On 11/24/2008 12:34 AM, Paul Wakfer wrote:
> On 11/13/2008 01:19 PM, Dave Brett wrote:
>
>> I found this recent study of canines treated for hypertension.
>> http://circ.ahajournals.org/cgi/content/full/118/10/1002
>>
>> The authors comment, in the Clinical Perspective, "Thus, aortic size
>> should be monitored carefully in clinical trials of these agents."
>>
>> The comment was in view of their findings that "A highly significant
>> effect of ALT to increase aortic dimension was observed. This
>> occurred despite lower BP over the course of the model and was
>> independent of distending pressure or body size".
>>
>> I wonder if this is a significant cause for concern in those of us
>> taking ALT-711 on a chronic basis and would be interested to read any
>> comments.
>
> Unfortunately, the link above goes only to a page that requires a US$20
> payment in order to access the full text of the paper and the abstract
> does not say anything related to your remarks above. In addition, my
> university access does not have that journal available. Without reading
> the full text any reasoned opinion about what you ask is impossible, but
> it seems to me if it were viewed as really important it would have been
> mentioned in the abstract. If you have the full text (pdf) and could
> send it to me by email attachment then I would be happy read it and
> comment further.

I was just sent (and have now read) the full text - thanks Larry.
I now realize that the "aortic dilation" *was* mentioned in the
abstract, but in such a way that my too quick reading did not
distinguish that result from increased aortic distensibility at systole
(the systolic - high - pressure point). In analysis of this somewhat
concerning apparent dilation of the aorta, not related to blood
pressure, I would suggest that perhaps the fairly short duration of the
experiment (only 8 weeks) was not sufficient time for the aorta to
remodel its wall structure to a younger composition and strength after
so abruptly being jolted into change by the administration of ALT-711.
This may be similar to the report by some people that use of ALT-711 has
made their knee joints more flexible, but also more "loose". I think this
is likely a result of taking too much ALT-711 too early and not giving
sufficient time for the knee ligaments and other structural components
to remodel themselves.

BTW, one other very important point brought out by this study is that
CML (N{epsilon}-(carboxymethyl)lysine), which is the standard measure
of the presence and amount of AGEs (but is not itself a crosslink AGE),
may not be a very good measure of all AGEs present.

--Paul