Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An experimental model of disc herniation in tail discs of rats is described. Constant result on nucleus hernia and intervertebral narrowing were obtained by an easy manipulation on numerous rats. Intradiscal injection of aprotinin produced a widening of the disc height. Trypsin, collagenase, chymopapain, and hyaluronidase induced a narrowing of disc height; trypsin induced macroscopic necrosis of the soft surrounding tissues; and collagenase had a destructive effect on nucleus pulposus, annulus fibrosus, and even on end-plates. Chymopapain and hyaluronidase acted mainly on nucleus pulposus. Hyaluronidase could be of interest as a nucleolytic drug and needs further studies on optimal dosage and lack of side effects in the surrounding tissues before injecting it into human discs.
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PMID:Experimental model of disc herniations in rats for study of nucleolytic drugs. 244 86

One hundred and twenty-two lumbar intervertebral discs from 43 mongrel dogs were used to study the effect of chemonucleolysis on the flexion, torsion, and lateral bending flexibilities of the disc. The dogs were killed 2, 4, 12, 26, and 52 weeks following injection with 0.1-0.15 ml of either crude collagenase, semipurified collagenase, or chymopapain. Controls consisted of saline-injected and uninjected discs. The bending and torsional properties of each disc were determined by applying incremental moments up to 0.8 Nm and measuring the resultant rotations 60 seconds after each load increment was applied. The discs were then sectioned for morphologic evaluation. Increases in disc flexibilities ranging from 1.4 to 5.8-fold were found 2 weeks after injection with all three enzymes. The largest increase was noted in flexion in discs injected with chymopapain. By 3 months, all lateral bending flexibilities had returned to control values. In general, however, flexion and torsion flexibilities did not return to control values 6 months following chemonucleolysis. The extent of the gross morphologic changes produced by each of the three enzyme preparations did not correlate with the acute increases in disc flexibilities. Chymopapain and semipurified collagenase had similar morphologic and mechanical effects. The temporary increases in flexibility appeared to be due to decreases in the overall compression, tensile and shear stiffness of the annulus caused by the enzymes.
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PMID:The effects of chemonucleolysis on the mechanical properties of the canine lumbar disc. 300 45

In order to test the safety and efficacy of Nucleolysin, a collagenase for intradiscal chemotherapy, laminectomies were performed on the L2-3 intervertebral discs of four groups of three young adult Cynomolgus monkeys. One primate from each group was injected with half the recommended human dose of Nucleolysin, chymopapain, or the same volume of sterile water. The remaining half of the human dose of each drug or equal volume of sterile water was equally divided and placed upon the right L-3 and L-4 nerve roots at their vertebral foramina. The right L-4 nerve root was first compressed for 10 seconds with an aneurysm clip. These procedures were done to simulate inadvertent contact of enzyme with spinal nerves in patients undergoing chemonucleolysis. After 4 weeks of observation, the 12 primates were humanely killed and examined post mortem. The effects of both enzymes were limited to those tissues with which they came in direct contact. Complete digestion of the nucleus pulposus of all enzyme-injected intervertebral discs was observed. Variable portions of the anulus fibrosus (from 2.3% to 57.4%) were also dissolved. Direct contact of Nucleolysin with lumbar nerve roots caused minor perineural reaction and no more intraneural changes than seen in sterile water controls. Chymopapain induced mild to severe perineural skeletal muscle necrosis and fibrosis with perineural arterial lesions as well as a degenerative neuropathy which was more marked in the traumatized nerve. The results of this study suggest that Nucleolysin and chymopapain are approximately equally effective on intervertebral discs, and that Nucleolysin is less injurious to spinal nerve roots and perineural tissue at the doses used.
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PMID:Effects of collagenase and chymopapain on spinal nerves and intervertebral discs of cynomolgus monkeys. 300 29