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Sample records for intact human intervertebral

  1. Elastin in the human intervertebral disk. A histological and biochemical study comparing it with elastin in the human yellow ligament.

    Science.gov (United States)

    Mikawa, Y; Hamagami, H; Shikata, J; Yamamuro, T

    1986-01-01

    The elastic fiber and elastin in the human yellow ligament and intervertebral disk were studied histologically and biochemically. The elastic fiber in the human intervertebral disk, which until now had not been clearly identified microscopically, was observed clearly. We found the distribution of the elastic fiber in the intervertebral disk to be very sparse and irregular, and its diameter was small, being about one-tenth of that found in the yellow ligament. The elastin contents of the yellow ligament and intervertebral disk were 46.7% +/- 0.9% and 1.7% +/- 0.2% respectively (mean +/- SE) of the total dry weight. The amino acid composition of elastin in the yellow ligament is similar to that of other tissue, as reported in the literature; however, that found in the intervertebral disk is significantly different. It would appear, therefore, that the elastin in the intervertebral disk is of a different type from that found elsewhere.

  2. Structural behavior of human lumbar intervertebral disc under direct shear.

    Science.gov (United States)

    Schmidt, Hendrik; Häussler, Kim; Wilke, Hans-Joachim; Wolfram, Uwe

    2015-03-18

    The intervertebral disc (IVD) is a complex, flexible joint between adjacent vertebral bodies that provides load transmission while permitting movements of the spinal column. Finite element models can be used to help clarify why and how IVDs fail or degenerate. To do so, it is of importance to validate those models against controllable experiments. Due to missing experimental data, shear properties are not used thus far in validating finite element models. This study aimed to investigate the structural shear properties of human lumbar IVDs in posteroanterior (PA) and laterolateral (LL) loading directions. Fourteen lumbar IVDs (median age: 49 years) underwent direct shear in PA and LL loading directions. A custom-build shear device was used in combination with a materials testing machine to load the specimens until failure. Shear stiffness, ultimate shear force and displacement, and work to failure were determined. Each specimen was tested until complete or partial disruption. Median stiffness in PA direction was 490 N/mm and in LL direction 568 N/mm. Median ultimate shear force in the PA direction was 2,877 N and in the LL direction 3,199 N. Work to failure was 12 Nm in the PA and 9 Nm in the LL direction. This study was an experiment to subject IVDs to direct shear. The results could help us to understand the structure and function of IVDs with regard to mechanical spinal stability, and they can be used to validate finite element models of the IVD.

  3. Degenerated human intervertebral discs contain autoantibodies against extracellular matrix proteins

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    S Capossela

    2014-04-01

    Full Text Available Degeneration of intervertebral discs (IVDs is associated with back pain and elevated levels of inflammatory cells. It has been hypothesised that discogenic pain is a direct result of vascular and neural ingrowth along annulus fissures, which may expose the avascular nucleus pulposus (NP to the systemic circulation and induce an autoimmune reaction. In this study, we confirmed our previous observation of antibodies in human degenerated and post-traumatic IVDs cultured in vitro. We hypothesised that the presence of antibodies was due to an autoimmune reaction against specific proteins of the disc. Furthermore we identified antigens which possibly trigger an autoimmune response in degenerative disc diseases. We demonstrated that degenerated and post-traumatic IVDs contain IgG antibodies against typical extracellular proteins of the disc, particularly proteins of the NP. We identified IgGs against collagen type II and aggrecan, confirming an autoimmune reaction against the normally immune privileged NP. We also found specific IgGs against collagens types I and V, but not against collagen type III. In conclusion, this study confirmed the association between disc degeneration and autoimmunity, and may open the avenue for future studies on developing prognostic, diagnostic and therapy-monitoring markers for degenerative disc diseases.

  4. Nonlinear dynamics of the human lumbar intervertebral disc.

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    Marini, Giacomo; Huber, Gerd; Püschel, Klaus; Ferguson, Stephen J

    2015-02-05

    Systems with a quasi-static response similar to the axial response of the intervertebral disc (i.e. progressive stiffening) often present complex dynamics, characterized by peculiar nonlinearities in the frequency response. However, such characteristics have not been reported for the dynamic response of the disc. The accurate understanding of disc dynamics is essential to investigate the unclear correlation between whole body vibration and low back pain. The present study investigated the dynamic response of the disc, including its potential nonlinear response, over a range of loading conditions. Human lumbar discs were tested by applying a static preload to the top and a sinusoidal displacement at the bottom of the disc. The frequency of the stimuli was set to increase linearly from a low frequency to a high frequency limit and back down. In general, the response showed nonlinear and asymmetric characteristics. For each test, the disc had different response in the frequency-increasing compared to the frequency-decreasing sweep. In particular, the system presented abrupt changes of the oscillation amplitude at specific frequencies, which differed between the two sweeps. This behaviour indicates that the system oscillation has a different equilibrium condition depending on the path followed by the stimuli. Preload and amplitude of the oscillation directly influenced the disc response by changing the nonlinear dynamics and frequency of the jump-phenomenon. These results show that the characterization of the dynamic response of physiological systems should be readdressed to determine potential nonlinearities. Their direct effect on the system function should be further investigated. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Correlations between radiographic, magnetic resonance and histological examinations on the degeneration of human lumbar intervertebral discs

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    Delio Eulalio Martins

    Full Text Available CONTEXT AND OBJECTIVE: There is controversy regarding which imaging method is best for identifying early degenerative alterations in intervertebral discs. No correlations between such methods and histological finds are presented in the literature. The aim of this study was to correlate the thickness of intervertebral discs measured on simple radiographs with the degree of degeneration seen on magnetic resonance images and the histological findings relating to nerve ends inside the discs. DESIGN AND SETTING: Cross-sectional correlation study on the lumbar spines of human cadavers, at Universidade Federal de São Paulo (Unifesp, São Paulo, Brazil. METHODS: Ten lumbar spinal columns were extracted from human cadavers and subjected to magnetic resonance imaging and simple radiography. They were classified according to the degree of disc degeneration seen on magnetic resonance, and the thickness of the discs was measured on radiographs. The intervertebral discs were then extracted, embedded in paraffin and analyzed immunohistochemically with protein S100, and the nerve fibers were counted and classified. RESULTS: No correlation was observed between the thickness of the intervertebral discs and the degree of degeneration seen on magnetic resonance images. Only the uppermost lumbar discs (L1/L2 and L2/L3 presented a correlation between their thickness and type I and IV nerve endings. CONCLUSION: Reduced disc thickness is unrelated to increased presence of nerve ends in intervertebral discs, or to the degree of disc degeneration.

  6. The presence and absence of lymphatic vessels in the adult human intervertebral disc: relation to disc pathology

    International Nuclear Information System (INIS)

    Kliskey, Karolina; Williams, Kelly; Yu, J.; Urban, Jill; Athanasou, Nick; Jackson, David

    2009-01-01

    Although the normal adult human intervertebral disc is considered to be avascular, vascularised cellular fibrous tissue can be found in pathological conditions involving the disc such as disc herniation. Whether lymphatics vessels form a component of this reparative tissue is not known as the presence or absence of lymphatics in herniated and normal disc tissue is not known. We examined spinal tissues and discectomy specimens for the presence of lymphatics. The examination used immunohistochemistry to identify the specific lymphatic endothelial cell markers, podoplanin and LYVE1. Lymphatic vessels were not found in the nucleus pulposus or annulus fibrosus of intact, non-herniated lumbar and thoracic discs but were present in the surrounding ligaments. Ingrowth of fibrous tissue was seen in 73% of herniated disc specimens of which 36% contained LYVE1+/podoplanin + lymphatic vessels. Lymphatic vessels were not seen in the sacrum and coccyx or biopsies of four sacrococcygeal chordomas, but they were noted in surrounding extra-osseous fat and fibrous tissue at the edge of the infiltrating tumour. Our findings indicate that lymphatic vessels are not present in the normal adult intervertebral disc but that, when there is extrusion of disc material into surrounding soft tissue, there is ingrowth of reparative fibrous tissue containing lymphatic vessels. Our findings also indicate that chordoma, a tumour of notochordal origin, spreads to regional lymph nodes via lymphatics in para-spinal soft tissues. (orig.)

  7. Aggrecan turnover in human intervertebral disc as determined by the racemization of aspartic acid

    NARCIS (Netherlands)

    Sivan, S.S.; Tsitron, E.; Wachtel, E.; Roughley, P.J.; Sakkee, N.; Ham, F. van der; Groot, J.de; Roberts, S.; Maroudas, A.

    2006-01-01

    We have used the racemization of aspartic acid as a marker for the "molecular age" of aggrecan components of the human intervertebral disc matrix (aggregating and non-aggregating proteoglycans as well as the different buoyant density fractions of aggrecan). By measuring the D/L Asp ratio of the

  8. Longevity of elastin in human intervertebral disc as probed by the racemization of aspartic acid

    DEFF Research Database (Denmark)

    Sivan, Sarit-Sara; Van El, Benno; Merkher, Yulia

    2012-01-01

    BACKGROUND: Aging and degeneration of human intervertebral disc (IVD) are associated with biochemical changes, including racemization and glycation. These changes can only be counteracted by protein turnover. Little is known about the longevity of IVD elastin in health or disease. Yet, such knowl...

  9. Knockdown of asporin affects transforming growth factor-β1-induced matrix synthesis in human intervertebral annulus cells

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    Xu Jiang

    2016-10-01

    Conclusion: Our results have verified a functional feedback loop between TGF-β1 and asporin in human intervertebral annulus cells indicating that TGF-β1-induced annulus matrix biosynthesis can be significantly upregulated by knockdown of asporin. Therefore, asporin could be a potential new therapeutic target and inhibition of asporin could be adopted to enhance the anabolic effect of TGF-β1 in human intervertebral annulus cells in degenerative IVD diseases.

  10. Are specific gene expressions of extracellular matrix and nucleus pulposus affected by primary cell cultures prepared from intact or degenerative intervertebral disc tissues?

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    Karaarslan, Numan; Yilmaz, Ibrahim; Ozbek, Hanefi; Sirin Yasar, Duygu; Kaplan, Necati; Akyuva, Yener; Gonultas, Aylin; Ates, Ozkan

    2018-01-22

    In this scientific research project, the researchers aimed to determine the gene expression patterns of nucleus pulposus (NP) in cell cultures obtained from degenerated or intact tissues. Whereas 12 of the cases were diagnosed with lumbar disc hernia and had undergone lumbar microdiscectomy, 12 cases had undergone traumatic intervertebral discectomy and corpectomy, along with discectomy after spinal trauma. NP-specific markers and gene expressions of the reagents of the extracellular matrix in the experimental setup were tested at the 0th, 24th, and 48th hours by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Visual evaluations were simultaneously made in all samples using invert and fluorescence microscopy. Vitality and proliferation analyses were evaluated by UV spectrophotometer. As a method of statistical evaluation, Spearman was used for categorical variants, and the Pearson correlation was used for variants with numerical and plain distribution. No association was found either between the tissue type and times (r=0.000; p=1.000) or between the region that the tissue was obtained from and hypoxia transcription factor-1 alpha (HIF-1α) gene expression (r=0.098; p=0.245). There was no correlation between cell proliferation and chondroadherin (CHAD) expression or between type II collagen (COL2A1) and CHAD gene expressions. It was found that CHAD and HIF-1α gene expressions and HIF-1α and COL2A1 gene expressions affected cell proliferation. Cell culture setups are of paramount importance because they may influence the pattern of changes in the gene expressions of the cells used in these setups.

  11. Does human leukocyte elastase degrade intact skin elastin?

    DEFF Research Database (Denmark)

    Schmelzer, Christian E H; Jung, Michael C; Wohlrab, Johannes

    2012-01-01

    This study aimed to investigate the susceptibility of intact fibrillar human elastin to human leukocyte elastase and cathepsin G. Elastin is a vital protein of the extracellular matrix of vertebrates, and provides exceptional properties including elasticity and tensile strength to many tissues...... and organs, including the aorta, lung, cartilage, elastic ligaments and skin, and is thus critical for their long-term function. Mature elastin is an insoluble and extremely durable protein that undergoes very little turnover, but sustained exposure to proteases may lead to irreversible and severe damage......, and thus to functional loss of the elastic fiber network. Hence, it is a key issue to understand which enzymes actually initiate elastolysis under certain pathological conditions or during intrinsic aging. In this paper, we provide a complete workflow for isolation of pure and intact elastin from very...

  12. Collagen turnover in normal and degenerate human intervertebral discs as determined by the racemization of aspartic acid

    NARCIS (Netherlands)

    Sivan, S.-S.; Wachtel, E.; Tsitron, E.; Sakkee, N.; Ham, F. van der; Groot, J.de; Roberts, S.; Maroudas, A.

    2008-01-01

    Knowledge of rates of protein turnover is important for a quantitative understanding of tissue synthesis and catabolism. In this work, we have used the racemization of aspartic acid as a marker for the turnover of collagen obtained from healthy and pathological human intervertebral disc matrices. We

  13. Finite element based nonlinear normalization of human lumbar intervertebral disc stiffness to account for its morphology.

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    Maquer, Ghislain; Laurent, Marc; Brandejsky, Vaclav; Pretterklieber, Michael L; Zysset, Philippe K

    2014-06-01

    Disc degeneration, usually associated with low back pain and changes of intervertebral stiffness, represents a major health issue. As the intervertebral disc (IVD) morphology influences its stiffness, the link between mechanical properties and degenerative grade is partially lost without an efficient normalization of the stiffness with respect to the morphology. Moreover, although the behavior of soft tissues is highly nonlinear, only linear normalization protocols have been defined so far for the disc stiffness. Thus, the aim of this work is to propose a nonlinear normalization based on finite elements (FE) simulations and evaluate its impact on the stiffness of human anatomical specimens of lumbar IVD. First, a parameter study involving simulations of biomechanical tests (compression, flexion/extension, bilateral torsion and bending) on 20 FE models of IVDs with various dimensions was carried out to evaluate the effect of the disc's geometry on its compliance and establish stiffness/morphology relations necessary to the nonlinear normalization. The computed stiffness was then normalized by height (H), cross-sectional area (CSA), polar moment of inertia (J) or moments of inertia (Ixx, Iyy) to quantify the effect of both linear and nonlinear normalizations. In the second part of the study, T1-weighted MRI images were acquired to determine H, CSA, J, Ixx and Iyy of 14 human lumbar IVDs. Based on the measured morphology and pre-established relation with stiffness, linear and nonlinear normalization routines were then applied to the compliance of the specimens for each quasi-static biomechanical test. The variability of the stiffness prior to and after normalization was assessed via coefficient of variation (CV). The FE study confirmed that larger and thinner IVDs were stiffer while the normalization strongly attenuated the effect of the disc geometry on its stiffness. Yet, notwithstanding the results of the FE study, the experimental stiffness showed consistently

  14. Geometry of the Intervertebral Volume and Vertebral Endplates of the Human Spine

    NARCIS (Netherlands)

    van der Houwen, E. B.; Baron, P.; Veldhuizen, A. G.; Burgerhof, J. G. M.; van Ooijen, P. M. A.; Verkerke, G. J.

    Replacement of a degenerated vertebral disc with an artificial intervertebral disc (AID) is currently possible, but poses problems, mainly in the force distribution through the vertebral column. Data on the intervertebral disc space geometry will provide a better fit of the prosthesis to the

  15. Geometry of the Intervertebral Volume and Vertebral Endplates of the Human Spine

    NARCIS (Netherlands)

    van der Houwen, E.B.; Baron, P.; Veldhuizen, A.G.; Burgerhof, J.G.M.; van Ooijen, P.M.A.; Verkerke, Gijsbertus Jacob

    2010-01-01

    Replacement of a degenerated vertebral disc with an artificial intervertebral disc (AID) is currently possible, but poses problems, mainly in the force distribution through the vertebral column. Data on the intervertebral disc space geometry will provide a better fit of the prosthesis to the

  16. Mechanical Characterization of the Human Lumbar Intervertebral Disc Subjected to Impact Loading Conditions

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    Jamison, David, IV

    Low back pain is a large and costly problem in the United States. Several working populations, such as miners, construction workers, forklift operators, and military personnel, have an increased risk and prevalence of low back pain compared to the general population. This is due to exposure to repeated, transient impact shocks, particularly while operating vehicles or other machinery. These shocks typically do not cause acute injury, but rather lead to pain and injury over time. The major focus in low back pain is often the intervertebral disc, due to its role as the major primary load-bearing component along the spinal column. The formation of a reliable standard for human lumbar disc exposure to repeated transient shock could potentially reduce injury risk for these working populations. The objective of this project, therefore, is to characterize the mechanical response of the lumbar intervertebral disc subjected to sub-traumatic impact loading conditions using both cadaveric and computational models, and to investigate the possible implications of this type of loading environment for low back pain. Axial, compressive impact loading events on Naval high speed boats were simulated in the laboratory and applied to human cadaveric specimen. Disc stiffness was higher and hysteresis was lower than quasi-static loading conditions. This indicates a shift in mechanical response when the disc is under impact loads and this behavior could be contributing to long-term back pain. Interstitial fluid loss and disc height changes were shown to affect disc impact mechanics in a creep study. Neutral zone increased, while energy dissipation and low-strain region stiffness decreased. This suggests that the disc has greater clinical instability during impact loading with progressive creep and fluid loss, indicating that time of day should be considered for working populations subjected to impact loads. A finite element model was developed and validated against cadaver specimen

  17. Ultrastructure of inclusion bodies in annulus cells in the degenerating human intervertebral disc.

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    Gruber, H E; Hanley, E N

    2009-06-01

    The rough endoplasmic reticulum (rER) of the cell has an architectural editing function that checks whether protein structure and three-dimensional assembly have occurred properly prior to export of newly synthesized material out of the cell. If these have been faulty, the material is retained within the rER as an inclusion body. Inclusion bodies have been identified previously in chondrocytes and osteoblasts in chondrodysplasias and osteogenesis imperfecta. Inclusion bodies in intervertebral disc cells, however, have only recently been recognized. Our objectives were to use transmission electron microscopy to analyze more fully inclusion bodies in the annulus pulposus and to study the extracellular matrix (ECM) surrounding cells containing inclusion bodies. ECM frequently encapsulated cells with inclusion bodies, and commonly contained prominent banded aggregates of Type VI collagen. Inclusion body material had several morphologies, including relatively smooth, homogeneous material, or a rougher, less homogeneous feature. Such findings expand our knowledge of the fine structure of the human disc cell and ECM during disc degeneration, and indicate the potential utility of ultrastructural identification of discs with intracellular inclusion bodies as a screening method for molecular studies directed toward identification of defective gene products in degenerating discs.

  18. The role of inorganic phosphate in intact human erythrocytes

    International Nuclear Information System (INIS)

    Nishiguchi, Eiko; Umeda, Masahiro.

    1988-01-01

    The role of inorganic phosphate in intact human erythrocytes was investigated by phosphorus-31 nuclear magnetic resonance ( 31 P NMR). When erythrocytes stored for 5 weeks were incubated at 37 deg C, pH 7.4, in medium containing 2 mM adenine and 10 mM inosine, with or without 5 mM glucose, a substance of around 4 ppm, as assessed by 31 P NMR chemical shift, was detected in the mixture. However, this substance disappeared by the addition of inorganic phosphate. When erythrocytes stored for 4 weeks in acid citrate dextrose (ACD) solution were incubated with 2 mM adenine, 10 mM inosine, 5 mM glucose, 50 mM inorganic phosphate and 10 mM pyruvate at 37 deg C, pH 7.4, the 2,3-DPG level increased gradually, whereas the ATP level initially increased and then decreased. Intracellular inorganic phosphate appeared to be used for the synthesis of ATP and 2,3-DPG during the first 30 min. of the reaction. These results suggests that the inorganic phosphate accelerates glycolysis by increasing the activity of glycolytic enzymes rather than its direct involvement in synthesizing organic phosphorus compounds in stored erythrocytes. The results also suggests that the reserve energy from ATP synthesis is not sufficient for the synthesis of 2,3-DPG. (author)

  19. Axial Creep Loading and Unloaded Recovery of the Human Intervertebral Disc and the Effect of Degeneration

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    O'Connell, Grace D.; Jacobs, Nathan T.; Sen, Sounok; Vresilovic, Edward J.; Elliott, Dawn M.

    2011-01-01

    The intervertebral disc maintains a balance between externally applied loads and internal osmotic pressure. Fluid flow plays a key role in this process, causing fluctuations in disc hydration and height. The objectives of this study were to quantify and model the axial creep and recovery responses of nondegenerate and degenerate human lumbar discs. Two experiments were performed. First, a slow compressive ramp was applied to 2000 N, unloaded to allow recovery for up to 24 hours, and re-applied. The linear-region stiffness and disc height were within 5% of the initial condition for recovery times greater than 8 hours. In the second experiment, a 1000 N creep load was applied for four hours, unloaded recovery monitored for 24 hours, and the creep load repeated. A viscoelastic model comprised of a “fast” and “slow” exponential response was used to describe the creep and recovery, where the fast response is associated with flow in the nucleus pulposus (NP) and endplate, while the slow response is associated with the annulus fibrosus (AF). The study demonstrated that recovery is 3-4X slower than loading. The fast response was correlated with degeneration, suggesting larger changes in the NP with degeneration compared to the AF. However, the fast response comprised only 10-15% of the total equilibrium displacement, with the AF-dominated slow response comprising 40-70%. Finally, the physiological loads and deformations and their associated long equilibrium times confirm that diurnal loading does not represent “equilibrium” in the disc, but that over time the disc is in steady-state. PMID:21783103

  20. Phosphorylation of intact erythrocytes in human muscular dystrophy

    International Nuclear Information System (INIS)

    Johnson, R.M.; Nigro, M.

    1986-01-01

    The uptake of exogenous 32 Pi into the membrane proteins of intact erythrocytes was measured in 8 patients with Duchenne muscular dystrophy. No abnormalities were noted after autoradiographic analysis. This contrasts with earlier results obtained when isolated membranes were phosphorylated with gamma-[ 32 P]ATP, and suggests a possible reinterpretation of those experiments

  1. The Changes in the Expression of NF-KB in a Degenerative Human Intervertebral Disc model.

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    Sun, Zhongyi; Yin, Zhanmin; Liu, Chao; Tian, Jiwei

    2015-05-01

    We aim at determining the changes in the expression of NF-kB signaling pathway in degenerative intervertebral discs. We collected normal and degenerated intervertebral discs tissues. The normal and degenerated cells were cultivated and their histopathology and immunofluoresence studies were used to observe the position of NF-kB p65 in the cell. We also treated the nucleus pulposus cells with inflammatory factors and inhibitors. Western blot was used to analyze the expression of different proteins. Real time fluorescence-based quantitative PCR was used for observation of NF-kB regulation of change in gene expression. Immunofluorescence showed that in the non-degenerative group the p65 was found in the cytoplasm of the nucleus pulposus cell while in the degenerated cell group the p65 protein was found in the nucleus of the cell. The expression of p65 increased with increase in the degree of degenerative change of the nucleus pulposus cell. RT-PCR showed that the expression of matrix metalloproteinases, aggrecanases and IL-6 was higher in the degenerative group. The amount of aggrecan and type II collagen was significantly decreased in the degenerative group. IL-1β was able to upregulate the activation of NF-kB and the expression of MMP-13 and ADAMTS-4 was also significantly increased. The effect of these proteins can be inhibited by the NF-kB inhibitor, BAY11-7082. The activation of the NK-kB signaling pathway in a degenerative intervertebral disc is gradually increased, regulating the over-expression of matrix-degrading enzymes. It plays an important role in the degradation of extracellular matrix.

  2. Poroelastic behaviour of the degenerating human intervertebral disc: a ten-day study in a loaded disc culture system

    NARCIS (Netherlands)

    Emanuel, K. S.; Vergroesen, P.-P. A.; Peeters, M.; Holewijn, R. M.; Kingma, I.; Smit, T. H.

    2015-01-01

    The intervertebral disc (IVD) allows flexibility to the vertebral column, and transfers the predominant axial loads during daily activities. Its axial biomechanical behaviour is poroelastic, due to the water-binding and releasing capacity of the nucleus pulposus. Degeneration of the intervertebral

  3. Gene expression profile identifies potential biomarkers for human intervertebral disc degeneration.

    Science.gov (United States)

    Guo, Wei; Zhang, Bin; Li, Yan; Duan, Hui-Quan; Sun, Chao; Xu, Yun-Qiang; Feng, Shi-Qing

    2017-12-01

    The present study aimed to reveal the potential genes associated with the pathogenesis of intervertebral disc degeneration (IDD) by analyzing microarray data using bioinformatics. Gene expression profiles of two regions of the intervertebral disc were compared between patients with IDD and controls. GSE70362 containing two groups of gene expression profiles, 16 nucleus pulposus (NP) samples from patients with IDD and 8 from controls, and 16 annulus fibrosus (AF) samples from patients with IDD and 8 from controls, was downloaded from the Gene Expression Omnibus database. A total of 93 and 114 differentially expressed genes (DEGs) were identified in NP and AF samples, respectively, using a limma software package for the R programming environment. Gene Ontology (GO) function enrichment analysis was performed to identify the associated biological functions of DEGs in IDD, which indicated that the DEGs may be involved in various processes, including cell adhesion, biological adhesion and extracellular matrix organization. Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that the identified DEGs were potentially involved in focal adhesion and the p53 signaling pathway. Further analysis revealed that there were 35 common DEGs observed between the two regions (NP and AF), which may be further regulated by 6 clusters of microRNAs (miRNAs) retrieved with WebGestalt. The genes in the DEG‑miRNA regulatory network were annotated using GO function and KEGG pathway enrichment analysis, among which extracellular matrix organization was the most significant disrupted biological process and focal adhesion was the most significant dysregulated pathway. In addition, the result of protein‑protein interaction network modules demonstrated the involvement of inflammatory cytokine interferon signaling in IDD. These findings may not only advance the understanding of the pathogenesis of IDD, but also identify novel potential

  4. Poroelastic behaviour of the degenerating human intervertebral disc: a ten-day study in a loaded disc culture system

    Directory of Open Access Journals (Sweden)

    KS Emanuel

    2015-06-01

    Full Text Available The intervertebral disc (IVD allows flexibility to the vertebral column, and transfers the predominant axial loads during daily activities. Its axial biomechanical behaviour is poroelastic, due to the water-binding and releasing capacity of the nucleus pulposus. Degeneration of the intervertebral disc presumably affects both the instantaneous elastic response to the load on the IVD and the subsequent interstitial flow of fluid. This study aims to quantify the poroelastic behaviour of the IVD and its change with degeneration, as defined by the magnetic resonance imaging-based Pfirrmann Score (PS. For a period of ten days, 36 human lumbar IVDs were loaded with a simulated physiological axial loading regime, while deformation was monitored. The IVDs responded to the loads with instantaneous elastic and slow poroelastic axial deformation. Several mechanical parameters changed throughout the first five days of the experiment, until the IVDs settled into a dynamic equilibrium. In this equilibrium, degeneration was significantly related to a decrease in disc height loss during the daytime high load phase (ρ = -0.49, and to a decrease in the rate of this deformation during the final half hour of each day (ρ = -0.53. These properties were related to the nucleus glycosaminoglycan/hydroxyproline (GAG/HYP ratio, rather than GAG content alone, indicating that remodelling of the extracellular matrix reduces poroelastic properties of the IVD. This implies that the degenerated discs have a reduced capacity to bind water and/or a reduced resistance against fluid flow. The resulting loss in hydrostatic pressure may further change cell behaviour in the nucleus pulposus.

  5. Covert spatial attention is functionally intact in amblyopic human adults

    OpenAIRE

    Roberts, Mariel; Cymerman, Rachel; Smith, R. Theodore; Kiorpes, Lynne; Carrasco, Marisa

    2016-01-01

    Certain abnormalities in behavioral performance and neural signaling have been attributed to a deficit of visual attention in amblyopia, a neurodevelopmental disorder characterized by a diverse array of visual deficits following abnormal binocular childhood experience. Critically, most have inferred attention's role in their task without explicitly manipulating and measuring its effects against a baseline condition. Here, we directly investigate whether human amblyopic adults benefit from cov...

  6. Intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bergknut, N.

    2011-01-01

    Back pain is common in both dogs and humans, and is often associated with intervertebral disc (IVD) degeneration. The IVDs are essential structures of the spine and degeneration can ultimately result in diseases such as IVD herniation or spinal instability. In order to design new treatments halting

  7. Intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bergknut, Niklas

    Back pain is common in both dogs and humans, and is often associated with intervertebral disc (IVD) degeneration. The IVDs are essential structures of the spine and degeneration can ultimately result in diseases such as IVD herniation or spinal instability. In order to design new treatments halting

  8. Human cartilaginous endplate degeneration is induced by calcium and the extracellular calcium-sensing receptor in the intervertebral disc

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    MP Grant

    2016-07-01

    Full Text Available The cartilaginous endplates (CEPs are thin layers of hyaline cartilage found adjacent to intervertebral discs (IVDs. In addition to providing structural support, CEPs regulate nutrient and metabolic exchange in the disc. In IVD pathogenesis, CEP undergoes degeneration and calcification, compromising nutrient availability and disc cell metabolism. The mechanism(s underlying the biochemical changes of CEP in disc degeneration are currently unknown. Since calcification is often observed in later stages of IVD degeneration, we hypothesised that elevations in free calcium (Ca2+ impair CEP homeostasis. Indeed, our results demonstrated that the Ca2+ content was consistently higher in human CEP tissue with grade of disc degeneration. Increasing the levels of Ca2+ resulted in decreases in the secretion and accumulation of collagens type I, II and proteoglycan in cultured human CEP cells. Ca2+ exerted its effects on CEP matrix protein synthesis through activation of the extracellular calcium-sensing receptor (CaSR; however, aggrecan content was also affected independent of CaSR activation as increases in Ca2+ directly enhanced the activity of aggrecanases. Finally, supplementing Ca2+ in our IVD organ cultures was sufficient to induce degeneration and increase the mineralisation of CEP, and decrease the diffusion of glucose into the disc. Thus, any attempt to induce anabolic repair of the disc without addressing Ca2+ may be impaired, as the increased metabolic demand of IVD cells would be compromised by decreases in the permeability of the CEP.

  9. Quantitative Analysis of Human Salivary Gland-Derived Intact Proteome Using Top-Down Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Si; Brown, Joseph N.; Tolic, Nikola; Meng, Da; Liu, Xiaowen; Zhang, Haizhen; Zhao, Rui; Moore, Ronald J.; Pevzner, Pavel A.; Smith, Richard D.; Pasa-Tolic, Ljiljana

    2014-05-31

    There are several notable challenges inherent to fully characterizing the entirety of the human saliva proteome using bottom-up approaches, including polymorphic isoforms, post-translational modifications, unique splice variants, deletions, and truncations. To address these challenges, we have developed a top-down based liquid chromatography-mass spectrometry (LC-MS) approach, which cataloged 20 major human salivary proteins with a total of 83 proteoforms, containing a broad range of post-translational modifications. Among these proteins, several previously reported disease biomarker proteins were identified at the intact protein level, such as beta-2 microglobulin (B2M). In addition, intact glycosylated proteoforms of several saliva proteins were also characterized, including intact N-glycosylated protein prolactin inducible protein (PIP) and O-glycosylated acidic protein rich protein (aPRP). These characterized proteoforms constitute an intact saliva proteoform database, which was used for quantitative comparison of intact salivary proteoforms among six healthy individuals. Human parotid (PS) and submandibular/sublingual gland (SMSL) secretion samples (2 μg of protein each) from six healthy individuals were compared using RPLC coupled with the 12T FTICR mass spectrometer. Significantly different protein and PTM patterns were resolved with high reproducibility between PS and SMSL glands. The results from this study provide further insight into the potential mechanisms of PTM pathways in oral glandular secretion, expanding our knowledge of this complex yet easily accessible fluid. Intact protein LC-MS approach presented herein can potentially be applied for rapid and accurate identification of biomarkers from only a few microliters of human glandular saliva.

  10. The action of cobra venom phospholipase A2 isoenzymes towards intact human erythrocytes

    NARCIS (Netherlands)

    Roelofsen, B.; Sibenius Trip, M.; Verheij, H.M.; Zevenbergen, J.L.

    1980-01-01

    1. 1. Cobra venom phospholipase A2 from three different sources has been fractionated into different isoenzymes by DEAE ion-exchange chromatography. 2. 2. Treatment of intact human erythrocytes with the various isoenzymes revealed significant differences in the degree of phosphatidylcholine

  11. Regenerative and immunogenic characteristics of cultured nucleus pulposus cells from human cervical intervertebral discs.

    Directory of Open Access Journals (Sweden)

    Stefan Stich

    Full Text Available Cell-based regenerative approaches have been suggested as primary or adjuvant procedures for the treatment of degenerated intervertebral disc (IVD diseases. Our aim was to evaluate the regenerative and immunogenic properties of mildly and severely degenerated cervical nucleus pulposus (NP cells with regard to cell isolation, proliferation and differentiation, as well as to cell surface markers and co-cultures with autologous or allogeneic peripheral blood mononuclear cells (PBMC including changes in their immunogenic properties after 3-dimensional (3D-culture. Tissue from the NP compartment of 10 patients with mild or severe grades of IVD degeneration was collected. Cells were isolated, expanded with and without basic fibroblast growth factor and cultured in 3D fibrin/poly (lactic-co-glycolic acid transplants for 21 days. Real-time reverse-transcription polymerase chain reaction (RT-PCR showed the expression of characteristic NP markers ACAN, COL1A1 and COL2A1 in 2D- and 3D-culture with degeneration- and culture-dependent differences. In a 5,6-carboxyfluorescein diacetate N-succinimidyl ester-based proliferation assay, NP cells in monolayer, regardless of their grade of degeneration, did not provoke a significant proliferation response in T cells, natural killer (NK cells or B cells, not only with donor PBMC, but also with allogeneic PBMC. In conjunction with low inflammatory cytokine expression, analyzed by Cytometric Bead Array and fluorescence-activated cell sorting (FACS, a low immunogenicity can be assumed, facilitating possible therapeutic approaches. In 3D-culture, however, we found elevated immune cell proliferation levels, and there was a general trend to higher responses for NP cells from severely degenerated IVD tissue. This emphasizes the importance of considering the specific immunological alterations when including biomaterials in a therapeutic concept. The overall expression of Fas receptor, found on cultured NP cells, could have

  12. Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc.

    Science.gov (United States)

    Le Maitre, Christine L; Richardson, Stephen M A; Baird, Pauline; Freemont, Anthony J; Hoyland, Judith A

    2005-12-01

    Low back pain (LBP) is a common, debilitating and economically important disorder. Current evidence implicates loss of intervertebral disc (IVD) matrix consequent upon 'degeneration' as a major cause of LBP. Degeneration of the IVD involves increases in degradative enzymes and decreases in the extracellular matrix (ECM) component in a process that is controlled by a range of cytokines and growth factors. Studies have suggested using anabolic growth factors to regenerate the normal matrix of the IVD, hence restoring disc height and reversing degenerative disc disease. However, for such therapies to be successful it is vital that the target cells (i.e. the disc cells) express the appropriate receptors. This immunohistochemical study has for the first time investigated the expression and localization of four potentially beneficial growth factor receptors (i.e. TGFbetaRII, BMPRII, FGFR3 and IGFRI) in non-degenerate and degenerate human IVDs. Receptor expression was quantified across regions of the normal and degenerate disc and showed that cells of the nucleus pulposus (NP) and inner annulus fibrosus (IAF) expressed significantly higher levels of the four growth factor receptors investigated. There were no significant differences between the four growth factor expression in non-degenerate and degenerate biopsies. However, expression of TGFbetaRII, FGFR3 and IGFRI, but not BMP RII, were observed in the ingrowing blood vessels that characterize part of the disease aetiology. In conclusion, this study has demonstrated the expression of the four growth factor receptors at similar levels in the chondrocyte-like cells of the NP and IAF in both non-degenerate and degenerate discs, implicating a role in normal disc homeostasis and suggesting that the application of these growth factors to the degenerate human IVD would stimulate matrix production. However, the expression of some of the growth factor receptors on ingrowing blood vessels might be problematic in a therapeutic

  13. Superresolution and Fluorescence Dynamics Evidence Reveal That Intact Liposomes Do Not Cross the Human Skin Barrier

    DEFF Research Database (Denmark)

    Dreier, Jes; Sørensen, Jens A; Brewer, Jonathan R

    2016-01-01

    In this study we use the combination of super resolution optical microscopy and raster image correlation spectroscopy (RICS) to study the mechanism of action of liposomes as transdermal drug delivery systems in human skin. Two different compositions of liposomes were applied to newly excised human...... skin, a POPC liposome and a more flexible liposome containing the surfactant sodium cholate. Stimulated emission depletion microscopy (STED) images of intact skin and cryo-sections of skin treated with labeled liposomes were recorded displaying an optical resolution low enough to resolve the 100 nm...... liposomes in the skin. The images revealed that virtually none of the liposomes remained intact beneath the skin surface. RICS two color cross correlation diffusion measurements of double labeled liposomes confirmed these observations. Our results suggest that the liposomes do not act as carriers...

  14. Bioengineered human IAS reconstructs with functional and molecular properties similar to intact IAS

    Science.gov (United States)

    Singh, Jagmohan

    2012-01-01

    Because of its critical importance in rectoanal incontinence, we determined the feasibility to reconstruct internal anal sphincter (IAS) from human IAS smooth muscle cells (SMCs) with functional and molecular attributes similar to the intact sphincter. The reconstructs were developed using SMCs from the circular smooth muscle layer of the human IAS, grown in smooth muscle differentiation media under sterile conditions in Sylgard-coated tissue culture plates with central Sylgard posts. The basal tone in the reconstructs and its changes were recorded following 0 Ca2+, KCl, bethanechol, isoproterenol, protein kinase C (PKC) activator phorbol 12,13-dibutyrate, and Rho kinase (ROCK) and PKC inhibitors Y-27632 and Gö-6850, respectively. Western blot (WB), immunofluorescence (IF), and immunocytochemical (IC) analyses were also performed. The reconstructs developed spontaneous tone (0.68 ± 0.26 mN). Bethanechol (a muscarinic agonist) and K+ depolarization produced contraction, whereas isoproterenol (β-adrenoceptor agonist) and Y-27632 produced a concentration-dependent decrease in the tone. Maximal decrease in basal tone with Y-27632 and Gö-6850 (each 10−5 M) was 80.45 ± 3.29 and 17.76 ± 3.50%, respectively. WB data with the IAS constructs′ SMCs revealed higher levels of RhoA/ROCK, protein kinase C-potentiated inhibitor or inhibitory phosphoprotein for myosin phosphatase (CPI-17), phospho-CPI-17, MYPT1, and 20-kDa myosin light chain vs. rectal smooth muscle. WB, IF, and IC studies of original SMCs and redispersed from the reconstructs for the relative distribution of different signal transduction proteins confirmed the feasibility of reconstruction of IAS with functional properties similar to intact IAS and demonstrated the development of myogenic tone with critical dependence on RhoA/ROCK. We conclude that it is feasible to bioengineer IAS constructs using human IAS SMCs that behave like intact IAS. PMID:22790596

  15. Palladium nanoparticles exposure: Evaluation of permeation through damaged and intact human skin.

    Science.gov (United States)

    Larese Filon, Francesca; Crosera, Matteo; Mauro, Marcella; Baracchini, Elena; Bovenzi, Massimo; Montini, Tiziano; Fornasiero, Paolo; Adami, Gianpiero

    2016-07-01

    The intensified use of palladium nanoparticles (PdNPs) in many chemical reactions, jewellery, electronic devices, in car catalytic converters and in biomedical applications lead to a significant increase in palladium exposure. Pd can cause allergic contact dermatitis when in contact with the skin. However, there is still a lack of toxicological data related to nano-structured palladium and information on human cutaneous absorption. In fact, PdNPs, can be absorbed through the skin in higher amounts than bulk Pd because NPs can release more ions. In our study, we evaluated the absorption of PdNPs, with a size of 10.7 ± 2.8 nm, using intact and damaged human skin in Franz cells. 0.60 mg cm(-2) of PdNPs were applied on skin surface for 24 h. Pd concentrations in the receiving solutions at the end of experiments were 0.098 ± 0.067 μg cm(-2) and 1.06 ± 0.44 μg cm(-2) in intact skin and damaged skin, respectively. Pd flux permeation after 24 h was 0.005 ± 0.003 μg cm(-2) h(-1) and 0.057 ± 0.030 μg cm(-2) h(-1) and lag time 4.8 ± 1.7 and 4.2 ± 3.6 h, for intact and damaged skin respectively. This study indicates that Pd can penetrate human skin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Human skin penetration of silver nanoparticles through intact and damaged skin

    International Nuclear Information System (INIS)

    Larese, Francesca Filon; D'Agostin, Flavia; Crosera, Matteo; Adami, Gianpiero; Renzi, Nadia; Bovenzi, Massimo; Maina, Giovanni

    2009-01-01

    There is a growing interest on nanoparticle safety for topical use. The benefits of nanoparticles have been shown in several scientific fields, but little is known about their potential to penetrate the skin. This study aims at evaluating in vitro skin penetration of silver nanoparticles. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. Physiological solution was used as receiving phase and 70 μg/cm 2 of silver nanoparticles coated with polyvinylpirrolidone dispersed in synthetic sweat were applied as donor phase to the outer surface of the skin for 24 h. The receptor fluid measurements were performed by electro thermal atomic absorption spectroscopy (ETAAS). Human skin penetration was also determined by using transmission electron microscope (TEM) to verify the location of silver nanoparticles in exposed membranes. Median silver concentrations of 0.46 ng cm -2 (range -2 (range 0.43-11.6) were found in the receiving solutions of cells where the nanoparticles solution was applied on intact skin (eight cells) and on damaged skin (eight cells), respectively. Twenty-four hours silver flux permeation in damaged skin was 0.62 ± 0.2 ng cm -2 with a lag time <1 h. Our experimental data showed that silver nanoparticles absorption through intact and damaged skin was very low but detectable, and that in case of damaged skin it was possible an increasing permeation of silver applied as nanoparticles. Moreover, silver nanoparticles could be detected in the stratum corneum and the outermost surface of the epidermis by electron microscopy. We demonstrated for the first time that silver applied as nanoparticles coated with polyvinylpirrolidone is able to permeate the damaged skin in an in vitro diffusion cell system

  17. Superresolution and Fluorescence Dynamics Evidence Reveal That Intact Liposomes Do Not Cross the Human Skin Barrier.

    Directory of Open Access Journals (Sweden)

    Jes Dreier

    Full Text Available In this study we use the combination of super resolution optical microscopy and raster image correlation spectroscopy (RICS to study the mechanism of action of liposomes as transdermal drug delivery systems in human skin. Two different compositions of liposomes were applied to newly excised human skin, a POPC liposome and a more flexible liposome containing the surfactant sodium cholate. Stimulated emission depletion microscopy (STED images of intact skin and cryo-sections of skin treated with labeled liposomes were recorded displaying an optical resolution low enough to resolve the 100 nm liposomes in the skin. The images revealed that virtually none of the liposomes remained intact beneath the skin surface. RICS two color cross correlation diffusion measurements of double labeled liposomes confirmed these observations. Our results suggest that the liposomes do not act as carriers that transport their cargo directly through the skin barrier, but mainly burst and fuse with the outer lipid layers of the stratum corneum. It was also found that the flexible liposomes showed a greater delivery of the fluorophore into the stratum corneum, indicating that they functioned as chemical permeability enhancers.

  18. Intraneural stimulation elicits discrimination of textural features by artificial fingertip in intact and amputee humans.

    Science.gov (United States)

    Oddo, Calogero Maria; Raspopovic, Stanisa; Artoni, Fiorenzo; Mazzoni, Alberto; Spigler, Giacomo; Petrini, Francesco; Giambattistelli, Federica; Vecchio, Fabrizio; Miraglia, Francesca; Zollo, Loredana; Di Pino, Giovanni; Camboni, Domenico; Carrozza, Maria Chiara; Guglielmelli, Eugenio; Rossini, Paolo Maria; Faraguna, Ugo; Micera, Silvestro

    2016-03-08

    Restoration of touch after hand amputation is a desirable feature of ideal prostheses. Here, we show that texture discrimination can be artificially provided in human subjects by implementing a neuromorphic real-time mechano-neuro-transduction (MNT), which emulates to some extent the firing dynamics of SA1 cutaneous afferents. The MNT process was used to modulate the temporal pattern of electrical spikes delivered to the human median nerve via percutaneous microstimulation in four intact subjects and via implanted intrafascicular stimulation in one transradial amputee. Both approaches allowed the subjects to reliably discriminate spatial coarseness of surfaces as confirmed also by a hybrid neural model of the median nerve. Moreover, MNT-evoked EEG activity showed physiologically plausible responses that were superimposable in time and topography to the ones elicited by a natural mechanical tactile stimulation. These findings can open up novel opportunities for sensory restoration in the next generation of neuro-prosthetic hands.

  19. Investigations on the role of hemoglobin in sulfide metabolism by intact human red blood cells.

    Science.gov (United States)

    Bianco, Christopher L; Savitsky, Anton; Feelisch, Martin; Cortese-Krott, Miriam M

    2018-03-01

    In addition to their role as oxygen transporters, red blood cells (RBCs) contribute to cardiovascular homeostasis by regulating nitric oxide (NO) metabolism via interaction of hemoglobin (Hb) with nitrite and NO itself. RBCs were proposed to also participate in sulfide metabolism. Although Hb is known to react with sulfide, sulfide metabolism by intact RBCs has not been characterized so far. Therefore we explored the role of Hb in sulfide metabolism in intact human RBCs. We find that upon exposure of washed RBCs to sulfide, no changes in oxy/deoxyhemoglobin (oxy/deoxyHb) are observed by UV-vis and EPR spectroscopy. However, sulfide reacts with methemoglobin (metHb), forming a methemoglobin-sulfide (metHb-SH) complex. Moreover, while metHb-SH is stable in cell-free systems even in the presence of biologically relevant thiols, it gradually decomposes to produce oxyHb, inorganic polysulfides and thiosulfate in intact cells, as detected by EPR and mass spectrometry. Taken together, our results demonstrate that under physiological conditions RBCs are able to metabolize sulfide via intermediate formation of a metHb-SH complex, which subsequently decomposes to oxyHb. We speculate that decomposition of metHb-SH is preceded by an inner-sphere electron transfer, forming reduced Hb (which binds oxygen to form oxyHb) and thiyl radical (a process we here define as "reductive sulfhydration"), which upon release, gives rise to the oxidized products, thiosulfate and polysulfides. Thus, not only is metHb an efficient scavenger and regulator of sulfide in blood, intracellular sulfide itself may play a role in keeping Hb in the reduced oxygen-binding form and, therefore, be involved in RBC physiology and function. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  20. In vitro permeation of palladium powders through intact and damaged human skin.

    Science.gov (United States)

    Crosera, Matteo; Mauro, Marcella; Bovenzi, Massimo; Adami, Gianpiero; Baracchini, Elena; Maina, Giovanni; Larese Filon, Francesca

    2018-05-01

    The use of palladium (Pd) has grown in the last decades, commonly used in automotive catalytic converters, jewellery and dental restorations sectors. Both general and working population can be exposed to this metal, which may act as skin sensitizer. This study investigated in vitro palladium powders permeation through excised intact and damaged human skin using the Franz diffusion cell method and the effect of rapid skin decontamination using sodium laureth-sulphate. 1 mL of a 10 min sonicated suspension made of 2.5 g of Pd powder in 50 mL synthetic sweat at pH 4.5 and room temperature was applied to the outer surface of the skin membranes for 24 h. Pd permeation, assessed by ICP-MS, was higher when damaged skin was used (p = 0.03). Final flux permeation values and lag times were 0.02 ± 0.01 μg cm -2  h -1 and 6.00 ± 3.95 h for intact, and 0.10 ± 0.02 μg cm -2  h -1 and 2.05 ± 1.49 h for damaged skin samples, respectively. Damaged skin protocol enhances Pd skin penetration inside dermal layer (p = 0.04), thus making the metal available for systemic uptake. Pd penetration (p = 0.02) and permeation (p = 0.012) through intact skin decreased significantly when a cleaning procedure was applied. This study demonstrates that after skin exposure to Pd powders a small permeation of the metal happen both through intact and damaged skin and that an early decontamination with a common cleanser can significantly decrease the final amount of metal available forsystemic uptake. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. In vitro comparison of human fibroblasts from intact and ruptured ACL for use in tissue engineering

    Directory of Open Access Journals (Sweden)

    T Brune

    2007-12-01

    Full Text Available The present study compares fibroblasts extracted from intact and ruptured human anterior cruciate ligaments (ACL for creation of a tissue engineered ACL-construct, made of porcine small intestinal submucosal extracellular matrix (SIS-ECM seeded with these ACL cells. The comparison is based on histological, immunohistochemical and RT-PCR analyses. Differences were observed between cells in a ruptured ACL (rACL and cells in an intact ACL (iACL, particularly with regard to the expression of integrin subunits and smooth muscle actin (SMA. Despite these differences in the cell source, both cell populations behaved similarly when seeded on an SIS-ECM scaffold, with similar cell morphology, connective tissue organization and composition, SMA and integrin expression. This study shows the usefulness of naturally occurring scaffolds such as SIS-ECM for the study of cell behaviour in vitro, and illustrates the possibility to use autologous cells extracted from ruptured ACL biopsies as a source for tissue engineered ACL constructs.

  2. Radioassays for quantitation of intact complement proteins C2 and B in human serum

    Energy Technology Data Exchange (ETDEWEB)

    Oglesby, T J; Ueda, A; Volanakis, J E

    1988-05-25

    Availability of polyclonal and monoclonal antibodies recognizing determinants on the major cleavage fragments of complement proteins C2 and B enabled development of sensitive radioassays which can be used to quantitate the intact proteins in human sera. Changes in C2 and B concentrations indicative of classical or alternative pathway activation, or both, were seen in normal serum after incubation with complement activators. The authors determined the normal range of C2 concentration to be 11-35 ..mu..g/ml in 32 healthy individuals, and that of protein B to be 74-286 ..mu..g/ml. Sera from patients with systemic lupus erythematosus (SLE), septic shock, infections, and following orthopedic surgery were then assayed. Mean protein B concentration was significantly higher in SLE sera and in the infected and post-operative sera, and the mean C2 concentration in the septic shock group was significantly lower than the mean of healthy individuals. Intact C2 was not detected in known C2-deficient individuals. These assays allow parallel quantitation of the structurally and functionally homologous proteins of the classical (C2) and alternative (B) pathways, which is of interest in patients with genetic and acquired hypocomplementemia. 22 refs.; 3 figs.

  3. Inflammatory microRNA-194 and -515 attenuate the biosynthesis of chondroitin sulfate during human intervertebral disc degeneration.

    Science.gov (United States)

    Hu, Bo; Xu, Chen; Tian, Ye; Shi, Changgui; Zhang, Ying; Deng, Lianfu; Zhou, Hongyu; Cao, Peng; Chen, Huajiang; Yuan, Wen

    2017-07-25

    Intervertebral disc degeneration (IDD) is characterized by dehydration and loss of extracellular matrixes in the nucleus pulposus region. Chondroitin sulfate has been found to be the water-binding molecule that played a key role in IDD. Although investigators have reported that inflammatory cytokines are involved in the reduction of chondroitin sulfate in IDD, but the underlying mechanism is unrevealed. Since chondroitin sulfate synthesis is controlled by chondroitin sulfate glycosyltransferases CHSY-1/2/3 and CSGALNACT-1/2, their functional role and regulatory mechanism in IDD is not fully studied. Here, we set out to investigate the function and regulatory roles of these factors during IDD development. We found that among these chondroitin sulfate glycosyltransferases, CHSY-1/2/3 are significantly down-regulated in severe IDD samples than mild IDD samples. In vitro experiments revealed that Interleukin-1β and Tumor Necrosis Factor-α stimulation led to significant reduction of CHSY-1/2/3 at protein level than mRNA level in NP cells, indicating a post-transcriptional regulatory mechanisms are involved. By computational prediction and analysis, we found that inflammatory cytokines stimulated microRNA-194 and -515 target CHSY-1/2/3 mRNA and significantly interrupt their translation and downstream chondroitin sulfate deposition. Inhibition of microRNA-194 and -515 however, significantly rescued CHSY-1/2/3 expressions and chondroitin sulfate deposition. These findings together demonstrated a vital role of inflammatory stimulated microRNAs in promoting intervertebral disc degeneration by interrupt chondroitin sulfate synthesis, which may provide new insights into the mechanism and therapeutic approaches in IDD.

  4. Dysregulated miR-127-5p contributes to type II collagen degradation by targeting matrix metalloproteinase-13 in human intervertebral disc degeneration.

    Science.gov (United States)

    Hua, Wen-Bin; Wu, Xing-Huo; Zhang, Yu-Kun; Song, Yu; Tu, Ji; Kang, Liang; Zhao, Kang-Cheng; Li, Shuai; Wang, Kun; Liu, Wei; Shao, Zeng-Wu; Yang, Shu-Hua; Yang, Cao

    2017-08-01

    Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression in human NP cells was detected by qPCR, western blotting, and immunofluorescence staining. We confirmed that miR-127-5p was significantly downregulated in nucleus pulposus (NP) tissue of degenerative discs and its expression was inversely correlated with MMP-13 mRNA levels. We reveal that MMP-13 may act as a target of miR-127-5p. Expression of miR-127-5p was inversely correlated with type II collagen expression in human NP cells. Moreover, suppression of MMP-13 expression by siRNA blocked downstream signaling and increased type II collagen expression. Dysregulated miR-127-5p contributed to the degradation of type II collagen by targeting MMP-13 in human IDD. Our findings highlight that miR-127-5p may serve as a new therapeutic target in IDD. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  5. Cobalt Oxide Nanoparticles: Behavior towards Intact and Impaired Human Skin and Keratinocytes Toxicity

    Directory of Open Access Journals (Sweden)

    Marcella Mauro

    2015-07-01

    Full Text Available Skin absorption and toxicity on keratinocytes of cobalt oxide nanoparticles (Co3O4NPs have been investigated. Co3O4NPs are commonly used in industrial products and biomedicine. There is evidence that these nanoparticles can cause membrane damage and genotoxicity in vitro, but no data are available on their skin absorption and cytotoxicity on keratinocytes. Two independent 24 h in vitro experiments were performed using Franz diffusion cells, using intact (experiment 1 and needle-abraded human skin (experiment 2. Co3O4NPs at a concentration of 1000 mg/L in physiological solution were used as donor phase. Cobalt content was evaluated by Inductively Coupled–Mass Spectroscopy. Co permeation through the skin was demonstrated after 24 h only when damaged skin protocol was used (57 ± 38 ng·cm−2, while no significant differences were shown between blank cells (0.92 ± 0.03 ng cm−2 and those with intact skin (1.08 ± 0.20 ng·cm−2. To further investigate Co3O4NPs toxicity, human-derived HaCaT keratinocytes were exposed to Co3O4NPs and cytotoxicity evaluated by MTT, Alamarblue® and propidium iodide (PI uptake assays. The results indicate that a long exposure time (i.e., seven days was necessary to induce a concentration-dependent cell viability reduction (EC50 values: 1.3 × 10−4 M, 95% CL = 0.8–1.9 × 10−4 M, MTT essay; 3.7 × 10−5 M, 95% CI = 2.2–6.1 × 10−5 M, AlamarBlue® assay that seems to be associated to necrotic events (EC50 value: 1.3 × 10−4 M, 95% CL = 0.9–1.9 × 10−4 M, PI assay. This study demonstrated that Co3O4NPs can penetrate only damaged skin and is cytotoxic for HaCat cells after long term exposure.

  6. [Meniscoids of the intervertebral joints].

    Science.gov (United States)

    Kos, J; Hert, J; Sevcík, P

    2002-01-01

    A large amount of material was used to study the distribution, location and shape of meniscoids in intervertebral joints of the human spine, from the atlanto-occipital joint to the sacrum, in order to find out how many of intervertebral joints had mobile meniscoids. These might be regarded as possible causes of spinal blockade or other vertebrogenous complaints. The materials provided by the Department of Anatomy and Department of Forensic Medicine at the Faculty of Medicine of Charles University in Pilznen included 20 cadaverous spines from humans aged 20 to 80 years. Access to each joint was provided by dissection of the articular capsule from the lower articular processes of the vertebra situated above. In the orthograde view, all meniscoids were described in terms of shape, size, consistence and location. Their structure was ascertained by histological examination of cross sections stained with haematoxylin and eosin. Meniscoids varying in shape and size were found in all of the intervertebral joints. They were classified by their histological structure as synovial, fat and fibrous meniscoids. The first category was observed frequently, the last only rarely. A total of 29 mobile meniscoids were recorded, most of them in the lumbar spine. Most of the meniscoids present in the cervical spine were of synovial and less frequently of fat types. Meniscoids found in the thoracic spine were poorly developed synovial ones and those present in the lumbar spine were of all types and were also largest in size. The most conspicuous meniscoids were seen in the spines that showed degenerative changes in intervertebral joints. Large fat pads were found in atlanto-occipital and atlanto-axial joints. Mobile meniscoids, most of them present in the lumbar spine (6.4% of all joints.), were connected with the capsule by a thin pedicle and it was possible to move them over a half of the articular surface. Some inter-individual changes were also found; in some spines, the most

  7. Permeation of platinum and rhodium nanoparticles through intact and damaged human skin

    International Nuclear Information System (INIS)

    Mauro, Marcella; Crosera, Matteo; Bianco, Carlotta; Adami, Gianpiero; Montini, Tiziano; Fornasiero, Paolo; Jaganjac, Morana; Bovenzi, Massimo; Filon, Francesca Larese

    2015-01-01

    The aim of the study was to evaluate percutaneous penetration of platinum and rhodium nanoparticles (PtNPs: 5.8 ± 0.9 nm, RhNPs: 5.3 ± 1.9 nm) through human skin. Salts compounds of these metals are sensitizers and some also carcinogenic agents. In vitro permeation experiments were performed using Franz diffusion cells with intact and damaged skin. PtNPs and RhNPs, stabilized with polyvinylpyrrolidone, were synthesized by reduction of Na 2 PtC l6 and RhCl 3 ·3H 2 O respectively. Suspensions with a concentration of 2.0 g/L of PtNPs and RhNPs were dispersed separately in synthetic sweat at pH 4.5 and applied as donor phases to the outer surface of the skin for 24 h. Measurements of the content of the metals in the receiving solution and in the skin were performed subsequently. Rhodium skin permeation was demonstrated through damaged skin, with a permeation flux of 0.04 ± 0.04 μg cm −2  h −1 and a lag time of 7.9 ± 1.1 h, while no traces of platinum were found in receiving solutions. Platinum and rhodium skin-analysis showed significantly higher concentrations of the metals in damaged skin. Rh and Pt applied as NPs can penetrate the skin barrier and Rh can be found in receiving solutions. These experiments pointed out the need for skin contamination prevention, since even a minor injury to the skin barrier can significantly increase penetration

  8. Permeation of platinum and rhodium nanoparticles through intact and damaged human skin

    Energy Technology Data Exchange (ETDEWEB)

    Mauro, Marcella [University of Trieste, Clinical Unit of Occupational Medicine, Department of Medical Sciences (Italy); Crosera, Matteo; Bianco, Carlotta; Adami, Gianpiero; Montini, Tiziano; Fornasiero, Paolo [University of Trieste, Department of Chemical and Pharmaceutical Sciences (Italy); Jaganjac, Morana [Rudjer Boskovic Institute, Laboratory for Oxidative Stress, Department of Molecular Medicine (Croatia); Bovenzi, Massimo; Filon, Francesca Larese, E-mail: larese@units.it [University of Trieste, Clinical Unit of Occupational Medicine, Department of Medical Sciences (Italy)

    2015-06-15

    The aim of the study was to evaluate percutaneous penetration of platinum and rhodium nanoparticles (PtNPs: 5.8 ± 0.9 nm, RhNPs: 5.3 ± 1.9 nm) through human skin. Salts compounds of these metals are sensitizers and some also carcinogenic agents. In vitro permeation experiments were performed using Franz diffusion cells with intact and damaged skin. PtNPs and RhNPs, stabilized with polyvinylpyrrolidone, were synthesized by reduction of Na{sub 2}PtC{sub l6} and RhCl{sub 3}·3H{sub 2}O respectively. Suspensions with a concentration of 2.0 g/L of PtNPs and RhNPs were dispersed separately in synthetic sweat at pH 4.5 and applied as donor phases to the outer surface of the skin for 24 h. Measurements of the content of the metals in the receiving solution and in the skin were performed subsequently. Rhodium skin permeation was demonstrated through damaged skin, with a permeation flux of 0.04 ± 0.04 μg cm{sup −2} h{sup −1} and a lag time of 7.9 ± 1.1 h, while no traces of platinum were found in receiving solutions. Platinum and rhodium skin-analysis showed significantly higher concentrations of the metals in damaged skin. Rh and Pt applied as NPs can penetrate the skin barrier and Rh can be found in receiving solutions. These experiments pointed out the need for skin contamination prevention, since even a minor injury to the skin barrier can significantly increase penetration.

  9. Fas ligand exists on intervertebral disc cells: a potential molecular mechanism for immune privilege of the disc.

    Science.gov (United States)

    Takada, Toru; Nishida, Kotaro; Doita, Minoru; Kurosaka, Masahiro

    2002-07-15

    Rat and human intervertebral disc specimens were examined immunohistochemically. Reverse transcription polymerase chain reaction (RT-PCR) analysis was also performed on rat disc tissue to demonstrate the existence of Fas ligand. To clarify the existence of Fas ligand on intact intervertebral disc cells. The nucleus pulposus has been reported to be an immune-privileged site. The immune-privileged characteristic in other tissues such as the retina and testis has been attributed to the local expression of Fas ligand, which acts by inducing apoptosis of invading Fas-positive T-cells. The existence of Fas ligand in normal disc cells has not yet been addressed. Skeletally mature SD male rats were killed, and the coccygeal discs were harvested. Human disc specimens were obtained from idiopathic scoliosis patients during surgical procedures. Immunohistochemical staining for Fas ligand was performed for cross-sections of the discs by standard procedures. Reverse transcription polymerase chain reaction analysis was also carried out to demonstrate Fas ligand mRNA expression on rat intervertebral discs. Testes of the rats were used for positive controls, and muscles were used for negative controls. The sections were observed by light microscopy. The nucleus pulposus cells exhibited intense positive immune staining for Fas ligand. The outer anulus fibrosus cells and notochordal cells exhibited little immunopositivity. The positive controls exhibited positive immune staining, and the negative control showed no immunopositivity. The result of RT-PCR confirmed the existence of Fas ligand in disc cells. The human nucleus pulposus cells showed a similar predilection to rat disc cells. We demonstrated the existence of Fas ligand on disc cells, which should play a key role in the potential molecular mechanism to maintain immune privilege of the disc. Immune privilege and Fas ligand expression of the intervertebral disc may provide a new insight for basic science research as well as

  10. Nonviral Gene Delivery of Growth and Differentiation Factor 5 to Human Mesenchymal Stem Cells Injected into a 3D Bovine Intervertebral Disc Organ Culture System

    Directory of Open Access Journals (Sweden)

    Christian Bucher

    2013-01-01

    Full Text Available Intervertebral disc (IVD cell therapy with unconditioned 2D expanded mesenchymal stem cells (MSC is a promising concept yet challenging to realize. Differentiation of MSCs by nonviral gene delivery of growth and differentiation factor 5 (GDF5 by electroporation mediated gene transfer could be an excellent source for cell transplantation. Human MSCs were harvested from bone marrow aspirate and GDF5 gene transfer was achieved by in vitro electroporation. Transfected cells were cultured as monolayers and as 3D cultures in 1.2% alginate bead culture. MSC expressed GDF5 efficiently for up to 21 days. The combination of GDF5 gene transfer and 3D culture in alginate showed an upregulation of aggrecan and SOX9, two markers for chondrogenesis, and KRT19 as a marker for discogenesis compared to untransfected cells. The cells encapsulated in alginate produced more proteoglycans expressed in GAG/DNA ratio. Furthermore, GDF5 transfected MCS injected into an IVD papain degeneration organ culture model showed a partial recovery of the GAG/DNA ratio after 7 days. In this study we demonstrate the potential of GDF5 transfected MSC as a promising approach for clinical translation for disc regeneration.

  11. Evaluation of an intact, an ACL-deficient, and a reconstructed human knee joint finite element model.

    Science.gov (United States)

    Vairis, Achilles; Stefanoudakis, George; Petousis, Markos; Vidakis, Nectarios; Tsainis, Andreas-Marios; Kandyla, Betina

    2016-02-01

    The human knee joint has a three-dimensional geometry with multiple body articulations that produce complex mechanical responses under loads that occur in everyday life and sports activities. Understanding the complex mechanical interactions of these load-bearing structures is of use when the treatment of relevant diseases is evaluated and assisting devices are designed. The anterior cruciate ligament (ACL) in the knee is one of four main ligaments that connects the femur to the tibia and is often torn during sudden twisting motions, resulting in knee instability. The objective of this work is to study the mechanical behavior of the human knee joint and evaluate the differences in its response for three different states, i.e., intact, ACL-deficient, and surgically treated (reconstructed) knee. The finite element models corresponding to these states were developed. For the reconstructed model, a novel repair device was developed and patented by the author in previous work. Static load cases were applied, as have already been presented in a previous work, in order to compare the calculated results produced by the two models the ACL-deficient and the surgically reconstructed knee joint, under the exact same loading conditions. Displacements were calculated in different directions for the load cases studied and were found to be very close to those from previous modeling work and were in good agreement with experimental data presented in literature. The developed finite element model for both the intact and the ACL-deficient human knee joint is a reliable tool to study the kinematics of the human knee, as results of this study show. In addition, the reconstructed human knee joint model had kinematic behavior similar to the intact knee joint, showing that such reconstruction devices can restore human knee stability to an adequate extent.

  12. Viable acrosome-intact human spermatozoa in the ejaculate as a marker of semen quality and fertility status

    DEFF Research Database (Denmark)

    Egeberg Palme, Dorte Louise; Rehfeld, Anders; Bang, Anne Kirstine

    2018-01-01

    STUDY QUESTION: Is it possible, in an unbiased and clinical relevant way, to determine the number of viable acrosome-intact human spermatozoa in ejaculates and to use this as a measure of fertility chances? SUMMARY ANSWER: Image cytometry enables easy and unbiased quantification of viable acrosome......-intact spermatozoa and it correlates with semen quality and fertility status. WHAT IS KNOWN ALREADY: The presence of the acrosome and its ability to respond to physiological inducers (e.g. progesterone) in the female reproductive tract at the appropriate time and place is required for fertilization. However......, the available assays are labor intensive and therefore not used clinically. STUDY DESIGN, SIZE, DURATION: Washed semen samples and capacitated swim-up fractions from volunteers were used to develop the assay. Subsequently washed ejaculates from patients in fertility treatment (n = 156), proven fertile men (n...

  13. Role of hypoxia and growth and differentiation factor-5 on differentiation of human mesenchymal stem cells towards intervertebral nucleus pulposus-like cells

    Directory of Open Access Journals (Sweden)

    JV Stoyanov

    2011-06-01

    Full Text Available There is evidence that mesenchymal stem cells (MSCs can differentiate towards an intervertebral disc (IVD-like phenotype. We compared the standard chondrogenic protocol using transforming growth factor beta-1 (TGFß to the effects of hypoxia, growth and differentiation factor-5 (GDF5, and coculture with bovine nucleus pulposus cells (bNPC. The efficacy of molecules recently discovered as possible nucleus pulposus (NP markers to differentiate between chondrogenic and IVD-like differentiation was evaluated. MSCs were isolated from human bone marrow and encapsulated in alginate beads. Beads were cultured in DMEM (control supplemented with TGFß or GDF5 or under indirect coculture with bNPC. All groups were incubated at low (2 % or normal (20 % oxygen tension for 28 days. Hypoxia increased aggrecan and collagen II gene expression in all groups. The hypoxic GDF5 and TGFß groups demonstrated most increased aggrecan and collagen II mRNA levels and glycosaminoglycan accumulation. Collagen I and X were most up-regulated in the TGFß groups. From the NP markers, cytokeratin-19 was expressed to highest extent in the hypoxic GDF5 groups; lowest expression was observed in the TGFß group. Levels of forkhead box F1 were down-regulated by TGFß and up-regulated by coculture with bNPC. Carbonic anhydrase 12 was also down-regulated in the TGFß group and showed highest expression in the GDF5 group cocultured with bNPC under hypoxia. Trends in gene expression regulation were confirmed on the protein level using immunohistochemistry. We conclude that hypoxia and GDF5 may be suitable for directing MSCs towards the IVD-like phenotype.

  14. Enzymatic methylation of band 3 anion transporter in intact human erythrocytes

    International Nuclear Information System (INIS)

    Lou, L.L.; Clarke, S.

    1987-01-01

    Band 3, the anion transport protein of erythrocyte membranes, is a major methyl-accepting substrate of the intracellular erythrocyte protein carboxyl methyltransferase (S-adenosyl-L-methionine: protein-D-aspartate O-methyltransferase; EC 2.1.1.77). The localization of methylation sites in intact cells by analysis of proteolytic fragments indicated that sites were present in the cytoplasmic N-terminal domain as well as the membranous C-terminal portion of the polypeptide. The amino acid residues that serve as carboxyl methylation sites of the erythrocyte anion transporter were also investigated. 3 H-Methylated band 3 was purified from intact erythrocytes incubated with L-[methyl- 3 H]methionine and from trypsinized and lysed erythrocytes incubated with S-adenosyl-L-[methyl- 3 H]methionine. After proteolytic digestion with carboxypeptidase Y, D-aspartic acid beta-[ 3 H]methyl ester was isolated in low yields (9% and 1%, respectively) from each preparation. The bulk of the radioactivity was recovered as [ 3 H]methanol, and the amino acid residue(s) originally associated with these methyl groups could not be determined. No L-aspartic acid beta-[ 3 H]methyl ester or glutamyl gamma-[ 3 H]methyl ester was detected. The formation of D-aspartic acid beta-[ 3 H]methyl esters in this protein in intact cells resulted from protein carboxyl methyltransferase activity since it was inhibited by adenosine and homocysteine thiolactone, which increases the intracellular concentration of the potent product inhibitor S-adenosylhomocysteine, and cycloleucine, which prevents the formation of the substrate S-adenosyl-L-[methyl- 3 H]methionine

  15. The autoradiographic pattern of the in vitro uptake of proline by the coronal areas of intact and carious human teeth

    International Nuclear Information System (INIS)

    Karjalainen, S.; Soederling, E.

    1979-01-01

    The biosynthesis of collagen in teeth was studied by following the uptake of proline in vitro. Whole crowns of human teeth were incubated for 6 h with ( 14 C)- or ( 3 H)-proline. Autoradiographs were prepared from sections of intact teeth and teeth with carious lesions of varying depths and location. The number of silver grains per cm 2 in the predentine, odontoblast layer and pulp were counted in selected fields magnified x 430 representing the deepest parts of the carious lesions. No differences in the labelling pattern were observed between the intact teeth incubated freshly after extraction and those preserved in liquid nitrogen. The densest labelling of intact teeth was seen in the predentine and odontoblast layer. The alterations under initial dentine caries appeared as increased labelling of the predentine and decreased labelling of the odontoblast layer; no alterations were observed in the underlying pulp. In advanced lesions, the predentine labelling decreased and that in the odontoblast layer and pulp increased. In the initial stages, caries seem to activate collagen synthesis in a relatively restricted area of the underlying structures, but in advanced stages, caries seem to increase the odontoblastic cellular polypeptide chain formation but prevent further maturation of the collagen. (author)

  16. Autoradiographic pattern of the in vitro uptake of proline by the coronal areas of intact and carious human teeth

    Energy Technology Data Exchange (ETDEWEB)

    Karjalainen, S; Soederling, E [Turku Univ. (Finland)

    1979-01-01

    The biosynthesis of collagen in teeth was studied by following the uptake of proline in vitro. Whole crowns of human teeth were incubated for 6 h with (/sup 14/C)- or (/sup 3/H)-proline. Autoradiographs were prepared from sections of intact teeth and teeth with carious lesions of varying depths and location. The number of silver grains per cm/sup 2/ in the predentine, odontoblast layer and pulp were counted in selected fields magnified x 430 representing the deepest parts of the carious lesions. No differences in the labelling pattern were observed between the intact teeth incubated freshly after extraction and those preserved in liquid nitrogen. The densest labelling of intact teeth was seen in the predentine and odontoblast layer. The alterations under initial dentine caries appeared as increased labelling of the predentine and decreased labelling of the odontoblast layer; no alterations were observed in the underlying pulp. In advanced lesions, the predentine labelling decreased and that in the odontoblast layer and pulp increased. In the initial stages, caries seem to activate collagen synthesis in a relatively restricted area of the underlying structures, but in advanced stages, caries seem to increase the odontoblastic cellular polypeptide chain formation but prevent further maturation of the collagen.

  17. Gene Expression Profiling of the Intact Dermal Sheath Cup of Human Hair Follicles.

    Science.gov (United States)

    Niiyama, Shiro; Ishimatsu-Tsuji, Yumiko; Nakazawa, Yosuke; Yoshida, Yuzo; Soma, Tsutomu; Ideta, Ritsuro; Mukai, Hideki; Kishimoto, Jiro

    2018-04-24

    Cells that constitute the dermal papillae of hair follicles might be derived from the dermal sheath, the peribulbar component of which is the dermal sheath cup. The dermal sheath cup is thought to include the progenitor cells of the dermal papillae and possesses hair inductive potential; however, it has not yet been well characterized. This study investigated the gene expression profile of the intact dermal sheath cup, and identified dermal sheath cup signature genes, including extracellular matrix components and BMP-binding molecules, as well as TGF-b1 as an upstream regulator. Among these, GREM2, a member of the BMP antagonists, was found by in situ hybridization to be highly specific to the dermal sheath cup, implying that GREM2 is a key molecule contributing to maintenance of the properties of the dermal sheath cup.

  18. The generation and functional characterization of induced pluripotent stem cells from human intervertebral disc nucleus pulposus cells.

    Science.gov (United States)

    Zhu, Yanxia; Liang, Yuhong; Zhu, Hongxia; Lian, Cuihong; Wang, Liang; Wang, Yiwei; Gu, Hongsheng; Zhou, Guangqian; Yu, Xiaoping

    2017-06-27

    Disc degenerative disease (DDD) is believed to originate in the nucleus pulposus (NP) region therefore, it is important to obtain a greater number of active NP cells for the study and therapy of DDD. Human induced pluripotent stem cells (iPSCs) are a powerful tool for modeling the development of DDD in humans, and have the potential to be applied in regenerative medicine. NP cells were isolated from DDD patients following our improved method, and then the primary NP cells were reprogramed into iPSCs with Sendai virus vectors encoding 4 factors. Successful reprogramming of iPSCs was verified by the expression of surface markers and presence of teratoma. Differentiation of iPSCs into NP-like cells was performed in a culture plate or in hydrogel, whereby skin fibroblast derived-iPSCs were used as a control. Results demonstrated that iPSCs derived from NP cells displayed a normal karyotype, expressed pluripotency markers, and formed teratoma in nude mice. NP induction of iPSCs resulted in the expression of NP cell specific matrix proteins and related genes. Non-induced NP derived-iPSCs also showed some NP-like phenotype. Furthermore, NP-derived iPSCs differentiate much better in hydrogel than that in a culture plate. This is a novel method for the generation of iPSCs from NP cells of DDD patients, and we have successfully differentiated these iPSCs into NP-like cells in hydrogel. This method provides a novel treatment of DDD by using patient-specific NP cells in a relatively simple and straightforward manner.

  19. Comparison of rat epidermal keratinocyte organotypic culture (ROC) with intact human skin

    DEFF Research Database (Denmark)

    Pappinen, Sari; Hermansson, Martin; Kuntsche, Judith

    2008-01-01

    study was to compare the stratum corneum lipid content of ROC with the corresponding material from human skin. The lipid composition was determined by thin-layer chromatography (TLC) and mass-spectrometry, and the thermal phase transitions of stratum corneum were studied by differential scanning...... calorimetry (DSC). All major lipid classes of the stratum corneum were present in ROC in a similar ratio as found in human stratum corneum. Compared to human skin, the level of non-hydroxyacid-sphingosine ceramide (NS) was increased in ROC, while alpha-hydroxyacid-phytosphingosine ceramide (AP) and non...... compared to human skin, in agreement with the results from DSC. ROC underwent a lipid lamellar order to disorder transition (T2) at a slightly lower temperature (68 degrees C) than human skin (74 degrees C). These differences in stratum corneum lipid composition and the thermal phase transitions may...

  20. Localization by whole-body autoradiography of intact and fragmented radiolabeled antibodies in a metastatic human colonic cancer model

    International Nuclear Information System (INIS)

    Fand, Irwin; Sharkey, R.M.; Grundy, J.P.; Goldenberg, D.M.

    1992-01-01

    In this report, we have employed macroautoradiography to compare the tumor targeting of 125 I-labeled anti-carcinoembryonic antigen (CEA) MAb (NP-4) to 125 I-labeled anti-colon-specific antigen-p (CSAp) MAb (Mu-9) and their labeled F(ab') 2 and Fab' fragments, in nude mice each bearing large dorsal human colonic tumor xenografts, and small nodular tumors in the liver and lungs. Using intact MAbs (NP-4 and Mu-9), clearance of background radioactivity was delayed to 3-7 days post-treatment. Treatment with F(ab') 2 and Fab' fragments of both NP-4 and Mu-9 MAbs, however, promoted clearance of background 125 I-radioactivity which was well advanced by 6-24 h and complete by 24-48 h after injection. Localization of 125 I-radioactivity in large and micrometastatic tumor perimeters was the most characteristic uptake pattern observed for both intact and fragmented MAbs. Qualitative analysis of macroautoradiographic images and quantitative densitometry indicated that the higher tumor-to-blood ratios achieved with labeled F(ab') 2 and Fab' fragments at early time points, compared to labeled whole immunoglobulin, appeared to be more a function of rapid plasma clearance, tumor mass, location of xenografts and specific tumor growth patterns than increased tumor penetrance by lower molecular weight univalent and bivalent immune fragments. (Author)

  1. Optical effects of exposing intact human lenses to ultraviolet radiation and visible light

    DEFF Research Database (Denmark)

    Kessel, Line; Eskildsen, Lars; Lundeman, Jesper Holm

    2011-01-01

    region of incoming visible light. The aim of the present study was to examine the optical effects on human lenses of short wavelength visible light and ultraviolet radiation. METHODS: Naturally aged human donor lenses were irradiated with UVA (355 nm), violet (400 and 405 nm) and green (532 nm) lasers......: Irradiation with high intensity lasers caused scattering lesions in the human lenses. These effects were more likely to be seen when using pulsed lasers because of the high pulse intensity. Prolonged irradiation with UVA led to photodarkening whereas no detrimental effects were observed after irradiation...

  2. Optical effects of exposing intact human lenses to ultraviolet radiation and visible light

    DEFF Research Database (Denmark)

    Kessel, Line; Eskildsen, Lars Baunsgaard; Lundeman, Jesper Holm

    2011-01-01

    wavelength region of incoming visible light. The aim of the present study was to examine the optical effects on human lenses of short wavelength visible light and ultraviolet radiation. METHODS: Naturally aged human donor lenses were irradiated with UVA (355 nm), violet (400 and 405 nm) and green (532 nm....... RESULTS: Irradiation with high intensity lasers caused scattering lesions in the human lenses. These effects were more likely to be seen when using pulsed lasers because of the high pulse intensity. Prolonged irradiation with UVA led to photodarkening whereas no detrimental effects were observed after...

  3. The effect of cryo-storage on the beta 2-adrenoceptor density and responsiveness in intact human lymphocytes

    DEFF Research Database (Denmark)

    Ahlquist, P; Johansen, Torben; Friis, U G

    1994-01-01

    This study evaluates the effect of cryo-storage on beta 2-adrenoceptor number and formation of adenosine 3':5'-cyclic monophosphate (cAMP) in intact human lymphocytes as a measure of the beta 2-adrenoceptor responsiveness. Cryo-storage at -196 degrees C up to 12 months caused no significant......), but changed significantly after long-term storage (3-12 months). We can conclude that lymphocytes can be stored for months for later determination of beta-adrenoceptors. The cryo-storage method described in this paper are, however, only useful for measurements of very large changes in cAMP formation, and our...... results indicate that the method should be further modified in order to preserve the lymphocyte responsiveness after cryo-storage....

  4. RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter.

    Science.gov (United States)

    Rattan, Satish; Singh, Jagmohan

    2012-04-01

    The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10(-8) to 10(-4) M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC(20) in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC(20), before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.

  5. New treatment strategies for canine intervertebral disc degeneration

    NARCIS (Netherlands)

    Smolders, L.A.

    2013-01-01

    Degeneration of the intervertebral disc (IVD) is a common problem in dogs and humans. IVD degeneration can lead to herniation of the IVD with subsequent compression of neural structures and various clinical signs, including back pain. Current treatment of IVD disease is conservative or surgical.

  6. Subdermal penetration of topically applied clobetasol propionate in ointment base through intact human skin

    DEFF Research Database (Denmark)

    Petersen, Lars Jelstrup; Sindrup, J H; Kristensen, J K

    1992-01-01

    Some data have demonstrated a substantial subdermal accumulation of topically applied drugs in animals. The aim of this study was to evaluate a possible effect of epicutaneously applied clobetasol propionate on blood flow in human subcutaneous adipose tissue. Nine healthy subjects were studied...

  7. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation.

    Directory of Open Access Journals (Sweden)

    Geoffrey K Aguirre

    2007-06-01

    Full Text Available RPE65 is an essential molecule in the retinoid-visual cycle, and RPE65 gene mutations cause the congenital human blindness known as Leber congenital amaurosis (LCA. Somatic gene therapy delivered to the retina of blind dogs with an RPE65 mutation dramatically restores retinal physiology and has sparked international interest in human treatment trials for this incurable disease. An unanswered question is how the visual cortex responds after prolonged sensory deprivation from retinal dysfunction. We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans with LCA due to RPE65 mutations (RPE65-LCA.RPE65-mutant dogs were studied with fMRI. Prior to therapy, retinal and subcortical responses to light were markedly diminished, and there were minimal cortical responses within the primary visual areas of the lateral gyrus (activation amplitude mean +/- standard deviation [SD] = 0.07% +/- 0.06% and volume = 1.3 +/- 0.6 cm(3. Following therapy, retinal and subcortical response restoration was accompanied by increased amplitude (0.18% +/- 0.06% and volume (8.2 +/- 0.8 cm(3 of activation within the lateral gyrus (p < 0.005 for both. Cortical recovery occurred rapidly (within a month of treatment and was persistent (as long as 2.5 y after treatment. Recovery was present even when treatment was provided as late as 1-4 y of age. Human RPE65-LCA patients (ages 18-23 y were studied with structural magnetic resonance imaging. Optic nerve diameter (3.2 +/- 0.5 mm was within the normal range (3.2 +/- 0.3 mm, and occipital cortical white matter density as judged by voxel-based morphometry was slightly but significantly altered (1.3 SD below control average, p = 0.005. Functional magnetic resonance imaging in human RPE65-LCA patients revealed cortical responses with a markedly diminished activation volume (8.8 +/- 1.2 cm(3 compared to controls

  8. Phorbol ester induced phosphorylation of the estrogen receptor in intact MCF-7 human breast cancer cells

    International Nuclear Information System (INIS)

    Knabbe, C.; Lippman, M.E.; Greene, G.L.; Dickson, R.B.

    1986-01-01

    Recent studies with a variety of cellular receptors have shown that phorbol ester induced phosphorylation modulates ligand binding and function. In this study the authors present direct evidence that the estrogen receptor in MCF-7 human breast cancer cells is a phosphoprotein whose phosphorylation state can be enhanced specifically by phorbol-12-myristate-13-acetate (PMA). Cells were cultured to 6h in the presence of [ 32 P]-orthophosphate. Whole cell extracts were immunoprecipitated with a monoclonal antibody (D58) against the estrogen receptor and subjected to SDS-polyacrylamide electrophoresis. Autoradiography showed a specific band in the region of 60-62 kDa which was significantly increased in preparations from PMA treated cells. Phospho-amino acid analysis demonstrated specific phosphorylation of serine and threonine residues. Cholera toxin or forskolin did not change the phosphorylation state of this protein. In a parallel binding analysis PMA led to a rapid decrease of estrogen binding sites. The estrogen induction of both progesterone receptors and growth in semisolid medium was blocked by PMA, whereas the estrogen induction of the 8kDa protein corresponding to the ps2 gene product and of the 52 kDa protein was not affected. In conclusion, phorbol esters can induce phosphorylation of the estrogen receptor. This process may be associated with the inactivation of certain receptor functions

  9. [Research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration].

    Science.gov (United States)

    Liang, Hang; Deng, Xiangyu; Shao, Zengwu

    2017-10-01

    To summarize the research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration and deduce the therapeutic potential of endogenous repair for intervertebral disc degeneration. The original articles about intervertebral disc endogenous stem cells for intervertebral disc regeneration were extensively reviewed; the reparative potential in vivo and the extraction and identification in vitro of intervertebral disc endogenous stem cells were analyzed; the prospect of endogenous stem cells for intervertebral disc regeneration was predicted. Stem cell niche present in the intervertebral discs, from which stem cells migrate to injured tissues and contribute to tissues regeneration under certain specific microenvironment. Moreover, the migration of stem cells is regulated by chemokines system. Tissue specific progenitor cells have been identified and successfully extracted and isolated. The findings provide the basis for biological therapy of intervertebral disc endogenous stem cells. Intervertebral disc endogenous stem cells play a crucial role in intervertebral disc regeneration. Therapeutic strategy of intervertebral disc endogenous stem cells is proven to be a promising biological approach for intervertebral disc regeneration.

  10. Optimization of PMAxx pretreatment to distinguish between human norovirus with intact and altered capsids in shellfish and sewage samples.

    Science.gov (United States)

    Randazzo, Walter; Khezri, Mohammad; Ollivier, Joanna; Le Guyader, Françoise S; Rodríguez-Díaz, Jesús; Aznar, Rosa; Sánchez, Gloria

    2018-02-02

    Shellfish contamination by human noroviruses (HuNoVs) is a serious health and economic problem. Recently an ISO procedure based on RT-qPCR for the quantitative detection of HuNoVs in shellfish has been issued, but these procedures cannot discriminate between inactivated and potentially infectious viruses. The aim of the present study was to optimize a pretreatment using PMAxx to better discriminate between intact and heat-treated HuNoVs in shellfish and sewage. To this end, the optimal conditions (30min incubation with 100μM of PMAxx and 0.5% of Triton, and double photoactivation) were applied to mussels, oysters and cockles artificially inoculated with thermally-inactivated (99°C for 5min) HuNoV GI and GII. This pretreatment reduced the signal of thermally-inactivated HuNoV GI in cockles and HuNoV GII in mussels by >3 log. Additionally, this pretreatment reduced the signal of thermally-inactivated HuNoV GI and GII between 1 and 1.5 log in oysters. Thermal inactivation of HuNoV GI and GII in PBS, sewage and bioaccumulated oysters was also evaluated by the PMAxx-Triton pretreatment. Results showed significant differences between reductions observed in the control and PMAxx-treated samples in PBS following treatment at 72 and 95°C for 15min. In sewage, the RT-qPCR signal of HuNoV GI was completely removed by the PMAxx pretreatment after heating at 72 and 95°C, while the RT-qPCR signal for HuNoV GII was completely eliminated only at 95°C. Finally, the PMAxx-Triton pretreatment was applied to naturally contaminated sewage and oysters, resulting in most of the HuNoV genomes quantified in sewage and oyster samples (12 out of 17) corresponding to undamaged capsids. Although this procedure may still overestimate infectivity, the PMAxx-Triton pretreatment represents a step forward to better interpret the quantification of intact HuNoVs in complex matrices, such as sewage and shellfish, and it could certainly be included in the procedures based on RT-qPCR. Copyright

  11. Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice.

    Science.gov (United States)

    Jaiswal, Smita; Smith, Kenneth; Ramirez, Alejandro; Woda, Marcia; Pazoles, Pamela; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

    2015-01-01

    The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγ(null) mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. © 2014 by the Society for Experimental Biology and Medicine.

  12. Magnetic resonance imaging of intervertebral disc degeneration

    International Nuclear Information System (INIS)

    Maeda, Hiroshi; Noguchi, Masao; Kira, Hideaki; Fujiki, Hiroshi; Shimokawa, Isao; Hinoue, Kaichi.

    1993-01-01

    The aim of this study was to correlate the degree of lumbar intervertebral disc degeneration with findings of magnetic resonance imaging (MRI). Seventeen autopsied (from 7 patients) and 21 surgical (from 20 patients) intervertebral discs were used as specimens for histopathological examination. In addition, 21 intervertebral discs were examined on T2-weighted images. Histopathological findings from both autopsied and surgical specimens were well correlated with MRI findings. In particular, T2-weighted images reflected increased collagen fibers and rupture within the fibrous ring accurately. However, when severely degenerated intervertebral discs and hernia protruding the posterior longitudinal ligament existed, histological findings were not concordant well with T2-weighted images. Morphological appearances of autopsy specimens, divided into four on T2-weighted images, were well consistent with histological degeneration. This morphological classification, as shown on T2-weighted images, could also be used in the evaluation of intervertebral disc degeneration. (N.K.)

  13. Magnetic resonance imaging of intervertebral disc degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Hiroshi; Noguchi, Masao (Kitakyushu City Yahata Hospital, Fukuoka (Japan)); Kira, Hideaki; Fujiki, Hiroshi; Shimokawa, Isao; Hinoue, Kaichi

    1993-02-01

    The aim of this study was to correlate the degree of lumbar intervertebral disc degeneration with findings of magnetic resonance imaging (MRI). Seventeen autopsied (from 7 patients) and 21 surgical (from 20 patients) intervertebral discs were used as specimens for histopathological examination. In addition, 21 intervertebral discs were examined on T2-weighted images. Histopathological findings from both autopsied and surgical specimens were well correlated with MRI findings. In particular, T2-weighted images reflected increased collagen fibers and rupture within the fibrous ring accurately. However, when severely degenerated intervertebral discs and hernia protruding the posterior longitudinal ligament existed, histological findings were not concordant well with T2-weighted images. Morphological appearances of autopsy specimens, divided into four on T2-weighted images, were well consistent with histological degeneration. This morphological classification, as shown on T2-weighted images, could also be used in the evaluation of intervertebral disc degeneration. (N.K.).

  14. Effects of C5/C6 Intervertebral Space Distraction Height on Pressure on the Adjacent Intervertebral Disks and Articular Processes and Cervical Vertebrae Range of Motion.

    Science.gov (United States)

    Lu, Tingsheng; Luo, Chunshan; Ouyang, Beiping; Chen, Qiling; Deng, Zhongliang

    2018-04-25

    BACKGROUND This study aimed to investigate the association between range of motion of the cervical vertebrae and various C5/C6 intervertebral space distraction heights. MATERIAL AND METHODS The cervical vertebrae from 6 fresh adult human cadavers were used to prepare the models. Changes in C4/C5 and C6/C7 intervertebral disk pressures, articular process pressure, and range of motion of the cervical vertebrae before and after the distraction of the C5/C6 intervertebral space at benchmark heights of 100%, 120%, 140%, and 160% were tested under different exercise loads. RESULTS The pressure on the adjacent intervertebral disks was highest with the standing upright position before distraction, varied with different positions of the specimens and distraction heights after distraction, and was closest to that before distraction at a distraction height of 120% (Particular processes was highest with left and right rotations before distraction, varied with different positions of the specimens and distraction heights after distraction, and was lowest under the same exercise load with different positions at a distraction height of 120% (Pdistraction and at a distraction height of 120% after distraction, respectively (Particular processes and range of motion of the cervical vertebrae and is therefore an appropriate intervertebral space distraction height.

  15. The collagen structure of bovine intervertebral disc studied using polarization-sensitive optical coherence tomography

    Energy Technology Data Exchange (ETDEWEB)

    Matcher, Stephen J; Winlove, C Peter; Gangnus, Sergei V [Present address: JSC ' Saratovneftegeophysics' , Saratov (Russian Federation)

    2004-04-07

    Polarization-sensitive optical coherence tomography (PS-OCT) is used to measure the birefringence properties of bovine intervertebral disc and equine flexor tendon. For equine tendon the birefringence {delta}n is (6.0 {+-} 0.2) x 10{sup -3} at a wavelength of 1.3 {mu}m. This is somewhat larger than the values reported for bovine tendon. The surface region of the annulus fibrosus of a freshly excised intact bovine intervertebral disc displays an identical value of birefringence, {delta}n = (6.0 {+-} 0.6) x 10{sup -3} at 1.3 {mu}m. The nucleus pulposus does not display birefringence, the measured apparent value of {delta}n = (0.39 {+-} 0.01) x 10{sup -3} being indistinguishable from the effects of depolarization due to multiple scattering. A clear difference is found between the depth-resolved retardance of equine tendon and that of bovine intervertebral disc. This apparently relates to the lamellar structure of the latter tissue, in which the collagen fibre orientation alternates between successive lamellae. A semi-empirical model based on Jones calculus shows that the measurements are in reasonable agreement with previous optical and x-ray data. These results imply that PS-OCT could be a useful tool to study collagen organization within the intervertebral disc in vitro and possibly in vivo and its variation with applied load and disease.

  16. The collagen structure of bovine intervertebral disc studied using polarization-sensitive optical coherence tomography

    International Nuclear Information System (INIS)

    Matcher, Stephen J; Winlove, C Peter; Gangnus, Sergei V

    2004-01-01

    Polarization-sensitive optical coherence tomography (PS-OCT) is used to measure the birefringence properties of bovine intervertebral disc and equine flexor tendon. For equine tendon the birefringence Δn is (6.0 ± 0.2) x 10 -3 at a wavelength of 1.3 μm. This is somewhat larger than the values reported for bovine tendon. The surface region of the annulus fibrosus of a freshly excised intact bovine intervertebral disc displays an identical value of birefringence, Δn = (6.0 ± 0.6) x 10 -3 at 1.3 μm. The nucleus pulposus does not display birefringence, the measured apparent value of Δn = (0.39 ± 0.01) x 10 -3 being indistinguishable from the effects of depolarization due to multiple scattering. A clear difference is found between the depth-resolved retardance of equine tendon and that of bovine intervertebral disc. This apparently relates to the lamellar structure of the latter tissue, in which the collagen fibre orientation alternates between successive lamellae. A semi-empirical model based on Jones calculus shows that the measurements are in reasonable agreement with previous optical and x-ray data. These results imply that PS-OCT could be a useful tool to study collagen organization within the intervertebral disc in vitro and possibly in vivo and its variation with applied load and disease

  17. Biomaterials for intervertebral disc regeneration and repair.

    Science.gov (United States)

    Bowles, Robert D; Setton, Lori A

    2017-06-01

    The intervertebral disc contributes to motion, weight bearing, and flexibility of the spine, but is susceptible to damage and morphological changes that contribute to pathology with age and injury. Engineering strategies that rely upon synthetic materials or composite implants that do not interface with the biological components of the disc have not met with widespread use or desirable outcomes in the treatment of intervertebral disc pathology. Here we review bioengineering advances to treat disc disorders, using cell-supplemented materials, or acellular, biologically based materials, that provide opportunity for cell-material interactions and remodeling in the treatment of intervertebral disc disorders. While a field still in early development, bioengineering-based strategies employing novel biomaterials are emerging as promising alternatives for clinical treatment of intervertebral disc disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Comparative study of intact A7 MoAc and F(ab')2 fragments for radioimmunoimaging of human colon cancer in nude mice

    International Nuclear Information System (INIS)

    Kojima, Shuji; Suzuki, Naomi; Shimura, Noriko; Kubodera, Akiko; Kubota, Kazuhiko; Yamaguchi, Toshiharu; Takahashi, Toshio; Oyamada, Hiyoshimaru

    1993-01-01

    Differences of pharmacokinetics and tumor imaging ability between intact monoclonal antibody A7 (A7 MoAb) and F(ab) 2 fragments were studied in human colon cancer (LS-174T)-bearing nude mice. The authors examined the yield and the immunoreactivity of F(ab) 2 fragments after treatment with ficin as a function of time. The yield of F(ab) 2 fragments reached about 50% after ficin treatment for 8 h, and the F(ab) 2 retained about 80% of the immunoreactivity of the corresponding MoAb. Longer digestion with ficin produced smaller fragments (less than 92 kDa) with a lower yield and most of the immunoreactivity was lost. In pharmacokinetics studies, the F(ab') 2 was preferentially taken up by the tumor, cleared more rapidly from the blood circulation and seemed to have less non-specific tissue binding than intact A7 MoAb. The tumor image obtained at an early time using 131 I-F(ab') 2 was much superior in quality to that with intact 131 I-A7 MoAb. The use of F(ab') 2 fragments may be effective for tumor diagnosis and therapy. (author)

  19. Spectroscopic Parameters of Lumbar Intervertebral Disc Material

    Science.gov (United States)

    Terbetas, G.; Kozlovskaja, A.; Varanius, D.; Graziene, V.; Vaitkus, J.; Vaitkuviene, A.

    2009-06-01

    There are numerous methods of investigating intervertebral disc. Visualization methods are widely used in clinical practice. Histological, imunohistochemical and biochemical methods are more used in scientific research. We propose that a new spectroscopic investigation would be useful in determining intervertebral disc material, especially when no histological specimens are available. Purpose: to determine spectroscopic parameters of intervertebral disc material; to determine emission spectra common for all intervertebral discs; to create a background for further spectroscopic investigation where no histological specimen will be available. Material and Methods: 20 patients, 68 frozen sections of 20 μm thickness from operatively removed intervertebral disc hernia were excited by Nd:YAG microlaser STA-01-TH third harmonic 355 nm light throw 0, 1 mm fiber. Spectrophotometer OceanOptics USB2000 was used for spectra collection. Mathematical analysis of spectra was performed by ORIGIN multiple Gaussian peaks analysis. Results: In each specimen of disc hernia were found distinct maximal spectral peaks of 4 types supporting the histological evaluation of mixture content of the hernia. Fluorescence in the spectral regions 370-700 nm was detected in the disc hernias. The main spectral component was at 494 nm and the contribution of the components with the peak wavelength values at 388 nm, 412 nm and 435±5 nm were varying in the different groups of samples. In comparison to average spectrum of all cases, there are 4 groups of different spectral signatures in the region 400-500 nm in the patient groups, supporting a clinical data on different clinical features of the patients. Discussion and Conclusion: besides the classical open discectomy, new minimally invasive techniques of treating intervertebral disc emerge (PLDD). Intervertebral disc in these techniques is assessed by needle, no histological specimen is taken. Spectroscopic investigation via fiber optics through the

  20. Can Exercise Positively Influence the Intervertebral Disc?

    Science.gov (United States)

    Belavý, Daniel L; Albracht, Kirsten; Bruggemann, Gert-Peter; Vergroesen, Pieter-Paul A; van Dieën, Jaap H

    2016-04-01

    To better understand what kinds of sports and exercise could be beneficial for the intervertebral disc (IVD), we performed a review to synthesise the literature on IVD adaptation with loading and exercise. The state of the literature did not permit a systematic review; therefore, we performed a narrative review. The majority of the available data come from cell or whole-disc loading models and animal exercise models. However, some studies have examined the impact of specific sports on IVD degeneration in humans and acute exercise on disc size. Based on the data available in the literature, loading types that are likely beneficial to the IVD are dynamic, axial, at slow to moderate movement speeds, and of a magnitude experienced in walking and jogging. Static loading, torsional loading, flexion with compression, rapid loading, high-impact loading and explosive tasks are likely detrimental for the IVD. Reduced physical activity and disuse appear to be detrimental for the IVD. We also consider the impact of genetics and the likelihood of a 'critical period' for the effect of exercise in IVD development. The current review summarises the literature to increase awareness amongst exercise, rehabilitation and ergonomic professionals regarding IVD health and provides recommendations on future directions in research.

  1. Pharmacology of a selective cyclooxygenase-2 inhibitor, HN-56249: a novel compound exhibiting a marked preference for the human enzyme in intact cells.

    Science.gov (United States)

    Berg, J; Fellier, H; Christoph, T; Kremminger, P; Hartmann, M; Blaschke, H; Rovensky, F; Towart, R; Stimmeder, D

    2000-04-01

    HN-56249 (3-(2,4-dichlorothiophenoxy)-4-methylsulfonylamino-benzenesu lfonamide), a highly selective cyclooxygenase (COX)-2 inhibitor, is the prototype of a novel series of COX inhibitors comprising bicyclic arylethersulfonamides; of this series HN-56249 is the most potent and selective human COX-2 inhibitor. HN-56249 inhibited platelet aggregation as a measure of COX-1 activity only moderately (IC50 26.5+/-1.7 microM). In LPS-stimulated monocytic cells the release of prostaglandin (PG) F1alpha as a measure of COX-2 was markedly inhibited (IC50 0.027+/-0.001 microM). Thus, HN-56249 showed an approximately 1000-fold selectivity for COX-2 in intact cells. In whole blood assays HN-56249 showed a potent inhibitory activity for COX-2 (IC50 0.78+/-0.37 microM) only. COX-1 was only weakly inhibited (IC50 867+/-181 microM). Hence, HN-56249 exhibited a greater than 1000-fold selectivity for whole blood COX-2. HN-56249 surpassed the COX-2 selectivities of the COX-2 selective inhibitors 3-cyclohexyloxy-4-methylsulfonylamino-nitrobenzene (NS-398) and 6-(2,4-difluorophenoxy)-5-methyl-sulfonylamino-1-indanone (flosulide) in the intact cell assays by eight- and threefold, respectively, and in the whole blood assays by approximately 40-fold. Following i.v. administration HN-56249 inhibited carrageenan-induced rat paw oedema only moderately (ID50 26.2+/-5.7 mg/kg, mean +/- SEM), approximately tenfold less potent than indomethacin (ID50 2.1+/-0.2 mg/kg, mean +/- SEM). After oral administration HN-56249 reversed thermal hyperalgesia in the carrageenan-induced rat paw oedema test, however, some 30-fold less potently than diclofenac. Comparing the inhibitory potency of HN-56249 against human COX-2 with that against murine COX-2 in intact cells revealed a 300-fold selectivity for the human enzyme. Similar effects were observed with other COX-2-selective arylethersulfonamides. In contrast, non-COX-2-selective arylethersulfonamides, including a highly selective COX-1 inhibitor, inhibited

  2. Evaluation of apoptotic cell death in normal and chondrodystrophic canine intervertebral discs

    Directory of Open Access Journals (Sweden)

    Marie Klauser

    2012-02-01

    Full Text Available Disc degeneration occurs commonly in dogs. A variety of factors is thought to contribute an inappropriate disc matrix that isolate cells in the disc and lead to apoptosis. Disc herniation with radiculopathy and discogenic pain are the results of the degenerative process. The objective of this prospective study was to determine the extent of apoptosis in intact and herniated intervertebral discs of chondrodystrophic dogs and non-chondrodystrophic dogs. In addition, the nucleus pulposus (NP was histologically compared between non-chondrodystrophic and chondrodystrophic dogs. Thoracolumbar intervertebral discs and parts of the extruded nucleus pulposus were harvested from 45 dogs. Samples were subsequently stained with haematoxylin-eosin and processed to detect cleaved caspase-3 and poly(ADP-ribose polymerase. A significant greater degree of apoptosis was observed in herniated NPs of chondrodystrophic dogs compared to non- chondrodystrophic dogs with poly (ADP-ribose polymerase and cleaved caspase- 3 detection. Within the group of chondrodystrophic dogs, dogs with an intact disc and younger than 6 years showed a significant lower incidence of apoptosis in the NP compared to the herniated NP of chondrodystrophic dogs. The extent of apoptosis in the annulus fibrosus was not different between the intact disc from chondrodystrophic and non- chondrodystrophic dogs. An age-related increase of apoptotic cells in NP and annulus fibrosus was found in the intact non-herniated intervertebral discs. Histologically, absence of notochordal cells and occurrence of chondroid metaplasia were observed in the nucleus pulposus of chondrodystrophic dogs. As a result, we found that apoptosis plays a role in disc degeneration in chondrodystrophic dogs.

  3. Curcuma DMSO extracts and curcumin exhibit an anti-inflammatory and anti-catabolic effect on human intervertebral disc cells, possibly by influencing TLR2 expression and JNK activity

    Science.gov (United States)

    2012-01-01

    Background As proinflammatory cytokines seem to play a role in discogenic back pain, substances exhibiting anti-inflammatory effects on intervertebral disc cells may be used as minimal-invasive therapeutics for intradiscal/epidural injection. The purpose of this study was to investigate the anti-inflammatory and anti-catabolic potential of curcuma, which has been used in the Indian Ayurvedic medicine to treat multiple ailments for a long time. Methods Human disc cells were treated with IL-1β to induce an inflammatory/catabolic cascade. Different extracts of curcuma as well as curcumin (= a component selected based on results with curcuma extracts and HPLC/MS analysis) were tested for their ability to reduce mRNA expression of proinflammatory cytokines and matrix degrading enzymes after 6 hours (real-time RT-PCR), followed by analysis of typical inflammatory signaling mechanisms such as NF-κB (Western Blot, Transcription Factor Assay), MAP kinases (Western Blot) and Toll-like receptors (real-time RT-PCR). Quantitative data was statistically analyzed using a Mann Whitney U test with a significance level of p curcuma DMSO extract significantly reduced levels of IL-6, MMP1, MMP3 and MMP13. The DMSO-soluble component curcumin, whose occurrence within the DMSO extract was verified by HPLC/MS, reduced levels of IL-1β, IL-6, IL-8, MMP1, MMP3 and MMP13 and both caused an up-regulation of TNF-α. Pathway analysis indicated that curcumin did not show involvement of NF-κB, but down-regulated TLR2 expression and inhibited the MAP kinase JNK while activating p38 and ERK. Conclusions Based on its anti-inflammatory and anti-catabolic effects, intradiscal injection of curcumin may be an attractive treatment alternative. However, whether the anti-inflammatory properties in vitro lead to analgesia in vivo will need to be confirmed in an appropriate animal model. PMID:22909087

  4. In Vivo Mouse Intervertebral Disc Degeneration Model Based on a New Histological Classification.

    Directory of Open Access Journals (Sweden)

    Takashi Ohnishi

    Full Text Available Although human intervertebral disc degeneration can lead to several spinal diseases, its pathogenesis remains unclear. This study aimed to create a new histological classification applicable to an in vivo mouse intervertebral disc degeneration model induced by needle puncture. One hundred six mice were operated and the L4/5 intervertebral disc was punctured with a 35- or 33-gauge needle. Micro-computed tomography scanning was performed, and the punctured region was confirmed. Evaluation was performed by using magnetic resonance imaging and histology by employing our classification scoring system. Our histological classification scores correlated well with the findings of magnetic resonance imaging and could detect degenerative progression, irrespective of the punctured region. However, the magnetic resonance imaging analysis revealed that there was no significant degenerative intervertebral disc change between the ventrally punctured and non-punctured control groups. To induce significant degeneration in the lumbar intervertebral discs, the central or dorsal region should be punctured instead of the ventral region.

  5. Angiogenesis in the degeneration of the lumbar intervertebral disc

    OpenAIRE

    David, Gh; Ciurea, AV; Iencean, SM; Mohan, A

    2010-01-01

    The goal of the study is to show the histological and biochemical changes that indicate the angiogenesis of the intervertebral disc in lumbar intervertebral disc hernia and the existence of epidemiological correlations between these changes and the risk factors of lumbar intervertebral disc hernia, as well as the patient's quality of life (QOL). We have studied 50 patients aged between 18 and 73 years old, who have undergone lumbar intervertebral disc hernia surgery, making fibroblast growth ...

  6. [Treatment of lumbar intervertebral disc displacement with chondroitinase ABC--experimental basis for clinical application].

    Science.gov (United States)

    Takahashi, Toyomi

    2004-07-01

    After single intradiscal injection of C-ABC in rabbit inter-vertebral discs, water content in the matrix of nucleus pulposus diminished clearly. After similar injection of C-ABC in sheep discs, disc inner pressure was diminished. After single intradiscal injection of C-ABC in dog inter-vertebral discs suffering disc herniation, the syndromes coming from the herniation diminished or disappeared. Based on these observations C-ABC is expected to be a chemonucleolytic agent and a human clinical trial is now in progress.

  7. Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord-specific markers during early human intervertebral disc development.

    Science.gov (United States)

    Rodrigues-Pinto, Ricardo; Berry, Andrew; Piper-Hanley, Karen; Hanley, Neil; Richardson, Stephen M; Hoyland, Judith A

    2016-08-01

    In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte-like cells. Although animal studies indicate that notochord-derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5-18 weeks post-conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E-cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co-expressed by sclerotomal cells. CD90, Tie2, and E-cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord-specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327-1340, 2016. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc.

  8. Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord‐specific markers during early human intervertebral disc development

    Science.gov (United States)

    Rodrigues‐Pinto, Ricardo; Berry, Andrew; Piper‐Hanley, Karen; Hanley, Neil; Richardson, Stephen M.

    2016-01-01

    ABSTRACT In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte‐like cells. Although animal studies indicate that notochord‐derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5–18 weeks post‐conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E‐cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co‐expressed by sclerotomal cells. CD90, Tie2, and E‐cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord‐specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327–1340, 2016. PMID:26910849

  9. Kinematics of Different Components of the Posterolateral Corner of the Knee in the Lateral Collateral Ligament-intact State: A Human Cadaveric Study.

    Science.gov (United States)

    Domnick, Christoph; Frosch, Karl-Heinz; Raschke, Michael J; Vogel, Nils; Schulze, Martin; von Glahn, Mathias; Drenck, Tobias C; Herbort, Mirco

    2017-10-01

    To determine the static stabilizing effects of different anatomical structures of the posterolateral corner (PLC) of the knee in the lateral collateral ligament (LCL)-intact state. Thirteen fresh-frozen human cadaveric knees were dissected and tested using an industrial robot with an optical tracking system. Kinematics were determined for 134 N anterior/posterior loads, 10 N m valgus/varus loads, and 5 N m internal/external rotatory loads in 0°, 20°, 30°, 60°, and 90° of knee flexion. The PLC structures were dissected and consecutively released: (I) intact knee joint, (II) with released posterior cruciate ligament (PCL), (III) popliteomeniscal fibers, (IV) popliteofibular ligament, (V) arcuat and popliteotibial fibers, (VI) popliteus tendon (PLT), and (VII) LCL. Repeated-measures analysis of variance was performed with significance set at P < .05. After releasing the PCL, posterior tibial translation increased by 5.2 mm at 20° to 9.4 mm at 90° of joint flexion (P < .0001). A mild 1.8° varus instability was measured in 0° of flexion (P = .0017). After releasing the PLC structures, posterior tibial translation further increased by 2.9 mm at 20° to 5.9 mm at 90° of flexion (P < .05) and external rotation angle increased by 2.6° at 0° to 7.9° at 90° of flexion (P < .05, vs II). Varus stability did not decrease. Mild differences between states V and VI were found in 60° and 90° external rotation tests (2.1° and 3.1°; P < .05). The connecting ligaments/fibers to the PLT act as a primary static stabilizer against external rotatory loads and a secondary stabilizer against posterior tibial loads (when PCL is injured). After releasing these structures, most static stabilizing function of the intact PLT is lost. The PLC has no varus-stabilizing function in the LCL-intact knee. Anatomy and function of these structures for primary and secondary joint stability should be considered for clinical diagnostics and when performing surgery in

  10. Auto fluorescence of intervertebral disc tissue: a new diagnostic tool.

    Science.gov (United States)

    Hoell, T; Huschak, G; Beier, A; Hüttmann, G; Minkus, Y; Holzhausen, H J; Meisel, H J

    2006-08-01

    The paper reports on auto fluorescence phenomena of inter-vertebral human discs. It systematically investigates the auto fluorescence effects of ex vivo disc specimen and reports on surgical cases to demonstrate the potential value of the new method. The paper offers biologic explanations of the phenomenon and discusses the potential value of the UV auto fluorescence technique as a diagnostic tool. Intra- and postoperative observations are made by a surgical microscope with an integrated UV light source. Quantitative measurements were carried out using a photon counter and a spectrometer ex vivo. The auto fluorescence phenomenon allows the differentiation of traumatized and degenerated disc tissue intraoperatively in some cases, it allows the differentiation of bony and collagen endplate in cervical disc surgery. The source of the auto fluorescent light emission are amino acids of the collagen molecules. The proteoglycan components and the liquid components of the disc do not show relevant auto fluorescence. Emission wavelength of disc material is equivalent to color perception. It differs due to different collagen composition of the intervertebral disc components from yellow-green to blue-green and can be visualized in situ by naked eye.UV-auto fluorescence of inter-vertebral discs is a new clinical tool that has the potential to differentiate disc material from the anatomical surrounding, to distinguish between different fractions of the disc and to give information on the quality and status of the disc material. Since the technology has just emerged, it needs further investigations to quantify the clinical observations reported in this paper.

  11. Intervertebral disc herniation: prevalence and association with ...

    African Journals Online (AJOL)

    Background: Low back pain is one of the common health problems encountered in life with intervertebral disc herniation being a common cause of its occurrence. Magnetic resonance imaging has emerged the gold standard for diagnosing a herniated disc. Aims and Objectives: To assess the frequency and pattern of ...

  12. Intervertebral disk prolapse in a ferret.

    Science.gov (United States)

    Morera, Neus; Valls, Xavier; Mascort, Joan

    2006-09-01

    This case report describes the diagnosis and resolution of an inter-vertebral disk prolapse in a 6-year-old ferret. No predisposing causes were found in the patient's history. A right hemilaminectomy, performed 1 week after presentation, was chosen to treat the patient surgically, and complete remission of clinical signs was achieved 2 months after presentation.

  13. Can Exercise Positively Influence the Intervertebral Disc?

    NARCIS (Netherlands)

    Belavý, Daniel L.; Albracht, Kirsten; Bruggemann, Gert Peter; Vergroesen, Pieter Paul A; van Dieën, Jaap H.

    2016-01-01

    To better understand what kinds of sports and exercise could be beneficial for the intervertebral disc (IVD), we performed a review to synthesise the literature on IVD adaptation with loading and exercise. The state of the literature did not permit a systematic review; therefore, we performed a

  14. Third harmonic generation imaging of intact human cerebral organoids to assess key components of early neurogenesis in Rett Syndrome (Conference Presentation)

    Science.gov (United States)

    Yildirim, Murat; Feldman, Danielle; Wang, Tianyu; Ouzounov, Dimitre G.; Chou, Stephanie; Swaney, Justin; Chung, Kwanghun; Xu, Chris; So, Peter T. C.; Sur, Mriganka

    2017-02-01

    Rett Syndrome (RTT) is a pervasive, X-linked neurodevelopmental disorder that predominantly affects girls. It is mostly caused by a sporadic mutation in the gene encoding methyl CpG-binding protein 2 (MeCP2).The clinical features of RTT are most commonly reported to emerge between the ages of 6-18 months and implicating RTT as a disorder of postnatal development. However, a variety of recent evidence from our lab and others demonstrates that RTT phenotypes are present at the earliest stages of brain development including neurogenesis, migration, and patterning in addition to stages of synaptic and circuit development and plasticity. We have used RTT patient-derived induced pluripotent stem cells to generate 3D human cerebral organoids that can serve as a model for human neurogenesis in vitro. We aim to expand on our existing findings in order to determine aberrancies at individual stages of neurogenesis by performing structural and immunocytochemical staining in isogenic control and MeCP2-deficient organoids. In addition, we aim to use Third Harmonic Generation (THG) microscopy as a label-free, nondestructive 3D tissue visualization method in order to gain a complete understanding of the structural complexity that underlies human neurogenesis. As a proof of concept, we have performed THG imaging in healthy intact human cerebral organoids cleared with SWITCH. We acquired an intrinsic THG signal with the following laser configurations: 400 kHz repetition rate, 65 fs pulse width laser at 1350 nm wavelength. In these THG images, nuclei are clearly delineated and cross sections demonstrate the depth penetration capacity (< 1mm) that extends throughout the organoid. Imaging control and MeCP2-deficient human cerebral organoids in 2D sections reveals structural and protein expression-based alterations that we expect will be clearly elucidated via both THG and three-photon fluorescence microscopy.

  15. Uptake of intact TPGS (d-alpha-tocopheryl polyethylene glycol 1000 succinate) a water-miscible form of vitamin E by human cells in vitro

    International Nuclear Information System (INIS)

    Traber, M.G.; Thellman, C.A.; Rindler, M.J.; Kayden, H.J.

    1988-01-01

    The mechanism by which TPGS (alpha-tocopheryl succinate esterified to polyethylene glycol 1000 [PEG 1000]) delivers tocopherol (vitamin E) was studied in human fibroblasts and erythrocytes and a human intestinal cell line, Caco-2. The total cellular tocopherol content of saponified samples of fibroblasts or Caco-2 incubated for 4 h with TPGS (4 mumol/L) increased 10-fold without an increase in the free tocopherol content of nonsaponified samples. A 24-h incubation resulted in a free tocopherol content of approximately 20%, suggesting that intracellular hydrolysis of ester bonds had occurred. The increase in total tocopherol content after a 4-h incubation with TPGS was temperature dependent; no change was measurable at 4 degrees C. Addition of metabolic inhibitors during incubation with TPGS at 37 degrees C did not prevent the increase. [ 14 C]TPGS (synthesized from [ 14 C]PEG 1000) was taken up by Caco-2 cells but [ 14 C]PEG 1000 was not. The intracellular total tocopherol (pmol) equaled the [ 14 C]TPGS (pmol), unequivocally demonstrating uptake of the intact TPGS molecule

  16. Vascular complications of prosthetic inter-vertebral discs

    OpenAIRE

    Daly, Kevin J.; Ross, E. Raymond S.; Norris, Heather; McCollum, Charles N.

    2006-01-01

    Five consecutive cases of prosthetic inter-vertebral disc displacement with severe vascular complications on revisional surgery are described. The objective of this case report is to warn spinal surgeons that major vascular complications are likely with anterior displacement of inter-vertebral discs. We have not been able to find a previous report on vascular complications associated with anterior displacement of prosthetic inter-vertebral discs. In all five patients the prosthetic disc had e...

  17. Analysis of rabbit intervertebral disc physiology based on water metabolism. II. Changes in normal intervertebral discs under axial vibratory load

    International Nuclear Information System (INIS)

    Hirano, N.; Tsuji, H.; Ohshima, H.; Kitano, S.; Itoh, T.; Sano, A.

    1988-01-01

    Metabolic changes induced by axial vibratory load to the spine were investigated based on water metabolism in normal intervertebral discs of rabbits with or without pentobarbital anesthesia. Tritiated water concentration in the intervertebral discs of unanesthetized rabbits was reduced remarkably by axial vibration for 30 minutes using the vibration machine developed for this study. Repeated vibratory load for 18 and 42 hours duration showed the recovery of 3 H 2 O concentration of the intervertebral disc without anesthesia. Computer simulation suggested a reduction of blood flow surrounding the intervertebral disc following the vibration stress. However, no reduction of the 3 H 2 O concentration in the intervertebral disc was noted under anesthesia. Emotional stress cannot be excluded as a factor in water metabolism in the intervertebral disc

  18. CT morphometry of adult thoracic intervertebral discs.

    Science.gov (United States)

    Fletcher, Justin G R; Stringer, Mark D; Briggs, Christopher A; Davies, Tilman M; Woodley, Stephanie J

    2015-10-01

    Despite being commonly affected by degenerative disorders, there are few data on normal thoracic intervertebral disc dimensions. A morphometric analysis of adult thoracic intervertebral discs was, therefore, undertaken. Archival computed tomography scans of 128 recently deceased individuals (70 males, 58 females, 20-79 years) with no known spinal pathology were analysed to determine thoracic disc morphometry and variations with disc level, sex and age. Reliability was assessed by intraclass correlation coefficients (ICCs). Anterior and posterior intervertebral disc heights and axial dimensions were significantly greater in men (anterior disc height 4.0±1.4 vs 3.6±1.3 mm; posterior disc height 3.6±0.90 vs 3.4±0.93 mm; p<0.01). Disc heights and axial dimensions at T4-5 were similar or smaller than at T2-3, but thereafter increased caudally (mean anterior disc height T4-5 and T10-11, 2.7±0.7 and 5.4±1.2 mm, respectively, in men; 2.6±0.8 and 5.1±1.3 mm, respectively, in women; p<0.05). Except at T2-3, anterior disc height decreased with advancing age and anteroposterior and transverse disc dimensions increased; posterior and middle disc heights and indices of disc shape showed no consistent statistically significant changes. Most parameters showed substantial to almost perfect agreement for intra- and inter-rater reliability. Thoracic disc morphometry varies significantly and consistently with disc level, sex and age. This study provides unique reference data on adult thoracic intervertebral disc morphometry, which may be useful when interpreting pathological changes and for future biomechanical and functional studies.

  19. FoxC2 Enhances BMP7-Mediated Anabolism in Nucleus Pulposus Cells of the Intervertebral Disc

    OpenAIRE

    Wang, Zheng; Fu, Changfeng; Chen, Yong; Xu, Feng; Wang, Zhenyu; Qu, Zhigang; Liu, Yi

    2016-01-01

    Bone-morphogenetic protein-7 (BMP-7) is a growth factor that plays a major role in mediating anabolism and anti-catabolism of the intervertebral disc matrix and cell homeostasis. In osteoblasts, Forkhead box protein C2 (FoxC2) is a downstream target of BMPs and promotes cell proliferation and differentiation. However, the role FoxC2 may play in degenerative human intervertebral disc tissue and the relationship between FoxC2 and BMP-7 in nucleus pulposus (NP) cells remain to be elucidated. Thi...

  20. Label-free morphology-based prediction of multiple differentiation potentials of human mesenchymal stem cells for early evaluation of intact cells.

    Directory of Open Access Journals (Sweden)

    Hiroto Sasaki

    Full Text Available Precise quantification of cellular potential of stem cells, such as human bone marrow-derived mesenchymal stem cells (hBMSCs, is important for achieving stable and effective outcomes in clinical stem cell therapy. Here, we report a method for image-based prediction of the multiple differentiation potentials of hBMSCs. This method has four major advantages: (1 the cells used for potential prediction are fully intact, and therefore directly usable for clinical applications; (2 predictions of potentials are generated before differentiation cultures are initiated; (3 prediction of multiple potentials can be provided simultaneously for each sample; and (4 predictions of potentials yield quantitative values that correlate strongly with the experimental data. Our results show that the collapse of hBMSC differentiation potentials, triggered by in vitro expansion, can be quantitatively predicted far in advance by predicting multiple potentials, multi-lineage differentiation potentials (osteogenic, adipogenic, and chondrogenic and population doubling potential using morphological features apparent during the first 4 days of expansion culture. In order to understand how such morphological features can be effective for advance predictions, we measured gene-expression profiles of the same early undifferentiated cells. Both senescence-related genes (p16 and p21 and cytoskeleton-related genes (PTK2, CD146, and CD49 already correlated to the decrease of potentials at this stage. To objectively compare the performance of morphology and gene expression for such early prediction, we tested a range of models using various combinations of features. Such comparison of predictive performances revealed that morphological features performed better overall than gene-expression profiles, balancing the predictive accuracy with the effort required for model construction. This benchmark list of various prediction models not only identifies the best morphological feature

  1. A method for quantitative measurement of lumbar intervertebral disc structures

    DEFF Research Database (Denmark)

    Tunset, Andreas; Kjær, Per; Samir Chreiteh, Shadi

    2013-01-01

    There is a shortage of agreement studies relevant for measuring changes over time in lumbar intervertebral disc structures. The objectives of this study were: 1) to develop a method for measurement of intervertebral disc height, anterior and posterior disc material and dural sac diameter using MR...

  2. Influence of degenerative changes of intervertebral disc

    Directory of Open Access Journals (Sweden)

    WANG Yi

    2012-04-01

    Full Text Available 【Abstract】Objective: To investigate the material properties of normal and degenerated intervertebral discs (IVDs and examine the effect of degenerative changes on IVD pathology. Methods: A computer-based online search was under-taken to identify English articles about material properties of IVDs published from January 1950 to 2011 in PubMed database. The retrieved keywords included material properties, intervertebral disc and degeneration. Based on the principles of reliability, advancement and efficiency, the obtained data were primarily examined, and the original source was retrieved to read the full-text. Repetitive articles were excluded. The data of material properties of normal and degenerated IVDs were summarized and analyzed by meta-analysis. Results: The data of Young's modulus, Poisson's ratio, shear modulus, hydraulic permeability and intradiscal pres-sure of normal and degenerated IVDs were obtained. Com-pared with normal IVDs, the Young's modulus and shear modulus of annulus fibrosus and nucleus pulposus were higher in degenerated IVDs, the Poisson's ratio was lower while the hydraulic permeability and intradiscal pressure were higher. Besides, the degeneration-related alterations in IVDs had an influence both on itself and other spinal structures, leading to diseases such as bulging disc, discogenic pain and spinal stenosis. Meanwhile, the heavy mechanical loading and injury indicated important pathways to IVD degeneration. Conclusions: To a certain extent, the degenerative changes of IVD influence its material properties. And the degeneration-related alterations of composition can cause structural failure of IVDs, leading to injuries and diseases. Key words: Intervertebral disc; Mechanical phenomena; Degeneration; Elastic modulus; Permeability; Pathology

  3. Interactions between Activation and Repolarization Restitution Properties in the Intact Human Heart: In-Vivo Whole-Heart Data and Mathematical Description.

    Directory of Open Access Journals (Sweden)

    Michele Orini

    Full Text Available The restitution of the action potential duration (APDR and conduction velocity (CVR are mechanisms whereby cardiac excitation and repolarization adapt to changes in heart rate. They modulate the vulnerability to dangerous arrhythmia, but the mechanistic link between restitution and arrhythmogenesis remains only partially understood.This paper provides an experimental and theoretical study of repolarization and excitation restitution properties and their interactions in the intact human epicardium. The interdependence between excitation and repolarization dynamic is studied in 8 patients (14 restitution protocols, 1722 restitution curves undergoing global epicardial mapping with multi-electrode socks before open heart surgery. A mathematical description of the contribution of both repolarization and conduction dynamics to the steepness of the APDR slope is proposed.This study demonstrates that the APDR slope is a function of both activation and repolarization dynamics. At short cycle length, conduction delay significantly increases the APDR slope by interacting with the diastolic interval. As predicted by the proposed mathematical formulation, the APDR slope was more sensitive to activation time prolongation than to the simultaneous shortening of repolarization time. A steep APDR slope was frequently identified, with 61% of all cardiac sites exhibiting an APDR slope > 1, suggesting that a slope > 1 may not necessarily promote electrical instability in the human epicardium. APDR slope did not change for different activation or repolarization times, and it was not a function of local baseline APD. However, it was affected by the spatial organization of electrical excitation, suggesting that in tissue APDR is not a unique function of local electrophysiological properties. Spatial heterogeneity in both activation and repolarization restitution contributed to the increase in the modulated dispersion of repolarization, which for short cycle length was

  4. Cells and Biomaterials for Intervertebral Disc Regeneration

    CERN Document Server

    Grad, Sibylle

    2010-01-01

    Disorders related to the intervertebral disc (IVD) are common causes of morbidity and of severe life quality deterioration. IVD degeneration, although in many cases asymptomatic, is often the origin of painful neck and back diseases. In Western societies IVD related pain and disability account for enormous health care costs as a result of work absenteeism and thus lost production, disability benefits, medical and insurance expenses. Although only a small percentage of patients with disc disorders finally will undergo surgery, spinal surgery has been one of the fastest growing disciplines in th

  5. Estudo comparativo dos mecanorreceptores dos discos intervertebrais normais e degenerados da coluna lombar de humanos pela radiografia, ressonância magnética e estudo anatomopatológico Comparative study of normal and degenerated intervertebral discs' mechanoreceptors of human lumar spine X-ray, magnetic resonance and anatomopathologic study

    Directory of Open Access Journals (Sweden)

    Valdeci Manoel de Oliveira

    2007-01-01

    Full Text Available Os autores fizeram um estudo da coluna lombar de humanos, objetivando avaliar e determinar os diferentes tipos de fibras nervosas no disco intervertebral normal e no degenerado. Foram usadas dez colunas lombares de cadáveres com aproximadamente 48 a 72 horas de óbito. As peças foram submetidas a exames de radiografia simples e ressonância magnética. Após os exames, os discos foram classificados em normais e degenerados. Em seguida, foram dissecados, divididos em regiões anterior e posterior, incluídos em parafina e realizado estudo de imuno-histoquímica com a proteína S100. Com o auxílio de um programa de computador Image-Pro Plus (media cybernetics®, as fibras nervosas tiveram seu diâmetro medidos em micrômetros e classificadas em quatro tipos de fibras. Foram encontrados quatro tipos de fibras nervosas nas diferentes regiões discais. O número e o tipo de fibras variaram de acordo com a região e grau de degeneração do disco intervertebral. Concluíram que as fibras do tipo III são mais freqüentes na região anterior; as fibras dos tipos II e IV são mais freqüentes na região posterior, e as fibras do tipo I não apresentaram diferenças entre a região anterior e a posterior; além disso, o disco degenerado tem mais fibras nervosas que o disco normal.The authors conducted a study on human lumbar spine, aiming to assess and determine the different kinds of nervous fibers in normal and degenerated intervertebral discs. Ten cadaver’s lumbar spines with approximately 48 - 72 of death have been used. The pieces were submitted to simple X-ray and magnetic resonance tests. Subsequently to the tests, discs were divided into normal and degenerated. Then, they were dissected, divided into anterior and posterior according to the region, included in paraffin and an immunohistochemical study with S100 protein was performed. With the aid of Image-Pro Plus computer software (media cybernetics ®, nervous fibers’ diameters were

  6. Intervertebral Disc Characteristic on Progressive Neurological Deficit

    Directory of Open Access Journals (Sweden)

    Farid Yudoyono

    2017-09-01

    Full Text Available Objective: To examine the intervertebral disc characteristic on magnetic resonance imaging (MRI in lumbar herniated disc (LHD patients with progressive neurological deficit. Methods: Patients were collected retrospectively from Dr. Hasan Sadikin General Hospital Database from 2011–2013 with LHD, had neurological deficit such as radiculopathy and cauda equine syndrome for less than four weeks with a positive sign confirmed by neurological examination and confirmatory with MRI examination. Results: A total of 14 patients with lumbar herniated disc disease (10 males, 4 females suffered from progressive neurological deficit with an average age of (52.07±10.9 years old. Early disc height was 9.38±0.5 mm and progressive neurological deficit state disc height was 4.03±0.53 mm, which were significantly different statisticaly (p<0.01. Symptoms of radiculopathy were seen in 11 patients and cauda equine syndrome in three patients. Modic changes grade 1 was found in five patients, grade 2 in eight patients,grade 3 in one patient, Pfirmman grade 2 in eleven patients and grade 3 in three patients. Thecal sac compression 1/3 compression was seen in four patients and 2/3 compression in ten patients. Conclusions: Neurosurgeon should raise concerns on the characteristic changes of intervertebral disc in magnetic resonance imaging examination to avoid further neural injury in lumbar herniated disc patients.

  7. Molecular signaling in intervertebral disk development.

    Science.gov (United States)

    DiPaola, Christian P; Farmer, James C; Manova, Katia; Niswander, Lee A

    2005-09-01

    The purpose of this investigation is to identify and study the expression pattern of pertinent molecular factors involved in the differentiation of the intervertebral disk (IVD). It is likely that hedgehog genes and the BMP inhibitors are key factors involved in spinal joint formation. Radioactive in situ hybridization with mRNA probes for pax-1, SHH, IHH and Noggin gene was performed on mouse embryo and adult tissue. Immunohistochemistry was performed to localize hedgehog receptor, "patched" (ptc). From 14.5 dpc until birth pax-1 mRNA was expressed in the developing anulus fibrosus (AF). During the same developmental period Noggin mRNA is highly expressed throughout the spine, in the developing AF, while ptc protein and SHH mRNA were expressed in the developing nucleus pulposus (NP). IHH mRNA was expressed by condensing chondrocytes of the vertebral bodies and later becomes confined to the vertebral endplate. We show for the first time that pax-1 is expressed in the adult intervertebral disk. Ptc expression in the NP is an indicator of hedgehog protein signaling in the developing IVD. The expression pattern of the BMP inhibitor Noggin appears to be important for the normal formation of the IVD and may prove to play a role in its segmental pattern formation.

  8. A CLINICAL STUDY OF OPERATIVE TREATMENT FOR LUMBAR INTERVERTEBRAL DISC PROLAPSE

    Directory of Open Access Journals (Sweden)

    Anilkumar S. D

    2016-09-01

    Full Text Available BACKGROUND Amongst painful diseases, sciatica occupies a foremost place by reason of its prevalence, its production by a great variety of conditions, the great disablement it may produce and its tending to relapse all of which have led to its recognition as one of the great scourges of humanity. Intervertebral disc prolapse is the important and common cause of low back pain and sciatica. Here, the subject of laminectomy and discectomy in the treatment of proven intervertebral disc prolapse in the lower lumbar region is reviewed and its results examined. AIM OF STUDY This study was undertaken in order to evaluate the following objectives. PRIMARY Analysis of clinical parameters and per operative findings of lumbar intervertebral disc prolapse. SECONDARY Analysis of clinical parameters and surgical outcome in lumbar intervertebral disc prolapse with respect to improvement in pain and neurological status. MATERIALS AND METHODS The study was undertaken in 22 patients who attended the Orthopaedic Department of Mount Zion Medical College, Adoor, between August 2014 to July 2015. All of them were suffering from a prolapsed lumbar vertebral disc as shown by clinical examination and investigations. Lumbar laminectomy and discectomy constituted the operative procedure for all of them. RESULTS In acute onset cases and cases with short duration, results were good. By six months, 80% of patients recorded of good pain relief, 80% of patients returned to work within six 6 months, 60% of patients showed good neurological recovery by 6 months. Laminectomy and discectomy in proven cases of lumbar intervertebral disc prolapse is a rewarding procedure. LT definitely relieved pain in all cases and improved morbidity and neurological deficits in most of the cases. CONCLUSION 1. Laminectomy and discectomy is an effective method of treatment in herniation of lumbar intervertebral disc. 2. The procedure is ideally done in those with the disc prolapse proved with the

  9. Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype.

    Science.gov (United States)

    Ngo, Kevin; Patil, Prashanti; McGowan, Sara J; Niedernhofer, Laura J; Robbins, Paul D; Kang, James; Sowa, Gwendolyn; Vo, Nam

    2017-09-01

    Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1 -/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss. Published by Elsevier B.V.

  10. (Photosynthesis in intact plants)

    Energy Technology Data Exchange (ETDEWEB)

    1990-01-01

    Progress in the two years since the last renewal application has been excellent. We have made substantial contributions on both main fronts of the projects, and are particularly happy with the progress of our research on intact plants. The approach of basing our field work on a sound foundation of laboratory studies has enabled is to use methods which provide unambiguous assays of well characterized reactions. We have also made excellent progress in several laboratory studies which will have direct applications in future field work, and have introduced to the laboratory a range of molecular genetics techniques which will allow us to explore new options in the attempt to understand function at the level of molecular structure.

  11. Calcification of intervertebral discs in children

    International Nuclear Information System (INIS)

    Hoermann, D.

    1984-01-01

    Thirteen children with intervertebral disc calcifications of the cervical, thoracal and lumbar spine have been diagnosed since 1970. Most of them were observed over a period of several years. Ten children fell ill with acute pains, but only 2 of them sufferred from a trauma. In 3 cases the features were discovered accidentally combined with malformations of vertebral bodies and congenital diseases. Our results suggest a primary structural inferiority of the calcified discs. The calcifications arise partially from a birth trauma, partially from an unknown etiology. They can last for a long time without symptoms. An acute event effects the pains due to shifting or herniation of calcified disc-fragments. Secondary findings such as decrease of the height of cervical vertebral bodies or destructions of the endplates of thoracal and lumbar vertebral bodies disappear retarded and often incompletely and demand a control for a long time. (orig.)

  12. Biomechanical analysis of the camelid cervical intervertebral disc

    Directory of Open Access Journals (Sweden)

    Dean K. Stolworthy

    2015-01-01

    Full Text Available Chronic low back pain (LBP is a prevalent global problem, which is often correlated with degenerative disc disease. The development and use of good, relevant animal models of the spine may improve treatment options for this condition. While no animal model is capable of reproducing the exact biology, anatomy, and biomechanics of the human spine, the quality of a particular animal model increases with the number of shared characteristics that are relevant to the human condition. The purpose of this study was to investigate the camelid (specifically, alpaca and llama cervical spine as a model of the human lumbar spine. Cervical spines were obtained from four alpacas and four llamas and individual segments were used for segmental flexibility/biomechanics and/or morphology/anatomy studies. Qualitative and quantitative data were compared for the alpaca and llama cervical spines, and human lumbar specimens in addition to other published large animal data. Results indicate that a camelid cervical intervertebral disc (IVD closely approximates the human lumbar disc with regard to size, spinal posture, and biomechanical flexibility. Specifically, compared with the human lumbar disc, the alpaca and llama cervical disc size are approximately 62%, 83%, and 75% with regard to area, depth, and width, respectively, and the disc flexibility is approximately 133%, 173%, and 254%, with regard to range of motion (ROM in axial-rotation, flexion-extension, and lateral-bending, respectively. These results, combined with the clinical report of disc degeneration in the llama lower cervical spine, suggest that the camelid cervical spine is potentially well suited for use as an animal model in biomechanical studies of the human lumbar spine.

  13. Human kinetic distribution of I-123 F(Ab')/sub 2/ and FAb compared to the parent I-123 intact antibody

    International Nuclear Information System (INIS)

    De Nardo, S.J.; De Nardo, G.L.; O'Grady, L.F.; Peng, J.S.; Macey, D.J.; Mills, S.L.; Caridiff, R.D.; Epstein, A.L.

    1985-01-01

    Studies of radiolabeled monoclonal antibodies are being performed by many investigators using a variety of molecular forms of the antibody. This study evaluates two I-123-labeled antibodies (Lym-1 IgG2a and B6.01 IgG1) and their I-123-labeled FAb and F(Ab')/sub 2/ for relative whole body distribution and kinetics, selected organ kinetics, and site of degradation. Evidence of immunocomplex formation, circulating antigen, and HAMA, were monitored by HPLC-TSK analysis and appropriate radioassays of the plasma. Each antibody and each I-123-labeled fragment has been evaluated in 5 patients. One patient had serial comparisons of the radiolabeled parent molecule, F(Ab')/sub 2/ (100μg and 5 mg) and FAb (100μg) of Lym-1. Blood clearance, urine excretion rate, and plasma and urine HPLC fractionation of the radioactive species were determined. Whole body clearance by total body scans and organ clearance were obtained by geometric mean of anterior and posterior areas of interest. The FAb and F(Ab')/sub 2/ fragments had similar blood pool recovery 5 minutes after the 5-minute injection. These were the same as blood levels when 5mg of intact I-123-labeled antibody was given. The second phase of the blood curves for F(Ab')/sub 2/ had a T1/2 of 35-40 hours and for FAb was 15-20 hours. Urine excretion varied, but agreed with total body loss from body scan information. The patient with serial studies had a 24-hour residual dose of 82% for FAb, 62% for 10μg for F(Ab')/sub 2/ and 61% for 5mg of F(Ab')/sub 2/. Renal uptake for all patients was higher and more persistent with both fragments than intact antibody, but hepatic uptake was less

  14. Percutaneous treatment of intervertebral disc herniation.

    Science.gov (United States)

    Buy, Xavier; Gangi, Afshin

    2010-06-01

    Interventional radiology plays a major role in the management of symptomatic intervertebral disc herniations. In the absence of significant pain relief with conservative treatment including oral pain killers and anti-inflammatory drugs, selective image-guided periradicular infiltrations are generally indicated. The precise control of needle positioning allows optimal distribution of steroids along the painful nerve root. After 6 weeks of failure of conservative treatment including periradicular infiltration, treatment aiming to decompress or remove the herniation is considered. Conventional open surgery offers suboptimal results and is associated with significant morbidity. To achieve minimally invasive discal decompression, different percutaneous techniques have been developed. Their principle is to remove a small volume of nucleus, which results in an important reduction of intradiscal pressure and subsequently reduction of pressure inside the disc herniation. However, only contained disc herniations determined by computed tomography or magnetic resonance are indicated for these techniques. Thermal techniques such as radiofrequency or laser nucleotomy seem to be more effective than purely mechanical nucleotomy; indeed, they achieve discal decompression but also thermal destruction of intradiscal nociceptors, which may play a major role in the physiopathology of discal pain. The techniques of image-guided spinal periradicular infiltration and percutaneous nucleotomy with laser and radiofrequency are presented with emphasis on their best indications.

  15. Intervertebral Disc Degeneration : The Role of the Mitochondrial Pathway in Annulus Fibrosus Cell Apoptosis Induced by Overload

    OpenAIRE

    Rannou, François; Lee, Tzong-Shyuan; Zhou, Rui-Hai; Chin, Jennie; Lotz, Jeffrey C.; Mayoux-Benhamou, Marie-Anne; Barbet, Jacques Patrick; Chevrot, Alain; Shyy, John Y.-J.

    2004-01-01

    Degeneration of the intervertebral disk (IVD) is a major pathological process implicated in low back pain and is a prerequisite to disk herniation. Although mechanical stress is an important modulator of the degeneration, the underlying molecular mechanism remains unclear. The association of human IVD degeneration, assessed by magnetic resonance imaging, with annulus fibrosus cell apoptosis and anti-cytochrome c staining revealed that the activation of the mitochondria-dependent apoptosome wa...

  16. A role for TNFα in intervertebral disc degeneration: A non-recoverable catabolic shift

    International Nuclear Information System (INIS)

    Purmessur, D.; Walter, B.A.; Roughley, P.J.; Laudier, D.M.; Hecht, A.C.; Iatridis, James

    2013-01-01

    Highlights: ► TNFα induced catabolic changes similar to human intervertebral disc degeneration. ► The metabolic shift induced by TNFα was sustained following removal. ► TNFα induced changes suggestive of cell senescence without affecting cell viability. ► Interventions are required to stimulate anabolism and increase cell proliferation. -- Abstract: This study examines the effect of TNFα on whole bovine intervertebral discs in organ culture and its association with changes characteristic of intervertebral disc degeneration (IDD) in order to inform future treatments to mitigate the chronic inflammatory state commonly found with painful IDD. Pro-inflammatory cytokines such as TNFα contribute to disc pathology and are implicated in the catabolic phenotype associated with painful IDD. Whole bovine discs were cultured to examine cellular (anabolic/catabolic gene expression, cell viability and senescence using β-galactosidase) and structural (histology and aggrecan degradation) changes in response to TNFα treatment. Control or TNFα cultures were assessed at 7 and 21 days; the 21 day group also included a recovery group with 7 days TNFα followed by 14 days in basal media. TNFα induced catabolic and anti-anabolic shifts in the nucleus pulposus (NP) and annulus fibrosus (AF) at 7 days and this persisted until 21 days however cell viability was not affected. Data indicates that TNFα increased aggrecan degradation products and suggests increased β-galactosidase staining at 21 days without any recovery. TNFα treatment of whole bovine discs for 7 days induced changes similar to the degeneration processes that occur in human IDD: aggrecan degradation, increased catabolism, pro-inflammatory cytokines and nerve growth factor expression. TNFα significantly reduced anabolism in cultured IVDs and a possible mechanism may be associated with cell senescence. Results therefore suggest that successful treatments must promote anabolism and cell proliferation in

  17. Oxidative stress participates in age-related changes in rat lumbar intervertebral discs.

    Science.gov (United States)

    Hou, Gang; Lu, Huading; Chen, Mingjuan; Yao, Hui; Zhao, Huiqing

    2014-01-01

    Aging is a major factor associated with lumber intervertebral disc degeneration, and oxidative stress is known to play an essential role in the pathogenesis of many age-related diseases. In this study, we investigated oxidative stress in intervertebral discs of Wistar rats in three different age groups: youth, adult, and geriatric. Age-related intervertebral disc changes were examined by histological analysis. In addition, oxidative stress was evaluated by assessing nitric oxide (NO), superoxide dismutase (SOD), malondialdehyde (MDA), and advanced oxidation protein products (AOPPs). Intervertebral disc, but not serum, NO concentrations significantly differed between the three groups. Serum and intervertebral disc SOD activity gradually decreased with age. Furthermore, both serum and intervertebral disc MDA and AOPP levels gradually increased with age. Our studies suggest that oxidative stress is associated with age-related intervertebral disc changes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Refinement of elastic, poroelastic, and osmotic tissue properties of intervertebral disks to analyze behavior in compression.

    Science.gov (United States)

    Stokes, Ian A F; Laible, Jeffrey P; Gardner-Morse, Mack G; Costi, John J; Iatridis, James C

    2011-01-01

    Intervertebral disks support compressive forces because of their elastic stiffness as well as the fluid pressures resulting from poroelasticity and the osmotic (swelling) effects. Analytical methods can quantify the relative contributions, but only if correct material properties are used. To identify appropriate tissue properties, an experimental study and finite element analytical simulation of poroelastic and osmotic behavior of intervertebral disks were combined to refine published values of disk and endplate properties to optimize model fit to experimental data. Experimentally, nine human intervertebral disks with adjacent hemi-vertebrae were immersed sequentially in saline baths having concentrations of 0.015, 0.15, and 1.5 M and the loss of compressive force at constant height (force relaxation) was recorded over several hours after equilibration to a 300-N compressive force. Amplitude and time constant terms in exponential force-time curve-fits for experimental and finite element analytical simulations were compared. These experiments and finite element analyses provided data dependent on poroelastic and osmotic properties of the disk tissues. The sensitivities of the model to alterations in tissue material properties were used to obtain refined values of five key material parameters. The relaxation of the force in the three bath concentrations was exponential in form, expressed as mean compressive force loss of 48.7, 55.0, and 140 N, respectively, with time constants of 1.73, 2.78, and 3.40 h. This behavior was analytically well represented by a model having poroelastic and osmotic tissue properties with published tissue properties adjusted by multiplying factors between 0.55 and 2.6. Force relaxation and time constants from the analytical simulations were most sensitive to values of fixed charge density and endplate porosity.

  19. MR imaging of spondylolytic spondylolisthesis: changes of intervertebral foramen and nerve root compression

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hyung [Ajou Univ. College of Medicine, Seoul (Korea, Republic of); Chung, Tae Sub; Kim, Young Soo [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-08-01

    To evaluate the factors affecting intervertebral foramen stenosis and nerve root compression in spondylolytic spondylolisthesis. We investigated 120 intervertebral foramina of 60 patients with spondylolytic spondylolisthesis who had undergone lumbar MRI. A retrospective review of their MR images revealed the degree of intervertebral foramen stenosis and causes of nerve root compression. The relationship between disk height diminution following spondylolysis and degree of intervertebral foramen stenosis was also evaluated. Forty eight of 60 patients showed a similar degree of intervertebral foramen stenosis, and in 12 patients the degree of stenosis was different. In 110 intervertebral foramina, stenosis of both the superior and inferior compartments of intervertebral foramina was demonstrated. In 37 of 120 cases (30.8%), stenosis was mild ; in 44 of 120 (36.7%) it was modcrate, and in 29 of 120 (24.2%) it was severe. Stenosis of the inferior compartment was demonstrated in ten of 120 intervertebral foramina (8.3%). Nerve root compression was caused by posterior bulging of the intervertebral disk (65/120), descent of the pedicle (51/120), an isthmic bony segment above the site of spondylolytic (44/120), a bony spur formed at a spondylolytic site (11/120), and fibrocartilaginous callus at a spondylolytic site (5/48). In all cases there was degenerative change of the intervertebral disk at the affected level. There was no relationship between degree of disk height diminution and degree of intervertebral foramen stenosis (p > 0.05). The degree of intervertebral foramen stenosis and causes of nerve root compression in spondylolytic spondylolisthesis are variable, and MRI demonstrates them precisely. There was no positive relationship between degree of nerve root compression at an intervertebral foramen and degree of spondylolysis and degeneration of an intervertebral foramen. The degree of nerve root compression is believed to be another criterion for describing

  20. MR imaging of spondylolytic spondylolisthesis: changes of intervertebral foramen and nerve root compression

    International Nuclear Information System (INIS)

    Kim, Ji Hyung; Chung, Tae Sub; Kim, Young Soo

    1999-01-01

    To evaluate the factors affecting intervertebral foramen stenosis and nerve root compression in spondylolytic spondylolisthesis. We investigated 120 intervertebral foramina of 60 patients with spondylolytic spondylolisthesis who had undergone lumbar MRI. A retrospective review of their MR images revealed the degree of intervertebral foramen stenosis and causes of nerve root compression. The relationship between disk height diminution following spondylolysis and degree of intervertebral foramen stenosis was also evaluated. Forty eight of 60 patients showed a similar degree of intervertebral foramen stenosis, and in 12 patients the degree of stenosis was different. In 110 intervertebral foramina, stenosis of both the superior and inferior compartments of intervertebral foramina was demonstrated. In 37 of 120 cases (30.8%), stenosis was mild ; in 44 of 120 (36.7%) it was modcrate, and in 29 of 120 (24.2%) it was severe. Stenosis of the inferior compartment was demonstrated in ten of 120 intervertebral foramina (8.3%). Nerve root compression was caused by posterior bulging of the intervertebral disk (65/120), descent of the pedicle (51/120), an isthmic bony segment above the site of spondylolytic (44/120), a bony spur formed at a spondylolytic site (11/120), and fibrocartilaginous callus at a spondylolytic site (5/48). In all cases there was degenerative change of the intervertebral disk at the affected level. There was no relationship between degree of disk height diminution and degree of intervertebral foramen stenosis (p > 0.05). The degree of intervertebral foramen stenosis and causes of nerve root compression in spondylolytic spondylolisthesis are variable, and MRI demonstrates them precisely. There was no positive relationship between degree of nerve root compression at an intervertebral foramen and degree of spondylolysis and degeneration of an intervertebral foramen. The degree of nerve root compression is believed to be another criterion for describing

  1. Vascular complications of prosthetic inter-vertebral discs.

    Science.gov (United States)

    Daly, Kevin J; Ross, E Raymond S; Norris, Heather; McCollum, Charles N

    2006-10-01

    Five consecutive cases of prosthetic inter-vertebral disc displacement with severe vascular complications on revisional surgery are described. The objective of this case report is to warn spinal surgeons that major vascular complications are likely with anterior displacement of inter-vertebral discs. We have not been able to find a previous report on vascular complications associated with anterior displacement of prosthetic inter-vertebral discs. In all five patients the prosthetic disc had eroded into the bifurcation of the inferior vena cava and the left common iliac vein. In three cases the aortic bifurcation was also involved. The fibrosis was so severe that dissecting out the arteries and veins to provide access to the relevant disc proved impossible. Formal division of the left common iliac vein and artery with subsequent repair was our solution. Anterior inter-vertebral disc displacement was associated with severe vascular injury. Preventing anterior disc displacement is essential in disc design. In the event of anterior displacement, disc removal should be planned with a Vascular Surgeon.

  2. Potential regenerative treatment strategies for intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bach, Frances C; Willems, Nicole; Penning, Louis C; Ito, Keita; Meij, Björn P; Tryfonidou, Marianna A

    Pain due to spontaneous intervertebral disc (IVD) disease is common in dogs. In chondrodystrophic (CD) dogs, IVD disease typically develops in the cervical or thoracolumbar spine at about 3-7 years of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or

  3. Genetic Alterations in Intervertebral Disc Disease

    Directory of Open Access Journals (Sweden)

    Nikolay L. Martirosyan

    2016-11-01

    Full Text Available Background: Intervertebral disc degeneration (IVDD is considered a multifactorial disease. The last two decades of research strongly demonstrate that genetic factors contribute about 75% of the IVDD etiology. Recent total genome sequencing studies have shed light on the various single nucleotide polymorphisms (SNPs that are associated with IVDD.Aim: This review explores and presents updated information about the diversity of genetic factors in the inflammatory, degradative, homeostatic, and structural systems involved in the IVDD.Results: SNPs in the genes coding for structural proteins linked with IVDD or disc bulging include the Sp1 polymorphism of COL1A1, Trp3 polymorphism of COL9A3, several polymorphisms of COL11A1 and COL11A2, and a variable number tandem repeat polymorphism of ACAN. The rs4148941 SNP of CHST3 coding for an aggrecan sulfation enzyme is also associated with IVDD. The FokI, TaqI, and ApaI SNPs of the vitamin D receptor gene that is involved in chondrocyte functioning are also associated with IVDD. SNPs relevant to cytokine imbalance in IVDD include 889C/T of IL1a and 15T/A, as well as other SNPs (rs1800795, rs1800796, and rs1800797, of IL6, with effects limited to certain genders and populations. SNPs in collagenase genes include -1605G/D (guanine insertion/deletion of MMP1, -1306C/T of MMP2, -1562C/T and a 5-adenosine (5A variant (in the promotor region of MMP3, -1562C/T of MMP9, and -378T/C of MMP-14. SNPs in aggrecanase genes include 1877T/U of ADAMTS-4 and rs162509 of ADAMTS-5. Among the apoptosis-mediating genes, 1595T/C of the caspase 9 gene, 1525A/G and 1595T/C of the TRAIL gene, and 626C/G of the death receptor 4 gene (DR4 are SNPs associated with IVDD. Among the growth factors involved in disc homeostasis, the rs4871857 SNP of GDF5 was associated with IVDD. VEGF SNPs -2578C/A and -634G/C could foster neovascularization observed in IVDD.Conclusion: Improved understanding of the numerous genetic variants behind various

  4. Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Hård, K.; Mekking, A.; Damm, J.B.L.; Kamerling, J.P.; Boer, W. de; Wijnands, R.A.

    1990-01-01

    Biologically active recombinant human follitropin has been expressed in Chinese hamster ovary cells. The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. The oligosaccharides were separated from

  5. Stem cell therapy for intervertebral disc regeneration: review article

    Directory of Open Access Journals (Sweden)

    Mohsen Sheykhhasan

    2017-02-01

    Full Text Available Intervertebral disks (IVD acts as shock absorber between each of the vertebrae in the spinal column by keeping the vertebrae separated when the shock caused by the action. They also serve to protect the nerves that run down the middle of the spine and intervertebral disks. The disks are made of fibrocartilaginous material. The outside of the disk is made of a strong material called the annulus fibrosus. Inside this protective covering is a jelly-like substance known as mucoprotein gel. This interior is known as the nucleus pulposus. The nucleus pulposus consists of large vacuolated notochord cells, small chondrocyte-like cells, collagen fibrils, and aggrecan, a proteoglycan that aggregates by binding to hyaluronan. Attached to each aggrecan molecule are glycosaminoglycan (GAG chains of chondroitin sulfate and keratan sulfate. Intervertebral disks degeneration is frequently associated with low back and neck pain, which accounts as a disability. Despite the known outcomes of the Intervertebral disks degeneration cascade, the treatment of IVD degeneration is limited in that available conservative and surgical treatments do not reverse the pathology or restore the IVD tissue. Regenerative medicine for IVD degeneration, by injection of Intervertebral disks cells, chondrocytes or stem cells, has been extensively studied in the past decade in various animal models of induced IVD degeneration, and has progressed to clinical trials in the treatment of various spinal disease. Despite preliminary results showing positive effects of cell-injection strategies for IVD regeneration, detailed basic research on Intervertebral disks cells and their niche demonstrates that transplanted cells are unable to survive and adapt in the avascular niche of the IVD. For this therapeutic strategy to succeed, the indications for its use and the patients who would benefit need to be better defined. To surmount these obstacles, the solution will be identified only by focused

  6. Magnetic resonance imaging of diseased cervical and lumbar intervertebral discs

    International Nuclear Information System (INIS)

    Kadoya, Satoru; Nakamura, Tsutomu; Takarada, Akira; Yamamoto, Itaru; Sato, Shuji.

    1989-01-01

    Magnetic resonance images (MRI) of diseased cervical and lumbar intervertebral discs involving both intrinsic and extrinsic cord lesions were examined using either a 0.15 T resistive or a 0.5 T superconductive magnetic imaging system. The vertebrae, intervertebral discs, and spinal cord were delineated on spin-echo (SE) images with a long repetition time (TR) and a short echo time (proton density-weighted image). Protrusion of degenerated intervertebral discs into the spinal canal was clearly demonstrated not only on sagittal but also on parasagittal and transverse views. The location of protruded discs and compression of the spinal cord, caudal sac, and nerve roots were well visualized three-dimensionally. Pathological features of intervertebral discs were well appreciated on T 2 -weighted images with long TR and SE pulse sequences. Degeneration of intervertebral discs resulted in decreased signal intensity in cases of lumbar disc involvement. For suspected myelomalacia, the intrinsic cord lesion resulting from traumatic disc protrusion appeared as focal low signal intensity on T 1 -weithed images and as somewhat high intensity on T 2 weighted images. The inversion recovery sequence with median inversion time displayed an inferior image of low contrast and was judged uninformative in comparison to SE imags. The findings showed MRI to be an essential diagnostic technique for spinal cord disorders. It clearly pinpoints the anatomic structures of the spine and the features of disc degeneration. Both extrinsic and intrinsic cord abnormalities can be identified with MRI. The selection of proper pulse sequences is required for the differentiation of the object of interest. (Namekawa, K)

  7. Magnetic resonance imaging of diseased cervical and lumbar intervertebral discs

    Energy Technology Data Exchange (ETDEWEB)

    Kadoya, Satoru; Nakamura, Tsutomu; Takarada, Akira; Yamamoto, Itaru; Sato, Shuji.

    1989-02-01

    Magnetic resonance images (MRI) of diseased cervical and lumbar intervertebral discs involving both intrinsic and extrinsic cord lesions were examined using either a 0.15 T resistive or a 0.5 T superconductive magnetic imaging system. The vertebrae, intervertebral discs, and spinal cord were delineated on spin-echo (SE) images with a long repetition time (TR) and a short echo time (proton density-weighted image). Protrusion of degenerated intervertebral discs into the spinal canal was clearly demonstrated not only on sagittal but also on parasagittal and transverse views. The location of protruded discs and compression of the spinal cord, caudal sac, and nerve roots were well visualized three-dimensionally. Pathological features of intervertebral discs were well appreciated on T/sub 2/-weighted images with long TR and SE pulse sequences. Degeneration of intervertebral discs resulted in decreased signal intensity in cases of lumbar disc involvement. For suspected myelomalacia, the intrinsic cord lesion resulting from traumatic disc protrusion appeared as focal low signal intensity on T/sub 1/-weithed images and as somewhat high intensity on T/sub 2/ weighted images. The inversion recovery sequence with median inversion time displayed an inferior image of low contrast and was judged uninformative in comparison to SE imags. The findings showed MRI to be an essential diagnostic technique for spinal cord disorders. It clearly pinpoints the anatomic structures of the spine and the features of disc degeneration. Both extrinsic and intrinsic cord abnormalities can be identified with MRI. The selection of proper pulse sequences is required for the differentiation of the object of interest. (Namekawa, K).

  8. Application of pressure ultrafiltration in determining the binding capacity of drugs to human albumin and to plasma proteins of intact and irradiated rat females

    International Nuclear Information System (INIS)

    Zima, M.

    1976-01-01

    The significance of the binding of drugs to plasma proteins has repeatedly been demonstrated and draws the interest of many pharmacologists. The described experiments served to study the binding of isoniazid (INH) to human albumin of various dilution and to whole plasma proteins of irradiated (on the Oth, 3rd and 6th day after exposure to 154.8 mC/kg=600 R) and non-irradiated rats using the technique of modified accelerated ultrafiltration through cellophane. The total characteristics of the binding and its changes were demonstrated by the equilibrium constant, the numbers of binding sites and the changes of free binding energy. The results show that the dilution of human albumin affects the strength of the INH binding on this albumin and further that the normally weak INH binding is diminished even more in irradiated rats. This cannot be explained by the change in the percentage composition of the rat plasma. (author)

  9. Monomethylfumarate induces γ-globin expression and fetal hemoglobin production in cultured human retinal pigment epithelial (RPE) and erythroid cells, and in intact retina.

    Science.gov (United States)

    Promsote, Wanwisa; Makala, Levi; Li, Biaoru; Smith, Sylvia B; Singh, Nagendra; Ganapathy, Vadivel; Pace, Betty S; Martin, Pamela M

    2014-05-13

    Sickle retinopathy (SR) is a major cause of vision loss in sickle cell disease (SCD). There are no strategies to prevent SR and treatments are extremely limited. The present study evaluated (1) the retinal pigment epithelial (RPE) cell as a hemoglobin producer and novel cellular target for fetal hemoglobin (HbF) induction, and (2) monomethylfumarate (MMF) as an HbF-inducing therapy and abrogator of oxidative stress and inflammation in SCD retina. Human globin gene expression was evaluated by RT-quantitative (q)PCR in the human RPE cell line ARPE-19 and in primary RPE cells isolated from Townes humanized SCD mice. γ-Globin promoter activity was monitored in KU812 stable dual luciferase reporter expressing cells treated with 0 to 1000 μM dimethylfumarate, MMF, or hydroxyurea (HU; positive control) by dual luciferase assay. Reverse transcriptase-qPCR, fluorescence-activated cell sorting (FACS), immunofluorescence, and Western blot techniques were used to evaluate γ-globin expression and HbF production in primary human erythroid progenitors, ARPE-19, and normal hemoglobin producing (HbAA) and homozygous β(s) mutation (HbSS) RPE that were treated similarly, and in MMF-injected (1000 μM) HbAA and HbSS retinas. Dihydroethidium labeling and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), IL-1β, and VEGF expression were also analyzed. Retinal pigment epithelial cells express globin genes and synthesize adult and fetal hemoglobin MMF stimulated γ-globin expression and HbF production in cultured RPE and erythroid cells, and in HbSS mouse retina where it also reduced oxidative stress and inflammation. The production of hemoglobin by RPE suggests the potential involvement of this cell type in the etiology of SR. Monomethylfumarate influences multiple parameters consistent with improved retinal health in SCD and may therefore be of therapeutic potential in SR treatment. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  10. Simultaneous RNA quantification of human and retroviral genomes reveals intact interferon signaling in HTLV-1-infected CD4+ T cell lines

    Directory of Open Access Journals (Sweden)

    Moens Britta

    2012-08-01

    Full Text Available Abstract Background IFN-α contributes extensively to host immune response upon viral infection through antiviral, pro-apoptotic, antiproliferative and immunomodulatory activities. Although extensively documented in various types of human cancers and viral infections, controversy exists in the exact mechanism of action of IFN-α in human immunodeficiency virus type 1 (HIV-1 and human T-lymphotropic virus type 1 (HTLV-1 retroviral infections. Results IFN-α displayed strong anti-HIV-1 effects in HIV-1/HTLV-1 co-infected MT-4 cells in vitro, demonstrated by the dose-dependent inhibition of the HIV-1-induced cytopathic effect (IC50 = 83.5 IU/ml, p 50 = 1.2 IU/ml, p  Conclusions Taken together, our results indicate that both the absence of in vitro antiproliferative and pro-apoptotic activity as well as the modest post-transcriptional antiviral activity of IFN-α against HTLV-1, were not due to a cell-intrinsic defect in IFN-α signalisation, but rather represents a retrovirus-specific phenomenon, considering the strong HIV-1 inhibition in co-infected cells.

  11. Ozone therapy for t he complex prolapse of lumbar intervertebral disc: a clinical observation

    International Nuclear Information System (INIS)

    Peng Yong; Wei Mengqi; Wu Juan; Zhou Jianshou; Yang Yong; Zhao Hongliang; Shi Mingguo

    2010-01-01

    Objective: To evaluate the therapeutic outcome of ozone injection therapy for the treatment of complex prolapse of lumbar intervertebral disc, which is accompanied with spinal stenosis due to hypertrophy of ligamentum flavum, degeneration of intervertebral facet joints, intervertebral hyperosteogeny and degeneration, lumbar muscle strain and negative pressure in intervertebral discs. Methods: Seventy patients with simple intervertebral disc prolapse (simple group) and 70 patients with complex intervertebral disc prolapse (complex group) were selected for the study. The complex intervertebral disc prolapse included negative pressure in intervertebral disc (n=11), recurrence after resection of nucleus polposus of intervertebral disc (n=5), spinal stenosis (n=10), degeneration of intervertebral facet joints and interver-tebral hyperosteogeny (n=30), stenosis of lateral recess (n=4) and lumbar muscle strain (n=10). All patients were treated with ozone injection under the CT guidance. A total of 2-3 ml ozone with the concentration of 40-50 μg / ml was injected into the intervertebral disk and a total of 5-8 ml ozone with the concentration of 30-40 μg / ml was injected into the paraspinal space. Infiltration injection into the pain spots with 20 ml ozone was carried out in patients with lumbar muscle strain. Results: A comparison of the therapeutic outcomes between simple group and complex group was made. Immediate relief from clinical symptoms was obtained in 80% of all treated patients. The effective rate one week after the procedure was 95%, which became 96% at 3-6 months after the treatment. Conclusion: Correct clinical diagnosis, skilled and accurate manipulation during the surgery and reasonable use of ozone injection in the treatment of soft tissue injury, etc. can markedly improve the therapeutic effect for complex lumbar intervertebral disc prolase. (authors)

  12. Ethyl cellulose nanocarriers and nanocrystals differentially deliver dexamethasone into intact, tape-stripped or sodium lauryl sulfate-exposed ex vivo human skin - assessment by intradermal microdialysis and extraction from the different skin layers.

    Science.gov (United States)

    Döge, Nadine; Hönzke, Stefan; Schumacher, Fabian; Balzus, Benjamin; Colombo, Miriam; Hadam, Sabrina; Rancan, Fiorenza; Blume-Peytavi, Ulrike; Schäfer-Korting, Monika; Schindler, Anke; Rühl, Eckart; Skov, Per Stahl; Church, Martin K; Hedtrich, Sarah; Kleuser, Burkhard; Bodmeier, Roland; Vogt, Annika

    2016-11-28

    Understanding penetration not only in intact, but also in lesional skin with impaired skin barrier function is important, in order to explore the surplus value of nanoparticle-based drug delivery for anti-inflammatory dermatotherapy. Herein, short-term ex vivo cultures of (i) intact human skin, (ii) skin pretreated with tape-strippings and (iii) skin pre-exposed to sodium lauryl sulfate (SLS) were used to assess the penetration of dexamethasone (Dex). Intradermal microdialysis was utilized for up to 24h after drug application as commercial cream, nanocrystals or ethyl cellulose nanocarriers applied at the therapeutic concentration of 0.05%, respectively. In addition, Dex was assessed in culture media and extracts from stratum corneum, epidermis and dermis after 24h, and the results were compared to those in heat-separated split skin from studies in Franz diffusion cells. Providing fast drug release, nanocrystals significantly accelerated the penetration of Dex. In contrast to the application of cream and ethyl cellulose nanocarriers, Dex was already detectable in eluates after 6h when applying nanocrystals on intact skin. Disruption of the skin barrier further accelerated and enhanced the penetration. Encapsulation in ethyl cellulose nanocarriers delayed Dex penetration. Interestingly, for all formulations highly increased concentrations in the dialysate were observed in tape-stripped skin, whereas the extent of enhancement was less in SLS-exposed skin. The results were confirmed in tissue extracts and were in line with the predictions made by in vitro release studies and ex vivo Franz diffusion cell experiments. The use of 45kDa probes further enabled the collection of inflammatory cytokines. However, the estimation of glucocorticoid efficacy by Interleukin (IL)-6 and IL-8 analysis was limited due to the trauma induced by the probe insertion. Ex vivo intradermal microdialysis combined with culture media analysis provides an effective, skin-sparing method for

  13. Effect of DNA polymerase inhibitors on DNA repair in intact and permeable human fibroblasts: Evidence that DNA polymerases δ and β are involved in DNA repair synthesis induced by N-methyl-N'-nitro-N-nitrosoguanidine

    International Nuclear Information System (INIS)

    Hammond, R.A.; Miller, M.R.; McClung, J.K.

    1990-01-01

    The involvement of DNA polymerases α, β, and δ in DNA repair synthesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in human fibroblasts (HF). The effects of anti-(DNA polymerase α) monoclonal antibody, (p-n-butylphenyl)deoxyguanosine triphosphate (BuPdGTP), dideoxythymidine triphosphate (ddTTP), and aphidicolin on MNNG-induced DNA repair synthesis were investigated to dissect the roles of the different DNA polymerases. A subcellular system (permeable cells), in which DNA repair synthesis and DNA replication were differentiated by CsCl gradient centrifugation of BrdUMP density-labeled DNA, was used to examine the effects of the polymerase inhibitors. Another approach investigated the effects of several of these inhibitors of MNNG-induced DNA repair synthesis in intact cells by measuring the amount of [ 3 H]thymidine incorporated into repair DNA as determined by autoradiography and quantitation with an automated video image analysis system. In permeable cells, MNNG-induced DNA repair synthesis was inhibited 56% by 50 μg of aphidicolin/mL, 6% by 10 μM BuPdGTP, 13% by anti-(DNA polymerse α) monoclonal antibodies, and 29% by ddTTP. In intact cells, MNNG-induced DNA repair synthesis was inhibited 57% by 50 μg of aphidicolin/mL and was not significantly inhibited by microinjecting anti-(DNA polymerase α) antibodies into HF nuclei. These results indicate that both DNA polymerase δ and β are involved in repairing DNA damage caused by MNNG

  14. Multijunction Capillary Isoelectric Focusing Device Combined with Online Membrane-Assisted Buffer Exchanger Enables Isoelectric Point Fractionation of Intact Human Plasma Proteins for Biomarker Discovery.

    Science.gov (United States)

    Pirmoradian, Mohammad; Astorga-Wells, Juan; Zubarev, Roman A

    2015-12-01

    Prefractionation of proteins is often employed to improve analysis specificity in proteomics. Prefractionation based on the isoelectric point (pI) is particularly attractive because pI is a well-defined parameter and it is orthogonal to hydrophobicity on which reversed-phase chromatography is based. However, direct capillary electrophoresis of blood proteins is challenging due to its high content of salts and charged small molecules. Here, we couple an online desalinator device to our multijunction capillary isoelectric focusing (MJ-CIEF) instrument and perform direct isoelectric separation of human blood plasma. In a proof-of-principle experiment, pooled samples of patients with progressive mild cognitive impairment and corresponding healthy controls were investigated. Injection of 3 μL of plasma containing over 100 μg of proteins into the desalinator was followed by pI fractionation with MJ-CIEF in less than 1 h. Shotgun proteomics of 12 collected fractions from each of the 5 replicates of pooled samples resulted in the identification and accurate quantification (median CV between the replicates is <4%) of nearly 365 protein groups from 4030 unique peptides (with <1% FDR for both peptides and proteins). The obtained results include several proteins previously reported as AD markers. The isoelectric point of each quantified protein was calculated using a set of 7 synthetic peptides spiked into the samples. Several proteins with a significant pI shift between their isoforms in the patient and control samples were identified. The presented method is straightforward, robust, and scalable; therefore, it can be used in both biological and clinical applications.

  15. How can we conserve intact tropical peatlands?

    Science.gov (United States)

    Lawson, Ian; Roucoux, Katherine

    2017-04-01

    The scientific community has, for more than three decades, been expressing increasing alarm about the fate of peatlands in parts of Indonesia and Malaysia, where extensive land-use conversion and drainage for rice and oil palm have greatly compromised peatland hydrology, ecology, biological richness, and carbon storage. The discourse in the literature on these peatlands is now moving on from attempts to preserve the last remaining fragments of peat-swamp forest, towards discussion of how best to restore damaged ecosystems, and whether it is possible to manage plantations more 'sustainably'. It is becoming increasingly clear, however, that peatlands occur quite widely in other parts of the lowland tropics, including parts of Amazonia and the Congo Basin, and many of these peatlands can reasonably be described as 'intact': although few if any parts of the tropics are totally unaffected by human actions, the hydrology and functional ecology of these systems appear to be close to a 'natural' state. The question then arises as to what should be done with the knowledge of their existence. Here we analyse the arguments in favour of protecting intact peatlands, and the potential conflicts with other priorities such as economic development and social justice. We evaluate alternative mechanisms for protecting intact peatlands, focusing on the particular issues raised by peatlands as opposed to other kinds of tropical ecosystem. We identify ways in which natural science agendas can help to inform these arguments, using our own contributions in palaeoecology and carbon mapping as examples. Finally, we argue for a radical reconsideration of research agendas in tropical peatlands, highlighting the potential contribution of methodologies borrowed from the social sciences and humanities.

  16. Inter-vertebral flexibility of the ostrich neck: implications for estimating sauropod neck flexibility.

    Science.gov (United States)

    Cobley, Matthew J; Rayfield, Emily J; Barrett, Paul M

    2013-01-01

    The flexibility and posture of the neck in sauropod dinosaurs has long been contentious. Improved constraints on sauropod neck function will have major implications for what we know of their foraging strategies, ecology and overall biology. Several hypotheses have been proposed, based primarily on osteological data, suggesting different degrees of neck flexibility. This study attempts to assess the effects of reconstructed soft tissues on sauropod neck flexibility through systematic removal of muscle groups and measures of flexibility of the neck in a living analogue, the ostrich (Struthio camelus). The possible effect of cartilage on flexibility is also examined, as this was previously overlooked in osteological estimates of sauropod neck function. These comparisons show that soft tissues are likely to have limited the flexibility of the neck beyond the limits suggested by osteology alone. In addition, the inferred presence of cartilage, and varying the inter-vertebral spacing within the synovial capsule, also affect neck flexibility. One hypothesis proposed that flexibility is constrained by requiring a minimum overlap between successive zygapophyses equivalent to 50% of zygapophyseal articular surface length (ONP50). This assumption is tested by comparing the maximum flexibility of the articulated cervical column in ONP50 and the flexibility of the complete neck with all tissues intact. It is found that this model does not adequately convey the pattern of flexibility in the ostrich neck, suggesting that the ONP50 model may not be useful in determining neck function if considered in isolation from myological and other soft tissue data.

  17. Inter-vertebral flexibility of the ostrich neck: implications for estimating sauropod neck flexibility.

    Directory of Open Access Journals (Sweden)

    Matthew J Cobley

    Full Text Available The flexibility and posture of the neck in sauropod dinosaurs has long been contentious. Improved constraints on sauropod neck function will have major implications for what we know of their foraging strategies, ecology and overall biology. Several hypotheses have been proposed, based primarily on osteological data, suggesting different degrees of neck flexibility. This study attempts to assess the effects of reconstructed soft tissues on sauropod neck flexibility through systematic removal of muscle groups and measures of flexibility of the neck in a living analogue, the ostrich (Struthio camelus. The possible effect of cartilage on flexibility is also examined, as this was previously overlooked in osteological estimates of sauropod neck function. These comparisons show that soft tissues are likely to have limited the flexibility of the neck beyond the limits suggested by osteology alone. In addition, the inferred presence of cartilage, and varying the inter-vertebral spacing within the synovial capsule, also affect neck flexibility. One hypothesis proposed that flexibility is constrained by requiring a minimum overlap between successive zygapophyses equivalent to 50% of zygapophyseal articular surface length (ONP50. This assumption is tested by comparing the maximum flexibility of the articulated cervical column in ONP50 and the flexibility of the complete neck with all tissues intact. It is found that this model does not adequately convey the pattern of flexibility in the ostrich neck, suggesting that the ONP50 model may not be useful in determining neck function if considered in isolation from myological and other soft tissue data.

  18. Notochord Cells in Intervertebral Disc Development and Degeneration

    Science.gov (United States)

    McCann, Matthew R.; Séguin, Cheryle A.

    2016-01-01

    The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID:27252900

  19. Notochord Cells in Intervertebral Disc Development and Degeneration

    Directory of Open Access Journals (Sweden)

    Matthew R. McCann

    2016-01-01

    Full Text Available The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches.

  20. Feasibility of minimally-invasive fiber-based evaluation of chondrodystrophoid canine intervertebral discs by light absorption and scattering spectroscopy

    Science.gov (United States)

    Jiang, Yuanyuan; McKeirnan, Kelci; Piao, Daqing; Bartels, Kenneth E.

    2011-03-01

    Extrusion or protrusion of an intervertebral disc is a common, frequently debilitating, painful, and sometimes fatal neurologic disease in the chondrodystrophic dog (dachshund, Pekingese, etc.). A similar condition of intervertebral disc degeneration with extrusion/protrusion is also a relatively common neurologic condition in human patients. Degeneration of the relatively avascular chondrodystrophoid intervertebral disc is associated with loss of water content, increased collagen, and deposits of calcified mineral in the nucleus pulposus. Current diagnostic methods have many limitations for providing accurate information regarding disc composition in situ prior to surgical intervention. Disc composition (i.e., mineralization), can influence the type of treatment regime and potentially prognosis and recurrence rates. The objective of this study is to investigate the feasibility of using a fiber-needle spectroscopy sensor to analyze the changes of tissue compositions involved in the chondrodystrophoid condition of the canine intervertebral disc. The nucleous pulposus, in which the metaplastic process / degeneration develops, is approximately 2mm thick and 5mm in diameter in the dachshund-sized dog. It lies in the center of the disc, surrounded by the annulus fibrosis and is enclosed by cartilaginous vertebral endplates cranially and caudally. This "shallow-and-small-slab" geometry limits the configuration of a fiber probe to sense the disc tissue volume without interference from the vertebrae. A single-fiber sensor is inserted into a 20 gauge myelographic spinal needle for insertion into the disc in situ and connected via a bifurcated fiber to the light source and a spectrometer. A tungsten light source and a 940nm light-emitting-diode are combined for spectral illumination covering VIS/NIR with expected improved sensitivity to water. Analysis of the reflectance spectra is expected to provide information of scattering and absorption compositions of tissue in

  1. Assessment of Intervertebral Disc Degeneration With Magnetic Resonance Single-Voxel Spectroscopy

    Science.gov (United States)

    Zuo, Jin; Saadat, Ehsan; Romero, Adan; Loo, Kimberly; Li, Xiaojuan; Link, Thomas M.; Kurhanewicz, John; Majumdar, Sharmila

    2014-01-01

    This study examined the feasibility of using short-echo water-suppressed point-resolved spectroscopy (PRESS) on a clinical 3T magnetic resonance (MR) scanner for evaluating biochemical changes in degenerated bovine and cadaveric human inter-vertebral discs. In bovine discs (N = 17), degeneration was induced with papain injections. Degeneration of human cadaveric discs (N = 27) was assessed using the Pfirrmann grading on T2-weighted images. Chemicals in the carbohydrate region (Carb), the choline head group (Cho), the N-acetyl region (N-acetyl), and the lipid and lactate region (Lac+Lip) were quantified using 1H PRESS, and were compared between specimens with different degrees of degeneration. The correlation between the spectroscopic findings and glycosaminoglycan (GAG) quantification using biochemical assays was determined. Significant differences were found between the ratios (N-acetyl/Cho, N-acetyl/Lac+Lip) acquired before and after papain injection in bovine discs. For human cadaveric discs, significant differences in the ratios (N-acetyl/Carb, N-acetyl/Lac+Lip) were found between discs having high and low Pfirrmann scores. Significant correlations were found between N-acetyl/Lac+Lip and GAG content in bovine discs (R = 0.77, P = 0.0007) and cadaveric discs (R = 0.83, P < 0.0001). Significant correlation between N-acetyl/Cho and GAG content was also found in cadaver discs (R = 0.64, P = 0.0039). This study demonstrates for the first time that short-echo PRESS on a clinical 3T MR scanner can be used to noninvasively and can reproducibly quantify metabolic changes associated with degeneration of intervertebral discs. PMID:19780173

  2. MRI-based relationships between spine pathology, intervertebral disc degeneration, and muscle fatty infiltration in chondrodystrophic and non-chondrodystrophic dogs.

    Science.gov (United States)

    Lerer, Assaf; Nykamp, Stephanie G; Harriss, Alexandra B; Gibson, Thomas W G; Koch, Thomas G; Brown, Stephen H M

    2015-11-01

    Human studies have revealed a link between muscle degeneration and low back pain, although the cause and effect of this relationship is not clear. Dogs provide a naturally developing model of intervertebral disc (IVD)-related low back pain that may provide insight into relationships between IVD and muscle degeneration. This study aimed to quantify, via magnetic resonance imaging (MRI), the magnitude and location of fatty infiltration in spine muscles of chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs suffering from both intervertebral disc herniation (IVDH) and non-disc-related spinal disorders, and relate this to intervertebral disc degeneration (IVDD). This study used retrospective MRI-based analysis of IVDD and muscle fatty infiltration in CD and NCD dogs. A portion of this study was funded ($1,000) by the Pet Trust Fund, Ontario Veterinary College. Magnetic resonance imaging from 180 dogs were separated into four groups: (1) CD with IVDH; (2) CD with non-IVDH spinal pathology; (3) NCD with IVDH; (4) NCD with non-IVDH spinal pathology. For each dog at intervertebral levels T12-T13 to L6-L7, IVDD was subjectively graded and muscle-fat indices (MFIndices) were quantified for multifidus, erector spinae, and psoas muscle groups. Intervertebral disc degeneration grade was higher (ppathology. Muscle-fat indices of multifidus and psoas were higher (ppathology compared with dogs with IVDH. Erector spinae demonstrated higher (ppathology. Dog groups with higher average IVDD grades demonstrated less fatty infiltration within their multifidus and psoas muscles, compared with groups with lower IVDD grades. This finding was consistent across both CD and NCD breeds as well as across dogs presenting with IVDH and those presenting with a non-IVDH spinal pathology. Thus, the presence or severity of IVDD is not uniquely related to fatty infiltration in these muscles, but rather the presence, or possibly severity or chronicity, of general spine pathology is likely a

  3. Intact Protein Analysis at 21 Tesla and X-Ray Crystallography Define Structural Differences in Single Amino Acid Variants of Human Mitochondrial Branched-Chain Amino Acid Aminotransferase 2 (BCAT2)

    Science.gov (United States)

    Anderson, Lissa C.; Håkansson, Maria; Walse, Björn; Nilsson, Carol L.

    2017-09-01

    Structural technologies are an essential component in the design of precision therapeutics. Precision medicine entails the development of therapeutics directed toward a designated target protein, with the goal to deliver the right drug to the right patient at the right time. In the field of oncology, protein structural variants are often associated with oncogenic potential. In a previous proteogenomic screen of patient-derived glioblastoma (GBM) tumor materials, we identified a sequence variant of human mitochondrial branched-chain amino acid aminotransferase 2 as a putative factor of resistance of GBM to standard-of-care-treatments. The enzyme generates glutamate, which is neurotoxic. To elucidate structural coordinates that may confer altered substrate binding or activity of the variant BCAT2 T186R, a 45 kDa protein, we applied combined ETD and CID top-down mass spectrometry in a LC-FT-ICR MS at 21 T, and X-Ray crystallography in the study of both the variant and non-variant intact proteins. The combined ETD/CID fragmentation pattern allowed for not only extensive sequence coverage but also confident localization of the amino acid variant to its position in the sequence. The crystallographic experiments confirmed the hypothesis generated by in silico structural homology modeling, that the Lys59 side-chain of BCAT2 may repulse the Arg186 in the variant protein (PDB code: 5MPR), leading to destabilization of the protein dimer and altered enzyme kinetics. Taken together, the MS and novel 3D structural data give us reason to further pursue BCAT2 T186R as a precision drug target in GBM. [Figure not available: see fulltext.

  4. CT-guided intradiscal ozone injection combined with intervertebral facet joint steroid injection for lumbar disk herniation accompanied with intervertebral arthritis

    International Nuclear Information System (INIS)

    Zhang Li; Chen Zhaohui; Sun Xijun; Liu Jianping; Li Jiakai

    2009-01-01

    Objective: To compare the clinical effectiveness of ozone (O 3 ) nucleus pulposus ablation only with that of O 3 nucleus pulposus ablation combined with intervertebral facet joint injection of compound Betamethasome in treating lumbar disk herniation accompanied with intervertebral facet arthritis. Methods: Eighty patients with lumbar disk herniation and intervertebral facet arthritis were equally and randomly divided into two groups. Under CT guidance, O 3 nucleus pulposus ablation was performed in patients of group A(n=40), while O 3 nucleus pulposus ablation combined with intervertebral facet joint injection of compound Betamethasome (0.5-1 ml) was carried out in patients of group B(n=40). Using double blind method the therapeutic effectiveness was evaluated before and 1 week,3,6-months after the procedure by an Oswestry Low Back Pain Disability Questionnaire. Results: One week after the procedure the effective rate of group A and group B was 65% and 82.5% respectively. Three and six months after the treatment, the effective rate was 75% and 70% respectively for group A, while it was 90% and 92.5% respectively for group B. The difference between two groups was significant (P 3 combined with intervertebral facet joint injection of compound Betamethasome is an effective and safe treatment for lumbar disk herniation accompanied with intervertebral facet arthritis.It is worth popularizing this technique in clinical practice. (authors)

  5. Reconciling certification and intact forest landscape conservation.

    Science.gov (United States)

    Kleinschroth, Fritz; Garcia, Claude; Ghazoul, Jaboury

    2018-05-29

    In 2014, the Forest Stewardship Council (FSC) added a new criterion to its principles that requires protection of intact forest landscapes (IFLs). An IFL is an extensive area of forest that lacks roads and other signs of human activity as detected through remote sensing. In the Congo basin, our analysis of road networks in formally approved concessionary logging areas revealed greater loss of IFL in certified than in noncertified concessions. In areas of informal (i.e., nonregulated) extraction, road networks are known to be less detectable by remote sensing. Under the current definition of IFL, companies certified under FSC standards are likely to be penalized relative to the noncertified as well as the informal logging sector on account of their planned road networks, despite an otherwise better standard of forest management. This could ultimately undermine certification and its wider adoption, with implications for the future of sustainable forest management.

  6. Is tomography of intervertebral disc calcification useful in children?

    International Nuclear Information System (INIS)

    Ginalski, J.M.; Landry, M.; Gudinchet, F.; Schnyder, P.

    1992-01-01

    In the past ten years, we have found cervical intervertebral disc calcification in three children on plain films of the cervical spine made because of cervical pain. In each case, we required further radiological investigations, antero-posterior and lateral linear tomography for two children and an axial computed tomography for one child. In each case, tomography revealed no supplementary useful information. On retrospect, we think that these examinations caused unnecessary irradiation and that they should only be carried out in the rare circumstances when disc calcification is associated with neurological symptoms. (orig.)

  7. Is tomography of intervertebral disc calcification useful in children

    Energy Technology Data Exchange (ETDEWEB)

    Ginalski, J M; Landry, M; Gudinchet, F; Schnyder, P [Lausanne Univ. Hospital (Switzerland). Dept. of Radiology

    1992-04-01

    In the past ten years, we have found cervical intervertebral disc calcification in three children on plain films of the cervical spine made because of cervical pain. In each case, we required further radiological investigations, antero-posterior and lateral linear tomography for two children and an axial computed tomography for one child. In each case, tomography revealed no supplementary useful information. On retrospect, we think that these examinations caused unnecessary irradiation and that they should only be carried out in the rare circumstances when disc calcification is associated with neurological symptoms. (orig.).

  8. In vivo effects of bupivacaine and gadobutrol on the intervertebral disc following discoblock and discography: a histological analysis.

    Science.gov (United States)

    Strube, Patrick; Pfitzner, Berit M; Streitparth, Florian; Hartwig, Tony; Putzier, Michael

    2017-01-01

    The aim of the present study was to histologically compare chondrotoxicity in surgically harvested intervertebral discs (IVDs) of patients following discoblock, discography, or no preoperative intervention. Thirty patients (IVD degeneration Modic ≥ 2°, Pfirrmann 3° or 4°) at L4/5 or L5/S1 who were planned for anterior lumbar interbody fusion were randomly assigned to three groups (open MRI: group DG - discography with gadobutrol; group DB - discoblock with bupivacaine at 4 weeks prior to surgery; group C - no intervention). The intervertebral discs were histologically evaluated and compared using ANOVA and Bonferroni tests for cell count, apoptosis, and proliferation. A reduced cell count (groups DG vs. DB vs. C: 14.9 ± 7.1, 9.2 ± 3.8, and 16.6 ± 5.2 cells/mm 2 , respectively; p ANOVA  = 0.016), increased apoptosis (groups DG vs. DB vs. C: 34.9 ± 10.2, 47.4 ± 16.3, 32.6 ± 12.2 %, respectively; p ANOVA  = 0.039) and increased cell proliferation (post hoc pDB vs. DG or C p bupivacaine but not after gadobutrol administration. • Local bupivacaine administration to intervertebral discs leads to cell toxicity and proliferation. • Gadobutrol demonstrated no significant effect on cell count, apoptosis, or cell proliferation. • In vivo cytotoxicity was demonstrated histologically in humans for the first time. • Addition/administration of bupivacaine during discographies must be judged critically.

  9. Association between intervertebral disc degeneration and the Oswestry Disability Index.

    Science.gov (United States)

    Middendorp, Marcus; Vogl, Thomas J; Kollias, Konstantinos; Kafchitsas, Konstantinos; Khan, M Fawad; Maataoui, Adel

    2017-01-01

    Low back pain and lumbar intervertebral disc degeneration (IDD) are common findings. Valid data on correlation between clinical pain scores and grades of IDD are not available. To investigate the correlation of intervertebral disc degeneration (IDD) at lumbar levels L4/5 and L5/S1 and the Oswestry Disability Index (ODI). The lumbar discs L4/5 and L5/S1 of 591 patients were evaluated according to the 5-point (Grade I to Grade V) grading system as published by Pfirrmann et al. Functional status was assessed using the Oswestry Disability Index. Spearman's coefficient of rank correlation was used for statistical analysis (p disability (ODI score between 21 and 40%). There was a weak, but statistically significant positive correlation between IDD and ODI for both evaluated lumbar levels. Increased lumbar IDD in MRI goes along with an increased ODI. Thus, MRI is a strong indicator of a patient's clinical appearance. However, low back pain cannot be explained by imaging alone. Clinical correlation is imperative for an adequate diagnostic advance in patients with low back pain.

  10. Mechanical design criteria for intervertebral disc tissue engineering.

    Science.gov (United States)

    Nerurkar, Nandan L; Elliott, Dawn M; Mauck, Robert L

    2010-04-19

    Due to the inability of current clinical practices to restore function to degenerated intervertebral discs, the arena of disc tissue engineering has received substantial attention in recent years. Despite tremendous growth and progress in this field, translation to clinical implementation has been hindered by a lack of well-defined functional benchmarks. Because successful replacement of the disc is contingent upon replication of some or all of its complex mechanical behaviors, it is critically important that disc mechanics be well characterized in order to establish discrete functional goals for tissue engineering. In this review, the key functional signatures of the intervertebral disc are discussed and used to propose a series of native tissue benchmarks to guide the development of engineered replacement tissues. These benchmarks include measures of mechanical function under tensile, compressive, and shear deformations for the disc and its substructures. In some cases, important functional measures are identified that have yet to be measured in the native tissue. Ultimately, native tissue benchmark values are compared to measurements that have been made on engineered disc tissues, identifying where functional equivalence was achieved, and where there remain opportunities for advancement. Several excellent reviews exist regarding disc composition and structure, as well as recent tissue engineering strategies; therefore this review will remain focused on the functional aspects of disc tissue engineering. Copyright 2009 Elsevier Ltd. All rights reserved.

  11. Correlation between T2 relaxation time and intervertebral disk degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Takashima, Hiroyuki; Takebayashi, Tsuneo; Yoshimoto, Mitsunori; Terashima, Yoshinori; Tsuda, Hajime; Ida, Kazunori; Yamashita, Toshihiko [Sapporo Medical University, Department of Orthopedic Surgery, School of Medicine, Sapporo, Hokkaido (Japan)

    2012-02-15

    Magnetic resonance T2 mapping allows for the quantification of water and proteoglycan content within tissues and can be used to detect early cartilage abnormalities as well as to track the response to therapy. The goal of the present study was to use T2 mapping to quantify intervertebral disk water content according to the Pfirrmann classification. This study involved 60 subjects who underwent lumbar magnetic resonance imaging (a total of 300 lumbar disks). The degree of disk degeneration was assessed in the midsagittal section on T2-weighted images according to the Pfirrmann classification (grades I to V). Receiver operating characteristic (ROC) analysis was performed among grades to determine the cut-off values. In the nucleus pulposus, T2 values tended to decrease with increasing grade, and there was a significant difference in T2 values between each grade from grades I to IV. However, there was no significant difference in T2 values in the anterior or posterior annulus fibrosus. T2 values according to disk degeneration level classification were as follows: grade I (>116.8 ms), grade II (92.7-116.7 ms), grade III (72.1-92.6 ms), grade IV (<72.0 ms). T2 values decreased with increasing Pfirrmann classification grade in the nucleus pulposus, likely reflecting a decrease in proteoglycan and water content. Thus, T2 value-based measurements of intervertebral disk water content may be useful for future clinical research on degenerative disk diseases. (orig.)

  12. Developments in intervertebral disc disease research: pathophysiology, mechanobiology, and therapeutics.

    Science.gov (United States)

    Weber, Kathryn T; Jacobsen, Timothy D; Maidhof, Robert; Virojanapa, Justin; Overby, Chris; Bloom, Ona; Quraishi, Shaheda; Levine, Mitchell; Chahine, Nadeen O

    2015-03-01

    Low back pain is a leading cause of disability worldwide and the second most common cause of physician visits. There are many causes of back pain, and among them, disc herniation and intervertebral disc degeneration are the most common diagnoses and targets for intervention. Currently, clinical treatment outcomes are not strongly correlated with diagnoses, emphasizing the importance for characterizing more completely the mechanisms of degeneration and their relationships with symptoms. This review covers recent studies elucidating cellular and molecular changes associated with disc mechanobiology, as it relates to degeneration and regeneration. Specifically, we review findings on the biochemical changes in disc diseases, including cytokines, chemokines, and proteases; advancements in disc disease diagnostics using imaging modalities; updates on studies examining the response of the intervertebral disc to injury; and recent developments in repair strategies, including cell-based repair, biomaterials, and tissue engineering. Findings on the effects of the omega-6 fatty acid, linoleic acid, on nucleus pulposus tissue engineering are presented. Studies described in this review provide greater insights into the pathogenesis of disc degeneration and may define new paradigms for early or differential diagnostics of degeneration using new techniques such as systemic biomarkers. In addition, research on the mechanobiology of disease enriches the development of therapeutics for disc repair, with potential to diminish pain and disability associated with disc degeneration.

  13. THE CONSTRUCTION OF PHYSICAL REHABILITATION PROGRAMS IN THE PREOPERATIVE PERIOD FOR PATIENTS THAT WILL REMOVE OF INTERVERTEBRAL DISC’ PROLAPSE IN THE LUMBAR SPINE

    Directory of Open Access Journals (Sweden)

    E.B. Lazarieva

    2014-06-01

    Full Text Available The ineffectiveness of conservative treatment will make the need for surgery in 4-5% of patients suffering from low back pain with hernias of the lumbar and sacral spine. Despite the surgical removal of the source of compressed roots, nerves and blood vessels, require a comprehensive system of rehabilitation therapy in order to eliminate manifestations of disease and relief of disease progression. The aim of the work is to substantiate the general approaches for the using of physical rehabilitation and diagnostics static component of the dynamic stereotype in the preoperative period in patients to remove intervertebral disc prolapse. The materials and methods. There was examined 96 with low back pain. Methods are applied in this research: analysis of a literature, observation methods. Results. In conjunction with the physician was determined "diagnosis for rehabilitation" and "prognosis of the rehabilitation". The formulation of the basis of the diagnosis for rehabilitation was performed through the examination during the rehabilitation (as a taking an anamnestic data, examination and palpation, studies of intact sensory and motor functions, the results of objective research tool. Conclusions. The identification of preserved anatomical and functional entities, the definition of the initial level of compensation for lost functions and forecast further recovery is a fundamental approach to program development in the preoperative period in patients with low back pain aimed at the removal of intervertebral disc herniations.

  14. Digested BLG can induce tolerance when co-administered with intact BLG in Brown Norway rats

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Barkholt, Vibeke; Madsen, Charlotte Bernhard

    the human gastro-duodenal digestion process. Four different fractions of BLG-digest was made, based on sizes of peptides or aggregates hereof. Intact BLG and the four fractions of BLG-digesta were characterized by protein chemical analyses. Brown Norway (BN) rats were immunised i.p. three times without......Background: Milk is a major constituent of small children’s diet. Milk allergy is also one of the most common allergies in small children. Prevention, treatment and general understanding of this allergy are therefore important. Methods: Intact BLG was digested in an in vitro model simulating...... the use of adjuvant with either PBS (control), 200 µg of intact BLG, 30 µg of intact BLG, 200 µg of digested BLG (with 30 µg of intact BLG), 200 µg of digested BLG, 200 µg of a fraction of large complexes or 200 µg of a fraction of small complexes (all three without intact BLG). Sera from BN rats were...

  15. Acid-sensing ion channel 2 (asic 2) and trkb interrelationships within the intervertebral disc.

    Science.gov (United States)

    Cuesta, Antonio; Viña, Eliseo; Cabo, Roberto; Vázquez, Gorka; Cobo, Ramón; García-Suárez, Olivia; García-Cosamalón, José; Vega, José A

    2015-01-01

    The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. They express acid-sensing ion channels (ASICs), gated by extracellular protons and mechanical forces, as well as neurotrophins and their signalling receptors. In the nervous tissues some neurotrophins regulate the expression of ASICs. The expression of ASIC2 and TrkB in human normal and degenerated IVD was assessed using quantitative-PCR, Western blot, and immunohistochemistry. Moreover, we investigated immunohistochemically the expression of ASIC2 in the IVD of TrkB-deficient mice. ASIC2 and TrkB mRNAs were found in normal human IVD and both increased significantly in degenerated IVD. ASIC2 and TrkB proteins were also found co-localized in a variable percentage of cells, being significantly higher in degenerated IVD than in controls. The murine IVD displayed ASIC2 immunoreactivity which was absent in the IVD of TrkB-deficient mice. Present results demonstrate the occurrence of ASIC2 and TrkB in the human IVD, and the increased expression of both in pathological IVD suggest their involvement in IVD degeneration. These data also suggest that TrkB-ligands might be involved in the regulation of ASIC2 expression, and therefore in mechanisms by which the IVD cells accommodate to low pH and hypertonicity.

  16. Strategies for Analyzing Data from Intact Groups.

    Science.gov (United States)

    Cross, Lawrence H.; Lane, Carolyn E.

    Action research often necessitates the use of intact groups for the comparison of educational treatments or programs. This paper considers several analytical methods that might be used for such situations when pretest scores indicate that these intact groups differ significantly initially. The methods considered include gain score analysis of…

  17. Exploratory investigations of hypervelocity intact capture spectroscopy

    Science.gov (United States)

    Tsou, P.; Griffiths, D. J.

    1993-01-01

    The ability to capture hypervelocity projectiles intact opens a new technique available for hypervelocity research. A determination of the reactions taking place between the projectile and the capture medium during the process of intact capture is extremely important to an understanding of the intact capture phenomenon, to improving the capture technique, and to developing a theory describing the phenomenon. The intact capture of hypervelocity projectiles by underdense media generates spectra, characteristic of the material species of projectile and capture medium involved. Initial exploratory results into real-time characterization of hypervelocity intact capture techniques by spectroscopy include ultra-violet and visible spectra obtained by use of reflecting gratings, transmitting gratings, and prisms, and recorded by photographic and electronic means. Spectrometry proved to be a valuable real-time diagnostic tool for hypervelocity intact capture events, offering understanding of the interactions of the projectile and the capture medium during the initial period and providing information not obtainable by other characterizations. Preliminary results and analyses of spectra produced by the intact capture of hypervelocity aluminum spheres in polyethylene (PE), polystyrene (PS), and polyurethane (PU) foams are presented. Included are tentative emission species identifications, as well as gray body temperatures produced in the intact capture process.

  18. Intact glycopeptide characterization using mass spectrometry

    OpenAIRE

    Cao, Li; Qu, Yi; Zhang, Zhaorui; Wang, Zhe; Prykova, Iya; Wu, Si

    2016-01-01

    Glycosylation is one of the most prominent and extensively studied protein post-translational modifications. However, traditional proteomic studies at the peptide level (bottom-up) rarely characterize intact glycopeptides (glycosylated peptides without removing glycans), so no glycoprotein heterogeneity information is retained. Intact glycopeptide characterization, on the other hand, provides opportunities to simultaneously elucidate the glycan structure and the glycosylation site needed to r...

  19. Formation of the sacrum requires down-regulation of sonic hedgehog signaling in the sacral intervertebral discs.

    Science.gov (United States)

    Bonavita, Raffaella; Vincent, Kathleen; Pinelli, Robert; Dahia, Chitra Lekha

    2018-05-21

    In humans, the sacrum forms an important component of the pelvic arch, and it transfers the weight of the body to the lower limbs. The sacrum is formed by collapse of the intervertebral discs (IVDs) between the five sacral vertebrae during childhood, and their fusion to form a single bone. We show that collapse of the sacral discs in the mouse is associated with the down-regulation of sonic hedgehog (SHH) signaling in the nucleus pulposus (NP) of the disc, and many aspects of this phenotype can be reversed by experimental postnatal activation of HH signaling. We have previously shown that SHH signaling is essential for the normal postnatal growth and differentiation of intervertebral discs elsewhere in the spine, and that loss of SHH signaling leads to pathological disc degeneration, a very common disorder of aging. Thus, loss of SHH is pathological in one region of the spine but part of normal development in another. © 2018. Published by The Company of Biologists Ltd.

  20. Genome-Wide Association Study in Dachshund: Identification of a Major Locus Affecting Intervertebral Disc Calcification

    DEFF Research Database (Denmark)

    Mogensen, Mette Sloth; Karlskov-Mortensen, Peter; Proschowsky, Helle Friis

    2011-01-01

    Intervertebral disc calcification and herniation commonly affects Dachshund where the predisposition is caused by an early onset degenerative process resulting in disc calcification. A continuous spectrum of disc degeneration is seen within and among clog breeds, suggesting a multifactorial etiol...

  1. Aging and degeneration of the intervertebral disc: review of basic science

    Directory of Open Access Journals (Sweden)

    Josemberg da Silva Baptista

    2015-06-01

    Full Text Available Currently there is a growing interest in the study of intervertebral discs due to loss of manpower brought to society by low back and neck pains. These papers seek to delineate the difference between normal aging and disc degeneration, trying to understand what factor would be determining for the second condition. Thus, the morphology field was expanded and knowledge on the structure of intervertebral discs currently uses the research field of cell and molecular biology, and genetics. The results indicate that regardless of age or condition, the intervertebral disc undergoes long and extensive remodeling of its constituents, which are influenced by several factors: environmental, soluble, cell growth and extracellular matrix. In this literature review we describe the biological characteristics of the cervical and lumbar intervertebral disc with a focus on basic science of aging and degeneration, selecting the latest findings and discussions of the area, which influence future research and clinical thoughts.

  2. The impact of the artificial intervertebral disc on functioning the lumbar spine

    Directory of Open Access Journals (Sweden)

    Mańsko M.

    2015-12-01

    Full Text Available In the hereby thesis the anatomy of the lumbar vertebra and intervertebral disc were presented. Functioning and kinematics of the spine and intervertebral forces were described.Full three – dimensional model of the lumbar vertebrae L2 – L4 was created. On the basis of it model of artificial intervertebral disc was constructed (between L2 and L3. The simplified model of vertebra L2 was formulated via finite elements method. Processed model has been used for biomechanical analysis.Strength calculations were made and appropriate conclusions were drawn. Presented results show behavior influenced of three – dimensional model of the lumbar vertebra with artificial intervertebral disc by operation of loads.

  3. Bovine annulus fibrosus cell lines isolated from intervertebral discs

    Directory of Open Access Journals (Sweden)

    Petra Kraus

    2016-12-01

    Full Text Available The adult bovine (Bos taurus intervertebral disc is primarily comprised of two major tissue types: The outer annulus fibrosus (AF and the central nucleus pulposus (NP. We isolated several primary cell lineages of passage (P 0 cells from the AF tissue omitting typically used enzymatic tissue digestion protocols. The cells grow past p10 without signs of senescence in DMEM + 10% FCS on 0.1% gelatin coated/uncoated surfaces of standard cell culture plates and survive freeze-thawing. Preliminary analysis of the AF derived cells for expression of the two structural genes Col1a1 and Col2a1 was performed by PISH recapitulating the expression observed in vivo.

  4. Mechanoreceptors in Diseased Cervical Intervertebral Disc and Vertigo.

    Science.gov (United States)

    Yang, Liang; Yang, Cheng; Pang, Xiaodong; Li, Duanming; Yang, Hong; Zhang, Xinwu; Yang, Yi; Peng, Baogan

    2017-04-15

    We collected the samples of cervical intervertebral discs from patients with vertigo to examine the distribution and types of mechanoreceptors in diseased cervical disc. The aim of this study was to determine whether mechanoreceptors are distributed more abundantly in cervical discs from patients with cervical spondylosis, and whether they are related to vertigo. Previous limited studies have found that normal cervical intervertebral discs are supplied with mechanoreceptors that have been considered responsible for proprioceptive functions. Several clinical studies have indicated that the patients with cervical spondylosis manifested significantly impaired postural control and subjective balance disturbance. We collected 77 samples of cervical discs from 62 cervical spondylosis patients without vertigo, 61 samples from 54 patients with vertigo, and 40 control samples from 8 cadaveric donors to investigate distribution of mechanoreceptors containing neurofilament (NF200) and S-100 protein immunoreactive nerve endings. The immunohistochemical investigation revealed that the most frequently encountered mechanoreceptors were the Ruffini corpuscles in all groups of cervical disc samples. They were obviously increased in the number and deeply ingrown into inner annulus fibrosus and even into nucleus pulposus in the diseased cervical discs from patients with vertigo in comparison with the discs from patients without vertigo and control discs. Only three Golgi endings were seen in the three samples from patients with vertigo. No Pacinian corpuscles were found in any samples of cervical discs. The diseased cervical discs from patients with vertigo had more abundant distribution of Ruffini corpuscles than other discs. A positive association between the increased number and ingrowth of Ruffini corpuscles in the diseased cervical disc and the incidence of vertigo in the patients with cervical spondylosis was found, which may indicate a key role of Ruffini corpuscles in the

  5. Pedicle distraction increases intervertebral and spinal canal area in a cadaver and bone model

    OpenAIRE

    Hughes Matthew; Papadakos Nikolaos; Bishop Tim; Bernard Jason

    2018-01-01

    Introduction: Lumbar spinal stenosis is degenerative narrowing of the spinal canal and/or intervertebral foramen causing compression of the spinal cord and nerve roots. Traditional decompression techniques can often cause significant trauma and vertebral instability. This paper evaluates a method of increasing pedicle length to decompress the spinal and intervertebral foramen, which could be done minimally invasive. Methods: Three Sawbone (Sawbones Europe, Sweden) and 1 cadaveric lumbar sp...

  6. A developmental transcriptomic analysis of Pax1 and Pax9 in embryonic intervertebral disc development

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    V. Sivakamasundari

    2017-02-01

    Full Text Available Pax1 and Pax9 play redundant, synergistic functions in the patterning and differentiation of the sclerotomal cells that give rise to the vertebral bodies and intervertebral discs (IVD of the axial skeleton. They are conserved in mice and humans, whereby mutation/deficiency of human PAX1/PAX9 has been associated with kyphoscoliosis. By combining cell-type-specific transcriptome and ChIP-sequencing data, we identified the roles of Pax1/Pax9 in cell proliferation, cartilage development and collagen fibrillogenesis, which are vital in early IVD morphogenesis. Pax1 is up-regulated in the absence of Pax9, while Pax9 is unaffected by the loss of Pax1/Pax9. We identified the targets compensated by a single- or double-copy of Pax9. They positively regulate many of the cartilage genes known to be regulated by Sox5/Sox6/Sox9 and are connected to Sox5/Sox6 by a negative feedback loop. Pax1/Pax9 are intertwined with BMP and TGF-B pathways and we propose they initiate expression of chondrogenic genes during early IVD differentiation and subsequently become restricted to the outer annulus by the negative feedback mechanism. Our findings highlight how early IVD development is regulated spatio-temporally and have implications for understanding kyphoscoliosis.

  7. Discussion on the method to increase the successful rate of L5/S1 intervertebral disc puncture

    International Nuclear Information System (INIS)

    Zhong Xianyi; Li Liangjun; Yu Chengxin

    2007-01-01

    Objective: To study the effective methods of L 5 /S 1 intervertebral disc puncture without drilling to solve the barriers from iliaca. Methods: (1) puncturing with belly-buttock sticking out: to enlarge waist sacro-iliaca angle to move the puncture point up; (2) puncturing through intervertebral edge: puncturing through L 5 to 1/3 intervertebral disc to make the puncture point move Up; (3) puncturing through L 5 /S 1 intervertebral disc with the self-made puncture location instrument. Results with the methods, 280 cases with L 5 /S 1 intervertebral disc protrusion have been successfully punctured, with successful rate 100%. Conclusion: These methods are ideal and easy to use to treat L 5 /S 1 intervertebral disc protrusion puncture, and worth popularizing. (authors)

  8. [Expression and distribution of xenoantigen alpha-Gal in intervertebral disk of Chinese banna minipig inbred line].

    Science.gov (United States)

    Shou, Jian-guo; Mi, Jian-hong; Ying, Da-jun

    2002-09-01

    To investigate the expression and distribution of xenoantigen in intervertebral disk of Chinese banna minipig inbred line, and to study the availability of xenograft transplantation of intervertebral disk. Samples of intervertebral disk were collected from six Banna pigs of 8 to 11-month-old. The fixation, embedment and slice were performed. alpha-Gal specific binding lection (BSI-B4) were used as affinity reagents and affinity-immunohistochemistry assays (SABC methods and DAB stain) were conducted to detect the expression and distribution of xenoantigen (alpha-Gal). alpha-Gal was found in chondrocyte cell and chondrocyte-like cell in intervertebral disk which have the positive yellow-stained particulate aggradation. There was no stain in the matrix, elastic fiber and collagen fiber. The distribution of xenoantigen is locally in the tissue of intervertebral disk and its expression is weak. This suggests that the intervertebral disk of Banna pig may be alternative donor for xenotransplantation.

  9. Relationships between lumbar inter-vertebral motion and lordosis in healthy adult males: a cross sectional cohort study.

    OpenAIRE

    du Rose, A.; Breen, Alan C.

    2016-01-01

    Background Intervertebral motion impairment is widely thought to be related to chronic back disability, however, the movements of inter-vertebral pairs are not independent of each other and motion may also be related to morphology. Furthermore, maximum intervertebral range of motion (IV-RoMmax) is difficult to measure accurately in living subjects. The purpose of this study was to explore possible relationships between (IV-RoMmax) and lordosis, initial attainment rate and IV-RoMmax at other l...

  10. Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs

    OpenAIRE

    Choi, Kyung-Suk; Harfe, Brian D.

    2011-01-01

    The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Remo...

  11. Link-N: The missing link towards intervertebral disc repair is species-specific.

    Directory of Open Access Journals (Sweden)

    Frances C Bach

    Full Text Available Degeneration of the intervertebral disc (IVD is a frequent cause for back pain in humans and dogs. Link-N stabilizes proteoglycan aggregates in cartilaginous tissues and exerts growth factor-like effects. The human variant of Link-N facilitates IVD regeneration in several species in vitro by inducing Smad1 signaling, but it is not clear whether this is species specific. Dogs with IVD disease could possibly benefit from Link-N treatment, but Link-N has not been tested on canine IVD cells. If Link-N appears to be effective in canines, this would facilitate translation of Link-N into the clinic using the dog as an in vivo large animal model for human IVD degeneration.This study's objective was to determine the effect of the human and canine variant of Link-N and short (s Link-N on canine chondrocyte-like cells (CLCs and compare this to those on already studied species, i.e. human and bovine CLCs. Extracellular matrix (ECM production was determined by measuring glycosaminoglycan (GAG content and histological evaluation. Additionally, the micro-aggregates' DNA content was measured. Phosphorylated (p Smad1 and -2 levels were determined using ELISA.Human (sLink-N induced GAG deposition in human and bovine CLCs, as expected. In contrast, canine (sLink-N did not affect ECM production in human CLCs, while it mainly induced collagen type I and II deposition in bovine CLCs. In canine CLCs, both canine and human (sLink-N induced negligible GAG deposition. Surprisingly, human and canine (sLink-N did not induce Smad signaling in human and bovine CLCs. Human and canine (sLink-N only mildly increased pSmad1 and Smad2 levels in canine CLCs.Human and canine (sLink-N exerted species-specific effects on CLCs from early degenerated IVDs. Both variants, however, lacked the potency as canine IVD regeneration agent. While these studies demonstrate the challenges of translational studies in large animal models, (sLink-N still holds a regenerative potential for humans.

  12. Rabbit model of intervertebral disc degeneration by external compression device characterized by X-ray, MRI, histology, and cell viability

    Directory of Open Access Journals (Sweden)

    Ismail Ismail

    2006-12-01

    Full Text Available Appropriate experimental animal models, which mimic the degenerative process occurring in human intervertebral disc (IVD breakdown and can be used for new treatment studies such as tissue engineering or disc distraction are lacking. We studied the external compression device that used by Kroeber et al to create intervertebral disc degeneration in rabbit model characterized by X-ray, MRI, Histology, and Cell Viability. Ten NZW rabbit were randomly assigned to one of five groups. Intervertebral disc VL4-L5 are compressed using an external loading device, 1.9 MPa. First group rabbit are loaded for 14 days, second loaded for 28 days, thirth group are loaded for 14 days, and unloaded for 14 days, fourth group loaded for 28 days and unloaded for 28 days. The fifth group, rabbits underwent a sham operation. Additional, rabbits were used as sample for cell viability study. In disc height : sample in group one have biggest decreasing of disc height, that is 23.9 unit. In MRI assessment, the worst grade is grade 3. In histological score, the worst group is group three (58.69, and the best is group 4 (45.69. Group one have the largest dead cell, that are 403.5, and the smallest is group four (124.75. Trypan blue staining showed that group four have better viable cell (91.1 compare than group three (86.4. The study conclude disc degeneration can be created by external axial loading for 14 days in rabbit intervertebral disc. Duration of 28 days unloading gave better result for cells to recover. (Med J Indones 2006; 15:199-207  Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Keywords: Rabbit model –intervertebral disc degeneration- external compression device-X-ray, MRI, Histology, and Cell viabilty /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso

  13. Intact glycopeptide characterization using mass spectrometry.

    Science.gov (United States)

    Cao, Li; Qu, Yi; Zhang, Zhaorui; Wang, Zhe; Prytkova, Iya; Wu, Si

    2016-05-01

    Glycosylation is one of the most prominent and extensively studied protein post-translational modifications. However, traditional proteomic studies at the peptide level (bottom-up) rarely characterize intact glycopeptides (glycosylated peptides without removing glycans), so no glycoprotein heterogeneity information is retained. Intact glycopeptide characterization, on the other hand, provides opportunities to simultaneously elucidate the glycan structure and the glycosylation site needed to reveal the actual biological function of protein glycosylation. Recently, significant improvements have been made in the characterization of intact glycopeptides, ranging from enrichment and separation, mass spectroscopy (MS) detection, to bioinformatics analysis. In this review, we recapitulated currently available intact glycopeptide characterization methods with respect to their advantages and limitations as well as their potential applications.

  14. Cell-seeded polyurethane-fibrin structures – A possible system for intervertebral disc regeneration

    Directory of Open Access Journals (Sweden)

    C Mauth

    2009-10-01

    Full Text Available Nowadays, intervertebral disc (IVD degeneration is one of the principal causes of low back pain involving high expense within the health care system. The long-term goal is the development of a medical treatment modality focused on a more biological regeneration of the inner nucleus pulposus (NP. Hence, interest in the endoscopic implantation of an injectable material took center stage in the recent past. We report on the development of a novel polyurethane (PU scaffold as a mechanically stable carrier system for the reimplantation of expanded autologous IVD-derived cells (disc cells to stimulate regenerative processes and restore the chondrocyte-like tissue within the NP. Primary human disc cells were seeded into newly developed PU spheroids which were subsequently encapsulated in fibrin hydrogel. The study aims to analyze adhesion properties, proliferation capacity and phenotypic characterization of these cells. Polymerase chain reaction was carried out to detect the expression of genes specifically expressed by native IVD cells. Biochemical analyses showed an increased DNA content, and a progressive enhancement of total collagen and glycosaminoglycans (GAG was observed during cell culture. The results suggest the synthesis of an appropriate extracellular matrix as well as a stable mRNA expression of chondrogenic and/or NP specific markers. In conclusion, the data presented indicate an alternative medical approach to current treatment options of degenerated IVD tissue.

  15. Aerosol preparation of intact lipoproteins

    Science.gov (United States)

    Benner, W Henry [Danville, CA; Krauss, Ronald M [Berkeley, CA; Blanche, Patricia J [Berkeley, CA

    2012-01-17

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  16. Antimicrobial activity of a new intact skin antisepsis formulation.

    Science.gov (United States)

    Russo, Antonello; Viotti, Pier Luigi; Vitali, Matteo; Clementi, Massimo

    2003-04-01

    Different antiseptic formulations have shown limitations when applied to disinfecting intact skin, notably short-term tolerability and/or efficacy. The purpose of this study was optimizing a new antiseptic formulation specifically targeted at intact skin disinfection and evaluating its in vitro microbicidal activity and in vivo efficacy. The biocidal properties of the antiseptic solution containing 0.5% chloramine-T diluted in 50% isopropyl alcohol (Cloral; Eurospital SpA Trieste, Italy) were measured in vitro versus gram-positive-, gram-negative-, and acid-alcohol-resistant germs and fungi with standard suspension tests in the presence of fetal bovine serum. Virus-inhibiting activity was evaluated in vitro against human cytomegalovirus, herpes simplex virus, poliovirus, hepatitis B virus, and hepatitis C virus. Tests used different methods for the different biologic and in vitro replication capacity of these human viruses. Lastly, Cloral tolerability and skin colonization retardation efficacy after disinfection were studied in vivo. The antiseptic under review showed fast and sustained antimicrobial activity. The efficacy of Cloral against clinically important bacterial and viral pathogens and fungi was highlighted under the experimental conditions described in this article. Finally, microbial regrowth lag and no side effects were documented in vivo after disinfection of 11 volunteers. A stable chloramine-T solution in isopropyl alcohol may be suggested for intact skin antisepsis.

  17. [Research progress on mechanical performance evaluation of artificial intervertebral disc].

    Science.gov (United States)

    Li, Rui; Wang, Song; Liao, Zhenhua; Liu, Weiqiang

    2018-03-01

    The mechanical properties of artificial intervertebral disc (AID) are related to long-term reliability of prosthesis. There are three testing methods involved in the mechanical performance evaluation of AID based on different tools: the testing method using mechanical simulator, in vitro specimen testing method and finite element analysis method. In this study, the testing standard, testing equipment and materials of AID were firstly introduced. Then, the present status of AID static mechanical properties test (static axial compression, static axial compression-shear), dynamic mechanical properties test (dynamic axial compression, dynamic axial compression-shear), creep and stress relaxation test, device pushout test, core pushout test, subsidence test, etc. were focused on. The experimental techniques using in vitro specimen testing method and testing results of available artificial discs were summarized. The experimental methods and research status of finite element analysis were also summarized. Finally, the research trends of AID mechanical performance evaluation were forecasted. The simulator, load, dynamic cycle, motion mode, specimen and test standard would be important research fields in the future.

  18. Experimental chemonucleolysis with chymopapain in canine intervertebral disks

    International Nuclear Information System (INIS)

    Kudo, T.; Sumi, A.; Hashimoto, A.

    1993-01-01

    The present study describes the radiological and histological changes in the canine intervertebral disk after the experimental injection of chymopapain as the chemical reagent, and determines the appropriate dose of the enzyme for treatment of herniated disks. By radiography, narrowing of the disk space was observed within 2 weeks after the injection of chymopapain, and recovered to 74.1% in the 0.1 mg group, 61.1% in the 1.0 mg group and 71.7% in the 10.0 mg group at 12 weeks. The disk space recovery showed a tendency to delay with aging. Microscopically, proteoglycan positive matrix appeared and the nuclear space was reduced in each disk at 2 weeks after chymopapain injection. The nucleus pulposus contained an irregularly-defined mass consisting of clusters of degenerated notochordal cells surrounded by proliferated chondrocytes and collagen matrix. In each disk at 12 weeks after chymopapain injection, the center of the nucleus pulposus was replaced by fibrocartilage tissue. In the disk into which 10.0 mg chymopapain was injected, the nuclear space filled with dense fibrocartilage tissue without a regenerated matrix component and narrowing of the disk were maintained. It is suggested that canine chemonucleolysis with 10.0 mg of chymopapain reduces the interdiskal pressure. This treatment may therefore relieve the signs and symptoms of herniation of the nucleus pulposus, and may effect chemical disk decompression

  19. Passive Stretch Versus Active Stretch on Intervertebral Movement in Non - Specific Neck Pain

    International Nuclear Information System (INIS)

    Abd El - Aziz, A.H.; Amin, D.I.; Moustafa, I.

    2016-01-01

    Neck pain is one of the most common and painful musculoskeletal conditions. Point prevalence ranges from 6% to 22% and up to 38% of the elderly population, while lifetime prevalence ranges from 14,2% to 71%. Up till now no randomized study showed the effect between controversy of active and passive stretch on intervertebral movement. The purpose: the current study was to investigate the effect of the passive and active stretch on intervertebral movement in non - specific neck pain. Material and methods: Forty five subjects from both sexes with age range between 18 and 30 years and assigned in three groups, group I (15) received active stretch, ultrasound and TENS. Group II (15) received passive stretch, ultrasound and TENS. Group III (15) received ultrasound and TENS. The radiological assessment was used to measure rotational and translational movement of intervertebral movement before and after treatment. Results: MANOVA test was used for radiological assessment before and after treatment there was significant increase in intervertebral movement in group I as p value =0.0001. Conclusion: active stretch had a effect in increasing the intervertebral movement compared to the passive stretch

  20. Molecular Imaging Agents Specific for the Annulus Fibrosus of the Intervertebral Disk

    Directory of Open Access Journals (Sweden)

    Summer L. Gibbs-Strauss

    2010-05-01

    Full Text Available Low back pain is a prevalent medical condition that is difficult to diagnose and treat. Current imaging methods are unable to correlate pain reliably with spinal structures, and surgical removal of painful damaged or degenerating disks is technically challenging. A contrast agent specific for the intervertebral disk could assist in the detection, diagnosis, and surgical treatment of low back pain. The styryl pyridinium (FM fluorophores were characterized and structure-activity relationships between chemical structure and in vivo uptake were established. Two novel FM fluorophores with improved optical properties for imaging the intervertebral disks were synthesized and evaluated in mice, rats, and pigs. After a single systemic injection, eight of eight FM fluorophores provided high-contrast imaging of the trigeminal ganglia, whereas six of eight provided high-contrast imaging of the dorsal root ganglia. Unexpectedly, three of eight FM fluorophores provided high-contrast imaging of annulus fibrosus tissue of the intervertebral disks, confirmed histologically. We present the first known contrast agent specific for the intervertebral disks and identify the chemical structural motif that mediates uptake. FM fluorophores could be used for image-guided surgery to assist in the removal of intervertebral disk and lay the foundation for derivatives for magnetic resonance imaging and positron emission tomography.

  1. Formation of lamellar cross bridges in the annulus fibrosus of the intervertebral disc is a consequence of vascular regression.

    Science.gov (United States)

    Smith, Lachlan J; Elliott, Dawn M

    2011-05-01

    Cross bridges are radial structures within the highly organized lamellar structure of the annulus fibrosus of the intervertebral disc that connect two or more non-consecutive lamellae. Their origin and function are unknown. During fetal development, blood vessels penetrate deep within the AF and recede during postnatal growth. We hypothesized that cross bridges are the pathways left by these receding blood vessels. Initially, the presence of cross bridges was confirmed in cadaveric human discs aged 25 and 53 years. Next, L1-L2 intervertebral discs (n=4) from sheep ranging in age from 75 days fetal gestation to adult were processed for paraffin histology. Mid-sagittal sections were immunostained for endothelial cell marker PECAM-1. The anterior and posterior AF were imaged using differential interference contrast microscopy, and the following parameters were quantified: total number of distinct lamellae, total number of cross bridges, percentage of cross bridges staining positive for PECAM-1, cross bridge penetration depth (% total lamellae), and PECAM-1 positive cross bridge penetration depth. Cross bridges were first observed at 100 days fetal gestation. The overall number peaked in neonates then remained relatively unchanged. The percentage of PECAM-1 positive cross bridges declined progressively from almost 100% at 100 days gestation to less than 10% in adults. Cross bridge penetration depth peaked in neonates then remained unchanged at subsequent ages. Depth of PECAM-1 positive cross bridges decreased progressively after birth. Findings were similar for both the anterior and posterior. The AF lamellar architecture is established early in development. It later becomes disrupted as a consequence of vascularization. Blood vessels then recede, perhaps due to increasing mechanical stresses in the surrounding matrix. In this study we present evidence that the pathways left by receding blood vessels remain as lamellar cross bridges. It is unclear whether the presence

  2. On the modeling of the intervertebral joint in multibody models for the spine

    International Nuclear Information System (INIS)

    Christophy, Miguel; Curtin, Maurice; Faruk Senan, Nur Adila; Lotz, Jeffrey C.; O’Reilly, Oliver M.

    2013-01-01

    The need to develop feasible computational musculoskeletal models of the spine has led to the development of several multibody models. Central features in these works are models for the ligaments, muscles, and intervertebral joint. The purpose of the present paper is to show how experimental measurements of joint stiffnesses can be properly incorporated using a bushing element. The required refinements to existing bushing force functions in musculoskeletal software platforms are discussed and further implemented using a SpineBushing element specific to the intervertebral joint. Four simple lumbar spine models are then used to illustrate the accompanying improvements. Electronic supplemental material for this article includes a complementary review of formulations of stiffness matrices for the intervertebral joint

  3. Design Concepts of Polycarbonate-Based Intervertebral Lumbar Cages: Finite Element Analysis and Compression Testing

    Directory of Open Access Journals (Sweden)

    J. Obedt Figueroa-Cavazos

    2016-01-01

    Full Text Available This work explores the viability of 3D printed intervertebral lumbar cages based on biocompatible polycarbonate (PC-ISO® material. Several design concepts are proposed for the generation of patient-specific intervertebral lumbar cages. The 3D printed material achieved compressive yield strength of 55 MPa under a specific combination of manufacturing parameters. The literature recommends a reference load of 4,000 N for design of intervertebral lumbar cages. Under compression testing conditions, the proposed design concepts withstand between 7,500 and 10,000 N of load before showing yielding. Although some stress concentration regions were found during analysis, the overall viability of the proposed design concepts was validated.

  4. Intervertebral Fusion with Mobile Microendoscopic Discectomy for Lumbar Degenerative Disc Disease.

    Science.gov (United States)

    Xu, Bao-Shan; Liu, Yue; Xu, Hai-Wei; Yang, Qiang; Ma, Xin-Long; Hu, Yong-Cheng

    2016-05-01

    The aim of this article is to introduce a technique for lumbar intervertebral fusion that incorporates mobile microendoscopic discectomy (MMED) for lumbar degenerative disc disease. Minimally invasive transforaminal lumbar interbody fusion is frequently performed to treat degenerative diseases of the lumbar spine; however, the scope of such surgery and vision is limited by what the naked eye can see through the expanding channel system. To expand the visual scope and reduce trauma, we perform lumbar intervertebral fusion with the aid of a MMED system that provides a wide field through freely tilting the surgical instrument and canals. We believe that this technique is a good option for treating lumbar degenerative disc disease that requires lumbar intervertebral fusion. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

  5. Clinical anatomy and clinical significance of the cervical intervertebral foramen: a review.

    Science.gov (United States)

    Sioutas, G; Kapetanakis, S

    2016-01-01

    The aim of this paper is to summarise the knowledge about the anatomy of the cervical intervertebral foramen as a whole. Such reviews are rare in the literature. The intervertebral or neural foramen is the opening between the spinal canal and the extraspinal region. It is located between the vertebral pedicles at all spinal levels. A number of structures pass through the foramen: nerves, vessels and ligaments. We describe the bony borders and dimensions of the foramen, the adjacent ligaments, the arteries and veins passing through or neighbouring it, and the neural components. Many procedures are performed in the area of the cervical intervertebral foramen. Knowledge of the anatomy of the foramen is essential in order to operate to the area and to minimize iatrogenic injuries.

  6. Acute pyogenic discitis in a degenerative intervertebral disc in an adult

    Directory of Open Access Journals (Sweden)

    Masamitsu Tanaka

    2010-08-01

    Full Text Available Masamitsu Tanaka1,2, Hiroshi Shimizu2, Yoshiyuki Yato1, Takashi Asazuma1, Koichi Nemoto11Department of Orthopedic Surgery, National Defense Medical College, Tokorozawa, Saitama; 2Department of Orthopedic Surgery, Self Defense Force Fukuoka Hospital, Kasuga, Fukuoka, JapanAbstract: A 35-year-old male who had been receiving conservative treatment for L4 isthmic spondylolisthesis suffered from pyogenic spondylodiscitis in the degenerative L4/L5 intervertebral disc space, which could be identified by comparison with previous images. Symptoms improved with conservative antibiotic treatment. Neovascularization may occur in the annulus fibrosus of a degenerative intervertebral disc, which may increase the risk of hematogenous infection, leading to “discitis” even in adults.Keywords: spondylodiscitis, spondylitis, discitis, isthmic spondylolisthesis, spondylolysis, intervertebral disc degeneration

  7. Global forest loss disproportionately erodes biodiversity in intact landscapes.

    Science.gov (United States)

    Betts, Matthew G; Wolf, Christopher; Ripple, William J; Phalan, Ben; Millers, Kimberley A; Duarte, Adam; Butchart, Stuart H M; Levi, Taal

    2017-07-27

    Global biodiversity loss is a critical environmental crisis, yet the lack of spatial data on biodiversity threats has hindered conservation strategies. Theory predicts that abrupt biodiversity declines are most likely to occur when habitat availability is reduced to very low levels in the landscape (10-30%). Alternatively, recent evidence indicates that biodiversity is best conserved by minimizing human intrusion into intact and relatively unfragmented landscapes. Here we use recently available forest loss data to test deforestation effects on International Union for Conservation of Nature Red List categories of extinction risk for 19,432 vertebrate species worldwide. As expected, deforestation substantially increased the odds of a species being listed as threatened, undergoing recent upgrading to a higher threat category and exhibiting declining populations. More importantly, we show that these risks were disproportionately high in relatively intact landscapes; even minimal deforestation has had severe consequences for vertebrate biodiversity. We found little support for the alternative hypothesis that forest loss is most detrimental in already fragmented landscapes. Spatial analysis revealed high-risk hot spots in Borneo, the central Amazon and the Congo Basin. In these regions, our model predicts that 121-219 species will become threatened under current rates of forest loss over the next 30 years. Given that only 17.9% of these high-risk areas are formally protected and only 8.9% have strict protection, new large-scale conservation efforts to protect intact forests are necessary to slow deforestation rates and to avert a new wave of global extinctions.

  8. A method for quantifying intervertebral disc signal intensity on T2-weighted imaging

    International Nuclear Information System (INIS)

    Nagashima, Masaki; Abe, Hitoshi; Amaya, Kenji; Matsumoto, Hideo; Yanaihara, Hisashi; Nishiwaki, Yuji; Toyama, Yoshiaki; Matsumoto, Morio

    2012-01-01

    Background Quantification of intervertebral disc degeneration based on intensity of the nucleus pulposus in magnetic resonance imaging (MRI) often uses the mean intensity of the region of interest (ROI) within the nucleus pulposus. However, the location and size of ROI have varied in different reports, and none of the reported methods can be considered fully objective. Purpose To develop a more objective method of establishing ROIs for quantitative evaluation of signal intensity in the nucleus pulposus using T2-weighted MRI. Material and Methods A 1.5-T scanner was used to obtain T2-weighted mid-sagittal images. A total of 288 intervertebral discs from 48 patients (25 men, 23 women) were analyzed. Mean age was 47.4 years (range, 17-69 years). All discs were classified into five grades according to Pfirrmann et al. Discs in grades I and II were defined as bright discs, and discs in grades IV and V were defined as dark discs. Eight candidate methods of ROI determination were devised. The method offering the highest degree of discrimination between bright and dark discs was investigated among these eight methods. Results The method with the greatest degree of discrimination was as follows. The quadrangle formed by anterior and posterior edges of the upper and lower end plates in contact with the intervertebral disc to be measured was defined as the intervertebral area. A shape similar to the intervertebral area but with one-quarter the area was drawn. The geometrical center of the shape was matched to the center of intensity, and this shape was then used as the ROI. Satisfactory validity and reproducibility were obtained using this method. Conclusion The present method offers adequate discrimination and could be useful for longitudinal tracking of intervertebral disc degeneration with sufficient reproducibility

  9. Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development.

    Science.gov (United States)

    McCann, Matthew R; Tamplin, Owen J; Rossant, Janet; Séguin, Cheryle A

    2012-01-01

    Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration.

  10. A method for quantifying intervertebral disc signal intensity on T2-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nagashima, Masaki [Dept. of Orthopaedic Surgery, Keio Univ. School of Medicine, Tokyo (Japan); Dept. of Orthopaedic Surgery, Kitasato Univ. Kitasato Inst. Hospital, Tokyo (Japan); Abe, Hitoshi [Dept. of Orthopaedic Surgery, Kitasato Univ. Kitasato Inst. Hospital, Tokyo (Japan)], E-mail: hit-abe@insti.kitasato-u.ac.jp; Amaya, Kenji [Graduate School of Information Science and Engineering, Tokyo Inst. of Technology, Tokyo (Japan); Matsumoto, Hideo [Inst. for Integrated Sports Medicine, Keio Univ. School of Medicine, Tokyo (Japan); Yanaihara, Hisashi [Dept. of Diagnostic Radiology, Kitasato Univ. Kitasato Inst. Hospital, Tokyo (Japan); Nishiwaki, Yuji [Dept. of Environmental and Occupational Health, Toho Univ. School of Medicine, Tokyo (Japan); Toyama, Yoshiaki; Matsumoto, Morio [Dept. of Orthopaedic Surgery, Keio Univ. School of Medicine, Tokyo (Japan)

    2012-11-15

    Background Quantification of intervertebral disc degeneration based on intensity of the nucleus pulposus in magnetic resonance imaging (MRI) often uses the mean intensity of the region of interest (ROI) within the nucleus pulposus. However, the location and size of ROI have varied in different reports, and none of the reported methods can be considered fully objective. Purpose To develop a more objective method of establishing ROIs for quantitative evaluation of signal intensity in the nucleus pulposus using T2-weighted MRI. Material and Methods A 1.5-T scanner was used to obtain T2-weighted mid-sagittal images. A total of 288 intervertebral discs from 48 patients (25 men, 23 women) were analyzed. Mean age was 47.4 years (range, 17-69 years). All discs were classified into five grades according to Pfirrmann et al. Discs in grades I and II were defined as bright discs, and discs in grades IV and V were defined as dark discs. Eight candidate methods of ROI determination were devised. The method offering the highest degree of discrimination between bright and dark discs was investigated among these eight methods. Results The method with the greatest degree of discrimination was as follows. The quadrangle formed by anterior and posterior edges of the upper and lower end plates in contact with the intervertebral disc to be measured was defined as the intervertebral area. A shape similar to the intervertebral area but with one-quarter the area was drawn. The geometrical center of the shape was matched to the center of intensity, and this shape was then used as the ROI. Satisfactory validity and reproducibility were obtained using this method. Conclusion The present method offers adequate discrimination and could be useful for longitudinal tracking of intervertebral disc degeneration with sufficient reproducibility.

  11. CT Fluoroscopy-Guided Transsacral Intervertebral Drainage for Pyogenic Spondylodiscitis at the Lumbosacral Junction

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Tomohiro, E-mail: t-matsu@tokai-u.jp; Mine, Takahiko, E-mail: mine@tsc.u-tokai.ac.jp; Hayashi, Toshihiko, E-mail: t.hayashi@tokai.ac.jp [Tokai University School of Medicine, Department of Radiology, Tokai University Hachioji Hospital (Japan); Kamono, Masahiro, E-mail: kamono@tsc.u-tokai.ac.jp; Taoda, Akiko, E-mail: acco@is.icc.u-tokai.ac.jp; Higaki, Megumu, E-mail: higaki@hachioji-hosp.tokai.ac.jp [Tokai University School of Medicine, Department of General Internal Medicine, Tokai University Hachioji Hospital (Japan); Hasebe, Terumitsu, E-mail: hasebe@tokai-u.jp [Tokai University School of Medicine, Department of Radiology, Tokai University Hachioji Hospital (Japan)

    2017-01-15

    PurposeTo retrospectively describe the feasibility and efficacy of CT fluoroscopy-guided transsacral intervertebral drainage for pyogenic spondylodiscitis at the lumbosacral junction with a combination of two interventional radiological techniques—CT-guided bone biopsy and abscess drainage.Materials and methodsThree patients with pyogenic spondylodiscitis at the lumbosacral junction were enrolled in this study between July 2013 and December 2015. The procedure of CT fluoroscopy-guided transsacral intervertebral drainage for pyogenic spondylodiscitis at the lumbosacral junction was as follows: the sacrum at S1 pedicle was penetrated with an 11-gauge (G) bone biopsy needle to create a path for an 8-French (F) pigtail drainage catheter. The bone biopsy needle was withdrawn, and an 18-G needle was inserted into the intervertebral space of the lumbosacral junction. Then, a 0.038-inch guidewire was inserted into the intervertebral space. Finally, the 8-F pigtail drainage catheter was inserted over the guidewire until its tip reached the intervertebral space. All patients received six-week antibiotics treatment.ResultsSuccessful placement of the drainage catheter was achieved for each patient without procedural complications. The duration of drainage was 17–33 days. For two patients, specific organisms were isolated; thus, definitive medical therapy was possible. All patients responded well to the treatment.ConclusionsCT fluoroscopy-guided transsacral intervertebral drainage for pyogenic spondylodiscitis at the lumbosacral junction is feasible and can be effective with a combination of two interventional techniques—CT fluoroscopy-guided bone biopsy and abscess drainage.

  12. Effect of intervertebral disc disease on scoliosis in the lumbar spine

    Directory of Open Access Journals (Sweden)

    Wojcik Gustaw

    2014-09-01

    Full Text Available Lumbar intervertebral discopathy is a common clinical problem and a significant cause of low back pain. Usually it is associated with overload and damage to the intervertebral disc, which directly relates to the instability of the motion segment. Renal normal anatomy between tissues within the spinal canal is a cause of the reflex curvature of the spine, the goal is to increase the volume of the spinal channel and reduce the compression of the nerve tissue. Knee-jerk reaction to pain is an non physiological change of the setting of the spine in the frontal plane.

  13. Computerized tomography of the lumbar vertebral column after intervertebral disk operation. Pt. 1

    International Nuclear Information System (INIS)

    Schindler, G.; Klott, K.

    1984-01-01

    Problems after intervertebral disk operations are to be expected in about 25-40% of the patients operated. Progressive degnerative alterations at the disks, the vertebrae and the intervertebral joints entail chronic mechanical pain resulting from the sensitive innervation of the structures mentioned, or lead in severe cases to the alteration of the epidural space respectively the spinal nerves with corresponding peripheral neurological symptoms. As post-surgical complications spondylodiscitis, spondylitis, haematomae, liquor fistulae, and split-off bone fragments can be the cause of complaints, for which computerized tomography is a better diagnostical method than myelography. (BWU) [de

  14. Standards of Practice: Quality Assurance Guidelines for Percutaneous Treatments of Intervertebral Discs

    International Nuclear Information System (INIS)

    Kelekis, Alexis D.; Filippiadis, Dimitris K.; Martin, Jean-Baptiste; Brountzos, Elias

    2010-01-01

    Percutaneous treatments are used in the therapy of small- to medium-sized hernias of intervertebral discs to reduce the intradiscal pressure in the nucleus and theoretically create space for the herniated fragment to implode inward, thus reducing pain and improving mobility and quality of life. These techniques involve the percutaneous removal of the nucleus pulposus by using a variety of chemical, thermal, or mechanical techniques and consist of removal of all or part of nucleus pulposus to induce more rapid healing of the abnormal lumbar disc. These guidelines are written to be used in quality improvement programs for assessing fluoroscopy- and/or computed tomography-guided percutaneous intervertebral disc ablative techniques.

  15. Effects of Lead Intoxication on Intervertebral Disc (Experimental Study

    Directory of Open Access Journals (Sweden)

    V.Ye. Maltseva

    2012-02-01

    Full Text Available The article presents the results of experimental study of the effectы of lead intoxication on the intervertebral disc of laboratory rats. It was revealed that in lead intoxication degenerative disorders occur in all parts of the intervertebral disc of rats, affecting both the structure of the annulus fibrosus and the nucleus pulposus. At the same time degenerative changes of the annulus fibrosus can be expressed in disturbance of foliation, due to the appearance of cracks in plates and between them, banding of collagen fibers, reducing the density of fibrochondrocytes. In the nucleus pulposus fragmentation of syncytium structure occurs as well as disturbance of the interconnection between notochordal cells.

  16. Intacting Integrity in coping with health issues

    DEFF Research Database (Denmark)

    Jepsen, Stine Leegaard; Bastrup Jørgensen, Lene; Fridlund, Bengt

    2017-01-01

    The aim of this study was to develop a formal substantive theory (FST) on the multidimensional behavioral process of coping with health issues. Intacting integrity while coping with health issues emerged as the core category of this FST. People facing health issues strive to safeguard and keep...

  17. Epispadias in boys with an intact prepuce

    NARCIS (Netherlands)

    Bos, E. M. E.; Kuijper, C. F.; Chrzan, R. J.; Dik, P.; Klijn, A. J.; de Jong, T. P. V. M.

    2014-01-01

    To present an overview of the clinical presentation and pathological anatomy, and the results of surgical correction of 7 cases of epispadias with intact prepuce; a rare condition that has only occasionally been reported in literature. A retrospective search was performed in the surgical and

  18. HYDROCARBON VAPOR DIFFUSION IN INTACT CORE SLEEVES

    Science.gov (United States)

    The diffusion of 2,2,4-trimethylpentane (TMP) and 2,2,5-trimethylhexane (TMH) vapors put of residually contaminated sandy soil from the U.S. Environmental Protection Agency (EPA) field research site at Traverse City, Michigan, was measured and modeled. The headspace of an intact ...

  19. Small Particles Intact Capture Experiment (SPICE)

    Science.gov (United States)

    Nishioka, Ken-Ji; Carle, G. C.; Bunch, T. E.; Mendez, David J.; Ryder, J. T.

    1994-01-01

    The Small Particles Intact Capture Experiment (SPICE) will develop technologies and engineering techniques necessary to capture nearly intact, uncontaminated cosmic and interplanetary dust particles (IDP's). Successful capture of such particles will benefit the exobiology and planetary science communities by providing particulate samples that may have survived unaltered since the formation of the solar system. Characterization of these particles may contribute fundamental data to our knowledge of how these particles could have formed into our planet Earth and, perhaps, contributed to the beginnings of life. The term 'uncontaminated' means that captured cosmic and IDP particles are free of organic contamination from the capture process and the term 'nearly intact capture' means that their chemical and elemental components are not materially altered during capture. The key to capturing cosmic and IDP particles that are organic-contamination free and nearly intact is the capture medium. Initial screening of capture media included organic foams, multiple thin foil layers, and aerogel (a silica gel); but, with the exception of aerogel, the requirements of no contamination or nearly intact capture were not met. To ensure no contamination of particles in the capture process, high-purity aerogel was chosen. High-purity aerogel results in high clarity (visual clearness), a useful quality in detection and recovery of embedded captured particles from the aerogel. P. Tsou at the Jet Propulsion Laboratory (JPL) originally described the use of aerogel for this purpose and reported laboratory test results. He has flown aerogel as a 'GAS-can Lid' payload on STS-47 and is evaluating the results. The Timeband Capture Cell Experiment (TICCE), a Eureca 1 experiment, is also flying aerogel and is scheduled for recovery in late April.

  20. The comparative study of radiograph, MRI and pathology in degeneration of lumbar intervertebral disc

    International Nuclear Information System (INIS)

    Shang Tiesong; Wang Yunzhao

    2002-01-01

    Objective: To investigate the pathology, and MRI features of the degeneration of lumbar intervertebral discs (IVD). Methods: Thirteen human lumbar spine segments with 31 IVDs were harvested from fresh cadavers. High quality radiographs were taken for all specimens. Five segments with 20 IVD underwent MRl. Then, the radiographic and MRI findings were correlated with corresponding 87 pathologic sections. Results: Variant degeneration was observed in pathologic sections in all 31 IVDs. With MRI T 2 WI images, 20 IVDs showed linear and spotty high signal in the annular fibers, or most of the IVD showed high signal. On pathologic cuts, 22 of 31 IVDs showed infolding of annular fibers, 18 of 31 showed outfolding of annular fibers. On MRI T 1 WI and T 2 WI images, infolding and outfolding of annular fibers were seen as low signal. 20 of 31 IVDs had necrotic debris of cells in the nucleus pulposus. 14 of 20 demonstrated spotty low signal areas on MRI T 2 WI images. 7 Schmorl nodules were found. On pathologic sections Schmorl nodules were seen as IVD tissue protruding into vertebral endplates, they were seen as high signal on T 2 WI images. Two large fissures found on sections were seen as low signal on T 2 WI. Degenerative fibrosis seen on 6 IVD, which showed intermediate signal on T 2 WI images. However, radiographs only demonstrated osteophytes on 3 vertebrae, 7 Schmorl's nodules. Sclerotic, concave and irregular endplates were seen in 11 IVDs, the tatter is the indication of cartilaginous endplate disruption, Conclusion: MRI is very useful in demonstrating the degeneration of IVD, radiograph is able to indirectly show the disappearance of cartilaginous endplate

  1. Lactoferricin mediates anabolic and anti-catabolic effects in the intervertebral disc.

    Science.gov (United States)

    Kim, Jae-Sung; Ellman, Michael B; An, Howard S; Yan, Dongyao; van Wijnen, Andre J; Murphy, Gillian; Hoskin, David W; Im, Hee-Jeong

    2012-04-01

    Lactoferricin (LfcinB) antagonizes biological effects mediated by angiogenic and catabolic growth factors, in addition to pro-inflammatory cytokines and chemokines in human endothelial cells and tumor cells. However, the effect of LfcinB on intervertebral disc (IVD) cell metabolism has not yet been investigated. Using bovine nucleus pulposus (NP) cells, we analyzed the effect of LfcinB on proteoglycan (PG) accumulation, PG synthesis, and anabolic gene expression. We assessed expression of genes for matrix-degrading enzymes such as matrix metalloproteases (MMPs) and a disintegrin-like and metalloprotease with thrombospondin motifs (ADAMTS family), as well as their endogenous inhibitors, tissue inhibitor of metalloproteases (TIMPs). In order to understand the specific molecular mechanisms by which LfcinB exerts its biological effects, we investigated intracellular signaling pathways in NP cells. LfcinB increased PG accumulation mainly via PG synthesis in a dose-dependent manner. Simultaneously, LfcinB dose-dependently downregulated catabolic enzymes. LfcinB's anti-catabolic effects were further demonstrated by a dose-dependent increase in multiple TIMP family members. Our results demonstrate that ERK and/or p38 mitogen-activated protein kinase pathways are the key signaling cascades that exert the biological effects of LfcinB in NP cells, regulating transcription of aggrecan, SOX-9, TIMP-1, TIMP-2, TIMP-3, and iNOS. Our results suggest that LfcinB has anabolic and potent anti-catabolic biological effects on bovine IVD cells that may have considerable promise in the treatment of disc degeneration in the future. Copyright © 2011 Wiley Periodicals, Inc.

  2. Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells

    Directory of Open Access Journals (Sweden)

    BA Walter

    2016-07-01

    Full Text Available The mechanical behaviour and cellular metabolism of intervertebral discs (IVDs and articular cartilage are strongly influenced by their proteoglycan content and associated osmotic properties. This osmotic environment is a biophysical signal that changes with disease and may contribute to the elevated matrix breakdown and altered biologic response to loading observed in IVD degeneration and osteoarthritis. This study tested the hypothesis that changes in osmo-sensation by the transient receptor potential vallinoid-4 (TRPV4 ion channel occur with disease and contribute to the inflammatory environment found during degeneration. Immunohistochemistry on bovine IVDs from an inflammatory organ culture model were used to investigate if TRPV4 is expressed in the IVD and how expression changes with degeneration. Western blot, live-cell calcium imaging, and qRT-PCR were used to investigate whether osmolarity changes or tumour necrosis factor α (TNFα regulate TRPV4 expression, and how altered TRPV4 expression influences calcium signalling and pro-inflammatory cytokine expression. TRPV4 expression correlated with TNFα expression, and was increased when cultured in reduced medium osmolarity and unaltered with TNFα-stimulation. Increased TRPV4 expression increased the calcium flux following TRPV4 activation and increased interleukin-1β (IL-1β and IL-6 gene expression in IVD cells. TRPV4 expression was qualitatively elevated in regions of aggrecan depletion in degenerated human IVDs. Collectively, results suggest that reduced tissue osmolarity, likely following proteoglycan degradation, can increase TRPV4 signalling and enhance pro-inflammatory cytokine production, suggesting changes in TRPV4 mediated osmo-sensation may contribute to the progressive matrix breakdown in disease.

  3. Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Issy, A.C.; Castania, V.; Castania, M. [Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Salmon, C.E.G. [Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Nogueira-Barbosa, M.H. [Divisão de Radiologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Bel, E. Del [Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Defino, H.L.A. [Departamento de Biomecânica, Medicina e Reabilitação do Sistema Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2013-03-15

    Animal models of intervertebral disc degeneration play an important role in clarifying the physiopathological mechanisms and testing novel therapeutic strategies. The objective of the present study is to describe a simple animal model of disc degeneration involving Wistar rats to be used for research studies. Disc degeneration was confirmed and classified by radiography, magnetic resonance and histological evaluation. Adult male Wistar rats were anesthetized and submitted to percutaneous disc puncture with a 20-gauge needle on levels 6-7 and 8-9 of the coccygeal vertebrae. The needle was inserted into the discs guided by fluoroscopy and its tip was positioned crossing the nucleus pulposus up to the contralateral annulus fibrosus, rotated 360° twice, and held for 30 s. To grade the severity of intervertebral disc degeneration, we measured the intervertebral disc height from radiographic images 7 and 30 days after the injury, and the signal intensity T2-weighted magnetic resonance imaging. Histological analysis was performed with hematoxylin-eosin and collagen fiber orientation using picrosirius red staining and polarized light microscopy. Imaging and histological score analyses revealed significant disc degeneration both 7 and 30 days after the lesion, without deaths or systemic complications. Interobserver histological evaluation showed significant agreement. There was a significant positive correlation between histological score and intervertebral disc height 7 and 30 days after the lesion. We conclude that the tail disc puncture method using Wistar rats is a simple, cost-effective and reproducible model for inducing disc degeneration.

  4. Development of a computerized intervertebral motion analysis of the cervical spine for clinical application.

    Science.gov (United States)

    Piché, Mathieu; Benoît, Pierre; Lambert, Julie; Barrette, Virginie; Grondin, Emmanuelle; Martel, Julie; Paré, Amélie; Cardin, André

    2007-01-01

    The objective of this study was to develop a measurement method that could be implemented in chiropractic for the evaluation of angular and translational intervertebral motion of the cervical spine. Flexion-extension radiographs were digitized with a scanner at a ratio of 1:1 and imported into a software, allowing segmental motion measurements. The measurements were obtained by selecting the most anteroinferior point and the most posteroinferior point of a vertebral body (anterior and posterior arch, respectively, for C1), with the origin of the reference frame set at the most posteroinferior point of the vertebral body below. The same procedure was performed for both the flexion and extension radiographs, and the coordinates of the 2 points were used to calculate the angular movement and the translation between the 2 vertebrae. This method provides a measure of intervertebral angular and translational movement. It uses a different reference frame for each joint instead of the same reference frame for all joints and thus provides a measure of motion in the plane of each articulation. The calculated values obtained are comparable to other studies on intervertebral motion and support further development to validate the method. The present study proposes a computerized procedure to evaluate intervertebral motion of the cervical spine. This procedure needs to be validated with a reliability study but could provide a valuable tool for doctors of chiropractic and further spinal research.

  5. MRI findings and diagnostic value of intervertebral disc free pulpiform nucleus in lumbar intraspinal

    International Nuclear Information System (INIS)

    Cai Jinhua; Fang Huasheng; Li Dongyuan

    2011-01-01

    Objective: To determine the MRI findings and diagnostic value of intervertebral disc free pulpiform nucleus in lumbar intraspinal. Methods: MRI findings of 46 cases with free pulpiform nucleus proved by surgery and pathology were retrospectively analyzed, and compared with pathological results. Results: Of all cases, the free pulpiform nucleus located at extradural foreside. 9 cases of the free pulpiform nucleus dissociated upon in spinal, 32 cases moved down and 5 cases removed backwards. Of 46 patients, 22 cases of the free pulpiform nucleus inhabited right, 17 cases left and 7 cases in midline. The lesion was single in all case with round, oval or anormaly shape. The free pulpiform nucleus had the same equal or low signal with provided intervertebral disc. The calcification, if any, presented as low -signal area. Among these 11 cases which were injected with GD-DTPA had no enhancement in the center, mild and high enhancement at periphery. Among all cases, MRI diagnosis were agreed with the pathology results with diagnosis accuracy of 100%. Conclusion: MRI can clearly demonstrate the intervertebral disc free pulpiform nucleus in lumbar intraspinal and make a correct diagnosis. Therefore, MRI is the best choice for diagnosis of intervertebral disc free pulpiform nucleus in lumbar intraspinal. (authors)

  6. Increased MMP-2 activity during intervertebral disc degeneration is correlated to MMP-14 levels

    NARCIS (Netherlands)

    Rutges, J. P. H. J.; Kummer, J. A.; Oner, F. C.; Verbout, A. J.; Roestenburg, H. J. A.; Dhert, W. J. A.; Creemers, L. B.

    Intervertebral disc (IVD) degeneration is associated with the increased expression of several matrix metalloproteinases (MMPs), in particular MMP-2. However, little is known about the actual activity of MMP-2 in healthy and degenerated discs, or what mechanisms are involved in its activation. A

  7. Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats

    International Nuclear Information System (INIS)

    Issy, A.C.; Castania, V.; Castania, M.; Salmon, C.E.G.; Nogueira-Barbosa, M.H.; Bel, E. Del; Defino, H.L.A.

    2013-01-01

    Animal models of intervertebral disc degeneration play an important role in clarifying the physiopathological mechanisms and testing novel therapeutic strategies. The objective of the present study is to describe a simple animal model of disc degeneration involving Wistar rats to be used for research studies. Disc degeneration was confirmed and classified by radiography, magnetic resonance and histological evaluation. Adult male Wistar rats were anesthetized and submitted to percutaneous disc puncture with a 20-gauge needle on levels 6-7 and 8-9 of the coccygeal vertebrae. The needle was inserted into the discs guided by fluoroscopy and its tip was positioned crossing the nucleus pulposus up to the contralateral annulus fibrosus, rotated 360° twice, and held for 30 s. To grade the severity of intervertebral disc degeneration, we measured the intervertebral disc height from radiographic images 7 and 30 days after the injury, and the signal intensity T2-weighted magnetic resonance imaging. Histological analysis was performed with hematoxylin-eosin and collagen fiber orientation using picrosirius red staining and polarized light microscopy. Imaging and histological score analyses revealed significant disc degeneration both 7 and 30 days after the lesion, without deaths or systemic complications. Interobserver histological evaluation showed significant agreement. There was a significant positive correlation between histological score and intervertebral disc height 7 and 30 days after the lesion. We conclude that the tail disc puncture method using Wistar rats is a simple, cost-effective and reproducible model for inducing disc degeneration

  8. Fluid flow and convective transport of solutes within the intervertebral disc

    NARCIS (Netherlands)

    Ferguson, S.J.; Ito, K.; Nolte, L.P.

    2004-01-01

    Previous experimental and analytical studies of solute transport in the intervertebral disc have demonstrated that for small molecules diffusive transport alone fulfils the nutritional needs of disc cells. It has been often suggested that fluid flow into and within the disc may enhance the transport

  9. Treatment of the degenerated intervertebral disc; closure, repair and regeneration of the annulus fibrosus

    NARCIS (Netherlands)

    Sharifi, Shahriar; Bulstra, S.K.; Grijpma, Dirk W.; Kuijer, R.

    2015-01-01

    Degeneration of the intervertebral disc (IVD) and disc herniation are two causes of low back pain. The aetiology of these disorders is unknown, but tissue weakening, which primarily occurs due to inherited genetic factors, ageing, nutritional compromise and loading history, is the basic factor

  10. Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs.

    Science.gov (United States)

    Choi, Kyung-Suk; Lee, Chanmi; Harfe, Brian D

    2012-01-01

    The intervertebral discs, located between adjacent vertebrae, are required for stability of the spine and distributing mechanical load throughout the vertebral column. All cell types located in the middle regions of the discs, called nuclei pulposi, are derived from the embryonic notochord. Recently, it was shown that the hedgehog signaling pathway plays an essential role during formation of nuclei pulposi. However, during the time that nuclei pulposi are forming, Shh is expressed in both the notochord and the nearby floor plate. To determine the source of SHH protein sufficient for formation of nuclei pulposi we removed Shh from either the floor plate or the notochord using tamoxifen-inducible Cre alleles. Removal of Shh from the floor plate resulted in phenotypically normal intervertebral discs, indicating that Shh expression in this tissue is not required for disc patterning. In addition, embryos that lacked Shh in the floor plate had normal vertebral columns, demonstrating that Shh expression in the notochord is sufficient for pattering the entire vertebral column. Removal of Shh from the notochord resulted in the absence of Shh in the floor plate, loss of intervertebral discs and vertebral structures. These data indicate that Shh expression in the notochord is sufficient for patterning of the intervertebral discs and the vertebral column. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Radiofrequency thermocoagulation for the treatment of lumbar intervertebral disc protrusion: a clinical observation of 30 cases

    International Nuclear Information System (INIS)

    Gong Weidong; Li Yazhou; Cao Wei; Yang Wei; Zhang Peng; Wang Zhimin; Wu Zhiqun

    2010-01-01

    Objective: To observe the clinical effects and safety of radiofrequency thermocoagulation in treating the lumbar intervertebral disc protrusion. Methods: Thirty patients with lumbar intervertebral disc protrusion, whose diagnoses were confirmed by clinical manifestations and CT findings, were involved in this study. The needle was punctured to the target point of the diseased intervertebral space under C-arm fluoroscopic guidance. After the testing of sensory nerve, motor nerve and temperature was made, the target needles were heated until the nerve radiofrequency temperature meter reached the point of 92 degree C. This point of temperature was held for 100 seconds and the procedure was repeated for four cycles. Results: Six months after the treatment, all patients showed an obvious improvement in VAS, which decreased from 7.83 ± 0.33 before operation to 2.37 ± 0.48 after treatment (P < 0.05). According to the modified Macnab therapeutic evaluation criteria, excellent result was seen in 9, good result in 12, fair result in 5 and poor result in 4 cases, with a total effective rate of 86.7%. No serious complications occurred in all patients. Conclusion: Radiofrequency thermocoagulation is an effective and safe method for the treatment of lumbar intervertebral disc protrusion. (authors)

  12. Putting pressure on the spine : an osmoviscoelastic FE model of the intervertebral disc

    NARCIS (Netherlands)

    Schroder, Y.

    2008-01-01

    Back pain is a frequently occurring complaint in adults, having a relatively large impact on the European economy due to the fact that it often partially incapacitates the patient. Intervertebral discs are believed to be a key element of back pain. Apart from providing flexibility to the spine,

  13. Validation of Triphasic Mixture Theory for a Mimic of Intervertebral Disk Tissue

    NARCIS (Netherlands)

    Oomens, C.W.J.; Heus, de H.J.; Huyghe, J.M.R.J.; Nelissen, J.G.L.; Janssen, J.D.

    1995-01-01

    This paper describes experimental studies an synthetic madel materials that mimic the mechanical behavior af intervertebral disk tissue. The results are used ta validate the triphasic mixture theory to describe soft charged hydrated materiais. Permeability and swelling pressure experiments were used

  14. Intervertebral disc (IVD): Structure, degeneration, repair and regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Whatley, Benjamin R.; Wen Xuejun, E-mail: xjwen@clemson.edu

    2012-02-01

    Low back pain affects a large portion of the population, resulting in high care costs for therapy and treatment. One primary cause of low back pain is the degeneration of the intervertebral disc (IVD) resulting in the compression of the spinal nerves and adjacent vertebrae. Exact causes of degeneration are unknown, but it is thought that natural aging, and both biological and genetic factors may play a significant role in the degenerative process. Conventional methods to alleviate low back pain include spinal fusion and artificial disc replacement. Traditional treatments through spinal fusion may eliminate pain yet do not restore disc function and lead to further degeneration of adjacent levels by altering disc biomechanics and natural kinematics. Recently, artificial IVD replacements have started to gain interest, with two IVD implants currently approved in the United States. Although these implants facilitate the preservation of motions and disc space height, they are unable to sustain compressive forces due to their lack of elasticity. In addition, the implants may produce wear debris that can cause osteolysis and other deleterious effects. As an alternative to these conventional approaches, tissue engineered IVD constructs offer the advantage of biointegration while preserving the essential attributes of natural motion and disc space restoration. There is a great need for the development of tissue engineered scaffolds that simulate the natural 3D morphology and microenvironment of the targeted tissue. Scaffolds should facilitate biological transport to satisfy nutrition and waste removal requirements within the IVD. The discrete tissue architectures of the nucleus pulposus (NP) and annulus fibrosus (AF) have posed great challenges to IVD tissue engineering. Current attempts have not been able to satisfy the biological functions and/or mechanical properties of native tissue. Therefore, these current scaffolds are far from satisfactory. This review highlights the

  15. Measurement of diffusive properties of intact rock

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, K B

    1996-12-01

    In the Postclosure Assessment of a Reference System for the Disposal of Canada`s Nuclear Fuel Waste (Goodwin et al. 1994) the disposal vault is assumed to be surrounded by a zone of intact rock, referred to as the `exclusion zone.` A sensitivity analysis of the relative effectiveness of the several engineered and natural barriers that contribute to the safety of the reference disposal system has shown that this zone of intact rock is the most effective of these barriers to the movement of radionuclides through the reference system. Peer review of the geosphere model used in the case study for the EIS (Environmental Impact Statement) of the Canadian Nuclear Fuel Waste Management Program has identified the need to quantify the properties of the intact rock surrounding the disposal vault that would control the transport of radionuclides by diffusion. The Postclosure Assessment also identified the need for appropriate values of the free water diffusion coefficient (D{sub o}) for {sup 129}1 and {sup 14}C. The measurement of rock resistivity allows the calculation of the Formation Factor for a rock This review describes the Formation Factor, diffusivity, permeability, and porosity, and how these properties might be measured or inferred for insitu rock under the conditions that apply to the intact rock surrounding a potential disposal vault. The importance of measuring the intrinsic diffusion coefficient (D{sup i}) of diffusing species under solution salinities simulating those of groundwaters is emphasised, and a method of measurement is described that is independent of the diffusing medium, and which would be appropriate for measurements made in chemically complex media such as groundwaters. (author). 95 refs., 4 tabs., 39 figs.

  16. Measurement of diffusive properties of intact rock

    International Nuclear Information System (INIS)

    Harvey, K.B.

    1996-12-01

    In the Postclosure Assessment of a Reference System for the Disposal of Canada's Nuclear Fuel Waste (Goodwin et al. 1994) the disposal vault is assumed to be surrounded by a zone of intact rock, referred to as the 'exclusion zone.' A sensitivity analysis of the relative effectiveness of the several engineered and natural barriers that contribute to the safety of the reference disposal system has shown that this zone of intact rock is the most effective of these barriers to the movement of radionuclides through the reference system. Peer review of the geosphere model used in the case study for the EIS (Environmental Impact Statement) of the Canadian Nuclear Fuel Waste Management Program has identified the need to quantify the properties of the intact rock surrounding the disposal vault that would control the transport of radionuclides by diffusion. The Postclosure Assessment also identified the need for appropriate values of the free water diffusion coefficient (D o ) for 129 1 and 14 C. The measurement of rock resistivity allows the calculation of the Formation Factor for a rock This review describes the Formation Factor, diffusivity, permeability, and porosity, and how these properties might be measured or inferred for insitu rock under the conditions that apply to the intact rock surrounding a potential disposal vault. The importance of measuring the intrinsic diffusion coefficient (D i ) of diffusing species under solution salinities simulating those of groundwaters is emphasised, and a method of measurement is described that is independent of the diffusing medium, and which would be appropriate for measurements made in chemically complex media such as groundwaters. (author). 95 refs., 4 tabs., 39 figs

  17. Autism Spectrum Disorder and intact executive functioning.

    Science.gov (United States)

    Ferrara, R; Ansermet, F; Massoni, F; Petrone, L; Onofri, E; Ricci, P; Archer, T; Ricci, S

    2016-01-01

    Earliest notions concerning autism (Autism Spectrum Disorders, ASD) describe the disturbance in executive functioning. Despite altered definition, executive functioning, expressed as higher cognitive skills required complex behaviors linked to the prefrontal cortex, are defective in autism. Specific difficulties in children presenting autism or verbal disabilities at executive functioning levels have been identified. Nevertheless, the developmental deficit of executive functioning in autism is highly diversified with huge individual variation and may even be absent. The aim of the present study to examine the current standing of intact executive functioning intact in ASD. Analysis of ASD populations, whether high-functioning, Asperger's or autism Broad Phenotype, studied over a range of executive functions including response inhibition, planning, cognitive flexibility, cognitive inhibition, and alerting networks indicates an absence of damage/impairment compared to the typically-developed normal control subjects. These findings of intact executive functioning in ASD subjects provide a strong foundation on which to construct applications for growth environments and the rehabilitation of autistic subjects.

  18. Small vertebral cross-sectional area and tall intervertebral disc in adolescent idiopathic scoliosis

    International Nuclear Information System (INIS)

    Ponrartana, Skorn; Fisher, Carissa L.; Aggabao, Patricia C.; Chavez, Thomas A.; Broom, Alexander M.; Wren, Tishya A.L.; Skaggs, David L.; Gilsanz, Vicente

    2016-01-01

    When compared to boys, girls have smaller vertebral cross-sectional area, which conveys a greater spinal flexibility, and a higher prevalence of adolescent idiopathic scoliosis. To test the hypothesis that small vertebral cross-sectional area and tall intervertebral disc height are structural characteristics of patients with adolescent idiopathic scoliosis. Using multiplanar imaging techniques, measures of vertebral cross-sectional area, vertebral height and intervertebral disc height in the lumbar spine were obtained in 35 pairs of girls and 11 pairs of boys with and without adolescent idiopathic scoliosis of the thoracic spine matched for age, height and weight. Compared to adolescents without spinal deformity, girls and boys with adolescent idiopathic scoliosis had, on average, 9.8% (6.68 ± 0.81 vs. 7.40 ± 0.99 cm 2 ; P = 0.0007) and 13.9% (8.22 ± 0.84 vs. 9.55 ± 1.61 cm 2 ; P = 0.009) smaller vertebral cross-sectional dimensions, respectively. Additionally, patients with adolescent idiopathic scoliosis had significantly greater values for intervertebral disc heights (9.06 ± 0.85 vs. 7.31 ± 0.62 mm and 9.09 ± 0.87 vs. 7.61 ± 1.00 mm for girls and boys respectively; both P ≤ 0.011). Multiple regression analysis indicated that the presence of scoliosis was negatively associated with vertebral cross-sectional area and positively with intervertebral disc height, independent of sex, age and body mass index. We provide new evidence that girls and boys with adolescent idiopathic scoliosis have significantly smaller vertebral cross-sectional area and taller intervertebral disc heights - two major structural determinants that influence trunk flexibility. With appropriate validation, these findings may have implications for the identification of children at the highest risk for developing scoliosis. (orig.)

  19. Small vertebral cross-sectional area and tall intervertebral disc in adolescent idiopathic scoliosis

    Energy Technology Data Exchange (ETDEWEB)

    Ponrartana, Skorn; Fisher, Carissa L.; Aggabao, Patricia C. [Keck School of Medicine, University of Southern California, Department of Radiology, Children' s Hospital Los Angeles, Los Angeles, CA (United States); Chavez, Thomas A. [Keck School of Medicine, University of Southern California, Department of Pediatrics, Children' s Hospital Los Angeles, Los Angeles, CA (United States); Broom, Alexander M.; Wren, Tishya A.L.; Skaggs, David L. [Keck School of Medicine, University of Southern California, Department of Orthopaedic Surgery, Children' s Hospital Los Angeles, Los Angeles, CA (United States); Gilsanz, Vicente [Keck School of Medicine, University of Southern California, Department of Radiology, Children' s Hospital Los Angeles, Los Angeles, CA (United States); Keck School of Medicine, University of Southern California, Department of Pediatrics, Children' s Hospital Los Angeles, Los Angeles, CA (United States); Keck School of Medicine, University of Southern California, Department of Orthopaedic Surgery, Children' s Hospital Los Angeles, Los Angeles, CA (United States)

    2016-09-15

    When compared to boys, girls have smaller vertebral cross-sectional area, which conveys a greater spinal flexibility, and a higher prevalence of adolescent idiopathic scoliosis. To test the hypothesis that small vertebral cross-sectional area and tall intervertebral disc height are structural characteristics of patients with adolescent idiopathic scoliosis. Using multiplanar imaging techniques, measures of vertebral cross-sectional area, vertebral height and intervertebral disc height in the lumbar spine were obtained in 35 pairs of girls and 11 pairs of boys with and without adolescent idiopathic scoliosis of the thoracic spine matched for age, height and weight. Compared to adolescents without spinal deformity, girls and boys with adolescent idiopathic scoliosis had, on average, 9.8% (6.68 ± 0.81 vs. 7.40 ± 0.99 cm{sup 2}; P = 0.0007) and 13.9% (8.22 ± 0.84 vs. 9.55 ± 1.61 cm{sup 2}; P = 0.009) smaller vertebral cross-sectional dimensions, respectively. Additionally, patients with adolescent idiopathic scoliosis had significantly greater values for intervertebral disc heights (9.06 ± 0.85 vs. 7.31 ± 0.62 mm and 9.09 ± 0.87 vs. 7.61 ± 1.00 mm for girls and boys respectively; both P ≤ 0.011). Multiple regression analysis indicated that the presence of scoliosis was negatively associated with vertebral cross-sectional area and positively with intervertebral disc height, independent of sex, age and body mass index. We provide new evidence that girls and boys with adolescent idiopathic scoliosis have significantly smaller vertebral cross-sectional area and taller intervertebral disc heights - two major structural determinants that influence trunk flexibility. With appropriate validation, these findings may have implications for the identification of children at the highest risk for developing scoliosis. (orig.)

  20. Heme oxygenase-1 modulates degeneration of the intervertebral disc after puncture in Bach 1 deficient mice.

    Science.gov (United States)

    Ohta, Ryo; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Nakamae, Toshio; Izumi, Bunichiro; Fujioka, Yuki; Ochi, Mitsuo

    2012-09-01

    Intervertebral disc degeneration is considered to be a major feature of low back pain. Furthermore, oxidative stress has been shown to be an important factor in degenerative diseases such as osteoarthritis and is considered a cause of intervertebral disc degeneration. The purpose of this study was to clarify the correlation between oxidative stress and intervertebral disc degeneration using Broad complex-Tramtrack-Bric-a-brac and cap'n'collar homology 1 deficient (Bach 1-/-) mice which highly express heme oxygenase-1 (HO-1). HO-1 protects cells from oxidative stress. Caudal discs of 12-week-old and 1-year-old mice were evaluated as age-related models. Each group and period, 5 mice (a total of 20 mice, a total of 20 discs) were evaluated as age-related model. C9-C10 caudal discs in 12-week-old Bach 1-/- and wild-type mice were punctured using a 29-gauge needle as annulus puncture model. Each group and period, 5 mice (a total of 60 mice, a total of 60 discs) were evaluated. The progress of disc degeneration was evaluated at pre-puncture, 1, 2, 4, 8 and 12 weeks post-puncture. Radiographic, histologic and immunohistologic analysis were performed to compare between Bach 1-/- and wild-type mice. In the age-related model, there were no significant differences between Bach 1-/- and wild-type mice radiologically and histologically. However, in the annulus puncture model, histological scoring revealed significant difference at 8 and 12 weeks post-puncture. The number of HO-1 positive cells was significantly greater in Bach 1-/- mice at every period. The apoptosis rate was significantly lower at 1 and 2 weeks post-puncture in Bach 1-/- mice. Oxidative stress prevention may avoid the degenerative process of the intervertebral disc after puncture, reducing the number of apoptosis cells. High HO-1 expression may also inhibit oxidative stress and delay the process of intervertebral disc degeneration.

  1. Lumber intervertebral disk; Correlation with the signal intensity of magnetic resonance imaging and the histological changes

    Energy Technology Data Exchange (ETDEWEB)

    Uchida, Ryusei; Takahashi, Sadao; Ando, Tadashi; Kumano, Kiyoshi; Hiranuma, Kenji; Kanazawa, Yousuke; Konishi, Seiji; Eguchi, Masanobu; Tanioka, Hisaya (KantoRosai Hospital, Kawasaki, Kanagawa (Japan))

    1989-11-01

    We studied to provide precise correlations between the intensity of MRI signals and the degenerative changes of the nucleus pulposes of the L4/5 intervertebral disk herniations. 23 cases with the L4/5 intervertebral disk herniations having surgical treatment were examined using Magnetom H 15 (1.5 tesla) with surface coil. The images were obtained with T2 images (long TR (1000{approx}1600 msec), TE (60{approx}90 msec)). The intensity was measured using FUJI densitometer FD 101 at the lumber vertebral body and the intervertebral disk. We calculated the L4/5 intervertebral disk degeneration ratio (determined by comparing the modified L4/5 MR signal intensity with the modified L2/3 MR signal itensity). Histological changes were examined in the cellular components of the nucleus pulposus (such as the number of the nucleus cells, nucleus cell nesting and HE stainability of the nucleus cell) and the matrics substance (such as fibrillation, hyaline degeneration and granular degeneration). Histochemical studies were performed using Scott's Method (AB-0.4 M MgCl{sub 2} Alcinophilia, AB-09 M, MgCl{sub 2} Alcinophilia) to investigate glycosaminoglycans of the nucleus pulposus. We compared the histological and histochemical changes with the MR L4/5 intervetebral disk degeneration ratio. The decreasing MRI signal intensity of the nucleous pulposus was (1) corresponded to the pathological changes such as the increasing number of the cell nesting, fibrillation and hyaline degeneration of the nucleus polposus. (2) corresponded to the decrease in the total glycosaminoglycans of the nucleus pulposus. (3) corresponded to the early stage of degeneration of the nucleus polposus, but in aging when all levels of intervertebral disk degeneration appeared, we could not know the degree of the disk degeneration from the signal intensity of MRI. (J.P.N.).

  2. Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

    NARCIS (Netherlands)

    Willems, Nicole; Mihov, George; Grinwis, Guy C M; van Dijk, Maarten; Schumann, Detlef; Bos, Clemens; Strijkers, Gustav J; Dhert, Wouter J A; Meij, Björn P; Creemers, Laura B.; Tryfonidou, Marianna A

    Repair of degenerated intervertebral discs (IVD) might be established via intradiscal delivery of biologic therapies. Polyester amide polymers (PEA) were evaluated for in vitro cytotoxicity and in vivo biocompatibility, and thereafter intradiscal application of PEA microspheres (PEAMs) in a canine

  3. Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

    NARCIS (Netherlands)

    Willems, Nicole; Mihov, George; Grinwis, Guy C. M.; van Dijk, Maarten; Schumann, Detlef; Bos, Clemens; Strijkers, Gustav J.; Dhert, Wouter J. A.; Meij, Björn P.; Creemers, Laura B.; Tryfonidou, Marianna A.

    2017-01-01

    Repair of degenerated intervertebral discs (IVD) might be established via intradiscal delivery of biologic therapies. Polyester amide polymers (PEA) were evaluated for in vitro cytotoxicity and in vivo biocompatibility, and thereafter intradiscal application of PEA microspheres (PEAMs) in a canine

  4. Restriction of Cervical Intervertebral Movement with Different Types of External Immobilizers : A Cadaveric 3D Analysis Study

    NARCIS (Netherlands)

    Holla, Micha; Hannink, Gerjon; Eggen, Thomas G.E.; Daanen, Robin A.; Hosman, Allard J.F.; Verdonschot, Nico

    2017-01-01

    Study Design. Cadaveric radiostereometric analysis study. Objective. To quantify the ability of five commonly used immobilizers to restrict cervical spine movement, including intervertebral movement, in three directions. Summary of Background Data. Evidence about the ability of many clinically used

  5. Restriction of Cervical Intervertebral Movement With Different Types of External Immobilizers: A Cadaveric 3D Analysis Study

    NARCIS (Netherlands)

    Holla, M.; Hannink, G.J.; Eggen, T.G.E.; Daanen, R.A.; Hosman, A.J.F.; Verdonschot, N.J.

    2017-01-01

    STUDY DESIGN: Cadaveric radiostereometric analysis study. OBJECTIVE: To quantify the ability of five commonly used immobilizers to restrict cervical spine movement, including intervertebral movement, in three directions. SUMMARY OF BACKGROUND DATA: Evidence about the ability of many clinically used

  6. Parametric modeling of the intervertebral disc space in 3D: application to CT images of the lumbar spine.

    Science.gov (United States)

    Korez, Robert; Likar, Boštjan; Pernuš, Franjo; Vrtovec, Tomaž

    2014-10-01

    Gradual degeneration of intervertebral discs of the lumbar spine is one of the most common causes of low back pain. Although conservative treatment for low back pain may provide relief to most individuals, surgical intervention may be required for individuals with significant continuing symptoms, which is usually performed by replacing the degenerated intervertebral disc with an artificial implant. For designing implants with good bone contact and continuous force distribution, the morphology of the intervertebral disc space and vertebral body endplates is of considerable importance. In this study, we propose a method for parametric modeling of the intervertebral disc space in three dimensions (3D) and show its application to computed tomography (CT) images of the lumbar spine. The initial 3D model of the intervertebral disc space is generated according to the superquadric approach and therefore represented by a truncated elliptical cone, which is initialized by parameters obtained from 3D models of adjacent vertebral bodies. In an optimization procedure, the 3D model of the intervertebral disc space is incrementally deformed by adding parameters that provide a more detailed morphometric description of the observed shape, and aligned to the observed intervertebral disc space in the 3D image. By applying the proposed method to CT images of 20 lumbar spines, the shape and pose of each of the 100 intervertebral disc spaces were represented by a 3D parametric model. The resulting mean (±standard deviation) accuracy of modeling was 1.06±0.98mm in terms of radial Euclidean distance against manually defined ground truth points, with the corresponding success rate of 93% (i.e. 93 out of 100 intervertebral disc spaces were modeled successfully). As the resulting 3D models provide a description of the shape of intervertebral disc spaces in a complete parametric form, morphometric analysis was straightforwardly enabled and allowed the computation of the corresponding

  7. Sorption of cesium in intact rock

    International Nuclear Information System (INIS)

    Puukko, E.

    2014-04-01

    The mass distribution coefficient K d is used in performance assessment (PA) to describe sorption of a radionuclide on rock. The R d is determined using crushed rock which causes uncertainty in converting the R d values to K d values for intact rock. This work describes a method to determine the equilibrium of sorption on intact rock. The rock types of the planned Olkiluoto waste disposal site were T-series mica gneiss (T-MGN), T-series tonalite granodiorite granite gneiss (T-TGG), P-series tonalite granodiorite granite gneiss (P-TGG) and pegmatitic granite (PGR). These rocks contain different amount of biotite which is the main sorbing mineral. The sorption of cesium on intact rock slices was studied by applying an electrical field to speed up migration of cesium into the rock. Cesium is in the solution as a noncomplex cation Cs + and it is sorbed by ion exchange. The tracer used in the experiments was 134 Cs. The experimental sorption on the intact rock is compared with values calculated using the in house cation exchange sorption model (HYRL model) in PHREEQC program. The observed sorption on T-MGN and T-TGG rocks was close to the calculated values. Two PGR samples were from a depth of 70 m and three samples were from a depth of 150 m. Cesium sorbed more than predicted on the two 70 m PGR samples. The sorption of Cs on the three 150 m PGR samples was small which was consistent with the calculations. The pegmatitic granite PGR has the smallest content of biotite of the four rock types. In the case of P-TGG rock the observed values of sorption were only half of the calculated values. Two kind of slices were cut from P-TGG drill core. The slices were against and to the direction of the foliation of the biotite rims. The sorption of cesium on P-TGG rock was same in both cases. The results indicated that there was no effect of the directions of the electric field and the foliation of biotite in the P-TGG rock. (orig.)

  8. Quantitative proteomic analysis of intact plastids.

    Science.gov (United States)

    Shiraya, Takeshi; Kaneko, Kentaro; Mitsui, Toshiaki

    2014-01-01

    Plastids are specialized cell organelles in plant cells that are differentiated into various forms including chloroplasts, chromoplasts, and amyloplasts, and fulfill important functions in maintaining the overall cell metabolism and sensing environmental factors such as sunlight. It is therefore important to grasp the mechanisms of differentiation and functional changes of plastids in order to enhance the understanding of vegetality. In this chapter, details of a method for the extraction of intact plastids that makes analysis possible while maintaining the plastid functions are provided; in addition, a quantitative shotgun method for analyzing the composition and changes in the content of proteins in plastids as a result of environmental impacts is described.

  9. Oxidation of molecular tritium by intact soils

    International Nuclear Information System (INIS)

    Sweet, C.W.; Murphy, C.E. Jr.

    1980-01-01

    The effects of environmental factors on the rate of oxidation of molecular tritium (T 2 ) to tritiated water (HTO) were determined for intact soils during field exposures. Maximum deposition velocities of approximately 0.03 cm/sec were measured for T 2 at low wind speeds for a variety of soils over a wide range of conditions. Deposition velocities were slightly inhibited in wet soils and at 0 0 C. In dry soils, oxidation of T 2 to HTO occurred deeper in the soil profile, but deposition velocities were unaffected

  10. The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs

    OpenAIRE

    Taylor, Michael P; Wedel, Mathew J.

    2013-01-01

    The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joi...

  11. Effects of hydrolysed casein, intact casein and intact whey protein on energy expenditure and appetite regulation

    DEFF Research Database (Denmark)

    Bendtsen, Line Quist; Lorenzen, Janne Kunchel; Gomes, Sisse

    2014-01-01

    Casein and whey differ in amino acid composition and in the rate of absorption; however, the absorption rate of casein can be increased to mimic that of whey by exogenous hydrolysis. The objective of the present study was to compare the effects of hydrolysed casein (HC), intact casein (IC......) and intact whey (IW) on energy expenditure (EE) and appetite regulation, and thereby to investigate the influence of amino acid composition and the rate of absorption. In the present randomised cross-over study, twenty-four overweight and moderately obese young men and women consumed three isoenergetic...

  12. Xenopus egg cytoplasm with intact actin.

    Science.gov (United States)

    Field, Christine M; Nguyen, Phuong A; Ishihara, Keisuke; Groen, Aaron C; Mitchison, Timothy J

    2014-01-01

    We report optimized methods for preparing Xenopus egg extracts without cytochalasin D, that we term "actin-intact egg extract." These are undiluted egg cytoplasm that contains abundant organelles, and glycogen which supplies energy, and represents the least perturbed cell-free cytoplasm preparation we know of. We used this system to probe cell cycle regulation of actin and myosin-II dynamics (Field et al., 2011), and to reconstitute the large, interphase asters that organize early Xenopus embryos (Mitchison et al., 2012; Wühr, Tan, Parker, Detrich, & Mitchison, 2010). Actin-intact Xenopus egg extracts are useful for analysis of actin dynamics, and interaction of actin with other cytoplasmic systems, in a cell-free system that closely mimics egg physiology, and more generally for probing the biochemistry and biophysics of the egg, zygote, and early embryo. Detailed protocols are provided along with assays used to check cell cycle state and tips for handling and storing undiluted egg extracts. © 2014 Elsevier Inc. All rights reserved.

  13. An intact sequence-specific DNA-binding domain is required for human cytomegalovirus-mediated sequestration of p53 and may promote in vivo binding to the viral genome during infection

    International Nuclear Information System (INIS)

    Rosenke, Kyle; Samuel, Melanie A.; McDowell, Eric T.; Toerne, Melissa A.; Fortunato, Elizabeth A.

    2006-01-01

    The p53 protein is stabilized during infection of primary human fibroblasts with human cytomegalovirus (HCMV). However, the p53 in HCMV-infected cells is unable to activate its downstream targets. HCMV accomplishes this inactivation, at least in part, by sequestering p53 into viral replication centers within the cell's nucleus soon after they are established. In order to better understand the interplay between HCMV and p53 and the mechanism of sequestration, we constructed a panel of mutant p53-GFP fusion constructs for use in transfection/infection experiments. These mutants affected several post-translational modification sites and several sites within the central sequence-specific DNA-binding domain of the protein. Two categories of p53 sequestration were observed when the mutant constructs were transfected into primary fibroblasts and then infected at either high or low multiplicity. The first category, including all of the post-translational modification mutants, showed sequestration comparable to a wild-type (wt) control, while the second category, mutants affecting the DNA-binding core, were not specifically sequestered above control GFP levels. This suggested that the DNA-binding ability of the protein was required for sequestration. When the HCMV genome was analyzed for p53 consensus binding sites, 21 matches were found, which localized either to the promoters or the coding regions of viral proteins involved in DNA replication and processing as well as structural proteins. An analysis of in vivo binding to these identified sites via chromatin immunoprecipitation assays revealed differential binding to several of the sites over the course of infection

  14. Contrast myelography in the diagnosis of posterior hernias of lumbar intervertebral disks

    International Nuclear Information System (INIS)

    Maratkanova, T.V.; Morozova, T.D.

    1997-01-01

    Based on the analysis of the results of 297 contrast myelographies (MG) by means of water soluble agents made in patients with posterior hernias of lumbar intervertebral disks (PHLID), the authors define the potentialities of this technique in the diagnosis of PHLID. Additionally, two oblique X-ray films have been included into the exicting filming routine, which may detect all specific features of intervertebral disk damage at MG. The authors make additions into the wellknown myelographic symptomatology of PHLID, by outlining the abnormal anterior configuration of a contrast column at the level of a diseased disk in PHLID at the foraminal site. The findings suggest that contrast MG with nonionic water-soluble agents is a rather effective technique in the diagnosis of PHLID

  15. Continuous lumbar hemilaminectomy for intervertebral disc disease in an Amur tiger (Panthera tigris altaica).

    Science.gov (United States)

    Flegel, Thomas; Böttcher, Peter; Alef, Michaele; Kiefer, Ingmar; Ludewig, Eberhard; Thielebein, Jens; Grevel, Vera

    2008-09-01

    A 13-yr-old Amur tiger (Panthera tigris altaica) was presented for an acute onset of paraplegia. Spinal imaging that included plain radiographs, myelography, and computed tomography performed under general anesthesia revealed lateralized spinal cord compression at the intervertebral disc space L4-5 caused by intervertebral disc extrusion. This extrusion was accompanied by an extensive epidural hemorrhage from L3 to L6. Therefore, a continuous hemilaminectomy from L3 to L6 was performed, resulting in complete decompression of the spinal cord. The tiger was ambulatory again 10 days after the surgery. This case suggests that the potential benefit of complete spinal cord decompression may outweigh the risk of causing clinically significant spinal instability after extensive decompression.

  16. Calcification of intervertebral discs in the Dachshund: An estimation of heritability

    Energy Technology Data Exchange (ETDEWEB)

    Stigen, Ø. [Norges Veterinaerhoegskole, Oslo (Norway); Christensen, K.

    1993-07-01

    The heritability of calcified intervertebral discs in the dachshund was estimated using data gathered from a radiographic study. Radiographs of the vertebral columns of 274 clinically normal, 12 to 18 months old dachshunds, were examined. The dogs were offspring from 75 different sires, representing the same number of half sib groups. There were 2 to 14 offspring in each half-sib group. The number of full sib groups was 81. Calcified intervertebral discs were identified in 20.4% of the dogs. An analysis of variance that used the data as a continuous and as an either/or-variable estimated the heritability of calcified discs to be 0.22 and 0.15 respectively. A genetic factor was found to be essential for the occurrence of calcified discs in a dog while a common environmental factor presumably resulting from non-genetic causes was significant in determining the number of discs to undergo calcification in affected dogs.

  17. Remodelamento da matriz extracelular em degeneração experimental do disco intervertebral

    OpenAIRE

    Oliveira,Cintia Pereira de; Rodrigues,Luciano Miller Reis; Fregni,Maria Vitória Ventura Dias; Gotfryd,Alberto; Made,Ana Maria; Pinhal,Maria Aparecida da Silva

    2013-01-01

    OBJETIVO: Avaliar a remodelação da matriz extracelular na degeneração do disco intervertebral através do modelo experimental degeneração do disco intervertebral. MÉTODOS: O modelo de indução da degeneração discal, utilizando agulha 20G e rotação de 360º, foi aplicado por 30 segundos entre a sexta/sétima e oitava / nona vértebras coccígeas de ratos machos da linhagem Wistar. O nível intermediário, entre a sétima e oitava vértebras, foi tomado como controle, não sendo submetido à punção. A dist...

  18. Evaluation on vertebral endplate injury and adjacent intervertebral disk injury of patients with osteoporotic vertebral compression fractures by MRI and its clinical significance

    International Nuclear Information System (INIS)

    Shen Yu; Shen Huiliang; Fang Xiutong; Zhang Wenbo

    2012-01-01

    Objective: To investigate the relationship between vertebral endplate injury and adjacent intervertebral disk injury of patients with acute or sub-acute osteoporotic vertebral compression fractures (OVC-F) by MRI, and to provide basis for diagnosis of OVCF. Methods: The clinical data of a total of 66 patients with OVCF underwent vertebroplasty (76 fracture of vertebral bodies) were selected. The vertebral endplate injury and adjacent intervertebral disk injury of OVCF patients were detected by MRI. Results: There were 57 vertebral endplate injury in 76 fracture vertebral bodies (75% ). There were only 27 vertebral bodies with vertebral endplate injury in 57 fracture vertebral bodies with endplate injury (47% ), and 22 vertebral with superior and inferior vertebral endplate injury (39% ), and 8 vertebral bodies with inferior vertebral endplate injury (14% ). There were 48 vertebral bodies with intervertebral disc injury in 76 fracture vertebral bodies (63% ). There were 22 intervertebral disc injury located above the fracture of the lumbar spine in 48 vertebral bodies with intervertebral disc injury (45% ), and 19 fracture vertebral bodies with upper and lower intervertebral disc injury (40% ), and 7 intervertebral injuries located below the fracture of the lumbar spine (15% ). Conclusion: Vertebral endplate injury is frequently associated with the adjacent intervertebral disk injury. The clinical diagnosis and treatment should be emphasized in the fracture vertebral endplate damage and adjacent intervertebral disc injury. (authors)

  19. Relationships between Paraspinal Muscle Activity and Lumbar Inter-Vertebral Range of Motion

    OpenAIRE

    du Rose, Alister; Breen, Alan

    2016-01-01

    Abstract: Control of the lumbar spine requires contributions from both the active and passive sub-systems. Identifying interactions between these systems may provide insight into the mechanisms of low back pain. However, as a first step it is important to investigate what is normal. The purpose of this study was to explore the relationships between the lumbar inter-vertebral range of motion and paraspinal muscle activity during weight-bearing flexion in healthy controls using quantitative flu...

  20. Imaging of degenerative lumbar intervertebral discs; linking anatomy, pathology and imaging.

    Science.gov (United States)

    Adams, Ashok; Roche, Oran; Mazumder, Asif; Davagnanam, Indran; Mankad, Kshitij

    2014-09-01

    Low back pain is a common medical condition that has significant implications for healthcare providers and the UK economy. Low back pain can be classified as 'specific' in which an underlying pathophysiological mechanism is identified (eg, herniated intervertebral disc). Advanced imaging should be performed in this situation and in those patients in whom systemic disease is strongly suspected. In the majority (approximately 90%), low back pain in 'non specific' and there is a weak correlation with imaging abnormalities. This is an area of ongoing research and remains controversial in terms of imaging approach and treatment (eg, theory of discogenic pain, interpretation and treatment of endplate changes). With regards Modic endplate changes, current research suggests that an infective component may be involved that may identify novel potential treatments in patients with chronic low back pain refractory to other treatment modalities. MRI is the imaging modality of choice for the assessment of degenerative changes in intervertebral discs. MRI has superior soft tissue contrast resolution when compared to other imaging modalities (eg, plain radiography, CT). An understanding of normal anatomy and MR appearances of intervertebral discs, particularly with regards to how these appearances change with advancing age, is required to aid image interpretation. Knowledge of the spectrum of degenerative processes that may occur in the intervertebral discs is required in order to identify and explain abnormal MRI appearances. As the communication of MRI findings may guide therapeutic decision making and surgical intervention, the terminology used by radiologists must be accurate and consistent. Therefore, description of degenerative disc changes in the current paper is based on the most up-to-date recommendations, the aim being to aid reporting by radiologists and interpretation of reports by referring clinicians. Published by the BMJ Publishing Group Limited. For permission to

  1. Quantifying the effect of intervertebral cartilage on neutral posture in the necks of sauropod dinosaurs

    OpenAIRE

    Taylor, Michael P.

    2014-01-01

    Attempts to reconstruct the neutral neck posture of sauropod dinosaurs, or indeed any tetrapod, are doomed to failure when based only on the geometry of the bony cervical vertebrae. The thickness of the articular cartilage between the centra of adjacent vertebrae affects posture. It extends (raises) the neck by an amount roughly proportional to the thickness of the cartilage. It is possible to quantify the angle of extension at an intervertebral joint: it is roughly equal, in radians, to the ...

  2. Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc.

    Science.gov (United States)

    Teixeira, Graciosa Q; Leite Pereira, Catarina; Castro, Flávia; Ferreira, Joana R; Gomez-Lazaro, Maria; Aguiar, Paulo; Barbosa, Mário A; Neidlinger-Wilke, Cornelia; Goncalves, Raquel M

    2016-09-15

    Intervertebral disc (IVD) degeneration is one of the most common causes of low back pain (LBP), the leading disorder in terms of years lived with disability. Inflammation can play a role in LPB, while impairs IVD regeneration. In spite of this, different inflammatory targets have been purposed in the context of IVD regeneration. Anti-inflammatory nanoparticles (NPs) of Chitosan and Poly-(γ-glutamic acid) with a non-steroidal anti-inflammatory drug, diclofenac (Df), were previously shown to counteract a pro-inflammatory response of human macrophages. Here, the effect of intradiscal injection of Df-NPs in degenerated IVD was evaluated. For that, Df-NPs were injected in a bovine IVD organ culture in pro-inflammatory/degenerative conditions, upon stimulation with needle-puncture and interleukin (IL)-1β. Df-NPs were internalized by IVD cells, down-regulating IL-6, IL-8, MMP1 and MMP3, and decreasing PGE2 production, compared with IL-1β-stimulated IVD punches. Interestingly, at the same time, Df-NPs promoted an up-regulation of extracellular matrix (ECM) proteins, namely collagen type II and aggrecan. Allover, this study suggests that IVD treatment with Df-NPs not only reduces inflammation, but also delays and/or decreases ECM degradation, opening perspectives to new intradiscal therapies for IVD degeneration, based on the modulation of inflammation. Degeneration of the IVD is an age-related progressive process considered to be the major cause of spine disorders. The pro-inflammatory environment and biomechanics of the degenerated IVD is a challenge for regenerative therapies. The novelty of this work is the intradiscal injection of an anti-inflammatory therapy based on Chitosan (Ch)/Poly-(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) with an anti-inflammatory drug (diclofenac, Df), previously developed by us. This drug delivery system was tested in a pro-inflammatory/degenerative intervertebral disc ex vivo model. The main findings support the success of an anti

  3. Treatment of intervertebral disc degenerative disease using percutaneous nucleotomy–an overview of less invasive procedures

    Directory of Open Access Journals (Sweden)

    Miran Jeromel

    2014-04-01

    Full Text Available Background: Less invasive treatment methods for intervertebral disc disease and decompression of neural structures as a consequence of contained disc herniation represent an alternative to surgical procedure. Percutaneus nucleotomy uses a percutaneous approach to the intervertebral disc. The article presents the evolution of numerous procedureds in clinical practice.Methods: Percutaneous nucleoplasty is a fluoroscopy-guided procedure which enables controlled and safe entrance into the intervertebral disc. The procedure is performed under strict aseptic conditions, using a local anaesthesia with the patient under analgosedation. Based on the principle of therapeutic intradiscal action, the procedures can be divided into three groups: chemical (chemonucleolysis with chimopapain, alcohol, ozone, mechanical (automated percutaneous lumbar discectomy – APLD, arthroscopic discectomy and thermical methods (laser, radiofrequency ablation, intradiscal electrothermal annuloplasty – IDET, Coblation®.Results: Percutaneous nucleotomy by the majority of the mentioned procedures results in a therapeutic effect (reduction of pain and decompression of neural structures. Fast recovery represents a major advantage of less invasive treatment.Conclusions: Less invasive method (nucleotomy using different procedures represents a successful alternative approach to surgical discectomy. Proper patient selection and safe technique are mandatory in order to achieve a good clinical outcome.

  4. Evaluation of effects of selected factors on inter-vertebral fusion-a simulation study.

    Science.gov (United States)

    Wang, Xiaobo; Dumas, Geneviève A

    2005-04-01

    This study simulated the effects of inter-vertebral disc degeneration and bone density distribution on the structural stiffness and strength provided by inter-vertebral fusion. Based on the original and redistributed bone density distributions, the effects of selected factors, including contact area between device/graft and vertebral endplates, endplate conditions, and bone growth capacity were evaluated using a factorial design of experiment. The simulation results suggested that the degeneration of inter-vertebral disc significantly affected the bone density and density distribution in adjacent vertebrae. The mechanical strength immediately after instrumentation is the worst case of device/graft subsidence. After that procedure, bone will adapt itself to the changed loading conditions and therefore reduce the risk of subsidence. A deficiency in structural stiffness immediately after instrumentation could be the "worst-case scenario" depending on the combinations of selected factors. The simulation results demonstrated that the contact area and initial bone density distribution should be considered jointly while estimating the risk of device/graft subsidence. The endplate condition is a secondary factor on the subsidence risk, compared with the contact area and initial bone density distribution.

  5. Quantitative evaluation of degenerative lumbar intervertebral disc applying an equivalent cross-relaxation rate using MRI

    International Nuclear Information System (INIS)

    Obata, Hideaki; Inaba, Tadashi; Kato, Takaya; Tokuda, Masataka; Matsushima, Shigeru; Yamada, Michiaki; Kinosada, Yasutomi

    2004-01-01

    The equivalent cross-relaxation rate (ECR) is a measurement method to evaluate a change in organizational structure quantitatively utilizing MRI. The objectives of this study are to understand the characteristics related to water contents in degenerative lumbar intervertebral discs, and to investigate the usefulness of quantitative evaluation using ECR in order to find as early as possible disordered discs. Seven normal volunteers and four asymptomatic volunteers with degeneration in lumbar intervertebral discs, 21 to 26 years of age, were studied using a SIGNA model of GE Medical Systems equipped with a 1.5 T clinical scanner and spine coil. The ECR values were defined as the percentage of signal loss between unsaturated and saturated images. The results showed that the ECR value of annulus fibrosus in an intervertebral disc was higher than nucleus pulposus. Furthermore, it was found that the ECR value of nucleus pulposus (L5-S1) with degeneration was significantly higher than that without degeneration. It was considered that this result reflected an increase of water contents in the degenerative nucleus. This study suggests that the ECR value of a nucleus could be an effective parameter to diagnosis of degenerated discs or grades of disorder. (author)

  6. Follow-up radiographs of the cervical spine after anterior fusion with titanium intervertebral disc

    International Nuclear Information System (INIS)

    Biederer, J.; Hutzelmann, A.; Heller, M.; Rama, B.

    1999-01-01

    Purpose: We examined the postoperative changes of the cervical spine after treatment of cervical nerve root compression with anterior cervical discectomy and fusion with a new titanium intervertebral disc. Patients and Methods: 37 patients were examined prior to, as well as 4 days, 6 weeks, and 7 months after surgery. Lateral view X-rays and functional imaging were used to evaluate posture and mobility of the cervical spine, the position of the implants, and the reactions of adjacent bone structures. Results: Implantation of the titanium disc led to post-operative distraction of the intervertebral space and slight lordosis. Within the first 6 months a slight loss of distraction and re-kyphosis due to impression of the implants into the vertebral end-plates were found in all patients. We noted partial infractions into the vertebral end-plates in 10/42 segments and slight mobility of the implants in 14/42 segments. Both groups of patients showed reactive spondylosis and local symptoms due to loosening of the implants. The pain subsided after onset of bone bridging and stable fixation of the loosened discs. Conclusions: The titanium intervertebral disc provides initial distraction of the fusioned segments with partial recurrence of kyphosis during the subsequent course. Loosening of the implants with local symptoms can be evaluated with follow-up X-rays and functional imaging. (orig.) [de

  7. Protective effects of cannabidiol on lesion-induced intervertebral disc degeneration.

    Directory of Open Access Journals (Sweden)

    João W Silveira

    Full Text Available Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content. Cannabidiol is the main non-psychotropic component of the Cannabis sativa with protective and anti-inflammatory properties. However, possible therapeutic effects of cannabidiol on intervertebral disc degeneration have not been investigated yet. The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI and histological analyses. Disc injury was induced in the tail of male Wistar rats via a single needle puncture. The discs selected for injury were punctured percutaneously using a 21-gauge needle. MRI and histological evaluation were employed to assess the results. The effects of intradiscal injection of cannabidiol (30, 60 or 120 nmol injected immediately after lesion were analyzed acutely (2 days by MRI. The experimental group that received cannabidiol 120 nmol was resubmitted to MRI examination and then to histological analyses 15 days after lesion/cannabidiol injection. The needle puncture produced a significant disc injury detected both by MRI and histological analyses. Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration.

  8. Effects of intervertebral disc disorders of low back on the mandibular kinematic: kinesiographic study.

    Science.gov (United States)

    Spadaro, Alessandro; Ciarrocchi, Irma; Masci, Chiara; Cozzolino, Vincenzo; Monaco, Annalisa

    2014-08-26

    Intervertebral disc disorders are one of the most common causes of low back pain. Neuromuscular dysfunction frequently is present in patients with lumbar disc herniation.When considering joint dysfunction, it is important to remember that the spine functions as a unit. Dysfunction on one level can trigger compensatory changes in other spinal levels or in other areas of the musculoskeleton. Findings demonstrated the relationship between stomatognathic and postural systems justifying the hypothesis that muscular-skeletal impairment in one system could affect the other one. However, evidence that a lumbar intervertebral disc herniation could influence the mandibular kinematics is still lacking. Aim of this study was to analyse the effects that intervertebral disc herniation of low back could have on the mandibular kinematics. Kinesiographic evaluations of the mandibular dynamics of 23 adult patients suffering L4/L5 and L5/S1 lumbosacral disc hernation were compared with a non pathological control group. A statistically significant difference of maximal mouth opening (p mandibular kinematics both in rate and quality of movement. The study suggests the existence of connections between masticatory system and lumbar disk herniation.

  9. Comparison between cranial thoracic intervertebral disc herniations in German Shepherd dogs and other large breed dogs.

    Science.gov (United States)

    Gaitero, Luis; Nykamp, Stephanie; Daniel, Rob; Monteith, Gabrielle

    2013-01-01

    Cranial thoracic intervertebral disc herniations have been reported to be rare in dogs due to the presence of the intercapital ligament, however some studies have proposed they may not be uncommon in German Shepherd dogs. The purpose of this retrospective study was to compare cranial thoracic intervertebral disc herniations in German Shepherd dogs and other large breed dogs (control group). Medical records at the Ontario Veterinary College were searched for German Shepherd dogs and other large breed dogs that had magnetic resonance imaging studies including the T1-T9 region. For each dog and each disc space from T1-T9, three variables (compression, disc degeneration, and herniation) were recorded and graded based on review of sagittal T2-weighted images. Twenty-three German Shepherd dogs and 47 other large breed dogs met inclusion criteria. The German Shepherd dog group had higher scores than the control group for compression (P = 0.0099) and herniation (P dog group, intervertebral discs T2-T3 and T4-T5 had an increased risk for compression and T3-T4 had an increased risk for compression and herniation. Findings from this study indicated that German Shepherd dogs may be more likely than other large breed dogs to have spinal cord compression due to cranial thoracic disc herniations. Imaging of the cranial thoracic spine, including T2-T3, is recommended for German Shepherd dogs with T3-L3 neurological signs. © 2012 Veterinary Radiology & Ultrasound.

  10. Formation, function, and exhaustion of notochordal cytoplasmic vacuoles within intervertebral disc: current understanding and speculation

    Science.gov (United States)

    Sinkemani, Arjun; Xie, Zhi-Yang; Shi, Rui; Wei, Ji-Nan; Wu, Xiao-Tao

    2017-01-01

    Notochord nucleus pulposus cells are characteristic of containing abundant and giant cytoplasmic vacuoles. This review explores the embryonic formation, biological function, and postnatal exhaustion of notochord vacuoles, aiming to characterize the signal network transforming the vacuolated nucleus pulposus cells into the vacuole-less chondrocytic cells. Embryonically, the cytoplasmic vacuoles within vertebrate notochord originate from an evolutionarily conserved vacuolation process during neurulation, which may continue to provide mechanical and signal support in constructing a mammalian intervertebral disc. For full vacuolation, a vacuolating specification from dorsal organizer cells, synchronized convergent extension, well-structured notochord sheath, and sufficient post-Golgi trafficking in notochord cells are required. Postnatally, age-related and species-specific exhaustion of vacuolated nucleus pulposus cells could be potentiated by Fas- and Fas ligand-induced apoptosis, intolerance to mechanical stress and nutrient deficiency, vacuole-mediated proliferation check, and gradual de-vacuolation within the avascular and compression-loaded intervertebral disc. These results suggest that the notochord vacuoles are active and versatile organelles for both embryonic notochord and postnatal nucleus pulposus, and may provide novel information on intervertebral disc degeneration to guide cell-based regeneration. PMID:28915712

  11. Matrix Remodeling During Intervertebral Disc Growth and Degeneration Detected by Multichromatic FAST Staining

    Science.gov (United States)

    Leung, Victor Y.L.; Chan, Wilson C.W.; Hung, Siu-Chun; Cheung, Kenneth M.C.; Chan, Danny

    2009-01-01

    Various imaging techniques have been used to assess degeneration of the intervertebral disc, including many histological methods, but cartilage-oriented histological stains do not clearly show the comparatively complex structures of the disc. In addition, there is no integrated method to assess efficiently both the compartmental organization and matrix composition in disc samples. In this study, a novel histological method, termed FAST staining, has been developed to investigate disc growth and degeneration by sequential staining with fast green, Alcian blue, Safranin-O, and tartrazine to generate multichromatic histological profiles (FAST profiles). This identifies the major compartments of the vertebra-disc region, including the cartilaginous endplate and multiple zones of the annulus fibrosus, by specific FAST profile patterns. A disc degeneration model in rabbit established using a previously described puncture method showed gradual but profound alteration of the FAST profile during disc degeneration, supporting continual alteration of glycosaminoglycan. Changes of the FAST profile pattern in the nucleus pulposus and annulus fibrosus of the postnatal mouse spine suggested matrix remodeling activity during the growth of intervertebral discs. In summary, we developed an effective staining method capable of defining intervertebral disc compartments in detail and showing matrix remodeling events within the disc. The FAST staining method may be used to develop a histopathological grading system to evaluate disc degeneration or malformation. (J Histochem Cytochem 57:249–256, 2009) PMID:19001641

  12. Protein methylation reactions in intact pea chloroplasts

    International Nuclear Information System (INIS)

    Niemi, K.J.

    1989-01-01

    Post-translational protein methylation was investigated in Pisum sativum chloroplasts. Intact pea chloroplasts were incubated with ( 3 H-methyl)-S-adenosylmethionine under various conditions. The chloroplasts were then separated into stromal and thylakoid fractions and analyzed for radioactivity transferred to protein. Light enhanced the magnitude of labeling in both fractions. One thylakoid polypeptide with an apparent molecular mass of 43 kDa was labeled only in the light. Several other thylakoid and stromal proteins were labeled in both light and dark-labeling conditions. Both base-labile methylation, carboxy-methylesters and base-stable groups, N-methylations were found. Further characterization of the methyl-transfer reactions will be presented

  13. A new infusion pathway intactness monitoring system.

    Science.gov (United States)

    Ogawa, Hidekuni; Yonezawa, Yoshiharu; Maki, Hiromichi; Ninomiya, Ishio; Sata, Koji; Hamada, Shingo; Caldwell, W Morton

    2006-01-01

    A new infusion pathway monitoring system has been developed for hospital and home use. The system consists of linear integrated circuits and a low-power 8-bit single chip microcomputer which constantly monitors the infusion pathway intactness. An AC (alternating current) voltage is induced on the patient's body by electrostatic coupling from the normal 100 volt, 60 Hz AC power line wiring field in the patient's room. The induced AC voltage can be recorded by a main electrode wrapped around the infusion polyvinyl chloride tube. A reference electrode is wrapped on the electrode to monitor the AC voltage around the main electrode. If the injection needle or infusion tube becomes detached, then the system detects changes in the induced AC voltages and alerts the nursing station, via the nurse call system or PHS (personal handy phone system).

  14. EXPRESSION AND CHARACTERIZATION OF FULL-LENGTH HUMAN HEME OXYGENASE-1: PRESENCE OF INTACT MEMBRANE-BINDING REGION LEADS TO INCREASED BINDING AFFINITY FOR NADPH-CYTOCHROME P450 REDUCTASE

    Science.gov (United States)

    Huber, Warren J.; Backes, Wayne L.

    2009-01-01

    Heme oxygenase (HO) is the chief regulatory enzyme in the oxidative degradation of heme to biliverdin. In the process of heme degradation, this NADPH and cytochrome P450 reductase (CPR)-dependent oxidation of heme also releases free iron and carbon monoxide. Much of the recent research involving heme oxygenase is done using a 30-kDa soluble form of the enzyme, which lacks the membrane binding region (C-terminal 23 amino acids). The goal of this study was to express and purify a full-length human HO-1 (hHO-1) protein; however, due to the lability of the full-length form, a rapid purification procedure was required. This was accomplished by use of a GST-tagged hHO-1 construct. Although the procedure permitted the generation of a full-length HO-1, this form was contaminated with a 30-kDa degradation product that could not be eliminated. Therefore, we attempted to remove a putative secondary thrombin cleavage site by a conservative mutation of amino acid 254, which replaces lysine with arginine. This mutation allowed the expression and purification of a full length hHO-1 protein. Unlike wild-type HO-1, the K254R mutant could be purified to a single 32-kDa protein capable of degrading heme at the same rate as the wild-type enzyme. The K254R full-length form had a specific activity of ~200–225 nmol bilirubin hr−1nmol−1 HO-1 as compared to ~140–150 nmol bilirubin hr−1nmol−1 for the WT form, which contains the 30-kDa contaminant. This is a 2–3-fold increase from the previously reported soluble 30-kDa HO-1, suggesting that the C-terminal 23 amino acids are essential for maximal catalytic activity. Because the membrane spanning domain is present, the full-length hHO-1 has the potential to incorporate into phospholipid membranes, which can be reconstituted at known concentrations, in combination with other ER-resident enzymes. PMID:17915953

  15. Expression and characterization of full-length human heme oxygenase-1: the presence of intact membrane-binding region leads to increased binding affinity for NADPH cytochrome P450 reductase.

    Science.gov (United States)

    Huber, Warren J; Backes, Wayne L

    2007-10-30

    Heme oxygenase-1 (HO-1) is the chief regulatory enzyme in the oxidative degradation of heme to biliverdin. In the process of heme degradation, HO-1 receives the electrons necessary for catalysis from the flavoprotein NADPH cytochrome P450 reductase (CPR), releasing free iron and carbon monoxide. Much of the recent research involving heme oxygenase has been done using a 30 kDa soluble form of the enzyme, which lacks the membrane binding region (C-terminal 23 amino acids). The goal of this study was to express and purify a full-length human HO-1 (hHO-1) protein; however, due to the lability of the full-length form, a rapid purification procedure was required. This was accomplished by use of a glutathione-s-transferase (GST)-tagged hHO-1 construct. Although the procedure permitted the generation of a full-length HO-1, this form was contaminated with a 30 kDa degradation product that could not be eliminated. Therefore, attempts were made to remove a putative secondary thrombin cleavage site by a conservative mutation of amino acid 254, which replaces arginine with lysine. This mutation allowed the expression and purification of a full-length hHO-1 protein. Unlike wild type (WT) HO-1, the R254K mutant could be purified to a single 32 kDa protein capable of degrading heme at the same rate as the WT enzyme. The R254K full-length form had a specific activity of approximately 200-225 nmol of bilirubin h-1 nmol-1 HO-1 as compared to approximately 140-150 nmol of bilirubin h-1 nmol-1 for the WT form, which contains the 30 kDa contaminant. This is a 2-3-fold increase from the previously reported soluble 30 kDa HO-1, suggesting that the C-terminal 23 amino acids are essential for maximal catalytic activity. Because the membrane-spanning domain is present, the full-length hHO-1 has the potential to incorporate into phospholipid membranes, which can be reconstituted at known concentrations, in combination with other endoplasmic reticulum resident enzymes.

  16. Transbilayer distribution and mobility of phosphatidylcholine in intact erythrocyte membranes. A study with phosphatidylcholine exchange protein

    NARCIS (Netherlands)

    van Meer, G.; Poorthuis, B. J.; Wirtz, K. W.; Op den Kamp, J. A.; van Deenen, L. L.

    1980-01-01

    1. The exchange of phosphatidylcholine between intact human or rat erythrocytes and rat liver microsomes was greatly stimulated by phosphatidylcholine-specific exchange proteins from rat liver and beef liver. It was found, however, that compared to the exchange reaction between phospholipid vesicles

  17. Transbilayer distribution and mobility of phosphatidylcholine in intact erythrocyte membranes. A study with phosphatidylcholine exchange protein

    NARCIS (Netherlands)

    van Meer, G.|info:eu-repo/dai/nl/068570368; Poorthuis, B.J.H.M.; Wirtz, K.W.A.|info:eu-repo/dai/nl/068427956; op den Kamp, J.A.F.; van Deenen, L.L.M.

    1980-01-01

    The exchange of phosphatidylcholine between intact human or rat erythrocytes and rat liver microsomes was greatly stimulated by phosphatidylcholine-specific exchange proteins from rat liver and beef liver. It was found, however, that compared to the exchange reaction between phospholipid vesicles

  18. A Systematic Review of Mesenchymal Stem Cells in Spinal Cord Injury, Intervertebral Disc Repair and Spinal Fusion.

    Science.gov (United States)

    Khan, Shujhat; Mafi, Pouya; Mafi, Reza; Khan, Wasim

    2018-01-01

    Spinal surgery presents a challenge for both neurosurgery and orthopaedic surgery. Due to the heterogeneous differentiation potential of mesenchymal stem cells, there is much interest in the treatment of spine surgery. Animal and human trials focussing on the efficacy of mesenchymal stem cells in spinal cord injury, spine fusion and disc degeneration were included in this systematic review. Published articles up to January 2016 from MEDLINE, PubMed and Ovid were used by searching for specific terms. Of the 2595 articles found, 53 met the selection criteria and were included for analysis (16 on spinal cord injury, 28 on intervertebral disc repair and 9 on spinal fusion). Numerous studies reported better results when the mesenchymal stem cells were used in co-culture with other cells or used in scaffolds. Mesenchymal stem cells were also found to have an immune-modulatory role, which can improve surgical outcome. This systematic review suggests that mesenchymal stem cells can be used safely and effectively for these spinal surgery treatments. Whilst, in certain studies, mesenchymal stem cells did not necessarily show improved results from existing treatments, they provide an alternative option. This can reduce morbidity that arises from current surgical treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Acidic pH promotes intervertebral disc degeneration: Acid-sensing ion channel -3 as a potential therapeutic target.

    Science.gov (United States)

    Gilbert, Hamish T J; Hodson, Nathan; Baird, Pauline; Richardson, Stephen M; Hoyland, Judith A

    2016-11-17

    The aetiology of intervertebral disc (IVD) degeneration remains poorly understood. Painful IVD degeneration is associated with an acidic intradiscal pH but the response of NP cells to this aberrant microenvironmental factor remains to be fully characterised. The aim here was to address the hypothesis that acidic pH, similar to that found in degenerate IVDs, leads to the altered cell/functional phenotype observed during IVD degeneration, and to investigate the involvement of acid-sensing ion channel (ASIC) -3 in the response. Human NP cells were treated with a range of pH, from that of a non-degenerate (pH 7.4 and 7.1) through to mildly degenerate (pH 6.8) and severely degenerate IVD (pH 6.5 and 6.2). Increasing acidity of pH caused a decrease in cell proliferation and viability, a shift towards matrix catabolism and increased expression of proinflammatory cytokines and pain-related factors. Acidic pH resulted in an increase in ASIC-3 expression. Importantly, inhibition of ASIC-3 prevented the acidic pH induced proinflammatory and pain-related phenotype in NP cells. Acidic pH causes a catabolic and degenerate phenotype in NP cells which is inhibited by blocking ASIC-3 activity, suggesting that this may be a useful therapeutic target for treatment of IVD degeneration.

  20. Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc.

    Science.gov (United States)

    Mwale, F; Roughley, P; Antoniou, J

    2004-12-15

    Tissue engineering of intervertebral discs (IVD) using mesenchymal stem cells (MSCs) induced to differentiate into a disc-cell phenotype has been considered as an alternative treatment for disc degeneration. However, since there is no unique marker characteristic of discs and since hyaline cartilage and immature nucleus pulposus (NP) possess similar macromolecules in their extracellular matrix, it is currently difficult to recognize MSC conversion to a disc cell. This study was performed to compare the proteoglycan to collagen ratio (measured as GAG to hydroxyproline ratio) in the NP of normal disc to that of the hyaline cartilage of the endplate within the same group of individuals and test the hypothesis that this ratio can be used for in vivo studies to distinguish between a normal NP and hyaline cartilage phenotype. Whole human lumbar spine specimens from fresh cadavers, ranging in age from 12 weeks to 79 years, were used to harvest the IVDs and adjacent endplates. The GAG to hydroxyproline ratio within the NP of young adults is approximately 27:1, whereas the ratio within the hyaline cartilage endplate of the same aged individuals is about 2:1. The production of an extracellular matrix with a high proteoglycan to collagen ratio can be used in vivo to distinguish NP cells from chondrocytes, and could help in identifying a NP-like phenotype in vivo as opposed to a chondrocyte when MSCs are induced to differentiate for tissue engineering of a disc.

  1. Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc

    Directory of Open Access Journals (Sweden)

    Mwale F.

    2004-12-01

    Full Text Available Tissue engineering of intervertebral discs (IVD using mesenchymal stem cells (MSCs induced to differentiate into a disc-cell phenotype has been considered as an alternative treatment for disc degeneration. However, since there is no unique marker characteristic of discs and since hyaline cartilage and immature nucleus pulposus (NP possess similar macromolecules in their extracellular matrix, it is currently difficult to recognize MSC conversion to a disc cell. This study was performed to compare the proteoglycan to collagen ratio (measured as GAG to hydroxyproline ratio in the NP of normal disc to that of the hyaline cartilage of the endplate within the same group of individuals and test the hypothesis that this ratio can be used for in vivo studies to distinguish between a normal NP and hyaline cartilage phenotype. Whole human lumbar spine specimens from fresh cadavers, ranging in age from 12 weeks to 79 years, were used to harvest the IVDs and adjacent endplates. The GAG to hydroxyproline ratio within the NP of young adults is approximately 27:1, whereas the ratio within the hyaline cartilage endplate of the same aged individuals is about 2:1. The production of an extracellular matrix with a high proteoglycan to collagen ratio can be used in vivo to distinguish NP cells from chondrocytes, and could help in identifying a NP-like phenotype in vivo as opposed to a chondrocyte when MSCs are induced to differentiate for tissue engineering of a disc.

  2. Precision of lumbar intervertebral measurements: does a computer-assisted technique improve reliability?

    Science.gov (United States)

    Pearson, Adam M; Spratt, Kevin F; Genuario, James; McGough, William; Kosman, Katherine; Lurie, Jon; Sengupta, Dilip K

    2011-04-01

    Comparison of intra- and interobserver reliability of digitized manual and computer-assisted intervertebral motion measurements and classification of "instability." To determine if computer-assisted measurement of lumbar intervertebral motion on flexion-extension radiographs improves reliability compared with digitized manual measurements. Many studies have questioned the reliability of manual intervertebral measurements, although few have compared the reliability of computer-assisted and manual measurements on lumbar flexion-extension radiographs. Intervertebral rotation, anterior-posterior (AP) translation, and change in anterior and posterior disc height were measured with a digitized manual technique by three physicians and by three other observers using computer-assisted quantitative motion analysis (QMA) software. Each observer measured 30 sets of digital flexion-extension radiographs (L1-S1) twice. Shrout-Fleiss intraclass correlation coefficients for intra- and interobserver reliabilities were computed. The stability of each level was also classified (instability defined as >4 mm AP translation or 10° rotation), and the intra- and interobserver reliabilities of the two methods were compared using adjusted percent agreement (APA). Intraobserver reliability intraclass correlation coefficients were substantially higher for the QMA technique THAN the digitized manual technique across all measurements: rotation 0.997 versus 0.870, AP translation 0.959 versus 0.557, change in anterior disc height 0.962 versus 0.770, and change in posterior disc height 0.951 versus 0.283. The same pattern was observed for interobserver reliability (rotation 0.962 vs. 0.693, AP translation 0.862 vs. 0.151, change in anterior disc height 0.862 vs. 0.373, and change in posterior disc height 0.730 vs. 0.300). The QMA technique was also more reliable for the classification of "instability." Intraobserver APAs ranged from 87 to 97% for QMA versus 60% to 73% for digitized manual

  3. Comparison of Intact PTH and Bio-Intact PTH Assays Among Non-Dialysis Dependent Chronic Kidney Disease Patients.

    Science.gov (United States)

    Einbinder, Yael; Benchetrit, Sydney; Golan, Eliezer; Zitman-Gal, Tali

    2017-09-01

    The third-generation bio-intact parathyroid hormone (PTH) (1-84) assay was designed to overcome problems associated with the detection of C-terminal fragments by the second-generation intact PTH assay. The two assays have been compared primarily among dialysis populations. The present study evaluated the correlations and differences between these two PTH assays among patients with chronic kidney disease (CKD) stages 3 to 5 not yet on dialysis. Blood samples were collected from 98 patients with CKD stages 3 to 5. PTH concentrations were measured simultaneously by using the second-generation - PTH intact-STAT and third-generation bio-intact 1-84 PTH assays. Other serum biomarkers of bone mineral disorders were also assessed. CKD stage was calculated by using the CKD-Epidemiology Collaboration (EPI) formula. Serum bio-intact PTH concentrations were strongly correlated but significantly lower than the intact PTH concentrations (r=0.963, Pbio-intact PTH) positively correlated with urea (r=0.523, r=0.504; P=0.002, respectively), phosphorus (r=0.532, r=0.521; Pbio-intact PTH assay detected significantly lower PTH concentrations compared with intact PTH assay. Additional studies that correlate the diagnosis and management of CKD mineral and bone disorders with bone histomorphometric findings are needed to determine whether bio-intact PTH assay results are better surrogate markers in these early stages of CKD. © The Korean Society for Laboratory Medicine

  4. The effect of ex vivo flexion and extension on intervertebral foramina dimensions in the equine cervical spine.

    Science.gov (United States)

    Sleutjens, J; Voorhout, G; Van Der Kolk, J H; Wijnberg, I D; Back, W

    2010-11-01

    In dressage, the head and neck position has become an issue of concern as certain extreme positions may imply a welfare risk for the horse. In man, extension and flexion of the cervical spine cause a decrease and increase in intervertebral foramina dimensions, respectively. However, in horses, the influence of flexion and extension on foramina dimensions and its possible interference with peripheral nerve functioning remains unknown. To determine the effect of ex vivo flexion and extension on intervertebral foramina dimensions in the equine cervical spine. Computed tomography was performed on 6 cadaver cervical spines from adult Warmblood horses subjected to euthanasia for reasons unrelated to cervical spine abnormalities, in a neutral position, in 20 and 40° extension, and in 20 and 40° flexion. Multiplanar reconstructions were made to obtain transverse images perpendicular to the long axis of each pair of intervertebral foramina from C2-T1. Intervertebral foramina dimensions were measured in the 5 positions. Compared to the neutral position, 40° extension caused a decrease in foramina dimensions at segments C4-C5, C5-C6, C6-C7 (P dimensions at segments C5-C6 (P dimensions at segments C4-T1, similar to that found in man. In vivo extension of the cervical spine could possibly interfere with peripheral nerve functioning at segments C4-T1. This effect may be even more profound in patients with a reduced intervertebral foramina space, for example in the presence of facet joint arthrosis. © 2010 EVJ Ltd.

  5. Pathophysiology of preterm labor with intact membranes.

    Science.gov (United States)

    Talati, Asha N; Hackney, David N; Mesiano, Sam

    2017-11-01

    Preterm labor with intact membranes is a major cause of spontaneous preterm birth (sPTB). To prevent sPTB a clear understanding is needed of the hormonal interactions that initiate labor. The steroid hormone progesterone acting via its nuclear progesterone receptors (PRs) in uterine cells is essential for the establishment and maintenance of pregnancy and disruption of PR signaling (i.e., functional progesterone/PR withdrawal) is key trigger for labor. The process of parturition is also associated with inflammation within the uterine tissues and it is now generally accepted that inflammatory stimuli from multiple extrinsic and intrinsic sources induce labor. Recent studies suggest inflammatory stimuli induce labor by affecting PR transcriptional activity in uterine cells to cause functional progesterone/PR withdrawal. Advances in understanding the functional interaction of inflammatory load on the pregnancy uterus and progesterone/PR signaling is opening novel areas of research and may lead to rational therapeutic strategies to effectively prevent sPTB. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Excitons in intact cells of photosynthetic bacteria.

    Science.gov (United States)

    Freiberg, Arvi; Pajusalu, Mihkel; Rätsep, Margus

    2013-09-26

    Live cells and regular crystals seem fundamentally incompatible. Still, effects characteristic to ideal crystals, such as coherent sharing of excitation, have been recently used in many studies to explain the behavior of several photosynthetic complexes, especially the inner workings of the light-harvesting apparatus of the oldest known photosynthetic organisms, the purple bacteria. To this date, there has been no concrete evidence that the same effects are instrumental in real living cells, leaving a possibility that this is an artifact of unnatural study conditions, not a real effect relevant to the biological operation of bacteria. Hereby, we demonstrate survival of collective coherent excitations (excitons) in intact cells of photosynthetic purple bacteria. This is done by using excitation anisotropy spectroscopy for tracking the temperature-dependent evolution of exciton bands in light-harvesting systems of increasing structural complexity. The temperature was gradually raised from 4.5 K to ambient temperature, and the complexity of the systems ranged from detergent-isolated complexes to complete bacterial cells. The results provide conclusive evidence that excitons are indeed one of the key elements contributing to the energetic and dynamic properties of photosynthetic organisms.

  7. Positive Youth Development, Life Satisfaction and Problem Behaviors of Adolescents in Intact and Non-Intact Families in Hong Kong

    Directory of Open Access Journals (Sweden)

    Daniel Tan Lei Shek

    2013-08-01

    Full Text Available This study investigated whether Chinese adolescents living in intact and non-intact families differed in their positive development, life satisfaction, and risk behavior. A total of 3,328 Secondary 1 students responded to measures of positive youth development (such as resilience and psychosocial competencies, life satisfaction, and risk behavior (substance abuse, delinquency, Internet addiction, consumption of pornographic materials, self-harm, and behavioral intention to engage in problem behavior. Findings revealed that adolescents growing up in intact families reported higher levels of positive developmental outcomes and life satisfaction as compared with adolescents from non-intact families. Adolescents in non-intact families also reported higher levels of risk behaviors than those growing up in intact families.

  8. Doença do disco intervertebral em trabalhadores da perfuração de petróleo Intervertebral disk disease among oil drilling workers

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Pereira Fernandes

    2000-09-01

    Full Text Available Estudo transversal em 1.026 trabalhadores em distrito de perfuração de petróleo do Nordeste brasileiro mostrou prevalência global de doença do disco intervertebral lombar de 5%, variando de 1,8% (atividades sem manuseio de carga, 4,5% (manuseio ocasional até 7,2% (manuseio habitual. Tal prevalência foi de 11,4% em operadores de sonda de perfuração de petróleo com mais de 40 anos de idade e de 10,5% naqueles com mais de 15 anos de empresa. A razão de prevalência (R.P. à associação entre trabalho em operação de sonda e doença do disco foi 2,3 (I.C. 95%: 1,3, 4,0. Para minimizar o efeito sobrevivência do trabalhador sadio foram usadas informações retrospectivas acerca da exposição. A informação referente à ocupação atual em lugar do histórico ocupacional resultaria em RP subestimada de 1,1 (I.C. 95%: 0,6, 1,9. A regressão logística ratificou os achados da análise tabular. Não houve confundimento nem interação. O incremento da indústria de petróleo no país e as alterações na gestão e contratação da força de trabalho implicam mudanças no gerenciamento de risco e controle de saúde, além de pronta intervenção ergonômica para controle da doença.A cross-sectional study among 1,026 oil drilling workers in Northeast Brazil found a prevalence rate of 5% for intervertebral disk disease, varying from 1.8% (activities without heavy lifting and 4.5% (occasional lifting to 7.2% (routine lifting. Disease prevalence was 10.5% among drilling workers with more than 15 years in the industry and 11.3% among those over 40 years of age. Prevalence ratio (PR for the association between working in oil drilling operations and intervertebral disk disease was 2.3 (95% CI: 1.3-4.0. Retrospective information about exposure was collected to minimize the healthy worker survival effect. Using information on current occupation instead of occupational life history would cause an underestimated PR of 1.1 (95% CI: 0.6-1.9. Logistic

  9. Measurement of intervertebral cervical motion by means of dynamic x-ray image processing and data interpolation.

    Science.gov (United States)

    Bifulco, Paolo; Cesarelli, Mario; Romano, Maria; Fratini, Antonio; Sansone, Mario

    2013-01-01

    Accurate measurement of intervertebral kinematics of the cervical spine can support the diagnosis of widespread diseases related to neck pain, such as chronic whiplash dysfunction, arthritis, and segmental degeneration. The natural inaccessibility of the spine, its complex anatomy, and the small range of motion only permit concise measurement in vivo. Low dose X-ray fluoroscopy allows time-continuous screening of cervical spine during patient's spontaneous motion. To obtain accurate motion measurements, each vertebra was tracked by means of image processing along a sequence of radiographic images. To obtain a time-continuous representation of motion and to reduce noise in the experimental data, smoothing spline interpolation was used. Estimation of intervertebral motion for cervical segments was obtained by processing patient's fluoroscopic sequence; intervertebral angle and displacement and the instantaneous centre of rotation were computed. The RMS value of fitting errors resulted in about 0.2 degree for rotation and 0.2 mm for displacements.

  10. Finite element study of a lumbar intervertebral disc nucleus replacement device

    Directory of Open Access Journals (Sweden)

    Jessica S Coogan

    2016-12-01

    Full Text Available Nucleus replacement technologies are a minimally invasive alternative to spinal fusion and total disc replacement that have the potential to reduce pain and restore motion for patients with degenerative disc disease. Finite element modeling can be used to determine the biomechanics associated with nucleus replacement technologies. The current study focuses on a new nucleus replacement device designed as a conforming silicone implant with an internal void. A validated finite element model of the human lumbar L3-L4 motion segment was developed and used to investigate the influence of the nucleus replacement device on spine biomechanics. In addition, the effect of device design changes on biomechanics was determined. A 3D, L3-L4 finite element model was constructed from medical imaging data. Models were created with the normal intact nucleus, the nucleus replacement device, and a solid silicone implant. Probabilistic analysis was performed on the normal model to provide quantitative validation metrics. Sensitivity analysis was performed on the silicone Shore A durometer of the device. Models were loaded under axial compression followed by flexion/extension, lateral bending, or axial rotation. Compressive displacement, endplate stresses, reaction moment, and annulus stresses were determined and compared between the different models. The novel nucleus replacement device resulted in similar compressive displacement, endplate stress, and annulus stress and slightly higher reaction moment compared with the normal nucleus. The solid implant resulted in decreased displacement, increased endplate stress, decreased annulus stress, and decreased reaction moment compared with the novel device. With increasing silicone durometer, compressive displacement decreased, endplate stress increased, reaction moment increased, and annulus stress decreased. Finite element analysis was used to show that the novel nucleus replacement device results in similar biomechanics

  11. Evaluation of Water Retention in Lumbar Intervertebral Disks Before and After Exercise Stress With T2 Mapping.

    Science.gov (United States)

    Chokan, Kou; Murakami, Hideki; Endo, Hirooki; Mimata, Yoshikuni; Yamabe, Daisuke; Tsukimura, Itsuko; Oikawa, Ryosuke; Doita, Minoru

    2016-04-01

    T2 mapping was used to quantify moisture content of the lumbar spinal disk nucleus pulposus (NP) and annulus fibrosus before and after exercise stress, and after rest, to evaluate the intervertebral disk function. To clarify water retention in intervertebral disks of the lumbar vertebrae by performing magnetic resonance imaging before and after exercise stress and quantitatively measuring changes in moisture content of intervertebral disks with T2 mapping. To date, a few case studies describe functional evaluation of articular cartilage with T2 mapping; however, T2 mapping to the functional evaluation of intervertebral disks has rarely been applied. Using T2 mapping might help detect changes in the moisture content of intervertebral disks, including articular cartilage, before and after exercise stress, thus enabling the evaluation of changes in water retention shock absorber function. Subjects, comprising 40 healthy individuals (males: 26, females: 14), underwent magnetic resonance imaging T2 mapping before and after exercise stress and after rest. Image J image analysis software was then used to set regions of interest in the obtained images of the anterior annulus fibrosus, posterior annulus fibrosus, and NP. T2 values were measured and compared according to upper vertebrae position and degeneration grade. T2 values significantly decreased in the NP after exercise stress and significantly increased after rest. According to upper vertebrae position, in all of the upper vertebrae positions, T2 values for the NP significantly decreased after exercise stress and significantly increased after rest. According to the degeneration grade, in the NP of grade 1 and 2 cases, T2 values significantly decreased after exercise stress and significantly increased after rest. T2 mapping could be used to not only diagnose the degree of degeneration but also evaluate intervertebral disk function. 3.

  12. Low virulence bacterial infections in cervical intervertebral discs: a prospective case series.

    Science.gov (United States)

    Chen, Yilei; Wang, Xianjun; Zhang, Xuyang; Ren, Hong; Huang, Bao; Chen, Jian; Liu, Junhui; Shan, Zhi; Zhu, Zhihai; Zhao, Fengdong

    2018-04-19

    A prospective cross-sectional case series study. To investigate the prevalence of low virulence disc infection and its associations with characteristics of patients or discs in the cervical spine. Low virulence bacterial infections could be a possible cause of intervertebral disc degeneration and/or back pain. Controversies are continuing over whether these bacteria, predominantly Propionibacterium acnes (P. acnes), represent infection or contamination. However, the current studies mainly focus on the lumbar spine, with very limited data on the cervical spine. Thirty-two patients (20 men and 12 women) who underwent anterior cervical fusion for degenerative cervical spondylosis or traumatic cervical cord injury were enrolled. Radiological assessments included X-ray, CT, and MRI of the cervical spine. Endplate Modic changes, intervertebral range of motion, and disc herniation type were evaluated. Disc and muscle tissues were collected under strict sterile conditions. Samples were enriched in tryptone soy broth and subcultured under anaerobic conditions, followed by identification of the resulting colonies by the PCR method. Sixty-six intervertebral discs were excised from thirty-two patients. Positive disc cultures were noted in eight patients (25%) and in nine discs (13.6%). The muscle biopsy (control) cultures were negative in 28 patients and positive in 4 patients (12.5%); three of whom had a negative disc culture. Seven discs (10.6%) were positive for coagulase-negative Staphylococci (CNS) and two discs were positive for P. acnes (3.0%). A younger patient age and the extrusion or sequestration type of disc herniation, which represented a complete annulus fibrous failure, were associated with positive disc culture. Our data show that CNS is more prevalent than P. acnes in degenerative cervical discs. The infection route in cervical discs may be predominantly through an annulus fissure. Correlation between these infections and clinical symptoms is uncertain

  13. Ho:YAG laser: intervertebral disk cell interaction using three-dimensional cell culture system

    Science.gov (United States)

    Sato, Masato; Ishihara, Miya; Arai, Tsunenori; Asazuma, Takashi; Kikuchi, Toshiyuki; Kikuchi, Makoto; Fujikawa, Kyosuke

    2000-06-01

    The purpose of this study is to evaluate the influence on the intervertebral disc cells after laser irradiation using three- dimensional culture system and to clarify the optimum Ho:YAG laser irradiation condition on percutaneous laser disc decompression (PLDD) for lumbar disc herniation. Since the Ho:YAG laser ablation is characterized by water-vapor bubble dynamics, not only thermal effect but also acoustic effect on cell metabolism might occur in the intervertebral disc. We studied the disc cell reaction from the metabolic point of view to investigate photothermal and photoacoustic effects on three-dimensional cultured disc cell. Intervertebral discs were obtained from female 30 Japanese white rabbits weighing about 1 kg. A pulsed Ho:YAG laser (wavelength: 2.1 micrometer, pulse width: about 200 microseconds) was delivered through a 200 micrometer-core diameter single silica glass fiber. We used the Ho:YAG laser irradiation fluence ranging from 60 to approximately 800 J/cm2 at the fiber end. To investigate acoustic effect, the acoustic transducer constructed with polyvinylidene fluoride (PVdF) film and acoustic absorber was used to detect the stress wave. Thermocouple and thermography were used to investigate thermal effect. Concerning damage of plasma membrane and ability of matrix synthesis, thermal effect might mainly affect cell reaction in total energy of 54 J (closed to practically used condition), but in 27 J, acoustic effect might contribute to it. We found that total energy was key parameter among the optimum condition, so that temperature and/or stress wave may influence Ho:YAG laser-disc cell interactions.

  14. [Total cervical disk replacement--implant-specific approaches: keel implant (Prodisc-C intervertebral disk prosthesis)].

    Science.gov (United States)

    Korge, Andreas; Siepe, Christoph J; Heider, Franziska; Mayer, H Michael

    2010-11-01

    Dynamic intervertebral support of the cervical spine via an anterolateral approach using a modular artificial disk prosthesis with end-plate fixation by central keel fixation. Cervical median or mediolateral disk herniations, symptomatic cervical disk disease (SCDD) with anterior osseous, ligamentous and/or discogenic narrowing of the spinal canal. Cervical fractures, tumors, osteoporosis, arthrogenic neck pain, severe facet degeneration, increased segmental instability, ossification of posterior longitudinal ligament (OPLL), severe osteopenia, acute and chronic systemic, spinal or local infections, systemic and metabolic diseases, known implant allergy, pregnancy, severe adiposity (body mass index > 36 kg/m2), reduced patient compliance, alcohol abuse, drug abuse and dependency. Exposure of the anterior cervical spine using the minimally invasive anterolateral approach. Intervertebral fixation of retainer screws. Intervertebral diskectomy. Segmental distraction with vertebral body retainer and vertebral distractor. Removal of end-plate cartilage. Microscopically assisted decompression of spinal canal. Insertion of trial implant to determine appropriate implant size, height and position. After biplanar image intensifier control, drilling for keel preparation using drill guide and drill bit, keel-cut cleaner to remove bone material from the keel cut, radiologic control of depth of the keel cut using the corresponding position gauge. Implantation of original implant under lateral image intensifier control. Removal of implant inserter. Functional postoperative care and mobilization without external support, brace not used routinely, soft brace possible for 14 days due to postoperative pain syndromes. Implantation of 100 cervical Prodisc-C disk prostheses in 78 patients (average age 48 years) at a single center. Clinical and radiologic follow-up 24 months postoperatively. Significant improvement based on visual analog scale and Neck Disability Index. Radiologic

  15. The viscoelastic standard nonlinear solid model: predicting the response of the lumbar intervertebral disk to low-frequency vibrations.

    Science.gov (United States)

    Groth, Kevin M; Granata, Kevin P

    2008-06-01

    Due to the mathematical complexity of current musculoskeletal spine models, there is a need for computationally efficient models of the intervertebral disk (IVD). The aim of this study is to develop a mathematical model that will adequately describe the motion of the IVD under axial cyclic loading as well as maintain computational efficiency for use in future musculoskeletal spine models. Several studies have successfully modeled the creep characteristics of the IVD using the three-parameter viscoelastic standard linear solid (SLS) model. However, when the SLS model is subjected to cyclic loading, it underestimates the load relaxation, the cyclic modulus, and the hysteresis of the human lumbar IVD. A viscoelastic standard nonlinear solid (SNS) model was used to predict the response of the human lumbar IVD subjected to low-frequency vibration. Nonlinear behavior of the SNS model was simulated by a strain-dependent elastic modulus on the SLS model. Parameters of the SNS model were estimated from experimental load deformation and stress-relaxation curves obtained from the literature. The SNS model was able to predict the cyclic modulus of the IVD at frequencies of 0.01 Hz, 0.1 Hz, and 1 Hz. Furthermore, the SNS model was able to quantitatively predict the load relaxation at a frequency of 0.01 Hz. However, model performance was unsatisfactory when predicting load relaxation and hysteresis at higher frequencies (0.1 Hz and 1 Hz). The SLS model of the lumbar IVD may require strain-dependent elastic and viscous behavior to represent the dynamic response to compressive strain.

  16. Isolation of intact elastin fibers devoid of microfibrils.

    NARCIS (Netherlands)

    Daamen, W.F.; Hafmans, T.G.M.; Veerkamp, J.H.; Kuppevelt, A.H.M.S.M. van

    2005-01-01

    Purification protocols for elastin generally result in greatly damaged elastin fibers and this likely influences the biological response. We here describe a novel protocol for the isolation of elastin whereby the fibers stay intact, and introduce the term "elastin fiber" for intact elastic fibers

  17. 50 CFR 622.38 - Landing fish intact.

    Science.gov (United States)

    2010-10-01

    ... that is operating under the respective trip limits. Such cut-off fish also may be sold. A maximum of... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Landing fish intact. 622.38 Section 622.38... Landing fish intact. The operator of a vessel that fishes in the EEZ is responsible for ensuring that fish...

  18. [Research advances of three-dimension printing technology in vertebrae and intervertebral disc tissue engineering].

    Science.gov (United States)

    Yang, Zechuan; Li, Chunde; Sun, Haolin

    2016-03-01

    Three-dimensional (3D) printing technology is characterized by "inside-out" stack manufacturing. Compared with conventional technologies, 3D printing has the advantage of personalization and precision. Therefore, the shape and internal structure of the scaffolds made by 3D printing technology are highly biomimetic. Besides, 3D bioprinting can precisely deposit the biomaterials, seeding cells and cytokines at the same time, which is a breakthrough in printing technique and material science. With the development of 3D printing, it will make great contributions to the reconstruction of vertebrae and intervertebral disc in the future.

  19. THE INTERVERTEBRAL DISK PROTHESIS INSTALLATION AFTER ABLATION OF A DISK‘S HERNIA AT CERVICAL LEVEL

    OpenAIRE

    I.A.Norkin; A.A.Chekhonatsky; I.I.Sholomov

    2008-01-01

    The purpose ofthe present work was to study the possibility of use the artificial disk «PRODISK» at cervical level after ablation of intervertebraldisk’s hernia. The basis of this research is complexexamination and surgical treatment of a 52-years-old-woman with osteochondrosis of cervical spine and with radiculopathy syndrome because of compression of spinal hernia roots of intervertebral disk On May, 29th, 2007 the patientwas operated: «diskectomyC6-C7' disk’s hernia removal, implantat...

  20. Is a purpose of REM sleep atonia to help regenerate intervertebral disc volumetric loss?

    Directory of Open Access Journals (Sweden)

    Fryer Jerome CJ

    2009-01-01

    Full Text Available Abstract The nature of atonia in sleep continues to be enigmatic. This article discusses a new hypothesis for complete core muscle relaxation in REM sleep, suggesting a bottom-up recuperative perspective. That is, does the atonia in REM sleep provide a utility to help restore the mechanobiology and respective diurnal intervertebral disc hydraulic loss? By combining the effects of gravity with current compressive concepts in spinal stability, this article looks at vertebral approximation as a deleterious experience with an intrinsic biological need to keep vertebrae separated. Methods using polysomnography and recumbent MRI are discussed.

  1. Cartilage of the Intervertebral Disc Eng-Plate, A Histological, Histochemical, Fine Structure Study.

    Science.gov (United States)

    1982-08-01

    degeneration (Nachemson et al., 1970). These and related studies consider the end-plates to be composed of hyaline cartilage and thus homologues of articular...results of this study in rhesus indicate, that while present, the cartilage of the end-plate is quite different in structure and presumably...HZSTOLO6ZCAL,-ETCfU) I AUG 82 N 5 NUSSBAUM IUNCLASSIFDATRL8R-1222NL.rnximommmB~iIEND2 AFAMRL-TR-81 - 122 " CARTILAGE OF THE INTERVERTEBRAL DISC END-PLATE A

  2. BACK PAIN ASSOCIATED WITH INTERVERTEBRAL DISK DEGENERATION: MORPHOLOGICAL, GENETIC AND CLINICO-INSTRUMENTAL ASPECTS

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2014-07-01

    Full Text Available Degenerative spine disease is one of the causes of back pain. Clinical types of pain and severity of inflammatory changes in the vertebral bodies depend on the activity of pro-inflammatory cytokines. Rate of development and progression of degenerative changes in the spine structures is genetically determined. Therapy of pain syndrome associated with a degenerative disc disease may include use of methods to restore damaged intervertebral disc structures, and also use of different combinations of anti-inflammatory and analgesics therapy.

  3. BACK PAIN ASSOCIATED WITH INTERVERTEBRAL DISK DEGENERATION: MORPHOLOGICAL, GENETIC AND CLINICO-INSTRUMENTAL ASPECTS

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2011-01-01

    Full Text Available Degenerative spine disease is one of the causes of back pain. Clinical types of pain and severity of inflammatory changes in the vertebral bodies depend on the activity of pro-inflammatory cytokines. Rate of development and progression of degenerative changes in the spine structures is genetically determined. Therapy of pain syndrome associated with a degenerative disc disease may include use of methods to restore damaged intervertebral disc structures, and also use of different combinations of anti-inflammatory and analgesics therapy.

  4. LASER BIOLOGY AND MEDICINE: Effect of repetitive laser pulses on the electrical conductivity of intervertebral disc tissue

    Science.gov (United States)

    Omel'chenko, A. I.; Sobol', E. N.

    2009-03-01

    The thermomechanical effect of 1.56-μm fibre laser pulses on intervertebral disc cartilage has been studied using ac conductivity measurements with coaxial electrodes integrated with an optical fibre for laser radiation delivery to the tissue. The observed time dependences of tissue conductivity can be interpreted in terms of hydraulic effects and thermomechanical changes in tissue structure. The laserinduced changes in the electrical parameters of the tissue are shown to correlate with the structural changes, which were visualised using shadowgraph imaging. Local ac conductivity measurements in the bulk of tissue can be used to develop a diagnostic/monitoring system for laser regeneration of intervertebral discs.

  5. Clinical efficacy of bone cement injectable pedicle screw system combined with intervertebral fusion in treatment of lumbar spondylolysis and osteoporosis

    Directory of Open Access Journals (Sweden)

    Peng-yi DAI

    2016-10-01

    Full Text Available Objective  To observe the therapeutic effect of bone cement injectable pedicle screw system combined with intervertebral fusion for lumbar spondylolysis and osteoporosis. Methods  The clinical data were analyzed retrospectively of 21 patients with lumbar spondylolysis and osteoporosis who received treatment of bone cement injectable pedicle screw system and intervertebral fusion from Aug. 2013 to Nov. 2015. The 21 patients (9 males and 12 females aged from 60 to 80 years (mean 64 years old; 6 of them presented degenerative spondylolysis, 15 with isthmic spondylolisthesis; 2 cases had I degree slippage, 13 had Ⅱdegree slippage, 6 had Ⅲdegree slippage, and all the cases were unisegmental slippage including 9 cases in L4 and 12 cases in L5. Bone mineral density of lumbar vertebrae (L2-L5 was measured with dual-energy X-ray absorptiometry, and T values conforming to the diagnostic criteria of osteoporosis were less than or equal to -2.5; All patients were operated with whole lamina resection for decompression, bone cement injectable pedicle screws system implantation, propped open reduction and fixation intervertebral fusion. The clinical outcomes were determined by the radiographic evaluation including intervertebral height, height of intervertebral foramen, slip distance, slip rate and slip angle, and Oswestry disability index (ODI on preoperative, 3 months after operation and the end of the time, and the interbody fusion were followed up. Results  Cerebrospinal fluid leakage of incision was observed in two cases after operation, compression and dressing to incision, Trendelenburg position, dehydration and other treatments were taken, and the stitches of incisions were taken out on schedule. Slips in the 21 patients were reset to different extent, and lumbar physiological curvatures were recovered. The intervertebral height and height of intervertebral foramen were obviously higher 3 months after operation than that before operation (P0

  6. Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy.

    Science.gov (United States)

    Lund, L; Henmar, H; Würtzen, P A; Lund, G; Hjortskov, N; Larsen, J N

    2007-04-01

    Specific immunotherapy with intact allergen vaccine is a well-documented treatment for allergic diseases. Different vaccine formulations are currently commercially available, the active ingredient either being intact allergens or chemically modified allergoids. The rationale behind allergoids is to decrease allergenicity while maintaining immunogenicity. However, data from the German health authorities based on reporting of adverse events over a 10-year period did not indicate increased safety of allergoids over intact allergens. The objective of this study was to investigate the effect of chemical modification on allergenicity and immunogenicity comparing four commercial allergoid products for birch pollen immunotherapy with an intact allergen vaccine. Solid-phase IgE inhibition and histamine release assays were selected as model systems for allergenicity, and a combination of human T cell proliferation and IgG titres following mouse immunizations were used to address the immunogenicity of the intact allergen vaccine and the four allergoids. In all assays, the products were normalized with respect to the manufacturer's recommended maintenance dose. IgE inhibition experiments showed a change in epitope composition comparing intact allergen vaccine with allergoid. One allergoid product induced enhanced histamine release compared to the intact allergens, while the other three allergoids showed reduced release. Standard T cell stimulation assays using lines from allergic patients showed a reduced response for all allergoids compared with the intact allergen vaccine regardless of the cell type used for antigen presentation. All allergoids showed reduced capacity to induce allergen-specific IgG responses in mice. While some allergoids were associated with reduced allergenicity, a clear reduction in immunogenicity was observed for all allergoid products compared with the intact allergen vaccine, and the commercial allergoids tested therefore do not fulfil the allergoid

  7. Serum steroid levels in intact and endocrine ablated BALB/c nude mice and their intact littermates

    DEFF Research Database (Denmark)

    Brünner, N; Svenstrup, B; Spang-Thomsen, M

    1986-01-01

    An investigation was made of the serum steroid levels found in intact and endocrine ablated nude mice of both sexes and in their intact homozygous littermates. The results showed that nude mice have a normal steroidogenesis, but with decreased levels of circulating steroids compared to those...

  8. Diagnostic imaging of spinal stenosis and intervertebral disc disease

    International Nuclear Information System (INIS)

    Howe, J.W.; Yochum, T.R.; Rowe, L.J.

    1987-01-01

    Back and neck pain are among the most common of human ailments. Low back pain, with or without leg pain, will affect most people at least once in their lifetime. Neck and shoulder pain, headache of cervical origin, and other neck-related problems are not far behind low back pain as to their incidence. Despite the widespread incidence of these complaints and the considerable associated disabilities, they remain enigmas both as to cause and treatment. A discussion of the complex etiological factors involved and the many mechanisms which interact in the production of spinal-related pain far exceeds the scope of this presentation. One area integrally related to such problems, the several causes of spinal stenosis, is the focus of this chapter

  9. Effect of intervertebral disk degeneration on spinal stenosis during magnetic resonance imaging with axial loading

    International Nuclear Information System (INIS)

    Ahn, Tae-Joon; Lee, Sang-Ho; Choi, Gun; Ahn, Yong; Liu, Wei-Chiang; Kim, Ho-Jin; Lee, Ho-Yeon

    2009-01-01

    Magnetic resonance (MR) imaging with axial loading can simulate the physiological standing state and disclose spinal stenosis undetected or underestimated in the conventional position. Intervertebral disk degeneration may be an important factor in spinal stenosis. This study investigated whether intervertebral disk degeneration increases spinal stenosis during axial loading. MR imaging with and without axial loading was obtained in 51 patients with neurogenic intermittent claudication and/or sciatica and reviewed retrospectively. The grade of disk degeneration was rated in four disk spaces from L2-3 to L5-S1. The dural sac cross-sectional area (DCSA) was measured on MR images taken in both conventional and axial loading positions, and the change in the DCSA was calculated. The effect of disk degeneration on the DCSA was statistically analyzed. Significant decreases in the DCSA occurred with grade 4 disk degeneration (mean±standard deviation, 20.1±14.1 mm 2 ), followed by grade 3 (18.3±15.1 mm 2 ) and grade 2 (8.9±13.1 mm 2 ). DCSA decreased considerably with increased severity of disk degeneration with axial loading, except for grade 5 disk degeneration. More accurate diagnosis of stenosis can be achieved using MR imaging with axial loading, especially if grade 2 to 4 disk degeneration is present. (author)

  10. Calcification of intervertebral discs in the dachshund: a radiographic study of 327 young dogs

    International Nuclear Information System (INIS)

    Stigen, Ø.

    1991-01-01

    The vertebral columns of 327 clinically normal, 12 to 18 months old dachshunds, were x-rayed. This sample represented 16.1% of all dachshunds registered with the Norwegian Kennel Club in the period 1986-1988. Calcified intervertebral discs were identified in 79 (24.2%) of the dogs and the number of calcified discs in each individual varied from 1 to 11 with a mean of 2.3. Calcified discs were estimated to occur in 23.5% of Norwegian dachshunds. The occurrence of calcified discs in standard-sized dachshunds was higher in the wirehaired variety (27.1%) than in the smoothcoated (16.4%) or longhaired (9.1%) varieties. However, within the longhaired variety the occurrence was higher in dwarfs and kaninchens (36.0%) than in standard-sized dachshunds (9.1%). Calcification was identified in all cervical, thoracic and lumbar intervertebral discs other than T1-2, and was found to be most frequent in the caudal thoracic vertebral column

  11. Comparison of disability duration of lumbar intervertebral disc disorders among types of insurance in Korea.

    Science.gov (United States)

    Lee, Choong Ryeol; Kim, Joon Youn; Hong, Young Seoub; Lim, Hyun Sul; Lee, Yong Hwan; Lee, Jong Tae; Moon, Jai Dong; Jeong, Baek Geun

    2005-10-01

    The incidence of work-related musculoskeletal disorder including low back pain sharply increased since 2000 in Korea. The objectives of the present study are to compare disability duration of lumbar intervertebral disc displacement among types of insurances, and to obtain its appropriate duration. The medical records of all patients whose final diagnosis in discharge summary of chart was lumber specified intervertebral disc displacement (LIVD) in 6 large general hospitals in Korea were reviewed to compare the length of admission and disability among different types of insurances. The information on age, gender, the length of admission, the length of follow-up for LIVD, occupation, operation, combined musculoskeletal diseases, and type of insurance was investigated. 552 cases were selected and analyzed to calculate arithmetic mean, median, mode, and geometric mean of disability duration. There was a significant difference in the length of admission and disability among types of insurance after controlling covariates such as age and combined diseases by the analysis of covariance. The length of admission in cases of IACI and AI was much longer than that of HI, and the length of disability in cases of IACI was much longer than that of HI. Prolonged duration of admission and disability was not assumed due to combined diseases, complication or other unexplainable personal factors in cases of those with industrial accidents compensation insurance and automobile insurance. This means that proper management of evidence-based disability duration guidelines is urgently needed in Korea.

  12. [Treatment of postoperative nonunion of fracture of lower limb with bone grafting by intervertebral disc endoscope].

    Science.gov (United States)

    Zhang, Jianlin; Tan, Yu'e; Ye, Jun; Han, Fangmin

    2012-02-01

    To explore the effectiveness of bone grafting by intervertebral disc endoscope for postoperative nonunion of fracture of lower limb. Between August 2004 and August 2008, 40 patients (23 males and 17 females) with postoperative nonunion of femoral and tibial fracture, aged 20-63 years (mean, 41.5 years) were treated. Nonunion of fracture occurred at 10-16 months after internal fixation. During the first operation, the internal fixation included interlocking intramedullary nailing of femoral fracture in 12 cases and plate in 16 cases, and interlocking intramedullary nailing of tibial fractures in 9 cases and plate in 3 cases. The X-ray films showed hypertrophic nonunion in 24 cases, common nonunion in 3 cases, and atrophic nonunion in 13 cases. The average operation time was 61 minutes (range, 40-80 minutes), and the blood loss was 80-130 mL (mean, 100 mL). The hospitalization time were 6-11 days (mean, 8.1 days). Incisions healed by first intention in all patients with no complication of infection or neurovascular injury. Forty patients were followed up 10-16 months (mean, 12.3 months). The X-ray films showed that all patients achieved healing of fracture after 4-10 months (mean, 6.8 months). No pain, disfunction, or internal fixation failure occurred. Bone grafting by intervertebral disc endoscope is an effective method for treating postoperative nonunion of femoral and tibial fracture.

  13. Cervical spine degenerative changes (narrowed intervertebral disc spaces and osteophytes) in coal miners

    International Nuclear Information System (INIS)

    Zejda, J. E.; Stasiow, B.

    2003-01-01

    A series of 685 x-rays films of the cervical spine obtained in coal miners was analyzed to explore the occurrence of narrowed disc spaces and osteophytes in this occupational group, and to examine the association of x-rays changes with age, duration of employment, and duration of occupational exposure to hand-arm vibration. All data were extracted from individual medical files of coal miners examined for suspected hand-arm vibration-related disorders in 1989-1999 at the Occupational Medicine Center in Katowice. The narrowed intervertebral disc spaces were found in 188 coal miners (26.9%) and osteophytes in 332 coal miners (47.5%). The occurrence of degenerative changes in coal miners was similar to that observed in a small group of 68 blue-collar workers (no exposure to hand-arm vibration) employed in the coal industry. Univariate comparisons showed that intervertebral disc spaces and osteophytes were more frequent among older subjects and among subjects with longer duration of employment. The results of logistic regression analysis confirmed statistically significant effect of age, but not of other factors included in the model. When both x-ray changes were grouped together (a combined dependent variable) age remained the only statistically significant explanatory variable. The findings do not support the view that the examined degenerative changes in cervical spine are more prevalent in coal miners and depend on duration of physical work or local exposure to hand-arm vibration in this occupational group. (author)

  14. Magnetic resonance imaging of lumbar intervertebral disks with its pathological cerrelation

    Energy Technology Data Exchange (ETDEWEB)

    Kakitsubata, Yousuke; Nabeshima, Kazuki; Kihara, Yasushi; Harada, Kuniko; Mori, Yukiko; Kakitsubata, Sachiko; Watanabe, Katsushi

    1988-02-01

    Three cadaver spines were examined by magnetic resonance imaging (MRI) with 0.1 tesla resistive magnet. Anatomic sections of lumbar intervertebral disks were compared with various MR images, saturation recovery (SR), inversion recovery (IR), T1 and T2 weighted spin echo (SE) images. And the signal intensity of degenerated disks on T2 weighted images were correlated with the histological studies. The disks were well delineated by SR and their degenerative changes were detected most sensitively by T2 weighted SE image. Two parts of disk were delineated on T2 weighted SE image. The central portion of disk showed high signal intensity and the periphery a low signal intensity. The central high signal intensity area corresponded to the combination of annulus fibrosus and nucleus pulposus, which cannot be differenciated by MR. And the peripheral low signal intensity area corresponded to the collagenous fibers of annulus fibrosus. Histologically, disks with decreased signal intensity had marked increase of collagen fibers. The intranuclear cleft were evident on T2 weighted image, and the corresponding structures thought to be caused by invagination of the lamellae of the annulus into the nucleus in the histological specimens. MRI were useful modality for evaluation of intervertebral disks, but biochemical analysis may be needed for precise interpretation of MR images of disks in addition to histological studies.

  15. THE INTERVERTEBRAL DISK PROTHESIS INSTALLATION AFTER ABLATION OF A DISK‘S HERNIA AT CERVICAL LEVEL

    Directory of Open Access Journals (Sweden)

    I.A.Norkin

    2008-12-01

    Full Text Available The purpose ofthe present work was to study the possibility of use the artificial disk «PRODISK» at cervical level after ablation of intervertebraldisk’s hernia. The basis of this research is complexexamination and surgical treatment of a 52-years-old-woman with osteochondrosis of cervical spine and with radiculopathy syndrome because of compression of spinal hernia roots of intervertebral disk On May, 29th, 2007 the patientwas operated: «diskectomyC6-C7' disk’s hernia removal, implantation of an artificial disk« PRODISK»at the level C6- C7». The patient became active on the third day after the operation, and she was discharged in eight days. Her neurologic symptoms regressed completely. Range of cervical motions was in the normal condition (flexia/anteflexia-35 °-40 °. The pain syndrome was arrested (VAS-2, VRS-1. We consider that any operation causes disorder of structural and functional properties and requires prosthetics of intervertebral disk’s, which can fully reconstruct biomechanical qualities of the operated segment

  16. Changes in intervertebral disk dimensions after a loading task and the relationship with stature change measurements.

    Science.gov (United States)

    Lewis, Sandra E; Fowler, Neil E

    2009-10-01

    Lewis SE, Fowler NE. Changes in intervertebral disk dimensions after a loading task and the relationship with stature change measurements. To test the hypothesis that there would be a linear relationship between overall stature change determined by stadiometry and markers of lumbar disk height loss determined from magnetic resonance imaging (MRI). The short-term loading response of the lumbar spine was evaluated with both stadiometry and MRI, using a within-subject repeated-measures design. Measures were obtained both before and after 15 minutes of walking wearing a weighted vest (20% of body mass). Stature loss measured on the stadiometer was compared with change in lumbar spine length assessed from the MRI images. A university laboratory. Participants (N=13; mean age +/- SD, 28.5+/-5.2y; mean height +/- SD, 1.76+/-0.10m; mean body mass +/- SD, 76.6+/-14.9kg) were invited to take part in the investigation. The group was mixed (9 men, 4 women) and comprised people with no history of low back pain. Not applicable. Lumbar spine length assessed via MRI and stature change measured via stadiometry. A significant height loss was observed over the complete lumbar spine (Pstature loss (r=.61). The results were supportive of the use of stadiometry as an indirect measure of changes in intervertebral disk height.

  17. Calcification of intervertebral discs in the dachshund: a radiographic study of 21 stud-dogs

    International Nuclear Information System (INIS)

    Stigen, O.

    1995-01-01

    The vertebral columns of 21 clinically normal, 4.9 to 13.2 year old dachshunds were x-rayed. This sample represented 55.3% of all male dachshunds with 20 or more offspring registered with the Norwegian Kennel Club in the period 1985-1989. Calcified intervertebral discs were identified in 9 (42.9%) of the stud-dogs, and the number of calcified discs in each individual varied from 2 to 5 with a mean of 3.7. The frequency of stud-dogs with 1 or more calcified discs was compared with the corresponding frequency in a material of 327 one-year-old dachshunds. In this comparison, the relative risk was estimated with 95% confidence bounds. When the different composition of size and coat varieties in the 2 materials was not considered, the relative risk of calcified discs was found to be 1.77 (0.99-3.2) times higher in stud-dogs than in young dogs. When the different composition of varieties in the 2 materials was considered, the relative risk was found to be 1.9 (1.1-3.4) times higher in stud-dogs than in young dogs. The results of the present study strongly suggest that an increase in the frequency of dachshunds with 1 or more calcified intervertebral discs occurs after 1 year of age

  18. Calcification of intervertebral discs in the dachshund: a radiographic study of 327 young dogs

    Energy Technology Data Exchange (ETDEWEB)

    Stigen, Ø. [Norwegian Coll. of Veterinary Medicine, Oslo (Norway)

    1991-07-01

    The vertebral columns of 327 clinically normal, 12 to 18 months old dachshunds, were x-rayed. This sample represented 16.1% of all dachshunds registered with the Norwegian Kennel Club in the period 1986-1988. Calcified intervertebral discs were identified in 79 (24.2%) of the dogs and the number of calcified discs in each individual varied from 1 to 11 with a mean of 2.3. Calcified discs were estimated to occur in 23.5% of Norwegian dachshunds. The occurrence of calcified discs in standard-sized dachshunds was higher in the wirehaired variety (27.1%) than in the smoothcoated (16.4%) or longhaired (9.1%) varieties. However, within the longhaired variety the occurrence was higher in dwarfs and kaninchens (36.0%) than in standard-sized dachshunds (9.1%). Calcification was identified in all cervical, thoracic and lumbar intervertebral discs other than T1-2, and was found to be most frequent in the caudal thoracic vertebral column.

  19. Intercellular signaling pathways active during intervertebral disc growth, differentiation, and aging.

    Science.gov (United States)

    Dahia, Chitra Lekha; Mahoney, Eric J; Durrani, Atiq A; Wylie, Christopher

    2009-03-01

    Intervertebral discs at different postnatal ages were assessed for active intercellular signaling pathways. To generate a spatial and temporal map of the signaling pathways active in the postnatal intervertebral disc (IVD). The postnatal IVD is a complex structure, consisting of 3 histologically distinct components, the nucleus pulposus, fibrous anulus fibrosus, and endplate. These differentiate and grow during the first 9 weeks of age in the mouse. Identification of the major signaling pathways active during and after the growth and differentiation period will allow functional analysis using mouse genetics and identify targets for therapy for individual components of the disc. Antibodies specific for individual cell signaling pathways were used on cryostat sections of IVD at different postnatal ages to identify which components of the IVD were responding to major classes of intercellular signal, including sonic hedgehog, Wnt, TGFbeta, FGF, and BMPs. We present a spatial/temporal map of these signaling pathways during growth, differentiation, and aging of the disc. During growth and differentiation of the disc, its different components respond at different times to different intercellular signaling ligands. Most of these are dramatically downregulated at the end of disc growth.

  20. Polyetheretherketone (PEEK) intervertebral cage as a cause of chronic systemic allergy: a case report.

    Science.gov (United States)

    Maldonado-Naranjo, Andres L; Healy, Andrew T; Kalfas, Iain H

    2015-07-01

    Polyetheretherketone (PEEK) is an organic polymer thermoplastic with strong mechanical and chemical resistance properties. It has been used in industry to fabricate items for demanding applications such as bearings, piston parts, compressor plate valves, and cable insulation. Since the early 1980s, polyetheretherketone polymers have been increasingly used in orthopedic and spinal surgery applications. Numerous studies and years of clinical experience have confirmed the biocompatibility of this material. The purpose of the study was to report a case of chronic systemic allergy after anterior cervical decompression and fusion (ACDF) and implantation of an intervertebral PEEK cage, with resolution of symptoms after removal of PEEK cage. This study is a case report with clinical evidence for allergy to PEEK. The methods involve clinical findings and review of current literature. After ACDF and implantation of an intervertebral PEEK cage, the patient had developed an angioedema-like picture marked by severe redness, itching, swelling of his tongue, and skin thickening. A skin patch test was positive for PEEK. Removal of the implant resulted in the resolution of his allergy symptoms shortly after surgery. Tissue reactions to PEEK are extremely rare. Herein, we present the first report of a chronic allergic response to interbody PEEK material. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. An experimental study of percutaneous laser nucleotomy of the intervertebral cervical disc

    International Nuclear Information System (INIS)

    Wang Yiqing; Wang Zhimin; Guo Weiping; Zhang Hongxin; Guan Yan; Li Wenxian; Ni Daihui

    2002-01-01

    Objective: To study the effectiveness and safety of laser nucleotomy of the intervertebral cervical disc. Methods: The experimental study was performed in 10 dogs, and each dog was treated with laser nucleolysis in C3-4 and C4-5. The laser energy was turned on in 1.0-second pulses with 1.0 second (C3-4) and 5.0 second (C4-5) pause interval, and the total energy was up to 1000 joules. The temperatures were measured at the place between the posterior longitudinal ligament and the dura and at the vertebral foramen by using a tip type thermometer. Chronic histologic changes were observed by light microscopy at 2-4 weeks after laser irradiation. Results: The temperatures at the place between the posterior longitudinal ligament and the dura and at the vertebral Forman did not exceed 40 degree C when the pause interval was 5 second. Two dogs were euthanized immediately after treatment, and the oval-shaped cavity was observed on the macroscopic view in the nucleus. The cavity measured between 5 mm and 6 mm in long axis and between 2 mm and 4 mm in short. 4 weeks after the laser irradiation, the nucleus pulposus was replaced by cartilaginous cells and fibrous tissues. Conclusion: The laser nucleotomy of the intervertebral cervical disc is effective and feasible at the suitable condition

  2. Quantifying the effect of intervertebral cartilage on neutral posture in the necks of sauropod dinosaurs

    Directory of Open Access Journals (Sweden)

    Michael P. Taylor

    2014-12-01

    Full Text Available Attempts to reconstruct the neutral neck posture of sauropod dinosaurs, or indeed any tetrapod, are doomed to failure when based only on the geometry of the bony cervical vertebrae. The thickness of the articular cartilage between the centra of adjacent vertebrae affects posture. It extends (raises the neck by an amount roughly proportional to the thickness of the cartilage. It is possible to quantify the angle of extension at an intervertebral joint: it is roughly equal, in radians, to the cartilage thickness divided by the height of the zygapophyseal facets over the centre of rotation. Applying this formula to published measurements of well-known sauropod specimens suggests that if the thickness of cartilage were equal to 4.5%, 10% or 18% of centrum length, the neutral pose of the Apatosaurus louisae holotype CM 3018 would be extended by an average of 5.5, 11.8 or 21.2 degrees, respectively, at each intervertebral joint. For the Diplodocus carnegii holotype CM 84, the corresponding angles of additional extension are even greater: 8.4, 18.6 or 33.3 degrees. The cartilaginous neutral postures (CNPs calculated for 10% cartilage—the most reasonable estimate—appear outlandish. But it must be remembered that these would not have been the habitual life postures, because tetrapods habitually extend the base of their neck and flex the anterior part, yielding the distinctive S-curve most easily seen in birds.

  3. Quantifying the effect of intervertebral cartilage on neutral posture in the necks of sauropod dinosaurs.

    Science.gov (United States)

    Taylor, Michael P

    2014-01-01

    Attempts to reconstruct the neutral neck posture of sauropod dinosaurs, or indeed any tetrapod, are doomed to failure when based only on the geometry of the bony cervical vertebrae. The thickness of the articular cartilage between the centra of adjacent vertebrae affects posture. It extends (raises) the neck by an amount roughly proportional to the thickness of the cartilage. It is possible to quantify the angle of extension at an intervertebral joint: it is roughly equal, in radians, to the cartilage thickness divided by the height of the zygapophyseal facets over the centre of rotation. Applying this formula to published measurements of well-known sauropod specimens suggests that if the thickness of cartilage were equal to 4.5%, 10% or 18% of centrum length, the neutral pose of the Apatosaurus louisae holotype CM 3018 would be extended by an average of 5.5, 11.8 or 21.2 degrees, respectively, at each intervertebral joint. For the Diplodocus carnegii holotype CM 84, the corresponding angles of additional extension are even greater: 8.4, 18.6 or 33.3 degrees. The cartilaginous neutral postures (CNPs) calculated for 10% cartilage-the most reasonable estimate-appear outlandish. But it must be remembered that these would not have been the habitual life postures, because tetrapods habitually extend the base of their neck and flex the anterior part, yielding the distinctive S-curve most easily seen in birds.

  4. Influence of Porcine Intervertebral Disc Matrix on Stem Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Hans-Lothar Fuchsbauer

    2011-08-01

    Full Text Available For back disorders, cell therapy is one approach for a real regeneration of a degenerated nucleus pulposus. Human mesenchymal stem cells (hMSC could be differentiated into nucleus pulposus (NP-like cells and used for cell therapy. Therefore it is necessary to find a suitable biocompatible matrix, which supports differentiation. It could be shown that a differentiation of hMSC in a microbial transglutaminase cross-linked gelatin matrix is possible, but resulted in a more chondrocyte-like cell type. The addition of porcine NP extract to the gelatin matrix caused a differentiation closer to the desired NP cell phenotype. This concludes that a hydrogel containing NP extract without any other supplements could be suitable for differentiation of hMSCs into NP cells. The NP extract itself can be cross-linked by transglutaminase to build a hydrogel free of NP atypical substrates. As shown by side-specific biotinylation, the NP extract contains molecules with free glutamine and lysine residues available for the transglutaminase.

  5. Spectrophotometric Evaluation of the Pulpal Peroxide Levels in Intact and Restored Teeth - An Invitro Study.

    Science.gov (United States)

    Patri, Gaurav; Acharya, Gourismita; Agrawal, Pratik; Panda, Vijeta

    2016-08-01

    Hydrogen peroxide (30%) is a commonly used "in office" bleaching agent. Deleterious effects of hydrogen peroxide on the pulp have been observed. The present study was conducted with the aim to evaluate the penetration of 30% hydrogen peroxide into the pulp chamber through intact teeth and through the surface of teeth, restored with either hybrid composite or Resin Modified Glass Ionomer Cement (RMGIC). Sixty extracted human maxillary central incisors were selected and divided into six groups. Two groups were restored with hybrid composite resin and two with RMGIC, while two groups were left intact. The teeth with acetate buffer solution in their pulp cavity were then immersed in either 30% hydrogen peroxide or distilled water depending upon the group, for 60 minutes at 37°C. Then horseradish peroxidase and leucocrystal violet were added to the acetate buffer solution present in the pulp chamber after it was transferred to a test tube and the optical density of the resultant blue solution obtained was measured spectrophotometrically. The data obtained were analyzed using one way ANOVA and Student's t-test. The data obtained established that hydrogen peroxide penetrated into the pulp from the bleaching agent used. Hydrogen peroxide (30%) showed the highest pulpal peroxide level in teeth restored with RMGIC followed by teeth restored with hybrid composite resin and the least amount of penetration was observed in intact teeth. The amount of peroxide penetration into the tooth is more through restored tooth than intact tooth and is also dependant on the type of restorative materials used.

  6. Using Spores for Fusarium spp. Classification by MALDI-Based Intact Cell/Spore Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Wolfgang Winkler

    2012-01-01

    Full Text Available Fusarium is a widespread genus of filamentous fungi and a member of the soil microbial community. Certain subspecies are health threatening because of their mycotoxin production that affects the human and animal food chain. Thus, for early and effective pest control, species identification is of particular interest; however, differentiation on the subspecies level is challenging and time-consuming for this fungus. In the present study, we show the possibilities of intact cell mass spectrometry for spore analysis of 22 different Fusarium strains belonging to six Fusarium subspecies. We found that species differentiation is possible if mass spectrometric analyses are performed under well-defined conditions with fixed parameters. A critical point for analysis is a proper sample preparation of spores, which increases the quality of mass spectra with respect to signal intensity and m/z value variations. It was concluded that data acquistion has to be performed automatically; otherwise, user-specific variations are introduced generating data which cannot fit the existing datasets. Data that show clearly that matrix-assisted laser desorption ionization-based intact cell/intact spore mass spectrometry (IC/ISMS can be applied to differentiate closely related Fusarium spp. are presented. Results show a potential to build a database on Fusarium species for accurate species identification, for fast response in the case of infections in the cornfield. We furthermore demonstrate the high precision of our approach in classification of intact Fusarium species according to the location of their collection.

  7. Secretion of intact proteins and peptide fragments by lysosomal pathways of protein degradation

    International Nuclear Information System (INIS)

    Isenman, L.D.; Dice, J.F.

    1989-01-01

    We report that degradation of proteins microinjected into human fibroblasts is accompanied by release into the culture medium of peptide fragments and intact proteins as well as single amino acids. For the nine proteins and polypeptides microinjected, acid-precipitable radioactivity, i.e. peptide fragments and/or intact proteins, ranged from 10 to 67% of the total released radioactivity. Peptide fragments and/or intact protein accounted for 60% of the radioactivity released into the medium by cells microinjected with ribonuclease A. Two major radiolabeled peptide fragments were found, and one was of an appropriate size to function as an antigen in antigen-presenting cells. The peptides released from microinjected ribonuclease A were derived from lysosomal pathways of proteolysis based on several lines of evidence. Previous studies have shown that microinjected ribonuclease A is degraded to single amino acids entirely within lysosomes. We show that release of free amino acids and peptide fragments and/or intact protein was equivalently stimulated by serum deprivation and equivalently inhibited by NH4Cl. We also show that lysosomal degradation of endocytosed [3H]ribonuclease A was accompanied by the release of two peptide fragments similar in size and charge to those from microinjected [ 3 H]ribonuclease A. These findings demonstrate that degradation within lysosomes occurs in a manner that spares specific peptides; they also suggest a previously unsuspected pathway by which cells can secrete cytosol-derived polypeptides

  8. Temperature dependence of 1H NMR relaxation time, T2, for intact and neoplastic plant tissues

    Science.gov (United States)

    Lewa, Czesław J.; Lewa, Maria

    Temperature dependences of the spin-spin proton relaxation time, T2, have been shown for normal and tumorous tissues collected from kalus culture Nicotiana tabacum and from the plant Kalanchoe daigremontiana. For neoplastic plant tissues, time T2 was increased compared to that for intact plants, a finding similar to that for animal and human tissues. The temperature dependences obtained were compared to analogous relations observed with animal tissues.

  9. Inter-examiner reliability of passive assessment of intervertebral motion in the cervical and lumbar spine: A systematic review

    NARCIS (Netherlands)

    van Trijffel, E.; Anderegg, Q.; Bossuyt, P. M. M.; Lucas, C.

    2005-01-01

    A systematic review was conducted to determine inter-examiner reliability of passive assessment of segmental intervertebral motion in the cervical and lumbar spine as well as to explore sources of heterogeneity. Passive assessment of motion is used to decide on treatments for neck and low-back pain

  10. Geometry of the vertebral bodies and the intervertebral discs in lumbar segments adjacent to spondylolysis and spondylolisthesis: pilot study.

    Science.gov (United States)

    Been, Ella; Li, Ling; Hunter, David J; Kalichman, Leonid

    2011-07-01

    The objective is to evaluate the geometric parameters of vertebral bodies and intervertebral discs in spinal segments adjacent to spondylolysis and spondylolisthesis. This pilot cross-sectional study was an ancillary project to the Framingham Heart Study. The presence of spondylolysis and spondylolisthesis as well as measurements of spinal geometry were identified on CT imaging of 188 individuals. Spinal geometry measurements included lordosis angle, wedging of each lumbar vertebra and intervertebral disc. Last measurements were used to calculate ΣB, the sum of the lumbar L1-L5 body wedge angles; and ΣD, the sum of the lumbar L1-L5 intervertebral disc angles. Using Wilcoxon-Mann-Whitney test we compared the geometric parameters between individuals with no pathology and ones with spondylolysis (with no listhesis) at L5 vertebra, ones with isthmic spondylolisthesis at L5-S1 level, and ones with degenerative spondylolisthesis at L5-S1 level. Spinal geometry in individuals with spondylolysis or listhesis at L5 shows three major patterns: In spondylolysis without listhesis, spinal morphology is similar to that of healthy individuals; In isthmic spondylolisthesis there is high lordosis angle, high L5 vertebral body wedging and very high L4-5 disc wedging; In degenerative spondylolisthesis, spinal morphology shows more lordotic wedging of the L5 vertebral body, and less lordotic wedging of intervertebral discs. In conclusion, there are unique geometrical features of the vertebrae and discs in spondylolysis or listhesis. These findings need to be reproduced in larger scale study.

  11. MRI T2* mapping correlates with biochemistry and histology in intervertebral disc degeneration in a large animal model

    NARCIS (Netherlands)

    Detiger, Suzanne E. L.; Holewijn, Roderick M.; Hoogendoorn, Roel J. W.; van Royen, Barend J.; Helder, Marco N.; Berger, Ferco H.; Kuijer, Joost P. A.; Smit, Theo H.

    2015-01-01

    To evaluate intervertebral disc (IVD) degeneration and treatments, an objective diagnostic tool is needed. Recently, T2* relaxation time mapping was proposed as a technique to assess early IVD degeneration, yet the correlation with biochemical content and histological features has not been

  12. MRI T2* mapping correlates with biochemistry and histology in intervertebral disc degeneration in a large animal model

    NARCIS (Netherlands)

    Detiger, S.E.L.; Holewijn, R.M.; Hoogendoorn, R.J.W.; van Royen, B.J.; Helder, M.N.; Berger, F.H.; Kuijer, J.P.A.; Smit, T.H.

    2015-01-01

    Purpose: To evaluate intervertebral disc (IVD) degeneration and treatments, an objective diagnostic tool is needed. Recently, T2* relaxation time mapping was proposed as a technique to assess early IVD degeneration, yet the correlation with biochemical content and histological features has not been

  13. Combined Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation

    Directory of Open Access Journals (Sweden)

    Chunyue Cai

    2018-01-01

    Full Text Available Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group (n=35 and control group (n=35. The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA score, and simplified McGill pain questionnaire (MPQ were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group (P=0.036. The scores of JOA and MPQ detected in the patients of the two groups (P<0.05 also showed statistically significant differences. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical

  14. Combined Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation.

    Science.gov (United States)

    Cai, Chunyue; Gong, Yuefeng; Dong, Dayong; Xue, Jinbiao; Zheng, Xiaoting; Zhong, Zhangfeng; Shao, Jialong; Mi, Daguo

    2018-01-01

    Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM) including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group ( n = 35) and control group ( n = 35). The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA) score, and simplified McGill pain questionnaire (MPQ) were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group ( P = 0.036). The scores of JOA and MPQ detected in the patients of the two groups ( P cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications.

  15. Qualitative and quantitative assessment of collagen and elastin in annulus fibrosus of the physiologic and scoliotic intervertebral discs.

    Science.gov (United States)

    Kobielarz, Magdalena; Szotek, Sylwia; Głowacki, Maciej; Dawidowicz, Joanna; Pezowicz, Celina

    2016-09-01

    The biophysical properties of the annulus fibrosus of the intervertebral disc are determined by collagen and elastin fibres. The progression of scoliosis is accompanied by a number of pathological changes concerning these structural proteins. This is a major cause of dysfunction of the intervertebral disc. The object of the study were annulus fibrosus samples excised from intervertebral discs of healthy subjects and patients treated surgically for scoliosis in the thoracolumbar or lumbar spine. The research material was subjected to structural analysis by light microscopy and quantitative analysis of the content of collagen types I, II, III and IV as well as elastin by immunoenzymatic test (ELISA). A statistical analysis was conducted to assess the impact of the sampling site (Mann-Whitney test, α=0.05) and scoliosis (Wilcoxon matched pairs test, α=0.05) on the obtained results. The microscopic studies conducted on scoliotic annulus fibrosus showed a significant architectural distortion of collagen and elastin fibres. Quantitative biochemical assays demonstrated region-dependent distribution of only collagen types I and II in the case of healthy intervertebral discs whereas in the case of scoliotic discs region-dependent distribution concerned all examined proteins of the extracellular matrix. Comparison of scoliotic and healthy annulus fibrosus revealed a significant decrease in the content of collagen type I and elastin as well as a slight increase in the proportion of collagen types III and IV. The content of collagen type II did not differ significantly between both groups. The observed anomalies are a manifestation of degenerative changes affecting annulus fibrosus of the intervertebral disc in patients suffering from scoliosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Qualitative and quantitative assessment of degeneration of cervical intervertebral discs and facet joints.

    Science.gov (United States)

    Walraevens, Joris; Liu, Baoge; Meersschaert, Joke; Demaerel, Philippe; Delye, Hans; Depreitere, Bart; Vander Sloten, Jos; Goffin, Jan

    2009-03-01

    Degeneration of intervertebral discs and facet joints is one of the most frequently encountered spinal disorders. In order to describe and quantify degeneration and evaluate a possible relationship between degeneration and biomechanical parameters, e.g., the intervertebral range of motion and intradiscal pressure, a scoring system for degeneration is mandatory. However, few scoring systems for the assessment of degeneration of the cervical spine exist. Therefore, two separate objective scoring systems to qualitatively and quantitatively assess the degree of cervical intervertebral disc and facet joint degeneration were developed and validated. The scoring system for cervical disc degeneration consists of three variables which are individually scored on neutral lateral radiographs: "height loss" (0-4 points), "anterior osteophytes" (0-3 points) and "endplate sclerosis" (0-2 points). The scoring system for facet joint degeneration consists of four variables which are individually scored on neutral computed tomography scans: "hypertrophy" (0-2 points), "osteophytes" (0-1 point), "irregularity" on the articular surface (0-1 point) and "joint space narrowing" (0-1 point). Each variable contributes with varying importance to the overall degeneration score (max 9 points for the scoring system of cervical disc degeneration and max 5 points for facet joint degeneration). Degeneration of 20 discs and facet joints of 20 patients was blindly assessed by four raters: two neurosurgeons (one senior and one junior) and two radiologists (one senior and one junior), firstly based on first subjective impression and secondly using the scoring systems. Measurement errors and inter- and intra-rater agreement were determined. The measurement error of the scoring system for cervical disc degeneration was 11.1 versus 17.9% of the subjective impression results. This scoring system showed excellent intra-rater agreement (ICC = 0.86, 0.75-0.93) and excellent inter-rater agreement (ICC = 0

  17. Acquired degenerative changes of the intervertebral segments at and suprajacent to the lumbosacral junction. A radioanatomic analysis of the nondiskal structures of the spinal column and perispinal soft tissues.

    Science.gov (United States)

    Jinkins, J R

    2001-01-01

    In earlier evolutionary times, mammals were primarily quadrupeds. However, other bipeds have also been represented during the course of the Earth's several billion year history. In many cases, either the bipedal stance yielded a large tail and hypoplastic upper extremities (e.g., Tyrannosaurus rex and the kangaroo), or it culminated in hypoplasia of the tail and further development and specialization of the upper extremities (e.g., nonhuman primates and human beings). In the human species this relatively recently acquired posture resulted in a more or less pronounced lumbosacral kyphosis. In turn, certain compensatory anatomic features have since occurred. These include the normal characteristic posteriorly directed wedge-shape of the L5 vertebral body and the L5-S1 intervertebral disk; the L4 vertebral body and the L4-L5 disk may be similarly visibly affected. These compensatory mechanisms, however, have proved to be functionally inadequate over the long term of the human life span. Upright posture also leads to increased weight bearing in humans that progressively causes excess stresses at and suprajacent to the lumbosacral junction. These combined factors result in accelerated aging and degenerative changes and a predisposition to frank biomechanical failure of the subcomponents of the spinal column in these spinal segments. One other specific problem that occurs at the lumbosacral junction that predisposes toward premature degeneration is the singular relationship that exists between a normally mobile segment of spine (i.e., the lumbar spine) and a normally immobile one (i.e., the sacrum). It is well known that mobile spinal segments adjacent to congenitally or acquired fused segments have a predilection toward accelerated degenerative changes. The only segment of the spine in which this is invariably normally true is at the lumbosacral junction (i.e., the unfused lumbar spine adjoining the fused sacrum). Nevertheless, biomechanical failures of the human spine

  18. Comparison of Farfan modified and Frobin methods to evaluate the intervertebral disc height

    Directory of Open Access Journals (Sweden)

    Michel Kanas

    2014-03-01

    Full Text Available OBJECTIVE: To evaluate the reliability and reproducibility of Farfan modified and Frobin methods to measure the intervertebral disc height in radiographs with inter- and intraobserver comparison. METHOD: Six radiographs of different patients treated for low back pain have been collected and digitized, and five lumbar disc of each patient were evaluated by six examiners with different levels of experience. The measures were done in Image Pro Plus 6.0 software. RESULTS: When compared, both methods showed more than 95% concordance. In intraexaminer analysis, both also shown to be reliable and reproducible, with a high level of concordance. By comparing the correlation between classes of examiners, the higher the level of experience, the greater the agreement for both methods. CONCLUSION: Farfan modified and Frobin are reliable methods to measure the disc height in the lateral radiographs. The higher level of experience of the examiner, the higher was the correlation between measurements.

  19. Prognosis of intervertebral disc loss from diagnosis of degenerative disc disease

    Science.gov (United States)

    Li, S.; Lin, A.; Tay, K.; Romano, W.; Osman, Said

    2015-03-01

    Degenerative Disc Disease (DDD) is one of the most common causes of low back pain, and is a major factor in limiting the quality of life of an individual usually as they enter older stages of life, the disc degeneration reduces the shock absorption available which in turn causes pain. Disc loss is one of the central processes in the pathogenesis of DDD. In this study, we investigated whether the image texture features quantified from magnetic resonance imaging (MRI) could be appropriate markers for diagnosis of DDD and prognosis of inter-vertebral disc loss. The main objective is to use simple image based biomarkers to perform prognosis of spinal diseases using non-invasive procedures. Our results from 65 subjects proved the higher success rates of the combination marker compared to the individual markers and in the future, we will extend the study to other spine regions to allow prognosis and diagnosis of DDD for a wider region.

  20. Conservative therapy for lumbar intervertebral disc hernia. Intradiscal compressive injection and MRI findings

    International Nuclear Information System (INIS)

    Yoshida, Tohru; Nanba, Hiromichi; Kasai, Tsutomu; Ohta, Susumu

    1996-01-01

    To herniating intervertebral discs, 3-20 ml physiological saline was pressurized and injected. To avoid excessive force, the injection pressure was set at less than 3 kg/cm 2 . Between January 1993 and December 1994, 380 cases were studied (286 men and 94 women with a mean age of 45.5 years). After the compressive injection there were 259 (68.2%) effective cases in which symptoms were relieved and 121 ineffective cases (31.8%). The proportion of effective cases was higher in women than in men and in older than in younger patients. After intradiscal pressurized injection, the effective cases were investigated with MRI and a tendency to relatively early shrinkage of herniated mass was noted. (author)

  1. Conservative therapy for lumbar intervertebral disc hernia. Intradiscal compressive injection and MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Tohru; Nanba, Hiromichi; Kasai, Tsutomu; Ohta, Susumu [Yoshida Orthopaedic Hospital, Toyota, Aichi (Japan)

    1996-01-01

    To herniating intervertebral discs, 3-20 ml physiological saline was pressurized and injected. To avoid excessive force, the injection pressure was set at less than 3 kg/cm{sup 2}. Between January 1993 and December 1994, 380 cases were studied (286 men and 94 women with a mean age of 45.5 years). After the compressive injection there were 259 (68.2%) effective cases in which symptoms were relieved and 121 ineffective cases (31.8%). The proportion of effective cases was higher in women than in men and in older than in younger patients. After intradiscal pressurized injection, the effective cases were investigated with MRI and a tendency to relatively early shrinkage of herniated mass was noted. (author).

  2. Experiences of intervertebral motion palpation in osteopathic practice - A qualitative interview study among Swedish osteopaths.

    Science.gov (United States)

    Sposato, Niklas S; Bjerså, Kristofer

    2017-01-01

    Assessment in manual therapy includes quantitative and qualitative procedures, and intervertebral motion palpation (IMP) is one of the core assessment methods in osteopathic practice. The aim of this study was to explore osteopathic practitioners' experiences of clinical decision-making and IMP as a diagnostic tool for planning and evaluation of osteopathic interventions. The study was conducted with semi-structured interviews that included eight informants. Content analysis was used as the analytical procedure. In total, three categories emerged from the analysis: strategic decision-making, diagnostic usability of IMP, and treatment applicability of IMP. The study indicated that IMP was considered relevant and was given particular importance in cases where IMP findings confirmed clinical information attained from other stages in the diagnostic process as a whole. However, IMP findings were experienced as less important if they were not correlated to other findings. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. A study of sodium alginate and calcium chloride interaction through films for intervertebral disc regeneration uses

    International Nuclear Information System (INIS)

    Laia, Andreia Grossi Santos de; Costa Junior, Ezequiel de Souza; Costa, Hermes de Souza

    2014-01-01

    The injured intervertebral disc (IVD) requires some measures in order to promote its regeneration. The sodium alginate in conjunction with CaCl_2 forms a net, potentiating its mechanical properties so it may be an alternative for IVD treatment. In this work, the viability of films of sodium alginate crosslinked with CaCl_2 and submitted to variations in their solutions' preparations is verified, comparing the effects of the addition of CaCl_2 through their immersions, before and after drying the films. The films had their physicochemical properties analyzed by FTIR, DSC and XRD. The results indicated that films with a greater proportion of CaCl_2 were more stable in the DSC analysis when compared to films with smaller proportions of CaCl_2. These results indicate alginate's modulation capacity which may be useful for IVD regeneration. (author)

  4. Discoscopic Findings of High Signal Intensity Zones on Magnetic Resonance Imaging of Lumbar Intervertebral Discs

    Directory of Open Access Journals (Sweden)

    Kosuke Sugiura

    2014-01-01

    Full Text Available A 32-year-old man underwent radiofrequency thermal annuloplasty (TA with percutaneous endoscopic discectomy (PED under local anesthesia for chronic low back pain. His diagnosis was discogenic pain with a high signal intensity zone (HIZ in the posterior corner of the L4-5 disc. Flexion pain was sporadic, and steroid injection was given twice for severe pain. After the third episode of strong pain, PED and TA were conducted. The discoscope was inserted into the posterior annulus and revealed a migrated white nucleus pulposus which was stained blue. Then, after moving the discoscope to the site of the HIZ, a migrated slightly red nucleus pulposus was found, suggesting inflammation and/or new vessels penetrating the mass. After removing the fragment, the HIZ site was ablated by TA. To our knowledge, this is the first report of the discoscopic findings of HIZ of the lumbar intervertebral disc.

  5. Mapping the World's Intact Forest Landscapes by Remote Sensing

    Directory of Open Access Journals (Sweden)

    Peter Potapov

    2008-12-01

    Full Text Available Protection of large natural forest landscapes is a highly important task to help fulfill different international strategic initiatives to protect forest biodiversity, to reduce carbon emissions from deforestation and forest degradation, and to stimulate sustainable forest management practices. This paper introduces a new approach for mapping large intact forest landscapes (IFL, defined as an unbroken expanse of natural ecosystems within areas of current forest extent, without signs of significant human activity, and having an area of at least 500 km2. We have created a global IFL map using existing fine-scale maps and a global coverage of high spatial resolution satellite imagery. We estimate the global area of IFL within the current extent of forest ecosystems (forest zone to be 13.1 million km2 or 23.5% of the forest zone. The vast majority of IFL are found in two biomes: Dense Tropical and Subtropical Forests (45.3% and Boreal Forests (43.8%. The lowest proportion of IFL is found in Temperate Broadleaf and Mixed Forests. The IFL exist in 66 of the 149 countries that together make up the forest zone. Three of them - Canada, Russia, and Brazil - contain 63.8% of the total IFL area. Of the world's IFL area, 18.9% has some form of protection, but only 9.7% is strictly protected, i.e., belongs to IUCN protected areas categories I-III. The world IFL map presented here is intended to underpin the development of a general strategy for nature conservation at the global and regional scales. It also defines a baseline for monitoring deforestation and forest degradation that is well suited for use with operational and cost-effective satellite data. All project results and IFL maps are available on a dedicated web site (http://www.intactforests.org.

  6. Relationships between Paraspinal Muscle Activity and Lumbar Inter-Vertebral Range of Motion

    Directory of Open Access Journals (Sweden)

    Alister du Rose

    2016-01-01

    Full Text Available Control of the lumbar spine requires contributions from both the active and passive sub-systems. Identifying interactions between these systems may provide insight into the mechanisms of low back pain. However, as a first step it is important to investigate what is normal. The purpose of this study was to explore the relationships between the lumbar inter-vertebral range of motion and paraspinal muscle activity during weight-bearing flexion in healthy controls using quantitative fluoroscopy (QF and surface electromyography (sEMG. Contemporaneous lumbar sEMG and QF motion sequences were recorded during controlled active flexion of 60° using electrodes placed over Longissimus thoracis pars thoracis (TES, Longissimus thoracis pars lumborum (LES, and Multifidus (LMU. Normalised root mean square (RMS sEMG amplitude data were averaged over five epochs, and the change in amplitude between epochs was calculated. The sEMG ratios of LMU/LES LMU/TES and LES/TES were also determined. QF was used to measure the maximum inter-vertebral range of motion from L2-S1, and correlation coefficients were calculated between sEMG amplitude variables and these measurements. Intra- and inter-session sEMG amplitude repeatability was also assessed for all three paraspinal muscles. The sEMG amplitude measurements were highly repeatable, and sEMG amplitude changes correlated significantly with L4-5 and L5-S1 IV-RoMmax (r = −0.47 to 0.59. The sEMG amplitude ratio of LES/TES also correlated with L4-L5 IV-RoMmax (r = −0.53. The relationships found may be important when considering rehabilitation for low back pain.

  7. Relationships between Paraspinal Muscle Activity and Lumbar Inter-Vertebral Range of Motion.

    Science.gov (United States)

    du Rose, Alister; Breen, Alan

    2016-01-05

    Control of the lumbar spine requires contributions from both the active and passive sub-systems. Identifying interactions between these systems may provide insight into the mechanisms of low back pain. However, as a first step it is important to investigate what is normal. The purpose of this study was to explore the relationships between the lumbar inter-vertebral range of motion and paraspinal muscle activity during weight-bearing flexion in healthy controls using quantitative fluoroscopy (QF) and surface electromyography (sEMG). Contemporaneous lumbar sEMG and QF motion sequences were recorded during controlled active flexion of 60° using electrodes placed over Longissimus thoracis pars thoracis (TES), Longissimus thoracis pars lumborum (LES), and Multifidus (LMU). Normalised root mean square (RMS) sEMG amplitude data were averaged over five epochs, and the change in amplitude between epochs was calculated. The sEMG ratios of LMU/LES LMU/TES and LES/TES were also determined. QF was used to measure the maximum inter-vertebral range of motion from L2-S1, and correlation coefficients were calculated between sEMG amplitude variables and these measurements. Intra- and inter-session sEMG amplitude repeatability was also assessed for all three paraspinal muscles. The sEMG amplitude measurements were highly repeatable, and sEMG amplitude changes correlated significantly with L4-5 and L5-S1 IV-RoMmax (r = -0.47 to 0.59). The sEMG amplitude ratio of LES/TES also correlated with L4-L5 IV-RoMmax (r = -0.53). The relationships found may be important when considering rehabilitation for low back pain.

  8. Cadaveric Study of Male Lumbar Intervertebral Foramina Morphometry in Ile-Ife

    Directory of Open Access Journals (Sweden)

    Sunday E. C

    2018-04-01

    Full Text Available Background: This study was designed to investigate the mean lumbar foramina height and length in male cadaveric specimens in Ile-Ife. Aim and Objectives: Two hundred and fifty intervertebral foramina derived from twenty-five male cadaveric specimens were analyzed, were studied. They were obtained from the Department of Anatomy, Obafemi Awolowo University, Ile-Ife, Osun State in Southwestern Nigeria. The cadavers were positioned prone and a routine paraspinal approach was employed to gain exposure to the posterior spinal element following meticulous soft tissue dissection. An osteotomy of the iliac crest was performed to adequately expose the fifth lumbar (L1-S1 foramina.Parameters assessed were; the foramen height and the foraminal length. The measurement was performed three times on each side using vernier calipers. The variations of the different measurements in the cephalo-caudal direction were analyzed for statistical differences using the “One way ANOVA” with post hoc test. Results: The result showed a gradual increase of the foramina height were observed on both right and left side from L1-L2 to L3- L4 and from then on decreased progressively towards the L5-S1 level. No statistical difference was noted in the measurements derived (p<0.05. Conclusion: A good understanding of the lumbar intervertebral foraminal are essential in surgical planning of suitably sized cannulas necessary for less invasive spine surgeries as well as help in diagnosis of pathologies surrounding this important region following adequate clinical evaluation and measurements using imaging.

  9. Clinical characterization of thoracolumbar and lumbar intervertebral disk extrusions in English Cocker Spaniels.

    Science.gov (United States)

    Cardy, Thomas J A; Tzounos, Caitlin E; Volk, Holger A; De Decker, Steven

    2016-02-15

    To assess the anatomic distribution of thoracolumbar and lumbar intervertebral disk extrusions (IVDEs) in English Cocker Spaniels as compared with findings in Dachshunds and to characterize clinical findings in English Cocker Spaniels with thoracolumbar or lumbar IVDEs affecting various regions of the vertebral column. Retrospective observational study. 81 English Cocker Spaniels and 81 Dachshunds with IVDEs. Signalment, clinical signs, neurologic examination findings, and affected intervertebral disk spaces (IVDSs) were recorded for both breeds. Management methods and outcomes were recorded for English Cocker Spaniels. Lesions were categorized as thoracolumbar (IVDSs T9-10 through L1-2), midlumbar (L2-3 through L4-5), or caudal lumbar (L5-6 through L7-S1). Midlumbar and caudal lumbar IVDEs were significantly more common in English Cocker Spaniels than in Dachshunds. English Cocker Spaniels with caudal lumbar IVDEs had a longer median duration of clinical signs before evaluation and more commonly had unilateral pelvic limb lameness or spinal hyperesthesia as the predominant clinical sign than did those with IVDEs at other sites. Those with caudal lumbar IVDEs less commonly had neurologic deficits and had a higher median neurologic grade (indicating lesser severity), shorter mean postoperative hospitalization time, and faster mean time to ambulation after surgery than those with other sites affected. These variables did not differ between English Cocker Spaniels with thoracolumbar and midlumbar IVDEs. Caudal and midlumbar IVDEs were more common in English Cocker Spaniels than in Dachshunds. English Cocker Spaniels with caudal lumbar IVDE had clinical signs and posttreatment responses that differed from those in dogs with midlumbar or thoracolumbar IVDE.

  10. Fluid flow and convective transport of solutes within the intervertebral disc.

    Science.gov (United States)

    Ferguson, Stephen J; Ito, Keita; Nolte, Lutz P

    2004-02-01

    Previous experimental and analytical studies of solute transport in the intervertebral disc have demonstrated that for small molecules diffusive transport alone fulfils the nutritional needs of disc cells. It has been often suggested that fluid flow into and within the disc may enhance the transport of larger molecules. The goal of the study was to predict the influence of load-induced interstitial fluid flow on mass transport in the intervertebral disc. An iterative procedure was used to predict the convective transport of physiologically relevant molecules within the disc. An axisymmetric, poroelastic finite-element structural model of the disc was developed. The diurnal loading was divided into discrete time steps. At each time step, the fluid flow within the disc due to compression or swelling was calculated. A sequentially coupled diffusion/convection model was then employed to calculate solute transport, with a constant concentration of solute being provided at the vascularised endplates and outer annulus. Loading was simulated for a complete diurnal cycle, and the relative convective and diffusive transport was compared for solutes with molecular weights ranging from 400 Da to 40 kDa. Consistent with previous studies, fluid flow did not enhance the transport of low-weight solutes. During swelling, interstitial fluid flow increased the unidirectional penetration of large solutes by approximately 100%. Due to the bi-directional temporal nature of disc loading, however, the net effect of convective transport over a full diurnal cycle was more limited (30% increase). Further study is required to determine the significance of large solutes and the timing of their delivery for disc physiology.

  11. Proportional lumbar spine inter-vertebral motion patterns: a comparison of patients with chronic, non-specific low back pain and healthy controls

    OpenAIRE

    Mellor, Fiona E.; Thomas, Peter; Thompson, Paul W.; Breen, Alan C.

    2014-01-01

    Introduction: Identifying biomechanical subgroups in chronic, non-specific low back pain (CNSLBP) populations from inter-vertebral displacements has proven elusive. Quantitative fluoroscopy (QF) has excellent repeatability and provides continuous standardised inter-vertebral kinematic data from fluoroscopic sequences allowing assessment of mid-range motion. The aim of this study was to determine whether proportional continuous IV rotational patterns were different in patients and controls. A ...

  12. Ultrashort time-to-echo MRI of the cartilaginous endplate: technique and association with intervertebral disc degeneration

    International Nuclear Information System (INIS)

    Law, Travis; Anthony, Marina-Portia; Kim, Mina; Khong, Pek-Lan; Chan, Queenie; Samartzis, Dino

    2013-01-01

    The purpose of this study was to report the feasibility of the ultrashort time-to-echo (UTE) MRI technique to assess cartilaginous endplate (CEP) defects in humans in vivo and to assess their relationship with intervertebral disc (IVD) degeneration. Nine volunteer subjects (mean age=43.9 years; range=22–61 years) were recruited, representing 54 IVDs and 108 CEPs. The subjects underwent T2-weighted and UTE MRI to assess for the presence and severity of IVD degeneration, and for the presence of CEP defects, respectively, from T12 to S1. IVD degeneration was graded according to the Schneiderman et al. classification on T2-weighted MRI. CEP defects were defined on UTE MRI as discontinuity of high signal over four consecutive images and were independently assessed by two observers. Thirty-seven out of 108 (34.3%) CEPs had defects, which mainly occurred at T12/L1, L1/L2 and L4/L5 (P=0.008). Multivariate logistic regression revealed that lower body mass index (P=0.009) and younger (P=0.034) individuals had a decreased likelihood of having CEP defects. A statistically significant association was found to exist between the presence of CEP defects and IVD degeneration (P=0.036). A higher prevalence of degenerated IVDs with CEP defects was found at L4/5 and L5/S1, while degenerated IVDs with no CEP defects were found throughout the whole lumbar region. Mean IVD degeneration scores of the L4/5 and L5/S1 levels with CEP defects were higher in comparison with those with no CEP defects. Our study demonstrates the feasibility of using UTE MRI in humans in vivo to assess the integrity of the CEP. A statistically significant association was found to exist between the presence of CEP defects and IVD degeneration. In the lower lumbar region, more severe degeneration was found to occur in the IVDs with CEP defects than in those without defects.

  13. [The possibilities for diagnostics of prescription of death coming based on the changes in the lumbar intervertebral disks (the comparison of the morphological, immunohistochemical and topographical findings)].

    Science.gov (United States)

    Byval'tsev, V A; Stepanov, I A; Semenov, A V; Perfil'ev, D V; Belykh, E G; Bardonova, L A; Nikiforov, S B; Sudakov, N P; Bespyatykh, I V; Antipina, S L

    The objective of the present study was the comprehensive analysis of the postmortem changes in the lumbar intervertebral disks within different periods after death. A total of seven vertebromotor segments were distinguished in the lumbosacral region of the vertebral column based on the examination of 7 corpses. All these segments were divided into three groups in accordance with the prescription of death coming as follows: up to 12 hours (group 1), between 12 and 24 hours (group 2), and between 24 and 36 hours (group 3) after death. The models of the segments thus obtained were subjected to the study by means of diffusion weighted MRI. The removed intervertebral disks were used for morphological and immunohistochemical investigations. The comparison of the diffusion coefficients (DI) revealed the significant difference between the intervertebral disks assigned to groups 1 and 2 (p<0.01). The number of the cells in the pulpal core, the vertebral end plate, and the fibrous ring in all the above groups of the intervertebral disks was significantly reduced (p<0.01). The analysis of the correlation dependence between cell density and diffusion coefficients has demonstrated the well apparent relationship between these characteristics of the intervertebral disks comprising groups 1 and 2. It is concluded that diffusion weighted MRI in the combination with the calculation of diffusion coefficients for the intervertebral disks provides a tool for diagnostics of prescription of death coming as confirmed by the results of the morphometric studies and immunohistochemical analysis.

  14. Fatores genéticos e ambientais envolvidos na degeneração do disco intervertebral Genetic and environmental factors involved on intervertebral disc degeneration

    Directory of Open Access Journals (Sweden)

    Francine Teresa Brioni Nunes

    2007-01-01

    Full Text Available A etiologia da degeneração do disco intervertebral (DDI ainda não está totalmente esclarecida. O gene do receptor da vitamina D (VDR tem sido apontado como um dos possíveis envolvidos no surgimento das discopatias. Por outro lado, este estudo relaciona pela primeira vez, a participação dos genes das glutatião transferases M1 e T1 (GSTT1 e GSTM1, responsáveis pela inativação dos componentes do cigarro, na DDI. Foi extraído DNA de leucócitos de 66 pacientes e 88 controles, pareados por gênero e idade. O polimorfismo VDR-FokI foi amplificado por reação em cadeia da polimerase (PCR seguido de restrição com a enzima FokI. Os polimorfismos das GSTT1/M1 foram determinados por meio da PCR multiplex. A história familial e a gravidade da doença se destacaram nos pacientes portadores do alelo f do gene VDR-FokI (P=0,000 e 0,0012, respectivamente. A idade de surgimento da doença mostrou-se precoce nos indivíduos com genótipo _/f (média de 26 anos. Foi encontrada associação do polimorfismo FokI com a degeneração precoce e gravidade da DDI, sendo que o hábito de fumar também interferiu nesse processo, independente da presença ou não do genótipo favorável para GSTT1/M1.The etiology of intervertebral disc degeneration (IDD has not been fully clarified yet. Vitamin D receptor’s gene (VDR has been suggested as one of the potential entities involved in disc pathologies onset. On the other hand, this study correlates, for the first time, glutathione transferases M1 and T1 genes (GSTT1 and GSTM1 participation, which are responsible for cigarette components’ inactivation, in IDD. DNA was extracted from leukocytes of 66 patients and 88 controls, paired by gender and age. The VDR-Fokl polymorphism was amplified by polymerase chain reaction (PCR followed by restriction with Fokl enzyme. GSTT1/M1 polymorphisms were determined by means of PCR multiplex. Family history and disease severity were highlighted in patients carrying the f

  15. Assessment of geomechanical properties of intact Opalinus Clay - Expert report

    International Nuclear Information System (INIS)

    Amann, F.; Vogelhuber, M.

    2015-11-01

    This comprehensive report published by the Swiss Federal Nuclear Safety Inspectorate ENSI presents an expert report published on the assessment of the geomechanical properties of intact Opalinus Clay. This review report addresses the conceptual constitutive framework for repositories in Opalinus Clay. The author addresses the geomechanical fundamentals that are necessary in order to adequately judge experiments on intact Opalinus Clay and the interpretation of the results. The report assesses in detail the various test series on intact Opalinus Clay carried out along with the interpretations made by experts and NAGRA. Further assessments are quoted including those on sample geometries tested, effective strength properties, undrained shear strength properties and elastic properties. The results of work done by other experts are also presented and discussed. The report is completed with a list of relevant literature

  16. Assessment of geomechanical properties of intact Opalinus Clay - Expert report

    Energy Technology Data Exchange (ETDEWEB)

    Amann, F. [Eidgenössische Technische Hochschule ETHZ, Zürich (Switzerland); Vogelhuber, M. [Dr. von Moos AG, Geotechnisches Büro, Zürich (Switzerland)

    2015-11-15

    This comprehensive report published by the Swiss Federal Nuclear Safety Inspectorate ENSI presents an expert report published on the assessment of the geomechanical properties of intact Opalinus Clay. This review report addresses the conceptual constitutive framework for repositories in Opalinus Clay. The author addresses the geomechanical fundamentals that are necessary in order to adequately judge experiments on intact Opalinus Clay and the interpretation of the results. The report assesses in detail the various test series on intact Opalinus Clay carried out along with the interpretations made by experts and NAGRA. Further assessments are quoted including those on sample geometries tested, effective strength properties, undrained shear strength properties and elastic properties. The results of work done by other experts are also presented and discussed. The report is completed with a list of relevant literature.

  17. Are animal models useful for studying human disc disorders / degeneration?

    NARCIS (Netherlands)

    Alini, M.; Eisenstein, S.M.; Ito, K.; Little, C.; Kettler, A.A.; Masuda, K.; Melrose, J.; Ralphs, J.; Stokes, I.; Wilke, H.J.

    2008-01-01

    Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo

  18. Beta Adrenergic Regulation of Intrapulmonary Arteriovenous Anastomoses in Intact Rat and Isolated Rat Lungs

    Directory of Open Access Journals (Sweden)

    Melissa L. Bates

    2017-04-01

    Full Text Available Intrapulmonary arteriovenous anastomoses (IPAVA allow large diameter particles of venous origin to bypass the pulmonary capillary bed and embolize the systemic arterial circulation. IPAVA have been routinely observed in healthy humans with exercise, hypoxia, and catecholamine infusion, but the mechanism by which they are recruited is not well-defined. We hypothesized that beta-adrenergic receptor stimulation recruits IPAVA and that receptor blockade would limit hypoxia-induced IPAVA recruitment. To test our hypothesis, we evaluated the transpulmonary passage of microspheres in intact rats and isolated rats lung infused with the beta-adrenergic receptor agonist isoproterenol. We also evaluated IPAVA recruitment in intact rats with hypoxia and the beta-adrenergic receptor blocker propranolol. We found that IPAVA are recruited in the intact rat by isoproterenol and their recruitment by hypoxia can be minimized by propranolol, suggesting a role for the adrenergic system in the recruitment of IPAVA by hypoxia. IPAVA recruitment is completely abolished by ventilation with 100% oxygen. Isoproterenol also recruits IPAVA in isolated rat lungs. The fact that isoproterenol can recruit IPAVA in isolated lungs, without increased pulmonary flow, suggests that elevated cardiac output is not required for IPAVA recruitment.

  19. Effect of Capsaicin Cream on Chronic Low Back Pain in Patients With Inter-Vertebral Disc Herniation

    OpenAIRE

    Fayazi; Farokhpyam; Talali

    2015-01-01

    Background Low back pain is one of the most common debilitating disorders worldwide and the third cause of visiting a physician. One of the most common causes of low back pain is spinal disc herniation. Still there is no general agreement on the most effective treatment for it. Objectives This study aimed to determine the effect of Capsaicin cream on low back pain in patients with inter-vertebral disc herniation in Ahvaz. ...

  20. Cervical intervertebral disk herniation in chondrodystrophoid and nonchondrodystrophoid small-breed dogs: 187 cases (1993-2013).

    Science.gov (United States)

    Hakozaki, Takaharu; Iwata, Munetaka; Kanno, Nobuo; Harada, Yasuji; Yogo, Takuya; Tagawa, Masahiro; Hara, Yasushi

    2015-12-15

    To identify characteristics of chondrodystrophoid and nonchondrodystrophoid small-breed dogs with cervical intervertebral disk herniation (IVDH). Retrospective case series. 187 small-breed (≤ 15 kg [33 lb]) dogs that underwent surgery because of cervical IVDH. Medical records were reviewed for information on breed, sex, age, weight, location of affected intervertebral disks, duration and severity of neurologic signs, and recovery time. 55 of the 187 (29.4%) dogs were Beagles. The most frequently affected intervertebral disk was C2-3 (81/253 [32.0%]), and this was the more frequently affected intervertebral disk in dogs of several chondrodystrophoid breeds, including Beagles (29/66 [43.9%]), Dachshunds (13/37 [35.1%]), Shih Tzus (16/41 [39.0%]), and Pekingese (3/10 [30.0%]). However, caudal disks (C5-6 or C6-7) were more frequently affected in Yorkshire Terriers (13/24 [54.2%]) and Chihuahuas (9/13 [69%]). Shih Tzus and Yorkshire Terriers were significantly older at the time of surgery (mean ± SD age, 9.6 ± 2.3 years and 9.5 ± 2.5 years, respectively) than were Pomeranians (6.2 ± 2.3 years), and Yorkshire Terriers had a significantly higher number of affected disks (2.0 ± 0.9) than did Dachshunds (1.1 ± 0.3). Mean recovery time was significantly longer in Yorkshire Terriers (36.7 ± 13.0 days) than in Beagles (16.5 ± 17.1 days), Shih Tzus (17.8 ± 14.5 days), or Chihuahuas (12.2 ± 7. 2 days). Results suggested that there may be breed-specific differences in the characteristics of cervical IVDH in small-breed dogs.

  1. The distribution of lumbar intervertebral angles in upright standing and extension is related to low back pain developed during standing.

    Science.gov (United States)

    Viggiani, Daniel; Gallagher, Kaitlin M; Sehl, Michael; Callaghan, Jack P

    2017-11-01

    Lumbar lordosis measures are poorly related to clinical low back pain, however using a controlled exposure such as prolonged standing to identify pain groups may clarify this relationship. The purpose of this study was to determine the distribution of lumbar intervertebral angles in asymptomatic persons who do (pain developers) and do not (non-pain developers) develop low back pain during standing. Sagittal plane lumbar spine radiographs of eight pain developers and eight non-pain developers were taken in three poses: upright standing, full extension and full flexion. Measures of vertebral end plate orientations from L1 to S1 were taken in each pose to compute: intervertebral angles, contribution of each level to the total curve, total lordosis, ranges of motion, relative pose positioning within the range of motion, vertebral shape, and lumbar spine recurve. Measures were compared between pain groups and lumbar levels. Pain group differences in intervertebral angles and level contributions were greatest in the full extension pose, with pain developers having greater contributions from higher lumbar levels and fewer contributions from lower levels than non-pain developers. Pain group differences in intervertebral angle distributions were less pronounced in upright standing and non-existent in full flexion. No other measures differentiated pain groups. Although participants had similar gross-lumbar spine curvature characteristics, non-pain developers have more curvature at lower levels in upright standing and full extension. These differences in regional vertebral kinematics may partially be responsible for standing-induced low back pain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. A computational study of intervertebral disc degeneration in relation to changes in regional tissue composition and disc nutrition

    OpenAIRE

    Ruiz Wills, Carlos

    2015-01-01

    Up to 85% of the world population suffers from low back pain, a clinical condition often related to the intervertebral disc (IVD) degeneration (DD). Altered disc cell nutrition affects cell viability and can generate catabolic cascades that degrade the extracellular matrix (ECM). Also, a major degenerative biochemical change in the disc is the proteoglycan (PG) loss, which affects the osmotic pressure and hydration that is critical for cell nutrition. However, the relationship between biochem...

  3. Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc

    OpenAIRE

    Mwale F.; Roughley P.; Antoniou J.

    2004-01-01

    Tissue engineering of intervertebral discs (IVD) using mesenchymal stem cells (MSCs) induced to differentiate into a disc-cell phenotype has been considered as an alternative treatment for disc degeneration. However, since there is no unique marker characteristic of discs and since hyaline cartilage and immature nucleus pulposus (NP) possess similar macromolecules in their extracellular matrix, it is currently difficult to recognize MSC conversion to a disc cell. This study was performed to c...

  4. The morphometric analysis of the intervertebral foramen and the spinal nerve root in the cervical spine

    International Nuclear Information System (INIS)

    Yoshida, Yasuo

    2008-01-01

    The purpose of this study was to clarify the onset of cervical myelopathy and cervical spondylotic radiculopathy as well as what influence the anatomy of the cervical spine and cervical nerves have on their onset and occurrence of various types of disease state. We conducted imaging and morphological measurements on specimens of cervical spine of Japanese people, focusing attention on the running of intervertebral foramen and dorsal nerve rootlets of the cervical spine. The subjects were cervical spine specimens from 12 cadavers (7 males and 5 females, age at the time of death ranged from 48 to 93 years with a mean of 71 years) obtained at Showa University School of Dentistry in 2005 and 2006. Specimens were prepared by removing the atlas through the 1st thoracic vertebra from the cadavers, then resecting the soft tissue such as muscles to expose the cervical spine in whole circumference. The removed cervical spine specimens, from 1st to 7th cervical spines, were imaged by volume scan of radiographic helical CT at 0.6 mm spatial resolution, and their images were stored as Digital Imaging and Communications in Medicine (DICOM) data. Image measurement on the vertebral body, vertebral foramen, and intervertebral foramen was conducted based on DICOM data. Furthermore, macroscopic observation and measurement were conducted on the dorsal nerve rootlets of cervical spine specimens. The image measurement of cervical spine specimens showed that the intervertebral foramen at C5/6 was the narrowest, followed by C3/4, C4/5, C6/7, and C2/3, respecting. With regard to angles in the frontal section and horizontal section of the groove for the spinal nerve, there was no significant difference in the angle between the right and the left. In the frontal section, the angle was about 63deg at C3, about 57deg at C4, about 52deg at C5, and about 55deg at C6, showing a significantly acute angle at C5, while in the horizontal section, it was about 54deg at C3, about 59deg at C4, about 63

  5. Measurement of Intervertebral Cervical Motion by Means of Dynamic X-Ray Image Processing and Data Interpolation

    Directory of Open Access Journals (Sweden)

    Paolo Bifulco

    2013-01-01

    Full Text Available Accurate measurement of intervertebral kinematics of the cervical spine can support the diagnosis of widespread diseases related to neck pain, such as chronic whiplash dysfunction, arthritis, and segmental degeneration. The natural inaccessibility of the spine, its complex anatomy, and the small range of motion only permit concise measurement in vivo. Low dose X-ray fluoroscopy allows time-continuous screening of cervical spine during patient’s spontaneous motion. To obtain accurate motion measurements, each vertebra was tracked by means of image processing along a sequence of radiographic images. To obtain a time-continuous representation of motion and to reduce noise in the experimental data, smoothing spline interpolation was used. Estimation of intervertebral motion for cervical segments was obtained by processing patient’s fluoroscopic sequence; intervertebral angle and displacement and the instantaneous centre of rotation were computed. The RMS value of fitting errors resulted in about 0.2 degree for rotation and 0.2 mm for displacements.

  6. Posterior Decompression, Lumber Interbody Fusion and Internal Fixation in the Treatment of Upper Lumbar Intervertebral Disc Herniation

    Directory of Open Access Journals (Sweden)

    DONG Zhan

    2014-12-01

    Full Text Available Objective: To assess the clinical outcomes of posterior decompression, interbody fusion and internal fixationfor the treatment of the upper lumbar intervertebral disc herniation. Methods: Twelve patients with the upper lumbar intervertebral disc herniation were treated by posterior decompression, interbosy fusion and internal fixation. The time of the operation, the amount of bleeding and the clinical efficacy were evaluated. Results: The time of operation was (143±36 min and the amount of bleeding during operation was (331.5±47.9 mL. There was no spinal cord and injuries, nerve injury, epidural damage and leakage of cerebrospinal fluid. All patients were followed up for 10~19 months with the average being 12.6 months. The functional scoring of Japanese Orthopedic Association (JOA before the operation was (11.4±3.3 scores and final score after follow-up was (22.9±3.1 scores and there were statistical difference (P<0.01. Lumber interbody fusion of all patients completed successfully and the good rate after the operation was 91.7%. Conclusion: Posterior decompression, interbody fusion and internal fixation for the treatment of the upper lumbar intervertebral disc herniation was characterized by full exposure, safety and significant efficacy.

  7. Biomechanical effect of altered lumbar lordosis on intervertebral lumbar joints during the golf swing: a simulation study.

    Science.gov (United States)

    Bae, Tae Soo; Cho, Woong; Kim, Kwon Hee; Chae, Soo Won

    2014-11-01

    Although the lumbar spine region is the most common site of injury in golfers, little research has been done on intervertebral loads in relation to the anatomical-morphological differences in the region. This study aimed to examine the biomechanical effects of anatomical-morphological differences in the lumbar lordosis on the lumbar spinal joints during a golf swing. The golf swing motions of ten professional golfers were analyzed. Using a subject-specific 3D musculoskeletal system model, inverse dynamic analyses were performed to compare the intervertebral load, the load on the lumbar spine, and the load in each swing phase. In the intervertebral load, the value was the highest at the L5-S1 and gradually decreased toward the T12. In each lumbar spine model, the load value was the greatest on the kypholordosis (KPL) followed by normal lordosis (NRL), hypolordosis (HPL), and excessive lordosis (EXL) before the impact phase. However, results after the follow-through (FT) phase were shown in reverse order. Finally, the load in each swing phase was greatest during the FT phase in all the lumbar spine models. The findings can be utilized in the training and rehabilitation of golfers to help reduce the risk of injury by considering individual anatomical-morphological characteristics.

  8. Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs.

    Science.gov (United States)

    Choi, Kyung-Suk; Harfe, Brian D

    2011-06-07

    The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Removal of hedgehog signaling in the notochord and nearby floorplate resulted in the formation of an aberrant notochord sheath that normally surrounds this structure. In the absence of the notochord sheath, small nuclei pulposi were formed, with most notochord cells dispersed throughout the vertebral bodies during embryogenesis. Our data suggest that the formation of the notochord sheath requires hedgehog signaling and that the sheath is essential for maintaining the rod-like structure of the notochord during early embryonic development. As notochord cells form nuclei pulposi, we propose that the notochord sheath functions as a "wrapper" around the notochord to constrain these cells along the vertebral column.

  9. Quantitative in vivo MRI evaluation of lumbar facet joints and intervertebral discs using axial T2 mapping.

    Science.gov (United States)

    Stelzeneder, David; Messner, Alina; Vlychou, Marianna; Welsch, Goetz H; Scheurecker, Georg; Goed, Sabine; Pieber, Karin; Pflueger, Verena; Friedrich, Klaus M; Trattnig, Siegfried

    2011-11-01

    To assess the feasibility of T2 mapping of lumbar facet joints and intervertebral discs in a single imaging slab and to compare the findings with morphological grading. Sixty lumbar spine segments from 10 low back pain patients and 5 healthy volunteers were examined by axial T2 mapping and morphological MRI at 3.0 Tesla. Regions of interest were drawn on a single slice for the facet joints and the intervertebral discs (nucleus pulposus, anterior and posterior annulus fibrosus). The Weishaupt grading was used for facet joints and the Pfirrmann score was used for morphological disc grading ("normal" vs. "abnormal" discs). The inter-rater agreement was excellent for the facet joint T2 evaluation (r = 0.85), but poor for the morphological Weishaupt grading (kappa = 0.15). The preliminary results show similar facet joint T2 values in segments with normal and abnormal Pfirrmann scores. There was no difference in mean T2 values between facet joints in different Weishaupt grading groups. Facet joint T2 values showed a weak correlation with T2 values of the posterior annulus (r = 0.32) This study demonstrates the feasibility of a combined T2 mapping approach for the facet joints and intervertebral discs using a single axial slab.

  10. Quantitative in vivo MRI evaluation of lumbar facet joints and intervertebral discs using axial T2 mapping

    International Nuclear Information System (INIS)

    Stelzeneder, David; Messner, Alina; Scheurecker, Georg; Goed, Sabine; Friedrich, Klaus M.; Trattnig, Siegfried; Vlychou, Marianna; Welsch, Goetz H.; Pieber, Karin; Pflueger, Verena

    2011-01-01

    To assess the feasibility of T2 mapping of lumbar facet joints and intervertebral discs in a single imaging slab and to compare the findings with morphological grading. Sixty lumbar spine segments from 10 low back pain patients and 5 healthy volunteers were examined by axial T2 mapping and morphological MRI at 3.0 Tesla. Regions of interest were drawn on a single slice for the facet joints and the intervertebral discs (nucleus pulposus, anterior and posterior annulus fibrosus). The Weishaupt grading was used for facet joints and the Pfirrmann score was used for morphological disc grading (''normal'' vs. ''abnormal'' discs). The inter-rater agreement was excellent for the facet joint T2 evaluation (r = 0.85), but poor for the morphological Weishaupt grading (kappa = 0.15). The preliminary results show similar facet joint T2 values in segments with normal and abnormal Pfirrmann scores. There was no difference in mean T2 values between facet joints in different Weishaupt grading groups. Facet joint T2 values showed a weak correlation with T2 values of the posterior annulus (r = 0.32) This study demonstrates the feasibility of a combined T2 mapping approach for the facet joints and intervertebral discs using a single axial slab. (orig.)

  11. Ingested soluble CD14 from milk is transferred intact into the blood of newborn rats.

    Science.gov (United States)

    Ward, Tonya L; Spencer, William J; Davis, Laura D R; Harrold, Joann; Mack, David R; Altosaar, Illimar

    2014-02-01

    Milk acts as an edible immune system that is transferred from mother to newborn. Soluble Cluster of Differentiation 14 (sCD14) is a protein found in significant quantities in human milk (~8-29 µg/ml). At a 10-fold lower concentration in the blood (~3 µg/ml), the most notable role of sCD14 is to sequester lipopolysaccharides of Gram-negative bacteria from immune cells. To explore the pharmacodynamics of this milk protein and its biological fate, the biodistribution of radiolabeled sCD14 ((14)C, (125)I) was monitored in 10-d-old rat pups. Up to 3.4 ± 2.2% of the radiolabeled sCD14 administered was observed, intact, in the pup blood for up to 8 h post-ingestion. Additionally, 30.3 ± 13.0% of the radiolabeled sCD14 administered was observed degraded in the stomach at 8 h post-ingestion. A reservoir of intact, administered sCD14 (3.2 ± 0.3%), however, remained in the stomach at 8 h post-ingestion. Intact sCD14 was observed in the small intestine at 5.5 ± 1.6% of the dose fed at 8 h post-ingestion. The presence of intact sCD14 in the blood and the gastrointestinal tract of newborns post-ingestion has implications in the development of allergies, obesity, and other inflammation-related pathogeneses later in life.

  12. Discrimination between intact and decayed pulp regions in carious teeth by ADC mapping.

    Science.gov (United States)

    Cankar, Ksenija; Nemeth, Lidija; Bajd, Franci; Vidmar, Jernej; Serša, Igor

    2014-01-01

    The aim of this study was to evaluate an advanced magnetic resonance imaging (MRI) method, apparent diffusion coefficient (ADC) mapping, in the functional assessment of carious teeth. 38 extracted human teeth with scores of 0, 3 and 6 according to International Caries Detection and Assessment System (ICDAS) criteria were screened and subsequently analyzed by MRI at 2.35 T. Histology sectioning of teeth was used for the gold standard by analyzing two extreme cases (intact and severely decayed). ADC maps of the same teeth were calculated from corresponding diffusion-weighted images and used to obtain ADC distributions along dental pulp as functions of the relative pulp length measured from the occlusal pulp side. The measured distributions were analyzed for the best fit by a four-parameter three-segment linear regression model for ADC distribution along the pulp. MRI results were in good agreement with findings in histological sections of identical teeth. The best fit model parameters, relative decayed region depth, relative transition region width and ADC values of intact and decayed pulp tissue, showed statistically significant differences between the ADC values of intact and decayed pulp tissue (1.0 × 10(-9) m(2)/s vs. 0.74-0.89 × 10(-9) m(2)/s) and the relative decayed region depth progressing with ICDAS score (3 vs. 46% with ICDAS 3 vs. ICDAS 6). The results of this feasibility study confirmed relevance of ADC mapping for the discrimination and localization of intact and decayed regions in dental pulps of carious teeth. © 2014 S. Karger AG, Basel.

  13. Bioavailability and in vivo metabolism of intact glucosinolates

    DEFF Research Database (Denmark)

    Sørensen, Jens Christian; Frandsen, Heidi Blok; Jensen, Søren Krogh

    2016-01-01

    Health benefits associated with consumption of cruciferous vegetables have received considerable attention with a hitherto focus on the role and bioactivity of glucosinolate degradation products. We investigated the in vivo metabolism of intact glucosinolates by following their fate in digesta an...

  14. Capillary zone electrophoresis-mass spectromet of intact proteins

    NARCIS (Netherlands)

    Domínguez-Vega, Elena; Haselberg, Rob; Somsen, Govert W.

    2016-01-01

    Capillary electrophoresis (CE) coupled with mass spectrometry (MS) has proven to be a powerful analytical tool for the characterization of intact proteins. It combines the high separation efficiency, short analysis time, and versatility of CE with the mass selectivity and sensitivity offered by MS

  15. Intact collagen and atelocollagen sponges: Characterization and ESEM observation

    International Nuclear Information System (INIS)

    Ruozi, Barbara; Tosi, Giovanni; Leo, Eliana; Parma, Bruna; Vismara, Susanna; Forni, Flavio; Vandelli, Maria Angela

    2007-01-01

    In this study we have investigated the chemical-physical and morphological properties of intact and atelocollagen sponges used for tissue engineering. The porous sponges were prepared by lyophilization and their physico-chemical characteristics (water binding capacity, denaturing temperature, amino group content) were investigated. Considering the importance of the 'in vivo' interactions between these sponges and the tissue, our attention was addressed (a) to clarify the relationships between the morphology and the amount of water absorbed and (b) to evaluate the influence of pepsin-alkaline treatment on the reorganization of the atelocollagen fibres. Conventional scanning electron microscopy (SEM) and environmental scanning electron microscopy (ESEM) were employed to study the morphology and wetting behaviour of the intact and atelocollagen sponges. The observations by SEM indicated remarkable differences both in the structure and dimension of the pores between intact and atelocollagen sponges. At the data are related to a different water binding capacity. However, the ESEM observations, achieved by changing the relative humidity in the operative chamber, demonstrated that the water adsorbed can be removed with major difficulty from atelocollagen sponges than from intact ones

  16. Behavior Management Style of Single Parents and Intact Families.

    Science.gov (United States)

    Smith, Douglas K.; And Others

    Studies examining the behavior management styles of parents as a function of family intactness and parent employment status are lacking. To assess parental style of behavior management, the Parental Management Questionnaire (PMQ) was completed by 1,957 parents of elementary school children (50% response rate). The PMQ is based on Aronfreed's…

  17. Non-intact zona improves development of murine preimplantation ...

    African Journals Online (AJOL)

    ajl5

    2012-09-25

    Sep 25, 2012 ... 2College of Animal Science and Technology, Northwest A & F University, Yangling, ... Key words: Mouse, non-intact zona embryos, adenovirus vector with green fluorescent protein (pAd-GFP), .... Based on microscopic examination, the ZP of some ..... permeable structure of ZP that allowed penetration of.

  18. Pharmacokinetics of erythropoietin in intact and anephric dogs

    International Nuclear Information System (INIS)

    Fu, J.S.; Lertora, J.J.; Brookins, J.; Rice, J.C.; Fisher, J.W.

    1988-01-01

    The present studies were performed to determine the pharmacokinetic parameters of erythropoietin in intact and anephric dogs by use of unlabeled crude native erythropoietin (nEp) and iodine 125-labeled purified recombinant erythropoietin (rEp) given by intravenous infusion for 15 minutes. Sephadex G-75 gel filtration was used to confirm that the 125I-rEp molecule remained iodinated in dog plasma during the 24-hour period of these studies. The plasma disappearance of erythropoietin conformed to a biexponential equation for both nEp and 125I-rEp, with the central compartment being larger than the peripheral compartment. The mean distribution half-life of 75.3 +/- 21.2 minutes for nEp was significantly (p less than 0.05) longer than that of 125I-rEp (23.7 +/- 5.0 minutes) in intact dogs. The intercompartmental clearance (CIic) for nEp (0.018 +/- 0.006 L/kg/hr) was significantly smaller than that of 125I-rEp (0.068 +/- 0.018 L/kg/hr) in intact dogs (p less than 0.05). There were no significant differences in apparent volume of distribution, elimination half-life, and elimination clearance (CIe) for nEp and rEp in intact dogs. The mean elimination half-life for 125I-rEp in intact dogs (9.0 +/- 0.6 hours) and anephric dogs (13.8 +/- 1.4 hours) was significantly different (p less than 0.05). The CIe for 125I-rEp in anephric dogs (0.008 +/- 0.001 L/kg/hr) was significantly (p less than 0.05) smaller than that of 125I-rEp in intact dogs (0.011 +/- 0.001 L/kg/hr). There were no significant differences in apparent volume of distribution, distribution half-life, and CIic for 125I-rEp in intact and anephric dogs

  19. Threats to intact tropical peatlands and opportunities for their conservation.

    Science.gov (United States)

    Roucoux, K H; Lawson, I T; Baker, T R; Del Castillo Torres, D; Draper, F C; Lähteenoja, O; Gilmore, M P; Honorio Coronado, E N; Kelly, T J; Mitchard, E T A; Vriesendorp, C F

    2017-12-01

    Large, intact areas of tropical peatland are highly threatened at a global scale by the expansion of commercial agriculture and other forms of economic development. Conserving peatlands on a landscape scale, with their hydrology intact, is of international conservation importance to preserve their distinctive biodiversity and ecosystem services and maintain their resilience to future environmental change. We explored threats to and opportunities for conserving remaining intact tropical peatlands; thus, we excluded peatlands of Indonesia and Malaysia, where extensive deforestation, drainage, and conversion to plantations means conservation in this region can protect only small fragments of the original ecosystem. We focused on a case study, the Pastaza-Marañón Foreland Basin (PMFB) in Peru, which is among the largest known intact tropical peatland landscapes in the world and is representative of peatland vulnerability. Maintenance of the hydrological conditions critical for carbon storage and ecosystem function of peatlands is, in the PMFB, primarily threatened by expansion of commercial agriculture linked to new transport infrastructure that is facilitating access to remote areas. There remain opportunities in the PMFB and elsewhere to develop alternative, more sustainable land-use practices. Although some of the peatlands in the PMFB fall within existing legally protected areas, this protection does not include the most carbon-dense (domed pole forest) areas. New carbon-based conservation instruments (e.g., REDD+, Green Climate Fund), developing markets for sustainable peatland products, transferring land title to local communities, and expanding protected areas offer pathways to increased protection for intact tropical peatlands in Amazonia and elsewhere, such as those in New Guinea and Central Africa which remain, for the moment, broadly beyond the frontier of commercial development. © 2017 The Authors. Conservation Biology published by Wiley Periodicals, Inc

  20. A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain.

    Science.gov (United States)

    Makino, Hiroto; Seki, Shoji; Yahara, Yasuhito; Shiozawa, Shunichi; Aikawa, Yukihiko; Motomura, Hiraku; Nogami, Makiko; Watanabe, Kenta; Sainoh, Takeshi; Ito, Hisakatsu; Tsumaki, Noriyuki; Kawaguchi, Yoshiharu; Yamazaki, Mitsuaki; Kimura, Tomoatsu

    2017-12-05

    Intervertebral disc (IVD) degeneration is a major cause of low back pain. The transcription factor c-Fos/Activator Protein-1 (AP-1) controls the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) that contribute to the pathogenesis IVD degeneration. We investigated the effects of inhibition of c-Fos/AP-1 on IVD degeneration and associated pain. A selective inhibitor, T-5224, significantly suppressed the interleukin-1β-induced up-regulation of Mmp-3, Mmp-13 and Adamts-5 transcription in human nucleus pulposus cells and in a mouse explant culture model of IVD degeneration. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of disc height, T2-magnetic resonance imaging (MRI) findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain and that T-5224 may serve as a drug for the prevention of IVD degeneration.

  1. Ablation of intervertebral discs in dogs using a MicroJet-assisted dye-enhanced injection device coupled with the diode laser

    Science.gov (United States)

    Bartels, Kenneth E.; Henry, George A.; Dickey, D. Thomas; Stair, Ernest L.; Powell, Ronald; Schafer, Steven A.; Nordquist, Robert E.; Frederickson, Christopher J.; Hayes, Donald J.; Wallace, David B.

    1998-07-01

    Use of holmium laser energy for vaporization/coagulation of the nucleus pulposus in canine intervertebral discs has been previously reported and is currently being applied clinically in veterinary medicine. The procedure was originally developed in the canine model and intended for potential human use. Since the pulsed (15 Hz) holmium laser energy exerts photomechanical and photothermal effects, the potential for extrusion of additional disc material to the detriment of the patient is possible using the procedure developed for the dog. To reduce this potential complication, use of diode laser (805 nm - CW mode) energy, coupled with indocyanine green (ICG) as a selective laser energy absorber, was formulated as a possible alternative. Delivery of the ICG and diode laser energy was through a MicroJet device that could dispense dye interactively between individual laser 'shots.' Results have shown that it is possible to selectively ablate nucleus pulposus in the canine model using the device described. Acute observations (gross and histopathologic) illustrate that accurate placement of the spinal needle before introduction of the MicroJet device is critically dependent on the expertise of the interventional radiologist. In addition, the success of the overall technique depends on consistent delivery of both ICG and diode laser energy. Minimizing tissue carbonization on the tip of the MicroJet device is also of crucial importance for effective application of the technique in clinical veterinary medicine.

  2. [Treatment of lumbar intervertebral disc herniation and sciatica with percutaneous transforaminal endoscopic technique].

    Science.gov (United States)

    Jiang, Yi; Song, Hua-Wei; Wang, Dong; Yang, Ming-Lian

    2013-10-01

    To analyze the clinical effects of percutaneous transforaminal endoscopic technique in treating lumbar intervertebral disc herniation and sciatica. From June 2011 to January 2012,the clinical data of 46 patients with lumbar intervertebral disc herniation and sciatica underwent percutaneous transforaminal endoscopic technique were retrospectively analyzed. There were 28 males and 18 females,ranging in age from 11 to 77 years old with an average of (39.7_ 15.3) years old,20 cases were L5S1 and 26 cases were L4,5. All patients had the symptoms such as lumbago and sciatica and their straight-leg raising test were positive. Straight-leg raising test of patients were instantly repeated after operation;operative time,volume of blood loss,complication, length of stay and duration of back to work or daily life were recorded. The clinical effects were assessed according to the VAS,JOA and JOABPEQ score. All operations were successful,postoperative straight-leg raising test were all negative. Operative time,volume of blood loss,length of stay,duration of back to work or daily life,follow-up time were (93.0+/-28.0) min, (20.0+/-9.0)ml, (3.1+/-1.5) d, (11.6+/-4.2) d, (13.9+/-1.6) months,respectively. VAS score of lumbar before operation and at the 1st and 3rd,6th,12th month after operation were 5.3+/-1.2,1.9+/-1.1,1.0+/-0.8,0.9+/-0.8,0.8+/-0.6,respectively;VAS score of leg before operation and at the 1st and 3rd,6th,12th month after operation were 7.2+ 1.2,0.8+/-1.2,0.5+/-0.8,0.5+/-0.8,0.3+/-0.8,respectively. Five factors of JOABPEQ score,including lumbar pain,lumbar function, locomotor activity,social life viability and mental status,were respectively 27.0+/-30.6,37.3+/-27.4,38.5+/-26.6,33.0+/-13.7,55.4+/-19.0 before operation and 83.6+/-24.8,89.4+/-15.7,87.0+/-17.9,58.4+/-14.6,79.5+/-13.4 at final follow-up. Preoperative and postoperative JOA score were 9.1+/-2.6 and 27.3+/- 1.7, respectively. The postoperative VAS,JOA and JOABPEQ score had significantly improved (Psciatica

  3. Lactoferricin enhances BMP7-stimulated anabolic pathways in intervertebral disc cells.

    Science.gov (United States)

    Ellman, Michael B; Kim, Jaesung; An, Howard S; Chen, Di; Kc, Ranjan; Li, Xin; Xiao, Guozhi; Yan, Dongyao; Suh, Joon; van Wjnen, Andre J; Wang, James H-C; Kim, Su-Gwan; Im, Hee-Jeong

    2013-07-25

    Bone-morphogenetic protein-7 (BMP7) is a well-known anabolic and anti-catabolic growth factor on intervertebral disc (IVD) matrix and cell homeostasis. Similarly, Lactoferricin B (LfcinB) has recently been shown to have pro-anabolic, anti-catabolic, anti-oxidative and/or anti-inflammatory effects in bovine disc cells in vitro. In this study, we investigated the potential benefits of using combined peptide therapy with LfcinB and BMP7 for intervertebral disc matrix repair and to understand cellular and signaling mechanisms controlled by these factors. We studied the effects of BMP7 and LfcinB as individual treatments and combined therapy on bovine nucleus pulposus (NP) cells by assessing proteoglycan (PG) accumulation and synthesis, and the gene expression of matrix protein aggrecan and transcription factor SOX-9. We also analyzed the role of Noggin, a BMP antagonist, in IVD tissue and examined its effect after stimulation with LfcinB. To understand the molecular mechanisms by which LfcinB synergizes with BMP7, we investigated the ERK-SP1 axis as a downstream intracellular signaling regulator involved in BMP7 and LfcinB-mediated activities. Treatment of bovine NP cells cultured in alginate with LfcinB plus BMP7 synergistically stimulates PG synthesis and accumulation in part by upregulation of aggrecan gene expression. The synergism results from LfcinB-mediated activation of Sp1 and SMAD signaling pathways by (i) phosphorylation of SMAD 1/5/8; (ii) downregulation of SMAD inhibitory factors [i.e., noggin and SMAD6 (inhibitory SMAD)]; and (iii) upregulation of SMAD4 (universal co-SMAD). These data indicate that LfcinB-suppression of Noggin may eliminate the negative feedback of BMP7, thereby maximizing biological activity of BMP7 and ultimately shifting homeostasis to a pro-anabolic state in disc cells. We propose that combination growth factor therapy using BMP7 and LfcinB may be beneficial for treatment of disc degeneration. Copyright © 2013 Elsevier B.V. All

  4. Pedicle distraction increases intervertebral and spinal canal area in a cadaver and bone model.

    Science.gov (United States)

    Hughes, Matthew; Papadakos, Nikolaos; Bishop, Tim; Bernard, Jason

    2018-01-01

    Lumbar spinal stenosis is degenerative narrowing of the spinal canal and/or intervertebral foramen causing compression of the spinal cord and nerve roots. Traditional decompression techniques can often cause significant trauma and vertebral instability. This paper evaluates a method of increasing pedicle length to decompress the spinal and intervertebral foramen, which could be done minimally invasive. Three Sawbone (Sawbones Europe, Sweden) and 1 cadaveric lumbar spine underwent bilateral pedicle distraction at L4. A pedicle channel was drilled between the superior articular process and transverse process into the vertebral body. The pedicles underwent osteotomy at the midpoint. Screws were inserted bilaterally and fixated distraction of 0 mm, 2 mm, 4 mm and 6 mm. CT images were taken at each level of distraction. Foramen area was measured in the sagittal plane at L3/4. Spinal canal area was measured at L4 in the axial images. The cadaver was used to evaluate safety of osteotomy and soft tissue interactions preventing distraction. Statistical analysis was by student paired t-test and Pearson rank test. Increasing distraction led to greater Spinal canal area. From 4.27 cm 2 to 5.72 cm 2 (p = 0.002) with 6 mm distraction. A Maximal increase of 34.1%. Vertebral foramen area also increased with increasing pedicle distraction. From 2.43 cm 2 to 3.22 cm 2 (p = 0.022) with 6 mm distraction. A maximal increase of 32.3%. The cadaver spinal canal increased in area by 21.7%. The vertebral foramen increased in area by 36.2% (left) and 22.6% (right). For each increase in pedicle distraction the area of the spinal and vertebral foramen increases. Pedicle distraction could potentially be used to alleviate spinal stenosis and root impingement. A potential osteotomy plane could be at the midpoint of the pedicle with minimal risk to nerve roots and soft tissue restrictions to prevent distraction. © The Authors, published by EDP Sciences, 2018.

  5. Assessment of mechanical properties of isolated bovine intervertebral discs from multi-parametric magnetic resonance imaging.

    Science.gov (United States)

    Recuerda, Maximilien; Périé, Delphine; Gilbert, Guillaume; Beaudoin, Gilles

    2012-10-12

    The treatment planning of spine pathologies requires information on the rigidity and permeability of the intervertebral discs (IVDs). Magnetic resonance imaging (MRI) offers great potential as a sensitive and non-invasive technique for describing the mechanical properties of IVDs. However, the literature reported small correlation coefficients between mechanical properties and MRI parameters. Our hypothesis is that the compressive modulus and the permeability of the IVD can be predicted by a linear combination of MRI parameters. Sixty IVDs were harvested from bovine tails, and randomly separated in four groups (in-situ, digested-6h, digested-18h, digested-24h). Multi-parametric MRI acquisitions were used to quantify the relaxation times T1 and T2, the magnetization transfer ratio MTR, the apparent diffusion coefficient ADC and the fractional anisotropy FA. Unconfined compression, confined compression and direct permeability measurements were performed to quantify the compressive moduli and the hydraulic permeabilities. Differences between groups were evaluated from a one way ANOVA. Multi linear regressions were performed between dependent mechanical properties and independent MRI parameters to verify our hypothesis. A principal component analysis was used to convert the set of possibly correlated variables into a set of linearly uncorrelated variables. Agglomerative Hierarchical Clustering was performed on the 3 principal components. Multilinear regressions showed that 45 to 80% of the Young's modulus E, the aggregate modulus in absence of deformation HA0, the radial permeability kr and the axial permeability in absence of deformation k0 can be explained by the MRI parameters within both the nucleus pulposus and the annulus pulposus. The principal component analysis reduced our variables to two principal components with a cumulative variability of 52-65%, which increased to 70-82% when considering the third principal component. The dendograms showed a natural

  6. Relationships between lumbar inter-vertebral motion and lordosis in healthy adult males: a cross sectional cohort study.

    Science.gov (United States)

    du Rose, Alister; Breen, Alan

    2016-03-10

    Intervertebral motion impairment is widely thought to be related to chronic back disability, however, the movements of inter-vertebral pairs are not independent of each other and motion may also be related to morphology. Furthermore, maximum intervertebral range of motion (IV-RoMmax) is difficult to measure accurately in living subjects. The purpose of this study was to explore possible relationships between (IV-RoMmax) and lordosis, initial attainment rate and IV-RoMmax at other levels during weight-bearing flexion using quantitative fluoroscopy (QF). Continuous QF motion sequences were recorded during controlled active sagittal flexion of 60° in 18 males (mean age 27.6 SD 4.4) with no history of low back pain in the previous year. IV-RoMmax, lordotic angle, and initial attainment rate at all inter-vertebral levels from L2-S1 were extracted. Relationships between IV-RoMmax and the other variables were explored using correlation coefficients, and simple linear regression was used to determine the effects of any significant relationships. Within and between observer repeatability of IV-RoMmax and initial attainment rate measurements were assessed in a sub-set of ten participants, using the intra-class correlation coefficient (ICC) and standard error of measurement (SEM). QF measurements were highly repeatable, the lowest ICC for IV-RoMmax, being 0.94 (0.80-0.99) and highest SEM (0.76°). For initial attainment rate the lowest ICC was 0.84 (0.49-0.96) and the highest SEM (0.036). The results also demonstrated significant positive and negative correlations between IV-RoMmax and IV-RoMmax at other lumbar levels (r = -0.64-0.65), lordosis (r = -0.52-0.54), and initial attainment rate (r = -0.64-0.73). Simple linear regression analysis of all significant relationships showed that these predict between 28 and 42 % of the variance in IV-RoMmax. This study found weak to moderate effects of individual kinematic variables and lumbar lordosis on IV-RoMmax at

  7. Level of Education as a Risk Factor for Extensive Prevalence of Cervical Intervertebral Disc Degenerative Changes and Chronic Neck Pain.

    Science.gov (United States)

    Markotić, Vedran; Zubac, Damir; Miljko, Miro; Šimić, Goran; Zalihić, Amra; Bogdan, Gojko; Radančević, Dorijan; Šimić, Ana Dugandžić; Mašković, Josip

    2017-09-01

    The aim of this study was to document the prevalence of degenerative intervertebral disc changes in the patients who previously reported symptoms of neck pain and to determine the influence of education level on degenerative intervertebral disc changes and subsequent chronic neck pain. One hundred and twelve patients were randomly selected from the University Hospital in Mostar, Bosna and Herzegovina, (aged 48.5±12.7 years) and submitted to magnetic resonance imaging (MRI) of the cervical spine. MRI of 3.0 T (Siemens, Skyrim, Erlangen, Germany) was used to obtain cervical spine images. Patients were separated into two groups based on their education level: low education level (LLE) and high education level (HLE). Pfirrmann classification was used to document intervertebral disc degeneration, while self-reported chronic neck pain was evaluated using the previously validated Oswestry questionnaire. The entire logistic regression model containing all predictors was statistically significant, (χ 2 (3)=12.2, p=0.02), and was able to distinguish between respondents who had chronic neck pain and vice versa. The model explained between 10.0% (Cox-Snell R 2 ) and 13.8% (Nagelkerke R 2 ) of common variance with Pfirrmann classification, and it had the strength to discriminate and correctly classify 69.6% of patients. The probability of a patient being classified in the high or low group of degenerative disc changes according to the Pfirrmann scale was associated with the education level (Wald test: 5.5, p=0.02). Based on the Pfirrmann assessment scale, the HLE group was significantly different from the LLE group in the degree of degenerative changes of the cervical intervertebral discs (U=1,077.5, p=0.001). A moderate level of intervertebral disc degenerative changes (grade II and III) was equally matched among all patients, while the overall results suggest a higher level of education as a risk factor leading to cervical disc degenerative changes, regardless of age

  8. The Multilevel Mixed Intact Group Analysis: A Mixed Method to Seek, Detect, Describe, and Explain Differences Among Intact Groups

    Science.gov (United States)

    Schoonenboom, Judith

    2016-01-01

    Educational innovations often involve intact subgroups, such as school classes or university departments. In small-scale educational evaluation research, typically involving 1 to 20 subgroups, differences among these subgroups are often neglected. This article presents a mixed method from a qualitative perspective, in which differences among…

  9. The Multilevel Mixed Intact Group Analysis: A Mixed Method to Seek, Detect, Describe and Explain Differences Between Intact Groups

    NARCIS (Netherlands)

    Schoonenboom, J.I.

    2014-01-01

    Educational innovations often involve intact subgroups, such as school classes or university departments. In small-scale educational evaluation research, typically involving 1 to 20 subgroups, differences among these subgroups are often neglected. This article presents a mixed method from a

  10. A minimally invasive in-fiber Bragg grating sensor for intervertebral disc pressure measurements

    International Nuclear Information System (INIS)

    Dennison, Christopher R; Wild, Peter M; Wilson, David R; Cripton, Peter A

    2008-01-01

    We present an in-fiber Bragg grating (FBG) based intervertebral disc (IVD) pressure sensor that has pressure sensitivity seven times greater than that of a bare fiber, and a major diameter and sensing area of only 400 µm and 0.03 mm 2 , respectively. This is the only optical, the smallest and the most mechanically compliant disc pressure sensor reported in the literature. This is also an improvement over other FBG pressure sensors that achieve increased sensitivity through mechanical amplification schemes, usually resulting in major diameters and sensing lengths of many millimeters. Sensor sensitivity is predicted using numerical models, and the predicted sensitivity is verified through experimental calibrations. The sensor is validated by conducting IVD pressure measurements in porcine discs and comparing the FBG measurements to those obtained using the current standard sensor for IVD pressure. The predicted sensitivity of the FBG sensor matched with that measured experimentally. IVD pressure measurements showed excellent repeatability and agreement with those obtained from the standard sensor. Unlike the current larger sensors, the FBG sensor could be used in discs with small disc height (i.e. cervical or degenerated discs). Therefore, there is potential to conduct new measurements that could lead to new understanding of the biomechanics

  11. In-situ photopolymerized and monitored implants: successful application to an intervertebral disc replacement

    Science.gov (United States)

    Schmocker, Andreas M.; Khoushabi, Azadeh; Bourban, Pierre-Etienne; Schizas, Constantin; Pioletti, Dominique; Moser, Christophe

    2016-02-01

    Photopolymerization is a common method to harden materials initially in a liquid state. A surgeon can directly trigger the solidification of a dental implant or a bone or tissue filler by using ultra-violet light. Traditionally, photopolymerization has been used mainly in dentistry. Over the last decade advances in material development including a wide range of biocompatible gel- and cement-systems open up a new avenue for in-situ photopolymerization. We designed a miniaturized light probe where a photoactive material can be 1) mixed, pressurized and injected 2) photopolymerized or photoactivated and 3) monitored during the chemical reaction. The device enables surgeries to be conducted through a hole smaller than 500 μm in diameter. Using a combination of Raman and fluorescence spectroscopy, the current state of the photopolymerization was inferred and monitored in real time within an in-vitro tissue model. It was also possible to determine roughly the position of the probe within the tissue cavity by analysing the fluorescence signal. Using the technique hydrogels were successfully implanted into a bovine intervertebral disc model. Mechanical tests could not obstruct the functionality of the implant. Finally, the device was also used for other application such as the implantation of a hydrogel into an aneurysm tissue cavity which will be presented at the conference.

  12. Localized strain measurements of the intervertebral disc annulus during biaxial tensile testing.

    Science.gov (United States)

    Karakolis, Thomas; Callaghan, Jack P

    2015-01-01

    Both inter-lamellar and intra-lamellar failures of the annulus have been described as potential modes of disc herniation. Attempts to characterize initial lamellar failure of the annulus have involved tensile testing of small tissue samples. The purpose of this study was to evaluate a method of measuring local surface strains through image analysis of a tensile test conducted on an isolated sample of annular tissue in order to enhance future studies of intervertebral disc failure. An annulus tissue sample was biaxial strained to 10%. High-resolution images captured the tissue surface throughout testing. Three test conditions were evaluated: submerged, non-submerged and marker. Surface strains were calculated for the two non-marker conditions based on motion of virtual tracking points. Tracking algorithm parameters (grid resolution and template size) were varied to determine the effect on estimated strains. Accuracy of point tracking was assessed through a comparison of the non-marker conditions to a condition involving markers placed on tissue surface. Grid resolution had a larger effect on local strain than template size. Average local strain error ranged from 3% to 9.25% and 0.1% to 2.0%, for the non-submerged and submerged conditions, respectively. Local strain estimation has a relatively high potential for error. Submerging the tissue provided superior strain estimates.

  13. Hyaluronic Acid (HA)-Polyethylene glycol (PEG) as injectable hydrogel for intervertebral disc degeneration patients therapy

    Science.gov (United States)

    Putri Kwarta, Cityta; Widiyanti, Prihartini; Siswanto

    2017-05-01

    Chronic Low Back Pain (CLBP) is one health problem that is often encountered in a community. Inject-able hydrogels are the newest way to restore the disc thickness and hydration caused by disc degeneration by means of minimally invasive surgery. Thus, polymers can be combined to improve the characteristic properties of inject-able hydrogels, leading to use of Hyaluronic Acid (a natural polymer) and Polyethylene glycol (PEG) with Horse Radish Peroxide (HRP) cross linker enzymes. The swelling test results, which approaches were the ideal disc values, were sampled with variation of enzyme concentrations of 0.25 µmol/min/mL. The enzyme concentrations were 33.95%. The degradation test proved that the sample degradation increased along with the decrease of the HRP enzyme concentration. The results of the cytotoxicity assay with MTT assay method showed that all samples resulted in the 90% of living cells are not toxic. In vitro injection, models demonstrated that higher concentration of the enzymes was less state of gel which would rupture when released from the agarose gel. The functional group characterization shows the cross linking bonding in sample with enzyme adding. The conclusion of this study is PEG-HA-HRP enzyme are safe polymer composites which have a potential to be applied as an injectable hydrogel for intervertebral disc degeneration.

  14. Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.

    Science.gov (United States)

    Tran, Cassie M; Shapiro, Irving M; Risbud, Makarand V

    2013-08-08

    Connective tissue growth factor (CCN2/CTGF) plays an important role in extracellular matrix synthesis, especially in skeletal tissues such as cartilage, bone, and the intervertebral disc. As a result there is a growing interest in examining the function and regulation of this important molecule in the disc. This review discusses the regulation of CCN2 by TGF-β and hypoxia, two critical determinants that characterize the disc microenvironment, and discusses known functions of CCN2 in the disc. The almost ubiquitous regulation of CCN2 by TGF-β, including that seen in the disc, emphasizes the importance of the TGF-β-CCN2 relationship, especially in terms of extracellular matrix synthesis. Likewise, the unique cross-talk between CCN2 and HIF-1 in the disc highlights the tissue and niche specific mode of regulation. Taken together the current literature supports an anabolic role for CCN2 in the disc and its involvement in the maintenance of tissue homeostasis during both health and disease. Further studies of CCN2 in this tissue may reveal valuable targets for the biological therapy of disc degeneration. © 2013 Elsevier B.V. All rights reserved.

  15. MRI histogram analysis enables objective and continuous classification of intervertebral disc degeneration.

    Science.gov (United States)

    Waldenberg, Christian; Hebelka, Hanna; Brisby, Helena; Lagerstrand, Kerstin Magdalena

    2018-05-01

    Magnetic resonance imaging (MRI) is the best diagnostic imaging method for low back pain. However, the technique is currently not utilized in its full capacity, often failing to depict painful intervertebral discs (IVDs), potentially due to the rough degeneration classification system used clinically today. MR image histograms, which reflect the IVD heterogeneity, may offer sensitive imaging biomarkers for IVD degeneration classification. This study investigates the feasibility of using histogram analysis as means of objective and continuous grading of IVD degeneration. Forty-nine IVDs in ten low back pain patients (six males, 25-69 years) were examined with MRI (T2-weighted images and T2-maps). Each IVD was semi-automatically segmented on three mid-sagittal slices. Histogram features of the IVD were extracted from the defined regions of interest and correlated to Pfirrmann grade. Both T2-weighted images and T2-maps displayed similar histogram features. Histograms of well-hydrated IVDs displayed two separate peaks, representing annulus fibrosus and nucleus pulposus. Degenerated IVDs displayed decreased peak separation, where the separation was shown to correlate strongly with Pfirrmann grade (P histogram appearances. Histogram features correlated well with IVD degeneration, suggesting that IVD histogram analysis is a suitable tool for objective and continuous IVD degeneration classification. As histogram analysis revealed IVD heterogeneity, it may be a clinical tool for characterization of regional IVD degeneration effects. To elucidate the usefulness of histogram analysis in patient management, IVD histogram features between asymptomatic and symptomatic individuals needs to be compared.

  16. Pericellular colocalisation and interactive properties of type VI collagen and perlecan in the intervertebral disc

    Directory of Open Access Journals (Sweden)

    AJ Hayes

    2016-07-01

    Full Text Available The aim of this study was to immunolocalise type VI collagen and perlecan and determine their interactive properties in the intervertebral disc (IVD. Confocal laser scanning microscopy co-localised perlecan with type VI collagen as pericellular components of IVD cells and translamellar cross-bridges in ovine and murine IVDs. These cross-bridges were significantly less abundant in the heparin sulphate deficient Hspg2 exon 3 null mouse IVD than in wild type. This association of type VI collagen with elastic components provides clues as to its roles in conveying elastic recoil properties to annular tissues. Perlecan and type VI collagen were highly interactive in plasmon resonance studies. Pericellular colocalisation of perlecan and type VI collagen provides matrix stabilisation and cell-matrix communication which allows IVD cells to perceive and respond to perturbations in their biomechanical microenvironment. Perlecan, at the cell surface, provides an adhesive interface between the cell and its surrounding extracellular matrix. Elastic microfibrillar structures regulate tensional connective tissue development and function. The 2010 Global Burden of Disease study examined 291 disorders and identified disc degeneration and associated low back pain as the leading global musculoskeletal disorder emphasising its massive socioeconomic impact and the need for more effective treatment strategies. A greater understanding of how the IVD achieves its unique biomechanical functional properties is of great importance in the development of such therapeutic measures.

  17. Postoperative changes of herniated intervertebral disc: Normal and discitis MR findings

    International Nuclear Information System (INIS)

    Lim, Seung Jae; Ryu, Kyung Nam; Choi, Woo Suk; Yoon, Yup; Kim, Ki Tack

    1994-01-01

    To describe normal postoperative MR findings and MR findings of postoperative discitis in patients who underwent operation due to herniated intervertebral disc. We retrospectively reviewed normal postoperative MR findings and MR findings of discitis in 30 patients(21-61 yrs) (13 cases diagnosed as discitis and 17 cases as normal) who previously underwent laminectomy and discectomy, or bony fusion. We analyzed signal intensity of end plate and disc, end plate destruction,and enhancement of end plate and disc on T1- and T2-weighted images(WI) of 1.5 T MRI. Among 14 out 17 patients with no evidence of discitis, 7 patients showed high signal of the posterior portion of disc on T1- and T2-WI and 11 patients revealed enhancement at the same sites. In all 13 patients suspected of having discitis, end plate and disc showed low signal on T1-WI, high signal on T2-WI, heterogeneous enhancement,and irregular destruction of end plate. Meanwhile, 3 cases with no evidence of postoperative discitis clinically who underwent bony fusion showed similar findings to those of the above 13 patients, except for homogeneous enhancement of end plate and vertebral body. The MR findings of postoperative discitis were low signal on T1-WI, high signal on T2-WI, and heterogeneous enhancement of and plate and disc, and destruction of end plate

  18. Cytokine Involvement in Biological Inflammation Related to Degenerative Disorders of the Intervertebral Disk: A Narrative Review.

    Science.gov (United States)

    De Geer, Christopher M

    2018-03-01

    The purpose of this narrative literature review is to discuss the literature regarding the potential role that cytokines play in degenerative disk disease. The inclusion criteria were studies that used inflammatory mediators in advancing disk disease processes. Research studies were limited to the last 3 decades that had free full-text available online in English. Exclusion criteria were review articles and articles pertaining to temporomandibular joints and other joints of the body other than the intervertebral disk. The following databases were searched: PubMed, EBSCOhost, and Google Scholar through March 13, 2017. A total of 82 studies were included in this review. The papers were reviewed for complex mechanisms behind the degenerative cascade, emphasizing the role of proinflammatory cytokines, which may be instrumental in processes of inflammation, neurologic pain, and disk degeneration. Interleukin-1β and tumor necrosis factor α were among the more notable cytokines involved in this cascade. Because monocyte chemoattractant protein-1 stimulates and activates macrophages in the event of infiltration, additional proinflammatory cytokines are released to act on molecules to promote blood and nerve ingrowth, resulting in pain signaling and tissue degradation. Excessive inflammation and/or tissue damage initiates a pathologic imbalance between anabolic and catabolic processes. This literature review describes how inflammatory and biochemical changes may trigger disk degeneration. Proinflammatory cytokines stimulate microvascular blood and nerve ingrowth, resulting in pain signaling and tissue degradation. This may sensitize a person to chemical and/or mechanical stimuli, contributing to severe low back pain.

  19. Gene expression analysis in response to osmotic stimuli in the intervertebral disc with DNA microarray.

    Science.gov (United States)

    Zhang, Wenzhi; Li, Xu; Shang, Xifu; Zhao, Qichun; Hu, Yefeng; Xu, Xiang; He, Rui; Duan, Liqun; Zhang, Feng

    2013-12-27

    Intervertebral disc (IVD) cells experience a broad range of physicochemical stimuli under physiologic conditions, including alterations in their osmotic environment. At present, the molecular mechanisms underlying osmotic regulation in IVD cells are poorly understood. This study aims to screen genes affected by changes in osmotic pressure in cells of subjects aged 29 to 63 years old, with top-scoring pair (TSP) method. Gene expression data set GSE1648 was downloaded from Gene Expression Omnibus database, including four hyper-osmotic stimuli samples, four iso-osmotic stimuli samples, and three hypo-osmotic stimuli samples. A novel, simple method, referred to as the TSP, was used in this study. Through this method, there was no need to perform data normalization and transformation before data analysis. A total of five pairs of genes ((CYP2A6, FNTB), (PRPF8, TARDBP), (RPS5, OAZ1), (SLC25A3, NPM1) and (CBX3, SRSF9)) were selected based on the TSP method. We inferred that all these genes might play important roles in response to osmotic stimuli and age in IVD cells. Additionally, hyper-osmotic and iso-osmotic stimuli conditions were adverse factors for IVD cells. We anticipate that our results will provide new thoughts and methods for the study of IVD disease.

  20. Foxa1 and Foxa2 are required for formation of the intervertebral discs.

    Directory of Open Access Journals (Sweden)

    Jennifer A Maier

    Full Text Available The intervertebral disc (IVD is composed of 3 main structures, the collagenous annulus fibrosus (AF, which surrounds the gel-like nucleus pulposus (NP, and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreER(T2, we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1(-/-;Foxa2(c/c;ShhcreER(T2 double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord.

  1. Foxa1 and Foxa2 Are Required for Formation of the Intervertebral Discs

    Science.gov (United States)

    Maier, Jennifer A.; Lo, YinTing; Harfe, Brian D.

    2013-01-01

    The intervertebral disc (IVD) is composed of 3 main structures, the collagenous annulus fibrosus (AF), which surrounds the gel-like nucleus pulposus (NP), and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreERT2), we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1−/−;Foxa2c/c;ShhcreERT2 double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord. PMID:23383217

  2. Histological and reference system for the analysis of mouse intervertebral disc.

    Science.gov (United States)

    Tam, Vivian; Chan, Wilson C W; Leung, Victor Y L; Cheah, Kathryn S E; Cheung, Kenneth M C; Sakai, Daisuke; McCann, Matthew R; Bedore, Jake; Séguin, Cheryle A; Chan, Danny

    2018-01-01

    A new scoring system based on histo-morphology of mouse intervertebral disc (IVD) was established to assess changes in different mouse models of IVD degeneration and repair. IVDs from mouse strains of different ages, transgenic mice, or models of artificially induced IVD degeneration were assessed. Morphological features consistently observed in normal, and early/later stages of degeneration were categorized into a scoring system focused on nucleus pulposus (NP) and annulus fibrosus (AF) changes. "Normal NP" exhibited a highly cellularized cell mass that decreased with natural ageing and in disc degeneration. "Normal AF" consisted of distinct concentric lamellar structures, which was disrupted in severe degeneration. NP/AF clefts indicated more severe changes. Consistent scores were obtained between experienced and new users. Altogether, our scoring system effectively differentiated IVD changes in various strains of wild-type and genetically modified mice and in induced models of IVD degeneration, and is applicable from the post-natal stage to the aged mouse. This scoring tool and reference resource addresses a pressing need in the field for studying IVD changes and cross-study comparisons in mice, and facilitates a means to normalize mouse IVD assessment between different laboratories. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:233-243, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  3. Gradient-echo imaging of intervertebral disk degeneration and facet joint disease

    International Nuclear Information System (INIS)

    Berns, D.H.; Kormos, D.; Modic, M.T.; Carter, J.; Masaryk, T.J.; Ross, J.S.

    1988-01-01

    The purpose of this study was to evaluate the accuracy of gradient-echo, partial-flip angle images in the evaluation of components of degenerative spine disease. First, cadaveric spines were studied with plain radiographs, high-resolution CT, T1-weighted spin-echo (SE) MR images (repetition time msec/echo time msec=500/17). T2-weighted SE images (2,000/30-90), and fast low-angle shot (FLASH) images (200/10.50 0 ) before and after intradiskal injection of air (0.1-1cc). Second, lumbar spine MR images were retrospectively evaluated to compare gradient-echo and SE sequences. Results indicate that the signal intensity changes of the intervertebral disk related to degeneration were best appreciated on T2-weighted SE studies in both groups. Vacuum phenomenon and calcification were most accurately assessed with FLASH imaging (based on susceptibility changes) and CT images. SE images appeared more sensitive to adjacent marrow change. In the facet joints, CT was more accurate for changes in the subarticular bone, but FLASH images were more sensitive to change in the articular cartilage

  4. Anisotropic Multishell Analytical Modeling of an Intervertebral Disk Subjected to Axial Compression.

    Science.gov (United States)

    Demers, Sébastien; Nadeau, Sylvie; Bouzid, Abdel-Hakim

    2016-04-01

    Studies on intervertebral disk (IVD) response to various loads and postures are essential to understand disk's mechanical functions and to suggest preventive and corrective actions in the workplace. The experimental and finite-element (FE) approaches are well-suited for these studies, but validating their findings is difficult, partly due to the lack of alternative methods. Analytical modeling could allow methodological triangulation and help validation of FE models. This paper presents an analytical method based on thin-shell, beam-on-elastic-foundation and composite materials theories to evaluate the stresses in the anulus fibrosus (AF) of an axisymmetric disk composed of multiple thin lamellae. Large deformations of the soft tissues are accounted for using an iterative method and the anisotropic material properties are derived from a published biaxial experiment. The results are compared to those obtained by FE modeling. The results demonstrate the capability of the analytical model to evaluate the stresses at any location of the simplified AF. It also demonstrates that anisotropy reduces stresses in the lamellae. This novel model is a preliminary step in developing valuable analytical models of IVDs, and represents a distinctive groundwork that is able to sustain future refinements. This paper suggests important features that may be included to improve model realism.

  5. Distribution pattern of surgically treated symptomatic prolapsed lumbar and sacral intervertebral discs in males.

    Science.gov (United States)

    Nnamdi, Ibe Michael Onwuzuruike

    2013-09-01

    The pattern of distribution of surgically treated symptomatic prolapsed lumbar and sacral intervertebral discs has been published, though scantily, especially in males. We decided to look at our own series, compare and contrast ours with some of those published. We treated 88 locations of this lesion in 68 males. The clinical features were those of lower back pains, with or without radiation into the lower extremities, sensory loss and paresis of the limbs. There was a case of loss of urinary bladder and ano-rectal control. All lesions were confirmed through cauda-equinograms and treated under general anaesthesia in knee-chest position (MECCA position). The patients were followed up for 3-6 months post-operatively. There were 88 locations in 68 males of 21-70 years of age, with 29 prolapses occurring during the age range 31-40 years, while 54 locations were on the left and 48 at L4/5. The procedures were well tolerated by all patients and there were no post-operative complications. This lesion in our series occurred mostly on the left, at the L4/5 level and peaked at 31-40 years age range. The predictability of occurrence of this disease, using side, level and age is still not feasible in males from our series.

  6. Organotypic Cultures of Intervertebral Disc Cells: Responses to Growth Factors and Signaling Pathways Involved

    Directory of Open Access Journals (Sweden)

    Harris Pratsinis

    2015-01-01

    Full Text Available Intervertebral disc (IVD degeneration is strongly associated with low back pain, a major cause of disability worldwide. An in-depth understanding of IVD cell physiology is required for the design of novel regenerative therapies. Accordingly, aim of this work was the study of IVD cell responses to mitogenic growth factors in a three-dimensional (3D organotypic milieu, comprising characteristic molecules of IVD’s extracellular matrix. In particular, annulus fibrosus (AF cells were cultured inside collagen type-I gels, while nucleus pulposus (NP cells in chondroitin sulfate A (CSA supplemented collagen gels, and the effects of Platelet-Derived Growth Factor (PDGF, basic Fibroblast Growth Factor (bFGF, and Insulin-Like Growth Factor-I (IGF-I were assessed. All three growth factors stimulated DNA synthesis in both AF and NP 3D cell cultures, with potencies similar to those observed previously in monolayers. CSA supplementation inhibited basal DNA synthesis rates, without affecting the response to growth factors. ERK and Akt were found to be phosphorylated following growth factor stimulation. Blockade of these two signaling pathways using pharmacologic inhibitors significantly, though not completely, inhibited growth factor-induced DNA synthesis. The proposed culture systems may prove useful for further in vitro studies aiming at future interventions for IVD regeneration.

  7. Radioimmunolocalization and selective delivery of radiation in a rat model system: comparison of intact and fragmented antibody

    International Nuclear Information System (INIS)

    Walker, K.Z.; Seymour-Munn, K.; Axiak, S.M.; Raison, R.L.; Basten, A.; Towson, J.E.; Bautovitch, G.J.; Morris, J.

    1988-01-01

    Monoclonal antibody (MoAb) fragments are known to have advantages over intact immunoglobulins for radioimmunoscintigraphy. It is less clear whether they are as effective in the delivery of radioimmunotherapy. The imaging and dosimetric properties of an intact MoAb, K-1-21, reactive against human kappa light chains (LC) were compared with that of its F(ab') 2 and Fab fragments using a normal rat model system. Two days after injection of 131 I-K-1-21 into rats bearing antigen-sepharose implants, gamma camera images showed specific localization of the MoAb to the target (kappa LC) but not to the control (lambda LC) implant. Better images were obtained with K-1-21 F(ab') 2 than with Fab or intact antibody. Mean kappa implant: blood ratios were 8.6 ± 3.9 for Fab, 7.9 ± 1.8 for F(ab') 2 and 2.0 ± 0.3 for intact K-1-21. The improvement associated with the use of 131 I-K-1-21 fragments was, however, achieved at the expense of lower absolute values of activity at the target site. Thus the absorbed dose delivered to the implant by the intact K-1-21 was double that delivered with F(ab') 2 and six times that delivered with Fab. As intact K-1-21 also delivered a greater radiation dose to normal tissues, F(ab') 2 fragments may have the greatest overall advantages for therapy with radionuclide MoAb conjugates. (author)

  8. Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy.

    Science.gov (United States)

    Henmar, H; Lund, G; Lund, L; Petersen, A; Würtzen, P A

    2008-09-01

    Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients.

  9. Structural determination of intact proteins using mass spectrometry

    Science.gov (United States)

    Kruppa, Gary [San Francisco, CA; Schoeniger, Joseph S [Oakland, CA; Young, Malin M [Livermore, CA

    2008-05-06

    The present invention relates to novel methods of determining the sequence and structure of proteins. Specifically, the present invention allows for the analysis of intact proteins within a mass spectrometer. Therefore, preparatory separations need not be performed prior to introducing a protein sample into the mass spectrometer. Also disclosed herein are new instrumental developments for enhancing the signal from the desired modified proteins, methods for producing controlled protein fragments in the mass spectrometer, eliminating complex microseparations, and protein preparatory chemical steps necessary for cross-linking based protein structure determination.Additionally, the preferred method of the present invention involves the determination of protein structures utilizing a top-down analysis of protein structures to search for covalent modifications. In the preferred method, intact proteins are ionized and fragmented within the mass spectrometer.

  10. SOLITARY CHEMORECEPTOR CELL SURVIVAL IS INDEPENDENT OF INTACT TRIGEMINAL INNERVATION

    Science.gov (United States)

    Gulbransen, Brian; Silver, Wayne; Finger, Tom

    2008-01-01

    Nasal solitary chemoreceptor cells (SCCs) are a population of specialized chemosensory epithelial cells presumed to broaden trigeminal chemoreceptivity in mammals (Finger et al., 2003). SCCs are innervated by peptidergic trigeminal nerve fibers (Finger et al., 2003) but it is currently unknown if intact innervation is necessary for SCC development or survival. We tested the dependence of SCCs on innervation by eliminating trigeminal nerve fibers during development with neurogenin-1 knockout mice, during early postnatal development with capsaicin desensitization, and during adulthood with trigeminal lesioning. Our results demonstrate that elimination of innervation at any of these times does not result in decreased SCC numbers. In conclusion, neither SCC development nor mature cell maintenance is dependent on intact trigeminal innervation. PMID:18300260

  11. Direct detection of radicals in intact soybean nodules

    DEFF Research Database (Denmark)

    Mathieu, C; Moreau, S; Frendo, P

    1998-01-01

    Electron paramagnetic resonance spectroscopy has been employed to examine the nature of the metal ions and radicals present in intact root nodules of soybean plants grown in the absence of nitrate. The spectra obtained from nodules of different ages using this non-invasive technique show dramatic...... differences, suggesting that there are both qualitative and quantitative changes in the metal ion and radical species present. A major component of the spectra obtained from young nodules is assigned to a complex (Lb-NO) of nitric oxide (NO.) with the heme protein leghemoglobin (Lb). This Lb-NO species, which...... has not been previously detected in intact root nodules of plants grown in the absence of nitrate, is thought to be formed by reaction of nitric oxide with iron(II) leghemoglobin. The nitric oxide may be generated from arginine via a nitric oxide synthase-like activity present in the nodules...

  12. Isolation and Properties of Intact Chromoplasts from Tomato Fruits

    OpenAIRE

    Norio, Iwatsuki; Ryuichi, Moriyama; Tadashi, Asahi; Laboratory of Biochemistry, Faculty of Agriculture, Nagoya University; Laboratory of Biochemistry, Faculty of Agriculture, Nagoya University; Laboratory of Biochemistry, Faculty of Agriculture, Nagoya University

    1984-01-01

    Intact chromoplasts were isolated from tomato fruits at different ripening stages by Percoll density gradient centrifugation. The isolated chromoplast fractions were contaminated very little by other organelles, although the fraction from fully ripened fruits contained some mitochondria and microbodies. As the transformation of chloroplasts to chromoplasts proceeded, the density of the plastids decreased from 1.096 to 1.075g・cm^ and the decrease was related to a decrease in chlorophyll and an...

  13. Magnetic Resonance Imaging Follow-up Study on Two Cases of Lumbar intervertebral Disc Sequestration Patients Treated with Oriental Medicine Treatment

    Directory of Open Access Journals (Sweden)

    Ki-Su Lee

    2011-09-01

    Full Text Available Objectives: The purpose of this study is to report the image changes of two cases of Lumbar intervertebral Disc Sequestration after oriental medical treatment. Methods: We examined 2 patients with Lumbar intervertebral Disc Sequestration who showed changes on MRI images before/after the treatment. And we assessed clinical symptoms by using numeric rating scale(NRS and straight leg raising test(SLRT. Results & Conclusions : In this study, the first MRI examination of Lumbar intervertebral Disc Sequestration patients was performed at the first visit and re-examination of MRI was done after treatment. In each case, the size of the disc sequestration was considerably reduced in MRI image. And both patients represented effective improvment in NRS score and SLRT test angle.

  14. Real T1 relaxation time measurement and diurnal variation analysis of intervertebral discs in a healthy population of 50 volunteers

    International Nuclear Information System (INIS)

    Galley, J.; Maestretti, G.; Koch, G.; Hoogewoud, H-M.

    2017-01-01

    Purpose: To measure the real T1 relaxation time of the lumbar intervertebral discs in a young and healthy population, using different inversion recovery times, and assess diurnal variation. Material and methods: Intervertebral discs from D12 to S1 of 50 healthy volunteers from 18 to 25 years old were evaluated twice the same day, in the morning and in the late afternoon. Dedicated MRI sequences with different inversion recovery times (from 100 to 2500 ms) were used to calculate the real T1 relaxation time. Three regions of interest (ROIs) were defined in each disc, the middle representing the nucleus pulposus (NP) and the outer parts the annulus fibrosus (AF) anterior and posterior. Diurnal variation and differences between each disc level were analyzed. Results: T1 mean values in the NP were 1142 ± 12 ms in the morning and 1085 ± 13 ms in the afternoon, showing a highly significant decrease of 57 ms (p < 0.001). A highly significant difference between the levels of the spine was found. The mean T1 of the anterior part of the AF was 577 ± 9 ms in the morning and 554 ± 8 ms in the afternoon. For the posterior part, the mean values were 633 ± 8 ms in the morning and 581 ± 7 ms in the evening. It shows a highly significant decrease of 23 ms for the anterior part and 51 ms for the posterior part (all p < 0.001). Conclusion: T1 mapping is a promising method of intervertebral disc evaluation. Significant diurnal variation and difference between levels of the lumbar spine were demonstrated. A potential use for longitudinal study in post-operative follow up or sport medicine needs to be evaluated.

  15. Effect of Capsaicin Cream on Chronic Low Back Pain in Patients With Inter-Vertebral Disc Herniation

    Directory of Open Access Journals (Sweden)

    Fayazi

    2015-07-01

    Full Text Available Background Low back pain is one of the most common debilitating disorders worldwide and the third cause of visiting a physician. One of the most common causes of low back pain is spinal disc herniation. Still there is no general agreement on the most effective treatment for it. Objectives This study aimed to determine the effect of Capsaicin cream on low back pain in patients with inter-vertebral disc herniation in Ahvaz. Patients and Methods This was a double blind clinical trial in which 43 patients with chronic low back pain, according to characteristics of the subjects, were randomly divided into two groups of treatment (n = 23 and control (n = 20. Data collection instruments included demographic specifications and visual analogue scale (VAS questionnaire completed on arrival and at the first, second and third weeks after intervention. The treatment and placebo groups used the ointment for three weeks and three times a day as a thin layer on the painful position. Data entered SPSS (version 18 and analyzed using the analytical descriptive statistics. Results There was a significant difference in the average pain intensity between the groups of study pre-and post-intervention (P = 0.0001 and the rate of using analgesics in the treatment group significantly decreased (P = 0.008. Also patients’ satisfaction was significantly different between the two groups using the ointment (P = 0.0001. Conclusions Capsaicin cream has beneficial effects on pain relieving and reducing analgesic use in patients with inter-vertebral disc herniation. Therefore, the ointment can be recommended in the treatment of low back pain caused by inter-vertebral disc herniation.

  16. Real T1 relaxation time measurement and diurnal variation analysis of intervertebral discs in a healthy population of 50 volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Galley, J., E-mail: galleyjulien@gmail.com [Department of Radiology, HFR Fribourg, Hôpital Cantonal (Switzerland); Maestretti, G. [Department of Orthopedic Surgery, HFR Fribourg, Hôpital Cantonal (Switzerland); Koch, G.; Hoogewoud, H-M. [Department of Radiology, HFR Fribourg, Hôpital Cantonal (Switzerland)

    2017-02-15

    Purpose: To measure the real T1 relaxation time of the lumbar intervertebral discs in a young and healthy population, using different inversion recovery times, and assess diurnal variation. Material and methods: Intervertebral discs from D12 to S1 of 50 healthy volunteers from 18 to 25 years old were evaluated twice the same day, in the morning and in the late afternoon. Dedicated MRI sequences with different inversion recovery times (from 100 to 2500 ms) were used to calculate the real T1 relaxation time. Three regions of interest (ROIs) were defined in each disc, the middle representing the nucleus pulposus (NP) and the outer parts the annulus fibrosus (AF) anterior and posterior. Diurnal variation and differences between each disc level were analyzed. Results: T1 mean values in the NP were 1142 ± 12 ms in the morning and 1085 ± 13 ms in the afternoon, showing a highly significant decrease of 57 ms (p < 0.001). A highly significant difference between the levels of the spine was found. The mean T1 of the anterior part of the AF was 577 ± 9 ms in the morning and 554 ± 8 ms in the afternoon. For the posterior part, the mean values were 633 ± 8 ms in the morning and 581 ± 7 ms in the evening. It shows a highly significant decrease of 23 ms for the anterior part and 51 ms for the posterior part (all p < 0.001). Conclusion: T1 mapping is a promising method of intervertebral disc evaluation. Significant diurnal variation and difference between levels of the lumbar spine were demonstrated. A potential use for longitudinal study in post-operative follow up or sport medicine needs to be evaluated.

  17. The Relationship amongst Intervertebral Disc Vertical Diameter, Lateral Foramen Diameter and Nerve Root Impingement in Lumbar Vertebra

    Directory of Open Access Journals (Sweden)

    Yusof MI

    2018-03-01

    Full Text Available Introduction: The vertical diameter of the foramen is dependent upon the vertical diameter of the corresponding intervertebral disc. A decrease in disc vertical diameter has direct anatomic consequences to the foraminal diameter and area available for the nerve root passing through it. This study is to establish the relationship amongst the intervertebral disc vertical diameter, lateral foramen diameters and nerve root compression in the lumbar vertebra. Materials and Methods: Measurements of the study parameters were performed using sagittal MRI images. The parameters studied were: intervertebral disc vertical diameter (DVD, foraminal vertical diameter (FVD, foraminal transverse diameter (FTD and nerve root diameter (NRD of both sides. The relationship between the measured parameters were then analyzed. Results: A total of 62 MRI images were available for this study. Statistical analysis showed moderate to strong correlation between DVD and FVD at all the lumbar levels except at left L23 and L5S1 and right L3L4 and L4L5. Correlation between DVD and FTD were not significant at all lumbar levels. Regression analysis showed that a decrease of 1mm of DVD was associated with 1.3, 1.7, 3.3, 3.3 and 1.3mm reduction of FVD at L1L2, L2L3, L3L4, L4L5 and L5S1 respectively. Conclusion: Reduction of DVD was associated with reduction of FVD. However, FVD was relatively wide for the nerve root even with complete loss of DVD. FTD was much narrower than the FVD making it more likely to cause nerve root compression at the exit foramina. These anatomical details should be given consideration in treating patients with lateral canal stenosis.

  18. The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs.

    Directory of Open Access Journals (Sweden)

    Michael P Taylor

    Full Text Available The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised.

  19. The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs.

    Science.gov (United States)

    Taylor, Michael P; Wedel, Mathew J

    2013-01-01

    The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised.

  20. Role of LncRNA TUG1 in intervertebral disc degeneration and nucleus pulposus cells via regulating Wnt/β-catenin signaling pathway.

    Science.gov (United States)

    Chen, Jiang; Jia, Yu-Song; Liu, Gen-Zhe; Sun, Qi; Zhang, Fan; Ma, Sheng; Wang, Yong-Jun

    2017-09-23

    To investigate the role of TUG1 in intervertebral disc degeneration (IDD) and human nucleus pulposus cells (NPCs) via regulating Wnt/β-catenin pathway. The study collected nucleus pulposus (NP) tissue samples from 30 patients with lumbar disc herniation (LDH) (Case group) and 18 patients with lumbar spine trauma (Control group). NPCs induced by TNF-α in vitro were divided into Blank, Vector, TUG1, TUG1-siRNA, XAV-939, TUG1 + XAV-939 groups. qRT-PCR was used to detect the expression of TUG1 and ECM-related genes, Western blot to determine the expression of Wnt/β-catenin pathway and apoptosis-related proteins, and ELISA to measure the expression of ECM-related proteins. The apoptosis was detected by TUNEL and Annexin V-FITC/PI double-staining. The proliferation and senescence were tested by CCK-8 and SA-β-gal staining respectively. TUG1 was upregulated in patients with IDD, which was positively related to Wnt and β-catenin. Besides, TUG1, Wnt1 and β-catenin were greatly increased in the NPCs after TNF-α induction. Compared with the Blank group, TUG1-siRNA and XAV-939 can appreciably down-regulate the expressions of Wnt1, β-catenin, Caspase-3, Bax, MMP3 and ADAMTS5, up-regulate the expression of Bcl-2, Aggrecan and COL2A1, inhibit the apoptosis and senescence, and promote cell proliferation; however, the TUG1 group had the completely opposite results. Silencing TUG1 may not only protect human NPCs from TNF-α-induced apoptosis and senescence, but also promote cell proliferation by blocking Wnt/β-catenin pathway, which provides a theoretical basis for the clinical treatment of IDD. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. A new method for lumbar herniated inter-vertebral disc diagnosis based on image analysis of transverse sections.

    Science.gov (United States)

    Tsai, Ming Dar; Jou, Shyan Bin; Hsieh, Ming Shium

    2002-01-01

    This paper describes an image analysis method that uses automatic algorithms for the evaluation of herniation classification and geometry in the diagnosis of lumbar herniated inter-vertebral disc (HIVD). The method uses boundary approximation that uses a B-spline curve to approximate circle-like disc boundary and excludes the herniation from other normal parts of the disc boundary and, feature recognition that classifies the herniation, and herniation shape reconstruction that infers the 3D geometry from one or more transverse sections. This method can be used as a qualitative and quantitative tool for the diagnosis of lumbar HIVD using transverse sections.

  2. Lumbar spine intervertebral disc gene delivery: a pilot study in lewis rats.

    Science.gov (United States)

    Damle, Sheela R; Rawlins, Bernard A; Boachie-Adjei, Oheneba; Crystal, Ronald G; Hidaka, Chisa; Cunningham, Matthew E

    2013-02-01

    Basic research toward understanding and treating disc pathology in the spine has utilized numerous animal models, with delivery of small molecules, purified factors, and genes of interest. To date, gene delivery to the rat lumbar spine has only been described utilizing genetically programmed cells in a matrix which has required partial disc excision, and expected limitation of treatment diffusion into the disc. This study was designed to develop and describe a surgical technique for lumbar spine exposure and disc space preparation, and use of a matrix-free method for gene delivery. Naïve or genetically programmed isogeneic bone marrow stromal cells were surgically delivered to adolescent male Lewis rat lumbar discs, and utilizing quantitative biochemical and qualitative immunohistological assessments, the implanted cells were detected 3 days post-procedure. Statistically significant differences were noted for recovery of the β-galactosidase marker gene comparing delivery of naïve or labeled cells (10(5) cells per disc) from the site of implantation, and between delivery of 10(5) or 10(6) labeled cells per disc at the site of implantation and the adjacent vertebral body. Immunohistology confirmed that the β-galactosidase marker was detected in the adjacent vertebra bone in the zone of surgical implantation. The model requires further testing in larger cohorts and with biologically active genes of interest, but the observations from the pilot experiments are very encouraging that this will be a useful comparative model for basic spine research involving gene or cell delivery, or other locally delivered therapies to the intervertebral disc or adjacent vertebral bodies in rats.

  3. Long-Term Creep Behavior of the Intervertebral Disk: Comparison between Bioreactor Data and Numerical Results

    Energy Technology Data Exchange (ETDEWEB)

    Castro, A. P. G., E-mail: apgcastro@dem.uminho.pt [Center for Mechanical and Materials Technologies, Department of Mechanical Engineering, University of Minho, Guimarães (Portugal); INSIGNEO Institute for in silico Medicine, Department of Mechanical Engineering, University of Sheffield, Sheffield (United Kingdom); Paul, C. P. L. [Department of Orthopaedic Surgery, VU Medical Center, Amsterdam (Netherlands); Research Institute MOVE, Faculty of Human Movement Sciences, VU Medical Center, Amsterdam (Netherlands); Detiger, S. E. L.; Smit, T. H.; Royen, B. J. van [Department of Orthopaedic Surgery, VU Medical Center, Amsterdam (Netherlands); Research Institute MOVE, Faculty of Human Movement Sciences, VU Medical Center, Amsterdam (Netherlands); Skeletal Tissue Engineering Group Amsterdam, VU Medical Center, Amsterdam (Netherlands); Pimenta Claro, J. C. [Center for Mechanical and Materials Technologies, Department of Mechanical Engineering, University of Minho, Guimarães (Portugal); Mullender, M. G. [Department of Orthopaedic Surgery, VU Medical Center, Amsterdam (Netherlands); Research Institute MOVE, Faculty of Human Movement Sciences, VU Medical Center, Amsterdam (Netherlands); Department of Plastic, Reconstructive and Hand Surgery, VU Medical Center, Amsterdam (Netherlands); Alves, J. L. [Center for Mechanical and Materials Technologies, Department of Mechanical Engineering, University of Minho, Guimarães (Portugal)

    2014-11-20

    The loaded disk culture system is an intervertebral disk (IVD)-oriented bioreactor developed by the VU Medical Center (VUmc, Amsterdam, The Netherlands), which has the capacity of maintaining up to 12 IVDs in culture, for approximately 3 weeks after extraction. Using this system, eight goat IVDs were provided with the essential nutrients and submitted to compression tests without losing their biomechanical and physiological properties, for 22 days. Based on previous reports (Paul et al., 2012, 2013; Detiger et al., 2013), four of these IVDs were kept in physiological condition (control) and the other four were previously injected with chondroitinase ABC (CABC), in order to promote degenerative disk disease (DDD). The loading profile intercalated 16 h of activity loading with 8 h of loading recovery to express the standard circadian variations. The displacement behavior of these eight IVDs along the first 2 days of the experiment was numerically reproduced, using an IVD osmo-poro-hyper-viscoelastic and fiber-reinforced finite element (FE) model. The simulations were run on a custom FE solver (Castro et al., 2014). The analysis of the experimental results allowed concluding that the effect of the CABC injection was only significant in two of the four IVDs. The four control IVDs showed no signs of degeneration, as expected. In what concerns to the numerical simulations, the IVD FE model was able to reproduce the generic behavior of the two groups of goat IVDs (control and injected). However, some discrepancies were still noticed on the comparison between the injected IVDs and the numerical simulations, namely on the recovery periods. This may be justified by the complexity of the pathways for DDD, associated with the multiplicity of physiological responses to each direct or indirect stimulus. Nevertheless, one could conclude that ligaments, muscles, and IVD covering membranes could be added to the FE model, in order to improve its accuracy and properly describe the

  4. The biomechanical assessment of the cervical inter-vertebral kinematics, between DDD patients ICR based study

    Science.gov (United States)

    Saveh, Amir Hossein; Zali, Ali Reza; Seddighi, Amir Saeed; Zarghi, Afsaneh; Chizari, Mahmoud; Hanafiah, Yussof

    2012-01-01

    Abstract: It is very important to pay more attention to spine from the biomechanical perspective. It would allow the analysis of initial conditions of the vertebral disc degeneration syndrome and adopting of normal spine kinematics to compare and match it with a degenerated disc and providing a biomechanical index as an indicator for the conduct of any surgical intervention including arthroplasty to maximize restoring spinal biomechanical motion. It is clear that the head movement is possible with the help of muscles. However, the shape and type of motion depends on the structure and shape of the cervical spine and the interaction between them. Cervical spine kinematics depends on the anatomy of the bones and joints. Bazhdok et al (2000) investigated the cervical kinematics and mechanical behavior of the spine and its anatomical connections. They have examined the atlanto- occipital joint motion during flexion-extension and rotation as well as the mechanism of paradoxical motion of atlanto- axial joint by radiography. Bifalkou et al (2011) studied the inter-vertebral motion based on arc kinematic commentary of video fluoroscopy. They showed that the diagnosis of biomechanical instability can be done based on the kinematic examination of the spine obtained in sagittal images. They also declared that the fluoroscopy can be used as a tool for study. Using an automated algorithm, image adaption was carried out and the motion direction of vertebrae was tracked. In the present study, some patients were selected among patients with cervical disc degeneration. Following imaging by fluoroscopy, the instantaneous center of the spinal action was calculated. It was used as a biomechanical criterion and the treatment group was compared with the healthy group. The loci of the instantaneous centers of the two groups were compared and its difference with the value of healthy group was calculated. A biomechanical criterion was introduced as a basis for comparison of normal and

  5. Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics

    Directory of Open Access Journals (Sweden)

    LM Benneker

    2014-05-01

    Full Text Available Intervertebral disc (IVD degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encouraging results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium "Where Science meets Clinics", sponsored by the AO Foundation and held in Davos, Switzerland, from September 5-7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imaging methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neuro-genesis. Discogenic pain, originating from "black discs" or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.

  6. An intervertebral disc whole organ culture system to investigate proinflammatory and degenerative disc disease condition.

    Science.gov (United States)

    Lang, Gernot; Liu, Yishan; Geries, Janna; Zhou, Zhiyu; Kubosch, David; Südkamp, Norbert; Richards, R Geoff; Alini, Mauro; Grad, Sibylle; Li, Zhen

    2018-04-01

    The aim of this study was to compare the effect of different disease initiators of degenerative disc disease (DDD) within an intervertebral disc (IVD) organ culture system and to understand the interplay between inflammation and degeneration in the early stage of DDD. Bovine caudal IVDs were cultured within a bioreactor for up to 11 days. Control group was cultured under physiological loading (0.02-0.2 MPa; 0.2 Hz; 2 hr/day) and high glucose (4.5 g/L) medium. Detrimental loading (0.32-0.5 MPa, 5 Hz; 2 hr/day) and low glucose (2 g/L) medium were applied to mimic the condition of abnormal mechanical stress and limited nutrition supply. Tumour necrosis factor alpha (TNF-α) was injected into the nucleus pulposus (100 ng per IVD) as a proinflammatory trigger. TNF-α combined with detrimental loading and low glucose medium up-regulated interleukin 1β (IL-1β), IL-6, and IL-8 gene expression in disc tissue, nitric oxide, and IL-8 release from IVD, which indicate a proinflammatory effect. The combined initiators up-regulated matrix metalloproteinase 1 gene expression, down-regulated gene expression of Type I collagen in annulus fibrosus and Type II collagen in nucleus pulposus, and reduced the cell viability. Furthermore, the combined initiators induced a degradative effect, as indicated by markedly higher glycosaminoglycan release into conditioned medium. The combination of detrimental dynamic loading, nutrient deficiency, and TNF-α intradiscal injection can synergistically simulate the proinflammatory and degenerative disease condition within DDD. This model will be of high interest to screen therapeutic agents in further preclinical studies for early intervention and treatment of DDD. Copyright © 2018 John Wiley & Sons, Ltd.

  7. Long-Term Creep Behavior of the Intervertebral Disc: Comparison between Bioreactor Data and Numerical Results

    Directory of Open Access Journals (Sweden)

    APG eCastro

    2014-11-01

    Full Text Available The Loaded Disc Culture System (LDCS is an Intervertebral Disc (IVD-oriented bioreactor developed by the VU Medical Center (VUmc, Amsterdam, The Netherlands, which has the capacity of maintaining up to 12 IVDs in culture, for approximately 3 weeks after extraction. Using this system, 8 goat IVDs were provided with the essential nutrients and submitted to compression tests without losing their biomechanical and physiological properties, for 22 days. Based on previous reports (Detiger et al., 2013; Paul et al., 2013, 2012, 4 of these IVDs were kept in physiological condition (control and the other 4 were previously injected with chondroitinase ABC (CABC, in order to promote Degenerative Disc Disease (DDD. The loading profile intercalated 16h of activity loading with 8h of loading recovery to express the standard circadian variations.The displacement behavior of these 8 IVDs along the first 2 days of the experiment was numerically reproduced, using an IVD osmo-poro-hyper-viscoelastic and fiber-reinforced Finite Element (FE model. The simulations were run on a custom FE solver (Castro et al., 2014.The analysis of the experimental results allowed concluding that the effect of the CABC injection was only significant in 2 of the 4 IVDs. The 4 control IVDs showed no signs of degeneration, as expected. In what concerns to the numerical simulations, the IVD FE model was able to reproduce the generic behavior of the two groups of goat IVDs (control and injected. However, some discrepancies were still noticed on the comparison between the injected IVDs and the numerical simulations, namely on the recovery periods. This may be justified by the complexity of the pathways for DDD, associated with the multiplicity of physiological responses to each direct or indirect stimulus. Nevertheless, one could conclude that ligaments, muscles and IVD covering membranes could be added to the FE model, in order to improve its accuracy and properly describe the recovery

  8. Differential response of nucleus pulposus intervertebral disc cells to high salt, sorbitol, and urea.

    Science.gov (United States)

    Mavrogonatou, Eleni; Kletsas, Dimitris

    2012-03-01

    Nucleus pulposus intervertebral disc cells are routinely confronted with high osmolality in their microenvironment and respond to this stress in vitro by regulating cell cycle progression and by activating a DNA repair machinery in order to counteract its genotoxic effect. In the present study, we attempted to identify the origin of this osmo-regulatory response, by using an ionic NaCl/KCl solution, the compatible osmolyte sorbitol, and the readily permeant urea. High salt and sorbitol were found to activate similar molecular pathways, including the p38 MAPK and the p53-p21(WAF1)-pRb axis, that were not stimulated by high urea. On the other hand, only high urea led to the phosphorylation of ERKs and JNKs. Furthermore, salt- and sorbitol-treated cells were able to phosphorylate histone H2A.X on Ser139, in contrast to cells exposed to urea, indicating a common mechanism for DNA repair, which was achieved by a p53-dependent activation of the G1 checkpoint by both solutes. DNA repair, as directly measured by a host cell reactivation assay, occurred under conditions of hyperosmolar salt and sorbitol, although to a lesser extent in sorbitol-treated cells than in cells exposed to high salinity. Taken as a whole, our findings suggest that the hyperosmolality-provoked DNA damage and the responses of nucleus pulposus cells induced by this genotoxic stress most probably originate from cell volume alterations mediated by hypertonicity and not from increased intracellular ionic concentration. Copyright © 2011 Wiley Periodicals, Inc.

  9. Total disc replacement using tissue-engineered intervertebral discs in the canine cervical spine.

    Directory of Open Access Journals (Sweden)

    Yu Moriguchi

    Full Text Available The most common reason that adults in the United States see their physician is lower back or neck pain secondary to degenerative disc disease. To date, approaches to treat degenerative disc disease are confined to purely mechanical devices designed to either eliminate or enable flexibility of the diseased motion segment. Tissue engineered intervertebral discs (TE-IVDs have been proposed as an alternative approach and have shown promise in replacing native IVD in the rodent tail spine. Here we demonstrate the efficacy of our TE-IVDs in the canine cervical spine. TE-IVD components were constructed using adult canine annulus fibrosis and nucleus pulposus cells seeded into collagen and alginate hydrogels, respectively. Seeded gels were formed into a single disc unit using molds designed from the geometry of the canine spine. Skeletally mature beagles underwent discectomy with whole IVD resection at levels between C3/4 and C6/7, and were then divided into two groups that received only discectomy or discectomy followed by implantation of TE-IVD. Stably implanted TE-IVDs demonstrated significant retention of disc height and physiological hydration compared to discectomy control. Both 4-week and 16-week histological assessments demonstrated chondrocytic cells surrounded by proteoglycan-rich matrices in the NP and by fibrocartilaginous matrices in the AF portions of implanted TE-IVDs. Integration into host tissue was confirmed over 16 weeks without any signs of immune reaction. Despite the significant biomechanical demands of the beagle cervical spine, our stably implanted TE-IVDs maintained their position, structure and hydration as well as disc height over 16 weeks in vivo.

  10. Prevalence and pattern of radiographic intervertebral disc degeneration in Vietnamese: a population-based study.

    Science.gov (United States)

    Ho-Pham, Lan T; Lai, Thai Q; Mai, Linh D; Doan, Minh C; Pham, Hoa N; Nguyen, Tuan V

    2015-06-01

    Intervertebral disc degeneration (IDD) is one of the most common skeletal disorders, yet few data are available in Asian populations. We sought to assess the prevalence and pattern of radiographic IDD in a Vietnamese population. This population-based cross-sectional investigation involved 170 men and 488 women aged ≥40 years, who were randomly sampled from the Ho Chi Minh City (Vietnam). Anthropometric data, clinical history and self-reported back and neck pain were ascertained by a questionnaire. Plain radiographs (from the cervical spine, thoracic spine to the lumbar spine) were examined for the presence of disc space narrowing and/or osteophytosis using the Kellgren-Lawrence (KL) grading system. The presence of radiographic IDD was defined if the KL grade was 2 or greater in at least one disc. The prevalence of radiographic IDD was 62.4% (n = 106) in men and 54.7% (n = 267) in women. The most frequently affected site was the lumbar spine with prevalence being 50.6 and 43.2% in men and women, respectively. The prevalence of IDD increased with advancing age: 18.8% among those aged 40-49 years, and increased to 83.4% in those aged ≥60 years. Self-reported neck pain and lower back pain were found in 30 and 44% of individuals, respectively. There was no statistically significant association between self-reported neck pain and cervical spine OA. These data suggest that radiographic IDD is highly prevalent in the Vietnamese population, and that self-reported back pain is not a sensitive indicator of IDD.

  11. Fabrication of a biomimetic elastic intervertebral disk scaffold using additive manufacturing

    International Nuclear Information System (INIS)

    Whatley, Benjamin R; Kuo, Jonathan; Shuai, Cijun; Wen Xuejun; Damon, Brooke J

    2011-01-01

    A custom-designed three-dimensional additive manufacturing device was developed to fabricate scaffolds for intervertebral disk (IVD) regeneration. This technique integrated a computer with a device capable of 3D movement allowing for precise motion and control over the polymer scaffold resolution. IVD scaffold structures were designed using computer-aided design to resemble the natural IVD structure. Degradable polyurethane (PU) was used as an elastic scaffold construct to mimic the elastic nature of the native IVD tissue and was deposited at a controlled rate using ultra-fine micropipettes connected to a syringe pump. The elastic PU was extruded directly onto a collecting substrate placed on a freezing stage. The three-dimensional movement of the computer-controlled device combined with the freezing stage enabled precise control of polymer deposition using extrusion. The addition of the freezing stage increased the polymer solution viscosity and hardened the polymer solution as it was extruded out of the micropipette tip. This technique created scaffolds with excellent control over macro- and micro-structure to influence cell behavior, specifically for cell adhesion, proliferation, and alignment. Concentric lamellae were printed at a high resolution to mimic the native shape and structure of the IVD. Seeded cells aligned along the concentric lamellae and acquired cell morphology similar to native tissue in the outer portion of the IVD. The fabricated scaffolds exhibited elastic behavior during compressive and shear testing, proving that the scaffolds could support loads with proper fatigue resistance without permanent deformation. Additionally, the mechanical properties of the scaffolds were comparable to those of native IVD tissue.

  12. Fabrication of a biomimetic elastic intervertebral disk scaffold using additive manufacturing.

    Science.gov (United States)

    Whatley, Benjamin R; Kuo, Jonathan; Shuai, Cijun; Damon, Brooke J; Wen, Xuejun

    2011-03-01

    A custom-designed three-dimensional additive manufacturing device was developed to fabricate scaffolds for intervertebral disk (IVD) regeneration. This technique integrated a computer with a device capable of 3D movement allowing for precise motion and control over the polymer scaffold resolution. IVD scaffold structures were designed using computer-aided design to resemble the natural IVD structure. Degradable polyurethane (PU) was used as an elastic scaffold construct to mimic the elastic nature of the native IVD tissue and was deposited at a controlled rate using ultra-fine micropipettes connected to a syringe pump. The elastic PU was extruded directly onto a collecting substrate placed on a freezing stage. The three-dimensional movement of the computer-controlled device combined with the freezing stage enabled precise control of polymer deposition using extrusion. The addition of the freezing stage increased the polymer solution viscosity and hardened the polymer solution as it was extruded out of the micropipette tip. This technique created scaffolds with excellent control over macro- and micro-structure to influence cell behavior, specifically for cell adhesion, proliferation, and alignment. Concentric lamellae were printed at a high resolution to mimic the native shape and structure of the IVD. Seeded cells aligned along the concentric lamellae and acquired cell morphology similar to native tissue in the outer portion of the IVD. The fabricated scaffolds exhibited elastic behavior during compressive and shear testing, proving that the scaffolds could support loads with proper fatigue resistance without permanent deformation. Additionally, the mechanical properties of the scaffolds were comparable to those of native IVD tissue.

  13. Quantitative evaluation of lumbar intervertebral disc degeneration by axial T2* mapping.

    Science.gov (United States)

    Huang, Leitao; Liu, Yuan; Ding, Yi; Wu, Xia; Zhang, Ning; Lai, Qi; Zeng, Xianjun; Wan, Zongmiao; Dai, Min; Zhang, Bin

    2017-12-01

    To quantitatively evaluate the clinical value and demonstrate the potential benefits of biochemical axial T2* mapping-based grading of early stages of degenerative disc disease (DDD) using 3.0-T magnetic resonance imaging (MRI) in a clinical setting.Fifty patients with low back pain and 20 healthy volunteers (control) underwent standard MRI protocols including axial T2* mapping. All the intervertebral discs (IVDs) were classified morphologically. Lumbar IVDs were graded using Pfirrmann score (I to IV). The T2* values of the anterior annulus fibrosus (AF), posterior AF, and nucleus pulposus (NP) of each lumbar IVD were measured. The differences between groups were analyzed regarding specific T2* pattern at different regions of interest.The T2* values of the NP and posterior AF in the patient group were significantly lower than those in the control group (P T2* value of the anterior AF was not significantly different between the patients and the controls (P > .05). The mean T2*values of the lumbar IVD in the patient group were significantly lower, especially the posterior AF, followed by the NP, and finally, the anterior AF. In the anterior AF, comparison of grade I with grade III and grade I with grade IV showed statistically significant differences (P = .07 and P = .08, respectively). Similarly, in the NP, comparison of grade I with grade III, grade I with grade IV, grade II with grade III, and grade II with grade IV showed statistically significant differences (P T2 values decreased linearly with increasing degeneration based on the Pfirrmann scoring system (ρ T2* value can signify early degenerative IVD diseases. Hence, T2* mapping can be used as a diagnostic tool for quantitative assessment of IVD degeneration. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  14. Quantitative evaluation of lumbar intervertebral disc degeneration by axial T2∗ mapping

    Science.gov (United States)

    Huang, Leitao; Liu, Yuan; Ding, Yi; Wu, Xia; Zhang, Ning; Lai, Qi; Zeng, Xianjun; Wan, Zongmiao; Dai, Min; Zhang, Bin

    2017-01-01

    Abstract To quantitatively evaluate the clinical value and demonstrate the potential benefits of biochemical axial T2∗ mapping-based grading of early stages of degenerative disc disease (DDD) using 3.0-T magnetic resonance imaging (MRI) in a clinical setting. Fifty patients with low back pain and 20 healthy volunteers (control) underwent standard MRI protocols including axial T2∗ mapping. All the intervertebral discs (IVDs) were classified morphologically. Lumbar IVDs were graded using Pfirrmann score (I to IV). The T2∗ values of the anterior annulus fibrosus (AF), posterior AF, and nucleus pulposus (NP) of each lumbar IVD were measured. The differences between groups were analyzed regarding specific T2∗ pattern at different regions of interest. The T2∗ values of the NP and posterior AF in the patient group were significantly lower than those in the control group (P T2∗ value of the anterior AF was not significantly different between the patients and the controls (P > .05). The mean T2∗values of the lumbar IVD in the patient group were significantly lower, especially the posterior AF, followed by the NP, and finally, the anterior AF. In the anterior AF, comparison of grade I with grade III and grade I with grade IV showed statistically significant differences (P = .07 and P = .08, respectively). Similarly, in the NP, comparison of grade I with grade III, grade I with grade IV, grade II with grade III, and grade II with grade IV showed statistically significant differences (P T2∗ values decreased linearly with increasing degeneration based on the Pfirrmann scoring system (ρ T2∗ value can signify early degenerative IVD diseases. Hence, T2∗ mapping can be used as a diagnostic tool for quantitative assessment of IVD degeneration. PMID:29390547

  15. Segmental Quantitative MR Imaging analysis of diurnal variation of water content in the lumbar intervertebral discs

    International Nuclear Information System (INIS)

    Zhu, Ting Ting; Ai, Tao; Zhang, Wei; Li, Tao; Li, Xiao Ming

    2015-01-01

    To investigate the changes in water content in the lumbar intervertebral discs by quantitative T2 MR imaging in the morning after bed rest and evening after a diurnal load. Twenty healthy volunteers were separately examined in the morning after bed rest and in the evening after finishing daily work. T2-mapping images were obtained and analyzed. An equally-sized rectangular region of interest (ROI) was manually placed in both, the anterior and the posterior annulus fibrosus (AF), in the outermost 20% of the disc. Three ROIs were placed in the space defined as the nucleus pulposus (NP). Repeated-measures analysis of variance and paired 2-tailed t tests were used for statistical analysis, with p < 0.05 as significantly different. T2 values significantly decreased from morning to evening, in the NP (anterior NP = -13.9 ms; central NP = -17.0 ms; posterior NP = -13.3 ms; all p < 0.001). Meanwhile T2 values significantly increased in the anterior AF (+2.9 ms; p = 0.025) and the posterior AF (+5.9 ms; p < 0.001). T2 values in the posterior AF showed the largest degree of variation among the 5 ROIs, but there was no statistical significance (p = 0.414). Discs with initially low T2 values in the center NP showed a smaller degree of variation in the anterior NP and in the central NP, than in discs with initially high T2 values in the center NP (10.0% vs. 16.1%, p = 0.037; 6.4% vs. 16.1%, p = 0.006, respectively). Segmental quantitative T2 MRI provides valuable insights into physiological aspects of normal discs.

  16. Application of a handheld Pressure Application Measurement device for the characterisation of mechanical nociceptive thresholds in intact pig tails

    DEFF Research Database (Denmark)

    Di Giminiani, Pierpaolo; Sandercock, Dale A.; Malcolm, Emma M.

    2016-01-01

    The assessment of nociceptive thresholds is employed in animals and humans to evaluate changes in sensitivity potentially arising from tissue damage. Its application on the intact pig tail might represent a suitable method to assess changes in nociceptive thresholds arising from tail injury...... to the body was observed (P knowledge, no other...... nociceptive threshold in pig tails. This methodological approach is possibly suitable for assessing changes in tail stump MNTs after tail injury caused by tail docking and biting....

  17. Feasible pickup from intact ossicular chain with floating piezoelectric microphone.

    Science.gov (United States)

    Kang, Hou-Yong; Na, Gao; Chi, Fang-Lu; Jin, Kai; Pan, Tie-Zheng; Gao, Zhen

    2012-02-22

    Many microphones have been developed to meet with the implantable requirement of totally implantable cochlear implant (TICI). However, a biocompatible one without destroying the intactness of the ossicular chain still remains under investigation. Such an implantable floating piezoelectric microphone (FPM) has been manufactured and shows an efficient electroacoustic performance in vitro test at our lab. We examined whether it pick up sensitively from the intact ossicular chain and postulated whether it be an optimal implantable one. Animal controlled experiment: five adult cats (eight ears) were sacrificed as the model to test the electroacoustic performance of the FPM. Three groups were studied: (1) the experiment group (on malleus): the FPM glued onto the handle of the malleus of the intact ossicular chains; (2) negative control group (in vivo): the FPM only hung into the tympanic cavity; (3) positive control group (Hy-M30): a HiFi commercial microphone placed close to the site of the experiment ear. The testing speaker played pure tones orderly ranged from 0.25 to 8.0 kHz. The FPM inside the ear and the HiFi microphone simultaneously picked up acoustic vibration which recorded as .wav files to analyze. The FPM transformed acoustic vibration sensitively and flatly as did the in vitro test across the frequencies above 2.0 kHz, whereas inefficiently below 1.0 kHz for its overloading mass. Although the HiFi microphone presented more efficiently than the FPM did, there was no significant difference at 3.0 kHz and 8.0 kHz. It is feasible to develop such an implantable FPM for future TICIs and TIHAs system on condition that the improvement of Micro Electromechanical System and piezoelectric ceramic material technology would be applied to reduce its weight and minimize its size.

  18. Feasible pickup from intact ossicular chain with floating piezoelectric microphone

    Directory of Open Access Journals (Sweden)

    Kang Hou-Yong

    2012-02-01

    Full Text Available Abstract Objectives Many microphones have been developed to meet with the implantable requirement of totally implantable cochlear implant (TICI. However, a biocompatible one without destroying the intactness of the ossicular chain still remains under investigation. Such an implantable floating piezoelectric microphone (FPM has been manufactured and shows an efficient electroacoustic performance in vitro test at our lab. We examined whether it pick up sensitively from the intact ossicular chain and postulated whether it be an optimal implantable one. Methods Animal controlled experiment: five adult cats (eight ears were sacrificed as the model to test the electroacoustic performance of the FPM. Three groups were studied: (1 the experiment group (on malleus: the FPM glued onto the handle of the malleus of the intact ossicular chains; (2 negative control group (in vivo: the FPM only hung into the tympanic cavity; (3 positive control group (Hy-M30: a HiFi commercial microphone placed close to the site of the experiment ear. The testing speaker played pure tones orderly ranged from 0.25 to 8.0 kHz. The FPM inside the ear and the HiFi microphone simultaneously picked up acoustic vibration which recorded as .wav files to analyze. Results The FPM transformed acoustic vibration sensitively and flatly as did the in vitro test across the frequencies above 2.0 kHz, whereas inefficiently below 1.0 kHz for its overloading mass. Although the HiFi microphone presented more efficiently than the FPM did, there was no significant difference at 3.0 kHz and 8.0 kHz. Conclusions It is feasible to develop such an implantable FPM for future TICIs and TIHAs system on condition that the improvement of Micro Electromechanical System and piezoelectric ceramic material technology would be applied to reduce its weight and minimize its size.

  19. The uptake of radioactive iodine in rat intact Graafian follicles

    International Nuclear Information System (INIS)

    Lieberman, L.M.; Lieberman, G.L.; Lieberman, M.E.

    1984-01-01

    The concentration of iodine-131 in the ovaries of mammals has important implications in the use of I-131 for the diagnosis and treatment of thyroid disease in women. The authors studied the I-131 uptake in whole ovaries and in isolated Graafian follicles of sexually mature rats. Adult female Sprague-Dawley rats, in groups of 5-6 animals, were injected IP with 10-50 μCi of I-131, at 3, 12, and 24 hrs prior to the day of proestrus and killed on the day of proestrus. The thyroid gland and ovaries were removed intact and these organs, as well as eight other tissue specimens, were weighed. The large preovulatory follicles (6-9/ovary) were then isolated under a dissecting microscope and the remaining ovary weighed. All samples were counted in a gamma well counter and the % dose/g estimated. The thyroid gland showed 23.7% dose/organ at 24 hrs. Blood decreased from 1.6% dose/g at 3 hrs to 0.5% dose/g at 24 hrs with the uterus showing 1.1% dose/g and 0.4% dose/g at the same times. Ovarian tissue was 0.5, 0.1, and 0.1% dose/g at 3,12, and 24 hrs respectively, while the intact Graafian follicles had from one-tenth to one-third the concentration of the ovary at the same times. (0.05, 0.03, and 0.03% dose/g). The authors found that the intact Graafian follicle concentrates approximately one-thirtieth to one-sixteenth of the I-131 in the blood and one-tenth to one-third of the I-131 in the ovary. This suggests that there is no active uptake of I-131 in the follicle or follicular fluid

  20. Radionuclide sorption on crushed and intact granitic rock

    International Nuclear Information System (INIS)

    Eriksen, Tryggve E.; Locklund, Birgitta

    1989-05-01

    The specific surface areas and distribution ratios for sorption of 85 Sr, 137 Cs and 152 Eu were measured for crushed and intact granite rock. The experimental data can be accommodated by a sorption model encompassing sorption on outer and inner surface. It is clearly demonstrated that the time required to obtain reliable Kd-values for the sorption of strongly sorbing radionuclides like 152 Eu is very long due to solution depletion and slow diffusion into the rock. A combination of surface area measurements and batch sorption with small particles may therefore be preferable when studying strongly sorbing nuclides. (authors) (17 figs., 6 tabs.)

  1. Radioiodination of an outer membrane protein in intact Rickettsia prowazekii

    International Nuclear Information System (INIS)

    Smith, D.K.; Winkler, H.H.

    1980-01-01

    Intact Rickettsia prowazekii was radiolabeled with the glucose oxidase-lactoperoxidase method of iodination. Separation of the rickettsial extract into cytoplasmic, outer and inner membrane fractions demonstrated that the outer membrane was preferentially labeled. Analysis of the polypeptides of these fractions on high-resolution slab polyacrylamide gels showed that most of the 125 I was in polypeptide T49, an outer membrane constituent. Additional outer membrane polypeptides were iodinated in broken envelope preparations, demonstrating that T49 is uniquely accessible to the external environment and the asymmetric polypeptide organization of the outer membrane

  2. Mixed-mode reversed phase/positively charged repulsion chromatography for intact protein separation.

    Science.gov (United States)

    Ding, Ling; Guo, Zhimou; Hu, Zhuo; Liang, Xinmiao

    2017-05-10

    A mixed-mode reversed phase/positively charged repulsion stationary phase C8PN composed of octyl and amino group has been developed for separation of intact protein. Before the separation of proteins, a set of probe compounds were employed to evaluate the chromatographic properties of C8PN, demonstrating typical reversed phase/positively charged repulsion interaction on this stationary phase as estimated. Then the new C8PN stationary phase was used to separate a standard protein mixture on the reversed phase mode. Compared with a commercial C4 stationary phase, it showed different selectivity for some proteins. In order to better understand the properties of C8PN, the effect of acetonitrile content was investigated based on retention equation. Higher values of the equation parameters on C8PN demonstrated that the protein retentions were more sensitive to the change of acetonitrile content. Besides, the influences of buffer salt additives on the protein retentions were also studied. The retention factors of the proteins got larger with the increase of buffer salt concentration, which confirmed the positively charged repulsion interaction on the column. Finally, the C8PN was further applied to separate oxidized- and reduced- forms of Recombinant Human Growth Hormone. Our study indicated the advantages and application potential of mixed-mode reversed phase/positively charged repulsion stationary phase for intact protein separation. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Screening of intact yeasts and cell extracts to reduce Scrapie prions during biotransformation of food waste.

    Science.gov (United States)

    Huyben, David; Boqvist, Sofia; Passoth, Volkmar; Renström, Lena; Allard Bengtsson, Ulrika; Andréoletti, Olivier; Kiessling, Anders; Lundh, Torbjörn; Vågsholm, Ivar

    2018-02-08

    Yeasts can be used to convert organic food wastes to protein-rich animal feed in order to recapture nutrients. However, the reuse of animal-derived waste poses a risk for the transmission of infectious prions that can cause neurodegeneration and fatality in humans and animals. The aim of this study was to investigate the ability of yeasts to reduce prion activity during the biotransformation of waste substrates-thereby becoming a biosafety hurdle in such a circular food system. During pre-screening, 30 yeast isolates were spiked with Classical Scrapie prions and incubated for 72 h in casein substrate, as a waste substitute. Based on reduced Scrapie seeding activity, waste biotransformation and protease activities, intact cells and cell extracts of 10 yeasts were further tested. Prion analysis showed that five yeast species reduced Scrapie seeding activity by approximately 1 log10 or 90%. Cryptococcus laurentii showed the most potential to reduce prion activity since both intact and extracted cells reduced Scrapie by 1 log10 and achieved the highest protease activity. These results show that select forms of yeast can act as a prion hurdle during the biotransformation of waste. However, the limited ability of yeasts to reduce prion activity warrants caution as a sole barrier to transmission as higher log reductions are needed before using waste-cultured yeast in circular food systems.

  4. IgE epitopes of intact and digested Ara h 1

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Nielsen, H.; Madsen, Charlotte Bernhard

    2012-01-01

    epitopes have been suggested to be of great importance. ObjectiveThe aim of this study was to identify IgE specific epitopes of intact and digested Ara h 1, and to compare epitope patterns between humans and rats. MethodsSera from five peanut allergic patients and five Brown Norway rats were used...... to identify intact and digested Ara h 1-specific IgE epitopes by competitive immunoscreening of a phage-displayed random hepta-mer peptide library using polyclonal IgE from the individual sera. The resulting peptide sequences were mapped on the surface of a three-dimensional structure of the Ara h 1 molecule...... to mimic epitopes using a computer-based algorithm. ResultsPatients as well as rats were shown to have individual IgE epitope patterns. All epitope mimics were conformational and found to cluster into three different areas of the Ara h 1 molecule. Five epitope motifs were identified by patient IgE, which...

  5. Metabolism of inhaled ethane and pentane by the intact rat

    International Nuclear Information System (INIS)

    Daugherty, M.S.; Luddent, T.M.; Burk, R.F.

    1986-01-01

    Measurement of exhaled ethane or pentane is a noninvasive technique for studying in vivo lipid peroxidation. Many past studies have assumed that pentane and ethane are not metabolized. Radiolabeled ( 14 C) ethane and pentane were used to study the disposition of these compounds in intact rats. Rats were placed for 8 h in a closed plexiglass chamber fitted with a system for replenishing chamber atmospheric O 2 . Evolved CO 2 was trapped by recirculating chamber air through 3 N NaOH contained in a vessel external to the chamber. Radiolabeled ethane or pentane was injected into the chamber at the start of each experiment. The percent of 14 C-activity added to the chamber recovered in the CO 2 trap, urine, and chamber air at the end of the experiment (8 h) in the [ 14 C]-ethane (n=5) and [ 14 C]-pentane (n=4) studies are presented. Results indicate that both ethane and pentane are metabolized to CO 2 in the intact rat. Possible changes in ethane and pentane metabolism must be considered if the exhalation rates of these hydrocarbons are to be used as indices of in vivo lipid peroxidation

  6. Surface plasmon resonance sensing: from purified biomolecules to intact cells.

    Science.gov (United States)

    Su, Yu-Wen; Wang, Wei

    2018-04-12

    Surface plasmon resonance (SPR) has become a well-recognized label-free technique for measuring the binding kinetics between biomolecules since the invention of the first SPR-based immunosensor in 1980s. The most popular and traditional format for SPR analysis is to monitor the real-time optical signals when a solution containing ligand molecules is flowing over a sensor substrate functionalized with purified receptor molecules. In recent years, rapid development of several kinds of SPR imaging techniques have allowed for mapping the dynamic distribution of local mass density within single living cells with high spatial and temporal resolutions and reliable sensitivity. Such capability immediately enabled one to investigate the interaction between important biomolecules and intact cells in a label-free, quantitative, and single cell manner, leading to an exciting new trend of cell-based SPR bioanalysis. In this Trend Article, we first describe the principle and technical features of two types of SPR imaging techniques based on prism and objective, respectively. Then we survey the intact cell-based applications in both fundamental cell biology and drug discovery. We conclude the article with comments and perspectives on the future developments. Graphical abstract Recent developments in surface plasmon resonance (SPR) imaging techniques allow for label-free mapping the mass-distribution within single living cells, leading to great expansions in biomolecular interactions studies from homogeneous substrates functionalized with purified biomolecules to heterogeneous substrates containing individual living cells.

  7. Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration

    International Nuclear Information System (INIS)

    Kang, Liang; Hu, Jia; Weng, Yuxiong; Jia, Jie; Zhang, Yukun

    2017-01-01

    Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptional activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity. - Highlights: • SIRT6 expression is decreased in degenerative nucleus pulposus (NP) tissues. • SIRT6 overexpression lowers IL-1β-induced matrix degradation of NP. • SIRT6 inhibition induces matrix degradation of NP. • SIRT6 prevents matrix degradation of NP via the NF-κB signaling pathway.

  8. Electroacupuncture improves microcirculation and neuronal morphology in the spinal cord of a rat model of intervertebral disc extrusion

    Directory of Open Access Journals (Sweden)

    Dai-xun Jiang

    2015-01-01

    Full Text Available Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spinal cord injury and repair research. Therefore, in this study, we established a rat model of intervertebral disc extrusion by inserting a silica gel pad into the left ventral surface of T 13 . Electroacupuncture was used to stimulate the bilateral Zusanli point (ST36 and Neiting point (ST44 for 14 days. Compared with control animals, blood flow in the first lumbar vertebra (L 1 was noticeably increased in rats given electroacupuncture. Microvessel density in the T 13 segment of the spinal cord was increased significantly as well. The number of normal neurons was higher in the ventral horn of the spinal cord. In addition, vacuolation in the white matter was lessened. No obvious glial cell proliferation was visible. Furthermore, hindlimb motor function was improved significantly. Collectively, our results suggest that electroacupuncture can improve neuronal morphology and microcirculation, and promote the recovery of neurological functions in a rat model of intervertebral disc extrusion.

  9. Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Liang [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Hu, Jia [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Weng, Yuxiong [Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Jia, Jie [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Zhang, Yukun, E-mail: zhangyukuncom@126.com [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

    2017-03-15

    Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptional activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity. - Highlights: • SIRT6 expression is decreased in degenerative nucleus pulposus (NP) tissues. • SIRT6 overexpression lowers IL-1β-induced matrix degradation of NP. • SIRT6 inhibition induces matrix degradation of NP. • SIRT6 prevents matrix degradation of NP via the NF-κB signaling pathway.

  10. Calcification of the intervertebral discs and curvature of the radius and ulna: A radiographic survey of Finnish miniature dachshunds

    International Nuclear Information System (INIS)

    Lappalainen, A.; Norrgaard, M.; Alm, K.; Snellman, M.; Laitinen, O.

    2001-01-01

    The vertebral column of 124 randomly selected miniature dachshunds, representing 4.5% of the population registered by the Finnish Kennel Club during the years 1988 to 1996, were radiographed. The front legs were also radiographed in order to evaluate the curvature of the radius and ulna. Calcified discs were found in 75.9% of the longhaired miniature dachshunds and in 86.7% of the wirehaired ones. The occurrence of signs associated with IDD was 16.5% in longhaired and 15.6% in wirehaired miniature dachshunds. The occurrence of signs of IDD in dogs with calcified discs was 20.0% and 17.9% in longhaired and wirehaired miniature dachshunds, respectively. In dogs without calcifications only one dog showed signs of IDD. The curvature of the radius and the ulna did not differ between the dogs with signs of IDD and the healthy ones, or between the dogs with and without intervertebral calcifications. Our results indicate that radiographic eradication based on the presence of intervertebral calcifications is not suitable for breeding purposes for the Finnish miniature dachshund population because the percentage of dogs without calcifications is small

  11. Influence of patient position and implant material on the stress distribution in an artificial intervertebral disc of the lumbar vertebrae

    Directory of Open Access Journals (Sweden)

    Karpiński Robert

    2017-01-01

    Full Text Available The aim of this paper was to determine the effect of using cobalt and titanium-based alloys as implant materials for the lumbar vertebrae with an artificial intervertebral disc on the stress distribution. The lumbar vertebrae were chosen for the study because they carry considerably higher loads, especially while standing or sitting. Finite element method (FEM simulations were conducted for three standard loads reflecting three patient's positions: recumbent, standing and sitting. The FEM analysis was performed using the SolidWorks Simulation module. Artificial units containing a pair of vertebrae with a prosthesis between them were designed by the Solid Edge software, based on micro-computed tomography CT scans of the patient's spine. The implant model was designed with its shape based on the geometry of surrounding vertebrae, consisting of an upper pad, a bottom pad and an insert (intervertebral disc. Two implant material configurations were studied. One involved the use of titanium alloy for the upper and bottom pads, while in the other, these pads were made of cobalt alloy. In both cases, a polyethylene insert was used. The FEM results demonstrate that both material configurations meet the requirements for prosthesis design. In both material configurations, the maximum stresses in each prosthesis element are almost twice higher in a sitting posture than in a recumbent position.

  12. The impact of office chair features on lumbar lordosis, intervertebral joint and sacral tilt angles: a radiographic assessment.

    Science.gov (United States)

    De Carvalho, Diana; Grondin, Diane; Callaghan, Jack

    2017-10-01

    The purpose of this study was to determine which office chair feature is better at improving spine posture in sitting. Participants (n = 28) were radiographed in standing, maximum flexion and seated in four chair conditions: control, lumbar support, seat pan tilt and backrest with scapular relief. Measures of lumbar lordosis, intervertebral joint angles and sacral tilt were compared between conditions and sex. Sitting consisted of approximately 70% of maximum range of spine flexion. No differences in lumbar flexion were found between the chair features or control. Significantly more anterior pelvic rotation was found with the lumbar support (p = 0.0028) and seat pan tilt (p < 0.0001). Males had significantly more anterior pelvic rotation and extended intervertebral joint angles through L1-L3 in all conditions (p < 0.0001). No one feature was statistically superior with respect to minimising spine flexion, however, seat pan tilt resulted in significantly improved pelvic posture. Practitioner Summary: Seat pan tilt, and to some extent lumbar supports, appear to improve seated postures. However, sitting, regardless of chair features used, still involves near end range flexion of the spine. This will increase stresses to the spine and could be a potential injury generator during prolonged seated exposures.

  13. Lactoferricin mediates Anti-Inflammatory and Anti-Catabolic Effects via Inhibition of IL-1 and LPS Activity in the Intervertebral Disc†

    Science.gov (United States)

    Kim, Jae-Sung; Ellman, Michael B.; Yan, Dongyao; An, Howard S.; Kc, Ranjan; Li, Xin; Chen, Di; Xiao, Guozhi; Cs-Zabo, Gabriella; Hoskin, David W.; Buechter, D.D.; Van Wijnen, Andre J.; Im, Hee-Jeong

    2013-01-01

    The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. PMID:23460134

  14. Lactoferricin mediates anti-inflammatory and anti-catabolic effects via inhibition of IL-1 and LPS activity in the intervertebral disc.

    Science.gov (United States)

    Kim, Jae-Sung; Ellman, Michael B; Yan, Dongyao; An, Howard S; Kc, Ranjan; Li, Xin; Chen, Di; Xiao, Guozhi; Cs-Szabo, Gabriella; Hoskin, David W; Buechter, Doug D; Van Wijnen, Andre J; Im, Hee-Jeong

    2013-09-01

    The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production, and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. Copyright © 2013 Wiley Periodicals, Inc.

  15. Intervertebral disc disease in dogs - Part 2: Comparison of clinical, magnetic resonance imaging, and histological findings in 74 surgically treated dogs

    NARCIS (Netherlands)

    Kranenburg, H.C.; Grinwis, G.C.M.; Bergknut, N.; Gahrmann, Ninke; Voorhout, G.; Hazewinkel, H.A.W.

    The relationship between intervertebral disc (IVD) disease and IVD degeneration remains unclear. The aim of the present study was to compare the clinical severity of IVD herniation (IVDH), determined with a neurological grading system, with findings of magnetic resonance imaging (MRI) and

  16. Osmosis and viscoelasticity both contribute to time-dependent behaviour of the intervertebral disc under compressive load: A caprine in vitro study

    NARCIS (Netherlands)

    Emanuel, Kaj S.; van der Veen, Albert J.; Rustenburg, Christine M. E.; Smit, Theodoor H.; Kingma, Idsart

    2017-01-01

    The mechanical behaviour of the intervertebral disc highly depends on the content and transport of interstitial fluid. It is unknown, however, to what extent the time-dependent behaviour can be attributed to osmosis. Here we investigate the effect of both mechanical and osmotic loading on water

  17. [Epidural pharmacotherapy in the treatment of the pain syndrome in osteochondrosis complicated by intervertebral discs protrusion of lumbar part of the vertebral column].

    Science.gov (United States)

    Khizhniak, M V; Priĭmak, E V

    2013-03-01

    Experience of application of intralaminar epidural pharmacotherapy for the treatment of the pain syndrome in the patients, suffering osteochondrosis of lumbar portion of vertebral column, complicated by intervertebral discs protrusion, was summarized. The method introduction permits to escape the operative intervention performance for complicated osteochondrosis.

  18. Measurement of Intervertebral Motion Using Quantitative Fluoroscopy: Report of an International Forum and Proposal for Use in the Assessment of Degenerative Disc Disease in the Lumbar Spine

    Directory of Open Access Journals (Sweden)

    Alan C. Breen

    2012-01-01

    Full Text Available Quantitative fluoroscopy (QF is an emerging technology for measuring intervertebral motion patterns to investigate problem back pain and degenerative disc disease. This International Forum was a networking event of three research groups (UK, US, Hong Kong, over three days in San Francisco in August 2009. Its aim was to reach a consensus on how best to record, analyse, and communicate QF information for research and clinical purposes. The Forum recommended that images should be acquired during regular trunk motion that is controlled for velocity and range, in order to minimise externally imposed variability as well as to correlate intervertebral motion with trunk motion. This should be done in both the recumbent passive and weight bearing active patient configurations. The main recommended outputs from QF were the true ranges of intervertebral rotation and translation, neutral zone laxity and the consistency of shape of the motion patterns. The main clinical research priority should initially be to investigate the possibility of mechanical subgroups of patients with chronic, nonspecific low back pain by comparing their intervertebral motion patterns with those of matched healthy controls.

  19. The role and position of passive intervertebral motion assessment within clinical reasoning and decision-making in manual physical therapy: a qualitative interview study

    NARCIS (Netherlands)

    van Trijffel, Emiel; Plochg, Thomas; van Hartingsveld, Frank; Lucas, Cees; Oostendorp, Rob A. B.

    2010-01-01

    Passive intervertebral motion (PIVM) assessment is a characterizing skill of manual physical therapists (MPTs) and is important for judgments about impairments in spinal joint function. It is unknown as to why and how MPTs use this mobility testing of spinal motion segments within their clinical

  20. Does inter-vertebral range of motion increase after spinal manipulation? A prospective cohort study.

    Science.gov (United States)

    Branney, Jonathan; Breen, Alan C

    2014-01-01

    Spinal manipulation for nonspecific neck pain is thought to work in part by improving inter-vertebral range of motion (IV-RoM), but it is difficult to measure this or determine whether it is related to clinical outcomes. This study undertook to determine whether cervical spine flexion and extension IV-RoM increases after a course of spinal manipulation, to explore relationships between any IV-RoM increases and clinical outcomes and to compare palpation with objective measurement in the detection of hypo-mobile segments. Thirty patients with nonspecific neck pain and 30 healthy controls matched for age and gender received quantitative fluoroscopy (QF) screenings to measure flexion and extension IV-RoM (C1-C6) at baseline and 4-week follow-up between September 2012-13. Patients received up to 12 neck manipulations and completed NRS, NDI and Euroqol 5D-5L at baseline, plus PGIC and satisfaction questionnaires at follow-up. IV-RoM accuracy, repeatability and hypo-mobility cut-offs were determined. Minimal detectable changes (MDC) over 4 weeks were calculated from controls. Patients and control IV-RoMs were compared at baseline as well as changes in patients over 4 weeks. Correlations between outcomes and the number of manipulations received and the agreement (Kappa) between palpated and QF-detected of hypo-mobile segments were calculated. QF had high accuracy (worst RMS error 0.5o) and repeatability (highest SEM 1.1o, lowest ICC 0.90) for IV-RoM measurement. Hypo-mobility cut offs ranged from 0.8o to 3.5o. No outcome was significantly correlated with increased IV-RoM above MDC and there was no significant difference between the number of hypo-mobile segments in patients and controls at baseline or significant increases in IV-RoMs in patients. However, there was a modest and significant correlation between the number of manipulations received and the number of levels and directions whose IV-RoM increased beyond MDC (Rho=0.39, p=0.043). There was also no agreement

  1. Radiation-induced adaptive response in the intact mouse

    International Nuclear Information System (INIS)

    Yonezawa, Morio

    2009-01-01

    The author and coworkers have revealed that radiation adaptive response (AR) is seen also in the bone marrow of the intact mouse, of which details are described here. First, SPF ICR mice were pre-irradiated (PI) with 0-0.1 Gy of X-ray and after 2 months, subsequently irradiated (SI) with 7.75 Gy. Survival rates at 30 days after SI were about 14% in mice with PI 0-0.025 Gy whereas 40% or more in animals with PI 0.05-0.1 Gy: bone marrow death was found significantly suppressed in this effective PI dose range. The death 2 weeks after SI was found also inhibited at PI 0.3-0.5 Gy. Second, PI doses and interval between PI and SI for acquiring the radio-resistance (RR) were studied and third, the PI 0.3-0.5 Gy with SI 8.0 Gy at 9-17 days later revealed that regional PI of the head (central nervous system) was found unnecessary for RR and of abdomen (systems of hemopoiesis, immunity and digestion), essential. Fourth, strain difference of RR was shown by the fact that RR was observed only in C57BL mouse as well, but neither in BALB/c nor C3H strain. Next, at 12 days after SI 4.25-6.75 Gy (PI 0.5 Gy at 14 days before), mouse spleen cells were subjected to colony formation analysis by counting the endogenous hemopoietic stem cells, which revealed that those cells were increased to about 5 times by PI. Suppression of SI-induced hemorrhage was found in mice with PI by the decreased fecal hemoglobin content. Finally, AR was similarly studied in p53 +/+ and its knockout C57BL mice and was not found in the latter animal, indicating the participation of p53 in AR of the intact mouse. Elucidation of AR mechanisms in the intact animal seems to require somewhat different aspect from that in cells. The results were controvertible to the general concept that radiation risk is proportional to cumulative dose, suggesting that low dose radiation differs from high dose one in biological effect. (K.T.)

  2. Quantification of intervertebral displacement with a novel MRI-based modeling technique: Assessing measurement bias and reliability with a porcine spine model.

    Science.gov (United States)

    Mahato, Niladri K; Montuelle, Stephane; Goubeaux, Craig; Cotton, John; Williams, Susan; Thomas, James; Clark, Brian C

    2017-05-01

    0 ) of 0.62 (±0.12)° was detected for the 2D HYCE S sequence (pmodel also demonstrated an additional bias (β 1 Displacement) of 0.05° with each degree increase in the experimental rotation (p0.05). ICC values for the T 1 and 2D HYCE S pulse sequences were recorded 0.97 and 0.91, respectively. This novel quasi-static approach to quantifying intervertebral relationship demonstrates a reasonable degree of accuracy and reliability using the model-to-image matching technique with both static and dynamic sequences in a porcine model. Future work is required to explore multi-planar assessment of real-time spine motion and to examine the reliability of our approach in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Transport of indoleacetic acid in intact corn coleoptiles

    International Nuclear Information System (INIS)

    Parker, K.E.; Briggs, W.R.

    1990-01-01

    We have characterized the transport of [ 3 H]indoleacetic acid (IAA) in intact corn (Zea mays L.) coleoptiles. We have used a wide range of concentrations of added IAA (28 femtomoles to 100 picomoles taken up over 60 minutes). The shape of the transport curve varies with the concentration of added IAA, although the rate of movement of the observed front of tracer is invariant with concentration. At the lowest concentration of tracer used, the labeled IAA in the transport stream is not detectably metabolized or immobilized, curvature does not develop as a result of tracer application, and normal phototropic and gravitropic responsiveness are not affected. Therefore we believe we are observing the transport of true tracer quantities of labeled auxin at this lowest concentration

  4. Simple Genome Editing of Rodent Intact Embryos by Electroporation.

    Directory of Open Access Journals (Sweden)

    Takehito Kaneko

    Full Text Available The clustered regularly interspaced short palindromic repeat (CRISPR/CRISPR-associated (Cas system is a powerful tool for genome editing in animals. Recently, new technology has been developed to genetically modify animals without using highly skilled techniques, such as pronuclear microinjection of endonucleases. Technique for animal knockout system by electroporation (TAKE method is a simple and effective technology that produces knockout rats by introducing endonuclease mRNAs into intact embryos using electroporation. Using TAKE method and CRISPR/Cas system, the present study successfully produced knockout and knock-in mice and rats. The mice and rats derived from embryos electroporated with Cas9 mRNA, gRNA and single-stranded oligodeoxynucleotide (ssODN comprised the edited targeted gene as a knockout (67% of mice and 88% of rats or knock-in (both 33%. The TAKE method could be widely used as a powerful tool to produce genetically modified animals by genome editing.

  5. Selective dansylation of M protein within intact influenza virions

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, B.H.; Bennett, J.C.; Compans, R.W.

    1982-12-01

    Exposure of purified influenza virions to (/sup 14/C)dansyl chloride resulted in the covalent attachment of the dansyl chromophore to the virion. Gel electrophoresis revealed that the dansyl chromophore was specifically coupled to the internal membrane (M) protein. Purification of the M protein by gel filtration followed by cyanogen bromide cleavage and peptide fractionation revealed that four of six peptide peaks contained dansyl label. Acid hydrolysis of the separated peptide peaks followed by thin-layer chromatography revealed that dansyl label was coupled to lysine residues present in these peptides. The results of these investigations have demonstrated that the M protein molecule is the major viral polypeptide labeled when intact virions are exposed to dansyl chloride.

  6. Selective dansylation of M protein within intact influenza virions

    International Nuclear Information System (INIS)

    Robertson, B.H.; Bennett, J.C.; Compans, R.W.

    1982-01-01

    Exposure of purified influenza virions to [ 14 C]dansyl chloride resulted in the covalent attachment of the dansyl chromophore to the virion. Gel electrophoresis revealed that the dansyl chromophore was specifically coupled to the internal membrane (M) protein. Purification of the M protein by gel filtration followed by cyanogen bromide cleavage and peptide fractionation revealed that four of six peptide peaks contained dansyl label. Acid hydrolysis of the separated peptide peaks followed by thin-layer chromatography revealed that dansyl label was coupled to lysine residues present in these peptides. The results of these investigations have demonstrated that the M protein molecule is the major viral polypeptide labeled when intact virions are exposed to dansyl chloride

  7. In-vivo Intervertebral Disc Characterization using Magnetic Resonance Spectroscopy and T1ρ Imaging: Association with Discography and Oswestry Disability Index and SF-36

    Science.gov (United States)

    Zuo, Jin; Joseph, Gabby B.; Li, Xiaojuan; Link, Thomas M.; Hu, Serena S.; Berven, Sigurd H.; Kurhanewitz, John; Majumdar, Sharmila

    2011-01-01

    Study Design An in vivo study of intervertebral disc degeneration using quantitative MRI and MRS. Objective To quantify water and proteoglycan (PG) content in the intervertebral disc using in vivo magnetic resonance spectroscopy (MRS), and to evaluate the relationship between MRS- quantified water/PG content, T1ρ, Pfirrmann score, clinical self-assessment, and discography. Summary of Background Data Previous in vitro studies have investigated the relationship between MRS-quantified water/PG content, and degenerative grade using cadaveric intervertebral discs. T1ρ has been shown to relate to Pfirmann grade and clinical self-assessment. However, the associations between MRS-quantified water/PG content, MR imaging-based T1ρ, self-assessment of health status and clinical response to discography have not been studied in vivo. Methods MRS and MR imaging were performed in 26 patients (70 discs) with symptomatic intervertebral degenerative disc (IVDD) and 23 controls (41 discs). Patients underwent evaluation of intervertebral discs with provocative discography. All subjects completed the SF-36 Health Survey and Oswestry Disability Index questionnaires. Results The water/PG peak area ratio was significantly elevated in a) patients (compared to controls) and in b) discs with positive discography (compared to negative discography). MR T1ρ exhibited similar trends. A significant association was found between T1ρ and normalized PG content (R2 = 0.61, p 0.05). The water/PG peak area ratio, normalized water, normalized PG, and Pfirrmann grade were significantly associated with patient self-assessment of disability and physical composite score, while disc height was not. Conclusion This study demonstrated a relationship between in vivo MRS spectroscopy (water content, PG content), imaging parameters (T1ρ, Pfirrmann Grade), discography results, and clinical self-assessment, suggesting that MRS-quantified water, PG and MR T1ρ relaxation time may potentially serve as

  8. In vivo intervertebral disc characterization using magnetic resonance spectroscopy and T1ρ imaging: association with discography and Oswestry Disability Index and Short Form-36 Health Survey.

    Science.gov (United States)

    Zuo, Jin; Joseph, Gabby B; Li, Xiaojuan; Link, Thomas M; Hu, Serena S; Berven, Sigurd H; Kurhanewitz, John; Majumdar, Sharmila

    2012-02-01

    An in vivo study of intervertebral disc degeneration by using quantitative magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). To quantify water and proteoglycan (PG) content in the intervertebral disc by using in vivo MRS and to evaluate the relationship between MRS-quantified water/PG content, T1ρ, Pfirrmann score, clinical self-assessment, and discography. Previous in vitro studies have investigated the relationship between MRS-quantified water/PG content and degenerative grade by using cadaveric intervertebral discs. T1ρ has been shown to relate to Pfirrmann grade and clinical self-assessment. However, the associations between MRS-quantified water/PG content, MRI-based T1ρ, self-assessment of health status, and clinical response to discography have not been studied in vivo. MRS and MRI were performed in 26 patients (70 discs) with symptomatic intervertebral degenerative disc (IVDD) and 23 controls (41 discs). Patients underwent evaluation of intervertebral discs with provocative discography. All subjects completed the Short Form-36 Health Survey and Oswestry Disability Index questionnaires. The water/PG peak area ratio was significantly elevated in (a) patients (compared with controls) and in (b) discs with positive discography (compared with negative discography). Magnetic resonance (MR) T1ρ exhibited similar trends. A significant association was found between T1ρ and normalized PG content (R = 0.61, P 0.05). The water/PG peak area ratio, normalized water, normalized PG, and Pfirrmann grade were significantly associated with patient self-assessment of disability and physical composite score, while disc height was not. This study demonstrated a relationship between in vivo MRS spectroscopy (water content and PG content), imaging parameters (T1ρ and Pfirrmann grade), discography results, and clinical self-assessment, suggesting that MRS-quantified water, PG, and MR T1ρ relaxation time may potentially serve as biomarkers of

  9. Isolation of intact sub-dermal secretory cavities from Eucalyptus

    Directory of Open Access Journals (Sweden)

    Goodger Jason QD

    2010-09-01

    Full Text Available Abstract Background The biosynthesis of plant natural products in sub-dermal secretory cavities is poorly understood at the molecular level, largely due to the difficulty of physically isolating these structures for study. Our aim was to develop a protocol for isolating live and intact sub-dermal secretory cavities, and to do this, we used leaves from three species of Eucalyptus with cavities that are relatively large and rich in essential oils. Results Leaves were digested using a variety of commercially available enzymes. A pectinase from Aspergillus niger was found to allow isolation of intact cavities after a relatively short incubation (12 h, with no visible artifacts from digestion and no loss of cellular integrity or cavity contents. Several measurements indicated the potential of the isolated cavities for further functional studies. First, the cavities were found to consume oxygen at a rate that is comparable to that estimated from leaf respiratory rates. Second, mRNA was extracted from cavities, and it was used to amplify a cDNA fragment with high similarity to that of a monoterpene synthase. Third, the contents of the cavity lumen were extracted, showing an unexpectedly low abundance of volatile essential oils and a sizeable amount of non-volatile material, which is contrary to the widely accepted role of secretory cavities as predominantly essential oil repositories. Conclusions The protocol described herein is likely to be adaptable to a range of Eucalyptus species with sub-dermal secretory cavities, and should find wide application in studies of the developmental and functional biology of these structures, and the biosynthesis of the plant natural products they contain.

  10. Intact calcium signaling in adrenergic-deficient embryonic mouse hearts.

    Science.gov (United States)

    Peoples, Jessica N; Taylor, David G; Katchman, Alexander N; Ebert, Steven N

    2018-01-22

    Mouse embryos that lack the ability to produce the adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), due to disruption of the dopamine beta-hydroxylase (Dbh -/- ) gene inevitably perish from heart failure during mid-gestation. Since adrenergic stimulation is well-known to enhance calcium signaling in developing as well as adult myocardium, and impairments in calcium signaling are typically associated with heart failure, we hypothesized that adrenergic-deficient embryonic hearts would display deficiencies in cardiac calcium signaling relative to adrenergic-competent controls at a developmental stage immediately preceding the onset of heart failure, which first appears beginning or shortly after mouse embryonic day 10.5 (E10.5). To test this hypothesis, we used ratiometric fluorescent calcium imaging techniques to measure cytosolic calcium transients, [Ca 2+ ] i in isolated E10.5 mouse hearts. Our results show that spontaneous [Ca 2+ ] i oscillations were intact and robustly responded to a variety of stimuli including extracellular calcium (5 mM), caffeine (5 mM), and NE (100 nM) in a manner that was indistinguishable from controls. Further, we show similar patterns of distribution (via immunofluorescent histochemical staining) and activity (via patch-clamp recording techniques) for the major voltage-gated plasma membrane calcium channel responsible for the L-type calcium current, I Ca,L , in adrenergic-deficient and control embryonic cardiac cells. These results demonstrate that despite the absence of vital adrenergic hormones that consistently leads to embryonic lethality in vivo, intracellular and extracellular calcium signaling remain essentially intact and functional in embryonic mouse hearts through E10.5. These findings suggest that adrenergic stimulation is not required for the development of intracellular calcium oscillations or extracellular calcium signaling through I Ca,L and that aberrant calcium signaling does not likely contribute

  11. Optimized Planning Target Volume for Intact Cervical Cancer

    International Nuclear Information System (INIS)

    Khan, Alvin; Jensen, Lindsay G.; Sun Shuai; Song, William Y.; Yashar, Catheryn M.; Mundt, Arno J.; Zhang Fuquan; Jiang, Steve B.; Mell, Loren K.

    2012-01-01

    Purpose: To model interfraction clinical target volume (CTV) variation in patients with intact cervical cancer and design a planning target volume (PTV) that minimizes normal tissue dose while maximizing CTV coverage. Methods and Materials: We analyzed 50 patients undergoing external-beam radiotherapy for intact cervical cancer using daily online cone-beam computed tomography (CBCT). The CBCTs (n = 972) for each patient were rigidly registered to the planning CT. The CTV was delineated on the planning CT (CTV 0 ) and the set of CBCTs ({CTV 1 –CTV 25 }). Manual (n = 98) and automated (n = 668) landmarks were placed over the surface of CTV 0 with reference to defined anatomic structures. Normal vectors were extended from each landmark, and the minimum length required for a given probability of encompassing CTV 1 –CTV 25 was computed. The resulting expansions were used to generate an optimized PTV. Results: The mean (SD; range) normal vector length to ensure 95% coverage was 4.3 mm (2.7 mm; 1–16 mm). The uniform expansion required to ensure 95% probability of CTV coverage was 13 mm. An anisotropic margin of 20 mm anteriorly and posteriorly and 10 mm superiorly, inferiorly, and laterally also would have ensured a 95% probability of CTV coverage. The volume of the 95% optimized PTV (1470 cm 3 ) was significantly lower than both the anisotropic PTV (2220 cm 3 ) and the uniformly expanded PTV (2110 cm 3 ) (p 0 , 5–10 mm along the interfaces of CTV 0 with the bladder and rectum, and 10–14 mm along the anterior surface of CTV 0 at the level of the uterus. Conclusion: Optimizing PTV definition according to surface landmarking resulted in a high probability of CTV coverage with reduced PTV volumes. Our results provide data justifying planning margins to use in practice and clinical trials.

  12. Replacing the nucleus pulposus of the intervertebral disk: prediction of suitable properties of a replacement material using finite element analysis.

    Science.gov (United States)

    Meakin, J R

    2001-03-01

    An axisymmetric finite element model of a human lumbar disk was developed to investigate the properties required of an implant to replace the nucleus pulposus. In the intact disk, the nucleus was modeled as a fluid, and the annulus as an elastic solid. The Young's modulus of the annulus was determined empirically by matching model predictions to experimental results. The model was checked for sensitivity to the input parameter values and found to give reasonable behavior. The model predicted that removal of the nucleus would change the response of the annulus to compression. This prediction was consistent with experimental results, thus validating the model. Implants to fill the cavity produced by nucleus removal were modeled as elastic solids. The Poisson's ratio was fixed at 0.49, and the Young's modulus was varied from 0.5 to 100 MPa. Two sizes of implant were considered: full size (filling the cavity) and small size (smaller than the cavity). The model predicted that a full size implant would reverse the changes to annulus behavior, but a smaller implant would not. By comparing the stress distribution in the annulus, the ideal Young's modulus was predicted to be approximately 3 MPa. These predictions have implications for current nucleus implant designs. Copyright 2001 Kluwer Academic Publishers

  13. Prótese para substituição total de disco intervertebral: desenvolvimento de modelo computacional e análise por elementos finitos Prótese de reemplazo total del disco intervertebral: modelo de desarrollo computacional y análisis de elementos finitos Prosthesis for total intervertebral disc replacement: computacional model development and finite element analysis

    Directory of Open Access Journals (Sweden)

    Tiago Nunes Campello

    2009-03-01

    Full Text Available INTRODUÇÃO: a idéia de um disco intervertebral artificial não é nova. O campo de estudos sobre próteses para artroplastia de coluna desenvolve-se ao passo que novas tecnologias na área de materiais e engenharia médica são desenvolvidas ou introduzidas para o surgimento de novos projetos. OBJETIVO: estabelecer metodologia de desenvolvimento de produto em um projeto de prótese para substituição total de disco intervertebral pela utilização de ferramentas computacionais de engenharia. MÉTODOS: a metodologia de desenvolvimento de prótese para substituição total de disco iniciou-se com a definição do seu modelo virtual, seguida pela a análise mecânica virtual por elementos finitos. RESULTADOS: a prótese de disco foi concebida com três componentes, sendo eles o flange superior, o flange inferior e o núcleo. Aplicando o critério de von Mises para solução da análise virtual, verificou-se que o núcleo da prótese é o componente mais solicitado durante compressão axial e compressão/cisalhamento. CONCLUSÃO: este estudo demonstra a viabilidade do desenvolvimento de um projeto para fabricação de prótese para substituição total de disco intervertebral, por meio de metodologia computacional já consagrada em projetos mecânicos de engenharia, principalmente, nos ramos automotivo e aeronáutico.INTRODUCCIÓN: la idea de un disco intervertebral artificial no es nueva. Los estudios de la columna vertebral artroplastia prótesis están en desarrollo, mientras las nuevas tecnologías en el ámbito de la ingeniería y los materiales médicos son desarr llados o introducidos a la aparición de nuevos proyectos. OBJETIVO: establecer una metodología para el desarrollo de producto en un proyecto de prótesis para reemplazo total del disco intervertebral, a través del uso de herramientas de ingeniería computacional. MÉTODOS: la metodología de desarrollo de prótesis para reemplazo total del disco se inició con la definici

  14. Para-muscular and trans-muscular approaches to the lumbar inter-vertebral foramen: an anatomical comparison.

    Science.gov (United States)

    Poetscher, Arthur Werner; Ribas, Guilherme Carvalhal; Yasuda, Alexandre; Nishikuni, Koshiro

    2005-03-01

    Foraminal and extra-foraminal disc herniations comprise up to 11.7% of all lumbar disc herniations. Facetectomy, which had been the classic approach, is now recognized as cause of pain and instability after surgery. Otherwise, posterior lateral approaches through a trans-muscular or a para-muscular technique offer no significant damage to key structures for spinal stability. The surgical anatomy of these approaches has already been described, but they were not compared. In order to quantify the angle of vision towards the intervertebral foramen offered by each technique, 12 fresh cadavers were dissected and studied regarding these approaches. The angle presented by trans-muscular approach was wider in all studied lumbar levels. Surgery through the trans-muscular approach is performed with a better working angle, requiring a smaller resection of surrounding tissues. Therefore, minor surgical trauma can be expected. Our measurements support previously published data that point the trans-muscular approach as the best surgical option.

  15. The Comparison of Effective between Acupuncture and Bee Venom Acupuncture on the Treatment of Acute Lumbar Herniation of Intervertebral Disc

    Directory of Open Access Journals (Sweden)

    Chang So-Young

    2006-06-01

    Full Text Available Objective : Herniation of Intervertebral Disc(HIVD is the most common disease causing low back pain. Acupuncture and Bee Venom Acupuncture has been used for treatment of HIVD. This study is to investigate the effective of Bee Venom Acupuncture for HIVD. Methods : We researched 18 patients who were diagnosed by CT and MRI as having HIVD, and treated them Acupuncture only or Acupuncture and Bee Venom Acupuncture. We compared the VAS and ROM angle of two groups. Results & Conclusions : 1. In admission date, no significant improvement between Acupuncture group and Bee Venom Acupuncture group 2. In variation of flexion and extension, Bee Venom Acupuncture group shows statistically significant improvement 3. In VAS, Bee Venom Acupuncture group shows statistically significant improvement for 1 week and discharge day

  16. Biochemical imaging of cervical intervertebral discs with glycosaminoglycan chemical exchange saturation transfer magnetic resonance imaging: feasibility and initial results

    International Nuclear Information System (INIS)

    Schleich, Christoph; Mueller-Lutz, Anja; Zimmermann, Lisa; Boos, Johannes; Wittsack, Hans-Joerg; Antoch, Gerald; Miese, Falk; Schmitt, Benjamin

    2016-01-01

    To evaluate glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging at 3T in the assessment of the GAG content of cervical IVDs in healthy volunteers. Forty-two cervical intervertebral discs of seven healthy volunteers (four females, three males; mean age: 21.4 ± 1.4 years; range: 19-24 years) were examined at a 3T MRI scanner in this prospective study. The MRI protocol comprised standard morphological, sagittal T2 weighted (T2w) images to assess the magnetic resonance imaging (MRI) based grading system for cervical intervertebral disc degeneration (IVD) and biochemical imaging with gagCEST to calculate a region-of-interest analysis of nucleus pulposus (NP) and annulus fibrosus (AF). GagCEST of cervical IVDs was technically successful at 3T with significant higher gagCEST values in NP compared to AF (1.17 % ± 1.03 % vs. 0.79 % ± 1.75 %; p = 0.005). We found topological differences of gagCEST values of the cervical spine with significant higher gagCEST effects in lower IVDs (r = 1; p = 0). We could demonstrate a significant, negative correlation between gagCEST values and cervical disc degeneration of NP (r = -0.360; p = 0.019). Non-degenerated IVDs had significantly higher gagCEST effects compared to degenerated IVDs in NP (1.76 % ± 0.92 % vs. 0.52 % ± 1.17 %; p < 0.001). Biochemical imaging of cervical IVDs is feasible at 3T. GagCEST analysis demonstrated a topological GAG distribution of the cervical spine. The depletion of GAG in the NP with increasing level of morphological degeneration can be assessed using gagCEST imaging. (orig.)

  17. Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2.

    Science.gov (United States)

    Bedore, Jake; Sha, Wei; McCann, Matthew R; Liu, Shangxi; Leask, Andrew; Séguin, Cheryle A

    2013-10-01

    Currently, our ability to treat intervertebral disc (IVD) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including CCN2, during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in IVD tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific CCN2 deletion. Expression of CCN proteins was assessed in IVD tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of CCN2 in notochord-derived tissues, we generated notochord-specific CCN2-null mice to assess the impact on the IVD structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), IVD health was assessed. Loss of the CCN2 gene in notochord-derived cells disrupted the formation of IVDs in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. CCN2-knockout mice also had altered expression of CCN1 (Cyr61) and CCN3 (Nov). Mirroring its role during early development, notochord-specific CCN2 deletion accelerated age-associated degeneration of IVDs. Using a notochord-specific gene targeting strategy, this study demonstrates that CCN2 expression by nucleus pulposus cells is essential to the regulation of IVD development and age-associated tissue maintenance. The ability of CCN2 to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration. Copyright © 2013 by the American College of Rheumatology.

  18. Status Report on the High-Throughput Characterization of Complex Intact O-Glycopeptide Mixtures

    Science.gov (United States)

    Pap, Adam; Klement, Eva; Hunyadi-Gulyas, Eva; Darula, Zsuzsanna; Medzihradszky, Katalin F.

    2018-05-01

    A very complex mixture of intact, human N- and O-glycopeptides, enriched from the tryptic digest of urinary proteins of three healthy donors using a two-step lectin affinity enrichment, was analyzed by LC-MS/MS, leading to approximately 45,000 glycopeptide EThcD spectra. Two search engines, Byonic and Protein Prospector, were used for the interpretation of the data, and N- and O-linked glycopeptides were assigned from separate searches. The identification rate was very low in all searches, even when results were combined. Thus, we investigated the reasons why was it so, to help to improve the identification success rate. Focusing on O-linked glycopeptides, we noticed that in EThcD, larger glycan oxonium ions better survive the activation than those in HCD. These fragments, combined with reducing terminal Y ions, provide important information about the glycan(s) present, so we investigated whether filtering the peaklists for glycan oxonium ions indicating the presence of a tetra- or hexasaccharide structure would help to reveal all molecules containing such glycans. Our study showed that intact glycans frequently do not survive even mild supplemental activation, meaning one cannot rely on these oxonium ions exclusively. We found that ETD efficiency is still a limiting factor, and for highly glycosylated peptides, the only information revealed in EThcD was related to the glycan structures. The limited overlap of results delivered by the two search engines draws attention to the fact that automated data interpretation of O-linked glycopeptides is not even close to being solved. [Figure not available: see fulltext.

  19. Intervertebral anticollision constraints improve out-of-plane translation accuracy of a single-plane fluoroscopy-to-CT registration method for measuring spinal motion

    International Nuclear Information System (INIS)

    Lin, Cheng-Chung; Tsai, Tsung-Yuan; Hsu, Shih-Jung; Lu, Tung-Wu; Shih, Ting-Fang; Wang, Ting-Ming

    2013-01-01

    Purpose: The study aimed to propose a new single-plane fluoroscopy-to-CT registration method integrated with intervertebral anticollision constraints for measuring three-dimensional (3D) intervertebral kinematics of the spine; and to evaluate the performance of the method without anticollision and with three variations of the anticollision constraints via an in vitro experiment. Methods: The proposed fluoroscopy-to-CT registration approach, called the weighted edge-matching with anticollision (WEMAC) method, was based on the integration of geometrical anticollision constraints for adjacent vertebrae and the weighted edge-matching score (WEMS) method that matched the digitally reconstructed radiographs of the CT models of the vertebrae and the measured single-plane fluoroscopy images. Three variations of the anticollision constraints, namely, T-DOF, R-DOF, and A-DOF methods, were proposed. An in vitro experiment using four porcine cervical spines in different postures was performed to evaluate the performance of the WEMS and the WEMAC methods. Results: The WEMS method gave high precision and small bias in all components for both vertebral pose and intervertebral pose measurements, except for relatively large errors for the out-of-plane translation component. The WEMAC method successfully reduced the out-of-plane translation errors for intervertebral kinematic measurements while keeping the measurement accuracies for the other five degrees of freedom (DOF) more or less unaltered. The means (standard deviations) of the out-of-plane translational errors were less than −0.5 (0.6) and −0.3 (0.8) mm for the T-DOF method and the R-DOF method, respectively. Conclusions: The proposed single-plane fluoroscopy-to-CT registration method reduced the out-of-plane translation errors for intervertebral kinematic measurements while keeping the measurement accuracies for the other five DOF more or less unaltered. With the submillimeter and subdegree accuracy, the WEMAC method was

  20. Basic timing abilities stay intact in patients with musician's dystonia.

    Directory of Open Access Journals (Sweden)

    M C van der Steen

    Full Text Available Task-specific focal dystonia is a movement disorder that is characterized by the loss of voluntary motor control in extensively trained movements. Musician's dystonia is a type of task-specific dystonia that is elicited in professional musicians during instrumental playing. The disorder has been associated with deficits in timing. In order to test the hypothesis that basic timing abilities are affected by musician's dystonia, we investigated a group of patients (N = 15 and a matched control group (N = 15 on a battery of sensory and sensorimotor synchronization tasks. Results did not show any deficits in auditory-motor processing for patients relative to controls. Both groups benefited from a pacing sequence that adapted to their timing (in a sensorimotor synchronization task at a stable tempo. In a purely perceptual task, both groups were able to detect a misaligned metronome when it was late rather than early relative to a musical beat. Overall, the results suggest that basic timing abilities stay intact in patients with musician's dystonia. This supports the idea that musician's dystonia is a highly task-specific movement disorder in which patients are mostly impaired in tasks closely related to the demands of actually playing their instrument.

  1. Basic Timing Abilities Stay Intact in Patients with Musician's Dystonia

    Science.gov (United States)

    van der Steen, M. C.; van Vugt, Floris T.; Keller, Peter E.; Altenmüller, Eckart

    2014-01-01

    Task-specific focal dystonia is a movement disorder that is characterized by the loss of voluntary motor control in extensively trained movements. Musician's dystonia is a type of task-specific dystonia that is elicited in professional musicians during instrumental playing. The disorder has been associated with deficits in timing. In order to test the hypothesis that basic timing abilities are affected by musician's dystonia, we investigated a group of patients (N = 15) and a matched control group (N = 15) on a battery of sensory and sensorimotor synchronization tasks. Results did not show any deficits in auditory-motor processing for patients relative to controls. Both groups benefited from a pacing sequence that adapted to their timing (in a sensorimotor synchronization task at a stable tempo). In a purely perceptual task, both groups were able to detect a misaligned metronome when it was late rather than early relative to a musical beat. Overall, the results suggest that basic timing abilities stay intact in patients with musician's dystonia. This supports the idea that musician's dystonia is a highly task-specific movement disorder in which patients are mostly impaired in tasks closely related to the demands of actually playing their instrument. PMID:24667273

  2. Intact information sampling in mesial temporal lobe epilepsy.

    Science.gov (United States)

    Zamarian, Laura; Trinka, Eugen; Kuchukhidze, Giorgi; Bodner, Thomas; Unterberger, Iris; Luef, Gerhard; Delazer, Margarete

    2015-11-01

    Previous studies have reported deficits in decision making under ambiguity for patients with mesial temporal lobe epilepsy (mTLE). It is unknown whether mTLE is also associated with alterations at a predecisional stage. This study aimed to gain insight into predecisional processing of patients with mTLE. We compared performance of patients with mTLE (n = 25) with that of healthy controls (n = 75) on the information sampling task (IST), a task assessing reflection-impulsivity and predecisional information sampling. Patients and healthy controls showed a similar performance pattern in both conditions of the IST as indicated by the amount of information gathered, the degree of uncertainty tolerated, and the number of decision errors made. They both also demonstrated a significant sensitivity to the different reward characteristics of the task. For the patient group, we found no significant effects on performance on the IST of epilepsy lateralization, abnormality side, structural abnormality (hippocampus vs. amygdala), and medication (monotherapy vs. polytherapy). Reflection processes and predecisional information sampling as tested by the IST are intact in mTLE. Patients collect as much information as healthy individuals and adapt their behavior according to the changing reward conditions. Our findings indicate that in well-defined risk situations, where memory demands are sufficiently minimized, patients with mTLE should be able to gather sufficient information, weight risks and benefits, and make advantageous decisions. (c) 2015 APA, all rights reserved).

  3. Assessment of mechanical strain in the intact plantar fascia.

    Science.gov (United States)

    Clark, Ross A; Franklyn-Miller, Andrew; Falvey, Eanna; Bryant, Adam L; Bartold, Simon; McCrory, Paul

    2009-09-01

    A method of measuring tri-axial plantar fascia strain that is minimally affected by external compressive force has not previously been reported. The purpose of this study was to assess the use of micro-strain gauges to examine strain in the different axes of the plantar fascia. Two intact limbs from a thawed, fresh-frozen cadaver were dissected, and a combination of five linear and one three-way rosette gauges were attached to the fascia of the foot and ankle. Strain was assessed during two trials, both consisting of an identical controlled, loaded dorsiflexion. An ICC analysis of the results revealed that the majority of gauge placement sites produced reliable measures (ICC>0.75). Strain mapping of the plantar fascia indicates that the majority of the strain is centrally longitudinal, which provides supportive evidence for finite element model analysis. Although micro-strain gauges do possess the limitation of calibration difficulty, they provide a repeatable measure of fascial strain and may provide benefits in situations that require tri-axial assessment or external compression.

  4. Temporal Ventriloquism Reveals Intact Audiovisual Temporal Integration in Amblyopia.

    Science.gov (United States)

    Richards, Michael D; Goltz, Herbert C; Wong, Agnes M F

    2018-02-01

    We have shown previously that amblyopia involves impaired detection of asynchrony between auditory and visual events. To distinguish whether this impairment represents a defect in temporal integration or nonintegrative multisensory processing (e.g., cross-modal matching), we used the temporal ventriloquism effect in which visual temporal order judgment (TOJ) is normally enhanced by a lagging auditory click. Participants with amblyopia (n = 9) and normally sighted controls (n = 9) performed a visual TOJ task. Pairs of clicks accompanied the two lights such that the first click preceded the first light, or second click lagged the second light by 100, 200, or 450 ms. Baseline audiovisual synchrony and visual-only conditions also were tested. Within both groups, just noticeable differences for the visual TOJ task were significantly reduced compared with baseline in the 100- and 200-ms click lag conditions. Within the amblyopia group, poorer stereo acuity and poorer visual acuity in the amblyopic eye were significantly associated with greater enhancement in visual TOJ performance in the 200-ms click lag condition. Audiovisual temporal integration is intact in amblyopia, as indicated by perceptual enhancement in the temporal ventriloquism effect. Furthermore, poorer stereo acuity and poorer visual acuity in the amblyopic eye are associated with a widened temporal binding window for the effect. These findings suggest that previously reported abnormalities in audiovisual multisensory processing may result from impaired cross-modal matching rather than a diminished capacity for temporal audiovisual integration.

  5. Evidence for an intact polysaccharide capsule in Bordetella pertussis.

    Science.gov (United States)

    Neo, YiLin; Li, Rui; Howe, Josephine; Hoo, Regina; Pant, Aakanksha; Ho, SiYing; Alonso, Sylvie

    2010-03-01

    Polysaccharide capsules contribute to the pathogenesis of many bacteria species by providing resistance against various defense mechanisms. The production of a capsule in Bordetella pertussis, the etiologic agent of whooping cough, has remained controversial; earlier studies reported this pathogen as a capsulated microorganism whereas the recent B. pertussis genome analysis revealed the presence of a truncated capsule locus. In this work, using transmission electron microscopy and immunostaining approaches, we provide a formal evidence for the presence of an intact microcapsule produced at the surface of both laboratory strain and clinical isolates of B. pertussis. In agreement with previous studies, we found that the capsule is optimally produced in avirulent phase. Unexpectedly, the presence of the capsule was also detected at the surface of virulent B. pertussis bacteria. Consistently, a substantial transcriptional activity of the capsule operon was detected in virulent phase, suggesting that the capsular polysaccharide may play a role during pertussis pathogenesis. In vitro assays indicated that the presence of the capsule does not affect B. pertussis adherence to mammalian cells and does not further protect the bacterium from phagocytosis, complement-mediated killing or antimicrobial peptide attack. Copyright 2009. Published by Elsevier SAS.

  6. Intact unconscious processing of eye contact in schizophrenia

    Directory of Open Access Journals (Sweden)

    Kiley Seymour

    2016-03-01

    Full Text Available The perception of eye gaze is crucial for social interaction, providing essential information about another person’s goals, intentions, and focus of attention. People with schizophrenia suffer a wide range of social cognitive deficits, including abnormalities in eye gaze perception. For instance, patients have shown an increased bias to misjudge averted gaze as being directed toward them. In this study we probed early unconscious mechanisms of gaze processing in schizophrenia using a technique known as continuous flash suppression. Previous research using this technique to render faces with direct and averted gaze initially invisible reveals that direct eye contact gains privileged access to conscious awareness in healthy adults. We found that patients, as with healthy control subjects, showed the same effect: faces with direct eye gaze became visible significantly faster than faces with averted gaze. This suggests that early unconscious processing of eye gaze is intact in schizophrenia and implies that any misjudgments of gaze direction must manifest at a later conscious stage of gaze processing where deficits and/or biases in attributing mental states to gaze and/or beliefs about being watched may play a role.

  7. Stress dependence of permeability of intact and fractured shale cores.

    Science.gov (United States)

    van Noort, Reinier; Yarushina, Viktoriya

    2016-04-01

    Whether a shale acts as a caprock, source rock, or reservoir, understanding fluid flow through shale is of major importance for understanding fluid flow in geological systems. Because of the low permeability of shale, flow is thought to be largely confined to fractures and similar features. In fracking operations, fractures are induced specifically to allow for hydrocarbon exploration. We have constructed an experimental setup to measure core permeabilities, using constant flow or a transient pulse. In this setup, we have measured the permeability of intact and fractured shale core samples, using either water or supercritical CO2 as the transporting fluid. Our measurements show decreasing permeability with increasing confining pressure, mainly due to time-dependent creep. Furthermore, our measurements show that for a simple splitting fracture, time-dependent creep will also eliminate any significant effect of this fracture on permeability. This effect of confinement on fracture permeability can have important implications regarding the effects of fracturing on shale permeability, and hence for operations depending on that.

  8. Research on intact marine ecosystems: a lost era.

    Science.gov (United States)

    Stachowitsch, Michael

    2003-07-01

    It is proposed that a new, fifth era should be added to the four historical phases of marine research identified by Rupert Riedl, specifically an era devoted to studying and ameliorating disturbed marine ecosystems. In an age of global environmental deterioration, many marine ecosystems and organisms are high on the list of threatened entities. This poor status prompts research that would otherwise have been unnecessary and hinders research that would normally have been conducted. I argue that research into intact marine ecosystems is becoming increasingly difficult, and that most of our future insights into marine habitats will stem from knowledge gained by examining various disfunctions of those systems rather than their functions. The new era will therefore differ from past research in its underlying aim, the range of topics studied, the selection and funding of those topics, the validity of its conclusions, and in its urgency. Sea turtles and cetaceans are cited as case studies at the organismic level, shallow-water benthic communities, including coral reefs, at the ecosystem level.

  9. Measurement of tritiated norepinephrine metabolism in intact rat brain

    International Nuclear Information System (INIS)

    Levitt, M.; Kowalik, S.; Barkai, A.I.

    1983-01-01

    A procedure for the study of NE metabolism in the intact rat brain is described. The method involves ventriculocisternal perfusion of the adult male rat with artificial CSF containing [ 3 H]NE. Radioactivity in the perfusate associated with NE and its metabolites 3,4-dihydroxymandelic acid (DOMA), 3,4-dihydroxphenylethyleneglycol (DHPG), 3-methoxy-4-hydroxymandelic acid (VMA), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), and normetanephrine (NMN) is separated using high-performance liquid chromatography (HPLC). After 80 min the radioactivity in the perfusate reaches an apparent steady-state. Analysis of the steady-state samples shows higher activity in the fractions corresponding to DHPG and MHPG than in those corresponding to DOMA and VMA, confirming glycol formation as the major pathway of NE metabolism in rat brain. Pretreatment with an MAO inhibitor (tranylcypromine) results in a marked decrease in the deaminated metabolites DHPG and MHPG and a concurrent increase in NMN. The results indicate this to be a sensitive procedure for the in vivo determination of changes in NE metabolism. (Auth.)

  10. Structure of the intact ATM/Tel1 kinase

    Science.gov (United States)

    Wang, Xuejuan; Chu, Huanyu; Lv, Mengjuan; Zhang, Zhihui; Qiu, Shuwan; Liu, Haiyan; Shen, Xuetong; Wang, Weiwu; Cai, Gang

    2016-05-01

    The ataxia-telangiectasia mutated (ATM) protein is an apical kinase that orchestrates the multifaceted DNA-damage response. Normally, ATM kinase is in an inactive, homodimer form and is transformed into monomers upon activation. Besides a conserved kinase domain at the C terminus, ATM contains three other structural modules, referred to as FAT, FATC and N-terminal helical solenoid. Here we report the first cryo-EM structure of ATM kinase, which is an intact homodimeric ATM/Tel1 from Schizosaccharomyces pombe. We show that two monomers directly contact head-to-head through the FAT and kinase domains. The tandem N-terminal helical solenoid tightly packs against the FAT and kinase domains. The structure suggests that ATM/Tel1 dimer interface and the consecutive HEAT repeats inhibit the binding of kinase substrates and regulators by steric hindrance. Our study provides a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents.

  11. Genetic disruptions of Drosophila Pavlovian learning leave extinction learning intact.

    Science.gov (United States)

    Qin, H; Dubnau, J

    2010-03-01

    Individuals who experience traumatic events may develop persistent posttraumatic stress disorder. Patients with this disorder are commonly treated with exposure therapy, which has had limited long-term success. In experimental neurobiology, fear extinction is a model for exposure therapy. In this behavioral paradigm, animals are repeatedly exposed in a safe environment to the fearful stimulus, which leads to greatly reduced fear. Studying animal models of extinction already has lead to better therapeutic strategies and development of new candidate drugs. Lack of a powerful genetic model of extinction, however, has limited progress in identifying underlying molecular and genetic factors. In this study, we established a robust behavioral paradigm to study the short-term effect (acquisition) of extinction in Drosophila melanogaster. We focused on the extinction of olfactory aversive 1-day memory with a task that has been the main workhorse for genetics of memory in flies. Using this paradigm, we show that extinction can inhibit each of two genetically distinct forms of consolidated memory. We then used a series of single-gene mutants with known impact on associative learning to examine the effects on extinction. We find that extinction is intact in each of these mutants, suggesting that extinction learning relies on different molecular mechanisms than does Pavlovian learning.

  12. Assessment of lumbar intervertebral disc glycosaminoglycan content by gadolinium-enhanced MRI before and after 21-days of head-down-tilt bedrest.

    Directory of Open Access Journals (Sweden)

    Timmo Koy

    Full Text Available During spaceflight, it has been shown that intervertebral discs (IVDs increase in height, causing elongation of the spine up to several centimeters. Astronauts frequently report dull lower back pain that is most likely of discogenic origin and may result from IVD expansion. It is unknown whether disc volume solely increases by water influx, or if the content of glycosaminoglycans also changes in microgravity. Aim of this pilot study was to investigate effects of the spaceflight analog of bedrest on the glycosaminoglycan content of human lumbar IVDs. Five healthy, non-smoking, male human subjects of European descent were immobilized in 6° head-down-tilt bedrest for 21 days. Subjects remained in bed 24 h a day with at least one shoulder on the mattress. Magnetic Resonance Imaging (MRI scans were taken according to the delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC protocol before and after bedrest. The outcome measures were T1 and ΔT1. Scans were performed before and after administration of the contrast agent Gd-DOTA, and differences between T1-values of both scans (ΔT1 were computed. ΔT1 is the longitudinal relaxation time in the tissue and inversely related to the glycosaminoglycan-content. For data analysis, IVDs L1/2 to L4/5 were semi-automatically segmented. Zones were defined and analyzed separately. Results show a highly significant decrease in ΔT1 (p<0.001 after bedrest in all IVDs, and in all areas of the IVDs. The ΔT1-decrease was most prominent in the nucleus pulposus and in L4/5, and was expressed slightly more in the posterior than anterior IVD. Unexpected negative ΔT1-values were found in Pfirrmann-grade 2-discs after bedrest. Significantly lower T1 before contrast agent application was found after bedrest compared to before bedrest. According to the dGEMRIC-literature, the decrease in ΔT1 may be interpreted as an increase in glycosaminoglycans in healthy IVDs during bedrest. This interpretation seems

  13. The intact capture of hypervelocity dust particles using underdense foams

    Science.gov (United States)

    Maag, Carl R.; Borg, J.; Tanner, William G.; Stevenson, T. J.; Bibring, J.-P.

    1994-01-01

    probability of survival for the impacting particle. The primary objectives of the experiment are to (1) Examine the morphology of primary and secondary hypervelocity impact craters. Primary attention will be paid to craters caused by ejecta during hypervelocity impacts of different substrates. (2) Determine the size distribution of ejecta by means of witness plates and collect fragments of ejecta from craters by means of momentum-sensitive mcropore foam. (3) Assess the directionality of the flux by means of penetration-hole alignment of thin films placed above the cells. (4) Capture intact the particles that perforated the thin film and entered the cell. Capture media consisted of both previously flight-tested micropore foams and aerogel. The foams had different latent heats of fusion and, accordingly, will capture particles over a range of momenta. Aerogel was incorporated into the cells to determine the minimum diameter than can be captured intact.

  14. Intensity modulated tangential beam irradiation of the intact breast

    International Nuclear Information System (INIS)

    Hong, L.; Hunt, M.; Chui, C.; Forster, K.; Lee, H.; Lutz, W.; Yahalom, J.; Kutcher, G.J.; McCormick, B.

    1997-01-01

    Purpose/Objective: The purpose of this study was to evaluate the potential benefits of intensity modulated tangential beams in the irradiation of the intact breast. The primary goal was to develop an intensity modulated treatment which would substantially decrease the dose to coronary arteries, lung and contralateral breast while still using a standard tangential beam arrangement. Improved target dose homogeneity, within the limits imposed by opposed fields, was also desired. Since a major goal of the study was the development of a technique which was practical for use on a large population of patients, the design of 'standard' intensity profiles analogous in function to conventional wedges was also investigated. Materials and Methods: Three dimensional treatment planning was performed using both conventional and intensity modulated tangential beams. Plans were developed for both the right and left breast for a range of patient sizes and shapes. For each patient, PTV, lung, heart, origin and peripheral branches of the coronary artery, and contralateral breast were contoured. Optimum tangential beam direction and shape were designed using Beams-Eye-View display and then used for both the conventional and intensity modulated plans. For the conventional plan, the optimum wedge combination and beam weighting were chosen based on the dose distribution in a single transverse plane through the field center. Intensity modulated plans were designed using an algorithm which allows the user to specify the prescribed, maximum and minimum acceptable doses and dose volume constraints for each organ of interest. Plans were compared using multiple dose distributions and DVHs. Results: Significant improvements in the doses to critical structures were achieved using the intensity modulated plan. Coronary artery dose decreased substantially for patients treated to the left breast. Ipsilateral lung and contralateral breast doses decreased for all patients. For one patient treated to

  15. Intact suppression of increased false recognition in schizophrenia.

    Science.gov (United States)

    Weiss, Anthony P; Dodson, Chad S; Goff, Donald C; Schacter, Daniel L; Heckers, Stephan

    2002-09-01

    Recognition memory is impaired in patients with schizophrenia, as they rely largely on item familiarity, rather than conscious recollection, to make mnemonic decisions. False recognition of novel items (foils) is increased in schizophrenia and may relate to this deficit in conscious recollection. By studying pictures of the target word during encoding, healthy adults can suppress false recognition. This study examined the effect of pictorial encoding on subsequent recognition of repeated foils in patients with schizophrenia. The study included 40 patients with schizophrenia and 32 healthy comparison subjects. After incidental encoding of 60 words or pictures, subjects were tested for recognition of target items intermixed with 60 new foils. These new foils were subsequently repeated following either a two- or 24-word delay. Subjects were instructed to label these repeated foils as new and not to mistake them for old target words. Schizophrenic patients showed greater overall false recognition of repeated foils. The rate of false recognition of repeated foils was lower after picture encoding than after word encoding. Despite higher levels of false recognition of repeated new items, patients and comparison subjects demonstrated a similar degree of false recognition suppression after picture, as compared to word, encoding. Patients with schizophrenia displayed greater false recognition of repeated foils than comparison subjects, suggesting both a decrement of item- (or source-) specific recollection and a consequent reliance on familiarity in schizophrenia. Despite these deficits, presenting pictorial information at encoding allowed schizophrenic subjects to suppress false recognition to a similar degree as the comparison group, implying the intact use of a high-level cognitive strategy in this population.

  16. Preferential flow through intact soil cores: Effects of matrix head

    Energy Technology Data Exchange (ETDEWEB)

    Langner, H.W.; Gaber, H.M.; Wraith, J.M.; Huwe, B.; Inskeep, W.P.

    1999-12-01

    Continuous soil pores may act as pathways for preferential flow depending on their size and water status (filled or drained), the latter being largely controlled by the soil matrix head (h). The literature contains a wide range of proposed minimal pore sizes that may contribute to preferential flow. The objective of this study was to examine the relationship between h (and corresponding pore sizes) and preferential solute transport in a naturally structured soil. Tracer ({sup 3}H{sub 2}O and pentafluorobenzoic acid, [PFBA]) miscible displacement experiments were performed at several h values in intact soil cores (15-cm diameter, 30-cm length) using an apparatus especially suited to maintain constant h while collecting large effluent volumes. To test for the occurrence of preferential flow, observed breakthrough curves (BTCs) were evaluated for physical nonequilibrium (PNE) using a comparison between fitted local equilibrium (PNE) and PNE models. Fitting results of the observed BTCs indicated absence of PNE in all solute transport experiments at h {le} {minus}10 cm. Experiments at h {ge} {minus}5 cm consistently exhibited PNE conditions, indicating the presence of preferential flow. These results suggest that soil pores with effective radii of 150 {micro}m and smaller (water-filled at h = {minus}10 cm) do not contribute to preferential flow. Observed pore water velocities were not indicative of the presence or absence of preferential flow conditions. Continuous measurements of soil water content ({theta}) using time domain reflectometry (TDR) revealed that at h = {minus}10 cm, <2% of the soil volume had drained.

  17. The effect of cyclic compression on the mechanical properties of the inter-vertebral disc: an in vivo study in a rat tail model.

    Science.gov (United States)

    Ching, Congo T S; Chow, Daniel H K; Yao, Fiona Y D; Holmes, Andrew D

    2003-03-01

    To assess the changes in the mechanical properties of inter-vertebral discs in vivo following static and cyclic compressive loading of different frequencies. An in vivo biomechanical study using a rat-tail model of the inter-vertebral disc.Background. Mechanical loading has been suggested as playing a major role in the etiology of disc degeneration, but the relationship is still not fully understood. Sixty Sprague-Dawley rats were subject to daily compressive stress via pins inserted in the 6th and 7th caudal vertebrae over a two-week loading period. Animals were randomly divided into a sham group (pin insertion, no loading), a static loading group, or cyclic loading groups of 0.5, 1.5, or 2.5 Hz. Loading was applied for 1 h each day from the 3rd to 17th day following pin insertion, and the angular compliance, angular laxity, and inter-pin distance were measured in vivo at days 0, 3, 10 and 17. Changes in the inter-vertebral disc height depended on the frequency of loading, with the decrease in disc height in the static compression group significantly greater than that in all other groups, whereas the decrease in the 1.5 Hz cyclic compression group was significantly smaller than that in all other compression groups. Changes in disc properties depend on both the total load exposure and the frequency of loading. Cyclic loading in general produced less marked changes than static loading, but loading at particular frequencies may result in more severe changes. Previous studies have shown the in vivo changes in the mechanical properties of inter-vertebral discs to depend on the magnitude and duration of loading. In this study, a frequency dependent response to cyclic loading is also demonstrated.

  18. [Peculiarities of clinico-neurological signs of the intervertebral discs protrusions in lumbar portion of vertebral column in patients of various age].

    Science.gov (United States)

    Khyzniak, M V; Pryĭmak, E V

    2013-11-01

    Clinico-neurological signs of the discogenic pain syndromes, caused by intervertebral disc (IVD) protrusion in a lumbar portion of vertebral column, were analyzed. The strict indications were substantiated for application of the puncture treatment methods for the discogenic pain syndromes in patients of various ages. Clinico-neurological signs of the IVD protrusions constitute the important criterion while the treatment method selection. Differentiated application of the puncture methods permits to improve the treatment results in the patients of various age.

  19. Differences in School Behavior and Achievement between Children from Intact, Reconstituted, and Single-Parent Families.

    Science.gov (United States)

    Featherstone, Darin R.; And Others

    1992-01-01

    Analyzed differences in school behavior and achievement among students (n=530) in grades six through nine from intact, reconstituted, and single-parent families. Students from intact, two-parent families had fewer absences and tardies, higher grade point averages, and fewer negative and more positive teacher behavioral ratings than did those from…

  20. Visual Speech Fills in Both Discrimination and Identification of Non-Intact Auditory Speech in Children

    Science.gov (United States)

    Jerger, Susan; Damian, Markus F.; McAlpine, Rachel P.; Abdi, Herve

    2018-01-01

    To communicate, children must discriminate and identify speech sounds. Because visual speech plays an important role in this process, we explored how visual speech influences phoneme discrimination and identification by children. Critical items had intact visual speech (e.g. baez) coupled to non-intact (excised onsets) auditory speech (signified…

  1. Para-muscular and trans-muscular approaches to the lumbar inter-vertebral foramen: an anatomical comparison Acessos paramuscular e transmuscular ao forame intervertebral lombar: comparação anatômica

    Directory of Open Access Journals (Sweden)

    Arthur Werner Poetscher

    2005-03-01

    Full Text Available Foraminal and extra-foraminal disc herniations comprise up to 11.7% of all lumbar disc herniations. Facetectomy, which had been the classic approach, is now recognized as cause of pain and instability after surgery. Otherwise, posterior lateral approaches through a trans-muscular or a para-muscular technique offer no significant damage to key structures for spinal stability. The surgical anatomy of these approaches has already been described, but they were not compared. In order to quantify the angle of vision towards the intervertebral foramen offered by each technique, 12 fresh cadavers were dissected and studied regarding these approaches. The angle presented by trans-muscular approach was wider in all studied lumbar levels. Surgery through the trans-muscular approach is performed with a better working angle, requiring a smaller resection of surrounding tissues. Therefore, minor surgical trauma can be expected. Our measurements support previously published data that point the trans-muscular approach as the best surgical option.As hérnias de disco lombares apresentam-se como foraminais ou extra-foraminais em até 11,7% dos casos. Seu tratamento cirúrgico através de facetectomias pode causar dor e instabilidade,