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Current Research
CURRENT RESEARCH RECORD $1.2 MILLION IN EQUINE RESEARCH IN 2008 Grayson-Jockey Club Research Foundation’s board of directors has approved a record allocation of $1,226,457 for equine research in 2008. The funds will underwrite a slate of 14 start-up projects and 10 secondyear proposals. This marks the foundation’s fourth consecutive year of record funding and the second consecutive year that it is providing more than $1 million for equine research. This year’s slate of projects brings the Foundation’s totals during the last 25 years to more than $15.5 million for 239 projects at 35 institutions. In addition to funding the 12 new grants described herein, the Foundation set aside funds for special projects on racetrack surface management and the effects of various surgical procedures to correct limb deformities in young foals. Both of these subjects are among key considerations in the industry’s ability to protect the soundness and safety of racehorses.
NEW PROJECTS HYDROCORTISONE REPLACEMENT THERAPY IN SEPTIC FOALS Dr. Michelle Henry Barton, University of Georgia Infection is regarded as the number one cause for illness and death in newborn foals. This research team— involving scientists at the Universities of Georgia and Florida as well as Cor-
0737-0806/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jevs.2008.04.008
372
nell University—reports that approximately 75% of newborn foals admitted to referral hospitals have the condition, and at least 25% of those are lost. Production of the hormone cortisol is a defense against infection, but perhaps as many as 50% of infected newborns (septic foals) suffer from insufficiency of cortisol. A synthetic cortisol product, hydrocortisone, is used in human medicine to reduce incidence of death in such cases. This project will seek to determine a safe dose of hydrocortisone that will reduce severity of disease and improve survival rates of septic foals, in a controlled hospital setting. DOES AIRBORNE EXPOSURE PREDICT PNEUMONIA? Dr. Noah Cohen, Texas A & M The foundation has funded several projects on viral pneumonia, a major cause of death in foals. There is no effective vaccine, and among questions unanswered are why some farms experience a higher incidence than others and why some foals on a given farm become infected while others do not. This project is a continuation of research by one of the leading epidemiologists in North America. (It was Dr. Cohen whom the foundation called on to head the epidemiologic team when it partnered with the Commonwealth of Kentucky in an initial study on mare reproductive loss syndrome.) In this proposal, Dr. Cohen will test whether existence of virulent Rhodococcus equi in the air predicts the outset of the disease. If the answer is positive, farms could initiate strategies to reduce the amount of contamination. MAPPING OCCLUSION OF VEINS IN EXERCISE-INDUCED PULMONARY HEMORRHAGE Dr. Fred Derksen, Michigan State University This is another approach in the series of attempts to understand fully why so many horses experience bleeding (exercise-induced pulmonary hemorrhage: EIPH) in the lungs as a result of high exercise. In past research
funded by the foundation, this research team discovered scarring around blood vessels, which obstructs the veins and causes backup in the lungs and rupture of its small blood vessels. This new project is designed to determine the location and extent of vein scarring in the lungs and compare it with horses that have not raced, also relating the location of the scarring with the location of the bleeding. Another aspect will be investigating why vein scarring occurs by studying molecules in the vein walls that signal scarring to occur. This project has the potential to guide research in a new direction for effective prevention or treatment of a widespread occurrence. DIFFERENTIATION OF STEM CELLS FOR CARTILAGE REPAIR Dr. Alan Nixon, Cornell University Cartilage damage affects both yearlings and horses in training and commonly triggers the development of arthritis. The resultant stress of the joint also can lead to fractures of the pastern or cannon bone. Dr. Nixon points out that ‘‘despite popular perception, cultured stem cells or marrow-derived mixtures so far seem incapable of forming durable cartilage.’’ Past attempts have created only transitory effects on cartilage. His current approach is to use and test robust gene-based methods to turn stem cells from the animal’s own marrow into dedicated cartilage cells: ‘‘These equine-specific genes have been recombined into nonviral vectors that insert them into the chromosomal DNA of target cells.’’ EFFECTS OF COMBINING LIDOCAINE AND FLUNIXIN Dr. Butch KuKanich, Kansas State University This grant examines the dosages of lidocaine and flunixin to ensure safety of the animals being treated. The two medications are often used together, especially after surgery for colic and other intestinal problems. Lidocaine has narrow parameters for dosages and can create toxicity, which results in seizure and collapse—putting the
Journal of Equine Veterinary Science Vol 28, No 6 (2008)
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horse, and its handlers, in danger. The study will seek to determine whether commonly used dosages need to be adjusted because of how these drugs interact.
of more effective treatments for the disease.
A RESPIRATORY MODEL ON INTERACTIONS OF VIRUS AND HOST
Dr. Udeni Balasuriya, University of Kentucky Because the University of Kentucky is a designated reference laboratory for the World Organization of Animal Health, many tissue and serum samples from the 10-state outbreak of equine viral arteritis (EVA) of 2006 07 are available there for research. This project will characterize the genes that encode structural protein of the virus and sequence the genome of EVA samples from different states involved in the outbreak. Because the samples were collected over nearly a year, the evolution of the EVA virus over time can be studied. The researchers should be able to identify ‘‘mutational hot spots’’ and ‘‘hopefully have a greater understanding of the genetic basis of persistent EVA infection in the carrier stallion.’’ The researchers are confident their work will ‘‘impact the nature of control measure to prevent EVA infection . . . as well as allow us to develop more reliable molecular diagnostic tests.’’
Dr. Gisela Sobol, Colorado State University Dr. Sobol points out that ‘‘despite years of research, major epidemics of equine influenza virus and equine herpes virus-1 (EHV-1) remain a worldwide problem.’’ This project seeks understanding of why initial encounters of a pathogen determine downstream events and the outcome of the disease. Little is known about that initial situation. This project will employ a specific equine cell culture system to study the initial defense mechanisms to develop the necessary knowledge that can lead to immune modulators and anti-inflammatory drugs.
XENOGRAFTING TO STUDY TESTICULAR FUNCTION IN STALLIONS Drs. Ina Dobrinski and Regina Turner, University of Pennsylvania ‘‘Age-related testicular degeneration is a common cause of progressive infertility,’’ the researchers point out. Underlying causes are not well understood, so no satisfactory treatment has been developed. These researchers found in 2006 that in severe cases it is the testis itself and not the extratesticular environment that is defective. A process known as xenografting will further verify that finding and will also test whether common treatments for testicular degeneration actually have a positive effect on the diseased tissue. Xenografting ‘‘will allow us to answer these questions . . . without having to perform experiments on the horses.’’ Improved understanding could lead to creation and evaluation
MOLECULAR EPIDEMIOLOGY OF THE 2006 OUTBREAK OF EQUINE VIRAL ARTERITIS
NEUROPATHOGENESIS OF EHV-1 INFECTION Dr. Lutz S. Goehring, Colorado State University The foundation has been funding research on the sometimes deadly EHV1 infection for a number of years and last year launched two projects chosen as a result of a special call for research on that subject. The Research Advisory Committee scored this project very highly as a worthy addition to work being done on the subject. Currently there is no effective vaccine, and in fact, there are indications that the vaccines in use might actually be detrimental to horses suffering from this particular type of herpesvirus (EHV1). The nonexistence of experimental
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models has hampered research. As a solution, these researchers ‘‘propose to establish an endothelial cell culture system and . . . to study how the process of virus transfer from white blood cells into endothelial cells occurs.’’ They will also seek methods to intervene with the various processes involved in a horse developing EHV-1. MOLECULAR AND CELLULAR LEVEL STUDIES OF LAMINITIS Dr. Hannah Galantino-Homer, University of Pennsylvania This project takes an approach to laminitis that is aimed, the researchers explain, ‘‘to further our understanding by focusing our efforts at the molecular and cellular levels.’’ Currently, laminitis still is so baffling to scientists that researchers tend to be split into two camps (theories) as to the cause of the problem—vascular and enzymatic. ‘‘The lack of agreement about the basic pathophysiology of laminitis explains why standard guidelines for therapy are not yet available,’’ noted Dr. Galantino-Homer. If this project can identify which specific genes and proteins are upregulated or downregulated during the first phase of the disease—when identifiable symptoms are not yet manifested—it ‘‘will determine the pathways of the disease and allow institution of preventive or interventional treatments sooner.’’ The first phase of laminitis, the developmental phase, is followed, of course, by the acute phase, and one of the frustrations of dealing with the disease is that often by the time it is diagnosed, the horse may be gravely threatened. These researchers believe the study ‘‘will provide information that we and other investigators can use to verify or elaborate on existing theories about laminitis, explore previously unrecognized cellular and molecular events during laminitis, and validate in vitro models of laminitis.’’ The latter will facilitate research projects that do not require laminitic horses.
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MECHANISMS OF MAINTENANCE OF EARLY PREGNANCY Dr. Keith Betteridge, Guelph University This project addresses the frequent scenario of a mare being diagnosed as pregnant soon after breeding, but quickly losing the pregnancy. The 3week stage has been identified as the point when the conceptus (embryo and associated tissues and fluids) has to become immobilized at the position in the uterus where the placenta will develop. The research is aimed at understanding the processes by which this either occurs, and the pregnancy continues, or fails to occur successfully. This research team utilizes various physiologic, biochemical, proteomic, and molecular methods to identify changes in proteins, steroid hormones, and other molecules that are altered during the critical phase: ‘‘Several distinct differences between normal and failing pregnancies have already’’ been identified. Continuing understanding from this project could lead to diagnostic tests of the reproductive health of mares as well as treatments that improve the success rate of early pregnancies.
CORD BLOOD STEM CELLS: FROM FARM TO POINT OF CARE Dr. Dean Betts, Guelph University This is another project seeking to overcome the problem of stem cells being unsuccessful so far as an antidote to cartilage lesions. Research in human medicine indicates that umbilical cord cells are more effective than stem cells from fat or bone marrow. The researchers have already isolated umbilical cord blood stem cells in horses and have ‘‘demonstrated their potential to form bone, cartilage, and fat in petri dishes.’’ This project will continue the learning curve, not only in use of cord stem cells in the horse from which they were harvested, but also allogenic stem cell therapies
(use in horses other than the donor). As stated by Dr. Betts, ‘‘This knowledge has the potential to greatly enhance clinicians’ ability to make rational decisions regarding the choice of stem cell to use in specific situations.’’
CONTINUING PROJECTS LEVOTHYROXINE AS A TREATMENT FOR INSULIN RESISTANCE IN HORSES (TOWARD A DEFENSE AGAINST LAMINITIS) Nicholas Frank, University of Tennessee; Ray Boston, University of Pennsylvania
CALCIUM/MAGNESIUM AND HORMONES IN SEPTIC FOALS R. E. Toribio, C. Kohn, S. Hurcombe, and Nathan Slovis, The Ohio State University, and Hagyard-DavidsonMcGee, Lexington, KY THE CHANGING SHAPE OF THE FETLOCK JOINT AND ITS IMPORTANCE TO INCIDENCE OF JOINT DISEASE AND INJURY Chris Kawcak, C. Puttlitz, C. W. McIlwraith, K. Parkin, and K. Morgan Colorado State University, Animal Health Trust, Newmarket, England, and University of Liverpool
REDUCING WOUND INFECTIONS OF ORTHOPEDIC SURGERIES
EFFICACY OF VALACYCLOVIR AGAINST NEUROPATHOGENIC EHV-1
Dean Richardson, Thomas Schaer, Noreen Hickok and Christopher Adams, University of Pennsylvania and Thomas Jefferson University
Lara Maxwell, Oklahoma State University, and Brad Bentz, Richard Eberle, Charles MacAllister, and Jerry Ritche
CONTROL OF RHODOCOCCUS EQUI PNEUMONIA USING GALLIUM
THE NEUROLOGIC EHV-1 MARKER: CORRELATION OR CAUSATION?
Keith Chaffin, Noah Cohen, and Ronald Martens, Texas A & M University
Nikolaus Osterrieder, Cornell University
BLOOD SUPPLY TO THE MARE’S UTERUS IS RELATED TO INFERTILITY: EVALUATION AND TREATMENT
Reprinted with permission from GraysonJockey Club Research Foundation, Research Today Vol. 25, No. 1.
RESEARCH MANAGER’S REPORT, RURAL Irwin Liu and Eugene Steffey, Univer- INDUSTRIES RESEARCH AND sity of California-Davis DEVELOPMENT CORPORATION HORSE PROGRAM, AUSTRALIA PROMOTING SPECIFIC IMMUNITY IN FOALS D. W. Horohov, C. Merant, and C. Breathnach, University of Kentucky NORMAL AND ABNORMAL FUNCTIONS OF SPECIFIC PROTEINS IN STALLION SEMEN M.H.T. Troedsson, W. C. Buhi, J. P. Verstegen, and M. L. MacPherson, University of Florida
by: Nigel Perkins, RIRDC Horse Program Research Manager The Rural Industries Research and Development Corporation (RIRDC) Horse R&D Program has received a recent boost to its research budget through significant contributions made by Racing Victoria Limited (RVL). Contributions made to the Program are doubled in terms of funds available for research because of the
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dollar-for-dollar matching of industry funds by the Australian Government through RIRDC core funds. I take my hat off to the Horse Program Committee, its Chairperson Jane Vincent, and the previous Research Managers, Reuben Rose, John Freestone, and David Hodgson for their hard work in helping the dream of increased research funds for the Program come to fruition. The RIRDC Horse Program has funded quality, world-recognized research from a relatively small funding base. The Program is grateful to its supporters; the achievements of the Program to date would not have been possible without their ongoing financial contributions. The Horse Committee, its Research Managers, and its Chairperson, Jane Vincent, have worked tirelessly to maintain the support of the groups that support the Program and to attract new funds through their communication with the horse industry. Since the Program began in 1995 more than 130 projects have been produced, and these RIRDC-funded projects have made an outstanding contribution to the depth of knowledge of horse health and management. The journey has been a frustrating one in some ways, because many potentially important research proposals could not be funded because of budget restraints. The additional funds available to the Horse Program through the contributions of the RVL will enhance RIRDC’s ability to support horse research in Australia. Information for researchers is available on the RIRDC website www. rirdc.gov.au, and researchers should be looking ahead to prepare for the 2008 2009 round of project proposals. The RIRDC Horse Program Committee is looking for quality, well-thought-through proposals that meet the priorities identified in the project prospectus. The RIRDC Horse Program is also in a position to fund scholarships and commis-
sioned research into a range of highpriority topics, and we will report on this in future issues of the newsletter. The Australian horse industry is battling an outbreak of equine influenza virus—the first ever in Australia—and the impact has been felt across all segments of the industry, from racing and breeding involving Thoroughbreds and Standardbreds, competition, and Pony Club horses, working horses involved in contract mustering, and the weekend riding enthusiast. All stakeholders in the broader equine industries are united in their determination to assist authorities in containing the disease and then eradicating it from Australian shores. We look forward to resumption of the full range of activities showcasing the horse. The RIRDC Horse Program is aware that the outbreak may impact future R&D priorities and we will continue to liaise with industry stakeholders about this issue as the response unfolds. Reprinted from the RIRDC Equine Research News with the permission of the RIRDC Horse Program Committee.
NEW TREATMENT FOR ENDOTOXEMIA Endotoxemia, a condition that is a common complication of colic, is a serious problem that occurs when toxic substances associated with bacteria (endotoxins) enter the bloodstream. These substances are usually confined to the gut but may cross the gut wall when horses are suffering conditions such as colic. The entry of endotoxins into the bloodstream causes widespread organ problems and can lead to severe shock and death in some cases. Studies in humans and pigs have shown that the infusion of a phospholipid emulsion into the bloodstream significantly reduces the effects of endotoxins. The emulsion contains fatty acids and phospholipids, which are cell membrane components that are present in all plants and animals. Phos-
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pholipids can mimic or enhance physiologic processes, and they have been shown to bind and neutralize endotoxins. Early research of phospholipid emulsion to treat endotoxemia in horses showed that the emulsion reduced the effects of endotoxins. However, the studies found that the treatment caused an unacceptable level of damage to red blood cells of horses, leading to serious kidney problems. Researchers in the United States recently investigated the use of a much lower dose of phospholipids given at a slower rate than that used in previous studies. Their treatment regimen was very successful in reducing the clinical signs of endotoxemia with negligible effects on red blood cells. This method will be further developed, and it promises to be an extremely useful treatment option for horses suffering, or at risk of developing, endotoxemia. REFERENCE Moore JN, Norton N, Barton MH, Hurley DJ, Reber AJ, Donovan DC, et al. Rapid infusion of a phospholipid emulsion attenuates the effects of endotoxaemia in horses. Equine Vet J 2007;39:243 248. Reprinted from the RIRDC Equine Research News with the permission of the RIRDC Horse Program Committee.
LINKING LAMENESS AND BACK PAIN The relationship between back pain and lameness has long been debated. Some studies have shown an association between the two problems, and other studies have suggested there is no link. With recent developments in methods used to analyze kinematics (movement), researchers in the Netherlands have been able to accurately study changes in the movement of the horses back when mild lameness is present. Mild lameness was induced using a modified shoe that had a small nut
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welded to the inner surface of the toe region. A bolt could be tightened in the nut to exert pressure on the sole. The degree of lameness induced was so subtle that it could not easily be judged by the human eye but was confirmed using high-tech equipment that calculated the amount of weight that the horse put on each limb as it moved. Light reflecting markers were placed at a number of points on the head, neck, along the spine, on the hips and hooves of the horses. The horses were videotaped at the walk and trot, and movement data were analyzed. Not surprisingly, the researchers found significant movement of the head and neck in lame horses at the trot. It is well established that lameness results in an increased up and down movement of the head and neck. It has been a commonly held belief by some that, apart from an increased movement of the head and neck, the effect of subtle lameness would be absorbed by the limbs and would not be transferred to the upper body and spine. This study established that with mild lameness there is a significant change in the movement of the entire back when the horse is walking and trotting. This finding has implications for the management and investigation of back problems and lameness in horses. The changes in back movement with mild lameness could affect muscle tension and normal back function, leading to back pain and associated problems. This raises a question of whether some horses with back pain should also be investigated for subtle lameness issues as an underlying cause. Also, horses with known chronic lameness that does not otherwise impede their
training should be monitored for the development of back pain. REFERENCE Alvarez CB, Wennerstrand J, Bobbert MF, Lamers L, Johnston C, Back W, et al. The effect of induced forelimb lameness on thoracolumbar kinematics during treadmill locomotion. Equine Vet J 2007;39:197 201. Reprinted from the RIRDC Equine Research News with the permission of the RIRDC Horse Program Committee.
CREATINE SUPPLEMENTATION Creatine is an organic compound that is abundant in muscles and plays a role in the availability of energy to muscle tissues. Creatine can be purchased as a dietary supplement, and some owners and trainers add it to horse feeds with a view to increasing the muscle bulk of their horses. A recent study compared the development of muscle in two groups of horses, with one group receiving creatine as a dietary supplement and the other group receiving no supplement. Horses were unfit at the beginning of the study, and they all underwent the same training program to assess the affects of creatine supplementation. The findings showed that exercise increased muscle bulk in all of the horses in the study. There was no beneficial effect on body composition in the horses supplemented with creatine. REFERENCE D’Angelo HFD, Mota MDS, Greitas EVV, Ferraz GC, Abrahao AR, Lacerda-Neto JC, et al. Aerobic training,
but not creatine, modifies longissimus dorsi muscle composition. J Equine Vet Sci 2007;27:118 122. Reprinted from the RIRDC Equine Research News with the permission of the RIRDC Horse Program Committee.
COVER UP AFTER COLIC SURGERY After exploratory laparotomy for colic, some practitioners choose to cover the surgical site with a bandage while others choose to leave the site uncovered. The value of these strategies in reducing the incidence of postsurgical complications has not previously been investigated. A recent study in the United Kingdom has shown that the application of an abdominal bandage after exploratory laparotomy for colic can reduce the risk of complications, such as infections, by up to 45%. In the study, the surgical site was bandaged after surgery and the bandages were changed 24 hours later. The bandages were then changed every 2 days until the horse was discharged from hospital. Owners were asked to change the bandages a week later and to remove the bandages 2 weeks after discharge from hospital. REFERENCE Smith LJ, Mellor DJ, Marr CM, Reid SWJ, Mair TS. Incisional complications following exploratory celiotomy: does an abdominal bandage reduce risk? Equine Vet J 2007;39:277 283. Reprinted from the RIRDC Equine Research News with the permission of the RIRDC Horse Program Committee.
NEW PROJECTS HYDROCORTISONE REPLACEMENT THERAPY IN SEPTIC FOALS Dr. Michelle Henry Barton, University of Georgia Infection is regarded as the number one cause for illness and death in newborn foals. This research team— involving scientists at the Universities of Georgia and Florida as well as Cor-
0737-0806/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jevs.2008.04.008
372
nell University—reports that approximately 75% of newborn foals admitted to referral hospitals have the condition, and at least 25% of those are lost. Production of the hormone cortisol is a defense against infection, but perhaps as many as 50% of infected newborns (septic foals) suffer from insufficiency of cortisol. A synthetic cortisol product, hydrocortisone, is used in human medicine to reduce incidence of death in such cases. This project will seek to determine a safe dose of hydrocortisone that will reduce severity of disease and improve survival rates of septic foals, in a controlled hospital setting. DOES AIRBORNE EXPOSURE PREDICT PNEUMONIA? Dr. Noah Cohen, Texas A & M The foundation has funded several projects on viral pneumonia, a major cause of death in foals. There is no effective vaccine, and among questions unanswered are why some farms experience a higher incidence than others and why some foals on a given farm become infected while others do not. This project is a continuation of research by one of the leading epidemiologists in North America. (It was Dr. Cohen whom the foundation called on to head the epidemiologic team when it partnered with the Commonwealth of Kentucky in an initial study on mare reproductive loss syndrome.) In this proposal, Dr. Cohen will test whether existence of virulent Rhodococcus equi in the air predicts the outset of the disease. If the answer is positive, farms could initiate strategies to reduce the amount of contamination. MAPPING OCCLUSION OF VEINS IN EXERCISE-INDUCED PULMONARY HEMORRHAGE Dr. Fred Derksen, Michigan State University This is another approach in the series of attempts to understand fully why so many horses experience bleeding (exercise-induced pulmonary hemorrhage: EIPH) in the lungs as a result of high exercise. In past research
funded by the foundation, this research team discovered scarring around blood vessels, which obstructs the veins and causes backup in the lungs and rupture of its small blood vessels. This new project is designed to determine the location and extent of vein scarring in the lungs and compare it with horses that have not raced, also relating the location of the scarring with the location of the bleeding. Another aspect will be investigating why vein scarring occurs by studying molecules in the vein walls that signal scarring to occur. This project has the potential to guide research in a new direction for effective prevention or treatment of a widespread occurrence. DIFFERENTIATION OF STEM CELLS FOR CARTILAGE REPAIR Dr. Alan Nixon, Cornell University Cartilage damage affects both yearlings and horses in training and commonly triggers the development of arthritis. The resultant stress of the joint also can lead to fractures of the pastern or cannon bone. Dr. Nixon points out that ‘‘despite popular perception, cultured stem cells or marrow-derived mixtures so far seem incapable of forming durable cartilage.’’ Past attempts have created only transitory effects on cartilage. His current approach is to use and test robust gene-based methods to turn stem cells from the animal’s own marrow into dedicated cartilage cells: ‘‘These equine-specific genes have been recombined into nonviral vectors that insert them into the chromosomal DNA of target cells.’’ EFFECTS OF COMBINING LIDOCAINE AND FLUNIXIN Dr. Butch KuKanich, Kansas State University This grant examines the dosages of lidocaine and flunixin to ensure safety of the animals being treated. The two medications are often used together, especially after surgery for colic and other intestinal problems. Lidocaine has narrow parameters for dosages and can create toxicity, which results in seizure and collapse—putting the
Journal of Equine Veterinary Science Vol 28, No 6 (2008)
CURRENT RESEARCH Vol 28, No 6 (2008)
horse, and its handlers, in danger. The study will seek to determine whether commonly used dosages need to be adjusted because of how these drugs interact.
of more effective treatments for the disease.
A RESPIRATORY MODEL ON INTERACTIONS OF VIRUS AND HOST
Dr. Udeni Balasuriya, University of Kentucky Because the University of Kentucky is a designated reference laboratory for the World Organization of Animal Health, many tissue and serum samples from the 10-state outbreak of equine viral arteritis (EVA) of 2006 07 are available there for research. This project will characterize the genes that encode structural protein of the virus and sequence the genome of EVA samples from different states involved in the outbreak. Because the samples were collected over nearly a year, the evolution of the EVA virus over time can be studied. The researchers should be able to identify ‘‘mutational hot spots’’ and ‘‘hopefully have a greater understanding of the genetic basis of persistent EVA infection in the carrier stallion.’’ The researchers are confident their work will ‘‘impact the nature of control measure to prevent EVA infection . . . as well as allow us to develop more reliable molecular diagnostic tests.’’
Dr. Gisela Sobol, Colorado State University Dr. Sobol points out that ‘‘despite years of research, major epidemics of equine influenza virus and equine herpes virus-1 (EHV-1) remain a worldwide problem.’’ This project seeks understanding of why initial encounters of a pathogen determine downstream events and the outcome of the disease. Little is known about that initial situation. This project will employ a specific equine cell culture system to study the initial defense mechanisms to develop the necessary knowledge that can lead to immune modulators and anti-inflammatory drugs.
XENOGRAFTING TO STUDY TESTICULAR FUNCTION IN STALLIONS Drs. Ina Dobrinski and Regina Turner, University of Pennsylvania ‘‘Age-related testicular degeneration is a common cause of progressive infertility,’’ the researchers point out. Underlying causes are not well understood, so no satisfactory treatment has been developed. These researchers found in 2006 that in severe cases it is the testis itself and not the extratesticular environment that is defective. A process known as xenografting will further verify that finding and will also test whether common treatments for testicular degeneration actually have a positive effect on the diseased tissue. Xenografting ‘‘will allow us to answer these questions . . . without having to perform experiments on the horses.’’ Improved understanding could lead to creation and evaluation
MOLECULAR EPIDEMIOLOGY OF THE 2006 OUTBREAK OF EQUINE VIRAL ARTERITIS
NEUROPATHOGENESIS OF EHV-1 INFECTION Dr. Lutz S. Goehring, Colorado State University The foundation has been funding research on the sometimes deadly EHV1 infection for a number of years and last year launched two projects chosen as a result of a special call for research on that subject. The Research Advisory Committee scored this project very highly as a worthy addition to work being done on the subject. Currently there is no effective vaccine, and in fact, there are indications that the vaccines in use might actually be detrimental to horses suffering from this particular type of herpesvirus (EHV1). The nonexistence of experimental
373
models has hampered research. As a solution, these researchers ‘‘propose to establish an endothelial cell culture system and . . . to study how the process of virus transfer from white blood cells into endothelial cells occurs.’’ They will also seek methods to intervene with the various processes involved in a horse developing EHV-1. MOLECULAR AND CELLULAR LEVEL STUDIES OF LAMINITIS Dr. Hannah Galantino-Homer, University of Pennsylvania This project takes an approach to laminitis that is aimed, the researchers explain, ‘‘to further our understanding by focusing our efforts at the molecular and cellular levels.’’ Currently, laminitis still is so baffling to scientists that researchers tend to be split into two camps (theories) as to the cause of the problem—vascular and enzymatic. ‘‘The lack of agreement about the basic pathophysiology of laminitis explains why standard guidelines for therapy are not yet available,’’ noted Dr. Galantino-Homer. If this project can identify which specific genes and proteins are upregulated or downregulated during the first phase of the disease—when identifiable symptoms are not yet manifested—it ‘‘will determine the pathways of the disease and allow institution of preventive or interventional treatments sooner.’’ The first phase of laminitis, the developmental phase, is followed, of course, by the acute phase, and one of the frustrations of dealing with the disease is that often by the time it is diagnosed, the horse may be gravely threatened. These researchers believe the study ‘‘will provide information that we and other investigators can use to verify or elaborate on existing theories about laminitis, explore previously unrecognized cellular and molecular events during laminitis, and validate in vitro models of laminitis.’’ The latter will facilitate research projects that do not require laminitic horses.
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374
MECHANISMS OF MAINTENANCE OF EARLY PREGNANCY Dr. Keith Betteridge, Guelph University This project addresses the frequent scenario of a mare being diagnosed as pregnant soon after breeding, but quickly losing the pregnancy. The 3week stage has been identified as the point when the conceptus (embryo and associated tissues and fluids) has to become immobilized at the position in the uterus where the placenta will develop. The research is aimed at understanding the processes by which this either occurs, and the pregnancy continues, or fails to occur successfully. This research team utilizes various physiologic, biochemical, proteomic, and molecular methods to identify changes in proteins, steroid hormones, and other molecules that are altered during the critical phase: ‘‘Several distinct differences between normal and failing pregnancies have already’’ been identified. Continuing understanding from this project could lead to diagnostic tests of the reproductive health of mares as well as treatments that improve the success rate of early pregnancies.
CORD BLOOD STEM CELLS: FROM FARM TO POINT OF CARE Dr. Dean Betts, Guelph University This is another project seeking to overcome the problem of stem cells being unsuccessful so far as an antidote to cartilage lesions. Research in human medicine indicates that umbilical cord cells are more effective than stem cells from fat or bone marrow. The researchers have already isolated umbilical cord blood stem cells in horses and have ‘‘demonstrated their potential to form bone, cartilage, and fat in petri dishes.’’ This project will continue the learning curve, not only in use of cord stem cells in the horse from which they were harvested, but also allogenic stem cell therapies
(use in horses other than the donor). As stated by Dr. Betts, ‘‘This knowledge has the potential to greatly enhance clinicians’ ability to make rational decisions regarding the choice of stem cell to use in specific situations.’’
CONTINUING PROJECTS LEVOTHYROXINE AS A TREATMENT FOR INSULIN RESISTANCE IN HORSES (TOWARD A DEFENSE AGAINST LAMINITIS) Nicholas Frank, University of Tennessee; Ray Boston, University of Pennsylvania
CALCIUM/MAGNESIUM AND HORMONES IN SEPTIC FOALS R. E. Toribio, C. Kohn, S. Hurcombe, and Nathan Slovis, The Ohio State University, and Hagyard-DavidsonMcGee, Lexington, KY THE CHANGING SHAPE OF THE FETLOCK JOINT AND ITS IMPORTANCE TO INCIDENCE OF JOINT DISEASE AND INJURY Chris Kawcak, C. Puttlitz, C. W. McIlwraith, K. Parkin, and K. Morgan Colorado State University, Animal Health Trust, Newmarket, England, and University of Liverpool
REDUCING WOUND INFECTIONS OF ORTHOPEDIC SURGERIES
EFFICACY OF VALACYCLOVIR AGAINST NEUROPATHOGENIC EHV-1
Dean Richardson, Thomas Schaer, Noreen Hickok and Christopher Adams, University of Pennsylvania and Thomas Jefferson University
Lara Maxwell, Oklahoma State University, and Brad Bentz, Richard Eberle, Charles MacAllister, and Jerry Ritche
CONTROL OF RHODOCOCCUS EQUI PNEUMONIA USING GALLIUM
THE NEUROLOGIC EHV-1 MARKER: CORRELATION OR CAUSATION?
Keith Chaffin, Noah Cohen, and Ronald Martens, Texas A & M University
Nikolaus Osterrieder, Cornell University
BLOOD SUPPLY TO THE MARE’S UTERUS IS RELATED TO INFERTILITY: EVALUATION AND TREATMENT
Reprinted with permission from GraysonJockey Club Research Foundation, Research Today Vol. 25, No. 1.
RESEARCH MANAGER’S REPORT, RURAL Irwin Liu and Eugene Steffey, Univer- INDUSTRIES RESEARCH AND sity of California-Davis DEVELOPMENT CORPORATION HORSE PROGRAM, AUSTRALIA PROMOTING SPECIFIC IMMUNITY IN FOALS D. W. Horohov, C. Merant, and C. Breathnach, University of Kentucky NORMAL AND ABNORMAL FUNCTIONS OF SPECIFIC PROTEINS IN STALLION SEMEN M.H.T. Troedsson, W. C. Buhi, J. P. Verstegen, and M. L. MacPherson, University of Florida
by: Nigel Perkins, RIRDC Horse Program Research Manager The Rural Industries Research and Development Corporation (RIRDC) Horse R&D Program has received a recent boost to its research budget through significant contributions made by Racing Victoria Limited (RVL). Contributions made to the Program are doubled in terms of funds available for research because of the
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dollar-for-dollar matching of industry funds by the Australian Government through RIRDC core funds. I take my hat off to the Horse Program Committee, its Chairperson Jane Vincent, and the previous Research Managers, Reuben Rose, John Freestone, and David Hodgson for their hard work in helping the dream of increased research funds for the Program come to fruition. The RIRDC Horse Program has funded quality, world-recognized research from a relatively small funding base. The Program is grateful to its supporters; the achievements of the Program to date would not have been possible without their ongoing financial contributions. The Horse Committee, its Research Managers, and its Chairperson, Jane Vincent, have worked tirelessly to maintain the support of the groups that support the Program and to attract new funds through their communication with the horse industry. Since the Program began in 1995 more than 130 projects have been produced, and these RIRDC-funded projects have made an outstanding contribution to the depth of knowledge of horse health and management. The journey has been a frustrating one in some ways, because many potentially important research proposals could not be funded because of budget restraints. The additional funds available to the Horse Program through the contributions of the RVL will enhance RIRDC’s ability to support horse research in Australia. Information for researchers is available on the RIRDC website www. rirdc.gov.au, and researchers should be looking ahead to prepare for the 2008 2009 round of project proposals. The RIRDC Horse Program Committee is looking for quality, well-thought-through proposals that meet the priorities identified in the project prospectus. The RIRDC Horse Program is also in a position to fund scholarships and commis-
sioned research into a range of highpriority topics, and we will report on this in future issues of the newsletter. The Australian horse industry is battling an outbreak of equine influenza virus—the first ever in Australia—and the impact has been felt across all segments of the industry, from racing and breeding involving Thoroughbreds and Standardbreds, competition, and Pony Club horses, working horses involved in contract mustering, and the weekend riding enthusiast. All stakeholders in the broader equine industries are united in their determination to assist authorities in containing the disease and then eradicating it from Australian shores. We look forward to resumption of the full range of activities showcasing the horse. The RIRDC Horse Program is aware that the outbreak may impact future R&D priorities and we will continue to liaise with industry stakeholders about this issue as the response unfolds. Reprinted from the RIRDC Equine Research News with the permission of the RIRDC Horse Program Committee.
NEW TREATMENT FOR ENDOTOXEMIA Endotoxemia, a condition that is a common complication of colic, is a serious problem that occurs when toxic substances associated with bacteria (endotoxins) enter the bloodstream. These substances are usually confined to the gut but may cross the gut wall when horses are suffering conditions such as colic. The entry of endotoxins into the bloodstream causes widespread organ problems and can lead to severe shock and death in some cases. Studies in humans and pigs have shown that the infusion of a phospholipid emulsion into the bloodstream significantly reduces the effects of endotoxins. The emulsion contains fatty acids and phospholipids, which are cell membrane components that are present in all plants and animals. Phos-
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pholipids can mimic or enhance physiologic processes, and they have been shown to bind and neutralize endotoxins. Early research of phospholipid emulsion to treat endotoxemia in horses showed that the emulsion reduced the effects of endotoxins. However, the studies found that the treatment caused an unacceptable level of damage to red blood cells of horses, leading to serious kidney problems. Researchers in the United States recently investigated the use of a much lower dose of phospholipids given at a slower rate than that used in previous studies. Their treatment regimen was very successful in reducing the clinical signs of endotoxemia with negligible effects on red blood cells. This method will be further developed, and it promises to be an extremely useful treatment option for horses suffering, or at risk of developing, endotoxemia. REFERENCE Moore JN, Norton N, Barton MH, Hurley DJ, Reber AJ, Donovan DC, et al. Rapid infusion of a phospholipid emulsion attenuates the effects of endotoxaemia in horses. Equine Vet J 2007;39:243 248. Reprinted from the RIRDC Equine Research News with the permission of the RIRDC Horse Program Committee.
LINKING LAMENESS AND BACK PAIN The relationship between back pain and lameness has long been debated. Some studies have shown an association between the two problems, and other studies have suggested there is no link. With recent developments in methods used to analyze kinematics (movement), researchers in the Netherlands have been able to accurately study changes in the movement of the horses back when mild lameness is present. Mild lameness was induced using a modified shoe that had a small nut
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welded to the inner surface of the toe region. A bolt could be tightened in the nut to exert pressure on the sole. The degree of lameness induced was so subtle that it could not easily be judged by the human eye but was confirmed using high-tech equipment that calculated the amount of weight that the horse put on each limb as it moved. Light reflecting markers were placed at a number of points on the head, neck, along the spine, on the hips and hooves of the horses. The horses were videotaped at the walk and trot, and movement data were analyzed. Not surprisingly, the researchers found significant movement of the head and neck in lame horses at the trot. It is well established that lameness results in an increased up and down movement of the head and neck. It has been a commonly held belief by some that, apart from an increased movement of the head and neck, the effect of subtle lameness would be absorbed by the limbs and would not be transferred to the upper body and spine. This study established that with mild lameness there is a significant change in the movement of the entire back when the horse is walking and trotting. This finding has implications for the management and investigation of back problems and lameness in horses. The changes in back movement with mild lameness could affect muscle tension and normal back function, leading to back pain and associated problems. This raises a question of whether some horses with back pain should also be investigated for subtle lameness issues as an underlying cause. Also, horses with known chronic lameness that does not otherwise impede their
training should be monitored for the development of back pain. REFERENCE Alvarez CB, Wennerstrand J, Bobbert MF, Lamers L, Johnston C, Back W, et al. The effect of induced forelimb lameness on thoracolumbar kinematics during treadmill locomotion. Equine Vet J 2007;39:197 201. Reprinted from the RIRDC Equine Research News with the permission of the RIRDC Horse Program Committee.
CREATINE SUPPLEMENTATION Creatine is an organic compound that is abundant in muscles and plays a role in the availability of energy to muscle tissues. Creatine can be purchased as a dietary supplement, and some owners and trainers add it to horse feeds with a view to increasing the muscle bulk of their horses. A recent study compared the development of muscle in two groups of horses, with one group receiving creatine as a dietary supplement and the other group receiving no supplement. Horses were unfit at the beginning of the study, and they all underwent the same training program to assess the affects of creatine supplementation. The findings showed that exercise increased muscle bulk in all of the horses in the study. There was no beneficial effect on body composition in the horses supplemented with creatine. REFERENCE D’Angelo HFD, Mota MDS, Greitas EVV, Ferraz GC, Abrahao AR, Lacerda-Neto JC, et al. Aerobic training,
but not creatine, modifies longissimus dorsi muscle composition. J Equine Vet Sci 2007;27:118 122. Reprinted from the RIRDC Equine Research News with the permission of the RIRDC Horse Program Committee.
COVER UP AFTER COLIC SURGERY After exploratory laparotomy for colic, some practitioners choose to cover the surgical site with a bandage while others choose to leave the site uncovered. The value of these strategies in reducing the incidence of postsurgical complications has not previously been investigated. A recent study in the United Kingdom has shown that the application of an abdominal bandage after exploratory laparotomy for colic can reduce the risk of complications, such as infections, by up to 45%. In the study, the surgical site was bandaged after surgery and the bandages were changed 24 hours later. The bandages were then changed every 2 days until the horse was discharged from hospital. Owners were asked to change the bandages a week later and to remove the bandages 2 weeks after discharge from hospital. REFERENCE Smith LJ, Mellor DJ, Marr CM, Reid SWJ, Mair TS. Incisional complications following exploratory celiotomy: does an abdominal bandage reduce risk? Equine Vet J 2007;39:277 283. Reprinted from the RIRDC Equine Research News with the permission of the RIRDC Horse Program Committee.