Talk:Hormesis

Starting article on "hormesis"

Encouraging collaboration.

Hoping this is a reasonable approach

One of the first thing that hormesis brings to mind is type-0 and type-1 pharmacokinetics, especially drug (or toxin) clearance. Obviously simplified, zero-order kinetics has a basic model that the excretion process has infinite capacity, while first-order kinetics has a saturation point. More precisely, zero-order kinetics asssume a constant absolute rate of clearance, while first-order clearance assumes a constant fraction of the total body concentraion over time.

Such effects are at the high-end range of dose-effect mechanisms.

At a low end -- thinking of infection rather than drugs -- in biohazard mitigation and biological warfare work, there is a well-established "minimum infective concentration" (often expressed as the 50th percentile). Tularemia, for example, can establish disease with only a few cells, where more dangerous agents require a considerably larger concenntration.

Howard C. Berkowitz 12:32, 1 October 2008 (CDT)

Interesting, Howard. Will give this some thought, and check 'hormesis' references to see if anyone touches on the subject.--Anthony.Sebastian 16:51, 12 October 2008 (UTC)

Michaelis-Menten work relevant here?

Is this an area that should be in this discussion? Howard C. Berkowitz 13:08, 1 October 2008 (CDT)

Howard, how would you approach this? Would Briggs-Haldane kinetics serve better? Hope you will elaborate. --Anthony.Sebastian 16:51, 12 October 2008 (UTC)

I've worked less with Briggs-Haldane, but isn't there a significant range in which they both apply? [1]? Briggs-Haldane appears to be an extension. When talking about the general issues of hormesis, is the difference really significant, or could many hormetic effects be explained by competitive inhibition of enough receptors to block the present effect of some toxic substance at constant concentration? (see note below about another possible mechanism)

Let me answer directly, and also a little indirectly. Michaelis-Menten is about competitive inhibition. Assume chemical X is a toxin, even naturally produced. Further, there are cellular X-receptors, and there is a minimum trigger number of X-receptors that will cause an undesirable effect.

If chemical Y competes for X-receptors, and the quantity of X does not increase, the physiological effect of X is blocked. Receptor blocking (or interfering in the pathway that creates the substance for which the receptor is sensitized) is common to many effective drugs.

By receptor blocking, there actually are a number of places that the hormetic substance could work, such as being a presynaptic reuptake agonist or antagonist.

Pathway up/downregulation

A slightly different but not completely unrelated issue: could a hormetic dose of Z still be sufficient to activate or suppress an excretion pathway, such as one of the cytochrome P240 variants