Wednesday, March 22, 2017

Silent, but not deadly

Today's topic is flatulence. Everyone passes gas. The trick is to have no one notice when it happens, which requires both silence and an absence of noticeable odor. Where does the offensive odor come from? Sulfur! Yes, brimstone (an archaic word for sulfur) really does deserve to be associated with imagined conceptions of hell. Specifically, hydrogen sulfide (H2S) correlates with the level of stinkiness of flatulence. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1727181/)

Happily, we know how to bind H2S. Bismuth, zinc, iron, and nitrate are able to do so. (https://www.ncbi.nlm.nih.gov/pubmed/12927694) Nitrate is considered toxic, but the other three are commonly ingested by people. Bismuth is in Pepto-Bismol, and zinc and iron are in many foods and taken as vitamin supplements. Treatment with bismuth has been proven to bind fecal H2S in humans (http://www.gastrojournal.org/article/S0016-5085(98)70311-7/fulltext), but long-term supplementation with bismuth is possibly connected to encephalopathy; brain dysfunction is too high a price for me to pay to get rid of bad-smelling flatulence, so I won't run out and buy myself a bottle of Pepto-Bismol for that purpose. But zinc...that's in common use as a supplement, especially in connection with fighting colds, and appears relatively safe as long as one keeps zinc intake below 40 mg in a day. (https://umm.edu/health/medical/altmed/supplement/zinc) Moreover, the body has no specialized zinc storage system. People occasionally eat oysters, which are extremely high in zinc, and don't appear to be negatively affected by eating the oysters. Zinc is worth a try.

My husband's digestive system doesn't handle onions well. I was sad as a newlywed to realize that onions were going to have to be cut out of the household menu for his sake. And over time my gut bacteria seem to have altered so that I also have a hard time with onions now. This was a very unfortunate change to a woman who loves salsa. But then two days ago, I discovered from the studies cited above that H2S can be bound with easily obtained minerals, and so we experimented. Last night for dinner, we ate a packaged, reconstituted potato and onion soup that gave us both extraordinarily unpleasant gas about a year after our marriage. We adults took some chelated zinc right before eating the soup. We both had some gas today, but it didn't stink. Hurrah! We are fairly confident that the zinc helped us because our seven-year-old, who didn't get any zinc and did eat two bowls of the soup, had decidedly malodorous gas this morning.

Next step: Mexican food (well, American-style "Mexican" food, which really isn't the same thing as authentic Mexican food) with some zinc in our accompanying beverage. I really hope this works so that I can go back to cooking with onions.

Thursday, March 16, 2017

Natural remedies over the millennia

A promising trend I see on PubMed recently is a swelling of interest in and scientific research on natural compounds from herbs and foods that have been used by humans for thousands of years. There is relatively little profit motive for pharmaceutical companies to fund such research, so it has been neglected. There's certainly a need for new, patentable molecules designed to selectively inhibit certain processes in the body and to correct for genetic faults, but we have a lot of naturally occurring molecules to investigate, as well.

LDS people (Mormons) have scriptures that say

"And again, verily I say unto you, all wholesome herbs God hath ordained for the constitution, nature, and use of man— Every herb in the season thereof, and every fruit in the season thereof; all these to be used with prudence and thanksgiving.

But which herbs are wholesome? And for what conditions? Despite attempts to keep track of herbs and their effects for the past 5000 years, if Chinese oral tradition is accurate, humanity still has a long way to go in figuring them out.

Only 5000 years did I say? It looks like the Neanderthals might have been using natural remedies to treat their physical ailments well over 40,000 years ago:

"One of the most surprising finds, however, was in a Neanderthal from El Sidrón, who suffered from a dental abscess visible on the jawbone. The plaque showed that he also had an intestinal parasite that causes acute diarrhoea, so clearly he was quite sick. He was eating poplar, which contains the pain killer salicylic acid (the active ingredient of aspirin), and we could also detect a natural antibiotic mould (Penicillium) not seen in the other specimens.""Apparently, Neanderthals possessed a good knowledge of medicinal plants and their various anti-inflammatory and pain-relieving properties, and seem to be self-medicating. The use of antibiotics would be very surprising, as this is more than 40,000 years before we developed penicillin. Certainly our findings contrast markedly with the rather simplistic view of our ancient relatives in popular imagination."
http://popular-archaeology.com/issue/winter-2017/article/dental-plaque-dna-opens-new-window-on-neanderthal-life-ways

Reading that makes me think we should routinely reevaluate all the traditional remedies and "old wives' tales" to see whether new research has found out something indicating whether and how there might be something to those old uses of plants and other natural substances. (While we're at it, we should also probably stop maligning Neanderthals as stupid nonhumans if they were using penicillin intentionally that long ago.) Giving barley water a fresh look helped me see how molybdenum can help with migraines and nausea. Who knows what other real natural remedies we modern humans are missing?

Monday, February 27, 2017

"That which cometh out of the mouth"

I have another new theory. No, it's not exactly received medical wisdom. That's what makes it new. :D

In the past few days, I've learned a lot about how atherosclerosis (plaques building up on artery walls) can lead to stroke. I had previously hazily envisioned strokes being caused by a blood clot that just magically appeared in the brain. To the contrary, the blood clot generally comes from somewhere besides the brain. Typically, an atherosclerosis-related stroke-causing blood clot originates in the carotid arteries, right at the point where the carotid artery divides into two arteries, the internal carotid artery and the external carotid artery. Atherosclerotic plaques build up in the vicinity of that "Y"-shaped fork, and rupturing of the plaques triggers formation of a blood clot which then moves up into the head and gets stuck in a smaller artery in the brain.

What causes plaques in the first place? An influential theory is that oxidized LDL cholesterol starts the process of atherosclerosis. (https://academic.oup.com/cardiovascres/article/68/3/353/309912/Oxidized-LDL-a-critical-factor-in-atherogenesis) My questions then are 1) how does the LDL get oxidized and 2) why does it cause plaques right at that carotid junction?

First I looked into what causes the oxidization. A major culprit behind oxidizing of LDL is hypochlorous acid produced by the enzyme myeloperoxidase, which uses hydrogen peroxide (H2O2) and a chloride ion (Cl-) to do so. (https://link.springer.com/article/10.1007/s12170-013-0291-3, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315351/, http://onlinelibrary.wiley.com/doi/10.1002/biof.5520060208/abstract, http://atvb.ahajournals.org/content/20/7/1716.long?related-urls=yesl20/7/1716)

H2O2 is supposed to be broken down in our bodies by catalase, glutathione peroxidase, and peroxiredoxins. Glutathione peroxidase activity appears to decrease as we age. (https://www.ncbi.nlm.nih.gov/pubmed/18511755) It's not clear exactly why, but our ability to break down H2O2 with our saliva appears to go down by approximately half as we age (https://academic.oup.com/biomedgerontology/article/62/4/361/629357/Age-Related-Changes-in-Salivary-Antioxidant), which means that there is likely going to be some extra H2O2 in our mouths in our later years. Excess H2O2 is harmful to gum tissue (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730038/), and in the gum tissue H2O2 can apparently diffuse in such a way as to end up in the jugular vein (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745256/).

The jugular vein travels down through the neck, taking all the "used" blood from the head back to the heart. In the neck, the jugular vein is covered by the carotid sheath, which holds the jugular vein next to the carotid artery. My novel hypothesis is this:

Excess aging-related H2O2 from the mouth goes into the jugular vein and then makes its way over to the carotid artery next door, boosting the amount of oxidized LDL in the carotid artery just before it hits the "Y"-shaped fork, where the oxidized LDL hits the sides of the branching arteries and starts the process of forming atherosclerotic plaques. 

I think the weakest link in my theory is that I can't find a lot of clear proof that H2O2 can migrate from a vein into a neighboring artery; however, it does seem to be generally accepted that H2O2 diffuses through tissues:

It is now widely accepted that this low molecular weight molecule is utilized in metabolic regulation in ways similar to diffusible gases such as NO, CO, or H2S. Even more so, H2O2 is recognized as being in the forefront of transcription-independent signals, in one line with Ca2+ and ATP. H2O2 diffuses through tissues to initiate immediate cellular effects, such as cell shape changes, the formation of functional actomyosin structures, and the recruitment of immune cells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979367/

I suppose this will have to suffice for now. It's time to go eat dinner with my family...a nice, low-fat, high-soluble-fiber, and antioxidant-full meal.

(I almost forgot to explain the title of my post. In Matthew 15:11, it is recorded that Jesus said, "Not that which goeth into the mouth defileth a man; but that which cometh out of the mouth, this defileth a man." My research above points to oxidizing substances from the mouth contributing to the formation of atherosclerotic plaques in the carotid arteries.)

Friday, February 24, 2017

Possible transient ischemic attack

My husband, who is barely "middle-aged," experienced something on Tuesday that appears to have been a transient ischemic stroke (TIA), which is considered a warning mini-stroke. He'll be getting a possible-TIA workup done at the hospital in the next few weeks, and he has begun taking a baby aspirin daily.

This is a man who is at a healthy weight and who cycles about 25 miles per week. He doesn't smoke, drink alcohol, or use drugs. He is, however, cursed genetically (his grandfather died at age 45 of an enlarged heart) and likes desserts and fast food pizza too much.

The episode happened within 24 hours of a daughter's birthday party, which featured triple meat pizza from Little Caesar's, birthday cake made with lots of butter, and ice cream. And we think he had an egg for breakfast the following morning. He has had high cholesterol and triglycerides for years, but he had hoped to stay healthy by dint of lots of exercise and fruits and vegetables. It looks as though he'll also have to largely cut out some favorite treats, too, though. :(

On the bright side, he did escape the illness I posted about last time.

Wednesday, February 15, 2017

H1N1?

Over the past five days, 6/7 family members have been struck with a cold or flu virus. Because it started with an intense sore throat for me, I thought it might be strep throat, but the tell-tale symptoms in the throat never showed up. What was weird was that instead of a bunch of coughing and sneezing initially, it started with a day of fatigue just lying in bed with no/little hunger. I found out last night that friends from our church congregation have confirmed H1N1 ("swine") flu. I compared H1N1 symptoms with the symptoms we have, and they seem to be a pretty good fit.

So life is on hold for us while everyone rests. Except for Daddy, who insists he'll escape it, we're self-quarantined at home. The heat is turned up, and the air humidifier is turned up. I'm also taking a lot of melatonin to see if it helps shorten the course of the illness. I felt better yesterday, so I stayed up to my normal time (past 11 pm). I ended up regretting that, so I don't think just taking melatonin is an adequate substitute for insufficient rest. The evidence I found last year did only point to melatonin being possibly helpful for avoiding ARDS (acute respiratory distress syndrome), and I have to admit, my lungs seem to be doing OK. So maybe there's merit still to my hypothesis, but right now I'm dissatisfied with anything that doesn't make me feel better immediately.

Friday, February 10, 2017

A definition with a difference

I don't care to get political on my blog for the most part. I'm bending my usual course today for a very good legal reason, which I'll lay out below.

On January 27, President Trump signed an executive order temporarily staying entry under the Immigration and Nationality Act (INA) for aliens (i.e., non-citizens and non-nationals of the USA) from countries previously identified as being of higher risk due to harboring/sponsoring of terrorists. Here's the relevant paragraph:

    (c)  To temporarily reduce investigative burdens on relevant agencies during the review period described in subsection (a) of this section, to ensure the proper review and maximum utilization of available resources for the screening of foreign nationals, and to ensure that adequate standards are established to prevent infiltration by foreign terrorists or criminals, pursuant to section 212(f) of the INA, 8 U.S.C. 1182(f), I hereby proclaim that the immigrant and nonimmigrant entry into the United States of aliens from countries referred to in section 217(a)(12) of the INA, 8 U.S.C. 1187(a)(12), would be detrimental to the interests of the United States, and I hereby suspend entry into the United States, as immigrants and nonimmigrants, of such persons for 90 days from the date of this order (excluding those foreign nationals traveling on diplomatic visas, North Atlantic Treaty Organization visas, C-2 visas for travel to the United Nations, and G-1, G-2, G-3, and G-4 visas).

The following day, a DHS spokesperson emailed a journalist that the order would bar green card holders (i.e., legal permanent residents or LPRs; the residency cards haven't been green for decades), which of course set off a panic with all the LPRs who rightfully thought they were done dealing with immigration roadblocks. So the following day, DHS said that it was in the national interest to use the flexibility of the order to not bar LPRs. What did DHS miss in all this? The definitions section of the INA specifically exempts LPRs from needing "admission" (which includes "entry" authorized by an immigration officer) under the immigration laws unless they've done something to lose their LPR status. Here's the relevant statute:

  INA Section 101(13)     (A) The terms "admission" and "admitted" mean, with respect to an alien, the lawful entry of the alien into the United States after inspection and authorization by an immigration officer.          (C) An alien lawfully admitted for permanent residence in the United States shall not be regarded as seeking an admission into the United States for purposes of the immigration laws unless the alien-[and then there is a short list of things saying what an LPR can have done to lose LPR status, which is primarily commit a crime or overstay outside the USA].  

An LPR is considered already "admitted for permanent residence." They don't have to "enter" the USA under the umbrella of the immigration laws. Which makes sense because they already immigrated. Immigrate is a verb meaning to move to a place to settle down, and once you've done it, you don't have to do it again, so no more messing around with immigrant petitions, immigrant visas, or immigrant admission. LPRs are simply coming home when they return back to the USA after a short stay abroad. Hence the executive order doesn't do anything to bar LPRs because they require no "immigration benefits" to reenter the USA once inspection reveals that they are indeed LPRs who remain in status.

Why am I talking about all this now? Because no one, from DHS to the White House counsel to the DOJ to the Ninth Circuit Court of Apppeals seems to have caught this point of law. Yesterday's ruling from the Ninth Circuit openly and clearly makes this mistake, as seen on page 20 of its ruling:

In the district court, the States argued that the Executive Order violates the procedural due process rights of various aliens in at least three independent ways. First, section 3(c) denies re-entry to certain lawful permanent residents and non-immigrant visaholders without constitutionally sufficient notice and an opportunity to respond. Second, section 3(c) prohibits certain lawful permanent residents and non-immigrant visaholders from exercising their separate and independent constitutionally protected liberty interests in travelling abroad and thereafter re-entering the United States. 

Do you see what the Ninth Circuit did there? They interpreted "immigrants" from the executive order to mean LPRs. This is a dumb mistake showing that of all the lawyers involved no one, even at the penultimately-supreme court level, has looked at INA Section 101 and realized that LPRs aren't treated by the law "as immigrants" when it comes to entering the USA. Any DHS agent working a port of entry knows that LPRs aren't the same thing as someone entering the USA with an immigrant visa in hand; the first category already did immigration paperwork in the past (huge hassle that it all was for them) at the border and/or in the USA, while the second is currently immigrating and has to be "processed" as an "immigrant" in "secondary." The executive order couldn't deny immigration benefits to LPRs entering the USA because they don't need immigration benefits to enter.

I know the INA is tricky, but this mistake should never happened. Every lawyer in the executive branch and courts who let this through should be embarrassed that they didn't check the INA definitions.

Friday, February 3, 2017

Another one out the door

I just submitted another medical hypothesis to the journal Medical Hypotheses this week. I put a lot of hours into it, and it's nice to be getting back into normal life now. I'll post a summary of the hypothesis after it is published.

Yesterday I turned in a pre-enrollment packet for child #4, who will be starting kindergarten in August. That is the same child who gave herself a haircut last month. It's hard to believe she'll be sitting quietly in a classroom and being a "pupil" six months from now. And I'll probably only believe it when I see it! She's a handful.

Thursday, January 19, 2017

Family life goes on

Last night my four-year-old used child-safe art scissors to hack off almost all the hair on the front of her head after we thought we'd gotten her safely to bed. She even cut off part of an eyebrow. It looks quite terrible. But I gave her a short bob haircut, and in a few months her hair should look cute again.

Part of me cried, and part of me worries what other foolish things she will do when I'm not looking. And part of me is resigned to this as inevitable. After all, when I was close to her age, I cut off some of a playmate's hair just before the little girl was scheduled for a professional photo session.

Tuesday, January 10, 2017

Putting dessert in the middle

As I was looking into adipocytes, ghrelin, acylation of ghrelin by GOAT, stomach pH in the fundus, etc., I started realizing that stretching out the stomach (i.e., eating past filling "full") is simply a bad idea no matter what one eats. Because my husband, one daughter, and I are displeased with our current weights, I came up with a sustainable way to avoid overfilling our stomachs quite so much.

I observed that we always ate dinner until satiated, and then we had dessert. Which meant we were overeating every night. Trying to go without dessert won't work, for my husband bikes to and from work and would feel cheated without any dessert. (Being an adult, he would have just eaten goodies independently afterward anyway.) Everyone else would feel cheated, too, to be honest.

People frequently debate whether to eat dessert first or last. I've never heard anyone say they eat it in the middle, though.

We're now eating our evening dessert right in the middle of dinner. First we eat vegetables. Then we bring out dessert and serve small portions of it to everyone who ate vegetables (I have to motivate the toddlers to eat squash somehow...). Last we eat the main dish and other side dishes. Everyone eats some of the main dish and sides, but they eat noticeably less because main dishes don't stimulate the appetite as much as a cookie does.

It feels a little odd to be offering ice cream before the entree, but it seems to be working at decreasing overeating. I'll give an update in a month about whether we're still doing it and what results we have seen.

Friday, January 6, 2017

Two Elbert Hubbard quotes

“The world is moving so fast these days that the man who says it can't be done is generally interrupted by someone doing it.” 

― Elbert Hubbard

Elbert Hubbard was an interesting man. While I don't agree with all his anarchist ideas, he said some very encouraging things in support of those who work to do good in their position in society, whatever it may be. Unfortunately, his life was cut short in the sinking of the Lusitania during WWI.

Here's another good quote from Hubbard:
One machine can do the work of fifty ordinary men. No machine can do the work of one extraordinary man.

Doesn't that just restore some hope after hearing gloomy predictions about people losing their jobs to robots and software? Everyone can be extraordinary at something.

Tuesday, January 3, 2017

New slide show on acetylcholine excess and depression

Last summer, I saw an article reporting that botox treatment for wrinkles sometimes results in a lessening of clinical depression symptoms. So I looked into depression and found that research in recent years points to the possibility that an excess of acetylcholine--which, incidentally, botox blocks--could be a root cause of depression. And then last month I was looking into depression again because of the mental health problems facing a friend's daughter and realized that an acidic mouth environment might get in the way of proper breakdown of acetylcholine in nearby regions of the head.

So, I made a PowerPoint presentation giving three basic, safe actions one could try in order to prevent a chronic excess of acetylcholine:

1) Keep the mouth from being too acidic.
2) Garden sometimes.
3) Try a low-choline diet for a few days.

Numbers one and two are good things to do for other reasons, too.

Here is the presentation:


Friday, December 30, 2016

Melatonin to lessen severity of colds

In my Christmas post, I mentioned using melatonin to lessen the severity of colds. Here's how I got to that idea:

Three years ago my older sister, a health-conscious woman who was only in her forties, came close to dying from acute respiratory distress syndrome (ARDS) after coming down with the flu over Christmas break, during which she overtaxed herself playing hostess despite being sick. To save her, the hospital staff put her in very expensive rotating bed that kept the fluid in her lungs from pooling in any one place in her lungs. (http://www.theindychannel.com/lifestyle/health/rotating-bed-credited-with-saving-lives) Why did she get so ill? How do we prevent such illness in the future?

In the near-century since the 1918 flu epidemic, which killed many otherwise healthy younger adults, researchers have come to realize that an immune system overreaction was a probable cause of many of those flu deaths. (https://www.sciencedaily.com/releases/2006/09/060927201707.htm) Many touted cures for colds (especially vitamin C) are promised to "boost the immune system," but when it comes to otherwise healthy people, they might be feeling terrible due to an already vigorous immune response.

A study a few years ago found that inoculating 17 healthy people with the flu virus resulted in only around half of them "getting sick" even though all of them showed some kind of immune response to the flu virus. (http://ns.umich.edu/new/releases/8511http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002234) Apparently, healthy people can sometimes fight off a virus without suffering from a week or two of the sniffles, sneezing, and coughing. So then my question became how? Because if I can forgo a week or two of Kleenex, I want to!

I looked into runny noses (rhinorrhea), the excess nasal discharge that generally starts clear then becomes nasty, thick stuff that messes with the sinuses. Histamine often causes runny noses, which is why people take anti-histamines for colds. Anti-histamines do help lessen severity of cold symptoms for a short time:
In adults, there is a short-term beneficial effect on severity of overall symptoms on the first or second day of treatment (45% felt better versus 38% with placebo), but there was no difference between antihistamines and placebo in the mid to long term. The effect of sedating antihistamines on rhinorrhoea and sneezing is too small to be relevant to the patient and involves a risk of side effects such as sedation (9% versus 5.2% with placebo). Trials in children were smaller and of lower quality and lacked evidence of effectiveness.

http://www.cochrane.org/CD009345/ARI_antihistamines-common-cold

There has got to be a longer term way to lessen severity of colds. I kept digging to see where the histamine was coming from, and came up with neutrophils, a kind of white blood cell. Neutrophils have been connected to exacerbation of allergy and bacterial lung infection:

In both models, depletion of neutrophils or neutrophil FcγRs protects mice from anaphylaxis. Amazingly, adoptive transfer of human neutrophils into the FcγR-deficient mice restored the response, suggesting that human cells can induce systemic anaphylactic reactions in response to IgG. In this model, anaphylaxis is mediated not by histamine but by neutrophil-derived platelet-activating factor, a known vasoactive lipid. By contrast, neutrophil-derived histamine is the major contributor to pulmonary allergic inflammation in chronic mycoplasma infection (). Neutrophils may also contribute to the sensitization phase of allergic skin diseases. This idea is suggested by the surprising finding that depletion of neutrophils protects mice from the development of contact dermatitis, which suggests that these cells are important in facilitating the development of allergen-specific T cell responses ().

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277181/. Also see "Neutrophil histamine contributes to inflammation in mycoplasma pneumonia" at http://jem.rupress.org/content/203/13/2907.

A 2013 study found that influenza fatality could be prevented by reducing, but not removing, neutrophils. (http://www.cell.com/abstract/S0092-8674(13)00715-0) So how do we keep the number of neutrophils from getting too high without messing with the immune system as it carries out its necessary function of killing enemy bacteria and viruses? An answer appears to lie in preventing some of the neutrophils from having the extended lifespan they tend to have once burrowed into inflamed tissue. (http://isites.harvard.edu/fs/docs/icb.topic1445350.files/Neutrophil%20functions%20review.pdf, http://rheumatology.oxfordjournals.org/content/49/9/1618.full) It turns out that melatonin--made by the body and used regularly as an over-the-counter sleep aid--helps keep neutrophils from migrating into areas of tissue injury. (https://www.ncbi.nlm.nih.gov/pubmed/26031343) Giving melatonin appears to attenuate neutrophil inflammation and mucus secretion. (https://www.ncbi.nlm.nih.gov/pubmed/26303298https://www.ncbi.nlm.nih.gov/pubmed/25388990)

How do we help the body get more melatonin? The easiest way is to be in the dark, which stimulates the body's synthesis of melatonin; this is usually done by sleeping. Getting too little sleep is definitively connected to susceptibility to colds and respiratory illnesses. (http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/414701, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899278/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115328/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242683/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548567/) Exposure to light, especially blue light, suppresses melatonin production. (https://www.ncbi.nlm.nih.gov/pubmed/26017927) (This is why computers and phones now offer settings that block blue light at nighttime; I utilize those settings on my primary desktop and tablet.)

What if a person can't go hide in a dark cave the next time they sneeze a couple of times? Perhaps they have work, small children, or other pressing commitments that force them to stay awake. Taking a melatonin supplement would logically give part of the benefit of a good nap, in that it would lessen the lifespan of some neutrophils and decrease overall histamine production. Of course, it would probably be unwise to purposely take melatonin for this purpose if one already has a depressed immune system (e.g., patients going through AIDS, cancer treatment, etc.) However, melatonin is widely used and seems to be quite safe for most people. (http://www.mayoclinic.org/drugs-supplements/melatonin/safety/HRB-20059770)

A work colleague of my husband was telling me recently about his insomnia, for which he takes three kinds of melatonin on a rotating basis. The melatonin hasn't cured his insomnia, but he has had much stronger resistance to colds while taking it.

Wednesday, December 28, 2016

English translation of "Lulajze, Jezuniu" ("Lullaby, Jesus")

"Lulajze, Jezuniu" is a pretty, haunting Polish Christmas carol that dates back centuries. For Christmas, my church choir sang it. It's been translated into English a few times, but I made a few tweaks to better fit the music and our choir. Our choir accompanist improvised his own arrangement and put in short preludes and interludes. The second verse highlighted the voices of a mother and her two young daughters. It ended up being very nice, even with just an amateur choir performing it. Our music director said it was the loveliest number of the Christmas service.

If you'd like to add a new carol to your Christmas library, here is the version we used.  On the second and third verses, I indicated with all caps which syllables should have two notes sung to them for a pleasing rhythm.

Friday, December 23, 2016

Merry Christmas! Here are some hypotheses for your stockings!

I've had such a fun year doing research on intersections of nutrition, global cuisines, epidemiology, and medical advances. Here are what I consider the most valuable of the hypotheses I formulated in 2016:

1) Molybdenum in large-ish, as-needed doses can help alleviate (or even obliterate) migraines and nausea (at least nausea from pregnancy, travel, migraines, and stomach bugs). 

2) To delay dementia, work to lessen the amount of hydrogen peroxide in your mouth as you age, for the ability of saliva to break down hydrogen peroxide goes down with age. Fresh (or reconstituted dried) horseradish and daikon radish in the mouth help with that because of their high peroxidase content.

3) Some fetal malformations like those resulting from thalidomide might be caused by common vetch or nigella sativa (kalonji) consumption at inopportune moments during early pregnancy, for both of those contain compounds that interfere with angiogenesis (creation of new blood vessels from existing ones).

4) An excess of folic acid and cyanocobalamin disrupts the folate cycle and is linked to autism and ADHD (and who knows what else). Stick to forms of folate and B12 that naturally occur in foods instead of using folic acid and cyanocobalamin. Also include some betaine in your diet.

5) Manganese in skin care products seems like a good idea to fight acne.

6) Addictive behavior, including "falling in love," is the brain forming and working to promote the supremacy of efficient pathways to pleasure. To lessen the strength of unwanted pathways, look at reducing delta-fosB during withdrawal periods via ellagic acid; to form new pathways, look at manipulating c-fos via light at night, MSG, etc.

7) Food allergies seem less likely to occur in the presence of sufficient magnesium chloride, so use sea salt instead of straight NaCl (table salt). Maybe even try some Dead Sea salt, which is half MgCl. Also, look at other ways of supporting and not inhibiting RALDH2.

8) The licorice root in tobacco products might be behind the protective effect smoking has against Parkinson's.

9) Take a melatonin when you first start sneezing with a new cold. It helps neutrophils not dig into the inflamed tissue and live quite so long, which lessens cold symptoms because during neutrophils' lifetimes they pump out lots of histamine. I would only use melatonin for this purpose if you feel your cold is your immune system OVER-reacting to a virus.

10) Vary your diet and your vitamin supplements because of homeostasis, i.e., your body's adaptations over time to high, continuous amounts of any substance.

11) Endogenous hydrogen cyanide in the brain could be connected to seizures, especially epileptic grand mal seizures.

12) Carbon monoxide buildup in the leg muscles could be behind restless legs syndrome.

My two biggest wishes for 2017 research are to 1) help my nine-year-old daughter not be overweight (why her and not my other four daughters? what did I do differently when I was pregnant with her in South America that predisposed her to heaviness? and can I do anything to help her before she reaches puberty?) and 2) figure out a topical way to harness the immune system to fight skin cancers (biopsies and Mohs surgery aren't fun).

Thursday, December 15, 2016

Update on molybdenum for migraines and nausea

Friends and family are starting to spread my hypotheses about molybdenum around. My father-in-law a few states away gave a bottle of molybdenum to a young woman that suffered from migraine-related nausea recently. He emailed me two days ago to say that she used molybdenum twice and it resolved her migraine-related nausea. Unfortunately, he forgot to ask her whether it helped with the migraines, too, although when I asked him, he said that she isn't currently suffering from a migraine. (If you want someone interrogated right, you've got to do it yourself....)

A local friend had her youngest child come down with projectile vomiting from a gastrointestinal virus last week. She gave molybdenum to everyone else in the family, and although others had lower GI tract symptoms, only one other person threw up (it was a teenager, and she stopped vomiting soon after taking more molybdenum). This friend is convinced that molybdenum kept her from ending up with the whole household vomiting.

I should probably keep a running tally of anecdotes of when molybdenum has shown effective for preventing or alleviating nausea and migraines. Here goes:
  • 3 women used molybdenum-rich diets and sulfite avoidance to lessen "morning sickness."
  • 1 woman used molybdenum (supplement) to end motion sickness-caused headache and nausea.
  • 2 women used molybdenum for relief from migraine-related nausea.
  • 3 households with multiple young children used molybdenum to stave off the vomiting due to gastrointestinal illnesses (all have found it's most effective to give molybdenum before the vomiting has begun, probably because it's harder to absorb molybdenum once vomiting has started).
  • 3 women used molybdenum to lessen or avoid migraine headaches (3 different etiologies of migraine headache: old neck injury, menstruation-related, and unknown trigger).
To be objective, I will also keep a tally of anecdotes where molybdenum has not shown any positive effect:
  • 1 teenage girl already suffering from a severe migraine. She took a molybdenum (given to her by a relative of mine), but she still ended up having to go to the hospital a few hours later. (I do not know her or her background, so I have no idea what is causing her headaches.)

Monday, December 12, 2016

Nigella sativa (black cumin, czarnuszka, etc.) also helps mice come off morphine addiction

I posted earlier about a study wherein it was observed that ellagic acid helped mice cope with coming off morphine. I came across another study from 2016 finding that thymoquinone, which is found in the spice nigella sativa (also called czarnuszka, kalonji, and black cumin), also helps mice come off morphine addiction:

Abstract
OBJECTIVE:
Dependence and tolerance are major restricting factors in the clinical use of opioid analgesics. In the present study, the effects of thymoquinone, the major constituent of Nigella sativa seeds, on morphine dependence and tolerance were investigated in mice.MATERIALS AND METHODS:
Male adult NMRI mice were made tolerant and dependent by repeated injections of morphine (50, 50, and 75 mg/kg, i.p. on 9 a.m., 1 p.m., and 5 p.m., respectively) during a 3-day administration schedule. The hot-plate test was used to assess tolerance to the analgesic effects of morphine. Naloxone (2 mg/kg, i.p.) was injected to precipitate withdrawal syndrome in order to assess the morphine dependence. To evaluate the effects of thymoquinone on tolerance and dependence to morphine, different single or repeated doses of thymoquinone were administered in mice. Rotarod was used to assess the motor coordination.RESULTS:
Administration of single or repeated doses of thymoquinone (20 and 40 mg/kg, i.p.) significantly decreased the number of jumps in morphine dependent animals. Repeated administration of thymoquinone (20 and 40 mg/kg, for 3 days) and also single injection of thymoquinone (40 mg/kg, on the fourth day) attenuated tolerance to the analgesic effect of morphine. None of the thymoquinone doses (10, 20, and 40 mg/kg) produced any antinociceptive effects on their own. Motor coordination of animals was impaired by the high dose of thymoquinone (40 mg/kg).CONCLUSION:
Based on these results, it can be concluded that thymoquinone prevents the development of tolerance and dependence to morphine.


Both studies were done in Iran, although in different cities. Why would Iran be so interested in morphine addiction? Because Iran apparently has the highest prevalence of opium addiction in the world. (http://www.irishtimes.com/news/world/middle-east/hooked-in-iran-where-addiction-rates-are-world-s-highest-1.1834386) Iran borders Afghanistan, the world's leading producer of opium. 

Nigella sativa is a peppery spice that is widely used in some of the same areas where opium is grown, so if it turns out to have a compound that can help end opium addiction, that would be convenient.

However, thymoquinone does appear to inhibit angiogenesis (https://www.ncbi.nlm.nih.gov/pubmed/18644991), which appears connected to fetal limb deformities per a prior post of mine, so pregnant women should probably avoid it (sorry, Bengali curry fans - http://www.bongcookbook.com/2007/10/myspice-kalonji.html).

Recent US news headlines on heroin say that overdoses now kill more people in the USA than do gun deaths. Many heroin addicts get started down the road to heroin use by becoming dependent on legitimately-needed prescription opiate medications after an injury or surgery. If ellagic acid and thymoquinone can help these people end their addiction to pain meds, perhaps they'll not go down the heroin road at all. One can hope.

Tuesday, December 6, 2016

C-fos at night

Being exposed to light during what should be our "night" appears to elevate c-fos levels in the mammalian brain, per a 1990 study:
Photic information entrains a circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the mammalian hypothalamus to environmental light/dark cycles. To determine whether light regulates c-fos gene expression in the SCN, we have measured c-fos mRNA levels in the SCN of the golden hamster. We report that, during the subjective night, light causes a rapid increase in levels of c-fos mRNA in the SCN. Light pulses of 5 min duration are sufficient to induce c-fos mRNA, and the highest mRNA levels occur 30 min following the onset of light. The minimum level of illumination required to induce an increase in c-fos mRNA is indistinguishable from the minimum irradiance that produces a phase shift in the hamster's circadian rhythm of activity. In addition, the induction of c-fos mRNA in the SCN by light is itself under circadian regulation. Light induction of c-fos mRNA occurs only during the subjective night, at circadian times when photic phase shifting of activity occurs. Taken together, these data suggest that c-fos may be a molecular component of the photic pathway for entrainment of mammalian circadian rhythms.

https://www.ncbi.nlm.nih.gov/pubmed/2116813

If elevated c-fos is connected to the creation of addictive neural assemblies in the brain (briefly discussed in the preceding post), then being exposed to light during what should be our sleeping period might increase the possibility of becoming addicted to whatever pleasurable thing we are doing while up at night.

Why do casinos keep the lights on constantly? Is it just so that casino patrons don't notice how much time they've been inside gambling, or have the casinos observed an increase in gambling addiction-like behavior as a result of their exposing their patrons to light when the patrons ought to be in bed?

Why are night owls more prone to addictive disorders than early risers? (https://www.ncbi.nlm.nih.gov/pubmed/26250146) Is it because they are engaged in their addictions when their bodies should be asleep?

Being an evening person, rather than a morning person, was recently found to be linked to a higher risk of becoming addicted to smartphones in German adolescents. (https://www.ncbi.nlm.nih.gov/pubmed/27499228) Is that because the evening people are more likely to have a smartphone shining in their faces when they should be asleep?

All very interesting. It almost makes me want to go to bed earlier. Actually, why don't I? I can read in the early morning just as easily as in the late evening. Perhaps it's time to make my bedtime firm.

Wednesday, November 30, 2016

Up c-fos to increase brain learning/unlearning?

C-fos increases in the brain right after administration of drugs such as cocaine (http://www.pnas.org/content/87/17/6912.full.pdf), and it appears to be elevated in some brain areas when the brain is "unlearning" a previous memory pattern, such as in this study looking at c-fos levels in rats just after they brought about extinction of a previously-reinforced behavior (i.e., it's as though they stopped feeding Pavlov's dog after ringing bells, observed how long it took for the dog to stop salivating after bell ringing, then examined the dog's brain tissue) (https://www.ncbi.nlm.nih.gov/pubmed/24315832):
Taking into account that c-Fos activity reflects the last part of this process of extinction in this study, we cannot preclude the possibility of a new inhibitory learning taking place at the time. According to some authors, the extinguished memory is not erased but inhibited, so that the observed c-Fos changes may reflect this new learning process that could be occurring at the end of the extinction procedure.

Researchers seem reluctant to say that c-fos is a causative part of making the neuronal assemblies associated with addiction, but they do find a strong correlational link:
The described neurochemical and molecular biological mechanisms all support the idea that c-fos promoter activation is an indicator of strong and persistent calcium influx into synapses of MSNs that received the most excitatory glutamatergic input. Drug-induced dopamine can synergistically enhance c-fos promoter activation in these strongly activated MSNs. It should be noted that a lack of Fos expression in a neuron does not imply a complete lack of neural activity, only that it is not depolarized strongly or persistently enough to produce enough intracellular calcium to activate the ERK signaling pathway. The earlier section describing in vivo electrophysiology and cellular imaging studies indicate that the neurons receiving the most excitatory glutamatergic input are determined by the context and cues present during drug administration. Altogether these data support the hypothesis that Fos-expressing neurons in corticostriatal circuitry can act together as a unit to form neuronal ensembles that encode and mediate conditioned drug behaviors. It is important to note that we treat c-fos and Fos only as markers of activated neurons in this hypothesis and do not imply that these molecules are directly involved in neuronal ensemble function. 

Suppose someone wants to learn a new behavior or lessen the pull of a learned, unhelpful behavior. Might it be helpful to increase c-fos somehow during the learning/unlearning period? Delta-fosB, which I discussed in previous posts, accumulates in addiction and represses c-fos, which repression could be preventing addiction-breaking learning/unlearning. That gives support to the idea that not increasing c-fos is unhelpful when overcoming an addiction. But it does not logically follow that increasing c-fos will therefore be helpful in overcoming an addiction. I'll have to look and see if there are studies done specifically on that.

There are studies that look at how to increase c-fos expression. Three tested ways to increase c-fos expression are forskolin (an herbal supplement already in use by some as a weight loss help), BDNF (brain-derived neurotrophic factor, a protein), and membrane depolarization (brought about via neurotransmitters or KCl) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696896/). BDNF is being looked at as a possible aid in cocaine addiction (https://www.ncbi.nlm.nih.gov/pubmed/26923993), and forskolin seems able to induce a strengthening of synapses involved in memory formation (but the effect is much smaller in older rat brain tissue--https://www.ncbi.nlm.nih.gov/pubmed/15911893). Glutamate is a neurotransmitter, and monosodium glutamate (MSG) is known to evoke c-fos activity (https://www.ncbi.nlm.nih.gov/pubmed/26762887); a quick Google search finds that many people feel MSG is addictive for them, for what that's worth.

Here's a fun idea to test whether upping c-fos helps develop new brain pathways associated with memory and addiction. Try a new activity that you would like to become slightly addicted to, and eat Nacho Cheese Doritos while you do it.  Nacho Cheese Doritos are a good source of MSG. Then see if you are more fixated on the new activity afterward than you would have expected. Even if the experiment bombs, you'll have gotten to eat Doritos in the name of science!

Monday, November 21, 2016

C-fos, addiction, and eros

Another molecule connected to addiction is c-fos (https://en.wikipedia.org/wiki/C-Fos), production of which is increased after using cocaine, methamphetamine (https://www.ncbi.nlm.nih.gov/pubmed/2118661), and other such drugs and possibly after mating (c-fos increases have been found in rats after mating--https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834303/). Various articles in the past few years have claimed that falling in love is the same to the brain as getting high on crack cocaine (e.g., http://www.salon.com/2015/02/14/love_is_like_cocaine_the_remarkable_terrifying_neuroscience_of_romance/, https://www.psychologytoday.com/blog/the-joint-adventures-well-educated-couples/201208/falling-in-love-is-smoking-crack-cocaine, http://www.medicaldaily.com/oxytocin-love-hormone-fuels-romance-how-your-brain-works-when-youre-love-269067). How very unromantic.

C-fos appears to be important in effectuating morphological changes in the brain (specifically, increased dendritic branching and dendritic spine density) as the process of addiction occurs, as well as in overcoming addiction after the object of the addiction has been removed (http://www.jneurosci.org/content/26/51/13287.full).

In a recent post, I cited a paper indicating that an accumulation of ΔFosB can be considered the molecular "on-switch" of addiction in the brain. A 2008 rat study found that ΔFosB represses c-fos (http://www.jneurosci.org/content/28/29/7344.full). Anhedonia--an inability to experience pleasure from positive life events--is more common in psychoactive substance-using populations, and it lessens as they get off drugs (https://www.ncbi.nlm.nih.gov/pubmed/24270310). It appears as though the brain could be homeostatically acting to remain "faithful" to the source of pleasure it became addicted to and so represses c-fos production that would allow formation of competing neural pathways associated with other pleasures. That would help explain the inability to find much pleasure outside of one's addiction and perhaps the occurrence of monogamy. Again, very unromantic.

I feel like I should repost this all on February 14th to be contrary. "Your mate might be faithful to you just because of an accumulation of ΔFosB that prevents him/her from finding the same pleasure with someone else." That won't show up on a Hallmark card anytime soon.... Still, you might as well face it if you are indeed addicted to love.



Saturday, November 19, 2016

Ellagic acid apparently helps with withdrawal symptoms from morphine, too

Last time I posted about ellagic acid possibly being a help to overcome addiction. Afterwards, I came across this study from two years ago finding that it helped alleviate morphine withdrawal symptoms:
Abstract
According to our previous study, ellagic acid has both dose-related central and peripheral antinociceptive effect through the opioidergic and l-arginine-NO-cGMP-ATP sensitive K+channel pathways. In the present study, the systemic antinociceptive effects of ellagic acid in animal models of pain, and functional interactions between ellagic acid and morphine in terms of analgesia, tolerance and dependence were investigated. Ellagic acid (1–30 mg/kg; i.p.) showed significant and dose-dependent antinociceptive effects in the acetic acid-induced writhing test. Intraperitoneal ellagic acid acutely interacted with morphine analgesia in a synergistic manner in this assay. Ellagic acid (1–10 mg/kg; i.p.) also exerted analgesic activity in the hot-plate test. Pre-treatment with naloxone (1 mg/kg; i.p.) significantly reversed ellagic acid, morphine as well as ellagic acid-morphine combination-induced antinociceptin in these two tests. More importantly, when co-administered with morphine, ellagic acid (1–10 mg/kg) effectively blocked the development of tolerance to morphine analgesia in the hot-plate test.
Likewise, ellagic acid dose-dependently prevented naloxone-precipitated withdrawal signs including jumping and weight loss. Ellagic acid treatment (1–30 mg/kg; i.p.) had no significant effect on the locomotion activity of animals using open-field task. Therefore, these results showed that ellagic acid has notable systemic antinociceptive activity for both tonic and phasic pain models. Altogether, ellagic acid might be used in pain relief alone or in combination with opioid drugs because of enhancing morphine analgesia and preventing morphine-induced tolerance to analgesia and dependence.
http://www.sciencedirect.com/science/article/pii/S0014299914006293

Naloxone (trade name Narcan) causes opioid-withdrawal symptoms in those who are dependent on opioids.

Opiate withdrawal symptoms can be extremely unpleasant:

Early symptoms of withdrawal include:
  • Agitation
  • Anxiety
  • Muscle aches
  • Increased tearing
  • Insomnia
  • Runny nose
  • Sweating
  • Yawning
Late symptoms of withdrawal include:
  • Abdominal cramping
  • Diarrhea
  • Dilated pupils
  • Goose bumps
  • Nausea
  • Vomiting
Opioid withdrawal reactions are very uncomfortable but are not life-threatening. Symptoms usually start within 12 hours of last heroin usage and within 30 hours of last methadone exposure.
http://www.nytimes.com/health/guides/disease/opiate-withdrawal/overview.html

If ellagic acid, a component of easily-obtainable berries and walnuts, can reduce opiate withdrawal symptoms, that seems like something that should become common knowledge, doesn't it? I hope someone tests ellagic acid in humans for relief from opiate addiction withdrawal symptoms.

Tuesday, November 15, 2016

A way to lessen withdrawal anxiety?

In a land of plenty where many cases of cancer and other physical illness have become curable due to medical advances, the problem of intractable mental illness is beginning to be far more apparent. One form of mental disorder that seems to be very prevalent is addictive disorders. One study estimated that approximately half the US population suffers from addictive disorder symptoms in the course of a year:
An increasing number of research studies over the last three decades suggest that a wide range of substance and process addictions may serve similar functions. The current article considers 11 such potential addictions (tobacco, alcohol, illicit drugs, eating, gambling, Internet, love, sex, exercise, work, and shopping), their prevalence, and co-occurrence, based on a systematic review of the literature. Data from 83 studies (each study n = at least 500 subjects) were presented and supplemented with small-scale data. Depending on which assumptions are made, overall 12-month prevalence of an addiction among U.S. adults varies from 15% to 61%. The authors assert that it is most plausible that 47% of the U.S. adult population suffers from maladaptive signs of an addictive disorder over a 12-month period and that it may be useful to think of addictions as due to problems of lifestyle as well as to person-level factors.
http://ehp.sagepub.com/content/34/1/3.short

If nearly half of adults are "addicted" in any given year, then addiction by definition would seem to be a fairly normal process of the brain. When the addiction is to something that helps increase our ability to enjoy and function in life, we call it things like "enthusiasm" or "dedication," but when it robs us of our ability to function productively and healthily, we consider it a disease. (http://www.iflscience.com/health-and-medicine/theres-no-such-thing-as-an-addictive-personality-heres-why/all/) One element of an addictive disorder is that the addicted person suffers from withdrawal symptoms when deprived of the substance or behavior to which he/she is addicted.

What chemically happens in the brain during withdrawal? We know that ΔFosB (delta-FosB), a gene transcription factor is a chemical on-switch for both substance and behavior addictions:
The longevity of some of the behavioral abnormalities that characterize drug addiction has suggested that regulation of neural gene expression may be involved in the process by which drugs of abuse cause a state of addiction. Increasing evidence suggests that the transcription factor ΔFosB represents one mechanism by which drugs of abuse produce relatively stable changes in the brain that contribute to the addiction phenotype. ΔFosB, a member of the Fos family of transcription factors, accumulates within a subset of neurons of the nucleus accumbens and dorsal striatum (brain regions important for addiction) after repeated administration of many kinds of drugs of abuse. Similar accumulation of ΔFosB occurs after compulsive running, which suggests that ΔFosB may accumulate in response to many types of compulsive behaviors. Importantly, ΔFosB persists in neurons for relatively long periods of time because of its extraordinary stability. Therefore, ΔFosB represents a molecular mechanism that could initiate and then sustain changes in gene expression that persist long after drug exposure ceases. Studies in inducible transgenic mice that overexpress either ΔFosB or a dominant negative inhibitor of the protein provide direct evidence that ΔFosB causes increased sensitivity to the behavioral effects of drugs of abuse and, possibly, increased drug seeking behavior. This work supports the view that ΔFosB functions as a type of sustained “molecular switch” that gradually converts acute drug responses into relatively stable adaptations that contribute to the long-term neural and behavioral plasticity that underlies addiction.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC58680/

When mice are given the opportunity to become addicted to ethanol (alcohol) and then deprived of it, the level of ΔFosB in their brain dramatically rises during the withdrawal period. (http://www.sciencedirect.com/science/article/pii/S0091305713003419) If ΔFosB levels can be kept from rising during the withdrawal period, perhaps that will weaken the power of the addiction and make it easier to get past.

Why does ΔFosB hang around for so long in the brain? Is there a way we can keep it from hanging around for so long so that levels of ΔFosB don't rise as much during withdrawal periods?
The transcription factor ΔFosB (also referred to as FosB2 or FosB[short form]) is an important mediator of the long-term plasticity induced in brain by chronic exposure to several types of psychoactive stimuli, including drugs of abuse, stress, and electroconvulsive seizures. A distinct feature of ΔFosB is that, once induced, it persists in brain for relatively long periods of time in the absence of further stimulation. The mechanisms underlying this apparent stability, however, have remained unknown. Here, we demonstrate that ΔFosB is a relatively stable transcription factor, with a half-life of ∼10 h in cell culture. Furthermore, we show that ΔFosB is a phosphoprotein in brain and that phosphorylation of a highly conserved serine residue (Ser27) in ΔFosB protects it from proteasomal degradation. We provide several lines of evidence suggesting that this phosphorylation is mediated by casein kinase 2. These findings constitute the first evidence that ΔFosB is phosphorylated and demonstrate that phosphorylation contributes to its stability, which is at the core of its ability to mediate long-lasting adaptations in brain.
http://www.jneurosci.org/content/26/19/5131.long

This suggests that inhibiting casein kinase 2 could diminish the amount by which ΔFosB increases in the brain during withdrawal periods. What inhibits casein kinase 2? Two commonly consumed inhibitors of casein kinase 2 are apigenin (highest in chamomile, parsley, and celery) and ellagic acid (highest in berries and walnuts). Chamomile extract containing apigenin has been observed to reduce anxiety (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3600408/), and ellagic acid has been observed to lessen withdrawal symptoms in nicotine-addicted mice (https://www.uaeh.edu.mx/investigacion/producto.php?producto=5628).

Therefore, if trying to overcome a behavior that has started to drift into "addiction" territory, I would be sure to include high levels of foods containing ellagic acid and apigenin if I felt anxiety at suspending the behavior to which I'd become addicted. Wild strawberries appear to be one of the very best sources of ellagic acid (http://pub.jki.bund.de/index.php/JABFQ/article/viewFile/3114/3485), which tidbit would no doubt please Ingmar Bergman--a Swedish film producer whose film Wild Strawberries is about a very old man overcoming a lifetime of habitual aloofness--were he still alive.

Monday, November 7, 2016

High altitude link to depression

I live nearly 2000 m above sea level, so I'm especially interested in a finding last year that female mice put in conditions simulating high altitudes are more prone to developing symptoms of depression:

Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

The researchers housed rats for a week at simulated altitudes of sea level, 10,000 feet and 20,000 feet using altitude chambers, and at local conditions of 4,500 feet, the elevation of Salt Lake City where the research took place. They then used a widely accepted behavioral test in which depression is gauged by how much persistence rodents demonstrate in a swim test. “In female rats, increasing altitude of housing from sea level to 20,000 feet caused a parallel increase in depression-like behavior,” Kanekar says.
The correlation between altitude and high rates of depression and suicide is strikingly obvious in the Intermountain West region of the United States where elevations are considerably higher than in the rest of the country. In 2012, the eight states that comprise the Intermountain West–Utah, Colorado, Wyoming, Montana, Idaho, Nevada, Arizona and New Mexico–had suicide rates exceeding 18 per 100,000 people compared with the national average of 12.5 per 100,000, according to the American Foundation for Suicide Prevention. The high rates of self-inflicted death in the West have earned the region a gloomy moniker: the Suicide Belt.
....
“The fact that both depression and suicide rates increase with altitude implies that current antidepressant treatments are not adequate for those suffering from depression at altitude, leading to high levels of unresolved depression that can contribute to higher levels of suicidal ideation and suicide attempts,” says Kanekar.
http://healthcare.utah.edu/publicaffairs/news/2015/03/03-25-15_KankekarRats.php; full text of study online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376288/.

I know of a couple of people--both of whom are female, which fits the finding of this mice study--dealing with difficult-to-treat depression here in Colorado. (Although most of my regular contacts are LDS, neither of these two people is LDS, which doesn't seem to fit with occasional claims that LDS people are more prone to depression than non-LDS people.) Could their depression be in part due to the lower barometric pressure and oxygen content of Colorado air?

Despite my adoring the mountains, if my daughters were to suffer from chronic depression, I would consider moving to a lower elevation if I couldn't somehow up the amount of oxygen they inhale.

Thursday, November 3, 2016

Learning to conduct

I was asked to be a church choir director a month ago. In my church, we have a lay ministry where we give our time freely in positions as we are called upon to fill them. The choir rehearses most Sundays for about 45 minutes and includes everyone from beginners and children up to very talented instrumental and vocal musicians. And yet, it doesn't actually have many people.

My mother taught me how to wave my hand around in a 4/4 pattern when I was around 11 years old, but she never taught me about ictus, how to bring in singers, or how to cut off a note. She put me in voice lessons with a professional opera singer back when I was in grade school and singing Shirley Temple songs, so I can produce notes well enough. Unfortunately, I am now expected to NOT sing and instead focus on teaching others to sing and directing them appropriately. Thankfully, there are YouTube videos available to help. Here is a good one on ictus, in case you're wondering what that is:


https://www.youtube.com/watch?v=6GmrlY0pA_Q

Wish me luck at this directing gig! (I'm going to need it.)

Thursday, October 27, 2016

Impressive results in overcoming allergies

Yesterday ScienceDaily published a press release about a new technique of developing immune tolerance of anaphylaxis-causing allergens in mice. The treatment resulted in significant effects with just one treatment in 90% of test cases.
The discovery involves generating a type of naturally occurring immune cell that sends a signal to reverse the hyper-immune response present in allergic reactions. That signal triggers another "off switch" that turns off reactive cells further along the allergic pathway.*Here's how the technique works:
•The key component of this research is dendritic cells, which serve as the gate-keepers of the immune system and are present in tissues in contact with the external environment, such as the skin and the inner lining of the nose, lungs, stomach and intestines.
•Gordon's pioneering treatment involves producing dendritic cells in a test tube and then exposing them to a unique mix of proteins, a vitamin A-related acid naturally occurring in the human gut, and to the allergen, in this case, peanut or ovalbumin (egg white protein). The modified dendritic cells are then reintroduced into the mouse.
•Using this technique, the researchers were able to nearly eliminate the allergic reaction by converting allergen-sensitive immune cells into cells that mimic the response seen in healthy, non-allergic individuals.
The treatment reduced the observed symptoms of anaphylaxis, and lowered other key protein markers in the allergic response by up to 90 per cent.
https://www.sciencedaily.com/releases/2016/10/161026133229.htm

Per the abstract, they "generated and characterized mature retinoic acid-skewed dendritic cells." (http://www.jacionline.org/article/S0091-6749(16)30969-1/abstract) I can't read the whole study, but I'm very curious about what exactly they did with the retinoic acid. A few months ago, I hypothesized that excess retinoic acid was connected to developing food allergies (http://petticoatgovernment.blogspot.com/2016/07/celiac-food-allergies-connected-to.html) and not in an inverse way; I thought that too much retinoic acid and its precursor retinal were interfering with RALDH2 activity, which appears crucial to immune tolerance. Perhaps I erred lumping retinal and retinoic acid together, or perhaps the timing of the exposure of the retinoic acid is crucial to developing the right kind of dendritic cell for reversing allergy. Or maybe while some retinoic acid is necessary to immune tolerance, an excess of retinoic acid causes the same problems as a deficiency, such as in this mouse study on excess Vitamin A, which found that it resulted in lower RALDH transcription subsequently - http://www.pnas.org/content/109/34/13668.full.pdf). I will have to wait until the study has been published (it's still an "article in press") to evaluate whether my hypothesis is either weakened or strengthened by the success of this new technique. Either way, I'm pleased to see such solid progress in this field!

Wednesday, October 26, 2016

Buckwheat

ScienceDaily just reported on a mouse study that found that the plant extract rutin helped diminish adiposity (i.e., lose weight):
To make their discovery, Jin and colleagues used both genetically obese mice and mice with diet-induced obesity as models. These mice were fed a regular diet, and supplemental rutin (1 mg/ml) was added to their drinking water. Rutin treatment significantly reduced adiposity, increased energy expenditure, and improved glucose homeostasis in both the genetically obese mice and the mice with diet-induced obesity. Specifically, the researchers found that rutin directly binds to and stabilizes SIRT1 (NAD-dependent deacetylase sirtuin-1), leading to hypoacetylation of PGC1α protein, which stimulates Tfam transactivation and eventually augments mitochondrial number and UCP1 activity in BAT. Rutin functions as a cold mimetic through activating a SIRT1-PGC1α-Tfam signaling cascade and increasing mitochondrial number and UCP1 activity in BAT. Rutin also induced brown-like (beige) adipocyte formation in subcutaneous adipose tissue in both obesity mouse models.
https://www.sciencedaily.com/releases/2016/10/161026105132.htm

Among other things, rutin is an aldose reductase inhibitor. (https://www.researchgate.net/publication/285826861_Inhibition_of_aldose_reductase_and_sorbitol_accumulation_by_dietary_rutin) Rutin is found in buckwheat, cranberries, citrus fruits, and many other edible plants (http://www.icpjonline.com/documents/Vol1Issue12/07.pdf). The rutin in buckwheat exhibits chelating and antioxidant activity, too. (https://www.ncbi.nlm.nih.gov/pubmed/27709826) I wonder how buckwheat tastes....