Saturday, May 1, 2010

Hyaluronic acid (sodium hyaluronate)

Hyaluronic acid (hyaluronate) is a naturally-occurring polysaccharide containing alternating N-acetyl-D-glucosamine and D-glucuronic acid monosaccharide units linked with beta 1-4 bonds and the disaccharide units linked with beta 1-3 glycoside bonds. It is a straight-chained polymer with a molecular weight varying between 50,000 and 13,000,000 Da, depending on the source from which it is obtained and the methods of preparation and determination used. Hyaluronic acid belongs to the group of glycosaminoglycans which also includes compounds containing sulfate groups (chondroitins, keratans and the heparans). Hyaluronic acid is a critical component of connective tissue and typically exists in a state of strong association with proteins and other glycosoaminoglycans such as heparin and chondroitin sulfate. It is one of the chief components of the extracellular matrix, contributes significantly to cell proliferation and migration, and may also be involved in the progression of some malignant tumors. Hyaluronic acid is naturally present in the pericellular gels, in the fundamental substance of connective tissue and in vertebrate organisms, of which it is one of the chief components, in the synovial fluid of joints, in the vitreous humor, in the human umbilical cord tissues and in rooster combs.

Health benefits of hyaluronic acid


Hyaluronic acid plays a vital role in many biological processes such as tissue hydration, proteoglycan organisation, cell differentiation, proliferation and angiogenesis. Hyaluronic acid plays a fundamental role in tissue repair processes, especially in
the first stages of the process of the formation of granulation tissue, by stabilizing the coagulation matrix and controlling its degradation, favoring the recruitment of inflammatory cells, such as polymorphonucleocytes and monocytes, of mesenchymal cells, such as fibroblasts and endothelial cells, and directing the subsequent migration of epithelial cells.

Administration of hyaluronic acid by intraarticular injection has been shown to be effective in the treatment of osteoarthritis. Osteoarthritis is characterized by a progressive loss of the particular cartilage of synovial joints with concomitant bony changes, including sclerosis and osteophyte formation. This is due not only to the unique viscoelastic properties of hyaluronic acid but also to its potential pharmacological properties. In the healthy knee joint, hyaluronic acid is present both in the cartilage covering the ends of bone and in the synovial joint fluid. The HA of the synovium is produced primarily by the synoviocytes that line the intima layer of the synovium, and proteins and nutrients that are drawn from the lymphatic system. The synovial fluid is a liquid form of an extracellular matrix that maintains the synovium volume and hydrostatic pressure, provides chondrocytes in the avascular particular cartilage with a steady flow of nutrients, lubricates the cartilage surface, and cushions the synovial tissue from the deforming forces of movements.

Its natural occurrence in the body and its ability to retain water have lead to the development and use of hyaluronic acid for various other therapeutic applications, e.g., the use of hyaluronic acid as a vitreous humor substitute, the prevention or inhibition of adhesions following surgery, and the protection of wounds during healing. Hyaluronan is also now a common skin care ingredient. In skin tissue, hyaluronic acid helps transport of essential nutrients from the bloodstream to living skin cells, hydrates the skin by retaining water, and acts as a cushioning and lubricating agent against mechanical and chemical damage. Since 2003 the FDA has approved hyaluronan injections for filling soft tissue defects such as facial wrinkles. These products are analgous to collagen injections but have the advantages of longer lasting effects and decreased risk of allergic reaction.

Hyaluronic acid may also be used postoperatively to induce tissue healing, notably after cataract surgery. Current models of wound healing propose that larger polymers of hyaluronic acid appear in the early stages of healing to physically make room for white blood cells, which mediate the immune response. In some cancers, hyaluronic acid levels correlate well with malignancy and poor prognosis. Hyaluronic acid is thus often used as a tumor marker for prostate and breast cancer. It may also be used to monitor the progression of the disease. Hyaluronic acid is effective in decreasing the adverse effects of autoimmune disease where the disease is mediated by T cells.

Sources of hyaluronic acid


Hyaluronic acid is widely distributed in animal tissues, present in high concentrations in synovial fluid and the vitreous body of the eye, and in connective tissues of rooster comb, umbilical cord, and dermis. Hyaluronic acid is commercially available and is prepared from the intracellular matrices of animal connective tissue, such as rooster combs and bovine tissue sources, mammalian umbilical cords, and bacterial organisms such as streptococcus zoepidicus. Hyaluronic acid is obtainable not only by extraction from cockscombs and umbilical cords, but also as purified products from the culture broth of streptococci. Examples of the microorganisms capable of producing hyaluronic acid may include Streptococcus pyogenes, Streptococcus equisimilis, Streptococcus equi, Streptococcus dysgalactiae, Streptococcus zooepidemicus and the like.

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