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IRAP, PRP and Stem Cell Therapies  

Scott Hopper, DVM, MS, Dipl. ACVS

Several advanced scientific therapies for previously untreatable joint disease and equine injuries have been introduced into equine veterinary medicine over the last decade.  Veterinarians use IRAP, PRP and stem cell therapies to manipulate the body’s biological mechanisms to stimulate healing.
There is ongoing research for these therapies and new information is gathered each day. While the promise of cure is very exciting for both veterinary professionals and horse owners, it is important for the owner to understand the science behind each therapy in order to have a reasonable expectation for success.

IRAP
IRAP stands for Interluekin-1 Receptor Antagonist Protein and recently is being referred to as autologous conditioned serum.Equine athletes are susceptible to musculoskeletal injuries and osteoarthritis or degenerative joint disease. Osteoarthritis is a common cause of lameness in horses. Clinical signs include lameness, joint swelling and inflammation. These signs are a result of cartilage damage within the joint and inflammation of the joint lining or synovitis. Joint trauma results in the release of inflammatory mediators such as IL-1 and other cytokines. These cytokines including IL-1 can lead to further cartilage damage causing a vicious cycle of cartilage and joint damage which result in joint inflammation and lameness.

IRAP was developed to counteract IL-1 that is produced in the traumatized joint and to slow the progression of osteoarthritis. IRAP works by preventing IL-1 binding to the IL-1 receptors in the joint therefore blocking the damage and inflammation caused by IL-1.

IRAP involves drawing approximately 50 mls of your horse’s blood into a specialized syringe which stimulates the production of the antagonist protein.  The blood is incubated in the syringe for 24 hours.  After incubation the blood is placed in a centrifuge and the plasma which is rich in the antagonist protein is separated from the blood cells in multiple syringes.  IRAP is then injected into the joint once every 7-10 days for 3-5 treatments. Samples are stored in a -80 C freezer until use.

There are currently two products on the market - IRAP and IRAP II. IRAP is from Dechra Pharmaceuticals and IRAP II is from Arthrex Vet Systems. Recent research has compared the 2 products and concluded that IRAP II has a modestly improved cytokine profile but both products produced a significant increase in interleukin-1 receptor antagonist. These 2 products have not been compared clinically to determine if there is a clinically significant difference between the 2 products.

Platelet Rich Plasma (PRP)
PRP is another product that is derived from your horse’s own blood.  Platelets are loaded with numerous growth factors that are released upon platelet activation. Large amounts of transforming growth factor beta (TGF-β) and platelet derived growth factor and smaller amounts of insulin-like growth (IGF), epidermal growth factor (EGF) and TGF-αare released upon activation. These growth factors and others act synergistically to enhance access of healthy inflammatory cells to the area of tissue injury, formation of new blood vessels (angiogenesis), formation of new connective tissue (fibroplasia) and regeneration of skin (re-epithelialization).
 
PRP can be obtained in a matter of minutes. There are currently a variety of PRP kits available. Usually a centrifuge is used to help concentrate the platelets into the plasma which then can be used for treatment. (Centrifuge vile shown above left) PRP has been most commonly used to treat tendon and ligament injuries. The goal of treatment is to accelerate and improve the quality of healing. Recently veterinarians have begun to use PRP intra-articular to treat osteoarthritis.
 
Stem Cell Therapy
Stem cell therapy is an exciting new area of treatment for equine injuries.  Although there is much we still need to learn, early research is very encouraging. Current ongoing research will begin to offer answers and to shed some light on the best applications and techniques for the use of stem cell therapy.

Stem cells are undifferentiated cells that have the ability to replicate and differentiate into a diverse range of cell types. These cell types include tendon, ligament, cartilage, muscle and bone. There are two basic types of stem cells, hematopoetic and mesenchymal. We are primarily concerned with mesenchymal stem cells (MSC) because they appear to have the best potential for regenerative medicine. These MSC are found in bone marrow, fat, umbilical cord blood and tissue, and many other organs throughout the body. The younger or more immature the stem cell, the more potential they may have.  The younger stem cells have an increased ability to heal and regenerate tissue compared to the adult stem cells.  This is the reason for the recent interest in storing umbilical cord blood in horses. 

In equine practice stem cells are commonly derived from bone marrow obtained from the sternum (photo, above right) or the tuber coxae. Once the bone marrow has been obtained it is sent to a lab where it is cultured and expanded into millions of stem cells.  The typical dose ranges from 10 to 25 million stem cells per treatment.  The culture and expansion process takes approximately 3-4 weeks.  The stem cells can then be injected into the affected tendon, ligament or joint.  Recently, we have also been using stem cells to treat chronic laminitis cases with encouraging results. The multiple uses for stem cells have yet to be determined.

The second source of stem cells is fat.  Fat derived stem cells only contain 2-4% stem cells unless they are cultured and expanded.  Therefore adipose derived stromal fraction is the more appropriate term used to describe this therapy. 

Research comparing bone marrow derived to fat derived stem cells indicate that bone marrow derived stem cells are superior to fat derived stem cells.

IRAP, PRP and stem cell therapies offer the possibility of successful treatment of previously life-threatening or career-ending injuries. Consult your veterinarian to determine if one of these treatments may be appropriate for your horse. 

Equine Protozoal Myeloencephalitis - The Latest Information
Steve Reed, DVM, Dipl. ACVIM

Equine protozoal myeloencephalopathy (EPM) is one of the most important neurologic diseases in the horse and remains a problem for horses and their owners. Over the past several years’ work has been directed at better understanding this disease problem in horses along with how to treat and prevent the problem.  Prevention has been more difficult than anyone imagined. Wildlife management, risk-factor manipulation and preventative medications remain the center of attention.  Thus far efforts towards vaccine development have proven ineffective.

Original research in the mid-1990s led to the discovery of the opossum as the definitive host (carrier) for Sarcocystis neurona, the primary parasite that causes EPM in horses. Skunks, raccoons, armadillo, sea otters, harbor seals and even domestic cats can be intermediate hosts.  While in an intermediate host,the parasite goes through several stages of its life cycle.  Although these hosts cannot infect the horse, they are responsible for infecting the definitive host (opossum).Neospora hughesi is another parasite that can cause EPM.

Diagnosis
Horses that have clinical signs of ataxia (inability to coordinate voluntary muscle movement) should be tested for neurologic disease. Testing should begin with a neurological examination followed by use of a validated test from a recognized diagnostic laboratory. Many horses will test serum (blood) positive due to exposure and antibodies against these protozoan parasites.  The test I most often use is the S. neurona titer ratio.  This was developed by Dr. Dan Howe of the Gluck Equine Research Center and is commercially available through the Equine Diagnostic Solutions (EDS) laboratory in Lexington, Kentucky. This test can be done on blood and/or cerebrospinal fluid (CSF). Other tests include western blot analysis and Fluorescent antibody testing (IFA), which are done at several diagnostic laboratories (i.e. -IDEXX, UC Davis, Michigan State, Neogen, EDS).  In my opinion and experience the best testing includes examination of both blood and CSF. 

Treatment
The standard treatments for EPM remain Marquis or Pyrimethamine and Sulfadiazine in combination.  The newest protocol for Marquis administration requires five tubes with one-half tube  (4200#dose) being administered for two days followed by 28 days of the regular dose (1200#).  The newest medication is Diclazuril, which has been used in other formulations and will soon be available as Protazil by Intervet Schering-Plough.  When treating neurologic cases, I recommend the additional administration of natural Vitamin E (i.e. Nano-E®, Elevate®) to combat nervous system inflammation.

Prevention
Recent research suggests that risk factors for the disease include age of the horse, occupation of the horse, season of the year, presence of woods on the premises, presence of opossums, lack of feed security, health events before diagnosis and previous cases of EPM being diagnosed on the farm.  Any stressful situation such as travel, another illness or undergoing general anesthetic could be aggravating factors.
 
The opossum is a scavenger by nature and will eat anything (omnivorous). Thus the prevention of EPM remains problematic. Horse owners should pick up carrion (raccoon, skunks etc.) to keep them from being eaten by opossums. Hay and grain should be kept in opossum-proof facilities, as preventing access of opossums to the horse’s environment is difficult.  But even if this is done, there is still the inability to protect pastures from contamination.   As many of the factors are difficult to manipulate, improving the immune status of the horse may be an important and effective criteria.

Conclusions
Although we have a good understanding of the clinical signs and treatments as well as the life cycle of S. neurona, the principal cause of EPM, we are still working on ways to prevent this disease. One important technique to help prevent EPM is the removal of any intermediate hosts that have died from the environment, as these are the source of infection for the opossum. Therefore, picking up dead skunks, raccoons, armadillos or cats to prevent opossums from eating them should prevent the deposition of sporocysts from contaminating the environment and help reduce the incidence of EPM.  Whether a vaccine will ever be developed to help prevent this disease remains an open question at this time.

 

Don't Forget the Basics!

There are many new and exciting treatments, procedures and medications in veterinary medicine but when it comes to your horse’s health don’t forget the basics. Every owner should have a good vaccination, deworming and dental program suited for their horse. Following preventive programs for vaccinations, deworming and dental health is the best safeguard against disease or other health conditions that require costly treatments to resolve. These basics are a good foundation for a long, healthy, productive life for your horse. 

Vaccinate now or treat later?
Vaccinations might seem like a simple topic but as the first line of defense to protect your horse from disease they are a vital component to your horse’s health. Vaccines are a biological preparation of either a weakened or killed strain of a particular virus or bacteria or its toxins that when given to a horse, will stimulate an immune response with the body producing antibodies against the disease and thereby providing protection for the horse. The cost of an effective vaccination program will always be less than the cost of treating a life threatening disease.
 
Vaccination programs should be tailored to the individual horse and his situation taking into consideration multiple factors such as region, environment, exposure to other horses, and what the horse is used for such as pleasure, competition or breeding. Your veterinarian is always the best resource for designing the vaccination program most suited for your horse’s needs.
 
Regardless of region or other contributing factors to your horse’s vaccination program, there are 5 core vaccinations recommended by the American Association of Equine Practitioners that every horse should receive annually. These include Tetanus, Eastern/Western Equine Encephalomyelitis, Rabies and West Nile Virus. Other risk based vaccines include Botulism, Equine Herpes Virus, Equine Influenza, Potomac Horse Fever, Rotavirus, Equine Viral Arteritis, Anthrax, and Strangles. Your veterinarian is familiar with the diseases most prevalent in your area and should be consulted on which vaccines need to be incorporated into your horse’s program.
 
 Adverse reactions to vaccines are very rare when administered appropriately. However, as with any injection there is always a potential risk of a reaction. Fortunately, the vast majority of these reactions are a local injection site reactions with moderate swelling which usually require very little, if any, medical attention from a veterinarian. However, although extremely rare, there are incidences of anaphylaxis(life-threatening allergic reaction) to the vaccine which require immediate attention by a veterinarian.
 
All vaccinations are intramuscular (IM) except Heska Flu-Avert, which is intra-nasal. It is not required to have a veterinarian administer vaccinations but owners who wish to handle their horse’s vaccinations should fully understand how to handle and store vaccines, be comfortable with giving IM injections, and know how to handle adverse reactions should they occur. Even if you are able to administer your own vaccinations it is always important to work with your veterinarian on proper vaccination guidelines and schedules.

New protocols for deworming management
For years, veterinarians and horse owners have correlated rotational deworming of horses with any number of paste dewormers on a predetermined schedule to be adequate control of internal parasites.  With the absence of any new class of deworming products over the past 20 years and with the overuse of dewormers available, anthelmintic resistance is becoming a problem and needs to be addressed.  Understanding that all dewormers vary in their clinical effectiveness on different species of parasites and at different stages of their lifecycle, we need to be more critical of which dewormers are used.  Other factors that influence this decision include length of time each dewormer is expected to be effective and timing of when each treatment should occur.
 
A targeted selective approach to deworming is the newest recommendation to aid in slowing anthelmintic resistance and managing intestinal parasites based on individual animals rather than a ‘blanket’ treatment of the entire herd. 
 
When designing an individual horse or herd program, we must consider the egg reappearance period of each dewormer, individual horse susceptibility, climatic factors, and current anthelmintic resistance.  The egg reappearance period (ERP) is the time from deworming until eggs are detectable in fecal float, and varies between the three classes of dewormers.  The ERP helps determine the timing between treatments, and varies based on which product is used from 4 weeks up to 12 weeks.  Horses possess varying levels of natural immunity to internal parasites, resulting in 25% of horses in a herd producing 80% of the eggs found on pastures.  This level of individual susceptibility can be determined by using fecal egg counts per gram (McMasters), following a period of 3-4 months (winter or summer) without deworming, and then designate each horse as a low (<200epg), moderate (200-500epg), or high (>500epg) egg shedder.  These groupings allow us to treat individuals based on need, and instead of overusing dewormers.
 
Climatic factors provide a great deal of natural parasite control, and needs to be considered when timing deworming.  Small strongyle larvae cannot survive on pasture above 85F, and the development of eggs to larvae is suspended under 45F.  These factors result in a period of time during the summer (June, July, and August) and winter (December, January, and February) when deworming is not necessary in all horses, except for the high egg shedders.  Anthelmintic resistance can be determined by performing a fecal egg count reduction test (FECRT) for each class of dewormer.  A fecal egg count should be done prior to administering the dewormer and repeated 14 days post treatment. Resistance can be defined as a less than 90% reduction in fecal egg numbers following a specific dewormer.  Once a farm’s parasite population has been identified as being resistant to a dewormer, that product should no longer be used on that farm for that parasite.
 
Horse owners should work closely with their veterinarian to test their horse’s parasite status before administering a dewormer. By being selective in choosing when to treat, what to treat with, and which horses to treat, the targeted selective approach can decrease deworming costs by up to 50% at the same time providing superior control of parasites and decreased resistance. 

Straight from the horse’s mouth
Dentistry is an important part of the overall health and well-being of the horse. Just as routine dental hygiene helps people prevent tooth decay and periodontal disease, routine dental re-equilibration (floating) performed by a knowledgeable and experienced practitioner can alleviate pain and prevent many dental disorders.  Tooth root infection in the horse is a relatively common disorder occurring primarily in the cheek teeth. Causes of tooth root infections are numerous including fractures, developmental disorders, blood borne pathogens, etc. Developmental disorders in young horses include too numerous cheek teeth, which creates overcrowding and can lead to incomplete eruption or impaction of cheek teeth.  Also, too few cheek teeth can leave gaps between teeth and increase the chance of periodontal disease.  Periodontal disease begins at the gum level surrounding the tooth.  Perhaps the most common cause of apical infections (infections of the tooth root area and surrounding tissue) is the spread of bacteria in the blood.  The horse has a tremendous blood supply to erupting teeth (eruption bumps) and may explain why we see more of these infections in young horses that have rapidly developing tooth roots.
 
Symptoms of dental disorders include loss of appetite, dropping excessive amounts of feed when chewing, swelling along the jaw, malodorous discharge from the nose or jaw, and a sudden resistance to accepting a bit.  These symptoms may be obvious or subtle. With these suspicious clinical signs, a thorough oral exam with mouth speculum is warranted to determine if there is a dental problem. You may also want to have your veterinarian show you how to safely examine your horse’s mouth. Regularly monitoring your horse’s teeth and gums will give you a baseline normal and enable you to notice any changes or abnormalities if they occur.
 
It is recommended that adult horses have their teeth “floated” once per year and that horses younger than 5 years of age have teeth “floated” twice per year.  In younger horses it is important to evaluate the development of permanent teeth as well as the shedding of immature teeth (caps). Geriatric horses have their own special needs and should be evaluated annually or more often if colic, choke or other medical concerns arise. Understanding your horse’s oral health needs and maintaining the appropriate exam and floating schedule will keep you and your horse smiling. 

From Last to First
A chance encounter at Rood & Riddle brings a horse and rider together 

Robin Murray


In January 2008, Marina King was a Thoroughbred without a home. After finishing out of the money in 7 starts,  including 4 last place finishes, the 4 year old colt was sent to Kentucky Equine Humane Center near Lexington, Kentucky in hope of finding a new home and possibly a new career.
 
At Rood & Riddle, technician Emily Brooks was having a pretty average day. There were only a few routine procedures on the day’s surgery list, nothing remarkable. Included on the schedule was a castration for Marina King, a Kentucky Equine Humane Center horse. On first appearance, the colt didn’t look like much. He was underweight and his feet were in poor condition. Even so, the colt’s gentle personality and kind eye caught Emily’s attention.
 
After the castration, Marina King returned to the KyHC to recuperate and wait for adoption. He didn’t wait long. Emily called KyHC the next day to ask about adopting Marina King. “I was not actively looking for a new horse as I already had one that I was actively showing, but Marina King definitely caught my eye” recalled Emily. One week later, Marina King, now renamed Charlie, was on a trailer heading to his new home.
 
Charlie’s initial job was that of pasture buddy for Emily’s Eventing horse, so he was turned out to acclimate to life as an “average Joe” horse. Emily also called on Rood & Riddle podiatrist, Dr. Vern Dryden to get Charlie’s feet back in good condition.
 
While Charlie was adapting to his new life, Emily’s other horse developed a lameness issue that required a long layoff.  With her first mount out of commission, Emily decided to see what Charlie would be like under saddle. Lounging under saddle was uneventful, so with caution she climbed into the saddle to see how he would respond to a rider. “The first time I got on him I was prepared for fireworks but once again he was wonderful,” stated Emily.
 
Charlie proved to be a willing mount and responded quickly to training as a sport horse. Three months later, Emily entered Charlie in his first event at Beginner Novice. He was a star and came in fourth. The duo has been Eventing steadily ever since, winning the February Poplar Place Horse Trials in the novice division one year after his adoption. He advanced through Training level competitions and is now moving up Preliminary level in 2011. Emily’s goal is to compete at the CCI* at the Kentucky Classique Horse Trial at the Kentucky Horse Park this fall.
 
Marina King’s days of finishing last are long past. He has a new owner, new name, new sport, and a new lease on life. Emily realizes she is lucky to have found Charlie and is fortunate he has not had any training or health challenges. “I would recommend to anyone that they try adopting a horse before purchasing one if they are willing to be patient and put in the time with the horse,” said Emily. The Kentucky Equine Humane Center could not agree more.
 
Emily Brooks is the MRI Technician and assistant to Rood & Riddle’s Diagnostic Imaging Director, Dr. Katie Garrett. Emily is also an avid equestrian and has been riding and competing for 15 years. Rood & Riddle Equine Hospital is proud to support the Kentucky Equine Humane Center and its mission to provide humane treatment and shelter while working to find adoptive homes for all of Kentucky's unwanted equines, regardless of breed.


Dr. Travis Tull Earns Diplomate Status from the American College of Veterinary Surgeons

Surgeon Dr. Travis Tull passed another milestone in his veterinary career by successfully completing the latest board examination administered by the American College of Veterinary Surgeons (ACVS).  Following graduation from the University of Georgia College of Veterinary Medicine in 2006, Dr. Tull joined the veterinary staff of Rood & Riddle Equine Hospital for a one-year hospital internship. Upon completion of his intern training, he was selected as the first resident in the inaugural year of Rood & Riddle’s Surgical Residency program in 2007. He completed the three-year program in June 2010, and was retained by Rood & Riddle as an associate surgeon while preparing for his board examination.

 “We are very proud of Travis’ accomplishment,” said Dr. Brett Woodie, Dr. Tull’s residency advisor at Rood  &Riddle. “This is a landmark achievement in his surgery career as well as for our surgery residency program.”

The ACVS board examination, given earlier this year in San Diego, tests all phases of surgery as well as competence in areas of specialization with separate examinations for small animal and large animal candidates. The examination consists of written, case-based and practical sections and is administered over a 2 day period. Eligibility to sit for the certification exam includes additional training in a one-year rotating internship and a supervised three-year surgical residency, during which the veterinarian works with board-certified specialists. The resident must also demonstrate a commitment to contributing to the scientific literature and maintaining a moral and ethical standing in the profession.

Founded in 1965, the American College of Veterinary Surgeons is the American Veterinary Medical Association specialty board which sets the standards for advanced professionalism in veterinary surgery and provides the latest in surgical educational programs. Board certification has been attained by about 1.6 percent of the more than 86,000 veterinarians in the United States. Prior to this year’s exam, the ACVS included more than 1,470 Diplomates of whom about 35% are large animal surgeons.
Dr. Tull has completed surgical duties at Rood & Riddle and is providing surgery services to Brown Equine Hospital in Pennsylvania and South Shore Equine Clinic in Massachusetts, until July, when he will become a full time surgical associate at South Shore.
 
“My time at Rood and Riddle Equine Hospital has provided me with the tools necessary to be a successful surgeon while emphasizing the importance of problem solving thorough diagnostics, patient management, and interpersonal communication,” stated Dr. Tull.  “The support and contributions of the staff and veterinarians have played a major role in my development as a clinician and completion of the residency program.”


Around the Practice . . .

Dr. Johanna Reimer’s (photo on right) study on ultrasound findings in horses with severe eyelid swelling was recently published in The Journal of Veterinary Ophthalmology.  The article, co-authored by Ophthalmology Specialist, Dr. Claire Latimer, reported that most horses with painful, severely swollen eyes, often assumed to be from blunt trauma, are actually due to a very inflamed swollen lacrimal gland (as confirmed with ultrasound in 5 of 10 cases) or an abscess within the lid with less severe swelling of the lacrimal gland (3 of 10 cases). Dr. Reimer’s study showed that horses that look like this more often than not have an inflamed lacrimal gland, and/or an eyelid abscess (diagnosed with ultrasound). This disorder, acute dacryoadenitis (acute inflammation of the lacrimal gland) has never been reported in the veterinary literature before, but has been seen in people.

Dr. Alex Emerson (photo at right) has ventured into the blogosphere posting the anecdotal tales of a sport horse veterinarian for Sidelines online magazine. Dr. Emerson is one of Rood & Riddle’s sport horse practitioners primarily based in Wellington, Florida in the winter, and the Kentucky Horse Park from spring through the fall. You can read about his unique adventures at www.sidelinenews.com/blogs.

Congratulations to Rood & Riddle Podiatry farriers Jeff Henderson and Rodney King (photo at left) for taking home honors at the Indiana Farriers Association Hoosier Classic Contest. Jeff won overall High Point in the Intermediate Division; Rodney won the overall High Point in the Open Division. Rodney also competed in another contest in Calgary, Canada, placing in multiple classes including a second place in the Judge’s Choice Forging Class for his lateral extension hind shoe with a French heel.   Rodney’s next competitions will be the Heavy Horse World Cup in his native country, New Zealand, and the World Championships in Calgary, Canada in July.

Hats Off to Kentucky’s Horse Industry Day, a grass roots initiative supported by local horse industry businesses to educate and promote Kentucky’s vital equine industry to the general public, will provide hospitality events to competitors at select equestrian events during the 2011 Horse Show season at the Kentucky Horse Park. These events include Eventing, Hunters, Jumpers, Dressage, Reining and Saddlebred competitions. The Hats Off Day Partner level sponsors, Rood & Riddle Equine Hospital, Alltech, Hallway Feeds and Spy Coast Farm are supporting these events and will be on hand to welcome competitors and thank them for participating in Kentucky’s equestrian events and supporting the local agricultural economy.

Please plan to attend Hats Off Day, Saturday, August 6, at the Kentucky Horse Park. 

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