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)

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