5 ms·

Don't get too excited about this — activation of the aryl hydrocarbon receptor is the mechanism of toxicity of things like tetrachlorodibenzodioxin: http://en.

by scythe 5y ago

Don't get too excited about this — activation of the aryl hydrocarbon receptor is the mechanism of toxicity of things like tetrachlorodibenzodioxin: http://en.wikipedia.org/wiki/2,3,7,8-Tetrachlorodibenzodioxin#Mechanism_of_action http://en.wikipedia.org/wiki/2,3,7,8-Tetrachlorodibenzodioxi... It's possible that the inherent toxicity will preclude use as a treatment. On the other hand, it would be ironic if one of the most toxic substances known turns out to treat COVID-19.

User23 5y ago
The dose makes the poison[1]. [1] https://en.m.wikipedia.org/wiki/The_dose_makes_the_poison https://en.m.wikipedia.org/wiki/The_dose_makes_the_poison
- hinkley 5y ago
  That model is not accurate as BPA has illustrated.
  - cybernautique 5y ago
    Is that in regards to this thread[1]? [1] https://news.ycombinator.com/item?id=28500508 https://news.ycombinator.com/item?id=28500508
  - User23 5y ago
    It’s true that sometimes the toxic dose is tiny, like for example dimethylmercury. I don’t see how that invalidates the principle though. As a precautionary measure though I do agree with avoiding BPA among other things.
    - fiddlerwoaroof 5y ago
      I think the exceptions to the rule are substances that aren’t eliminated by the body: small, “harmless”, doses can then accumulate with chronic exposure into a dangerous dose.
      - AstralStorm 5y ago
        Not just that, but anything that is persistent in the environment and readily absorbable fits the bill. It so happens that BPA and pthalates as part of the plastics made with these substances are persistent - they contain a high total and release the dosage extremely slowly into the environment. A good example for that is also a slow toxic spill (of e.g. azo dyes) from a factory giving many bladder cancer. (See Pakistan.) The release is persistent due to persistent manufacture of clothing using the toxic substance. Chronic exposures have a way of overwhelming or slipping by our internal detoxification - even though single dosage may be low and substance might not bioaccumulate, the damage does or probabilities get skewed towards certainty.
        dotancohen 5y ago
        > a slow toxic spill (of e.g. azo dyes) from a factory giving many bladder cancer. It should be noted in context that azo dyes are what the general public call "food colourings", at least the common, bright, inexpensive food colourings. And their accumulation in the body cause other types of damage as well, which is why there is no safe dose.
    - hinkley 5y ago
      I didn't say it invalidated the model. All models are wrong, some are useful. But what we've discovered is classes of chemicals that cause more damage at small doses, because they interfere with subtler communication pathways in the body such as hormones, and those effects diminish at higher accumulations. There are other categories, like 'no dose is safe', which GP is implying may be the case for this compound, in which case 'the dose is the poison' is a divide by zero error. You can't assume that the model works just because it worked (or we ignored the data that didn't fit the model) for 450 years. But the original quote is: "All things are poison, and nothing is without poison; the dosage alone makes it so a thing is not a poison." In the full quote it's clear we aren't talking about pesticides or arsenic. You can poison yourself with enough iron, or vitamin E. Somewhere along the way it became about how much perchlorate you can have in water before half the fish die.
      - User23 5y ago
        > But what we've discovered is classes of chemicals that cause more damage at small doses That's fascinating. Would you please give an example of a chemical whose toxicity decreases with increased dosage? > In the full quote it's clear we aren't talking about pesticides or arsenic. "All things" makes it pretty clear what we're talking about. I feel comfortable asserting that both pesticides and arsenic are members of the set of all things, along with vitamins, iron, and perchlorates. I think one might go so far as to say that an organism can be poisoned by any substance its body is capable of absorbing in sufficient quantity. Water poisoning is a fun example. Despite our bodies largely being composed of it, ingest too much and your cells swell up to the point it can cause brain failure. Even the non-reactive noble gasses can cause narcotic effects.
loonster 5y ago
I thought the main benefit from smoking (in regards to covid) was the nicotine itself. The nicotine gets oxidized and turned into nicotinc acid. If I wanted to mimic the benefits of smoking, I would take a nicotinic acid pill (flushing niacin)
- cbozeman 5y ago
  Good thing I just smoke cigars. I've found they mellow out me after a long, hard day. Maybe it's the atmosphere in which I immerse myself... on my patio, listening to music, reclining in a chair, but they seem to help me unwind.
  - King-Aaron 5y ago
    It'll certainly be the atmosphere that's primarily calming you, however I recall reading years ago (so don't quote me) about the catch-22 of smoking. When you're smoking - or rather in the breaks between smoking - the vascular system undergoes hypertension, which then is marginally reduced by the relaxation that another hit of nicotine provides. So your baseline 'stress' increases as a result of smoking, and having another cigarette/cigar temporarily reduces that. So the net effect of not smoking plus your relaxing environment would be more relaxing without the cigars in the first place.
    - eurasiantiger 5y ago
      That has nothing to do with nicotine and everything to do with monoamine oxidase inhibitors in tobacco smoke.
    - disgruntledphd2 5y ago
      > When you're smoking - or rather in the breaks between smoking - the vascular system undergoes hypertension, which then is marginally reduced by the relaxation that another hit of nicotine provides. So your baseline 'stress' increases as a result of smoking, and having another cigarette/cigar temporarily reduces that. So the net effect of not smoking plus your relaxing environment would be more relaxing without the cigars in the first place. This theory was popularised by Allen Carr in his Easy Way to Stop Smoking (or at least that's where I heard it, and the book was published in the early 80s).
himinlomax 5y ago
Omeprazole is already an approved drug. In fact, I was about to swallow a pill as I was reading this.

by scythe 5y ago

User23 5y ago

The dose makes the poison[1]. [1] https://en.m.wikipedia.org/wiki/The_dose_makes_the_poison https://en.m.wikipedia.org/wiki/The_dose_makes_the_poison

hinkley 5y ago
That model is not accurate as BPA has illustrated.
- cybernautique 5y ago
  Is that in regards to this thread[1]? [1] https://news.ycombinator.com/item?id=28500508 https://news.ycombinator.com/item?id=28500508
- User23 5y ago
  It’s true that sometimes the toxic dose is tiny, like for example dimethylmercury. I don’t see how that invalidates the principle though. As a precautionary measure though I do agree with avoiding BPA among other things.
  - fiddlerwoaroof 5y ago
    I think the exceptions to the rule are substances that aren’t eliminated by the body: small, “harmless”, doses can then accumulate with chronic exposure into a dangerous dose.
    - AstralStorm 5y ago
      Not just that, but anything that is persistent in the environment and readily absorbable fits the bill. It so happens that BPA and pthalates as part of the plastics made with these substances are persistent - they contain a high total and release the dosage extremely slowly into the environment. A good example for that is also a slow toxic spill (of e.g. azo dyes) from a factory giving many bladder cancer. (See Pakistan.) The release is persistent due to persistent manufacture of clothing using the toxic substance. Chronic exposures have a way of overwhelming or slipping by our internal detoxification - even though single dosage may be low and substance might not bioaccumulate, the damage does or probabilities get skewed towards certainty.
      - dotancohen 5y ago
        > a slow toxic spill (of e.g. azo dyes) from a factory giving many bladder cancer. It should be noted in context that azo dyes are what the general public call "food colourings", at least the common, bright, inexpensive food colourings. And their accumulation in the body cause other types of damage as well, which is why there is no safe dose.
  - hinkley 5y ago
    I didn't say it invalidated the model. All models are wrong, some are useful. But what we've discovered is classes of chemicals that cause more damage at small doses, because they interfere with subtler communication pathways in the body such as hormones, and those effects diminish at higher accumulations. There are other categories, like 'no dose is safe', which GP is implying may be the case for this compound, in which case 'the dose is the poison' is a divide by zero error. You can't assume that the model works just because it worked (or we ignored the data that didn't fit the model) for 450 years. But the original quote is: "All things are poison, and nothing is without poison; the dosage alone makes it so a thing is not a poison." In the full quote it's clear we aren't talking about pesticides or arsenic. You can poison yourself with enough iron, or vitamin E. Somewhere along the way it became about how much perchlorate you can have in water before half the fish die.
    - User23 5y ago
      > But what we've discovered is classes of chemicals that cause more damage at small doses That's fascinating. Would you please give an example of a chemical whose toxicity decreases with increased dosage? > In the full quote it's clear we aren't talking about pesticides or arsenic. "All things" makes it pretty clear what we're talking about. I feel comfortable asserting that both pesticides and arsenic are members of the set of all things, along with vitamins, iron, and perchlorates. I think one might go so far as to say that an organism can be poisoned by any substance its body is capable of absorbing in sufficient quantity. Water poisoning is a fun example. Despite our bodies largely being composed of it, ingest too much and your cells swell up to the point it can cause brain failure. Even the non-reactive noble gasses can cause narcotic effects.

loonster 5y ago

I thought the main benefit from smoking (in regards to covid) was the nicotine itself. The nicotine gets oxidized and turned into nicotinc acid. If I wanted to mimic the benefits of smoking, I would take a nicotinic acid pill (flushing niacin)

cbozeman 5y ago
Good thing I just smoke cigars. I've found they mellow out me after a long, hard day. Maybe it's the atmosphere in which I immerse myself... on my patio, listening to music, reclining in a chair, but they seem to help me unwind.
- King-Aaron 5y ago
  It'll certainly be the atmosphere that's primarily calming you, however I recall reading years ago (so don't quote me) about the catch-22 of smoking. When you're smoking - or rather in the breaks between smoking - the vascular system undergoes hypertension, which then is marginally reduced by the relaxation that another hit of nicotine provides. So your baseline 'stress' increases as a result of smoking, and having another cigarette/cigar temporarily reduces that. So the net effect of not smoking plus your relaxing environment would be more relaxing without the cigars in the first place.
  - eurasiantiger 5y ago
    That has nothing to do with nicotine and everything to do with monoamine oxidase inhibitors in tobacco smoke.
  - disgruntledphd2 5y ago
    > When you're smoking - or rather in the breaks between smoking - the vascular system undergoes hypertension, which then is marginally reduced by the relaxation that another hit of nicotine provides. So your baseline 'stress' increases as a result of smoking, and having another cigarette/cigar temporarily reduces that. So the net effect of not smoking plus your relaxing environment would be more relaxing without the cigars in the first place. This theory was popularised by Allen Carr in his Easy Way to Stop Smoking (or at least that's where I heard it, and the book was published in the early 80s).

himinlomax 5y ago

Omeprazole is already an approved drug. In fact, I was about to swallow a pill as I was reading this.