Combination of insulin and ascorbate to enhance wound healing

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Scleroproteins – e.g. – fibroin – elastin – silk – etc.

Reexamination Certificate

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C424S078060

Reexamination Certificate

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07834153

ABSTRACT:
Provided is a method of stimulating collagen synthesis and proteoglycan (lumican and keratocan) accumulation. Collagenase isolated keratocytes were cultured with or without insulin with or without ascorbate. Insulin stimulates the synthesis of collagen but does not affect the accumulation of lumican and keratocan. Insulin plus ascorbate, however, stimulates the synthesis of collagen and increased the accumulation of these proteoglycans. The accumulation of PGDS, a KSPG that does not interact with collagen, is not affected by ascorbate. Only the collagen made in the presence of ascorbate was pepsin resistant. EDB overrode the effects of ascorbate on pepsin resistance and proteoglycan accumulation.

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Madibally, S. V., Solomon, V., Mitchell, R. N., Van De Water, L., Yarmush, M. L., and Toner, M. 2003. Influence of Insulin Therapy on Burn Wound Healing in Rats. Journal of Surgical Research vol. 109, pp. 92-100.
Brodovsky, S. C., Mccarty, C. A., Snibson, G., Loughnan, M., Sullivan, L., Daniell, M., and Taylor, H. R. 2000. Management of Alkali Burns an 11-Year Retrospective Review. Ophthalmology. vol. 107. pp. 1829-1835.
Ramirez, R. J., Wolf, S. E., Barrow, R. E., and Herndon, D. N. 1998. Growth Hormone Treatment in Pediatric Burns: A Safe Therapeutic Approach. Annals of Surgery vol. 228. No. 4, pp. 439-448.
Pierre, E. J., Barrow, R. E., Hawkins, H. K., Hal, K., Nguyen, T. T., Sakuri, Y., Desai, M., Wolfe, R. R., and Herndon, D. N. 1998. Effects of Insulin on Wound Healing. The Journal of Trauma, Injury, Infection and Critical Care. vol. 44(2), pp. 342-345.
Whitson, S. W., Whitson, M. A., Bowers, Jr D. E. And Falk, M. C. 2004. Factors Influencing Synthesis and Mineralization of Bone Matrix from Fetal Bovine Bone Cells Grown In Vitro. Journal of Bone and Mineral Research. vol. 7, No. 7. Alton, IL.
Qutob, S., Dixon, S. J., and Wilson, J. X. 1998. Insulin Stimulates Vitamen C Recycling and Ascorbate Accumulation in Osteoblastic Cells. Endocrinology. vol. 139. No. 1. United States.
Libby, P. and O'Brien, K. V. 1983. Culture of Quiescent Arterial Smooth Muscle Cells in a Defined Serum-Free Medium. J Cell Physiol. vol. 115, No. 2. United States.
Prehm, P., Dessau, W., and Timpl, R. 1982. Rates of Synthesis of Basement Membrane Proteins by Differentiating Teratocarcinoma Stem Cells and Their Modulation by Hormones. Connect Tissue Res. vol. 10, No. 3-4. England.
Guerriero, E., Chen, J., Sado, Y., Mohan, R. R., Wilson, S., Funderburgh, J. L., and Sundarraj, N. 2007. Loss of Alpha3(IV) Collagen Expression Associated with Corneal Keratocyte Activation. Investgative Ophthalmology & Visual Science. vol. 48, No. 2 United States.
Provenzano, P. P., Alejandro-Osorio, k, Grorud, K. W., Martinez, D. A., Vailas, A. C., Grindeland, R. E., Vanderby Jr., R. 2007. Systemic Administration of IGF-I Enhances Healing in Collagenous Extracellular Matrices: Evaluation of Loaded and Unloaded Ligaments. BMC Physiology vol. 7:2.
Saragas, S., Arffa, R., Rabin, B., Kronish, J., Miller, D., and Mayman, C. 1985. Reversal of Wound Strength Retardation by Addition of Insulin to Corticosteroid Therapy. Ann Ophthalmol 17(7):428-30.
Madibally, S. V., Solomon, V., Mitchell, R. N., Van De Water, L., Yarmush, M. L., and Toner, M. 2003. Influence of Insulin Therapy on Burn Wound Healing in Rats. Journal of Surgical Research vol. 109, pp. 92-100.
Brodovsky, S. C., Mccarty, C. A., Snibson, G., Loughnan, M., Sullivan, L., Daniell, M., and Taylor, H. R. 2000. Management of Alkali Burns an 11-Year Retrospective Review. Ophthalmology. vol. 107. pp. 1829-1835.
Ramirez, R. J., Wolf, S. E., Barrow, R. E., and Herndon, D. N. 1998. Growth Hormone Treatment in Pediatric Burns: A Safe Therapeutic Approach. Annals of Surgery vol. 228. No. 4, pp. 439-448.
Pierre, E. J., Barrow, R. E., Hawkins, H. K, Hal, K, Nguyen, T. T., Sakuri, Y., Desai, M., Wolfe, R. R., and Herndon, D. N. 1998. Effects of Insulin on Wound Healing. The Journal of Trauma, Injury, Infection and Critical Care. vol. 44(2), pp. 342-345.

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