Showing posts with label anti-inflammatory. Show all posts
Showing posts with label anti-inflammatory. Show all posts

Thursday, November 15, 2012

Laminitis Treatment: UC Davis Experimental Anti-Inflammatory Shows Promise in Test Case



Can an anti-inflammatory medication have curative power over a disease like laminitis? Researchers at the University of California at Davis are beginning clinical testing of a new medication that might be an outside-the-box hope for relieving horses suffering with the disease. Here's a report from UC Davis School of Veterinary Medicine:

Four horses suffering from laminitis have been treated with the investigational anti-inflammatory drug so far. One experienced a complete remission that has lasted for more than a year, and three others have shown some improvement.

A paper on the first laminitis case has been accepted for publication by the peer-reviewed Journal of Veterinary Anaesthesia and Analgesia. The paper is expected to be published in the journal’s February issue, but journal editors authorized the authors to disclose their findings ahead of publication.

Alonso Guedes, an assistant professor of veterinary medicine, treated this four-year-old Thoroughbred mare by administering an experimental anti-inflammatory drug to treat laminitis. (Don Preisler/UC Davis photo)
“This is an unusual step for us to announce this so far in advance, but because euthanasia is often the only way to alleviate pain in severe laminitis, we felt that it was important to let the veterinarians and horse owners know that this compound has shown potential as a treatment,” said Alonso Guedes, an assistant professor in the School of Veterinary Medicine.

The horses were treated under a “compassionate use” protocol approved by the UC Davis Institutional Animal Care and Use Committee. That protocol allows animals to be treated with an experimental drug if no approved alternative treatment exists.

A clinical trial to assess the drug’s safety and establish a tolerable dose for the compound is expected to begin in the spring. Further clinical trials would be needed to establish the drug’s effectiveness as a laminitis treatment.

The experimental compound, known as t-TUCB, belongs to a group of anti-inflammatory compounds called sEH (soluble epoxide hydrolases) inhibitors. It stems from a discovery made more than 40 years ago by UC Davis entomology professor Bruce Hammock while doing basic insect biology research.

The "cure" for laminitis is
the rehabilitation of the
horse's foot and the
elimination of the triggering
cause. (Plastination model
of advanced laminitis by
Christoph von Horst DVM PhD)
  
Originally interested in finding biological insect control methods, Hammock has since broadened his research to also search for biomedical applications. He and colleagues have identified a group of anti-inflammatory compounds, including the sEH inhibitors, that have proven to be effective in relieving inflammatory discomfort and pain related to nervous system disorders in mice and rats. Their work has been published in scientific journals including the Proceedings of the National Academy of Sciences and the Journal of Medicinal Chemistry.

Guedes noted that the safe management of laminitis-related pain is one of the biggest challenges for equine veterinarians. Often, euthanasia is the only humane alternative for alleviating pain and suffering in horses afflicted with the condition.

Consequently, according to UC Davis, the survival rate for laminitis is estimated to be only 25 percent. Very few surviving horses return to their previous levels of activity, and laminitis often reappears.

In his upcoming paper, Guedes reports the case of a four-year old Thoroughbred mare named Hulahalla. The horse had been retired from racing following a tendon injury and donated to the UC Davis School of Veterinary Medicine, where it was participating in a study focused on healing tendon injuries using stem cell treatments. She developed laminitis.

Veterinarians from UC Davis’ William R. Pritchard Veterinary Medical Teaching Hospital treated the laminitis with conventional therapies including cold immersion, antibiotics, leg wraps, and two commonly-used nonsteroidal drugs intended to reduce inflammation and relieve pain — but the horse only got worse. At the point that the mare was spending most of the day lying down, Guedes got involved.

Before resorting to euthanasia, Guedes and the veterinary team decided to try one last treatment, t-TUCB.

The veterinarians administered the experimental compound intravenously early on the eighth day of Hulahalla’s illness. After receiving the first dose, the horse remained standing in the stall most of the day, became interested in her surroundings and walked voluntarily.

The mare’s demeanor, posture and mobility continued to improve over four days of treatment, and her high blood pressure gradually returned to normal. No adverse affects from t-TUCB were observed, and Hulahalla has remained laminitis-free for a full year.

The sEH inhibitors, including t-TUCB, are currently available from the Hammock lab, which has provided the experimental compounds to more than 100 academic scientists around the world for basic investigation into their role in treating disease.

Hammock said that work aimed at moving t-TUCB and related compounds toward clinical use is advancing in several areas. He and Guedes are working on compounds with potential for targeting pain and arthritis in companion animals. And they are working with UC Davis to move the intellectual property from this research into a company to develop medications for difficult-to-manage neuropathic pain associated with diabetes and nerve injury.

Funding was provided by the National Institute of Environmental Health Sciences and the UC Davis Center for Equine Health.

The University of California at Davis provided this article.

Click to order this award-winning anatomy reference graphic for the wall of your clinic, forge or office.

© 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.

Thursday, September 27, 2012

Chronic Laminitis Research: Comparison of Normal vs Chronic Laminitis Horses Shows Difference in Immune, Digestive and Laminar Proteins

"Laminitis is not limited to the foot and chronic laminitis should be considered a multi-system disease" -- Steelman, Chowdhary, 2012


Chronic laminitis treatment usually focuses directly on the feet. The authors define chronic laminitis as the condition of horses who survive acute laminitis but are left with after-effects like coffin bone rotation. They state that 75% of horses with acute laminitis go on to the chronic stage, which they describe as causing permanent lameness. (file photo, courtesy of Vetmoves)

A new paper from the world of laminitis research finds that the anti-inflammatory protein apolipoprotein A-IV (APOA-IV) is raised in chronic laminitis, which suggests that the chronic form of the disease is linked to a more general inflammation, especially of the digestive system, than was previously documented.

Most research into laminitis is conducted on horses suffering from acute laminitis, usually after the ingestion of a large doses of fructans or black walnut in a controlled setting. Chronic laminitis is usually studied because of links to insulin resistance and/or equine metabolic syndrome and Cushing's disease, with minimal testing of systemic findings in horses with lameness in their feet. The focus of most chronic laminitis research is on how the endocrine system's irregular function affects the laminar tissue of the foot.

According to research published this week in the open-access journal BMC Veterinary ResearchDr Samantha Steelman and Professor Bhanu Chowdhary from the College of Veterinary Medicine at Texas A&M University, found 16 proteins that have different levels in the blood of horses with chronic laminitis, but which are not reflected in normal horses. They compared nine foundered horses with 30 healthy control horses collected from horses residing at the private Hoof Diagnostic and Rehabilitation Clinic in Bryan, Texas, where horses are in treatment under the direction of David Hood PhD DVM.

Horses in both groups were in good health, apart from the laminitis. Eleven of the 16 proteins measured are involved in response to wounding, coagulation and inflammation. The remaining proteins included fetuin A and B, both of which are involved in acute immune response, immunoglobin, an indicator of increased antibody levels, and most importantly APOA-IV.

Dr Steelman explained, "APOA-IV is produced by the small intestine. One of its functions is to tell the animal when it is full. It also has antioxidant and anti-inflammatory properties, which might explain the raised levels of APOA-IV."

At 2011's Sixth International Equine Conference on Laminitis and Diseases of the Foot in West Palm Beach, Florida, Dr. Steelman presented a poster titled, "Characterization of laminar, gastrointestinal, and immune system dysregulation in chronic equine laminitis", which was related to the research detailed in today's paper.

In the abstract accompanying her poster, she wrote that it was her team's goal to study the immune system, the gastrointestinal system, and the integumentary system (laminar tissue) using a combination of proteomics, next-generation DNA sequencing, and real time PCR, rather than to focus solely on the foot.

Steelman and Chowdhary's comparative study found interesting variations in all three systems between the laminitic and normal horses. Ultimately, their results support their hypothesis that localized laminar inflammation may be linked to systemic alterations in immune regulation, particularly in the gastrointestinal system.

Research published in BMC Veterinary Research that laminitis is linked to general inflammation, especially of the digestive system, via elevated levels of an anti-inflammatory protein that was not present in horses that do not have laminitis. Proteomics is the study of protein's presence, type and activity level in a condition. (Image courtesy of BMC Veterinary Research)

In other words: Chronic laminitis may show up most in displacement of the coffin bone, prolonged or intermittent lameness and hoof capsule deformity, but the digestive and immune systems are also affected. Most treatment of chronic laminitis currently focuses on making the feet more comfortable.

"From these data we conclude that the pathology of chronic laminitis is not limited to the foot and that chronic laminitis should be considered as a multi-system disease," was Steelman's interesting conclusion in Palm Beach. She recommended that her data be used in developing a more directed therapeutic approach as an alternative to current treatment strategies.

To learn more: Increased Plasma proteomics shows an elevation of the anti-inflammatory protein APOA-IV in chronic equine laminitis by Samantha M Steelman and Bhanu P Chowdhary. (full paper, free download) in the journal BMC Veterinary Research, an open access, peer-reviewed journal.

Dr. Steelman is curator of the Equine Tissue Sharing Program at Texas A&M.

Dr Chowdhary is an expert on equine genetics and also collaborates on research at the Laminitis Institute at PennVet's New Bolton Center, where he collaborates with Drs. Hannah Galantino-Homer and Chris Pollitt.

Dr. David Hood Launches the Hoof Diagnostic and Rehabilitation Clinic in Texas

© 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
Read this blog's headlines on the Hoofcare + Lameness Facebook Page
 

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, August 27, 2010

FEI NSAID Background: Alex Atock Explains When and Why Bute Was Banned


Many people I meet in the horse world are shocked and even a bit put off sometimes when they first learn that the FEI does not allow horses to compete on even the smallest amount of non-steroidal anti-inflammatory drugs (NSAIDs, pronounced "en-saids"). If it's ok for horses in the United States to race and show on Bute and other NSAIDS, why are the other countries so backward?

Or is it the other way around?

Whether it is horse racing or horse sports like eventing, driving, showjumping and dressage, the world's perception of horses competing on even the lowest dose of therapeutic medication are polarized.

Last week's congress on NSAIDs, organized by the Federation Equestre Internationale (FEI) in Lausanne, Switzerland, was designed to fully educate all interested parties before the FEI's General Assembly vote in November which will ask the world's equestrian bodies if it would like to liberalize the FEI's NSAID policy by going with a "progressive list" of allowed medications for competition horses.

Much of the NSAID Congress was scientific presentations by leading experts like the USA's Dr. Wayne McIlwraith but there were some ethical considerations as well. So far, the FEI has posted 12 videos of lectures from the Congress on YouTube for us to watch. That's a lot of pharmacology research.

But perhaps most important of all the lectures was a bit of a history lesson from horse welfare specialist veterinarian Alex Atock of Ireland, who was in the middle of the FEI's upheaval over NSAID reform in the late 1980s and early 1990s, when he served as head of the FEI's veterinary department. Bute was banned under Alex Atock's watch; who better to take us back in time to find out when and why the ban was initiated?

Listening to this video, I felt like I was thumbing through old issues of Hoofcare & Lameness. As the FEI strugged with the issue of banning Bute, I was writing about it, and about all the horror stories that were happening in the horse industry at the same time. Were they related to Bute? No, but they were related to horse welfare and the perception that people in horse sports had little regard for the well-being and even the lives of their horses. Somehow, this all spilled over to the drug debate, though.

As Atock says, we had German pole rapping scandals, American insurance-collecting horse killers, and the 1990 Breeders Cup had been called the blackest day in horse racing history, as three horses were euthanized as a result of breakdowns in one day's races, including the magnificent three-year-old filly Go For Wand. It's amazing horse sports of any kind survived that era.

The FEI's decision to completely ban Bute from competition horses was painful. It has been painful all along the way since then, but never more painful than the past year, when the old dichotomy opened up again.

Which way will the FEI vote in November--with the liberalized science-is-God view or with the welfare-ethics old guard of Europe who staunchly maintain that Bute and NSAIDs were banned for a reason and horse sport needs to distance itself from the perception that equine athletes are drugged in order to perform?

Does a horse on Bute deserve a Gold Medal if the Silver goes to a horse that is "clean"? On the other hand, should a horse be forced to withdraw from a world-championship competition because of a minor episode of colic a week beforehand that has nothing to do with a performance-enhancing effect of a drug that could be given to treat the colic? Should a vet have to hesitate to medicate a horse because of the performance-drug testing repercussions of a therapeutic substance?

These questions go around and around and around.


By way of education, here's a clip from a lecture by USEF veterinarian Kent Allen, explaining to event riders how to fill out forms to report the NSAID(s) their horses are on, since the USEF rules were changed this year. This clip is one of a 24-part YouTube series with Dr. Allen presented by US Eventing and sponsored by SmartPak to help riders through the process of understanding what is permissable for their horses and how to manage their horses within USEF rules while competing at USEF (as opposed to FEI) events. That's right: 24 videos to explain how to manage your horse's medications within the rules, and to help riders understand the issues and regulations surrounding the approved and unapproved medications themselves.

Dr. Allen is chairman of the USEF Drug and Medication Committee and vice-chair of the FEI Medication Advisory Group.  He is also official Veterinary Coordinator of the 2010 Alltech FEI World Equestrian Games. It is of critical importance to him that riders and trainers understand the medication process and that the American horse public understands the reasoning behind the USEF policies, which are different from the major European nations, but in line with some other countries around the world.

The one-med-or-two forms explanation is vaguely reminiscent of some of my phone calls with Blue Cross Blue Shield about my HMO care.

I highly recommend that ANYONE who even thinks of commenting one way or the other on the medication debate in the FEI watch all the FEI NSAID Congress videos AND Dr. Allen's USEF rules videos.

Educate yourself before you speak. The FEI and US Eventing have laid out a great menu of education for you, for free. You don't have to buy airplane tickets, stay in hotels, or sit all day in uncomfortable chairs. Just watch and listen and learn about medication rules, here, there and everywhere.

What do you want the future of the horse world to be like? How do you think international horse sports will be perceived if medications are allowed?

Most importantly, now that Alex Atock has reminded us where we have been, and opened up the closet where the skeletons have been hiding, where on earth is all this going?

© 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 the Hoof Blog on Twitter: @HoofcareJournal
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Tuesday, August 24, 2010

FEI NSAID Congress Presents Medication Facts and Philosophies for Equestrian Sport Decision Makers



Background: In November, the Federation Equestre Internationale, the world governing body of horse sports, will convene its General Assemby in Taipei. On the agenda is the groundbreaking and emotional vote whether or not international horse sports should allow horses to compete on low levels of mild anti-inflammatory medication, similar to what is now allowed in the United States. Currently the FEI operates under a zero tolerance policy, which is in keeping with many nations' national policies and even legal statutes. 
An attempt to pass this important rule change at last year's General Assembly was clouded in confusion and resulted in international furor that led to a decision to reconsider and re-vote in 2010. To make sure that the latest information was available to all voting nations, a congress convened in Switzerland last week with leading veterinary experts.
For this reason, the Alltech FEI World Equestrian Games in Kentucky next month will be competed under current FEI rules. Had last year's attempt passed permanently, horses from all over the world would have come to the USA and perhaps competed on medication for the first time in their careers, much like the international racehorses who come for our Breeders Cup. Some countries had grumbled about boycotting the 2010 WEG if the drugs were allowed. 
An emotional issue? It's hard to think of a more hot-button issue in international sport or racing. It is what sets the USA apart from the rest of the world. We think they should be like us. They think we should be like them. And so the world goes round.
Last week's FEI Congress on Non-Steroidal Anti-Inflammatory Drugs (NSAID) Usage and Medication in the Equine Athlete has been called an invaluable contribution to the debate on the in-competition use of NSAIDs. In a ground-breaking approach by the FEI, the Congress brought together both the most up-to-date scientific data and non-scientific aspects of NSAID usage for over 200 delegates from 29 countries at the two-day Congress, which was held at the Olympic Museum in Lausanne, Switzerland.
The second day of the Congress clearly demonstrated that this is a debate that cannot be viewed purely from a scientific perspective and that ethical values and legal issues also have to be taken into account.
Following Monday’s mainly science-based presentations, FEI General Counsel Lisa Lazarus opened Tuesday’s session by outlining details from nine European countries that prohibit or may prohibit the use of NSAIDs under national law.
In light of these legal issues, Ms Lazarus stated that the FEI has two options: either abandon any proposed change in the treatment of NSAIDs, maintaining the status quo that NSAIDs cannot be administered to sport horses during FEI competition anywhere in the world; or permit the use of NSAIDs at appropriate levels as far as the FEI and its members are concerned, but make it clear to all athletes and participants that the FEI’s rules do not supersede national law, and that anyone participating in the sport in any of the nine countries must note that national laws prohibit, or may prohibit, the use of NSAIDs.
Lynn Hillyer (GBR) of the British Horse Racing Authority, explained that the Racing Authorities of Europe, Hong Kong, North and South Africa, Australasia, Asia and the Middle East (except Saudi Arabia) rule that horses must not race under the effects of any drugs, but acknowledge that medication is necessary – off the racetrack – to ensure a horse’s physical well-being. “In other words, medication should be an aid to recovery, not a tool to enable a horse that should be resting and recuperating to race or train.”
Stephen Schumacher, Chief Administrator of the Equine Drugs and Medications Program of the United States Equestrian Federation (USEF), stated that the USEF Equine Drugs and Medications Rules allow NSAIDs usage with quantitative restrictions. “We believe that the welfare of our horses is not put into jeopardy with the judicious use of NSAIDs and their use may in fact be beneficial,” he said.
Dominik Burger, President of the Veterinary Commissions of the Breeding Associations for Swiss sport horses, spoke on the breeding perspective. He concluded that the issue would benefit from a pluralistic ethical analysis based not just on the welfare of horse and rider but also on regional and global public values like integrity, equity, justice, duties and responsibility.
Steve Maynard, Laboratory Director at Horseracing Forensic Laboratory Sport Science, outlined that quantitative analysis, applied to determine the exact level of a substance being present in the body, is significantly more costly than qualitative analysis carried out to detect the presence of a substance.
The public perception of equestrian sports, sponsors and the media perspective were all aired in Tuesday’s panel discussion, when British journalist Brough Scott asked some hard-hitting questions about the possible repercussions of reintroducing NSAIDs in competition.
Sven Holmberg, FEI First Vice President chaired the final debate on the pros and cons of the in-competition use of NSAIDs. Tim Ober (USA) and Mike Gallagher (CAN) spoke for the use of NSAIDs and Peter Kallings (SWE) and Christian Paillot (FRA) spoke against their use.
FEI Veterinary Director Graeme Cooke, who had earlier updated participants on the work of the FEI List Group, summarized both sides of the debate, drawing on key points from all the speakers over the two days. The FEI has achieved a number of key objectives through the Congress, he said, gathering up the science that had become available since 1993, bringing together the scientific and non-scientific, providing an opportunity to hear related views, and ensuring there will be a record of this unique event in order to inform not just National Federations, but everyone with an interest in the debate and allowing for further review before the FEI General Assembly in November.
In his final summing-up, Holmberg stressed the importance of keeping the debate alive between now and the vote on in-competition use of NSAIDs in November, so that the decision taken at the FEI General Assembly is one that is founded on sound knowledge and in the best interest of the sport and the horses.
“There is no doubt that both sides of the Atlantic and the rest of the world have the same clear goal in mind: that the welfare of the horse is really paramount to whatever we do,” he said.
A report on the Congress will be sent out to all National Federations, and the FEI website will continue to offer a feedback area for comments. To maintain the flow of information for National Federations that were unable to attend the Congress, videos of all speeches and power point presentations, as well as the panel sessions and full debate, will be made available on the FEI YouTube Channel later this week. 

A mini site for the Congress with documents and abstracts has been set up on the FEI web site. Comments on the medication issue are invited; please email your opinions to nsaidcongress2010@fei.org

© 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 the Hoof Blog on Twitter: @HoofcareJournal
Join the Hoofcare & Lameness Facebook Page