It's only Tuesday and I am already losing my freakin' mind this week. I need to get a manuscript and abstract out the door and I am giving a seminar at the end of the week. I am trying to solve some lab-based problems and have new students coming next week. I need to leave my office in four minutes to get to swimming lessons.
This evening I had the choice between a run and a de novo blog post. I can't lie, I chose the run and got a great workout in with a couple of supra-lactate threshold periods in specifically designed to kick my own ass. Still, I know you demand reading material, little monkeys, and so I offer you a post from the old blog on family time, pesto making, and why Dr. Isis is the hottest science blogger in the sphere. It's behind the cut.
XOXOXOXO,
Isis
Dr. Isis is a pretty good scientist. She is an amazing mother.
"Dr. Isis, you're quite cocky today," you might reply. And you would be absolutely correct. Dr. Isis does get a bit cocky about her family. She has often told students of the Women in Science and Engineering variety that there is no balance in life because balance implies that you do two things equally well at the same time. When Dr. Isis does her science, she does her science. When she does her family...never mind.
So, around here Saturday is "The Isis Family Super Fun Day Saturday." This morning The Isis Family visited our local producer to pick out an array of fruits and vegetables for the rest of the month. Later on, after the Isis Brood finishes napping, we'll visit the zoo and make faces at the monkeys. Dr. Isis sometimes wishes that she were a monkey so that she could throw poo at the people who annoy her.
But, this morning's events inspired Dr. Isis to blog about two things that she has been pondering and thinks are really important. First, the need to guard your family time. Second, how to get dinner on the table at night without resorting to frozen pizza.
When Dr. Isis was Undergraduate Isis she lived with a girl who, when it was her turn to do the cooking, would make enough of some type of baked pasta in red sauce with cheese (lasagna, ziti, etc.) to last the full week. This seemed like a good idea on Monday but by Friday we were ready to head to Carl's Jr. Dr. Isis promised when she met Mr. Isis, they fell madly in love, and got married that she would not make him live through the same experience. So, the purpose of this morning's trip to the green grocer was to pick up enough produce to last them a number of dinners.
But, what does this have to do with family time? It has everything to do with family time. Before I go any further, you'll need some of these:
Figure 1: Twist tie storage bags. Do not buy Ziploc bags. You'll be sorry.
Once a month on "The Isis Family Super Family Fun Day Saturday" we head to assorted food purchasing venues and buy quantities of food. We bag them up and pop them in the freezer. Then, when Dr. Isis gets home at night, she pops the bags out of the freezer, cooks 'em up, adds a couple of fresh items for good measure, and her family thinks she is a hero.
But that's where the family part comes in. You see, today The Isis Family worked together to bag and freeze the following:
1) Two pounds of spiced quinoa and fruit
2) Fifteen assorted zucchini and summer squash
3) Five dozen ears of corn
4) A couple of eggplants
5) Pounds and pounds and pounds of meats in assorted marinades
6) About 6 dinners' worth of pesto (see recipe below)
And Dr. Isis got to get her meals prepared in advance and spend time with the family. Sometimes The Isis Family watches movies while we do this, or we rock out to the radio, or we just sit and talk. Either way, we do it together and I get a little time freed up in the week to focus on science.
So, as a gift to you, to help inspire you to spend a little more time with the fam, allow Dr. Isis to offer her never-before-shared pesto recipe.
Dr. Isis's So-Good-You'll-Soil-Your-Knickers Pesto
Here's what you'll need:
Figure 2: Pesto stuff
1) A hot mess of basil. I don't actually know how much that is, but you'll know when you see it.
2) About two cups of olive oil
3) Six ounces of roasted pine nuts. Not lightly toasted. Man up already and let a few of them get dark.
4) A head of garlic. See above comment about manning up.
5) A teaspoon of rock salt and a teaspoon of black pepper. You're going to be tempted to cheat and use table salt, but don't do it. It won't taste the same. The only people who cheat and use table salt are the people who also cheat and fill the autoclave with tap water. When I find that jackass I am going to kill him.
6) A tablespoon of crushed red pepper. This is also a necessary ingredient and, if you leave it out, when you eat this pesto you'll wonder if there really is a god and, if there is, why he has forsaken you.
7) One half cup of water.
Put the garlic, pine nuts, red pepper, salt and pepper, and one cup of the olive oil into your blender/food processor and blend it to a yucky-looking paste. Then with the blender/food processor going, open the hole in the lid and start feeding in the basil.
It is essential to the making of good pesto that you add the basil with the blender/food processor running. If you are like Dr. Isis and have a blender, you are going to look like a teenage boy on prom night trying to awkwardly shove things in the hole, all the while trying not to lose a finger or (heaven forbid) your pipeting thumb. Still, your pesto will have a better texture and you will thank me for it. Alternate between the basil and remaining cup of olive oil until you have something pesto-y. Add the water and finish blending. If you don't add the water, you will again be sorry.
Figure 3: Dr. Isis's pesto in Dr. Isis's blender
"So what," you say? The next part is going to blow your mind...
Take your blender full of pesto and empty it into ice cube trays.
Figure 4: Dr. Isis's pesto in ice cube trays. The addition of one half cup water allows it to freeze.
Pop these bad boys in the freezer and the next day you will have pesto cubes. Partition them into the baggies and pop them back in the freezer. On days you want pesto, you'll only need to cook the pasta when you get home, add the pesto cubes, stir, and add a little cheese. As I mentioned, your family will think you're a hero.
Education & Careers
Life Science
Comments
Isis, be careful about supra-lactate threshold periods. When you start to feel great after a period of extreme exercise that can be a very bad sign. It may be a sign that you have started to have the delusion that you are not tired. That is a bad delusion to have (other than in an actual life-threatening situation, such as running from a bear).
http://daedalus2u.blogspot.com/2007/08/low-nitric-oxide-acute-psychosis.html
(warning, there are some disturbing ideas pertaining to postpartum psychosis)
You know enough physiology to know there is no emergency source of ATP that comes online after a period of acute exertion. The only place that ATP can come from is by turning stuff off.
The euphoria you feel may be your "fight or flight" state kicking in and diverting all resources into running; stuff that you need to be on to keep your physiology running properly.
Posted by: daedalus2u | January 6, 2009 9:54 PM
Supra-lactate threshold, supra-maximal and high intensity interval training aren't a good idea for untrained individuals, but improve mitochondrial function and performance in trained athletes. I'm pretty Isis knows what she's doing.
Posted by: Professor in Training | January 6, 2009 10:11 PM
Oh no, Daedalus!!! This is not good!!! I was actually feeling some runners high after my workout and I am totally at work at 12am thinking that I am on a roll. Shit! Can we call my new disease post-supralactate threshold psychosis?
Posted by: Isis the Scientist | January 6, 2009 11:52 PM
...
Can we call my new disease post-supralactate threshold psychosis?
... or maybe just 'whack-a-loonie'...
...tom...
.
Posted by: ...tom... | January 7, 2009 2:02 AM
Watch it ...tom..
Don't make me put you in time out young man.
Posted by: Isis the Scientist | January 7, 2009 2:31 AM
Bah hahahaha ....tom...
Still need to make that pesto... now that we cleaned out the freezer I have some room!
Posted by: Jenn, PhD | January 7, 2009 5:31 AM
Isis, I don't care what you call it, just be careful and don't push yourself until you break or until you cause permanent damage. That may be part of why you thought you were doing good science that later turned out to be not as good as you had first thought.
To have an exploitation-free home and work life, we have to not exploit ourselves either.
Posted by: daedalus2u | January 7, 2009 8:58 AM
Isis, regarding the term 'lactate threshold' and whatever exercise physiologists and coaches use it for, recent studies on energy metabolism both in muscle and brain, have actually debunked this term as a myth. Many investigations in these fields (muscle and brain) have demonstrated that lactate is an excellent oxidative energy substrate that is being used by both muscle and brain during exercise. Actually, lactate is a better and more efficient energy substrate than glucose, since it does not requires any investment of ATP in order to produce ATP, in contrast with glucose, which requires two steps of phosphorylation (2 moles of ATP per mole of glucose) before entering the mitochondrial TCA to produce 34 moles of ATP.
The long distance runners, like the new marathon olympic champion and world record holder from Ethiopia, who ran 26.2 miles in 2:04 h, is an excellent example for a beautiful balance between fast-twitch muscle fibres that consume glucose and produce lactate glycolytically and slow-twitch muscle fibres that consume oxidatively all the lactate they can, which is produced by the former. Similarly, glia in the brain are like the fast-twitch muscle fibers, consuming glucose and producing lactate, while neurons are lactate consumers. When you exert yourself by running a bit anaerobically, your brain avidly consumes great deal of the lactate that flood your blood stream. If anything, lactate is good for your brain; maybe very good.
Here's a recent paper and a percepective on the topic:
Larsen TS et al. (2008). J Physiol 586, 2807-2815
Schurr A (2008) J Physiol 586, 2665-2666
Posted by: S. Rivlin | January 7, 2009 11:39 AM
Oh, Dr. Isis!!! I think I love you.
Also, you must be from the same region as my son's educational assistant-- she's the only other person I've ever heard use the phrase "hot mess" as a measurable quantity! :D
Posted by: The Perky Skeptic | January 7, 2009 11:39 AM
Hot mess is so totally going in my next Methods section.
Indeed, I may have to fire up some TRPV1 expts just to enjoy the wildly recursive "hot mess of capsaicin".
Posted by: Nat | January 7, 2009 12:53 PM
Why, Rivlington, it is really quite hot when you come over here and leave a sciencey comment!!!! But on to lactate..
Part of the debunking of the idea of a "lactate threshold" has nothing to do with the lactate, but with the idea that there is some percentatge of VO2max at which the gross muscle transitions from primarily aerobic to anaerobic exercise and that this anaerobic transition is the cause of the sudden increase in plasma lactate during an incremental exercise test. In fact, even under aerobic conditions exercisng muscle produces some lactate. What causes it not to appear in blood is the fact that it is handled locally (more on that in a secnd)and you are right that lactate is an energy substrate. A more efficient one than glucose or lipid? I don't know about that, dear Sol-y, if your only measure of efficiency is whether it takes ATP to make ATP. Besides, in exercise it is typically O2 that is limiting.
But, as much as I hate to say this, you're probably right about the new marathon runner (although there is debate over whether these folks are self-selecting or where there really is an ability to train to elitism). It has only very recently been recognized that there are intercellular transporters for lactate (the H+-lactate cotransporters MCT1 and MCT4)that not only redistribute lactate, but serve to maintain intracellular pH. The idea that lactate is not a terminal waste product is relatively new though and still controversial to those who are holding on to old dogma. In fact, I remember Bruce Gladden giving a symposium at the American College of Sports Medicine's Integrative Physioloy meeting in 2006 on the intercellular lactate shuttle and chuckling knowing I just seen lactate discussed as a terminal metabolite in a physiology course.
Still, the lactate threshold, although the term threshold is inappropriate, is still a good marker of performance (see Messonnier, J Appl Physiol 2006) and training above this threshold has benefits (see Helgerud, Med Sci Sports Exer 2007). The presence of lactate in the blood is probably not a good measure of anaerobic/aerobic capacity, but it is a good marker of the muscles ability to handle lactate, which is improved with training.
PS: I love you too, Perky!
Posted by: Isis the Scientist | January 7, 2009 1:17 PM
Actually lactate transporters were discovered and recognized 30 years ago by Halestrap. People have been working on those proteins earnestly since the mid 1990s, producing different antibodies for the multiple subtypes of the monocarboxylate transporters (MCTs). If you noticed in my previous comment, I described lactate as an oxidative energy substrate. Surely, without oxygen it is usless as such. I know Bruce Gladden personally, admire his work and we both cite each other in our papers. I also know George Brooks, whose work on the lactate shuttle in muscle and his pioneering work on the existence of mitochondrial lactate dehydrogenase (LDH) has been doubted and rediculed for many years. Not only that it appears now that he was correct, there is also a large body of work showing that intercellular lactate shuttle also exists in the brain and that neural mitochondria contain both LDH, MCT and other proteins that involved in mitochondrial lactate uptake and utilization. I heartily recommend the reading of Brooks's papers, the most recent one in PLoS One and the excellent work from the lab of Salvatore Passarella in Bari, Italy. Where muscle pH and fatigue are concerned, read the important paper by TH Pedersen et al., in Science (2004) 305, 1144-1147, in which they have shown, very elegantly, that lactic acid has nothing to do with muscle fatigue. If any, the drop in pH actually helps the muscle continuing to produce action potentials despite its fatigue.
Posted by: S. Rivlin | January 7, 2009 4:18 PM
You're right about the discovery of the MCT protein, but the recognition of its important in exercising muscle is still relatively new. Just this last year people debated in JAP whether use of the term "lactic acid" was even correct (ie, whether there even is an exercising acidosis as a result of lactate production. Check out Robergs and Prakash.
I know Pederson's paper well. it's a nice piece of work but I remain skeptical as to whether one can diffinitively study excitation-contraction coupling in skinned fibers. Also, Pederson did his work at 25 degrees C. In cardiac myocytes, this can have a huge effect on contractile function. That being said, I don't necessarily know that pH is the cause of the fatigue as opposed to a simple, biochemical, energy demand/utilization issue. I mean, if you know Gladden's work so well then you know the article he published with David Poole showing that lactate infusion into a muscle decreases contractile force independent of pH (see Poole 1998). He's done similar work in the heart, right?
Still, lactate handling in exercise is a controversial area. All of this aside, there is clearly a point in incremental exercise where lactate begins to increase in the blood and it's no secret that this is the point around which the exercise starts to seriously kick my ass.
Posted by: Isis the Scientist | January 7, 2009 4:45 PM
Isis, first, I find it much more pleasant to discuss science with you than those other issues we have disagreed on in the past. Second, my interest is mainly in brain energy metabolism and cerbral ischemia/hypoxia. My attention to muscle energy metabolism arises from my participation over the past 20 years in US Track & Field competitions for old farts. I am a sprinter, competing in 100m, 200m, 400m and long jump. These events kick your anaerobic energy metabolism very quickly so I am familiar with the muscle pain that accompanies you in the last few meters of a race, especially in the 400m. Now, I know that it is only an anecdotal experience, however, most of my great and hot ideas in science always popped up shortly after a good anaerobic workout. During periods of injury, when such workouts were prohibited, my brain could not produce anything of substance.
My advice to you, in order to keep up your hot science, introduce some really strong anaerobic runs into your training (on the track during the spring, summer and fall and on the treadmill during the winter. At my university there are treadmills in the gym that can reach a speed of 15 miles/h. Any running at speeds over 10 miles/h for 30 to 60 s will produce enough lactate to fire your brain.
Posted by: S. Rivlin | January 7, 2009 5:29 PM
It is not O2 that is limiting; it is mitochondrial capacity to reduce O2 that is limiting. VO2max is not increased by that much by breathing pure O2. The increase in VO2max by blood doping is not due to extra O2 carrying capacity, it is due to extra NO destruction capacity. That lowers the NO level at the mitochondria, which reduces the inhibition of cytochrome c oxidase by NO, which allows O2 consumption at a high rate and (this is most important) to a low O2 partial pressure. The low O2 partial pressure at cytochrome c oxidase causes the flux of O2 to cytochrome c oxidase to increase. The O2 flux is proportional to the O2 concentration gradient times the distance (Fick�s Law). To increase the O2 flux by 10x (as muscle can do), the O2 concentration gradient has to increase also ~10x (because the distance isn't reduced that much by greater capillary recruitment). Because the O2 level in arterial blood doesn't change that much, the O2 level at the mitochondria has to go down a lot to increase the gradient by 10x.
Similarly, increased NO is the reason for the reduced VO2max with acute isovolemic anemia. In this paper, they measured VO2max which was not limited by heart output. What they found was that during isovolemic anemia, VO2max was decreased despite reserve heart capacity. The venous return O2 level was no different following isovolemic anemia.
http://ajpheart.physiology.org/cgi/content/full/273/4/H1787
If the venous return O2 level was the same, there was no hypoxia. The reduced work output was not due to insufficient O2 (which would have showed up as reduced venous PO2. The vascular conductance at a specific work output was considerably higher at lower Hb (due to higher NO levels due to the reduced Hb).
If I may add a comment, I find the use of the terms "oxygen extraction" and "oxygen delivery" to be annoying because the first is a completely non-physiologic concept and the second isn't terribly physiologic either. All movement of O2 is by passive diffusion down a concentration gradient (actually a chemical potential gradient). O2 is only "extracted" from blood when the chemical potential of O2 in the perfused tissue is lower than in the blood, so O2 passively diffuses out. Oxygen can only be "delivered" to tissues with a lower O2 chemical potential.
This is quite apparent when looking at exercise capacity at high altitude. What limits the O2 flux is the gradient of O2 between the blood and the mitochondria where it is consumed. The concentration at the mitochondria is limited by physiology. At zero NO there is a certain K for O2 on cytochrome c oxidase. It can't get any lower than that. The O2 chemical potential level in the blood is limited by the O2 partial pressure in the atmosphere. It can't get any higher than that no matter what the Hb level is. Those two O2 concentrations and the geometry of the distance between them sets the maximum O2 flux.
If I might add something regarding lactate, having the brain run on lactate generated by the muscles increases the maximum ATP that muscle can consume by shifting the consumption of the reducing equivalents from mitochondria in muscle to mitochondria in the brain. Then muscle can consume the ATP produced by glycolysis from glucose, as well as the maximum ATP that the mitochondria in the muscle can produce (either from lactate or from lipid). That also let the brain use the glycogen reserves that muscle has, without muscle exporting glucose.
It is pretty well known that mitochondria are turned off during hypoxia. I strongly suspect that a large part of fatigue is the temporary turn off of mitochondria that exceed the normal mitochondrial operating potential. It is important to keep all the mitochondria in a cell operating "in sync"; that can pretty much only be done by turning off the ones that are out of sync. With rest, some of them can turn back on. The most damaged ones get recycled via autophagy into new mitochondria (but that takes overnight). How that process is controlled (i.e. how the number of mitochondria is regulated) is critically important, especially in nerve cells such as motor neurons where the number of mitochondria may change by 3 or more orders of magnitude over the life of the cell. CNS mitochondria turn-over pretty fast (a month or so in rats), so ongoing feedback regulation of that number is absolutely critical. That feedback regulation is one of the things I am working on and where basal NO is absolutely critical.
Posted by: daedalus2u | January 7, 2009 7:25 PM
daedalus2u, nice rundown of some facts regarding oxygen consumption and energy metabolism.
Where lactate is concerned, one of the advantages that lactate has over glucose at the mitochodrial level is the fact that glycolysis is the rate-limiting process of supplying lactate to the mitochondria, at least in the brain, while lactate, when supplied by the blood or exogenously, at levels that exceed the ability of glycolysis to supply it, can push the mitochondrial ATP production rate much higher than glucose.
For more information on lactate and mitochondria see:
Neurosurgery (2006) 59, 1122-1131; Neuroscience (2007) 147, 613-619
Posted by: S. Rivlin | January 7, 2009 9:24 PM
My pesto goes into zippable sandwich bags, about 1/2 cup per bag, gets squished flat and air-free, then frozen in the protective shelter of a gallon Zip-Loc (or equivalent) freezer bag.
It thaws rapidly, because it's flat, and because I grow my own basil ... my "hot mess" is way bigger than your hot mess, even without cheating and adding an equal quantity of spinach.
I do non-traditional pesto. I was browning onions for something as I was making a large batch of pesto and thought that caramelized onions can improve anything, maybe even pesto. I was right. It's pungent from the basil, and mellow and sweet from the caramelized onions. It has a thick "stick to the pasta" texture, and is lower in fat than regular pesto.
Several large onions , chopped into chunks
1/4 cup or more chopped garlic
1/4 cup (or less) oil
Your favorite pesto recipe
Brown the onions in a small amount of oil in a 250-degree oven until they caramelize - it's a slow process, just stir them every half hour or so all day long, then add the garlic and continue until the mix is a deep tan. Make pesto, using a cup or two of the caramelized onions as a substitute for the oil in every batch of pesto.
I'll have to try adding a bit of red pepper powder to it next time.
Posted by: Tsu Dho Nimh | January 7, 2009 9:42 PM
Sol, I think a better explanation for your observation of increased mental acuity following exercise induced lactate is from NO. Lactate does cause release of NO and vasodilation.
http://dx.doi.org/10.1167/iovs.05-1224
NO is the neurotransmitter that causes the vasodilation measured via the fMRI BOLD technique, which is used as a measure of real-time brain activation and functional connectivity. It is my hypothesis that neurogenic NO is the neurotransmitter that the brain uses to activate and regulate activity in certain brain volumes.
The increased NO level from a higher basal NO level results in the neurogenic NO signal having a larger range and duration, activating a larger brain volume, allowing one to think "bigger" thoughts. I have had similar experiences following increasing my NO level with my bacteria. The neural networks of the brain are self-regulated in the near percolation threshold, where small changes in connectivity cause exponential changes.
I have a discussion of this in the context of observation of acute and temporary resolution of some behaviors of autism coincident with fever. I am quite sure the mechanism is the NO from iNOS caused by the immune system stimulation.
http://daedalus2u.blogspot.com/2008/01/resolution-of-asd-symptoms-with-fever.html
I very strongly suspect that ATP levels in the brain would be lower under conditions of high lactate due to high muscle activity. Are you aware of any measurements?
Posted by: daedalus2u | January 7, 2009 10:19 PM
I posted another comment, it had a couple links and hasn't made it through the spam filters yet.
I could only see the abstracts, I suspect the effect of lactate on ATP is mediated through regulation by NO, not via increased supply of substrate.
In thinking about it, I have a similar anecdote. Once when I was getting prepped for general anesthesia (for kidney stone shock-wave lithotripsy which really really sucks, drink lots of water so you never get kidney stones (but lemon juice works better, the citrate inhibits crystallization of calcium oxalate)) they gave me an IV and I did notice clear neurological effects (it made me giddy) which I commented on and they said they hadn't given me anything yet, just Ringer's.
Posted by: daedalus2u | January 8, 2009 10:00 AM
I understand that NO is your thing, but please read the paper in neurosurgery; the more lactate, the higher the rate of mitochondrial ATP production.
Kidney stones had bugged me for a while. Though the recommendation was to drink much more than I used to, I managed to catch one of those suckers as it shot out, sent it for analysis, which came back as calcium oxalate. Since then I am taking daily dose of 300 mg Alopurinol and had no kidney stone problem for the past 4 years.
BTW, wasn't the IV infusion lactate Ringer's?
Posted by: S. Rivlin | January 8, 2009 11:38 AM
I've made non-traditional pesto, too... Mostly it was I had a more-than hot mess of parsley & basil. So one batch was basil & pine nuts, the other was flat-leaf parsley & walnuts. Curly parsley didn't taste very good, but I did try it. I've never added the water, and it still freezes very nicely, just takes a bit longer. I'll have to try roasting the nuts beforehand, add a different flavor profile. Oh, a jalapeno or two can also be added instead of red pepper flakes, depending on your level of heat preference.
Posted by: marlana80 | January 8, 2009 12:14 PM
I have to get to the library to get the paper (if my library has it), but from the abstract, they don't mention ATP production, they only mention O2 consumption. There are multiple ways to consume O2 without generating ATP. From the abstract it looked like it was in vitro testing, and from quite damaged tissues. Lactate does couple to NADH, which can facilitate production of superoxide via cytosol enzymes. Many of the NADH oxidase enzymes are membrane bound and in disrupted tissue may generate more superoxide than in vivo.
You don't want substrate delivery to "regulate" ATP production. That is a recipe for disaster for something as critical as ATP.
High superoxide lowers ATP concentration. That is one of the mechanisms for ischemic preconditioning. You can't get a high ATP concentration from mitochondria because they turn off when the ATP level is high. The highest production rate of ATP from mitochondria occurs at low ATP levels (which are also low NO levels because the superoxide from the high mitochondrial potential pulls the NO level down).
There are a lot of misconceptions about ATP regulation. ATP is not kept constant. The ATP concentration is a control parameter that regulates the zillions of ATP consuming pathways. There are 3 independent parameters associated with ATP, ATP concentration, ATP production rate and ATP consumption rate. Production and consumption are very nearly equal. The concentration is independent of production and consumption (independent in that it can be (and is) regulated separately). Physiology uses ATP concentration as the control parameter to allocate ATP to the different pathways according to need. When you need every molecule of ATP to run from a bear, your physiology turns off every ATP consuming pathway that you don't need. It only needs to do that when consumption of ATP can't keep up with ATP production. When that happens, ATP concentration falls and the "luxury" pathways get turned off. Skeletal and heart muscle can consume ATP until the muscle necroses and dies. That is a "feature" because it is better to have a few muscle cells die than to be caught by the bear. But it hurts like hell. That pain is your body telling you that you have exceeded your ATP production capacity and that pathways are being turned off that will eventually cause damage and even fatal damage. Being able to run yourself to death while running from a bear is a "feature" a "feature" that must be used wisely.
Yes, it was lactate Ringer's. Alopurinol inhibits xanthine oxidoreductase and is indicated for uric acid stones, not calcium oxalate stones. XOR is very important in NO physiology because it reduces nitrate and nitrite to NO. It isn't clear to me that it has any effect on oxalate.
Lemon juice is almost pure citric acid. I have found that drinking ~5 ounces per day made a big difference (in the early evening because urine concentration goes up at night). But that much did (I think) cause depletion in Mg, which I fixed by adding a little milk of magnesia to it (just a little or you get the runs).
Posted by: daedalus2u | January 8, 2009 12:24 PM
Thanks for the vote of confidence! It was definitely a great workout!!!
Posted by: Dr. Isis | January 8, 2009 3:56 PM
Another reason why I think there is the dominance of marathon runners from Kenya and Ethiopia (8 of the top 10 men and 2 of the top 10 women are from Kenya or Ethiopia) may be due to the conditions they train under. If one trains under conditions of high NO, one's basal mitochondria level is set by the basal NO level that one trains under (actually the basal NO level that one sleeps under after training because that is when the mitochondria are replaced and the mitochondria number is set).
I think that this is the physiology behind the training strategy of "training low, sleeping high" where individuals train at low altitude where the high PO2 allows greater aerobic work and greater muscle utilization and a higher VO2max which conditions the liver to supply glucose at a higher rate, and then sleeping at high altitude where the low O2 partial pressure during sleep increases mitochondria biogenesis.
I think that training in a tropical region in the rural undeveloped world where a biofilm of NO/NOx bacteria produces a high basal NO level which inhibits cytochrome c oxidase will results in a greater excess of mitochondria over basal requirements. The only reason that you can increase your metabolic output is because you have excess mitochondria over what are needed to supply basal needs. How much excess do you have? That is going to depend on the normal regulation of mitochondria biogenesis (which is by NO).
http://jcs.biologists.org/cgi/content/full/119/14/2855
What might give these Kenyan and Ethiopian runners even more of an advantage is that while they can train under high NO conditions by not bathing in their rural homeland, when they compete in international events they can wash off the biofilm which then lowers their basal NO level and so disinhibits their cytochrome c oxidase. By doing that they can turn their more numerous mitochondria to 11 before the race even starts.
Posted by: daedalus2u | January 8, 2009 4:42 PM