X-Message-Number: 15122
Date: Sun, 17 Dec 2000 21:50:00 +0000
From: Phil Rhoades <>
Subject: Brain lipofuscin concentrations

Ben,

>Message #15119
>Date: Sat, 16 Dec 2000 07:26:50 -0500 (EST)
>From: Ben Best <>
>Subject: Re: An assist to CPAs and Ice-Blockers (Erratum)
>
>On Sat, 16 Dec 2000, Ben Best wrote:
>
> >    CryoProtective Agents (CPAs) and Ice-Blockers can prevent
> > ice-formation and promote vitrification. But Ice-Blockers
> > typically do not cross cell membranes. And CPAs are always
> > challenging to perfuse/diffuse because both their toxicity and
> > viscosity vary inversely with temperature.
>
>     In my efforts at pompous simplicity, I misstated the
>facts. CPA viscosity does vary inversely with temperature
>-- so that the lower the temperature of introduction, the
>more difficult it is to get the stuff to perfuse through
>blood vessels and diffuse into cells. However, CPA toxicity
>tends to vary DIRECTLY (not inversely) with temperature
>-- meaning that it is much less toxic when introduced at
>lower temperatures. Therein lies the trade-off: how to
>introduce the CPAs at a high enough temperature to
>minimize viscosity, but at a low enough temperature
>to minimize toxicity.
>
>    Also, by the time genetic engineering is sophisticated
>enough to modify genes so as to manufacture the "designer"
>insulin-receptor of my fantasy, genetic engineering should
>also be able to add genes for production of ice-blocker
>proteins in the cells of mammals. If these proteins are
>innocuous enough, they could be present at all times in
>the cell without much harm. After all, if cells can
>function adequately with large amounts of lipofuscin,

There is a group of inherited human disorders (and their equivalents in 
other animals) collectively called Batten's Disease that arise out of 
mutational defects in the removal/processing of lipofuscin - this causes 
very nasty terminal neuronal diseases in infants to adolescents.  It is 
true that lipofuscin does accumulate in older people but I would be careful 
about saying that people can "function adequately with large amounts of 
lipofuscin".

>they should be able to tolerate some otherwise non-functional
>ice-blocker proteins -- which don't need to be present in
>high quantities to be effective. This is an advantage over
>my proposed insulin receptor in that there is no time-critical
>procedure to be applied in a cryonics emergency -- although
>it is still time-critical that cooling occur rapidly after
>deanimation.
>                                   -- Ben

Phil.


-
Philip Rhoades

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