ORGOTEIN: a new antiinflammatory metalloprotein drug evaluation of clinical efficacy and safety in inflammatory conditions of the urinary tract

Elaboration of toxic oxygen by-products by neutrophils in a model of immune complex disease.

“…In support of this concept, it has been shown that superoxide dismutase or catalase can prevent depolymerization of synovial fluid by hydroxyl radicals derived from Oas and H202 (40), that injected superoxide dismutase apparently ameliorates inflammation (41)(42)(43), and that PMNs from patients receiving anti-inflammatory corticosteroid therapy may have decreased capacity to reduce the dye nitroblue tetrazolium (44,45), a reaction that depends upon the conversion of oxygen to 02-and, perhaps, other metabolites (10).…”

Superoxide production and reducing activity in human platelets.

“…There are now reports in the literature concerning the use of SOD for therapeutic purposes (50)(51)(52). On the basis of current in vitro (53,54) and in vivo (55) data, it can be speculated that inclusion of SOD in platelet and leukocyte concentrates would dismutate accumulating superoxide radicals and thereby prolong the functional capabilities of these components in the circulation of bleeding and (or) infected patients.…”

Free radicals and inflammation. Protection of phagocytosine leukocytes by superoxide dismutase.

“…2 indicates that a concentration of SOD of 200 /Ag/ml was required to produce a maximal protective effect. Other phenomena thought to proceed by essentially the same mechanism (i.e., hydroxyl radical production via reaction 2) have been approximately 100-fold more sensitive to inhibition by SOD (6,16 (19,20). It is clear that the death of leukocytes and the concomitant or subsequent release of hydrolytic enzymes and chemotactic factors play major roles in the perpetuation of the inflammatory cycle (21).…”

“…The cells of surrounding healthy tissue would, of course, also be subject to serious insult leading to death and lysis, either from primary attack by the radicals in the interstitial fluid or from secondary attack by hydrolytic enzymes released from lysed PMN. By intravenous injection, it may not be possible to maintain the necessary concentration of SOD in the extracellular fluids to protect PMN from their own free radical-induced destruction, since the protein is cleared quite rapidly from the circulation.2 By local injection, however, such a concentration may be realistically achieved at the site of the inflammation (19,20). The preparation of derivatives of SOD with longer circulating half-lives is currently under investigation.…”