JOCKEY CLUB NOTES
|Contact: Ed Bowen (859-224-2850)
NEW RESEARCH COVERS WIDE RANGE OF HORSE HEALTH ISSUES
The board of directors of Grayson-Jockey Club Research Foundation has authorized funding of 22 equine research projects for a total of $777,524 in the year 2002. The scientific research addresses various important issues of horse health, including Mare Reproductive Loss Syndrome, Laminitis, athletic soundness, and cutting-edge use of adult stem cells for cartilage repair. The 22 projects will be conducted simultaneously at 16 universities in the United States and Canada.
Nine of the projects are two year-grants entering their second year, while 13 are one- or two-year grants being begun in 2002.
Following are descriptions of the new grants, to be launched in 2002:
ROLE OF INTESTINAL DISEASE AS A CAUSE OF LAMINITIS
Laminitis (founder) continues to be one of the most common and baffling lameness issues in horses and frequently results in humane destruction. Recent work on laminitis has given rise to an hypothesis which this project will probe further. Namely, overgrowth of a specific bacteria (Streptococcus bovis) in the large intestine is thought to be associated with production of toxins which can cause laminitis. Several techniques will seek to determine whether this change of events includes creation of degradative enzymes (known to be connected with laminitis) and whether the toxins can induce separation of the hoof wall, which is one of the most serious and painful aspects of laminitis cases. Specific knowledge of any of the routes leading to laminitis, of course, would create opportunities to avoid onset of the disease.
This project was selected by the Foundation board of directors as recipient of the Dubai Millennium Equine Research grant, in honor of the European champion race horse who died in 2001. Sheikh Mohammed of the Maktoum family who raced Dubai Millennium in its Godolphin stable, had donated a season in the horse to Grayson-Jockey Club. The season was sold for $270,000 at the 2000 Keeneland November sale, the entire amount going to support equine research via the Foundation.
HORMONAL FUNCTION IN MARES SUFFERING FROM MRLS
MRLS (Mare Reproductive Loss Syndrome) is the name associated with whatever caused thousands of early and late term abortions in 2001. The underlying causes of the problem are not understood. This project is designed to evaluate changes in reproductive hormones during the outbreak, using cases that were sampled before, during, and after the occurrence. Clinical data and samples were provided by several Central Kentucky veterinarians, and the scientists are thus able to take advantage of that timely response to the problem. Clues as to when the sequence of events began may be evident in these tests and provide direction in the search for causes. In addition, further evidence is expected related to the inability of early aborting mares to breed back.
ACTIVITY OF GENES, AS RELATES TO DISEASES CAUSED BY A COMMON CATEGORY OF
In general, bacteria are categorized as one of two types, based on a system developed by a Dr. Gram more than a century ago. Hence, they are known as either Gram-negative or Gram-positive. This project seeks a new direction in addressing Gram-positive bacteria, which are associated with pneumonia, strangles, septic arthritis, etc. Relatively little research has been accomplished to examine the role of specific Gram-positive bacterial cell wall toxins in these diseases. The researchers will be the first to address that question by using a functional genetic approach that will allow them to follow simultaneously the activity of 2,000 equine genes in the disease process. This not only will help understand the effects of the bacterial toxins, but will also generate information beneficial to other researchers addressing the various diseases which are associated with the bacteria.
RESPIRATORY IMMUNE RESPONSE IN YOUNG FOALS
This is a project by a researcher whom we have funded in the past for work on effects of exercise on blood, which was directed at the horse but wound up related to HIV work and U. S. Army research on troop health. The present project will delve into the immune system of young foals, which are susceptible to respiratory infections not normally encountered in the adult horse. Although it is known that maternal antibodies play an important role in providing protection until the foal's own immune system becomes effective, little is understood about how this maturing of the foal's immune system takes place. Dr. Horohov notes that "there are repeated calls for earlier and earlier vaccinations in order to prevent respiratory disease." The goal of this project is to better characterize the immunity status of the foal's respiratory system. Study of what are called Th2 and Th1 cytokine responses will test the hypothesis that foals and adults exhibit different responses. Current opinion is that maturity of lung immunity requires exposure to certain viral and bacterial agents; otherwise, allergies and obstructive airway disease will develop later. This project will provide some insights into the consequences of the early viral exposure.
STUDY OF BACTERIA ASSOCIATED WITH MRLS
As research on Mare Reproductive Foal Loss continues on various fronts, this project will respond to the fact that bacteria were recovered from most of the fetuses collected at the Livestock Disease Diagnostic Center. Moreover, "preliminary data indicate that the bacteria may be a new species that has not previously been identified with abortions/stillbirths," notes the researcher. The aims of this project are to identify the type and origins of the bacteria species involved and determine what (antimicrobial) agents can be useful for treatment.
ADDRESSING POSSIBLE SIDE EFFECTS OF USE OF PHENYLBUTAZONE
Phenylbutazone is one of the most commonly used medications of a specific category (non-steroidal anti-inflammatory drugs, or NSAIDs). It is generally thought to be well-tolerated by horses at recommended dosage and frequency. However, the medication also has been associated with several adverse side-effects, including stomach ulcers, kidney dysfunction, and inflammation/ulceration of the large colon (right dorsal colitis, or RDC). Diagnosis is difficult due to the vagueness of clinical signs, and it is postulated that only severe cases are reported, skewing available frequency data. The specific mechanism of whatever colon damage might be caused by Phenylbutazone has not been determined. Meanwhile, advice is inconsistent from one veterinarian to another, and the researchers state that they are unaware of data supporting either of the most commonly prescribed dietary recommendations. This study will evaluate various clinical signs and specific phenomena with the intent of discovering mechanisms related to RDC and developing methods to help treat and prevent that condition.
USE OF STEM CELLS FOR CARTILAGE REPAIR TO COMBAT ARTHRITIS AND
We have funded this researcher in initial studies of how stem cells can be utilized in cartilage repair, and this new project represents another step. Stems cells answer the body's call for repair of tissues such as muscle, tendon, bone, and fat as well as cartilage. The specific aim of this project is to use stem-cell based cartilage resurfacing to lessen arthritis and stress-induced fetlock breakdown. (These are not embryonic stem cells, so their production does not involve a sacrificed pregnancy.) Knowledge of specific growth factors will be utilized to develop a dual impact: Stem cells that are transformed toward new cartilage cells at the time of implant and also contain active stimulus genes that promote deposit of new cartilage.
ELECTRICAL TREATMENT FOR HEART RHYTHM DISTURBANCE
When horses experience heart rhythm disturbance (atrial fibrillation), they are rendered useless as athletes of any sort if the condition cannot be corrected. Although commonly used therapies for atrial fibrillation have a high success rate, they also tend to cause adverse side effects. Treatment of atrial fibrillation in humans has been developed utilizing small electrical shock via special catheters threaded through veins and into the heart. This project now proposes to extend that treatment approach to horses. The hypothesis to be evaluated is that effective treatment of the equine can be achieved using short-term general anesthesia with little or no side effects. The ultimate objective would be an outpatient, standing procedure for atrial fibrillation in the horse.
PRODUCTION OF SYNTHETIC HORMONES ESSENTIAL FOR FERTILITY
The long-term goal of this project is to provide a continuous supply of two reproductive hormones that can be used as breeding management tools. These two hormones, follicle stimulating hormone and luteinizing hormone, are essential for stimulating follicle development in the mare and sperm production in the stallion. Since the natural source of these hormones is the equine brain, it is difficult to obtain and purify supplies for use in cases where individuals are deficient. This project seeks to utilize molecular biology technology which takes the DNA of the hormone and inserts it into a biological cell line able to produce the hormone in the laboratory. The researchers will test the efficacy of the resulting synthetic (recombinant) hormones. Successful production of effective hormones will allow for a supply to be available for veterinarians and would be applicable to Mare Reproductive Loss Syndrome, induction of ovulation, post-surgical cell tumors, subfertility in stallions, and other situations. In MRLS, these hormones would be used to stimulate follicle activity and ovulation for re-breeding. These hormones also could help fill a problem affecting many clinical laboratories since they are useful as reagents for diagnostic purposes.
ACCELERATED RETURN TO BREEDING NORMALCY AFTER FETAL LOSS
Mares which abort during early gestation (40-80 days) are at high risk of maintaining the hormonal state associated with pregnancy even after the fetal loss. This project seeks to speed their return to normal cycling and thus allow re-breeding. The block to return to normalcy is associated with a small band of cells which break loose from the outer surface of the developing placenta and migrate to the uterus. These cells develop what are known as endometrial cups, which secrete one hormone and indirectly stimulate producing of another, progesterone, which impedes estrus and ovulation. In seeking to accelerate the regression of endometrial cups, the researchers are equipped to test the effectiveness of several techniques, including use of stimulants of the immune system and use of cell surface molecules and Gonadotropin.
EFFECT OF AIRWAY INFLAMMATION AND MUCUS
The long-range goal of this research team is to understand how inflammation in the throat and trachea affects performance. The program in this specific project is to measure the airway inflammation and mucus in a large group of Thoroughbreds and correlate it to performance. Young horses frequently have large amounts of mucus in their airways. In the absence of other problems, the mucus may be blamed for poor racing performance or ignored. There is no information to determine if the mucus accumulation is a sign of more severe lung disease, or is normal for that particular horse. Also, young horses in training frequently have pharyngitis, or inflammation of the back of the throat, characterized by redness, swelling, and enlarged tonsils. The cause and possible results of this condition are unknown. Aims of this project are: Determining the relationship of presence of mucus and performance; determining whether upper and lower airway inflammation occur together or independently; determining if the amount of mucus in the trachea correlates with the severity and type of inflammation in the trachea, and determining if upper airway inflammation if associated with upper airway dysfunction.
FUNCTIONAL ANALYSES OF SPECIFIC ARTERIES INVOLVED WITH LAMINITIS
On the many fronts of research into the dreaded laminitis, this research team believes itself to be the first to isolate small arteries of the laminae for functional study. The hypothesis is that the arteries to be studied in addressing laminitis are those directly involved in the disease process, i. e., small arteries located in the front portion of the hoof. Among the steps to be taken in this project is to expose these arteries to specific medications, which might help understanding which mechanisms regulate constriction and dilation and whether these mechanisms are unique to laminar arteries. This work is perceived as a possible foundation, too, for work to determine new therapeutic strategies for horses at risk of developing laminitis or already afflicted.
ALTERED DOSE PATTERN OF FUROSEMIDE FOR PATIENTS WITH EXCESSIVE FLUIDS
Although furosemide commonly is associated with attempts to combat exercise induced pulmonary hemorrhage (bleeding), this project addresses another use, i. e., in dealing with various diseases. Specifically, furosemide is used to remove excessive accumulations of various of the bodily fluids, a condition often life-threatening. In such usage, furosemide is routinely administered in bolus doses 1-3 times daily, but this regimen can cause marked fluctuations in blood volume and electrolyte concentrations which can be toxic. Recent studies in humans indicate that continuous rate infusion (CRI) instead of intermittent doses improves the usefulness of the medication while also reducing side effects. The researchers plan to test whether similar beneficial effects can be achieved for the horse by using CRI.
Two-year grants entering their second year in 2002 are as follows:
Identification of Immunology Proteins Specific to Strangles
Analysis of Semen in Unexplained Infertility Cases
Practical Equine DNA Vaccination
Is Suspensory Apparatus Injury Related to Condylar Fracture?
Seeking Solutions to Problems of the Cecum (Related to Colic)
The Role of Volatile Fatty Acids in Equine Gastric Ulcers
Development of a Refined Equine Model for EPM
Further Evaluation of Shoes and Impact Trauma
Use of Serum Markers to Detect Pending Joint and Bone Injury
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