Banyan Laboratories Inc.

Alachua, FL, United States

Banyan Laboratories Inc.

Alachua, FL, United States
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Prima V.,Banyan Laboratories Inc. | Prima V.,University of Florida | Serebruany V.L.,Heart Drug Research LLC | Svetlov A.,Banyan Laboratories Inc. | And 3 more authors.
Journal of Neurotrauma | Year: 2013

Severe blast exposures are frequently complicated with fatal intracranial hemorrhages. However, many more sustain low level blasts without tissue damage detectable by brain imaging. To investigate effects of nonlethal blast on thrombin-related biomarkers, rats were subjected to two different types of head-directed blast: 1) moderate "composite" blast with strong head acceleration or 2) moderate primary blast, without head acceleration. Thrombin generation (TG) ex vivo after blast was studied by calibrated automated thrombography (CAT). In the same blood samples, we assessed maximal concentration of TG (TGmax), start time, peak time, mean time, and concentrations of protein markers for vascular/hemostatic dysfunctions: integrin α/β, soluble endothelial selectin (sE-selectin), soluble intercellular cell adhesion molecule-1 (sICAM-1), and matrix metalloproteinases (MMP)-2, MMP-8, and MMP-13. Blast remarkably affected all TG indices. In animals exposed to "composite" blast, TGmax peaked at 6 h (∼4.5-fold vs. control), sustained at day 1 (∼3.8-fold increase), and declined to a 2-fold increase over control at day 7 post-blast. After primary blast, TGmax also rose to ∼4.2-fold of control at 6 h, dropped to ∼1.7-fold of control at day 1, and then exhibited a slight secondary increase at 2-fold of control at day 7. Other TG indices did not differ significantly between two types of blast exposure. The changes were also observed in other microvascular/inflammatory/hemostatic biomarkers. Integrin α/β and sICAM-1 levels were elevated after both "composite" and primary blast at 6 h, 1 day, and 7 days. sE-selectin exhibited near normal levels after "composite" blast, but increased significantly at 7 days after primary blast; MMP-2, MMP-8, and MMP-13 slightly rose after "composite" blast and significantly increased (∼2-4-fold) after primary blast. In summary, CAT may have a clinical diagnostic utility in combination with selected set of microvascular/inflammatory biomarkers in patients subjected to low/moderate level blast exposures. © 2013 Mary Ann Liebert, Inc.


McGill M.R.,University of Kansas Medical Center | Cao M.,University of Florida | Cao M.,Banyan Laboratories Inc. | Svetlov A.,Banyan Laboratories Inc. | And 8 more authors.
Biomarkers | Year: 2014

Context: New biomarkers are needed in acetaminophen (APAP) hepatotoxicity. Plasma argininosuccinate synthetase (ASS) is a promising candidate. Objective: Characterize ASS in APAP hepatotoxicity. Methods: ASS was measured in plasma from rodents and humans with APAP hepatotoxicity. Results: In mice, ASS increased before injury, peaked before alanine aminotransferase (ALT) and decreased rapidly. Fischer rats had a greater increase in ASS relative to ALT. Patients with abnormal liver test results had very high ASS compared to controls. ASS appeared to increase early in some patients, and declined rapidly in all. Conclusions: ASS may be a useful biomarker of acute cell death in APAP hepatotoxicity. © 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.


Cao M.,Banyan Laboratories Inc. | George T.J.,University of Florida | Prima V.,Banyan Laboratories Inc. | Nelson D.,University of Florida | Svetlov S.,Banyan Laboratories Inc.
Biomarkers | Year: 2013

Argininosuccinate synthase (ASS) plays an important role in regulating metabolic functions in mammals. We previously reported that hepatic ASS is released into circulation at very high concentrations in response to endotoxin and acute liver injury. We propose that ASS may serve as a novel biomarker for various inflammatory conditions. Our data showed that ASS accumulated in serum and urine of septic, obese or tumor mice in a condition-dependent fashion. Moreover, ASS significantly increased in urine within the first week after tumor cell implantation in mice which subsequently develop tumors. These results suggest that ASS is a novel biomarker increased upon diverse inflammatory conditions. © 2013 Informa UK Ltd.


Svetlov S.I.,Banyan Laboratories Inc | Svetlov S.I.,University of Florida | Prima V.,Banyan Laboratories Inc | Glushakova O.,Banyan Laboratories Inc | And 7 more authors.
Frontiers in Neurology | Year: 2012

A number of experimental models of blast brain injury have been implemented in rodents and larger animals. However, the variety of blast sources and the complexity of blast wave biophysics have made data on injury mechanisms and biomarkers difficult to analyze and compare. Recently, we showed the importance of rat position toward blast generated by an external shock tube. In this study, we further characterized blast producing moderate traumatic brain injury and defined "composite" blast and primary blast exposure set-ups. Schlieren optics visualized interaction between the head and a shock wave generated by external shock tube, revealing strong head acceleration upon positioning the rat on-axis with the shock tube (composite blast), but negligible skull movement upon peak overpressure exposure off-axis (primary blast). Brain injury signatures of a primary blast hitting the frontal head were assessed and compared to damage produced by composite blast. Low to negligible levels of neurodegeneration were found following primary blast compared to composite blast by silver staining. However, persistent gliosis in hippocampus and accumulation of GFAP/CNPase in circulation was detected after both primary and composite blast. Also, markers of vascular/endothelial inflammation integrin alpha/beta, soluble intercellular adhesion molecule-1, and L-selectin along with neurotrophic factor nerve growth factor-beta were increased in serum within 6 h post-blasts and persisted for 7 days thereafter. In contrast, systemic IL-1, IL-10, fractalkine, neuroendocrine peptide Orexin A, andVEGF receptor Neuropilin-2 (NRP-2) were raised predominantly after primary blast exposure. In conclusion, biomarkers of major pathological pathways were elevated at all blast set-ups. The most significant and persistent changes in neuro-glial markers were found after composite blast, while primary blast instigated prominent systemic cytokine/chemokine, Orexin A, and Neuropilin-2 release, particularly when primary blast impacted rats with unprotected body. © 2012 Svetlov, Prima, Glushakova, Svetlov, Kirk, Gutierrez, Serebruany, Curley, Wang and Hayes.


Cao M.,Banyan Laboratories Inc. | Prima V.,Banyan Laboratories Inc. | Nelson D.,University of Florida | Svetlov S.,Banyan Laboratories Inc. | Svetlov S.,University of Florida
Cellular Oncology | Year: 2013

Background: The heterogeneity of liver cancer, in particular hepatocellular carcinoma (HCC), portrays the requirement of multiple targets for both its treatment and prevention. Multifaceted agents, minimally or non-toxic for normal hepatocytes, are required to address the molecular diversity of HCC, including the resistance of putative liver cancer stem cells to chemotherapy. Methods: We designed and synthesized two fatty acid ethers of isopropylamino propanol, C16:0-AIP-1 and C18:1-AIP-2 (jointly named AIPs), and evaluated their anti-proliferative effects on the human HCC cell line Huh7 and the murine hepatoma cell line BNL 1MEA.7R.1, both in vitro and in an in vivo allograft mouse model. Results: We found that AIP-1 and AIP-2 inhibited proliferation and caused cell death in both Huh7 and BNL 1MEA.7R.1 cells. Importantly, AIP-1 and AIP-2 were found to block the activation of putative liver cancer stem cells as manifested by suppression of clonal 'carcinosphere' development in growth factor-free and anchorage-free medium. The AIPs exhibited a relatively low toxicity against normal human or rat hepatocytes in primary cultures. In addition, we found that the AIPs utilized multifaceted pathways that mediate both autophagy and apoptosis in HCC, including the inhibition of AKTs and CAMK-1. In immune-competent mice, the AIPs significantly reduced BNL 1MEA.7R.1 cell-driven tumor allograft development, with a higher efficiency than sorafenib. A combination of AIP-1 + AIP-2 was most effective in reducing the tumor allograft incidence. Conclusions: AIPs represent a novel class of simple fatty acid derivatives that are effective against liver tumors via diverse pathways. They show a low toxicity towards normal hepatocytes. The addition of AIPs may represent a new avenue towards the management of chronic liver injury and, ultimately, the prevention and treatment of HCC. © 2013 International Society for Cellular Oncology.


PubMed | Banyan Laboratories Inc.
Type: Journal Article | Journal: Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals | Year: 2013

Argininosuccinate synthase (ASS) plays an important role in regulating metabolic functions in mammals. We previously reported that hepatic ASS is released into circulation at very high concentrations in response to endotoxin and acute liver injury. We propose that ASS may serve as a novel biomarker for various inflammatory conditions. Our data showed that ASS accumulated in serum and urine of septic, obese or tumor mice in a condition-dependent fashion. Moreover, ASS significantly increased in urine within the first week after tumor cell implantation in mice which subsequently develop tumors. These results suggest that ASS is a novel biomarker increased upon diverse inflammatory conditions.


PubMed | Banyan Laboratories Inc.
Type: Journal Article | Journal: Journal of liver | Year: 2013

Liver and kidney damage associated with polytrauma, endotoxic shock/sepsis, and organ transplantation, are among the leading causes of the multiple organ failure. Development of novel sensitive biomarkers that detect early stages of liver and kidney injury is vital for the effective diagnostics and treatment of these life-threatening conditions. Previously, we identified several hepatic proteins, including Argininosuccinate Synthase (ASS) and sulfotransferases which were degraded in the liver and rapidly released into circulation during Ischemia/Reperfusion (I/R) injury. Here we compared sensitivity and specificity of the newly developed sandwich ELISA assays for ASS and the sulfotransferase isoform SULT2A1 with the standard clinical liver and kidney tests Alanine Aminotransferase (ALT) and Aspartate Transaminase (AST) in various pre-clinical models of acute injury. Our data suggest that ASS and SULT2A1 have superior characteristics for liver and kidney health assessment in endotoxemia, Ischemia/Reperfusion (I/R), chemical and drug-induced liver injury and may be of high potential value for clinical applications.

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