Showing posts with label Belknap. Show all posts
Showing posts with label Belknap. Show all posts

Friday, June 29, 2012

Equine Laminitis Update: Belknap's Summary of Basic Facts

Laminitis terminology suggested by Dr Belknap in this article
A laminitis word cloud made from the words in this article. A lot of words and a lot of ideas circulate the world when it comes to preventing, treating and /or understanding laminitis. But what do we really know?
Laminitis: what does that word mean to you? Do you think you know all about it, or does hearing the very word have you shaking your head over all we just don't know.

The recent--and some would say long overdue--expansion in laminitis research has spawned a generation of geeks who can speak the lingo and conject about the future. Their ideas are exciting--but what do we really know about laminitis, and how much more do we know that a year ago, or ten years ago? 


Is it possible to find a cure for something you don't understand?

Dr. James Belknap, a leading laminitis researcher, recently wrote this succinct summary of what laminitis is, based on the few facts he and his researcher allies know to be the foundation of the disease. 



It's not far off to say that what he describes here is the laminitis base camp. Research expeditions head out from here. Sherpas lead the way, but it is one step at a time and sometimes bad weather forces an expedition back to the base just when the summit is in sight. Everyone wants to stand at the summit, on top of the world. Getting there has not been easy, but here's what the tents at base camp are built upon.

Laminitis is not a disease of the foot as much as a disease of the horse--yet the foot has a delicate structure--what Dr. Belknap calls "target tissue"--that is incredibly sensitive to changes from the many triggers. And the target tissue gets bullseyed more often than we'd like.

From Dr. Belknap:

Equine laminitis can be a devastating result of many different disease processes in the horse, including, most commonly, sepsis and endocrinopathies. The two primary types of endocrinopathic laminitis are equine metabolic syndrome (seen most often in the obese horse), and Cushing’s syndrome in older horses (characterized by high levels of circulating steroids produced by a pituitary tumor). Interestingly, the “target” tissue in the horse for sepsis, equine metabolic syndrome, and Cushing’s syndrome is the digital laminae.

Most likely the main reason the digital laminae are the primary target is because no other soft tissue structure in species injury/dysfunction will result in the entire collapse of the musculoskeletal system of the animal. The laminar basal epithelial cells are exposed to incredible forces (supporting the entire weight of the horse).

Laminitis researcher James Belknap from Fran Jurga's Hoof Blog/Hoofcare Publishing
Dr. James Belknap is a leading researcher in the pathophysiology of laminitis. He is a professor at
 The Ohio State University College of Veterinary Medicine's Galbreath Equine Center.


1. Laminitis related to septic conditions

Septic conditions in the horse that can lead to laminitis include gastrointestinal disease (surgical lesions, diarrhea/enteritis from infectious agents, or carbohydrate overload), retained placenta in the post-foaling broodmare leading to a uterine infection, pleuropneumonia, and any other infection in which enough tissue is compromised to result in systemic effects.

In most of these cases, toxins absorbed from Gram-negative bacteria are thought to be responsible for the systemic problems such as laminitis. However, bacterial infections from other types of organisms can also result in laminitis. Most progress has been made in studying sepsis-related laminitis, as most experimental models for laminitis mimic this condition.

Systemic inflammation leading to inflammatory injury to the laminar tissue has been reported in sepsis-related laminitis in horses. In the laminae, this injury is characterized by adhesion and migration of circulating white blood cells out of the blood vessels into the laminar tissue. This is accompanied by massive increases in expression of inflammatory proteins such as cytokines (a 10-fold to > 2,000 fold increase in expression) and cyclooxygenase-2 (COX -2, the enzyme which is targeted by non-steroidal antiinflammatory drugs such as phenylbutazone or flunixin).

Plastinated equine hoof specimen demonstrating laminitis damage Christoph von Horst and Hoofcare Publishing
Research attempts to sort out not only what happens, but when it happens,
to cause the horse's hoof to experience the freefall of chronic laminitis,
Plastinated hoof tissue courtesy of HC Biovision/Dr Christoph von Horst

2. Laminitis related to Equine Metabolic Syndrome and Equine Cushing Syndrome

These events most likely cause injury to the laminar basal epithelial cells, leading to disruption of their critical cellular events, including adhesion to the underlying matrix. The matrix itself may also be injured by the release of matrix-degrading enzymes by leukocytes, epithelial cells, and other cell types in the laminae.

Equine metabolic syndrome (EMS), which includes pasture-associated laminitis, is now the most common type of laminitis reported by veterinarians. Although the animals affected are commonly obese, animals in “show shape” that are not overtly obese also succumb to EMS-related laminitis.

A consistent factor in the horse or pony with EMS is insulin resistance, with the animals usually exhibiting increased circulating insulin concentrations. It has been suspected that laminar injury in EMS was from an inflammatory event as discovered in sepsis-related laminitis. However, recently presented data indicate that the high circulating insulin concentration itself can induce laminitis, with limited evidence of inflammation in the laminae.

The other type of endocrinopathic laminitis, Equine Cushing Syndrome (ECS), may have a pathophysiologic mechanism similar to that of EMS, as ECS horses similarly have high levels of circulating insulin. However, it is possible that the glucocorticoids (GCs) may be playing a role in disruption of the cell biology of the laminar keratinocytes in ECS.

3. Laminitis related to weightbearing (“supporting limb laminitis”)

The pathophysiology of supporting limb laminitis, the type suffered by Barbaro, is the type of laminitis about which we presently have the least knowledge. With this type, excessive weight bearing (usually due to a painful injury on the opposite limb) results in laminar failure. The recent interest supporting limb laminitis has resulted in several studies being funded by equine foundations.

Hopefully, these studies will further elucidate the pathologic mechanisms (and thus therapeutic targets) for this equally devastating form of laminitis. Thus, laminitis is likely the end product of a diverse array of disease processes that lead to disruption and failure of a highly evolved cell type that is exquisitely sensitive to injury—the laminar basal epithelial cell.

James Belknap, DVM, PhD, DACVS is Professor of Veterinary Clinical Sciences from The Ohio State University Galbreath Equine Center and a leading researcher in the pathophysiology of laminitis. He shared this succinct summary of the current knowledge based on the types of laminitis via the Equine Disease Quarterly of the University of Kentucky’s Gluck Equine Research Center.

Equine Hoof Wall Anatomy Lisa Lancaster Hoofcare Publishing
Easy online ordering and immediate shipping of our award-winning anatomy poster

© Fran Jurga and Hoofcare Publishing; Fran Jurga's Hoof Blog is a between-issues news service for subscribers to Hoofcare and Lameness Journal. Please, no use without permission. You only need to ask. This blog may be read online at the blog page, checked via RSS feed, or received via a digest-type email (requires signup in box at top right of blog page). To subscribe to Hoofcare and Lameness (the journal), please visit the main site, www.hoofcare.com, where many educational products and media related to equine lameness and hoof science can be found. Questions or problems with this blog? Send email to blog@hoofcare.com.  


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Disclosure of Material Connection: I have not received any direct compensation for writing this post. I have no material connection to the brands, products, or services that I have mentioned, other than Hoofcare Publishing. I am disclosing this in accordance with the Federal Trade Commission’s 16 CFR, Part 255: Guides Concerning the Use of Endorsements and Testimonials in Advertising.

Friday, March 16, 2012

Laminitis Research Highlights Grayson Jockey Club Foundation's Research Lists for 2012


The Grayson-Jockey Club Research Foundation announced today that the charitable organization will fund 16 projects in 2012, totaling $845,646. The research includes the launch of eight new projects, continuation of eight projects entering their second year, and the Storm Cat Career Development Award.

Of special interest is the announcement that a project on laminitis has received the Elastikon™ Equine Research Award. This is funded in part through a contribution by Johnson & Johnson’s Consumer Products Company, manufacturer of Elastikon tape and other equine products.

Of particular interest are the following projects:

LAMINITIS STUDIES

1. Digital Hypothermia in Laminitis: Timing and Signaling
Dr. James Belknap, The Ohio State University (Second Year)

Dr. Belknap
The most recent figures from a study involving the USDA and State Veterinary Medical Officers project that at any given time laminitis affects 8 of every 1,000 horses in the United States. Based on the American Horse Council survey that there are 9.5 million horses in the nation, that would indicate 76,000 horses being affected at any given time. Of those affected, the USDA survey found that 4.7% died or were euthanized, or about 3,572 deaths from laminitis annually.

The authors of this project report that “an integrated research effort over the last decade has enhanced the current understanding of the pathophysiology of equine sepsis-related laminitis (one of numerous causes of the disease). This has mirrored progression of sepsis research in human medicine by moving from (an earlier) concept . . .to determining that a marked inflammatory injury takes place and is likely to play a prominent role in tissue injury and subsequent failure.” However, there have been persistent failure of systemic therapies for organ/laminar injury in both human and equine medicine. One advantage laminitis presents is that it effects the hoof rather than visceral organs, lending itself to artificial cooling more readily.

In a present project funded by the Foundation, digital hypothermia (cooling of the hoof) prior to onset of carbohydrate overload-induced equine sepsis resulted in dramatic decrease in laminar inflammatory signaling. The next goal is to find pharmaceutical therapies which can accomplish the same without the cumbersome aspects of maintaining constant hypothermia to the equine hoof (hooves).

2. Laminar Energy Failure in Supporting-Limb Laminitis
Dr. Andrew Van Eps, University of Queensland (Second Year)

Dr. Van Eps
A frequent and disheartening result of injury repair is that the leg opposite the one injured develops laminitis. This is known as supporting-limb laminitis and is what eventually caused Barbaro to be euthanized. Although it is a common occurrence, the mechanisms of the malady have not been established.

Dr. Pollitt
This project is headed by a young researcher, Dr Andrew Van Eps, but the co-investigators are world renowned Drs. Dean Richardson and Chris Pollitt.

The project involves testing the hypothesis that supporting-limb laminitis is a result of reduced blood supply to the connection between hoof and bone (lamellar tissue). Further, that the blood supply in normal circumstances is encouraged by a regular loading and unloading of the legs and hooves (alternating which one is bearing the most weight). Injury to one leg interrupts that alternating pattern.

Dr. Richardson
The researchers will test the hypothesis with a state of the art, minimally invasive technique known as tissue microdialysis in conjunction with three dimensional computed tomography to develop effective methods of preventing or minimizing lamellar tissue energy failure. Comments in the Research Advisory Committee evaluations included “may well provide immediately applicable strategies to prevent supporting-limb laminitis” and “really nice grant, new idea about a devastating problem.”

Support-limb laminitis is a special area of research interest for the researchers funded by the Grayson Jockey Club Foundation. It is believed to be a unique form of the disease that is precipitated by prolonged weightbearing on one hind limb or one front limb, caused by the opposite (injured) limb's inability to bear weight after surgery or injury. Tragically, the overburdened "good" or "supporting" limb develops laminitis in this scenario. (Hoofcare + Lameness photo)

3. Laminar Signaling in Supporting-Limb Laminitis
Dr. James Belknap, The Ohio State University– First Year (2 Year Grant)

A recent USDA study indicates that approximately 1% of all horses in the USA suffer from laminitis at any given time, and approximately 5% of those animals die or are euthanized while many others remain crippled. Of the conditions which create laminitis, the development of the disease in the supporting limb of an already injured horse is one of the worst, since it is believed that 50% of those cases result in euthanasia.

The author reports that while there are hundreds of published papers in the literature about other forms of laminitis, reports on supporting-limb laminitis are restricted to clinical reports and case studies.

This project will “introduce a novel, non-painful model of supporting-limb laminitis and will allow for cutting edge bench research techniques to not only (1) test the current hypotheses on the cause of laminar failure, but also (2) provide an unbiased technique to determine the cellular events that occur . . .”

The investigator has performed a number of laminitis project for Grayson and the USDA, and has a well developed set of tools and techniques including laser micro-dissection of frozen laminar cells and an advanced “functional genomic” technique called RNA-Seq. By applying these techniques that have previously characterized laminitis caused by sepsis or metabolic syndrome to support limb laminitis, we will get our first understanding of what kind of drugs and treaments might prevent it.

This grant was selected by the board to receive the sixth annual Elastikon™ Equine Research Award.

4. Stem Cell Homing after IV Regional Limb Perfusion
Dr. Alan Nixon, Cornell University (First Year of Two-Year Grant)

Dr. Nixon
“The initial fervor associated with stem cell therapies has been tempered by mediocre clinical results,” states Dr. Nixon, long recognized as a key leader in quest to maximize use of stem cells. “More can be done, including pre-differentiation, gene-directed lineage targeting, and more efficient delivery.” This proposal will deliver by “local vein injection, to back-flow to bowed tendon and other disease conditions such as founder and traumatic arthritis.”

Transplanted cells then exert normalizing and restorative effects . . .” The long-range goal is to provide a simplified approach to stem cell therapy. We cannot do this without verification of cell homing and impact. (The project) will map stem cell distribution in the tendons, ligaments, and joints of the forelimb after direct venous injection.”

LAMENESS STUDIES

1. AAV-IRAP Gene Therapy to Prevent Osteoarthritis
Dr. Laurie Goodrich, Colorado State University (Second Year)

Dr, Goodrich
Osteoarthritis is a common affliction in horses, and current methods of treatment are effective only in reducing the pain, at best. This proposal will utilize gene therapy, which is a technique in which cells can be genetically modified or “re-programmed” to produce beneficial protein that will allow cartilage to heal. The initials in the project title stand for Adenoassociated Virus and Interluken Receptor Antagonist Protein. If cells in the joint could be re-programmed to produce IRAP, the devastating effects of joint inflammation could be halted and the progress of osteoarthritis could be reversed.

These researchers’ preliminary work utilizing AAV-IRAP suggests that cells of joints are easily re-programmed to produce beneficial protein. The aims of this project is to define the most appropriate dose of AAV-IRAP that will result in effective levels and answer the question of whether this approach can prevent osteoarthritis in the horse.

2. Investigation of Cell and Growth-Factor Dependent Tenogenesis
Dr. Martin A. Vidal, University of California-Davis (Second Year)

Dr. Vidal
The crux of this study is to test preliminary indications that a newly developed in vitro tendon/ligament culture model will prove effective at determining the optimal cell type from bone marrow, fat tissue, umbilical cord, tendons, ligaments, and muscle to use in tendon and ligament repair. The model also will allow investigators to learn the early molecular and cellular signals in tendon and ligament tissue formation.

The author states that current methods of healing result in inferior scar tissue and re-injury rates ranging from 23% to 67%. Transforming growth factor (TGF) combined with platelet rich plasma will be utilized, and tests will be done on how they affect tissue growth, strength, and composition. ”

3. Stem Generation of Equine Induced Pluripotent Cells for Regenerative Therapy
Dr. Lisa Fortier, Cornell University (Second Year)

Dr. Fortier
Stem cell based therapies are among avenues being tested with the goal of tendon cell regeneration to address tendonitis. The types of stem cells used so far may improve the structure of tendon healing, but appear to have limited regenerative ability or are limited due to potential issues of immune rejection.

The author explains that, “ . . . this proposal is to generate induced pluripotent stem cells (iPS cells) from equine adult dermal fibroblasts. iPS cells are the only stem cells that are both pluripotenent and autogenous, making them the most useful for clinical application. The expectation is that the results of the studies in this proposal will provide the first published description of the generation and characterization of equine iPS cells.” This is part of a process of testing the overall hypothesis that equine iPS cells will enhance tendon regeneration in cases of tendonitis.

Also, “the technical expertise gained in this study could be used in the future to generate autogenous iPS cells for use in equine cartilage and neuronal regeneration studies.”

Go inside the horse's hoof...you'll be amazed what you'll see--in 3-D, too!
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© Fran Jurga and Hoofcare Publishing; Fran Jurga's Hoof Blog is a between-issues news service for subscribers to Hoofcare and Lameness Journal. Please, no use without permission. You only need to ask. This blog may be read online at the blog page, checked via RSS feed, or received via a digest-type email (requires signup in box at top right of blog page). To subscribe to Hoofcare and Lameness (the journal), please visit the main site, www.hoofcare.com, where many educational products and media related to equine lameness and hoof science can be found. Questions or problems with this blog? Send email to blog@hoofcare.com.  
Follow Hoofcare + Lameness on Twitter: @HoofcareJournal
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Disclosure of Material Connection: I have not received any direct compensation for writing this post. I have no material connection to the brands, products, or services that I have mentioned, other than Hoofcare Publishing. I am disclosing this in accordance with the Federal Trade Commission’s 16 CFR, Part 255: Guides Concerning the Use of Endorsements and Testimonials in Advertising.

Wednesday, June 03, 2009

Video: Laminitis in Standardbreds at Ohio State's Vet Hospital

by Fran Jurga | 2 June 2009 | Fran Jurga's Hoof Blog


Part 1 features Ohio State clinician/researcher Dr. James Belknap



Part 2 features farrier Trey Green

The US Trotting Association's magazine Hoof Beats has a feature on laminitis this month and the magazine sent a video crew to the veterinary hospital at The Ohio State University College of Veterinary Medicine in Columbus, Ohio to film a supporting video to accompany the article.

I hope you will check out the article, and also watch these two short videos. The first features Ohio State's Dr. James Belknap, a respected leader in the study of the mechanism of the disease and of medications' effects. The article in Hoof Beats was written by Dr. Belknap. He obviously works in a hands-0n role at Ohio State, as well, and you'll see him giving some of his opinions about the clinical aspects of the disease.

On the second clip, you'll see Dr. Belknap work on the foot of the patient, and then Ohio State farrier Trey Green goes to work and finds the case ideal for the applicaion of a heart-bar shoe.

I wonder where and how the horse is now.

Many thanks to the USTA for posting the video.

© Fran Jurga and Hoofcare Publishing. No use without permission. You only need to ask.

Fran Jurga's Hoof Blog is a between-issues news service for subscribers to Hoofcare and Lameness Journal. This blog may be read online at the blog page, checked via RSS feed, or received via a digest-type email (requires signup in box at top right of blog page).

To subscribe to Hoofcare and Lameness (the journal), please visit the main site, www.hoofcare.com, where many educational products and media related to equine lameness and hoof science can be found.

Questions or problems with this blog? Send email to blog@hoofcare.com.

Friday, December 05, 2008

Belknap Laminitis Research at Ohio State Will Be Funded by Barbaro Legacy

by Fran Jurga | 5 December 2008 | www.hoofcare.blogspot.com

A new study of laminitis at the Ohio State University College of Veterinary Medicine has been approved by the Barbaro Memorial Fund, which is administered by NTRA Charities and the National Thoroughbred Racing Association. Funds for the study will flow through the Grayson-Jockey Club Research Foundation.

The new study, "Effect of Digital Hypothermia on Inflammatory Injury in Laminitis," by Dr. James Belknap, is a two-year project funded for $82,109. The study will examine the effects of extreme, isolated cold on the damage done to hoof tissue when laminitis damages the hoof wall's bond to the inner foot.

Barbaro funds also will support two continuing projects: "Targeting 5-HT in Equine Laminitis," by Dr. Douglas Allen at University of Georgia and "Treatment of Equine Laminitis with Doxycycline," by Dr. Susan Eades at Louisiana State University. Both studies were funded with a $100,000 contribution from the Barbaro fund to the Grayson-Jockey Club Research Foundation in 2007; an additional $8,692 completes the projects in 2008. Both projects are on schedule to produce research papers in peer-reviewed scientific journals.

The Barbaro Fund contributed an additional $60,000 in 2007 toward laminitis research projects and programs at the University of Pennsylvania, bringing its total disbursements to $250,801.

A distinguished panel of equine veterinarians, assembled by the Grayson-Jockey Club Foundation, evaluated several proposals before making final recommendations on the laminitis studies. The panel included Dr. Larry Bramlage, chairman of the Grayson-Jockey Club Research Foundation; Dr. Johnny Smith, the Foundation's veterinary consultant; Dr. Paul Lunn, Professor and Head of Clinical Studies at the College of Veterinary Medicine and Biomedical Sciences, Colorado State University; Dr. Scott Hay, President of the Teigland, Franklin, Brokken veterinary firm and a specialist in equine lameness; racetrack practitioner Dr. Tom Brokken, also of Teigland, Franklin, Brokken veterinary firm (and a past president of the American Association of Equine Practitioners); Dr. David Horohov, the William Robert Mills Chair at the Maxwell Gluck Research Center, University of Kentucky; Dr. Gary Lavin, a retired race track practitioner, past AAEP president, and Vice-Chairman of the Grayson-Jockey Club Foundation; Dr. Rick Arthur, Equine Medical Director for the California Horse Racing Board; Dr. John Stick, Professor and Chief of Staff at the Large Animal Clinic of Michigan State University School of Veterinary Medicine; and Dr. James Orsini, Director of The Laminitis Institute, and Associate Professor of Surgery at New Bolton Center, University of Pennsylvania.

Barbaro, winner of the 2007 Kentucky Derby, was euthanized while recovering from fracture surgery at the University of Pennsylvania's New Bolton Center. The horse developed laminitis, a common and often fatal complication of orthopedic procedures for some horses.

Photo: University of Pennsylviania, Hoof Blog archive

© Fran Jurga and Hoofcare Publishing. No use without permission. You only need to ask. Fran Jurga's Hoof Blog is a between-issues news service for subscribers to Hoofcare and Lameness Journal. This blog may be read online at the blog page, checked via RSS feed, or received via a digest-type email (requires signup in box at top right of blog page). To subscribe to Hoofcare and Lameness (the journal), please visit the main site, www.hoofcare.com, where many educational products and media related to equine lameness and hoof science can be found. Questions or problems with this blog? Send email to blog@hoofcare.com.

Tuesday, September 23, 2008

Belknap's Laminitis Paper Wins Scientific Publishing Award


(University news release)

Dr. James Belknap, associate professor of equine surgery in the Department of Veterinary Clinical Sciences at the Ohio State University College of Veterinary Medicine, has been awarded the annual Equine Veterinary Journal Open Award for 2007 for his work as senior author of a paper published in the Equine Veterinary Journal. The Open Award is funded by the British Equine Veterinary Association (BEVA) Trust and presented to the senior author in recognition of a paper considered by the judges to be of outstanding excellence.

The paper, "Lamellar pro-inflammatory cytokine expression patterns in laminitis at the developmental stage and at the onset of lameness innate vs. adaptive immune response," focused on inflammation of the laminae, which they recognized as present in early forms of laminitis.

"No matter what type of laminitis, inflammation is playing a large role in the developmental process," Dr. Belknap said. "Researchers used to believe that inflammation was not a major component of the disease, and that the disease was mainly caused by a decrease in blood flow."

Dr. Belknap said discovering that inflammation plays a key role in the developmental stages of the disease has caused a paradigm shift in the way the disease is researched worldwide. This opens up new opportunities for discovery of novel treatments for this disease, which commonly results in crippling lameness of affected horses.

"We still have a long way to go to answer the big questions," he explained. "We still must determine which specific pathologic will eventually allow us to formulate an effective therapeutic regimen for this devastating disease."

Dr. Belknap received his veterinary degree from Colorado State University and has worked at Ohio State for four years as a surgeon; he has a special interest in equine podiatry. He grew up in Kentucky on a farm where he developed an early interest in horses.

© Fran Jurga and Hoofcare Publishing. No use without permission. All images and text protected to full extent of law. Fran Jurga's Hoof Blog is a between-issues news service for subscribers to Hoofcare and Lameness Journal. This blog may be read online or received via a daily email through an automated delivery service. To subscribe to Hoofcare and Lameness, please visit our main site, www.hoofcare.com, where many educational products and media related to equine lameness and hoof science can be found.

This post originally appeared at http://www.hoofcare.blogspot.com on September 23, 2008.