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Thread: Rats vs humans

  1. #1 Rats vs humans 
    Forum Freshman Amaranth's Avatar
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    It's said that 12 days of rat life is equivalent to 1 year of human's. Does that literally mean their cells replicate approximately 30 times faster and you can transduct a medicine's impact on their cells to a 30 times longer period for humans?


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    Quote Originally Posted by Amaranth View Post
    It's said that 12 days of rat life is equivalent to 1 year of human's. Does that literally mean their cells replicate approximately 30 times faster
    Nope. Their cells probably replicate at a similar speed as us. Theirs however tend to be less restrictive to one another. This means their cell specialism proceeds slower, and the rat pup will grow to it's adult size faster. They heal from wounds at the same rate as most mammals, and humans (give or take a few percentages).

    Quote Originally Posted by Amaranth View Post
    and you can transduct a medicine's impact on their cells to a 30 times longer period for humans?
    Also nope. The medicine's halfworth time is the same, and thus the afflicted time is the same. Their cells don't replicate 30 times facter then humans, their metabolism is higher then hours, about twice as fast, but not 30 times as fast. Not sure how much faster their cells divide, if any faster at all, then humans.

    The 12 days equivalent to 1 year human compared to a rat, is probably taken from lifecycle. Where a human has to be around 15 to be able to (safely) reproduce. A rat can become sexually active in a half year.


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    Actually, the half-time is not the same. It can't be. If the rat's metabolism is twice as fast, it should also process the drug faster.
    And now I understand how much faulty science there actually is...
    Thank you for the reply!
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    Quote Originally Posted by Amaranth View Post
    Actually, the half-time is not the same. It can't be. If the rat's metabolism is twice as fast, it should also process the drug faster.
    Well yes, i know it's not the same, but i was talking about the 30 times faster.. Which its not. The actual halftime worth of the medicine i told was based on the medicine itself, that did not change, i doubt there would be a significant difference in degrading the medicine. Metabolism is higher yes, but i am not sure this has effect on the drug...
    The past teaches, the present watches and the future learns.

    Though religion is a concept that simply can not be ignored. The fact that a deity could stand idly by when one part of his creation slaughters another part, simply for his namesake, is a mystery i doubt theologist would dare touch.

    ~Zwolver...
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    So if a human adult (post-puberty) is 18, then a rat (Sprague-Dawley for example) is adult by the age of 0,6 years (29 weeks), right? A 9-week-old rat, for example, is considered a baby? This kind of info should be easily findable in the Internet, but I can't...

    Edit: found some good info now: http://www.ratbehavior.org/RatYears.htm
    Looks like a rat can become sexually active when 6 weeks old.
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    Do you guys mean 'half life' ?
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    Yes. By "half-time" I meant that, but the thread isn't only about that.
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    I can see it's not only about that. I just wanted to be clear on the terms you were using. Also, half life and half time are not exactly the same, as I understand it 'half time' is a subtype of 'half-life'
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    I'll ask the vet at my work that does mouse models about this. She's a frickin genius; I'm sure she'll be able to shed some light on the matter.
    Last edited by JoshuaL; October 8th, 2012 at 01:23 PM.
    "The only appropriate attitude for man to have about the big questions is... doubt. Doubt is humble, and that's what man needs to be, considering that human history is just a litany of getting sh*t dead wrong."

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    Hi guys. So I talked to our Comparative Pathologist and she says the half-life of a drug in a rat vs a human depends on many variables, not just having a high/low metabolism, and that results can be wildly different or unexpected from drug to drug, depending what parts of the body it affects. For one drug you might find that the half-life is comparable in a rat, but for another it might be much shorter. It really depends on the drug and on the species, and this is why a specific species will be chosen for a specific drug, because different species may have different parts that are similar to humans (use mice to study diabetes, but use pigs to study cystic fibrosis). She also gave me an example article from the literature, but it is a PDF too large to upload here. Happy to mail it if you are interested.
    "The only appropriate attitude for man to have about the big questions is... doubt. Doubt is humble, and that's what man needs to be, considering that human history is just a litany of getting sh*t dead wrong."

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    Is it open sourced.??. Can you provide reference, title of article, authors, etc.
    Last edited by Zwolver; October 12th, 2012 at 09:09 AM. Reason: typo
    The past teaches, the present watches and the future learns.

    Though religion is a concept that simply can not be ignored. The fact that a deity could stand idly by when one part of his creation slaughters another part, simply for his namesake, is a mystery i doubt theologist would dare touch.

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    Quote Originally Posted by JoshuaL View Post
    Hi guys. So I talked to our Comparative Pathologist and she says the half-life of a drug in a rat vs a human depends on many variables, not just having a high/low metabolism, and that results can be wildly different or unexpected from drug to drug, depending what parts of the body it affects. For one drug you might find that the half-life is comparable in a rat, but for another it might be much shorter. It really depends on the drug and on the species, and this is why a specific species will be chosen for a specific drug, because different species may have different parts that are similar to humans (use mice to study diabetes, but use pigs to study cystic fibrosis). She also gave me an example article from the literature, but it is a PDF too large to upload here. Happy to mail it if you are interested.
    What can she say about the cells? Do they proliferate as fast as human cells and are they more vulnerable to damage? Do tissue changes from drugs happen as fast as in humans? When is puberty?
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    As I said, tissue changes happening "as fast as in humans" will depend on the drug. Some drugs will affect as fast as humans, some will be faster than humans, and some will be slower than human. Different animals don't just look different, they have completely different organs than humans (obviously mostly the same organs, but there are several important differences). So we can NOT claim that in general a rat will metabolize drugs faster than a human, or slower than a human. We can only say that "this specific drug is metabolized faster in a rat" or that "this specific drug is metabolized slower in a rat" and will be different from drug to drug.

    The article she sent me is
    [edit: try this link, not sure if it will work for you]

    A Comprehensive Quantitative and Qualitative Evaluation of Extrapolation of Intravenous Pharmokinetic Parameters from Rat, Dog, and Monkey to Humans. I. Clearance

    Keith W. Ward and Brian R. Smith

    The abstract is not very informative (I should say does not directly address your question), but hints at how slippery the subject is. I'll paste it below:


    ABSTRACT:
    This study was conducted to comprehensively survey the available
    literature on intravenous pharmacokinetic parameters in the rat,
    dog, monkey, and human, and to compare common methods for
    extrapolation of clearance, to identify the most appropriate species
    to use in pharmacokinetic lead optimization, and to ascertain
    whether adequate prospective measures of predictive success are
    currently available. One hundred three nonpeptide xenobiotics
    were identified with intravenous pharmacokinetic data in rat, dog,
    monkey, and human; both body weight- and hepatic blood flowbased
    methods were used for scaling of clearance. Allometric
    scaling approaches, particularly those using data from only two of
    the preclinical species, were less successful at predicting human
    clearance than methods based on clearance as a set fraction of
    liver blood flow from an individual species. Furthermore, commonly
    used prospective measures of allometric scaling success,
    including correlation coefficient and allometric exponent, failed to
    discriminate between successful and failed allometric predictions.
    In all instances, the monkey tended to provide the most qualitatively
    and quantitatively accurate predictions of human clearance
    and also afforded the least biased predictions compared with other
    species. Additionally, the availability of data from both common
    nonrodent species (dog and monkey) did not ensure enhanced
    predictive quality compared with having only monkey data. The
    observations in this investigation have major implications for pharmacokinetic
    lead optimization and for prediction of human clearance
    from in vivo preclinical data and support the continued use of
    nonhuman primates in preclinical pharmacokinetics.
    "The only appropriate attitude for man to have about the big questions is... doubt. Doubt is humble, and that's what man needs to be, considering that human history is just a litany of getting sh*t dead wrong."

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  15. #14  
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    But what if we have a drug with the same kinetics in humans and in rats (or we have worked out a dose that's equivalent)? Aren't rat cells still more unstable to a change?
    What about rabbits? Are they more similar to humans?
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    Not sure how best to answer this, but let me start by making clear that rats do not have "unstable" cells, unless you are thinking of the fact that they are prone to tumor growth. Tumor growth is a result of faulty genetics [1], which is a separate issue from pharmacokinetics [2]. So, if we had a drug that had the same kinetics in humans and rats, they would be... well, they would be the same. There would not be any difference. HOWEVER, I realize that might be an unsatisfactory answer, so I'll try to attack the question from a different angle.

    What you really gotta understand is that an animal--and I mean any animal, including a human--has different kinds of cells. Your liver cells may react very differently to a drug than your skin cells would react, for example. So the kinetics of a drug in a human is going to be different in different types of cells, right? A drug might only affect your liver, or only affect your lungs, etc... Now, with that in mind, no one animal is more similar to humans than another animal--different animals have specific cell types that are similar to humans, but that's about it. That's why there are so many different animals used in testing medicines and such. A pig pancreas is similar to a human pancreas, but a rabbit pancreas is very very different from a human one.

    The end result is that you can't make a direct pharmacokinetic comparison between an entire human and an entire rat. You can only make meaningful comparisons at the level of specific kinds of cells/organs/etc. You can't claim, "This drug works fast in a human, so it will work even faster in a rat!" But, you can probably make educated guesses about different kinds of drugs based on what we already know. This one will work slower in a rat, this one will work faster, this one is about the same. But you won't actually know for sure until it has been tested in both the human and the rat.

    Not sure if that was helpful, but I think it might be confusing because the paradigm you're working in is incomplete. So, attacking it from one more angle: when we get right down to the chemical processes, we are talking about enzymes. It is true that the basics of metabolism are nearly identical in all animals [3], but in the larger process, different species create different enzymes in to deal with metabolism, and this means that different animals metabolize drugs in completely different ways. For a truly useful comparison between a rat and a human, you'd have to be sure the drug was being metabolized the same way, chemically speaking. Have a look at this chapter text book on the subject: http://books.mcgraw-hill.com/medical...s/CHAPTER3.pdf
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    Take this for example: http://www.asiaandro.com/archive/1008-682X/5/33.htm
    S
    o many men are taking this drug for cosmetical purposes, just to restore their hair, but there are reports of sexual dysfunction and even persistent sexual dysfunction (that doctors of course think are psychological) that could easily be related to fibrosis and diminished amount of muscle cells in the penis. They say a rat study isn't enough to prove the drug wrong. You can't make such a study on humans, because nobody would like to get their penis cut off.
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    Quote Originally Posted by Amaranth View Post
    but there are reports of sexual dysfunction and even persistent sexual dysfunction (that doctors of course think are psychological)
    I am very sad to report that doctors are usually not scientists. A truly excellent doctor will keep up with the literature so they know what the hell they're talking about, but in general, my previous statement says it all. However, doctors know a lot more than most of us and they are typically good at spotting problems, so please don't stop going to your doctor. If you are very concerned about something, you can always get a second opinion from another doctor.
    They say a rat study isn't enough to prove the drug wrong.
    Yes, this technically is true. Even though the study provides a likely explanation, we can't know for sure if the same mechanism is happening in humans. Even if the end result is the same (sexual dysfunction) the actual mechanism by which it happens could be different. There has been plenty of new research since that article was published (about 10 years ago) and I'm pretty sure if a doctor has read up thoroughly on this drug, they would not declare the sexual dysfunction to be psychological. Cases in point: [1][2][3][4] and very nice summary [5].
    "The only appropriate attitude for man to have about the big questions is... doubt. Doubt is humble, and that's what man needs to be, considering that human history is just a litany of getting sh*t dead wrong."

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    they would not declare the sexual dysfunction to be psychological
    Depends a lot on the doctor, regardless of the possible source of the problem. Unless the doctor in question is a urologist, you have no way of telling in advance whether they have or haven't been keeping up with the literature. You might even have a doctor whose initial training glossed over sexual functioning entirely or their medical school was overly enamoured of psychological approaches. And if you've already been referred to a psychiatrist/ psychologist/ counsellor, asking for a referral to a urologist should be a high priority.
    "Courage is what it takes to stand up and speak; courage is also what it takes to sit down and listen." Winston Churchill
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    Yes, we have learned ridiculous amounts in the last 100 years, and now there is so much information it is difficult for any mere human to keep track of everything. The utility of a doctor is simply that they know where to look. They know generally what to expect, and they know how to investigate further if there appears to be a problem. The downside is that they are only human. That's why new developments like computer assisted diagnosis of medical imagining are so exciting.
    "The only appropriate attitude for man to have about the big questions is... doubt. Doubt is humble, and that's what man needs to be, considering that human history is just a litany of getting sh*t dead wrong."

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    Quote Originally Posted by JoshuaL View Post
    Quote Originally Posted by Amaranth View Post
    but there are reports of sexual dysfunction and even persistent sexual dysfunction (that doctors of course think are psychological)
    I am very sad to report that doctors are usually not scientists. A truly excellent doctor will keep up with the literature so they know what the hell they're talking about, but in general, my previous statement says it all. However, doctors know a lot more than most of us and they are typically good at spotting problems, so please don't stop going to your doctor. If you are very concerned about something, you can always get a second opinion from another doctor.
    They say a rat study isn't enough to prove the drug wrong.
    Yes, this technically is true. Even though the study provides a likely explanation, we can't know for sure if the same mechanism is happening in humans. Even if the end result is the same (sexual dysfunction) the actual mechanism by which it happens could be different. There has been plenty of new research since that article was published (about 10 years ago) and I'm pretty sure if a doctor has read up thoroughly on this drug, they would not declare the sexual dysfunction to be psychological. Cases in point: [1][2][3][4] and very nice summary [5].
    http://www.ncbi.nlm.nih.gov/pubmed/17655657
    A
    nd then there's this. Yes, there are many men who SAY they have persistent side effects (many among finasteride users and many among normal people with psychological issues).
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    Yep. Happens in any drug trial though. Nothing special about finasteride!
    "The only appropriate attitude for man to have about the big questions is... doubt. Doubt is humble, and that's what man needs to be, considering that human history is just a litany of getting sh*t dead wrong."

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  23. #22  
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    http://onlinelibrary.wiley.com/doi/10.1111/j.1743-6109.2012.02846.x/abstract
    A
    nd when all the 54 men in the study you pointed out went to a doctor, the doctors will say it is psychological and they have depression. Even the pharmacology professor in my school told that the nocebo and placebo effects are becoming more and more prevalent as time goes on. The internet is full of scary information and conspiracy theories.
    Psy-World - Arizona Sexual Experience Scale -- the questionnaire used to evaluate their sexual dysfunction has aspects very affected by anxiety.
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    Quote Originally Posted by Amaranth View Post
    The internet is full of scary information and conspiracy theories.
    Yup.
    "The only appropriate attitude for man to have about the big questions is... doubt. Doubt is humble, and that's what man needs to be, considering that human history is just a litany of getting sh*t dead wrong."

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    And this thread now contributes to it .
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