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EagleBio Spotlight: Natriuretic Peptides

What
are Natriuretic peptides?

The natriuretic peptides belong to a family of
structurally similar but genetically different peptide hormones and include atrial, brain, and C type (ANP, BNP, and CNP, respectively). A-type and B-type have primarily have functions in the cardiovascular system and make up the cardiac natriuretic peptides. The discovery of this family was a major breakthrough in modern medicine and more specifically, cardiovascular physiology. This finding provided a direct connection between the heart and the kidneys with respect to the regulation of natriuresis.

These natriuretic peptides are modulated through their cognate receptors which are known as the ANP-A (a.k.a. NPR-A, GC-A), ANP-B (a.k.a. NPR-B, GC-B) and ANP-C (a.k.a NPR-C) receptors. ANP and BNP
preferentially bind to a membrane bound guanylyl cyclase (GC) receptor called
GC-A or NPR1, whereas CNP is the physiological ligand for GC-B (NPR2).

All natriuretic peptides are produced as propeptides,
which are then cleaved into the biologically active, C-terminal hormone
and the N-terminal fragment (NT-proANP 1-98, NT-proBNP 1-76 and NT-proCNP). It has been discovered that N-terminal fragments are
much more stable, and circulate in higher amounts than the active hormones. Thus, for these reasons the N-terminal fragments are easier and more reliable for measurement in serum or plasma.

The natriuretic peptides play an important role in the
regulation of cardiovascular and renal homeostasis and in the regulation of
fatty acid metabolism and body weight. In addition, in recent
studies natriuretic peptides have been proven to be valuable biomarkers for cardiac
pathology, including myocardial ischaemia and left ventricular dysfunction, as
well as risk stratification in congestive heart failure (CVD).

Natriuretic peptides have a wide range of roles and
effects on several biological functions within the body as seen below.

Biological Functions of Natriuretic
peptides:

Natriuresis
Vasodilation
Homeostasis
Inhibition of
aldosterone system
Inhibition of
renin-angiotensin system
Inhibition of
vascular smooth muscle growth (i.e. myocardial, endothelial, smooth
muscle)
Inhibition of
ADH hormone
Inhibition of
aldosterone hormone

References

Clerico A et al. “Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones.” Am J Physiol Heart Circ Physiol 2011; 301: H12-H20.
Doust, Jenny et al. “The Role of BNP Testing in Heart Failure.” American Family Phyisician; 2006 Dec 1;74(11):1893-190.
Lauridsen, Bo K et al. “ProANP Plasma Measurement Predicts All-Cause Mortality in Acutely Hospitalized Patients: A Cohort Study.” BMJ Open 2013;3:e003288 doi:10.1136/bmjopen-2013-003288
Moro, Cedric et al. “Natriuretic Peptides: New Players in Energy Homeostasis.” Diabetes 2009; 12: 2726-2728
Nazario, B et al. “Atrial and Brain Natriuretic Peptides Stimulate the Production and Secretion of C-type Natriuretic Peptide from Bovine Aortic Endothelial Cells.” Journal of Clinical Investigation 1995 Mar; 95(3): 1151–1157.
Schreibe, Donald et al. “Natriuretic Peptides in Congestive Heart Failure.” Medscape 2012: Jan 10.
Suzuki, T et al. “The Role of the Natriuretic Peptides in the Cardiovascular System.” Cardiovascular Research 2001; 51: 489–494.
Stanek, B. et al. “Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction” Journal of American Cardiology 2001; 38: 436-442

Related Resources Citing EagleBio Kits:

Stanek, B. et al. “Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction” Journal of American Cardiology 2001; 38: 436-442.

Related Kits:

proANP ELISA Assay Kit

BNP Fragment (Nt-proBNP 8-29) ELISA Assay Kit

NT-proCNP ELISA Assay Kit

Cardiovascular Assay Kits

Related News:

EagleBio Spotlight: ANP

EagleBio Spotlight: BNP

EagleBio Spotlight: CNP

Interesting Study Highlighting Eagle Biosciences’ BNP Fragment ELISA Assay Kit

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Antifreeze Proteins: Ticks Might Actually Be Good For Something

by Eagle Biosciences

Did you know that ticks have antifreeze proteins? A recent study conducted by a Yale professor of medicine focused on ticks and their unique cold resistant properties. These antifreeze proteins are called IAFGP (Ixodes scapularis anti-freeze glycoprotein) and are activated in ticks in the winter and prevent their cells and tissues from freezing. In fact, researchers have discovered that these proteins help to decrease the damage during frostbite, thus reducing or limiting the inflammatory cascade associated with cell death. Mice that were utilized for this study demonstrated a clear resistance to exposure to extreme cold when specially bred with genes to produce IAFGP. There is certainly an enormous amount of potential for such proteins in terms of numerous therapeutic applications. Read More

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EagleBio Spotlight: CNP

by Eagle Biosciences

What
is CNP?

CNP stands for C-type natriuretic peptide and it is
derived from a preprohormone of 126 amino acids and a prohormone of 53 amino
acids. CNP was originally found in the
central nervous system in much greater concentrations than ANP or BNP. CNP
is produced by cardiac tissue, but is expressed primarily in the brain,
pituitary gland, vascular endothelium, kidney and female reproductive tract. It
has been discovered that it is produced in the vascular endothelial cells and after
secretion of CNP from these endothelial cells, it is regulated by cytokines and
growth factors.

Unlike ANP and BNP, CNP has a very insignificant role
in natriuretic and diuretic processes. The
physiological role of CNP is not only studied in cardiac disease, but also in
bone developmental biology, bone research, renal diseases, embryonic
developmental research, and vascular diseases. In past studies, it has been
found to play an important paracrine regulatory role in the
vasculature and involvement in neural control.

Biochemical Structure of CNP:

CNP produces 22 and 53 amino acid fragments.
Unlike ANP and BNP, CNP terminates in the second cysteine residue, lacking a
further C-terminal extension.

What is NTproCNP?

NT-proCNP is the amino-terminal peptide derived from the cleavage of the prohormone proCNP. It is an equimolar product of CNP biosynthesis and is easily measured in plasma. NTproCNP is not subject to clearance pathways and it is found in the circulation at 20- to 50-fold higher concentrations than the biologically active forms of CNP.

Why Measure NTproCNP?

NTproCNP is considered to be a reliable and stable marker for measuring
CNP biosysthesis. Studies have revealed
that there is a high serum CNP concentration in critically ill subjects or individuals
who have undergone trauma. NT-proCNP has
been correlated to biomarkers of organ dysfunction and has been associated with
inflammatory and metabolic pathways.
Therefore, it has been recently been proposed as a novel biomarker for
predicting sepsis in traumatized patients.

Indications for CNP:

Vascular Disease
Diabetes
Skeletal Development
Sepsis
Renal Disease

References:

Related Resources Citing EagleBio Kits:

1. 1. 1. 1. Stanek, B. et al. “Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction” Journal of American Cardiology 2001; 38: 436-442.

Related Kits:

NT-proCNP ELISA Assay Kit

proANP ELISA Assay Kit

BNP Fragment (Nt-proBNP 8-29) ELISA Assay Kit

Cardiovascular Assay Kits

Related News:

EagleBio Spotlight: Natriuretic Peptides

EagleBio Spotlight: ANP

EagleBio Spotlight: BNP

Interesting Study Highlighting Eagle Biosciences’ BNP Fragment ELISA Assay Kit

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EagleBio Spotlight: ANP

by Eagle Biosciences

What
is ANP?

The first
natriuretic peptide was identified in 1983 and named atrial natriuretic peptide
(ANP). ANP is a 28-amino acid polypeptide resulting from the C-terminal end of
the prohormone proANP. It is largely produced in the cardiac atria, and ANP is
quickly secreted in response to atrial stretching. ANP has the following
physiological effects:

Increases glomerular
filtration rate by dilating afferent arterioles
Inhibits the collecting ducts from reabsorbing sodium,
both directly and indirectly (by inhibiting aldosterone secretion)
Inhibits release of renin

The renin-angiotensin system and ANP
function antagonistically in the maintenance of fluid/electrolyte balance and
blood pressure.

Normal hearts
secrete extremely small amounts of ANP, but elevated levels are found in
patients with left ventricular (LV) hypertrophy and mitral valve disease.

Biochemical structure of ANP:

ANP is synthesized as a 126 amino acidprecursor protein which is cleaved to produce a
96 aminoacid amino-terminal fragment and a 28 amino acid
carboxyl-terminal fragment. The carboxyl-terminal 28 amino acid fragment is the biologically active peptide and
has shorter half-life than the amino-terminal fragment.

^{Conserved residues are shaded and the line

within the ring represents the disulfide bond.}

What
is proANP?

ProANP is the prohormone of ANP (ANP is stored as a
126–amino acid prohormone (proANP1–126)). After this prohormone is released it is then cleaved into equimolar amounts of the biologically active C-terminal peptide (ANP (99–126)) and the residual N-terminal peptide (NT-proANP (1–98)) in response to atrial wall stretch.

α-ANP has a half-life of 3-4 minutes thus is quickly cleared from circulation. ProANP (1-98) on the other hand, has a significantly longer half-life of 60-120 minutes leading to much higher concentrations in blood as compared to α-ANP.

Why Measure proANP (1-98)?

Atrial natriuretic peptide (ANP) has an important physiological roles in fluid homeostasis and cardiac pathology. The longer half life of proANP (1-98) offers advantages for measuring the ANP in the blood over α-ANP due to its lack of sensitivity to the pulsatile secretion of ANP. In fact,proANP (1-98) may provide better insight to the ANP status and its chronic secretion in the blood. Studies have shown that proANP serves as a
valuable and stable marker for several areas of research ranging from sepsis to
predicting and aiding in risk stratification for heart failure.

Diseases/conditions associated with increased ANP levels:

Diabetes and Obesity
Renal Disease/Renal dysfunction
Hypertension
Pneumonia
Asthma attacks
Recent heart attack
Heart failure/Cardiac impairment
Cardiomyopathy
Sepsis
Sleep apnea

References:

Related Resources Citing EagleBio Kits:

Stanek, B. et al. “Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction” Journal of American Cardiology 2001; 38: 436-442.

Related Kits:

proANP ELISA Assay Kit

Cardiovascular Assay Kits

Related News:

EagleBio Spotlight: Natriuretic Peptides

EagleBio Spotlight: BNP

EagleBio Spotlight: CNP

Interesting Study Highlighting Eagle Biosciences’ BNP Fragment ELISA Assay Kit

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New Publication Describes Interesting Case Study: Baby Born “Pregnant” with Twins

by Eagle Biosciences

New Study Reveals Hong Kong Baby Girl Born 'Pregnant' with Twin Fetuses

A recent study just published in February of 2015 in the Hong-Kong Medical Journal discusses a medical case of a baby girl, born at Queen Elizabeth Hospital in Hong Kong in 2010. Doctors and other medical staff originally believed that the masses seen in prenatal ultrasounds were two tumors. It wasn’t until the baby was born that they discovered that the masses were two fetuses that gestated up to 10 weeks. Read More

image above from www.people.com

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EagleBio Spotlight: BNP

by Eagle Biosciences

What
is BNP?

BNP stands for Brain natriuretic peptide or otherwise
known as B-type natriuretic peptide (BNP) and is produced from a preprohormone
precursor. BNP was named after it was originally identified in extracts of
porcine brain, hence brain natriuretic peptide.
Even though in humans, this peptide is produced mainly in the cardiac
ventricles its name remains the same. Following cardiac hemodynamic stress,
both atrial natriutetic peptide (ANP) and BNP are secreted from the heart (primarily produced by atrial and
ventricular cardiomyocytes). BNP is mainly expressed by ventricular myocardium
in response to volume overload and increased filling pressure. BNP
may be only activated after a prolonged period of volume overload and thus
acting like a backup hormone in response to heart stress.

The release of BNP into the blood stream causes
dilation of the blood vessels, and thereby dilation of the arteries. This begins the process of the body’s natural
response to reduce blood pressure in the body, followed by blockage of adrenalin,
and finally the release of sodium and water into the urine (natriuresis). Healthy individuals typically exhibit the
highest BNP concentrations in the atria but BNP is shifted to the ventricles in
heart failure (HF). A high concentration of BNP in the bloodstream is
indicative of heart failure. In fact, BNP
is predictive of cardiac dysfunction, in particular left ventricular
dysfunction, and is a useful marker of future outcomes in patients with acute
coronary syndromes and congestive heart failure.

Biochemical structure of BNP:

BNP is produced as a 108 amino acid precursor protein
which is cleaved into a biologically active 32 amino acid carboxyl-terminal
fragment and a 76 amino acid amino- terminal fragment.

Conserved residues are shaded and the line
within the ring represents the disulfide bond.

The N-terminal peptide comprising amino acids 1-76 is further degraded proteolytically and thus BNP fragments in the circulation are very heterogeneous. There are a few different circulating forms of BNP such as BNP-32 (77-108), a high molecular weight BNP and and the NT-proBNP (1-76).

The BNP fragment (Nt-proBNP 8-29) is the preferred analyte for representation of BNP status for a few reasons. BNP Fragment is a stable molecule, has a long half-life and it circulates in high concentrations.

Why Measure BNP?

BNP has a key role in cardiovascular homeostasis with biological actions including natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion. Because of its broad range of functions in the body, measuring this analyte can be used for studying and/or monitoring the diseases/conditions below.

Diseases/conditions associated with elevated BNP levels:

Diabetes and
Obesity
Renal Disease/Renal
dysfunction
Hypertension
Pneumonia
Asthma
attacks
Recent
heart attack
Heart
failure/Cardiac impairment
Cardiomyopathy
Sepsis
Sleep
apnea

References

Related Resources Citing EagleBio Kits:

Stanek, B. et al. “Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction” Journal of American Cardiology 2001; 38: 436-442.

Related Kits:

BNP Fragment (Nt-proBNP 8-29) ELISA Assay Kit

proANP ELISA Assay Kit

NT-proCNP ELISA Assay Kit

EagleBio Spotlight: ANP

EagleBio Spotlight: CNP

Interesting Study Highlighting Eagle Biosciences’ BNP Fragment ELISA Assay Kit

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EagleBio’s Shikari Anti-Drug Antibody Kit Publications

by Eagle Biosciences

EagleBio is pleased to share a list below of publications referencing use of our Shikari Kits from Matriks Biotek. Our Shikari Kits are esoteric assays and are not only the gold standard of anti-drug antibody kits world worldwide but are also incredibly user friendly.

Click the links below for further details.

Publications:

Adisen E, et al, Anti-infliximab antibody status and its relation to clinical response in psoriatic patients: A pilot study, Journal of Dermatology (2010)

Aydın C, Ataoğlu H., Demonstration of β-1,2 Mannan Structures Expressed on the Cell Wall of Candida albicans Yeast Form But Not on the Hyphal Form by Using Monoclonal Antibodies(2015).

Bodini G, et
al, Clinical relevance of Adalimumab serum concentration and Anti-Adalimumab
antibodies in patients with Chrohn’s disease during long-term follow up, Italy
(2012)

Bortlik M, et al, Impact of Anti-Tumor Necrosis Factor Alpha Antibodies Administered to Pregnant Women With Inflammatory Bowel Disease on Long-term Outcome of Exposed Children

Bortlik
M, et al, Infliximab trough levels may predict sustained response to infliximab
in patients with Crohn’s disease, Journal of Crohn’s and Colitis (2012) Bortlik
M, et al, Infliximab trough levels may predict sustained response to infliximab
in patients with Crohn’s disease, Journal of Crohn’s and Colitis (2012)

Bortlik M et al. Pregnancy and newborn outcome of mothers with inflammatory bowel diseases exposed to anti-TNF-α therapy during pregnancy: three-center study, by using Matriks Biotek®, SHIKARI® Q-INFLIXI and SHIKARI® Q-ADA (infliximab and adalimumab)) ELISA Kits IBD Clinical and Research Centre, ISCARE, Charles University , Prague , Czech Republic

Chio C, et al, Etanercept Attenuates Traumatic
Brain Injury in Rats by Reducing Brain TNF-α Contents and by Stimulating Newly
Formed Neurogenesis, Mediators of Inflammation, (2013)

Erdemli Ö., et al, In vitro evaluation of effects of sustained anti-TNF release from MPEG-PCL-MPEG and PCL microspheres on human rheumatoid arthritis synoviocytes.

Gabriela Romero, et al, Poly(Lactide-co-Glycolide) Nanoparticles, Layer by Layer Engineered for the Sustainable Delivery of AntiTNF-α.

Grosen A., et al, Infliximab concentrations in the milk of nursing mothers with inflammatory bowel disease (2013).

Gutierrez A, et al, Genetic susceptibility to increased
bacterial translocation influences the response to biological therapy in
patients with Crohn’s disease, Gut (2013)

Jung Y, et al, Temperature-modulated noncovalent interaction controllable complex for the long-term delivery of etanercept to treat rheumatoid arthritis, (2013).

Kato S, et al, Elevated Serum IgE Prior to Acute Severe Infusion Reaction During Infliximab Maintenance Therapy in a Crohn’s Disease Patient, Crohn’s & Colitis Foundation of America (2011)

K ato S, et al, Elevated Serum IgE Prior to Acute Severe Infusion Reaction During Infliximab Maintenance Therapy in a Crohn’s Disease Patient, Crohn’s & Colitis Foundation of America (2011)

Krajcovicova A. et al., Delayed hypersensitivity reaction after initial dose of infliximab: a case report (2014)

Malickova K, et al, Phosphatidylserine-dependent
anti-prothrombin antibodies (aPS/PT) in infliximab-treated patients with
inflammatory bowel diseases, Autoimmun Highlights (2012)

Molnar T, et al, Importance of trough levels and antibody titers on the efficacy and safety of Infliximab therapy in inflammatory bowel disease, Hungary (2012)

Pallagi-Kunstár Éva et al., Utility of serum TNF-a, infliximab trough level, and antibody titers in inflammatory bowel disease (2014) Pallagi-Kunstár Éva et al., Utility of serum TNF-a, infliximab trough level, and antibody titers in inflammatory bowel disease (2014)

Takahashi H, et al, Plasma trough levels of adalimumab and infliximab in terms of clinical efficacy during the treatment of psoriasis, Journal of Dermatology (2012)

Seok Lee Y, et al, Efficacy of Early Infliximab Treatment for Pediatric Crohn’s Disease: A Three-year Follow-up, Pediatric Gastroenterology, Hepatology & Nutrition (2012)

New Publication Presented at UEG For Therapeutic Drug Monitoring Using EagleBio’s SHIKARI® ELISA Kits from Matriks

Related Kits:

Shikari ELISA Assay Kits

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EagleBio Spotlight: Endostatin

by Eagle Biosciences

What is Endostatin?

Angiogenesis is the formation of new capillaries from preexisting blood vessels. Endostatin is a 20-kDa C-terminal fragment of collagen XVIII that plays a key role as an angiogenesis inhibitor and consists of 183-184 amino acid residues (its molecular weight is 20 kD). As a potent inhibitor of angiogenesis, endostatin has been found in recent studies to activate a series of signaling pathways thereby inducing endothelial cell apoptosis. It binds to numerous membrane proteins including integrins and heparin sulfate and this binding is further evidence of this biomarker’s involvement with multiple signaling pathways in regards to angiogenesis. In addition, other functions of endostatin in relation to cell death processes include roles in reducing cell migration, adhesion, and proliferation.

Endostatin is generated by proteoltyic cleavage by proteases or matrix metalloproteinases (MMPs) (MMPs have a variety of actions influencing fibrinolysis and angiogenesis). It is localized in the vascular basement membrane zones in various organs. Following the proteolysis, once endostatin is formed it can either stay attached to basement membranes (immobilized) or be released into circulation (soluble). Research has demonstrated that both forms of endostatin have unique biological activities. These activities at the molecular level are still being studied but thus far, it has been discovered that endostatin in combination with angiogenic factors, have an integral role in endothelial response to tissue damage such as renal injury.

Reasons to Measure Endostatin

Endostatin is a vital component for angiogenesis which is necessary for numerous pathological functions, therefore it has been indicated in a vast variety of diseases and other medical conditions. Measuring endostatin can provide remarkable value for detecting and monitoring diseases/conditions, predicting disease risk, and offering a new target for multiple therapies in related areas of research.

Endostatin has been associated with many diseases such as:

Chronic Kidney Disease (CKD)
Renal Microvascular Disease
Atherosclerosis
Idiopathic Pulmonary Fibrosis (IPF)
Cancer

References:

Related Kits:

Endostatin ELISA

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Eagle Biosciences Launches Multispecies IGF-1 ELISA Assay Kit

by Eagle Biosciences

February 2015- Eagle Biosciences, Inc. is pleased to introduce a new Multispecies ELISA Assay kit. This assay was developed at IBT (Immunological and Biochemical
Testsystems GmbH) in Germany. IBT’s core business surrounds the production of
high quality products in the field of Endocrinology and other related areas of
research.

This kit is designed for the simple and very
sensitive determination of Insulin-like Growth Factor 1 (IGF-1). IGF-1 is also
known as somatomedin C, and is a polypeptide of 70 amino acids and is a growth factor
for a wide range of cell types. IGF-1 is associated with cancer, neuropathy,
stroke, growth/development, aging, malnutrition/malabsorption, hypothyroidism, obesity, liver
disease, kidney disease, diabetes mellitus complications, and chronic
inflammatory disease.

“This
ELISA kit has excellent specificity for multiple species such as human, porcine, bovine and guinea pig with results in under 4 hours.”
said Dan Keefe, President of Eagle. He continued, “This product certainly
offers a lot in terms of versatility and is an exceptional addition to our
Endocrine Assay Kit line.”

These
products are currently for research use only. Check out the links below, visit
the Eagle website, www.EagleBio.com, or call 866-411-8023 for full details.

Multispecies IGF-1 ELISA

Endocrine Assay Kits