, MMP-13), cell surface (CD-31, CD-45, CD-68) and proliferation (Ki-67) proteins. Normal canine mitral valve interstitial cells were positive for vimentin, but negative for α-actin, desmin, and non-muscle myosin (i.e. fibroblast phenotype). Interstitial cells from myxomatous valves showed increased positive staining for α-actin and desmin, but were negative for smooth muscle myosin (i.e. myofibroblast phenotype). Positive cells first appeared as clusters in the subendocardial region of the lamina atrialis and extended into deeper layers with increasing severity. Interstitial cells from myxomatous valves showed positive staining for non-muscle myosin (i.e. activated mesenchymal cell phenotype). Positive staining cells increased with disease severity and were dispersed throughout the valve layers. Expression of MMP-1 and MMP-13 correlated with disease severity. Interstitial cellularity increased in degenerative valves however Ki-67 staining was mildly increased. In conclusion, two patterns of interstitial cell phenotype transformation were identified in dogs with myxomatous mitral valve disease and both correlated with disease severity.
Open Access
Epidemiology and veterinary public policy
(Colorado State University. Libraries, 2008) Zepeda Sein, Cristóbal Andrés, author; Salman, Mo, advisor
Official Veterinary Services are increasingly required to base veterinary public policy decisions on scientific grounds, epidemiology and risk analysis play an important role in shaping these decisions. A formal, in-depth analysis of the multiple interactions between epidemiology, risk analysis and veterinary public policy was conducted to enable decision-makers to direct resources more efficiently and facilitate compliance with international agreements, in particular the Agreement on the Application of Sanitary and Phytosanitary Measures (SPS) of the World Trade Organization. The SPS Agreement recognizes the World Organization for Animal Health (OIE) as the international organization responsible for developing animal health standards. The OIE's Terrestrial Animal Health Code contains scientifically based recommendations for international trade in animals and animal products. However, to date, these recommendations have not been assessed from a risk-based perspective. The study is divided in two major sections: (1) the role of epidemiology in veterinary public policy and (2) the application of risk-based approaches to the assessment of international animal health standards. The first section addresses the international framework, risk analysis and its use worldwide, and the development of international standards. The second section focuses on quantitative risk assessment approaches for the international movement of animals and products, as well as the application of compartmentalization to aquaculture production systems emphasizing the use of a HACCP approach to biosecurity.
Open Access
Tissue engineering of heart valves: antigen removal from xenogeneic tissue scaffolds
(Colorado State University. Libraries, 2009) Arai, Shiori, author; Orton, E. Christopher, advisor
Tissue-engineered heart valves hold the promise of an ideal heart valve substitute by using appropriate and functional cells and scaffolds. An ideal heart valve should be durable, non-immunogenic, non-thrombogenic, resistant to infection and capable of regeneration and growth. Xenogeneic tissues are potential candidates for scaffolding of tissue-engineered heart valves. Anionic detergent-based decellularization has been employed to eliminate xenogeneic tissue immunogenicity. The present studies were performed to develop a technique to detect antigenic proteins in xenogeneic tissue scaffolds, to evaluate the efficacy of antigen removal of current detergent-based decellularization of xenogeneic tissues, to develop novel techniques to enhance antigen removal, and to address issues related to the cytotoxic effects of sodium dodecyl sulfate (SDS).
Open Access
Investigation into disease events at the wildlife/livestock interface: lessons learned from bovine viral diarrhea virus in Colorado cervids
(Colorado State University. Libraries, 2009) Duncan, Colleen, author; Salman, Mo, advisor; VanCampen, Hana, advisor
Infectious agents may be transmitted between wild and domestic animals; these so called 'interface diseases' can have significant economic consequences. As such, effective tools and techniques with which to study disease in free ranging, wild animals is essential. Principles of wildlife disease surveillance were reviewed and it was concluded that while wildlife disease research may require unique logistical adaptations; basic principles of surveillance remain the same. A review of wildlife data sources utilized for surveillance suggests that information collected, and shared, is dependent on the group involved and that there are opportunities to improve the type and quality of material available. Bovine viral diarrhea virus (BVDV) is an important virus of domestic cattle that has recently been identified in wild ruminants worldwide. To investigate the presence, prevalence, distribution and significance of BVDV in wild cervids of Colorado a series of projects were conducted. Persistently infected (PI) deer were studied post mortem; immunohistochemical and molecular techniques used to look for viral antigen in deer tissue were found to be effective supporting the use of these tests in further studies. The prevalence and distribution of PI cervids in the state was evaluated using an opportunistic sampling technique; the prevalence is extremely low, but naturally occurring infection is present within Colorado. The cost associated with testing animals for an uncommon disease may be very high; techniques like pooling samples can help to keep costs down during such investigations. The sensitivity and specificity of RT-PCR on pooled samples was investigated in an experimental study and revealed that supernatant from a single positive deer skin sample may be diluted up to 10,000 times and still be detected. Another technique to focus research efforts on high risk areas is the use of simulation modeling. A stochastic risk assessment model was developed to identify regions in Colorado where PI cattle were likely to be born following exposure to a PI deer. Results of the model were consistent with both the cross-sectional survey for PI cervids and other reports on BVDV in wildlife of Colorado.
Open Access
A holistic approach to veterinary public health in animal shelters and other sites
(Colorado State University. Libraries, 2009) Steneroden, Kay K., author; Salman, M. D., advisor; Hill, Ashley E., advisor
Animal health and human health are intimately linked. Directly, through contact with or exposure to animals and their environments, and indirectly by way of food production, food safety and antimicrobial drug residues, humans are dependent upon and vulnerable to the health of animals. Veterinary public health is concerned with the interface of human and animal health and addressing problems at that interface. The potential impact of such exploration is greater human and animal health. Epidemiological needs assessment, problem investigation and subsequent outreach programs are essential tools of veterinary public health practice. These tools are used to explore infection control, infectious and zoonotic disease awareness, environmental contamination with infectious/zoonotic agents and monitoring the consequences of treatment of infectious and zoonotic diseases with antimicrobial drugs (i.e. antimicrobial drug resistance). The specific venues for these explorations for this dissertation include animal shelters, a veterinary teaching hospital, a former Soviet country and a United States governmental program. A holistic approach is used with animal shelters to assess infection control and zoonotic disease awareness needs, investigate environmental contamination with a zoonotic disease, develop training tools and train animal shelter workers and volunteers. The needs assessment provided valuable information on characteristics of animal shelters, provided impetus for the problem investigation and the basis for outreach training. The problem investigation tool provided the first available information on the prevalence and extent of salmonella contamination in Colorado animal shelters. The outreach components provided a tool and reference for training; the training itself indicated gaps in knowledge in various aspects of infection control and zoonotic disease awareness that could be addressed with training. Further, problem investigation is explored through the success of active surveillance in discovery and control of a zoonotic disease outbreak in a veterinary teaching hospital. Results of a needs assessment survey in the Republic of Armenia provide the basis for development of outreach materials for veterinarians, farmers and school-age children on their national animal health program. And a system of antimicrobial drug resistance monitoring is examined and challenged for completeness. Taken together, these studies further the examination of veterinary public health issues and highlight a holistic approach to their exploration.
Open Access
Insights into the origins of functional mitral regurgitation and development of a corrective epicardial device
(Colorado State University. Libraries, 2010) Gleyzolle, Baptiste, author; Monnet, Eric, advisor; Orton, E. Christopher, committee member; Earley, Scott, committee member; James, Susan P., committee member
Functional mitral regurgitation (FMR) is a frequent complication of left ventricular remodeling and carries a significant adverse prognosis. While significant progress has recently been made in the understanding of the pathophysiology and treatment of this disease, failure to obtain acceptable outcomes is driving researchers and clinicians to investigate alternative approaches to the consensual treatments. A thorough understanding of the normal anatomy and physiology of the mitral valve is warranted to underline the pathophysiological mechanisms of left ventricular remodeling leading to functional mitral regurgitation. The accumulated experience with traditional techniques and the experimentation of emerging surgical procedures allowed us to identify strengths and points to be improved for each therapeutical approach. Based on this review, we defined the specifications of a new device designed to correct FMR. In the first study we tried to develop an acute model of myocardial ischemia to induce mitral valve regurgitation in sheep. In six sheep, acute myocardial infarction was induced by ligation of the second and third obtuse marginal branches of the left circumflex coronary artery, defining an ischemic (IZ) and non ischemic (NZ) zone. Aortic and left ventricular pressures, left ventricular volumes, ECG, and segmental length of the IZ and NZ were recorded. Aortic blood flow was measured with an aortic flow probe in three sheep. Maximum elastance, dP/dt, tau, left ventricular and myocardial stiffness, total mechanical energy (PVA), external work (Ew), contractile efficiency and the global and regional preload recruitable stroke work (PRSW and rPRSWX) were calculated. Myocardial perfusion was calculated with injection of microspheres. Mitral regurgitant volume was calculated as the difference between the aortic and the left ventricular stroke volume. The data was compared between baseline, after five to ten minutes and one hour of ischemia. Myocardial blood flow decreased from 1.53 ± 0.81 mL/g/min to 0.37 ± 0.37 mL/g/min (p=0.022) in the IZ. Mitral regurgitation was not observed at any time point. Ischemia reduced PRSW from 60.7 ± 9.1 mmHg at baseline to 42.3 ± 4.3 mmHg and t+60 min (p=0.002), and rPRSWIZ from 96.2 ± 33.9 mmHg.L.m-1 at baseline to 59.2 ± 28.6 mmHg.L.m-1 at t+5-10 min (p=0.026) and 63.7 ± 25.7 mmHg.L.m-1 at t+60 min (p=0.032). PVA decreased from 6260 ± 1387 mmHg.L at baseline to 4149 ± 1299 mmHg.L at t+5-10 min (p=0.019) and 4368 ± 1632 mmHg.L at t+60 min (p<0.001). Ew decreased from 3877 ± 1287 mmHg.L at baseline to 2334 ± 872 mmHg.L at t+5-10 min (p=0.037) and 2507 ± 883 mmHg.L (p=0.013) at t+60 min. Myocardial stiffness of the IZ decreased from 2.63 ± 1.23 mm-1 at baseline to 0.94 ± 0.57 mm-1 at t+5-10 min (p=0.014) before an increase to 3.56 ± 0.57 mm-1 at t + 60 min (p=0.033). In conclusion, acute occlusion of OM2 and OM3 did not induce acute functional mitral valve regurgitation. It did however, induce early systolic and diastolic regional dysfunction. The non-ischemic myocardium did not compensate for the left ventricular remodeling. In the second study, we used acute aortic banding to induce mitral valve regurgitation. This was done to assess the effects of an epicardial device designed to reposition the papillary muscles on FMR, considering that left ventricular remodeling with tethering of the papillary muscle is the most important factor leading to FMR. In seven sheep, aortic, left ventricular and atrial pressures, left ventricular volumes, aortic blood flow, mitral annulus diameter and ECG were recorded. Acute FMR was induced by aortic banding. Left ventricular end diastolic and end systolic volume, stroke volume, the constant of passive left ventricular stiffness and Tau were measured. Mitral regurgitant flow was calculated from the difference between aortic stroke volume and left ventricular stroke volume. Application of an epicardial device reduced FMR from 14.4 ± 5.4 to 7.7 ± 5.2 mL (p=0.001) without decreasing mitral annulus diameter in diastole (p=0.075) and systole (p=0.080). Left ventricular end diastolic volume decreased from 241.5 ± 52.5 to 227.6 ± 46.5 mL (p=0.044). Passive left ventricular stiffness increased from 0.92 ± 0.5 to 1.18 ± 0.59 mL-1 (p=0.044). Other parameters of diastolic dysfunction were not affected by the device. In conclusion, acute FMR was decreased by the application of an epicardial device. Diastolic function was not adversely affected by the device. Most likely, correction of FMR by the epicardial device was achieved by repositioning of the papillary muscles. The epicardial device was not in contact with blood and did not require cardiopulmonary bypass.
Open Access
Inflammation and apoptosis within the colon from horses with black walnut extract-induced laminitis: prognostic factors after esophageal obstruction in horses
(Colorado State University. Libraries, 2010) Chiavaccini, Ludovica, author; Hassel, Diana M., advisor; Boscan, Pedro, committee member; Bamburg, James R., committee member
To view the abstract, please see the full text of the document.
Open Access
Evaluation of strategies for eradication of Aujeszky's disease (Pseudorabies) in commercial swine farms in Chiang-Mai and Lampoon provinces, Thailand
(Colorado State University. Libraries, 2010) Ketusing, Naree, author; Salman, Mo, advisor; Olea-Popelka, Francisco, advisor; Keefe, Thomas, committee member
Several strategies for eradicating Aujeszky's disease (Pseudorabies) in Chiang-Mai and Lampoon Provinces, Thailand, were compared using a computer simulation model, the North American Animal Disease Spread Model (NAADSM). The duration of the outbreak, the number of infected herdss and the number destroyed herds were compared during these simulated outbreaks. Destruction, zoning for restricted movement and improved detection and vaccination strategies were studied. Destruction was found to be the most effective method to eradicate Pseudorabies. Although zoning and ring vaccination did not influence this model, the recommendations from this study are to apply both destruction and three zone (3, 8 and 16 kilometers) restricted movements along with enhanced detection and a 16 vaccination ring.
Unknown
Vaccination of white-tailed deer with Mycobacterium bovis bacille Calmette-Guerin: efficacy, immunology, and molecular detection
(Colorado State University. Libraries, 2010) Nol, Pauline, author; Salman, Mowafak Dauod, advisor; Rhyan, Jack, committee member; Belisle, John Theodore, committee member; Hill, Ashley E., committee member; Keefe, Thomas J., committee member
Wildlife reservoirs of Mycobacterium bovis are believed to play very important roles in the epidemiology of bovine tuberculosis in many countries throughout the world. In the United States, a free-ranging white-tailed deer (Odocoileus virginianus) population in northeastern Michigan serves as such a reservoir. Although changes in management have decreased prevalence of the disease, additional tools, such as vaccination, are needed to achieve eradication of bovine tuberculosis from Michigan deer. In this project, the efficacy of oral and parenteral Mycobacterium bovis bacille Calmette-Guerin Danish strain 1331 (BCG) was evaluated for its ability to protect white-tailed deer against disease caused by M. bovis infection. In addition, cellular and humoral immune responses in deer to BCG vaccination and M. bovis challenge were examined, and molecular detection techniques were developed to monitor shedding of BCG and M. bovis in vaccinated and infected animals. Results indicate that white-tailed deer vaccinated with BCG both orally and parenterally were protected from development of severe disease after experimental infection with virulent M. bovis when compared to unvaccinated deer. Antibody responses to M. bovis antigens by the deer in this study were evaluated over time using multiantigen (multiantigen print immunoassay, rapid test, and immunoblot to whole-cell sonicate) and single antigen tests (lipoarabinomannan [LAM] ELISA and immunoblot to MPB83). Multiantigen tests detected minimal to no antibody responses in vaccinated deer after challenge, whereas antibody responses were more readily detectable by these tests in unvaccinated deer with more advanced disease. The ELISA results indicated an overall decrease in detectable antibodies produced against LAM-enriched mycobacterial antigen in vaccinated animals as compared to unvaccinated animals after challenge. Few trends could be determined from the immunoblot results. Cellular immunity was measured via interferon gamma production and lymphocyte proliferation in response to mycobacterial antigens. Findings in regards to cellular immunity were inconclusive. Molecular techniques developed to detect M. tuberculosis complex in cervid feces, nasal and pharyngeal swabs, soil, feed, and hay produced data indicating that deer shed M. bovis and BCG only intermittently at 1-3 months after vaccination and 1-4 months after M. bovis challenge. The findings from these studies strongly support further research that could lead to the eventual use of BCG in wild white-tailed deer herds affected by bovine tuberculosis. The data also encourage the improvement and potential use of antibody-based assays, such as the multiantigen tests and the LAM-ELISA as ante-mortem tools to assess disease progression in white-tailed deer in both experimental and field vaccine trials. Finally, further improvements in the molecular detection of M. bovis could enable more effective monitoring of shedding of M. bovis by deer in both experimental and free-ranging environments.
Open Access
Oropharyngeal bacteria, with respect to animal health classification, and viral serology of Montana bighorn sheep (Ovis canadensis) and domestic (Ovis aries) near to and distant from the wildlife/domestic animal interface
(Colorado State University. Libraries, 2010) Miller, David Steven, author; Campbell, Terry W., advisor; Garry, Franklyn, advisor; Chapman, Phillip L., committee member; Kimberling, Cleon V., committee member; Rhyan, Jack C., committee member
Respiratory disease outbreaks attributed to pasteurellosis have lead to conflict at the wildlife/domestic interface, where domestic sheep have been hypothesized to be a reservoir of Pasteuerellaceae strains that cause disease in bighorn sheep. This dissertation compares bighorn sheep ( Ovis canadensis) and domestic sheep ( O. aries) oropharyngeal Pasteurellaceae biovariants from animals classified as diseased and healthy. It also compares bacteriology and viral serology of populations of these species near to and distant from the wildlife/domestic livestock interface. A retrospective study of clinical submissions (1990 - 2004) indicated that 94 Pasteurellaceae biovariants have been associated with domestic sheep classified as diseased. A second retrospective study (1989 - 2004) indicated that 37 Pasteurellaceae biovariants have been associated with bighorn sheep classified as diseased. A prospective study of domestic and bighorn sheep near to and distant from the wildlife/domestic interface indicated that Pasteurellaceae biovariants commonly associated with disease in the retrospective studies were also common in healthy animals, and that there was extensive interspecific sharing of biovariants. This suggests that a simple agent/disease relationship may not exist for Pasteurellaceae in these host species. In addition, it is not clear that either species serves as a reservoir for Pasteurellaceae that are pathogenic for the sympatric species. However, unstated assumptions that single samples represent an animal's Pasteurellaceae microflora are questionable, based on the minimal concordance of biovariants of individual domestic livestock (n = 118) sampled six months apart. Based on the populations in the prospective study, bighorn sheep populations were naive to Mycoplasma, and both Ovis species were largely naive to infectious bovine rhinotracheitis and bovine virus diarrhea 1 and 2. This suggests that these agents may cause outbreaks if introduced into these populations. Cluster analysis of Pasteurellaceae and viral serology results identified four different clusters (P < 0.0001), but these did not closely correspond to species and location categories. The results from this study suggest that emphasis on single determinants for causes of respiratory disease outbreaks in domestic and bighorn sheep, rather than determination of risk factors for multiple determinants, may not provide results that are useful for managing disease in these species.
Open Access
Glucose transporter-1 expression and the antiproliferative effects of 2-deoxy-d-glucose in osteosarcoma models
(Colorado State University. Libraries, 2010) Lori, Janet Carolyn, author; Lana, Susan E., advisor; Thamm, Douglas, advisor; Biller, Barbara J., committee member; Ehrhart, Eugene J., committee member
Osteosarcoma (OSA) is the most common bone tumor in the dog, more common in large to giant breed dogs. 90% of dogs diagnosed with OSA will die of metastatic disease within one year of diagnosis. There have been no great advances in therapy for canine OSA over the last 20 years. Hypoxia in tumors has been associated with an increased resistance to radiation and chemotherapy, and increased metastatic potential. Hypoxia-inducible factor 1-a (HIF-la) is a transcription factor stabilized by hypoxia. Glucose transporter 1 (GLUT-1), a downstream product of HIF-la pathway activation, is over-expressed in a variety of human tumors. We sought to determine if GLUT-1 is expressed in canine OSA and if expression is related to tumor necrosis and outcome. Immunohistochemistry was performed on 44 histologically confirmed OSA tissue samples to assess expression of GLUT-1. Of 44 cases, 27 (61%) expressed GLUT-1. There was no statistical correlation between GLUT-1 and disease-free interval, survival time, or percent necrosis. As hypothesized, GLUT-1 is present in most canine appendicular OSA. A more objective evaluation of GLUT-1 and other proteins in the HIF-la pathway may be warranted. Some cells within a tumor may be poorly perfused, and therefore less susceptible to traditional chemotherapy. Cancer cells, especially those hypoxic cells that are distant from the stromal blood vessels, require more glucose than normal cells as they utilize anaerobic glycolysis, rather than oxidative phosphorylation, to survive. 2-deoxy-Dglucose (2-DG) is a glucose analog that is preferentially captured by cancer cells, _ blocking the first step of glycolysis. We evaluated the sensitivity of various OSA (canine and murine) cell lines to 2-DG, and attempted correlation to the protein GLUT-1 with western analysis. There was no statistical correlation between 2-DG and GLUT-1 or Akt expression, although it did correlate with total ERK expression. In a murine OSA model, 2-DG was shown to inhibit metastasis, possibly through the inhibition of invasion and migration, as assessed by Boyden chamber assays in vitro using the same OSA murine cell line.
Open Access
The relationship between radiographic changes and performance outcome in Quarter Horse cutting horses
(Colorado State University. Libraries, 2010) Barrett Frisbie, Myra Frances, author; McIlwraith, C. Wayne, advisor; Park, Richard D., committee member; Kawcak, Christopher E., committee member; Werpy, Natasha, committee member
Reason for Performing the Study: Radiographic repositories are become increasingly popular in multiple disciplines as a screening tool prior to sale. However, the importance of the radiographic findings must be objectively assessed relative to potential significance. While studies have been done to correlate survey radiographic findings with performance outcomes in Thoroughbreds, no such published study exists in Quarter Horses. This paper serves as part two of a study examining the relationship between radiographic changes in survey radiographs relative to objective performance outcomes in Quarter Horse cutting horses. Objectives: The goal of this study is to better clarify the potential significance of radiographic changes on repository radiographs relative to performance. This in turn will allow veterinarians and their clients to make more objective, informed decisions prior to purchase about the potential implications of various radiographic changes. Methods: Radiographic changes of 436 Quarter Horses, which were quantified in a previous paper (Contino et al 2009), were compared to objective performance outcome parameters. The parameters were: 1) likelihood of competing, 2) likelihood of earning money as a three year old, four year old and as a three and four year old combined, 3) average amount of money earned as a three year old, four year old and as a three and four year old combined. Mailed questionnaires and phone calls to owners of horses that did not earn money were used to try to determine why the horse had no recorded earnings. Results: When the tarsometatarsal (TMT) and distal intertarsal (DIT) joints were examined together, the presence of mild (grade 2) osteophytes, which affected 19% of the horses, was associated with reduced chance of competing, earning money and mean money earned. Very mild and mild osteophytes of the third and central tarsal bone assessed individually at the level of the TMT and DIT also had some significant effects in multiple performance outcome categories. The presence of thickening of the dorsal cortex of the hind second phalanx as well as osteophytes as this location was associated with an increased likelihood of earning money. Several other potentially significant findings are reported but affect a relatively small number of the horses included in the study. Radiographic changes of the medial femoral condyle of the stifle were not significantly associated with performance outcome. Conclusions: Many radiographic changes were not found to be significantly associated with performance outcome. However, some mild changes were associated with decreased performance. In addition, some radiographic changes were correlated with improved performance outcome. Potential Relevance: The findings of this study can be used to help veterinarians make more objective assessments of survey radiographic findings prior to sale. This research helps lay the groundwork for further investigations of the significance of survey radiographic findings in individual breeds and disciplines.
Open Access
Dairy cow mortality
(Colorado State University. Libraries, 2010) McConnel, Craig Stephen, author; Garry, Franklyn B., advisor; Hill, Ashley E., committee member; Lombard, Jason E., committee member; Gould, Daniel H., committee member
Dairy cow mortality levels in the United States are excessive and increasing over time. This is both a financial concern and an important animal welfare issue. Summary studies of dairy cow removal have been in the literature for decades although information specifically related to dairy cow mortality has been sparse. Even though the increase in dairy cow mortality has generated concern within the industry, the reality is that there is no standard by which to define what might be considered the 'natural' or 'normal' level of mortality in dairy cow production. No evidence suggests that there is any one thing that has led to the rise in mortality and that could be reversed to lower death rates. Rather, numerous agents (influential persons, places, or things) apparently act in concert to influence specific outcomes that may lead to death. The "agents" intimated to be responsible for increasing mortality have been primarily described through the analysis of associations between mortality levels and descriptors such as days postpartum, parity, herd size, and genetics. Such analyses may provide a means for understanding populations at risk but can only illustrate broad principles related to manageable risk factors, potential mitigation procedures, or specific pathologic outcomes. Other studies have attempted to define individual occurrences of death based on the final outcome. Rather than looking at population levels of diseases and associated levels of death, these studies have focused on the pathophysiologic or anatomic descriptions of specific deaths. Such analyses fail to account for the non-biologic unconstrained inputs such as management and environmental factors that ultimately set a pathologic sequence in motion within an at-risk population. Ultimately, with regard to excessive and increasing dairy mortality the difficulty lies in defining the problem (establishing what distinguishes farms with higher death rates from those with more desirable rates) and locating the problem (finding where the trouble really lies within the complex of causal networks on a dairy). This leads to the problem of identifying the actions that might effectively narrow the gap between what-is and what-ought-to-be. Understanding the complexity within such a system demands the recognition of its evolving ecology. Within this evolving industry there is no legitimate means for resetting practices and outcomes back to some undefined acceptable level. Rather than attempting to reverse the irreversible, it would be wise to instead work within the system to improve outcomes through sound scientific principles. The intention of the following work is to characterize and elucidate such principles in an effort to facilitate best intentions becoming better outcomes.
Open Access
Prevalence and risk factors associated with bluetongue virus among Colorado sheep flocks
(Colorado State University. Libraries, 2010) Mayo, Christie Ellen, author; Hill, Ashley E., advisor; Bowen, Richard A., committee member; Van Metre, David C., committee member; Callan, Robert J., committee member
To view the abstract, please see the full text of the document.
Open Access
Nosocomial infection rates in veterinary referral hospitals: using syndromic surveillance to establish baseline rates
(Colorado State University. Libraries, 2011) Ruple-Czerniak, Audrey, author; Morley, Paul S., advisor; Lunn, Katharine F., committee member; Peel, Jennifer L., committee member; Van Metre, David C., committee member
Nosocomial, or hospital-acquired, infections are considered to be the most common complication affecting hospitalized human patients, but their impact on hospitalized veterinary patients is less well understood. In fact, the incidence of nosocomial infections that occur in veterinary hospitals has not been established. There is evidence, however, that nosocomial infections are of great consequence in veterinary medicine and can have considerable negative effects on the individual patient as well as on the veterinary hospital as a whole. Due to the increased risk of infection in hospitalized patients, it is anticipated that some nosocomial infections will occur. Establishing a baseline rate of infection using surveillance techniques will allow investigators to ascertain the proportion of infections that can be prevented using infection control measures. The purpose of this study was to establish baseline rates of infection using a syndromic surveillance system created for implementation in small animal and equine referral hospitals. This study included weaned dogs, cats, and horses (n=2248) that were hospitalized in the critical care unit of one of five participating veterinary hospitals during a 12 week period in 2006. Clinicians actively performed syndromic surveillance on hospitalized patients and reported their results no later than the time of the patient’s discharge from the hospital. Adjusted rates of nosocomial events were estimated using Poisson regression, and risk factors associated with an increased risk of developing a nosocomial event were analyzed using multivariable logistic regression. Adjusting for hospital of admission, 19.7% of horses, 16.3% of dogs, and 12% of cats included in this study were reported to have experienced a nosocomial event occur during hospitalization. The only risk factor found to have a positive association with the development of a nosocomial event in all three species was placement of a urinary catheter. Surgical site inflammation and intravenous catheter site inflammation were two of the most commonly reported events across all species. Results of this study suggest that nosocomial event rates can be established using syndromic surveillance systems in multiple hospitals. Data pertinent to risk factors for the occurrence of nosocomial events can also be effectively collected using the same technique. Further research is warranted in order to evaluate how generalizable these results are to other veterinary healthcare settings.