Anti-proteolytic effect

On the basis of this anti-proteolytic effect of sialic acids, a hypothetical model435 for the role of sialidase in clostridial infections is shown in Scheme 4. It is considered that the bacterial enzyme releases sialic acids from cell-surface glycoproteins of the infected tissue, which thereafter can be readily attacked by proteases. This cooperation between sialidase and protease may support the spreading of the bacteria. Acylneuraminate pyruvate-lyase, also shown in this model, degrades sialic acids for energy supply, and growth, of the bacteria. 

Bikunin (Bik), a peptide excreted in the urine, is one of the primary inhibitors of the trypsin family of serine proteases. This peptide plays a key role in inflammation and innate immunity because of its two Kunitz-type binding domains [1, 2], Bik suppresses proteolytic activity in a variety of tissues and can also exert localized anti-inflammatory effect [3-5], Inflammation is an important indicator of infection, cancer, and tissue injury in acute and chronic states. In acute inflammation, fluids and plasma components accumulate in the affected tissues due to vascular dilation. Subsequent activation of platelets and increased presence of immune cells occur during repair. Long-standing inflammation may be present before the disorder is identified. Due to its inhibitory role and potential use as an early marker of inflammation, we will review the synthesis, structure, pathophysiology of Bik as well as the various approaches for its measurement in this chapter. 

Tarayre JP, Lauressergues H. The anti-edematous effect of an association of proteolytic enzymes, flavonoids, sterolic heteroside of Ruscus aculeatus and ascorbic acid. Ann Pharm Fr 37(5-6), 191-198, 1979. in French. 

Purification entails use of an immunoaffinity column containing immobilized murine antifactor VII antibody. It is initially produced as an unactivated, single chain 406 amino acid polypeptide, which is subsequently proteolytically converted into the two-chain active factor Vila complex. After sterilization by filtration, the final product is aseptically filled into its final product containers and freeze-dried. The excipients present in the product include sodium chloride, calcium chloride, polysorbate 80, mannitol and glycylglycine. When freeze-dried in the presence of these stabilizing substances and stored under refrigerated conditions, the product displays a shelf-life of at least 2 years. It has proved effective in the treatment of serious bleeding events in patients displaying anti-factor VIII or IX antibodies. 

The anti-inflammatory mechanisms whereby corticosteroids exert their beneficial effect in COPD include (1) reduction in capillary permeability to decrease mucus, (2) inhibition of release of proteolytic enzymes from leukocytes, and (3) inhibition of prostaglandins. Unfortunately, the clinical benefits of systemic corticosteroid therapy in the chronic management of COPD are often not evident, and the risk of toxicity is extensive and far-reaching. Currently, the appropriate situations to consider corticosteroids in COPD include (1) short-term systemic use for acute exacerbations and (2) inhalation therapy for chronic stable COPD. 

The concept of a proteolytic mechanism in the production of inflammatory manifestations is supported by the demonstration of anti-inflammatory activity in various protease inhibitors, e.g. the trypsin inhibitors of the pancreas, soya bean, ovomucoid and potato . It is interesting to note that the inhibitor from potatoes exerts its effect even after the inflammation is well established , suggesting that protease action is a continuing feature of inflammation and not simply an initiating process. Various esterase inhibitors (dyflos, quinine, quinidine and chloroquine) also reduce capillary permeability induced by heat and the permeability globulins . 

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