I seem to have spent two months with no time to blog. What in the world was I doing?
The last you heard from me, dear readers, I was in the first week of our month-long shelter consult. The first week we digested a lot (a LOT) of data from the shelter. The second week we wrote up what we thought about that data. How many dogs did this shelter take in over the last few years? Cats? Are there changes in intake? How many of each species were euthanized? Why? What is the average length of stay for each species? Are pit bull type dogs treated differently? Etc.
The week after that, we were on site, crawling all over that poor shelter. That was a very busy week; in the evenings we were scrambling to write up everything we had seen and photographed during the day. On the last night of the consult, we generated our exit report, which was an overview of our findings. What did we think were this shelter’s greatest strengths? Its greatest challenges? What did we think they should address first? How? What was our five year plan for them?
The week after that, we were back on campus, writing, writing, writing. The complete consult report is traditionally quite a long document; in previous years it has been hundreds of pages long. The shelter medicine residents (the veterinarians who are specializing in shelter medicine) worked on the report for another week after that, but we interns were released after just one writing week.
After that, I spent two weeks at a truly lovely limited admission, adoption guarantee shelter about an hour and a half from home. I shadowed the shelter vet some of the time, and worked on my own some of the time. I did a lot of physical exams and surgeries! I also helped one day to select animals from the local municipal shelter (lots more animals, lots more euthanasias) for transfer to the adoption guarantee shelter. Our truck was almost full of animals when shelter staff pointed out an ancient, arthritic collie mix and asked if we might consider taking her. I argued against it, saying she was too old and decrepit to be adoptable. But in the end we felt sorry for her and took her (another dog had to ride on my lap on the way home to make room). Then I felt too bad for her to put her in the shelter kennels — her arthritis was so bad and she seemed so depressed. So I took her back to my room for the night. And the next night. And home over the weekend. And hung on to her my second week in the shelter. I officially adopted her on the last day. Her name is Rosie.
In mid November, I spent two weeks on campus, working with veterinary students as they learned how to spay and neuter animals. I am getting more and more confident in my own spay/neuter skills, but teaching still feels scary. Will I be able to tell ahead of time before someone does something wrong? I also got to amputate a badly broken leg off of a kitten. My first amputation! Terrifying. There are big arteries in there.
After Thanksgiving, I was on campus again for our shelter behavior course. This was a blast. A lot of reading about behavior (one of my favorite things to do), and a surprising amount of hands on work. We learned about different temperament tests for dogs and tried them out, both on shelter dogs and on our own dogs. We visited some different shelters in the area and talked about how they handled their dogs, and at the end of the two weeks we spent two days at one shelter, getting hands-on helping some of their dogs: setting up play groups, putting up cage barriers for those dogs who were over-stimulated by their surroundings, hanging treat buckets, etc.
Now I am in the hospital on the dermatology service. Skin problems are really, really common in shelter animals, particularly in the South. Flea allergies! Pollen allergies! Allergies allergies allergies! Also mites.
And that brings me to today. I finish up my dermatology rotation next week and head on to another week in the emergency room. And that is what I have been up to. I have been quiet, but I have not forgotten you guys.
Wednesday, December 19, 2012
Sunday, December 16, 2012
Will we ever be able to measure cortisol in real time?
In my Copious Free Time (CFT), I sometimes like to try to figure out how close we are to implementing some of the crazy technology I’d love to use in research. I want to learn more about the canid stress response, as a way of learning about canid domestication (domesticated animals have blunted stress responses, and this may be part of why they are so accepting of novelty and so easy to socialize). The hormone that most people use to study the stress response is cortisol.
I have written in the past about some of the many problems with studying cortisol. Two of those problems are
I asked a friend who works in research imaging. She obligingly sent me a review paper to read, about studying dopamine levels in humans using PET. The problem this paper addresses is getting at the dopamine levels in the brain without having to slice open the skull (something we definitely don’t like to do in humans — and although we might be willing to do it in rats or mice, it is going to be hard to retest the same animal later to see how its dopamine levels have changed, seeing as how a common side effect of skull sliceage is death). This is a pretty cool technology. It goes something like this:
Egerton A., Mehta M.A., Montgomery A.J., Lappin J.M., Howes O.D., Reeves S.J., Cunningham V.J. & Grasby P.M. (2009). The dopaminergic basis of human behaviors: A review of molecular imaging studies, Neuroscience & Biobehavioral Reviews, 33 (7) 1109-1132. DOI: 10.1016/j.neubiorev.2009.05.005
You could use something similar to monitor cortisol binding in the brains of dogs. That would be very interesting, actually, but the studies I tend to envision are more concerned with cortisol amounts that are released from the adrenals. We are actually in a better position here with cortisol, compared to the suckers studying dopamine in the brain: dopamine is released in the brain and stays in the brain, so you never get a chance to see it in the bloodstream. The bloodstream is actually easier to get at than the brain, obviously.
Conversely, cortisol comes from the adrenal glands (way down near the kidneys, far from the brain). The brain sends a signal to the adrenals via very long nerves, and then the adrenals release more or less cortisol, for a longer or shorter period of time. It’s the “more” or “less”, “longer” or “shorter” that are interesting. I actually don’t know enough about where cortisol binds to say if using a radiotracer-labelled cortisol agonist or antagonist, to sit on binding sites, would be interesting, but I suspect this is not the right direction for this technology. Cortisol binds in organs all over the body and affects a lot of processes. Unlike with dopamine, where researchers are interested in very specific (hence small) brain areas, we would want to scan the whole body for cortisol binding.
The radiotracer idea is interesting, though. Maybe we could attach a radiotracer to one of the precursors of cortisol, like cholesterol? We would inject labelled cholesterol. The adrenals would take it up and convert it to cortisol. Then when they released cortisol, we could see the label spreading across the body. No need to measure binding. We could in fact just scan one part of the body where there is a lot of blood — a vein coming out of the adrenals? — to watch cortisol levels rise and fall. The downside: the use of PET to monitor the changes in the radiotracer label. PET is expensive and it requires the subject to hold... perfectly... still. Something dogs are not very good at doing.
What I really wanted, I decided, was something that works sort of the way a pulse oximeter works. Pulse oxes are little devices that you hook up to an animal while it is under anesthesia to monitor their blood oxygenation (you know, to tell if they are dying or not, something which ironically is often easier to tell just by looking at the animal, but we use the things anyways). These devices work by shining a light through an area of non-pigmented skin (such as the tongue, an unpigmented paw pad, or if all else fails, a vulva) and measuring how much hemoglobin (hence oxygen) is in the blood based on color. Could some such device measure amounts of tracer label?
I was letting these ideas percolate and considering how I might write them up for you, dear readers, when I completely by chance came across the following announcement: Sano Intelligence is working on a wearable patch which will continuously monitor blood chemistry.
A wearable patch! That’s actually a much better solution to this problem. It operates wirelessly, so you slap it on (at a cost of $1-2 per patch for materials, though much more in the end to the company to pay for development costs, I imagine) and then remotely monitor changes in blood sugar, electrolytes, and — cortisol? Of course the company does not mention cortisol as one of the substances the patch would monitor. I wonder if there is any reason it couldn’t be included, though. It would help if I had any idea how this patch worked. The company asserts that it’s non-invasive and does not hurt to apply. So how does it get at the substances in the bloodstream? Apparently the company isn’t saying until the patch is released.
So now I wait. If any of you out there in internet land know more, or have thoughts on how this might work, let me know!
I have written in the past about some of the many problems with studying cortisol. Two of those problems are
- Getting hold of cortisol (from blood or even saliva) without increasing the animal’s stress and therefore invalidating your study, and
- Measuring cortisol frequently enough to actually be able to track its very rapid changes in the bloodstream (changes on the order of minutes, continuing to occur and be important over the course of hours).
I asked a friend who works in research imaging. She obligingly sent me a review paper to read, about studying dopamine levels in humans using PET. The problem this paper addresses is getting at the dopamine levels in the brain without having to slice open the skull (something we definitely don’t like to do in humans — and although we might be willing to do it in rats or mice, it is going to be hard to retest the same animal later to see how its dopamine levels have changed, seeing as how a common side effect of skull sliceage is death). This is a pretty cool technology. It goes something like this:
- Inject the individual with a radiotracer which is attached to dopamine agonist or antagonist. The agonist or antagonist will attach to dopamine receptors, and the radiotracer will allow us to use PET to monitor how much of it is attached in the part of the brain that we care about.
- Monitor the changes in the radiotracer in the region of interest. As dopamine levels in that region increase, the unlabelled dopamine will bump more and more labelled agonist or antagonist off of the receptors, which will mean there will be less radiotracer in the region. Less tracer implies more actual dopamine. Do math.
Egerton A., Mehta M.A., Montgomery A.J., Lappin J.M., Howes O.D., Reeves S.J., Cunningham V.J. & Grasby P.M. (2009). The dopaminergic basis of human behaviors: A review of molecular imaging studies, Neuroscience & Biobehavioral Reviews, 33 (7) 1109-1132. DOI: 10.1016/j.neubiorev.2009.05.005
You could use something similar to monitor cortisol binding in the brains of dogs. That would be very interesting, actually, but the studies I tend to envision are more concerned with cortisol amounts that are released from the adrenals. We are actually in a better position here with cortisol, compared to the suckers studying dopamine in the brain: dopamine is released in the brain and stays in the brain, so you never get a chance to see it in the bloodstream. The bloodstream is actually easier to get at than the brain, obviously.
Conversely, cortisol comes from the adrenal glands (way down near the kidneys, far from the brain). The brain sends a signal to the adrenals via very long nerves, and then the adrenals release more or less cortisol, for a longer or shorter period of time. It’s the “more” or “less”, “longer” or “shorter” that are interesting. I actually don’t know enough about where cortisol binds to say if using a radiotracer-labelled cortisol agonist or antagonist, to sit on binding sites, would be interesting, but I suspect this is not the right direction for this technology. Cortisol binds in organs all over the body and affects a lot of processes. Unlike with dopamine, where researchers are interested in very specific (hence small) brain areas, we would want to scan the whole body for cortisol binding.
The radiotracer idea is interesting, though. Maybe we could attach a radiotracer to one of the precursors of cortisol, like cholesterol? We would inject labelled cholesterol. The adrenals would take it up and convert it to cortisol. Then when they released cortisol, we could see the label spreading across the body. No need to measure binding. We could in fact just scan one part of the body where there is a lot of blood — a vein coming out of the adrenals? — to watch cortisol levels rise and fall. The downside: the use of PET to monitor the changes in the radiotracer label. PET is expensive and it requires the subject to hold... perfectly... still. Something dogs are not very good at doing.
What I really wanted, I decided, was something that works sort of the way a pulse oximeter works. Pulse oxes are little devices that you hook up to an animal while it is under anesthesia to monitor their blood oxygenation (you know, to tell if they are dying or not, something which ironically is often easier to tell just by looking at the animal, but we use the things anyways). These devices work by shining a light through an area of non-pigmented skin (such as the tongue, an unpigmented paw pad, or if all else fails, a vulva) and measuring how much hemoglobin (hence oxygen) is in the blood based on color. Could some such device measure amounts of tracer label?
I was letting these ideas percolate and considering how I might write them up for you, dear readers, when I completely by chance came across the following announcement: Sano Intelligence is working on a wearable patch which will continuously monitor blood chemistry.
A wearable patch! That’s actually a much better solution to this problem. It operates wirelessly, so you slap it on (at a cost of $1-2 per patch for materials, though much more in the end to the company to pay for development costs, I imagine) and then remotely monitor changes in blood sugar, electrolytes, and — cortisol? Of course the company does not mention cortisol as one of the substances the patch would monitor. I wonder if there is any reason it couldn’t be included, though. It would help if I had any idea how this patch worked. The company asserts that it’s non-invasive and does not hurt to apply. So how does it get at the substances in the bloodstream? Apparently the company isn’t saying until the patch is released.
So now I wait. If any of you out there in internet land know more, or have thoughts on how this might work, let me know!
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