Repost: Thalidomide, Melatonin, DHEA, TNF, and IL-2

Charles P. McCarthy pandoc at ix.netcom.com
Fri Nov 15 01:33:16 EST 1996


James Howard wrote:
[edit]
> My work suggests melatonin and DHEA act together in a cycle that is
> necessary for proper growth, development, and maintenance of all tissues.
> This material about melatonin and these cytokines further supports my
> theory of AIDS.  This all means that, in AIDS, as in aging, the melatonin -
> DHEA cycle has shut down.

In HIV infection and AIDS numerous metabolic cycles are affected.  
Gastric acid production by parietal cells is probably one of the 
earliest.  This and many factors contribute to the phenomenon of 
wasting and interfere with the growth and maintenance of host 
tissues.

All of the pathologically aberrant processes attending infection 
by HIV stem from the activity of the viral glycoprotein gp120 
that is secreted by infected host cells.  AIDS is the sequelae of 
this infection.

Increases in Gp120 and gp120/immune complex serum levels during 
the course of the disease in children and adults, the effects of 
gp120 on neural cells and the differentiation of CD34+ lymphoid 
progenitor cells and thymocytes, and on aberrant activation and 
cytokine secretion patterns of mature T cells, induction of 
apoptosis, B-cell hyperactivity, inhibition of T-cell dependent 
B-cell differentiation, modulation of macrophage functions, 
interactions with components of complement, production of anergy 
through molecular mimicry, and the requirement of this viral 
glycoprotein for cell entry, all point to gp120 as a primary 
pathogenic determinant.

If a bell-shaped curve represents average population serum 
concentrations of a small, natural, immunomodulating metabolite, 
like 7-hydroxycoumarin, 0-hydroxycinnamic acid, or the small 
hydroxylated aromatic acids, competition for common affinity 
sites with gp120 would explain a small group of longterm 
survivors, a small group of rapid progressors, and large group 
in between.

Although serum half-life for 7-hydroxycoumarin is extremely short,
this type of molecule inhibits HIV greater than 50% in vitro.  
I am currently screening compounds for longer half-life and higher 
activity that may be tolerated at higher doses.  

Therapies designed to support host tissues and metabolic 
processes may be limited in their approach by temporarily 
improving the generalized condition of the host without directly 
affecting the site of intimate contact between gp120 and host 
tissues. This may prove useful in extending survival, however, it
may also drastically shorten survival if it enhances conditions
for increased production and secretion of gp120.

A good analogy would be taking a shot of whiskey, a healthfood
shake, and anti-venom while a rattlesnake is still attached to 
your leg.  The whiskey will be beneficial.  In the case of HIV 
and gp120, it is a rattlesnake with an inexhaustible supply of 
venom.  

You can pump up your patient with all the nutrition and hormones
you like.  The question of outliving the snake is moot.  What is 
not open to argument is the painful reality of the loneliness of
the person to whom the snake is attached.

"Get thee behind me... "
          "Give a dying man strong drink... "

Good luck and good hunting,

Charlie

Charles P. McCarthy, Clinical Specialist
Healthcare Consulting and
  Medical Research
Carmichael, CA USA



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