The Department of Surgery at the University of Texas Medical School at Houston
Department of Surgery
Basic Science

Basic Science Research

 


Nucleotides

Nucleotides are structural units of RNA associated with metabolism. Dr. Van Buren has ongoing investigations in the use of dietary nucleotides to maintain host immunity, to maintain normal intestinal maturation, and to enhance wound healing with topical application of nucleotides. These experiments over the past thirty years have resulted in five patents, including the one commercialized patent for Impact, marketed by Novartis Nutrition.

Dietary nucleotides are required for maintenance of T cell-mediated immunity and resistance against infection.  Bioavailability of dietary nucleobases is limited, since only 5% of labeled adenine and approximately 10% of labeled pyrimidines are absorbed intact following oral administration.  Since T-lymphocytes are important in normal wound healing, the topical use of nucleotides or nucleosides to a wound may increase local availability of these substrates to enhance lymphocyte function and speed healing.5  The macrolide immunosuppressant sirolimus has been documented clinically to delay healing of surgical wounds, possibly due to inhibition of vascular endothelial growth factor (VGEF) production.  Pre-treatment with sirolimus could prove useful to establish an animal model of delayed wound healing secondary to defective angiogenesis. 

Publications

Kulkarni, A.D., Fanslow, W.C., Peng, C., Rudolph, F.B. and Van Buren, C.T.: Similarity of immunosuppression due to cyclosporine-A and nucleotide free diet. Fed. Proc. 44:1149, 1985.

Fanslow, W.C., Kulkarni, A.D., Peng, C., Rudolph, F.B. and Van Buren, C.T.:  Suppression of cell-mediated immune response in mice by a nucleotide-free diet:  effects on suppressor and helper cell activity.  Fed. Proc. 44:1708, 1985.

Van Buren, C.T., Kulkarni, A.D., Fanslow, W.C. and Rudolph, F.B.:  Nucleotide deprivation enhances bacterial sepsis.  J.P.E.N. 9(1):117, 1985.

Kulkarni, A.D., Martin, J., Kumar, S., Rudolph, F.B., and  Van Buren, C.T.:  Nucleotide dependent immunosurveillance function in mice.  J. Leuk., Biology, Supplement 1:131, 1990.

Bower R, Cerra F, Bershasley B, Licari J, Hoyt D, Jensen G, Van Buren C.T., Rothkopf M, Daly J, Adelsberg B.  Early enteral administration of a formula (Impact) supplemented with arginine,    nucleotides, and fish oil in intensive care unit patients: Results of a multicenter prospective,        randomized clinical trial.  Critical Care Medicine 23(3):436-449, 1995.

Van Buren, C.T. and Rudolph, FJ: “Dietary Nucleotides: A Conditional Requirement”, Nutrition        13:470-472, May, 1997.

Van Buren CT:  Letter to the Editor – Comment on “Arginine immunonutrition in critically ill patients. Am J Crit Care 13(4):290, July 2004.

Kahan BD, Stepkowski S. Kilic M, Katz SM, Van Buren CT, Welsh MS, Tami JA and Shanahan WR Jr.  Phase I and phase II safety and efficacy trial of intercellular adhesion molecule-1 antisense oligodeoxynucleotide (ISIS 2302) for the prevention of acute allograft rejection. Transplantation. 78(6):858-63,  September 2004.

Knight RJ, Villa M, Laskey R, Benavides C, Schoenberg L, Welsh M, Kerman RH, Podder H, Van Buren CT, Katz SM, Kahan BD: Risk factors for impaired wound healing in sirolimus-treated renal  transplant recipients. Clin Transplant; 21(4):460-5, 2007.