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)

Elevated serum levels of keratan sulfate (KS) and hyaluronate (HA) in patients with osteoarthritis (OA) have been reported. We measured KS and HA in dogs to determine if there was an elevation of these serum glycosaminoglycans in a canine model of OA. A single intraarticular injection of 1 mg of chymopapain into a shoulder joint increased serum KS by tenfold, and HA by less than twofold, in 24 hours. Serum KS and HA levels were 3-5-fold higher in dogs younger than 2 months of age than in older dogs. Serum KS and HA concentrations and synovial fluid KS concentrations were unrelated to spontaneous cartilage degeneration in 1-year-old dogs. Higher KS levels in synovial fluid correlated with higher KS levels in serum (r = 0.54, P less than 0.025). The mean KS concentration in sera of older dogs (greater than 3 years old) with OA was 37% higher than that in disease-free controls, but the difference between the groups was not statistically significant. Thus, elevated levels of serum KS and HA do not appear to have clinical significance in this model of OA.
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PMID:Canine serum keratan sulfate and hyaluronate concentrations. Relationship to age and osteoarthritis. 252 84

Following injection of chymopapain into a single knee joint in rabbits, serum keratan sulfate levels rose sharply and remained elevated for at least 48 hours before returning to preinjection levels. These changes were accompanied by depletion of proteoglycans from articular cartilage in the injected joint. We conclude that serum keratan sulfate levels rise predictably following acute loss of proteoglycan from a single joint.
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PMID:Increase in levels of serum keratan sulfate following cartilage proteoglycan degradation in the rabbit knee joint. 296 77

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

Continuous passive motion facilitates repair of full-thickness defects in the articular cartilage in rabbits. Studies were conducted to determine whether continuous passive motion would similarly affect the repair process after injection of chymopapain into the rabbit knee. Adolescent rabbits were injected with chymopapain and then given intermittent active motion in the form of free cage activity or continuous passive motion of the injected knee. After injection of either 0.2 or 2 mg chymopapain into the knee, serum keratan sulfate levels rose sharply, indicating proteoglycan loss, and, in all cases, peaked at 24 hours between 200-800% of preinjection levels. Importantly, serum keratan sulfate levels were significantly elevated within 1 hour when joints were submitted to immediate continuous passive motion after the injection. As shown previously, injection of either 0.2 or 2 mg chymopapain into the knee, followed by intermittent active motion, resulted in a pronounced loss of proteoglycans by Day 2, partial restoration of proteoglycans by Day 9, continued proteoglycan synthesis by Day 21 in animals receiving the lower dose, and severe degenerative changes by Day 21 in animals receiving the higher dose. In all animals that received either high or low doses of chymopapain, as well as 2 days of intermittent active motion and then continuous passive motion, the articular cartilage surface was intact by Day 9, and replenishment of proteoglycans had occurred in pericellular and interterritorial areas. By Day 21, the surface of the articular cartilage was still intact, and replenishment of proteoglycans in loaded regions continued in all animals receiving either dose of chymopapain. These results indicate that a period of intermittent active motion followed by continuous passive motion of a chymopapain injected knee may protect and stimulate repair of the articular cartilage matrix after chymopapain-induced injury.
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PMID:Continuous passive motion stimulates repair of rabbit knee articular cartilage after matrix proteoglycan loss. 802 Feb 26

Keratan sulfate (KS) is a glycosaminoglycan, distribution of which is confined mostly to hyaline cartilage. As such, it is a putative marker of hyaline cartilage catabolism. In experiment 1, a focal osteochondral defect was made arthroscopically in 1 radial carpal bone of 2 ponies, and in 2 other ponies, chymopapain was injected into the radiocarpal joint to induce cartilage catabolism. Sequential and concurrent plasma and synovial fluid concentrations of KS were measured, up to 13 months after induction of cartilage injury, to determine whether changes in KS concentrations reflected cartilage catabolism. In experiment 2, a large, bilateral osteochondral defect was made in the radial carpal bones of 18 ponies, which were subsequently given postoperative exercise and/or injected intra-articularly with 250 mg of polysulfated glycosaminoglycan (PSGAG). Medication was given at surgery, then weekly for 4 weeks. Blood samples were collected and synovial fluid was aspirated before surgery, when medication was given, and at postmortem examination (postoperative week 17). The KS concentration was measured in these fluids to determine whether changes in KS concentration indicated an effect of joint treatment. In experiment 1, the concentration of KS in synovial fluid was highest 1 day after joint injury, and the concentration in plasma peaked 2 days after joint injury. For ponies receiving chymopapain intra-articularly (generalized cartilage catabolism), a fivefold increase over baseline was observed in the concentration of KS in plasma (peak mean, 1.2 micrograms/ml), and a tenfold increase over baseline in synovial fluid (peak mean, 2.0 mg/ml) was observed. On average, these maxima were threefold higher than values in fluids of ponies with osteochondral defects (focal cartilage disease). In experiment 2, nonexercised ponies had lower KS concentration (as a percentage of the preoperative concentration) in synovial fluid than did exercised ponies at all postoperative times, and at postoperative week 17, this effect was significant (P < 0.05). This may be related to decreased turnover of KS in articular cartilage attributable to stall confinement and late increase in turnover related to exercise. Seventeen weeks after surgery, synovial fluid from exercised, medicated ponies had significantly (P < 0.05) higher KS content than did fluid from exercised, nomedicated ponies. This indicated that exercise, when combined with medication, may increase KS release from articular cartilage. Synovial fluid from medicated joints of nonexercised ponies had significantly (P < 0.05) lower KS concentration than did synovial fluid from nonmedicated joints of nonexercised ponies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Keratan sulfate as a marker of articular cartilage catabolism and joint treatment in ponies. 836 93

The intra-articular injection of 0.02, 0.2, or 2.0 mg of chymopapain (CP) into the knee of adolescent rabbits caused the loss of more than 50% of the proteoglycans (PGs) in the cartilaginous tissues within the joint. Sequential measurements of cartilage-derived keratan sulfate epitope in serum and analyses of articular cartilage slices 2 days after the injection revealed that 0.02 mg of CP was nearly as effective as higher doses (0.2 or 2.0 mg of CP) in causing the depletion. The degradation and depletion of PGs in articular cartilage were shown to be localized to the joint and did not affect articular cartilage in the contralateral knee joint (no injection) or other cartilaginous tissues in the body. On day 9, partial replenishment of the articular cartilage PGs had occurred, irrespective of the dose used, and the articular surface within the joint remained intact. However, by day 21, articular cartilage in joints injected with 2.0 mg of CP had begun to show progressive degenerative changes, and these changes became more severe with time. In contrast, joints injected with 0.2 mg of CP continued to repair successfully by the reestablishment of a matrix that retained its integrity and appeared to remain functional for at least 6 months. These results suggest that the model may prove useful for the study of the repair processes that follow matrix injury and severe depletion of PGs from the articular cartilage matrix.
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PMID:Repair of articular cartilage injury following intra-articular chymopapain-induced matrix proteoglycan loss. 841 Apr 71

The injection of 2.0 mg chymopapain into the adolescent rabbit knee causes severe loss of articular cartilage proteoglycans (PG). Although chondrocytes attempt to restore lost PG, failure to repair ensues. Pure chondroitin 4,6-sulfate (Condrosulf, IBSA Lugano, Switzerland) has been used in clinical studies of human osteoarthritis (OA) as a slow-acting drug for OA (SYSADOA). Using our model of articular cartilage injury, we examined the effects of oral and intramuscular administration of Condrosulf after chymopapain-induced cartilage injury. In this study, animals received an injection of 2.0 mg chymopapain (Chymodiactin, Boots Pharmaceuticals) into the left knee and were sacrificed after 84 days. The contralateral right knee served as a noninjected control. Some animals received oral Condrosulf while others received intramuscular injections of Condrosulf. Serum keratan sulfate (KS) levels were monitored to ensure degradation of the cartilage PG. Those animals not exhibiting at least a 100% increase of serum KS following chymopapain injection were excluded from the study. At sacrifice, cartilage PG contents were markedly reduced in animals receiving an injection of 2.0 mg chymopapain with no further treatment. In contrast, oral administration of Condrosulf beginning 11 days prior to chymopapain injury resulted in significantly higher (P = 0.0036) cartilage PG contents. Intramuscular administration of Condrosulf resulted in higher, but less significantly so (P = 0.0457), cartilage PG contents. These results suggest that daily Condrosulf treatment prior to and continuing after chymopapain injury may have a protective effect on the damaged cartilage, allowing it to continue to re-synthesize matrix PG after the treatment is discontinued.
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PMID:Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit. 974 13