Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemonucleolysis has recently become an established treatment for intervertebral disc protrusion. However, the exact mechanism of chemonucleolysis is still unknown. If mechanisms of chemonucleolysis include diminution of intradiscal pressure followed by subsequent regeneration of the nucleus pulposus, then a more selective enzyme for glycosaminoglycan, chondroitinase ABC, might be used for chemonucleolysis instead of chymopapain. Thus experimental chemonucleolysis with chondroitinase ABC compared with chymopapain was investigated. In rabbits, chondroitinase ABC is as effective for chemonucleolysis as chymopapain, but the chemonucleolysis process with chondroitinase ABC was milder than with chymopapain. At an early chemonucleolysis phase, chondroitinase ABC action was chiefly limited to digestion of the matrix, and a large number of cells in the nucleus pulposus remained. During long-term observations of chemonucleolysis with chondroitinase ABC, nuclear structure was restored to a nearly normal state. Although limited, this study indicates that chondroitinase ABC might be more suitable than chymopapain for chemonucleolysis.
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PMID:Experimental chemonucleolysis with chondroitinase ABC. 231 86

Immediate and long-term microvascular effects of chondroitinase ABC, 200 unit/ml, were analyzed in ten hamsters. The immediate effects on the microcirculation were studied by vital microscopy following local injection in the cheek pouch. There were no detectable effects on the microvascular blood flow during the 60 minutes of observation for chondroitinase ABC or the control. A therapeutic concentration (2000 pKat/ml) of chymopapain stopped the microcirculation in the injected area immediately, with numerous microbleedings at the border zone. Long-term effects were studied after subcutaneous injections in the ears of six rabbits. Chondroitinase ABC and the control did not cause any macroscopic or microangiographic effects. However, light microscopy showed a moderate inflammatory reaction in the subcutaneous layer for both chondroitinase ABC and the control. Chymopapain induced severe effects on the cartilage and surrounding tissues. Microangiography revealed a vessel-free zone at the injection site. Since 200 units/ml of chondroitinase ABC is four to eight times higher than the concentration that might be used for chemonucleolysis, i.e., dissolution of intervertebral discs by local enzyme injection, the present investigation suggests a wide margin of safety regarding the potential effects on blood vessels in tissues surrounding the disc.
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PMID:Microvascular effects of chondroitinase ABC and chymopapain. An in vivo experimental study on hamsters and rabbits. 237 64

Proteoglycans were extracted from nuclease-digested sonicates of 10(9) rat basophilic leukemia (RBL-1) cells by the addition of 0.1% Zwittergent 3-12 and 4 M guanidine hydrochloride and were purified by sequential CsCl density gradient ultracentrifugation, DE52 ion exchange chromatography, and Sepharose CL-6B gel filtration chromatography under dissociative conditions. Between 0.3 and 0.8 mg of purified proteoglycan was obtained from approximately 1 g initial dry weight of cells with a purification of 200-800-fold. The purified proteoglycans had a hydrodynamic size range of Mr 100,000-150,000 and were resistant to degradation by a molar excess of trypsin, alpha-chymotrypsin, Pronase, papain, chymopapain, collagenase, and elastase. Amino acid analysis of the peptide core revealed a preponderance of Gly (35.4%), Ser (22.5%), and Ala (9.5%). Approximately 70% of the glycosaminoglycan side chains of RBL-1 proteoglycans were digested by chondroitinase ABC and 27% were hydrolyzed by treatment with nitrous acid. Sephadex G-200 chromatography of glycosaminoglycans liberated from the intact molecule by beta-elimination demonstrated that both the nitrous acid-resistant (chondroitin sulfate) and the chondroitinase ABC-resistant (heparin/heparan sulfate) glycosaminoglycans were of approximately Mr 12,000. Analysis of the chondroitin sulfate disaccharides in different preparations by amino-cyano high performance liquid chromatography revealed that 9-29% were the unusual disulfated disaccharide chondroitin sulfate di-B (IdUA-2-SO4----GalNAc-4-SO4); the remainder were the monosulfated disaccharide GlcUA----GalNAc-4-SO4. Subpopulations of proteoglycans in one preparation were separated by anion exchange high performance liquid chromatography and were found to contain chondroitin sulfate glycosaminoglycans whose disulfated disaccharides ranged from 9-49%. However, no segregation of subpopulations without both chondroitin sulfate di-B and heparin/heparan sulfate glycosaminoglycans was achieved, suggesting that RBL-1 proteoglycans might be hybrids containing both classes of glycosaminoglycans. Sepharose CL-6B chromatography of RBL-1 proteoglycans digested with chondroitinase ABC revealed that less than 7% of the molecules in the digest chromatographed with the hydrodynamic size of undigested proteoglycans, suggesting that at most 7% of the proteoglycans lack chondroitin sulfate glycosaminoglycans.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Purification and characterization of protease-resistant secretory granule proteoglycans containing chondroitin sulfate di-B and heparin-like glycosaminoglycans from rat basophilic leukemia cells. 241 30

Nucleolysis using chondroitinase ABC was studied using the rabbit's intervertebral lumbar disc. The purpose was to find a possible alternative to chymopapain which is commonly used in the management of sciatica due to disc herniation. The injection of 1 U of the enzyme into the nucleus pulposus gave significant histological and biochemical changes in all twelve discs studied.
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PMID:[Nucleolytic action of chondroitinase ABC on the lumbar disc of the rabbit]. 314 53

Chondroitin sulfate E proteoglycan was extracted in the presence of protease inhibitors from 6 X 10(9) mouse bone marrow-derived, interleukin 3-dependent mast cells, of which 3 X 10(7) had been biosynthetically labeled with [35S]sulfate or [3H]glycine. Chondroitin sulfate E proteoglycan was purified to apparent homogeneity by density-gradient centrifugation, differential molecular weight dialysis, DEAE-52 ion exchange chromatography, and Sepharose CL-4B gel filtration chromatography. Chondroitin sulfate E proteoglycan, radiolabeled with [3H]glycine or [35S]sulfate, filtered as a single peak of radioactivity on Sepharose CL-4B with a Kav of 0.41. When purified [3H]glycine-labeled proteoglycan was digested with chondroitinase ABC and subjected to gel filtration, all of the radioactivity was shifted to a lower molecular weight. As assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis the Mr of the peptide core obtained by chondroitinase ABC treatment was approximately 10,000. The purified proteoglycan was resistant to degradation by collagenase, clostripain, trypsin, chymotrypsin, elastase, chymopapain, V8 protease, proteinase K, and Pronase, as assessed by gel filtration chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis of the core peptide of the intact proteoglycan revealed that glycine, serine, and glutamic acid/glutamine accounted for 70% of the total amino acids and were present in a molar ratio of 4.3/1.6/1.0. When analyzed for neutral hexose content by gas-liquid chromatography, the proteoglycan contained approximately 2% of its weight as mannose, fucose, galactose, and other sugars, indicating that oligosaccharides were linked to the peptide core. The mouse bone marrow-derived mast cell chondroitin sulfate E proteoglycan, like the rat serosal mast cell heparin proteoglycan, is markedly protease resistant, has highly sulfated glycosaminoglycans, and contains a peptide core that is rich in serine and glycine. These characteristics of the mast cell class of intracellular proteoglycans may contribute to their function in stimulus-induced granule secretion as well as in mediator storage, including retention of cationic neutral proteases.
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PMID:Purification and analysis of the core protein of the protease-resistant intracellular chondroitin sulfate E proteoglycan from the interleukin 3-dependent mouse mast cell. 393 50

The articular surface of adult BALB/c mouse femoral heads is covered by a fine granular electron dense material containing negative charges that bind electrostatically cationized ferritin. The material is of proteidic nature being digested by trypsin and chymopapain and resistant to testicular and microbial hyaluronidase, keratanase, chondroitinase ABC and AC. Mammalian collagenase disrupted the surface without digesting the material and allowed the penetration of cationized ferritin in the subsurface layers, where the label was bound on residual fibers. Sequential digestion with collagenase and chondroitinase ABC showed that the charges associated with the subsurface fibers are proteoglycans.
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PMID:Effects of enzymatic digestions on the negative charge of articular cartilage surfaces. 408 65

Calpain I is a calcium-dependent cysteine proteinase that has been recently shown to degrade proteoglycan in vitro. The authors injected calpain I, which was purified from human red blood cells, into the intervertebral discs of rabbits. Roentgenograms showed disc space narrowing 1 week after the injection. Histologically, proteoglycan of the nucleus pulposus and anulus fibrosus decreased and notochordal cells in the nucleus pulposus almost disappeared. Biochemical data of the nucleus pulposus showed that the amounts of smaller proteoglycans increased 1 and 4 weeks after the injection. Eight weeks after the injection, histologic and biochemical data showed recovery compared with the data 1 week after injection. These findings show that calpain I is as potent an enzyme as chondroitinase ABC and has milder chemonucleolytic action than chymopapain. Regarding its possible clinical application, autogenous calpain I as purified from the patient's own red blood cells may have advantages over chymopapain and chondroitinase ABC in that it will prevent anaphylactic reaction.
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PMID:Chemonucleolysis with calpain I in rabbits. 843 17

Although chemonucleolysis with chymopapain is an approved treatment for lumbar intervertebral disk herniation, recent serious complications have raised doubt concerning its safety. It is therefore necessary to search for a safer and more selective agent than chymopapain for chemonucleolysis. Experimental chemonucleolysis with chondroitinase ABC was thus tested and compared with chymopapain. Acute tissue reactions to chondroitinase ABC were investigated and compared with chymopapain. The epidural space, yellow ligament, sciatic nerve, knee joint, and Achilles tendon were examined. Chymopapain damaged nervous and ligamentous tissues as well as cartilaginous tissue. Chondroitinase ABC did not damage nervous and ligamentous tissue. Chondroitinase ABC affected only cartilaginous tissue, and its action was chiefly limited to digestion of the matrix. Chondroitinase ABC has high enzymatic specificity for matrix in vivo. In addition, chondroitinase ABC is less toxic to noncartilaginous tissues than chymopapain. Chondroitinase ABC might be a more suitable and safer enzyme than chymopapain for chemonucleolysis.
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PMID:Comparison of tissue reaction with chondroitinase ABC and chymopapain in rabbits as the basis of clinical application in chemonucleolysis. 764 53

A review of the world medical literature on chemonucleolysis with an emphasis on recent studies, meta-analyses, and the history of the procedure in North America from a regulatory, social, and medicolegal perspective was performed to determine the current status of chemonucleolysis in the management of disc displacement. The world literature supports the use of chymopapain for chemonucleolysis as a safe and effective alternative to surgical disc excision. The efficacy of chymopapain has been shown by prospective, randomized, placebo-controlled, double-blind trials with a minimum 10-year follow-up period. The safety of chymopapain injection compared with surgery has been demonstrated in meta-analyses and in extensive post-marketing surveillance in the United States and Europe. Clinical studies with collagenase and laboratory studies with chondroitinase ABC have shown that chemonucleolysis can be performed with enzymes other than chymopapain. Clinical trials have been performed with collagenase for chemonucleolysis, but all of the results have not been published. Preclinical research with chondroitinase ABC has demonstrated its usefulness for chemonucleolysis in the animal model, but human trials have not begun.
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PMID:Update on chemonucleolysis. 911 26

Experimental chemonucleolysis of the canine intervertebral disc with chondroitinase ABC and chymopapain was compared during a 52-week period. Roentgenograms and magnetic resonance imaging were used to examine changes in disc space and water content, respectively. Disc space narrowing and reductions in disc water content after chondroitinase ABC treatment were less than that after chymopapain. High-performance liquid chromatography was performed to measure changes in proteoglycans. Similarly to chymopapain, chondroitinase ABC degrades proteoglycans in the nucleus pulposus and decreases their quantity. However, large differences in the molecular weight and acidity of the resynthesized proteoglycans and in the chain length of the resynthesized glycosaminoglycans were observed between the two enzymes. The difference in disc space narrowing and the changes in disc water content between the two enzymes might result from differences in the characteristics of the resynthesized proteoglycans.
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PMID:Proteoglycans in the nucleus pulposus of canine intervertebral discs after chondroitinase ABC treatment. 965 53


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