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Dear all,
I have a question concerning White Blood cell Count (WBC) in rats
after a iv Bolus of Velcade in NaCl Solution.
after injection into the tail vain Blood was taken from the tail
tip (500 ul in big rats) and WBC count done after 1hr, 6hrs and
24hrs. W BC count raises up to four times higher (6h) than a control
value before application, and Numbers decrease after 24 hrs.
(Application solutions are of course sterile) . This was seen in 4
Animals.
I am interested if someone from the communiy has encountered this
effect, or might have an explanation.
Thank you very much in advance,
Maria Kissel
Dr. Maria Kissel
4SC AG
Am Klopferspitz 19a
82152 Martinsried
Tel 089 700763-0
Fax 089 700763-29
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Dear Maria,
it's not unusual to see significant changes in total WBC counts
after intravenous dosing in my experience too.
As your observation is about a "transient" change in total WBC and
you observed a rapid increase (6h), I suspect a possible direct
involvement of polimorfonuclear cells (PMN)recruitment (have you more
detailed information about the changes in WBC population? Have you
performed a differential count of WBC?).
PMN are constantly available to the recruitment by a lot of mediators
like cytokines (i.e. IL-1, TNF alfa, etc.) and chemokines (i.e. IL-8)
and these mediators are released after a lot of possible diverse
inflammatory stimuli.
Even if it's there are a lot of possible mechanisms involved in
generation of inflammatory stimuli able to increase the WBC number I
can give the two easiest hypothesis:
1) The easiest is a local effect, i.e. a direct effect able to
generate an inflammatory stimulus in the site of injection. This
might be followed by the systemic delivery of inflammatory mediators,
with a recruitment of polimorfonuuclear cells (or other WBC) in the
venous bloodstream;
2) Another possible effect is a systemic inflammatory effect of your
vehicle (is the vehicle apyrogenic?) able to generate an increase in
the WBC population in the venous bloodstream;
Other possible explanations exist, depending on the pharmacological
properties of your test system (rat strain, experimental conditions,
etc.) and/or pharmaceutical properties of your formulation, however,
in my opinion, the acute inflammatory effect involving PMN
recruitment remain the first advantaged possibility.
I hope this may be useful
Best regards
Stefano
Dr. Stefano Porzio
Sr. Pharmacokineticist
Inpharzam Ricerche SA - ZambonGroup
CH-6807 Taverne
Switzerland
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Dear Maria,
There could be an elevation of the WBC count after repeated intravenous
injections and if there is some degenerative and necrotic changes
anywhere in the body. Repeated puncture alone could be sufficient to
cause a leukocytosis. What was the differential leucocyte values with
these 4 animals you report a leukocytosis. Was there any alteration with
the general picture by blood smears. And does this proteasome inhibitor
has ay effect on bone marrow. Will be interested to know these things
and interact with you more.
Regards and Thanks,
Dr.Ravishankar.N
Ranbaxy Research Labs,
India
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Demargination of WBC can be caused by tissue damage, inflammation, and
physiological) stress, to name a few. Fear, excitement, and even
(strenuous) exercise can have similar effects.
Kind regards,
Frederik Pruijn
Frederik B. Pruijn PhD MSc (Senior Research Fellow)
Experimental Oncology Group
Auckland Cancer Society Research Centre
Faculty of Medical and Health Sciences
The University of Auckland
Private Bag 92019
Auckland
New Zealand
Phone: +64-9-3737 599 x86939 or x86090
Fax: +64-9-3737 571
E-mail: f.pruijn.-at-.auckland.ac.nz
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