However the sustained levels are unlikely with intravenous dosing of heparin although subcutaneous administration of contaminated heparin may have allowed for higher local levels of OSCS. A veterinary drug, polysulfated glycosaminoglycan that is very similar in structure to OSCS is still used in animals and administered locally. PSGAG is also a polysulfated chondroitin sulfate with 3 to 4 sulfate groups per disaccharide unit and is considered to be a disease-modifying veterinary drug for osteoarthritis. PSGAG is anti-inflammatory and many mechanisms have been postulated from preservation of joint glycosaminoglycans to inhibition of PGE2 synthesis, toxic oxygen radical generation, and complement activation. Studies have shown an impact of PSGAG at relatively higher doses on complementmediated lysis of red blood cells without a clear mechanism of action. Our in vitro experiments using bacteria as model indicate PSGAG is a very strong Maytansinol inhibitor of complement fixation of bacteria. The potentiation of C1inh interaction with C1s by OSCS can also explain the effect of PSGAG on complement lysis and provide a mechanism for studies suggesting an increased likelihood of infections with intra-articular injection of PSGAG and low levels of bacteria. Although there was an increase in the absolute numbers of infections reported during the 2007�C2008 timeframe of the OSCS contamination, the relative numbers decreased. It may be of value to further assess GAG EMD638683 R-Form related products including PSGAG, for infection related adverse events, although adverse event reporting has many limitations. Based on the concentrations heeded to inhibit complement, there may not be an in vivo effect unless high doses are administered locally rather than systemically. There have been suggestions that glycosaminoglycans can be used to inhibit the complement activity in situations such as autoimmune diseases. PSGAG treatment of animal arthritis is an example of such a use for a GAG. As PSGAG is not administered intravenously, a kallikrein mediated adverse effect, such as seen with OSCS contaminated heparin, may be less likely. A human version of such a product was marketed in Europe and withdrawn. Heparin has recently been shown to prevent fetal loss
