Posts Tagged ‘inflammation’

Raymond Geor, BVMS, College of Veterinary Medicine, Michigan State University

Dr. Raymond Geor, a veterinarian and researcher at the College of Veterinarian Medicine at Michigan State University, gave one of the first presentations I heard at the Mid-Atlantic Nutrition Conference.  His talk had big 6-syllable scientific terms- all delivered with the measured pace of a scientist. He packs a lot of information in his talk, and as a layperson I usually come away thinking, “What was he talking about?”

I am fortunate to have a tape recorder to help me keep track of the stuff I miss. The more I listen to his talk, the more I can skate around the moguls of language and studies: And the more I can see the landscape he is describing. There were no bunny slopes in sight; the good doctor took us to the top of the Matterhorn and it was an hour’s speed race the whole way down to the end.

The verbal description of his talk was only two paragraphs long. It stated that there are anecdotal impressions by veterinarians of a relationship between obesity, insulin resistance, equine metabolic syndrome and laminitis. The second paragraph stated Geor would review the current diet and nutrition management for reducing the risk of laminitis in these animals.

ah, the miracles of photoshop

We start with a wee background from last year where Dr. Nicholas Frank gave a presentation that I summarize as “ Obesity in a horse is a good clinical sign that you are courting problems.” This is where Geor picks up and in a nice way says- it has been noted that the observable characteristic of obesity often indicates a predisposition for pasture-induced laminitis in horses. This, then, would be the laminitic phenotype. These horses seem to respond to changes in dietary and environmental conditions differently than other members of their herd.

We were also reminded of the fact that at the heart of laminitis is inflammation that disrupts life in the laminae resulting in its death and, in some cases, severe coffin bone rotation and the demise of the horse as well. Furthermore, there is a pretty good hunch that there is a connection between a pasture-induced laminitis episode and disturbance in the animal’s hind-gut brought on by rapidly fermenting carbohydrates that in some way (death of microbes, toxin release, gut leakage?) causes an inflammatory response in the horse that takes it over the threshold into laminitis.

Currently there are three main theories scientists are working on.

  1. there is an underlying inflammatory condition in these horses and ponies.
  2. Insulin toxcity
  3. A perfect storm of multiple colliding factors

Why would a fat horse or pony be more susceptible to laminitis? Ah-ha. That’s a good question that has no answers. But, there have been some recent discoveries in other species (us humans for one) that merit consideration (and therefore research) for the equine species.

It would seem that fat, once thought of as a simple collection of  storage cells, actually is ALIVE! ( the monster within- I sense a movie in all of this.) Adipose tissue is very metabolically active. It regulates things like pro-inflammatory cytokines, which makes the scientist wonder if the obese horse is in a constant metabolic state of systemic inflammation. If so it would be easy enough to understand why anything that would contribute more inflammation would tip the horse over the laminitic threshold.

Wondering what insulin looks like?

In other species fat seems to have a pretty strong affect on insulin. Interestingly insulin actually has two pathways, one is use (sensitivity) and the other is production. Fat appears to decrease the use of insulin while increasing the production of it with the result that there ends up being a large concentration of insulin in the blood stream (hyperinsulinemia.) That’s a very bad thing for the circulation and results in vaso-constriction: in other words tissue (such as the laminae) starvation and death.

Then there is the perfect storm theory, fat, inflammation, insulin, gut mobility, gut bio-environment, gut motility, gut permeability, forage composition factors other than carbohydrates, genetics, climate, life-style. Whew. Oh, and what about the obese mom that predisposes her foal to metabolic disorders? Happens in humans – could the same be true in horses?

And here’s my own wild card questions. How about how the whole digestion process works in these laminitic phenotypes.  Does their system empty slower or faster than their healthy counterparts? There is always talk of the role of  GI micro-organisms in creating laminitis.

coprophagia: foal eating mom's manure

Well, perhaps the genetic pre-disposition component is the foal eating mom’s bacteria laden feces.Mom could have “laminitis-making-bacteria” in her GI track. Maybe it’s not a gene, maybe it’s being in a stall with predisposed, obese, laminitic mom and the foal’s natural and needed coprophagia.

So many of these conditions are tightly intertwined that it will be a galactic challenge to investigate. And, of course, there is very little money to support this research.

I have an insulin resistant horse and another overweight pony. After listening to Geor’s presentation I renewed my efforts to reduce their weight as I have seen and heard the devastation of laminitis.

And, personally, I’m going on a diet lest I become even more inflammatory in my remarks.

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new research on livestock nutrition

One of my annual March sojourns is to partake of the Mid-Atlantic Nutrition Conference. I come away filled with adrenaline and excitement: my brain neurons firing away at all the paths those little research tidbits lead me down. None of my conjectures  have any scientific backing, but they are still worth a moment  or two of wonder. I noticed some interesting directions from the conference this year.

It might help for you to understand what this conference is all about–– livestock nutrition. Primarily dairy cattle, poultry and equine. This is where the academic researchers, feed mills, veterinarians and large livestock producers go to find out what are the newest research studies and theories on animal nutrition. You are not going to get razzle-dazzle slides here; you are going to get charts and ugly photos. But you walk out with a good sense of what isn’t known, what needs to be studied and a few sentences of something that has finally been proven.

It always reminds me the road to knowledge is a long one and that the body is blessedly complex.  I hope to post a number of entries over the next several weeks on specific topics covered at the conference along with my thoughts and questions. But for now I am still cogitating on a number of overall directions and impressions from my time in Maryland.

  • There was a new word thrown around quite liberally phenotype. Phenotype refers to the OBSERVABLE characteristics of an organism that has resulted from the interaction of its genotype and environment. It is an old word, but is being picked up and used more regularly in the scientific community. One might say that I am a phenotype for heart attacks; I have a chicken physique. (we’re using silly examples here, folks.) All fat lands in a plumb Buddha belly with nary an ounce going into my legs or butt. Observable characteristics are the belly fat. My mother and father had the same structure. This predisposition is most likely a genetic code of where my family line should store fat. Environment characteristics are the incessant putting of a full fork into my mouth. And now we have research to show that belly fat is hormonally active and a leading cause of heart attack. So I could stand as a phenotype for humans courting heart attacks. Or I could be a fat horse and the phenotype for laminitis.

There was a lot of discussion of the laminitic, IR and obese horse phenotype.

  • I think this word is being used more often because of another trend- the researchers are looking really small. Better technology has helped here as well as directions in human medicine. And in looking really small they are finding that the organism is REALLY connected. A cure for laminitis isn’t going to come by just looking at the inflammation of the feet. That is a sign, but now they are realizing that there are a lot of things on the cellular level that might cause inflammation in a body structure that might send hormone signals to other parts of the body that might start another cascade of seemingly unrelated events that end up in the feet. In looking really small, researchers are broadening their horizons.
  • Researchers are starting to whisper in the hallways about the failures. No one studies the failures in a research project. Part of that is due to the “system” of publishing papers where talking about failures is likely to result in a failure of the paper to get published. One of the speakers mentioned that in a clinically induced challenge of horses with genetic predispositions for laminitis, 20% of them never get laminitis. Their results are left in the paper trail that hits the circular file. Yet, this researcher had the strength to pause and say, folks someone should study these failures- what have they got in their systems that the other horses don’t have. (Please remember a failure is what does not prove the hypothesis. So if the hypothesis is that lush green grass will produce laminitis and these predisposed horses didn’t get it. Well, they “failed” in that they did not prove the point where as the other 80% did get it and proved the hypothesis.- Okay, okay- it’s a very simplistic explanation to help get across a very complex point.)

I’m not a scientist, but I find this thrilling stuff.  Finally the research industry is connecting the smaller dots that make up the larger ones. I also find it overwhelming- the amount we now know we don’t know. Dr. Raymond Goer from the University of Michigan School of Veterinary Medicine said it nicely,

“I know a lot less than I did a year ago. And I know a whole lot less than I knew two years ago.”

We are having to step back to go forward, but it is putting us on a better path.

Oh, and that word “phenotype” bet you see it everywhere now.

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Earlier this week I attended the Rutgers Equine Science Update and got a peek into some of the research they are doing on horses. I have to hand these people a lot of credit for exposing themselves before a research project is complete. They are one of the few groups I know who really do try to be transparent, to use a word-of-the-moment.

The Equine Science Center looks at ways to prevent disease, as opposed to a veterinary hospital, which researches ways of treating and curing a disease. Throughout the years I’ve seen the Center produce some valuable information, and since they discuss the projects while “in progress” it gives the layperson, like myself, a better in-sight as to the complexity of research. A while back they did some research on the efficacy of supplements for joint pain. It took them a year to identify specific blood markers that would accurately predict joint inflammation.

Then they spent considerable time on sourcing specific ingredients in their pure form. After all, you may think it’s the yogurt in your daily dose of strawberry yogurt that makes you break out, when in fact, it may be the strawberries! Same with a supplement, you want to test the active ingredient by itself to eliminate the possibility that it really is the alfalfa meal that is providing all the benefit.

No wonder some medical cures take so long to come about.

So I was intrigued by one of the research studies the Center is sponsoring. Dr. Janet Onishi is actually a plant biologist with a pharmaceutical background. Doesn’t know a thing about horses and I wonder how she came out of the woodwork. How she came upon laminitis as an equine pathology and why it peeked her curiosity remains a mystery to me.

Janet Onishi, Mike Fannell, Dr. Michael Fugaro

Her interest is in the chronic laminitic situation. Chronic laminitis differs from the acute form in that the horse is never really free form it. The disease continually flares up in the horse’s life. An acute case can turn chronic, but many acute cases are one time events, are treated and the horse remains free from it afterward.

She also approached the question in a different light. The traditional thinking on causes of laminitis involve a carbohydrate overload killing-off bacteria and creating endotoxins, which churn up inflammation with a result of  laminitis in the hoof. Endotoxins are a structural component of the wall of gram-negative bacteria and are only released when the bacteria die.  What caused a big ‘Hmmm” from Onishi is that injecting the endotoxins directly in the horses blood stream does not create the same scenario. In fact, injecting these endotoxins in the blood stream doesn’t cause any laminitic conditions at all.

Coming from the outside, Onishi had no preconceived notions about the disease and her ponderings gave her wings. Looking at human literature she found evidence that microbes (bacteria) can cross out of the gastro-intestinal track into the lymph system and from there cross into the blood stream and have full access to the body. So she had a thought “What if the microbes were playing a different role in the disease then we imagined? Perhaps it is not the products of the microbes that are causing the problem, but the bacteria itself.”

So she got initiated into the world of animal research protocol, ethics and oversight and is working closely with area veterinarians on a current study. She has some initial findings that are showing there might be merit in her hypothesis. Lamina taken from horses who were euthanized due to causes other than laminitis had no, or very minute, bacteria counts in their hoof lamina. Horses euthanized due to chronic laminitis had significantly high bacterial counts in their hoof lamina.

There are over 77,000 horses suffering from chronic laminitis in the U.S. and I suspect there are an equal number of horse owners who are praying for a way to prevent or control this havoc in the lives of their animals.

The study has just started and even if the results prove the hypothesis, there is still the question of identifying the bacteria, what causes the movement, and how do you affect or interrupt the cascade. But, I find this project replicates one of the purposes of this blog. Talking to people in different mind-sets, careers, and experiences; crossing sectors of science, art, and sociology; going away from horses to bring back to them the best thoughts from other sectors, and not being afraid to say,  “I wonder, what would happen if…”

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