We recently established that fasted young, male ferrets, fed small amounts of arginine deficient (AD) diet develop hyperammonemia and encephalopathy within 2-3 hours. When infected intranasally with influenza B virus before fasting, such ferrets exhibited an extended and more severe encephalopathy with higher mortality rates. Aspirin treatment of infected ferrets, followed by AD diet caused rapidly developing encephalopathy progressing to coma and usually death. Many of the clinical, metabolic and histopathological disorders, commonly observed in Reye's Syndrome (RS) were noted in these ferrets. Using the conditions described, we have produced an animal model for RS. We plan to (1) further characterize the model, (2) identify and study the mechanism of action of host and environmental factors that can influence the duration, severity and outcome of the induced animal disorders, (3) determine the sequence of biochemical and histopathological changes associated with the development of animal disorders, (4) test various RS-related viruses and viral strains to determine whether severity of their effect on the model are related to other viral characteristics and to quantitative aspects of infection, including tropism, and (5) use the animal work to guide patient studies designed to improve diagnosis and management and to test treatment protocols.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020236-03
Application #
3129753
Study Section
Experimental Virology Study Section (EVR)
Project Start
1983-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Deshmukh, D R; Meert, K; Sarnaik, A P et al. (1991) Guanidino compound metabolism in arginine-free diet induced hyperammonemia. Enzyme 45:128-36
Deshmukh, D R; Singh, K R; Meert, K et al. (1990) Failure of L-carnitine to protect mice against hyperammonemia induced by ammonium acetate or urease injection. Pediatr Res 28:256-60
Deshmukh, D R; Mungre, S M (1989) Purification and properties of 2-aminoadipate: 2-oxoglutarate aminotransferase from bovine kidney. Biochem J 261:761-8
Deshmukh, D R; Rusk, C D (1989) Effects of arginine-free diet on urea cycle enzymes in young and adult ferrets. Enzyme 41:168-74
Deshmukh, D R; Shope, T C; Sarnaik, A P (1987) Serum isocitrate dehydrogenase activity in Reye's syndrome. Biochem Med Metab Biol 37:255-7
Thomas, P E; Deshmukh, D R (1986) Effect of arginine-free diet on ammonia metabolism in young and adult ferrets. J Nutr 116:545-51
Deshmukh, D R; Thomas, P E; McArthur, B et al. (1985) Serum glutamate dehydrogenase and ornithine carbamyl transferase in Reye's syndrome. Enzyme 33:171-4
Deshmukh, D R; Thomas, P E (1985) Arginine deficiency, hyperammonemia and Reye's syndrome in ferrets. Lab Anim Sci 35:242-5
Deshmukh, D R (1985) Animal models of Reye's syndrome. Rev Infect Dis 7:31-40