chondroitin-sulfates and Infections

Glycosaminoglycans (GAGs) are complex polysaccharides, which play important roles in cell growth, differentiation, morphogenesis, cell migration, and bacterial/viral infections. Major GAGs include heparin (Hep)/heparan sulfate, and chondroitin sulfate (CS)/dermatan sulfate (DS). Hep has been used for the treatment of thromboembolic disorders for more than 75 years, and has an established position in therapy today. CS/DS has attracted less attention and its clinical use is limited. However, CS/DS also have intriguing biological activities, which in turn should help in the development of CS/DS-based therapeutics. In this review, the following potential applications of CS/DS chains are discussed. (1) Sugar drugs for parasitic and viral infections. Particular CS variants appear to be involved in infections of various microbes, suggesting that CS/DS oligosaccharide sequences specifically interacting with microbes will lead to the development of inhibitory drugs for these infections. (2) Regenerative medicine. Biological activities of CS/DS chains possibly involve various growth factors, also known as Hep-binding growth factors. Specific CS/DS chains recruit growth/neurotrophic factors and/or potentiate their activities, suggesting that minute amounts of functional CS/DS chains can be utilized for tissue regeneration instead of signaling proteins. (3) Anti-tumor drugs. Specific saccharide structures in CS/DS chains appear to be involved in tumor cell proliferation and metastasis. The detection and identification of such CS/DS saccharide sequences would be an important contribution to cancer therapy.

Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Chondroitin Sulfates; Dermatan Sulfate; Drug Discovery; Glycosaminoglycans; Humans; Infections; Liver Regeneration; Neoplasms; Neurodegenerative Diseases; Osteoarthritis

The diabetic foot ulcer presents a therapeutic challenge with a high rate of limb infection and extremity amputation. Adequate debridement and stable coverage of exposed structures are paramount to preserving limb length. The authors reviewed their use of a collagen bilayer matrix in the diabetic population for the preservation of functional limb length. Salvage rates were stratified with patient comorbidities of severe peripheral arterial disease and/or persistent infection.. A retrospective review was performed of all consecutive patients who underwent application of Integra by the senior authors (J.S.S., C.E.A.) for lower extremity salvage between January of 2004 and December of 2008.. A total of 105 patients with 121 separate wounds were analyzed. Patient age ranged from 22 to 80 years (mean, 58 years). The average wound size was 25.9 cm2 in the diabetic population. Average follow-up was 325 days, and average number of operations before closure was 1.28. In the diabetic population, of the 59 patients identified as low risk for amputation, 10 (17 percent) progressed to amputation. Of the 28 patients identified as high risk for amputation, 15 (54 percent) progressed to amputation. In the nondiabetics, 31 patients were classified as low risk for amputation, and one (3 percent) went on to an amputation.. Use of a collagen bilayer matrix appears to be a viable option for reconstruction and stable closure in the diabetic patient at low risk for amputation, with risk based on available blood supply and evidence of infection. In the diabetic patient at high risk for amputation, however, the rate of salvage may not be improved with the use of Integra.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Chondroitin Sulfates; Collagen; Debridement; Diabetic Foot; Humans; Infections; Limb Salvage; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Risk Factors; Young Adult