Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bioreactors often contain porous particles of agarose because these provide an enormous surface area (50 m2/cc gel) onto which enzymes or antibodies can be immobilized. Although many investigators claim that contact with agarose induces significant blood damage, we find that the biocompatibility of immobilized agarose is significantly improved when a novel system is used to fluidize the particles within the bioreactor vessel. We have built a prototype device that is oscillated vigorously about the axis of fluid flow. This action produces secondary flow patterns within the vessel that suspend the particles. In our model system, the bioreactor contains agarose immobilized heparinase. The system is biocompatible for 2 hours in vitro (in human blood at 37 degrees C) as follows: 1) hematocrit, white cell, and platelet counts do not change, 2) levels of plasma hemoglobin increase to 15-34 mg/dl, and 3) levels of complement component C3a increase to 0.64-1.4 micrograms/cc. We hope these studies lead to the development of a heparin removal system that can improve the safety of a variety of extracorporeal procedures. In addition, the techniques and approach used are sufficiently general to permit their extension to any immobilized species bioreactor for blood detoxification.
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PMID:A novel bioreactor based on suspended particles of agarose-immobilized species. 319 92

Extracorporeal medical devices such as the hemodialyzer rely on systemic heparinization to prevent thrombus formation. Heparin, however, can lead to serious hemorrhagic complications. A blood filter containing immobilized heparinase, a heparin specific enzyme, was used to degrade heparin into small fragments which have significantly less anticoagulant activity than the parent compound. The heparinase filter was tested in the extracorporeal circuit during the hemodialysis of adult sheep. At a blood flow of 200 ml/min, the clearance of heparin varied from 50 to 70 ml/min (N = 16) depending on the amount of immobilized heparinase in the filter. Hemolysis was insignificant as measured by the animals' red cell counts, hematocrit, total hemoglobin and a plasma-free hemoglobin value of 89 +/- 33 mg/dl (N = 16) (less than 1% of the total hemoglobin). The white cell counts dropped to 47 +/- 7% (N = 16) of the initial value at 20 minutes and rebounded to 72 +/- 10% (N = 16) after one hour. The platelet counts decreased to 55 +/- 8% (N = 16) of the initial value after one hour. No change in heparin clearance was observed when reactors were used repeatedly in adult sheep over a 10 week period. The red cell counts, white cell counts, platelet counts, total hemoglobin and hematocrit did not change after 10 weeks of exposure to the device. These results suggest that with further study, heparinase may be useful in removing heparin used to anticoagulate blood in extracorporeal circuits.
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PMID:Extracorporeal enzymatic heparin removal: use in a sheep dialysis model. 343 Sep 48

Efficient and safe heparin anticoagulation has remained a problem for continuous renal replacement therapies and intermittent hemodialysis for patients with acute renal failure. To make heparin therapy safer for the patient with acute renal failure at high risk of bleeding, we have proposed regional heparinization of the circuit via an immobilized heparinase I filter. This study tested a device based on Taylor-Couette flow and simultaneous separation/reaction for efficacy and safety of heparin removal in a sheep model. Heparinase I was immobilized onto agarose beads via cyanogen bromide activation. The device, referred to as a vortex flow plasmapheretic reactor, consisted of two concentric cylinders, a priming volume of 45 ml, a microporous membrane for plasma separation, and an outer compartment where the immobilized heparinase I was fluidized separately from the blood cells. Manual white cell and platelet counts, hematocrit, total protein, and fibrinogen assays were performed. Heparin levels were indirectly measured via whole-blood recalcification times (WBRTs). The vortex flow plasmapheretic reactor maintained significantly higher heparin levels in the extracorporeal circuit than in the sheep (device inlet WBRTs were 1. 5 times the device outlet WBRTs) with no hemolysis. The reactor treatment did not effect any physiologically significant changes in complete blood cell counts, platelets, and protein levels for up to 2 hr of operation. Furthermore, gross necropsy and histopathology did not show any significant abnormalities in the kidney, liver, heart, brain, and spleen.
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PMID:Ex vivo evaluation of a Taylor-Couette flow, immobilized heparinase I device for clinical application. 1005 45