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Safety The ImSAIDs® are comprised of natural amino acids that have demonstrated no toxicity or immune suppression in numerous animal studies, including dogs, cats, and a variety of other species ImSAIDs® - Cellular Modulation in vivo and in vitro results have shown the ImSAIDs® to help support the following: reduce granulocyte acvaon and chemotaxis diminish oxidave burst capacity and the producon of reacve oxygen species aenuate the eects of endotoxin, and reduce allergic & anaphylacc reacons (type I hypersensivity and IgE-mediated reacons) Additional References on ImSAIDs® Immunopharmacology Mathison R, et al. Modulaon of neutrophil funcon by the tripepde feG. BMC Immunol. 2003 Mar 4;4:3. 2003 Mathison R, et al. Regulaon of leukocyte adhesion to heart by the tripepdes feG and feG(NH2). Can J Physiol Pharmacol . 2001 Sep; 79(9):785-92. Mathison RD and Davison JS. The Tripepde feG Regulates the Producon of Intracellular Reacve Oxygen Species by Neutrophils. J Inflamm (Lond). 2006 Jun 15;3(1):9 Mathison R, Davison JS, Befus AD. Neuroendocrine regulaon of inammaon and ssue repair by submandibular gland factors. Immunol Today.1994 Nov;15(11):527-32. Mathison RD, et al. The tripepde feG inhibits leukocyte adhesion. J Inflamm (Lond). 2008 May 20;5:6. Mathison R, Davison JS. Molecular characteriscs of the tripepde feG accounng for dierent biological acvies. Proc West Pharmacol Soc . 2007;50:101-4. Mathison RD, et al.. A pepde from the submandibular glands modulates inammatory responses. Int Arch Allergy Immunol . 1997 May-Jul;113(1-3):337-8. Mathison RD, et al. Submandibular glands: novel structures parcipang in thermoregulatory responses. Can J Physiol Pharmacol. 1997 May; 75(5):407-13. leukoSTAT™ ( ImSAIDs® Enabled) leukoSTAT™ contains the ImSAIDs®; patented amino acid complexes that maintain systemic health, by aiding in the reducon of leukocyte acvaon and chemotaxis. ImSAIDs® are Not COX/LOX inhibitors or steroids, but naturally occuring amino acid complexes that nature designed to posively influence the immune system, including leukocytes. leukoSTAT™ Product & Ordering IMULAN has developed a highly palatable, chewable tablet for dogs and cats. The small, 625mg chewable tablet can be used when only small amounts of material can be given orally. leukoSTAT™ is available in 30 and 120 count boles. To purchase LeukoSTAT™; please go to www.IMULAN.com and set up an account. You may also contact IMULAN at info@ imulan.com IMULAN BioTherapeucs 4221 Mitchell Avenue St. Joseph, MO 64507 www.IMULAN.com 480-248-2176 . Immuno-Nutrional Technology ALL Inflammation is Regulated by Leukocytes

LeukoSTAT Trifold

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LeukoSTAT positively influences the source of ALL inflammation, being immune cells (leukocytes). Leukocytes, or white blood cells, regulate inflammation and that is why leukoSTAT was created.

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Page 1: LeukoSTAT Trifold

Safety The ImSAIDs® are comprised of natural amino acids that have demonstrated no toxicity or immune suppression in numerous animal studies, including dogs, cats, and a variety of other species

ImSAIDs® - Cellular Modulation in vivo and in vitro results have shown the ImSAIDs® to help support the following: � reduce granulocyte activation and

chemotaxis � diminish oxidative burst capacity and the

production of reactive oxygen species � attenuate the effects of endotoxin, and

reduce allergic & anaphylactic reactions (type I hypersensitivity and IgE-mediated reactions)

Additional References on ImSAIDs®

Immunopharmacology Mathison R, et al. Modulation of neutrophil function by the tripeptide feG. BMC Immunol. 2003 Mar 4;4:3. 2003 Mathison R, et al. Regulation of leukocyte adhesion to heart by the tripeptides feG and feG(NH2). Can J Physiol Pharmacol. 2001 Sep; 79(9):785-92. Mathison RD and Davison JS. The Tripeptide feG Regulates the Production of Intracellular Reactive Oxygen Species by Neutrophils. J In�amm (Lond). 2006 Jun 15;3(1):9 Mathison R, Davison JS, Befus AD. Neuroendocrine regulation of inflammation and tissue repair by submandibular gland factors. Immunol Today. 1994 Nov;15(11):527-32. Mathison RD, et al. The tripeptide feG inhibits leukocyte adhesion. J In�amm (Lond). 2008 May 20;5:6. Mathison R, Davison JS. Molecular characteristics of the tripeptide feG accounting for different biological activities. Proc West Pharmacol Soc. 2007;50:101-4. Mathison RD, et al.. A peptide from the submandibular glands modulates inflammatory responses. Int Arch Allergy Immunol. 1997 May-Jul;113(1-3):337-8. Mathison RD, et al. Submandibular glands: novel structures participating in thermoregulatory responses. Can J Physiol Pharmacol. 1997 May; 75(5):407-13.

leukoSTAT™ ( ImSAIDs® Enabled) leukoSTAT™ contains the ImSAIDs®; patented amino acid complexes that maintain systemic health, by aiding in the reduction of leukocyte activation and chemotaxis. ImSAIDs® are Not COX/LOX inhibitors or steroids, but naturally occuring amino acid complexes that nature designed to positively influence the immune system, including leukocytes.

leukoSTAT™ Product & Ordering IMULAN has developed a highly palatable, chewable tablet for dogs and cats. The small, 625mg chewable tablet can be used when only small amounts of material can be given orally. leukoSTAT™ is available in 30 and 120 count bottles. To purchase LeukoSTAT™; please go to www.IMULAN.com and set up an account. You may also contact IMULAN at info@ imulan.com

IMULAN BioTherapeutics 4221 Mitchell Avenue St. Joseph, MO 64507

www.IMULAN.com 480-248-2176

.

Immuno-Nutritional Technology

ALL In�ammation is Regulated

by Leukocytes

Page 2: LeukoSTAT Trifold

ImSAIDs® Key Benefits The ImSAIDs® (Immune Selective Anti-Inflammatory Derivatives) are a brand new amino acid technology designed by Mother Nature. The ImSAIDs® are naturally occuring amino acid complexes that nature designed to help reduce over activation of the immune response.

Critical Care Medicine Models The ImSAIDs have been evaluated in a variety of comparative disease models of sepsis, endotoxemia, spinal trauma, pancreatitis, asthma, allergic and anaphylactic reactions. The following are models using one ImSAID® amino acid complex, phe-glu-gly, or feG.

Inhibition of neutrophil chemotaxis

0.05

0.1

0.15

0.2

0.25

0.3

0 0.35 1 3.5 10 100

ImSAID dosage, µg/kg

un

its

MP

O/m

g ti

ssu

e, m

ean

±se

m, n

=6

Chemotaxis, adhesion

Endotoxin/Sepsis Model Tan D, et al. The carboxamide feG(NH2) inhibits endotoxin perturbation of intestinal motility. Eur J Pharmacol. 2000 Dec 8;409(2):203-5. Mathison R, et al. The tripeptide feG reduces endotoxin-provoked perturbation of intestinal motility and inflammation. Neurogastroentero Motil. 2001 Dec;13(6):599-603.

0

1

2

3

4

5

6

7

8

**

Lip

as

e U

nit

s x

10

3/m

L

Normal, no

pancreatitis

No treatment ImSAIDs

(0hr)

ImSAIDs

(3hr)

Acute pancreatitis

Pancreatitis Model Rifai Y, et al. The tripeptide analog feG ameliorates severity of acute pancreatitis in a caerulein mouse model. Am J Physiol Gastrointest Liver Physiol.2008 Apr;294(4):G1094-9.

Neurological Trauma Model Bao F, et al. The tripeptide phenylalanine-(D) glutamate-(D) glycine modulates leukocyte infiltration and oxidative damage in rat injured spinal cord. Neuroscience. 2006 Jul 7;140(3):1011-22. John SM, Bao F, Chen Y, Mathison RD, Weaver LC.Effects of a novel tripeptide on neurological outcomes after spinal cord injury. Neuroreport. 2006 Nov 27;17(17):1793-6.

Neutrophil inhibition after after intestinal

anaphylaxis

0

5

10

15

20

25

30

35

0.5 3 24Hours after challenge

Ne

utr

op

hil

cou

nt,

mea

n ±

sem

, n=5

Sensitized control

ImSAID treated Dexamethasone

Anaphylaxis

Allergic/Anaphylaxis/IgE mediated Model Turesin F, et al.: The tripeptide FEG ameliorates systemic inflammatory responses to rat intestinal anaphylaxis. BMC Physiol 2002, 2:13

Inflammation/Asthma Model Dery RE, et al. Frontline: Inhibition of allergen-induced pulmonary inflammation by the tripeptide feG: a mimetic of a neuro-endocrine pathway. Eur J Immunol. 2004 Dec;34(12):3315-25.

ImSAIDs (1mg/kg); mild cellular infiltration

CONTROL; severe cellular infiltration (lung)