Malnutrition is associated with increased morbidity and mortality, especially when associated with trauma and infection. Impairment of one of a hosts' defense systems, the reticuloendothelial system, is seen in experimental starvation. Fibronectin, an opsonic glycoprotein, modulates R.E.S. phagocytic activity and has been noted to be adversely affected by starvation. Deficient plasma fibronectin impairs R.E.S. phagocytic function and is associated with decreased resistance to trauma and sepsis. It has been proposed that starvation induced fibronectin deficiency could be a major factor leading to the increased morbidity and mortality associated with malnutrition. This study proposes to assess the effects of different nutrients and their deficiencies on fibronectin and R.E.S. activity in the rat under different experimental conditions. Specifically, 1) the effects of various protein and glucose levels in the diet, and 2) the effects of vitamin A deficiency and excess on fibronectin and R.E.S. activity will be examined. Vitamin A was selected for this study because recent investigations reveal that vitamin A promotes cell-surface fibronectin. R.E.S. function will be assessed by a gelatinized lipid clearance test which measures R.E.S. phagocytic function of the test lipid and clearance from the blood. R.E.S. function will also be tested by measuring clearance of the Staphylococcus aureus from the blood in a septic animal subjected to various dietary protein and glucose levels or various dietary vitamin A levels. Fibronectin will be measured by both an immunoassay which measures protein quantity and a bioassay which measures functional opsonic activity. An R.E.S. blockade test which acutely depletes plasma fibronectin levels will be employed to test the ability of the animal to recover fibronectin levels while the animal is subjected to the various dietary regimens. Finally, the effect of vitamin A on tissue fibronectin levels will be assessed. The goal of this proposal is to test the effect of various nutrients and their deficiencies on fibronectin and R.E.S. activity in the hopes of being able to improve R.E.S. function through nutritional intervention, and therefore, improve the survival of the malnourished patient.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R23)
Project #
5R23GM032839-02
Application #
3447866
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Albany Medical College
Department
Type
Schools of Medicine
DUNS #
City
Albany
State
NY
Country
United States
Zip Code
12208