Category: Research

Laminitis researchers provide huge volume of free information

Posted on: November 11, 2012

Equine Veterinary Journal

Screen shot of the Equine Veterinary Journal’s new release of laminitis research.

The laminitis research community has released a huge volume of free work intended to set the record straight on all things laminitis, as of 2012.

Science papers released online often cost $35 per paper, beyond the budget of many a laminitis-poor horse owner. This “virtual” collection of papers released through the Equine Veterinary Journal is a gift. A big thank you to this publication and all those researchers who contributed their time and knowledge.

The release includes the full text and references of these papers and costs nothing. You don’t even have to log in or leave an email address, though no one would mind, I’m sure.

The material is written by all the big names in laminitis research: James Belnap, Chris Pollitt, Philip Johnson, James Orsini, etc.

Note that this is a very large body of work. I downloaded the provided PDFs (as far as I can tell, you have to download each individual PDF, as opposed to downloading the whole thing in one take — compiling all the papers into one PDF might have made it too large to download). I then made the mistake of printing the PDFs, and I used up maybe half a ream of paper.

Also, note that this material is written using a lot of scientific language, even though the editor states upfront that the purpose of this release is to combat the fact that much of the freely available material published online for horse owners “lacks rigor and quality.” So, these papers are for the average horse owner, but many words will be unfamiliar.

I’ve been reading science papers since 2007, and my first attempt seemed hopeless. I stopped at every new word to look it up, and it took me several days to get through one paper written by someone whom I consider very easy to understand in person. But this is how laminitis researchers write. My advice to anyone who wants to read these papers is perhaps to skip over something at first if it’s causing you great difficulty, because the more you read the material, the more familiar you will get with the terms. When you go back to a paper a second time, it will make more sense.

The takeaway message I see in the early going of my reading is as follows:

Scientists now consider there to be three forms of laminitis. The disease can be caused by sepsis (gastrointestinal injury), endocrine disease (insulin-resistance and Cushing’s disease) or excessive weight bearing. There may be some overlap between the forms based on the horse’s situation, but the changes in the foot are different for each.

There is much work to be done in studying each form. However, there is also a small glimmer of hope on the treatment front.

The paper titled “Progress toward effective prevention and therapy for laminitis” says these differences in the various forms of laminitis make it hard to target a failed process in the hoof and come up with a therapeutic intervention.

However, it also raises the possibility of reversing laminitis. It says new evidence suggests that the laminae do attain the ability to remodel, but this has been absent in the laminitic hoof, and it may be caused by reduced activity of p63, a regulator of epidermal stem cells. It suggests that transplantation of these stem cells from unaffected regions of the horse may have regenerative therapeutic potential for laminitic horses.

I talked to someone in the stem cell lab at Rood & Riddle Equine Hospital in Lexington, Ky., in May 2011 right before I put down my mare Angel, and, at that time, the rate of success for stem cells was not good, and I felt as if the trip alone would kill Angel, and the success rate at the time didn’t warrant trying, even if the monetary challenges could be overcome. I do not have any details on what the lab was using in terms of stem cells at that time. I’m guessing that this new development may bring stem cells to the forefront as a treatment.

As for new details on those various laminitic models:

The sepsis model includes carbohydrate overload and excess fructan scenarios. In the paper titled “Sepsis-related laminitis,” it gives a good explanation of the process: Excess starch arrives in the large intestine and is digested by intestinal bacteria, which results in a severe drop in intestinal pH, an ensuing die off of Gram-negative organisms and a moderate to severe enterocolitis, or inflammation of the colon and small intestine. This leads to injury to the mucosal barrier and absorption of numerous substances, including bacterial toxins. For years, people thought the bacterial toxins, called endotoxins, were the culprit. But this paper says experimental infusions of endotoxins did not result in lamellar failure, so investigators are looking for other trigger factors absorbed from the compromised gastrointestinal tract.

For the endocrine form of the disease, the paper titled “Endocrinological aspects of the pathophysiology of equine laminitis” raises some interesting points. Inducing laminitis in horses and ponies results in serum insulin concentrations much higher than those commonly associated with Cushing’s disease and some cases of pasture-associated endocrine-related laminitis, and it says “similarly high serum insulin concentrations have been documented in recurrently laminitic ponies in the absence of clinical signs of laminitis, such that very high serum insulin concentrations alone are not necessarily laminitis-inducing.” And, even more interesting to me, the feet of the ponies induced with the insulin form of laminitis showed a lack of basement membrane disintegration. Instead, the feet showed apoptosis (programmed cell death) and mitosis (cell division). Thus, these feet do not fall apart in the same manner as in the carbohydrate overload model or the naturally occurring disease. The paper says that debate continues over whether insulin resistance is associated with increased or decreased blood flow in the feet, and insulin resistance’s association with inflammation in the laminitic horse is also unclear. It says studies suggest that excess glucose does not play a role in insulin-induced laminitis.

It talks about identifying horses with insulin resistance. One study on a group of ponies combining five diagnostic tests did not result in higher diagnostic accuracy than individual tests of insulin or leptin. Leptin is a peptide secreted by adipose tissue. I’m not aware of ever having a leptin test done on my horses. The mention of that as a test was a surprise to me.

It says that phenomenal efforts by scientists have increased knowledge about this form of the disease dramatically over the last few years, but those efforts have probably generated as many questions as answers. And it closes with an interesting summary: “It should be remembered that not all laminitis-prone animals are obese and/or insulin resistant, not all obese animals are insulin resistant and not all insulin resistant animals are laminitis-prone.”

Perhaps the opening line of the support limb laminitis paper says a mouthful: “Supporting limb laminitis is a veritable dark hole when it comes to our goal of completely understanding the pathogenesis and therefore the prevention of all types and clinical presentations of laminitis.” However, if you read further, progress is being made on understanding how the laminae fail in this model. That is good news.

There is much to explore in these papers, and a quick study on my part can’t begin to cover the research included. Hopefully, the release of this information will move research forward in a meaningful way. Again, we should all be grateful for this information being given to us online at no charge. Thank you, Equine Veterinary Journal.

 

A study on iron overload and insulin resistance as it might relate to laminitic horses

Posted on: October 26, 2011

Since I wrote about iron and insulin resistance in horses two days ago, I stumbled over a paper by Dr. Eleanor Kellon that appears to have been created in 2006. The title is “Iron status of hyperinsulinemic/insulin resistant horses.”

Kellon conducted a study to determine if insulin resistant horses and ponies also show iron overload in their blood.

Insulin resistant horses and ponies were divided into two groups: those that received a balanced mineral diet and those that ate whatever minerals crossed their path. Another group of adult horses and ponies free of obvious disease served as controls.

There was a significant elevation in body iron in the insulin resistant horses on uncontrolled mineral intakes.

Kellon says: “Risk factors for equine insulin resistance have not been completed identified but likely represent an interaction between genetic predisposition, underlying disease states and the environment. Since genetic factors are beyond our control and drug therapy for PPID (Cushing’s) does not necessarily lead to resolution of IR, identifying external factors has the potential to improve control. The role of iron overload as a risk factor for IR and therapeutic effect of lowering body iron levels has been documented in man.”

And she concludes: “Animals on mineral balanced diets had normal TSI and ferritin levels, and improvement in their insulin resistance, but since other measures were undertaken concurrently (e.g. reduction in NSC of the diet), the effect of the mineral balancing per se could not be determined. More extensive prospective and intention to treat studies are necessary to clarify the role iron might play in equine IR.”

Guide to participating in a long-term laminitis study

Posted on: October 21, 2011

I’m hearing and reading about a lot of clinical trials and thought I’d share some of my own experiences for longer trials, which I define as 12 to 14 weeks. I would not be interested in doing another one that studied my horses’ metabolism under certain conditions. I would still be willing to test a new drug or supplement.

The problem with trials is the same as any agreement between two parties: If there is a miscommunication, it can lead to hard feelings on both sides. Everyone needs to be very clear up front what is going to happen during a study.

I debated whether to do a very sterile article that speaks to both the researcher and the horse owner. But, I feel like the horse owner is facing some big hurdles with studies, and I really needed to write this for the horse owner. So, with apologies to researchers the world over, here are my concerns for horse owners considering doing a study.

Before I get into specifics, let me lead off with this dose of reality: Research is all about money. Even if it seems to be a trial to collect statistics on a particular disease, someone is planning to use those statistics for monetary benefit. The research has to generate revenue, or it would not have been undertaken.

Your horse likely has the disease being studied, and you are working off emotion. In that state, you are going to agree to everything under the sun in the hopes that your horse might get better. That kind of thinking will get you nowhere. Check your emotion at the door and look at a potential study from all the following perspectives.

1) Participate in studies where you have control if you need to make changes. If someone wants to study how your horse reacts to eating so many pounds of hay a day, and halfway through a 12-week trial, your horse starts to balloon up, you need to be able to cut down on the hay rather than watch your horse founder just because you agreed to do a study. Don’t agree to stick to a rigid schedule if your horse is going to be the loser in the end. Have an out. Get that point in writing.

2) Agree only to studies where you are provided with all results in real time. Get in writing that you will be given all results related to your horse, and make sure the researcher keeps that end of the bargain. Researchers may be tempted to hold back information. For example, a researcher may not tell you your horse’s insulin level is rising as a result of something happening in the study. Be the advocate for your horse and require knowing the results, so you can change your horse’s living situation if necessary.

3) Set down the rules and have penalty clauses if the researcher does not fulfill his end of the bargain. Require payment or some other compensation if the researcher is late or spends an hour talking on the phone and wasting your time. Your time is just as valuable as his.

4) Clearly define who is doing what. If you researcher says he will provide a supplement being studied, document how that supplement will arrive, from where, who is paying for it, who will follow up to find out where it is if it doesn’t arrive on time (you should not have to make that call), whether you will have access to the same supplement once the trial is over and how much it will cost you after the study. If the researcher says he will take care of all medical bills for the horse during the trial, write down specific things you want covered (deworming, shots, teeth floating, colic treatment, other emergencies, etc.) and make sure that’s in your contract. Two people can have vastly different interpretations of what “medical bills” means. If the study is supposed to pay for hay, grain or board, get it in writing.

5) If you are being paid to be in a study, understand that your horses and time are being rented for the length of that study, and the cost of the researcher trying to do that study himself with a herd of his own would be enormous. Make sure you are compensated adequately for your work with your horse and the research documentation you must take care of during that time. Money does not come easily right now for researchers or horse owners. But, that researcher is not going to give you a break on a medical bill if your horse is a patient. Don’t undercompensate yourself for your own time when doing work for him.

6) Understand what you’re getting into time-wise. It may not sound like such a big deal to weigh your horse’s hay, but you might be weighing it every day three times a day for 12 weeks, and you might be documenting every day how your horse walks and whether it has a pulse in its feet. It gets old fast. If drawing blood is included, make sure your horse has the type of personality to withstand being a pin cushion for the duration of the study.

7) Make sure your goals and those of the researcher are the same. If you want to know why your horse foundered, and your researcher just wants to test how long it takes your horse to founder in a particular environment because that’s the project he’s working on, you’re not going to get out of that study what you want. Your researcher is not going to change course and do what you want. Ultimately, you will be unhappy.

8) Require credit for you and your horse if you want it. When the researcher writes up the study, you and your horse should be named at the end of the study if that’s your wish.

9) If there’s equipment involved, make sure the contract includes the dates for the arrival and pickup of that equipment. If the equipment takes up most of your kitchen, charge rental space for the time that it occupies your kitchen. If your horse were in a stall at the researcher’s facility, you’d be paying plenty in rent for that space.

10) Remember these words: Your time is not free. When’s the last time someone did something for you for free?

11) If these tips are at odds with the desires of the researcher, and the researcher won’t agree to your terms, that’s OK. The world will not end if you don’t do the study, and your horse’s welfare and your sanity are your only concern.