Fhl

From: AFERRETVET@cs.com
Date: 2010-04-07 00:30:04 UTC
Subject: [ferrethealth] Digest Number 1836
To: ferrethealth@yahoogroups.com

Hi Stephanie,
Yes, there is a GnRH vaccine (Adrenal vaccine) that is being used to hopefu=
lly prevent adrenal gland disease.
The lead investigator is Dr Robert Wagner from the U of Pitt. Dr Mark Finkl=
er (Va Tech) and I (in Dallas) are also
involved in the clinical trial. Dr Wagner has been using the vaccine for 4+=
years now, and it appears to be very safe.
There will be a presentation at the AFA ferret conference in May on use of =
this vaccine, but so far all good news.
Hope that helps,
Jerry Murray, DVM

-----Original Message-----
From: ferrethealth@yahoogroups.com
To: ferrethealth@yahoogroups.com
Sent: Mon, Apr 5, 2010 7:26 am

There are 9 messages in this issue.
Topics in this digest:
1a. Re: personal ferret emergency: Hilbert post-op=20=20=20
From: sukiedaviscrandall
2. Ferret reacting badly to Diazoxide & stevia and insulinoma Q=20=20=20
From: Ulrike
3a. Re: Ferret dribbling urine after adrenal surgery=20=20=20
From: Barbara Wiborg
b. Re: Ferret dribbling urine after adrenal surgery=20=20=20
From: Tressie
c. Re: Ferret dribbling urine after adrenal surgery=20=20=20
From: Tressie
4a. Ferret weightloss and hair loss=20=20=20
From: micky6608
b. Re: Ferret weightloss and hair loss=20=20=20
From: micky6608
5. GnRH Vaccine?=20=20=20
From: aleu101002
6. beta cells arising from Alpha cells instead of from stem cells =

From: Sukie Crandall

essages
_______________________________________________________________________
a. Re: personal ferret emergency: Hilbert post-op
Posted by: "sukiedaviscrandall" sukie@mac.com sukiedaviscrandall
Date: Sun Apr 4, 2010 10:53 am ((PDT))

ilbert is home but there is a new concern, too, now.
First: the good news is that his kidney values are back to normal.
hat is major good news.
The bad news is multifold:
1. There is now a cloudiness in his mediastinum and the cranial
ediastinum is enlarged so there are several possibilities
ith hypertrophic cardiomyopathy one of the things that absolutely
ave to be ruled out when this is compared to earlier x-rays.
ypertrophic is the form that that can be hidden well. So, he will
e having a chest ultrasound in his near future.
2. He is at risk for vascilating between high and low blood glucose
o a crash could be either of those. He's hard to get blood from.=20
ail is worthless in his case, paw rarely useful. We'll be trying
is ear next, and will be trying syringe needles for getting it. He does
ot bleed easily but he does clot easily. The chances are greater at
his point for low blood glucose. So, since he over-responded to meds
teve and I will sleep shifts for frequent small meals...
3. BUT he had the acute kidney episode, past kidney problems, and
e is genetically prone to cystine stones so we have to be careful to
ot overdo the protein during those meals which means also
ncouraging him to eat kibbles at those times and that can be harder,
4. AND we are increasing his Fludrocort to make sure of no Addisons
hile he is under so much stress. (His adrenals had come out
s a preventative measure when he was very young because they were
o inflamed by being rubbed by huge kidneys when he had hydronephrosis
ack then due to the cystine stones and a bladder malformation.)
We are also:
1. Adding Carafate once a day. Yes, we know about timing.
2. Giving two antibiotics
He does have mild neural crest genetic variant markings. Neural Crest
enetic variants do increase the chances of cardiomyopathy, especially
ypertrophic cardiomyopathy in multiple species.
For those who have not read earlier, he is 7 years old.=20
We have another terminal ferret, too, Mornie, who has carcinoma but is
o far doing well despite it.

essages in this topic (8)
_______________________________________________________________________
_______________________________________________________________________
. Ferret reacting badly to Diazoxide & stevia and insulinoma Q
Posted by: "Ulrike" ferretlove.uk@googlemail.com ferrets4ever_uk
Date: Sun Apr 4, 2010 11:12 am ((PDT))
I am writing about my friend again. His ferret Willie has insulinoma
nd seems to be reacting badly to the Diazoxide. My friend had
ifferent batches done, the last one was done with Ora-Sweet SF and
ra-Plus (I think) and when he got the Diazoxide after food, Willie's
yes would inmediately dim, half closed, and he'd shiver. My friend
ust had another batch done without sweetener, just plain Diazoxide
ith a suspending agent, water and that's it and now Willie reacts by
obbing his heand back and forth and salivating which I know sounds
ike a low blood glucose but it seems to happen straight after the
iazoxide and stops when he goes to sleep. Could it be that Willie is
ot reacting to something that is used to make the suspension but to
he Diazoxide itself? Has anybody else had these reactions to
iazoxide? Willie still eats fine and has no problem with nausea.
Another question I have is about stevia. The compounding pharmacy
aid they could use stevia in the suspension and I was wondering if it
s okay to use stevia in medications for ferrets with insulinoma as my
riend read on Wikipedia
ttp://en.wikipedia.org/wiki/Stevia
hat some studies have shown stevia to improve insulin sensitivity in
ats and possibly even to promote additional insulin production.
Ulrike
[There is some research which indicates that stevia
ay drop blood glucose and should be avoided with
ny pancreatic problems.
See:
http://www.webmd.com/vitamins-supplements/ingredientmono-682-STEVIA.aspx?ac=
tiveIngredientId=3D682&activeIngredientName=3DSTEVIA&source=3D2>
<http://www.ncbi.nlm.nih.gov/pubmed/20303371>
indicates that it can reduce both blood glucose and
nsulin levels, so all that you need is to have EITHER
f those shift too much in relation to the other and there
s trouble.
That is the most recent study mentioning such effects.
n
ttp://www.ncbi.nlm.nih.gov/sites/entrez
8 study abstracts come up for the search terms
tevia glucose
sed for a search.
It sounds like it possibly could cause a crash in EITHER direction.
--Moderator]

Messages in this topic (1)
_______________________________________________________________________
_______________________________________________________________________
a. Re: Ferret dribbling urine after adrenal surgery
Posted by: "Barbara Wiborg" weaselwardancers@msn.com westonkagirl
Date: Sun Apr 4, 2010 11:13 am ((PDT))
My ferret Yogi did that when he had adrenal cancer. He didn't have surgery=
tho.=20
was told it was probably due to an enlarged prostate that was pushing on h=
is
ladder. I had to isolate him to the kitchen where there was tile flooring =
so
t was easier to see to clean up. He had the ferretonin implants for a year=

ince he was too old for the surgery. He also had insulinoma which may also=
be
cause of the dribbling. Not sure tho.=20

Messages in this topic (6)
_______________________________________________________________________
b. Re: Ferret dribbling urine after adrenal surgery
Posted by: "Tressie" tressiedu@hotmail.com tressiedook
Date: Sun Apr 4, 2010 11:13 am ((PDT))
Hi xxxxxxx,
>From 'Ferret Urogenital Diseases, CJ Orcutt, 2003, p. 124':
Once a urine sample has been submitted for bacterial culture
nd antimicrobial sensitivity testing, broad-spectrum antibiotic treatment
hould be initiated pending test results. The preferred antibiotic is one th=
at
aintains eff

This message arrived truncated, but the meaning may be clear enough.
-Moderator]

essages in this topic (6)
_______________________________________________________________________
c. Re: Ferret dribbling urine after adrenal surgery
Posted by: "Tressie" tressiedu@hotmail.com tressiedook
Date: Sun Apr 4, 2010 2:31 pm ((PDT))

previewed it before sending this time, not sure what the problem was, but =
I
elieve it should now arrive in its entirety:
Here is the entire excerpt:
A CBC and serum biochemical analysis should be evaluated for signs of
yelonephritis. Once a urine sample has been submitted for bacterial culture=
and
ntimicrobial sensitivity testing, broad-spectrum antibiotic treatment shoul=
d be
nitiated pending test results. The preferred antibiotic is one that maintai=
ns
ffective concentrations in the urinary tract, and drugs suitable for
se in dogs or cats can be used in ferrets on a per kilogram basis. Choices =
for
mpirical treatment pending culture results include amoxicillin/clavulinic
cid (12.5 mg/kg orally every 12 hours), trimethoprim sulfa (30 mg/kg orally=

very 12 hours), or enrofloxacin (10 mg/kg orally every 12 hours) [20]. Anti=
-
iotic therapy should be continued for at least 3 weeks then discontinued fo=
r
=E2=80=937 days prior to repeating the urine culture.
--- In ferrethealth@yahoogroups.com, "Tressie" <tressiedu@...> wrote:

Hi xxxxxxx,

From 'Ferret Urogenital Diseases, CJ Orcutt, 2003, p. 124':

Once a urine sample has been submitted for bacterial culture
and antimicrobial sensitivity testing, broad-spectrum antibiotic treatment=

hould be initiated pending test results. The preferred antibiotic is one th=
at
aintains eff

[This message arrived truncated, but the meaning may be clear enough.
--Moderator]

Messages in this topic (6)
_______________________________________________________________________
_______________________________________________________________________
a. Ferret weightloss and hair loss
Posted by: "micky6608" micky6608@yahoo.com micky6608
Date: Sun Apr 4, 2010 11:29 am ((PDT))
My ferret Riley is 3.5 yrs old. in the last month he has lost hair. Norm=
ally
n the winter he weighs almost 4 pounds. he didnt gain weight this winter=
and
ow he is very skinny. His bones by his back legs feel like they are poking =
out.
took him to the vet and she did a skin scrape to check for mites and she d=
idnt
ind any he dosent have fleas. She gave him a cortizone shot put some mite f=
lea
epellant on him and put him on antibiotics for 10 days. She wanted to try t=
hat
o see if that would help. He is suppose to go back in ten days for a check =
up.
e has been on the med for 5 days and hes not getting better. Im going to ca=
ll
er monday and tell her to do the blood test for adrenal disease. Does this=

ound like adrenal disease? He is fed 8n1 kibble but his main food is gerber=

aby food (chicken) 1/2 jar in the morning and 1/2 jar at night. I also have=
2
irl ferrets one is 3 yrs and the other is about 5 months. They are both fat=
and
ealthy. Any advise?

When I read my note I realize that I replied as if there is
ur loss. Is there? Is that why the vet checked for fleas?
id the vet check for fleas for another reason such as anemia?
es, many things can cause anemia. Even the wrong amounts
f certain minerals and vitamins (such as too much C (megadoses)
r too little copper, if memory serves) can cause iron to not be
rocessed normally, resulting in iron deficiency anemia even if the
iet has enough iron.=20
On that diet IF IT HAS BEEN LONG TERM he could also be
uffering mineral deficiencies, and some of those also can
ause fur/hair loss. If there is fur loss or another adrenal
ymptom then adrenal disease is among the possibilities,
ut so is malnutrition, and certain a malignancy could be
mong the possibilities with the weight loss. A knowledgeable
et will look for all so be frank with the vet about the diet.
emember, too, that we are in a natural shedding season right
ow. (Comb ferrets to remove excess fur, please, and to
void a possible stomach or intestinal blockage from fur.)
Please, if this is the standard diet used long term, reduce the
abyfood and add more of any of the quality kibbles, or
therwise find a way to provide a balanced diet. Meat alone is
ot balanced, being very low in many nutrients, especially a
ange of minerals. Organs are better for some minerals (like
iver for more copper) but organs and meats alone also do
ot provide a balanced diet for long term use. For one thing
calcium source is needed.
Fat is not a health sign, but muscularity is.
--Moderator.]

essages in this topic (2)
_______________________________________________________________________
b. Re: Ferret weightloss and hair loss
Posted by: "micky6608" micky6608@yahoo.com micky6608
Date: Sun Apr 4, 2010 7:33 pm ((PDT))

i thank you for the reply. Yes there is hair loss up his back and on his ta=
il.
s far as his diet he has access to his kibble any time. I was told that his=

iet was healthy If I would of known It wasnt I wouldnt have been spending =
the
xtra money for the babyfood. I will defanatley change that.
Anyways the vet checked him for fleas because In the fall I found a flea o=
n him
nd he was itching so I give him a flea bath with kitten flea shampoo that w=
as
ecomended to me on a ferret forrum and I thought maybe that could have been=
the
roblem an alergic reaction from a flea bite.
The vet told me that itching and hairloss on the back were not typical sign=
s of
drenal disease. Well the more I have read itching and hair loss on the back=
and
ail are typical and with weight loss He has all the signs Im just not confi=
dent
n this vet anymore.
I found an exotic pet near me that only deals with small animals and ferret=
s
ere on their list.
Im also going to call a ferret rescue near me and see if they can refer me =
to
ome one.
I have read that adrenal disease is from an over production of cortizone an=
d
strogen.
[Ferrets don't typically have the cortical steroid type of
isease that most mammals get; instead their adrenal
isease is just hormonal. See expert resources such as
ttp://www.afip.org/consultation/vetpath/ferrets/aae.html
-Moderator]
Do you think the cortizone shot made his symtoms worse because I swear he h=
as
ost alot of muscle mass in his hind legs Its only been 5 days.
Another question should I keep giving him the antibiotics ( .25 evry 12 hrs=
)?
Is there anything I can do for him until I get him in he seems so tired.
Is this as urgent as I feel it is? I dont want to wait another minute
This little guy is like one of my kids. I have 2 girl ferrets that are heal=
thy
s can be. But hes my first one Im so attached. These will be the last becau=
se I
ant handle the loss I didnt even want one of these things I got him for my =
son.
omething about them steals your heart its devastating to me my friends and=

amily think im nuts but they have no clue. Im not this attached to the dogs=
Ive
ad for 12 yrs. sorry for rambling...lol any more advice you have Id be happ=
y to
ear and thatnks again for the reply
[With muscle loss that rapid and weight loss, too, I'm
ith you about getting expert care rapidly.=20
No, the shot likely had nothing to do with this.=20
Since the flea bath was in Autumn that also probably
orked out okay, but be warned that some of those are
angerous for ferrets, and some over the counter flea
eds can destroy ferret bone marrow and more.
Here are some other places to check into ferret vets:
ttp://ferrethealth.org/vets/
hich can be reached from BOTH the FHL Files section
nd the FHL Links section, and
ttp://www.ferret-universe.com/vets/vetlist.asp
--Moderator]

essages in this topic (2)
_______________________________________________________________________
_______________________________________________________________________
. GnRH Vaccine?
Posted by: "aleu101002" Aleu1010@MSN.com aleu101002
Date: Sun Apr 4, 2010 7:22 pm ((PDT))
Hello my name is Stephanie, and I was directed here by another ferret forum=
with
he hopes that I could find some help and good advice here.
have two ferrets, Twilight (3 years) and Sora (7 months), who both see Dr.=
X.
ecently Dr. X was telling me about a study being done on ferrets to see if =
a
ew vaccination could help to prevent adrenal in ferrets.
he idea of my ferrets being less likely to get adrenal in their older age i=
s
ppealing for obvious reasons, but I'm having a hard time finding more
nformation on these shots.
'm basically trying to find out how safe it really is, and if it's worth th=
e
isk. Any help would be very much appreciated.
apologize if I missed anything already posted- I couldn't find anything wi=
th a
asic search through past messages, and I had a heck of a time using the arc=
hive
I don't believe I got any results, but I might have been using it incorrect=
ly).
hank you,
tephanie
[Hospital and vet names removed according to the
HL rules. Names can be mentioned in relation to
hings like study abstracts but not in relation to
ases. The FHL Rules are in the Files section of the
ebsite.
There is a study underway by Doctors Mark Finkler
nd Robert Wagner to study Gonadotropin Releasing
ormone vaccines. This is still a new area of study
nd they are the experts for current performance and
afety.
--Moderator]

essages in this topic (1)
_______________________________________________________________________
_______________________________________________________________________
. beta cells arising from Alpha cells instead of from stem cells
Posted by: "Sukie Crandall" sukie@mac.com sukiedaviscrandall
Date: Sun Apr 4, 2010 11:01 pm ((PDT))
<http://www.sciencenews.org/view/generic/id/57902/title/Insulin-producing_c=
ells_can_renegerate_in_diabetic_mice
>
Not work in ferrets, but a shift in the data, so if it also applies to=20
errets it may help with future understanding of pancreatic diseases=20
hat affect them.
> Alpha cells in the pancreas can spontaneously transform into insulin-
producing beta cells, researchers from the University of Geneva in=20
Switzerland report online in Nature April 4.
..
The exciting discovery from this study is that alpha cells can=20
spontaneously convert to beta cells without any interference...
> it opens up the idea that reprogramming is not just something we=20
have to force cells to do, that it=E2=80=99s an intrinsic property of the =

cells...
> some of the insulin-producing cells also made glucagon, which is=20
normally made by alpha cells...
In the mice that creation required most beta cells to first be killed=20
ff, but I wonder if anyone has considered looking at it from the=20
pposite vantage point, to see if insulinomae also contain cells that=20
roduce glucagon in any species because if so that could point to a=20
enetic component, or if to a trigger component then it could allow=20
etter formation of hypotheses about mechanisms.
Okay, yes, they have and guess what they found:
http://www.ncbi.nlm.nih.gov/pubmed/20138042
> Gastroenterology. 2010 Feb 2. [Epub ahead of print]
alpha Cell-Specific Men1 Ablation Triggers the Transdifferentiation=20
of Glucagon-Expressing Cells and Insulinoma Development.
Lu J, Herrera PL, Carreira C, Bonnavion R, Seigne C, Calender A,=20
Bertolino P, Zhang CX.
Laboratoire G=C3=A9n=C3=A9tique Mol=C3=A9culaire, Signalisation et Cancer,=
Centre=20
National de la Recherche Scientifique, UMR5201, Facult=C3=A9 de M=C3=A9dec=
ine,=20
Universit=C3=A9 Claude Bernard Lyon1, Centre LEON-BERARD, Lyon, France.
BACKGROUND & AIMS: The tumor suppressor menin is recognized as a key=20
regulator of pancreatic islet development, proliferation, and beta-
cell function, whereas its role in alpha cells remains poorly=20
understood. The purpose of the current study was to address this=20
issue in relation to islet tumor histogenesis. METHODS: We generated=20
alpha cell-specific Men1 mutant mice with Cre/loxP technology and=20
carried out analyses of pancreatic lesions developed in the mutant=20
mice during aging. RESULTS: We showed that, despite the alpha-cell=20
specificity of the GluCre transgene, both glucagonomas and a large=20
amount of insulinomas developed in mutant mice older than 6 months,=20
accompanied by mixed islet tumors. Interestingly, the cells sharing=20
characteristics of both alpha and beta cells were identified shortly=20
after the appearance of menin-deficient alpha cells but well before=20
the tumor onset. Using a genetic cell lineage tracing analysis, we=20
demonstrated that insulinoma cells were directly derived from=20
transdifferentiating glucagon-expressing cells. Furthermore, our=20
data indicated that the expression of Pdx1, MafA, Pax4, and Ngn3 did=20
not seem to be required for the initiation of this=20
transdifferentiation. CONCLUSIONS: Our work shows cell=20
transdifferentiation as a novel mechanism involved in islet tumor=20
development and provides evidence showing that menin regulates the=20
plasticity of differentiated pancreatic alpha cells in vivo,=20
shedding new light on the mechanisms of islet tumorigenesis.=20
Copyright =C2=A9 2010 AGA Institute. Published by Elsevier Inc. All=20
rights reserved.
PMID: 20138042 [PubMed - as supplied by publisher]
Also interesting in relation to slowed rates of cellular death of such=20
ells:
> Endocrinology. 2010 Mar 10. [Epub ahead of print]
Exendin-4 Prevents c-Jun N-Terminal Protein Kinase Activation by=20
Tumor Necrosis Factor-{alpha} (TNF{alpha}) and Inhibits TNF{alpha}-
Induced Apoptosis in Insulin-Secreting Cells.
Natalicchio A, De Stefano F, Orlando MR, Melchiorre M, Leonardini A,=20
Cignarelli A, Labarbuta R,Marchetti P, Perrini S, Laviola L,=20
Giorgino F.
Department of Emergency and Organ Transplantation (A.N., F.D.S.,=20
M.R.O., M.M., A.L., A.C., R.L., S.P., L.L., F.G.), Section on=20
Internal Medicine, Endocrinology, Andrology, and Metabolic Diseases,=20
University of Bari, I-70124 Bari, Italy; and Endocrinology and=20
Metabolism of Transplantation (P.M.), Azienda Ospedaliera=20
Universitaria Pisa, 56126 Pisa, Italy.
Glucagon-like peptide-1 and its analogs may preserve pancreatic beta-
cell mass by promoting resistance to cytokine-mediated apoptosis.=20
The mechanisms of TNFalpha-induced apoptosis and of its inhibition=20
by exendin-4 were investigated in insulin-secreting cells. INS-1 and=20
MIN6 insulinoma cells were exposed to 20 ng/ml TNFalpha, with or=20
without pretreatment with 10 nM exendin-4. Treatment with TNFalpha=20
increased c-Jun N-terminal protein kinase (JNK) phosphorylation 2-
fold, reduced inhibitor-kappaBalpha (IkappaBalpha) protein content=20
by 50%, induced opposite changes in caspase-3 and Bcl-2 protein=20
content, and increased cellular apoptosis. Moreover, exposure to=20
TNFalpha resulted in increased serine phosphorylation of both=20
insulin receptor substrate (IRS)-1 and IRS-2 and reduced basal and=20
insulin-induced Akt phosphorylation. However, in the presence of a=20
JNK inhibitor, TNFalpha-induced apoptosis was diminished and serine=20
phosphorylation of IRS proteins was prevented. When cells were=20
pretreated with exendin-4, TNFalpha-induced JNK and IRS-1/2 serine=20
phosphorylation was markedly reduced, Akt phosphorylation was=20
increased, caspase-3 and Bcl-2 protein levels were restored to=20
normal, and TNFalpha-induced apoptosis was inhibited by 50%. This=20
was associated with a 2-fold increase in IRS-2 expression levels. A=20
similar ability of exendin-4 to prevent TNFalpha-induced JNK=20
phosphorylation was found in isolated pancreatic human islets. The=20
inhibitory effect of exendin-4 on TNFalpha-induced JNK=20
phosphorylation was abrogated in the presence of the protein kinase=20
A inhibitor H89. In conclusion, JNK activation mediates TNFalpha-
induced apoptosis and impairment of the IRS/Akt signaling pathway in=20
insulin-secreting cells. By inhibiting JNK phosphorylation in a PKA-
dependent manner, exendin-4 counteracts TNFalpha-mediated apoptosis=20
and reverses the inhibitory events in the IRS/Akt pathway, resulting=20
in promotion of cell survival.
PMID: 20219981 [PubMed - as supplied by publisher]
and
http://www.ncbi.nlm.nih.gov/pubmed/20110682
> Cell Physiol Biochem. 2010;25(2-3):211-20. Epub 2010 Jan 12.
Protective role of glucagon-like peptide-1 against glucosamine-
induced cytotoxicity in pancreatic beta cells.
Kim YK, Park JH, Park SH, Lim B, Baek WK, Suh SI, Lim JG, Ryu GR,=20
Song DK.
Department of Physiology & Chronic Disease Research Center, Daegu=20
700-712, Republic of Korea.
High doses of glucosamine have been known to induce apoptosis of=20
pancreatic beta cells. The mechanism for this phenomenon has not=20
been clearly elucidated. We aimed to explore the potential=20
mechanisms for glucosamine toxicity in the rat insulinoma cell line=20
INS-1 and in rat native beta cells. We also investigated whether=20
glucagon-like peptide (GLP)-1 could be protective against=20
glucosamine. Glucosamine exhibited dose-dependent inhibition of cell=20
survival and an increase in the cell population at the sub-G1 phase.=20
Glucosamine was revealed to inhibit cellular glucose uptake,=20
resulting in the activation of AMP-activated protein kinase (AMPK).=20
Accordingly, phosphorylation of P70S6K and ribosomal protein S6=20
(S6RP) was decreased. Protein glycosylation appeared not to be=20
involved in this cytotoxicity. Pretreatment with GLP-1 alleviated=20
glucosamine-mediated inhibition of glucose uptake and lessened AMPK=20
activation, thus allowing recovery of the phosphorylation levels of=20
P70S6K and S6RP. The effect of GLP-1 was blocked by the adenylyl=20
cyclase inhibitor MDL12330A but not by the protein kinase A=20
inhibitor H89. Taken together, these data demonstrate that=20
glucosamine may inhibit beta-cell survival by diminishing cellular=20
glucose uptake independent of glycosylation. This glucosamine=20
toxicity can be blocked by GLP-1, which leads to recovery of the=20
glucose uptake through a PKA-independent, cAMP-dependent mechanism.=20
Copyright 2010 S. Karger AG, Basel.
PMID: 20110682 [PubMed - in process]
and imaging:
http://www.ncbi.nlm.nih.gov/pubmed/20111963
> Eur J Nucl Med Mol Imaging. 2010 Jan 29. [Epub ahead of print]
(68)Ga-labelled exendin-3, a new agent for the detection of=20
insulinomas with PET.
Brom M, Oyen WJ, Joosten L, Gotthardt M, Boerman OC.
Department of Nuclear Medicine, Radboud University Nijmegen Medical=20
Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
PURPOSE: Insulinomas are neuroendocrine tumours derived from=20
pancreatic beta-cells. The glucagon-like peptide 1 receptor (GLP-1R)=20
is expressed with a high incidence (>90%) and high density in=20
insulinomas. Glucagon-like peptide 1 (GLP-1), the natural ligand of=20
GLP-1R, is rapidly degraded in vivo. A more stable agonist of GLP-1R=20
is exendin-3. We investigated imaging of insulinomas with DOTA-
conjugated exendin-3 labelled with (68)Ga. METHODS: Targeting of=20
insulinomas with [Lys(40)(DOTA)]exendin-3 labelled with either=20
(111)In or (68)Ga was investigated in vitro using insulinoma tumour=20
cells (INS-1). [Lys(40)((111)In-DTPA)]Exendin-3 was used as a=20
reference in this study. In vivo targeting was investigated in BALB/
c nude mice with subcutaneous INS-1 tumours. PET imaging was=20
performed using a preclinical PET/CT scanner. RESULTS: In vitro=20
exendin-3 specifically bound and was internalized by GLP-1R-positive=20
cells. In BALB/c nude mice with subcutaneous INS-1 tumours a high=20
uptake of [Lys(40)((111)In-DTPA)]exendin-3 in the tumour was=20
observed (33.5 +/- 11.6%ID/g at 4 h after injection). Uptake was=20
specific, as determined by coinjection of an excess of unlabelled=20
[Lys(40)]exendin-3 (1.8 +/- 0.1%ID/g). The pancreas also exhibited=20
high and specific uptake (11.3 +/- 1.0%ID/g). High uptake was also=20
found in the kidneys (144 +/- 24%ID/g) and this uptake was not=20
receptor-mediated. In this murine tumour model optimal targeting of=20
the GLP-1R expressing tumour was obtained at exendin doses </=3D0.1=20
microg. Remarkably, tumour uptake of (68)Ga-labelled [Lys(40)
(DOTA)]exendin-3 was lower (8.9 +/- 3.1%ID/g) than tumour uptake of=20
(111)In-labelled [Lys(40)(DTPA)]exendin-3 (25.4 +/- 7.2%ID/g). The=20
subcutaneous tumours were clearly visualized by small-animal PET=20
imaging after injection of 3 MBq of [Lys(40)((68)Ga-DOTA)]exendin-3.=20
CONCLUSION: [Lys(40)((68)Ga-DOTA)]Exendin-3 specifically accumulates=20
in insulinomas, although the uptake is lower than that of [Lys(40)
((111)In-DTPA)]exendin-3. Therefore, [Lys(40)((68)Ga-DOTA)]exendin-3=20
is a promising tracer to visualize insulinomas with PET.
PMID: 20111963 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20056547
> Bioorg Med Chem. 2010 Feb;18(3):1265-72. Epub 2009 Dec 16.
Design, synthesis and in vitro characterization of Glucagon-Like=20
Peptide-1 derivatives for pancreatic beta cell imaging by SPECT.
Behnam Azad B, Rota VA, Breadner D, Dhanvantari S, Luyt LG.
Departments of Chemistry, The University of Western Ontario, 1151=20
Richmond Street, London, Ontario, Canada.
Novel Glucagon-Like Peptide-1 (GLP-1) derivatives containing the=20
metal chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-
tetraacetic acid) and naturally occurring Indium ((113/115)In) were=20
prepared using solid-phase Fmoc methods. All synthesized peptides=20
contained d-Ala-8, a modification known to improve resistance=20
towards degradation by dipeptidyl peptidase-IV. The effect of=20
increased distance between DOTA and the peptide chain was=20
investigated using an (aminoethyl) ethoxy acetyl linker, in order to=20
reduce steric effects imposed by DOTA. Placement of linker and DOTA=20
moieties were also varied within the GLP-1 sequence to test for=20
optimal metal-complex location. The binding affinity of the peptide=20
derivatives was determined in vitro with Chinese hamster ovary cells=20
stably transfected with a human GLP-1 receptor (CHO/GLP-1R) cell=20
line and was shown to be in the nM range. Gamma camera imaging of an=20
insulinoma cell line was carried out using (111)In-labeled peptides.=20
Our results suggest that the prepared GLP-1 derivatives are suitable=20
imaging probes for studying pancreatic islet function in vivo.=20
Copyright (c) 2009 Elsevier Ltd. All rights reserved.
PMID: 20056547 [PubMed - in process]
So, insulinoma tumors may be due to alpha cells gone wrong. The risk=20
f that can have a genetic component, and such cells are resistant to=20
ormal modes of cellular death.

ukie (not a vet)
Recommended ferret health links:
ttp://pets.groups.yahoo.com/group/ferrethealth/
ttp://ferrethealth.org/archive/
ttp://www.afip.org/ferrets/index.html
ttp://www.miamiferret.org/
ttp://www.ferrethealth.msu.edu/
ttp://www.ferretcongress.org/
ttp://www.trifl.org/index.shtml
ttp://homepage.mac.com/sukie/sukiesferretlinks.html
ll ferret topics:
ttp://listserv.ferretmailinglist.org/archives/ferret-search.html
"All hail the procrastinators for they shall rule the world tomorrow."
2010, Steve Crandall)

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