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At least 811 records · Page 45Linked to original sources
PubMed1975

Chymopapain treatment of intervertebral disc disease.

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.

Anaphylaxis↗
PubMed1990

Facet joint asymmetry and protrusion of the intervertebral disc.

In a study of 47 cases of lumbar disc protrusion, the hypothesis that asymmetry of the facet joints is correlated with the presence of a disc protrusion, was tested. Seventeen cases of protrusion of the L4-L5 disc and 30 cases of protrusion of the L5-S1 disc were measured on coronal computed tomography (CT) scans. The nonprotruded discs of each level were used as controls of the protruded discs of the same level. The transverse interfacet angle, the inclination and curvature of the facet joints, and the frequency of asymmetric facet joints showed no significant differences, whether there was a disc protrusion or not. The magnitude of the asymmetry was significantly greater only at the L4-L5 interspace in cases of disc protrusion. However, taking into consideration the error of measurement, the difference becomes highly questionable. These results do not indicate any relation between facet joint asymmetry and protrusion of the intervertebral disc.

Adult↗
PubMed1988

Nutrition of the intervertebral disc: acute effects of cigarette smoking. An experimental animal study.

We have in the present experimental study investigated the influence of cigarette smoking on some nutritional parameters of the porcine intervertebral disc. The results from the acute smoking tests show a significant reduction in solute transport. Diffusion of sulphate, oxygen and methyl glucose was reduced by 30-40 per cent. This effect was obtained after exposure to smoke for 20-30 minutes. A smoking period of three hours reduced the transport efficiency to about 50 per cent. The effect of smoking decreased when the exposure ceased. The concentration gradients were close to normal after 2 hours "recovery". These findings suggest that cigarette smoking not only significantly affects the circulatory system outside the intervertebral disc, where the most pronounced effect is the reduction in solute exchange capacity, but also significantly deteriorates the cellular uptake rate and metabolite production within the disc.

Animals↗
PubMed2000

COL9A2 allelotypes in intervertebral disc disease.

An allelic variation of the COL9A2 gene encoding the alpha(2)-chain of collagen IX has recently been identified as a genetic risk factor for intervertebral disc prolapse, resulting in a tryptophane (Trp) substitution at position 326 of the protein. To enable quick screening of a large population we established a single enzyme (BsmFI) restriction assay which was validated by screening disc tissue samples of 250 patients (age, 47.1 +/- 13.7 years). Positive results were confirmed by nucleotide sequencing. The Trp allele was found in three patients (1.2%) who suffered from their first prolapse and were significantly older (70.7 +/- 8.5 years) than the other 247 patients. Since the substitution affects a domain covalently linked to collagen II fibrils, we conclude that this allelotype may contribute to reduced collagen crosslinking, disc instability and eventually prolapse in the elderly.

Adolescent↗
PubMed1985

MR imaging of the intervertebral disc: a quantitative study.

The T1 and T2 relaxation times and the proton density of the nucleus pulposus have been measured in 107 normal and 18 surgically proven degenerate intervertebral discs. Data from total saturation recovery and spin echo sequences have been utilised in a robust multi-point method and relaxation times and proton density calculated. The results show that both the T1 and T2 values of the normal nucleus pulposus decrease with age. There was no significant correlation between proton density and age in normal discs. At all ages there was a highly significant difference between the T1 values of normal and degenerate discs. With T2 a highly significant difference in the younger age groups reduced to no distinction in the seventh decade. The observed change in the T1 and T2 values of the nucleus is in agreement with the reduction of water content known to occur with age. Our results indicate that quantitative MR imaging may assist in the diagnosis of intervertebral disc degeneration.

Adolescent↗
PubMed1993

Flat bed scanner in the quantitative assay of 35SO4-incorporation by X-ray film autoradiography of intervertebral disc sections.

A rapid quantitation of proteoglycan synthesis distribution in intervertebral disc and endplates is described. Tissue blocks of disc (C7-Th1) in the midsagittal plane from ten female beagles were incubated in the presence of 35SO4 and prepared as histological slides. For comparison, sulphate incorporation rates in the C5-C6 discs were assayed by liquid scintillation. Autoradiographic film exposed against the labelled sections was developed and digitized for image analysis using a 256 grey level flat bed table scanner connected to a microcomputer. The film density versus dpm (disintegrations per minute) calibration was performed using a set of 35SO4-labelled glycosaminoglycan standards applied on the same film. Since section thickness, dpm calibration of the film density and the specific activity of sulphate in the medium were known, the incorporations per tissue volume could be calculated. The average incorporation rates of the anterior and posterior annulus fibrosus, nucleus pulposus and vertebral endplates were 5.2 +/- 0.9, 5.2 +/- 0.8, 4.5 +/- 0.6 and 4.1 +/- 0.8 pmol/mm3 per h (+/- SE, n = 10), respectively and closely corresponded to those obtained by liquid scintillation. This method offers a convenient and reproducible way to measure the rate of proteoglycan synthesis in large tissue sections but also in thin cartilaginous tissues such as the vertebral endplate.

Animals↗
PubMed2002

Construction of recombinant adenoviral vector Ad-CMV-hTGFbeta1 for reversion of intervertebral disc degeneration by gene transfer.

OBJECTIVE: To provide a highly efficient adenoviral vector Ad-CMV-hTGFbeta1 for the study of gene therapy for reversion of the intervertebral disc degeneration. METHODS: A newly developed recombinant adenoviral vector construction system was used in the study. The cDNA of hTGFbeta1 was first subcloned into a shuttle plasmid pShuttle-CMV. The resultant plasmid was linearized by digesting with restriction endonuclease PmeI, and subsequently transformed into E.coli. BJ5183 cells with an adenoviral backbone plasmid pAdEasy-1. Recombinants were selected by kanamycin resistance and confirmed by restriction endonuclease analysis. Finally, the recombinant plasmid linearized by PmeI was transfected into 293 cells. Recombinant adenoviruses were generated within 2 weeks. RESULTS: The recombinant adenoviral plasmids were cut by BamHI and PacI respectively, and the diagnostic fragments appeared in 0.8% agarose electrophoresis. The infected 293 cells showed evident cytopathic effect (CPE). The productions of PCR confirmed the presence of recombinant adenovirus. The expression of hTGFbeta1 was verified by immunohistochemical staining. CONCLUSIONS: The successful generation of the adenoviral vector Ad-CMV-hTGFbeta1 and the confirmation of the interest gene expression make it possible for the experimental study of the reversion of the intervertebral disc degeneration by gene therapy.

Adenoviridae↗
PubMedDate not supplied

Three-dimensional architecture of lumbar intervertebral discs.

Three-dimensional observations of the collagen framework of lumbar intervertebral discs by scanning electron microscopy confirmed that the fibrillar framework of the annulus and the cartilage end-plate was made of nucleus as a closed pack system. The cartilage end-plate was made of dense collagen framework aligned horizontally. There was no interconnection between the cartilage end-plate and the lamellar subchondral collagen. In places, the vascular channels ran directly at the end-plate. In the inner one third of the annulus, obliquely oriented fibrillar lamellae interconnected with the cartilage end-plate. In the outer two thirds, the fibrillar lamellae were formed from fibrillar bundles and were firmly anchored into the vertebral bodies. Architectural relationships between the disc and the vertebral bodies are discussed.

Cartilage↗
PubMed1993

A poroelastic-swelling finite element model with application to the intervertebral disc.

The swelling process that occurs in soft tissue is incorporated into a poroelastic finite element model. The model is applied to a spinal segment consisting of two vertebrae and a single intervertebral disc. The theory is an extension of the poroelastic theory developed by Biot and the model is an adaptation of an axisymmetric poroelastic finite element model of the intervertebral disc by Simon. The model is completely three-dimensional although the results presented here assume symmetry about the sagittal plane. The theory is presented in two stages. First the development of the poroelastic theory. Following this, the effects of swelling caused by osmotic pressure are developed and expressed as a modification of the constitutive law and initial stresses. In the case of the disc, this pressure is produced mainly by the fixed negative charges on the proteoglycans within the disc. In this development we assume that the number of fixed charges remains constant over time and that the distribution of mobile ions has reached equilibrium. The variations over time in osmotic pressure, and thus in swelling effects are therefore only dependent on the initial state and the change in water content. Variations of the swelling effects caused by changes in mobile ion concentrations will be the subject of a future paper. The results reported in this article illustrate the dramatic effect of swelling on the load carrying mechanisms in the disc. The authors believe it is likely that this will have important useful implications for our understanding not only of normal disc function, but also of abnormal function, such as disc degeneration, herniation, and others.

Elasticity↗
PubMed1976

The chemical constitution of the proteoglycan of human intervertebral disc.

Proteoglycan was prepared from three pools of normal human intervertebral discs by extraction with buffered 4M-guanidinium chloride followed by CsCl-density-gradient ultracentrifugation. Chromatography on agarose (Bio-Gel A-150m) and on DEAE-cellulose suggested a single polydisperse proteoglycan species. The intrinsic viscosities of three preparations were 166, 122 and 168 ml/g. After degradation with 0.5M-KOH containing 0.02M-NaBH4, the glycosaminoglycans were recovered quantitatively and their Ca2+ salts separated into a hexuronate-rich fraction (fraction 1), which was precipitated in 0-45% (v/v) ethanol, and a hexose-rich fraction (fraction2), which was precipitated in 45-70% (v/v) ethanol. Qualitative and quantitative analyses of the glycosaminoglycans revealed fraction 1 to be chondroitin sulphate, and fraction 2 to be keratan sulphate; the latter was contaminated with protein and possibly a small amount of another glycosaminoglycan. For both glycosaminoglycans, plots of log(mol.wt.) against weight fell close to a normal distribution. The mode for chondroitin sulphate was close to 20000; that for keratan sulphate, 10000. A threefold range of molecular weight included the central 16-84% [+/- 1 S.D. of log(mol.wt.)] of the weight of both fractions.

Adult↗
PubMed1994

Mechanical evaluation of a canine intervertebral disc spacer: in situ and in vivo studies.

An elastomeric intervertebral disc spacer with hydroxyapatite ingrowth surfaces was implanted in a canine model. We studied (a) the mechanical behavior of motion segments at time 0 and at 3, 6, and 12 months and (b) the effect of the interface between the spacer and vertebral bone on implant stability and bone ingrowth. A polymeric spacer was designed with compressive and torsional properties similar to those of the isolated canine lumbar disc. Implantation of the spacer in canine cadaver motion segments permitted in situ biomechanical evaluation at time 0. An in vivo study permitted continuous neurological monitoring of animals, with evaluation of mechanical behavior, stability, and ingrowth at 3, 6, and 12 months. Mechanical testing of cadaver motion segments with the spacer in situ resulted in decreased compressive and torsional stiffnesses, averaging 25 and 42%, respectively. This decrease was due to a combination of the surgical insult to the annulus and decortication of adjacent vertebral endplates. In the in vivo study, all 12 animals tolerated the surgery well and none had permanent neurological impairment. The measured parameters indicated that behavior of the spacer-motion segment composite appeared to return to normal within 3-6 months. However, despite use of a porous hydroxyapatite on the implant surface, there was no significant bone ingrowth. Instead, a layer of dense fibrous connective tissue was formed at the spacer-vertebral bone interface. Early migration of five of the 12 spacers resulted in eccentric loading patterns with consistent reactive osteophyte formation.

Animals↗
PubMed2000

Matrix metalloproteinases and aggrecanase: their role in disorders of the human intervertebral disc.

STUDY DESIGN: A comprehensive immunohistochemical study of matrix metalloproteinase activity in discs from patients with different disc diseases. OBJECTIVES: To identify individual matrix metalloproteinase enzymes that could contribute to the degeneration of the matrix of the intervertebral disc, to identify the cells that produce matrix metalloproteinases (for example, the endogenous disc cells or invading cells associated with vascularisation), and to determine if "aggrecanase" contributes to degradation of proteoglycans in disc disorders. SUMMARY OF BACKGROUND DATA: Matrix disorganization and loss of substance are the most common findings in degenerate discs, and proteinase enzyme activity is one means of causing these changes. METHODS: Forty-nine discs from 46 patients with degenerative disc disease, posterior anular tears, spondylolisthesis, or disc herniation were studied immunohistochemically to determine the presence of matrix metalloproteinases 1, 2, 3, 7, 8, 9 and 13, tissue metalloproteinases 1 and 2, and proteoglycan degradation products generated by either matrix metalloproteinases or aggrecanase activity. In addition, in situ zymography was used to confirm matrix metalloproteinase activity. RESULTS: The most extensive staining was seen for matrix metalloproteinases 1, 2, 3, and 9, with 91%, 71%, 65%, and 72% of samples having some immunopositivity for the respective antibodies. In contrast, staining for matrix metalloproteinases 7 and 8 was much less (38% for both). Tissue inhibitor of metalloproteinases 1 and 2 were expressed in 34% and 79% of specimens, respectively. Matrix metalloproteinases were found particularly in cell clusters and blood vessels of degenerate discs, with staining correlating positively with macroscopic degenerative grade. For all of the enzymes, there was most staining in the herniation specimens and least in the autopsy samples. The opposite was true of staining for the matrix metalloproteinases inhibitor, tissue inhibitor of metalloproteinases 2, with most found in the autopsy specimens. Enzyme activity was confirmed by in situ zymography and staining for matrix metalloproteinase degradation products of proteoglycans. In addition, there was staining with antibodies demonstrating aggrecanase degradation products. CONCLUSIONS: Matrix metalloproteinase activity is more prevalent in herniated discs than in other disc disorders studied, although matrix metalloproteinases may have been more common earlier in the disease progression. Matrix metalloproteinases can be produced by invading blood vessels and associated cells, as well as by indigenous disc cells. Aggrecanase activity, although present in some samples, was not as obvious as that of matrix metalloproteinases. In addition to altered matrix metalloproteinase production, there appears to be a change in the balance between enzymes and endogenous inhibitors, tissue inhibitors of metalloproteinases. This study highlights specific matrix metalloproteinases that might be most efficient to target in developing therapeutics for minimizing degradation of the extracellular matrix of the disc.

Adolescent↗
PubMed1992

Induced narrowing and back adaptation of lumbar intervertebral discs in biomechanically stressed rats.

The purpose of this work was to develop an animal model of chronic low-back dysfunction induced by biomechanical stress. The intervertebral disc size was measured by radiography and histology in control rats, in rats intermittently forced to ambulate on a flat surface or in cylinders. Forced ambulation in cylinders caused rats to assume a relative extensive posture in the low back. Lumbar discs in biomechanically stressed rats initially narrowed, and after months of continued intermittent stress, regained near-normal size in vivo, shown by radiography. By using histologic methods, discs from rats that ambulated in any posture were shown to be larger than discs from rats not forced to ambulate. The results were consistent with the hypothesis that in vivo discs in biomechanically stressed rats initially narrow due to compressive loading and then widen back toward normal size because of an altered matrix which has increased imbibing properties. According to this hypothesis altered matrix synthesis in the nucleus pulposus was an adaptation induced by the cyclic compressive loading associated with ambulation.

Adaptation, Physiological↗
PubMed1993

Lymph and blood supply of the human intervertebral disc. Cadaver study of correlations to discitis.

Immunohistochemical (antibodies against laminin) and histochemical methods (Ulex europaeus lectin, 5'-nucleotidase activity) were used to describe the vascular pattern of human intervertebral discs and the surrounding tissue at different ages. Blood and lymph vessels were found in the connective tissue outside the annulus in all age groups. In the annulus blood vessels and lymphatics were detected up to 20 years of age, in the cartilage end-plate blood vessels appeared up to 7 years of age (cartilage canals). In the nucleus pulposus neither blood nor lymph vessels could be seen at any age. The occurrence of blood and lymph vessels in growing intervertebral discs help us to understand childhood discitis without simultaneous affection of the vertebral body.

Adolescent↗
PubMed1989

Excimer ablation of human intervertebral disc at 308 nanometers.

Excimer laser energy, which has been shown to photoablate tissue at a precisely controllable rate with minimal thermal damage, was applied to human intervertebral disc in an effort to develop a technique for percutaneous discectomy. Cadaveric samples of human disc were used. Excimer laser energy was produced by a XeCl, magnetically switched, long-pulse laser working at 308 nm, 20 Hz. Annulus tissue of approximately 1 mm thickness was placed in contact with the output tip of a 400 microns core diameter quartz fiber, and measurements of ablation rate were made at different radiant exposures. Ablation rates were found to vary linearly with radiant exposure, from 0.7 micron/pulse at 10 mJ/mm2 to 11.0 microns/pulse at 55 mJ/mm2, with a correlation coefficient of 0.984. Threshold radiant exposure, calculated by extrapolation, was found to be about 7 mJ/mm2. Histologic analysis showed a minimum of thermal damage in these specimens, and when ablated with modification to maintain constant fiber-tissue contact, thermal injury was nearly absent, as compared to samples ablated with Nd:YAG through a contact probe. Thermographic analysis, performed using the AGA 782 Digital Thermography system, showed increasing temperature with increasing radiant exposure, with a maximum temperature of 47.2 degrees C at 55 mJ/mm2. In that precise tissue ablation was demonstrated with minimal generated heat, and excimer energy at 308 nm is transmissible through fiber optics, excimer holds great promise for the development of a percutaneous discectomy technique.

Humans↗
PubMed2006

Accelerated intervertebral disc degeneration in scoliosis versus physiological ageing develops against a background of enhanced anabolic gene expression.

Molecular consequences of long-term deformation and altered mechanical loading of intervertebral disc (IVD) tissue in scoliosis have yet to be elucidated. We hypothesized that histological disc degeneration is faster in scoliosis than in normal ageing and that this is reflected by an altered gene expression profile. A semiquantitative histodegeneration score (HDS) revealed significantly enhanced degeneration in scoliosis (HDS 5.3) versus age-matched control IVDs (HDS 2.25; p = 0.001). Gene expression analysis by cDNA array and RT-PCR demonstrated higher mRNA levels for extracellular-matrix molecules like aggrecan, biglycan, decorin, lumican, chondromodulin, and COL2A1 in scoliotic discs versus normal discs of identical degeneration score. No differences were evident for catabolic molecules like MMP3, MMP13, MMP17, and TIMP1. In sum, morphologic disc degeneration was accelerated by about 2 decades in scoliosis versus physiological ageing and developed against a background of stronger anabolic matrix metabolism at younger age or in response to the altered mechanical environment of the tissue.

Adolescent↗