Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

In the first of a two-part study, the authors review the known biochemical, pharmacological, toxicological, and experimental data concerning chymopapain and the intervertebral disc. They describe the action of this proteolytic enzyme, which apparently disrupts the protein mucopolysaccharide component of disc material, most marked in the nucleus pulposus. A rapid conversion to collagen causes a loss of disc space height; toxicity appears to result from alteration of bonding between capillary endothelial cells that in turn produces hemorrhage. Part 2 reviews significant reported results and complications of clinical chemonucleolysis.
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PMID:Chymopapain treatment of intervertebral disc disease. 12 75

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 initial effects of chymopapain, a chemonucleolytic agent, on the intervertebral disc of dogs were studied by light and electron microscopic techniques. Fragments of nucleus pulposus and annulus fibrosis were incubated with chymopapain up to 24 h in vitro. Proteoglycans and matrix proteins were rapidly removed, while collagen fibers remained intact up to 24 h. For several hours, most cells remained normal in appearance with only slight swelling and an increased number of vacuoles. After exposure to the protease for 24 h cells in both the annulus and nucleus showed extensive membrane damage and some were necrotic, but many survived relatively intact. These results suggest that, similar to the results of the digestion of cartilage with other proteases, the cells of the disc can survive brief chymopapain exposure during chemonucleolysis procedures and could serve as a source for regenerating tissue. The nature of the regeneration may depend on the extracellular scaffold that remains and the nutrition available to tissue as well as the age and biomechanical state of the disc. As for clinical significance, chemonucleolysis is an important nonsurgical alternative for treating prolapsed disc. The cells of nucleus and annulus can survive short-term exposure to treatment, and thus be responsible for partial regeneration of the tissue. This regeneration may be important in preventing long-term degenerative disease in the facet joints caused by increased pressure due to decreased disc height.
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PMID:Ultrastructural study of the short-term effects of chymopapain on the intervertebral disc. 373 36

We studied the effect of nucleus pulposus (NP) on platelet aggregation. Our in vitro experiments showed that NP extract produced platelet aggregation and the addition of collagenase to the NP extract abolished this response. It was further shown that chymopapain did not affect the activity of the extract. We assume that collagen is the active platelet aggregant in the NP extract. Intravascular release of collagen may cause platelet aggregation, vascular obstruction, ischemia, and cord necrosis in a patient with acute transverse myelitis. Intradiskal chymopapain is known to cause transverse myelitis and it is possible that collagen released during the action of the enzyme initiates a similar chain of events.
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PMID:Possible role of collagen in transverse myelitis and chymopapain-induced paraplegia. 396 20

Lumbar disc tissue from 10 patients who had previously undergone chemonucleolysis without success was studied by light and scanning electron microscopy. Seven patients had a sequestrated disc; three had large protrusions. As a control, material from 10 patients subjected to disc surgery without previous chemonucleolysis was studied in the same way. The control discs revealed the characteristic signs of degeneration: alteration of the collagen, microcystic areas, and giant chondromas. Changes following chemonucleolysis were restricted exclusively to the ground substance and characterized by a marked loss of basophilia in the cartilage matrix. There was no involvement of the anulus fibrosus, cartilage plate, or bone. Following chymopapain administration, scanning electron microscopy showed a naked collagen network devoid of ground substance.
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PMID:Morphological alterations of the degenerated lumbar disc following chemonucleolysis with chymopapain. 636 58

The young male rabbit ear cartilage after intravenous injection of chymopapain was studied by electron microscope. Fibrous long spacing (FLS)-like fibers were observed in the cytoplasm of the cartilage cells. These fibers were then compared with segment long spacing (SLS) fibers within the golgi vacuoles in the secondary well differentiated chondrosarcoma cells. These collagen fiber formation do not represent a normal collagen fiber formation, but it may be possible that the tropocollagen molecules are aggregated in the golgi vacuoles in a manner characteristic to FLS or SLS fiber by the close relationship with lysosome.
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PMID:Intracytoplasmic collagen fibers observed in cartilage of the pathological conditions. 674

A direct ultrastructural study was carried out with a view to determining the changes brought about in vitro by chymopapain on the intervertebral disc and the vertebral growth plate. The tissues studied were: (A) fragments of protruded nucleus pulposus and extruded disc tissue; (B) portions of human and rabbit annulus fibrous; (C) fragments of rabbit vertebral growth plate. The fragments of tissue were incubated with chymopapain for three, six and twenty-four hours and were then fixed. In the protruded nucleus pulposus and extruded disc tissue, chymopapain produced disappearance of the electron-dense granules (which are presumably proteoglycans) and of the electron-dense granular material of the intercellular matrix. The enzyme probably also has an injurious action on the chondrocytes, but does not affect the fibrils and collagen fibres. Its action is also conditioned by the dimensions of the fragment of tissue incubated. If this is large, only the peripheral portion is completely digested. The action of the enzyme on the annulus fibrosus and the vertebral growth plate is similar to that on the nucleus pulposus. The present study indicates that the clinical effects of chymopapain are due to digestion of the proteoglycan granules and the electron-dense granular material of the herniated nucleus pulposus. These effects appear to be correlated with the collagen fibre content of the tissue, in the sense that the greater the collagen content, the more tissue mass remains unaffected.
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PMID:Effects of chymopapain on intervertebral disc and cartilage. (Ultrastructural study). 676 24

This study was undertaken to investigate the morphological action of chymopapain (CP) in intervertebral discs. Of 20 mature Japanese white rabbits, 19 lumbar intervertebral discs were used for electron microscopic examination, and 36 discs, for immunohistochemical examination. Discs from 3 hours to 8 weeks after injection were observed by light and electron microscopy using anti-CP rabbit antibody labeled with horseradish peroxidase. Using Kagami's DMF-dehydration, two types of fine fibers were observed in the extracellular matrix of normal nucleus pulposus, in addition to collagen fiber. After injection of CP, the thinner fibers disappeared, while the thicker fibers remained. The injected CP spread from the nucleus pulposus to the annulus fibrosus within several hours and remained as long as 4 weeks. By immunoelectron microscopy, positive granules were divided into Type 1 (lacking relationship to collagen fibers) and Type 2 (adhering to or surrounding collagen fibers). The thinner fibers appear to be proteoglycan monomer and are the target for CP.
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PMID:Immunohistochemical study of chymopapain injected into the rabbit intervertebral disc using anti-chymopapain antibody. 832 Apr 75

The present study describes the radiological and histological changes in the canine intervertebral disk after the experimental injection of chymopapain as the chemical reagent, and determines the appropriate dose of the enzyme for treatment of herniated disks. By radiography, narrowing of the disk space was observed within 2 weeks after the injection of chymopapain, and recovered to 74.1% in the 0.1 mg group, 61.1% in the 1.0 mg group and 71.7% in the 10.0 mg group at 12 weeks. The disk space recovery showed a tendency to delay with aging. Microscopically, proteoglycan positive matrix appeared and the nuclear space was reduced in each disk at 2 weeks after chymopapain injection. The nucleus pulposus contained an irregularly-defined mass consisting of clusters of degenerated notochordal cells surrounded by proliferated chondrocytes and collagen matrix. In each disk at 12 weeks after chymopapain injection, the center of the nucleus pulposus was replaced by fibrocartilage tissue. In the disk into which 10.0 mg chymopapain was injected, the nuclear space filled with dense fibrocartilage tissue without a regenerated matrix component and narrowing of the disk were maintained. It is suggested that canine chemonucleolysis with 10.0 mg of chymopapain reduces the interdiskal pressure. This treatment may therefore relieve the signs and symptoms of herniation of the nucleus pulposus, and may effect chemical disk decompression.
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PMID:Experimental chemonucleolysis with chymopapain in canine intervertebral disks. 851

We have used polarized light (POL) to monitor changes in the organization of the articular cartilage collagen network and matrix proteoglycans (PGs) after intra-articular injection of chymopapain (CP). POL viewing of sirius red stained sections revealed a loss of normal birefringence suggesting an apparent collapse of the collagen network following intra-articular CP. After 21 days, knees injected with 2.0 mg CP showed no return of normal birefringence, however, normal birefringence was noted in knees injected with only 0.2 mg CP. POL viewing of toluidine blue stained sections revealed a severe loss of matrix PGs followed by PG restoration in animals injected with 0.2 mg CP. The most important inference from the data is that articular cartilage can recover from enzyme-induced alterations in the spatial collapse of its fibrillar network. This is an important finding since it has often been inferred that damage to the collagen network leads invariably to progressive articular cartilage destruction.
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PMID:Alteration and recovery of the spatial orientation of the collagen network of articular cartilage in adolescent rabbits following intra-articular chymopapain injection. 890 75


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