Hyaluronidases spreading

Hyaluronidase and streptokinase are produced by the haemolytic streptococci and enable the organism to spread rapidly through the tissue. Hyaluronidase dissolves hyaluronic acid (intercellular cement), whereas streptokinase (Chapter 25) dissolves blood clots. 

Hyaluronidase is the antidote of choice for vinca alkaloid and high-concentration epipodophyllotoxin extravasations. Hyaluronidase breaks down hyaluronic acid, which functions as tissue cement. This promotes absorption of the extravasated drug away from the local site. Hyaluronidase also may be used for paclitaxel extravasations, but there are conflicting reports regarding its efficacy.39 Hyaluronidase should not be used with anthracycline extravasations because enhancement of local spread may occur. 

The action of spreading factors, e. g., hyaluronidases on hyaluronic acid both in vivo and in vitro is often quite dramatic, and the effect in vitro appears to go in three stages (a) a separation of the protein residue ... 

By constricting the vascular bed, such coadministered vasoactive excipients as epinephrine can reduce the rate of uptake from the SC sites (4a). By contrast, the excipient hyaluronidase breaks down the interstitial barrier by lysing hyaluronic acid, a polysaccharide that helps form the intercellular ground substance of connective tissue (4b). This in effect spreads the injected drug solution over a larger area of connective tissue, increasing the absorption surface, and thereby increasing both the volume that can normally be injected SC (Table 1) and the rate of uptake (6). 

Phospholipase A Hyaluronidase Increased spreading and penetration of tissues... 

A. T. Tu and R. R. Hendon. Characterization of timid venom hyaluronidase and evidence for its action as a spreading factor. Comp. Biochem. PhyxioL 765 377 (1983). 

F-1) Hyalnrotridase cleaves hyaluronic acid. It is produced by certain bacteria and may facilitate their spread through tissue planes. Sometimes hyaluronidase is administered with drug injections to facilitate the spread of the drug through the injected tissues. 

This can be achieved by making a soluble salt of the drug which is rapidly absorbed from the site of administration. In the case of s.c. or i.m. injections the same objective may be obtained with hyaluronidase, an eri2yme which deploymerises hyaluronic acid, a constituent of connective tissue that prevents the spread of foreign substences, e.g. bacteria, drugs. Hyaluronidase combined with an i.m. injection e.g. a local anaesthetic, or a subcutaneous infusion, leads to increased permeation with more rapid absorption. Hyaluronidase can also be used to promote resorp>-tion of tissue accumulation of blood and fluid. 

A 76-year-old man undergoing trabeculectomy developed bilateral amaurosis after a peribulbar block with 6 ml of a mixture of 2% lidocaine, 0.5% bupivacaine, and hyaluronidase (318). The authors thought it unlikely that the optic nerve sheath had been penetrated and suggested that local spread to the optic nerves via the subarachnoid or subdural space had been responsible. 

Hyaluronidase is practically nontoxic, but caution must be exercised in tbe presence of infection because tbc enzyme may cause a local infection to spread, througb tbc same meebanism. It should never be injected in an infected area. Sensitivity to tbe drug is rare. 

In humans, the specific disposition of venom is not well understood. The local distribution of venom is enhanced by the presence of hyaluronidase and other spreading factors found in the venom. Systemic absorption of venom components is likely dependent on lymphatic transport. The onset of local symptoms such as redness and pain may develop within a few hours of the bite. 

Brown Recluse spider venom contains many diverse protein fractions including spreading factors and enzymes such as hyaluronidase, collagenase, protease, phospholipase, and others. These venom components cause coagulation of blood and, ultimately, the occlusion of small blood vessels at the bite site. This leads to local skin and tissue necrosis due to ischemia. Hemolysis of red blood cells may also occur. The normal inflammatory processes that follow, such as edema and hemorrhage, contribute to the tissue damage caused by the venom. 

The wound-healing actions of Echinacea stem from two effects inhibition of hyaluronidase, an enzyme produced by bacteria that enables them to spread throughout a wound, and stimulation of fibroblasts to produce granulation tis-... 

The term hyaluronidase was introduced in 1940 to denote enzymes that degrade hyaluronan. Hyaluronidase has been used by many authors as a synonym for spreading factors." This is only partly correct, as all hyaluronidases act as spreading factors, but not all spreading factors are hyaluronidases [1]. 

Enhanced spreading of injectables hyaluronidase animal testis —... 

A recent paper (Reppert et al., 1951) has drawn attention to the remarkable speed with which ascorbic acid corrects the increased capillary fragility in scurvy. It is argued that this could hardly allow time for the repair of intercellular cement substance and suggests rather a direct chemical or enzymic response. Some experiments, reported in the barest outline, claim to show that ascorbic acid in large doses inhibits the hyaluronidase-hyaluronic reaction in rabbits and, to a small extent, in vitro. It is suggested that this inhibition of the spreading factor may account for the rapid improvement in capillary fragility. Obviously more experimental evidence is needed before this supposition can be seriously considered. 

Hyaluronidase has been reported to elicit an oedematous reaction in the rat [58,160, 352, 353, 487, 534, 563] however, Benditt, Schiller, Mathews and Dorfman [62] showed that the spreading-factor activity and the oedema-producing factor of hyaluronidase are not the same. Other oedema-producing agents include the protein globulin [261, 303, 365,443, 563, 605,606], compound 48/80 [171, 371, 489], duodenal intrinsic factor and partially purified gastric mucin [308], soluble glycogen [10, 303] and Imferon - an iron-dextran complex [198-200, 307]. 

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