Preface - Ous-research.no

Surgical Intensive Care Medicine
Leader:
Ansgar O. Aasen, Professor, MD, PhD (UiO/OUH)
Scientific staff:
Ola Sveen, Prof., MD, PhD (UiO)
Tom Erik Ruud, Senior scientist, MD, PhD (OUH)
Yngvar Gundersen, Senior scientist, MD, PhD (OUH)
Claus Danckert Krohn, Consultant, MD, PhD (OUH)
Johanna Samulin-Erdem, Senior scientist, PhD (OUH)
David Kunke, Senior scientist, PhD (OUH)
Kristin Bjørnland, Consultant, MD, PhD (OUH)
Yun Yong Wang, MD, PhD (OUH)
Claus Vinter Bødker Hviid, MD, PhD-student (OUH)
Signe Flood Kjeldsen, Research engineer, MSc (UiO)
Research area
Infections following surgery or trauma continue to be a
major clinical problem. Due to the immunological consequences
of surgery, infections frequently develop into severe
septic complications and multiple organ injuries. The problem
in severe sepsis is a paradoxical and self-destructing
inflammation leading to dysfunctional host defense and
lethal injury to vital organ systems.
More than one million patients are expected to die annually
from severe sepsis world wide.
Aims
Our aim is to develop novel means to prevent or ameliorate
the self-destructive inflammation in patients with infection.
A major focus of our work is research into the cellular
mechanisms involved.
Ongoing Projects in 2010:
Molecular mechanisms in the development of sepsis-induced
Multiple organ dysfunction
Sepsis remains a challenging problem in intensive care
medicine. Much is known about the immune-pathophysiological
mechanisms in sepsis, but the mechanisms behind
sepsis-induced organ failure are still a matter of debate.
The clinical outcome of sepsis is directly correlated to the
number of organs failing, as the mortality inclines from 25%
in single organ failure to above 72% with failure of three or
more organs.
Professor Ansgar O. Aasen
To address this critical aspect of sepsis two novel projects to
investigate molecular mechanisms involved in the development
of sepsis-induced organ failure, have been initiated.
CCN proteins in the development of sepsis-induced organ
failure
The CCN proteins belong to a group of extracellular matrix
(ECM)-associated proteins that have emerged as potential
candidates in the regulation of parenchyma function.
The protein family has a regulatory rather than structural
role in the ECM and includes the six proteins CCN1 (Cyr61),
CCN2 (CTGF), CCN3 (NOV), CCN4 (Wisp-1), CCN5 (Wisp-2)
and CCN6 (Wisp-3). Their synthesis is induced by multiple
factors including serum growth factors, cytokines, steroids,
hypoxia, and mechanical and environmental stressors. The
proteins function primarily through interaction with cell adhesion
receptor integrins, which allows for variation in the
response due to integrin subtype specific effects in different
cell types. The role of CCN proteins in the development of
sepsis-induced organ failure has not been investigated.
Research has previously worked with the role of CCN2 in
development of liver fibrosis as well as the roles of several
CCN proteins in the development of cardiovascular failure.
However, possible roles of these proteins have also been
indicated during acute lung and kidney injury. Interestingly,
the CCN proteins also affect inflammatory responses by
modulating the production of cytokines and reactive oxygen
species, and by stimulating adhesion and migration of
lymphocytes and monocytes/macrophages.
Initial studies have been conducted in two different rodent
models of abdominal sepsis induced by cecal ligation and
puncture (CLP). In a short-term model using male wistar
rats the animals were divided in three groups; Baseline,
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