Hyaluronidase tissue

The second type of material includes spores, which may or may not produce disease symptoms but which can germinate in the insect gut and give rise to vegetative bacterial cells which in turn may produce, and exoenzymes such as phospholipases (lecithinases) or hyaluronidase. The phospholipases may produce direct toxic symptoms owing to their action on nervous or other phospholipid-containing tissue. Hyaluronidase breaks down hyaluronic acid and produces effects on animal tissue which are morphologically similar to the breakdown of insect gut wall in the presence of microbial insecticide preparations. 

Collagenases and hyaluronidases are produced by most of the aggressive invaders. These are able to dissolve eollagen fibres and hyaluronie aeids which function as intracellular cements. Their loss causes the tissues to breakup and produce oedematous lesions. 

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. 

Extravasation Extravasation of IV hypertonic solutions of sodium bicarbonate may cause chemical cellulitis (because of their alkalinity), with tissue necrosis, ulceration, or sloughing at the site of infiltration. Prompt elevation of the part, warmth, and local injection of lidocaine or hyaluronidase are recommended to prevent sloughing. 

Intramuscular and subcutaneous injections are by far the most common means of parenteral drug administration. Because of the high tissue blood flow and the ability of the injected solution to diffuse laterally, drug absorption generally is more rapid after intramuscular than after subcutaneous injection. Drug absorption from intramuscular and subcutaneous sites depends on the quantity and composition of the connective tissue, the capillary density, and the rate of vascular perfusion of the area. These factors can be influenced by the coinjection of agents that alter local blood flow (e.g., vasoconstrictors or vasodilators) or by substances that decrease tissue resistance to lateral diffusion (e.g., hyaluronidase). 

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). 

Hyaluronidase Local edema (subacute and chronic stage] Appears to increase permeability in connective tissue by hydrolyzing hyaluronic acid, thus decreasing encapsulation and allowing disbursement of local edema Reconstitute with 0.9% sodium chloride to provide a 150 mg/ mL solution from positive pole ... 

Hyaluronidase Hydrolysis of Mammalian testes Renders tissues more... 

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

Boiler et al. [11] demonstrated the presence of hyaluronidase activity in various mammalian tissues. They showed foot this type of hyaluronidase differed from... 

Testicular hyaluronidase is extracted from testicular tissue or semen. The crude material is homogenized and centrifuged. The supernatant is subjected to direct precipitation with (NHjJiSOi rjjji nr tn Krtigntinn with HittjQ X and h niiw. followed by precipitation with ethanol [51] or (NBO2SO4 [52], Harrison, however reported a simple extraction of hyaluronidase from ram semen after... 

De Oliveira et al. explained the effects of hyaluronidase in terms of a reduction of the water content of the ischemic myocardium [107]. Hyaluronidase would reduce the edema during the acute phase following coronary occlusion and thereby reduce the injury. Intramyocardial edema occurs after the occlusion of coronary arteries, resulting in an increased water content of the myocardial tissues. Hyaluronidase produces a faster diffusion of fluids and thereby reduces edema in the damaged area. To examine the effects of hvaluronidase on in fere-... 

Tissues that contain high molecular weight HA are unusually resistant to invasion and penetration.49 Blood vessels are unable to penetrate joint synovium, cartilage, and the vitreous of the eye. It is also unusual for tumor metastases to develop in these structures. It may be the large size of the HA polymer that also protects such structures from invasion by parasites. The mechanism by which such high molecular weight structures resist hyaluronidase degradation, and avoid the rapid HA turnover characteristic of the rest of the body is not known. Potent hyaluronidase inhibitors may be involved, a class of molecules about which little is known. 

Hyaluronan is very metabolically active, with a half-life of 3 to 5 min in the circulation,less than one day in skin, and even in an inert a tissue as cartilage, the HA turns over with a half-life of 1 to 3 weeks.66,67,184 This catabolic activity is primarily the result of hyaluronidases, endoglycolytic enzymes with a specificity in most cases for the ft 1 1 glycosidic bond. 

Hyal-1, an acid-active lysosomal enzyme, was the first somatic hyaluronidase to be isolated and characterized.191,192 It is a 57 kDa single polypeptide glycoprotein that also occurs in a processed 45 kDa form, the result of two endoprotease reactions. The resulting two chains are bound by disulfide bonds. This is not a zymogen-active enzyme relationship, since the two isoforms have similar specific activities. Why two forms should occur is unknown. Only the larger form is present in the circulation, while both isoforms occur in urine,193 in tissue extracts, and in cultured cells. Why an acid-active hyaluronidase should occur in plasma is not clear. Some species do not have detectable enzymatic activity in their circulation,194 but an inactive 70 kDa precursor form of the enzyme is present in such sera, detectable by Western blot (L. Shifrin, M. Neeman, and R. Stern, unpubl. data). Hyal-1 is able to utilize HA of any size as substrate, and generates predominantly tetrasaccharides. 

Cultured cells secrete hyaluronidases into the culture media, away from the cells. Such a phenomenon does not occur within tissues. The production of unopposed hyaluronidase activity would cause great havoc in tissues. Simultaneous deposition of hyaluronidases and their inhibitors is a reasonable scenario, one that parallels control of the matrix metalloproteinases by their TIMPs (tissue inhibitors of MMPs). 

Since protein complex formation and Ca2+ are critical to cell fixation within a tissue, dissociation media usually contain some type of proteolytic enzyme and the Ca2+ chelator, EDTA. The proteolytic enzyme can be of general specificity, such as trypsin, or can be a more targeted enzyme, such as a collagenase selective for the collagen-type characteristic of the tissue of interest. Hyaluronidase has been also used with matrix rich in hyaluronic acid, such as for isolation of duodenal entero-cytes. In all cases, the appropriate incubation times and concentrations to achieve cell dispersal, but retain high viability, need to be determined empirically. One factor... 

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. 

---