Message Number: FHL4527 | New FHL Archives Search

From: Sukie Crandall
Date: 2008-04-08 17:26:18 UTC
Subject: [ferrethealth] Re: Melatonin Implants-Your Opinion
To: fhl <ferrethealth@yahoogroups.com>

Added melatonin may not be the best potential preventative of adrenal
disease. Other things have more promise, though melatonin may also be
useful and should not be ignored by anyone just because it is not
perfect.

Suprelorin/deslorelin depot may wind up being very useful and it has a
long effect in the body but in the U.S. the needed depot version for
ferrets has not yet been approved -- though the process to get it
approved began something like 3 (?) years ago meaning that maybe
(hopefully) it will happen soon. There is a large and life-span long
study on this use for ferrets happening in Europe. See the work of
Dr. Nico Shoemaker especially, and Dr. Bob Wagner has some excellent
work on that compound here in the U.S.

A related compound which is also a GnRH agonist but with a much
shorter term effect and higher current cost, Lupron/Prostap/
Leuprorelin/leuprolide depot, has been studied in the Northwest U.S.
in a small and shorter term study for prevention, and luckily that
study is expanding to include more animals and more locations. It may
be that in areas with more light that the use of this class of
medications needs to be approached differently. Most of the published
work on this compound has been done by Dr. Cathy Delaney-Johnson, but
also search for the work by Dr. Bob Wagner.

At least one other related compound has also been under study (Dr. Bob
Wagner) for treatment though not for prevention as far as i know. In
humans that one (Trelstar) appears to have a stronger effect on
androgen reduction so it being considered to see if it might help any
more with some specific difficult situations.

Notice that these are depots meaning that the medication releases
gradually over time.

A new study has been begun which -- if it meets hopes -- could be
wonderful, and that is to develop a vaccine that would hopefully
prevent the cycle that leads to adrenal tumors right at the
gonadotropin-releasing hormone (GnRH) level. Doctors Bob Wagner and
Mark Finkler are involved in that work.

I think that Dr. Bob Wagner might be among the speakers at the
November IFC Symposium in PA. See
http://www.ferretcongress.org/
to learn how to attend or help.

Melatonin (especially the implants, Ferretonin), and meds like Lupron
and Suprelorlin are approaches which have all been also used in
treatment of adrenal disease, and it is often -- but not always --
recommended that when a non-surgical route is used that melatonin be
used in conjunction with either Lupron or Suprelorlin. Melatonin by
itself appears to have the least effect on the tumors themselves of
the options in carefully designed studies, but is more useful in
combination.

Two good places to learn more about melatonin:
http://www.miamiferret.org/fhc/
and
http://ferrethealth.org/archive/
(just skim down the results and pull out the ones from vets on your
first reading, ro search for names mentioned in this non-vet post)

Melatonin is a very old hormone with a great many functions in the
body, but like anything else it has things it does wonderfully, things
for which it is best as a supporting player, and other things for
which it is weak or useless, even perhaps some things for which added
melatonin is bad.

There is no such thing as cure-all or prevent-all. The single best
thing in existing studies (a huge number of them in many species) on
that score may well be exercise, yet we all know that exercise has its
limitations and even times and situations when it or variations of it
are best avoided.

One thing for which melatonin is not often used but can be very useful
is helping those ferret who lose fur for causes other than adrenal
disease. People think of it in relation to fur regrowth when there is
fur loss from adrenal disease but not when there is fur loss from
other things yet it can be useful in addition to having the vet treat
the cause behind the fur loss. I do NOT know when it is counter-
indicated so ask your vet about that, of course, but some other causes
of fur loss can be allergies, bacterial dermatitis, bacterial
dermatitis secondary to allergy, parasites, mechanical abrasion, and
more. Adrenal disease is the most common cause of fur loss here in
the U.S. where we are careful about external parasite control but have
neutered ferrets who wind up without a lot of darkness and where our
genetic lines may be too narrowed down in vulnerable ways, but adrenal
disease is not alone as a cause of fur loss. Our Hilbert has
allergies, including some pollen ones and in bad years he will lose
fur and get horrid skins sores from a combination of allergic reaction
and secondary bacterial dermatitis. Each time he gets a TN Panel just
in case -- and I wonder if he holds the record for having the most TN
Panels without adrenal disease ever having been present -- as well as
scrapings, skin biopsies or both, and is treated for the found
cause(s). He needs a TN Panel frequent-flier option... We have found
that including a melatonin implant in his treatment helps him greatly
and he is more comfy once the fur regrows.

Now, you may wonder why a melatonin implant would help when there is
not adrenal disease. It is because one of the *many* parts of the
body on which melatonin also has direct action in ferrets is the hair/
fur follicle:

BEGIN QUOTE

J Histochem Cytochem. 1996 Apr;44(4):377-87. Links
Transforming growth factor-alpha immunoreactivity during induced hair
follicle growth cycles in sheep and ferrets.

Nixon AJ,
Broad L,
Saywell DP,
Pearson AJ.
AgResearch, Ruakura Research Centre, Hamilton, New Zealand.
Transforming growth factor-alpha (TGF-alpha) has been associated with
cell proliferation of keratinocytes and implicated in hair growth. We
therefore examined changes in the immunocytochemical localization of
TGF-alpha and cell proliferation markers in the skin of two unrelated
species in which hair cycles could be induced, to elucidate the role
of this
growth factor in the control of fiber growth. Skin was collected from
melatonin-treated ferrets (Mustela putorius furo), untreated Romney
sheep (Ovis aries), and New Zealand Wiltshire sheep in which
interruption
of wool growth had been photoperiodically induced. Immunostaining
patterns were very similar in ferrets and sheep. TGF-alpha
immunoreactivity was observed in epithelial tissues of the skin but was
not co-localized with cell proliferation markers. In anagen follicles,
specific
staining was most intense in the innermost cells of the outer root
sheath
and cortical cells in the keratogenous zone but was absent from inner
root
sheath or dermal papilla. TGF-alpha immunostaining diminished during
catagen, although faint staining was retained in all epithelial cells.
In
telogen and early proanagen follicles, staining remained faint or was
restricted to cells on the margin of the brush end and follicle neck.
Immunoreactivity in the outer root sheath was reestablished in late
proanagen. Sebaceous glands and epidermis were stained intensely
throughout the hair cycle. TGF-alpha-immunoreactive components of skin
extracts, analyzed by Western blotting, showed mobility corresponding to
approximately 32 KD, but not to the size of the fully cleaved peptide.
These
results are consistent with an epithelial autocrine or juxtacrine, but
not a
mitogenic, function of TGF-alpha.
PMID: 8601697 [PubMed - indexed for MEDLINE]

END QUOTE

Still, there are no cure-alls and some things which are good for some
bodily functions can be bad in other ways. You already know this
about estrogen which is a very old hormone that all of us (of any
gender) have in our bodies. It performs hundreds of useful functions
( even being involved in some brain functions) and the body can switch
both the estrogens and androgens (also in all of us) back and forth to
each other. The very similar (but thought to possibly be younger)
androgens (like testosterone) perform at least dozens of found useful
functions (including helping have very healthy levels of
muscularity). Still, as everyone knows there can be ways and times
and places in the body where too much of some types of estrogen or
androgen can be risk factors.

So, it is important to realize that may also be the case for melatonin
-- in specific situations.

One possibility on that score might be certain, specific cases of
insulinoma (but not necessarily insulinoma in general). Insulinoma is
a medical disorder seen rather often in ferrets in some locations (and
that may partly relate to genetic vulnerabilities which are under
study) for which very, very little is actually known. Some diabetes
studies point to some places to look: diet (some of this hypothetical
-- i.e. speculation -- still even for diabetes but easy to do to be
safest), levels of exercise (diabetes only studied), neural
alterations (some exciting new work from last year done in Canada and
the U.S. if my memory serves on diabetes which still needs independent
verification), and how beta cells develop (a still-to-be-independently-
verified study which can be found in PLoS if I recall right
indicates that it appears that a number of them develop at the same
time in waves -- which may help explain why insulinoma can be seeded
in many locations in the pancreas), etc. There is a lot more that is
not known than is known about insulinoma. Some people are beginning
to wonder what pancreatic functions may involve melatonin -- and that
is still an area in its infancy -- but there may be functions -- which
may at least sometimes be opposing ones -- that involve melatonin.
That might explain why some clinicians have found some ferrets with
insulinoma to be helped by melatonin while others have found some
other ferrets whose insulinoma worsened when melatonin was given, and
others say they see no difference. We simply don't know enough about
melatonin's actions in the pancreas and definitely don't know enough
about insulinoma to easily tell apart how it will affect the
situation when insulinoma is present or even if factors other than the
melatonin affected the situations yet -- which might mean that the
oral version in a trial may be best to see the effect before trying
melatonin *if insulinoma is present* before trying an implant for any
given individual.


Sukie (not a vet)

Recommended ferret health links:
http://pets.groups.yahoo.com/group/ferrethealth/
http://ferrethealth.org/archive/
http://www.afip.org/ferrets/index.html
http://www.miamiferret.org/fhc/
http://www.ferretcongress.org/
http://www.trifl.org/index.shtml
http://homepage.mac.com/sukie/sukiesferretlinks.html




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