Research

Mechanisms of Injury Control after Hepatic Ischemia-Reperfusion

Mechanisms of Injury Control after Hepatic Ischemia-Reperfusion

langdale2011Lorrie A. Langdale, MD Professor and Director Veterans Affairs PSHCS Surgical ICU & Chief of General Surgery Liver failure is often preceded by a period of inadequate tissue and cellular perfusion (ischemia). Hypoxia/re-oxia initiates early activation of Kupffer cells, producing a wave of reactive oxygen species (ROS) and proinflammatory cytokines, in particular TNFα, IL-1β, and IL-6, as well as chemokines. These cytokines, together with reactive oxygen species, act in a paracrine manner on adjacent hepatocytes and endothelial cells, resulting in direct cytotoxic effects. Hepatocytes (HC), in turn, amplify the Kupffer cell (KC) response by expressing and releasing mediators such as IL-6 to further activate neighboring cells. Cytokines released into the circulation may also initiate secondary organ injury, setting the stage for multiple organ failure. Activated neutrophils are recruited by chemokines to the sites of primary and secondary injury. Working in concert with activated compliment, these mediators exacerbate the initial injury through microcirculatory vasoconstriction and release of additional reactive oxygen products. This late phase may continue to progress, culminating in liver necrosis with attendant organ failure, or resolve with resumption of normal liver function and a return to homeostasis. Complete Research Report >>

The Vascular Research Program at the VA Puget Sound Health Care System

The Vascular Research Program at the VA Puget Sound Health Care System

sobel2011Michael Sobel, MD Professor Veterans Affairs PSHCS The VA Puget Sound has a robust research infrastructure that supports two principal investigators in the Division of Vascular Surgery: Dr. Michael Sobel, Professor of Vascular Surgery, and Errol Wijelath, Research Associate Professor. Current projects include the following:

  1. Preventing Vein Graft Stenosis in Peripheral Vascular Surgery
  2. Oncostatin M in Atherosclerosis and Vascular Disease
  3. Modulating Endothelialization of Cardiovascular Grafts

Complete Research Report >>

Gastrointestinal Cancer Treatment and Cellular Senescence

Gastrointestinal Cancer Treatment and Cellular Senescence

wu2011Peter C. Wu, MD Assistant Professor Advanced gastrointestinal (GI) cancers treated with chemotherapy and radiation exhibit disappointingly low 5–30% complete response rates. The majority of tumors are limited to only partial responses, and surgery continues to be the mainstay treatment for most GI cancers despite poor overall survival rates. For example, chemoradiotherapy for advanced rectal cancer often results in detectable tumor volume reduction following early treatment, but is often succeeded by tumor progression despite additional therapy. Complete Research Report >>