Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.6 (chymopapain)
 407 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chymopapain (Discase) was injected at a dose of 0.125 nanokatal unit into the intervertebral discs of rabbits, and sequential changes in the metabolism of water, proteoglycan, collagen, and noncollagenous protein were investigated separately in the nucleus pulposus, anterior, and posterior anulus fibrosus. One week after chymopapain injection, the water and proteoglycan content was lower in all of the fractionated tissues of the anterior and posterior anulus and nucleus pulposus of the discs than in the control discs. In the anterior and posterior anulus, the proteoglycan content recovered after 12 weeks, but there was no recovery in the nucleus pulposus. The collagen content continued to increase up to the 12th week in the nucleus pulposus, while the noncollagenous protein content decreased in all tissue fractions after 1 week. In the anterior and posterior anulus, the content of noncollagenous protein recovered after 3 to 6 weeks, but there was no recovery in the nucleus pulposus. The lysine incorporation in collagen and noncollagenous protein was inhibited in all tissue fractions after 12 weeks, suggesting a decrease in synthetic activity. The intradiscal pressure calculated from proteoglycan hydration at 1 to 6 weeks after chymopapain injection showed a marked decrease to 0.8 to 0.9 atm, but it recovered to 1.6 atm after 12 weeks.
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PMID:Water, fixed charge density, protein contents, and lysine incorporation into protein in chymopapain-digested intervertebral disc of rabbit. 251 52

The effect of diatrizoate on the chronic toxicity of chymopapain in the epidural space was studied. Chymopapain was injected epidurally into four monkeys; chymopapain plus diatrizoate meglumine, into four. In 3 months, neither group developed significantly more arachnoiditis than a control group of animals that had received epidural injections of physiologic saline. No synergistic effect of chymopapain and diatrizoate on the meninges was detected.
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PMID:Synergy of chymopapain and diatrizoate studied in an experimental model. 270 13

Chymopapain is a proteolytic enzyme used in the chemonucleolysis of the herniated nucleus pulposus of lumbar intervertebral discs. It causes rapid hydrolysis of the noncollagenous polypeptides that maintain the tertiary structure of the chondromucoprotein of the nucleus pulposus. We report here an anaphylactoid reaction after the intervertebral injection of chymopapain.
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PMID:Anaphylactoid reaction to chymopapain. 239 12

Short and long-term effects of chymopapain on nervous transmission were studied in rats. The drug was injected into the lumbar spinal canal. Action potentials evoked by electrical stimulation of the sciatic nerve were recorded at the dorsal root entry zone of the lumbar cord. One group of rats was pre-treated with dexamethasone. Chymopapain prolongs impulse latency compared to that of control rats treated with isotonic saline. The effect is dose dependent and can last for several weeks. Rats pre-treated with dexamethasone showed milder impairment of nervous transmission after chymopapain injection compared to the rats treated only with papain.
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PMID:[Animal experiment studies of the diagnosis and therapy of chymopapain-induced spinal complications]. 282 93

Using magnetic resonance imaging, conventional histology, and spinal evoked potentials, the authors studied the short-term effects of chymopapain on nerve tissue in the lumbar vertebral canal region in rats. Chymopapain in different concentrations was injected into the subarachnoid space in 31 rats. As early as 20 minutes later latency changes in the evoked potentials were observed; the histologic examinations after two hours showed bleeding, swelling of the myelin, and vascular changes. Magnetic resonance imaging of the lumbar spine, performed after six hours, showed a markedly stronger signal, indicative of an intraspinal edema, as compared to the control group. The authors' studies are clear proof that changes in nerve tissue following contact with chymopapain occur considerably faster than hitherto assumed in the literature.
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PMID:[Early functional and structural changes in the nerve tissue following contact with chymopapain]. 285 34

The American experience concerning the epidemiology of anaphylactic reactions following chemonucleolysis with chymopapain (Chymodiactin) were presented. The first study involved 1,585 patients of whom 17% were premedicated with some drug with either an H1 or H2 antagonist or both. The rate of anaphylaxis was 0.82%. Following its clinical introduction, a postmarketing surveillance study was undertaken. During the first 30,000 cases of which 93% were premedicated with combined H1 and H2 antagonists, the frequency of anaphylactic reactions was 0.78%. Subsequently, following the introduction of an immunologic test to screen for circulating IgE, the reaction rate fell to 0.44% in 45,000 cases of which 92% were premedicated with combined H1 and H2 antagonists. Females were far more likely to experience an anaphylactic event. Overall mortality from anaphylaxis decreased from one in 800 to one in 25,000 administrations. The decreased number and severity of these reactions correspond to the development of an immunologic screening test and utilization of prophylactic antihistamines.
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PMID:Use of prophylactic combined H1 and H2 antagonists reduces mortality in chymopapain anaphylaxis. 286 Aug 28

Skin tests (prick tests) with chymopapain were performed on 3 groups of patients: 75 patients awaiting chemonucleolysis with chymopapain (group I), 42 of these 75 patients 2-3 weeks after chemonucleolysis (group II), and 60 atopic patients suffering from asthma and/or rhinitis with positive skin tests to at least one of the airborne allergens (group III). A positive skin test was found in one patient of group I (1.33%), one patient of group III (1.7%) and 11 patients of group II (26.2%). Thus, sensitization to chymopapain is not more frequent among atopic patients, and chemonucleolysis has a highly significant (P less than 0.001) sensitizing effect. Chymopapain-specific IgE's were found in one out of 75 patients (1.33%) before, and in 14 out of 45 patients (31%) after chemonucleolysis; the difference was significant (P less than 0.001). Concordance between skin tests and specific IgE's reached the 74% level. Our results are consistent with those of the literature. They show that prick tests with a 10 mg/ml solution of chymopapain constitute, for the time being, a simple, reliable and cheap method for detecting subjects at risk.
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PMID:[Skin tests and chymopapain-specific immunoglobulins E after chemonucleolysis]. 295 17

Chymopapain (1 mg) was injected into each of four-lumbar intervertebral discs of adult mongrel dogs. As expected, at 2 weeks, all injected discs exhibited marked loss of height (mean: 50% of original height) indicative of severe proteoglycan depletion. The appearance of keratan sulfate-bearing fragments in plasma was monitored by an ELISA-inhibition assay which uses a monoclonal antibody (1/20/5-D-4) specific for an epitope present only in the longest keratan sulfate chains. Levels of plasma keratan sulfate rose within 30 minutes and reached a maximum between 24 and 72 hours later. Levels then declined progressively but were still elevated at 2 weeks postinjection. Keratan sulfate-bearing fragments in plasma were purified by ion exchange chromatography on DEAE-Sephacryl and fractionated by sieve chromatography on Sepharose CL-6B. These plasma keratan sulfate-bearing fragments were found to be similar in size to keratan sulfate-bearing fragments generated by chymopapain digestion of dog nucleus pulposus proteoglycans, but slightly larger than single keratan sulfate chains obtained by alkaline borohydride treatment of dog nucleus pulposus proteoglycans. The results of this study show that measurements of blood levels of keratan sulfate could prove useful in monitoring effective degradation of disc proteoglycans in chemonucleolysis in man and help discriminate between ineffective enzyme placement, and alternative mechanisms of treatment failure.
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PMID:Levels of keratan sulfate-bearing fragments rise predictably following chemonucleolysis of dog intervertebral discs with chymopapain. 297 75

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


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