Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC Disc Chemolysis: The dissolving of the nucleus pulposus, the semi-gelatinous tissue of a displaced INTERVERTEBRAL DISC. It is usually achieved by the direct injection of a proteolytic enzyme, especially CHYMOPAPAIN, into the herniated disc.Ficain: A sulfhydryl proteinase with cysteine at the active site from ficus latex. Preferential cleavage is at tyrosine and phenylalanine residues. EC Protein-digesting and milk-clotting enzymes found in PINEAPPLE fruit juice and stem tissue. Enzymes from the two sources are distinguished as fruit bromelain and stem bromelain. This enzyme was formerly listed as EC A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and CHYMOPAPAIN that is used as a topical enzymatic debriding agent. EC A homologous group of endogenous CYSTEINE PROTEINASE INHIBITORS. The cystatins inhibit most CYSTEINE ENDOPEPTIDASES such as PAPAIN, and other peptidases which have a sulfhydryl group at the active site.2,2'-Dipyridyl: A reagent used for the determination of iron.Intervertebral Disc Displacement: An INTERVERTEBRAL DISC in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region.Drug Information Services: Services providing pharmaceutic and therapeutic drug information and consultation.Carica: A plant genus of the family Caricaceae, order Violales, subclass Dilleniidae, class Magnoliopsida. It is the source of edible fruit and PAPAIN.Sulfhydryl Compounds: Compounds containing the -SH radical.Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Bone Morphogenetic Protein 2: A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.Bone Morphogenetic Protein 4: A bone morphogenetic protein that is a potent inducer of bone formation. It also functions as a regulator of MESODERM formation during EMBRYONIC DEVELOPMENT.Bone Morphogenetic Protein 7: A bone morphogenetic protein that is widely expressed during EMBRYONIC DEVELOPMENT. It is both a potent osteogenic factor and a specific regulator of nephrogenesis.Bone and Bones: A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.Bone Morphogenetic Protein Receptors, Type I: A subtype of bone morphogenetic protein receptors with high affinity for BONE MORPHOGENETIC PROTEINS. They can interact with and undergo PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II. They signal primarily through RECEPTOR-REGULATED SMAD PROTEINS.Agave: A genus known for fibers obtained from their leaves: sisal from A. sisalana, henequen from A. fourcroyoides and A. cantala, or Manila-Maguey fiber from A. cantala. Some species provide a sap that is fermented to an intoxicating drink, called pulque in Mexico. Some contain agavesides.Nematode Infections: Infections by nematodes, general or unspecified.Anthelmintics: Agents destructive to parasitic worms. They are used therapeutically in the treatment of HELMINTHIASIS in man and animal.Pyrantel: A depolarizing neuromuscular-blocking agent, that causes persistent nicotinic activation resulting in spastic paralysis of susceptible nematodes. It is a drug of second-choice after benzimidazoles for treatment of ascariasis, hookworm, and pinworm infections, being effective after a single dose. (From Smith and Reynard, Textbook of Pharmacology, 1992, p920)Trichuris: A genus of nematode worms comprising the whipworms.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Myelin Basic Protein: An abundant cytosolic protein that plays a critical role in the structure of multilamellar myelin. Myelin basic protein binds to the cytosolic sides of myelin cell membranes and causes a tight adhesion between opposing cell membranes.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Manuscripts as Topic: Compositions written by hand, as one written before the invention or adoption of printing. A manuscript may also refer to a handwritten copy of an ancient author. A manuscript may be handwritten or typewritten as distinguished from a printed copy, especially the copy of a writer's work from which printed copies are made. (Webster, 3d ed)Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.HLA-DR2 Antigen: A broad specificity HLA-DR antigen that is associated with HLA-DRB1 CHAINS encoded by DRB1*01:15 and DRB1*01:16 alleles.

Enrichment of peripheral blood CD34+ cells for transplantation using a fully automated immunomagnetic cell selection system and a novel octapeptide releasing agent. (1/37)

Positive selection of CD34+ cells is being increasingly performed to support hematological reconstitution following high-dose and dose-intensive chemotherapy and to reduce the non-target cell content of transplants. The present study was designed to evaluate the performance of an immunomagnetic cell selection system, including comparison of enzyme and peptide releasing agents and of semi-automated and fully automated selection systems. A total of 74 immunomagnetic CD34+ cell selection procedures were performed involving 55 subjects, the majority of whom had hematologic malignancies. Median CD34+ cell purity with a newly developed specific octapeptide releasing agent (98.5%; 81.0-99.0%) was significantly higher (P = 0.002) than that with chymopapain (85.8%; 28.1-99.7%). No significant differences were observed between semi-automated and fully automated systems in CD34+ cell purity or yield or time to WBC or platelet recovery. Immunomagnetic selection was found to provide highly purified populations of CD34+ cells in sufficient numbers for use in transplantation procedures. CD34+ cell transplants supported rapid and reliable hematologic reconstitution. Use of a fully automated system markedly reduced the time and labor required for immunomagnetic selection, potentially affording more standardized and reproducible positive selection of CD34+ cells.  (+info)

Single-blind randomised controlled trial of chemonucleolysis and manipulation in the treatment of symptomatic lumbar disc herniation. (2/37)

This single-blind randomised clinical trial compared osteopathic manipulative treatment with chemonucleolysis (used as a control of known efficacy) for symptomatic lumbar disc herniation. Forty patients with sciatica due to this diagnosis (confirmed by imaging) were treated either by chemonucleolysis or manipulation. Outcomes (leg pain, back pain and self-reported disability) were measured at 2 weeks, 6 weeks and 12 months. The mean values for all outcomes improved in both groups. By 12 months, there was no statistically significant difference in outcome between the treatments, but manipulation produced a statistically significant greater improvement for back pain and disability in the first few weeks. A similar number from both groups required additional orthopaedic intervention; there were no serious complications. Crude cost analysis suggested an overall financial advantage from manipulation. Because osteopathic manipulation produced a 12-month outcome that was equivalent to chemonucleolysis, it can be considered as an option for the treatment of symptomatic lumbar disc herniation, at least in the absence of clear indications for surgery. Further study into the value of manipulation at a more acute stage is warranted.  (+info)

Intradiscal pressure after intradiscal injection of hypertonic saline: an experimental study. (3/37)

Although chemonucleolysis with chymopapain is a long-established treatment for lumbar intervertebral disc herniation, serious complications have been reported. Accordingly, alternative substances for chemonucleolysis have been sought. The main beneficial effect of chemonucleolysis derives from the decrease in intradiscal pressure. Several previous studies have investigated the relationship between physiological saline injection and disc mechanics in cadaveric specimens [2, 5, 16]. However, no previous study has assessed the intradiscal pressure after intradiscal injection of "hypertonic saline" in living animals. The present study compared the changes in intradiscal pressure after intradiscal injection of hypertonic saline with those after chymopapain injection. The lumbar intervertebral discs of 26 living rabbits were examined: 10% hypertonic saline was injected in ten rabbits, and chymopapain (10 pikokatal units) was injected intradiscally in another ten, with the remaining six being used as controls. The intradiscal pressure was measured at 1, 4, and 12 weeks after injection. The intradiscal pressure of the hypertonic saline-injected group at 4 weeks was significantly lower than that of the control group, but by 12 weeks it had recovered. On the other hand, that of the chymopapain-injected group remained significantly lower than that of the control group at 12 weeks. The results of this study found that hypertonic saline injected into the intervertebral discs temporarily decreased the intradiscal pressure.  (+info)

Chemonucleolysis: the state of the art. (4/37)

This review presents the history of chemonucleolysis, the techniques, indications, contraindications, and complications. Presenting an historical overview and comparison of success rates with surgical discectomy may provide a fresh understanding of the controversy surrounding chemonucleolysis and establish its efficacy in relation to more invasive treatments. A review of the literature from 1973 through 1998 for chemonucleolysis, open discectomy, and microdiscectomy provided published success rates for these procedures, and a mean rate with standard deviation was determined. In the experience and opinion of the authors, chemonucleolysis remains a viable alternative for patients who have exhausted all conservative means of treatment. Proper patient selection leads to success rates comparable to open discectomy and microdiscectomy.  (+info)

Insight to structural subsite recognition in plant thiol protease-inhibitor complexes : understanding the basis of differential inhibition and the role of water. (5/37)

BACKGROUND: This work represents an extensive MD simulation / water-dynamics studies on a series of complexes of inhibitors (leupeptin, E-64, E-64-C, ZPACK) and plant cysteine proteases (actinidin, caricain, chymopapain, calotropin DI) of papain family to understand the various interactions, water binding mode, factors influencing it and the structural basis of differential inhibition. RESULTS: The tertiary structure of the enzyme-inhibitor complexes were built by visual interactive modeling and energy minimization followed by dynamic simulation of 120 ps in water environment. DASA study with and without the inhibitor revealed the potential subsite residues involved in inhibition. Though the interaction involving main chain atoms are similar, critical inspection of the complexes reveal significant differences in the side chain interactions in S2-P2 and S3-P3 pairs due to sequence differences in the equivalent positions of respective subsites leading to differential inhibition. CONCLUSION: The key finding of the study is a conserved site of a water molecule near oxyanion hole of the enzyme active site, which is found in all the modeled complexes and in most crystal structures of papain family either native or complexed. Conserved water molecules at the ligand binding sites of these homologous proteins suggest the structural importance of the water, which changes the conventional definition of chemical geometry of inhibitor binding domain, its shape and complimentarity. The water mediated recognition of inhibitor to enzyme subsites (Pn.H2O.Sn) of leupeptin acetyl oxygen to caricain, chymopapain and calotropinDI is an additional information and offer valuable insight to potent inhibitor design.  (+info)

The effect of bone remodeling inhibition by zoledronic acid in an animal model of cartilage matrix damage. (6/37)

OBJECTIVE: The purpose of this work was to test the effect of inhibition of bone remodeling, through the use of the bisphosphonate, zoledronic acid, on cartilage matrix damage in an animal model of cartilage matrix damage. DESIGN: New Zealand white rabbits were divided into four groups for treatment purposes: (1) untreated controls; (2) injected into one knee joint with the cartilage matrix degradation enzyme, chymopapain; (3) injected into one knee joint with chymopapain and also given subcutaneous injections of the bisphosphonate, zoledronic acid, three times per week until sacrifice at either day 28 or 56 post-chymopapain-injection; (4) received only the zoledronic acid injections. At sacrifice, the knee joints were examined grossly and histologically, and biochemically for proteoglycan content. Urine samples were analysed, at intervals, for levels of collagen cross-links which are biochemical markers of cartilage and bone. RESULTS: Animals receiving both intraarticular chymopapain injections and subcutaneous zoledronic acid injections displayed a significantly lower degree of grossly and histologically detectable cartilage degeneration on the tibial articular surfaces (the articular surface displaying the greatest degree of degeneration) than did animals only receiving the chymopapain injections. In addition, urinary levels of collagen cross-links for bone and cartilage were significantly higher in those animals only receiving chymopapain injections. CONCLUSION: The bone resorption observed after chymopapain injection into the rabbit knee joint can be inhibited through the use of the bisphosphonate, zoledronic acid. Furthermore, zoledronic acid does not increase the level of cartilage degeneration and appears to provide some level of chondroprotection in this model.  (+info)

Effect of oral glucosamine on cartilage and meniscus in normal and chymopapain-injected knees of young rabbits. (7/37)

OBJECTIVE: To determine if oral glucosamine (GlcN) improves joint biology after acute damage by a protease. METHODS: The effect of 8 weeks of dietary GlcN (20 or 100 mg/kg/day) on knee joint cartilage was evaluated in 2.2-kg male NZW rabbits with and without damage introduced by intraarticular injection of chymopapain (CP). Cartilage was evaluated histologically and scored according to the Mankin scale. Analyses of total hydroxyproline and glycosaminoglycan (GAG) contents and reverse transcription-polymerase chain reaction (RT-PCR) analysis of selected genes were performed. RESULTS: After 8 weeks, there was no effect of GlcN on the GAG content of normal cartilage. Both levels of GlcN treatment significantly increased the sulfated GAG content in the cartilage of the medial femoral condyle in damaged and contralateral knees, but did not change the collagen content. In CP-injected knees, there was still some loss of surface proteoglycan (PG) that was not completely corrected by dietary GlcN. Even after 8 weeks, levels of messenger RNA (mRNA) detected by RT-PCR showed changes indicative of damage and repair, such as elevated type II collagen mRNA, and these levels were not influenced by GlcN treatment. Meniscal GAG content was increased in the contralateral knee of rabbits receiving high-dose GlcN, but was decreased in those receiving no GlcN or low-dose GlcN. Neither diet nor treatment affected the meniscal collagen content. CONCLUSION: These results suggest that oral GlcN treatment might be useful in a situation where GlcN is limiting, such as where there is a rapid replacement of cartilage PG.  (+info)

Chemonucleolysis. (8/37)

A prospective study of 480 patients who underwent enzymatic dissolution of the nucleus pulposus with chymopapain is reported. Seventy per cent of patients with the clincial criteria for a disc herniation had a favourable response to chemonucleolysis. The commonest cause of failure was persistent back pain. In patients with sequestered discs or lateral recess stenosis surgical intervention was not made more difficult by chemonucleolysis. Those with a previous operation, spinal stenosis or psychogenic components to the disability had very poor results. Complications were few and easily managed.  (+info)

  • Studies on chymopapain have been done only in adult patients, and there is no specific information comparing use of chymopapain in children with use in other age groups. (
  • Chymopapain (EC, chymopapain A, chymopapain B, chymopapain S, brand name Chymodiactin) is a proteolytic enzyme isolated from the latex of papaya (Carica papaya). (
  • Plant peptidases such as papain (EC, ficin (EC, chymopapain (EC, asclepain A (EC, actinidin (EC, glycyl endopeptidase (EC, caricain (EC, ananain (EC, stem bromelain (EC and fruit bromelain (EC (
  • Chymopapain chemonuclolysis is the least invasive technique to treat lumbar disc herniation and relieve pain from related sciatica. (
  • Chemonucleolysis is a treatment in which an enzyme, chymopapain, is injected directly into a herniated lumbar disc in an effort to dissolve material around the disc, thus reducing pressure and pain. (
  • Chymopapain and semipurified collagenase had similar morphologic and mechanical effects. (
  • Even though injecting chymopapain simply required placing the tip of a needle in the nucleus pulposus of a disc many practitioners learned that this was not as simple as it seemed. (
  • The 561 antibody recognizes a class III group epitope, which is resistant to sialidase/glycolyprotease and chymopapain treatment. (
  • Proteases such as chymopapain and trypsin can be used in some instances to release cells or interrupt antigen-antibody interaction. (
  • Chymopapain - A thiol protease that catalyzes the hydrolysis of proteins and polypeptides to smaller polypeptides. (
  • The latter procedure was used to produce fully active enzyme containing one essential thiol group per molecule of protein, to establish that the chymopapain A molecule contains, in addition, one non-essential thiol group per molecule and to recalculate the literature value of epsilon 280 for the enzyme as 36 000 M−1 × cm −1. (
  • The environment of the catalytic site of chymopapain A is markedly different from those of other cysteine proteinases studied to date, as evidenced by the pH-dependence of the second-order rate constant (k) for the reaction of the catalytic-site thiol group with 2,2′-dipyridyl disulphide. (
  • A therapeutic concentration (2000 pKat/ml) of chymopapain stopped the microcirculation in the injected area immediately, with numerous microbleedings at the border zone. (
  • The Michaelis parameters for the hydrolysis of L-benzoylarginine p-nitroanilide and of benzyloxy-carbonyl-lysine nitrophenyl ester at 25 degrees C, and I 0.1 at several pH values catalysed by chymopapain A, papaya proteinase omega, papain (EC and actinidin (EC were determined. (
  • Two spines, each of which consists of seven discs, were used for each of the following procedures: (I) unilateral approach using rongeurs alone, (II) bilateral approach using rongeurs alone, (III) unilateral approach using rongeurs followed by chymopapain and (IV) bilateral approach using rongeurs followed by chymopapain. (
  • The largest increase was noted in flexion in discs injected with chymopapain. (
  • Chymopapain is injected directly into a herniated ("slipped'') disk in the spine to dissolve part of the disk and relieve the pain and other problems caused by the disk pressing on a nerve. (
  • One prominent Canadian orthopedic chymopapain advocate stated at a medical meeting that all he required was a "few cc's of chymopapain" to take care of all of his spine patients! (
  • The sad part of this tale is that the inadvertent deposition of chymopapain into nerve tissue as well as the sub-arachnoid space created some horrendous problems (including stroke, paraplegia, and death) for a significant number of patients. (
  • Studies on chymopapain have been done only in adult patients, and there is no specific information comparing use of chymopapain in children with use in other age groups. (
  • Its fruits, stems, leaves, and roots are used in a wide range of medical applications, including the production of two important bioactive compounds (chymopapain and papain), which are widely used for digestive diseases [ 19 - 21 ]. (
  • Why, he reasoned couldn't chymopapain also dissolve the collagen in a herniated disc? (
  • From this basic observation the saga of chemonucleolysis (enzymatic dissolution of disc collagen) with chymopapain (the active ingredient in Adolf's meat tenderizer) was born. (
  • The results of many studies involving removal of nucleus, including chemonucleolysis, using chymopapain, have been published but we are not aware of any previous quantitative studies on procedures for removing as much nucleus as possible from the disc. (
  • The presence of other medical problems may affect the use of chymopapain. (
  • Despite the tale of chymopapain and its unfortunate demise the M2H phenomenon is still alive and well in the over-promoting of medical devices and techniques even today. (
  • Chymopapain is an enzyme that has been used successfully in the treatment of herniated nucleus, as alternative [ 7 - 9 ] or as an adjunct [ 10 ] to surgery. (
  • Microvascular effects of chondroitinase ABC and chymopapain. (
  • As it turned out, even when chymopapain was injected into the right location there were important associated liabilities. (