2417: Serum total histones in dogs with acute pancreatitis, their association with laboratory findings, markers of inflammation and outcome: a prospective longitudinal study

Grant Status: Open

Grant Amount: $14,200
Dr. Ran Nivy, DVM, The Koret School of Veterinary Medicine, The Hebrew University of Jerusalem
December 1, 2017 - November 30, 2018
Breed(s): Miniature Schnauzer
Research Program Area: Endocrinology

Abstract

Acute pancreatitis (AP) is a common, potentially fatal, inflammatory disease in dogs. Miniature Schnauzers and several Terrier and non-sporting breeds are predisposed to develop AP. The spectrum of clinical signs greatly varies, from transient inappetence in mild cases, to intractable gastro-intestinal signs and jaundice in severe ones. The result of aberrant activation of pancreatic digestive enzymes, the ensuing inflammatory reaction within the pancreas and its surrounding tissues induces edema formation and tissue necrosis. In severe cases, inflammation spreads to other organs, leading to hemostatic disturbances, multi-organ dysfunction and ultimately, to death. Several measurable inflammation markers increase in canine pancreatitis. Recently, studies of human and murine AP have demonstrated significant increases in extracellular serum histones. Histones are evolutionally conserved nuclear proteins, constituting the basic structure with which DNA interacts. Histones exert proinflammatory properties, with many deleterious effects on various body cells, and hemostasis. Interestingly, their pernicious effects can be partly or completely abrogated therapeutically (e.g., administering heparin or activated protein C). Recently, circulating histones have shown excellent performance in predicting persistent organ failure and mortality in humans with AP. The investigators will measure, free total serum histones in dogs with naturally occurring AP, and examine their association with other laboratory analytes, and with the prognosis. Should serum histones be found to increase in canine AP, as in humans, this may open up new therapeutic and research avenues for this serious disease.

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