The ability of some component of human urine to dissolve fibrin clots was first noted in 1885. It was not until the 1950s, however, that the active substance was isolated and named urokinase.

Urokinase is a serine protease produced by the kidney and is found in both the plasma and urine. It is capable of proteolytically converting plasminogen into plasmin. Two variants of the enzyme have been isolated: a 54 kDa species and a lower molecular mass (33 kDa) variant. The lower molecular mass form appears to be derived from the higher molecular mass moiety by proteolytic processing. Both forms exhibit enzymatic activity against plasminogen.

Urokinase is used clinically under the same circumstances as streptokinase; because of its human origin, adverse immunological responses are less likely. Following acute medical events such as pulmonary embolism, the product is normally administered to the patient at initial high doses (by infusion) for several minutes. This is followed by hourly i.v. injections for up to 12 h.

Urokinase utilized medically is generally purified directly from human urine. It binds to a range of adsorbents, such as silica gel and, especially, kaolin (hydrated aluminium silicate), which can be used initially to concentrate and partially purify the product. It may also be concentrated and partially purified by precipitation using sodium chloride, ammonium sulfate or ethanol as precipitants.

Various chromatographic techniques may be utilized to purify urokinase further. Commonly employed methods include anion-exchange (DEAE-based) chromatography, gel filtration on Sephadex G-100 and chromatography on hydroxyapatite columns. Urokinase is a relatively stable molecule. It remains active subsequent to incubation at 60 °C for several hours, or brief incubation at pHs as low as 1.0 or as high as 10.0.

After its purification, sterile filtration and aseptic filling, human urokinase is normally freeze-dried. Because of its heat stability, the final product may also be heated to 60 °C for up to 10 h in an effort to inactivate any undetected viral particles present. The product utilized clinically contains both molecular mass forms, with the higher molecular mass moiety predominating. Urokinase can also be produced by techniques of animal cell culture utilizing human kidney cells or by recombinant DNA technology.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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