Sample records for studying human disc

  1. The presence of pleiotrophin in the human intervertebral disc is associated with increased vascularization: an immunohistologic study.

    PubMed

    Johnson, William E B; Patterson, Angela M; Eisenstein, Stephen M; Roberts, Sally

    2007-05-20

    An immunohistological study of surgical specimens of human intervertebral disc. To examine the presence of pleiotrophin in diseased or damaged intervertebral disc tissue and the association between its presence and the extent of tissue vascularization and innervation. Increased levels of pleiotrophin, a growth and differentiation factor that is active in various pathophysiologic processes, including angiogenesis, has been associated with osteoarthritic changes of human articular cartilage. The association between pleiotrophin expression and pathologic conditions of the human intervertebral disc is unknown. Specimens of human lumbar intervertebral discs, obtained following surgical discectomy, were divided into 3 groups: non-degenerated discs (n = 7), degenerated discs (n = 6), and prolapsed discs (n = 11). Serial tissue sections of each specimen were immunostained to determine the presence of pleiotrophin, blood vessels (CD34-positive endothelial cells), and nerves (neurofilament 200 kDa [NF200]-positive nerve fibers). Pleiotrophin immunoreactivity was seen in disc cells, endothelial cells, and in the extracellular matrix in most specimens of intervertebral disc but was most prevalent in vascularized tissue in prolapsed discs. There was a significant correlation between the presence of pleiotrophin-positive disc cells and that of CD34-positive blood vessels. NF200-positive nerves were seen in vascularized areas of more degenerated discs, but nerves did not appear to codistribute with blood vessels or pleiotrophin positivity in prolapsed discs. Pleiotrophin is present in pathologic human intervertebral discs, and its prevalence and distribution suggest that it may play a role in neovascularization of diseased or damaged disc tissue.

  2. Are animal models useful for studying human disc disorders/degeneration?

    PubMed Central

    Eisenstein, Stephen M.; Ito, Keita; Little, Christopher; Kettler, A. Annette; Masuda, Koichi; Melrose, James; Ralphs, Jim; Stokes, Ian; Wilke, Hans Joachim

    2007-01-01

    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 models have often been used for this purpose. However, there are many differences in cell population, tissue composition, disc and spine anatomy, development, physiology and mechanical properties, between animal species and human. Both naturally occurring and induced degenerative changes may differ significantly from those seen in humans. This paper reviews the many animal models developed for the study of IVD degeneration aetiopathogenesis and treatments thereof. In particular, the limitations and relevance of these models to the human condition are examined, and some general consensus guidelines are presented. Although animal models are invaluable to increase our understanding of disc biology, because of the differences between species, care must be taken when used to study human disc degeneration and much more effort is needed to facilitate research on human disc material. PMID:17632738

  3. Which iodinated contrast media is the least cytotoxic to human disc cells?

    PubMed

    Kim, Kyung-Hyun; Park, Jeong-Yoon; Park, Hyo-Suk; Kuh, Sung-Uk; Chin, Dong-Kyu; Kim, Keun-Su; Cho, Yong-Eun

    2015-05-01

    Iodinated contrast media (CM) is commonly used for various intradiscal injections such as in discography and endoscopic spinal surgery. However, CM has been shown to be toxic to renal tissue due to its ionic strength and osmolarity and as a result of iodine-induced cytotoxicity, which has raised concern over whether there are similar negative effects on disc cells. This in vitro study was designed to identify the least cytotoxic iodinated CM to the human disc cell among four different physiochemical iodinated contrast dyes. In vitro laboratory study. Intervertebral disc tissue was obtained by discectomy from a total of 10 lumbar disc patients undergoing surgery and disc cells were isolated. The human disc cells were grown in 3D alginate bead culture with 0, 0.1, 10, and 100 mg/mL CM solutions (ionic dimer, ionic monomer, non-ionic dimer, and non-ionic monomer) and mannitol as a control for 2 days. The living cells were analyzed with trypan blue staining. Fluorescence-activated cell sorting analysis was performed using Annexin V and propidium iodide (PI) and 3D alginate bead immunostaining to identify live, apoptotic, and necrotic cells. Human disc cell death was time- and dose-dependent in response to CM and more necrosis was observed than apoptosis. In addition, non-ionic dimeric CM (iodixanol) showed the least toxic effect on human disc cells, followed by non-ionic monomeric (iopromide), ionic dimeric (ioxaglate), and ionic monomeric CM (ioxithalamate). Contrast media is cytotoxic to human disc cells in a dose- and time-dependent manner. This in vitro study revealed that, among four different CM preparations, non-ionic dimeric CM is the least detrimental to human disc cell viability. Careful attention should be paid to the type of CM chosen for discography and endoscopic spinal surgery. It is also necessary to investigate the detrimental effects of CM on disc cells and disc degeneration in further in vivo studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Comparison of Animal Discs Used in Disc Research to Human Lumbar Disc: Torsion Mechanics and Collagen Content

    PubMed Central

    Showalter, Brent L.; Beckstein, Jesse C.; Martin, John T.; Beattie, Elizabeth E.; Orías, Alejandro A. Espinoza; Schaer, Thomas P.; Vresilovic, Edward J.; Elliott, Dawn M.

    2012-01-01

    Study Design Experimental measurement and normalization of in vitro disc torsion mechanics and collagen content for several animal species used in intervertebral disc research and comparing these to the human disc. Objective To aid in the selection of appropriate animal models for disc research by measuring torsional mechanical properties and collagen content. Summary of Background Data There is lack of data and variability in testing protocols for comparing animal and human disc torsion mechanics and collagen content. Methods Intervertebral disc torsion mechanics were measured and normalized by disc height and polar moment of inertia for 11 disc types in 8 mammalian species: the calf, pig, baboon, goat, sheep, rabbit, rat, and mouse lumbar, and cow, rat, and mouse caudal. Collagen content was measured and normalized by dry weight for the same discs except the rat and mouse. Collagen fiber stretch in torsion was calculated using an analytical model. Results Measured torsion parameters varied by several orders of magnitude across the different species. After geometric normalization, only the sheep and pig discs were statistically different from human. Fiber stretch was found to be highly dependent on the assumed initial fiber angle. The collagen content of the discs was similar, especially in the outer annulus where only the calf and goat discs were statistically different from human. Disc collagen content did not correlate with torsion mechanics. Conclusion Disc torsion mechanics are comparable to human lumbar discs in 9 of 11 disc types after normalization by geometry. The normalized torsion mechanics and collagen content of the multiple animal discs presented is useful for selecting and interpreting results for animal models of the disc. Structural composition of the disc, such as initial fiber angle, may explain the differences that were noted between species after geometric normalization. PMID:22333953

  5. The Yucatan Minipig Temporomandibular Joint Disc Structure-Function Relationships Support Its Suitability for Human Comparative Studies.

    PubMed

    Vapniarsky, Natalia; Aryaei, Ashkan; Arzi, Boaz; Hatcher, David C; Hu, Jerry C; Athanasiou, Kyriacos A

    2017-11-01

    Frequent involvement of the disc in temporomandibular joint (TMJ) disorders warrants attempts to tissue engineer TMJ disc replacements. Physiologically, a great degree of similarity is seen between humans and farm pigs (FPs), but the pig's rapid growth confers a significant challenge for in vivo experiments. Minipigs have a slower growth rate and are smaller than FPs, but minipig TMJ discs have yet to be fully characterized. The objective of this study was to determine the suitability of the minipig for TMJ studies by extensive structural and functional characterization. The properties of minipig TMJ discs closely reproduced previously reported morphological, biochemical, and biomechanical values of human and FP discs. The width/length dimension ratio of the minipig TMJ disc was 1.95 (1.69 for human and 1.94 for FP). The biochemical evaluation revealed, on average per wet weight, 24.3% collagen (22.8% for human and 24.9% for FP); 0.8% glycosaminoglycan (GAG; 0.5% for human and 0.4% for FP); and 0.03% DNA (0.008% for human and 0.02% for FP). Biomechanical testing revealed, on average, compressive relaxation modulus of 50 kPa (37 kPa for human and 32 kPa for FP), compressive instantaneous modulus of 1121 kPa (1315 kPa for human and 1134 kPa for FP), and coefficient of viscosity of 13 MPa·s (9 MPa·s for human and 3 MPa·s for FP) at 20% strain. These properties also varied topographically in accordance to those of human and FP TMJ discs. Anisotropy, quantified by bidirectional tensile testing and histology, again was analogous among minipig, human, and FP TMJ discs. The minipig TMJ's ginglymoarthrodial nature was verified through cone beam computer tomography. Collectively, the similarities between minipig and human TMJ discs support the use of minipig as a relevant model for TMJ research; considering the practical advantages conferred by its growth rate and size, the minipig may be a preferred model over FP.

  6. Genome-wide analysis of pain-, nerve- and neurotrophin -related gene expression in the degenerating human annulus

    PubMed Central

    2012-01-01

    Background In spite of its high clinical relevance, the relationship between disc degeneration and low back pain is still not well understood. Recent studies have shown that genome-wide gene expression studies utilizing ontology searches provide an efficient and valuable methodology for identification of clinically relevant genes. Here we use this approach in analysis of pain-, nerve-, and neurotrophin-related gene expression patterns in specimens of human disc tissue. Control, non-herniated clinical, and herniated clinical specimens of human annulus tissue were studied following Institutional Review Board approval. Results Analyses were performed on more generated (Thompson grade IV and V) discs vs. less degenerated discs (grades I-III), on surgically operated discs vs. control discs, and on herniated vs. control discs. Analyses of more degenerated vs. less degenerated discs identified significant upregulation of well-recognized pain-related genes (bradykinin receptor B1, calcitonin gene-related peptide and catechol-0-methyltransferase). Nerve growth factor was significantly upregulated in surgical vs. control and in herniated vs. control discs. All three analyses also found significant changes in numerous proinflammatory cytokine- and chemokine-related genes. Nerve, neurotrophin and pain-ontology searches identified many matrix, signaling and functional genes which have known importance in the disc. Immunohistochemistry was utilized to confirm the presence of calcitonin gene-related peptide, catechol-0-methyltransferase and bradykinin receptor B1 at the protein level in the human annulus. Conclusions Findings point to the utility of microarray analyses in identification of pain-, neurotrophin and nerve-related genes in the disc, and point to the importance of future work exploring functional interactions between nerve and disc cells in vitro and in vivo. Nerve, pain and neurotrophin ontology searches identified numerous changes in proinflammatory cytokines and chemokines which also have significant relevance to disc biology. Since the degenerating human disc is primarily an avascular tissue site into which disc cells have contributed high levels of proinflammatory cytokines, these substances are not cleared from the tissue and remain there over time. We hypothesize that as nerves grow into the human annulus, they encounter a proinflammatory cytokine-rich milieu which may sensitize nociceptors and exacerbate pain production. PMID:22963171

  7. Histochemical study of the elastic fibers in pathologic human temporomandibular joint discs.

    PubMed

    Leonardi, R; Villari, L; Bernasconi, G; Caltabiano, M

    2001-10-01

    This study investigated histochemically the elastic fibers in human temporomandibular joint (TMJ) discs with varying degrees of tissue degeneration/regeneration to determine whether there are differences that correlate with the histologic findings. Ten diseased human TMJ discs and 2 control specimens were studied histochemically by staining with Weigert's resorcin-fuchsin after oxidation with peracetic acid. This technique selectively stains elastic, elaunin, (pre-elastic), and oxytalan fibers. In TMJ discs with an abnormal collagen fiber arrangement, an increased number of oxytalan fibers could be observed, contrary to discs with scar-like tissue transformation in which oxytalan fibers were decreased in number. In discs showing tears and clefts, the oxytalan fibers run perpendicular to the defects, whereas elaunin and elastic fibers were mainly circumferentially arranged. In discs with chondroid metaplasia, elastic, elaunin, and oxytalan fibers were extensively detected. It is hypothesized that the elastic, elaunin, and oxytalan fibers found in severely damaged discs appear to ensure biomechanical compliance by reinforcing regions devoid of collagen bundles and thus function as shock absorbers of stretch and compression. Copyright 2001 American Association of Oral and Maxillofacial Surgeons

  8. A new in vivo animal model to create intervertebral disc degeneration characterized by MRI, radiography, CT/discogram, biochemistry, and histology.

    PubMed

    Zhou, HaoWei; Hou, ShuXun; Shang, WeiLin; Wu, WenWen; Cheng, Yao; Mei, Fang; Peng, BaoGan

    2007-04-15

    A new in vivo sheep model was developed that produced disc degeneration through the injection of 5-bromodeoxyuridine (BrdU) into the intervertebral disc. This process was studied using magnetic resonance imaging (MRI), radiography, CT/discogram, histology, and biochemistry. To develop a sheep model of intervertebral disc degeneration that more faithfully mimics the pathologic hallmarks of human intervertebral disc degeneration. Recent studies have shown age-related alterations in proteoglycan structure and organization in human intervertebral discs. An animal model that involves the use of age-related changes in disc cells can be beneficial over other more invasive degenerative models that involves directly damaging the matrix of disc tissue. Twelve sheep were injected with BrdU or vehicle (phosphate-buffered saline) into the central region of separate lumbar discs. Intact discs were used as controls. At the 2-, 6-, 10-, and 14-week time points, discs underwent MRI, radiography, histology, and biochemical analyses. A CT/discogram study was performed at the 14-week time point. MRI demonstrated a progressive loss of T2-weighted signal intensity at BrdU-injected discs over the 14-week study period. Radiograph findings included osteophyte and disc space narrowing formed by 10 weeks post-BrdU treatment. CT discography demonstrated internal disc disruption in several BrdU-treated discs at the 14-week time point. Histology showed a progressive loss of the normal architecture and cell density of discs from the 2-week time point to the 14-week time point. A progressive loss of cell proliferation capacity, water content, and proteoglycans was also documented. BrdU injection into the central region of sheep discs resulted in degeneration of intervertebral discs. This progressive, degenerative process was confirmed using MRI, histology, and by observing changes in biochemistry. Degeneration occurred in a manner that was similar to that observed in human disc degeneration.

  9. Rat disc torsional mechanics: effect of lumbar and caudal levels and axial compression load.

    PubMed

    Espinoza Orías, Alejandro A; Malhotra, Neil R; Elliott, Dawn M

    2009-03-01

    Rat models with altered loading are used to study disc degeneration and mechano-transduction. Given the prominent role of mechanics in disc function and degeneration, it is critical to measure mechanical behavior to evaluate changes after model interventions. Axial compression mechanics of the rat disc are representative of the human disc when normalized by geometry, and differences between the lumbar and caudal disc have been quantified in axial compression. No study has quantified rat disc torsional mechanics. Compare the torsional mechanical behavior of rat lumbar and caudal discs, determine the contribution of combined axial load on torsional mechanics, and compare the torsional properties of rat discs to human lumbar discs. Cadaveric biomechanical study. Cyclic torsion without compressive load followed by cyclic torsion with a fixed compressive load was applied to rat lumbar and caudal disc levels. The apparent torsional modulus was higher in the lumbar region than in the caudal region: 0.081+/-0.026 (MPa/degrees, mean+/-SD) for lumbar axially loaded; 0.066+/-0.028 for caudal axially loaded; 0.091+/-0.033 for lumbar in pure torsion; and 0.056+/-0.035 for caudal in pure torsion. These values were similar to human disc properties reported in the literature ranging from 0.024 to 0.21 MPa/degrees. Use of the caudal disc as a model may be appropriate if the mechanical focus is within the linear region of the loading regime. These results provide support for use of this animal model in basic science studies with respect to torsional mechanics.

  10. Rat Disc Torsional Mechanics: Effect of Lumbar and Caudal Levels and Axial Compression Load

    PubMed Central

    Elliott, Dawn M; Espinoza Orías, Alejandro A; Malhotra, Neil R

    2009-01-01

    Background Context Rat models with altered loading are used to study disc degeneration and mechano-transduction. Given the prominent role of mechanics in disc function and degeneration, it is critical to measure mechanical behavior in order to evaluate changes following model interventions. Axial compression mechanics of the rat disc are representative of the human disc when normalized by geometry, and differences between the lumbar and caudal disc have been quantified in axial compression. No study has quantified rat disc torsional mechanics. Purpose Compare the torsional mechanical behavior of rat lumbar and caudal discs, determine the contribution of combined axial load on torsional mechanics, and compare the torsional properties of rat discs to human lumbar discs. Study Design Cadaveric biomechanical study. Methods Cyclic torsion without compressive load followed by cyclic torsion with a fixed compressive load was applied to rat lumbar and caudal disc levels. Results The apparent torsional modulus was higher in the lumbar region than in the caudal region,: 0.081±0.026 (MPa/°, Mean±SD) for lumbar axially loaded; 0.066±0.028 caudal axially loaded; 0.091±0.033 for lumbar in pure torsion; and 0.056±0.035 for caudal in pure torsion. These values were similar to human disc properties reported in the literature ranging from 0.024 to 0.21 MPa/°. Conclusions Use of the caudal disc as a model may be appropriate if the mechanical focus is within the linear region of the loading regime. These results provide support for use of this animal model in basic science studies with respect to torsional mechanics. PMID:18495544

  11. Microarray analysis of laser capture microdissected-anulus cells from the human intervertebral disc.

    PubMed

    Gruber, Helen E; Mougeot, Jean-Luc; Hoelscher, Gretchen; Ingram, Jane A; Hanley, Edward N

    2007-05-15

    Five Thompson Grade I/II discs (Group 1), 7 Grade III discs (Group 2), and 3 Grade IV discs (Group IV) were studied here in a project approved by the authors' Human Subjects Institutional Review Board. Our objective was to use laser capture microdissection (LCM) to harvest cells from the human anulus and to derive gene expression profiles using microarray analysis. Appropriate gene expression is essential in the intervertebral disc for maintenance of extracellular matrix (ECM), ECM remodeling, and maintenance of a viable disc cell population. During disc degeneration, cell numbers drop, making gene expression studies challenging. LCM was used to harvest cells from paraffin-embedded sections of human anulus tissue. Gene profiling used Affymetrix GeneChip Human X3P arrays. ANOVA and SAM permutation analysis were applied to dCHIP normalized, filtered, and log-transformed gene expression data ( approximately 33,500 probes), and data analyzed to identify genes that were significantly differentially expressed between the 3 groups. We identified 47 genes that were significantly differentially expressed between the 3 groups (P < 0.001 and lowest q values). Compared with the healthiest discs (Grade I/II), 13 genes were up-regulated and 19 down-regulated in both the Grade III and the Grade IV discs. Genes with biologic significance regulated during degeneration involved cell senescence, low cell division rates, hypoxia-related genes, heat-shock protein 70 interacting protein, neuropilin 2, and interleukin-23p19 (interleukin-12 family). Results expand our understanding of disc aging and degeneration and show that LCM is a valuable technique that can be used to collect mRNA amounts adequate for microarray analysis from the sparse cell population of the human anulus.

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

    PubMed

    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.

  13. Comparison of animal discs used in disc research to human lumbar disc: torsion mechanics and collagen content.

    PubMed

    Showalter, Brent L; Beckstein, Jesse C; Martin, John T; Beattie, Elizabeth E; Espinoza Orías, Alejandro A; Schaer, Thomas P; Vresilovic, Edward J; Elliott, Dawn M

    2012-07-01

    Experimental measurement and normalization of in vitro disc torsion mechanics and collagen content for several animal species used in intervertebral disc research and comparing these with the human disc. To aid in the selection of appropriate animal models for disc research by measuring torsional mechanical properties and collagen content. There is lack of data and variability in testing protocols for comparing animal and human disc torsion mechanics and collagen content. Intervertebral disc torsion mechanics were measured and normalized by disc height and polar moment of inertia for 11 disc types in 8 mammalian species: the calf, pig, baboon, goat, sheep, rabbit, rat, and mouse lumbar discs, and cow, rat, and mouse caudal discs. Collagen content was measured and normalized by dry weight for the same discs except the rat and the mouse. Collagen fiber stretch in torsion was calculated using an analytical model. Measured torsion parameters varied by several orders of magnitude across the different species. After geometric normalization, only the sheep and pig discs were statistically different from human discs. Fiber stretch was found to be highly dependent on the assumed initial fiber angle. The collagen content of the discs was similar, especially in the outer annulus where only the calf and goat discs were statistically different from human. Disc collagen content did not correlate with torsion mechanics. Disc torsion mechanics are comparable with human lumbar discs in 9 of 11 disc types after normalization by geometry. The normalized torsion mechanics and collagen content of the multiple animal discs presented are useful for selecting and interpreting results for animal disc models. Structural organization of the fiber angle may explain the differences that were noted between species after geometric normalization.

  14. Morphometric analysis of the relationships between intervertebral disc and vertebral body heights: an anatomical and radiographic study of the human thoracic spine

    PubMed Central

    Kunkel, Maria E; Herkommer, Andrea; Reinehr, Michael; Böckers, Tobias M; Wilke, Hans-Joachim

    2011-01-01

    The main aim of this study was to provide anatomical data on the heights of the human intervertebral discs for all levels of the thoracic spine by direct and radiographic measurements. Additionally, the heights of the neighboring vertebral bodies were measured, and the prediction of the disc heights based only on the size of the vertebral bodies was investigated. The anterior (ADH), middle (MDH) and posterior heights (PDH) of the discs were measured directly and on radiographs of 72 spine segments from 30 donors (age 57.43 ± 11.27 years). The radiographic measurement error and the reliability of the measurements were calculated. Linear and non-linear regression analyses were employed for investigation of statistical correlations between the heights of the thoracic disc and vertebrae. Radiographic measurements displayed lower repeatability and were shorter than the anatomical ones (approximately 9% for ADH and 37% for PDH). The thickness of the discs varied from 4.5 to 7.2 mm, with the MDH approximately 22.7% greater. The disc heights showed good correlations with the vertebral body heights (R2, 0.659–0.835, P-values < 0.005; anova), allowing the generation of 10 prediction equations. New data on thoracic disc morphometry were provided in this study. The generated set of regression equations could be used to predict thoracic disc heights from radiographic measurement of the vertebral body height posterior. For the creation of parameterized models of the human thoracic discs, the use of the prediction equations could eliminate the need for direct measurement on intervertebral discs. Moreover, the error produced by radiographic measurements could be reduced at least for the PDH. PMID:21615399

  15. Novel Human Intervertebral Disc Strain Template to Quantify Regional Three-Dimensional Strains in a Population and Compare to Internal Strains Predicted by a Finite Element Model

    PubMed Central

    Showalter, Brent L.; DeLucca, John F.; Peloquin, John M.; Cortes, Daniel H.; Yoder, Jonathon H.; Jacobs, Nathan T.; Wright, Alexander C.; Gee, James C.; Vresilovic, Edward J.; Elliott, Dawn M.

    2017-01-01

    Tissue strain is an important indicator of mechanical function, but is difficult to noninvasively measure in the intervertebral disc. The objective of this study was to generate a disc strain template, a 3D average of disc strain, of a group of human L4–L5 discs loaded in axial compression. To do so, magnetic resonance images of uncompressed discs were used to create an average disc shape. Next, the strain tensors were calculated pixel-wise by using a previously developed registration algorithm. Individual disc strain tensor components were then transformed to the template space and averaged to create the disc strain template. The strain template reduced individual variability while highlighting group trends. For example, higher axial and circumferential strains were present in the lateral and posterolateral regions of the disc, which may lead to annular tears. This quantification of group-level trends in local 3D strain is a significant step forward in the study of disc biomechanics. These trends were compared to a finite element model that had been previously validated against the disc-level mechanical response. Depending on the strain component, 81–99% of the regions within the finite element model had calculated strains within one standard deviation of the template strain results. The template creation technique provides a new measurement technique useful for a wide range of studies, including more complex loading conditions, the effect of disc pathologies and degeneration, damage mechanisms, and design and evaluation of treatments. PMID:26694516

  16. Disabled infectious single cycle-herpes simplex virus (DISC-HSV) as a vector for immunogene therapy of cancer.

    PubMed

    Rees, Robert C; McArdle, Stephanie; Mian, Shahid; Li, Geng; Ahmad, Murrium; Parkinson, Richard; Ali, Selman A

    2002-02-01

    Disabled infectious single cycle-herpes simplex viruses (DISC-HSV) have been shown to be safe for use in humans and may be considered efficacious as vectors for immunogene therapy in cancer. Preclinical studies show that DISC-HSV is an efficient delivery system for cytokine genes and antigens. DISC-HSV infects a high proportion of cells, resulting in rapid gene expression for at least 72 h. The DISC-HSV-mGM-CSF vector, when inoculated into tumors, induces tumor regression in a high percentage of animals, concomitant with establishing a cytotoxic T-cell response, which is MHC class I restricted and directed against peptides of known tumor antigens. The inherent properties of DISC-HSV makes it a suitable vector for consideration in human immunogene therapy trials.

  17. Intradiscal pressure study of percutaneous disc decompression with nucleoplasty in human cadavers.

    PubMed

    Chen, Yung C; Lee, Sang-heon; Chen, Darwin

    2003-04-01

    Intradiscal pressure was measured after percutaneous disc decompression by nucleoplasty in human cadavers with different degrees of disc degeneration. To assess intradiscal pressure change after disc decompression, and to analyze the influence of degeneration on the intradiscal pressure change. Partial removal of the nucleus has been shown to decompress herniated discs, relieving pressure on nerve roots and, in some cases, offering relief from disc pain. Nucleoplasty, a new minimally invasive procedure using patented Coblation technology, combines coagulation and ablation for partial removal of the nucleus. Coblated channels remove the tissue volume and may decrease the disc pressure. Three fresh human cadaver spinal specimens (T8-L5; age, 54-84 years; mean age, 70.7 years) were used in this investigation. The intradiscal pressure was measured at three points: before treatment, after each channel was created, and after treatment using a 25-guage 6-inch needle connected to a Merit Medical Systems Intellisystem Inflation Monitor. The needles were calibrated initially to approximately 30 pounds per square inch. For the control, the change in disc pressure was recorded by the same procedure without using Coblation energy. To evaluate the effectiveness of nucleoplasty, disc pressure changes were compared between treatment with and without Coblation energy. Intradiscal pressure was markedly reduced in the younger, healthy disc cadaver. In the older, degenerative disc cadavers, the change in intradiscal pressure after nucleoplasty was very small. There was an inverse correlation between the degree of disc degeneration and the change in intradiscal pressure. Pressure reduction through nucleoplasty is highly dependent on the degree of spine degeneration. Nucleoplasty markedly reduced intradiscal pressure in nondegenerative discs, but had a negligible effect on highly degenerative discs.

  18. The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration

    PubMed Central

    Le Maitre, Christine Lyn; Freemont, Anthony J; Hoyland, Judith Alison

    2005-01-01

    In this study, we investigated the hypotheses that in human intervertebral disc (IVD) degeneration there is local production of the cytokine IL-1, and that this locally produced cytokine can induce the cellular and matrix changes of IVD degeneration. Immunohistochemistry was used to localize five members of the IL-1 family (IL-1α, IL-1β, IL-1Ra (IL-1 receptor antagonist), IL-1RI (IL-1 receptor, type I), and ICE (IL-1β-converting enzyme)) in non-degenerate and degenerate human IVDs. In addition, cells derived from non-degenerate and degenerate human IVDs were challenged with IL-1 agonists and the response was investigated using real-time PCR for a number of matrix-degrading enzymes, matrix proteins, and members of the IL-1 family. This study has shown that native disc cells from non-degenerate and degenerate discs produced the IL-1 agonists, antagonist, the active receptor, and IL-1β-converting enzyme. In addition, immunopositivity for these proteins, with the exception of IL-1Ra, increased with severity of degeneration. We have also shown that IL-1 treatment of human IVD cells resulted in increased gene expression for the matrix-degrading enzymes (MMP 3 (matrix metalloproteinase 3), MMP 13 (matrix metalloproteinase 13), and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs)) and a decrease in the gene expression for matrix genes (aggrecan, collagen II, collagen I, and SOX6). In conclusion we have shown that IL-1 is produced in the degenerate IVD. It is synthesized by native disc cells, and treatment of human disc cells with IL-1 induces an imbalance between catabolic and anabolic events, responses that represent the changes seen during disc degeneration. Therefore, inhibiting IL-1 could be an important therapeutic target for preventing and reversing disc degeneration. PMID:15987475

  19. A Systematic Review of the Safety and Efficacy of Mesenchymal Stem Cells for Disc Degeneration: Insights and Future Directions for Regenerative Therapeutics

    PubMed Central

    Yim, Rita Lok-Hay; Lee, Juliana Tsz-Yan; Bow, Cora H.; Meij, Björn; Leung, Victor; Cheung, Kenneth M.C.; Vavken, Patrick

    2014-01-01

    Intervertebral disc degeneration is associated with low-back pain. Mesenchymal stem cells (MSCs) have been used to “regenerate” the disc. The aim of this study was to perform a systematic review of comparative controlled studies that have assessed the safety and efficacy of using MSCs for disc regeneration. Literature databases were extensively searched. Trial design, subject-type, MSC sources, injection method, disc assessment, outcome intervals, and complication events were assessed. Validity of each study was performed. Twenty-four animal studies were included with 20.8% of the studies reporting randomization of groups. Trials in humans fulfilling inclusion criteria were not noted. The studies represented 862 discs that were injected with MSCs and 1,603 discs as controls. All three types of MSCs (ie, bone marrow, synovial, and adipose tissues) showed successful inhibition of disc degeneration. Bone-marrow-derived MSCs demonstrated superior quality of repair compared with other non-MSC treatments. A 2.7% overall complication rate was noted, whereby complications were noted only in rabbits. Overall, evidence suggested that MSCs increased disc space height in the majority of animal models. This is the first systematic review to assess the safety and efficacy of MSCs for the treatment of disc degeneration. Short-term MSC transplantation is safe and effective; however, additional, larger, and higher-quality studies are needed to assess the long-term safety and efficacy. Inconsistencies in methodological design and outcome parameters prevent any robust conclusions. Human-based clinical trials are needed. Recommendations are further made to improve efficacy, reduce potential complications, and standardize techniques for future studies. PMID:25050446

  20. Contribution of facet joints, axial compression, and composition to human lumbar disc torsion mechanics.

    PubMed

    Bezci, Semih E; Eleswarapu, Ananth; Klineberg, Eric O; O'Connell, Grace D

    2018-02-12

    Stresses applied to the spinal column are distributed between the intervertebral disc and facet joints. Structural and compositional changes alter stress distributions within the disc and between the disc and facet joints. These changes influence the mechanical properties of the disc joint, including its stiffness, range of motion, and energy absorption under quasi-static and dynamic loads. There have been few studies evaluating the role of facet joints in torsion. Furthermore, the relationship between biochemical composition and torsion mechanics is not well understood. Therefore, the first objective of this study was to investigate the role of facet joints in torsion mechanics of healthy and degenerated human lumbar discs under a wide range of compressive preloads. To achieve this, each disc was tested under four different compressive preloads (300-1200 N) with and without facet joints. The second objective was to develop a quantitative structure-function relationship between tissue composition and torsion mechanics. Facet joints have a significant contribution to disc torsional stiffness (∼60%) and viscoelasticity, regardless of the magnitude of axial compression. The findings from this study demonstrate that annulus fibrosus GAG content plays an important role in disc torsion mechanics. A decrease in GAG content with degeneration reduced torsion mechanics by more than an order of magnitude, while collagen content did not significantly influence disc torsion mechanics. The biochemical-mechanical and compression-torsion relationships reported in this study allow for better comparison between studies that use discs of varying levels of degeneration or testing protocols and provide important design criteria for biological repair strategies. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  1. Expression of Mutant Human DISC1 in Mice Supports Abnormalities in Differentiation of Oligodendrocytes

    PubMed Central

    Katsel, Pavel; Tan, Weilun; Abazyan, Bagrat; Davis, Kenneth L; Ross, Christopher; Pletnikov, Mikhail V; Haroutunian, Vahram

    2011-01-01

    Abnormalities in oligodendrocyte (OLG) differentiation and OLG gene expression deficit have been described in schizophrenia (SZ). Recent studies revealed a critical requirement for Disrupted-in-Schizophrenia 1 (DISC1) in neural development. Transgenic mice with forebrain restricted expression of mutant human DISC1 (ΔhDISC1) are characterized by neuroanatomical and behavioral abnormalities reminiscent of some features of SZ. We sought to determine whether the expression of ΔhDISC1 may influence the development of OLGs in this mouse model. OLG- and cell cycle-associated gene and protein expression were characterized in the forebrain of ΔhDISC1 mice during different stages of neurodevelopment (E15 and P1 days) and in adulthood. The results suggest that the expression of ΔhDISC1 exerts a significant influence on oligodendrocyte differentiation and function, evidenced by premature OLG differentiation and increased proliferation of their progenitors. Additional findings showed that neuregulin 1 and its receptors may be contributing factors to the observed upregulation of OLG genes. Thus, OLG function may be perturbed by mutant hDISC1 in a model system that provides new avenues for studying aspects of the pathogenesis of SZ. PMID:21605958

  2. Human Cartilage Endplate Permeability Varies with Degeneration and Intervertebral Disc Site

    PubMed Central

    DeLucca, John F.; Cortes, Daniel H.; Jacobs, Nathan T.; Vresilovic, Edward J.; Duncan, Randall L.; Elliott, Dawn M.

    2016-01-01

    Despite the critical functions the human cartilage endplate (CEP) plays in the intervertebral disc, little is known about its structural and mechanical properties and their changes with degeneration. Quantifying these changes with degeneration is important for understanding how the CEP contributes to the function and pathology of the disc. Therefore the objectives of this study were to quantify the effect of disc degeneration on human CEP mechanical properties, determine the influence of superior and inferior disc site on mechanics and composition, and simulate the role of collagen fibers in CEP and disc mechanics using a validated finite element model. Confined compression data and biochemical composition data were used in a biphasic-swelling model to calculate compressive extrafibrillar elastic and permeability properties. Tensile properties were obtained by applying published tensile test data to an ellipsoidal fiber distribution. Results showed that with degeneration CEP permeability decreased 50–60% suggesting that transport is inhibited in the degenerate disc. CEP fibers are organized parallel to the vertebrae and nucleus pulposus and may contribute to large shear strains (0.1–0.2) and delamination failure of the CEP commonly seen in herniated disc tissue. Fiber-reinforcement also reduces CEP axial strains thereby enhancing fluid flux by a factor of 1.8. Collectively, these results suggest that the structure and mechanics of the CEP may play critical roles in the solute transport and disc mechanics. PMID:26874969

  3. A Large Animal Model that Recapitulates the Spectrum of Human Intervertebral Disc Degeneration

    PubMed Central

    Gullbrand, Sarah E.; Malhotra, Neil R.; Schaer, Thomas P.; Zawacki, Zosia; Martin, John T.; Bendigo, Justin R.; Milby, Andrew H.; Dodge, George R.; Vresilovic, Edward J.; Elliott, Dawn M.; Mauck, Robert L.; Smith, Lachlan J.

    2016-01-01

    Objective The objective of this study was to establish a large animal model that recapitulates the spectrum of intervertebral disc degeneration that occurs in humans and which is suitable for pre-clinical evaluation of a wide range of experimental therapeutics. Design Degeneration was induced in the lumbar intervertebral discs of large frame goats by either intradiscal injection of chondroitinase ABC (ChABC) over a range of dosages (0.1U, 1U or 5U) or subtotal nucleotomy. Radiographs were used to assess disc height changes over 12 weeks. Degenerative changes to the discs and endplates were assessed via magnetic resonance imaging (MRI), semi-quantitative histological grading, micro-computed tomography (µCT), and measurement of disc biomechanical properties. Results Degenerative changes were observed for all interventions that ranged from mild (0.1U ChABC) to moderate (1U ChABC and nucleotomy) to severe (5U ChABC). All groups showed progressive reductions in disc height over 12 weeks. Histological scores were significantly increased in the 1U and 5U ChABC groups. Reductions in T2 and T1ρ, and increased Pfirrmann grade were observed on MRI. Resorption and remodeling of the cortical boney endplate adjacent to ChABC injected discs also occurred. Spine segment range of motion was greater and compressive modulus was lower in 1U ChABC and nucleotomy discs compared to intact. Conclusions A large animal model of disc degeneration was established that recapitulates the spectrum of structural, compositional and biomechanical features of human disc degeneration. This model may serve as a robust platform for evaluating the efficacy of therapeutics targeted towards varying degrees of disc degeneration. PMID:27568573

  4. Human cartilage endplate permeability varies with degeneration and intervertebral disc site.

    PubMed

    DeLucca, John F; Cortes, Daniel H; Jacobs, Nathan T; Vresilovic, Edward J; Duncan, Randall L; Elliott, Dawn M

    2016-02-29

    Despite the critical functions the human cartilage endplate (CEP) plays in the intervertebral disc, little is known about its structural and mechanical properties and their changes with degeneration. Quantifying these changes with degeneration is important for understanding how the CEP contributes to the function and pathology of the disc. Therefore the objectives of this study were to quantify the effect of disc degeneration on human CEP mechanical properties, determine the influence of superior and inferior disc site on mechanics and composition, and simulate the role of collagen fibers in CEP and disc mechanics using a validated finite element model. Confined compression data and biochemical composition data were used in a biphasic-swelling model to calculate compressive extrafibrillar elastic and permeability properties. Tensile properties were obtained by applying published tensile test data to an ellipsoidal fiber distribution. Results showed that with degeneration CEP permeability decreased 50-60% suggesting that transport is inhibited in the degenerate disc. CEP fibers are organized parallel to the vertebrae and nucleus pulposus and may contribute to large shear strains (0.1-0.2) and delamination failure of the CEP commonly seen in herniated disc tissue. Fiber-reinforcement also reduces CEP axial strains thereby enhancing fluid flux by a factor of 1.8. Collectively, these results suggest that the structure and mechanics of the CEP may play critical roles in the solute transport and disc mechanics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Disabled infectious single cycle herpes simplex virus (DISC-HSV) is a candidate vector system for gene delivery/expression of GM-CSF in human prostate cancer therapy.

    PubMed

    Parkinson, Richard J; Mian, Shahid; Bishop, Michael C; Gray, Trevor; Li, Geng; McArdle, Stephanie E B; Ali, Selman; Rees, Robert C

    2003-06-15

    DISC-HSV is a replication incompetent herpes simplex virus that is a highly efficient vector for the transduction of genes in vivo and in vitro. We examine the ability of DISC-HSV to infect human prostate cancer cell-lines and xenograft tumor models, and induce expression of reporter and therapeutic cytokine genes. Infection was confirmed by cellular staining for the beta-galactosidase reporter gene product, and by EM. Human GM-CSF production following DISC-hGMCSF infection was measured using ELISA. The metabolic activity of infected cells was determined by NADP/NADPH assay. Cell death was estimated by cell-cycle analysis using flow cytometry with propidium iodide staining. Infection of DU145, PC3 and LNCaP cells with DISC-HSV was dose dependent. Cells infected with DISC-hGM-CSF released significant levels of hGM-CSF for 3 days. NADP/NADPH assay suggested that infected cells continued to be metabolically active for 3 days post-infection, which was consistent with flow cytometry findings that cell death did not occur within 7 days of infection. Tumor xenografts injected with DISC-HSV expressed beta-galactosidase, and intracellular viral particles were demonstrated using EM. We have previously reported the rejection of established tumors following intra-tumoral injection of DISC-GMCSF. This study demonstrates the ability of DISC-HSV to infect prostate cancer and express GMCSF at significant levels. We suggest that prostate cancer is a potential target for therapy using DISC-HSV containing GM-CSF. Copyright 2003 Wiley-Liss, Inc.

  6. Quantitating Human Optic Disc Topography

    NASA Astrophysics Data System (ADS)

    Graebel, William P.; Cohan, Bruce E.; Pearch, Andrew C.

    1980-07-01

    A method is presented for quantitatively expressing the topography of the human optic disc, applicable in a clinical setting to the diagnosis and management of glaucoma. Pho-tographs of the disc illuminated by a pattern of fine, high contrast parallel lines are digitized. From the measured deviation of the lines as they traverse the disc surface, disc topography is calculated, using the principles of optical sectioning. The quantitators applied to express this topography have the the following advantages : sensitivity to disc shape; objectivity; going beyond the limits of cup-disc ratio estimates and volume calculations; perfect generality in a mathematical sense; an inherent scheme for determining a non-subjective reference frame to compare different discs or the same disc over time.

  7. Biochemical validity of imaging techniques (X-ray, MRI, and dGEMRIC) in degenerative disc disease of the human cervical spine-an in vivo study.

    PubMed

    Bostelmann, Richard; Bostelmann, Tamara; Nasaca, Adrian; Steiger, Hans Jakob; Zaucke, Frank; Schleich, Christoph

    2017-02-01

    On a molecular level, maturation or degeneration of human intervertebral disc is among others expressed by the content of glycosaminoglycans (GAGs). According to the degenerative status, the disc content can differ in nucleus pulposus (NP) and annulus fibrosus (AF), respectively. Research in this area was conducted mostly on postmortem samples. Although several radiological classification systems exist, none includes biochemical features. Therefore, we focused our in vivo study on a widely spread and less expensive imaging technique for the cervical spine and the correlation of radiological patterns to biochemical equivalents in the intervertebral discs. The aim of this pilot study was to (1) measure the GAG content in human cervical discs, (2) to investigate whether a topographic biochemical GAG pattern can be found, and (3) whether there is a correlation between imaging data (X-ray and magnetic resonance imaging [MRI] including delayed gadolinium-enhanced MRI of cartilage [dGEMRIC] as a special imaging technique of cartilage) and the biochemical data. We conducted a prospective experimental pilot study. Only non-responders to conservative therapy were included. All subjects were physically and neurologically examined, and they completed their questionnaires. Visual analogue scale neck and arm, Neck Disability Index score, radiological parameters (X-rays, MRI, dGEMRIC), and the content of GAG in the cervical disc were assessed. After surgical removal of 12 discs, 96 fractions of AF and NP were biochemically analyzed for the GAG content using dimethylmethylene blue assay. A quantitative pattern of GAGs in the human cervical disc was identified. There were (1) significantly (p<.001) higher values of GAGs (µg GAG/mg tissue) in the NP (169.9 SD 37.3) compared with the AF (132.4 SD 42.2), and (2) significantly (p<.005) higher values of GAGs in the posterior (right/left: 149.9/160.2) compared with the anterior (right/left: 112.0/120.2) part of the AF. Third, we found in dGEMRIC imaging a significantly (p<.008) different distribution of GAGs in the cervical disc (NP 1083.3 ms [SD 248.6], AF 925.9 ms [SD 137.6]). Finally, we found that grading of disc degeneration in X-ray and MRI was significantly correlated with neither AF- nor NP-GAG content. The GAG content in human cervical discs can be detected in vivo and is subject to a significantly (p<.05) region-specific pattern (AF vs. NP; anterior vs. posterior in the AF). Up to the levels of AF and NP, this is reproducible in MRI in dGEMRIC technique, but not in X-ray or standard MRI sequences. Potentially, the MRI in dGEMRIC technique can be used as a non-invasive in vivo indicator for disc degeneration in the cervical spine. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Human Disc Nucleus Properties and Vertebral Endplate Permeability

    PubMed Central

    Rodriguez, Azucena G.; Slichter, Chloe K.; Acosta, Frank L.; Rodriguez-Soto, Ana E.; Burghardt, Andrew J.; Majumdar, Sharmila; Lotz, Jeffrey C.

    2010-01-01

    Study of human cadaveric discs quantifying endplate permeability and porosity and correlating these with measures of disc quality: cell density, proteoglycan content, and overall degeneration. Permeability and porosity increased with age and were not correlated with cell density or overall degeneration, suggesting that endplate calcification may not accelerate disc degeneration. Study Design Experimental quantification of relationships between vertebral endplate morphology, permeability, disc cell density, glycosaminoglycan content and degeneration in samples harvested from human cadaveric spines. Objective To test the hypothesis that variation in endplate permeability and porosity contribute to changes in intervertebral disc cell density and overall degeneration. Summary of Background Data Cells within the intervertebral disc are dependent on diffusive exchange with capillaries in the adjacent vertebral bone. Previous findings suggest that blocked routes of transport negatively affect disc quality, yet there are no quantitative relationships between human vertebral endplate permeability, porosity, cell density and disc degeneration. Such relationships would be valuable for clarifying degeneration risk factors, and patient features that may impede efforts at disc tissue engineering. Methods Fifty-one motion segments were harvested from 13 frozen cadaveric human lumbar spines (32 to 85 years) and classified for degeneration using the MRI-based Pfirrmann scale. A cylindrical core was harvested from the center of each motion segment that included vertebral bony and cartilage endplates along with adjacent nucleus tissue. The endplate mobility, a type of permeability, was measured directly using a custom-made permeameter before and after the cartilage endplate was removed. Cell density within the nucleus tissue was estimated using the picogreen method while the nuclear GAG content was quantified using the DMMB technique. Specimens were imaged at 8 μm resolution using microCT, bony porosity was calculated. Analysis of variance, linear regression, and multiple comparison tests were used to analyze the data. Results Nucleus cell density increased as the disc height decreased (R2=0.13; p=0.01) but was not related to subchondral bone porosity (p>0.5), total mobility (p>0.4) or age (p>0.2). When controlling for disc height however, a significant, negative effect of age on cell density was observed (p=0.03). In addition to this, GAG content decreased with age non-linearly (R2=0.83, p<0.0001) and a cell function measurement, GAGs/cell decreased with degeneration (R2=0.24; p<0.0001). Total mobility (R2=0.14; p<0.01) and porosity (R2=0.1, p<0.01) had a positive correlation with age. Conclusion Although cell density increased with degeneration, cell function indicated that GAGs/cell decreased. Since permeability and porosity increase with age and degeneration, this implies that cell dysfunction, rather than physical barriers to transport, accelerate disc disease. PMID:21240044

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

    PubMed

    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 approach. Copyright 2005 Pathological Society of Great Britain and Ireland.

  10. Evaluation of Electrospun Nanofiber-Anchored Silicone for the Degenerative Intervertebral Disc

    PubMed Central

    Riahanizad, S.

    2017-01-01

    The nucleus pulposus (NP) substitution by polymeric gel is one of the promising techniques for the repair of the degenerative intervertebral disc (IVD). Silicone gel is one of the potential candidates for a NP replacement material. Electrospun fiber anchorage to silicone disc, referred as ENAS disc, may not only improve the biomechanical performances of the gel but it can also improve restoration capability of the gel, which is unknown. This study successfully produced a novel process to anchor any size and shape of NP gel with electrospun fiber mesh. Viscoelastic properties of silicone and ENAS disc were measured using standard experimental techniques and compared with the native tissue properties. Ex vivo mechanical tests were conducted on ENAS disc-implanted rabbit tails to the compare the mechanical stability between intact and ENAS implanted spines. This study found that viscoelastic properties of ENAS disc are higher than silicone disc and comparable to the viscoelastic properties of human NP. The ex vivo studies found that the ENAS disc restore the mechanical functionality of rabbit tail spine, after discectomy of native NP and replacing the NP by ENAS disc. Therefore, the PCL ENF mesh anchoring technique to a NP implant can have clinical potential. PMID:29181144

  11. Human disc degeneration is associated with increased MMP 7 expression.

    PubMed

    Le Maitre, C L; Freemont, A J; Hoyland, J A

    2006-01-01

    During intervertebral disc (IVD) degeneration, normal matrix synthesis decreases and degradation of disc matrix increases. A number of proteases that are increased during disc degeneration are thought to be involved in its pathogenesis. Matrix metalloproteinase 7 (MMP 7) (Matrilysin, PUMP-1) is known to cleave the major matrix molecules found within the IVD, i.e., the proteoglycan aggrecan and collagen type II. To date, however, it is not known how its expression changes with degeneration or its exact location. We investigated the localization of MMP 7 in human, histologically graded, nondegenerate, degenerated and prolapsed discs to ascertain whether MMP 7 is up-regulated during disc degeneration. Samples of human IVD tissue were fixed in neutral buffered formalin, embedded in paraffin, and sections stained with hematoxylin and eosin to score the degree of morphological degeneration. Immunohistochemistry was performed to localize MMP 7 in 41 human IVDs with varying degrees of degeneration. We found that the chondrocyte-like cells of the nucleus pulposus and inner annulus fibrosus were MMP 7 immunopositive; little immunopositivity was observed in the outer annulus. Nondegenerate discs showed few immunopositive cells. A significant increase in the proportion of MMP 7 immunopositive cells was seen in the nucleus pulposus of discs classified as showing intermediate levels of degeneration and a further increase was seen in discs with severe degeneration. Prolapsed discs showed more MMP 7 immunopositive cells compared to nondegenerated discs, but fewer than those seen in cases of severe degeneration.

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

    PubMed

    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.

  13. In vivo Loads in the Lumbar L3-4 Disc during a Weight Lifting Extension

    PubMed Central

    Wang, Shaobai; Park, Won Man; Kim, Yoon Hyuk; Cha, Thomas; Wood, Kirkham; Li, Guoan

    2014-01-01

    Background Knowledge of in vivo human lumbar loading is critical for understanding the lumbar function and for improving surgical treatments of lumbar pathology. Although numerous experimental measurements and computational simulations have been reported, non-invasive determination of in vivo spinal disc loads is still a challenge in biomedical engineering. The object of the study is to investigate the in vivo human lumbar disc loads using a subject-specific and kinematic driven finite element approach. Methods Three dimensional (3D) lumbar spine models of three living subjects were created using MR images. A 3D finite element model of the L3-4 disc, including the annulus fibrosus and nucleus pulposus, was built for each subject. The endplate kinematics of the L3-4 segment of each subject during a dynamic weight lifting extension was determined using a dual fluoroscopic imaging technique. The endplate kinematics was used as displacement boundary conditions of the subject specific finite element model of the L3-4 disc to calculate the in-vivo disc forces and moments during the weight lifting activity. Findings During the weight lifting extension, the L3-4 disc experienced maximum shear load of about 230 N or 0.34 bodyweight at the flexion position and maximum compressive load of 1500 N or 2.28 bodyweight at the upright position. The disc experienced a primary flexion-extension moment during the motion which reached a maximum of 4.2 Nm at upright position with stretched arms holding the weight. Interpretation This study provided quantitative data on in vivo disc loading that could help understand intrinsic biomechanics of the spine and improve surgical treatment of pathological discs using fusion or arthroplasty techniques. PMID:24345591

  14. Integrating MRI-based geometry, composition and fiber architecture in a finite element model of the human intervertebral disc.

    PubMed

    Stadelmann, Marc A; Maquer, Ghislain; Voumard, Benjamin; Grant, Aaron; Hackney, David B; Vermathen, Peter; Alkalay, Ron N; Zysset, Philippe K

    2018-05-17

    Intervertebral disc degeneration is a common disease that is often related to impaired mechanical function, herniations and chronic back pain. The degenerative process induces alterations of the disc's shape, composition and structure that can be visualized in vivo using magnetic resonance imaging (MRI). Numerical tools such as finite element analysis (FEA) have the potential to relate MRI-based information to the altered mechanical behavior of the disc. However, in terms of geometry, composition and fiber architecture, current FE models rely on observations made on healthy discs and might therefore not be well suited to study the degeneration process. To address the issue, we propose a new, more realistic FE methodology based on diffusion tensor imaging (DTI). For this study, a human disc joint was imaged in a high-field MR scanner with proton-density weighted (PD) and DTI sequences. The PD image was segmented and an anatomy-specific mesh was generated. Assuming accordance between local principal diffusion direction and local mean collagen fiber alignment, corresponding fiber angles were assigned to each element. Those element-wise fiber directions and PD intensities allowed the homogenized model to smoothly account for composition and fibrous structure of the disc. The disc's in vitro mechanical behavior was quantified under tension, compression, flexion, extension, lateral bending and rotation. The six resulting load-displacement curves could be replicated by the FE model, which supports our approach as a first proof of concept towards patient-specific disc modeling. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Physico-chemical characteristics of ZnO nanoparticles-based discs and toxic effect on human cervical cancer HeLa cells

    NASA Astrophysics Data System (ADS)

    Sirelkhatim, Amna; Mahmud, Shahrom; Seeni, Azman; Kaus, Noor Haida Mohd.; Sendi, Rabab

    2014-10-01

    In this study, we investigated physico-chemical properties of zinc oxide nanoparticles (ZnO NPs)-based discs and their toxicity on human cervical cancer HeLa cell lines. ZnO NPs (80 nm) were produced by the conventional ceramic processing method. FESEM analysis indicated dominant structure of nanorods with dimensions 100-500 nm in length, and 20-100 nm in diameter. The high content of ZnO nanorods in the discs probably played significant role in toxicity towards HeLa cells. Structural defects (oxygen vacancies and zinc/oxygen interstitials) were revealed by PL spectra peaks at 370-376 nm and 519-533 nm for the ZnO discs. The structural, optical and electrical properties of prepared sample have influenced the toxicological effects of ZnO discs towards HeLa cell lines via the generation of reactive oxygen species (ROS), internalization, membrane damage, and eventually cell death. The larger surface to volume area of the ZnO nanorods, combined with defects, stimulated enhanced toxicity via ROS generation hydrogen peroxide, hydroxyl radicals, and superoxide anion. The preliminary results confirmed the ZnO-disc toxicity on HeLa cells was significantly associated with the unique physicochemical properties of ZnO NPs and to our knowledge, this is the first cellular study for treatment of HeLa cells with ZnO discs made from 80 nm ZnO particles.

  16. Replacing Shox2 with human SHOX leads to congenital disc degeneration of the temporomandibular joint in mice

    PubMed Central

    Li, Xihai; Liu, Hongbing; Gu, Shuping; Liu, Chao; Sun, Cheng; Zheng, Yuqian; Chen, YiPing

    2013-01-01

    The temporomandibular joint (TMJ) consists of the glenoid fossa arising from the otic capsule through intramembranous ossification, the fibrocartilaginous disc and the condyle, derived from the secondary cartilage by endochondral ossification. We have reported previously that cranial neural crest-specific inactivation of the homeobox gene Shox2, which is expressed in the mesenchymal cells of maxilla-mandibular junction and later in the progenitor cells and perichondrium of the developing chondyle, led to dysplasia and ankylosis of the TMJ, and replacement of the mouse Shox2 with the human SHOX gene rescued the dysplastic and ankylosis phenotypes but developed a prematurely worn out articular disc. In this study, we investigated the molecular and cellular bases for the premature wear out articular disc in the TMJ of mice carrying the human SHOX replacement allele in the Shox2 locus (referred as Shox2SHOX-KI/KI). We found that the developmental process and expression of several key genes in the TMJ of Shox2SHOX-KI/KI mice appeared similar to the controls. However, the disc of the Shox2SHOX-KI/KI TMJ exhibited a reduced level of Col I and Aggrecan, accompanied by increased activities of matrix metalloproteinases (MMPs) and a down-regulation of Ihh expression. Dramatically increased cell apoptosis in the disc was also observed. These combinatory cellular and molecular defects appear to contribute to the observed disc phenotype, suggesting that while the human SHOX can exert similar function as the mouse Shox2 in regulating early TMJ development, it apparently has a distinct function in the regulation of those molecules that are involved in tissue homeostasis. PMID:24248941

  17. Substance P stimulates production of inflammatory cytokines in human disc cells.

    PubMed

    Kepler, Christopher K; Markova, Dessislava Z; Hilibrand, Alan S; Vaccaro, Alexander R; Risbud, Makarand V; Albert, Todd J; Anderson, D Greg

    2013-10-01

    Laboratory study. The aims of this study were as follows: (1) to confirm that Substance P (SP) is expressed by nucleus pulposus (NP) and annulus fibrosus (AF) cells; (2) to determine the effect of SP on expression of inflammatory mediators in human disc cells and the effect of inflammatory mediators on the expression of SP; and (3) to characterize the relative expression of SP receptor isoforms in disc tissue and describe whether exposure to SP changes receptor expression. SP, classically described as a neurotransmitter, acts as an inflammatory regulator in other tissue types, but its role within the intervertebral disc has not been characterized. Human AF and NP cells from 7 individuals were expanded in monolayer and maintained in alginate bead culture. Cells were treated with SP or interleukin (IL)-1β/tumor necrosis factor-α (TNF-α). After treatment, the cells were recovered and then RNA was isolated and transcribed into cDNA. Quantitative reverse-transcriptase polymerase chain reaction was performed to evaluate expression of inflammatory mediators and SP and its receptors. Disc cells treated with SP demonstrated significant upregulation of IL-1β, IL-6, and IL-8 in NP and AF cells whereas significant upregulation of RANTES and TNF occurred only in the AF cells. AF and NP cells expressed SP at low levels; expression did not change significantly with SP treatment but was significantly upregulated after treatment with IL-1β/TNF-α. Both SP receptor isoforms were expressed by NP and AF cells. SP upregulates inflammatory mediators in disc cells. SP and its receptors were expressed in both NP and AF cells, and expression did not change after treatment with SP but increased after treatment with IL-1β/TNF-α. SP likely acts in an autocrine or paracrine manner in intervertebral disc cells and may be involved in "crosstalk" between disc cells and neurons, providing a potential mechanism for transmission of painful discogenic stimuli.

  18. Ranges of Cervical Intervertebral Disc Deformation During an In Vivo Dynamic Flexion–Extension of the Neck

    PubMed Central

    Yu, Yan; Mao, Haiqing; Li, Jing-Sheng; Tsai, Tsung-Yuan; Cheng, Liming; Wood, Kirkham B.; Li, Guoan; Cha, Thomas D.

    2017-01-01

    While abnormal loading is widely believed to cause cervical spine disc diseases, in vivo cervical disc deformation during dynamic neck motion has not been well delineated. This study investigated the range of cervical disc deformation during an in vivo functional flexion–extension of the neck. Ten asymptomatic human subjects were tested using a combined dual fluoroscopic imaging system (DFIS) and magnetic resonance imaging (MRI)-based three-dimensional (3D) modeling technique. Overall disc deformation was determined using the changes of the space geometry between upper and lower endplates of each intervertebral segment (C3/4, C4/5, C5/6, and C6/7). Five points (anterior, center, posterior, left, and right) of each disc were analyzed to examine the disc deformation distributions. The data indicated that between the functional maximum flexion and extension of the neck, the anterior points of the discs experienced large changes of distraction/compression deformation and shear deformation. The higher level discs experienced higher ranges of disc deformation. No significant difference was found in deformation ranges at posterior points of all the discs. The data indicated that the range of disc deformation is disc level dependent and the anterior region experienced larger changes of deformation than the center and posterior regions, except for the C6/7 disc. The data obtained from this study could serve as baseline knowledge for the understanding of the cervical spine disc biomechanics and for investigation of the biomechanical etiology of disc diseases. These data could also provide insights for development of motion preservation surgeries for cervical spine. PMID:28334358

  19. Ranges of Cervical Intervertebral Disc Deformation During an In Vivo Dynamic Flexion-Extension of the Neck.

    PubMed

    Yu, Yan; Mao, Haiqing; Li, Jing-Sheng; Tsai, Tsung-Yuan; Cheng, Liming; Wood, Kirkham B; Li, Guoan; Cha, Thomas D

    2017-06-01

    While abnormal loading is widely believed to cause cervical spine disc diseases, in vivo cervical disc deformation during dynamic neck motion has not been well delineated. This study investigated the range of cervical disc deformation during an in vivo functional flexion-extension of the neck. Ten asymptomatic human subjects were tested using a combined dual fluoroscopic imaging system (DFIS) and magnetic resonance imaging (MRI)-based three-dimensional (3D) modeling technique. Overall disc deformation was determined using the changes of the space geometry between upper and lower endplates of each intervertebral segment (C3/4, C4/5, C5/6, and C6/7). Five points (anterior, center, posterior, left, and right) of each disc were analyzed to examine the disc deformation distributions. The data indicated that between the functional maximum flexion and extension of the neck, the anterior points of the discs experienced large changes of distraction/compression deformation and shear deformation. The higher level discs experienced higher ranges of disc deformation. No significant difference was found in deformation ranges at posterior points of all the discs. The data indicated that the range of disc deformation is disc level dependent and the anterior region experienced larger changes of deformation than the center and posterior regions, except for the C6/7 disc. The data obtained from this study could serve as baseline knowledge for the understanding of the cervical spine disc biomechanics and for investigation of the biomechanical etiology of disc diseases. These data could also provide insights for development of motion preservation surgeries for cervical spine.

  20. Human and bovine spinal disc mechanics subsequent to trypsin injection.

    PubMed

    Alsup, Jeremy; Bishop, Timothy; Eggett, Dennis; Bowden, Anton E

    2017-10-01

    To investigate the biomechanical effects of injections of a protease on the characteristics of bovine coccygeal and human lumbar disc motion segments. Mechanics of treated tissues were measured immediately after injection and 3 h after injection. Motion segments underwent axial rotation and flexion-extension loading. Stiffness and neutral zone parameters experienced significant changes over time, with bovine tissues more strongly affected than human cadaver tissues. This was true in both axial rotation and flexion-extension. The treatment type significantly affected the neutral zone measurements in axial rotation. Hysteresis parameters were impacted by control injections. The extrapolation of bovine coccygeal motion testing results to human lumbar disc mechanics is not yet practical. The injected treatment may have a smaller impact on disc mechanics than time in testing. Viscoelasticity of human lumbar discs may be impacted by any damage to the annulus fibrosis induced by needlestick. Preclinical testing of novel spinal devices is essential to the design validation and regulatory processes, but current testing techniques rely on cadaveric testing of primarily older spines with essentially random amounts of disc degeneration. The present work investigates the viability of using trypsin injections to create a more uniform preclinical model of disc degeneration from a mechanics perspective, for the purpose of testing spinal devices. Such a model would facilitate translation of new spinal technologies to clinical practice.

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

    NASA Astrophysics Data System (ADS)

    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 subjected to impacts in the laboratory. Analysis showed greater total von Mises stress and pore pressure in the components of the disc under transient shocks compared to static or quasi-static loading. These findings support the idea that impact shocks cause a change in mechanical response and are potentially damaging to the disc in the long term.

  2. Nonlinear dynamics of the human lumbar intervertebral disc.

    PubMed

    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.

  3. The multidirectional bending properties of the human lumbar intervertebral disc.

    PubMed

    Spenciner, David; Greene, David; Paiva, James; Palumbo, Mark; Crisco, Joseph

    2006-01-01

    While the biomechanical properties of the isolated intervertebral disc have been well studied in the three principal anatomic directions of flexion/extension, axial rotation, and lateral bending, there is little data on the properties in the more functional directions that are combinations of these principal anatomic directions. To determine the bending flexibility, range of motion (ROM), and neutral zone (NZ) of the human lumbar disc in multiple directions and to determine if the values about the combined moment axes can be predicted from the values about principal moment axes. Three-dimensional biomechanical analysis of the elastic bending properties of human lumbar discs about principal and combined moment axes. Pure, unconstrained moments were applied about multiple axes. The bending properties (flexibility, ROM, and NZ) of isolated lumbar discs (n=4 for L2/L3 and n=3 for L4/L5) were determined in the six principal directions and in 20 combined directions. The experimental values were compared with those predicted from the linear combination of the six principal moment axes. The maximum and minimum values of the biomechanical properties were found at the principal moment axes. Among combined moment axes, ROM and NZ (but not flexibility) values were predicted from the principal moment axis values. The principal moment axes coincide with the primary mechanical axes of the intervertebral disc and demonstrate significant differences in direction for values of flexibility, ROM, and NZ. Not all combined moment axis values can be predicted from principal moment axis values.

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

    PubMed

    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 higher CV after normalization. Assuming that geometry and material properties affect the mechanical response, they can also compensate for one another. Therefore, the larger CV after normalization can be interpreted as a strong variability of the material properties, previously hidden by the geometry's own influence. In conclusion, a new normalization protocol for the intervertebral disc stiffness in compression, flexion, extension, bilateral torsion and bending was proposed, with the possible use of MRI and FE to acquire the discs' anatomy and determine the nonlinear relations between stiffness and morphology. Such protocol may be useful to relate the disc's mechanical properties to its degree of degeneration.

  5. MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine.

    PubMed

    Stolworthy, Dean K; Bowden, Anton E; Roeder, Beverly L; Robinson, Todd F; Holland, Jacob G; Christensen, S Loyd; Beatty, Amanda M; Bridgewater, Laura C; Eggett, Dennis L; Wendel, John D; Stieger-Vanegas, Susanne M; Taylor, Meredith D

    2015-12-01

    Animal models have historically provided an appropriate benchmark for understanding human pathology, treatment, and healing, but few animals are known to naturally develop intervertebral disc degeneration. The study of degenerative disc disease and its treatment would greatly benefit from a more comprehensive, and comparable animal model. Alpacas have recently been presented as a potential large animal model of intervertebral disc degeneration due to similarities in spinal posture, disc size, biomechanical flexibility, and natural disc pathology. This research further investigated alpacas by determining the prevalence of intervertebral disc degeneration among an aging alpaca population. Twenty healthy female alpacas comprised two age subgroups (5 young: 2-6 years; and 15 older: 10+ years) and were rated according to the Pfirrmann-grade for degeneration of the cervical intervertebral discs. Incidence rates of degeneration showed strong correlations with age and spinal level: younger alpacas were nearly immune to developing disc degeneration, and in older animals, disc degeneration had an increased incidence rate and severity at lower cervical levels. Advanced disc degeneration was present in at least one of the cervical intervertebral discs of 47% of the older alpacas, and it was most common at the two lowest cervical intervertebral discs. The prevalence of intervertebral disc degeneration encourages further investigation and application of the lower cervical spine of alpacas and similar camelids as a large animal model of intervertebral disc degeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. Clinical Trials: A Crucial Key to Human Health Research

    MedlinePlus

    ... Clinical Trials: A Crucial Key to Human Health Research Past Issues / Summer 2006 Table of Contents For ... Photo: PhotoDisc At the forefront of human health research today are clinical trials—studies that use human ...

  7. Vasodilatory effect of L-arginine on isolated rabbit and human posterior ciliary arteries in vitro and increased optic disc blood flow in vivo.

    PubMed

    Chuman, Hideki; Sugimoto, Takako; Nao-I, Nobuhisa

    2017-12-01

    This study aimed to clarify the vasodilatory effect of L-arginine on isolated rabbit and human posterior ciliary arteries (PCAs) and to investigate changes in optic disc blood flow after an infusion of L-arginine in vivo. Vascular ring segments were mounted on a double myograph system. After obtaining maximal contraction following administration of high-K solution, L-arginine was administrated. Six volunteers received an intravenous drip infusion of 100 ml of L-arginine or saline. Changes in optic disc blood flow were measured by laser speckle flowgraphy. L-arginine relaxed high-K solution-induced contracted rabbit PCAs. Carboxy-PTIO (nitric oxide scavenger) and L-NAME (nitric oxide synthase inhibitor) inhibited L-arginine-induced relaxation in rabbit PCAs. After removal of the endothelium of the rabbit PCAs, L-arginine still relaxed rabbit PCAs. L-arginine relaxed human PCAs, despite the lack of nitric oxide production. In the L-arginine infusion group, the mean blur rate was significantly greater than that of the control group in vivo. L-arginine has both nitric oxide-dependent and independent vasodilatory effect on high K- induced contractions in isolated rabbit and human PCAs. L-arginine increased optic disc blood flow in vivo.

  8. In Vitro Description of Macroscopic Changes of Dental Amalgam Discs Subject to High Temperatures to Forensic Purposes.

    PubMed

    Arcos, Carlos; Díaz, Juan-David; Canencio, Kenny; Rodríguez, Diana; Viveros, Carlos; Vega, Jonathan; Lores, Juliana; Sinisterra, Gustavo; Sepúlveda, Wilmer; Moreno, Freddy

    2015-07-01

    To describe the behavior of 45 discs of dental amalgam of known dimension prepared from three commercially available brands of dental amalgam (Contour® Kerr®-USA, Admix® SDI®-Australia and Nu Alloy® Newstethic®-Colombia) when subjected to the action of high temperatures (200 °C, 400 °C, 600 °C, 800 °C, 1000 °C). It was hoped to establish parameters that could be used for human dental identification in cases of charred, burned or incinerated human remains. A pseudo-experimental descriptive in-vitro study was designed to describe the macroscopic physical changes to the surface of 45 discs of pre-prepared amalgam of three commercially available brands exposed to a range of high temperatures. Characteristic and repetitive physical changes were a noticeable feature of the discs of amalgam of each brand of amalgam subjected to the different temperature ranges. These physical changes included changes in dimensional stability, changes in texture, changes in colour, changes in the appearance of fissures and cracks and changes in the fracture and fragmentation of the sample. The characteristics of dental amalgam may be of assistance in cases of human identification where charred, burned or incinerated human remains are a feature and where fingerprints or other soft tissue features are unavailable.

  9. Effect of Survivin gene therapy via lentivirus vector on the course of intervertebral disc degeneration in an in vivo rabbit model.

    PubMed

    Yue, Bin; Lin, Yazhou; Ma, Xuexiao; Zhang, Guoqing; Chen, Bohua

    2016-11-01

    The aim of the current study was to use gene therapy to attenuate or reverse the degenerative process within the intervertabral disc. The effect of survivin gene therapy via lentiviral vector transfection on the course of intervertebral disc degeneration was investigated in the current study in an in vivo rabbit model. A total of 15 skeletally mature female New Zealand White rabbits were randomly divided into three groups: Punctured blank control group (group A, n=5), punctured empty vector control group (group B, n=5) and the treatment group (group C, n=5). Computed tomography‑guided puncture was performed at the L3‑L4 and L4‑L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, a lentiviral vector (LV) carrying survivin was injected into the nucleus pulposus. The results demonstrated that through magnetic resonance imaging, histology, gene expression, protein content and apoptosis analyses, group A and B were observed to exhibit disc degeneration, which increased over time, and no significant difference was observed between the two groups (P>0.05). However, there was reduced disc degeneration in group C compared with the punctured control groups, and the difference was statistically significant (P<0.05). Overall, the results of the present study demonstrated that injection of the LV carrying survivin into punctured rabbit intervertebral discs acted to delay changes associated with the degeneration of the discs. Although data from animal models should be extrapolated to the human condition with caution, the present study suggests potential for the use of gene therapy to decelerate disc degeneration.

  10. A 1-D model of the nonlinear dynamics of the human lumbar intervertebral disc

    NASA Astrophysics Data System (ADS)

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

    2017-01-01

    Lumped parameter models of the spine have been developed to investigate its response to whole body vibration. However, these models assume the behaviour of the intervertebral disc to be linear-elastic. Recently, the authors have reported on the nonlinear dynamic behaviour of the human lumbar intervertebral disc. This response was shown to be dependent on the applied preload and amplitude of the stimuli. However, the mechanical properties of a standard linear elastic model are not dependent on the current deformation state of the system. The aim of this study was therefore to develop a model that is able to describe the axial, nonlinear quasi-static response and to predict the nonlinear dynamic characteristics of the disc. The ability to adapt the model to an individual disc's response was a specific focus of the study, with model validation performed against prior experimental data. The influence of the numerical parameters used in the simulations was investigated. The developed model exhibited an axial quasi-static and dynamic response, which agreed well with the corresponding experiments. However, the model needs further improvement to capture additional peculiar characteristics of the system dynamics, such as the change of mean point of oscillation exhibited by the specimens when oscillating in the region of nonlinear resonance. Reference time steps were identified for specific integration scheme. The study has demonstrated that taking into account the nonlinear-elastic behaviour typical of the intervertebral disc results in a predicted system oscillation much closer to the physiological response than that provided by linear-elastic models. For dynamic analysis, the use of standard linear-elastic models should be avoided, or restricted to study cases where the amplitude of the stimuli is relatively small.

  11. The Role of Adipokines in Intervertebral Disc Degeneration.

    PubMed

    Sharma, Anirudh

    2018-04-24

    Intervertebral disc degeneration (IDD) is an important cause of low back pain. Recent evidence suggests that in addition to abnormal and excessive mechanical loading, inflammation may be a key driver for both IDD and low back pain. Obesity, a known mechanical risk factor of IDD, is now increasingly being recognized as a systemic inflammatory state with adipokines being postulated as likely inflammatory mediators. The aim of this review was to summarize the current literature regarding the inflammatory role of adipokines in the pathophysiology of IDD. A systematic literature search was performed using the OVID Medline, EMBASE and PubMed databases to identify all studies assessing IDD and adipokines. Fifteen studies were included in the present review. Leptin was the most commonly assessed adipokine. Ten of 15 studies were conducted in humans; three in rats and two in both humans and rats. Studies focused on a variety of topics ranging from receptor identification, pathway analysis, genetic associations, and proteonomics. Currently, data from both human and animal experiments demonstrate significant effects of leptin and adiponectin on the internal milieu of intervertebral discs. However, future studies are needed to determine the molecular pathway relationships between adipokines in the pathophysiology of IDD as avenues for future therapeutic targets.

  12. Lead Neurotoxicity on Human Neuroblastoma Cell Line SH-SY5Y is Mediated via Transcription Factor EGR1/Zif268 Induced Disrupted in Scherophernia-1 Activation.

    PubMed

    You, Yuanyuan; Peng, Bo; Ben, Songbin; Hou, Weijian; Sun, Liguang; Jiang, Wei

    2018-07-01

    Lead (Pb 2+ ) is a well-known type of neurotoxin and chronic exposure to Pb 2+ induces cognition dysfunction. In this work, the potential role of early growth response gene 1 (EGR1) in the linkage of Pb 2+ exposure and disrupted in scherophernia-1 (DISC1) activity was investigated. Human neuroblastoma cell line SH-SY5Y was subjected to different concentrations of lead acetate (PbAc) to determine the effect of Pb 2+ exposure on the cell viability, apoptosis, and activity of EGR1 and DISC1. Then the expression of EGR1 in SH-SY5Y cells was knocked down with specific siRNA to assess the function of EGR1 in Pb 2+ induced activation of DISC1. The interaction between EGR1 and DISC1 was further validated with dual luciferase assay, Supershift electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation (ChIP)-PCR. Administration of PbAc decreased cell viability and induced apoptosis in SH-SY5Y cells in a dose-dependent manner. Additionally, exposure to PbAc also up-regulated expression of EGR1 and DISC1 at all concentrations. Knockdown of EGR1 blocked the effect of PbAc on SH-SY5Y cells, indicating the central role of EGR1 in the function of Pb 2+ on activity of DISC1. Based on the results of dual luciferase assay, Supershift EMSA, and ChIP-PCR, EGR1 mediated the effect of Pb 2+ on DISC1 by directly bound to the promoter region of DISC1 gene. The current study elaborated the mechanism involved in the effect of Pb 2+ exposure on expression of DISC1 for the first time: EGR1 activated by Pb 2+ substitution of zinc triggered the transcription of DISC1 gene by directly binding to its promoter.

  13. A study of the temporomandibular joint during bruxism.

    PubMed

    Commisso, María S; Martínez-Reina, Javier; Mayo, Juana

    2014-06-01

    A finite element model of the temporomandibular joint (TMJ) and the human mandible was fabricated to study the effect of abnormal loading, such as awake and asleep bruxism, on the articular disc. A quasilinear viscoelastic model was used to simulate the behaviour of the disc. The viscoelastic nature of this tissue is shown to be an important factor when sustained (awake bruxism) or cyclic loading (sleep bruxism) is simulated. From the comparison of the two types of bruxism, it was seen that sustained clenching is the most detrimental activity for the TMJ disc, producing an overload that could lead to severe damage of this tissue.

  14. A study of the temporomandibular joint during bruxism

    PubMed Central

    Commisso, María S; Martínez-Reina, Javier; Mayo, Juana

    2014-01-01

    A finite element model of the temporomandibular joint (TMJ) and the human mandible was fabricated to study the effect of abnormal loading, such as awake and asleep bruxism, on the articular disc. A quasilinear viscoelastic model was used to simulate the behaviour of the disc. The viscoelastic nature of this tissue is shown to be an important factor when sustained (awake bruxism) or cyclic loading (sleep bruxism) is simulated. From the comparison of the two types of bruxism, it was seen that sustained clenching is the most detrimental activity for the TMJ disc, producing an overload that could lead to severe damage of this tissue. PMID:24651655

  15. Photoreceptor disc shedding in the living human eye

    PubMed Central

    Kocaoglu, Omer P.; Liu, Zhuolin; Zhang, Furu; Kurokawa, Kazuhiro; Jonnal, Ravi S.; Miller, Donald T.

    2016-01-01

    Cone photoreceptors undergo a daily cycle of renewal and shedding of membranous discs in their outer segments (OS), the portion responsible for light capture. These physiological processes are fundamental to maintaining photoreceptor health, and their dysfunction is associated with numerous retinal diseases. While both processes have been extensively studied in animal models and postmortem eyes, little is known about them in the living eye, in particular human. In this study, we report discovery of the optical signature associated with disc shedding using a method based on adaptive optics optical coherence tomography (AO-OCT) in conjunction with post-processing methods to track and monitor individual cone cells in 4D. The optical signature of disc shedding is characterized by an abrupt transient loss in the cone outer segment tip (COST) reflection followed by its return that is axially displaced anteriorly. Using this signature, we measured the temporal and spatial properties of shedding events in three normal subjects. Average duration of the shedding event was 8.8 ± 13.4 minutes, and average length loss of the OS was 2.1 μm (7.0% of OS length). Prevalence of cone shedding was highest in the morning (14.3%) followed by the afternoon (5.7%) and evening (4.0%), with load distributed across the imaged patch. To the best of our knowledge these are the first images of photoreceptor disc shedding in the living retina. PMID:27895995

  16. The effect of simulated microgravity on lumbar spine biomechanics: an in vitro study.

    PubMed

    Laws, Cory J; Berg-Johansen, Britta; Hargens, Alan R; Lotz, Jeffrey C

    2016-09-01

    Disc herniation risk is quadrupled following spaceflight. This study tested the hypothesis that swelling-induced disc height increases (comparable to those reported in spaceflight) stiffen the spine and elevate annular strain and nuclear pressure during forward bending. Eight human lumbar motion segments were secured to custom-designed testing jigs and subjected to baseline flexion and compression and pure moment flexibility tests. Discs were then free-swelled in saline to varying supraphysiologic heights consistent with prolonged weightlessness and re-tested to assess biomechanical changes. Swelling-induced disc height changes correlated positively with intradiscal pressure (p < 0.01) and stiffening in flexion (p < 0.01), and negatively with flexion range of motion (p < 0.05). Swelling-induced increases in disc height also led to increased annular surface strain under combined flexion with compression. Disc wedge angle decreased with swelling (p < 0.05); this loss of wedge angle correlated with decreased flexion range of motion (R (2) = 0.94, p < 0.0001) and decreased stiffness fold change in extension (p < 0.05). Swelling-induced increases in disc height decrease flexibility and increase annular strain and nuclear pressure during forward bending. These changes, in combination with the measured loss of lordotic curvature with disc swelling, may contribute toward increased herniation risk. This is consistent with clinical observations of increased disc herniation rates after microgravity exposure and may provide the basis for future countermeasure development.

  17. The effect of simulated microgravity on lumbar spine biomechanics: an in vitro study

    PubMed Central

    Laws, Cory J.; Berg-Johansen, Britta; Hargens, Alan R.; Lotz, Jeffrey C.

    2015-01-01

    Purpose Disc herniation risk is quadrupled following spaceflight. This study tested the hypothesis that swelling-induced disc height increases (comparable to those reported in spaceflight) stiffen the spine and elevate annular strain and nuclear pressure during forward bending. Methods Eight human lumbar motion segments were secured to custom-designed testing jigs and subjected to baseline flexion and compression and pure moment flexibility tests. Discs were then free-swelled in saline to varying supraphysiologic heights consistent with prolonged weightlessness and re-tested to assess biomechanical changes. Results Swelling-induced disc height changes correlated positively with intradiscal pressure (p < 0.01) and stiffening in flexion (p < 0.01), and negatively with flexion range of motion (p < 0.05). Swelling-induced increases in disc height also led to increased annular surface strain under combined flexion with compression. Disc wedge angle decreased with swelling (p < 0.05); this loss of wedge angle correlated with decreased flexion range of motion (R2 = 0.94, p < 0.0001) and decreased stiffness fold change in extension (p < 0.05). Conclusion Swelling-induced increases in disc height decrease flexibility and increase annular strain and nuclear pressure during forward bending. These changes, in combination with the measured loss of lordotic curvature with disc swelling, may contribute toward increased herniation risk. This is consistent with clinical observations of increased disc herniation rates after microgravity exposure and may provide the basis for future countermeasure development. PMID:26403291

  18. Organotypic three-dimensional assays based on human leiomyoma–derived matrices

    PubMed Central

    Dourado, Mauricio Rocha; Sundquist, Elias; Apu, Ehsanul Hoque; Alahuhta, Ilkka; Tuomainen, Katja; Vasara, Jenni; Al-Samadi, Ahmed

    2018-01-01

    Alongside cancer cells, tumours exhibit a complex stroma containing a repertoire of cells, matrix molecules and soluble factors that actively crosstalk between each other. Recognition of this multifaceted concept of the tumour microenvironment (TME) calls for authentic TME mimetics to study cancer in vitro. Traditionally, tumourigenesis has been investigated in non-human, three-dimensional rat type I collagen containing organotypic discs or by means of mouse sarcoma-derived gel, such as Matrigel®. However, the molecular compositions of these simplified assays do not properly simulate human TME. Here, we review the main properties and benefits of using human leiomyoma discs and their matrix Myogel for in vitro assays. Myoma discs are practical for investigating the invasion of cancer cells, as are cocultures of cancer and stromal cells in a stiff, hypoxic TME mimetic. Myoma discs contain soluble factors and matrix molecules commonly present in neoplastic stroma. In Transwell, IncuCyte, spheroid and sandwich assays, cancer cells move faster and form larger colonies in Myogel than in Matrigel®. Additionally, Myogel can replace Matrigel® in hanging-drop and tube-formation assays. Myogel also suits three-dimensional drug testing and extracellular vesicle interactions. To conclude, we describe the application of our myoma-derived matrices in 3D in vitro cancer assays. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’. PMID:29158312

  19. Organotypic three-dimensional assays based on human leiomyoma-derived matrices.

    PubMed

    Salo, Tuula; Dourado, Mauricio Rocha; Sundquist, Elias; Apu, Ehsanul Hoque; Alahuhta, Ilkka; Tuomainen, Katja; Vasara, Jenni; Al-Samadi, Ahmed

    2018-01-05

    Alongside cancer cells, tumours exhibit a complex stroma containing a repertoire of cells, matrix molecules and soluble factors that actively crosstalk between each other. Recognition of this multifaceted concept of the tumour microenvironment (TME) calls for authentic TME mimetics to study cancer in vitro Traditionally, tumourigenesis has been investigated in non-human, three-dimensional rat type I collagen containing organotypic discs or by means of mouse sarcoma-derived gel, such as Matrigel ® However, the molecular compositions of these simplified assays do not properly simulate human TME. Here, we review the main properties and benefits of using human leiomyoma discs and their matrix Myogel for in vitro assays. Myoma discs are practical for investigating the invasion of cancer cells, as are cocultures of cancer and stromal cells in a stiff, hypoxic TME mimetic. Myoma discs contain soluble factors and matrix molecules commonly present in neoplastic stroma. In Transwell, IncuCyte, spheroid and sandwich assays, cancer cells move faster and form larger colonies in Myogel than in Matrigel ® Additionally, Myogel can replace Matrigel ® in hanging-drop and tube-formation assays. Myogel also suits three-dimensional drug testing and extracellular vesicle interactions. To conclude, we describe the application of our myoma-derived matrices in 3D in vitro cancer assays.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'. © 2017 The Authors.

  20. Expression and regulation of neurotrophins in the nondegenerate and degenerate human intervertebral disc

    PubMed Central

    Purmessur, Devina; Freemont, Anthony J; Hoyland, Judith A

    2008-01-01

    Introduction The neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been identified in the human intervertebral disc (IVD) and have been implicated in the mechanisms associated with nerve ingrowth and nociception in degeneration of the IVD. The aim of the current study was to investigate an association between neurotrophin expression in the IVD and the severity of disc degeneration, including the effect of disc-related proinflammatory cytokines on neurotrophin and neuropeptide expression in cells derived from the human IVD. Methods Immunohistochemical analysis was performed to examine the expression of NGF, BDNF and their high-affinity receptors Trk-A and Trk-B in human IVD samples, divided into three categories: non-degenerate, moderate degeneration and severe degeneration. In order to study the effect of disc-related cytokines on neurotrophin/neuropeptide gene expression, nucleus pulposus cells derived from non-degenerate and degenerate IVD samples were seeded in alginate and were stimulated with either IL-1β or TNFα for 48 hours. RNA was extracted, cDNA was synthesised and quantitative real-time PCR was performed to examine the expression of NGF, BDNF and substance P. Results Immunohistochemistry showed expression of NGF and BDNF in the native chondrocyte-like cells in all regions of the IVD and in all grades of degeneration. Interestingly only BDNF significantly increased with the severity of degeneration (P < 0.05). Similar expression was observed for Trk-A and Trk-B, although no association with disease severity was demonstrated. In cultured human nucleus pulposus cells, stimulation with IL-1β led to significant increases in NGF and BDNF gene expression (P < 0.05). Treatment with TNFα was associated with an upregulation of substance P expression only. Conclusion Our findings show that both the annulus fibrosus and nucleus pulposus cells of the IVD express the neurotrophins NGF and BDNF, factors that may influence and enhance innervation and pain in the degenerate IVD. Expression of Trk-A and Trk-B by cells of the nondegenerate and degenerate IVD suggests an autocrine role for neurotrophins in regulation of disc cell biology. Furthermore, modulation of neurotrophin expression by IL-1β and modulation of substance P expression by TNFα, coupled with their increased expression in the degenerate IVD, highlights novel roles for these cytokines in regulating nerve ingrowth in the degenerate IVD and associated back pain. PMID:18727839

  1. Preliminary optical coherence tomography investigation of the temporo-mandibular joint disc

    NASA Astrophysics Data System (ADS)

    Mărcăuteanu, Corina; Demjan, Enikö; Sinescu, Cosmin; Negrutiu, Meda; Motoc, Adrian; Lighezan, Rodica; Vasile, Liliana; Hughes, Mike; Bradu, Adrian; Dobre, George; Podoleanu, Adrian G.

    2010-02-01

    Aim and objectives. The morphology and position of the temporo-mandibular disc are key issues in the diagnosis and treatment of arthrogenous temporo-mandibular disorders. Magnetic resonance imaging and arthroscopy are used today to identify: flattening of the pars posterior of the disc, perforation and/or adhesions in the pars intermedia of the disc and disc displacements. The present study proposes the investigation of the temporo-mandibular joint disc by optical coherence tomography (OCT). Material and methods. 8 human temporo-mandibular joint discs were harvested from dead subjects, under 40 year of age, and conserved in formalin. They had a normal morphology, with a thicker pars posterior (2,6 mm on the average) and a thinner pars intermedia (1mm on the average). We investigated the disc samples using two different OCT systems: an en-face OCT (time domain (TD)-OCT) system, working at 1300 nm (C-scan and B-scan mode) and a spectral OCT system (a Fourier domain (FD)-OCT) system , working at 840 nm (B-scan mode). Results. The OCT investigation of the temporo-mandibular joint discs revealed a homogeneous microstructure. The longer wavelength of the TD-OCT offers a higher penetration depth (2,5 mm in air), which is important for the analysis of the pars posterior, while the FD-OCT is much faster. Conclusions: OCT is a promising imaging method for the microstructural characterization of the temporo-mandibular disc.

  2. Multidirectional testing of one- and two-level ProDisc-L versus simulated fusions.

    PubMed

    Panjabi, Manohar; Henderson, Gweneth; Abjornson, Celeste; Yue, James

    2007-05-20

    An in vitro human cadaveric biomechanical study. To evaluate intervertebral rotation changes due to lumbar ProDisc-L compared with simulated fusion, using follower load and multidirectional testing. Artificial discs, as opposed to the fusions, are thought to decrease the long-term accelerated degeneration at adjacent levels. A biomechanical assessment can be helpful, as the long-term clinical evaluation is impractical. Six fresh human cadaveric lumbar specimens (T12-S1) underwent multidirectional testing in flexion-extension, bilateral lateral bending, and bilateral torsion using the Hybrid test method. First, intact specimen total range of rotation (T12-S1) was determined. Second, using pure moments again, this range of rotation was achieved in each of the 5 constructs: A) ProDisc-L at L5-S1; B) fusion at L5-S1; C) ProDisc-L at L4-L5 and fusion at L5-S1; D) ProDisc-L at L4-L5 and L5-S1; and E) 2-level fusion at L4-L5 to L5-S1. Significant changes in the intervertebral rotations due to each construct were determined at the operated and nonoperated levels using repeated measures single factor ANOVA and Bonferroni statistical tests (P < 0.05). Adjacent-level effects (ALEs) were defined as the percentage changes in intervertebral rotations at the nonoperated levels due to the constructs. One- and 2-level ProDisc-L constructs showed only small ALE in any of the 3 rotations. In contrast, 1- and 2-level fusions showed increased ALE in all 3 directions (average, 7.8% and 35.3%, respectively, for 1 and 2 levels). In the disc plus fusion combination (construct C), the ALEs were similar to the 1-level fusion alone. In general, ProDisc-L preserved physiologic motions at all spinal levels, while the fusion simulations resulted in significant ALE.

  3. Hybrid testing of lumbar CHARITE discs versus fusions.

    PubMed

    Panjabi, Manohar; Malcolmson, George; Teng, Edward; Tominaga, Yasuhiro; Henderson, Gweneth; Serhan, Hassan

    2007-04-20

    An in vitro human cadaveric biomechanical study. To quantify effects on operated and other levels, including adjacent levels, due to CHARITE disc implantations versus simulated fusions, using follower load and the new hybrid test method in flexion-extension and bilateral torsion. Spinal fusion has been associated with long-term accelerated degeneration at adjacent levels. As opposed to the fusion, artificial discs are designed to preserve motion and diminish the adjacent-level effects. Five fresh human cadaveric lumbar specimens (T12-S1) underwent multidirectional testing in flexion-extension and bilateral torsion with 400 N follower load. Intact specimen total ranges of motion were determined with +/-10 Nm unconstrained pure moments. The intact range of motion was used as input for the hybrid tests of 5 constructs: 1) CHARITE disc at L5-S1; 2) fusion at L5-S1; 3) CHARITE discs at L4-L5 and L5-S1; 4) CHARITE disc at L4-L5 and fusion at L5-S1; and 5) 2-level fusion at L4-L5-S1. Using repeated-measures single factor analysis of variance and Bonferroni statistical tests (P < 0.05), intervertebral motion redistribution of each construct was compared with the intact. In flexion-extension, 1-level CHARITE disc preserved motion at the operated and other levels, while 2-level CHARITE showed some amount of other-level effects. In contrast, 1- and 2-level fusions increased other-level motions (average, 21.0% and 61.9%, respectively). In torsion, both 1- and 2-level discs preserved motions at all levels. The 2-level simulated fusion increased motions at proximal levels (22.9%), while the 1-level fusion produced no significant changes. In general, CHARITE discs preserved operated- and other-level motions. Fusion simulations affected motion redistribution at other levels, including adjacent levels.

  4. Therapeutic effects of naringin on degenerative human nucleus pulposus cells for discogenic low back pain.

    PubMed

    Li, Nianhu; Whitaker, Camden; Xu, Zhanwang; Heggeness, Michael; Yang, Shang-You

    2016-10-01

    Over half the population of the world will suffer from moderate or severe low back pain (LBP) during their life span. Studies have shown that naringin, a major flavonoid in grapefruit and an active compound extracted from a Chinese herbal medicine (Rhizoma Drynariae) possesses many pharmacological effects. The aim of this study was to evaluate the influence of naringin on the growth of degenerative human nucleus pulposus (NP) cells, and its repair effects on protein and gene expressions of the cells. This was an in vitro investigation of the human NP cells isolated from degenerated intervertebral discs that were interacted with various concentrated of naringin. This study was exempted by the institutional Human Subjects Committee-2, University of Kansas School of Medicine-Wichita. Degenerative human NP cells were isolated from intervertebral discs of patients with discogenic LBP and cultured at 37°C with 5% CO 2 . The proliferation of NP cells was determined following treatment with various concentrations of naringin. The protein expressions of tumor necrosis factor-α (TNF-α) and Bone morphogenetic protein 2 (BMP-2) were tested using enzyme-linked immunosorbent assay. Aggrecan and type II collagen levels were measured by immunohistological staining. Further examination of the gene expression of aggrecan, Sox6, and MMP3 was performed after intervention with naringin for 3 days. The human NP cells were successfully propagated in culture and stained positive with toluidine blue staining. Naringin effectively enhanced the cell proliferation at an optimal concentration of 20 µg/mL. Naringin treatment resulted in significant inhibition of TNF-α, but elevated protein expressions of BMP-2, collagen II, and aggrecan. Naringin also increased disc matrix gene activity including aggrecan and Sox6, and decreased the gene expression of MMP3. Naringin effectively promotes the proliferation of degenerative human NP cells and improves the recuperation of the cells from degeneration by increasing expression of aggrecan, BMP-2, and Sox6 while inhibiting the expression of TNF-α and MMP3. This study suggests that naringin may represent an alternative therapeutic agent for disc degeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. The chemokine, CXCL16, and its receptor, CXCR6, are constitutively expressed in human annulus fibrosus and expression of CXCL16 is up-regulated by exposure to IL-1ß in vitro.

    PubMed

    Gruber, H E; Marrero, E; Ingram, J A; Hoelscher, G L; Hanley, E N

    2017-01-01

    Chemokines are an important group of soluble molecules with specialized functions in inflammation. The roles of many specialized chemokines and their receptors remain poorly understood in the human intervertebral disc. We investigated CXCL16 and its receptor, CXCR6, to determine their immunolocalization in disc tissue and their presence following exposure of cultured human annulus fibrosus cells to proinflammatory cytokines. CXCL16 is a marker for inflammation; it also can induce hypoxia-inducible factor 1α (HIF-1α), which is a phenotypic marker of heathy nucleus pulposus tissue. We found CXCL16 and CXCR6 immunostaining in many cells of the annulus portion of the disc. Molecular studies showed that annulus fibrosus cells exposed to IL-1ß, but not TNF-α, exhibited significant up-regulation of CXCL16 expression vs. control cells. There was no significant difference in the percentage of annulus cells that exhibited immunolocalization of CXCL16 in grade I/II, grade III or grade IV/V specimens. The presence of CXCL16 and its receptor, CXCR6, in the annulus in vivo suggests the need for future research concerning the role of this chemokine in proinflammatory functions, HIF-1α expression and disc vascularization.

  6. [Partial nucleotomy of the ovine disc as an in vivo model for disc degeneration].

    PubMed

    Guder, E; Hill, S; Kandziora, F; Schnake, K J

    2009-01-01

    The aim of this study was to develop a suitable animal model for the clinical situation of progressive disc degeneration after microsurgical nucleotomy. Twenty sheep underwent standardised partial anterolateral nucleotomy at lumbar segment 3/4. After randomisation, 10 animals were sacrificed after 12 weeks (group 1). The remainder was sacrificed after 48 weeks (group 2). For radiological examination X-rays, MRI and post-mortem CT scans were performed. Lumbar discs L 3/4 with adjacent subchondral trabecular bone were harvested and analysed macroscopically and histologically. An image-analysing computer program was used to measure histomorphometric indices of bone structure. 17 segments could be evaluated. After 12 weeks (group 1) histological and radiological degenerative disc changes were noted. After 48 weeks (group 2), radiological signs in MRI reached statistical significance. Furthermore, group 2 showed significantly more osteophyte formations in CT scans. Histomorphometric changes of the disc and the adjacent vertebral bone structure suggest a significant progressive degenerative remodelling. The facet joints did not show any osteoarthrosis after 48 weeks. Partial nucleotomy of the ovine lumbar disc leads to radiological and histological signs of disc degeneration similar to those seen in humans after microsurgical nucleotomy. The presented in vivo model may be useful to evaluate new orthopaedic treatment strategies.

  7. Feasibility of using interstitial ultrasound for intradiscal thermal therapy: a study in human cadaver lumbar discs

    NASA Astrophysics Data System (ADS)

    Nau, William H.; Diederich, Chris J.; Shu, Richard

    2005-06-01

    Application of heat in the spine using resistive wire heating devices is currently being used clinically for minimally invasive treatment of discogenic low back pain. In this study, interstitial ultrasound was evaluated for the potential to heat intradiscal tissue more precisely by directing energy towards the posterior annular wall while avoiding vertebral bodies. Two single-element directional applicator design configurations were tested: a 1.5 mm OD direct-coupled (DC) applicator which can be implanted directly within the disc, and a catheter-cooled (CC) applicator which is inserted in a 2.4 mm OD catheter with integrated water cooling and implanted within the disc. The transducers were sectored to produce 90° spatial heating patterns for directional control. Both applicator configurations were evaluated in four human cadaver lumbar disc motion segments. Two heating protocols were employed in this study in which the temperature measured 5 mm away from the applicator was controlled to either T = 52 °C, or T > 70 °C for the treatment period. These temperatures (thermal doses) are representative of those required for thermal necrosis of in-growing nociceptor nerve fibres and disc cellularity alone, or with coagulation and restructuring of annular collagen in the high-temperature case. Steady-state temperature maps, and thermal doses (t43) were used to assess the thermal treatments. Results from these studies demonstrated the capability of controlling temperature distributions within selected regions of the disc and annular wall using interstitial ultrasound, with minimal vertebral end-plate heating. While directional heating was demonstrated with both applicator designs, the CC configuration had greater directional heating capabilities and offered better temperature control than the DC configuration, particularly during the high-temperature protocol. Further, ultrasound energy was capable of penetrating within the highly attenuating disc tissue to produce more extensive radial thermal penetration, lower maximum intradiscal temperature, and shorter treatment times than can be achieved with current clinical intradiscal heating technology. Thus, interstitial ultrasound offers potential as a more precise and faster heating modality for the clinical management of low back pain.

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

    PubMed

    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.

  9. MRI Quantification of Human Spine Cartilage Endplate Geometry: Comparison With Age, Degeneration, Level, and Disc Geometry

    PubMed Central

    DeLucca, John F.; Peloquin, John M.; Smith, Lachlan J.; Wright, Alexander C.; Vresilovic, Edward J.; Elliott, Dawn M.

    2017-01-01

    Geometry is an important indicator of disc mechanical function and degeneration. While the geometry and associated degenerative changes in the nucleus pulposus and the annulus fibrosus are well-defined, the geometry of the cartilage endplate (CEP) and its relationship to disc degeneration are unknown. The objectives of this study were to quantify CEP geometry in three dimensions using an MRI FLASH imaging sequence and evaluate relationships between CEP geometry and age, degeneration, spinal level, and overall disc geometry. To do so, we assessed the MRI-based measurements for accuracy and repeatability. Next, we measured CEP geometry across a larger sample set and correlated CEP geometric parameters to age, disc degeneration, level, and disc geometry. The MRI-based measures resulted in thicknesses (0.3–1 mm) that are comparable to prior measurements of CEP thickness. CEP thickness was greatest at the anterior/posterior (A/P) margins and smallest in the center. The CEP A/P thickness, axial area, and lateral width decreased with age but were not related to disc degeneration. Age-related, but not degeneration-related, changes in geometry suggest that the CEP may not follow the progression of disc degeneration. Ultimately, if the CEP undergoes significant geometric changes with aging and if these can be related to low back pain, a clinically feasible translation of the FLASH MRI-based measurement of CEP geometry presented in this study may prove a useful diagnostic tool. PMID:27232974

  10. Characterization and human gingival fibroblasts biocompatibility of hydroxyapatite/PMMA nanocomposites for provisional dental implant restoration

    NASA Astrophysics Data System (ADS)

    Zhang, Jingchao; Liao, Juan; Mo, Anchun; Li, Yubao; Li, Jidong; Wang, Xuejiang

    2008-11-01

    The aim of this study was to determine nHA/PMMA composites (H/P) in an optimal ratio with improved cytocompatibility as well as valid physical properties for provisional dental implant restoration. 20 wt.%, 30 wt.%, 40 wt.% and 50 wt.% H/P were developed and characterized using XPS, bending strength test and SEM. Human gingival fibroblasts cultured in extracts or directly on sample discs were investigated by fluorescent staining and MTT assay. Chemical integration in nHA/PMMA interface was indicated by XPS. Typical fusiform cells with adhesion spots were detected on H/P discs. MTT results also indicated higher cell viability in 30 wt.% and 40 wt.% H/P discs ( P < 0.05). We conclude that nHA addition to PMMA enhances cytocompatibility and the optimal nHA/PMMA ratio for provisional fixed crowns (PFC) is 0.4:1.

  11. Human cells derived from degenerate intervertebral discs respond differently to those derived from non-degenerate intervertebral discs following application of dynamic hydrostatic pressure.

    PubMed

    Le Maitre, Christine Lyn; Frain, Jennie; Fotheringham, Andrew P; Freemont, Anthony J; Hoyland, Judith Alison

    2008-01-01

    The intervertebral disc (IVD) is one of the body's most important load-bearing structures with the major mechanical force experienced in the nucleus pulposus (NP) being hydrostatic pressure (HP). Physiological levels of HP have an anabolic effect on IVD matrix metabolism in cells derived from non-degenerate animal and herniated IVD while excessive HP has a catabolic effect. However, no studies have investigated the response of non-degenerate and degenerate human disc cells derived from non-herniated discs to HP. Here we investigate the effect of physiological HP on such cells using a novel loading rig. Human IVD cells (both NP and AF) cultured in alginate were subjected to dynamic HP (0.8-1.7 MPa 0.5 Hz) for 2 h. Cell viability was assessed, RNA extracted and qRT-PCR for 18 s, c-fos, Sox-9, collagen type II, aggrecan and MMP-3 performed. Cell viability was unaffected by the loading regime. In non-degenerate NP cells, HP increased c-fos, aggrecan, Sox-9 and collagen type II (significantly so in the case of c-fos and aggrecan), but not MMP-3 gene expression. In contrast, application of HP to AF or degenerate NP cells had no effect on target gene expression. Our data shows that cells obtained from the healthy NP respond to dynamic HP by up-regulating genes indicative of healthy matrix homeostasis. However, responses differed in degenerate NP cells suggesting that an altered mechanotransduction pathway may be operational.

  12. Symbiotic Bacteria Associated with Stomach Discs of Human Lice▿ †

    PubMed Central

    Sasaki-Fukatsu, Kayoko ; Koga, Ryuichi; Nikoh, Naruo; Yoshizawa, Kazunori; Kasai, Shinji; Mihara, Minoru; Kobayashi, Mutsuo; Tomita, Takashi; Fukatsu, Takema

    2006-01-01

    The symbiotic bacteria associated with the stomach disc, a large aggregate of bacteriocytes on the ventral side of the midgut, of human body and head lice were characterized. Molecular phylogenetic analysis of 16S rRNA gene sequences showed that the symbionts formed a distinct and well-defined clade in the Gammaproteobacteria. The sequences exhibited AT-biased nucleotide composition and accelerated molecular evolution. In situ hybridization revealed that in nymphs and adult males, the symbiont was localized in the stomach disc, while in adult females, the symbiont was not in the stomach disc but in the lateral oviducts and the posterior pole of the oocytes due to female-specific symbiont migration. We propose the designation “Candidatus Riesia pediculicola” for the louse symbionts. PMID:16950915

  13. Biomechanical comparison of a two-level Maverick disc replacement with a hybrid one-level disc replacement and one-level anterior lumbar interbody fusion.

    PubMed

    Erkan, Serkan; Rivera, Yamil; Wu, Chunhui; Mehbod, Amir A; Transfeldt, Ensor E

    2009-10-01

    Multilevel lumbar disc disease (MLDD) is a common finding in many patients. Surgical solutions for MLDD include fusion or disc replacement. The hybrid model, combining fusion and disc replacement, is a potential alternative for patients who require surgical intervention at both L5-S1 and L4-L5. The indications for this hybrid model could be posterior element insufficiency, severe facet pathology, calcified ligamentum flavum, and subarticular disease confirming spinal stenosis at L5-S1 level, or previous fusion surgery at L5-S1 and new symptomatic pathology at L4-L5. Biomechanical data of the hybrid model with the Maverick disc and anterior fusion are not available in the literature. To compare the biomechanical properties of a two-level Maverick disc replacement at L4-L5, L5-S1, and a hybrid model consisting of an L4-L5 Maverick disc replacement with an L5-S1 anterior lumbar interbody fusion using multidirectional flexibility test. An in vitro human cadaveric biomechanical study. Six fresh human cadaveric lumbar specimens (L4-S1) were subjected to unconstrained load in axial torsion (AT), lateral bending (LB), flexion (F), extension (E), and flexion-extension (FE) using multidirectional flexibility test. Four surgical treatments-intact, one-level Maverick at L5-S1, two-level Maverick between L4 and S1, and the hybrid model (anterior fusion at L5-S1 and Maverick at L4-L5) were tested in sequential order. The range of motion of each treatment was calculated. The Maverick disc replacement slightly reduced intact motion in AT and LB at both levels. The total FE motion was similar to the intact motion. However, the E motion is significantly increased (approximately 50% higher) and F motion is significantly decreased (30%-50% lower). The anterior fusion using a cage and anterior plate significantly reduced spinal motion compared with the condition (p<.05). No significant differences were found between two-level Maverick disc prosthesis and the hybrid model in terms of all motion types at L4-L5 level (p>.05). The Maverick disc preserved total motion but altered the motion pattern of the intact condition. This result is similar to unconstrained devices such as Charité. The motion at L4-L5 of the hybrid model is similar to that of two-level Maverick disc replacement. The fusion procedure using an anterior plate significantly reduced intact motion. Clinical studies are recommended to validate the efficacy of the hybrid model.

  14. Propionibacterium acnes infected intervertebral discs cause vertebral bone marrow lesions consistent with Modic changes.

    PubMed

    Dudli, Stefan; Liebenberg, Ellen; Magnitsky, Sergey; Miller, Steve; Demir-Deviren, Sibel; Lotz, Jeffrey C

    2016-08-01

    Modic type I change (MC1) are vertebral bone marrow lesions adjacent to degenerated discs that are specific for discogenic low back pain. The etiopathogenesis is unknown, but occult discitis, in particular with Propionibacteria acnes (P. acnes), has been suggested as a possible etiology. If true, antibiotic therapy should be considered for patients with MC1. However, this hypothesis is controversial. While some studies report up to 40% infection rate in herniated discs, others fail to detect infected discs and attribute reports of positive cultures to contamination during sampling procedure. Irrespective of the clinical controversy, whether it is biologically plausible for P. acnes to cause MC1 has never been investigated. Therefore, the objective of this study was to test if P. acnes can proliferate within discs and cause reactive changes in the adjacent bone marrow. P. acnes was aseptically isolated from a symptomatic human L4/5 disc with MC1 and injected into rat tail discs. We demonstrate proliferation of P. acnes and up-regulation of IL-1 and IL-6 within three days of inoculation. At day-7, disc degeneration was apparent along with fibrotic endplate erosion. TNF-α immunoreactivity was enhanced within the effected endplates along with cellular infiltrates. The bone marrow appeared normal. At day-14, endplates and trabecular bone close to the disc were almost completely resorbed and fibrotic tissue extended into the bone marrow. T-cells and TNF-α immunoreactivity were identified at the disc/marrow junction. On MRI, bone marrow showed MC1-like changes. In conclusion, P. acnes proliferate within the disc, induce degeneration, and cause MC1-like changes in the adjacent bone marrow. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1447-1455, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. [In situ analysis of pathomechanisms of human intervertebral disc degeneration].

    PubMed

    Weiler, C

    2013-11-01

    Low back pain is one of the major causes of pain and disability in the western world, with a constantly rising life-time prevalence of approximately 60-85 %. Degeneration of the intervertebral disc is believed to be a major cause of low back pain. Semiquantitative macroscopic and microscopic changes of the intervertebral disc were assessed and classified. Furthermore additional methods, such as immunohistochemistry, in situ hybridization and in situ zymography were used to analyze phenotypic cellular and matrix changes. We have developed and tested a practicable, valid and reliable histological classification system for lumbar discs which can serve as a morphological reference framework to allow more sophisticated molecular biological studies on the pathogenesis of ageing and degeneration of discs. Secondly, we were able to demonstrate that intrinsic (genetic) and extrinsic (e.g. overweight) factors have a profound effect on the process of disc degeneration. Cells with a notochord-like phenotype are present in a considerable fraction of adult lumbar intervertebral discs. The presence of these cells is associated with distinct features of (early) age-related disc degeneration. During the process of disc degeneration, the intervertebral disc shows a progressive and significant reduction in height due to tissue resorption. This matrix loss is related to an imbalance between matrix synthesis and degradation. During this process an inflammatory reaction takes place and resident disc cells are causatively involved. In summary, disc degeneration is a multifactorial disease with a strong intrinsic (hereditary) and extrinsic (e.g. mechanical factors) background. The process starts as early as in the second decade of life and shows high interindividual differences. The loss of regenerative capacity in the intervertebral disc is probably related to the loss of stem cells, e.g. notochord-like cells. Resident disc cells are involved in the inflammatory reaction with increased matrix degradation, resorption and reduced matrix synthesis.

  16. Regionally variant collagen alignment correlates with viscoelastic properties of the disc of the human temporomandibular joint.

    PubMed

    Gutman, Shawn; Kim, Daniel; Tarafder, Solaiman; Velez, Sergio; Jeong, Julia; Lee, Chang H

    2018-02-01

    To determine the regionally variant quality of collagen alignment in human TMJ discs and its statistical correlation with viscoelastic properties. For quantitative analysis of the quality of collagen alignment, horizontal sections of human TMJ discs with Pricrosirius Red staining were imaged under circularly polarized microscopy. Mean angle and angular deviation of collagen fibers in each region were analyzed using a well-established automated image-processing for angular gradient. Instantaneous and relaxation moduli of each disc region were measured under stress-relaxation test both in tensile and compression. Then Spearman correlation analysis was performed between the angular deviation and the moduli. To understand the effect of glycosaminoglycans on the correlation, TMJ disc samples were treated by chondroitinase ABC (C-ABC). Our imaging processing analysis showed the region-variant direction of collagen alignment, consistently with previous findings. Interestingly, the quality of collagen alignment, not only the directions, was significantly different in between the regions. The angular deviation of fiber alignment in the anterior and intermediate regions were significantly smaller than the posterior region. Medial and lateral regions showed significantly bigger angular deviation than all the other regions. The regionally variant angular deviation values showed statistically significant correlation with the tensile instantaneous modulus and the relaxation modulus, partially dependent on C-ABC treatment. Our findings suggest the region-variant degree of collagen fiber alignment is likely attributed to the heterogeneous viscoelastic properties of TMJ disc that may have significant implications in development of regenerative therapy for TMJ disc. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Upregulation of BDNF and NGF in cervical intervertebral discs exposed to painful whole-body vibration.

    PubMed

    Kartha, Sonia; Zeeman, Martha E; Baig, Hassam A; Guarino, Benjamin B; Winkelstein, Beth A

    2014-09-01

    In vivo study defining expression of the neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in cervical intervertebral discs after painful whole-body vibration (WBV). The goal of this study is to determine if BDNF and NGF are expressed in cervical discs after painful WBV in a rat model. WBV is a possible source of neck pain and has been implicated as increasing the risk for disc disorders. Typically, aneural regions of painful human lumbar discs exhibit hyperinnervation, suggesting nerve ingrowth as potentially contributing to disc degeneration and pain. BDNF and NGF are upregulated in painfully degenerate lumbar discs and hypothesized to contribute to this pathology. Male Holtzman rats underwent 7 days of repeated WBV (15 Hz, 30 min/d) or sham exposures, followed by 7 days of rest. Cervical discs were collected for analysis of BDNF and NGF expression through RT-qPCR and Western blot analysis. Immunohistochemistry also evaluated their regional expression in the disc. Vibration significantly increases BDNF messenger ribonucleic acid (mRNA) levels (P=0.036), as well as total-NGF mRNA (P=0.035). Protein expression of both BDNF (P=0.006) and the 75-kDa NGF (P=0.045) increase by nearly 4- and 10-fold, respectively. Both BDNF mRNA (R=0.396; P=0.012) and protein (R=0.280; P=0.035) levels are significantly correlated with the degree of behavioral sensitivity (i.e., pain) at day 14. Total-NGF mRNA is also significantly correlated with the extent of behavioral sensitivity (R=0.276; P=0.044). Both neurotrophins are most increased in the inner annulus fibrosus and nucleus pulposus. The increases in BDNF and NGF in the cervical discs after painful vibration are observed in typically aneural regions of the disc, consistent with reports of its hyperinnervation. Yet, the induction of nerve ingrowth into the disc was not explicitly investigated. Neurotrophin expression also correlates with behavioral sensitivity, suggesting a role for both neurotrophins in the development of disc pain. N/A.

  18. In vitro and in silico investigations of disc nucleus replacement

    PubMed Central

    Reitmaier, Sandra; Shirazi-Adl, Aboulfazl; Bashkuev, Maxim; Wilke, Hans-Joachim; Gloria, Antonio; Schmidt, Hendrik

    2012-01-01

    Currently, numerous hydrogels are under examination as potential nucleus replacements. The clinical success, however, depends on how well the mechanical function of the host structure is restored. This study aimed to evaluate the extent to and mechanisms by which surgery for nucleus replacements influence the mechanical behaviour of the disc. The effects of an annulus defect with and without nucleus replacement on disc height and nucleus pressure were measured using 24 ovine motion segments. The following cases were considered: intact; annulus incision repaired by suture and glue; annulus incision with removal and re-implantation of nucleus tissue repaired by suture and glue or plug. To identify the likely mechanisms observed in vitro, a finite-element model of a human disc (L4–L5) was employed. Both studies were subjected to physiological cycles of compression and recovery. A repaired annulus defect did not influence the disc behaviour in vitro, whereas additional nucleus removal and replacement substantially decreased disc stiffness and nucleus pressure. Model predictions demonstrated the substantial effects of reductions in replaced nucleus water content, bulk modulus and osmotic potential on disc height loss and pressure, similar to measurements. In these events, the compression load transfer in the disc markedly altered by substantially increasing the load on the annulus when compared with the nucleus. The success of hydrogels for nucleus replacements is not only dependent on the implant material itself but also on the restoration of the environment perturbed during surgery. The substantial effects on the disc response of disruptions owing to nucleus replacements can be simulated by reduced nucleus water content, elastic modulus and osmotic potential. PMID:22337630

  19. Notochordal cells in the adult intervertebral disc: new perspective on an old question.

    PubMed

    Risbud, Makarand V; Shapiro, Irving M

    2011-01-01

    The intervertebral disc is a tissue positioned between each of the vertebrae that accommodates applied biomechanical forces to the spine. The central compartment of the disc contains the nucleus pulposus (NP) which is enclosed by the annulus fibrosus and the endplate cartilage.The NP is derived from the notochord, a rod-like structure of mesodermal origin. Development of the notochord is tightly regulated by interactive transcription factors and target genes. Since a number of these molecules are unique they have be used for cell lineage and fate mapping studies of tissues of the intervertebral disc. These studies have shown that in a number of species including human, NP tissue retains notochordal cells throughout life. In the adult NP, there are present both large and small notochordal cells, as well as a progenitor cell population which can differentiate along the mesengenic pathway. Since tissue renewal in the intervertebral disc is dependent on the ability of these cells to commit to the NP lineage and undergo terminal differentiation, studies have been performed to assess which signaling pathways may regulate these activities. The notch signaling pathway is active in the intervertebral disc and is responsive to hypoxia, probably through HIF-1a. From a disease viewpoint, it is hypothesized that an oxemic shift, possibly mediated by alterations in the vascular supply to the tissues of the disc would be expected to lead to a failure in notochordal progenitor cell activation and a decrease in the number of differentiated cells. In turn, this would lead to decrements in function and enhancement of the effect of agents that are known to promote disc degeneration.

  20. A preliminary in vitro study into the use of IL-1Ra gene therapy for the inhibition of intervertebral disc degeneration

    PubMed Central

    Le Maitre, Christine L; Freemont, Anthony J; Hoyland, Judith A

    2006-01-01

    Conventional therapies for low back pain (LBP) are purely symptomatic and do not target the cause of LBP, which in approximately 40% of cases is caused by degeneration of the intervertebral disc (DIVD). Targeting therapies to inhibit the process of degeneration would be a potentially valuable treatment for LBP. There is increasing evidence for a role for IL-1 in DIVD. A natural inhibitor of IL-1 exists, IL-1Ra, which would be an ideal molecular target for inhibiting IL-1-mediated effects involved in DIVD and LBP. In this study, the feasibility of ex vivo gene transfer of IL-1Ra to the IVD was investigated. Monolayer and alginate cultures of normal and degenerate human intervertebral disc (IVD) cells were infected with an adenoviral vector carrying the IL-1Ra gene (Ad-IL-1Ra) and protein production measured using an enzyme-linked immunosorbent assay. The ability of these infected cells to inhibit the effects of IL-1 was also investigated. In addition, normal and degenerate IVD cells infected with Ad-IL-1Ra were injected into degenerate disc tissue explants and IL-1Ra production in these discs was assessed. This demonstrated that both nucleus pulposus and annulus fibrosus cells infected with Ad-IL-1Ra produced elevated levels of IL-1Ra for prolonged time periods, and these infected cells were resistant to IL-1. When the infected cells were injected into disc explants, IL-1Ra protein expression was increased which was maintained for 2 weeks of investigation. This in vitro study has shown that the use of ex vivo gene transfer to degenerate disc tissue is a feasible therapy for the inhibition of IL-1-mediated events during disc degeneration. PMID:16436110

  1. Human Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease

    ClinicalTrials.gov

    2017-09-14

    Lumbar Degenerative Disc Disease; Spinal Stenosis; Spondylolisthesis; Spondylosis; Intervertebral Disk Displacement; Intervertebral Disk Degeneration; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Spondylolysis

  2. Insulin released from titanium discs with insulin coatings-Kinetics and biological activity.

    PubMed

    Malekzadeh, B Ö; Ransjo, M; Tengvall, P; Mladenovic, Z; Westerlund, A

    2017-10-01

    Local administration of insulin from a titanium surface has been demonstrated to increase bone formation in non-diabetic rats. The authors hypothesized that insulin was released from the titanium surface and with preserved biological activity after the release. Thus, in the present in vitro study, human recombinant insulin was immobilized onto titanium discs, and the insulin release kinetics was evaluated using Electro-chemiluminescence immunoassay. Neutral Red uptake assay and mineralization assay were used to evaluate the biological effects of the released insulin on human osteoblast-like MG-63 cells. The results confirmed that insulin was released from titanium surfaces during a six-week period. Etching the disc prior to insulin coating, thickening of the insulin coating and incubation of the discs in serum-enriched cell culture medium increased the release. However, longer storage time decreased the release of insulin. Furthermore, the released insulin had retained its biological activity, as demonstrated by the significant increase in cell number and a stimulated mineralization process, upon exposure to released insulin. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1847-1854, 2017. © 2016 Wiley Periodicals, Inc.

  3. Substance P Receptor Antagonist Suppresses Inflammatory Cytokine Expression in Human Disc Cells.

    PubMed

    Kepler, Christopher K; Markova, Dessislava Z; Koerner, John D; Mendelis, Joseph; Chen, Chiu-Ming; Vaccaro, Alexander R; Risbud, Makarand V; Albert, Todd J; Anderson, D Greg

    2015-08-15

    Laboratory study. To evaluate whether blockade of the Substance P (SP) NK1R attenuates its proinflammatory effect on human intervertebral disc cells (IVD), and to evaluate the signaling pathways associated with SP. SP and its receptors are expressed in human IVD cells, and cause upregulation of inflammatory mediators; however, the effects of blocking these receptors have not been studied in human IVD cells. Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were expanded in monolayer, and then suspended in alginate beads. The alginate beads were treated with culture medium first containing a high affinity NK1R antagonist (L-760735) at different concentrations, and then with medium containing both NK1R antagonist and SP at 2 concentrations. Ribonucleic acid was isolated and transcribed into cDNA. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to evaluate expression of interleukin (IL)-1β, IL-6, and IL-8. Western blot analysis was performed to examine levels of the phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB p65). The cells were pretreated with specific inhibitors of p38 (SB203580), ERK1/2 (PD98059), and p65 (SM7368) and then stimulated with SP. We detected expression of NK1R, neurokinin receptor 2 (NK2R), and neurokinin receptor 3 (NK3R) in AF and NP cells. Treatment of disc cells with the NK1R antagonist was able to suppress expression of IL-1β, IL-6, and IL-8 in a dose-dependent manner. SP stimulation increased phosphorylation of p38-MAPK and ERK1/2, but not of NFκB p65. This indicates that p38-MAPK and ERK1/2 control SP-induced cytokine expression independently from NF-kB p65. Inhibition of p38 and ERK1/2 activation reduced SP-induced IL-6 production in human disc cells. NK1R is responsible for the proinflammatory effect of SP on IVD cells and this effect can be blocked by preventing binding of SP to NK1R. This study shows for the first time that SP mediates signaling in disc cells through NK1R and that SP activates the proinflammatory p38-MAPK and ERK1/2 pathways. 4.

  4. Early onset of disc degeneration in SM/J mice is associated with changes in ion transport systems and fibrotic events.

    PubMed

    Zhang, Ying; Xiong, Chi; Kudelko, Mateusz; Li, Yan; Wang, Cheng; Wong, Yuk Lun; Tam, Vivian; Rai, Muhammad Farooq; Cheverud, James; Lawson, Heather A; Sandell, Linda; Chan, Wilson C W; Cheah, Kathryn S E; Sham, Pak C; Chan, Danny

    2018-04-09

    Intervertebral disc degeneration (IDD) causes back pain and sciatica, affecting quality of life and resulting in high economic/social burden. The etiology of IDD is not well understood. Along with aging and environmental factors, genetic factors also influence the onset, progression and severity of IDD. Genetic studies of risk factors for IDD using human cohorts are limited by small sample size and low statistical power. Animal models amenable to genetic and functional studies of IDD provide desirable alternatives. Despite differences in size and cellular content as compared to human intervertebral discs (IVDs), the mouse is a powerful model for genetics and assessment of cellular changes relevant to human biology. Here, we provide evidence for early onset disc degeneration in SM/J relative to LG/J mice with poor and good tissue healing capacity respectively. In the first few months of life, LG/J mice maintain a relatively constant pool of notochordal-like cells in the nucleus pulposus (NP) of the IVD. In contrast, chondrogenic events are observed in SM/J mice beginning as early as one-week-old, with progressive fibrotic changes. Further, the extracellular matrix changes in the NP are consistent with IVD degeneration. Leveraging on the genomic data of two parental and two recombinant inbred lines, we assessed the genetic contribution to the NP changes and identified processes linked to the regulation of ion transport systems. Significantly, "transport" system is also in the top three gene ontology (GO) terms from a comparative proteomic analysis of the mouse NP. These findings support the potential of the SM/J, LG/J and their recombinant inbred lines for future genetic and biological analysis in mice and validation of candidate genes and biological relevance in human cohort studies. The proteomic data has been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD008784. Copyright © 2017. Published by Elsevier B.V.

  5. Glucosamine Supplementation Demonstrates a Negative Effect On Intervertebral Disc Matrix in an Animal Model of Disc Degeneration

    PubMed Central

    Jacobs, Lloydine; Vo, Nam; Coehlo, J. Paulo; Dong, Qing; Bechara, Bernard; Woods, Barrett; Hempen, Eric; Hartman, Robert; Preuss, Harry; Balk, Judith; Kang, James; Sowa, Gwendolyn

    2013-01-01

    Study Design Laboratory based controlled in vivo study Objective To determine the in vivo effects of oral glucosamine sulfate on intervertebral disc degeneration Summary of Background Data Although glucosamine has demonstrated beneficial effect in articular cartilage, clinical benefit is uncertain. A CDC report from 2009 reported that many patients are using glucosamine supplementation for low back pain (LBP), without significant evidence to support its use. Because disc degeneration is a major contributor of LBP, we explored the effects of glucosamine on disc matrix homeostasis in an animal model of disc degeneration. Methods Eighteen skeletally mature New Zealand White rabbits were divided into four groups: control, annular puncture, glucosamine, and annular puncture+glucosamine. Glucosamine treated rabbits received daily oral supplementation with 107mg/day (weight based equivalent to human 1500mg/day). Annular puncture surgery involved puncturing the annulus fibrosus (AF) of 3 lumbar discs with a 16G needle to induce degeneration. Serial MRIs were obtained at 0, 4, 8, 12, and 20 weeks. Discs were harvested at 20 weeks for determination of glycosaminoglycan(GAG) content, relative gene expression measured by RT-PCR, and histological analyses. Results The MRI index and NP area of injured discs of glucosamine treated animals with annular puncture was found to be lower than that of degenerated discs from rabbits not supplemented with glucosamine. Consistent with this, decreased glycosaminoglycan was demonstrated in glucosamine fed animals, as determined by both histological and GAG content. Gene expression was consistent with a detrimental effect on matrix. Conclusions These data demonstrate that the net effect on matrix in an animal model in vivo, as measured by gene expression, MRI, histology, and total proteoglycan is anti-anabolic. This raises concern over this commonly used supplement, and future research is needed to establish the clinical relevance of these findings. PMID:23324939

  6. SEM evaluation of human gingival fibroblasts growth onto CAD/CAM zirconia and veneering ceramic for zirconia

    PubMed Central

    Zizzari, Vincenzo; Borelli, Bruna; De Colli, Marianna; Tumedei, Margherita; Di Iorio, Donato; Zara, Susi; Sorrentino, Roberto; Cataldi, Amelia; Gherlone, Enrico Felice; Zarone, Fernando; Tetè, Stefano

    2013-01-01

    Summary Aim To evaluate the growth of Human Gingival Fibroblasts (HGFs) cultured onto sample discs of CAD/CAM zirconia and veneering ceramic for zirconia by means of Scanning Electron Microscope (SEM) analysis at different experimental times. Methods A total of 26 experimental discs, divided into 2 groups, were used: Group A) CAD/CAM zirconia (3Y-TZP) discs (n=13); Group B) veneering ceramic for zirconia discs (n=13). HGFs were obtained from human gingival biopsies, isolated and placed in culture plates. Subsequently, cells were seeded on experimental discs at 7,5×103/cm2 concentration and cultured for a total of 7 days. Discs were processed for SEM observation at 3h, 24h, 72h and 7 days. Results In Group A, after 3h, HGFs were adherent to the surface and showed a flattened profile. The disc surface covered by HGFs resulted to be wider in Group A than in Group B samples. At SEM observation, after 24h and 72h, differences in cell attachment were slightly noticeable between the groups, with an evident flattening of HGFs on both surfaces. All differences between Group A and group B became less significant after 7 days of culture in vitro. Conclusions SEM analysis of HGFs showed differences in terms of cell adhesion and proliferation, especially in the early hours of culture. Results showed a better adhesion and cell growth in Group A than in Group B, especially up to 72h in vitro. Differences decreased after 7 days, probably because of the rougher surface of CAD/CAM zirconia, promoting better cell adhesion, compared to the smoother surface of veneering ceramic. PMID:24611089

  7. A finite element model of the L4-L5-S1 human spine segment including the heterogeneity and anisotropy of the discs.

    PubMed

    Jaramillo, Hector E; Gómez, Lessby; García, Jose J

    2015-01-01

    With the aim to study disc degeneration and the risk of injury during occupational activities, a new finite element (FE) model of the L4-L5-S1 segment of the human spine was developed based on the anthropometry of a typical Colombian worker. Beginning with medical images, the programs CATIA and SOLIDWORKS were used to generate and assemble the vertebrae and create the soft structures of the segment. The software ABAQUS was used to run the analyses, which included a detailed model calibration using the experimental step-wise reduction data for the L4-L5 component, while the L5-S1 segment was calibrated in the intact condition. The range of motion curves, the intradiscal pressure and the lateral bulging under pure moments were considered for the calibration. As opposed to other FE models that include the L5-S1 disc, the model developed in this study considered the regional variations and anisotropy of the annulus as well as a realistic description of the nucleus geometry, which allowed an improved representation of experimental data during the validation process. Hence, the model can be used to analyze the stress and strain distributions in the L4-L5 and L5-S1 discs of workers performing activities such as lifting and carrying tasks.

  8. Developmental mechanisms of intervertebral disc and vertebral column formation.

    PubMed

    Lawson, Lisa Y; Harfe, Brian D

    2017-11-01

    The vertebral column consists of repeating units of ossified vertebrae that are adjoined by fibrocartilagenous intervertebral discs. These structures form from the embryonic notochord and somitic mesoderm. In humans, congenital malformations of the vertebral column include scoliosis, kyphosis, spina bifida, and Klippel Feil syndrome. In adulthood, a common malady affecting the vertebral column includes disc degeneration and associated back pain. Indeed, recent reports estimate that low back pain is the number one cause of disability worldwide. Our review provides an overview of the molecular mechanisms underlying vertebral column morphogenesis and intervertebral disc development and maintenance, with an emphasis on what has been gleaned from recent genetic studies in mice. The aim of this review is to provide a developmental framework through which vertebral column formation can be understood so that ultimately, research scientists and clinicians alike can restore disc health with appropriately designed gene and cell-based therapies. WIREs Dev Biol 2017, 6:e283. doi: 10.1002/wdev.283 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

  9. Fibrotic-like changes in degenerate human intervertebral discs revealed by quantitative proteomic analysis.

    PubMed

    Yee, A; Lam, M P Y; Tam, V; Chan, W C W; Chu, I K; Cheah, K S E; Cheung, K M C; Chan, D

    2016-03-01

    Intervertebral disc degeneration (IDD) can lead to symptomatic conditions including sciatica and back pain. The purpose of this study is to understand the extracellular matrix (ECM) changes in disc biology through comparative proteomic analysis of degenerated and non-degenerated human intervertebral disc (IVD) tissues of different ages. Seven non-degenerated (11-46 years of age) and seven degenerated (16-53 years of age) annulus fibrosus (AF) and nucleus pulposus (NP) samples were used. Proteins were extracted using guanidine hydrochloride, separated from large proteoglycans (PGs) by caesium chloride (CsCl) density gradient ultracentrifugation, and identified using liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS). For quantitative comparison, proteins were labeled with iTRAQ reagents. Collagen fibrils in the NP were assessed using scanning electron microscopy (SEM). In the AF, quantitative analysis revealed increased levels of HTRA1, COMP and CILP in degeneration when compared with samples from older individuals. Fibronectin showed increment with age and degeneration. In the NP, more CILP and CILP2 were present in degenerated samples of younger individuals. Reduced protein solubility was observed in degenerated and older non-degenerated samples correlated with an accumulation of type I collagen in the insoluble fibers. Characterization of collagen fibrils in the NP revealed smaller mean fibril diameters and decreased porosity in the degenerated samples. Our study identified distinct matrix changes associated with aging and degeneration in the intervertebral discs (IVDs). The nature of the ECM changes, together with observed decreased in solubility and changes in fibril diameter is consistent with a fibrotic-like environment. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  10. Extradiscal ultrasound thermal therapy (ExDUSTT): evaluation in ex vivo and in vivo spine models (Invited Paper)

    NASA Astrophysics Data System (ADS)

    Diederich, Chris J.; Kinsey, Adam; Nau, William H.; Shu, Richard; Lotz, Jeffrey C.

    2005-04-01

    The application of heat to intervertebral discs is being clinically investigated for the treatment of discogenic back pain. The purpose of this study was to develop and test the feasibility of small ultrasound applicators that can be endoscopically placed adjacent to the disc, and deliver heating energy into the disc without puncturing the annular wall. Prototype devices were fabricated using curvilinear transducers (2.5-3.5 mm wide x 10 mm long, 5.4 - 6.5 MHz) that produce a narrow penetrating beam extending along the length of the ultrasound element. The transducer was affixed to either a flexible or rigid delivery catheter, and enclosed within an asymmetric coupling balloon with water-cooling flow. Bench measurements demonstrated 35-60% acoustic efficiencies, high-power output capabilities, and lightly focused beam patterns. The heating characteristics of these devices were evaluated with ex vivo and in vivo experiments within lumbar and cervical spine segments from sheep models and human cadaveric spine. The applicators were positioned adjacent to the annular wall of the surgically exposed discs. Ultrasound energy was focused directly into the disc to avoid heating the vertebral bodies. Multi-point thermocouple probes were placed throughout the disc to characterize the resultant temperature distributions. These studies demonstrated that ultrasound energy from these applicators penetrated the annular wall of the disc, and produced thermal coagulative temperatures of >60-65°C as far as 10 mm into the tissue. This study also showed that lower power levels and temperatures delivered for 10 minutes can generate a cytotoxic thermal dose of t43°C >240 min penetrating 5-10 mm from the annular wall.

  11. ISSLS PRIZE IN CLINICAL SCIENCE 2017: Is infection the possible initiator of disc disease? An insight from proteomic analysis.

    PubMed

    Rajasekaran, S; Tangavel, Chitraa; Aiyer, Siddharth N; Nayagam, Sharon Miracle; Raveendran, M; Demonte, Naveen Luke; Subbaiah, Pramela; Kanna, Rishi; Shetty, Ajoy Prasad; Dharmalingam, K

    2017-05-01

    Proteomic and 16S rDNA analysis of disc tissues obtained in vivo. To address the controversy of infection as an aetiology for disc disorders through protein profiling. There is raging controversy over the presence of bacteria in human lumbar discs in vivo, and if they represent contamination or infection. Proteomics can provide valuable insight by identifying proteins signifying bacterial presence and, also host defence response proteins (HDRPs), which will confirm infection. 22 discs (15-disc herniations (DH), 5-degenerate (DD), 2-normal in MRI (NM) were harvested intraoperatively and immediately snap frozen. Samples were pooled into three groups and proteins extracted were analysed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Post identification, data analysis was performed using Uniprotdb, Pantherdb, Proteome discoverer and STRING network. Authentication for bacterial presence was performed by PCR amplification of 16S rDNA. LC-MS/MS analysis using Orbitrap showed 1103 proteins in DH group, compared to 394 in NM and 564 in DD. 73 bacterial specific proteins were identified (56 specific for Propionibacterium acnes; 17 for Staphylococcus epidermidis). In addition, 67 infection-specific HDRPs, unique or upregulated, such as Defensin, Lysozyme, Dermcidin, Cathepsin-G, Prolactin-Induced Protein, and Phospholipase-A2, were identified confirming presence of infection. Species-specific primers for P. acnes exhibited amplicons at 946 bp (16S rDNA) and 515 bp (Lipase) confirming presence of P. acnes in both NM discs, 11 of 15 DH discs, and all five DD discs. Bioinformatic search for protein-protein interactions (STRING) documented 169 proteins with close interactions (protein clustering co-efficient 0.7) between host response and degenerative proteins implying that infection may initiate degradation through Ubiquitin C. Our study demonstrates bacterial specific proteins and host defence proteins to infection which strengthen the hypothesis of infection as a possible initiator of disc disease. These results can lead to a paradigm shift in our understanding and management of disc disorders.

  12. Geometry of the intervertebral volume and vertebral endplates of the human spine.

    PubMed

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

    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 vertebrae, but current literature on vertebral disc geometry is very scarce or not suitable. In this study, existing CT-scans of 77 patients were analyzed to measure the intervertebral disc and vertebral endplate geometry of the lumbar spine. Ten adjacent points on both sides of the vertebrae (S1-superior to T12-inferior) and sagittal and transverse diameters were measured to describe the shape of the caudal and cranial vertebral planes of the vertebrae. It was found that the largest endplate depth is located in the middle or posterior regions of the vertebra, that there is a linear relationship between all inferior endplate depths and the endplate location (p < 0.0001) within the spinal column, and that the superior endplate depth increases with age by about 0.01 mm per year (p < 0.02). The wedge angle increases from T12-L1 to L5-S1. The results allow for improvement of the fit of intervertebral disc-prostheses to the vertebrae and optimized force transmission through the vertebral column.

  13. Argonaute-based programmable RNase as a tool for cleavage of highly-structured RNA.

    PubMed

    Dayeh, Daniel M; Cantara, William A; Kitzrow, Jonathan P; Musier-Forsyth, Karin; Nakanishi, Kotaro

    2018-06-12

    The recent identification and development of RNA-guided enzymes for programmable cleavage of target nucleic acids offers exciting possibilities for both therapeutic and biotechnological applications. However, critical challenges such as expensive guide RNAs and inability to predict the efficiency of target recognition, especially for highly-structured RNAs, remain to be addressed. Here, we introduce a programmable RNA restriction enzyme, based on a budding yeast Argonaute (AGO), programmed with cost-effective 23-nucleotide (nt) single-stranded DNAs as guides. DNA guides offer the advantage that diverse sequences can be easily designed and purchased, enabling high-throughput screening to identify optimal recognition sites in the target RNA. Using this DNA-induced slicing complex (DISC) programmed with 11 different guide DNAs designed to span the sequence, sites of cleavage were identified in the 352-nt human immunodeficiency virus type 1 5'-untranslated region. This assay, coupled with primer extension and capillary electrophoresis, allows detection and relative quantification of all DISC-cleavage sites simultaneously in a single reaction. Comparison between DISC cleavage and RNase H cleavage reveals that DISC not only cleaves solvent-exposed sites, but also sites that become more accessible upon DISC binding. This study demonstrates the advantages of the DISC system for programmable cleavage of highly-structured, functional RNAs.

  14. Organ culture bioreactors--platforms to study human intervertebral disc degeneration and regenerative therapy.

    PubMed

    Gantenbein, Benjamin; Illien-Jünger, Svenja; Chan, Samantha C W; Walser, Jochen; Haglund, Lisbet; Ferguson, Stephen J; Iatridis, James C; Grad, Sibylle

    2015-01-01

    In recent decades the application of bioreactors has revolutionized the concept of culturing tissues and organs that require mechanical loading. In intervertebral disc (IVD) research, collaborative efforts of biomedical engineering, biology and mechatronics have led to the innovation of new loading devices that can maintain viable IVD organ explants from large animals and human cadavers in precisely defined nutritional and mechanical environments over extended culture periods. Particularly in spine and IVD research, these organ culture models offer appealing alternatives, as large bipedal animal models with naturally occurring IVD degeneration and a genetic background similar to the human condition do not exist. Latest research has demonstrated important concepts including the potential of homing of mesenchymal stem cells to nutritionally or mechanically stressed IVDs, and the regenerative potential of "smart" biomaterials for nucleus pulposus or annulus fibrosus repair. In this review, we summarize the current knowledge about cell therapy, injection of cytokines and short peptides to rescue the degenerating IVD. We further stress that most bioreactor systems simplify the real in vivo conditions providing a useful proof of concept. Limitations are that certain aspects of the immune host response and pain assessments cannot be addressed with ex vivo systems. Coccygeal animal disc models are commonly used because of their availability and similarity to human IVDs. Although in vitro loading environments are not identical to the human in vivo situation, 3D ex vivo organ culture models of large animal coccygeal and human lumbar IVDs should be seen as valid alternatives for screening and feasibility testing to augment existing small animal, large animal, and human clinical trial experiments.

  15. Variations of the attachment of the superior head of human lateral pterygoid muscle.

    PubMed

    Antonopoulou, Maria; Iatrou, Ioannis; Paraschos, Alexandros; Anagnostopoulou, Sophia

    2013-09-01

    The superior head of the lateral pterygoid muscle (LPM), is closely related to the temporomandibular joint (TMJ) and plays a role in the aetiology of temporomandibular disorders. Increased activity of this muscle has been implicated in the anterior displacement of the TMJ disc. However, there is uncertainty about the manner of the LPM attachment to the disc-condyle complex. The aim of this study was to investigate the exact anatomy of the attachment of the superior head of the LPM (SLPM) to the disc-condyle complex of the TMJ. Thirty-six TMJs were examined - both sides of 18 Greek cadavers (eight males and 10 females, mean age 79.6 years). Examination of the attachment of the SLPM was undertaken viewed under the dissecting microscope. Variation in the attachment of the SLPM was categorized into three types: in type I, the SLPM inserted into the condyle and the disc-capsule complex (55.5%). In type II, the SLPM only inserted into the condyle (27.8%). In type III, the SLPM inserted purely into the disc-capsule complex (16.7%). This study demonstrates that there are three different attachment types of the SLPM to the disc-condyle complex. The type III variation could be involved in the TMJ pathology. The knowledge of the variations of the SLPM attachment could be useful for precise surgical and pharmaceutical approaches. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  16. Growth Inhibition Test for Identification of Mycoplasma Species Utilizing Dried Antiserum-Impregnated Paper Discs

    PubMed Central

    Stanbridge, Eric; Hayflick, Leonard

    1967-01-01

    The growth inhibition test for identifying Mycoplasma species has been modified by drying antibody-impregnated paper discs at 5 C. When stored at −20 C, these discs have been found to retain their inhibitory activity for longer than 7 months. Since these discs can be stored for long period of time, significant advantages over present methods result. When, for example, discs are arranged on a ring, a single test can be used for the identification of an unknown human species. Valuable antisera can be distributed to other laboratories on paper discs in much less volume than can fluid antiserum. Considerable savings of time result from prior preparation of many discs that can then be stored and used over a long period of time. The growth-inhibiting antibody is stable, and the activity is not enhanced by a heat-labile accessory factor from fresh guinea pig serum which increases the antibody titer in the metabolic inhibition test. Images PMID:5340308

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

    PubMed

    Sivan, Sarit-Sara; Wachtel, Ellen; Tsitron, Eve; Sakkee, Nico; van der Ham, Frits; Degroot, Jeroen; Roberts, Sally; Maroudas, Alice

    2008-04-04

    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 measured the ratio of the d- and l-isomers in collagen extracted from these tissues as a function of age between 16 and 77 years. For collagen taken from healthy discs, the fractional increase of d-Asp was found to be 6.74 x 10(-4)/year; for degenerate discs, the corresponding rate was 5.18 x 10(-4)/year. Using the racemization rate found previously for the stable population of collagen molecules in dentin, we found that the rate of collagen turnover (k(T)) in discs is not constant but rather a decreasing function of age. The average turnover rate in normal disc between the ages of 20 and 40 is 0.00728 +/- 0.00275/year, and that between the ages of 50 and 80 is 0.00323 +/- 0.000947/year, which correspond to average half-lives of 95 and 215 years, respectively. Turnover of collagen from degenerate discs may be more rapid than that found for normal discs; however, statistical analysis leaves this point uncertain. The finding of a similar correlation between the accumulation of d-Asp and that of pentosidine for three normal collagenous tissues further supports the idea that the accumulation of pentosidine in a particular tissue can, along with the racemization of aspartic acid, be used as a reliable measure of protein turnover.

  18. Minimally-invasive Ultrasound Devices for Treating Low Back Pain

    NASA Astrophysics Data System (ADS)

    Nau, William; Diederich, C.; Shu, R.; Kinsey, A.; Lotz, J.; Ferrier, W.; Sutton, J.; Pellegrino, R.

    2006-05-01

    Catheter-based ultrasound is being investigated for the potential to deliver heat to disc tissue for the treatment of discogenic low back pain. Two ultrasound applicator design configurations were tested: an intradiscal (IDUS) applicator which can be implanted directly within the disc, and an extradiscal (EDUS) applicator which is placed adjacent to the disc. In vitro heating trials were performed in human lumbar cadaveric disc segments instrumented with 24 thermocouples to obtain detailed maps of the temperature distributions. A low temperature elevation heating protocol in which the maximum temperature measured 5 mm away from the applicator is controlled to 52° C for the treatment period, and a high temperature elevation protocol (maximum temperature controlled to >70° C) were evaluated in this study. In vivo experiments were performed in sheep cervical spine using both applicator configurations, and both heating protocols. Steady-state temperature maps, and thermal doses (t43) calculated from the transient temperature data were used to assess regions of thermal damage within the disc. During the in vitro human disc studies using the high temperature protocol, temperatures were maintained at 71.5° ± 0.4°C 5 mm from an IDUS applicator implanted within the annular wall, with a maximum temperature (Tmax) of 78.6°C (t43 > 4.85 × 1010 min) measured 2 mm from the applicator. For the EDUS applicator, the temperature was maintained at 78.7° °C 5 mm from the applicator, with a Tmax of 86.3°C within 1 mm of the applicator surface. In the in vivo sheep studies, steady-state temperatures were maintained at 49.4° ± 0.3°C (t43 = 8.74 × 102 min) and 73.2° ± 0.6°C (t43 = 1.34 × 1010 min) with the IDUS applicator for the low and high temperature protocols, respectively. Using the EDUS applicator, temperatures were maintained at 54.4° ± 3.2°C (t43 = 4.11 × 104 min) and 69.4° ± 2.8°C (t43 = 2.81 × 109 min) for the two protocols. Directional heating was demonstrated with both applicator design configurations. Results from these studies demonstrated the capability to control temperature distributions within targeted regions of the disc using interstitial ultrasound with greater thermal penetration than can be achieved with the RF heating devices currently in clinical use. Thus interstitial ultrasound offers a potential alternative heating modality for the clinical management of low back pain.

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

    PubMed

    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.

  20. Extracellular matrix components and culture regimen selectively regulate cartilage formation by self-assembling human mesenchymal stem cells in vitro and in vivo.

    PubMed

    Ng, Johnathan; Wei, Yiyong; Zhou, Bin; Burapachaisri, Aonnicha; Guo, Edward; Vunjak-Novakovic, Gordana

    2016-12-09

    Cartilage formation from self-assembling mesenchymal stem cells (MSCs) in vitro recapitulate important cellular events during mesenchymal condensation that precedes native cartilage development. The goal of this study was to investigate the effects of cartilaginous extracellular matrix (ECM) components and culture regimen on cartilage formation by self-assembling human MSCs in vitro and in vivo. Human bone marrow-derived MSCs (hMSCs) were seeded and compacted in 6.5-mm-diameter transwell inserts with coated (type I, type II collagen) or uncoated (vehicle) membranes, at different densities (0.5 × 10 6 , 1.0 × 10 6 , 1.5 × 10 6 per insert). Pellets were formed by aggregating hMSCs (0.25 × 10 6 ) in round-bottomed wells. All tissues were cultured for up to 6 weeks for in vitro analyses. Discs (cultured for 6, 8 or 10 weeks) and pellets (cultured for 10 weeks) were implanted subcutaneously in immunocompromised mice to evaluate the cartilage stability in vivo. Type I and type II collagen coatings enabled cartilage disc formation from self-assembling hMSCs. Without ECM coating, hMSCs formed dome-shaped tissues resembling the pellets. Type I collagen, expressed in the prechondrogenic mesenchyme, improved early chondrogenesis versus type II collagen. High seeding density improved cartilage tissue properties but resulted in a lower yield of disc formation. Discs and pellets exhibited compositional and organizational differences in vitro and in vivo. Prolonged chondrogenic induction of the discs in vitro expedited endochondral ossification in vivo. The outcomes of cartilage tissues formed from self-assembling MSCs in vitro and in vivo can be modulated by the control of culture parameters. These insights could motivate new directions for engineering cartilage and bone via a cartilage template from self-assembling MSCs.

  1. Evaluation of intervertebral disc cartilaginous endplate structure using magnetic resonance imaging.

    PubMed

    Moon, Sung M; Yoder, Jonathon H; Wright, Alexander C; Smith, Lachlan J; Vresilovic, Edward J; Elliott, Dawn M

    2013-08-01

    The cartilaginous endplate (CEP) is a thin layer of hyaline cartilage positioned between the vertebral endplate and nucleus pulposus (NP) that functions both as a mechanical barrier and as a gateway for nutrient transport into the disc. Despite its critical role in disc nutrition and degeneration, the morphology of the CEP has not been well characterized. The objective of this study was to visualize and report observations of the CEP three-dimensional morphology, and quantify CEP thickness using an MRI FLASH (fast low-angle shot) pulse sequence. MR imaging of ex vivo human cadaveric lumbar spine segments (N = 17) was performed in a 7T MRI scanner with sequence parameters that were selected by utilizing high-resolution T1 mapping, and an analytical MRI signal model to optimize image contrast between CEP and NP. The CEP thickness at five locations along the mid-sagittal AP direction (center, 5 mm, 10 mm off-center towards anterior and posterior) was measured, and analyzed using two-way ANOVA and a post hoc Bonferonni test. For further investigation, six in vivo volunteers were imaged with a similar sequence in a 3T MRI scanner. In addition, decalcified and undecalcified histology was performed, which confirmed that the FLASH sequence successfully detected the CEP. CEP thickness determined by MRI in the mid-sagittal plane across all lumbar disc levels and locations was 0.77 ± 0.24 mm ex vivo. The CEP thickness was not different across disc levels, but was thinner toward the center of the disc. This study demonstrates the potential of MRI FLASH imaging for structural quantification of the CEP geometry, which may be developed as a technique to evaluate changes in the CEP with disc degeneration in future applications.

  2. Experimental Studies of Spray Deposition on a Flat Surface in a Vacuum Environment

    NASA Technical Reports Server (NTRS)

    Golliher, Eric L.; Yao, S. C.

    2015-01-01

    Cooling of spacecraft components in the space environment is an on-going research effort. The electronics used in modern spacecraft are always changing and the heat flux is increasing. New, one-of-a-kind missions require new approaches to thermal control. In this research, under vacuum conditions, a pulsed water spray impinged on a small disc, while a high speed data acquisition system recorded the temperature histories of this copper disc. The water droplets froze quickly and accumulated on the disc as the spray continued. After the spray stopped, the frozen water that remained on the disc then sublimated into the vacuum environment and cooled the disc. This paper examines two important aspects of this process: 1) the difference in spray start up and shutdown in a vacuum environment versus in a standard atmospheric pressure environment, and 2) the water utilization efficiency in a vacuum environment due to the effects of drop trajectories and drop bouncing on the surface. Both phenomena play a role during spray cooling in a vacuum. This knowledge should help spacecraft designers plan for spray cooling as an option to cool spacecraft electronics, human metabolic generated heat, and heat from other sources.

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

    NASA Astrophysics Data System (ADS)

    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 proximity to the fiber-tip. Preliminary measurements on cadaveric canine intervertebral discs indicated significant reduction of scattering constituents and possible diminishment of water content after percutaneous laser disc ablation (PLDA). This fiber-needle based sensing configuration may be feasible for integrating the evaluation of calcification and water content into the work-flow of holmium:YAG laser disc ablation for pre-operative in-line detection and post-operative evaluation of therapeutic interventions regarding the chondrodystrophic disc.

  4. Biomechanical Analysis of Cervical Disc Replacement and Fusion Using Single Level, Two Level, and Hybrid Constructs.

    PubMed

    Gandhi, Anup A; Kode, Swathi; DeVries, Nicole A; Grosland, Nicole M; Smucker, Joseph D; Fredericks, Douglas C

    2015-10-15

    A biomechanical study comparing arthroplasty with fusion using human cadaveric C2-T1 spines. To compare the kinematics of the cervical spine after arthroplasty and fusion using single level, 2 level and hybrid constructs. Previous studies have shown that spinal levels adjacent to a fusion experience increased motion and higher stress which may lead to adjacent segment disc degeneration. Cervical arthroplasty achieves similar decompression but preserves the motion at the operated level, potentially decreasing the occurrence of adjacent segment disc degeneration. 11 specimens (C2-T1) were divided into 2 groups (BRYAN and PRESTIGE LP). The specimens were tested in the following order; intact, single level total disc replacement (TDR) at C5-C6, 2-level TDR at C5-C6-C7, fusion at C5-C6 and TDR at C6-C7 (Hybrid construct), and lastly a 2-level fusion. The intact specimens were tested up to a moment of 2.0 Nm. After each surgical intervention, the specimens were loaded until the primary motion (C2-T1) matched the motion of the respective intact state (hybrid control). An arthroplasty preserved motion at the implanted level and maintained normal motion at the nonoperative levels. Arthrodesis resulted in a significant decrease in motion at the fused level and an increase in motion at the unfused levels. In the hybrid construct, the TDR adjacent to fusion preserved motion at the arthroplasty level, thereby reducing the demand on the other levels. Cervical disc arthroplasty with both the BRYAN and PRESTIGE LP discs not only preserved the motion at the operated level, but also maintained the normal motion at the adjacent levels. Under simulated physiologic loading, the motion patterns of the spine with the BRYAN or PRESTIGE LP disc were very similar and were closer than fusion to the intact motion pattern. An adjacent segment disc replacement is biomechanically favorable to a fusion in the presence of a pre-existing fusion.

  5. Feasibility of the runt cow for in vivo testing of a spinal interbody prosthesis with preliminary results.

    PubMed

    Buttermann, Glenn R; Mendenhall, H Vincent

    2012-04-01

    The optimal lumbar spinal disc prosthesis has yet to be developed. Failures of clinical device studies may be minimized by appropriate large animal preclinical studies. The lumbar spine of the mature "runt" cow, Corrientes breed, has been shown to have a number of desirable characteristics to the human. This study assessed the feasibility of the "runt" cow for in vivo testing of human-sized lumbar interbody implants and the ability to perform common analyses of explants. Eight cows (four experimental and four controls) were compared. The experimental animals had transosseous implantation of the disc prosthesis at L4-L5, and their spines were harvested at four or six months. They were evaluated for the ease of surgical access and healing, motion segment mobility, ability to remove the implant nondestructively, and microradiography and histomorphology. All animals had successful implantation. All explantations were performed without alteration to the devices. All animals had surgical healing and intended device motion, and histology found device stability by demonstrating bone ingrowth into the device's porous plates. There was a significant 46% increase in the amount of trabecular bone adjacent to the implants. The mature runt cow allows for implantation of human-sized interbody and intrabody spinal prostheses. This animal model allowed for macro- and histological analysis of the implant and surrounding tissues. In vivo stability was demonstrated for the disc prosthesis while also allowing for evaluation of intended mobility. Additionally, this is the first study to suggest increased bone density supporting an interbody prosthesis.

  6. Choosing sheep (Ovis aries) as animal model for temporomandibular joint research: Morphological, histological and biomechanical characterization of the joint disc.

    PubMed

    Angelo, D F; Morouço, P; Alves, N; Viana, T; Santos, F; González, R; Monje, F; Macias, D; Carrapiço, B; Sousa, R; Cavaco-Gonçalves, S; Salvado, F; Peleteiro, C; Pinho, M

    2016-12-01

    Preclinical trials are essential to the development of scientific technologies. Remarkable molecular and cellular research has been done using small animal models. However, significant differences exist regarding the articular behavior between these models and humans. Thus, large animal models may be more appropriate to perform trials involving the temporomandibular joint (TMJ). The aim of this work was to make a morphological (anatomic dissection and white light 3D scanning system), histological (TMJ in bloc was removed for histologic analysis) and biomechanical characterization (tension and compression tests) of sheep TMJ comparing the obtained results with human data. Results showed that sheep processus condylaris and fossa mandibularis are anatomically similar to the same human structures. TMJ disc has an elliptical perimeter, thinner in the center than in periphery. Peripheral area acts as a ring structure supporting the central zone. The disc cells display both fibroblast and chondrocyte-like morphology. Marginal area is formed by loose connective tissue, with some chondrocyte-like cells and collagen fibers in diverse orientations. Discs obtained a tensile modulus of 3.97±0.73MPa and 9.39±1.67MPa, for anteroposterior and mediolateral assessment. The TMJ discs presented a compressive modulus (E) of 446.41±5.16MPa and their maximum stress value (σmax) was 18.87±1.33MPa. Obtained results suggest that these animals should be considered as a prime model for TMJ research and procedural training. Further investigations in the field of oromaxillofacial surgery involving TMJ should consider sheep as a good animal model due to its resemblance of the same joint in humans. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

    PubMed Central

    Gantenbein, Benjamin; Illien-Jünger, Svenja; Chan, Samantha CW; Walser, Jochen; Haglund, Lisbet; Ferguson, Stephen J; Iatridis, James C; Grad, Sibylle

    2015-01-01

    In recent decades the application of bioreactors has revolutionized the concept of culturing tissues and organs that require mechanical loading. In intervertebral disc (IVD) research, collaborative efforts of biomedical engineering, biology and mechatronics have led to the innovation of new loading devices that can maintain viable IVD organ explants from large animals and human cadavers in precisely defined nutritional and mechanical environments over extended culture periods. Particularly in spine and IVD research, these organ culture models offer appealing alternatives, as large bipedal animal models with naturally occurring IVD degeneration and a genetic background similar to the human condition do not exist. Latest research has demonstrated important concepts including the potential of homing of mesenchymal stem cells to nutritionally or mechanically stressed IVDs, and the regenerative potential of “smart” biomaterials for nucleus pulposus or annulus fibrosus repair. In this review, we summarize the current knowledge about cell therapy, injection of cytokines and short peptides to rescue the degenerating IVD. We further stress that most bioreactor systems simplify the real in vivo conditions providing a useful proof of concept. Limitations are that certain aspects of the immune host response and pain assessments cannot be addressed with ex vivo systems. Coccygeal animal disc models are commonly used because of their availability and similarity to human IVDs. Although in vitro loading environments are not identical to the human in vivo situation, 3D ex vivo organ culture models of large animal coccygeal and human lumbar IVDs should be seen as valid alternatives for screening and feasibility testing to augment existing small animal, large animal, and human clinical trial experiments. PMID:25764196

  8. Intervertebral disc adaptation to wedging deformation.

    PubMed

    Stokes, Ian A F; Aronsson, David D; Clark, Katherine C; Roemhildt, Maria L

    2006-01-01

    Although scoliosis includes wedge deformities of both vertebrae and discs, little is known about the causes of the discal changes, and whether they result from mechanical influences on growth and/or remodelling. An external apparatus attached to transvertebral pins applied compression and 15 degrees of angulation to each of two adjacent young rat caudal intervertebral discs for 5 weeks (four animals), or for 10 weeks (four animals). Each week, micro-CT scanning documented the in vivo discal wedging. After euthanasia, tail segments (three vertebrae and the 2 angulated discs) were excised and their flexibility was measured over a range of lateral bending. The angle of maximum flexibility was recorded. Then discs were fixed in situ (with the external apparatus in place) and sectioned for polarized light microscopy. The disc-wedging deformity averaged 15 degrees initially, it averaged 20 degrees after 5 weeks, and then reduced to 10 degrees (in 10 week animals). The lateral bending flexibility showed a distinct maximum at an average of 1.1 degrees from the in vivo position in the 5-week animals, indicating structural remodeling of the discs almost to the deformed geometry. The 10-week animals had maximum flexibility at 1.4 degrees from the in vivo position (no significant difference between 5 and 10-week animals.) Collagen crimp angles [Cassidy et al., Conn Tiss Res 1989, 23:75-88] were not significantly different between convex and concave sides, again suggesting that remodeling had occurred. In a mechanically induced scoliosis deformity in skeletally immature rats, the intervertebral discs underwent remodeling within 5 weeks. This indicates that this animal model is suitable for studying adaptive wedging changes in human scoliosis.

  9. Cervical facet force analysis after disc replacement versus fusion.

    PubMed

    Patel, Vikas V; Wuthrich, Zachary R; McGilvray, Kirk C; Lafleur, Matthew C; Lindley, Emily M; Sun, Derrick; Puttlitz, Christian M

    2017-05-01

    Cervical total disc replacement was developed to preserve motion and reduce adjacent-level degeneration relative to fusion, yet concerns remain that total disc replacement will lead to altered facet joint loading and long-term facet joint arthrosis. This study is intended to evaluate changes in facet contact force, pressure and surface area at the treated and superior adjacent levels before and after discectomy, disc replacement, and fusion. Ten fresh-frozen human cadaveric cervical spines were potted from C2 to C7 with pressure sensors placed into the facet joints of C3-C4 and C4-C5 via slits in the facet capsules. Moments were applied to the specimens to produce axial rotation, lateral bending and extension. Facet contact force and pressure were measured at both levels for intact, discectomy at C4-C5, disc replacement with ProDisc-C (Synthes Spine, West Chester, Pennsylvania, USA) at C4-C5, and anterior discectomy and fusion with Cervical Spine Locking Plate (Synthes Spine, West Chester, Pennsylvania, USA) at C4-C5. Facet contact area was calculated from the force and pressure measurements. An analysis of variance was used to determine significant differences with P-values <0.05 indicating significance. Facet contact force was elevated at the treated level under extension following both discectomy and disc replacement, while facet contact pressure and area were relatively unchanged. Facet contact force and area were decreased at the treated level following fusion for all three loading conditions. Total disc replacement preserved facet contact force for all scenarios except extension at the treated level, highlighting the importance of the anterior disco-ligamentous complex. This could promote treated-level facet joint disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. 21 CFR 866.1620 - Antimicrobial susceptibility test disc.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Antimicrobial susceptibility test disc. 866.1620 Section 866.1620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Diagnostic Devices § 866.1620 Antimicrobial...

  11. 21 CFR 866.1620 - Antimicrobial susceptibility test disc.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antimicrobial susceptibility test disc. 866.1620 Section 866.1620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Diagnostic Devices § 866.1620 Antimicrobial...

  12. 21 CFR 866.1620 - Antimicrobial susceptibility test disc.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Antimicrobial susceptibility test disc. 866.1620 Section 866.1620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Diagnostic Devices § 866.1620 Antimicrobial...

  13. 21 CFR 866.1620 - Antimicrobial susceptibility test disc.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Antimicrobial susceptibility test disc. 866.1620 Section 866.1620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Diagnostic Devices § 866.1620 Antimicrobial...

  14. 21 CFR 866.1620 - Antimicrobial susceptibility test disc.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Antimicrobial susceptibility test disc. 866.1620 Section 866.1620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Diagnostic Devices § 866.1620 Antimicrobial...

  15. Comparing Blast Effects on Human Torso Finite Element Model against Existing Lethality Curves

    DTIC Science & Technology

    2010-07-15

    vertebrae, intervertebral discs, ribs, cartilage, sternum, scapula, and clavicle . The internal organs include the heart and aorta, lungs and trachea...Thoracic Vertebrae  Intervertebral Disc  Scapula  Clavicle Heritage Style Viewgraphs6 HTFEM Development Internal Organs Ten-noded tetrahedral

  16. 21 CFR 872.3970 - Interarticular disc prosthesis (interpositional implant).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Interarticular disc prosthesis (interpositional implant). 872.3970 Section 872.3970 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3970 Interarticular...

  17. Uniform and accelerated degradation of pure iron patterned by Pt disc arrays

    PubMed Central

    Huang, Tao; Zheng, Yufeng

    2016-01-01

    Pure iron has been confirmed as a promising biodegradable metal. However, the degradation rate of pure iron should be accelerated to meet the clinical requirements. In this work, two different designs of platinum disc arrays, including sizes of Φ20 μm × S5 μm and Φ4 μm × S4 μm, have been coated on the surface of pure iron. Corrosion tests showed the platinum discs formed plenty of galvanic cells with the iron matrix which significantly accelerated the degradation of pure iron. Simultaneously, due to the designability of the shape, size as well as distribution of Pt discs, the degradation rate as well as degradation uniformity of pure iron can be effectively controlled by coating with platinum discs. The cytotoxicity test results unveiled that Pt discs patterned pure iron exhibited almost no toxicity to human umbilical vein endothelial cells, but a significant inhibition on proliferation of vascular smooth muscle cells. In addition, the hemolysis rate of Pt discs patterned pure iron was lower than 1%. Moreover, Pt discs also effectively reduced the number of adhered platelets. All these results indicated that Pt discs patterning is an effective way to accelerate degradation and improve biocompatibility of pure iron. PMID:27033380

  18. Relationship between disc injury and manual lifting: a poroelastic finite element model study.

    PubMed

    Natarajan, R N; Williams, J R; Lavender, S A; An, H S; Anderson, G B

    2008-02-01

    Understanding how failure originates in a lumbar motion segment subjected to loading conditions that are representative of manual lifting is important because it will pave the way for a better formulation of the exposure-injury relationship. The aim of the current investigation was to use a poroelastic finite element model of a human lumbar disc to determine its biomechanical characteristics under loading conditions that corresponded to three different, commonly occurring lifting activities and to identify the most hazardous type of loading with regard to damage to the disc. The current study showed that asymmetric lifting may increase the risk of back injury and pain. Lifting that involved lateral bending (asymmetric lifting) of the trunk was found to produce stresses at a localized area in the annulus, annuluar fibres, end plates, and facet joints that were higher than their respective tissue failure strength. Thus asymmetric lifting, if performed over a large number of cycles, might help to propagate this localized failure of the disc tissue to a larger area, owing to fatigue. The analyses also showed that largest fluid exchange between the nucleus and the end plates occurred during asymmetric lifting. If the fluid exchange is restricted owing to end plate calcification or sclerosis of the subchondral bone, high intradiscal pressure might develop, leading to higher disc bulge causing back pain.

  19. [Intradiscal temperature variation resulting from radiofrequency thermal therapy. Cadaver study].

    PubMed

    Ramírez-León, J F; Rugeles-Ortiz, J G; Barreto-perea, J A; Alonso-cuéllar, G O

    2014-01-01

    Disc disease is one of the most common causes of lumbar pain. The new era of treatments for degenerative disc disease involves the use of minimally-invasive thermal technologies allowing for collagen remodeling and destruction of nociceptors in the annulus. However, a better understanding of the treatment pathophysiology is needed. The purpose of this study was to measure intradiscal temperature variation after thermodiscoplasty. A human cadaver spine specimen was obtained and divided into blocks, each composed of two intervertebral plates and an intact disc. Radio frequency was applied at five spots with three different time intervals. Temperature was measured in each of the combinations. Units were weighed before and after treatment. Finally, the disc was exposed and the tightening achieved with each radio frequency application was measured. Data were analyzed with the SPSS software. The mean weight reduction obtained was 1.4 g on average (SD 0.599), with values between 0.5 and 2.6 grams. Mean temperature in the posterior rim of the annulus was 37.6 degrees C and mean temperature variation was 3.0 degrees C (SD 6.407). Mean tightening achieved in all blocks overall was 1.4 mm. The results obtained show the effectiveness of radio frequency thermodiscoplasty when performed within the safety parameters. Temperature values with radio frequency were lower than those found in comparable studies. The weight and the tightening show the effect of disc shrinking and dehydration. This report is an effective tool to define time parameters for the application of this technology.

  20. Catabolic Effects of Endothelial Cell-Derived Microparticles on Disc Cells: Implications in Intervertebral Disc Neovascularization and Degeneration

    PubMed Central

    Pohl, Pedro H. I.; Lozito, Thomas P.; Cuperman, Thais; Yurube, Takashi; Moon, Hong J.; Ngo, Kevin; Tuan, Rocky S.; Croix, Claudette St.; Sowa, Gwendolyn A.; Rodrigues, Luciano M. R.; Kang, James D.; Vo, Nam V.

    2017-01-01

    Neovascularization of intervertebral discs, a phenomenon considered pathological since normal discs are primarily avascular structures, occurs most frequently in annulus fibrosus (AF) of degenerated discs. Endothelial cells (ECs) are involved in this process, but the mechanism of the interaction between AF and endothelial cells is unclear. In this study we evaluated the effects on matrix catabolic activity of AF cells by the extracellular endothelial microparticles (EMPs) and soluble protein factors (SUP fraction) produced from ECs. Passage 1 human AF cells grown in monolayer cultures were treated for 72 hours with 250μg of EMPs or SUP fraction isolated from culture of the microvascular endothelial cell line, HEMC-I. Live-cell imaging revealed uptake of EMPs by AF cells. RT-PCR analysis demonstrated increased mRNA expression of MMP-1 (50.3 fold), MMP-3 (4.5 fold) and MMP-13 (5.5 fold) in AF cell cultures treated with EMPs compared to untreated control. Western analysis also demonstrated increased MMP protein expression in EMP-treated AF cells. AF cells treated with the SUP fraction also exhibited a dramatic increase in MMP mRNA and protein expression. Increased MMP expression is primarily due to EMP or SUP stimulation of AF cells since EMPs or SUP fraction alone contained negligible amount of MMPs. Interestingly, MMP activity was elevated in AF cell cultures treated with EMPs but not with SUP. This study revealed enhanced matrix catabolism as a molecular consequence of action of ECs on AF cells via EMPs, which might be expected during neo-angiogenesis of degenerating disc. PMID:27246627

  1. Comparative study of the innervation of the facila disc of selected mammals.

    PubMed

    Montagna, W; Roman, N A; Macpherson, E

    1975-11-01

    The greatest concentration of sensory nerves in the muzzle and facial disc of mammals is in the nose. In most nocturnal mammals, these nerves penetrate the epidermis of the naked nose either or in bundles which resemble the corpuscles of Eimer. The hair follicles around the nose, lips, and eyes, as well as the heaviply innervated vibrissae follicles found in all hairy mammals except man, are well innervated; those elsewhaere are not. Everywhere on the human body both large and small follicles abound in sensory nerves. These morphologic observations suggest that in most mammals the most sensitivie areas of the skin are at the anterior and posterior ends (not reported here), and that human skin is better equipped for cutaneous sensibility than that of any other mammal.

  2. Hygroviscoelasticity of the Human Intervertebral Disc.

    DTIC Science & Technology

    1980-07-01

    the intervertebral disc (Figures 2(a) and 2(b)). -7- 7 CERVICAL CURVE (C1 -C7 (CERVICAL LORDOSIS CURVE) THORACIC CURVE (T I- T12) $ (DORSAL KYPHOSIS...CURVE) LUMBAR CURVE (L 1-1.5 ) (LUMBAR LORDOSIS CURVE) PELVIC CURVE (SACRUM) COCCYX FIGURE 1 Lateral View of Vertebral Column *1 -8- POSTERIOR

  3. Effect of hyaluronic acid on morphological changes to dentin surfaces and subsequent effect on periodontal ligament cell survival, attachment, and spreading.

    PubMed

    Mueller, Andrea; Fujioka-Kobayashi, Masako; Mueller, Heinz-Dieter; Lussi, Adrian; Sculean, Anton; Schmidlin, Patrick R; Miron, Richard J

    2017-05-01

    Hyaluronic acid (HA) is a natural constituent of connective tissues and plays an important role in their development, maintenance, and regeneration. Recently, HA has been shown to improve wound healing. However, no basic in vitro study to date has investigated its mode of action. Therefore, the purpose of this study was to examine morphological changes of dentin surfaces following HA coating and thereafter investigate the influence of periodontal ligament (PDL) cell survival, attachment, and spreading to dentin discs. HA was coated onto dentin discs utilizing either non-cross-linked (HA) or cross-linked (HA cl) delivery systems. Morphological changes to dentin discs were then assessed using scanning electron microscopy (SEM). Thereafter, human PDL cells were seeded under three in vitro conditions including (1) dilution of HA (1:100), (2) dilution of HA (1:10), and (3) HA coated directly to dentin discs. Samples were then investigated for PDL cell survival, attachment, and spreading using a live/dead assay, cell adhesion assay, and SEM imaging, respectively. While control dentin discs demonstrated smooth surfaces both at low and high magnification, the coating of HA altered surface texture of dentin discs by increasing surface roughness. HA cl further revealed greater surface texture/roughness likely due to the cross-linking carrier system. Thereafter, PDL cells were seeded on control and HA coated dentin discs and demonstrated a near 100 % survival rate for all samples demonstrating high biocompatibility of HA at dilutions of both 1:100 and 1:10. Interestingly, non-cross-linked HA significantly increased cell numbers at 8 h, whereas cross-linked HA improved cell spreading as qualitatively assessed by SEM. The results from the present study demonstrate that both carrier systems for HA were extremely biocompatible and demonstrated either improved cell numbers or cell spreading onto dentin discs. Future in vitro and animal research is necessary to further characterize the optimal delivery system of HA for improved clinical use. HA is a highly biocompatible material that may improve PDL cell attachment or spreading on dentin.

  4. The CCDC55 couples cannabinoid receptor CNR1 to a putative DISC1 schizophrenia pathway.

    PubMed

    Xie, J; Gizatullin, R; Vukojevic, V; Leopardi, R

    2015-12-03

    Our previous study suggested that the coiled coil domain-containing 55 gene (CCDC55), also named as NSRP1 (nuclear speckle splicing regulatory protein 1 (NSRP1)), was encompassed in a haplotype block spanning over the serotonin transporter (5-HTT) gene in patients with schizophrenia (SCZ). However, the neurobiological function of CCDC55 gene remains unknown. This study aims to uncover the potential role of CCDC55 in SCZ-associated molecular pathways. Using molecular cloning, sequencing and immune blotting to identify basic properties, yeast two-hybrid screening and glutathione S-transferase (GST) pull-down assay to test protein-protein interaction, and confocal laser scanning microscopy (CSLM) to show intracellular interaction of proteins. (i) CCDC55 is expressed as a nuclear protein in human neuronal cells; (ii) Protein-protein interaction analyses showed CCDC55 physically interacted with Ran binding protein 9 (RanBP9) and disrupted in schizophrenia 1 (DISC1); (iii) CCDC55 and RanBP9 co-localized in the nucleus of human neuronal cells; (iv) CCDC55 also interacted with the cannabinoid receptor 1 (CNR1), and with the brain cannabinoid receptor-interacting protein 1a (CNRIP1a); (v) CNR1 activation in differentiated human neuronal cells resulted in an altered RanBP9 localization. CCDC55 may be involved in a functional bridging between the CNR1 activation and the DISC1/RanBP9-associated pathways. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. The adult human pubic symphysis: a systematic review

    PubMed Central

    Becker, Ines; Woodley, Stephanie J; Stringer, Mark D

    2010-01-01

    The pubic symphysis is a unique joint consisting of a fibrocartilaginous disc sandwiched between the articular surfaces of the pubic bones. It resists tensile, shearing and compressive forces and is capable of a small amount of movement under physiological conditions in most adults (up to 2 mm shift and 1° rotation). During pregnancy, circulating hormones such as relaxin induce resorption of the symphyseal margins and structural changes in the fibrocartilaginous disc, increasing symphyseal width and mobility. This systematic review of the English, German and French literature focuses on the normal anatomy of the adult human pubic symphysis. Although scientific studies of the joint have yielded useful descriptive data, comparison of results is hampered by imprecise methodology and/or poorly controlled studies. Several aspects of the anatomy of the pubic symphysis remain unknown or unclear: the precise attachments of surrounding ligaments and muscles; the arrangement of connective tissue fibres within the interpubic disc and the origin, structure and function of its associated interpubic cleft; the biomechanical consequences of sexual dimorphism; potential ethnic variations in morphology; and its precise innervation and blood supply. These deficiencies hinder our understanding of the normal form and function of the joint, which is particularly relevant when attempting to understand the mechanisms underlying pregnancy-related pubic symphyseal pain, a neglected and relatively common cause of pubic pain. A better understanding of the normal anatomy of the human pubic symphysis should improve our understanding of such problems and contribute to better treatments for patients suffering from symphyseal pain and dysfunction. PMID:20840351

  6. Tracking dynamics of photoreceptor disc shedding with adaptive optics-optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Zhang, Furu; Liu, Zhuolin; Kurokawa, Kazuhiro; Miller, Donald T.

    2017-02-01

    Absorption of light by photoreceptors initiates vision, but also leads to accumulation of toxic photo-oxidative compounds in the photoreceptor outer segment (OS). To prevent this buildup, small packets of OS discs are periodically pruned from the distal end of the OS, a process called disc shedding. Unfortunately dysfunction in any part of the shedding event can lead to photoreceptor and RPE dystrophy, and has been implicated in numerous retinal diseases, including age related macular degeneration and retinitis pigmentosa. While much is known about the complex molecular and signaling pathways that underpin shedding, all of these advancements have occurred in animal models using postmortem eyes. How these translate to the living retina and to humans remain major obstacles. To that end, we have recently discovered the optical signature of cone OS disc shedding in the living human retina, measured noninvasively using optical coherence tomography equipped with adaptive optics in conjunction with post processing methods to track and monitor individual cones in 4D. In this study, we improve on this method in several key areas: increasing image acquisition up to MHz A-scan rates, improving reliability to detect disc shedding events, establishing system precision, and developing cone tracking for use across the entire awake cycle. Thousands of cones were successfully imaged and tracked over the 17 hour period in two healthy subjects. Shedding events were detected in 79.5% and 77.4% of the tracked cones. Similar to previous animal studies, shedding prevalence exhibited a diurnal rhythm. But we were surprised to find that for these two subjects shedding occurred across the entire day with broad, elevated frequency in the morning and decreasing frequency as the day progressed. Consistent with this, traces of the average cone OS length revealed shedding dominated in the morning and afternoon and renewal in the evening.

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

    PubMed

    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.

  8. Biomechanical Changes in Disc Pressure and Facet Strain after Lumbar Spinal Arthroplasty with CharitéTM in the Human Cadaveric Spine under Physiologic Compressive Follower Preload.

    PubMed

    Choi, Jong-Il; Kim, Se-Hoon; Lim, Dong-Jun; Ha, Sung-Kon; Kim, Sang-Dae

    2017-01-01

    Arthroplasty maintains the biomechanical features of a healthy disc, decreases the adjacent segment disease rate, and decreases the accelerated degeneration rate of the neighboring discs in traditional fusion procedures. However, there are only a few reports on adjacent disc pressure (DP) and facet strain (FS) after lumbar arthroplasty under a physiologic compressive preload. Baseline DP and FS measurements were obtained from five intact cadaveric human lumbosacral spines for different modes of motion. DP was measured by inserting pressure transducer needle tips into the L3-L4 and L5-S1 discs. FS gauges were fixed on both sides of the laminae near the L3-L4, L4-L5, and L5-S1 facet joints. After SB Charité < sup > TM < /sup > III implantation at the L4-L5 level, the measurements were repeated at preload and compared with those of the intact spine. Under the preload condition, the central DP of the upper disc was decreased during extension and bending, and it significantly increased during rotation (p < 0.05). In the lower disc, the central DP insignificantly decreased during bending and increased during extension and flexion. A statistically significant increase in FS was observed during rotation at the operative facet (p < 0.05). Compared to the intact spine, all FS values were insignificantly decreased during lateral bending but increased during axial rotation. In an ex-vivo physiologic preload setting, the SB Charité < sup > TM < /sup > III provided relatively inconsistent and sometimes increased DP or FS at the operative and adjacent levels after arthroplasty.

  9. C-130J Human Vibration

    DTIC Science & Technology

    2005-08-01

    Hulshof , 1999; Dupuis & Zerlett, 1986; Kittusamy & Buchholz, 2004; Seidel, 1993). There is also evidence of intervertebral disc problems and...Bovenzi, M., & Hulshof , C.T.J. (1999). An updated review of epidemiologic studies on the relationship between exposure to whole-body vibration and

  10. Why do some intervertebral discs degenerate, when others (in the same spine) do not?

    PubMed

    Adams, Michael A; Lama, Polly; Zehra, Uruj; Dolan, Patricia

    2015-03-01

    This review suggests why some discs degenerate rather than age normally. Intervertebral discs are avascular pads of fibrocartilage that allow movement between vertebral bodies. Human discs have a low cell density and a limited ability to adapt to mechanical demands. With increasing age, the matrix becomes yellowed, fibrous, and brittle, but if disc structure remains intact, there is little impairment in function, and minimal ingrowth of blood vessels or nerves. Approximately half of old lumbar discs degenerate in the sense of becoming physically disrupted. The posterior annulus and lower lumbar discs are most affected, presumably because they are most heavily loaded. Age and genetic inheritance can weaken discs to such an extent that they are physically disrupted during everyday activities. Damage to the endplate or annulus typically decompresses the nucleus, concentrates stress within the annulus, and allows ingrowth of nerves and blood vessels. Matrix disruption progresses by mechanical and biological means. The site of initial damage leads to two disc degeneration "phenotypes": endplate-driven degeneration is common in the upper lumbar and thoracic spine, and annulus-driven degeneration is common at L4-S1. Discogenic back pain can be initiated by tissue disruption, and amplified by inflammation and infection. Healing is possible in the outer annulus only, where cell density is highest. We conclude that some discs degenerate because they are disrupted by excessive mechanical loading. This can occur without trauma if tissues are weakened by age and genetic inheritance. Moderate mechanical loading, in contrast, strengthens all spinal tissues, including discs. © 2014 Wiley Periodicals, Inc.

  11. Multiple sensor integration for seizure onset detection in human patients comparing conventional disc versus novel tripolar concentric ring electrodes.

    PubMed

    Makeyev, Oleksandr; Ding, Quan; Martínez-Juárez, Iris E; Gaitanis, John; Kay, Steven M; Besio, Walter G

    2013-01-01

    As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Closed-loop systems that apply electrical stimulation when seizure onset is automatically detected require high accuracy of automatic seizure detection based on electrographic brain activity. To improve this accuracy we propose to use noninvasive tripolar concentric ring electrodes that have been shown to have significantly better signal-to-noise ratio, spatial selectivity, and mutual information compared to conventional disc electrodes. The proposed detection methodology is based on integration of multiple sensors using exponentially embedded family (EEF). In this preliminary study it is validated on over 26.3 hours of data collected using both tripolar concentric ring and conventional disc electrodes concurrently each from 7 human patients with epilepsy including five seizures. For a cross-validation based group model EEF correctly detected 100% and 80% of seizures respectively with <0.76 and <1.56 false positive detections per hour respectively for the two electrode modalities. These results clearly suggest the potential of seizure onset detection based on data from tripolar concentric ring electrodes.

  12. Prevalence of Age-Related Changes in Ovine Lumbar Intervertebral Discs during Computed Tomography and Magnetic Resonance Imaging

    PubMed Central

    Nisolle, Jean-François; Bihin, Benoît; Kirschvink, Nathalie; Neveu, Fabienne; Clegg, Peter; Dugdale, Alexandra; Wang, Xiaoqing; Vandeweerd, Jean-Michel

    2016-01-01

    Ovine models are used to study intervertebral disc (IVD) degeneration. The objective of the current study was to assess the naturally occurring age-related changes of the IVD that can be diagnosed by CT and MRI in the lumbar spine of sheep. We used CT and T2-weighted MR images to score the IVD (L6S1 to L1L2) in 41 sheep (age, 6 mo to 11 y) that were euthanized for reasons not related to musculoskeletal disease. T2 mapping and measurement of T2 time of L6S1 to L2L3 were performed in 22 of the sheep. Degenerative changes manifested as early as 2 y of age and occurred at every IVD level. Discs were more severely damaged in older sheep. The age effect of the L6S1 IVD was larger than the average age effect for the other IVD. The current study provides evidence that lesions similar to those encountered in humans can be identified by CT and MRI in lumbar spine of sheep. Ideally, research animals should be assessed at the initiation of preclinical trials to determine the extent of prevalent degenerative changes. The ovine lumbosacral disc seems particularly prone to degeneration and might be a favorable anatomic site for studying IVD degeneration. PMID:27538861

  13. Quantification of Propionic Acid in the Bovine Spinal Disk After Infection of the Tissue With Propionibacteria acnes Bacteria.

    PubMed

    Magnitsky, Sergey; Dudli, Stefan; Tang, Xinyan; Kaur, Jaskanwaljeet; Diaz, Joycelyn; Miller, Steve; Lotz, Jeffrey C

    2018-06-01

    Research. The goal of this study was to investigate whether Propionibacteria acnes infection of the intervertebral disc can be detected noninvasively by nuclear magnetic resonance (NMR) spectroscopy. Microbiological studies of surgical samples suggest that a significant subpopulation of back pain patients may have occult disc infection with P. acnes bacteria. This hypothesis is further supported by a double-blind clinical trial showing that back pain patients with Modic type 1 changes may respond to antibiotic treatment. Because significant side effects are associated with antibiotic treatment, there is a need for a noninvasive method to detect whether specific discs in back pain patients are infected with P acnes bacteria. P. acnes bacteria were obtained from human patients. NMR detection of a propionic acid (PA) in the bacteria extracts was conducted on 500 MHz high-resolution spectrometer, whereas in vivo NMR spectroscopy of an isolated bovine disk tissue infected with P. acnes was conducted on 7 T magnetic resonance imaging scanner. NMR spectra of P. acnes metabolites revealed a distinct NMR signal with identical chemical shits (1.05 and 2.18 ppm) as PA (a primary P. acne metabolite). The 1.05 ppm signal does not overlap with other bacteria metabolites, and its intensity increases linearly with P. acnes concentration. Bovine disks injected with P. acnes bacteria revealed a very distinct NMR signal at 1.05 ppm, which linearly increased with P. acnes concentration. The 1.05 ppm NMR signal from PA can be used as a marker of P. acnes infection of discs. This signal does not overlap with other disc metabolites and linearly depends on P. acnes concentration. Consequently, NMR spectroscopy may provide a noninvasive method to detect disc infection in the clinical setting. N/A.

  14. Catabolic effects of endothelial cell-derived microparticles on disc cells: Implications in intervertebral disc neovascularization and degeneration.

    PubMed

    Pohl, Pedro H I; Lozito, Thomas P; Cuperman, Thais; Yurube, Takashi; Moon, Hong J; Ngo, Kevin; Tuan, Rocky S; St Croix, Claudette; Sowa, Gwendolyn A; Rodrigues, Luciano M R; Kang, James D; Vo, Nam V

    2016-08-01

    Neovascularization of intervertebral discs, a phenomenon considered pathological since normal discs are primarily avascular structures, occurs most frequently in annulus fibrosus (AF) of degenerated discs. Endothelial cells (ECs) are involved in this process, but the mechanism of the interaction between AF and endothelial cells is unclear. In this study, we evaluated the effects on matrix catabolic activity of AF cells by the extracellular endothelial microparticles (EMPs) and soluble protein factors (SUP fraction) produced from ECs. Passage 1 human AF cells grown in monolayer cultures were treated for 72 h with 250 µg of EMPs or SUP fraction isolated from culture of the microvascular endothelial cell line, HEMC-I. Live-cell imaging revealed uptake of EMPs by AF cells. RT-PCR analysis demonstrated increased mRNA expression of MMP-1 (50.3-fold), MMP-3 (4.5-fold) and MMP-13 (5.5-fold) in AF cell cultures treated with EMPs compared to untreated control. Western analysis also demonstrated increased MMP protein expression in EMP-treated AF cells. AF cells treated with the SUP fraction also exhibited a dramatic increase in MMP mRNA and protein expression. Increased MMP expression is primarily due to EMP or SUP stimulation of AF cells since EMPs or SUP fraction alone contained negligible amount of MMPs. Interestingly, MMP activity was elevated in AF cell cultures treated with EMPs but not with SUP. This study revealed enhanced matrix catabolism as a molecular consequence of action of ECs on AF cells via EMPs, which might be expected during neo-angiogenesis of degenerating disc. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1466-1474, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. Relationship between Secchi disc readings and light penetration in Lake Huron

    USGS Publications Warehouse

    Beeton, Alfred M.

    1958-01-01

    Fifty-seven paired photometer and Secchi disc measurements made at 18 stations in Saginaw Bay and Lake Huron support the view that a counter-clockwise current usually occurs in the Bay with more transparent Lake Huron water flowing in along the northwest shore and less transparent Bay water flowing out along the southeast shore. The average percentage transmission of surface light intensity, at the Secchi disc depth, was 14.7 percent. Discrepancies in the relationship of disc readings to percentage transmission of surface light are related to the condition of the sky and sea. It is suggested that these discrepancies can best be explained on the basis of the spectral sensitivity of the human eye and its response to surface glare.

  16. Effects of air polishing and an amino acid buffered hypochlorite solution to dentin surfaces and periodontal ligament cell survival, attachment, and spreading.

    PubMed

    Schmidlin, Patrick R; Fujioka-Kobayashi, Masako; Mueller, Heinz-Dieter; Sculean, Anton; Lussi, Adrian; Miron, Richard J

    2017-06-01

    The aim of this study is to examine morphological changes of dentin surfaces following air polishing or amino acid buffered hypochlorite solution application and to assess their influence on periodontal ligament (PDL) cell survival, attachment, and spreading to dentin discs in vitro. Bovine dentin discs were treated with either (i) Classic, (ii) Plus, or (iii) Perio powder (EMS). Furthermore, Perisolv® a hypochlorite solution buffered with various amino acids was investigated. Untreated dentin discs served as controls. Morphological changes to dentin discs were assessed using scanning electron microscopy (SEM). Human PDL cells were seeded onto the respectively treated discs, and samples were then investigated for PDL cell survival, attachment, and spreading using a live/dead assay, adhesion assay, and SEM imaging, respectively. Both control and Perisolv®-rinsed dentin discs demonstrated smooth surfaces at low and high magnifications. The Classic powders demonstrated the thickest coating followed by the Powder Plus. The Perio powder demonstrated marked alterations of dentin discs by revealing the potential to open dentinal tubules even before rinsing. Seeding of PDL cells demonstrated an almost 100 % survival rate on all samples demonstrating very high biocompatibility for all materials. Significantly higher PDL cell numbers were observed on samples treated with the Perio powder and the Perisolv® solution (approximately 40 % more cells; p < 0.05). SEM imaging revealed the potential for PDL cells to attach and spread on all surfaces. The results from the present study demonstrate that cell survival and spreading of PDL cells on root surfaces is possible following either air polishing or application with Perisolv®. Future in vitro and animal testing is necessary to further characterize the beneficial effects of either system in a clinical setting. The use of air polishing or application with Perisolv amino acid buffered hypochlorite solution was effective in treating root surfaces and allowed for near 100 % PDL cell survival, attachment, and spreading onto all root surfaces.

  17. In Vitro Study of Dentin Hypersensitivity Treated by 980-nm Diode Laser.

    PubMed

    Liu, Ying; Gao, Jie; Gao, Yan; Xu, Shuaimei; Zhan, Xueling; Wu, Buling

    2013-01-01

    To investigate the ultrastructural changes of dentin irradiated with 980-nm diode laser under different parameters and to observe the morphological alterations of odontoblasts and pulp tissue to determine the safety parameters of 980-nm diode laser in the treatment of dentin hypersensitivity (DH). Twenty extracted human third molars were selected to prepare dentin discs. Each dentin disc was divided into four areas and was irradiated by 980-nm diode laser under different parameters: Group A: control group, 0 J/cm(2); Group B: 2 W/CW (continuous mode), 166 J/cm(2); Group C: 3W/CW, 250 J/cm(2); and Group D: 4W/CW, 333 J/cm(2). Ten additional extracted human third molars were selected to prepare dentin discs. Each dentin disc was divided into two areas and was irradiated by 980-nm diode laser: Group E: control group, 0 J/cm(2); and Group F: 2.0 W/CW, 166 J/cm(2). The morphological alterations of the dentin surfaces and odontoblasts were examined with scanning electron microscopy (SEM), and the morphological alterations of the dental pulp tissue irradiated by laser were observed with an upright microscope. The study demonstrated that dentinal tubules can be entirely blocked after irradiation by 980-nm diode laser, regardless of the parameter setting. Diode laser with settings of 2.0 W and 980-nm sealed exposed dentin tubules effectively, and no significant morphological alterations of the pulp and odontoblasts were observed after irradiation. Irradiation with 980-nm diode laser could be effective for routine clinical treatment of DH, and 2.0W/CW (166 J/cm(2)) was a suitable energy parameter due to its rapid sealing of the exposed dentin tubules and its safety to the odontoblasts and pulp tissue.

  18. In Vitro Study of Dentin Hypersensitivity Treated by 980-nm Diode Laser

    PubMed Central

    Liu, Ying; Gao, Jie; Gao, Yan; XU, Shuaimei; Zhan, Xueling; Wu, Buling

    2013-01-01

    Introduction: To investigate the ultrastructural changes of dentin irradiated with 980-nm diode laser under different parameters and to observe the morphological alterations of odontoblasts and pulp tissue to determine the safety parameters of 980-nm diode laser in the treatment of dentin hypersensitivity (DH). Methods: Twenty extracted human third molars were selected to prepare dentin discs. Each dentin disc was divided into four areas and was irradiated by 980-nm diode laser under different parameters: Group A: control group, 0 J/cm2; Group B: 2 W/CW (continuous mode), 166 J/cm2; Group C: 3W/CW, 250 J/cm2; and Group D: 4W/CW, 333 J/cm2. Ten additional extracted human third molars were selected to prepare dentin discs. Each dentin disc was divided into two areas and was irradiated by 980-nm diode laser: Group E: control group, 0 J/cm2; and Group F: 2.0 W/CW, 166 J/cm2. The morphological alterations of the dentin surfaces and odontoblasts were examined with scanning electron microscopy (SEM), and the morphological alterations of the dental pulp tissue irradiated by laser were observed with an upright microscope. Results: The study demonstrated that dentinal tubules can be entirely blocked after irradiation by 980-nm diode laser, regardless of the parameter setting. Diode laser with settings of 2.0 W and 980-nm sealed exposed dentin tubules effectively, and no significant morphological alterations of the pulp and odontoblasts were observed after irradiation. Conclusions: Irradiation with 980-nm diode laser could be effective for routine clinical treatment of DH, and 2.0W/CW (166 J/cm2) was a suitable energy parameter due to its rapid sealing of the exposed dentin tubules and its safety to the odontoblasts and pulp tissue. PMID:25606318

  19. Control of dental-derived induced pluripotent stem cells through modified surfaces for dental application.

    PubMed

    Choi, Hyunmin; Park, Kyu-Hyung; Lee, Ah-Reum; Mun, Chin Hee; Shin, Yong Dae; Park, Yong-Beom; Park, Young-Bum

    2017-07-01

    The aim of this study is to investigate the behaviour of iPSc derived from dental stem cells in terms of initial adhesion, differentiation potential on differently surface-treated titanium disc. iPSc derived from human gingival fibroblasts (hGFs) were established using 4-reprogramming factors transduction with Sendai virus. The hGF-iPSc established in this study exhibited the morphology and growth properties similar to human embryonic stem (ES) cells and expressed pluripotency makers. Alkaline Phosphatase (AP) staining, Embryoid Body (EB) formation and in vitro differentiation and karyotyping further confirmed pluripotency of hGF-iPSc. Then, hGF-iPSc were cultured on machined- and Sandblasted and acid etched (SLA)-treated titanium discs with osteogenic induction medium and their morphological as well as quantitative changes according to different surface types were investigated using Alizrin Red S staining, Scanning electron microscopy (SEM), Flow cytometry and RT-PCR. Time-dependent and surface-dependent morphological changes as well as quantitative change in osteogenic differentiation of hGF-iPSc were identified and osteogenic gene expression of hGF-iPSc cultured on SLA-treated titanium disc found to be greater than machined titanium disc, suggesting the fate of hGF-iPSc may be determined by the characteristics of surface to which hGF-iPSc first adhere. iPSc derived from dental stem cell can be one of the most promising and practical cell sources for personalized regenerative dentistry and their morphological change as well as quantitative change in osteogenic differentiation according to different surface types may be further utilized for future clinical application incorporated with dental implant.

  20. Measurement of occlusion of the spinal canal and intervertebral foramen by intervertebral disc bulge

    PubMed Central

    Cuchanski, Mathieu; Cook, Daniel; Whiting, Donald M.; Cheng, Boyle C.

    2011-01-01

    Background Disc protrusion has been proposed to be a possible cause of both pain and stenosis in the lower spine. No previous study has described the amount of disc occlusion of the spinal canal and intervertebral foramen that occurs under different loading conditions. The objective of this study was to quantitatively assess the percent occlusion of the spinal canal and intervertebral foramen by disc bulge under different loading conditions. Methods Spinal canal depth and foraminal width were measured on computed tomography–scanned images of 7 human lumbar spine specimens. In vitro disc bulge measurements were completed by use of a previously described method in which single functional spinal units were subjected to 3 separate load protocols in a spine test machine and disc bulge was recorded with an optoelectric motion system that tracked active light-emitting diodes placed on the posterior and posterolateral aspects of the intervertebral disc. Occlusion was defined as percentage of encroachment into area of interest by maximum measured disc bulge at corresponding point of interest (the spinal canal is at the posterior point; the intervertebral foramen is at the posterolateral point). Results The mean spinal canal depth and mean foraminal width were 19 4 ± mm and 5 ± 2 mm, respectively. Mean spinal canal occlusion under a 250-N axial load, ± 2.5 Nm of flexion/extension, and ± 2.5 Nm of lateral bend was 2.5% ± 1.9%, 2.5% ± 1.6%, and 1.5% ± 0.8%, respectively. Mean intervertebral foramen occlusion under a 250-N axial load, ± 2.5 Nm of flexion/extension, and ± 2.5 Nm of lateral bend was 7.8% ± 4.7%, 9.5% ± 5.7%, and 11.3% ± 6.2%, respectively. Conclusion Percent occlusion of the spinal canal and intervertebral foramen is dependent on magnitude and direction of load. Exiting neural elements at the location of the intervertebral foramen are the most vulnerable to impingement and generation of pain. PMID:25802663

  1. Disc cell clusters in pathological human intervertebral discs are associated with increased stress protein immunostaining.

    PubMed

    Sharp, Christopher A; Roberts, Sally; Evans, Helena; Brown, Sharon J

    2009-11-01

    Intervertebral disc (IVD) cells within the annulus fibrosus (AF) and nucleus pulposus (NP) maintain distinct functional extracellular matrices and operate within a potentially noxious and stressful environment. How disc cells respond to stress and whether stress is responsible for triggering degeneration is unknown. Disc cell proliferation and cluster formation are most marked in degenerate IVDs, possibly indicating attempts at matrix repair. In other tissues, stress proteins increase rapidly after stress protecting cell function and, although implicated in degeneration of articular cartilage, have received little attention in degenerative IVD pathologies. We have compared the distribution of stress protein immunolocalization in pathological and control IVDs. Disc tissues were obtained at surgery from 43 patients with degenerative disc disease (DDD) and herniation, and 12 controls at postmortem. Tissues were immunostained with a polyclonal antibody for heat shock factor 1 (HSF-1) and monoclonal antibodies for the heat shock proteins, Hsp27 and Hsp72, using an indirect immunoperoxidase method. Positively stained cells were expressed as a percentage of the total. Cell cluster formation was also assessed. The proportion of cells in clusters was similar in the AF (both 2%) and NP (8 and 9%) of control and DDD samples, whereas in herniated tissues this was increased (AF 12%, NP 14%). Stress antigen staining tended to be more frequent in clustered rather than in single/doublet cells, and this was significant (P < 0.005) in both the AF and NP of herniated discs. Clustered cells, which are most common in herniated discs, may be mounting a protective response to abnormal environmental factors associated with disc degeneration. A better understanding of the stress response in IVD cells may allow its utilization in disc cell therapies.

  2. Biomechanical Characterization of an Annulus Sparing Spinal Disc Prosthesis

    PubMed Central

    Buttermann, Glenn R.; Beaubien, Brian P.

    2009-01-01

    Background Context Current spine arthroplasty devices, require disruption of the annulus fibrosus for implantation. Preliminary studies of a unique annulus sparing intervertebral prosthetic disc (IPD), found that preservation of the annulus resulted in load sharing of the annulus with the prosthesis. Purpose Determine flexibility of the IPD versus fusion constructs in normal and degenerated human spines. Study design/Setting Biomechanical comparison of motion segments in the intact, fusion and mechanical nucleus replacement states for normal and degenerated states. Patient setting Thirty lumbar motion segments. Outcomes Measures Intervertebral height; motion segment range-of-motion (ROM), neutral zone (NZ), stiffness. Methods Motion segments had multi-directional flexibility testing to 7.5 Nm for intact discs, discs reconstructed using the IPD (n=12), or after anterior/posterior fusions (n=18). Interbody height and axial compression stiffness changes were determined for the reconstructed discs by applying axial compression to 1500 N. Analysis included stratifying results to normal mobile vs. rigid degenerated intact motion segments. Results The mean interbody height increase was 1.5 mm for IPD reconstructed discs. vs 3.0 mm for fused segments. Axial compression stiffness was 3.0 ± 0.9 kN/mm for intact compared to 1.2 ± 0.4 kN/mm for IPD reconstructed segments. Reconstructed disc ROM was 9.0° ± 3.7° in flexion-extension, 10.6° ± 3.4° in lateral bending and 2.8° ± 1.4° in axial torsion which was similar to intact values and significantly greater than respective fusion values (p<0.001). Mobile intact segments exhibited significantly greater rotation after fusion vs. their more rigid counterparts (p<0.05), however, intact motion was not related to motion after IPD reconstruction. The NZ and rotational stiffness followed similar trends. Differences in NZ between mobile and rigid intact specimens tended to decrease in the IPD reconstructed state. Conclusion The annulus sparing IPD generally reproduced the intact segment biomechanics in terms of ROM, NZ, and stiffness. Furthermore, the IPD reconstructed discs imparted stability by maintaining a small neutral zone. The IPD reconstructed discs were significantly less rigid than the fusion constructs and may be an attractive alternative for the treatment of DDD. PMID:19540816

  3. Fortifying the Bone-Implant Interface Part 1: An In Vitro Evaluation of 3D-Printed and TPS Porous Surfaces.

    PubMed

    MacBarb, Regina F; Lindsey, Derek P; Bahney, Chelsea S; Woods, Shane A; Wolfe, Mark L; Yerby, Scott A

    2017-01-01

    An aging society and concomitant rise in the incidence of impaired bone health have led to the need for advanced osteoconductive spinal implant surfaces that promote greater biological fixation ( e.g. for interbody fusion cages, sacroiliac joint fusion implants, and artificial disc replacements). Additive manufacturing, i.e. 3D-printing, may improve bone integration by generating biomimetic spinal implant surfaces that mimic bone morphology. Such surfaces may foster an enhanced cellular response compared to traditional implant surfacing processes. This study investigated the response of human osteoblasts to additive manufactured (AM) trabecular-like titanium implant surfaces compared to traditionally machined base material with titanium plasma spray (TPS) coated surfaces, with and without a nanocrystalline hydroxyapatite (HA) coating. For TPS-coated discs, wrought Ti6Al4V ELI was machined and TPS-coating was applied. For AM discs, Ti6Al4V ELI powder was 3D-printed to form a solid base and trabecular-like porous surface. The HA-coating was applied via a precipitation dip-spin method. Surface porosity, pore size, thickness, and hydrophilicity were characterized. Initial cell attachment, proliferation, alkaline phosphatase (ALP) activity, and calcium production of hFOB cells ( n =5 per group) were measured. Cells on AM discs exhibited expedited proliferative activity. While there were no differences in mean ALP expression and calcium production between TPS and AM discs, calcium production on the AM discs trended 48% higher than on TPS discs ( p =0.07). Overall, HA-coating did not further enhance results compared to uncoated TPS and AM discs. Results demonstrate that additive manufacturing allows for controlled trabecular-like surfaces that promote earlier cell proliferation and trends toward higher calcium production than TPS coating. Results further showed that nanocrystalline HA may not provide an advantage on porous titanium surfaces. Additive manufactured porous titanium surfaces may induce a more osteogenic environment compared to traditional TPS, and thus present as an attractive alternative to TPS-coating for orthopedic spinal implants.

  4. Expression and functional roles of estrogen receptor GPR30 in human intervertebral disc.

    PubMed

    Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Yan, Feng; Chong, Beng H; Diwan, Ashish D

    2016-04-01

    Estrogen withdrawal, a characteristic of female aging, is associated with age-related intervertebral disc (IVD) degeneration. The function of estrogen is mediated by two classic nuclear receptors, estrogen receptor (ER)-α and -β, and a membrane bound G-protein-coupled receptor 30 (GPR30). To date, the expression and function of GPR30 in human spine is poorly understood. This study aimed to evaluate GPR30 expression in IVD, and its role in estrogen-related regulation of proliferation and apoptosis of disc nucleus pulposus (NP) cells. GPR30 expression was examined in 30 human adult NP and 9 fetal IVD. Results showed that GPR30 was expressed in NP cells at both mRNA and protein levels. In human fetal IVD, GPR30 protein was expressed in the NP at 12-14 weeks gestation, but was undetectable at 8-11 weeks. The effect of 17β-estradiol (E2) on GPR30-mediated proliferation and interleukin-1β (IL-1β)-induced apoptosis of NP cells was investigated. Cultured NP cells were treated with or without E2, GPR30 antagonist G36, and ER antagonist ICI 182,780. NP cell viability was tested by MTS assay. Apoptosis was determined by flow cytometry using fluorescence labeled annexin-V, TUNEL assay and immumnocytochemical staining of activated caspase-3. E2 enhanced cell proliferation and prevented IL-1β-induced cell death, but the effect was partially blocked by G36 and completely abrogated by a combination of ICI 182,780 and G36. This study demonstrates that GPR30 is expressed in human IVD to transmit signals triggering E2-induced NP cell proliferation and protecting against IL-1β-induced apoptosis. The effects of E2 on NP cells require both GPR30 and classic estrogen receptors. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Can Exercise Positively Influence the Intervertebral Disc?

    PubMed

    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.

  6. Development of collagen fibers and vasculature of the fetal TMJ.

    PubMed

    Yang, L; Wang, H; Wang, M; Ohta, Y; Suwa, F

    1992-10-01

    Using 12 human fetuses, histological development and changes in connective fiber structure and fine vascular patterns have been investigated in various fetal gestational stages by light and scanning electron microscopy. The main arterial supply of the articular disc was from the bilaminar region and pterygoideus lateralis muscle. The vascular network on the disc surface was related with fluid secretion. When the bilaminar region was compressed, it caused ischemia and fibrosis as the main pathological changes in TMJ derangement. A decrease in fluid from blood vessels might occur in TMJ degeneration. Collagen fibers in the disc passed mainly anteroposteriorly. In the anterior and posterior bands, muscular tendon fibers came from the pterygoideus lateralis muscle and superior stratum of the bilaminar region. In the posterior band three-dimensional structures of collagen fibers suitable for load bearing were observed. The compass network and process on the disc showed the normal structure that is formed gradually and has functions including dispersion, pressure bearing, friction-proofing and storage of the synovial fluid. Attachments of the disc were suitable for disc function. Large elastic fibers in the posterolateral part of the superior stratum of the bilaminar region may be antagonistic to the upper head of the pterygoideus lateralis muscle fibers passing medioanteriorly, indicating that this antagonism is available for disc function.

  7. A new approach to optic disc detection in human retinal images using the firefly algorithm.

    PubMed

    Rahebi, Javad; Hardalaç, Fırat

    2016-03-01

    There are various methods and algorithms to detect the optic discs in retinal images. In recent years, much attention has been given to the utilization of the intelligent algorithms. In this paper, we present a new automated method of optic disc detection in human retinal images using the firefly algorithm. The firefly intelligent algorithm is an emerging intelligent algorithm that was inspired by the social behavior of fireflies. The population in this algorithm includes the fireflies, each of which has a specific rate of lighting or fitness. In this method, the insects are compared two by two, and the less attractive insects can be observed to move toward the more attractive insects. Finally, one of the insects is selected as the most attractive, and this insect presents the optimum response to the problem in question. Here, we used the light intensity of the pixels of the retinal image pixels instead of firefly lightings. The movement of these insects due to local fluctuations produces different light intensity values in the images. Because the optic disc is the brightest area in the retinal images, all of the insects move toward brightest area and thus specify the location of the optic disc in the image. The results of implementation show that proposed algorithm could acquire an accuracy rate of 100 % in DRIVE dataset, 95 % in STARE dataset, and 94.38 % in DiaRetDB1 dataset. The results of implementation reveal high capability and accuracy of proposed algorithm in the detection of the optic disc from retinal images. Also, recorded required time for the detection of the optic disc in these images is 2.13 s for DRIVE dataset, 2.81 s for STARE dataset, and 3.52 s for DiaRetDB1 dataset accordingly. These time values are average value.

  8. Engineering Human TMJ Discs with Protein-Releasing 3D-Printed Scaffolds.

    PubMed

    Legemate, K; Tarafder, S; Jun, Y; Lee, C H

    2016-07-01

    The temporomandibular joint (TMJ) disc is a heterogeneous fibrocartilaginous tissue positioned between the mandibular condyle and glenoid fossa of the temporal bone, with important roles in TMJ functions. Tissue engineering TMJ discs has emerged as an alternative approach to overcoming limitations of current treatments for TMJ disorders. However, the anisotropic collagen orientation and inhomogeneous fibrocartilaginous matrix distribution present challenges in the tissue engineering of functional TMJ discs. Here, we developed 3-dimensional (3D)-printed anatomically correct scaffolds with region-variant microstrand alignment, mimicking anisotropic collagen alignment in the TMJ disc and corresponding mechanical properties. Connective tissue growth factor (CTGF) and transforming growth factor beta 3 (TGFβ3) were then delivered in the scaffolds by spatially embedding CTGF- or TGFβ3-encapsulated microspheres (µS) to reconstruct the regionally variant fibrocartilaginous matrix in the native TMJ disc. When cultured with human mesenchymal stem/progenitor cells (MSCs) for 6 wk, 3D-printed scaffolds with CTGF/TGFβ3-µS resulted in a heterogeneous fibrocartilaginous matrix with overall distribution of collagen-rich fibrous structure in the anterior/posterior (AP) bands and fibrocartilaginous matrix in the intermediate zone, reminiscent of the native TMJ disc. High dose of CTGF/TGFβ3-µS (100 mg µS/g of scaffold) showed significantly more collagen II and aggrecan in the intermediate zone than a low dose (50 mg µS/g of scaffold). Similarly, a high dose of CTGF/TGFβ3-µS yielded significantly higher collagen I expression in the AP bands compared with the low-dose and empty µS. From stress relaxation tests, the ratio of relaxation modulus to instantaneous modulus was significantly smaller with CTGF/TGFβ3-µS than empty µS. Similarly, a significantly higher coefficient of viscosity was achieved with the high dose of CTGF/TGFβ3-µS compared with the low-dose and empty µS, suggesting the dose effect of CTGF and TGFβ3 on fibrocartilage formation. Together, our findings may represent an efficient approach to engineering the TMJ disc graft with anisotropic scaffold microstructure, heterogeneous fibrocartilaginous matrix, and region-dependent viscoelastic properties. © International & American Associations for Dental Research 2016.

  9. Expression of growth differentiation factor 6 in the human developing fetal spine retreats from vertebral ossifying regions and is restricted to cartilaginous tissues.

    PubMed

    Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Gulati, Twishi; Fang, Zhimin; Pathmanandavel, Sarennya; Diwan, Ashish D

    2016-02-01

    During embryogenesis vertebral segmentation is initiated by sclerotomal cell migration and condensation around the notochord, forming anlagen of vertebral bodies and intervertebral discs. The factors that govern the segmentation are not clear. Previous research demonstrated that mutations in growth differentiation factor 6 resulted in congenital vertebral fusion, suggesting this factor plays a role in development of vertebral column. In this study, we detected expression and localization of growth differentiation factor 6 in human fetal spinal column, especially in the period of early ossification of vertebrae and the developing intervertebral discs. The extracellular matrix proteins were also examined. Results showed that high levels of growth differentiation factor 6 were expressed in the nucleus pulposus of intervertebral discs and the hypertrophic chondrocytes adjacent to the ossification centre in vertebral bodies, where strong expression of proteoglycan and collagens was also detected. As fetal age increased, the expression of growth differentiation factor 6 was decreased correspondingly with the progress of ossification in vertebral bodies and restricted to cartilaginous regions. This expression pattern and the genetic link to vertebral fusion suggest that growth differentiation factor 6 may play an important role in suppression of ossification to ensure proper vertebral segmentation during spinal development. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  10. Three-dimensional finite element models of the human pubic symphysis with viscohyperelastic soft tissues.

    PubMed

    Li, Zuoping; Alonso, Jorge E; Kim, Jong-Eun; Davidson, James S; Etheridge, Brandon S; Eberhardt, Alan W

    2006-09-01

    Three-dimensional finite element (FE) models of human pubic symphyses were constructed from computed tomography image data of one male and one female cadaver pelvis. The pubic bones, interpubic fibrocartilaginous disc and four pubic ligaments were segmented semi-automatically and meshed with hexahedral elements using automatic mesh generation schemes. A two-term viscoelastic Prony series, determined by curve fitting results of compressive creep experiments, was used to model the rate-dependent effects of the interpubic disc and the pubic ligaments. Three-parameter Mooney-Rivlin material coefficients were calculated for the discs using a heuristic FE approach based on average experimental joint compression data. Similarly, a transversely isotropic hyperelastic material model was applied to the ligaments to capture average tensile responses. Linear elastic isotropic properties were assigned to bone. The applicability of the resulting models was tested in bending simulations in four directions and in tensile tests of varying load rates. The model-predicted results correlated reasonably with the joint bending stiffnesses and rate-dependent tensile responses measured in experiments, supporting the validity of the estimated material coefficients and overall modeling approach. This study represents an important and necessary step in the eventual development of biofidelic pelvis models to investigate symphysis response under high-energy impact conditions, such as motor vehicle collisions.

  11. Human body modeling method to simulate the biodynamic characteristics of spine in vivo with different sitting postures.

    PubMed

    Dong, Rui-Chun; Guo, Li-Xin

    2017-11-01

    The aim of this study is to model the computational model of seated whole human body including skeleton, muscle, viscera, ligament, intervertebral disc, and skin to predict effect of the factors (sitting postures, muscle and skin, buttocks, viscera, arms, gravity, and boundary conditions) on the biodynamic characteristics of spine. Two finite element models of seated whole body and a large number of finite element models of different ligamentous motion segments were developed and validated. Static, modal, and transient dynamic analyses were performed. The predicted vertical resonant frequency of seated body model was in the range of vertical natural frequency of 4 to 7 Hz. Muscle, buttocks, viscera, and the boundary conditions of buttocks have influence on the vertical resonant frequency of spine. Muscle played a very important role in biodynamic response of spine. Compared with the vertical posture, the posture of lean forward or backward led to an increase in stress on anterior or lateral posterior of lumbar intervertebral discs. This indicated that keeping correct posture could reduce the injury of vibration on lumbar intervertebral disc under whole-body vibration. The driving posture not only reduced the load of spine but also increased the resonant frequency of spine. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Missense mutation in DISC1 C-terminal coiled-coil has GSK3β signaling and sex-dependent behavioral effects in mice

    PubMed Central

    Dachtler, James; Elliott, Christina; Rodgers, R. John; Baillie, George S.; Clapcote, Steven J.

    2016-01-01

    Disrupted-in-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and affective disorders. The full-length DISC1 protein consists of an N-terminal ‘head’ domain and a C-terminal tail domain that contains several predicted coiled-coils, structural motifs involved in protein-protein interactions. To probe the in vivo effects of missense mutation of DISC1’s C-terminal tail, we tested mice carrying mutation D453G within a predicted α-helical coiled-coil region. We report that, relative to wild-type littermates, female DISC1D453G mice exhibited novelty-induced hyperlocomotion, an anxiogenic profile in the elevated plus-maze and open field tests, and reduced social exploration of unfamiliar mice. Male DISC1D453G mice displayed a deficit in passive avoidance, while neither males nor females exhibited any impairment in startle reactivity or prepulse inhibition. Whole brain homogenates showed normal levels of DISC1 protein, but decreased binding of DISC1 to GSK3β, decreased phospho-inhibition of GSK3β at serine 9, and decreased levels of β-catenin in DISC1D453G mice of either sex. Interrupted GSK3β signaling may thus be part of the mechanism underlying the behavioral phenotype associated with D453G, in common with the previously described N-terminal domain mutations Q31L and L100P in mice, and the schizophrenia risk-conferring variant R264Q in humans. PMID:26728762

  13. Effects of disc warping on the inclination evolution of star-disc-binary systems

    NASA Astrophysics Data System (ADS)

    Zanazzi, J. J.; Lai, Dong

    2018-07-01

    Several recent studies have suggested that circumstellar discs in young stellar binaries may be driven into misalignement with their host stars due to the secular gravitational interactions between the star, disc, and the binary companion. The disc in such systems is twisted/warped due to the gravitational torques from the oblate central star and the external companion. We calculate the disc warp profile, taking into account the bending wave propagation and viscosity in the disc. We show that for typical protostellar disc parameters, the disc warp is small, thereby justifying the `flat-disc' approximation adopted in previous theoretical studies. However, the viscous dissipation associated with the small disc warp/twist tends to drive the disc towards alignment with the binary or the central star. We calculate the relevant time-scales for the alignment. We find that the alignment is effective for sufficiently cold discs with strong external torques, especially for systems with rapidly rotating stars, but is ineffective for the majority of the star-disc-binary systems. Viscous warp-driven alignment may be necessary to account for the observed spin-orbit alignment in multiplanet systems if these systems are accompanied by an inclined binary companion.

  14. In Vitro Characterization of a Stem-Cell-Seeded Triple-Interpenetrating-Network Hydrogel for Functional Regeneration of the Nucleus Pulposus

    PubMed Central

    Smith, Lachlan J.; Gorth, Deborah J.; Showalter, Brent L.; Chiaro, Joseph A.; Beattie, Elizabeth E.; Elliott, Dawn M.; Mauck, Robert L.; Chen, Weiliam

    2014-01-01

    Intervertebral disc degeneration is implicated as a major cause of low-back pain. There is a pressing need for new regenerative therapies for disc degeneration that restore native tissue structure and mechanical function. To that end we investigated the therapeutic potential of an injectable, triple-interpenetrating-network hydrogel comprised of dextran, chitosan, and teleostean, for functional regeneration of the nucleus pulposus (NP) of the intervertebral disc in a series of biomechanical, cytotoxicity, and tissue engineering studies. Biomechanical properties were evaluated as a function of gelation time, with the hydrogel reaching ∼90% of steady-state aggregate modulus within 10 h. Hydrogel mechanical properties evaluated in confined and unconfined compression were comparable to native human NP properties. To confirm containment within the disc under physiological loading, toluidine-blue-labeled hydrogel was injected into human cadaveric spine segments after creation of a nucleotomy defect, and the segments were subjected to 10,000 cycles of loading. Gross analysis demonstrated no implant extrusion, and further, that the hydrogel interdigitated well with native NP. Constructs were next surface-seeded with NP cells and cultured for 14 days, confirming lack of hydrogel cytotoxicity, with the hydrogel maintaining NP cell viability and promoting proliferation. Next, to evaluate the potential of the hydrogel to support cell-mediated matrix production, constructs were seeded with mesenchymal stem cells (MSCs) and cultured under prochondrogenic conditions for up to 42 days. Importantly, the hydrogel maintained MSC viability and promoted proliferation, as evidenced by increasing DNA content with culture duration. MSCs differentiated along a chondrogenic lineage, evidenced by upregulation of aggrecan and collagen II mRNA, and increased GAG and collagen content, and mechanical properties with increasing culture duration. Collectively, these results establish the therapeutic potential of this novel hydrogel for functional regeneration of the NP. Future work will confirm the ability of this hydrogel to normalize the mechanical stability of cadaveric human motion segments, and advance the material toward human translation using preclinical large-animal models. PMID:24410394

  15. The DISC Quotient

    NASA Astrophysics Data System (ADS)

    Elliott, John R.; Baxter, Stephen

    2012-09-01

    D.I.S.C: Decipherment Impact of a Signal's Content. The authors present a numerical method to characterise the significance of the receipt of a complex and potentially decipherable signal from extraterrestrial intelligence (ETI). The purpose of the scale is to facilitate the public communication of work on any such claimed signal, as such work proceeds, and to assist in its discussion and interpretation. Building on a "position" paper rationale, this paper looks at the DISC quotient proposed and develops the algorithmic steps and comprising measures that form this post detection strategy for information dissemination, based on prior work on message detection, decipherment. As argued, we require a robust and incremental strategy, to disseminate timely, accurate and meaningful information, to the scientific community and the general public, in the event we receive an "alien" signal that displays decipherable information. This post-detection strategy is to serve as a stepwise algorithm for a logical approach to information extraction and a vehicle for sequential information dissemination, to manage societal impact. The "DISC Quotient", which is based on signal analysis processing stages, includes factors based on the signal's data quantity, structure, affinity to known human languages, and likely decipherment times. Comparisons with human and other phenomena are included as a guide to assessing likely societal impact. It is submitted that the development, refinement and implementation of DISC as an integral strategy, during the complex processes involved in post detection and decipherment, is essential if we wish to minimize disruption and optimize dissemination.

  16. Functional disorders of the temporomandibular joints: Internal derangement of the temporomandibular joint.

    PubMed

    Chang, Chih-Ling; Wang, Ding-Han; Yang, Mu-Chen; Hsu, Wun-Eng; Hsu, Ming-Lun

    2018-04-01

    Temporomandibular joint (TMJ) is one of the most complex joints of the human body. Due to its unique movement, in terms of combination of rotation and translator movement, disc of the joint plays an important role to maintain its normal function. In order to sustain the normal function of the TMJ, disc must be kept in proper position as well as maintain normal shape in all circumstances. Once the disc is not any more in its normal position during function of the joint, disturbance of the joint can be occurred which will lead to subsequent distortion of the disc. Shape of the disc can be influenced by many factors i.e.: abnormal function or composition of the disc itself. Etiology of the internal derangement of the disc remains controversial. Multifactorial theory has been postulated in most of previous manuscripts. Disc is composed of mainly extracellular matrix. Abnormal proportion of collagen type I & III may also leads to joint hypermobility which may be also a predisposing factor of this disorder. Thus it can be recognized as local manifestation of a systemic disorder. Different treatment modalities with from conservative treatment to surgical intervention distinct success rate have been reported. Recently treatment with extracellular matrix injection becomes more and more popular to strengthen the joint itself. Since multifactorial in character, the best solution of the treatment modalities should be aimed to resolve possible etiology from different aspects. Team work may be indication to reach satisfied results. Copyright © 2018. Published by Elsevier Taiwan.

  17. Effects of annulus defects and implantation of poly(lactic-co-glycolic acid) (PLGA)/fibrin gel scaffolds on nerves ingrowth in a rabbit model of annular injury disc degeneration.

    PubMed

    Xin, Long; Xu, Weixing; Yu, Leijun; Fan, Shunwu; Wang, Wei; Yu, Fang; Wang, Zhenbin

    2017-05-12

    Growth of nerve fibers has been shown to occur in a rabbit model of intravertebral disc degeneration (IVD) induced by needle puncture. As nerve growth may underlie the process of chronic pain in humans affected by disc degeneration, we sought to investigate the factors underlying nerve ingrowth in a minimally invasive annulotomy rabbit model of IVD by comparing the effects of empty disc defects with those of defects filled with poly(lactic-co-glycolic acid)/fibrin gel (PLGA) plugs. New Zealand white rabbits (n = 24) received annular injuries at three lumbar levels (L3/4, L4/5, and L5/6). The discs were randomly assigned to four groups: (a) annular defect (1.8-mm diameter; 4-mm depth) by mini-trephine, (b) annular defect implanted with a PLGA scaffold containing a fibrin gel, (c) annular puncture by a 16G needle (5-mm depth), and (d) uninjured L2/3 disc (control). Disc degeneration was evaluated by radiography, MRI, histology, real-time PCR, and analysis of proteoglycan (PG) content. Nerve ingrowth into the discs was assessed by immunostaining with the nerve marker protein gene product 9.5. Injured discs showed a progressive disc space narrowing with significant disc degeneration and proteoglycan loss, as confirmed by imaging results, molecular and compositional analysis, and histological examinations. In 16G punctured discs, nerve ingrowth was observed on the surface of scar tissue. In annular defects, nerve fibers were found to be distributed along small fissures within the fibrocartilaginous-like tissue that filled the AF. In discs filled with PLGA/ fibrin gel, more nerve fibers were observed growing deeper into the inner AF along the open annular track.  In addition, innervations scores showed significantly higher than those of punctured discs and empty defects. A limited vascular proliferation was found in the injured sites and regenerated tissues. Nerve ingrowth was significantly higher in PLGA/fibrin-filled discs than in empty defects. Possible explanations include (i) annular fissures along the defect and early loss of proteoglycan may facilitate the ingrowth process and (ii) biodegradable PLGA/fibrin gel may promote adverse growth of nerves and blood vessels into deeper parts of injured disc. The rabbit annular defect model of disc degeneration appears suitable to investigate the effects of nerve ingrowth in relation to pain generation.

  18. Running exercise strengthens the intervertebral disc

    PubMed Central

    Belavý, Daniel L.; Quittner, Matthew J.; Ridgers, Nicola; Ling, Yuan; Connell, David; Rantalainen, Timo

    2017-01-01

    There is currently no evidence that the intervertebral discs (IVDs) can respond positively to exercise in humans. Some authors have argued that IVD metabolism in humans is too slow to respond anabolically to exercise within the human lifespan. Here we show that chronic running exercise in men and women is associated with better IVD composition (hydration and proteoglycan content) and with IVD hypertrophy. Via quantitative assessment of physical activity we further find that accelerations at fast walking and slow running (2 m/s), but not high-impact tasks, lower intensity walking or static positions, correlated to positive IVD characteristics. These findings represent the first evidence in humans that exercise can be beneficial for the IVD and provide support for the notion that specific exercise protocols may improve IVD material properties in the spine. We anticipate that our findings will be a starting point to better define exercise protocols and physical activity profiles for IVD anabolism in humans. PMID:28422125

  19. Chronic hemodynamic overload of the atria is an important factor for gap junction remodeling in human and rat hearts.

    PubMed

    Rucker-Martin, Catherine; Milliez, Paul; Tan, Sisareuth; Decrouy, Xavier; Recouvreur, Michel; Vranckx, Roger; Delcayre, Claude; Renaud, Jean-François; Dunia, Irene; Segretain, Dominique; Hatem, Stéphane N

    2006-10-01

    The expression and distribution of connexins is abnormal in a number of cardiac diseases, including atrial fibrillation, and is believed to favor conduction slowing and arrhythmia. Here, we studied the role of atrial structural remodeling in the disorganization of gap junctions and whether redistributed connexins can form new functional junction channels. Expression of connexin-43 (Cx43) was characterized by immunoblotting and immunohistochemistry in human right atrial specimens and in rat atria after myocardial infarction (MI). Gap junctions were studied by electron and 3-D microscopy, and myocyte-myocyte coupling was determined by Lucifer yellow dye transfer. In both chronically hemodynamically overloaded human atria in sinus rhythm and in dilated atria from MI-rats, Cx43 were dephosphorylated and redistributed from the intercalated disc to the lateral cell membranes as observed during atrial fibrillation. In MI-rats, the gap junctions at the intercalated disc were smaller (20% decrease) and contained very little Cx43 (0 or 1 gold particle vs. 42 to 98 in sham-operated rats). In the lateral membranes of myocytes, numerous connexon aggregates comprising non-phosphorylated Cx43 were observed. These connexon aggregates were in no case assembled into gap junction plaque-like structures. However, N-cadherin was well organized in the intercalated disc. There was very little myocyte-myocyte coupling in MI-rat atria and no myocyte-fibroblast coupling. Regression of the atrial remodeling was associated with the normalization of Cx43 localization. Structural alteration of the atrial myocardium is an important factor in the disorganization of connexins and gap junction. Moreover, redistributed Cx43 do not form junction channels.

  20. Thermal analysis of disc brakes using finite element method

    NASA Astrophysics Data System (ADS)

    Jaenudin, Jamari, J.; Tauviqirrahman, M.

    2017-01-01

    Disc brakes are components of a vehicle that serve to slow or stop the rotation of the wheel. This paper discusses the phenomenon of heat distribution on the brake disc during braking. Heat distribution on the brake disc is caused by kinetic energy changing into mechanical energy. Energy changes occur during the braking process due to friction between the surface of the disc and a disc pad. The temperature resulting from this friction rises high. This thermal analysis on brake discs is aimed to evaluate the performance of an electric car in the braking process. The aim of this study is to analyze the thermal behavior of the brake discs using the Finite Element Method (FEM) through examining the heat distribution on the brake disc using 3-D modeling. Results obtained from the FEM reflect the effects of high heat due to the friction between the disc pad with the disc rotor. Results of the simulation study are used to identify the effect of the heat distribution that occurred during the braking process.

  1. Is there any relationship between proinflammatory mediator levels in disc material and myelopathy with cervical disc herniation and spondylosis? A non-randomized, prospective clinical study

    PubMed Central

    Asir, Alparslan; Cetinkal, Ahmet; Gedik, Nursal; Kutlay, Ahmet Murat; Çolak, Ahmet; Kurtar, Sedat; Simsek, Hakan

    2007-01-01

    The proinflammatory mediator (PIM) levels were assessed in surgically removed samples of herniated cervical intervertebral discs. The objective of this study was to investigate if there is a correlation between the levels of PIMs in disc material and myelopathy associated with cervical intervertebral disc herniation and spondylosis. The role of proinflammatory mediators in the degeneration of intervertebral disc and the inflammatory effects of disc herniations on radicular pain has been previously published. However, the possible relationship between PIMs and myelopathy related to cervical disc herniation and spondylosis has not been investigated before. Thirty-two patients undergoing surgery for cervical disc herniation and spondylosis were investigated. Surgically obtained disc materials, stored at 70°C, were classified into two groups: cervical disc herniation alone or with myelopathy. Biochemical preparation and solid phase enzyme amplified sensitivity immunoassay (ELISIA) analysis of the samples were performed to assess the concentration of mediators in the samples. Very similar values of interleukin-6 were found in both groups whereas the concentrations of mediators were significantly higher in myelopathy group. This study has demonstrated that PIMs are involved in cervical intervertebral disc degeneration with higher concentrations in the samples associated with myelopathy. PMID:17476536

  2. [The Autocad system for planimetric study of the optic disc in glaucoma: technique and reproducibility study].

    PubMed

    Sánchez Pérez, A; Honrubia López, F M; Larrosa Poves, J M; Polo Llorens, V; Melcon Sánchez-Frieras, B

    2001-09-01

    To develop a lens planimetry technique for the optic disc using AutoCAD. To determine variability magnitude of the optic disc morphological measurements. We employed AutoCAD R.14.0 Autodesk: image acquisition, contour delimitation by multiple lines fitting or ellipse adjustment, image sectorialization and measurements quantification (optic disc and excavation, vertical diameters, optic disc area, excavation area, neuroretinal sector area and Beta atrophy area). Intraimage or operator and interimage o total reproducibility was studied by coefficient of variability (CV) (n=10) in normal and myopic optic discs. This technique allows to obtain optic disc measurement in 5 to 10 minutes time. Total or interimage variability of measurements introduced by one observer presents CV range from 1.18-4.42. Operator or intraimage measurement presents CV range from 0.30-4.21. Optic disc contour delimitation by ellipse adjustment achieved better reproducibility results than multiple lines adjustment in all measurements. Computer assisted AutoCAD planimetry is an interactive method to analyse the optic disc, feasible to incorporate to clinical practice. Reproducibility results are comparable to other analyzers in quantification optic disc morphology. Ellipse adjustment improves results in optic disc contours delimitation.

  3. Gene Activated Titanium Surfaces Promote In Vitro Osteogenesis

    PubMed Central

    Atluri, Keerthi; Lee, Joun; Seabold, Denise; Elangovan, Satheesh; Salem, Aliasger K.

    2016-01-01

    Commercially pure titanium (CpTi) and its alloys possess favorable mechanical and biological properties for use as implants in orthopedics and dentistry. However, failures in osseointegration still exist and are common in select individuals with risk factors such as smoking. Therefore, in this study, a proposal was made to enhance the potential of CpTi discs for osseointegration by coating their surfaces with nanoplexes comprising polyethyleneimine (PEI) and plasmid DNA encoding bone morphogenetic protein-2 (pBMP-2). The nanoplexes were characterized for size and surface charge at a range of N/P ratios. CpTi discs were surface characterized for morphology and composition before and after nanoplex coating using scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and X-ray powder diffraction (XRD). The cytotoxicity and transfection ability of CpTi discs coated with nanoplexes of varying N/P ratios in human bone marrow derived mesenchymal stem cells (BMSCs) was measured via MTS assays and flow cytometry, respectively. The CpTi discs coated with nanoplexes prepared at an N/P ratio of 10 (N/P-10) were considered optimal, resulting in 75% cell viability and 14% transfection efficiency. ELISA results demonstrated a significant enhancement in BMP-2 protein secretion by BMSCs 7 days post-treatment with CpTi discs coated with PEI/pBMP-2 nanoplexes (N/P-10), compared to the controls. Real time PCR data demonstrated that the BMSCs treated with PEI/pBMP-2 nanoplex coated CpTi discs resulted in an enhancement of runx-2, alkaline phosphatase and osteocalcin gene expressions on day 7, post-treatment. In addition, these BMSCs demonstrated enhanced calcium deposition on day 30 post-treatment as determined by qualitative (alizarin red staining) and quantitative (atomic absorption spectroscopy) assays. Thus, from all the above data it can be concluded that PEI/pBMP-2 nanoplex (N/P-10) coated CpTi discs have the potential to induce osteogenesis and enhance osseointegration. PMID:27706263

  4. Cytotoxic Effects of the Radiocontrast Agent Iotrolan and Anesthetic Agents Bupivacaine and Lidocaine in Three-Dimensional Cultures of Human Intervertebral Disc Nucleus Pulposus Cells: Identification of the Apoptotic Pathways

    PubMed Central

    Iwasaki, Koji; Sudo, Hideki; Yamada, Katsuhisa; Ito, Manabu; Iwasaki, Norimasa

    2014-01-01

    Background Discography and discoblock are imaging procedures used to diagnose discogenic low back pain. Although needle puncture of the intervertebral disc (IVD) itself induces disc degeneration, the agents used in these procedures may also have harmful effects on IVD cells. The purpose of this study was to analyze whether radiocontrast agents and local anesthetic agents have detrimental effects on human nucleus pulposus (NP) cells. Methods Healthy human NP cells were cultured for 7 days in three-dimensional (3D) cell–alginate bead composites, and were then exposed to clinically relevant doses of a radiocontrast agent (iotrolan) or local anesthetic (lidocaine or bupivacaine). Cell viability and apoptosis were measured by confocal microscopy and flow cytometry. On the basis of caspase expression profiles, the apoptotic pathways activated by the agents were identified by Western blot analysis. Results The radiocontrast agent iotrolan did not affect NP cell viability or induce apoptosis. In contrast, both the anesthetic agents significantly decreased cell viability and increased the apoptotic cell number in a time- and dose-dependent manner. After 120 min, 2% lidocaine and 0.5% bupivacaine decreased percent live cells to 13% and 10%, respectively (p<0.05). The number of apoptotic cells was doubled by increasing lidocaine dosage from 1% to 2% (23% and 42%) and bupivacaine from 0.25% to 0.50% (25% and 48%) (p<0.05). Western blot analysis revealed that both anesthetic agents upregulated cleaved caspase-3 and caspase-8, whereas only bupivacaine upregulated cleaved caspase-9. Conclusions/Significance The present study demonstrates that iotrolan does not affect the viability of healthy human NP cells. In contrast, the two anesthetic agents commonly used in discography or discoblock may cause extensive damage to IVDs by inducing apoptotic cell death. PMID:24642945

  5. Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration

    PubMed Central

    Le Maitre, Christine Lyn; Freemont, Anthony John; Hoyland, Judith Alison

    2007-01-01

    Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated β-galactosidase (SA-β-gal), and replicative potential. Expression of P16INK4A (increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a disintegrin and metalloprotease with thrombospondin motifs 5), and P16INK4A. Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of P16INK4A. Cells from degenerate discs (even from young patients) exhibited increased expression of P16INK4A, increased SA-β-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between P16INK4A and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration. PMID:17498290

  6. [Characteristics of hydroxyapatite/PMMA nanocomposites for provisional restoration and its biocompatibility with human gingival fibroblasts].

    PubMed

    Zhang, Jing-chao; Mo, An-chun; Li, Ji-dong; Wang, Xue-jiang; Li, Yu-bao

    2014-05-01

    To formulate hydroxyapatite (HA)/polymethyl methacrylate (PMMA) composites with improved cytocompatibility for provisional restoration. Nanocomposites with 20 wt%, 30 wt%, 40 wt%, and 50 wt% HA/PMMA (H/P) were developed and examined using X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM). Human gingival fibroblasts were cultured on those HA/PMMA discs and investigated by fluorescent staining on 24 h and MTT assay at 1 d, 3 d, 5 d and 7 d. Chemical integration of HA/PMMA interface was confirmed by XPS. Typical fusiform cells with adhesion spots were detected on 40 wt% and 50 wt% H/P discs. MTT results showed insignificant differences in cell growth between 40 wt% H/P and pure titanium (Ti, P > 0.05), while the other H/P discs showed significantly lower cell growth than pure Ti (P < 0.05). 40 wt% H/P might be a promising candidate for provisional dental implant restoration and for esthetic gingival contour.

  7. Fortifying the Bone-Implant Interface Part 1: An In Vitro Evaluation of 3D-Printed and TPS Porous Surfaces

    PubMed Central

    Lindsey, Derek P.; Bahney, Chelsea S.; Woods, Shane A.; Wolfe, Mark L.; Yerby, Scott A.

    2017-01-01

    Background An aging society and concomitant rise in the incidence of impaired bone health have led to the need for advanced osteoconductive spinal implant surfaces that promote greater biological fixation (e.g. for interbody fusion cages, sacroiliac joint fusion implants, and artificial disc replacements). Additive manufacturing, i.e. 3D-printing, may improve bone integration by generating biomimetic spinal implant surfaces that mimic bone morphology. Such surfaces may foster an enhanced cellular response compared to traditional implant surfacing processes. Methods This study investigated the response of human osteoblasts to additive manufactured (AM) trabecular-like titanium implant surfaces compared to traditionally machined base material with titanium plasma spray (TPS) coated surfaces, with and without a nanocrystalline hydroxyapatite (HA) coating. For TPS-coated discs, wrought Ti6Al4V ELI was machined and TPS-coating was applied. For AM discs, Ti6Al4V ELI powder was 3D-printed to form a solid base and trabecular-like porous surface. The HA-coating was applied via a precipitation dip-spin method. Surface porosity, pore size, thickness, and hydrophilicity were characterized. Initial cell attachment, proliferation, alkaline phosphatase (ALP) activity, and calcium production of hFOB cells (n=5 per group) were measured. Results Cells on AM discs exhibited expedited proliferative activity. While there were no differences in mean ALP expression and calcium production between TPS and AM discs, calcium production on the AM discs trended 48% higher than on TPS discs (p=0.07). Overall, HA-coating did not further enhance results compared to uncoated TPS and AM discs. Conclusions Results demonstrate that additive manufacturing allows for controlled trabecular-like surfaces that promote earlier cell proliferation and trends toward higher calcium production than TPS coating. Results further showed that nanocrystalline HA may not provide an advantage on porous titanium surfaces. Clinical Relevance Additive manufactured porous titanium surfaces may induce a more osteogenic environment compared to traditional TPS, and thus present as an attractive alternative to TPS-coating for orthopedic spinal implants. PMID:28765799

  8. Dentin abrasivity of various desensitizing toothpastes.

    PubMed

    Arnold, W H; Gröger, Ch; Bizhang, M; Naumova, E A

    2016-04-02

    The aim of this study was to compare the abrasivity of various commercially available toothpastes that claim to reduce dentin hypersensitivity. Dentin discs were prepared from 70 human extracted molars. The discs were etched with lemon juice for 5 min, and one half of the discs were covered with aluminum tape. Following this, they were brushed with 6 different toothpastes, simulating a total brushing time of 6 months. As a negative control, discs were brushed with tap water only. The toothpastes contained pro-arginine and calcium carbonate, strontium acetate, stannous fluoride, zinc carbonate and hydroxyapatite, new silica, or tetrapotassium pyrophosphate and hydroxyapatite. After brushing, the height differences between the control halves and the brushed halves were determined with a profilometer and statistically compared using a Mann-Whitney U test for independent variables. A significant difference (p < 0.001) in height difference between the controls and the toothpaste-treated samples was found in all cases, except for the stannous fluoride-containing toothpaste (p = 0.583). The highest abrasion was found in the toothpaste containing zinc carbonate and hydroxyapatite, and the lowest was found in the toothpaste containing pro-arginine and calcium carbonate. Desensitizing toothpastes with different desensitizing ingredients have different levels of abrasivity, which may have a negative effect on their desensitizing abilities over a long period of time.

  9. Tumorigenic Properties of Drosophila Epithelial Cells Mutant for lethal giant larvae.

    PubMed

    Calleja, Manuel; Morata, Ginés; Casanova, Jordi

    2016-08-01

    Mutations in Drosophila tumor suppressor genes (TSGs) lead to the formation of invasive tumors in the brain and imaginal discs. Here we studied the tumorigenic properties of imaginal discs mutant for the TSG gene lethal giant larvae (lgl). lgl mutant cells display the characteristic features of mammalian tumor cells: they can proliferate indefinitely, induce additional tracheogenesis (an insect counterpart of vasculogenesis) and invade neighboring tissues. Lgl mutant tissues exhibit high apoptotic levels, which lead to the activation of the Jun-N-Terminal Kinase (JNK) pathway. We propose that JNK is a key factor in the acquisition of these tumorigenic properties; it promotes cell proliferation and induces high levels of Mmp1 and confers tumor cells capacity to invade wild-type tissue. Noteworthy, lgl RNAi-mediated down-regulation does not produce similar transformations in the central nervous system (CNS), thereby indicating a fundamental difference between the cells of developing imaginal discs and those of differentiated organs. We discuss these results in the light of the "single big-hit origin" of some human pediatric or developmental cancers. Down-regulation of lgl in imaginal discs is sufficient to enhance tracheogenesis and to promote invasion and colonization of other larval structures including the CNS. Developmental Dynamics 245:834-843, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain neurodevelopmental markers in schizophrenia and healthy subjects.

    PubMed

    Takahashi, Tsutomu; Nakamura, Mihoko; Nakamura, Yukako; Aleksic, Branko; Kido, Mikio; Sasabayashi, Daiki; Takayanagi, Yoichiro; Furuichi, Atsushi; Nishikawa, Yumiko; Noguchi, Kyo; Ozaki, Norio; Suzuki, Michio

    2015-01-02

    Increasing evidence has implicated the role of Disrupted-in-Schizophrenia-1 (DISC1), a potential susceptibility gene for schizophrenia, in early neurodevelopmental processes. However, the effect of its genotype variation on brain morphologic changes related to neurodevelopmental abnormalities in schizophrenia remains largely unknown. This magnetic resonance imaging study examined the association between DISC1 Ser704Cys polymorphism and a range of brain neurodevelopmental markers [cavum septi pellucidi (CSP), adhesio interthalamica (AI), olfactory sulcus depth, and sulcogyral pattern (Types I, II, III, and IV) in the orbitofrontal cortex (OFC)] in an all Japanese sample of 75 schizophrenia patients and 87 healthy controls. The Cys carriers had significantly larger CSP than the Ser homozygotes for both schizophrenia patients and healthy controls. The Cys carriers also exhibited a reduction in the Type I pattern of the right OFC in the healthy controls, but not in the schizophrenia patients. The DISC1 Ser704Cys polymorphism did not affect the AI and olfactory sulcus depth in either group. These results suggested a possible role of the DISC1 genotype in the early neurodevelopment of human brains, but failed to show its specific role in the neurodevelopmental pathology of schizophrenia. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Adjacent level effects of bi level disc replacement, bi level fusion and disc replacement plus fusion in cervical spine--a finite element based study.

    PubMed

    Faizan, Ahmad; Goel, Vijay K; Biyani, Ashok; Garfin, Steven R; Bono, Christopher M

    2012-03-01

    Studies delineating the adjacent level effect of single level disc replacement systems have been reported in literature. The aim of this study was to compare the adjacent level biomechanics of bi-level disc replacement, bi-level fusion and a construct having adjoining level disc replacement and fusion system. In total, biomechanics of four models- intact, bi level disc replacement, bi level fusion and fusion plus disc replacement at adjoining levels- was studied to gain insight into the effects of various instrumentation systems on cranial and caudal adjacent levels using finite element analysis (73.6N+varying moment). The bi-level fusion models are more than twice as stiff as compared to the intact model during flexion-extension, lateral bending and axial rotation. Bi-level disc replacement model required moments lower than intact model (1.5Nm). Fusion plus disc replacement model required moment 10-25% more than intact model, except in extension. Adjacent level motions, facet loads and endplate stresses increased substantially in the bi-level fusion model. On the other hand, adjacent level motions, facet loads and endplate stresses were similar to intact for the bi-level disc replacement model. For the fusion plus disc replacement model, adjacent level motions, facet loads and endplate stresses were closer to intact model rather than the bi-level fusion model, except in extension. Based on our finite element analysis, fusion plus disc replacement procedure has less severe biomechanical effects on adjacent levels when compared to bi-level fusion procedure. Bi-level disc replacement procedure did not have any adverse mechanical effects on adjacent levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Modeling and optimization of an elastic arthroplastic disc for a degenerated disc

    NASA Astrophysics Data System (ADS)

    Ghouchani, Azadeh; Ravari, Mohammad; Mahmoudi, Farid

    2011-10-01

    A three-dimensional finite element model (FEM) of the L3-L4 motion segment using ABAQUS v 6.9 has been developed. The model took into account the material nonlinearities and is imposed different loading conditions. In this study, we validated the model by comparison of its predictions with several sets of experimental data. Disc deformation under compression and segmental rotational motions under moment loads for the normal disc model agreed well with the corresponding in vivo studies. By linking ABAQUS with MATLAB 2010.a, we determined the optimal Young s modulus as well as the Poisson's ratio for the artificial disc under different physiologic loading conditions. The results of the present study confirmed that a well-designed elastic arthroplastic disc preferably has an annulus modulus of 19.1 MPa and 1.24 MPa for nucleus section and Poisson ratio of 0.41 and 0.47 respectively. Elastic artificial disc with such properties can then achieve the goal of restoring the disc height and mechanical function of intact disc under different loading conditions and so can reduce low back pain which is mostly caused due to disc degeneration.

  13. Patterns of lumbar disc degeneration are different in degenerative disc disease and disc prolapse magnetic resonance imaging analysis of 224 patients.

    PubMed

    Kanna, Rishi M; Shetty, Ajoy Prasad; Rajasekaran, S

    2014-02-01

    Existing research on lumbar disc degeneration has remained inconclusive regarding its etiology, pathogenesis, symptomatology, prevention, and management. Degenerative disc disease (DDD) and disc prolapse (DP) are common diseases affecting the lumbar discs. Although they manifest clinically differently, existing studies on disc degeneration have included patients with both these features, leading to wide variations in observations. The possible relationship or disaffect between DDD and DP is not fully evaluated. To analyze the patterns of lumbar disc degeneration in patients with chronic back pain and DDD and those with acute DP. Prospective, magnetic resonance imaging-based radiological study. Two groups of patients (aged 20-50 years) were prospectively studied. Group 1 included patients requiring a single level microdiscectomy for acute DP. Group 2 included patients with chronic low back pain and DDD. Discs were assessed by magnetic resonance imaging through Pfirmann grading, Schmorl nodes, Modic changes, and the total end-plate damage score for all the five lumbar discs. Group 1 (DP) had 91 patients and group 2 (DDD) had 133 patients. DP and DDD patients differed significantly in the number, extent, and severity of degeneration. DDD patients had a significantly higher number of degenerated discs than DP patients (p<.000). The incidence of multilevel and pan-lumbar degeneration was also significantly higher in DDD group. The pattern of degeneration also differed in both the groups. DDD patients had predominant upper lumbar involvement, whereas DP patients had mainly lower lumbar degeneration. Modic changes were more common in DP patients, especially at the prolapsed level. Modic changes were present in 37% of prolapsed levels compared with 9.9% of normal discs (p<.00). The total end-plate damage score had a positive correlation with disc degeneration in both the groups. Further the mean total end-plate damage score at prolapsed level was also significantly higher. The results suggest that patients with disc prolapse, and those with back pain with DDD are clinically and radiologically different groups of patients with varying patterns, severity, and extent of disc degeneration. This is the first study in literature to compare and identify significant differences in these two commonly encountered patient groups. In patients with single-level DP, the majority of the other discs are nondegenerate, the lower lumbar spine is predominantly involved and the end-plate damage is higher. Patients with back pain and DDD have larger number of degenerate discs, early multilevel degeneration, and predominant upper lumbar degeneration. The knowledge that these two groups of patients are different clinically and radiologically is critical for our improved understanding of the disease and for future studies on disc degeneration and disc prolapse. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. The Correlation between Insertion Depth of Prodisc-C Artificial Disc and Postoperative Kyphotic Deformity: Clinical Importance of Insertion Depth of Artificial Disc.

    PubMed

    Lee, Do-Youl; Kim, Se-Hoon; Suh, Jung-Keun; Cho, Tai-Hyoung; Chung, Yong-Gu

    2012-09-01

    This study was designed to investigate the correlation between insertion depth of artificial disc and postoperative kyphotic deformity after Prodisc-C total disc replacement surgery, and the range of artificial disc insertion depth which is effective in preventing postoperative whole cervical or segmental kyphotic deformity. A retrospective radiological analysis was performed in 50 patients who had undergone single level total disc replacement surgery. Records were reviewed to obtain demographic data. Preoperative and postoperative radiographs were assessed to determine C2-7 Cobb's angle and segmental angle and to investigate postoperative kyphotic deformity. A formula was introduced to calculate insertion depth of Prodisc-C artificial disc. Statistical analysis was performed to search the correlation between insertion depth of Prodisc-C artificial disc and postoperative kyphotic deformity, and to estimate insertion depth of Prodisc-C artificial disc to prevent postoperative kyphotic deformity. In this study no significant statistical correlation was observed between insertion depth of Prodisc-C artificial disc and postoperative kyphotic deformity regarding C2-7 Cobb's angle. Statistical correlation between insertion depth of Prodisc-C artificial disc and postoperative kyphotic deformity was observed regarding segmental angle (p<0.05). It failed to estimate proper insertion depth of Prodisc-C artificial disc effective in preventing postoperative kyphotic deformity. Postoperative segmental kyphotic deformity is associated with insertion depth of Prodisc-C artificial disc. Anterior located artificial disc leads to lordotic segmental angle and posterior located artificial disc leads to kyphotic segmental angle postoperatively. But C2-7 Cobb's angle is not affected by artificial disc location after the surgery.

  15. Intra-discal injection of autologous, hypoxic cultured bone marrow-derived mesenchymal stem cells in five patients with chronic lower back pain: a long-term safety and feasibility study.

    PubMed

    Elabd, Christian; Centeno, Christopher J; Schultz, John R; Lutz, Gregory; Ichim, Thomas; Silva, Francisco J

    2016-09-01

    Chronic low back pain due to disc degeneration represents a major social and economic burden worldwide. The current standard of care is limited to symptomatic relief and no current approved therapy promotes disc regeneration. Bone marrow-derived mesenchymal stem cells (MSCs) are easily accessible and well characterized. These MSCs are multipotent and exhibit great tissue regenerative potential including bone, cartilage, and fibrous tissue regeneration. The use of this cell-based biologic for treating protruding disc herniation and/or intervertebral disc degeneration is a promising therapeutic strategy, due to their known regenerative, immuno-modulatory and anti-inflammatory properties. Five patients diagnosed with degenerative disc disease received an intra-discal injection of autologous, hypoxic cultured, bone marrow-derived mesenchymal stem cells (15.1-51.6 million cells) as part of a previous study. These patients were re-consented to participate in this study in order to assess long-term safety and feasibility of intra-discal injection of autologous, hypoxic cultured, bone marrow-derived mesenchymal stem cells 4-6 years post mesenchymal stem cell infusion. The follow-up study consisted of a physical examination, a low back MRI, and a quality of life questionnaire. Patients' lower back MRI showed absence of neoplasms or abnormalities surrounding the treated region. Based on the physical examination and the quality of life questionnaire, no adverse events were reported due to the procedure or to the stem cell treatment 4-6 years post autologous, hypoxic cultured mesenchymal stem cell infusion. All patients self-reported overall improvement, as well as improvement in strength, post stem cell treatment, and four out of five patients reported improvement in mobility. This early human clinical data suggests the safety and feasibility of the clinical use of hypoxic cultured bone marrow-derived mesenchymal stem cells for the treatment of lower back pain due to degenerative disc disorders and support further studies utilizing hypoxic cultured bone marrow-derived stem cells. The overall improvements reported are encouraging, but a larger double-blind, controlled, randomized clinical study with significant number of patients and implementation of validated endpoint measurements are next steps in order to demonstrate efficacy of this cell-based biologic.

  16. CT morphometry of adult thoracic intervertebral discs.

    PubMed

    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.

  17. [Effects of hydrogen peroxide-containing bleaching on the growth of Streptococcus mutans biofilm on enamel disc surface].

    PubMed

    Zheng, Chun-yan; Pan, Jie; Wang, Zu-hua; Wang, Yang

    2014-02-18

    To evaluate the effects of a commercial bleaching agent containing 35% (mass fraction) hydrogen peroxide on the growth of Streptococcus mutans biofilm on enamel disc surface. A total of 20 enamel disks were made from human extracted teeth and the enamel surfaces were kept intact. The discs were autocalved and randomly divided into two groups: bleaching group and control group. Each group contained 10 discs. For bleaching group, the enamel discs were whitened by commercial 35% hydrogen peroxide according to the instruction (Beyond(TM) Professional Dental Whitening Kit, Beyond Technology, TX,USA ); no treatment for control group. All the discs were kept in sterile human saliva for 3.5 hours, and then the mixture of brain heart infusion broth (BHI) medium and Streptococcus mutans were added. The discs and Streptococcus mutans were incubated together in BHI medium with 5% CO(2) (volume fraction), at 37 °C. After 3, 7, 14, 21 and 28 d's incubation, two discs of each group were taken out and the biofilms on the enamel surfaces were evaluated by using conventional bacteria counts and confocal laser scanning microscope (CLSM). The bacteria in the biofilm on one disc enamel surface were analyzed by plating on BHIS agar and the colony-forming units were counted. The biofilm on the other disc surface was stained using a two-colour fluorescent dye kit (Bacerial Viability Kit L-7012) for CLSM. The vital bacteria counts of vital cells in the 3, 7, and 14 d's biofilms of the bleaching group were significantly fewer than those of the control group. Especially in the 3 days' biofilm on the whitened surface, the vital bacteria counts [(3 595 ± 2 903) μm(2) vs. (89 155 ± 65 963) μm(2),t = 8.71,P = 0.00] and proportion of vital bacteria [(26.0% ± 16.4%) vs.(92.2% ± 10.9%), t = 19.93, P = 0.00] were significantly fewer than those of the control. While, for the 21d's biofilm, the vital bacteria counts and the percentage of the vital cells of the bleaching group were more than those of the control group significantly [(66 262 ± 23 772) μm(2) vs. (51 184 ± 20 502) μm(2), t = 2.59, P = 0.012]. The hydrogen peroxide-containing bleaching agent may inhibit the growth of Streptococcus mutans biofilm for about 3 weeks; but after 3 weeks, it seems that the bleached surface will increase the growth of biofilm. Whether the whitening therapy will increase caries susceptibility of the bleached surface needs further research.

  18. Noncoding RNAs in human intervertebral disc degeneration: An integrated microarray study.

    PubMed

    Liu, Xu; Che, Lu; Xie, Yan-Ke; Hu, Qing-Jie; Ma, Chi-Jiao; Pei, Yan-Jun; Wu, Zhi-Gang; Liu, Zhi-Heng; Fan, Li-Ying; Wang, Hai-Qiang

    2015-09-01

    Accumulating evidence indicates that noncoding RNAs play important roles in a multitude of biological processes. The striking findings of miRNAs (microRNAs) and lncRNAs (long noncoding RNAs) as members of noncoding RNAs open up an exciting era in the studies of gene regulation. More recently, the reports of circRNAs (circular RNAs) add fuel to the noncoding RNAs research. Human intervertebral disc degeneration (IDD) is a main cause of low back pain as a disabling spinal disease. We have addressed the expression profiles if miRNAs, lncRNAs and mRNAs in IDD (Wang et al., J Pathology, 2011 and Wan et al., Arthritis Res Ther, 2014). Furthermore, we thoroughly analysed noncoding RNAs, including miRNAs, lncRNAs and circRNAs in IDD using the very same samples. Here we delineate in detail the contents of the aforementioned microarray analyses. Microarray and sample annotation data were deposited in GEO under accession number GSE67567 as SuperSeries. The integrated analyses of these noncoding RNAs will shed a novel light on coding-noncoding regulatory machinery.

  19. Rethinking Black Hole Accretion Discs

    NASA Astrophysics Data System (ADS)

    Salvesen, Greg

    Accretion discs are staples of astrophysics. Tapping into the gravitational potential energy of the accreting material, these discs are highly efficient machines that produce copious radiation and extreme outflows. While interesting in their own right, accretion discs also act as tools to study black holes and directly influence the properties of the Universe. Black hole X-ray binaries are fantastic natural laboratories for studying accretion disc physics and black hole phenomena. Among many of the curious behaviors exhibited by these systems are black hole state transitions -- complicated cycles of dramatic brightening and dimming. Using X-ray observations with high temporal cadence, we show that the evolution of the accretion disc spectrum during black hole state transitions can be described by a variable disc atmospheric structure without invoking a radially truncated disc geometry. The accretion disc spectrum can be a powerful diagnostic for measuring black hole spin if the effects of the disc atmosphere on the emergent spectrum are well-understood; however, properties of the disc atmosphere are largely unconstrained. Using statistical methods, we decompose this black hole spin measurement technique and show that modest uncertainties regarding the disc atmosphere can lead to erroneous spin measurements. The vertical structure of the disc is difficult to constrain due to our ignorance of the contribution to hydrostatic balance by magnetic fields, which are fundamental to the accretion process. Observations of black hole X-ray binaries and the accretion environments near supermassive black holes provide mounting evidence for strong magnetization. Performing numerical simulations of accretion discs in the shearing box approximation, we impose a net vertical magnetic flux that allows us to effectively control the level of disc magnetization. We study how dynamo activity and the properties of turbulence driven by the magnetorotational instability depend on the magnetized state of the gas, spanning weak-to-strong disc magnetization regimes. We also demonstrate that a background poloidal magnetic flux is required to form and sustain a strongly magnetized accretion disc. This thesis motivates the need for understanding how magnetic fields affect the observed spectrum from black hole accretion discs.

  20. Imaginal Disc Abnormalities in Lethal Mutants of Drosophila

    PubMed Central

    Shearn, Allen; Rice, Thomas; Garen, Alan; Gehring, Walter

    1971-01-01

    Late lethal mutants of Drosophila melanogaster, dying after the larval stage of development, were isolated. The homozygous mutant larvae were examined for abnormal imaginal disc morphology, and the discs were injected into normal larval hosts to test their capacities to differentiate into adult structures. In about half of the mutants analyzed, disc abnormalities were found. Included among the abnormalities were missing discs, small discs incapable of differentiating, morphologically normal discs with limited capacities for differentiation, and discs with homeotic transformations. In some mutants all discs were affected, and in others only certain discs. The most extreme abnormal phenotype is a class of “discless” mutants. The viability of these mutant larvae indicates that the discs are essential only for the development of an adult and not of a larva. The late lethals are therefore a major source of mutants for studying the genetic control of disc formation. Images PMID:5002822

  1. Mechanoreceptors in Diseased Cervical Intervertebral Disc and Vertigo.

    PubMed

    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 pathogenesis of vertigo of cervical origin. 1.

  2. Surface topography of hydroxyapatite promotes osteogenic differentiation of human bone marrow mesenchymal stem cells.

    PubMed

    Yang, Wanlei; Han, Weiqi; He, Wei; Li, Jianlei; Wang, Jirong; Feng, Haotian; Qian, Yu

    2016-03-01

    Effective and safe induction of osteogenic differentiation is one of the key elements of bone tissue engineering. Surface topography of scaffold materials was recently found to promote osteogenic differentiation. Utilization of this topography may be a safer approach than traditional induction by growth factors or chemicals. The aim of this study is to investigate the enhancement of osteogenic differentiation by surface topography and its mechanism of action. Hydroxyapatite (HA) discs with average roughness (Ra) of surface topography ranging from 0.2 to 1.65 μm and mean distance between peaks (RSm) ranging from 89.7 to 18.6 μm were prepared, and human bone-marrow mesenchymal stem cells (hBMSCs) were cultured on these discs. Optimal osteogenic differentiation was observed on discs with surface topography characterized by Ra ranging from 0.77 to 1.09 μm and RSm ranging from 53.9 to 39.3 μm. On this surface configuration of HA, hBMSCs showed oriented attachment, F-actin arrangement, and a peak in the expression of Yes-associated protein (YAP) and PDZ binding motif (TAZ) (YAP/TAZ). These results indicated that the surface topography of HA promoted osteogenic differentiation of hBMSCs, possibly by increasing cell attachment and promoting the YAP/TAZ signaling pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Radiologic study of disc behavior following compression fracture of the thoracolumbar hinge managed by kyphoplasty: A 52-case series.

    PubMed

    Teyssédou, S; Saget, M; Gayet, L E; Pries, P; Brèque, C; Vendeuvre, T

    2016-02-01

    Kyphoplasty has proved effective for durable correction of traumatic vertebral deformity following Magerl A fracture, but subsequent behavior of the adjacent discs is unclear. The objective of the present study was to analyze evolution according to severity of initial kyphosis and quality of fracture reduction. A single-center prospective study included cases of single compression fracture of the thoracolumbar hinge managed by Kyphon Balloon Kyphoplasty with polymethylmethacrylate bone cement. Radiology focused on traumatic vertebral kyphosis (VK), disc angulation (DA) and disc height index (DHI) in the adjacent discs. Linear regression assessed the correlation between superior disc height index (SupDHI) and postoperative VK on the one hand and correction gain on the other, using the Student t test for matched pairs and Pearson correlation coefficient. Fifty-two young patients were included, with mean follow-up of 18.6 months. VK fell from 13.9° preoperatively to 8.2° at last follow-up. DHI found significant superior disc subsidence (P=0.0001) and non-significant inferior disc subsidence (P=0.116). DA showed significantly reduced superior disc lordosis (P=4*10(-5)). SupDHI correlated with VK correction (r=0.32). Preoperative VK did not correlate with radiologic degeneration of the adjacent discs. Correction of traumatic vertebral deformity avoids subsidence and loss of mechanical function in the superior adjacent disc. The underlying disc compensates for residual deformity. Balloon kyphoplasty is useful in compression fracture, providing significant reduction of traumatic vertebral deformity while conserving free and healthy adjacent discs. IV. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Lumbar Disc Degenerative Disease: Disc Degeneration Symptoms and Magnetic Resonance Image Findings

    PubMed Central

    Saleem, Shafaq; Rehmani, Muhammad Asim Khan; Raees, Aisha; Alvi, Arsalan Ahmad; Ashraf, Junaid

    2013-01-01

    Study Design Cross sectional and observational. Purpose To evaluate the different aspects of lumbar disc degenerative disc disease and relate them with magnetic resonance image (MRI) findings and symptoms. Overview of Literature Lumbar disc degenerative disease has now been proven as the most common cause of low back pain throughout the world. It may present as disc herniation, lumbar spinal stenosis, facet joint arthropathy or any combination. Presenting symptoms of lumbar disc degeneration are lower back pain and sciatica which may be aggravated by standing, walking, bending, straining and coughing. Methods This study was conducted from January 2012 to June 2012. Study was conducted on the diagnosed patients of lumbar disc degeneration. Diagnostic criteria were based upon abnormal findings in MRI. Patients with prior back surgery, spine fractures, sacroiliac arthritis, metabolic bone disease, spinal infection, rheumatoid arthritis, active malignancy, and pregnancy were excluded. Results During the targeted months, 163 patients of lumbar disc degeneration with mean age of 43.92±11.76 years, came into Neurosurgery department. Disc degeneration was most commonly present at the level of L4/L5 105 (64.4%).Commonest types of disc degeneration were disc herniation 109 (66.9%) and lumbar spinal stenosis 37 (22.7%). Spondylolisthesis was commonly present at L5/S1 10 (6.1%) and associated mostly with lumbar spinal stenosis 7 (18.9%). Conclusions Results reported the frequent occurrence of lumbar disc degenerative disease in advance age. Research efforts should endeavor to reduce risk factors and improve the quality of life. PMID:24353850

  5. A biomechanical study of artificial cervical discs using computer simulation.

    PubMed

    Ahn, Hyung Soo; DiAngelo, Denis J

    2008-04-15

    A virtual simulation model of the subaxial cervical spine was used to study the biomechanical effects of various disc prosthesis designs. To study the biomechanics of different design features of cervical disc arthroplasty devices. Disc arthroplasty is an alternative approach to cervical fusion surgery for restoring and maintaining motion at a diseased spinal segment. Different types of cervical disc arthroplasty devices exist and vary based on their placement and degrees of motion offered. A virtual dynamic model of the subaxial cervical spine was used to study 3 different prosthetic disc designs (PDD): (1) PDD-I: The center of rotation of a spherical joint located at the mid C5-C6 disc, (2) PDD-II: The center of rotation of a spherical joint located 6.5 mm below the mid C5-C6 disc, and (3) PDD-III: The center of rotation of a spherical joint in a plane located at the C5-C6 disc level. A constrained spherical joint placed at the disc level (PDD-I) significantly increased facet loads during extension. Lowering the rotational axis of the spherical joint towards the subjacent body (PDD-II) caused a marginal increase in facet loading during flexion, extension, and lateral bending. Lastly, unconstraining the spherical joint to move freely in a plane (PDD-III) minimized facet load build up during all loading modes. The simulation model showed the impact simple design changes may have on cervical disc dynamics. The predicted facet loads calculated from computer model have to be validated in the experimental study.

  6. A combined approach for the assessment of cell viability and cell functionality of human fibrochondrocytes for use in tissue engineering.

    PubMed

    Garzón, Ingrid; Carriel, Victor; Marín-Fernández, Ana Belén; Oliveira, Ana Celeste; Garrido-Gómez, Juan; Campos, Antonio; Sánchez-Quevedo, María Del Carmen; Alaminos, Miguel

    2012-01-01

    Temporo-mandibular joint disc disorders are highly prevalent in adult populations. Autologous chondrocyte implantation is a well-established method for the treatment of several chondral defects. However, very few studies have been carried out using human fibrous chondrocytes from the temporo-mandibular joint (TMJ). One of the main drawbacks associated to chondrocyte cell culture is the possibility that chondrocyte cells kept in culture tend to de-differentiate and to lose cell viability under in in-vitro conditions. In this work, we have isolated human temporo-mandibular joint fibrochondrocytes (TMJF) from human disc and we have used a highly-sensitive technique to determine cell viability, cell proliferation and gene expression of nine consecutive cell passages to determine the most appropriate cell passage for use in tissue engineering and future clinical use. Our results revealed that the most potentially viable and functional cell passages were P5-P6, in which an adequate equilibrium between cell viability and the capability to synthesize all major extracellular matrix components exists. The combined action of pro-apoptotic (TRAF5, PHLDA1) and anti-apoptotic genes (SON, HTT, FAIM2) may explain the differential cell viability levels that we found in this study. These results suggest that TMJF should be used at P5-P6 for cell therapy protocols.

  7. Structure and function of the temporomandibular joint disc: implications for tissue engineering.

    PubMed

    Detamore, Michael S; Athanasiou, Kyriacos A

    2003-04-01

    The temporomandibular joint (TMJ) disc is a little understood structure that, unfortunately, exhibits a plethora of pathologic disorders. Tissue engineering approaches may be warranted to address TMJ disc pathophysiology, but first a clear understanding of structure-function relationships needs to be developed, especially as they relate to the regenerative potential of the tissue. In this review, we correlate the biochemical content of the TMJ disc to its mechanical behavior and discuss what this correlation infers for tissue engineering studies of the TMJ disc. The disc of the TMJ exhibits a somewhat biconcave shape, being thicker in the anterior and posterior bands and thinner in the intermediate zone. The disc, which is certainly an anisotropic and nonhomogeneous tissue, consists almost entirely of type I collagen with trace amounts of type II and other types. In general, collagen fibers in the intermediate zone appear to run primarily in an anteroposterior direction and in a ringlike fashion around the periphery. Collagen orientation is reflected in higher tensile stiffness and strength in the center anteroposteriorly than mediolaterally and in the anterior and posterior bands than the intermediate zone mediolaterally. Tensile tests have shown the disc is stiffer and stronger in the direction of the collagen fibers. Elastin fibers in general appear along the collagen fibers and most likely function in restoring and retaining disc form after loading. The 2 primary glycosaminoglycans of the disc by far are chondroitin sulfate and dermatan sulfate, although their distribution is not clear. Compression studies are conflicting, but evidence suggests the disc is compressively stiffest in the center. Only a few tissue engineering studies of the TMJ disc have been performed to date. Tissue engineering studies must take advantage of existing information for experimental design and construct validation, and more research is necessary to characterize the disc to create a clearer picture of our goals in tissue engineering the TMJ disc. Copyright 2003 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 61:494-506, 2003

  8. Detachment strength of human osteoblasts cultured on hydroxyapatite with various surface roughness. Contribution of integrin subunits.

    PubMed

    Kokkinos, Petros A; Koutsoukos, Petros G; Deligianni, Despina D

    2012-06-01

    Hydroxyapatite (HA) has been widely used as a bone substitute in dental, maxillofacial and orthopaedic surgery and as osteoconductive bone substitute or precoating of pedicle screws and cages in spine surgery. The aim of the present study was to investigate the osteoblastic adhesion strength on HA substrata with different surface topography and biochemistry (pre-adsorption of fibronectin) after blocking of specific integrin subunits with monoclonal antibodies. Stoichiometric HA was prepared by precipitation followed by ageing and characterized by SEM, EDX, powder XRD, Raman spectroscopy, TGA, and specific surface area analysis. Human bone marrow derived osteoblasts were cultured on HA disc-shaped substrata which were sintered and polished resulting in two surface roughness grades. For attachment evaluation, cells were incubated with monoclonal antibodies and seeded for 2 h on the substrata. Cell detachment strength was determined using a rotating disc device. Cell detachment strength was surface roughness, fibronectin preadsorption and intergin subunit sensitive.

  9. On the inner disc structure of MWC480: evidence for asymmetries?

    NASA Astrophysics Data System (ADS)

    Jamialahmadi, N.; Lopez, B.; Berio, Ph.; Matter, A.; Flament, S.; Fathivavsari, H.; Ratzka, T.; Sitko, M. L.; Spang, A.; Russell, R. W.

    2018-01-01

    Studying the physical conditions structuring the young circumstellar discs is required for understanding the onset of planet formation. Of particular interest is the protoplanetary disc surrounding the Herbig star MWC480. The structure and properties of the circumstellar disc of MWC480 are studied by infrared interferometry and interpreted from a modelling approach. New observations are driving this study, in particular, some recent Very Large Telescope Interferometer (VLTI)/MIDI data acquired in 2013 December. Our one-component disc model could not reproduce simultaneously all our data: the spectral energy distribution, the near-infrared Keck Interferometer data and the mid-infrared data obtained with the MIDI instrument. In order to explain all measurements, one possibility is to add an asymmetry in our one-component disc model with the assumption that the structure of the disc of MWC480 has not varied with time. Several scenarios are tested, and the one considering the presence of an azimuthal bright feature in the inner component of the disc model provides a better fit of the data.

  10. Kinematic Evaluation of Association between Disc Bulge Migration, Lumbar Segmental Mobility, and Disc Degeneration in the Lumbar Spine Using Positional Magnetic Resonance Imaging

    PubMed Central

    Hu, Jonathan K.; Morishita, Yuichiro; Montgomery, Scott R.; Hymanson, Henry; Taghavi, Cyrus E.; Do, Duc; Wang, Jeff C.

    2011-01-01

    Degenerative disc disease and disc bulge in the lumbar spine are common sources of lower back pain. Little is known regarding disc bulge migration and lumbar segmental mobility as the lumbar spine moves from flexion to extension. In this study, 329 symptomatic (low back pain with or without neurological symptoms) patients with an average age of 43.5 years with varying degrees of disc degeneration were examined to characterize the kinematics of the lumbar intervertebral discs through flexion, neutral, and extension weight-bearing positions. In this population, disc bulge migration associated with dynamic motion of the lumbar spine significantly increased with increased grade of disk degeneration. Although no obvious trends relating the migration of disc bulge and angular segmental mobility were seen, translational segmental mobility tended to increase with disc bulge migration in all of the degenerative disc states. It appears that many factors, both static (intervertebral disc degeneration or disc height) and dynamic (lumbar segmental mobility), affect the mechanisms of lumbar disc bulge migration. PMID:24353937

  11. Planet-disc interaction in laminar and turbulent discs

    NASA Astrophysics Data System (ADS)

    Stoll, Moritz H. R.; Picogna, Giovanni; Kley, Wilhelm

    2017-07-01

    In weakly ionised discs turbulence can be generated through the vertical shear instability (VSI). Embedded planets are affected by a stochastic component in the torques acting on them, which can impact their migration. In this work we study the interplay between a growing planet embedded in a protoplanetary disc and the VSI turbulence. We performed a series of 3D hydrodynamical simulations for locally isothermal discs with embedded planets in the mass range from 5 to 100 Earth masses. We study planets embedded in an inviscid disc that is VSI unstable, becomes turbulent, and generates angular momentum transport with an effective α = 5 × 10-4. This is compared to the corresponding viscous disc using exactly this α-value. In general we find that the planets have only a weak impact on the disc turbulence. Only for the largest planet (100 M⊕) does the turbulent activity become enhanced inside of the planet. The depth and width of a gap created by the more massive planets (30,100 M⊕) in the turbulent disc equal exactly that of the corresponding viscous case, leading to very similar torque strengths acting on the planet, with small stochastic fluctuations for the VSI disc. At the gap edges vortices are generated that are stronger and longer-lived in the VSI disc. Low mass planets (with Mp ≤ 10 M⊕) do not open gaps in the disc in either case, but generate for the turbulent disc an overdensity behind the planet that exerts a significant negative torque. This can boost the inward migration in VSI turbulent discs well above the Type I rate. Owing to the finite turbulence level in realistic 3D discs the gap depth will always be limited and migration will not stall in inviscid discs.

  12. Posterior epidural disc fragment masquerading as spinal tumor: Review of the literature.

    PubMed

    Park, Taejune; Lee, Ho Jun; Kim, Jae Seong; Nam, Kiyeun

    2018-03-09

    Posterior epidural lumbar disc fragment is infrequent because of anatomical barriers, and it is difficult to diagnose posterior epidural lumbar disc fragment because of its rare incidence and the ambiguity of radiologic evaluations. And it is difficult to differentiate it from other diseases such as spinal tumors. Differential diagnosis of posterior epidural lumbar disc fragment is clinically important because its diagnosis can affect treatment and prognosis. To investigate the incidence, anatomical concern, etiology, symptom, diagnostic tool, management and prognosis of posterior epidural lumbar disc fragment, we reviewed articles including case report. We performed a search of all clinical studies of posterior epidural lumbar disc fragment published to date. The following keywords were searched: Posterior epidural lumbar disc fragment, disc migration, posterior epidural disc, extradural migration, dorsal epidural migration, sequestrated disc, and disc fragment. We identified 40 patients of posterior epidural lumbar disc fragment from 28 studies. The most common presentation of posterior epidural lumbar disc fragment was sudden onset radiculopathy (70.0%), followed by cauda equina syndrome (27.5%). The most frequently used diagnostic modality was magnetic resonance imaging (MRI), conducted in 36 cases (90.0%), and followed by computed tomography in 14 cases (35.0%). After the imaging studies, the preoperative diagnoses were 45.0% masses, 20.0% lesions, and 12.5% tumors. Characteristic MRI findings in posterior epidural lumbar disc fragment are helpful for diagnosis; it typically displays low signals on T1-weighted images and high signals on T2-weighted images with respect to the parent disc. In addition, most of the disc fragments show peripheral rim enhancement on MRI with gadolinium administration. Electrodiagnostic testing is useful for verifying nerve damage. Surgical treatment was performed in all cases, and neurologic complications were observed in 12.5%. As posterior epidural lumbar disc fragment could be masqueraded as spinal tumor, if rim enhancement is observed in MRI scans with sudden symptoms of radiculopathy or cauda equina syndrome, it should be taken into consideration. Early diagnosis can lead to early surgery, which can reduce complications.

  13. Analysis of Long Bone and Vertebral Failure Patterns

    DTIC Science & Technology

    1985-02-14

    have disc-shaped epiphyses on the surfaces of the vertebral bodies (Schmorl and Junghanns, 1959). Humans, ]< orangutans , gorillas...The annular epiphysis has been previously reported in humans, orangutans , gorillas, and marmosets (Schmorl and Junghanns, 1959; Bernick, et al

  14. Vertebral Augmentation can Induce Early Signs of Degeneration in the Adjacent Intervertebral Disc: Evidence from a Rabbit Model.

    PubMed

    Feng, Zhiyun; Chen, Lunhao; Hu, Xiaojian; Yang, Ge; Wang, Yue; Chen, Zhong

    2018-04-11

    An experimental study. The aim of this study was to determine the effect of polymethylmethacrylate (PMMA) augmentation on the adjacent disc. Vertebral augmentation with PMMA reportedly may predispose the adjacent vertebra to fracture. The influence of PMMA augmentation on the adjacent disc, however, remains unclear. Using a retroperitoneal approach, PMMA augmentation was performed for 23 rabbits. For each animal, at least one vertebra was augmented with 0.2 to 0.3 mL PMMA. The disc adjacent to the augmented vertebra and a proximal control disc were studied using magnetic resonance (MR) imaging, histological and molecular level evaluation at 1, 3, and 6 months postoperatively. Marrow contact channels in the endplate were quantified in histological slices and number of invalid channels (those without erythrocytes inside) was rated. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was performed to determine disc cell apoptosis. On MR images, the signal and height of the adjacent disc did not change 6 months after vertebral augmentation. Histological scores of the adjacent disc increased over time, particularly for the nucleus pulposus. The adjacent disc had greater nucleus degeneration score than the control disc at 3 months (5.7 vs. 4.5, P < 0.01) and 6 months (6.9 vs. 4.4, P < 0.001). There were more invalid marrow contact channels in the endplate of augmented vertebra than the control (43.3% vs. 11.1%, P < 0.01). mRNA of ADAMTS-5, MMP-13, HIF-1α, and caspase-3 were significantly upregulated in the adjacent disc at 3 and 6 months (P < 0.05 for all). In addition, there were more TUNEL-positive cells in the adjacent disc than in the control disc (43.4% vs. 24.0%, P < 0.05) at 6 months postoperatively. Vertebral augmentation can induce early degenerative signs in the adjacent disc, which may be due to impaired nutrient supply to the disc. N/A.

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

    PubMed

    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.

  16. Early detection of glaucoma using fully automated disparity analysis of the optic nerve head (ONH) from stereo fundus images

    NASA Astrophysics Data System (ADS)

    Sharma, Archie; Corona, Enrique; Mitra, Sunanda; Nutter, Brian S.

    2006-03-01

    Early detection of structural damage to the optic nerve head (ONH) is critical in diagnosis of glaucoma, because such glaucomatous damage precedes clinically identifiable visual loss. Early detection of glaucoma can prevent progression of the disease and consequent loss of vision. Traditional early detection techniques involve observing changes in the ONH through an ophthalmoscope. Stereo fundus photography is also routinely used to detect subtle changes in the ONH. However, clinical evaluation of stereo fundus photographs suffers from inter- and intra-subject variability. Even the Heidelberg Retina Tomograph (HRT) has not been found to be sufficiently sensitive for early detection. A semi-automated algorithm for quantitative representation of the optic disc and cup contours by computing accumulated disparities in the disc and cup regions from stereo fundus image pairs has already been developed using advanced digital image analysis methodologies. A 3-D visualization of the disc and cup is achieved assuming camera geometry. High correlation among computer-generated and manually segmented cup to disc ratios in a longitudinal study involving 159 stereo fundus image pairs has already been demonstrated. However, clinical usefulness of the proposed technique can only be tested by a fully automated algorithm. In this paper, we present a fully automated algorithm for segmentation of optic cup and disc contours from corresponding stereo disparity information. Because this technique does not involve human intervention, it eliminates subjective variability encountered in currently used clinical methods and provides ophthalmologists with a cost-effective and quantitative method for detection of ONH structural damage for early detection of glaucoma.

  17. DISC1 Causes Associative Memory and Neurodevelopmental Defects in Fruit Flies

    PubMed Central

    Furukubo-Tokunaga, Katsuo; Kurita, Kazuki; Honjo, Ken; Pandey, Himani; Ando, Tetsuya; Takayama, Kojiro; Arai, Yuko; Mochizuki, Hiroaki; Ando, Mai; Kamiya, Atsushi; Sawa, Akira

    2016-01-01

    Originally found in a Scottish family with diverse mental disorders, the DISC1 protein has been characterized as an intracellular scaffold protein that associates with diverse binding partners in neural development. To explore its functions in a genetically tractable system, we expressed the human DISC1 in fruit flies (Drosophila melanogaster). As in mammalian neurons, DISC1 is localized to diverse subcellular domains of developing fly neurons including the nuclei, axons and dendrites. Overexpression of DISC1 impairs associative memory. Experiments with deletion/mutation constructs have revealed the importance of amino terminal domain (46–290) for memory suppression whereas carboxyl domain (598–854) and the amino terminal residues (1–45) including the nuclear localization signal (NLS1) are dispensable. DISC1 overexpression also causes suppression of axonal and dendritic branching of mushroom body neurons, which mediate a variety of cognitive functions in the fly brain. Analyses with deletion constructs reveal that protein domains 598–854 and 349–402 are both required for the suppression of axonal branching while amino-terminal domains including NLS1 are dispensable. In contrast, NLS1 was required for the suppression of dendritic branching, suggesting a mechanism involving gene expression. Moreover, domain 403–596 is also required for the suppression of dendritic branching. We also show that overexpression of DISC1 suppresses glutamatergic synaptogenesis in developing neuromuscular junctions. Deletion/mutation experiments have revealed the importance of protein domains 403–596 and 349–402 for synaptic suppression, while amino terminal domains including NLS1 are dispensable. Finally, we show that DISC1 functionally interacts with the fly homolog of Dysbindin (DTNBP1) via direct protein-protein interaction in developing synapses. PMID:26976042

  18. Are Collapsed Cervical Discs Amenable to Total Disc Arthroplasty?: Analysis of Prospective Clinical Data With 2-Year Follow Up.

    PubMed

    Patwardhan, Avinash G; Carandang, Gerard; Voronov, Leonard I; Havey, Robert M; Paul, Gary A; Lauryssen, Carl; Coric, Domagoj; Dimmig, Thomas; Musante, David

    2016-12-15

    Analysis of prospectively collected radiographic data. To investigate the influence of preoperative index-level range of motion (ROM) and disc height on postoperative ROM after cervical total disc arthroplasty (TDA) using compressible disc prostheses. Clinical studies demonstrate benefits of motion preservation over fusion; however, questions remain unanswered as to which preoperative factors have the ability to identify patients who are most likely to have good postoperative motion, which is the primary rationale for TDA. We analyzed prospectively collected data from a single-arm, multicenter study with 2-year follow up of 30 patients with 48 implanted levels. All received compressible cervical disc prostheses of 6 mm-height (M6C, Spinal Kinetics, Sunnyvale, CA). The influence of index-level preoperative disc height and ROM (each with two levels: below-median and above-median) on postoperative ROM was analyzed using 2 x 2 ANOVA. We further analyzed the radiographic outcomes of a subset of discs with preoperative height less than 3 mm, the so-called "collapsed" discs. Shorter (3.0 ± 0.4 mm) discs were significantly less mobile preoperatively than taller (4.4 ± 0.5 mm) discs (6.7° vs. 10.5°, P = 0.01). The postoperative ROM did not differ between the shorter and taller discs (5.6° vs. 5.0°, P = 0.63). Tall discs that were less mobile preoperatively had significantly smaller postoperative ROM than short discs with above-median preoperative mobility (P < 0.05). The "collapsed discs" (n = 8) were less mobile preoperatively compared with all discs combined (5.1° vs. 8.6°, P < 0.01). These discs were distracted to more than two times the preoperative height, from 2.6 to 5.7 mm, and had significantly greater postoperative ROM than all discs combined (7.6° vs. 5.3°, P < 0.05). We observed a significant interaction between preoperative index-level disc height and ROM in influencing postoperative ROM. Although limited by small sample size, the results suggest discs with preoperative height less than 3 mm may be amenable to disc arthroplasty using compressible disc prostheses. 2.

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

    PubMed

    Bach, Frances C; Laagland, Lisanne T; Grant, Michael P; Creemers, Laura B; Ito, Keita; Meij, Björn P; Mwale, Fackson; Tryfonidou, Marianna A

    2017-01-01

    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 (s)Link-N induced GAG deposition in human and bovine CLCs, as expected. In contrast, canine (s)Link-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 (s)Link-N induced negligible GAG deposition. Surprisingly, human and canine (s)Link-N did not induce Smad signaling in human and bovine CLCs. Human and canine (s)Link-N only mildly increased pSmad1 and Smad2 levels in canine CLCs. Human and canine (s)Link-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, (s)Link-N still holds a regenerative potential for humans.

  20. A study of the effect of bulges on bar formation in disc galaxies

    NASA Astrophysics Data System (ADS)

    Kataria, Sandeep Kumar; Das, Mousumi

    2018-04-01

    We use N-body simulations of bar formation in isolated galaxies to study the effect of bulge mass and bulge concentration on bar formation. Bars are global disc instabilities that evolve by transferring angular momentum from the inner to outer discs and to the dark matter halo. It is well known that a massive spherical component such as halo in a disc galaxy can make it bar stable. In this study, we explore the effect of another spherical component, the bulge, on bar formation in disc galaxies. In our models, we vary both the bulge mass and concentration. We have used two sets of models: one that has a dense bulge and high surface density disc, and the other model has a less concentrated bulge and a lighter disc. In both models, we vary the bulge to disc mass fraction from 0 to 0.7. Simulations of both the models show that there is an upper cut-off in bulge-to-disc mass ratio Mb/Md above which bars cannot form; the cut-off is smaller for denser bulges (Mb/Md = 0.2) compared to less denser ones (Mb/Md = 0.5). We define a new criterion for bar formation in terms of the ratio of bulge to total radial force (Fb/Ftot) at the disc scale lengths above which bars cannot form. We find that if Fb/Ftot > 0.35, a disc is stable and a bar cannot form. Our results indicate that early-type disc galaxies can still form strong bars in spite of having massive bulges.

  1. Proto-planetary disc evolution and dispersal

    NASA Astrophysics Data System (ADS)

    Rosotti, Giovanni Pietro

    2015-05-01

    Planets form from gas and dust discs in orbit around young stars. The timescale for planet formation is constrained by the lifetime of these discs. The properties of the formed planetary systems depend thus on the evolution and final dispersal of the discs, which is the main topic of this thesis. Observations reveal the existence of a class of discs called "transitional", which lack dust in their inner regions. They are thought to be the last stage before the complete disc dispersal, and hence they may provide the key to understanding the mechanisms behind disc evolution. X-ray photoevaporation and planet formation have been studied as possible physical mechanisms responsible for the final dispersal of discs. However up to now, these two phenomena have been studied separately, neglecting any possible feedback or interaction. In this thesis we have investigated what is the interplay between these two processes. We show that the presence of a giant planet in a photo-evaporating disc can significantly shorten its lifetime, by cutting the inner regions from the mass reservoir in the exterior of the disc. This mechanism produces transition discs that for a given mass accretion rate have larger holes than in models considering only X-ray photo-evaporation, constituting a possible route to the formation of accreting transition discs with large holes. These discs are found in observations and still constitute a puzzle for the theory. Inclusion of the phenomenon called "thermal sweeping", a violent instability that can destroy a whole disc in as little as 10 4 years, shows that the outer disc left can be very short-lived (depending on the X-ray luminosity of the star), possibly explaining why very few non accreting transition discs are observed. However the mechanism does not seem to be efficient enough to reconcile with observations. In this thesis we also show that X-ray photo-evaporation naturally explains the observed correlation between stellar masses and accretion rates and is therefore the ideal candidate for driving disc evolution. Another process that can influence discs is a close encounter with another star. In this thesis we develop a model to study the effect of stellar dynamics in the natal stellar cluster on the discs, following for the first time at the same time the stellar dynamics together with the evolution of the discs. We find that, although close encounters with stars are unlikely to change significantly the mass of a disc, they can change substantially its size, hence imposing an upper limit on the observed disc radii. Finally, we investigated in this thesis whether discs can be reformed after their dispersal. If a star happens to be in a region that is currently forming stars, it can accrete material from the interstellar medium. This mechanism may result in the production of "second generation" discs such that in a given star forming region a few percent of stars may still possess a disc, in tentative agreement with observations of so called "old accretors", which are difficult to explain within the current paradigm of disc evolution and dispersal.

  2. Histological study of the human temporo-mandibular joint and its surrounding muscles.

    PubMed

    Bravetti, P; Membre, H; El Haddioui, A; Gérard, H; Fyard, J P; Mahler, P; Gaudy, J F

    2004-10-01

    This is a histological study of the human temporo-mandibular joint and its surrounding muscles. Using a microscopic study of serial sections from anatomical specimens from six subjects, the detailed anatomy of the joint is presented with particular regard to the histology. This study has allowed, in particular, the description of the ligaments and capsule as well as the insertions of the masticatory muscles (temporalis, masseter, lateral pterygoid) on this joint. These observations are then compared with the anatomical and histological data already reported on this subject. This study shows that the bulk of the muscular fibres of the lateral pterygoid passes under the foot of the disc is attached over the whole height of the condylar, unite and extend as far as the medial pole of the joint under the insertion of the articular disc. An insertion of the temporo-masseter musculo-tendinous complex on the anterior and lateral capsulo-discal structures was observed. The lateral pterygoid is composed of a succession of tendinous and fleshy fibres. This study confirms the thickening of the lateral capsule that corresponds to a lateral collateral ligament, and the absence of a medial collateral ligament. Medial stability is conferred by the lateral ligament of the contralateral joint.

  3. Regional variations in the density and arrangement of elastic fibres in the anulus fibrosus of the human lumbar disc

    PubMed Central

    Smith, Lachlan J; Fazzalari, Nicola L

    2006-01-01

    Elastic fibres are critical components of the extracellular matrix in dynamic biological structures that undergo extension and recoil. Their presence has been demonstrated in the anulus fibrosus of the human lumbar intervertebral disc; however, a detailed regional analysis of their density and arrangement has not been undertaken, limiting our understanding of their structural and functional roles. In this investigation we have quantitatively described regional variations in elastic fibre density in the anulus fibrosus of the human L3–L4 intervertebral disc using histochemistry and light microscopy. Additionally, a multiplanar comparison of patterns of elastic fibre distribution in the intralamellar and interlamellar zones was undertaken. Novel imaging techniques were developed to facilitate the visualization of elastic fibres otherwise masked by dense surrounding matrix. Elastic fibre density was found to be significantly higher in the lamellae of the posterolateral region of the anulus than the anterolateral, and significantly higher in the outer regions than the inner, suggesting that elastic fibre density in each region of the anulus is commensurate with the magnitude of the tensile deformations experienced in bending and torsion. Elastic fibre arrangments in intralamellar and interlamellar zones were shown to be architecturally distinct, suggesting that they perform multiple functional roles within the anulus matrix structural hierarchy. PMID:16928204

  4. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Scott, F.; Stec, B; Pop, C

    The death inducing signalling complex (DISC) formed by Fas receptor, FADD (Fas-associated death domain protein) and caspase 8 is a pivotal trigger of apoptosis1, 2, 3. The Fas-FADD DISC represents a receptor platform, which once assembled initiates the induction of programmed cell death. A highly oligomeric network of homotypic protein interactions comprised of the death domains of Fas and FADD is at the centre of DISC formation4, 5. Thus, characterizing the mechanistic basis for the Fas-FADD interaction is crucial for understanding DISC signalling but has remained unclear largely because of a lack of structural data. We have successfully formed andmore » isolated the human Fas-FADD death domain complex and report the 2.7 A crystal structure. The complex shows a tetrameric arrangement of four FADD death domains bound to four Fas death domains. We show that an opening of the Fas death domain exposes the FADD binding site and simultaneously generates a Fas-Fas bridge. The result is a regulatory Fas-FADD complex bridge governed by weak protein-protein interactions revealing a model where the complex itself functions as a mechanistic switch. This switch prevents accidental DISC assembly, yet allows for highly processive DISC formation and clustering upon a sufficient stimulus. In addition to depicting a previously unknown mode of death domain interactions, these results further uncover a mechanism for receptor signalling solely by oligomerization and clustering events.« less

  5. The reports of thick discs' deaths are greatly exaggerated. Thick discs are NOT artefacts caused by diffuse scattered light

    NASA Astrophysics Data System (ADS)

    Comerón, S.; Salo, H.; Knapen, J. H.

    2018-02-01

    Recent studies have made the community aware of the importance of accounting for scattered light when examining low-surface-brightness galaxy features such as thick discs. In our past studies of the thick discs of edge-on galaxies in the Spitzer Survey of Stellar Structure in Galaxies - the S4G - we modelled the point spread function as a Gaussian. In this paper we re-examine our results using a revised point spread function model that accounts for extended wings out to more than 2\\farcm5. We study the 3.6 μm images of 141 edge-on galaxies from the S4G and its early-type galaxy extension. Thus, we more than double the samples examined in our past studies. We decompose the surface-brightness profiles of the galaxies perpendicular to their mid-planes assuming that discs are made of two stellar discs in hydrostatic equilibrium. We decompose the axial surface-brightness profiles of galaxies to model the central mass concentration - described by a Sérsic function - and the disc - described by a broken exponential disc seen edge-on. Our improved treatment fully confirms the ubiquitous occurrence of thick discs. The main difference between our current fits and those presented in our previous papers is that now the scattered light from the thin disc dominates the surface brightness at levels below μ 26 mag arcsec-2. We stress that those extended thin disc tails are not physical, but pure scattered light. This change, however, does not drastically affect any of our previously presented results: 1) Thick discs are nearly ubiquitous. They are not an artefact caused by scattered light as has been suggested elsewhere. 2) Thick discs have masses comparable to those of thin discs in low-mass galaxies - with circular velocities vc< 120 km s-1 - whereas they are typically less massive than the thin discs in high-mass galaxies. 3) Thick discs and central mass concentrations seem to have formed at the same epoch from a common material reservoir. 4) Approximately 50% of the up-bending breaks in face-on galaxies are caused by the superposition of a thin and a thick disc where the scale-length of the latter is the largest. Data of Figs. B.1 and C.1 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/610/A5

  6. Various Surface Treatments to Implant Provisional Restorations and Their Effect on Epithelial Cell Adhesion: A Comparative In Vitro Study.

    PubMed

    Luchinskaya, Darya; Du, Rong; Owens, David M; Tarnow, Dennis; Bittner, Nurit

    2017-02-01

    The aim of this in vitro study was to investigate the ability of epithelial cells to attach to or proliferate on various mechanical or chemical surface treatments of an implant provisional material. Polyethyl methacrylate discs 10 mm in diameter and ∼0.2 to 0.75 mm in width were used in the study. Experimental discs were treated with either a mechanical (pumice, varnish for shine, or high polishing) or a chemical agent (alcohol, chlorhexidine, or steam) to provide cleaning and/or polishing. Using primary human epidermal keratinocytes, experiments were performed to test the adhesion or proliferation of cells on the discs with various surface treatments. Scanning electron microscope analysis, rhodamine staining, and cell counting using a hemocytometer corroborated all findings and illustrated that the highest cell adhesion was found to be in the smooth surface treatment groups and the poorest adhesion was found to be in the rough surface groups and chemical treatment group. Within the limitations of this study, the following clinical protocol is recommended for finishing, polishing, and disinfecting implant provisional restorations: coarse, medium, fine pumice → high polishing (if desired) → steam. It is recommended to avoid applying varnish in the perimucosal area near the epithelium. This study could establish the most appropriate way to handle provisional restorations in the peri-implant sulcus for improved soft tissue health, esthetics, and long-term stability.

  7. Altered disc pressure profile after an osteoporotic vertebral fracture is a risk factor for adjacent vertebral body fracture

    PubMed Central

    Tzermiadianos, Michael N.; Renner, Susan M.; Phillips, Frank M.; Hadjipavlou, Alexander G.; Zindrick, Michael R.; Havey, Robert M.; Voronov, Michael

    2008-01-01

    This study investigated the effect of endplate deformity after an osteoporotic vertebral fracture in increasing the risk for adjacent vertebral fractures. Eight human lower thoracic or thoracolumbar specimens, each consisting of five vertebrae were used. To selectively fracture one of the endplates of the middle VB of each specimen a void was created under the target endplate and the specimen was flexed and compressed until failure. The fractured vertebra was subjected to spinal extension under 150 N preload that restored the anterior wall height and vertebral kyphosis, while the fractured endplate remained significantly depressed. The VB was filled with cement to stabilize the fracture, after complete evacuation of its trabecular content to ensure similar cement distribution under both the endplates. Specimens were tested in flexion-extension under 400 N preload while pressure in the discs and strain at the anterior wall of the adjacent vertebrae were recorded. Disc pressure in the intact specimens increased during flexion by 26 ± 14%. After cementation, disc pressure increased during flexion by 15 ± 11% in the discs with un-fractured endplates, while decreased by 19 ± 26.7% in the discs with the fractured endplates. During flexion, the compressive strain at the anterior wall of the vertebra next to the fractured endplate increased by 94 ± 23% compared to intact status (p < 0.05), while it did not significantly change at the vertebra next to the un-fractured endplate (18.2 ± 7.1%, p > 0.05). Subsequent flexion with compression to failure resulted in adjacent fracture close to the fractured endplate in six specimens and in a non-adjacent fracture in one specimen, while one specimen had no adjacent fractures. Depression of the fractured endplate alters the pressure profile of the damaged disc resulting in increased compressive loading of the anterior wall of adjacent vertebra that predisposes it to wedge fracture. This data suggests that correction of endplate deformity may play a role in reducing the risk of adjacent fractures. PMID:18795344

  8. Vortex stretching in self-gravitating protoplanetary discs

    NASA Astrophysics Data System (ADS)

    Regály, Zs.; Vorobyov, E.

    2017-10-01

    Horseshoe-shaped brightness asymmetries of several transitional discs are thought to be caused by large-scale vortices. Anticyclonic vortices efficiently collect dust particles, therefore they can play a major role in planet formation. Former studies suggest that the disc self-gravity weakens vortices formed at the edge of the gap opened by a massive planet in discs whose masses are in the range of 0.01 ≤ Mdisc/M* ≤ 0.1. Here, we present an investigation on the long-term evolution of the large-scale vortices formed at the viscosity transition of the discs' dead zone outer edge by means of two-dimensional hydrodynamic simulations taking disc self-gravity into account. We perform a numerical study of low-mass, 0.001 ≤ Mdisc/M* ≤ 0.01, discs, for which cases disc self-gravity was previously neglected. The large-scale vortices are found to be stretched due to disc self-gravity even for low-mass discs with Mdisc/M* ≳ 0.005, where initially the Toomre Q-parameter was ≲ 50 at the vortex distance. As a result of stretching, the vortex aspect ratio increases and a weaker azimuthal density contrast develops. The strength of the vortex stretching is proportional to the disc mass. The vortex stretching can be explained by a combined action of a non-vanishing gravitational torque caused by the vortex and the Keplerian shear of the disc. Self-gravitating vortices are subject to significantly faster decay than non-self-gravitating ones. We found that vortices developed at sharp viscosity transitions of self-gravitating discs can be described by a Goodman - Narayan - Goldreich (GNG) model as long as the disc viscosity is low, I.e. αdz ≤ 10-5.

  9. DISC1 Protein Regulates γ-Aminobutyric Acid, Type A (GABAA) Receptor Trafficking and Inhibitory Synaptic Transmission in Cortical Neurons.

    PubMed

    Wei, Jing; Graziane, Nicholas M; Gu, Zhenglin; Yan, Zhen

    2015-11-13

    Association studies have suggested that Disrupted-in-Schizophrenia 1 (DISC1) confers a genetic risk at the level of endophenotypes that underlies many major mental disorders. Despite the progress in understanding the significance of DISC1 at neural development, the mechanisms underlying DISC1 regulation of synaptic functions remain elusive. Because alterations in the cortical GABA system have been strongly linked to the pathophysiology of schizophrenia, one potential target of DISC1 that is critically involved in the regulation of cognition and emotion is the GABAA receptor (GABAAR). We found that cellular knockdown of DISC1 significantly reduced GABAAR-mediated synaptic and whole-cell current, whereas overexpression of wild-type DISC1, but not the C-terminal-truncated DISC1 (a schizophrenia-related mutant), significantly increased GABAAR currents in pyramidal neurons of the prefrontal cortex. These effects were accompanied by DISC1-induced changes in surface GABAAR expression. Moreover, the regulation of GABAARs by DISC1 knockdown or overexpression depends on the microtubule motor protein kinesin 1 (KIF5). Our results suggest that DISC1 exerts an important effect on GABAergic inhibitory transmission by regulating KIF5/microtubule-based GABAAR trafficking in the cortex. The knowledge gained from this study would shed light on how DISC1 and the GABA system are linked mechanistically and how their interactions are critical for maintaining a normal mental state. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Biomechanics of Hybrid Anterior Cervical Fusion and Artificial Disc Replacement in 3-Level Constructs: An In Vitro Investigation

    PubMed Central

    Liao, Zhenhua; Fogel, Guy R.; Pu, Ting; Gu, Hongsheng; Liu, Weiqiang

    2015-01-01

    Background The ideal surgical approach for cervical disk disease remains controversial, especially for multilevel cervical disease. The purpose of this study was to investigate the biomechanics of the cervical spine after 3-level hybrid surgery compared with 3-level anterior cervical discectomy and fusion (ACDF). Material/Methods Eighteen human cadaveric spines (C2-T1) were evaluated under displacement-input protocol. After intact testing, a simulated hybrid construct or fusion construct was created between C3 to C6 and tested in the following 3 conditions: 3-level disc plate disc (3DPD), 3-level plate disc plate (3PDP), and 3-level plate (3P). Results Compared to intact, almost 65~80% of motion was successfully restricted at C3-C6 fusion levels (p<0.05). 3DPD construct resulted in slight increase at the 3 instrumented levels (p>0.05). 3PDP construct resulted in significant decrease of ROM at C3-C6 levels less than 3P (p<0.05). Both 3DPD and 3PDP caused significant reduction of ROM at the arthrodesis level and produced motion increase at the arthroplasty level. For adjacent levels, 3P resulted in markedly increased contribution of both upper and lower adjacent levels (p<0.05). Significant motion increases lower than 3P were only noted at partly adjacent levels in some conditions for 3DPD and 3PDP (p<0.05). Conclusions ACDF eliminated motion within the construct and greatly increased adjacent motion. Artificial cervical disc replacement normalized motion of its segment and adjacent segments. While hybrid conditions failed to restore normal motion within the construct, they significantly normalized motion in adjacent segments compared with the 3-level ACDF condition. The artificial disc in 3-level constructs has biomechanical advantages compared to fusion in normalizing motion. PMID:26529430

  11. Biomechanics of Hybrid Anterior Cervical Fusion and Artificial Disc Replacement in 3-Level Constructs: An In Vitro Investigation.

    PubMed

    Liao, Zhenhua; Fogel, Guy R; Pu, Ting; Gu, Hongsheng; Liu, Weiqiang

    2015-11-03

    The ideal surgical approach for cervical disk disease remains controversial, especially for multilevel cervical disease. The purpose of this study was to investigate the biomechanics of the cervical spine after 3-level hybrid surgery compared with 3-level anterior cervical discectomy and fusion (ACDF). Eighteen human cadaveric spines (C2-T1) were evaluated under displacement-input protocol. After intact testing, a simulated hybrid construct or fusion construct was created between C3 to C6 and tested in the following 3 conditions: 3-level disc plate disc (3DPD), 3-level plate disc plate (3PDP), and 3-level plate (3P). Compared to intact, almost 65~80% of motion was successfully restricted at C3-C6 fusion levels (p<0.05). 3DPD construct resulted in slight increase at the 3 instrumented levels (p>0.05). 3PDP construct resulted in significant decrease of ROM at C3-C6 levels less than 3P (p<0.05). Both 3DPD and 3PDP caused significant reduction of ROM at the arthrodesis level and produced motion increase at the arthroplasty level. For adjacent levels, 3P resulted in markedly increased contribution of both upper and lower adjacent levels (p<0.05). Significant motion increases lower than 3P were only noted at partly adjacent levels in some conditions for 3DPD and 3PDP (p<0.05). ACDF eliminated motion within the construct and greatly increased adjacent motion. Artificial cervical disc replacement normalized motion of its segment and adjacent segments. While hybrid conditions failed to restore normal motion within the construct, they significantly normalized motion in adjacent segments compared with the 3-level ACDF condition. The artificial disc in 3-level constructs has biomechanical advantages compared to fusion in normalizing motion.

  12. Development and Validation of a Bioreactor System for Dynamic Loading and Mechanical Characterization of Whole Human Intervertebral Discs in Organ Culture

    PubMed Central

    Walter, BA; Illien-Junger, S; Nasser, P; Hecht, AC; Iatridis, JC

    2014-01-01

    Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48 hours of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error <2.5N and total harmonic distortion <2.45%), and precisely evaluated mechanical behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical behavior and retained >85% viable cells throughout the 3 week culture period. This organ culture loading system can closely mimic physiological conditions and be used to investigate response of living human and bovine IVDs to mechanical and chemical challenges and to screen therapeutic repair techniques. PMID:24725441

  13. Loss of notochordal cell phenotype in 3D-cell cultures: implications for disc physiology and disc repair.

    PubMed

    Omlor, G W; Nerlich, A G; Tirlapur, U K; Urban, J P; Guehring, T

    2014-12-01

    Embryonic notochordal disc nucleus cells (NC) have been identified to protect disc tissue against disc degeneration but in human beings NC phenotype gets lost with aging and the pathophysiological mechanisms are poorly understood. NC may stimulate other cells via soluble factors, and NC-conditioned medium can be used to stimulate matrix production of other disc cells and mesenchymal stem cells and thus may be of special interest for biological disc repair. As this stimulatory effect is associated with the NC phenotype, we investigated how cell morphology and gene-expression of the NC phenotype changes with time in 3D-cell culture. NC and inner annulus chondrocyte-like cells (CLC) from immature pigtails (freshly isolated cells/tissue, 3D-alginate beads, 3D-clusters) were cultured for up to 16 days under normoxia and hypoxia. Protein-expression was analysed by immunohistology and gene-expression analysis was carried out on freshly isolated cells and cultured cells. Cell morphology and proliferation were analysed by two-photon-laser-microscopy. Two-photon-laser-microscopy showed a homogenous and small CLC population in the inner annulus, which differed from the large vacuole-containing NC in the nucleus. Immunohistology found 93 % KRT8 positive cells in the nucleus and intracellular and pericellular Col2, IL6, and IL12 staining while CLC were KRT8 negative. Freshly isolated NC showed significantly higher KRT8 and CAIII but lower Col2 gene-expression than CLC. NC in 3D-cultures demonstrated significant size reduction and loss of vacuoles with culture time, all indicating a loss of the characteristic NC morphology. Hypoxia reduced the rate of decrease in NC size and vacuoles. Gene-expression of KRT8 and CAIII in NC fell significantly early in culture while Col2 did not decrease significantly within the culture period. In CLC, KRT8 and CAIII gene-expression was low and did not change noticeably in culture, whereas Col2 expression fell with time in culture. 3D-culture caused a rapid loss of NC phenotype towards a CLC phenotype with disappearance of vacuoles, reduced cell size, increased proliferation, and gene-expression changes. These findings may be related to NC nutritional demands and support the latest hypothesis of NC maturation into CLC opposing the idea that NC get lost in human discs by cell death or apoptosis to be replaced by CLC from the inner annulus.

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

    PubMed

    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.

  15. Effect of Air-Polishing on Titanium Surfaces, Biofilm Removal, and Biocompatibility: A Pilot Study

    PubMed Central

    Bennani, Vincent; Hwang, Linda; Tawse-Smith, Andrew; Dias, George J.; Cannon, Richard D.

    2015-01-01

    Purpose. The aims of this in vitro study were to evaluate morphological changes induced by glycine powder air-polishing on titanium surfaces, biofilm removal, and biocompatibility. Material and Methods. Titanium grade IV discs were allocated into two groups: (1) discs without biofilm and (2) discs for Streptococcus mutans biofilm formation. Discs in each group were further subdivided into (a) no treatment and (b) air-polishing treatment with glycine powder. Discs were characterized by scanning electron microscopy (SEM), electron-dispersive spectroscopy (EDS), and confocal microscopy. Bacterial biofilms were quantified using a crystal violet dye-binding assay. Biocompatibility was evaluated by measuring the coverage and viability of L929 fibroblast cells cultured on the discs. Results. Air-polishing increased the roughness of treated discs (P < 0.05). EDS analysis did not show significant differences in the chemical composition of treated and nontreated discs. The amount of residual biofilm on treated discs was 8.6-fold lower than untreated controls (P < 0.05). Coverage of treated discs by fibroblasts was half that of untreated discs (P < 0.05) although both groups had the same cell viability. Conclusions. Air-polishing removed a significant amount of biofilm from titanium surfaces. The “polishing” was accompanied by increased surface roughness, but there were no changes in chemical and elemental compositions, nor the biocompatibility. PMID:26881198

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

    PubMed Central

    Bach, Frances C.; Laagland, Lisanne T.; Grant, Michael P.; Creemers, Laura B.; Ito, Keita; Meij, Björn P.; Mwale, Fackson

    2017-01-01

    Introduction 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. Materials and methods 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. Results Human (s)Link-N induced GAG deposition in human and bovine CLCs, as expected. In contrast, canine (s)Link-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 (s)Link-N induced negligible GAG deposition. Surprisingly, human and canine (s)Link-N did not induce Smad signaling in human and bovine CLCs. Human and canine (s)Link-N only mildly increased pSmad1 and Smad2 levels in canine CLCs. Conclusions Human and canine (s)Link-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, (s)Link-N still holds a regenerative potential for humans. PMID:29117254

  17. Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: from bench towards bedside.

    PubMed

    Bach, Frances C; Tellegen, Anna R; Beukers, Martijn; Miranda-Bedate, Alberto; Teunissen, Michelle; de Jong, Willem A M; de Vries, Stefan A H; Creemers, Laura B; Benz, Karin; Meij, Björn P; Ito, Keita; Tryfonidou, Marianna A

    2018-05-29

    The socioeconomic burden of chronic back pain related to intervertebral disc (IVD) disease is high and current treatments are only symptomatic. Minimally invasive strategies that promote biological IVD repair should address this unmet need. Notochordal cells (NCs) are replaced by chondrocyte-like cells (CLCs) during IVD maturation and degeneration. The regenerative potential of NC-secreted substances on CLCs and mesenchymal stromal cells (MSCs) has already been demonstrated. However, identification of these substances remains elusive. Innovatively, this study exploits the regenerative NC potential by using healthy porcine NC-derived matrix (NCM) and employs the dog as a clinically relevant translational model. NCM increased the glycosaminoglycan and DNA content of human and canine CLC aggregates and facilitated chondrogenic differentiation of canine MSCs in vitro . Based on these results, NCM, MSCs and NCM+MSCs were injected in mildly (spontaneously) and moderately (induced) degenerated canine IVDs in vivo and, after six months of treatment, were analyzed. NCM injected in moderately (induced) degenerated canine IVDs exerted beneficial effects at the macroscopic and MRI level, induced collagen type II-rich extracellular matrix production, improved the disc height, and ameliorated local inflammation. MSCs exerted no (additive) effects. In conclusion, NCM induced in vivo regenerative effects on degenerated canine IVDs. NCM may, comparable to demineralized bone matrix in bone regeneration, serve as 'instructive matrix', by locally releasing growth factors and facilitating tissue repair. Therefore, intradiscal NCM injection could be a promising regenerative treatment for IVD disease, circumventing the cumbersome identification of bioactive NC-secreted substances.

  18. Culture of human anulus fibrosus cells on polyamide nanofibers: extracellular matrix production.

    PubMed

    Gruber, Helen E; Hoelscher, Gretchen; Ingram, Jane A; Hanley, Edward N

    2009-01-01

    Studies were approved by the authors' Human Subjects Institutional Review Board. Human anulus cells were tested for growth and extracellular matrix (ECM) production in vitro. To investigate cell attachment, cell proliferation, and ECM production of human intervertebral disc anulus cells seeded onto randomly oriented electrospun polyamide nanofibers. Because nanofibrillar matrices have the potential to promote microenvironments, which may mimic in vivo conditions and resemble connective tissue, their utilization opens new avenues for cell-based tissue engineering applications for disc cells. Anulus cells were isolated from 4 cervical spine surgical disc specimens, expanded, and seeded into either routine plastic culture (control) or a nanofiber surface of randomly oriented electrospun polyamide nanofibers (Ultra-Web-coated culture dish, Corning) with a positive charge or without a charge. Cells were cultured for 9 days, digital images captured, cells harvested, embedded in paraffin, and examined for production of extracellular matrix (ECM). Additional anulus cultures were tested to quantitatively assess total proteoglycan production and cell proliferation under control or nanofiber cultures. Cells attached well and exhibited cell extensions within the nanofiber layers; cells on the charged nanofiber surface deposited greater amounts of chondroitin sulfate than of type II collagen than cells cultured on the uncharged nanofiber surface. Results showed that culture of anulus cells on nanofibers was permissive for secretion and assembly of type II collagen and chondroitin sulfate. Significantly greater total proteoglycan formation was present after culture on the nanofiber with added charge conditions {control, 0.6116 microg/mL +/- 0.186 [4] [mean +/- sem(n)] vs. 1.201 +/- 0.2509 [4], P < 0.05}. Cell proliferation, however, did not differ among treatment groups. Culture of anulus cells on nanofibers was found to be permissive for secretion and assembly of type II collagen and chondroitin sulfate, and culture on nanofibers with added charge significantly increased total proteoglycan production. These novel findings point to the need for further examination of nanofibrillar 3D culture of anulus cells for tissue engineering applications.

  19. Real-Time Estimation of Small-Area Populations with Human Biomarkers in Sewage

    EPA Science Inventory

    A totally new approach is conceptualized for measuring small-area human populations by using biomarkers in sewage. The basis for the concept (SCIM: Sewage Chemical-Information Mining) is supported by a comprehensive examination and synthesis of data published across several disc...

  20. The Effect of CuO Nanoparticles on Antimicrobial Effects and Shear Bond Strength of Orthodontic Adhesives

    PubMed Central

    Toodehzaeim, Mohammad Hossein; Zandi, Hengameh; Meshkani, Hamidreza; Hosseinzadeh Firouzabadi, Azadeh

    2018-01-01

    Statement of the Problem: Orthodontic appliances facilitate microbial plaque accumulation and increase the chance of white spot lesions. There is a need for new plaque control methods independent of patient's cooperation. Purpose: The aim of this study was to determine the effects of incorporating copper oxide (CuO) nanoparticles on antimicrobial properties and bond strength of orthodontic adhesive. Materials and Method: CuO nanoparticles were added to the composite transbond XT at concentrations of 0.01, 0.5 and 1 wt.%. To evaluate the antimicrobial properties of composites containing nanoparticles, the disk agar diffusion test was used. For this purpose, 10 discs from each concentration of nano-composites (totally 30 discs) and 10 discs from conventional composite (as the control group) were prepared. Then the diameter of streptococcus mutans growth inhibition around each disc was determined in blood agar medium. To evaluate the shear bond strength, with each concentration of nano-composites as well as the control group (conventional composite), 10 metal brackets were bonded to the human premolars and shear bond strength was determined using a universal testing machine. Results: Nano-composites in all three concentrations showed significant antimicrobial effect compared to the control group (p< 0.001). With increasing concentration of nanoparticles, antimicrobial effect showed an upward trend, although statistically was not significant. There was no significant difference between the shear bond strength of nano-composites compared to control group (p= 0.695). Conclusion: Incorporating CuO nanoparticles into adhesive in all three studied concentrations added antimicrobial effects to the adhesive with no adverse effects on shear bond strength. PMID:29492409

  1. The Effect of CuO Nanoparticles on Antimicrobial Effects and Shear Bond Strength of Orthodontic Adhesives.

    PubMed

    Toodehzaeim, Mohammad Hossein; Zandi, Hengameh; Meshkani, Hamidreza; Hosseinzadeh Firouzabadi, Azadeh

    2018-03-01

    Orthodontic appliances facilitate microbial plaque accumulation and increase the chance of white spot lesions. There is a need for new plaque control methods independent of patient's cooperation. The aim of this study was to determine the effects of incorporating copper oxide (CuO) nanoparticles on antimicrobial properties and bond strength of orthodontic adhesive. CuO nanoparticles were added to the composite transbond XT at concentrations of 0.01, 0.5 and 1 wt.%. To evaluate the antimicrobial properties of composites containing nanoparticles, the disk agar diffusion test was used. For this purpose, 10 discs from each concentration of nano-composites (totally 30 discs) and 10 discs from conventional composite (as the control group) were prepared. Then the diameter of streptococcus mutans growth inhibition around each disc was determined in blood agar medium. To evaluate the shear bond strength, with each concentration of nano-composites as well as the control group (conventional composite), 10 metal brackets were bonded to the human premolars and shear bond strength was determined using a universal testing machine. Nano-composites in all three concentrations showed significant antimicrobial effect compared to the control group ( p < 0.001). With increasing concentration of nanoparticles, antimicrobial effect showed an upward trend, although statistically was not significant. There was no significant difference between the shear bond strength of nano-composites compared to control group ( p = 0.695). Incorporating CuO nanoparticles into adhesive in all three studied concentrations added antimicrobial effects to the adhesive with no adverse effects on shear bond strength.

  2. On the diversity and statistical properties of protostellar discs

    NASA Astrophysics Data System (ADS)

    Bate, Matthew R.

    2018-04-01

    We present results from the first population synthesis study of protostellar discs. We analyse the evolution and properties of a large sample of protostellar discs formed in a radiation hydrodynamical simulation of star cluster formation. Due to the chaotic nature of the star formation process, we find an enormous diversity of young protostellar discs, including misaligned discs, and discs whose orientations vary with time. Star-disc interactions truncate discs and produce multiple systems. Discs may be destroyed in dynamical encounters and/or through ram-pressure stripping, but reform by later gas accretion. We quantify the distributions of disc mass and radii for protostellar ages up to ≈105 yr. For low-mass protostars, disc masses tend to increase with both age and protostellar mass. Disc radii range from of order 10 to a few hundred au, grow in size on time-scales ≲ 104 yr, and are smaller around lower mass protostars. The radial surface density profiles of isolated protostellar discs are flatter than the minimum mass solar nebula model, typically scaling as Σ ∝ r-1. Disc to protostar mass ratios rarely exceed two, with a typical range of Md/M* = 0.1-1 to ages ≲ 104 yr and decreasing thereafter. We quantify the relative orientation angles of circumstellar discs and the orbit of bound pairs of protostars, finding a preference for alignment that strengths with decreasing separation. We also investigate how the orientations of the outer parts of discs differ from the protostellar and inner disc spins for isolated protostars and pairs.

  3. [Biology and mechanobiology of the intervertebral disc].

    PubMed

    González Martínez, Emilio; García-Cosamalón, José; Cosamalón-Gan, Iván; Esteban Blanco, Marta; García-Suarez, Olivia; Vega, José A

    The intervertebral disc (IVD) is noted for its low cell content, and being the largest avascular structure of human body. The low amount of cells in the disc have to adapt to an anaerobic metabolism with low oxygen pressure and acidic pH. Apart from surviving in an adverse microenvironment, they are exposed to a high level of mechanical stress. The biological adaptation of cells to acidosis and hyperosmolarity conditions are regulated by mechanoproteins, which are responsible for converting a mechanical signal into a cellular response, thus modifying its gene expression. Mechanobiology helps us to better understand the pathophysiology of IVD and its potential biological repair. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Observations of warm molecular gas and kinematics in the disc around HD 100546

    NASA Astrophysics Data System (ADS)

    Panić, O.; van Dishoeck, E. F.; Hogerheijde, M. R.; Belloche, A.; Güsten, R.; Boland, W.; Baryshev, A.

    2010-09-01

    Context. The disc around the Herbig Ae/Be star HD 100546 is one of the most extensively studied discs in the southern sky. Although there is a wealth of information about its dust content and composition, not much is known about its gas and large-scale kinematics. Many recent results have stressed the importance of studying both the gas and dust in discs. 12CO is an excellent gas tracer in the submillimetre, and the intensity ratio between lines originating from low and high rotational levels probes the gas temperature. Emerging submillimetre facilities in the Southern hemisphere allow us to characterise the gas and dust content in objects like HD 100546 better. Aims: Our aim is to establish whether the disc is gas-rich and to study the disc temperature and kinematics. Methods: We detected and studied the molecular gas in the disc at spatial resolution from 7.7 arcsec to 18.9 arcsec using the Atacama Pathfinder Experiment telescope (This publication is based on data acquired with the Atacama Pathfinder Experiment (APEX). APEX is a collaboration between the Max-Planck-Institut für Radioastronomie, the European Southern Observatory, and the Onsala Space Observatory.). We observed the lines 12CO J = 7-6, J = 6-5, J = 3-2, 13CO J = 3-2 and [C I] 3P2-3P1, as diagnostics of disc temperature, size, chemistry, and kinematics. We use parametric disc models that reproduce the low-J 12CO emission from Herbig Ae stars and we vary the basic disc parameters - temperature, mass, and size. With the help of a molecular excitation and radiative transfer code we fit the observed spectral line profiles. Results: Our observations are consistent with more than 10-3 M⊙ of molecular gas in a disc of ≈400 AU radius in Keplerian rotation around a 2.5 M⊙ star, seen at an inclination of 50°. The detected 12CO lines are dominated by gas at 30-70 K. Not detecting the [C I] line indicates excess ultraviolet emission above that of a B9 type model stellar atmosphere. Asymmetry in the 12CO line emission suggests that one side of the outer disc is colder by 10-20 K than the other. A plausible scenario is a warped geometry in the inner disc casting a partial shaddow on the outer disc. We exclude pointing offsets, foreground cloud absorption, and asymmetry in the disc extent as possible causes of the observed line asymmetry. Conclusions: Efficient heating of the outer disc by the star HD 100546 ensures that low- and high-J 12CO lines are dominated by the outermost disc regions, indicating a 400 AU radius. The 12CO J = 6-5 line arises from a disc layer higher than disc midplane, and warmer by 15-20 K than the layer emitting the J = 3-2 line. The existing models of discs around Herbig Ae stars, asuming a B9.5 type model stellar atmosphere, overproduce the [CI] 3P2-3P1 line intensity from HD 100546 by an order of magnitude.

  5. Dependence of optic disc parameters on disc area according to Heidelberg Retina Tomograph: Part II.

    NASA Astrophysics Data System (ADS)

    Machekhin, V.; Manaenkova, G.; Bondarenko, O.

    2007-05-01

    With the help of Heidelberg Retina Tomograph (HRT-II) optic disc parameters in 211 eyes of 115 healthy patients with refraction Em +/- 3,0 D and 96 eyes of 72 patients with myopia 3,5-14,0 D without any signs of glaucoma were studied. Analysis of optic disc parameters were carried out in 5 groups of patients according to disc area: less than 1,5 mm2, 1,5- 2,5 mm2, 2,5-3,0 mm2, 3,0-3,5 mm2 and more than 3,5 mm2. An accurate depending on disc area was revealed for all optic disc parameters in all sectors, which was manifested by increasing cup disc and rim disc (area and volume) and other parameters. We consider it is necessary to use the proper tables for right interpretation of received data for early diagnosis of glaucoma.

  6. Changes in intervertebral disc cross-sectional area with bed rest and space flight

    NASA Technical Reports Server (NTRS)

    LeBlanc, A. D.; Evans, H. J.; Schneider, V. S.; Wendt, R. E. 3rd; Hedrick, T. D.

    1994-01-01

    STUDY DESIGN. We measured the cross-sectional area of the intervertebral discs of normal volunteers after an overnight rest; before, during, and after 5 or 17 weeks of bed rest; and before and after 8 days of weightlessness. OBJECTIVES. This study sought to determine the degree of expansion of the lumbar discs resulting from bed rest and space flight. SUMMARY OF BACKGROUND DATA. Weightlessness and bed rest, an analog for weightlessness, reduce the mechanical loading on the musculoskeletal system. When unloaded, intervertebral discs will expand, increasing the nutritional diffusion distance and altering the mechanical properties of the spine. METHODS. Magnetic resonance imaging was used to measure the cross-sectional area and transverse relaxation time (T2) of the intervertebral discs. RESULTS. Overnight or longer bed rest causes expansion of the disc area, which reaches an equilibrium value of about 22% (range 10-40%) above baseline within 4 days. Increases in disc area were associated with modest increases in disc T2. During bed rest, disc height increased approximately 1 mm, about one-half of previous estimates based on body height measurements. After 5 weeks of bed rest, disc area returned to baseline within a few days of ambulation, whereas after 17 weeks, disc area remained above baseline 6 weeks after reambulation. After 8 days of weightlessness, T2, disc area, and lumbar length were not significantly different from baseline values 24 hours after landing. CONCLUSIONS. Significant adaptive changes in the intervertebral discs can be expected during weightlessness. These changes, which are rapidly reversible after short-duration flights, may be an important factor during and after long-duration missions.

  7. In Vitro Maturation and In Vivo Integration and Function of an Engineered Cell-Seeded Disc-like Angle Ply Structure (DAPS) for Total Disc Arthroplasty.

    PubMed

    Martin, J T; Gullbrand, S E; Kim, D H; Ikuta, K; Pfeifer, C G; Ashinsky, B G; Smith, L J; Elliott, D M; Smith, H E; Mauck, R L

    2017-11-17

    Total disc replacement with an engineered substitute is a promising avenue for treating advanced intervertebral disc disease. Toward this goal, we developed cell-seeded disc-like angle ply structures (DAPS) and showed through in vitro studies that these constructs mature to match native disc composition, structure, and function with long-term culture. We then evaluated DAPS performance in an in vivo rat model of total disc replacement; over 5 weeks in vivo, DAPS maintained their structure, prevented intervertebral bony fusion, and matched native disc mechanical function at physiologic loads in situ. However, DAPS rapidly lost proteoglycan post-implantation and did not integrate into adjacent vertebrae. To address this, we modified the design to include polymer endplates to interface the DAPS with adjacent vertebrae, and showed that this modification mitigated in vivo proteoglycan loss while maintaining mechanical function and promoting integration. Together, these data demonstrate that cell-seeded engineered discs can replicate many characteristics of the native disc and are a viable option for total disc arthroplasty.

  8. Angiogenesis in the degeneration of the lumbar intervertebral disc

    PubMed Central

    David, Gh; 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 factor and vascular endothelial growth factor level measurements, as elements in the process of appreciating the disc angiogenesis. Also, pre–surgery and post–surgery QOL has been measured, as well as the intensity of the pain syndrome. We have identified factors capable of stimulating vascular endothelial growth (VEGF, FGF–2) for the examined disc material, but histological examination did not show angiogenesis. The process of angiogenesis at the degenerated intervertebral disc level affects the patient's quality of life both pre and postoperatively, and may be a predictive factor for the post–operative results. Patients can prevent the appearance of angiogenesis type degenerative processes of the intervertebral disc by avoiding angiogenesis correlated factors (weight control, physical effort, and smoking). PMID:20968201

  9. Reduction of turbulent skin-friction drag by oscillating discs

    NASA Astrophysics Data System (ADS)

    Wise, Daniel; Ricco, Pierre

    2013-11-01

    A new drag-reduction method, based on the active technique proposed by Ricco & Hahn (2013), i.e. steadily rotating flush-mounted discs, is studied by DNS. The effect of sinusoidally oscillating discs on the turbulent channel-flow drag is investigated at Reτ = 180 , based on the friction velocity of the stationary-wall case and the half channel height. A parametric investigation on the disc diameter, tip velocity and oscillation period yielded a maximum drag reduction of 18.5%. Regions of net power saved, calculated by considering the power spent to enforce the disc motion against the viscous resistance of the fluid, are found to reach up to 6.5% for low disc tip velocities. Significantly, the characteristic time-scale for the oscillating disc forcing is double that for the steadily rotating discs, representing a further step towards industrial implementation. The oscillating disc forcing, similar to the steadily rotating disc forcing, creates streamwise-elongated structures between the discs. These structures - largely unaffected by the periodic wall forcing and persisting throughout the entire period of the oscillation - are the main contributor to the additional Reynolds stresses term created by the disc forcing, and are important for the drag reduction mechanism.

  10. Conservatively treated massive prolapsed discs: a 7-year follow-up

    PubMed Central

    Benson, RT; Tavares, SP; Robertson, SC; Sharp, R; Marshall, RW

    2010-01-01

    INTRODUCTION The natural history of a lumbar hernia of the nucleus pulposus (HNP) is not fully known and clear indications for operative intervention cannot be established from the literature. Several studies have shown that the largest discs appear to have the greatest tendency to resolve. The aim of this study was to investigate whether massive prolapsed discs can be safely managed conservatively once clinical improvement has occurred. PATIENTS AND METHODS Thirty-seven patients were studied by clinical assessments and serial magnetic resonance imaging (MRI) over 2 years. Patients had severe sciatica at first, but began to show clinical improvement despite the large disc hernia-tions. Clinical assessment included the Lasegue test and neurological appraisal. The Oswestry Disability Index was used to measure function and changes in function. Serial MRI studies allowed measurement of volume changes of the herniated disc material over a period of time. RESULTS Initial follow-up at an average of 23.2 months revealed that 83% had a complete and sustained recovery at the initial follow-up. Only four patients required a discectomy. The average Oswestry disability index improved from 58% to 15%. Volumetric analysis of serial MRI scans found an average reduction of 64% in disc size. There was a poor correlation between clinical improvement and the extent of disc resolution. CONCLUSIONS A massive disc herniation can pursue a favourable clinical course. If early progress is shown, the long-term prognosis is very good and even massive disc herniations can be treated conservatively. PMID:19887021

  11. Evidence for association between Disrupted-in-schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based association study

    PubMed Central

    2011-01-01

    Background Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism. Methods We genotyped seven tag single nucleotide polymorphisms (SNPs) in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software. Results We found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, p = 0.004; rs11585959: T > C, Z = 2.199, p = 0.028; rs6668845: A > G, Z = 2.326, p = 0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values. Conclusions Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism. PMID:21569632

  12. [Epidemiology investigation and biomechanics analyses for the correlation between sacroiliac joint disorder and lumbar intervertebral disc degeneration].

    PubMed

    Shi, Ning-Ning; Shen, Guo-Quan; He, Shui-Yong; Guo, Ru-Bao

    2014-07-01

    To study the correlation between lumber disc degeneration and sacroiliac joint disorder, in order to provides a new understanding concepts and therapeutic approach for the prevention and treatment of chronic intractable low back pain. From August 2009 to October 2010,129 cases with lumbar disc herniation were studied with epidemiological methods. Among them, 61 patients with L4, disc herniation included 37 males and 24 females, ranging in aged from 20 to 75 years old, duration of the disease ranged from 1 to 144 months; The other 68 patients with L5S1 disc herniation included 32 males and 36 females,ranging in aged froml8 to 76 years old,duration of the disease ranged from 0.5 to 240 months. The clinical data, symptoms and signs,X-ray characteristics of lumbar spine and pelvis of the patients were investigated by epidemiological. The risk of lumbar disc herniation was calculated with case-control study; independent variables were screened with single factor analysis; the risk factors for lumbar disc herniation were determined with logistic regression analysis, and biomechanics analyses were taken. Among 129 patients with lumbar disc herniation, 88 cases associated with sacroiliac joint disorders, sacroiliac joint disorder was a risk factor of lumbar disc herniation (OR = 4.61, P = 0.00); 47 cases associated with sacroiliac joint disorders in 61 patients with L4,5 disc herniation, iliac crest uneven caused by iliac rotational displacement was a high risk factor of L4,5 disc herniation (OR = 11.27, P = 0.00); 41 cases associated with sacroiliac joint disorders in 68 patients with L5S1 disc herniation, lumbar sacral angle abnormalities caused by sacral tilt shift was a high risk factor L5S1 disc herniation (OR = 2.31, P = 0.03). Lumbar disc herniation and sacroiliac joint disorder are two of fallot, the two factors affect each other and there is a causal relationship. They are common exists in low back pain.

  13. Injection of AAV2-BMP2 and AAV2-TIMP1 into the nucleus pulposus slows the course of intervertebral disc degeneration in an in vivo rabbit model.

    PubMed

    Leckie, Steven K; Bechara, Bernard P; Hartman, Robert A; Sowa, Gwendolyn A; Woods, Barrett I; Coelho, Joao P; Witt, William T; Dong, Qing D; Bowman, Brent W; Bell, Kevin M; Vo, Nam V; Wang, Bing; Kang, James D

    2012-01-01

    Intervertebral disc degeneration (IDD) is a common cause of back pain. Patients who fail conservative management may face the morbidity of surgery. Alternative treatment modalities could have a significant impact on disease progression and patients' quality of life. To determine if the injection of a virus vector carrying a therapeutic gene directly into the nucleus pulposus improves the course of IDD. Prospective randomized controlled animal study. Thirty-four skeletally mature New Zealand white rabbits were used. In the treatment group, L2-L3, L3-L4, and L4-L5 discs were punctured in accordance with a previously validated rabbit annulotomy model for IDD and then subsequently treated with adeno-associated virus serotype 2 (AAV2) vector carrying genes for either bone morphogenetic protein 2 (BMP2) or tissue inhibitor of metalloproteinase 1 (TIMP1). A nonoperative control group, nonpunctured sham surgical group, and punctured control group were also evaluated. Serial magnetic resonance imaging (MRI) studies at 0, 6, and 12 weeks were obtained, and a validated MRI analysis program was used to quantify degeneration. The rabbits were sacrificed at 12 weeks, and L4-L5 discs were analyzed histologically. Viscoelastic properties of the L3-L4 discs were analyzed using uniaxial load-normalized displacement testing. Creep curves were mathematically modeled according to a previously validated two-phase exponential model. Serum samples obtained at 0, 6, and 12 weeks were assayed for biochemical evidence of degeneration. The punctured group demonstrated MRI and histologic evidence of degeneration as expected. The treatment groups demonstrated less MRI and histologic evidence of degeneration than the punctured group. The serum biochemical marker C-telopeptide of collagen type II increased rapidly in the punctured group, but the treated groups returned to control values by 12 weeks. The treatment groups demonstrated several viscoelastic properties that were distinct from control and punctured values. Treatment of punctured rabbit intervertebral discs with AAV2-BMP2 or AAV2-TIMP1 helps delay degenerative changes, as seen on MRI, histologic sampling, serum biochemical analysis, and biomechanical testing. Although data from animal models should be extrapolated to the human condition with caution, this study supports the potential use of gene therapy for the treatment of IDD. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Magnetic fields in giant planet formation and protoplanetary discs

    NASA Astrophysics Data System (ADS)

    Keith, Sarah Louise

    2015-12-01

    Protoplanetary discs channel accretion onto their host star. How this is achieved is critical to the growth of giant planets which capture their massive gaseous atmosphere from the surrounding flow. Theoretical studies find that an embedded magnetic field could power accretion by hydromagnetic turbulence or torques from a large-scale field. This thesis presents a study of the inuence of magnetic fields in three key aspects of this process: circumplanetary disc accretion, gas flow across gaps in protoplanetary discs, and magnetic-braking in accretion discs. The first study examines the conditions needed for self-consistent accretion driven by magnetic fields or gravitational instability. Models of these discs typically rely on hydromagnetic turbulence as the source of effective viscosity. However, magnetically coupled,accreting regions may be so limited that the disc may not support sufficient inflow. An improved Shakura-Sunyaev ? disc is used to calculate the ionisation fraction and strength of non-ideal effects. Steady magnetically-driven accretion is limited to the thermally ionised, inner disc so that accretion in the remainder of the disc is time-dependent. The second study addresses magnetic flux transport in an accretion gap evacuated by a giant planet. Assuming the field is passively drawn along with the gas, the hydrodynamical simulation of Tanigawa, Ohtsuki & Machida (2012) is used for an a posteriori analysis of the gap field structure. This is used to post-calculate magnetohydrodynamical quantities. This assumption is self-consistent as magnetic forces are found to be weak, and good magnetic coupling ensures the field is frozen into the gas. Hall drift dominates across much of the gap, with the potential to facilitate turbulence and modify the toroidal field according to the global field orientation. The third study considers the structure and stability of magnetically-braked accretion discs. Strong evidence for MRI dead-zones has renewed interest in accretion powered by large-scale fields. An equilibrium model is presented for the radial structure of an axisymmetric, magnetically-braked accretion disc connected to a force-free external field. The accretion rate is multivalued at protoplanetary disc column densities, featuring an `S-curve' associated with models of accretion outbursting. A local, linear analysis of the stability of radial modes finds that the rapidly accreting, middle and upper solution branches are unstable, further highlighting the potential for eruptive accretion events.

  15. The effect of parental factors in children with large cup-to-disc ratios.

    PubMed

    Park, Hae-Young Lopilly; Ha, Min Ji; Shin, Sun Young

    2017-01-01

    To investigate large cup-to-disc ratios (CDR) in children and to determine the relationship between parental CDR and clinical characteristics associated with glaucoma. Two hundred thirty six children aged 6 to 12 years with CDR ≥ 0.6 were enrolled in this study. Subjects were classified into two groups based on parental CDR: disc suspect children with disc suspect (CDR ≥0.6) parents and disc suspect children without disc suspect parents. Ocular variables were compared between the two groups. Of the 236 disc suspect children, 100 (42.4%) had at least one disc suspect parent. Intraocular pressure (IOP) was higher in disc suspect children with disc suspect parents (16.52±2.66 mmHg) than in disc suspect children without disc suspect parents (14.38±2.30 mmHg, p = 0.023). In the group with disc suspect parents, vertical CDR significantly correlated with IOP (R = -0.325, p = 0.001), average retinal nerve fiber layer (RNFL) thickness (R = -0.319, p = 0.001), rim area (R = -0.740, p = 0.001), and cup volume (R = 0.499, p = 0.001). However, spherical equivalent (R = 0.333, p = 0.001), AL (R = -0.223, p = 0.009), and disc area (R = 0.325, p = 0.001) significantly correlated with vertical CDR in disc suspect children without disc suspect parents, in contrast to those with disc suspect parents. Larger vertical CDR was associated with the presence of disc suspect parents (p = 0.001), larger disc area (p = 0.001), thinner rim area (p = 0.001), larger average CDR (p = 0.001), and larger cup volume (p = 0.021). Family history of large CDR was a significant factor associated with large vertical CDR in children. In children with disc suspect parents, there were significant correlations between IOP and average RNFL thickness and vertical CDR.

  16. Growth promoting in vitro effect of synthetic cyclic RGD-peptides on human osteoblast-like cells attached to cancellous bone.

    PubMed

    Magdolen, Ursula; Auernheimer, Jörg; Dahmen, Claudia; Schauwecker, Johannes; Gollwitzer, Hans; Tübel, Jutta; Gradinger, Reiner; Kessler, Horst; Schmitt, Manfred; Diehl, Peter

    2006-06-01

    In tissue engineering, the application of biofunctional compounds on biomaterials such as integrin binding RGD-peptides has gained growing interest. Anchorage-dependent cells like osteoblasts bind to these peptides thus ameliorating the integration of a synthetic implant. In case sterilized bone grafts are used as substitutes for reconstruction of bone defects, the ingrowth of the implanted bone is often disturbed because of severe pretreatment such as irradiation or autoclaving, impairing the biological and mechanical properties of the bone. We report for the first time on the in vitro coating of the surface of freshly resected, cleaned bone discs with synthetic, cyclic RGD-peptides. For this approach, two different RGD-peptides were used, one containing two phosphonate anchors, the other peptide four of these binding moieties to allow efficient association of these reactive RGD-peptides to the inorganic bone matrix. Human osteoblast-like cells were cultured on RGD-coated bone discs and the adherence and growth of the cells were analyzed. Coating of bone discs with RGD-peptides did not improve the adhesion rate of osteoblast-like cells to the discs but significantly (up to 40%) accelerated growth of these cells within 8 days after attachment. This effect points to pretreatment of bone implants, especially at the critical interface area between the implanted bone and the non-resected residual bone structure, before re-implantation in order to stimulate and enhance osteointegration of a bone implant.

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

    PubMed

    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.

  18. Difference in occurrence of heterotopic ossification according to prosthesis type in the cervical artificial disc replacement.

    PubMed

    Yi, Seong; Kim, Keung Nyun; Yang, Moon Sul; Yang, Joong Won; Kim, Hoon; Ha, Yoon; Yoon, Do Heum; Shin, Hyun Chul

    2010-07-15

    Retrospective study of the difference of heterotopic ossification (HO) occurrence according to 3 different types of prosthesis. This study was designed to investigate the difference of HO occurrence according to different type of prosthesis. HO is defined as formation of the bone outside the skeletal system. Reported HO occurrence rate in cervical artificial disc replacement (ADR) was unexpectedly high and varied. But the influencing factors of HO in cervical ADR have not been elucidated well. The prosthesis-related factors for making difference of HO occurrence were investigated in this study. A total of 170 patients undergoing cervical arthroplasty with the Bryan cervical disc prosthesis (Medtroic Sofamor Danek, Memphis, TN), Mobi-C disc prosthesis (LDR Medical, Troyes, France), and ProDisc-C (Synthes, Inc., West Chester, PA) were included. Cervical lateral radiographs obtained before and after surgery were used to identify HO. Occurrence rate, occurrence-free period, location, and grade of HOs were investigated according to the different prosthesis. Each prosthesis group included patients as follows: Bryan disc, 81 patients; Mobi-C, 61 patients; and ProDisc-C, 28 patients. Overall HO rate was 40.6% (69 of 170 patients). Each HO occurrence rate by prosthesis was as follows: the Bryan disc group, 21.0%; Mobi-C group, 52.5%; and the ProDisc-C group, 71.4%. In the survival analysis, all patients showed 27.1 +/- 3.7 months as the median survival. The Bryan disc group showed statistically longer survival (48.4 +/- 7.4 months) than the other groups. Occurrence of HO is an inevitable postoperative complication after cervical ADR. The occurrence rate of HO was higher than our expectation. Moreover, definite differences in occurrence rate according to the prosthesis type were identified by this study.

  19. An unbiased study of debris discs around A-type stars with Herschel

    NASA Astrophysics Data System (ADS)

    Thureau, N. D.; Greaves, J. S.; Matthews, B. C.; Kennedy, G.; Phillips, N.; Booth, M.; Duchêne, G.; Horner, J.; Rodriguez, D. R.; Sibthorpe, B.; Wyatt, M. C.

    2014-12-01

    The Herschel DEBRIS (Disc Emission via a Bias-free Reconnaissance in the Infrared/Submillimetre) survey brings us a unique perspective on the study of debris discs around main-sequence A-type stars. Bias-free by design, the survey offers a remarkable data set with which to investigate the cold disc properties. The statistical analysis of the 100 and 160 μm data for 86 main-sequence A stars yields a lower than previously found debris disc rate. Considering better than 3σ excess sources, we find a detection rate ≥24 ± 5 per cent at 100 μm which is similar to the debris disc rate around main-sequence F/G/K-spectral type stars. While the 100 and 160 μm excesses slowly decline with time, debris discs with large excesses are found around some of the oldest A stars in our sample, evidence that the debris phenomenon can survive throughout the length of the main sequence (˜1 Gyr). Debris discs are predominantly detected around the youngest and hottest stars in our sample. Stellar properties such as metallicity are found to have no effect on the debris disc incidence. Debris discs are found around A stars in single systems and multiple systems at similar rates. While tight and wide binaries (<1 and >100 au, respectively) host debris discs with a similar frequency and global properties, no intermediate separation debris systems were detected in our sample.

  20. Effect of angular momentum alignment and strong magnetic fields on the formation of protostellar discs

    NASA Astrophysics Data System (ADS)

    Gray, William J.; McKee, Christopher F.; Klein, Richard I.

    2018-01-01

    Star-forming molecular clouds are observed to be both highly magnetized and turbulent. Consequently, the formation of protostellar discs is largely dependent on the complex interaction between gravity, magnetic fields, and turbulence. Studies of non-turbulent protostellar disc formation with realistic magnetic fields have shown that these fields are efficient in removing angular momentum from the forming discs, preventing their formation. However, once turbulence is included, discs can form in even highly magnetized clouds, although the precise mechanism remains uncertain. Here, we present several high-resolution simulations of turbulent, realistically magnetized, high-mass molecular clouds with both aligned and random turbulence to study the role that turbulence, misalignment, and magnetic fields have on the formation of protostellar discs. We find that when the turbulence is artificially aligned so that the angular momentum is parallel to the initial uniform field, no rotationally supported discs are formed, regardless of the initial turbulent energy. We conclude that turbulence and the associated misalignment between the angular momentum and the magnetic field are crucial in the formation of protostellar discs in the presence of realistic magnetic fields.

  1. A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain.

    PubMed

    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.

  2. Frequency response of pig intervertebral disc cells subjected to dynamic hydrostatic pressure.

    PubMed

    Kasra, Mehran; Merryman, W David; Loveless, Kristen N; Goel, Vijay K; Martin, James D; Buckwalter, Joseph A

    2006-10-01

    The pathogenesis of vibration-induced disorders of intervertebral disc at the cellular level is largely unknown. Dynamic loads with frequencies close to that of the in vivo human spine resonant frequency (4-6 Hz) have a destructive effect, which may induce extracellular disc matrix (ECM) degradation. To investigate this issue, three-dimensional (3D) alginate cultures of normal pig intervertebral disc nucleus and inner annulus cells were tested under dynamic hydrostatic loading. Alginate cultures of each region were divided into six groups; five groups were exposed to cyclic hydrostatic pressures of frequencies 1, 3, 5, 8, and 10 Hz with the same amplitude (1 MPa), and group 6 was the control group (no loading). Cultures of different groups were loaded for 3 days (30 min daily) in a hydraulic chamber. Effects of loading frequency on disc collagen and protein metabolism were investigated by measuring 3H-proline-labeled proteins associated with the cells in the extracellular matrix and release of 3H-proline-labeled molecules into culture medium. The results indicated a poor synthesis rate and more degradation near the 5 Hz frequency. The repeatability of experiments was verified by performing two experiments with the same protocol. Both experiments indicated that a threshold frequency of around 5 Hz disrupted protein metabolism. Copyright (c) 2006 Orthopaedic Research Society.

  3. Interleukin 1-beta upregulates brain-derived neurotrophic factor, neurotrophin 3 and neuropilin 2 gene expression and NGF production in annulus cells.

    PubMed

    Gruber, H E; Hoelscher, G L; Bethea, S; Hanley, E N

    2012-11-01

    The relationship between disc cells, nerves and pain production in the intervertebral disc is poorly understood. Neurotrophins, signaling molecules involved in the survival, differentiation and migration of neurons, and neurite outgrowth, are expressed in non-neuronal tissues including the disc. We hypothesized that three-dimensional exposure of human disc cells to the proinflammatory cytokine IL-1ß in vitro would elevate neurotrophin gene expression levels and production of nerve growth factor (NGF). Cells isolated from Thompson grade III and IV discs were cultured for 14 days under control conditions or with addition of 10(2) pM IL-1ß; mRNA was isolated and conditioned media assayed for NGF content. IL-1ß exposure in three-dimensional culture significantly increased expression of neurotrophin 3, brain-derived neurotrophic factor, and neuropilin 2 compared to controls. IL-1ß-exposed cells showed significantly increased NGF production compared to controls. Findings support our hypothesis, expand previous data concerning expression of neurotrophins, and provide the first documented expression of neurotrophin 3 and neuropilin 2. Our results have direct translational relevance, because they address the primary clinical issue of low back pain and open the possibility of novel analgesic therapies using specific small-molecular antagonists to neurotrophins.

  4. From the international space station to the clinic: how prolonged unloading may disrupt lumbar spine stability.

    PubMed

    Bailey, Jeannie F; Miller, Stephanie L; Khieu, Kristine; O'Neill, Conor W; Healey, Robert M; Coughlin, Dezba G; Sayson, Jojo V; Chang, Douglas G; Hargens, Alan R; Lotz, Jeffrey C

    2018-01-01

    Prolonged microgravity exposure is associated with localized low back pain and an elevated risk of post-flight disc herniation. Although the mechanisms by which microgravity impairs the spine are unclear, they should be foundational for developing in-flight countermeasures for maintaining astronaut spine health. Because human spine anatomy has adapted to upright posture on Earth, observations of how spaceflight affects the spine should also provide new and potentially important information on spine biomechanics that benefit the general population. This study compares quantitative measures of lumbar spine anatomy, health, and biomechanics in astronauts before and after 6 months of microgravity exposure on board the International Space Station (ISS). This is a prospective longitudinal study. Six astronaut crewmember volunteers from the National Aeronautics and Space Administration (NASA) with 6-month missions aboard the ISS comprised our study sample. For multifidus and erector spinae at L3-L4, measures include cross-sectional area (CSA), functional cross-sectional area (FCSA), and FCSA/CSA. Other measures include supine lumbar lordosis (L1-S1), active (standing) and passive (lying) flexion-extension range of motion (FE ROM) for each lumbar disc segment, disc water content from T2-weighted intensity, Pfirrmann grade, vertebral end plate pathology, and subject-reported incidence of chronic low back pain or disc injuries at 1-year follow-up. 3T magnetic resonance imaging and dynamic fluoroscopy of the lumbar spine were collected for each subject at two time points: approximately 30 days before launch (pre-flight) and 1 day following 6 months spaceflight on the ISS (post-flight). Outcome measures were compared between time points using paired t tests and regression analyses. Supine lumbar lordosis decreased (flattened) by an average of 11% (p=.019). Active FE ROM decreased for the middle three lumbar discs (L2-L3: -22.1%, p=.049; L3-L4: -17.3%, p=.016; L4-L5: -30.3%, p=.004). By contrast, no significant passive FE ROM changes in these discs were observed (p>.05). Disc water content did not differ systematically from pre- to post-flight. Multifidus and erector spinae changed variably between subjects, with five of six subjects experiencing an average decrease 20% for FCSA and 8%-9% for CSA in both muscles. For all subjects, changes in multifidus FCSA strongly correlated with changes in lordosis (r 2 =0.86, p=.008) and active FE ROM at L4-L5 (r 2 =0.94, p=.007). Additionally, changes in multifidus FCSA/CSA correlated with changes in lordosis (r 2 =0.69, p=.03). Although multifidus-associated changes in lordosis and ROM were present among all subjects, only those with severe, pre-flight end plate irregularities (two of six subjects) had post-flight lumbar symptoms (including chronic low back pain or disc herniation). We observed that multifidus atrophy, rather than intervertebral disc swelling, associated strongly with lumbar flattening and increased stiffness. Because these changes have been previously linked with detrimental spine biomechanics and pain in terrestrial populations, when combined with evidence of pre-flight vertebral end plate insufficiency, they may elevate injury risk for astronauts upon return to gravity loading. Our results also have implications for deconditioned spines on Earth. We anticipate that our results will inform new astronaut countermeasures that target the multifidus muscles, and research on the role of muscular stability in relation to chronic low back pain and disc injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The Boston Keratoprosthesis: Comparing Corneal Epithelial Cell Compatibility with Titanium and PMMA

    PubMed Central

    Ament, Jared D.; Spurr-Michaud, Sandra J.; Dohlman, Claes H.; Gipson, Ilene K.

    2014-01-01

    Purpose To determine in vitro whether titanium is superior in corneal cell compatibility to standard polymethyl-methacrylate (PMMA) for the Boston Keratoprosthesis (KPro). Methods Human corneal-limbal epithelial (HCLE) cells were cultured 24, 48, 72, 96, 120, 144, or 168 hours in culture plates alone (controls) or with PMMA or titanium discs. Experiments were performed in triplicate and repeated (final n = 6). To determine if a soluble, toxic factor is emitted from materials, concurrent experiments at 48 and 144 hours were performed with discs placed in Transwell Supports, with HCLE cells plated beneath. As an additional test for soluble factors, cells were incubated 24 hours with disc-conditioned media, and number of viable cells per well was quantified at each timepoint by proliferation assay. To determine if delayed cell proliferation was attributable to cell death, HCLE cell death was measured under all conditions and quantified at each timepoint by cytotoxicity assay. The effects of material on HCLE cell proliferation over time was determined by repeated measures ANOVA. P < 0.05 was statistically significant. Results HCLE cell proliferation was greater in wells with titanium discs compared to PMMA. Differences between the test discs and control non-disc cocultures were statistically significant over time for both cell proliferation (P = 0.001) and death (P = 0.0025). No significant difference was found using Transwells (P = 0.9836) or disc-conditioned media (P = 0.36). Conclusion This in vitro HCLE cell model demonstrates significantly increased cell proliferation and decreased cell death with cell/titanium contact compared to cell/PMMA contact. Moreover, differences are unlikely attributable to a soluble factor. Prospective in vivo analysis of the two KPro biomaterials is indicated. PMID:19574903

  6. A miniature fiber optic pressure sensor for intradiscal pressure measurements of rodents

    NASA Astrophysics Data System (ADS)

    Nesson, Silas; Yu, Miao; Hsieh, Adam H.

    2007-04-01

    Lower back pain continues to be a leading cause of disability in people of all ages, and has been associated with degenerative disc disease. It is well accepted that mechanical stress, among other factors, can play a role in the development of disc degeneration. Pressures generated in the intervertebral disc have been measured both in vivo and in vitro for humans and animals. However, thus far it has been difficult to measure pressure experimentally in rodent discs due to their small size. With the prevalent use of rodent tail disc models in mechanobiology, it is important to characterize the intradiscal pressures generated with externally applied stresses. In this paper, a miniature fiber optic Fabry-Perot interferometric pressure sensor with an outer diameter of 360 μm was developed to measure intradiscal pressures in rat caudal discs. A low coherence interferometer based optical system was used, which includes a broadband light source, a high-speed spectrometer, and a Fabry-Perot sensor. The sensor employs a capillary tube, a flexible, polymer diaphragm coated with titanium as a partial mirror, and a fiber tip as another mirror. The pressure induced deformation of the diaphragm results in a cavity length change of the Fabry-Perot interferometer which can be calculated from the wavelength shift of interference fringes. The sensor exhibited good linearity with small applied pressures. Our validation experiments show that owing to the small size, inserting the sensor does not disrupt the annulus fibrosus and will not alter intradiscal pressures generated. Measurements also demonstrate the feasibility of using this sensor to quantify external load intradiscal pressure relationships in small animal discs.

  7. Comparison of biomechanical function at ideal and varied surgical placement for two lumbar artificial disc implant designs: mobile-core versus fixed-core.

    PubMed

    Moumene, Missoum; Geisler, Fred H

    2007-08-01

    Finite element model. To estimate the effect of lumbar mobile-core and fixed-core artificial disc design and placement on the loading of the facet joints, and stresses on the polyethylene core. Although both mobile-core and fixed-core lumbar artificial disc designs have been used clinically, the effect of their design and the effect of placement within the disc space on the structural element loading, and in particular the facets and the implant itself, have not been investigated. A 3D nonlinear finite element model of an intact ligamentous L4-L5 motion segment was developed and validated in all 6 df based on previous experiments conducted on human cadavers. Facet loading of a mobile-core TDR and a fixed-core TDR were estimated with 4 different prosthesis placements for 3 different ranges of motion. Placing the mobile-core TDR anywhere within the disc space reduced facet loading by more than 50%, while the fixed-core TDR increased facet loading by more than 10% when compared with the intact disc in axial rotation. For central (ideal) placement, the mobile- and fixed-core implants were subjected to compressive stresses on the order of 3 MPa and 24 MPa, respectively. The mobile-core stresses were not affected by implant placement, while the fixed-core stresses increased by up to 40%. A mobile-core artificial disc design is less sensitive to placement, and unloads the facet joints, compared with a fixed-core design. The decreased core stress may result in a reduced potential for wear in a mobile-core prosthesis compared with a fixed-core prosthesis, which may increase the functional longevity of the device.

  8. The relationship between central corneal thickness and optic disc size in patients with primary open-angle glaucoma in a hospital-based population.

    PubMed

    Terai, Naim; Spoerl, Eberhard; Pillunat, Lutz E; Kuhlisch, Eberhard; Schmidt, Eckart; Boehm, Andreas G

    2011-09-01

    To investigate the relationship between central corneal thickness (CCT) and optic disc size in patients with primary open-angle glaucoma (POAG) in a hospital-based population. Data for the right eyes of 1435 White patients with POAG were included in a retrospective hospital-based study. All eyes underwent optic nerve head imaging using Heidelberg Retina Tomograph II (HRT II; Heidelberg Engineering, Heidelberg, Germany) and CCT measurement by ultrasound corneal pachymetry. Eyes with prior intraocular or corneal surgery were excluded. Low-quality HRT II images were also excluded. The impact of age, gender, CCT, intraocular pressure, cylindrical and spherical refractive error as independent factors on optic disc size was investigated in a multiple linear regression analysis. The data for 1104 right eyes qualified for participation in the study. The median age of these patients was 65 years. The median CCT was 547 μm (25th-75th percentile 522-575 μm). The median optic disc size was 2.21 mm(2) (25th-75th percentile 1.89-2.60 mm(2)). Multiple linear regression analysis revealed that age (p = 0.001), CCT (p = 0.001) and spherical equivalent (p = 0.049) were correlated to disc size according to the following formula: disc area = -0.004 × age - 0.001 × CCT - 0.014 × spherical equivalent +3.290. R(2) of the whole model was 0.021. Univariate regression analysis between age and disc area provided R(2) = 0.008 with p = 0.002. Univariate regression analysis between disc area and CCT provided R(2) = 0.005 with p = 0.02. In this retrospective hospital-based study we could not detect a clinically relevant correlation between optic disc size and CCT. The correlation between CCT and disc size and between age and disc size were statistically significant, but the R(2) values were very low. The results of the study are biased because of its hospital-based design, so the results of the study need to be confirmed in a large population-based study. © 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.

  9. PATHOGENESIS OF OPTIC DISC EDEMA IN RAISED INTRACRANIAL PRESSURE

    PubMed Central

    Hayreh, Sohan Singh

    2015-01-01

    Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with raised CSFP in patients, by evaluating optic disc and fundus changes by stereoscopic fundus photography and fluorescein fundus angiography. Based on the combined information from all the studies discussed above, it is clear that the pathogenesis of optic disc edema in raised intracranial pressure is a mechanical phenomenon. It is primarily due to a rise of CSFP in the optic nerve sheath, which produces axoplasmic flow stasis in the optic nerve fibers in the surface nerve fiber layer and prelaminar region of the optic nerve head. Axoplasmic flow stasis then results in swelling of the nerve fibers, and consequently of the optic disc. Swelling of the nerve fibers and of the optic disc secondarily compresses the fine, low-pressure venules in that region, resulting in venous stasis and fluid leakage; that leads to the accumulation of extracellular fluid. Contrary to the previous theories, the various vascular changes seen in optic disc edema are secondary and not primary. Thus, optic disc edema in raised CSFP is due to a combination of swollen nerve fibers and the accumulation of extracellular fluid. My studies also provided information about the pathogeneses of visual disturbances in raised intracranial pressure. PMID:26453995

  10. Pathogenesis of optic disc edema in raised intracranial pressure.

    PubMed

    Hayreh, Sohan Singh

    2016-01-01

    Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with raised CSFP in patients, by evaluating optic disc and fundus changes by stereoscopic fundus photography and fluorescein fundus angiography. Based on the combined information from all the studies discussed above, it is clear that the pathogenesis of optic disc edema in raised intracranial pressure is a mechanical phenomenon. It is primarily due to a rise of CSFP in the optic nerve sheath, which produces axoplasmic flow stasis in the optic nerve fibers in the surface nerve fiber layer and prelaminar region of the optic nerve head. Axoplasmic flow stasis then results in swelling of the nerve fibers, and consequently of the optic disc. Swelling of the nerve fibers and of the optic disc secondarily compresses the fine, low-pressure venules in that region, resulting in venous stasis and fluid leakage; that leads to the accumulation of extracellular fluid. Contrary to the previous theories, the various vascular changes seen in optic disc edema are secondary and not primary. Thus, optic disc edema in raised CSFP is due to a combination of swollen nerve fibers and the accumulation of extracellular fluid. My studies also provided information about the pathogeneses of visual disturbances in raised intracranial pressure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The NEtherlands Cervical Kinematics (NECK) trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study.

    PubMed

    Arts, Mark P; Brand, Ronald; van den Akker, Elske; Koes, Bart W; Peul, Wilco C

    2010-06-16

    Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prosthesis is necessary and cost-effective will be determined by this trial. Netherlands Trial Register NTR1289.

  12. The NEtherlands Cervical Kinematics (NECK) Trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study

    PubMed Central

    2010-01-01

    Background Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Methods/Design Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Discussion Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prothesis is necessary and cost-effective will be determined by this trial. Trial Registration Netherlands Trial Register NTR1289 PMID:20553591

  13. Total disc replacement using a tissue-engineered intervertebral disc in vivo: new animal model and initial results

    PubMed Central

    Gebhard, Harry; Bowles, Robby; Dyke, Jonathan; Saleh, Tatianna; Doty, Stephen; Bonassar, Lawrence; Härtl, Roger

    2010-01-01

    Study type: Basic science Introduction: Chronic back pain due to degenerative disc disease (DDD) is among the most important medical conditions causing morbidity and significant health care costs. Surgical treatment options include disc replacement or fusion surgery, but are associated with significant short- and long-term risks.1 Biological tissue-engineering of human intervertebral discs (IVD) could offer an important alternative.2 Recent in vitro data from our group have shown successful engineering and growth of ovine intervertebral disc composites with circumferentially aligned collagen fibrils in the annulus fibrosus (AF) (Figure 1).3 Figure 1 Tissue-engineered composite disc a Experimental steps to generate composite tissue-engineered IVDs3 b Example of different AF formulations on collagen alignment in the AF. Second harmonic generation and two-photon excited fluorescence images of seeded collagen gels (for AF) of 1 and 2.5 mg/ml over time. At seeding, cells and collagen were homogenously distributed in the gels. Over time, AF cells elongated and collagen aligned parallel to cells. Less contraction and less alignment is noted after 3 days in the 2.5 mg/mL gel. c Imaging-based creation of a virtual disc model that will serve as template for the engineered disc. Total disc dimensions (AF and NP) were retrieved from micro-computer tomography (CT) (left images), and nucleus pulposus (NP) dimensions alone were retrieved from T2-weighted MRI images (right images). Merging of MRI and micro-CT models revealed a composite disc model (middle image)—Software: Microview, GE Healthcare Inc., Princeton, NJ; and slicOmatic v4.3, TomoVision, Montreal, Canada. d Flow chart describing the process for generating multi-lamellar tissue engineered IVDs. IVDs are produced by allowing cell-seeded collagen layers to contract around a cell-seeded alginate core (NP) over time Objective: The next step is to investigate if biological disc implants survive, integrate, and restore function to the spine in vivo. A model will be developed that allows efficient in vivo testing of tissue-engineered discs of various compositions and characteristics. Methods: Athymic rats were anesthetized and a dorsal approach was chosen to perform a microsurgical discectomy in the rat caudal spine (Fig. 2,Fig. 3). Control group I (n = 6) underwent discectomy only, Control group II (n = 6) underwent discectomy, followed by reimplantation of the autologous disc. Two treatment groups (group III, n = 6, 1 month survival; group IV, n = 6, 6 months survival) received a tissue-engineered composite disc implant. The rodents were followed clinically for signs of infection, pain level and wound healing. X-rays and magnetic resonance imaging (MRI) were assessed postoperatively and up to 6 months after surgery (Fig. 6,Fig. 7). A 7 Tesla MRI (Bruker) was implemented for assessment of the operated level as well as the adjacent disc (hydration). T2-weighted sequences were interpreted by a semiquantitative score (0 = no signal, 1 = weak signal, 2 = strong signal and anatomical features of a normal disc). Histology was performed with staining for proteoglycans (Alcian blue) and collagen (Picrosirius red) (Fig. 4,Fig. 5). Figure 2 Disc replacement surgery a Operative situs with native disc that has been disassociated from both adjacent vertebrae b Native disc (left) and tissue-engineered implant (right) c Implant in situ before wound closureAF: Annulus fi brosus, nP: nucleus pulposus, eP: endplate, M: Muscle, T: Tendon, s: skin, art: artery, GP: Growth plate, B: Bone Figure 3 Disc replacement surgery. Anatomy of the rat caudal disc space a Pircrosirius red stained axial cut of native disc space b Saffranin-O stained sagittal cut of native disc space Figure 4 Histologies of three separate motion segments from three different rats. Animal one = native IVD, Animal two = status after discectomy, Animal three = tissue-engineered implant (1 month) a–c H&E (overall tissue staining for light micrsocopy) d–f Alcian blue (proteoglycans) g–i Picrosirius red (collagen I and II) Figure 5 Histology from one motion segment four months after implantation of a bio-engineered disc construct a Picrosirius red staining (collagen) b Polarized light microscopy showing collagen staining and collagen organization in AF region c Increased Safranin-O staining (proteoglycans) in NP region of the disc implant d Higher magnification of figure 5c: Integration between implanted tissue-engineered total disc replacement and vertebral body bone Figure 6 MRI a Disc space height measurements in flash/T1 sequence (top: implant (714.0 micrometer), bottom: native disc (823.5 micrometer) b T2 sequence, red circle surrounding the implant NP Figure 7 7 Tesla MRI imaging of rat tail IVDs showing axial images (preliminary pilot data) a Diffusion tensor imaging (DTI) on two explanted rat tail discs in Formalin b Higher magnification of a, showing directional alignment of collagen fibers (red and green) when compared to the color ball on top which maps fibers' directional alignment (eg, fibers directing from left to right: red, from top to bottom: blue) c Native IVD in vivo (successful imaging of top and bottom of the IVD (red) d Gradient echo sequence (GE) showing differentiation between NP (light grey) and AF (dark margin) e GE of reimplanted tail IVD at the explantation level f T1Rho sequence demonstrating the NP (grey) within the AF (dark margin), containing the yellow marked region of interest for value acquisition (preliminary data are consistent with values reported in the literature). g T2 image of native IVD in vivo for monitoring of hydration (white: NP) Results: The model allowed reproducible and complete discectomies as well as disc implantation in the rat tail spine without any surgical or postoperative complications. Discectomy resulted in immediate collapse of the disc space. Preliminary results indicate that disc space height was maintained after disc implantation in groups II, III and IV over time. MRI revealed high resolution images of normal intervertebral discs in vivo. Eight out of twelve animals (groups III and IV) showed a positive signal in T2-weighted images after 1 month (grade 0 = 4, grade 1 = 4, grade 2 = 4). Positive staining was seen for collagen as well as proteoglycans at the site of disc implantation after 1 month in each of the six animals with engineered implants (group III). Analysis of group IV showed positive T2 signal in five out of six animals and disc-height preservation in all animals after 6 months. Conclusions: This study demonstrates for the first time that tissue-engineered composite IVDs with circumferentially aligned collagen fibrils survive and integrate with surrounding vertebral bodies when placed in the rat spine for up to 6 months. Tissue-engineered composite IVDs restored function to the rat spine as indicated by maintenance of disc height and vertebral alignment. A significant finding was that maintenance of the composite structure in group III was observed, with increased proteoglycan staining in the nucleus pulposus region (Figure 4d–f). Proteoglycan and collagen matrix as well as disc height preservation and positive T2 signals in MRI are promising parameters and indicate functionality of the implants. PMID:23637671

  14. Age-related accumulation of pentosidine in aggrecan and collagen from normal and degenerate human intervertebral discs

    PubMed Central

    Sivan, Sarit Sara; Tsitron, Eve; Wachtel, Ellen; Roughley, Peter; Sakkee, Nico; van der Ham, Frits; Degroot, Jeroen; Maroudas, Alice

    2006-01-01

    During aging and degeneration, many changes occur in the structure and composition of human cartilaginous tissues, which include the accumulation of the AGE (advanced glycation end-product), pentosidine, in long-lived proteins. In the present study, we investigated the accumulation of pentosidine in constituents of the human IVD (intervertebral disc), i.e. collagen, aggrecan-derived PG (proteoglycan) (A1) and its fractions (A1D1–A1D6) in health and pathology. We found that, after maturity, pentosidine accumulates with age. Over the age range studied, a linear 6-fold increase was observed in pentosidine accumulation for A1 and collagen with respective rates of 0.12 and 0.66 nmol·(g of protein)−1·year−1. Using previously reported protein turnover rate constants (kT) obtained from measurements of the D-isomer of aspartic residue in collagen and aggrecan of human IVD, we could calculate the pentosidine formation rate constants (kF) for these constituents [Sivan, Tsitron, Wachtel, Roughley, Sakkee, van der Ham, DeGroot, Roberts and Maroudas (2006) J. Biol. Chem. 281, 13009–13014; Tsitron (2006) MSc Thesis, Technion-Israel Institute of Technology, Haifa, Israel]. In spite of the comparable formation rate constants obtained for A1D1 and collagen [1.81±0.25 compared with 3.71±0.26 μmol of pentosidine·(mol of lysine)−1·year−1 respectively], the higher pentosidine accumulation in collagen is consistent with its slower turnover (0.005 year−1 compared with 0.134 year−1 for A1D1). Pentosidine accumulation increased with decreasing buoyant density and decreasing turnover of the proteins from the most glycosaminoglycan-rich PG components (A1D1) to the least (A1D6), with respective kF values of 1.81±0.25 and 3.18±0.37 μmol of pentosidine·(mol of lysine)−1·year−1. We concluded that protein turnover is an important determinant of pentosidine accumulation in aggrecan and collagen of human IVD, as was found for articular cartilage. Correlation of pentosidine accumulation with protein half-life in both normal and degenerate discs further supports this finding. PMID:16787390

  15. Association between menopause and lumbar disc degeneration: an MRI study of 1,566 women and 1,382 men.

    PubMed

    Lou, Chao; Chen, Hongliang; Mei, Liangwei; Yu, Weiyang; Zhu, Kejun; Liu, Feijun; Chen, Zhenzhong; Xiang, Guangheng; Chen, Minjiang; Weng, Qiaoyou; He, Dengwei

    2017-10-01

    The aim of this study was to revisit and further investigate the association between menopause and disc degeneration in the lumbar spine using a magnetic resonance imaging-based eight-level grading system. This study cohort comprised of 1,566 women and 1,382 age-matched men who were admitted for low back pain from June 2013 to October 2016. Data on age, weight, height, body mass index, age at natural menopause, and years since menopause (YSM) were obtained. Lumbar disc degeneration was assessed using a magnetic resonance imaging-based eight-level grading system. After adjustment for the confounding factors of age, height, and weight, young age-matched men were more susceptible to disc degeneration than premenopausal women (P < 0.05). However, after menopause, postmenopausal women had a significant tendency to develop more severe disc degeneration than their age-matched men (P < 0.05), and also compared with premenopausal and perimenopausal women (P < 0.01). Postmenopausal women were divided into nine subgroups by every 5 YSM. When YSM was less than 15 years, a positive trend was observed between YSM and severity of disc degeneration, respectively, at L1/L2 (r = 0.241), L2/L3 (r = 0.193), L3/L4 (r = 0.191), L4/L5 (r = 0.165), L5/S1 (r = 0.153), and all lumbar discs (r = 0.237) (P < 0.05 or 0.01). The analysis of covariance indicated a significant difference in each disc level (P < 0.05 or 0.01) between every two groups. When YSM was more than 15 years, the significant difference, however, disappeared in each disc level (P > 0.05). Menopause is associated with lumbar disc degeneration. The association occurred in the first 15 YSM, suggesting estrogen deficiency might be a risk factor of disc degeneration of the lumbar spine. Further studies need to be carried out for deciding whether age or menopause plays a more important role in the progression of disc degeneration in the lumbar spine.

  16. Regulation of gene expression in intervertebral disc cells by low and high hydrostatic pressure.

    PubMed

    Neidlinger-Wilke, Cornelia; Würtz, Karin; Urban, Jill P G; Börm, Wolfgang; Arand, Markus; Ignatius, Anita; Wilke, Hans-Joachim; Claes, Lutz E

    2006-08-01

    Intervertebral disc structures are exposed to wide ranges of intradiscal hydrostatic pressure during different loading exercises and are at their minimum during lying or relaxed sitting and at maximum during lifting weights with a round back. We hypothesize that these different loading magnitudes influence the intervertebral disc (IVD) by alteration of disc matrix turnover depending on their magnitudes. Therefore the aim of this study was to assess changes in gene expression of human nucleus cells after the application of low hydrostatic pressure (0.25 MPa) and high hydrostatic pressure (2.5 MPa). IVD cells isolated from the nucleus of human (n = 18) and bovine (n = 24 from four animals) disc biopsies were seeded into three-dimensional collagen type-I matrices and exposed to the different loading magnitudes by specially developed pressure chambers. The lower pressure range (0.25 MPa, 30 min, 0.1 Hz) was applied with a recently published device by using an external compression cylinder. For the application of higher loads (2.5 MPa, 30 min, 0.1 Hz) the cell-loaded collagen gels were sealed into sterile bags with culture medium and stimulated in a newly developed water-filled compression cylinder by using a loading frame. These methods allowed the comparison of loading regimes in a wide physiological range under an equal three-dimensional culture conditions. Cells were harvested 24 h after the end of stimulation and changes in the expression of genes known to influence IVD matrix turnover (collagen-I, collagen-II, aggrecan, MMP1, MMP2, MMP3, MMP13) were analyzed by real-time RT-PCR. A Wilcoxon signed-rank test(1) and a Wilcoxon 2-sample test(2) were performed to detect differences between the stimulated and control samples(1) and differences between low and high hydrostatic pressure(2). Multiple testing was considered by adjusting the p value appropriately. Both regimes of hydrostatic pressure influenced gene expression in nucleus cells with opposite tendencies for the matrix forming proteins aggrecan and collagen type-I in response to the two different pressure magnitudes: Low hydrostatic-pressure (0.25 MPa) tended to increase collagen-I and aggrecan expression of human nucleus cells (P < 0.05) but only to a small degree. High hydrostatic pressure (2.5 MPa) tended to decrease gene expression of all anabolic proteins with significant effects on aggrecan expression of nucleus cells (P = 0.004). Low hydrostatic pressure had no influence on the expression of matrix metalloproteinases (MMP1, MMP2, MMP3 and MMP13). In contrast, high hydrostatic pressure tended to increase the expression of MMP1, MMP3 and MMP13 of human nucleus cells with high individual-individual variations. The decreased expression of aggrecan (P = 0.008) and collagen type II (P = 0.023) and the increased MMP3 expression (P = 0.008) in response to high hydrostatic pressure could be confirmed in additional experiments with bovine nucleus cells. These results suggest that hydrostatic pressure as one of the physiological stimuli of the IVD may influence matrix turnover in a magnitude dependent way. Low hydrostatic pressure (0.25 MPa) has quite small influences with a tendency to anabolic effects, whereas high hydrostatic pressure (2.5 MPa) tends to decrease the matrix protein expression with a tendency to increase some matrix-turnover enzymes. Therefore, hydrostatic pressure may regulate disc matrix turnover in a dose-dependent way.

  17. How do accretion discs break?

    NASA Astrophysics Data System (ADS)

    Dogan, Suzan

    2016-07-01

    Accretion discs are common in binary systems, and they are often found to be misaligned with respect to the binary orbit. The gravitational torque from a companion induces nodal precession in misaligned disc orbits. In this study, we first calculate whether this precession is strong enough to overcome the internal disc torques communicating angular momentum. We compare the disc precession torque with the disc viscous torque to determine whether the disc should warp or break. For typical parameters precession wins: the disc breaks into distinct planes that precess effectively independently. To check our analytical findings, we perform 3D hydrodynamical numerical simulations using the PHANTOM smoothed particle hydrodynamics code, and confirm that disc breaking is widespread and enhances accretion on to the central object. For some inclinations, the disc goes through strong Kozai cycles. Disc breaking promotes markedly enhanced and variable accretion and potentially produces high-energy particles or radiation through shocks. This would have significant implications for all binary systems: e.g. accretion outbursts in X-ray binaries and fuelling supermassive black hole (SMBH) binaries. The behaviour we have discussed in this work is relevant to a variety of astrophysical systems, for example X-ray binaries, where the disc plane may be tilted by radiation warping, SMBH binaries, where accretion of misaligned gas can create effectively random inclinations and protostellar binaries, where a disc may be misaligned by a variety of effects such as binary capture/exchange, accretion after binary formation.

  18. Total disc replacement for chronic back pain in the presence of disc degeneration.

    PubMed

    Jacobs, Wilco; Van der Gaag, Niels A; Tuschel, Alexander; de Kleuver, Marinus; Peul, Wilco; Verbout, A J; Oner, F Cumhur

    2012-09-12

    In the search for better surgical treatment of chronic low-back pain (LBP) in the presence of disc degeneration, total disc replacement has received increasing attention in recent years. A possible advantage of total disc replacement compared with fusion is maintained mobility at the operated level, which has been suggested to reduce the chance of adjacent segment degeneration. The aim of this systematic review was to assess the effect of total disc replacement for chronic low-back pain in the presence of lumbar disc degeneration compared with other treatment options in terms of patient-centred improvement, motion preservation and adjacent segment degeneration. A comprehensive search in Cochrane Back Review Group (CBRG) trials register, CENTRAL, MEDLINE, EMBASE, BIOSIS, ISI, and the FDA register was conducted. We also checked the reference lists and performed citation tracking of included studies. We included randomised controlled trials (RCTs) comparing total disc replacement with any other intervention for degenerative disc disease. We assessed risk of bias per study using the criteria of the CBRG. Quality of evidence was graded according to the GRADE approach. Two review authors independently selected studies and assessed risk of bias of the studies. Results and upper bounds of confidence intervals were compared against predefined clinically relevant differences. We included 40 publications, describing seven unique RCT's. The follow-up of the studies was 24 months, with only one extended to five years. Five studies had a low risk of bias, although there is a risk of bias in the included studies due to sponsoring and absence of any kind of blinding. One study compared disc replacement against rehabilitation and found a statistically significant advantage in favour of surgery, which, however, did not reach the predefined threshold for clinical relevance. Six studies compared disc replacement against fusion and found that the mean improvement in VAS back pain was 5.2 mm (of 100 mm) higher (two studies, 676 patients; 95% confidence interval (CI) 0.18 to 10.26) with a low quality of evidence while from the same studies leg pain showed no difference. The improvement of Oswestry score at 24 months in the disc replacement group was 4.27 points more than in the fusion group (five studies; 1207 patients; 95% CI 1.85 to 6.68) with a low quality of evidence. Both upper bounds of the confidence intervals for VAS back pain and Oswestry score were below the predefined clinically relevant difference. Choice of control group (circumferential or anterior fusion) did not appear to result in different outcomes. Although statistically significant, the differences between disc replacement and conventional fusion surgery for degenerative disc disease were not beyond the generally accepted clinical important differences with respect to short-term pain relief, disability and Quality of Life. Moreover, these analyses only represent a highly selected population. The primary goal of prevention of adjacent level disease and facet joint degeneration by using total disc replacement, as noted by the manufacturers and distributors, was not properly assessed and not a research question at all. Unfortunately, evidence from observational studies could not be used because of the high risk of bias, while these could have improved external validity assessment of complications in less selected patient groups. Non-randomised studies should however be very clear about patient selection and should incorporate independent, blinded outcome assessment, which was not the case in the excluded studies. Therefore, because we believe that harm and complications may occur after years, we believe that the spine surgery community should be prudent about adopting this technology on a large scale, despite the fact that total disc replacement seems to be effective in treating low-back pain in selected patients, and in the short term is at least equivalent to fusion surgery.

  19. The activL® Artificial Disc: a next-generation motion-preserving implant for chronic lumbar discogenic pain

    PubMed Central

    Yue, James J; Garcia, Rolando; Miller, Larry E

    2016-01-01

    Degeneration of the lumbar intervertebral discs is a leading cause of chronic low back pain in adults. Treatment options for patients with chronic lumbar discogenic pain unresponsive to conservative management include total disc replacement (TDR) or lumbar fusion. Until recently, only two lumbar TDRs had been approved by the US Food and Drug Administration − the Charité Artificial Disc in 2004 and the ProDisc-L Total Disc Replacement in 2006. In June 2015, a next-generation lumbar TDR received Food and Drug Administration approval − the activL® Artificial Disc (Aesculap Implant Systems). Compared to previous-generation lumbar TDRs, the activL® Artificial Disc incorporates specific design enhancements that result in a more precise anatomical match and allow a range of motion that better mimics the healthy spine. The results of mechanical and clinical studies demonstrate that the activL® Artificial Disc results in improved mechanical and clinical outcomes versus earlier-generation artificial discs and compares favorably to lumbar fusion. The purpose of this report is to describe the activL® Artificial Disc including implant characteristics, intended use, surgical technique, postoperative care, mechanical testing, and clinical experience to date. PMID:27274317

  20. Circumstellar disc lifetimes in numerous galactic young stellar clusters

    NASA Astrophysics Data System (ADS)

    Richert, A. J. W.; Getman, K. V.; Feigelson, E. D.; Kuhn, M. A.; Broos, P. S.; Povich, M. S.; Bate, M. R.; Garmire, G. P.

    2018-07-01

    Photometric detections of dust circumstellar discs around pre-main sequence (PMS) stars, coupled with estimates of stellar ages, provide constraints on the time available for planet formation. Most previous studies on disc longevity, starting with Haisch, Lada & Lada, use star samples from PMS clusters but do not consider data sets with homogeneous photometric sensitivities and/or ages placed on a uniform time-scale. Here we conduct the largest study to date of the longevity of inner dust discs using X-ray and 1-8 µm infrared photometry from the MYStIX and SFiNCs projects for 69 young clusters in 32 nearby star-forming regions with ages t ≤ 5 Myr. Cluster ages are derived by combining the empirical AgeJX method with PMS evolutionary models, which treat dynamo-generated magnetic fields in different ways. Leveraging X-ray data to identify disc-free objects, we impose similar stellar mass sensitivity limits for disc-bearing and disc-free young stellar objects while extending the analysis to stellar masses as low as M ˜ 0.1 M⊙. We find that the disc longevity estimates are strongly affected by the choice of PMS evolutionary model. Assuming a disc fraction of 100 per cent at zero age, the inferred disc half-life changes significantly, from t1/2 ˜ 1.3-2 Myr to t1/2 ˜ 3.5 Myr when switching from non-magnetic to magnetic PMS models. In addition, we find no statistically significant evidence that disc fraction varies with stellar mass within the first few Myr of life for stars with masses <2 M⊙, but our samples may not be complete for more massive stars. The effects of initial disc fraction and star-forming environment are also explored.

  1. Global variation of the dust-to-gas ratio in evolving protoplanetary discs

    NASA Astrophysics Data System (ADS)

    Hughes, Anna L. H.; Armitage, Philip J.

    2012-06-01

    Recent theories suggest planetesimal formation via streaming and/or gravitational instabilities may be triggered by localized enhancements in the dust-to-gas ratio, and one hypothesis is that sufficient enhancements may be produced in the pile-up of small solid particles inspiralling under aerodynamic drag from the large mass reservoir in the outer disc. Studies of particle pile-up in static gas discs have provided partial support for this hypothesis. Here, we study the radial and temporal evolution of the dust-to-gas ratio in turbulent discs that evolve under the action of viscosity and photoevaporation. We find that particle pile-ups do not generically occur within evolving discs, particularly if the introduction of large grains is restricted to the inner, dense regions of a disc. Instead, radial drift results in depletion of solids from the outer disc, while the inner disc maintains a dust-to-gas ratio that is within a factor of ˜2 of the initial value. We attribute this result to the short time-scales for turbulent diffusion and radial advection (with the mean gas flow) in the inner disc. We show that the qualitative evolution of the dust-to-gas ratio depends only weakly upon the parameters of the disc model (the disc mass, size, viscosity and value of the Schmidt number), and discuss the implications for planetesimal formation via collective instabilities. Our results suggest that in discs where there is a significant level of midplane turbulence and accretion, planetesimal formation would need to be possible in the absence of large-scale enhancements. Instead, trapping and concentration of particles within local turbulent structures may be required as a first stage of planetesimal formation.

  2. In vivo dynamic stiffness of the porcine lumbar spine exposed to cyclic loading: influence of load and degeneration.

    PubMed

    Kaigle, A; Ekström, L; Holm, S; Rostedt, M; Hansson, T

    1998-02-01

    The dynamic axial stiffness of the L2-3 motion segment subjected to vibratory loading under intact and injured states of the intervertebral disc was studied using an in vivo porcine model. Three groups of animals with the following states of the intervertebral discs were studied: intact disc, acutely injured disc, and degenerated disc. A miniaturized servo-hydraulic exciter was used to sinusoidally vibrate the motion segment from 0.05 to 25 Hz under a compressive load with a peak value of either 100 or 200 N. The dynamic axial stiffness of the intervertebral disc was calculated at 1-Hz intervals over the frequency range. The results showed that the dynamic axial stiffness was frequency dependent. A positive relationship was found between an increase in mean dynamic stiffness and load magnitude. An increase in mean stiffness with successive exposures at the same load magnitude was observed, despite the allowance of a recovery period between loading. The greatest difference was noted between the first and second load sets. No significant change in stiffness was found due to an acute disc injury, whereas a significant increase in mean stiffness was found for the degenerated disc group as compared with the intact group. The form of the frequency response curve, however, remained relatively unaltered regardless of the degenerated state of the disc. With heavier loads, repeated loading, and/or disc degeneration, the stiffness of the intervertebral disc increases. An increase in stiffness can mean a reduction in the amount of allowable motion within the motion segment or a potentially harmful increase in force to obtain the desired motion. This may locally result in greater stresses due to an altered ability of the disc to distribute loads.

  3. Star-disc interaction in galactic nuclei: formation of a central stellar disc

    NASA Astrophysics Data System (ADS)

    Panamarev, Taras; Shukirgaliyev, Bekdaulet; Meiron, Yohai; Berczik, Peter; Just, Andreas; Spurzem, Rainer; Omarov, Chingis; Vilkoviskij, Emmanuil

    2018-05-01

    We perform high-resolution direct N-body simulations to study the effect of an accretion disc on stellar dynamics in an active galactic nucleus (AGN). We show that the interaction of the nuclear stellar cluster (NSC) with the gaseous accretion disc (AD) leads to formation of a stellar disc in the central part of the NSC. The accretion of stars from the stellar disc on to the super-massive black hole is balanced by the capture of stars from the NSC into the stellar disc, yielding a stationary density profile. We derive the migration time through the AD to be 3 per cent of the half-mass relaxation time of the NSC. The mass and size of the stellar disc are 0.7 per cent of the mass and 5 per cent of the influence radius of the super-massive black hole. An AD lifetime shorter than the migration time would result in a less massive nuclear stellar disc. The detection of such a stellar disc could point to past activity of the hosting galactic nucleus.

  4. Does T2 mapping of the posterior annulus fibrosus indicate the presence of lumbar intervertebral disc herniation? A 3.0 Tesla magnetic resonance study.

    PubMed

    Messner, Alina; Stelzeneder, David; Trattnig, Stefan; Welsch, Götz H; Schinhan, Martina; Apprich, Sebastian; Brix, Martin; Windhager, Reinhard; Trattnig, Siegfried

    2017-03-01

    Indicating lumbar disc herniation via magnetic resonance imaging (MRI) T2 mapping in the posterior annulus fibrosus (AF). Sagittal T2 maps of 313 lumbar discs of 64 patients with low back pain were acquired at 3.0 Tesla (3T). The discs were rated according to disc herniation and bulging. Region of interest (ROI) analysis was performed on median, sagittal T2 maps. T2 values of the AF, in the most posterior 10% (PAF-10) and 20% of the disc (PAF-20), were compared. A significant increase in the T2 values of discs with herniations affecting the imaged area, compared to bulging discs and discs with lateral herniation, was shown in the PAF-10, where no association to the NP was apparent. The PAF-20 exhibited a moderate correlation to the nucleus pulposus (NP). High T2 values in the PAF-10 suggest the presence of disc herniation (DH). The results indicate that T2 values in the PAF-20 correspond more to changes in the NP.

  5. Segmentation of optic disc and optic cup in retinal fundus images using shape regression.

    PubMed

    Sedai, Suman; Roy, Pallab K; Mahapatra, Dwarikanath; Garnavi, Rahil

    2016-08-01

    Glaucoma is one of the leading cause of blindness. The manual examination of optic cup and disc is a standard procedure used for detecting glaucoma. This paper presents a fully automatic regression based method which accurately segments optic cup and disc in retinal colour fundus image. First, we roughly segment optic disc using circular hough transform. The approximated optic disc is then used to compute the initial optic disc and cup shapes. We propose a robust and efficient cascaded shape regression method which iteratively learns the final shape of the optic cup and disc from a given initial shape. Gradient boosted regression trees are employed to learn each regressor in the cascade. A novel data augmentation approach is proposed to improve the regressors performance by generating synthetic training data. The proposed optic cup and disc segmentation method is applied on an image set of 50 patients and demonstrate high segmentation accuracy for optic cup and disc with dice metric of 0.95 and 0.85 respectively. Comparative study shows that our proposed method outperforms state of the art optic cup and disc segmentation methods.

  6. Lumbar disc degeneration was not related to spine and hip bone mineral densities in Chinese: facet joint osteoarthritis may confound the association.

    PubMed

    Pan, Jianjiang; Lu, Xuan; Yang, Ge; Han, Yongmei; Tong, Xiang; Wang, Yue

    2017-12-01

    A sample of 512 Chinese was studied and we observed that greater disc degeneration on MRI was associated with greater spine DXA BMD. Yet, this association may be confounded by facet joint osteoarthritis. BMD may not be a risk factor for lumbar disc degeneration in Chinese. Evidence suggested that lumbar vertebral bone and intervertebral disc interact with each other in multiple ways. The current paper aims to determine the association between bone mineral density (BMD) and lumbar disc degeneration using a sample of Chinese. We studied 165 patients with back disorders and 347 general subjects from China. All subjects had lumbar spine magnetic resonance (MR) imaging and dual- energy X-ray absorptiometry (DXA) spine BMD studies, and a subset of general subjects had additional hip BMD measurements. On T2-weighted MR images, Pfirrmann score was used to evaluate the degree of lumbar disc degeneration and facet joint osteoarthritis was assessed as none, slight-moderate, and severe. Regression analyses were used to examine the associations between lumbar and hip BMD and disc degeneration, adjusting for age, gender, body mass index (BMI), lumbar region, and facet joint osteoarthritis. Greater facet joint osteoarthritis was associated with greater spine BMD (P < 0.01) in both patients and general subjects. For general subjects, greater spine BMD was associated with severe disc degeneration, controlling for age, gender, BMI, and lumbar region. When facet joint osteoarthritis entered the regression model, however, greater spine BMD was associated with greater facet joint osteoarthritis (P < 0.01) but not greater disc degeneration (P > 0.05). No statistical association was observed between spine BMD and lumbar disc degeneration in patients with back disorders (P > 0.05), and between hip BMD and disc degeneration in general subjects (P > 0.05). BMD may not be a risk factor for lumbar disc degeneration in Chinese. Facet joint osteoarthritis inflates DXA spine BMD measurements and therefore, may confound the association between spine BMD and disc degeneration.

  7. Analysis of the Function of Apoptosis during Imaginal Wing Disc Regeneration in Drosophila melanogaster.

    PubMed

    Diaz-Garcia, Sandra; Ahmed, Sara; Baonza, Antonio

    2016-01-01

    Regeneration is the ability that allows organisms to replace missing organs or lost tissue after injuries. This ability requires the coordinated activity of different cellular processes, including programmed cell death. Apoptosis plays a key role as a source of signals necessary for regeneration in different organisms. The imaginal discs of Drosophila melanogaster provide a particularly well-characterised model system for studying the cellular and molecular mechanisms underlying regeneration. Although it has been shown that signals produced by apoptotic cells are needed for homeostasis and regeneration of some tissues of this organism, such as the adult midgut, the contribution of apoptosis to disc regeneration remains unclear. Using a new method for studying disc regeneration in physiological conditions, we have defined the pattern of cell death in regenerating discs. Our data indicate that during disc regeneration, cell death increases first at the wound edge, but as regeneration progresses dead cells can be observed in regions far away from the site of damage. This result indicates that apoptotic signals initiated in the wound spread throughout the disc. We also present results which suggest that the partial inhibition of apoptosis does not have a major effect on disc regeneration. Finally, our results suggest that during disc regeneration distinct apoptotic signals might be acting simultaneously.

  8. Kinematics of a selectively constrained radiolucent anterior lumbar disc: comparisons to hybrid and circumferential fusion.

    PubMed

    Daftari, Tapan K; Chinthakunta, Suresh R; Ingalhalikar, Aditya; Gudipally, Manasa; Hussain, Mir; Khalil, Saif

    2012-10-01

    Despite encouraging clinical outcomes of one-level total disc replacements reported in literature, there is no compelling evidence regarding the stability following two-level disc replacement and hybrid constructs. The current study is aimed at evaluating the multidirectional kinematics of a two-level disc arthroplasty and hybrid construct with disc replacement adjacent to rigid circumferential fusion, compared to two-level fusion using a novel selectively constrained radiolucent anterior lumbar disc. Nine osteoligamentous lumbosacral spines (L1-S1) were tested in the following sequence: 1) Intact; 2) One-level disc replacement; 3) Hybrid; 4) Two-level disc replacement; and 5) Two-level fusion. Range of motion (at both implanted and adjacent level), and center of rotation in sagittal plane were recorded and calculated. At the level of implantation, motion was restored when one-level disc replacement was used but tended to decrease with two-level disc arthroplasty. The findings also revealed that both one-level and two-level disc replacement and hybrid constructs did not significantly change adjacent level kinematics compared to the intact condition, whereas the two-level fusion construct demonstrated a significant increase in flexibility at the adjacent level. The location of center of rotation in the sagittal plane at L4-L5 for the one-level disc replacement construct was similar to that of the intact condition. The one-level disc arthroplasty tended to mimic a motion profile similar to the intact spine. However, the two-level disc replacement construct tended to reduce motion and clinical stability of a two-level disc arthroplasty requires additional investigation. Hybrid constructs may be used as a surgical alternative for treating two-level lumbar degenerative disc disease. Published by Elsevier Ltd.

  9. New Challenges for Intervertebral Disc Treatment Using Regenerative Medicine

    PubMed Central

    Masuda, Koichi

    2010-01-01

    The development of tissue engineering therapies for the intervertebral disc is challenging due to ambiguities of disease and pain mechanisms in patients, and lack of consensus on preclinical models for safety and efficacy testing. Although the issues associated with model selection for studying orthopedic diseases or treatments have been discussed often, the multifaceted challenges associated with developing intervertebral disc tissue engineering therapies require special discussion. This review covers topics relevant to the clinical translation of tissue-engineered technologies: (1) the unmet clinical need, (2) appropriate models for safety and efficacy testing, (3) the need for standardized model systems, and (4) the translational pathways leading to a clinical trial. For preclinical evaluation of new therapies, we recommend establishing biologic plausibility of efficacy and safety using models of increasing complexity, starting with cell culture, small animals (rats and rabbits), and then large animals (goat and minipig) that more closely mimic nutritional, biomechanical, and surgical realities of human application. The use of standardized and reproducible experimental procedures and outcome measures is critical for judging relative efficacy. Finally, success will hinge on carefully designed clinical trials with well-defined patient selection criteria, gold-standard controls, and objective outcome metrics to assess performance in the early postoperative period. PMID:19903086

  10. [Role of different scale structures of titanium implant in the biological behaviors of human umbilical vein endothelial cells].

    PubMed

    Liang, N W; Shi, L; Huang, Y; Deng, X L

    2017-02-18

    To study the role of different scale structure of Ti implants on the biological behaviors of human umbilical vein endothelial cell (HUVECs) and to reveal the role of material surface topographical features on peri-implant angiogenesis. Titanium (Ti) discs with different surface structures (Ti discs with smooth surface, Ti discs with nano scale structure, Ti discs with micro scale structure and Ti discs with micro/nano scale structure, named as SM-Ti, Nano-Ti, Micro-Ti and Micro/Nano-Ti, respectively) were prepared and their surface topographical features were confirmed via scanning electron microscopy (SEM) observation. HUVECs were cultured on these Ti discs. Biological outcomes of HUVECs on different surfaces were carried out, including cell adhesive capacity, proliferation, vascular endothelial growth factor (VEGF) production and intracellular expression of Ca(2+). The results of SEM images and immunofluorescence double staining of rhodamine-phalloidin and DAPI showed that compared with the SM-Ti and Nano-Ti group, the adhesive capacity and proliferation behavior of HUVECs on the surfaces of Micro-Ti and Micro/Nano-Ti was decreased. The results of culturing HUVECs on different groups of Ti discs after 24 hours showed that the cells number grew from (18±4) to (42±6)/ vision on SM-Ti, (28±6) to (52±10)/vision on Nano-Ti, (20±4) to (21±6)/vision on Micro-Ti and (16±4) to (18±6)/vision on Micro/Nano-Ti. Moreover, compared with the adhesion and proliferation of HUVECs on SM-Ti group and Nano-Ti, the adhesion and proliferation of HUVECs on Micro-Ti group and Micro/Nano-Ti group was significantly reduced (P<0.05).The results of enzyme-linked immunosorbent assay (ELISA) showed that the VEGF productions of SM-Ti, Nano-Ti, Micro-Ti and Micro/Nano-Ti were (690±35) ng/L, (560±20) ng/L, (474±43) ng/L and (517±29) ng/L, respectively. Moreover, compared with the VEGF production of HUVECs on SM-Ti group, the VEGF production of HUVECs on Micro-Ti group and Micro/Nano-Ti group was significantly reduced (P<0.05). The results of Ca(2+) ion detection showed that the Ca(2+) expression of HUVECs on Micro-Ti and Micro/Nano-Ti was significantly higher than that on the surface of SM-Ti and Nano-Ti. These results implied that the over expressed Ca(2+) might contributed to the impaired biological function of HUVECs on Micro-Ti and Micro/Nano-Ti. Different topographical features on titanium influenced the biological behaviors of the HUVECs, which may illustrate how topographical features of Ti implant affect peri-implant angiogenesis. These results also suggest that the biological behaviors of HUVECs might be relative to the changed expression of intracellular Ca(2+).

  11. The Iconography and Symbolism of Sun God in Urartian Art

    NASA Astrophysics Data System (ADS)

    Poghosyan, Gayane

    2016-12-01

    The predominating symbol of the winged sun disc in Urartian religious iconography testifies the significant role and importance of the sun in worship. The stylistic variation and peculiar iconographic features of the winged discs, sacred animals and divine images associated with solar deity shows the relationship between the cult of the sun god, sequence of the different phases of the year and constellations in Urartian culture. Such kind of iconography is possibly formed and stylized in result of interaction of ancient human imaginations, influence of rock paintings and religious beliefs.

  12. Motivation, characterization, and strategy for tissue engineering the temporomandibular joint disc.

    PubMed

    Detamore, Michael S; Athanasiou, Kyriacos A

    2003-12-01

    The purpose of this review is to serve as the standard point of reference in guiding researchers investigating the tissue engineering of the temporomandibular joint (TMJ) disc. Tissue engineering of the TMJ disc is in its infancy, and currently there exists a gap between the tissue engineering community and the TMJ characterization community. The primary goal is to help bridge that gap by consolidating the characterization studies here as a reference to researchers attempting to tissue engineer the TMJ disc. A brief review of TMJ anatomy is provided, along with a description of relevant pathology, current treatment, and a rationale for engineering the TMJ disc. The biochemical composition and organization of the disc are reviewed, including glycosaminoglycan (GAG) and collagen content. The collagen of the disc is almost exclusively type I and primarily runs anteroposteriorly through the center and in a ringlike fashion around the periphery. The GAG content is approximately an order of magnitude less than that of hyaline cartilage, and although the distribution is not entirely clear, it seems as though chondroitin and dermatan sulfate are by far the primary GAGs. Cellular characterization and mechanical properties under compression, tension, and shear are reviewed as well. The cells of the disc are not chondrocytes, but rather resemble fibrocytes and fibrochondrocytes and may be of the same lineage. Mechanically, the disc is certainly anisotropic and nonhomogeneous. Finally, a review of efforts in tissue engineering and cell culture studies of the disc is provided and we close with a description of the direction we envision/propose for successful tissue engineering of the TMJ disc.

  13. Evaluation of Physiological and Psychological Impairment of Human Performance in Cold Stressed Subjects

    DTIC Science & Technology

    1990-03-23

    defined (personal communciation between R. Pozos and Simon, 1985). In summary, there have been studies dealing with shivering which indicate that the...microcomputer (IBM PS/2, Model 30/286). The Firearms Training System combines features of several technologies, notably: interactive video-disc/ computer ...technology and laser designator/camera/ computer /target-hit generation, which provides for immediate visual performance feedback. The subject is

  14. Accretion disc wind variability in the states of the microquasar GRS 1915+105

    NASA Astrophysics Data System (ADS)

    Neilsen, Joseph; Petschek, Andrew J.; Lee, Julia C.

    2012-03-01

    Continuing our study of the role and evolution of accretion disc winds in the microquasar GRS 1915+105, we present high-resolution spectral variability analysis of the β and γ states with the Chandra High-Energy Transmission Grating Spectrometer. By tracking changes in the absorption lines from the accretion disc wind, we find new evidence that radiation links the inner and outer accretion discs on a range of time-scales. As the central X-ray flux rises during the high-luminosity γ state, we observe the progressive overionization of the wind. In the β state, we argue that changes in the inner disc leading to the ejection of a transient 'baby jet' also quench the highly ionized wind from the outer disc. Our analysis reveals how the state, structure and X-ray luminosity of the inner accretion disc all conspire to drive the formation and variability of highly ionized accretion disc winds.

  15. Separate the Sheep from the Goats: Use and Limitations of Large Animal Models in Intervertebral Disc Research.

    PubMed

    Reitmaier, Sandra; Graichen, Friedmar; Shirazi-Adl, Aboulfazl; Schmidt, Hendrik

    2017-10-04

    Approximately 5,168 large animals (pigs, sheep, goats, and cattle) were used for intervertebral disc research in identified studies published between 1985 and 2016. Most of the reviewed studies revealed a low scientific impact, a lack of sound justifications for the animal models, and a number of deficiencies in the documentation of the animal experimentation. The scientific community should take suitable measures to investigate the presumption that animal models have translational value in intervertebral disc research. Recommendations for future investigations are provided to improve the quality, validity, and usefulness of animal studies for intervertebral disc research. More in vivo studies are warranted to comprehensively evaluate the suitability of animal models in various applications and help place animal models as an integral, complementary part of intervertebral disc research.

  16. ProDisc-L total disc replacement: a comparison of 1-level versus 2-level arthroplasty patients with a minimum 2-year follow-up.

    PubMed

    Hannibal, Matthew; Thomas, Derek J; Low, Jeffrey; Hsu, Ken Y; Zucherman, James

    2007-10-01

    This is a retrospective analysis of data that was collected prospectively from 2 concurrent FDA IDE lumbar arthroplasty clinical trials performed at a single center. To determine if there is a clinical difference between the 1-level ProDisc patients versus the 2-level ProDisc patients at a minimum of 2 years of follow-up. Marnay's work with ProDisc I prompted the U.S. Clinical Trials of the ProDisc II under the direction of the FDA. Disc replacement surgery in the United States has shown promising results for all types of prostheses up to 6 months. Marnay and colleagues showed that their results at 10 years were still promising, and they saw no significant difference between 1-level and multilevel disc replacements. The findings of Ipsen and colleagues suggest that multilevel arthroplasty cases may be less successful than disc replacement at a single level. Patients were part of the FDA clinical trial for the Prodisc II versus circumferential fusion study at a single institution. We identified 27 patients who received ProDisc at 1 level and 32 who received it at 2 levels with at least a 2-year follow-up, for a total of 59 patients. Unpaired t tests were performed on the mean results of Visual Analog Scale, Oswestry Disability Index, SF-36 Healthy Survey Physical Component Summary, and satisfaction using 10-cm line visual scale scores to determine a clinical difference if any between the 2 populations. While patients receiving ProDisc at 2 levels scored marginally lower in all evaluation indexes, score differences in each category were also found to hold no statistical significance. This study was unable to identify a statistically significant difference in outcome between 1- and 2-level ProDisc arthroplasty patients in a cohort from a single center. The equality of clinical effectiveness between 1- and 2-level ProDisc has yet to be determined.

  17. Thoracolumbar Intervertebral Disc Area Morphometry in Elderly Chinese Men and Women: Radiographic Quantifications at Baseline and Changes at Year-4 Follow-up.

    PubMed

    Wáng, Jùn-Qīng; Káplár, Zoltán; Deng, Min; Griffith, James F; Leung, Jason C S; Kwok, Anthony W L; Kwok, Timothy; Leung, Ping Chung; Wáng, Yì Xiáng J

    2018-05-15

    A population-based radiographic study with longitudinal follow-up. To develop a quantitative index for lumbar disc space narrowing (DSN) evaluation in elderly subjects; to determine how DSN in the elderly is influenced by osteoporosis and sex. There is paucity of research on quantitative classification of lumbar DSN based on disc areal morphometry. With the database of Osteoporotic Fractures in Men (Hong Kong) and Osteoporotic Fractures in Women (Hong Kong) Studies and those who attended the year-4 follow-up (n = 1519 for men and n = 1546 for women), data of 491 women and 592 men were randomly selected. The anterior, middle, and posterior heights; anteroposterior diameter; and area of intervertebral discs (T4T5 to L4L5) were measured on lateral radiographs. Disc area index for lumbar spine (DAIL, disc area divided by the mean of the sum of square of the adjacent upper and lower vertebrae mid-height anterior-posterior diameter) was developed and compared with semiquantitative DSN expert grading. DAIL correlated with semiquantitative grading, with sensitivity and specificity varying from 87.3% to 96.8% for grade 1 DSN (<30% reduction in disc height), and 92.9% to 100% for grade 3 DSN (>60% reduction in disc height). The thoracolumbar disc area loss among men and women during 4-years' follow-up period varied between 1.32% and 3.56%, and it was greater for women (mean: 2.44%) than for men (mean: 1.90%, P = 0.044). Majority of lumbar DSN progressions during 72 to 76 years old were progression from normal disc space to grade 1 DSN. Osteoporosis was associated with greater disc area decrease, both for thoracic and lumbar discs. Lumbar DSN can be quantified using DAIL. In elderly Chinese, intervertebral disc narrowing over a 4-year period was greater in women than men, and associated with the presence of osteoporosis. 3.

  18. X-ray and multiwavelength insights into the inner structure of high-luminosity disc-like emitters

    NASA Astrophysics Data System (ADS)

    Luo, B.; Brandt, W. N.; Eracleous, M.; Wu, Jian; Hall, P. B.; Rafiee, A.; Schneider, D. P.; Wu, Jianfeng

    2013-02-01

    We present X-ray and multiwavelength studies of a sample of eight high-luminosity active galactic nuclei (AGN) with disc-like Hβ emission-line profiles selected from the Sloan Digital Sky Survey Data Release 7. These sources have higher redshift (z ≈ 0.6) than the majority of the known disc-like emitters, and they occupy a largely unexplored space in the luminosity-redshift plane. Seven sources have typical AGN X-ray spectra with power-law photon indices of Γ ≈ 1.4-2.0; two of them show some X-ray absorption (column density NH ≈ 1021-1022 cm-2 for neutral gas). The other source, J0850+4451, has only three hard X-ray photons detected and is probably heavily obscured (NH ≳ 3 × 1023 cm-2). This object is also identified as a low-ionization broad absorption line (BAL) quasar based on Mg II λ2799 absorption; it is the first disc-like emitter reported that is also a BAL quasar. The infrared-to-ultraviolet (UV) spectral energy distributions (SEDs) of these eight sources are similar to the mean SEDs of typical quasars with a UV `bump', suggestive of standard accretion discs radiating with high efficiency, which differs from low-luminosity disc-like emitters. Studies of the X-ray-to-optical power-law slope parameters (αOX) indicate that there is no significant excess X-ray emission in these high-luminosity disc-like emitters. Energy budget analysis suggests that for disc-like emitters in general, the inner disc must illuminate and ionize the outer disc efficiently (≈15 per cent of the nuclear ionizing radiation is required on average) via direct illumination and/or scattering. Warped accretion discs are probably needed for direct illumination to work in high-luminosity objects, as their geometrically thin inner discs decrease the amount of direct illumination possible for a flat disc.

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

    PubMed

    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.

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

    PubMed Central

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

    2012-01-01

    SUMMARY 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. PMID:22028328

  1. Effects of Axial Torsion on Disc Height Distribution: An In Vivo Study.

    PubMed

    Espinoza Orías, Alejandro A; Mammoser, Nicole M; Triano, John J; An, Howard S; Andersson, Gunnar B J; Inoue, Nozomu

    2016-05-01

    Axial rotation of the torso is commonly used during manipulation treatment of low back pain. Little is known about the effect of these positions on disc morphology. Rotation is a three-dimensional event that is inadequately represented with planar images in the clinic. True quantification of the intervertebral gap can be achieved with a disc height distribution. The objective of this study was to analyze disc height distribution patterns during torsion relevant to manipulation in vivo. Eighty-one volunteers were computed tomography-scanned both in supine and in right 50° rotation positions. Virtual models of each intervertebral gap representing the disc were created with the inferior endplate of each "disc" set as the reference surface and separated into 5 anatomical zones: 4 peripheral and 1 central, corresponding to the footprint of the annulus fibrosus and nucleus pulposus, respectively. Whole-disc and individual anatomical zone disc height distributions were calculated in both positions and were compared against each other with analysis of variance, with significance set at P < .05. Mean neutral disc height was 7.32 mm (1.59 mm). With 50° rotation, a small but significant increase to 7.44 mm (1.52 mm) (P < .0002) was observed. The right side showed larger separation in most levels, except at L5/S1. The posterior and right zones increased in height upon axial rotation of the spine (P < .0001), whereas the left, anterior, and central decreased. This study quantified important tensile/compressive changes disc height during torsion. The implications of these mutually opposing changes on spinal manipulation are still unknown. Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

  2. Abdominal adipose tissue thickness measured using magnetic resonance imaging is associated with lumbar disc degeneration in a Chinese patient population.

    PubMed

    Yang, Lili; Mu, Liangshan; Huang, Kaiyu; Zhang, Tianyi; Mei, Zihan; Zeng, Wenrong; He, Jiawei; Chen, Wei; Liu, Xiaozheng; Ye, Xinjian; Yan, Zhihan

    2016-12-13

    The relationship between abdominal adiposity and disc degeneration remains largely uninvestigated. Here, we investigated the association between abdominal adipose tissue thickness and lumbar disc degeneration in a cross-sectional study of 2415 participants from The Second Affiliated Hospital of Wenzhou Medical University. All subjects were scanned with a 3T Magnetic Resonance Imaging system to evaluate the degree of lumbar disc degeneration. Multiple logistic regression analysis revealed that men in the highest quartiles for abdominal diameter (AD), sagittal diameter (SAD), and ventral subcutaneous thickness (VST) were at higher odds ratio for severe lumbar disc degeneration than men in the lowest quartiles. The adjusted model revealed that women in the highest quartiles for AD and SAD were also at higher odds ratio for severe lumbar disc degeneration than women in the lowest quartiles. Our results suggest that abdominal obesity might be one of underlying mechanisms of lumbar disc degeneration, and preventive strategies including weight control could be useful to reduce the incidence of lumbar disc degeneration. Prospective studies are needed to this confirm these results and to identify more deeper underlying mechanisms.

  3. A study of the wear behaviour of ion implanted pure iron

    NASA Astrophysics Data System (ADS)

    Goode, P. D.; Peacock, A. T.; Asher, J.

    1983-05-01

    The technique of Thin Layer Activation (TLA) has been used to monitor disc wear in pin-on-disc wear tests. By simultaneously monitoring the pin wear the relationship between the wear rates of the two components of the wear couple has been studied. Tests were carried out using untreated pins wearing against ion implanted and untreated pure iron discs. The ratio of pin/disc volumetric wear rates was found to be constant in tests with unimplanted discs. In the implanted case the ratio was 8 initially, rising to the unimplatned value of 24 by a sliding distance of 25 km. The relationship between pin and disc wear after nitrogen implantation of the disc was approximately independent of dose between values of 7×10 16 and 1.2×10 18 N atoms cm -2. The actual wear rates of both pin and disc were significantly lower after implantation with the greater effects being observed om the unimplanted pin. The effects are explained in terms of the model of oxidative wear. In the unimplanted case the high pin wear relative to disc wear is considered to result from the higher mean temperature of pin asperities. Implantation appears to alter the mean asperity temperatures in such a way as to reduce the oxidation rate of the pin preferentially. Alternatively the effect of the implantation could be to reduce the critical thickness for removal of oxide formed on disc asperities.

  4. Effect of collagen fibre orientation on intervertebral disc torsion mechanics.

    PubMed

    Yang, Bo; O'Connell, Grace D

    2017-12-01

    The intervertebral disc is a complex fibro-cartilaginous material, consisting of a pressurized nucleus pulposus surrounded by the annulus fibrosus, which has an angle-ply structure. Disc injury and degeneration are noted by significant changes in tissue structure and function, which significantly alters stress distribution and disc joint stiffness. Differences in fibre orientation are thought to contribute to changes in disc torsion mechanics. Therefore, the objective of this study was to evaluate the effect of collagen fibre orientation on internal disc mechanics under compression combined with axial rotation. We developed and validated a finite element model (FEM) to delineate changes in disc mechanics due to fibre orientation from differences in material properties. FEM simulations were performed with fibres oriented at [Formula: see text] throughout the disc (uniform by region and fibre layer). The initial model was validated by published experimental results for two load conditions, including [Formula: see text] axial compression and [Formula: see text] axial rotation. Once validated, fibre orientation was rotated by [Formula: see text] or [Formula: see text] towards the horizontal plane, resulting in a decrease in disc joint torsional stiffness. Furthermore, we observed that axial rotation caused a sinusoidal change in disc height and radial bulge, which may be beneficial for nutrient transport. In conclusion, including anatomically relevant fibre angles in disc joint FEMs is important for understanding stress distribution throughout the disc and will be important for understanding potential causes for disc injury. Future models will include regional differences in fibre orientation to better represent the fibre architecture of the native disc.

  5. In vivo biofunctional evaluation of hydrogels for disc regeneration.

    PubMed

    Reitmaier, Sandra; Kreja, Ludwika; Gruchenberg, Katharina; Kanter, Britta; Silva-Correia, Joana; Oliveira, Joaquim Miguel; Reis, Rui Luís; Perugini, Valeria; Santin, Matteo; Ignatius, Anita; Wilke, Hans-Joachim

    2014-01-01

    Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model. In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted. Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration. None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioning.

  6. New Brown Dwarf Discs in Upper Scorpius Observed with WISE

    NASA Technical Reports Server (NTRS)

    Dawson, P.; Scholz, A.; Ray, T. P.; Natta, A.; Marsh, K. A.; Padgett, D.; Ressler, M. E.

    2013-01-01

    We present a census of the disc population for UKIDSS selected brown dwarfs in the 5-10 Myr old Upper Scorpius OB association. For 116 objects originally identified in UKIDSS, the majority of them not studied in previous publications, we obtain photometry from the Wide-Field Infrared Survey Explorer data base. The resulting colour magnitude and colour colour plots clearly show two separate populations of objects, interpreted as brown dwarfs with discs (class II) and without discs (class III). We identify 27 class II brown dwarfs, 14 of them not previously known. This disc fraction (27 out of 116, or 23%) among brown dwarfs was found to be similar to results for K/M stars in Upper Scorpius, suggesting that the lifetimes of discs are independent of the mass of the central object for low-mass stars and brown dwarfs. 5 out of 27 discs (19 per cent) lack excess at 3.4 and 4.6 microns and are potential transition discs (i.e. are in transition from class II to class III). The transition disc fraction is comparable to low-mass stars.We estimate that the time-scale for a typical transition from class II to class III is less than 0.4 Myr for brown dwarfs. These results suggest that the evolution of brown dwarf discs mirrors the behaviour of discs around low-mass stars, with disc lifetimes of the order of 5 10 Myr and a disc clearing time-scale significantly shorter than 1 Myr.

  7. ISSLS PRIZE IN BIOENGINEERING SCIENCE 2017: Automation of reading of radiological features from magnetic resonance images (MRIs) of the lumbar spine without human intervention is comparable with an expert radiologist.

    PubMed

    Jamaludin, Amir; Lootus, Meelis; Kadir, Timor; Zisserman, Andrew; Urban, Jill; Battié, Michele C; Fairbank, Jeremy; McCall, Iain

    2017-05-01

    Investigation of the automation of radiological features from magnetic resonance images (MRIs) of the lumbar spine. To automate the process of grading lumbar intervertebral discs and vertebral bodies from MRIs. MR imaging is the most common imaging technique used in investigating low back pain (LBP). Various features of degradation, based on MRIs, are commonly recorded and graded, e.g., Modic change and Pfirrmann grading of intervertebral discs. Consistent scoring and grading is important for developing robust clinical systems and research. Automation facilitates this consistency and reduces the time of radiological analysis considerably and hence the expense. 12,018 intervertebral discs, from 2009 patients, were graded by a radiologist and were then used to train: (1) a system to detect and label vertebrae and discs in a given scan, and (2) a convolutional neural network (CNN) model that predicts several radiological gradings. The performance of the model, in terms of class average accuracy, was compared with the intra-observer class average accuracy of the radiologist. The detection system achieved 95.6% accuracy in terms of disc detection and labeling. The model is able to produce predictions of multiple pathological gradings that consistently matched those of the radiologist. The model identifies 'Evidence Hotspots' that are the voxels that most contribute to the degradation scores. Automation of radiological grading is now on par with human performance. The system can be beneficial in aiding clinical diagnoses in terms of objectivity of gradings and the speed of analysis. It can also draw the attention of a radiologist to regions of degradation. This objectivity and speed is an important stepping stone in the investigation of the relationship between MRIs and clinical diagnoses of back pain in large cohorts. Level 3.

  8. A Substance Exchanger-Based Bioreactor Culture of Pig Discs for Studying the Immature Nucleus Pulposus.

    PubMed

    Li, Pei; Gan, Yibo; Wang, Haoming; Xu, Yuan; Song, Lei; Wang, Liyuan; Ouyang, Bin; Zhou, Qiang

    2017-11-01

    Various research models have been developed to study the biology of disc cells. Recently, the adult disc nucleus pulposus (NP) has been well studied. However, the immature NP is underinvestigated due to a lack of a suitable model. This study aimed to establish an organ culture of immature porcine disc by optimizing culture conditions and using a self-developed substance exchanger-based bioreactor. Immature porcine discs were first cultured in the bioreactor for 7 days at various levels of glucose (low, medium, high), osmolarity (hypo-, iso-, hyper-) and serum (5, 10, 20%) to determine the respective optimal level. The porcine discs were then cultured under the optimized conditions in the novel bioreactor, and were compared with fresh discs at day 14. For high-glucose, iso-osmolarity, or 10% serum, cell viability, the gene expression profile (for anabolic genes and catabolic genes), and glycosaminoglycan (GAG) and hydroxyproline (HYP) contents were more favorable than for other levels of glucose, osmolarity, and serum. When the immature discs were cultured under the optimized conditions using the novel bioreactor for 14 days, the viability of the immature NP was maintained based on histology, cell viability, GAG and HYP contents, and matrix molecule expression. In conclusion, the viability of the immature NP in organ culture could be maintained under the optimized culture conditions (high-glucose, iso-osmolarity, and 10% serum) in the substance exchanger-based bioreactor. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  9. Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

    PubMed

    Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

    2014-04-01

    The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM.

  10. The simultaneous isolation of human pituitary hormones. I. Human growth hormone.

    PubMed

    Simionescu, L; Dimitriu, V; Zamfir-Grigorescu, D; Aman, E; Terbancea, M

    1982-01-01

    The main purposes of the present work are: a. the preparation of "clinical grade" human growth hormone (hGH), its physico-chemical analysis and the improvement of its solubility for clinical purposes; b. the development of a method for the isolation of high-purity hGH using frozen pituitaries. Nine batches of 20 g acetone powder were processed resulting in 4940 mg of "clinical grade" hGH. Samples of these batches randomly selected were analysed by Sephadex G-100 chromatography and by disc and preparative polyacrylamide gel electrophoresis (PAGE). Lyophilised hGH, soluble in NaCl 0.15 M was prepared and called "Hormcresc" and directions for use were elaborated. One hundred frozen glands were processed and the "crude" hGH was purified by gel filtration on Sephadex G-100 and tested using double diffusion in agar gel, radioimmunoassay (RIA), rechromatography on Sephadex G-100 and disc PAGE. The experiments led to an extraction yield of 550 +/- 165 (means +/- SD) mg "clinical grade" hGH per 20 g of acetone powder. The elution pattern of Sephadex G-100 chromatography and of preparative PAGE as well as the pattern of disc PAGE showed that the "clinical grade" hGH is similar to the already known GH hormones: Raben Somatrotropin, Crescormon (Sweden) and hGH (FRG) but different from Sotropin-H (DDR). The "clinical grade" hGH in lyophilised form is similar to the GH preparations accepted by the European pharmacopoea; it is soluble in NaCl 0.15 M and painless on injection by comparison to hGH in powder form. A method was worked out for the extraction, isolation and purification of "highly pure" hGH using frozen pituitaries, which made it possible to isolate from the same batch of glands not only hGH but also luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin and thyroid stimulating hormone (TSH). During the purification of "crude" hGH on Sephadex G-100 a rather abundant fraction of MW of about 5000-15000 daltons was observed; this fraction, codified provisionally the "X" fraction does not contain hGH, as results from the RIA measurements. On disc electrophoresis, the purified hGH is not homogeneous: behind the main fast band three slower bands are observed. Studies concerning the comparison of our "highly pure" hGH with the hGH preparations recommended by WHO, are in progress in our laboratory.

  11. Extended transiting discs and rings around planets and brown dwarfs: theoretical constraints

    NASA Astrophysics Data System (ADS)

    Zanazzi, J. J.; Lai, Dong

    2017-02-01

    Newly formed planets (or brown dwarfs) may possess discs or rings which occupy an appreciable fraction of the planet's Hill sphere and extend beyond the Laplace radius, where the tidal torque from the host star dominates over the torque from the oblate planet. Such a disc/ring can exhibit unique, detectable transit signatures, provided that the disc/ring is significantly misaligned with the orbital plane of the planet. There exists tentative evidence for an extended ring system around the young K5 star 1 SWASP J140747-354542. We present a general theoretical study of the inclination (warp) profile of circumplanetary discs under the combined influences of the tidal torque from the central star, the torque from the oblate planet, and the self-gravity of the disc. We calculate the equilibrium warp profile (`generalized Laplace surface') and investigate the condition for coherent precession of the disc. We find that to maintain a non-negligible misalignment between the extended outer disc and the planet's orbital plane, and to ensure coherent disc precession, the disc surface density must be sufficiently large so that the self-gravity torque overcomes the tidal torque from the central star. Our analysis and quantitative results can be used to constrain the parameters of transiting circumplanetary discs which may be detected in the future.

  12. Correlation between Clinical Features and Magnetic Resonance Imaging Findings in Lumbar Disc Prolapse.

    PubMed

    Thapa, S S; Lakhey, R B; Sharma, P; Pokhrel, R K

    2016-05-01

    Magnetic resonance imaging is routinely done for diagnosis of lumbar disc prolapse. Many abnormalities of disc are observed even in asymptomatic patient.This study was conducted tocorrelate these abnormalities observed on Magnetic resonance imaging and clinical features of lumbar disc prolapse. A This prospective analytical study includes 57 cases of lumbar disc prolapse presenting to Department of Orthopedics, Tribhuvan University Teaching Hospital from March 2011 to August 2012. All patientshad Magnetic resonance imaging of lumbar spine and the findings regarding type, level and position of lumbar disc prolapse, any neural canal or foraminal compromise was recorded. These imaging findings were then correlated with clinical signs and symptoms. Chi-square test was used to find out p-value for correlation between clinical features and Magnetic resonance imaging findings using SPSS 17.0. This study included 57 patients, with mean age 36.8 years. Of them 41(71.9%) patients had radicular leg pain along specific dermatome. Magnetic resonance imaging showed 104 lumbar disc prolapselevel. Disc prolapse at L4-L5 and L5-S1 level constituted 85.5%.Magnetic resonance imaging findings of neural foramina compromise and nerve root compression were fairly correlated withclinical findings of radicular pain and neurological deficit. Clinical features and Magnetic resonance imaging findings of lumbar discprolasehad faircorrelation, but all imaging abnormalities do not have a clinical significance.

  13. Stress in Lumbar Intervertebral Discs during Distraction

    PubMed Central

    Gay, Ralph E.; Ilharreborde, Brice; Zhao, Kristin D.; Berglund, Lawrence J.; Bronfort, Gert; An, Kai-Nan

    2008-01-01

    BACKGROUND CONTEXT The intervertebral disc is a common source of low back pain. Prospective studies suggest that treatments that intermittently distract the disc might be beneficial for chronic low back pain. Although the potential exists for distraction therapies to affect the disc biomechanically their effect on intradiscal stress is debated. PURPOSE To determine if distraction alone, distraction combined with flexion or distraction combined with extension can reduce nucleus pulposus pressure and posterior anulus compressive stress in cadaveric lumbar discs compared to simulated standing or lying. STUDY DESIGN Laboratory study using single cadaveric motion segments. OUTCOME MEASURES Strain gauge measures of nucleus pulposus pressure and compressive stress in the anterior and posterior annulus fibrosus METHODS Intradiscal stress profilometry was performed on 15 motion segments during 5 simulated conditions: standing, lying, and 3 distracted conditions. Disc degeneration was graded by inspection from 1 (normal) to 4 (severe degeneration). RESULTS All distraction conditions markedly reduced nucleus pressure compared to either simulated standing or lying. There was no difference between distraction with flexion and distraction with extension in regard to posterior annulus compressive stress. Discs with little or no degeneration appeared to distributed compressive stress differently than those with moderate or severe degeneration. CONCLUSIONS Distraction appears to predictably reduce nucleus pulposus pressure. The effect of distraction therapy on the distribution of compressive stress may be dependent in part on the health of the disc. PMID:17981092

  14. Lumbar disc herniation in young children.

    PubMed

    Haidar, R; Ghanem, I; Saad, S; Uthman, I

    2010-01-01

    This article explores lumbar disc herniation in young children through focusing on matters relevant to patient presentation, physical examination, differential diagnosis, imaging and treatment. Major databases were searched for studies that addressed lumbar disc herniation in young children. Diagnosis of lumbar disc herniation in young children is usually delayed because of the rarity and lack of experience with this entity and the difficulty in extracting a reliable medical history. Nevertheless, lumbar disc herniation should be considered in the differential diagnosis of any young child presenting with a chief complaint of back pain and/or radiculopathy, especially in the setting of recent trauma. This should be coupled with a directed physical examination to elicit signs and narrow the differential diagnosis. Imaging studies, mainly magnetic resonance imaging, will help establish a diagnosis; yet radiographs are still required to exclude other spinal lesions. The initial management of lumbar disc herniation in children is the same as that in adults and consists of conservative treatment unless lumbar disc herniation affects the patient's motor and neurological functions in which case, early surgical treatment must be undertaken. Although the latter remains more difficult, current experience suggests a favourable outcome. Awareness of lumbar disc herniation will help the paediatrician extract a relevant medical history, perform a directed physical examination, and order appropriate imaging studies. This will aid in initiating early intervention, be it conservative or operative, and achieving a favourable outcome.

  15. Data Mining Activities for Bone Discipline - Current Status

    NASA Technical Reports Server (NTRS)

    Sibonga, J. D.; Pietrzyk, R. A.; Johnston, S. L.; Arnaud, S. B.

    2008-01-01

    The disciplinary goals of the Human Research Program are broadly discussed. There is a critical need to identify gaps in the evidence that would substantiate a skeletal health risk during and after spaceflight missions. As a result, data mining activities will be engaged to gather reviews of medical data and flight analog data and to propose additional measures and specific analyses. Several studies are briefly reviewed which have topics that partially address these gaps in knowledge, including bone strength recovery with recovery of bone mass density, current renal stone formation knowledge, herniated discs, and a review of bed rest studies conducted at Ames Human Research Facility.

  16. On the formation of planetary systems in photoevaporating transition discs

    NASA Astrophysics Data System (ADS)

    Terquem, Caroline

    2017-01-01

    In protoplanetary discs, planetary cores must be at least 0.1 M⊕ at 1 au for migration to be significant; this mass rises to 1 M⊕ at 5 au. Planet formation models indicate that these cores form on million year time-scales. We report here a study of the evolution of 0.1 and 1 M⊕ cores, migrating from about 2 and 5 au, respectively, in million year old photoevaporating discs. In such a disc, a gap opens up at around 2 au after a few million years. The inner region subsequently accrete on to the star on a smaller time-scale. We find that, typically, the smallest cores form systems of non-resonant planets beyond 0.5 au with masses up to about 1.5 M⊕. In low-mass discs, the same cores may evolve in situ. More massive cores form systems of a few Earth-mass planets. They migrate within the inner edge of the disc gap only in the most massive discs. Delivery of material to the inner parts of the disc ceases with opening of the gap. Interestingly, when the heavy cores do not migrate significantly, the type of systems that are produced resembles our Solar system. This study suggests that low-mm flux transition discs may not form systems of planets on short orbits but may instead harbour Earth-mass planets in the habitable zone.

  17. Effects of axial compression and rotation angle on torsional mechanical properties of bovine caudal discs.

    PubMed

    Bezci, Semih E; Klineberg, Eric O; O'Connell, Grace D

    2018-01-01

    The intervertebral disc is a complex joint that acts to support and transfer large multidirectional loads, including combinations of compression, tension, bending, and torsion. Direct comparison of disc torsion mechanics across studies has been difficult, due to differences in loading protocols. In particular, the lack of information on the combined effect of multiple parameters, including axial compressive preload and rotation angle, makes it difficult to discern whether disc torsion mechanics are sensitive to the variables used in the test protocol. Thus, the objective of this study was to evaluate compression-torsion mechanical behavior of healthy discs under a wide range of rotation angles. Bovine caudal discs were tested under a range of compressive preloads (150, 300, 600, and 900N) and rotation angles (± 1, 2, 3, 4, or 5°) applied at a rate of 0.5°/s. Torque-rotation data were used to characterize shape changes in the hysteresis loop and to calculate disc torsion mechanics. Torsional mechanical properties were described using multivariate regression models. The rate of change in torsional mechanical properties with compression depended on the maximum rotation angle applied, indicating a strong interaction between compressive stress and maximum rotation angle. The regression models reported here can be used to predict disc torsion mechanics under axial compression for a given disc geometry, compressive preload, and rotation angle. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Study of the Radial Peripapillary Capillary Network in Congenital Optic Disc Anomalies With Optical Coherence Tomography Angiography.

    PubMed

    Cennamo, Gilda; Rossi, Claudia; Ruggiero, Pasquale; de Crecchio, Giuseppe; Cennamo, Giovanni

    2017-04-01

    To evaluate the radial peripapillary capillary network with optical coherence tomography angiography (angio-OCT) in morning glory syndrome (MGS), optic disc colobomas, and optic disc pits, and to explore possible correlations between the neural vascular structure and the pathogenesis of congenital optic disc anomalies. Prospective observational comparative case series. Fifteen eyes of 15 patients with congenital optic disc anomalies were enrolled in this study. All patients underwent angio-OCT. The scans were centered on optic discs. The mean age at presentation was 33 years (range: 19-50 years). Congenital optic disc anomalies were identified in all 15 eyes. Three eyes had the characteristic funduscopic signs of MGS, and angio-OCT scans of the peripapillary retina revealed a dense microvascular network. Optic disc colobomas were found in 5 eyes, and the characteristic funduscopic signs of optic pits were found in 7 eyes. Angio-OCT showed the absence of a radial peripapillary microvascular network in these 12 eyes. The finding that angio-OCT scans confirmed the presence of a peripapillary microvascular network only in MGS cases supports the hypothesis that a primary neuroectodermal abnormality and a secondary mesenchymal abnormality leads to MGS. Angio-OCT is a safe, rapid imaging technique that could shed light on the pathogenesis of rare diseases of the optic disc. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Translation of an Engineered Nanofibrous Disc-like Angle Ply Structure for Intervertebral Disc Replacement in a Small Animal Model

    PubMed Central

    Martin, John T.; Milby, Andrew H.; Chiaro, Joseph A.; Kim, Dong Hwa; Hebela, Nader M.; Smith, Lachlan J.; Elliott, Dawn M.; Mauck, Robert L.

    2015-01-01

    Intervertebral disc degeneration has been implicated in the etiology of low back pain; however the current surgical strategies for treating symptomatic disc disease are limited. A variety of materials have been developed to replace disc components, including the nucleus pulposus (NP), the annulus fibrosus (AF), and their combination into disc-like engineered constructs. We have previously shown that layers of electrospun poly(ε-caprolactone) scaffold, mimicking the hierarchical organization of the native AF, have functional parity with native tissue. Likewise, we have combined these structures with cell-seeded hydrogels (as an NP replacement) to form disc-like angle ply structures (DAPS). The objective of this study was to develop a model for the evaluation of DAPS in vivo. Through a series of studies, we developed a surgical approach to replace the rat caudal disc with an acellular DAPS and then stabilize the motion segment by external fixation. We then optimized cell infiltration into DAPS by including sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply structure. Our findings illustrate that DAPS are stable in the caudal spine, are infiltrated by cells from the peri-implant space, and that infiltration is expedited by providing additional routes for cell migration. These findings establish a new in vivo platform in which to evaluate and optimize the design of functional disc replacements. PMID:24560621

  20. Changes in the temporomandibular joint disc and temporal and masseter muscles secondary to bruxism in Turkish patients

    PubMed Central

    Garip, Hasan; Tufekcioglu, Sukran; Kaya, Emre

    2018-01-01

    Objectives: To analyze the relationships between temporalis and masseter muscle hypertrophy and temporomandibular joint (TMJ) disc displacement in patients with severe bruxism using magnetic resonance imaging (MRI). Methods: This retrospective study included 100 patients with severe bruxism, referred to the Department of Oral and Maxillofacial Surgery, University of Marmara and Istanbul Medipol University, Istanbul, Turkey, between January 2015 and December 2016. Patients underwent TMJ MRI with a 1.5-T system in open and closed mouth positions. The masseter and temporalis muscles were measured in the axial plane when the patient’s mouth was closed. Results: At its thinnest, the disc averaged was 1.11±0.24 mm. At their thickest, the masseter averaged was 13.65±2.19 mm and temporalis muscles was 12.98±2.4 mm. Of the discs, 24% were positioned normally, 74% were positioned anteriorly, and 2% were positioned posteriorly. The temporalis muscle was significantly thicker in patients with normally positioned discs than in those with anteriorly positioned discs (p=0.035). Conclusions: The temporalis muscle was significantly thicker in patients with normally positioned discs than in those with anteriorly positioned discs (p=0.035). Additional studies should be conducted to evaluate the relationships between all masticatory and surrounding muscles and disc movements in patients with bruxism. PMID:29332113

  1. Effect of ligamenta flava hypertrophy on lumbar disc herniation with contralateral symptoms and signs: a clinical and morphometric study

    PubMed Central

    Yildizhan, Ahmet; Atar, Elmas K.; Yaycioglu, Soner; Gocmen-Mas, Nuket; Yazici, Canan

    2010-01-01

    Introduction The purpose of this study was to determine whether ligamentum flavum hypertrophy among disc herniated patients causes contralateral pain symptoms. For this reason we measured the thickness of the ligament in disc herniated patients with ipsilateral or contralateral symptoms. Material and methods Two hundred disc herniated patients with ipsilateral symptoms as group I were compared with five disc herniated patients with only contralateral symptoms as group II. Ligamenta flava thicknesses and spinal canal diameters of both groups were measured on magnetic resonance imaging (MRI) with a micro-caliper. Results Both groups underwent surgery only on the disc herniated side. The total thicknesses of the ligamenta flava in group II was thicker than in group I. There was no spinal stenosis in either group and no significance difference between the groups. Statistically significant differences were found for both ipsilateral and contralateral thickness of the ligament flava in both groups. We also compared thickness of the ligamenta flava for each level of disc herniation in group I; ligamenta flava hypertrophy was more common at L3-L4 and L4-L5 levels of vertebrae in females. Conclusions Aetiology of contralateral sciatica among disc herniated patients may be related to hypertrophy of the ligamenta flava, especially on the opposite side. Surgical approaches of the disc herniated side alone may be sufficient for a good outcome. PMID:22371809

  2. Morphometric Study of the Lumbar Posterior Longitudinal Ligament

    PubMed Central

    Lee, Sang Beom; Chang, Jae Chil; Lee, Gwang Soo; Hwang, Jae Chan; Bae, Hack Gun; Doh, Jae Won

    2018-01-01

    Objective Morphometric data for the lumbar posterior longitudinal ligament (PLL) was investigated to identify whether there is a difference in the morphometry of the PLL of the lumbar spine at each level with respect to the pattern of intervertebral disc displacement. Methods In 14 formalin-fixed adult cadavers (12 males and 2 females), from L1 to L5, the authors measured the width and height of the PLL and compared them with other landmarks such as the disc and the pedicle. Results Horizontally, at the upper margin of the disc, the central portion of the superficial PLL covered 17.8–36.9% of the disc width and the fan-like portion of the PLL covered 63.9–76.7% of the disc width. At the level of the median portion of the disc, the PLL covered 69.1–74.5% of the disc width. Vertically, at the level of the medial margin of the pedicle, the fan-like portion of the PLL covered 23.5–29.9% of the disc height. In general, a significant difference in length was not found in the right-left and male-female comparisons. Conclusion This study presents the morphometric data on the pattern of intervertebral disc displacement and helps to improve the knowledge of the surgical anatomy of the lumbar PLL. PMID:29354240

  3. Biomechanics of a Fixed–Center of Rotation Cervical Intervertebral Disc Prosthesis

    PubMed Central

    Crawford, Neil R.; Baek, Seungwon; Sawa, Anna G.U.; Safavi-Abbasi, Sam; Sonntag, Volker K.H.; Duggal, Neil

    2012-01-01

    Background Past in vitro experiments studying artificial discs have focused on range of motion. It is also important to understand how artificial discs affect other biomechanical parameters, especially alterations to kinematics. The purpose of this in vitro investigation was to quantify how disc replacement with a ball-and-socket disc arthroplasty device (ProDisc-C; Synthes, West Chester, Pennsylvania) alters biomechanics of the spine relative to the normal condition (positive control) and simulated fusion (negative control). Methods Specimens were tested in multiple planes by use of pure moments under load control and again in displacement control during flexion-extension with a constant 70-N compressive follower load. Optical markers measured 3-dimensional vertebral motion, and a strain gauge array measured C4-5 facet loads. Results Range of motion and lax zone after disc replacement were not significantly different from normal values except during lateral bending, whereas plating significantly reduced motion in all loading modes (P < .002). Plating but not disc replacement shifted the location of the axis of rotation anteriorly relative to the intact condition (P < 0.01). Coupled axial rotation per degree of lateral bending was 25% ± 48% greater than normal after artificial disc replacement (P = .05) but 37% ± 38% less than normal after plating (P = .002). Coupled lateral bending per degree of axial rotation was 37% ± 21% less than normal after disc replacement (P < .001) and 41% ± 36% less than normal after plating (P = .001). Facet loads did not change significantly relative to normal after anterior plating or arthroplasty, except that facet loads were decreased during flexion in both conditions (P < .03). Conclusions In all parameters studied, deviations from normal biomechanics were less substantial after artificial disc placement than after anterior plating. PMID:25694869

  4. The Optic Nerve Head in Primary Open-Angle Glaucoma Eyes With High Myopia: Characteristics and Association With Visual Field Defects.

    PubMed

    Chen, Li-Wei; Lan, Yu-Wen; Hsieh, Jui-Wen

    2016-06-01

    To evaluate the morphologic characteristics of optic neuropathy and its association with visual field (VF) defects in primary open-angle glaucoma (POAG) eyes with high myopia. In this cross-sectional study, we reviewed data from 375 Taiwanese patients (375 eyes) of POAG, ages 20 to 60 years. Optic disc photographs were used for planimetric measurements of morphologic variables. The myopic refraction was divided into high myopia (<-6.0 D) and nonhigh myopia (moderate myopia to hyperopia). The optic disc area was classified as moderate (1.59 to 2.85 mm), large, and small. Differences in characteristics between groups, correlations with the disc area, and factors associated with VF defects were determined. Of the 142 highly myopic eyes, 33 (23%) had a large disc, 26 (18%) had a small disc, and 55 (39%) had a tilted disc. Large discs had a higher cup-to-disc (C/D) area ratio and a higher tilt ratio; small discs had a smaller rim area and a lower tilt ratio (all P<0.05). Characteristics associated with high myopia included a smaller rim area, a higher C/D area ratio, and a lower tilt ratio (all P<0.001). In logistic regression, the refraction, the C/D area ratio, the rim area, and the tilt ratio (all P<0.05) were associated with VF defects. In Taiwanese individuals with POAG, our study found that tilted, large, or small discs were prevalent in highly myopic eyes. Of these characteristics, only the disc tilt and high myopia by itself were associated with the severity of glaucomatous optic neuropathy.

  5. Lumbar spinal canal MRI diameter is smaller in herniated disc cauda equina syndrome patients

    PubMed Central

    Kruit, Mark C.; Peul, Wilco C.; Vleggeert-Lankamp, Carmen L. A.

    2017-01-01

    Introduction Correlation between magnetic resonance imaging (MRI) and clinical features in cauda equina syndrome (CES) is unknown; nor is known whether there are differences in MRI spinal canal size between lumbar herniated disc patients with CES versus lumbar herniated discs patients without CES, operated for sciatica. The aims of this study are 1) evaluating the association of MRI features with clinical presentation and outcome of CES and 2) comparing lumbar spinal canal diameters of lumbar herniated disc patients with CES versus lumbar herniated disc patients without CES, operated because of sciatica. Methods MRIs of CES patients were assessed for the following features: level of disc lesion, type (uni- or bilateral) and severity of caudal compression. Pre- and postoperative clinical features (micturition dysfunction, defecation dysfunction, altered sensation of the saddle area) were retrieved from the medical files. In addition, anteroposterior (AP) lumbar spinal canal diameters of CES patients were measured at MRI. AP diameters of lumbar herniated disc patients without CES, operated for sciatica, were measured for comparison. Results 48 CES patients were included. At MRI, bilateral compression was seen in 82%; complete caudal compression in 29%. MRI features were not associated with clinical presentation nor outcome. AP diameter was measured for 26 CES patients and for 31 lumbar herniated disc patients without CES, operated for sciatica. Comparison displayed a significant smaller AP diameter of the lumbar spinal canal in CES patients (largest p = 0.002). Compared to average diameters in literature, diameters of CES patients were significantly more often below average than that of the sciatica patients (largest p = 0.021). Conclusion This is the first study demonstrating differences in lumbar spinal canal size between lumbar herniated disc patients with CES and lumbar herniated disc patients without CES, operated for sciatica. This finding might imply that lumbar herniated disc patients with a relative small lumbar spinal canal might need to be approached differently in managing complaints of herniated disc. Since the number of studied patients is relatively small, further research should be conducted before clinical consequences are considered. PMID:29023556

  6. A detailed look at the cytoskeletal architecture of the Giardia lamblia ventral disc.

    PubMed

    Brown, Joanna R; Schwartz, Cindi L; Heumann, John M; Dawson, Scott C; Hoenger, Andreas

    2016-04-01

    Giardia lamblia is a protistan parasite that infects and colonizes the small intestine of mammals. It is widespread and particularly endemic in the developing world. Here we present a detailed structural study by 3-D negative staining and cryo-electron tomography of a unique Giardia organelle, the ventral disc. The disc is composed of a regular array of microtubules and associated sheets, called microribbons that form a large spiral, held together by a myriad of mostly unknown associated proteins. In a previous study we analyzed by cryo-electron tomography the central microtubule portion (here called disc body) of the ventral disc and found a large portion of microtubule associated inner (MIPs) and outer proteins (MAPs) that render these microtubules hyper-stable. With this follow-up study we expanded our 3-D analysis to different parts of the disc such as the ventral and dorsal areas of the overlap zone, as well as the outer disc margin. There are intrinsic location-specific characteristics in the composition of microtubule-associated proteins between these regions, as well as large differences between the overall architecture of microtubules and microribbons. The lateral packing of microtubule-microribbon complexes varies substantially, and closer packing often comes with contracted lateral tethers that seem to hold the disc together. It appears that the marginal microtubule-microribbon complexes function as outer, laterally contractible lids that may help the cell to clamp onto the intestinal microvilli. Furthermore, we analyzed length, quantity, curvature and distribution between different zones of the disc, which we found to differ from previous publications. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Effects of Axial Torsion on Disc Height Distribution: an In Vivo Study

    PubMed Central

    Espinoza Orías, Alejandro A.; Mammoser, Nicole M.; Triano, John J.; An, Howard S.; Andersson, Gunnar B.J.; Inoue, Nozomu

    2016-01-01

    Objectives Axial rotation of the torso is commonly used during manipulation treatment of low back pain. Little is known about the effect of these positons on disc morphology. Rotation is a three-dimensional event that is inadequately represented with planar images in the clinic. True quantification of the intervertebral gap can be achieved with a disc height distribution. The objective of this study was to analyze disc height distribution patterns during torsion relevant to manipulation in vivo. Methods Eighty-one volunteers were CT-scanned both in supine and in right 50° rotation positions. Virtual models of each intervertebral gap representing the disc were created with the inferior endplate of each ‘disc’ set as the reference surface and separated into five anatomical zones: four peripheral and one central, corresponding to the footprint of the annulus fibrosus and nucleus pulposus, respectively. Whole-disc and individual anatomical zone disc height distributions were calculated in both positions, and were compared against each other with ANOVA, with significance set at p < 0.05. Results Mean neutral disc height was 7.32 (1.59) mm. With 50° rotation, a small but significant increase to 7.44 (1.52) mm (p < 0.0002) was observed. The right side showed larger separation in most levels, except at L5/S1. The posterior and right zones increased in height upon axial rotation of the spine (p < 0.0001), while the left, anterior and central decreased. Conclusions This study quantified important tensile/compressive changes disc height during torsion. The implications of these mutually opposing changes on spinal manipulation are still unknown. PMID:27059249

  8. Full-Scale Linear Cutting Tests in Chongqing Sandstone to Study the Influence of Confining Stress on Rock Cutting Forces by TBM Disc Cutter

    NASA Astrophysics Data System (ADS)

    Pan, Yucong; Liu, Quansheng; Liu, Jianping; Peng, Xingxin; Kong, Xiaoxuan

    2018-06-01

    In order to study the influence of confining stress on rock cutting forces by tunnel boring machine (TBM) disc cutter, full-scale linear cutting tests are conducted in Chongqing Sandstone (uniaxial compressive strength 60.76 MPa) using five equal biaxial confining stressed conditions, i.e. 0-0, 5-5, 10-10, 15-15 and 20-20 MPa; disc cutter normal force, rolling force, cutting coefficient and normalized resultant force are analysed. It is found that confining stress can greatly affect disc cutter resultant force, its proportion in normal and rolling directions and its acting point for the hard Chongqing Sandstone and the confining stress range used in this study. For every confining stressed condition, as cutter penetration depth increases, disc cutter normal force increases with decreasing speed, rolling force and cutting coefficient both increase linearly, and acting point of the disc cutter resultant force moves downward at some extent firstly and then upward back to its initial position. For same cutter penetration depth, as confining stress increases, disc cutter normal force, rolling force, cutting coefficient and normalized resultant force all increase at some extent firstly and then decrease rapidly to very small values (quite smaller than those obtained under the non-stressed condition) after some certain confining stress thresholds. The influence of confining stress on rock cutting by TBM disc cutter can be generally divided into three stages as confining stress increases, i.e. strengthening effect stage, damaging effect stage and rupturing effect stage. In the former two stages (under low confining stress), rock remains intact and rock cutting forces are higher than those obtained under the non-stressed condition, and thus rock cutting by TBM disc cutter is restrained; in the last stage (under high confining stress), rock becomes non-intact and rock slabbing failure is induced by confining stress before disc cutting, and thus rock cutting by TBM disc cutter is facilitated. Meanwhile, some critical values of confining stress and cutter penetration depth are identified to represent the changes of rock cutting state. This study provides better understanding of the influence of confining stress on disc cutter performance and can guide to optimize the TBM operation under stressed condition.

  9. Gap formation by inclined massive planets in locally isothermal three-dimensional discs

    NASA Astrophysics Data System (ADS)

    Chametla, Raúl O.; Sánchez-Salcedo, F. J.; Masset, F. S.; Hidalgo-Gámez, A. M.

    2017-07-01

    We study gap formation in gaseous protoplanetary discs by a Jupiter mass planet. The planet's orbit is circular and inclined relative to the mid-plane of the disc. We use the impulse approximation to estimate the gravitational tidal torque between the planet and the disc, and infer the gap profile. For low-mass discs, we provide a criterion for gap opening when the orbital inclination is ≤30°. Using the fargo3d code, we simulate the disc response to an inclined massive planet. The dependence of the depth and width of the gap obtained in the simulations on the inclination of the planet is broadly consistent with the scaling laws derived in the impulse approximation. Although we mainly focus on planets kept on fixed orbits, the formalism permits to infer the temporal evolution of the gap profile in the cases where the inclination of the planet changes with time. This study may be useful to understand the migration of massive planets on inclined orbit, because the strength of the interaction with the disc depends on whether a gap is opened or not.

  10. Regression Analysis of Optical Coherence Tomography Disc Variables for Glaucoma Diagnosis.

    PubMed

    Richter, Grace M; Zhang, Xinbo; Tan, Ou; Francis, Brian A; Chopra, Vikas; Greenfield, David S; Varma, Rohit; Schuman, Joel S; Huang, David

    2016-08-01

    To report diagnostic accuracy of optical coherence tomography (OCT) disc variables using both time-domain (TD) and Fourier-domain (FD) OCT, and to improve the use of OCT disc variable measurements for glaucoma diagnosis through regression analyses that adjust for optic disc size and axial length-based magnification error. Observational, cross-sectional. In total, 180 normal eyes of 112 participants and 180 eyes of 138 participants with perimetric glaucoma from the Advanced Imaging for Glaucoma Study. Diagnostic variables evaluated from TD-OCT and FD-OCT were: disc area, rim area, rim volume, optic nerve head volume, vertical cup-to-disc ratio (CDR), and horizontal CDR. These were compared with overall retinal nerve fiber layer thickness and ganglion cell complex. Regression analyses were performed that corrected for optic disc size and axial length. Area-under-receiver-operating curves (AUROC) were used to assess diagnostic accuracy before and after the adjustments. An index based on multiple logistic regression that combined optic disc variables with axial length was also explored with the aim of improving diagnostic accuracy of disc variables. Comparison of diagnostic accuracy of disc variables, as measured by AUROC. The unadjusted disc variables with the highest diagnostic accuracies were: rim volume for TD-OCT (AUROC=0.864) and vertical CDR (AUROC=0.874) for FD-OCT. Magnification correction significantly worsened diagnostic accuracy for rim variables, and while optic disc size adjustments partially restored diagnostic accuracy, the adjusted AUROCs were still lower. Axial length adjustments to disc variables in the form of multiple logistic regression indices led to a slight but insignificant improvement in diagnostic accuracy. Our various regression approaches were not able to significantly improve disc-based OCT glaucoma diagnosis. However, disc rim area and vertical CDR had very high diagnostic accuracy, and these disc variables can serve to complement additional OCT measurements for diagnosis of glaucoma.

  11. Biometry and spectral domain optical coherence tomography parameters in children with large cupping.

    PubMed

    Jung, Jong Jin; Baek, Seung-Hee; Kim, Ungsoo Samuel

    2013-09-01

    The purpose of this study is to investigate optic nerve head using spectral domain optical coherence tomography (SD-OCT) in children with large cupping. 111 eyes (4-10 years) were divided into three groups according to the cup to disc ratio: group 1, ≤0.3; group 2, 0.4-0.6; and group 3, ≥0.7. The rim area, disc area, average cup to disc ratio, vertical cup to disc ratio, and cup volume were investigated using SD-OCT (Cirrus HD-OCT, Carl Zeiss, Jena, Germany), and the axial length and anterior chamber depth (ACD) were measured by IOL master (IOL master 500, Carl Zeiss, Jena, Germany). Next, we compared ocular biometry and SD-OCT between the three groups. The mean age of group 1 was 6.48 ± 1.42 years, 7.00 ± 1.75 years in group 2, and 6.63 ± 1.82 years in group 3 (p = 0.370). A significant difference was seen in the spherical equivalent between the groups (p = 0.001). Group 2 had the most myopic refractive errors. As the cup to disc ratio increases, disc area, average cup to disc ratio, vertical cup to disc ratio, and cup volume increase significantly. When the results of ocular biometry and SD-OCT are adjusted for axial length, only disc area showed a significant correlation with cup to disc ratio (ACD: p = 0.473, rim area: p = 0.639, disc area: p = 0.005, and cup volume: p = 0.325). Axial length is the key factor determining disc size, which in turn is important for determining cup to disc ratio. Normal children with large cupping should be examined for axial length, myopic refractive errors, and disc size.

  12. Engineered disc-like angle-ply structures for intervertebral disc replacement.

    PubMed

    Nerurkar, Nandan L; Sen, Sounok; Huang, Alice H; Elliott, Dawn M; Mauck, Robert L

    2010-04-15

    To develop a construction algorithm in which electrospun nanofibrous scaffolds are coupled with a biocompatible hydrogel to engineer a mesenchymal stem cell (MSC)-based disc replacement. To engineer a disc-like angle-ply structure (DAPS) that replicates the multiscale architecture of the intervertebral disc. Successful engineering of a replacement for the intervertebral disc requires replication of its mechanical function and anatomic form. Despite many attempts to engineer a replacement for ailing and degenerated discs, no prior study has replicated the multiscale hierarchical architecture of the native disc, and very few have assessed the mechanical function of formed neo-tissues. A new algorithm for the construction of a disc analogue was developed, using agarose to form a central nucleus pulposus (NP) and oriented electrospun nanofibrous scaffolds to form the anulus fibrosus region (AF). Bovine MSCs were seeded into both regions and biochemical, histologic, and mechanical maturation were evaluated with in vitro culture. We show that mechanical testing in compression and torsion, loading methods commonly used to assess disc mechanics, reveal equilibrium and time-dependent behaviors that are qualitatively similar to native tissue, although lesser in magnitude. Further, we demonstrate that cells seeded into both AF and NP regions adopt distinct morphologies that mirror those seen in native tissue, and that, in the AF region, this ordered community of cells deposit matrix that is organized in an angle-ply configuration. Finally, constructs demonstrate functional development with long-term in vitro culture. These findings provide a new approach for disc tissue engineering that replicates multi-scale form and function of the intervertebral disc, providing a foundation from which to build a multi-scale, biologic, anatomically and hierarchically relevant composite disc analogue for eventual disc replacement.

  13. Resolving the disc-halo degeneracy - I: a look at NGC 628

    NASA Astrophysics Data System (ADS)

    Aniyan, S.; Freeman, K. C.; Arnaboldi, M.; Gerhard, O. E.; Coccato, L.; Fabricius, M.; Kuijken, K.; Merrifield, M.; Ponomareva, A. A.

    2018-05-01

    The decomposition of the rotation curve of galaxies into contribution from the disc and dark halo remains uncertain and depends on the adopted mass-to-light ratio (M/L) of the disc. Given the vertical velocity dispersion of stars and disc scale height, the disc surface mass density and hence the M/L can be estimated. We address a conceptual problem with previous measurements of the scale height and dispersion. When using this method, the dispersion and scale height must refer to the same population of stars. The scale height is obtained from near-infrared (IR) studies of edge-on galaxies and is weighted towards older kinematically hotter stars, whereas the dispersion obtained from integrated light in the optical bands includes stars of all ages. We aim to extract the dispersion for the hotter stars, so that it can then be used with the correct scale height to obtain the disc surface mass density. We use a sample of planetary nebulae (PNe) as dynamical tracers in the face-on galaxy NGC 628. We extract two different dispersions from its velocity histogram - representing the older and younger PNe. We also present complementary stellar absorption spectra in the inner regions of this galaxy and use a direct pixel fitting technique to extract the two components. Our analysis concludes that previous studies, which do not take account of the young disc, underestimate the disc surface mass density by a factor of ˜2. This is sufficient to make a maximal disc for NGC 628 appear like a submaximal disc.

  14. A Structurally and Functionally Biomimetic Biphasic Scaffold for Intervertebral Disc Tissue Engineering

    PubMed Central

    Choy, Andrew Tsz Hang; Chan, Barbara Pui

    2015-01-01

    Tissue engineering offers high hopes for the treatment of intervertebral disc (IVD) degeneration. Whereas scaffolds of the disc nucleus and annulus have been extensively studied, a truly biomimetic and mechanically functional biphasic scaffold using naturally occurring extracellular matrix is yet to be developed. Here, a biphasic scaffold was fabricated with collagen and glycosaminoglycans (GAGs), two of the most abundant extracellular matrix components in the IVD. Following fabrication, the scaffold was characterized and benchmarked against native disc. The biphasic scaffold was composed of a collagen-GAG co-precipitate making up the nucleus pulposus-like core, and this was encapsulated in multiple lamellae of photochemically crosslinked collagen membranes comprising the annulus fibrosus-like lamellae. On mechanical testing, the height of our engineered disc recovered by ~82-89% in an annulus-independent manner, when compared with the 99% recovery exhibited by native disc. The annulus-independent nature of disc height recovery suggests that the fluid replacement function of the engineered nucleus pulposus core might mimic this hitherto unique feature of native disc. Biphasic scaffolds comprised of 10 annulus fibrosus-like lamellae had the best overall mechanical performance among the various designs owing to their similarity to native disc in most aspects, including elastic compliance during creep and recovery, and viscous compliance during recovery. However, the dynamic mechanical performance (including dynamic stiffness and damping factor) of all the biphasic scaffolds was similar to that of the native discs. This study contributes to the rationalized design and development of a biomimetic and mechanically viable biphasic scaffold for IVD tissue engineering. PMID:26115332

  15. Forming disc galaxies in major mergers - III. The effect of angular momentum on the radial density profiles of disc galaxies

    NASA Astrophysics Data System (ADS)

    Peschken, N.; Athanassoula, E.; Rodionov, S. A.

    2017-06-01

    We study the effect of angular momentum on the surface density profiles of disc galaxies, using high-resolution simulations of major mergers whose remnants have downbending radial density profiles (type II). As described in the previous papers of this series, in this scenario, most of the disc mass is acquired after the collision via accretion from a hot gaseous halo. We find that the inner and outer disc scalelengths, as well as the break radius, correlate with the total angular momentum of the initial merging system, and are larger for high-angular momentum systems. We follow the angular momentum redistribution in our simulated galaxies, and find that like the mass, the disc angular momentum is acquired via accretion, I.e. to the detriment of the gaseous halo. Furthermore, high-angular momentum systems give more angular momentum to their discs, which directly affects their radial density profile. Adding simulations of isolated galaxies to our sample, we find that the correlations are valid also for disc galaxies evolved in isolation. We show that the outer part of the disc at the end of the simulation is populated mainly by inside-out stellar migration, and that in galaxies with higher angular momentum, stars travel radially further out. This, however, does not mean that outer disc stars (in type II discs) were mostly born in the inner disc. Indeed, generally the break radius increases over time, and not taking this into account leads to overestimating the number of stars born in the inner disc.

  16. Diffusion-Weighted MRI Assessment of Adjacent Disc Degeneration After Thoracolumbar Vertebral Fractures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Noriega, David C., E-mail: dcnoriega1970@gmail.com; Marcia, Stefano, E-mail: stemarcia@gmail.com; Ardura, Francisco, E-mail: fardura@ono.com

    ObjectiveThe purpose of this study was to assess, by the mean apparent diffusion coefficient (ADC), if a relationship exists between disc ADC and MR findings of adjacent disc degeneration after thoracolumbar fractures treated by anatomic reduction using vertebral augmentation (VAP).Materials and MethodsTwenty non-consecutive patients (mean age 50.7 years; range 45–56) treated because of vertebral fractures, were included in this study. There were 10 A3.1 and 10 A1.2 fractures (AO classification). Surgical treatment using VAP was applied in 14 cases, and conservative in 6 patients. MRI T2-weighted images and mapping of apparent diffusion coefficient (ADC) of the intervertebral disc adjacent to themore » fractured segment were performed after a mean follow-up of 32 months. A total of 60 discs, 3 per patient, were analysed: infra-adjacent, supra-adjacent and a control disc one level above the supra-adjacent.ResultsNo differences between patients surgically treated and those following a conservative protocol regarding the average ADC values obtained in the 20 control discs analysed were found. Considering all discs, average ADC in the supra-adjacent level was lower than in the infra-adjacent (1.35 ± 0.12 vs. 1.53 ± 0.06; p < 0.001). Average ADC values of the discs used as a control were similar to those of the infra-adjacent level (1.54 ± 0.06). Compared to surgically treated patients, discs at the supra-adjacent fracture level showed statistically significant lower values in cases treated conservatively (p < 0.001). The variation in the delay of surgery had no influence on the average values of ADC at any of the measured levels.ConclusionsADC measurements of the supra-adjacent discs after a mean follow-up of 32 months following thoracolumbar fractures, showed that restoration of the vertebral collapse by minimally invasive VAP prevents posttraumatic disc degeneration.« less

  17. Optic disc size and other parameters from optical coherence tomography in Vietnamese-Americans.

    PubMed

    Peng, Pai-Huei; Fu, Sheena; Nguyen, Ngoc; Porco, Travis; Lin, Shan C

    2011-08-01

    To investigate the optic disc parameters by optical coherence tomography (OCT) in Vietnamese with various types of glaucoma. Medical charts of Vietnamese and White patients within a single practice were reviewed. Disc and rim areas by OCT were compared among nonglaucoma controls, different types of glaucoma, and glaucoma suspect. The association of these parameters with demographic and ocular features was evaluated. Data from 1416 Vietnamese and 57 White patients were included. A larger mean disc area was observed in eyes with primary angle-closure glaucoma than in eyes with primary angle-closure and primary angle-closure suspect (both P<0.001). There was no association between disc size with central corneal thickness (P=0.051) and sex (P=0.155). Vietnamese patients with glaucoma and glaucoma suspicion had larger discs than diagnosis-matched Whites (P=0.043 and 0.021, respectively). Vietnamese patients with glaucoma seem to have larger optic discs than White patients. Central corneal thickness had no association with disc area in this study population.

  18. Effects of human umbilical cord blood-derived mesenchymal stromal cells and dermal fibroblasts on diabetic wound healing.

    PubMed

    Moon, Kyung-Chul; Lee, Jong-Seok; Han, Seung-Kyu; Lee, Hyup-Woo; Dhong, Eun-Sang

    2017-07-01

    A previous study demonstrated that human umbilical cord blood-derived mesenchymal stromal cells (hUCB-MSCs) have superior wound-healing activity compared with fibroblasts in vitro. However, wound healing in vivo is a complex process that involves multiple factors. The purpose of this study was to compare the effects of hUCB-MSCs and fibroblasts on diabetic wound healing in vivo. This study especially focused on collagen synthesis and angiogenesis, which are considered to be the important factors affecting diabetic wound healing. Porous polyethylene discs were loaded with either fibroblasts or hUCB-MSCs, and a third group, which served as a control, was not loaded with cells. The discs were then implanted in the back of diabetic mice. During the first and the second week after implantation, the discs were harvested, and collagen level and microvascular density were compared. In terms of collagen synthesis, the hUCB-MSC group showed the highest collagen level (117.7 ± 8.9 ng/mL), followed by the fibroblast group (83.2 ± 5.2 ng/mL) and the no-cell group (60.0 ± 4.7 ng/mL) in the second week after implantation. In terms of angiogenesis, the microvascular density in the hUCB-MSC group was 56.8 ± 16.4, which was much higher than that in the fibroblast group (14.3 ± 4.0) and the no-cell group (5.7 ± 2.1) in the second week after implantation. These results demonstrate that hUCB-MSCs are superior to fibroblasts in terms of their effect on diabetic wound healing in vivo. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  19. Correlation between direction and severity of temporomandibular joint disc displacement and reduction ability during mouth opening.

    PubMed

    Litko, M; Berger, M; Szkutnik, J; Różyło-Kalinowska, I

    2017-12-01

    The most common temporomandibular joint (TMJ) internal derangement is an abnormal relationship of the disc with respect to the mandibular condyle, articular eminence and glenoid fossa-disc displacement. The aim of our study was to analyse the correlation between partial/complete disc displacement in the intercuspal position (IP) and its reduction in the open-mouth position (OMP) in both oblique sagittal and coronal planes on magnetic resonance imaging (MRI) in patients with temporomandibular disorders. Multisection MRI analysis of 382 TMJs was conducted in 191 patients with disc displacement according to the RDC/TMD criteria (148 women, 43 men; aged 14-60 years). The disc position was evaluated on all oblique sagittal and coronal images in the IP and the OMP. Univariate logistic regression analysis showed that the severity of disc displacement in the sagittal plane is a statistically significant predictor of reduction ability during mouth opening (B = 3.118; P < .001). Moreover, the severity of disc displacement in both planes is also a significant predictor of disc reduction in OMP (B = 2.200; P < .05). In conclusion, reduction ability during mouth opening is associated with the severity of disc displacement in IP, in both sagittal and coronal planes. Multisection analysis of all MR images allows distinguishing the correct disc position from disc displacement and can improve the ability to distinguish between various stages of TMJ internal derangement. © 2017 John Wiley & Sons Ltd.

  20. An investigation into the effect of surface roughness of stainless steel on human umbilical vein endothelial cell gene expression.

    PubMed

    McLucas, E; Moran, M T; Rochev, Y; Carroll, W M; Smith, T J

    2006-01-01

    The surface properties of vascular devices dictate the initial postimplantation reactions that occur and thus the efficacy of the implantation procedure. Over the last number of years, a number of different stent designs have emerged and stents are generally polished to a mirror finish during the manufacturing procedure. This study sought to investigate the effect of stainless steel surface roughness on endothelial cell gene expression using an appropriate cell culture in vitro assay system. Stainless steel discs were roughened by shot blasting or polished by mechanical polishing. The surface roughness of the treated and untreated discs was determined by atomic force microscopy (AFM). Cells were seeded on collagen type 1 gels and left to attach for 24 h. Stainless steel discs of varying roughness were then placed in contact with the cells and incubated for 24 h. RNA extractions and quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was then performed to determine the expression levels of candidate genes in the treated cells compared to suitable control cells. E-selectin and vascular cellular adhesion molecule (VCAM-1) were found to be significantly up-regulated in cells incubated with polished and roughened samples, indicating endothelial cell activation and inflammation. This study indicates that the surface roughness of stainless steel is an important surface property in the development of vascular stents.

  1. Total disc replacement using a tissue-engineered intervertebral disc in vivo: new animal model and initial results.

    PubMed

    Gebhard, Harry; Bowles, Robby; Dyke, Jonathan; Saleh, Tatianna; Doty, Stephen; Bonassar, Lawrence; Härtl, Roger

    2010-08-01

     Basic science Introduction:  Chronic back pain due to degenerative disc disease (DDD) is among the most important medical conditions causing morbidity and significant health care costs. Surgical treatment options include disc replacement or fusion surgery, but are associated with significant short- and long-term risks.1 Biological tissue-engineering of human intervertebral discs (IVD) could offer an important alternative.2 Recent in vitro data from our group have shown successful engineering and growth of ovine intervertebral disc composites with circumferentially aligned collagen fibrils in the annulus fibrosus (AF) (Figure 1).3 Figure 1 Tissue-engineered composite disc a Experimental steps to generate composite tissue-engineered IVDs3b Example of different AF formulations on collagen alignment in the AF. Second harmonic generation and two-photon excited fluorescence images of seeded collagen gels (for AF) of 1 and 2.5 mg/ml over time. At seeding, cells and collagen were homogenously distributed in the gels. Over time, AF cells elongated and collagen aligned parallel to cells. Less contraction and less alignment is noted after 3 days in the 2.5 mg/mL gel. c Imaging-based creation of a virtual disc model that will serve as template for the engineered disc. Total disc dimensions (AF and NP) were retrieved from micro-computer tomography (CT) (left images), and nucleus pulposus (NP) dimensions alone were retrieved from T2-weighted MRI images (right images). Merging of MRI and micro-CT models revealed a composite disc model (middle image)-Software: Microview, GE Healthcare Inc., Princeton, NJ; and slicOmatic v4.3, TomoVision, Montreal, Canada. d Flow chart describing the process for generating multi-lamellar tissue engineered IVDs. IVDs are produced by allowing cell-seeded collagen layers to contract around a cell-seeded alginate core (NP) over time Objective:  The next step is to investigate if biological disc implants survive, integrate, and restore function to the spine in vivo. A model will be developed that allows efficient in vivo testing of tissue-engineered discs of various compositions and characteristics.  Athymic rats were anesthetized and a dorsal approach was chosen to perform a microsurgical discectomy in the rat caudal spine (Fig. 2,Fig. 3). Control group I (n = 6) underwent discectomy only, Control group II (n = 6) underwent discectomy, followed by reimplantation of the autologous disc. Two treatment groups (group III, n = 6, 1 month survival; group IV, n = 6, 6 months survival) received a tissue-engineered composite disc implant. The rodents were followed clinically for signs of infection, pain level and wound healing. X-rays and magnetic resonance imaging (MRI) were assessed postoperatively and up to 6 months after surgery (Fig. 6,Fig. 7). A 7 Tesla MRI (Bruker) was implemented for assessment of the operated level as well as the adjacent disc (hydration). T2-weighted sequences were interpreted by a semiquantitative score (0 = no signal, 1 = weak signal, 2 = strong signal and anatomical features of a normal disc). Histology was performed with staining for proteoglycans (Alcian blue) and collagen (Picrosirius red) (Fig. 4,Fig. 5). Figure 2 Disc replacement surgery a Operative situs with native disc that has been disassociated from both adjacent vertebrae b Native disc (left) and tissue-engineered implant (right) c Implant in situ before wound closureAF: Annulus fi brosus, nP: nucleus pulposus, eP: endplate, M: Muscle, T: Tendon, s: skin, art: artery, GP: Growth plate, B: BoneFigure 3 Disc replacement surgery. Anatomy of the rat caudal disc space a Pircrosirius red stained axial cut of native disc space b Saffranin-O stained sagittal cut of native disc spaceFigure 4 Histologies of three separate motion segments from three different rats. Animal one = native IVD, Animal two = status after discectomy, Animal three = tissue-engineered implant (1 month) a-c H&E (overall tissue staining for light micrsocopy) d-f Alcian blue (proteoglycans) g-i Picrosirius red (collagen I and II)Figure 5 Histology from one motion segment four months after implantation of a bio-engineered disc construct a Picrosirius red staining (collagen) b Polarized light microscopy showing collagen staining and collagen organization in AF region c Increased Safranin-O staining (proteoglycans) in NP region of the disc implant d Higher magnification of figure 5c: Integration between implanted tissue-engineered total disc replacement and vertebral body boneFigure 6 MRI a Disc space height measurements in flash/T1 sequence (top: implant (714.0 micrometer), bottom: native disc (823.5 micrometer) b T2 sequence, red circle surrounding the implant NPFigure 7 7 Tesla MRI imaging of rat tail IVDs showing axial images (preliminary pilot data) a Diffusion tensor imaging (DTI) on two explanted rat tail discs in Formalin b Higher magnification of a, showing directional alignment of collagen fibers (red and green) when compared to the color ball on top which maps fibers' directional alignment (eg, fibers directing from left to right: red, from top to bottom: blue) c Native IVD in vivo (successful imaging of top and bottom of the IVD (red) d Gradient echo sequence (GE) showing differentiation between NP (light grey) and AF (dark margin) e GE of reimplanted tail IVD at the explantation level f T1Rho sequence demonstrating the NP (grey) within the AF (dark margin), containing the yellow marked region of interest for value acquisition (preliminary data are consistent with values reported in the literature). g T2 image of native IVD in vivo for monitoring of hydration (white: NP) Results:  The model allowed reproducible and complete discectomies as well as disc implantation in the rat tail spine without any surgical or postoperative complications. Discectomy resulted in immediate collapse of the disc space. Preliminary results indicate that disc space height was maintained after disc implantation in groups II, III and IV over time. MRI revealed high resolution images of normal intervertebral discs in vivo. Eight out of twelve animals (groups III and IV) showed a positive signal in T2-weighted images after 1 month (grade 0 = 4, grade 1 = 4, grade 2 = 4). Positive staining was seen for collagen as well as proteoglycans at the site of disc implantation after 1 month in each of the six animals with engineered implants (group III). Analysis of group IV showed positive T2 signal in five out of six animals and disc-height preservation in all animals after 6 months.  This study demonstrates for the first time that tissue-engineered composite IVDs with circumferentially aligned collagen fibrils survive and integrate with surrounding vertebral bodies when placed in the rat spine for up to 6 months. Tissue-engineered composite IVDs restored function to the rat spine as indicated by maintenance of disc height and vertebral alignment. A significant finding was that maintenance of the composite structure in group III was observed, with increased proteoglycan staining in the nucleus pulposus region (Figure 4d-f). Proteoglycan and collagen matrix as well as disc height preservation and positive T2 signals in MRI are promising parameters and indicate functionality of the implants.

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

    PubMed

    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 < 0.001), but not disc degeneration (P = 0.97). In the German Shepherd 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.

  3. Agreement of glaucoma specialists and experienced optometrists in gonioscopy and optic disc evaluation

    PubMed Central

    Kumar, Addepalli U.; Jonnadula, Ganesh B.; Garudadri, Chandrasekhar; Rao, Harsha L.; Senthil, Sirisha; Papas, Eric B.; Sankaridurg, Padmaja; Khanna, Rohit C.

    2013-01-01

    Purpose To compare the diagnostic performance of glaucoma specialists and experienced optometrists in gonioscopy and optic disc assessment. Methods This study was done to validate the diagnostic performance of two experienced optometrists for using their skills of detecting glaucoma using gonioscopy and optic disc assessment in a major epidemiological study, the L V Prasad Eye Institute Glaucoma Epidemiology and Molecular Genetics Study (LVPEI-GLEAMS). Gonioscopic findings for 150 eyes were categorized as 0, 1 and 2 for open angle, primary angle closure suspect (PACS) and primary angle closure (PAC) respectively. Optic disc findings for 200 eyes were categorized as 0, 1 and 2 for normal, suspects and glaucomatous respectively. Weighted kappa (κ) and diagnostic accuracy parameters were calculated. Two optometrists (#1 and #2) participated in the study. Results Agreement between glaucoma specialists and optometrist for interpretation of gonioscopy to discriminate PACS and PAC from open angles and for interpretation of optic disc to discriminate glaucomatous and suspicious discs from normal, the kappa (κ) was 0.92 and 0.84 and 0.90 and 0.89 for optometrists #1 and #2 respectively. Sensitivities and specificities were above 90% for gonioscopy. Optic disc evaluation had specificities greater than 95% to discriminate normal from glaucomatous discs while the sensitivities were 83% and 93% for optometrists #1 and #2 respectively. Conclusion Agreement between optometrists and glaucoma specialists, in diagnostic performance of gonioscopy and optic assessment was excellent with high sensitivity and specificity. Hence, we conclude that the experienced optometrists can detect glaucoma accurately in the LVPEI-GLEAMS.

  4. Sensitivity and specificity of a new MRI method evaluating temporo-mandibular joint disc-condyle relationships: an in vivo study.

    PubMed

    Benbelaïd, R; Fleiter, B

    2006-03-01

    The aim of this study was to evaluate sensitivity and specificity of a new method to locate temporo-mandibular joint (TMJ) disc using magnetic resonance imaging (MRI) and analyze disc-condyle relationships, in asymptomatic subjects and patients with disc displacement. Twenty-nine sagittal MRI of 16 subjects, 8 asymptomatic volunteers and 8 subjects with anterior disc displacement, were carried out during controlled opening from intercuspal position up to a 25 mm opening. Selected sections were analyzed with a graphic computerized system of coordinates. The total surface area (TS) of disc section was separated into anterior surface area (AS) and posterior surface area. Areas were determined by computer. Two trained examiners drew images at random. The reliability of AS/TS ratio index was evaluated in a previous study. AS/TS ratio sensitivity (Se) and specificity (Sp) were calculated closed mouth, 5 mm open and 25 mm open mouth. Best sensitivity (Se=0.63) and specificity (Sp=0.81) were obtained when MRI was realized with closed mouth and 25 mm open mouth. Lower sensitivity was observed when MRI was performed either with closed mouth (Se=0.54) or 25 mm open mouth (Se=0.18). Lower specificity was observed with 5 mm open mouth (Sp=0.68). In conclusion, it was confirmed as well that MRI of anterior disc displacement should be performed with closed mouth and opened mouth. Thus, further studies are required to assess disc displacement and mechanical alterations and to evaluate the risk of direct damage on TMJ tissues.

  5. Significant improvement in one-dimensional cursor control using Laplacian electroencephalography over electroencephalography

    NASA Astrophysics Data System (ADS)

    Boudria, Yacine; Feltane, Amal; Besio, Walter

    2014-06-01

    Objective. Brain-computer interfaces (BCIs) based on electroencephalography (EEG) have been shown to accurately detect mental activities, but the acquisition of high levels of control require extensive user training. Furthermore, EEG has low signal-to-noise ratio and low spatial resolution. The objective of the present study was to compare the accuracy between two types of BCIs during the first recording session. EEG and tripolar concentric ring electrode (TCRE) EEG (tEEG) brain signals were recorded and used to control one-dimensional cursor movements. Approach. Eight human subjects were asked to imagine either ‘left’ or ‘right’ hand movement during one recording session to control the computer cursor using TCRE and disc electrodes. Main results. The obtained results show a significant improvement in accuracies using TCREs (44%-100%) compared to disc electrodes (30%-86%). Significance. This study developed the first tEEG-based BCI system for real-time one-dimensional cursor movements and showed high accuracies with little training.

  6. Single-port gynecologic surgery with a novel surgical platform.

    PubMed

    Knight, Jason; Tunitsky-Britton, Elena; Muffly, Tyler; Michener, Chad M; Escobar, Pedro F

    2012-09-01

    Laparoendoscopic single-site surgery (LESS) allows better cosmesis and decreased pain when compared with traditional laparoscopy (TL). Instrument crowding and diminished triangulation are limitations. This study evaluates a novel single-port surgical platform (NSP) designed to facilitate the transition from TL to LESS (TransEnterix SPIDER, Durham, NC). NSP and TL were compared using standardized dry lab tasks. Feasibility of NSP in gynecology was assessed using the porcine model. Completion times with NSP were longer for ring transfer (P = .025) and trended longer for disc cutting (P = .074). Disc cutting accuracy was lower with NSP versus TL (P = .008). NSP operative times for hysterectomy, pelvic and para-aortic node dissection were 22.3, 13.3, and 26 minutes, respectively, without complications. Fatigue and lack of integrated bipolar cautery were limitations of NSP. While application of NSP to gynecology appears feasible, lower performance when compared with TL underscores the need for caution when applying NSP to humans.

  7. Doughnut strikes sandwich: the geometry of hot medium in accreting black hole X-ray binaries

    NASA Astrophysics Data System (ADS)

    Poutanen, Juri; Veledina, Alexandra; Zdziarski, Andrzej A.

    2018-06-01

    We study the effects of the mutual interaction of hot plasma and cold medium in black hole binaries in their hard spectral state. We consider a number of different geometries. In contrast to previous theoretical studies, we use a modern energy-conserving code for reflection and reprocessing from cold media. We show that a static corona above an accretion disc extending to the innermost stable circular orbit produces spectra not compatible with those observed. They are either too soft or require a much higher disc ionization than that observed. This conclusion confirms a number of previous findings, but disproves a recent study claiming an agreement of that model with observations. We show that the cold disc has to be truncated in order to agree with the observed spectral hardness. However, a cold disc truncated at a large radius and replaced by a hot flow produces spectra which are too hard if the only source of seed photons for Comptonization is the accretion disc. Our favourable geometry is a truncated disc coexisting with a hot plasma either overlapping with the disc or containing some cold matter within it, also including seed photons arising from cyclo-synchrotron emission of hybrid electrons, i.e. containing both thermal and non-thermal parts.

  8. The imprint of satellite accretion on the chemical and dynamical properties of disc galaxies

    NASA Astrophysics Data System (ADS)

    Ruiz-Lara, T.; Few, C. G.; Gibson, B. K.; Pérez, I.; Florido, E.; Minchev, I.; Sánchez-Blázquez, P.

    2016-02-01

    Aims: We study the effects of the cosmological assembly history on the chemical and dynamical properties of the discs of spiral galaxies as a function of radius. Methods: We made use of the simulated Milky Way mass, fully-cosmological discs from Ramses Disc Environment Study (RaDES). We analysed their assembly history by examining the proximity of satellites to the galactic disc, instead of their merger trees, to better gauge which satellites impact the disc. We presented stellar age and metallicity profiles, age-metallicity relation (AMR), age-velocity dispersion relation (AVR), and stellar age distribution (SAD) in several radial bins for the simulated galaxies. Results: Assembly histories can be divided into three different stages: I) a merger dominated phase, when a large number of mergers with mass ratios of ~1:1 take place (lasting ~3.2 ± 0.4 Gyr on average); II) a quieter phase, when ~1:10 mergers take place (lasting ~4.4 ± 2.0 Gyr); and III) a secular phase where the few mergers that take place have mass ratios below 1:100, which do not affect the disc properties (lasting ~5.5 ± 2.0 Gyr). The first two phases are able to kinematically heat the disc and produce a disc that is chemically mixed over its entire radial extension. Phase 2 ends with a final merger event (at time tjump) marking the onset of important radial differences in the AMR, AVR, and SAD. Conclusions: Inverted AMR trends in the outer parts of discs, for stars younger than tjump, are found as the combined effect of radial motions and star formation in satellites temporarily located in these outer parts. U-shaped stellar age profiles change to an old plateau (~10 Gyr) in the outer discs for the entire RaDES sample. This shape is a consequence of inside-out growth of the disc, radial motions of disc stars (inwards and outwards), and the accretion of old stars from satellites. We see comparable age profiles even when ignoring the influence of stellar migration due to the presence of early in situ star formation in the outer regions of the galaxy.

  9. MHD simulations of ram pressure stripping of a disc galaxy

    NASA Astrophysics Data System (ADS)

    Ramos-Martínez, Mariana; Gómez, Gilberto C.; Pérez-Villegas, Ángeles

    2018-05-01

    The removal of the interstellar medium (ISM) of disc galaxies through ram pressure stripping (RPS) has been extensively studied in numerous simulations. Nevertheless, the role of magnetic fields (MFs) on the gas dynamics in this process has been hardly studied, although the MF influence on the large-scale disc structure is well established. With this in mind, we present a 3D magnetohydrodynamic simulation of face-on RPS of a disc galaxy to study the impact of the galactic MF in the gas stripping. The main effect of including a galactic MF is a flared disc. When the intracluster medium wind hits this flared disc, oblique shocks are produced at the interaction interface, where the ISM is compressed, generating a gas inflow from large radii towards the central regions of the galaxy. This inflow is observed for {˜ } 150 {Myr} and may supply the central parts of the galaxy with material for star formation while the outskirts of the disc are being stripped of gas, thus the oblique shocks can induce and enhance the star formation in the remaining disc. We also observed that the MF alters the shape and structure of the swept gas, giving a smooth appearance in the magnetized case and clumpier and filamentary-like morphology in the hydro case. Finally, we estimated the truncation radius expected for our models using the Gunn-Gott criterion and found that that is in agreement with the simulations.

  10. Spectroscopic decomposition of NGC 3521: unveiling the properties of the bulge and disc

    NASA Astrophysics Data System (ADS)

    Coccato, Lodovico; Fabricius, Maximilian H.; Saglia, Roberto P.; Bender, Ralf; Erwin, Peter; Drory, Niv; Morelli, Lorenzo

    2018-06-01

    We study the kinematics and the stellar populations of the bulge and disc of the spiral galaxy NGC 3521. At each position in the field of view, we separate the contributions of the bulge and the disc from the total observed spectrum and study their kinematics, age, and metallicities independently. Their properties are clearly distinct: the bulge rotates more slowly, has a higher velocity dispersion, and is less luminous than the disc. We identify three main populations of stars in NGC 3521: old (≥7 Gyr), intermediate (≈3 Gyr), and young (≤1 Gyr). The mass and light of NGC 3521 are dominated by the intermediate stellar population. The youngest population contributes mostly to the disc component and its contribution increases with radius. We also study the luminosity-weighed properties of the stars in NGC 3521. Along the photometric major axis, we find (i) no age gradient for the stars in the bulge, and a negative age gradient for the stars in the disc; (ii) negative metallicity gradients and subsolar α-enhancement for both the bulge and the disc. We propose the following picture for the formation of NGC 3521: initial formation a long time ago (≥7 Gyr), followed by a second burst of star formation or a merger (≈3 Gyr ago), which contributed predominantly to the mass build-up of the bulge. Recently (≤1 Gyr), the disc of NGC 3521 experienced an additional episode of star formation that started in the innermost regions.

  11. Correlation between corneal thickness and optic disc morphology in normal tension glaucoma using modern technical analysis.

    PubMed

    Coman, Laurenţiu; Costescu, Monica; Alecu, Mihail; Coman, Oana Andreia

    2014-01-01

    The purpose of this study was to evaluate the relationship between central corneal thickness (CCT) and optic disc morphology in normal tension glaucoma (NTG). Patients with NTG underwent eye examination, optic disc imaging with Heildelberg Retina Tomograph II (HRT II) and ultrasound corneal pachymetry. The morphological parameters of the optic discs were used to classify the eyes into four groups: generalized enlargement (GE) type, myopic glaucomatous (MY) type, focal ischemic (FI) type and senile sclerotic (SS) type. A correlation between CCT and optic disc morphology obtained by HRT II was calculated. Multiple comparison and post hoc tests were performed in order to determine the significance of the differences between the four groups. The strongest correlation was between CCT and the parameters of optic disc imaging obtained at HRT II in the GE type of optic disc.

  12. STAT, Wingless, and Nurf-38 determine the accuracy of regeneration after radiation damage in Drosophila.

    PubMed

    Verghese, Shilpi; Su, Tin Tin

    2017-10-01

    We report here a study of regeneration in Drosophila larval wing imaginal discs after damage by ionizing radiation. We detected faithful regeneration that restored a wing disc and abnormal regeneration that produced an extra wing disc. We describe a sequence of changes in cell number, location and fate that occur to produce an ectopic disc. We identified a group of cells that not only participate in ectopic disc formation but also recruit others to do so. STAT92E (Drosophila STAT3/5) and Nurf-38, which encodes a member of the Nucleosome Remodeling Factor complex, oppose each other in these cells to modulate the frequency of ectopic disc growth. The picture that emerges is one in which activities like STAT increase after radiation damage and fulfill essential roles in rebuilding the tissue. But such activities must be kept in check so that one and only one wing disc is regenerated.

  13. Metallicity gradient of the thick disc progenitor at high redshift

    NASA Astrophysics Data System (ADS)

    Kawata, Daisuke; Allende Prieto, Carlos; Brook, Chris B.; Casagrande, Luca; Ciucă, Ioana; Gibson, Brad K.; Grand, Robert J. J.; Hayden, Michael R.; Hunt, Jason A. S.

    2018-01-01

    We have developed a novel Markov Chain Monte Carlo chemical 'painting' technique to explore possible radial and vertical metallicity gradients for the thick disc progenitor. In our analysis, we match an N-body simulation to the data from the Apache Point Observatory Galactic Evolution Experiment survey. We assume that the thick disc has a constant scaleheight and has completed its formation at an early epoch, after which time radial mixing of its stars has taken place. Under these assumptions, we find that the initial radial metallicity gradient of the thick disc progenitor should not be negative, but either flat or even positive, to explain the current negative vertical metallicity gradient of the thick disc. Our study suggests that the thick disc was built-up in an inside-out and upside-down fashion, and older, smaller and thicker populations are more metal poor. In this case, star-forming discs at different epochs of the thick disc formation are allowed to have different radial metallicity gradients, including a negative one, which helps to explain a variety of slopes observed in high-redshift disc galaxies. This scenario helps to explain the positive slope of the metallicity-rotation velocity relation observed for the Galactic thick disc. On the other hand, radial mixing flattens the slope of an existing gradient.

  14. Translation of an engineered nanofibrous disc-like angle-ply structure for intervertebral disc replacement in a small animal model.

    PubMed

    Martin, John T; Milby, Andrew H; Chiaro, Joseph A; Kim, Dong Hwa; Hebela, Nader M; Smith, Lachlan J; Elliott, Dawn M; Mauck, Robert L

    2014-06-01

    Intervertebral disc degeneration has been implicated in the etiology of low back pain; however, the current surgical strategies for treating symptomatic disc disease are limited. A variety of materials have been developed to replace disc components, including the nucleus pulposus (NP), the annulus fibrosus (AF) and their combination into disc-like engineered constructs. We have previously shown that layers of electrospun poly(ε-caprolactone) scaffold, mimicking the hierarchical organization of the native AF, can achieve functional parity with native tissue. Likewise, we have combined these structures with cell-seeded hydrogels (as an NP replacement) to form disc-like angle-ply structures (DAPS). The objective of this study was to develop a model for the evaluation of DAPS in vivo. Through a series of studies, we developed a surgical approach to replace the rat caudal disc with an acellular DAPS and then stabilized the motion segment via external fixation. We then optimized cell infiltration into DAPS by including sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply structure. Our findings illustrate that DAPS are stable in the caudal spine, are infiltrated by cells from the peri-implant space and that infiltration is expedited by providing additional routes for cell migration. These findings establish a new in vivo platform in which to evaluate and optimize the design of functional disc replacements. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  15. First results of the SONS survey: submillimetre detections of debris discs

    NASA Astrophysics Data System (ADS)

    Panić, O.; Holland, W. S.; Wyatt, M. C.; Kennedy, G. M.; Matthews, B. C.; Lestrade, J. F.; Sibthorpe, B.; Greaves, J. S.; Marshall, J. P.; Phillips, N. M.; Tottle, J.

    2013-10-01

    New detections of debris discs at submillimetre wavelengths present highly valuable complementary information to prior observations of these sources at shorter wavelengths. Characterization of discs through spectral energy distribution modelling including the submillimetre fluxes is essential for our basic understanding of disc mass and temperature, and presents a starting point for further studies using millimetre interferometric observations. In the framework of the ongoing SCUBA-2 Observations of Nearby Stars, the instrument SCUBA-2 on the James Clerk Maxwell Telescope was used to provide measurements of 450 and 850 μm fluxes towards a large sample of nearby main-sequence stars with debris discs detected previously at shorter wavelengths. We present the first results from the ongoing survey, concerning 850 μm detections and 450 μm upper limits towards 10 stars, the majority of which are detected at submillimetre wavelengths for the first time. One, or possibly two, of these new detections is likely a background source. We fit the spectral energy distributions of the star+disc systems with a blackbody emission approach and derive characteristic disc temperatures. We use these temperatures to convert the observed fluxes to disc masses. We obtain a range of disc masses from 0.001 to 0.1 M⊕, values similar to the prior dust mass measurements towards debris discs. There is no evidence for evolution in dust mass with age on the main sequence, and indeed the upper envelope remains relatively flat at ≈0.5 M⊕ at all ages. The inferred disc masses are lower than those from disc detections around pre-main-sequence stars, which may indicate a depletion of solid mass. This may also be due to a change in disc opacity, though limited sensitivity means that it is not yet known what fraction of pre-main-sequence stars have discs with dust masses similar to debris disc levels. New, high-sensitivity detections are a path towards investigating the trends in dust mass evolution.

  16. Cobb Angle Progression in Adolescent Scoliosis Begins at the Intervertebral Disc

    PubMed Central

    Will, Ryan E; Stokes, Ian A; Qiu, Xing; Walker, Matthew R.; Sanders, James O

    2009-01-01

    Study Design Longitudinal radiographic study of patients with progressive idiopathic scoliosis. Objective To determine the relative contributions of vertebral and disc wedging to the increase in Cobb angle during 3 phases of adolescent skeletal growth and maturation. Summary of Background Data Both disc wedging and vertebral body wedging are found in progressive scoliosis, but their relative contribution to curve progression over time is unknown. Which occurs first is important for understanding how scoliosis progresses and for developing methods to halt progression. Previous studies have not properly identified maturity and provide conflicting results. Methods Eighteen girls were followed through their adolescent growth spurt with serial spine and hand skeletal age radiographs. Each Cobb angle was divided into disc wedge angles and vertebral wedge angles. The corresponding hand radiographs provided a measure of maturity level, the Digital Skeletal Age (DSA). The disc versus bone contributions to the Cobb angle were then compared during 3 growth phases: prior to the growth spurt, during the growth spurt and after the growth spurt. Significance of relative changes was assessed with the Wilcoxon two-sided mean rank test. Results Prior to the growth spurt, there was no difference in relative contributions of the disc and the bone (3° vs 0°, p=0.38) to curve progression. During the growth spurt, the mean disc component progressed significantly more than that of the vertebrae (15° vs 0°, p=0.0002). This reversed following the growth spurt with the vertebral component progressing more than the disc (10° vs 0°, p=0.01). Conclusion Adolescent idiopathic scoliosis initially increases through disc wedging during the rapid growth spurt with progressive vertebral wedging occurring later. PMID:19940737

  17. Transcript Levels of Major Interleukins in Relation to the Clinicopathological Profile of Patients with Tuberculous Intervertebral Discs and Healthy Controls

    PubMed Central

    Liu, Chong; Zhan, Xinli; Xiao, Zengming; Fan, Qie; Deng, Li; Cui, Mingxing; Xiong, Chunxiang; Xue, Jingbo; Xie, Xiangtao

    2014-01-01

    Objectives The purpose of the present study was to simultaneously examine the transcript levels of a large number of interleukins (ILs; IL-9, IL-10, IL-12, IL-13, IL-16, IL-17, IL-18, IL-26, and IL-27) and investigate their correlation with the clinicopathological profiles of patients with tuberculous intervertebral discs. Methods Clinical data were collected from 150 patients participating in the study from January 2013 to December 2013. mRNA expression levels in 70 tuberculous, 70 herniated, and 10 control intervertebral disc specimens were determined by real-time polymerase chain reaction. Results IL-10, IL-16, IL-17, IL-18, and IL-27 displayed stronger expression in tuberculous spinal disc tissue than in normal intervertebral disc tissue (P<0.05). Our results illustrated multiple correlations among IL-10, IL-16, IL-17, IL-18, and IL-27 mRNA expression in tuberculous samples. Smoking habits were found to have a positive correlation with IL-17 transcript levels and a negative correlation with IL-10 transcript levels (P<0.05). Pain intensity, symptom duration, C-reactive protein levels, and the erythrocyte sedimentation rate exhibited multiple correlations with the transcript levels of several ILs (P<0.05). Conclusions The experimental data imply a double-sided effect on the activity of ILs in tuberculous spinal intervertebral discs, suggesting that they may be involved in intervertebral discs destruction. Our findings also suggest that smoking may affect the intervertebral discs destruction process of spinal tuberculosis. However, further studies are necessary to elucidate the exact role of ILs in the intervertebral discs destruction process of spinal tuberculosis. PMID:24971599

  18. Evaluation of a new approach to compute intervertebral disc height measurements from lateral radiographic views of the spine.

    PubMed

    Allaire, Brett T; DePaolis Kaluza, M Clara; Bruno, Alexander G; Samelson, Elizabeth J; Kiel, Douglas P; Anderson, Dennis E; Bouxsein, Mary L

    2017-01-01

    Current standard methods to quantify disc height, namely distortion compensated Roentgen analysis (DCRA), have been mostly utilized in the lumbar and cervical spine and have strict exclusion criteria. Specifically, discs adjacent to a vertebral fracture are excluded from measurement, thus limiting the use of DCRA in studies that include older populations with a high prevalence of vertebral fractures. Thus, we developed and tested a modified DCRA algorithm that does not depend on vertebral shape. Participants included 1186 men and women from the Framingham Heart Study Offspring and Third Generation Multidetector CT Study. Lateral CT scout images were used to place 6 morphometry points around each vertebra at 13 vertebral levels in each participant. Disc heights were calculated utilizing these morphometry points using DCRA methodology and our modified version of DCRA, which requires information from fewer morphometry points than the standard DCRA. Modified DCRA and standard DCRA measures of disc height are highly correlated, with concordance correlation coefficients above 0.999. Both measures demonstrate good inter- and intra-operator reproducibility. 13.9 % of available disc heights were not evaluable or excluded using the standard DCRA algorithm, while only 3.3 % of disc heights were not evaluable using our modified DCRA algorithm. Using our modified DCRA algorithm, it is not necessary to exclude vertebrae with fracture or other deformity from disc height measurements as in the standard DCRA. Modified DCRA also yields identical measurements to the standard DCRA. Thus, the use of modified DCRA for quantitative assessment of disc height will lead to less missing data without any loss of accuracy, making it a preferred alternative to the current standard methodology.

  19. Effectiveness of various toothpastes on dentine tubule occlusion.

    PubMed

    Arnold, W H; Prange, M; Naumova, E A

    2015-04-01

    Dentine hypersensitivity is an increasing problem in dentistry. Several products are available that claim to occlude open dentine tubules and to reduce dentine hypersensitivity. The aim of this study was to investigate the effectiveness of several different products on dentine tubule occlusion using qualitative and quantitative methods. Dentine discs were prepared from extracted human premolars and molars. The dentine discs were brushed with 6 different experimental toothpastes, 1 positive control toothpaste and 1 negative control without toothpaste; the brushing simulated a total brushing time of 1 year. Half of the discs were etched with lemon juice after toothpaste application. Standardized scanning electron microphotographs were taken and converted into binary black and white images. The black pixels, which represented the open dentine tubules, were counted and statistically evaluated. Then, half of the dentine discs were broken, and the occlusion of the dentine tubules was investigated using energy dispersive X-ray spectroscopy (EDS). The number of open dentine tubules decreased significantly after brushing with 5 of the 6 tested toothpastes. A significant effect was observed after acid erosion for 3 of the 6 tested toothpastes. EDS revealed partly closed dentine tubules after brushing with 3 toothpastes; however, no partly closed dentine tubules were observed after acid erosion. Some toothpastes are capable of partial dentine tubule occlusion. This occlusion is unstable and can be removed with acid erosion. Desensitizing toothpastes are the most common products that are used against dentine hypersensitivity, and these toothpastes affect dentine tubule occlusion. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Physical examination, magnetic resonance image, and electrodiagnostic study in patients with lumbosacral disc herniation or spinal stenosis.

    PubMed

    Lee, Jung Hwan; Lee, Sang-Ho

    2012-10-01

    To compare the clinical implications of electro-diagnostic study with those of magnetic resonance imaging in patients with lumbosacral intervertebral herniated disc or spinal stenosis. Retrospective study of clinical data. Patients with lumbosacral intervertebral herniated disc or spinal stenosis, diagnosed by clinical assessment and magnetic resonance imaging (MRI), were selected. A total of 753 patients (437 with lumbosacral intervertebral herniated disc and 316 with spinal stenosis) were included in the study. Clinical data for electrodiagnostic study (EDX)and MRI were compared and the sensitivity and specificity of these studies were evaluated. Among all subjects, 267 had radiculopathy on EDX (EDX (+)) and 486 no radiculopathy (EDX(-)). Furthermore, 391 had root compression on MRI (MRI (+)) and 362 no root compression on MRI (MRI (-)). Patients with radioculopathy on EDX (+) showed a significantly higher visual analogue scale score for radiating pain and a higher Oswestry Disability Index than those with negative findings by EDX (-) in the total subjects group and the lumbosacral intervertebral herniated disc subgroup, and there was a trend toward higher Oswestry Disability Index in the spinal stenosis subgroup. Although patients with radioculopathy on root compression on MRI (+) also had a higher visual analogue scale for radiating pain than patients with negative findings by MRI (-) in the total subjects group and the lumbosacral intervertebral herniated disc subgroup, no significant difference was seen in the Oswestry Disability Index. EDX revealed a significant correlation with muscle weakness in the total subjects group and the lumbosacral intervertebral herniated disc subgroup, and trends toward muscle weakness in the spinal stenosis subgroup, whereas there was no such significant correlation for MRI findings in any group. Electrodiagnostic study had a higher specificity in terms of physical examination data than MRI, in spite of its lower sensitivity. Electrodiagnostic study was significantly more correlated with clinical data, especially leg muscle weakness and functional status, and showed a higher specificity than MRI in patients with lumbosacral intervertebral herniated disc or spinal stenosis.

  1. Cloning and functional analysis of the promoter region of the human Disc large gene.

    PubMed

    Cavatorta, Ana Laura; Giri, Adriana A; Banks, Lawrence; Gardiol, Daniela

    2008-11-15

    A number of studies have demonstrated the involvement of human Disc large (DLG1) in the control of both cell polarity and maintenance of tissue architecture. However, the mechanisms controlling DLG1 transcription are not fully understood. This is relevant since DLG1 is lost in many tumours during the later stages of malignant progression. Therefore, we performed the cloning and functional analysis of a genomic 5' flanking region of the DLG1 open reading frame with promoter activity. We analyzed the activity of a series of 5' deletion constructs of the DLG1 promoter and determined the minimal essential sequences that are required for promoter activity as well as cis-elements that regulate transcription. We found, within the DLG1 promoter sequences, consensus-binding sites for the Snail family of transcription factors that repress the expression of epithelial markers and are up-regulated in a variety of tumours. Snail transcription factors repress the transcriptional activity of the DLG1 promoter and, ectopically expressed Snail proteins bind to the native DLG1 promoter. These data suggest a role for Snail transcription factors in the control of DLG1 expression and provide a basis for understanding the transcriptional regulation of DLG1.

  2. Disrupted-in-Schizophrenia-1 Attenuates Amyloid-β Generation and Cognitive Deficits in APP/PS1 Transgenic Mice by Reduction of β-Site APP-Cleaving Enzyme 1 Levels

    PubMed Central

    Deng, Qing-Shan; Dong, Xing-Yu; Wu, Hao; Wang, Wang; Wang, Zhao-Tao; Zhu, Jian-Wei; Liu, Chun-Feng; Jia, Wei-Qiang; Zhang, Yan; Schachner, Melitta; Ma, Quan-Hong; Xu, Ru-Xiang

    2016-01-01

    Disrupted-in-Schizophrenia-1 (DISC1) is a genetic risk factor for a wide range of major mental disorders, including schizophrenia, major depression, and bipolar disorders. Recent reports suggest a potential role of DISC1 in the pathogenesis of Alzheimer's disease (AD), by referring to an interaction between DISC1 and amyloid precursor protein (APP), and to an association of a single-nucleotide polymorphism in a DISC1 intron and late onset of AD. However, the function of DISC1 in AD remains unknown. In this study, decreased levels of DISC1 were observed in the cortex and hippocampus of 8-month-old APP/PS1 transgenic mice, an animal model of AD. Overexpression of DISC1 reduced, whereas knockdown of DISC1 increased protein levels, but not mRNA levels of β-site APP-Cleaving Enzyme 1 (BACE1), a key enzyme in amyloid-β (Aβ) generation. Reduction of BACE1 protein levels by overexpression of DISC1 was accompanied by an accelerating decline rate of BACE1, and was blocked by the lysosomal inhibitor chloroquine, rather than proteasome inhibitor MG-132. Moreover, overexpression of DISC1 in the hippocampus with an adeno-associated virus reduced the levels of BACE1, soluble Aβ40/42, amyloid plaque density, and rescued cognitive deficits of APP/PS1 transgenic mice. These results indicate that DISC1 attenuates Aβ generation and cognitive deficits of APP/PS1 transgenic mice through promoting lysosomal degradation of BACE1. Our findings provide new insights into the role of DISC1 in AD pathogenesis and link a potential function of DISC1 to the psychiatric symptoms of AD. PMID:26062786

  3. The vertical structure of gaseous galaxy discs in cold dark matter haloes

    NASA Astrophysics Data System (ADS)

    Benítez-Llambay, Alejandro; Navarro, Julio F.; Frenk, Carlos S.; Ludlow, Aaron D.

    2018-01-01

    We study the vertical structure of polytropic centrifugally supported gaseous discs embedded in cold dark matter (CDM) haloes. At fixed radius, R, the shape of the vertical density profile depends weakly on whether the disc is self-gravitating (SG) or non-self-gravitating (NSG). The disc 'characteristic' thickness, zH, set by the midplane sound speed and circular velocity, zNSG = (cs/Vc)R, in the NSG case, and by the sound speed and surface density, z_SG = c_s^2/GΣ, in SG discs, is smaller than zSG and zNSG. SG discs are typically Toomre unstable, NSG discs are stable. Exponential discs in CDM haloes with roughly flat circular velocity curves 'flare' outwards. Flares in mono abundance or coeval populations in galaxies like the Milky Way are thus not necessarily due to radial migration. For the polytropic equation of state of the Evolution and Assembly of GaLaxies and their Environments (EAGLE) simulations, discs that match observational constraints are NSG for Md < 3 × 109 M⊙ and SG at higher masses, if fully gaseous. We test these analytic results using a set of idealized smoothed particle hydrodynamic simulations and find excellent agreement. Our results clarify the role of the gravitational softening on the thickness of simulated discs, and on the onset of radial instabilities. EAGLE low-mass discs are NSG so the softening plays no role in their vertical structure. High-mass discs are expected to be SG and unstable, and may be artificially thickened and stabilized unless gravity is well resolved. Simulations with spatial resolution high enough to not compromise the vertical structure of a disc also resolve the onset of their instabilities, but the converse is not true.

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

    PubMed

    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 of cross bridges in the aging and degenerating intervertebral disc would be advantageous or detrimental, and this question should be addressed by future studies. Copyright © 2011 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  5. Analyzing notochord segmentation and intervertebral disc formation using the twhh:gfp transgenic zebrafish model.

    PubMed

    Haga, Yutaka; Dominique, Vincent J; Du, Shao Jun

    2009-10-01

    To characterize the process of vertebral segmentation and disc formation in living animals, we analyzed tiggy-winkle hedgehog (twhh):green fluorescent protein (gfp) and sonic hedgehog (shh):gfp transgenic zebrafish models that display notochord-specific GFP expression. We found that they showed distinct patterns of expression in the intervertebral discs of late stage fish larvae and adult zebrafish. A segmented pattern of GFP expression was detected in the intervertebral disc of twhh:gfp transgenic fish. In contrast, little GFP expression was found in the intervertebral disc of shh:gfp transgenic fish. Treating twhh:gfp transgenic zebrafish larvae with exogenous retinoic acid (RA), a teratogenic factor on normal development, resulted in disruption of notochord segmentation and formation of oversized vertebrae. Histological analysis revealed that the oversized vertebrae are likely due to vertebral fusion. These studies demonstrate that the twhh:gfp transgenic zebrafish is a useful model for studying vertebral segmentation and disc formation, and moreover, that RA signaling may play a role in this process.

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Influence of plasmon destructive interferences on optical properties of gold planar quadrumers.

    PubMed

    Rahmani, M; Tahmasebi, T; Lin, Y; Lukiyanchuk, B; Liew, T Y F; Hong, M H

    2011-06-17

    Arrays of planar symmetric gold quadrumers consisting of a central nano-disc surrounded by three similar nano-discs belonging to the D(3h) point group were designed and fabricated. Since the geometrical configuration of quadrumers is the same as planar trigonal molecules, nano-discs can play the roles of artificial atoms to study the coupling trends among them. The plasmonic properties of the nano-disc structures are investigated by reflection spectrum measurement and finite-difference time-domain calculation with good agreement. Plasmon interaction among the nano-discs is also studied via a mass-spring coupled oscillator model. A pronounced Fano resonance (FR) is observed for the fabricated nano-discs with inter-disk gaps of around 18 nm during light irradiation at normal incidence. Although the obtained FR is independent of the excitation polarization, the near-field energy spatial distribution can be flexibly tuned by the polarization direction. This has potential applications in nano-lithography, optical switching and nonlinear spectroscopy.

  8. Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.

    PubMed

    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.

  9. Simultaneous brightness contrast of foraging Papilio butterflies

    PubMed Central

    Kinoshita, Michiyo; Takahashi, Yuki; Arikawa, Kentaro

    2012-01-01

    This study focuses on the sense of brightness in the foraging Japanese yellow swallowtail butterfly, Papilio xuthus. We presented two red discs of different intensity on a grey background to butterflies, and trained them to select one of the discs. They were successfully trained to select either a high intensity or a low intensity disc. The trained butterflies were tested on their ability to perceive brightness in two different protocols: (i) two orange discs of different intensity presented on the same intensity grey background and (ii) two orange discs of the same intensity separately presented on a grey background that was either higher or lower in intensity than the training background. The butterflies trained to high intensity red selected the orange disc of high intensity in protocol 1, and the disc on the background of low intensity grey in protocol 2. We obtained similar results in another set of experiments with purple discs instead of orange discs. The choices of the butterflies trained to low intensity red were opposite to those just described. Taken together, we conclude that Papilio has the ability to learn brightness and darkness of targets independent of colour, and that they have the so-called simultaneous brightness contrast. PMID:22179808

  10. Migration of giant planets in a time-dependent planetesimal accretion disc

    NASA Astrophysics Data System (ADS)

    Del Popolo, A.; Ekşi, K. Y.

    2002-05-01

    In this paper we develop further the model for the migration of planets introduced in Del Popolo et al. We first model the protoplanetary nebula as a time-dependent accretion disc, and find self-similar solutions to the equations of the accretion disc that give us explicit formulae for the spatial structure and the temporal evolution of the nebula. These equations are then used to obtain the migration rate of the planet in the planetesimal disc, and to study how the migration rate depends on the disc mass, on its time evolution and on some values of the dimensionless viscosity parameter α . We find that planets that are embedded in planetesimal discs, having total mass of 10-4 -0.1Msolar , can migrate inward a large distance for low values of α (e.g., α ~=10-3 -10-2 ) and/or large disc mass, and can survive only if the inner disc is truncated or because of tidal interaction with the star. Orbits with larger a are obtained for smaller values of the disc mass and/or for larger values of α . This model may explain several orbital features of the recently discovered giant planets orbiting nearby stars.

  11. Truncated disc surface brightness profiles produced by flares

    NASA Astrophysics Data System (ADS)

    Borlaff, Alejandro; Eliche-Moral, M. Carmen; Beckman, John; Font, Joan

    2017-03-01

    Previous studies have discarded that flares in galactic discs may explain the truncation that are frequently observed in highly-inclined galaxies (Kregel et al. 2002). However, no study has systematically analysed this hypothesis using realistic models for the disc, the flare and the bulge. We derive edge-on and face-on surface brightness profiles for a series of realistic galaxy models with flared discs that sample a wide range of structural and photometric parameters across the Hubble Sequence, accordingly to observations. The surface brightness profile for each galaxy model has been simulated for edge-on and face-on views to find out whether the flared disc produces a significant truncation in the disc in the edge-on view compared to the face-on view or not. In order to simulate realistic images of disc galaxies, we have considered the observational distribution of the photometric parameters as a function of the morphological type for three mass bins (10 < log10(M/M ⊙) < 10.7, 10.7 < log10(M/M ⊙) < 11 and log10(M/M ⊙) > 11), and four morphological type bins (S0-Sa, Sb-Sbc, Sc-Scd and Sd-Sdm). For each mass bin, we have restricted the photometric and structural parameters of each modelled galaxy to their characteristic observational ranges (μ0, disc, μeff, bulge, B/T, M abs, r eff, n bulge, h R, disc) and the flare in the disc (h z, disc/h R, disc, ∂h z, disc/∂R, see de Grijs & Peletier 1997, Graham 2001, López-Corredoira et al. 2002, Yoachim & Dalcanton 2006, Bizyaev et al. 2014, Mosenkov et al. 2015). Contrary to previous claims, the simulations show that realistic flared disks can be responsible for the truncations observed in many edge-on systems, preserving the profile of the non-flared analogous model in face-on view. These breaks reproduce the properties of the weak-to-intermediate breaks observed in many real Type-II galaxies in the diagram relating the radial location of the break (R brkII) in units of the inner disk scale-length with the break strength S (Laine et al. 2014). Radial variation of the scale-height of the disc (flaring) can explain the existence of many breaks in edge-on galaxies, especially of those with low break strengths 10\\frac{ho}{hi} \\sim \\ [-0.3,-0.1]$ .

  12. Comparative analysis of the structure of temporomandibular joint in human and rabbit.

    PubMed

    Tomasello, Giovanni; Sorce, Alessandra; Mazzola, Margherita; Barone, Rosario; Lo Piccolo, Chiara; Farina, Felicia; Zummo, Giovanni; Carini, Francesco

    2017-01-16

    In order to increase knowledge on the morphology and structure of the articular disc of the TMJ for a better understanding of the functional role of the same, it proceeded with an investigation on histological samples in the block of 'TMJ and periarticular tissues of adult rabbits and human fetuses at different stage of development.

  13. Clinical and radiological factors related to the presence of motor deficit in lumbar disc prolapse: a prospective analysis of 70 consecutive cases with neurological deficit.

    PubMed

    Krishnan, Vibhu; Rajasekaran, Shanmuganathan; Aiyer, Siddharth N; Kanna, Rishi; Shetty, Ajoy Prasad

    2017-10-01

    To analyse the clinic-radiological factors associated with neurological deficit following lumbar disc herniation. A prospective, cross-sectional study was performed in 140 cases of micro-discectomy following lumbar disc herniation. Group 1 included 70 consecutive patients with motor deficit and group 2 (controls) included 70 patients with intact neurology. Motor deficit was defined as the occurrence of motor power ≤3/5 in L2-S1 myotomes. Multiple clinical and radiological parameters were studied between the two groups. Patients with diabetes (p 0.004), acute onset of symptoms (p 0.036), L3-4 discs (p 0.001), sequestrated discs (p 0.004), superiorly migrated discs (p 0.012) and central discs (p 0.004), greater antero-posterior disc dimension (p 0.023), primary canal stenosis (p 0.0001); and greater canal compromise (p 0.002) had a significant correlation with the development of neurological deficit. The presence of four or more of these risk factors showed a higher chance of the presence of motor deficit (sensitivity of 74%, specificity of 77%). Age, sex, previous precipitating events, severity of pain, smoking, and number of herniations levels did not affect the occurrence of deficit (p > 0.05 for all). Patients with or without bladder symptoms were similar with respect to all clinico-radiological parameters. However, the time delay since the occurrence of deficit was significantly shorter in patients with bladder involvement (p 0.001). Patients with diabetes, acute presentation, central, sequestrated and superiorly migrated discs, high lumbar disc prolapse, and greater spinal canal compromise are predisposed to the presence of motor deficit.

  14. Cervical intradural disc herniation.

    PubMed

    Iwamura, Y; Onari, K; Kondo, S; Inasaka, R; Horii, H

    2001-03-15

    A case report of anterior en bloc resected cervical intradural disc herniation and a review of the literature. To discuss the pathogenesis of cervical intradural disc herniation. Including this study case, only 17 cases of cervical intradural disc herniation have been reported. There have been few detailed reports concerning the pathogenesis of cervical intradural disc herniation. A cervical intradural disc herniation at C6-C7, with localized hypertrophy and segmentally ossified posterior longitudinal ligament, is reported in a 45-year-old man who had Brown-Sequard syndrome diagnosed on neurologic examination. Neuroradiologic, operative, and histologic findings, particularly the pathology of the anterior en bloc resected posterior vertebral portion of C6 and C7, were evaluated for discussion of the pathogenesis. Adhesion of dura mater and hypertrophic posterior longitudinal ligament was observed around a perforated portion of the herniated disc, and histologic study showed irregularity in fiber alignment accompanied by scattered inflammatory cell infiltration and hypertrophy in the posterior longitudinal ligament. The cervical intradural disc herniation was removed successfully and followed by C5-Th1 anterior interbody fusion with fibular strut graft. Neurologic recovery was complete except for minor residual sensory disturbance in the leg 7 years after the surgery. Cervical intradural disc herniation is an extremely rare condition. The pathogenesis remains obscure. Only 16 cases have been reported in the literature, and there has been little discussion concerning the local pathology of the herniated portion. The pathogenesis of the disease in the patient reported here was considered to be the adhesion and fragility of dura mater and posterior longitudinal ligament. This was caused by hypertrophy, with chronic inflammation and ossification of the posterior longitudinal ligament sustaining chronic mechanical irritation to the dura mater, leading to perforation of the herniated disc by an accidental force.

  15. A wireless sequentially actuated microvalve system

    NASA Astrophysics Data System (ADS)

    Baek, Seung-Ki; Yoon, Yong-Kyu; Jeon, Hye-Seon; Seo, Soonmin; Park, Jung-Hwan

    2013-04-01

    A wireless microvalve system was fabricated based on induction heating for flow control in microfluidics by sequential valve opening. In this approach, we used paraffin wax as a flow plug, which can be changed from solid to liquid with adjacent heating elements operated by induction heating. Programmable opening of valves was devised by using different thermal responses of metal discs to a magnetic field. Copper and nickel discs with a diameter of 2.5 mm and various thicknesses (50, 100 and 200 µm) were prepared as heating elements by a laser cutting method, and they were integrated in the microfluidic channel as part of the microvalve. A calorimetric test was used to measure the thermal properties of the discs in terms of kinds of metal and disc thickness. Sequential openings of the microvalves were performed using the difference in the thermal response of 100 µm thick copper disc and 50 µm thick nickel disc for short-interval openings and 200 µm thick copper disc and 100-µm-thick nickel disc for long-interval openings. The thermal effect on fluid samples as a result of induction heating of the discs was studied by investigating lysozyme denaturation. More heat was generated in heating elements made of copper than in those made of nickel, implying differences in the thermal response of heating elements made of copper and nickel. Also, the thickness of the heating elements affected the thermal response in the elements. Valve openings for short intervals of 1-5 s and long intervals of 15-23 s were achieved by using two sets of heating elements. There was no significant change in lysozyme activity by increasing the temperature of the heating discs. This study demonstrates that a wireless sequentially actuated microvalve system can provide programmed valve opening, portability, ease of fabrication and operation, disposability, and low cost.

  16. Gravitational Instabilities in a Protosolar-like Disc

    NASA Astrophysics Data System (ADS)

    Evans, Mark Graham

    2018-02-01

    This thesis presents a study of protoplanetary discs around young, low mass protostars. Such discs are believed to be massive enough to develop gravitational instabilities, which subsequently form spiral structures. The dynamical and chemical evolutions of a protosolar-like, gravitationally unstable disc are explored and the spiral structure in the disc is found to shock-heat material. This affects the chemical composition via enhanced desorption rates and endothermic reaction rates and through global mixing of the disc. As a result, the gravitational instability in the model disc leads to transient and permanent changes in the disc chemistry, and also provides a chemically-rich midplane in contrast to simulations of more evolved discs. Secondly, radiative transfer calculations are performed for the dust continuum, and model-tailored grid construction is found to improve the accuracy of the resultant flux images. Continuum observations of the model disc are synthesised and the spiral structure (driven by the gravitational instability) is shown to be readily detectable with ALMA across a range of frequencies, disc inclinations and dust opacities. The derivation of disc mass from the observed flux densities is explored but the method commonly utilised is found to be unreliable and underestimate the disc mass. Therefore, it is concluded that gravitational instabilities could be retrospectively validated in discs previously thought not massive enough to be self-gravitating. Finally, radiative transfer calculations are performed for molecular line transitions. Methods for improving the accuracy of line flux images are explored and the validity of assuming local thermodynamic equilibrium is assessed. Observations of the line fluxes are synthesised without noise and the spiral structure is found to be traced to an extent by all transitions considered, which is not necessarily congruent with the underlying distribution of the molecular species. The disc is seen in absorption in all transitions considered, due to the global mixing of the disc, which suggests absorption features could be a signature of gravitational instability in young protoplanetary discs. The sensitivities required to detect flux originating in spiral features are determined and it is found that a dedicated observation with ALMA should be capable of spatially resolving spiral structure in a Class 0 disc. Whether the spiral structure can be also be determined from spectral features is explored, which is shown to only be reliable with PV diagrams of nearly edge-on discs. The derivation of protostellar mass from PV diagrams is also explored and found to most likely be unreliable for gravitationally unstable discs.

  17. The evaluation of lateral pterygoid muscle pathologic changes and insertion patterns in temporomandibular joints with or without disc displacement using magnetic resonance imaging.

    PubMed

    Imanimoghaddam, M; Madani, A S; Hashemi, E M

    2013-09-01

    Temporomandibular joint (TMJ) disc displacement is a common disorder in patients with internal derangement. Certain anatomic features of TMJ may make the patient prone to this condition, namely lateral pterygoid muscle (LPM) insertion variations. The aim of this study was to investigate LPM attachments and their relationships with disc displacement and subsequent pathologic changes. A total of 26 patients with clinical temporomandibular disorders (TMDs) and a control group of 14 unaffected individuals were studied. Magnetic resonance images (MRIs) were taken to evaluate LPM insertion patterns, superior LPM head pathologic changes, and relative disc to condyle position. Data registration and analysis were done using SPSS v. 16.0. The most common variation (type I) was shown to be the superior head with two bundles, one attached to the disc and another to the condyle. No significant relationship between LPM insertion type and disc displacement or pathologic changes of the muscle was found. However, a link between disc displacement and muscle pathologic changes was established (P=0.001). Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  18. Reducing the anisotropy of a Brazilian disc generated in a bonded-particle model

    NASA Astrophysics Data System (ADS)

    Zhang, Q.; Zhang, X. P.; Ji, P. Q.

    2018-03-01

    The Brazilian test is a widely used method for determining the tensile strength of rocks and for calibrating parameters in bonded-particle models (BPMs). In previous studies, the Brazilian disc has typically been trimmed from a compacted rectangular specimen. The present study shows that different tensile strength values are obtained depending on the compressive loading direction. Several measures are proposed to reduce the anisotropy of the disc. The results reveal that the anisotropy of the disc is significantly influenced by the compactibility of the specimen from which it is trimmed. A new method is proposed in which the Brazilian disc is directly generated with a particle boundary, effectively reducing the anisotropy. The stiffness (particle and bond) and strength (bond) of the boundary are set at less than and greater than those of the disc assembly, respectively, which significantly decreases the stress concentration at the boundary contacts and prevents breakage of the boundary particle bonds. This leads to a significant reduction in the anisotropy of the disc and the discreteness of the tensile strength. This method is more suitable for carrying out a realistic Brazilian test for homogeneous rock-like material in the BPM.

  19. Lessons from the Auriga discs: the hunt for the Milky Way's ex situ disc is not yet over

    NASA Astrophysics Data System (ADS)

    Gómez, Facundo A.; Grand, Robert J. J.; Monachesi, Antonela; White, Simon D. M.; Bustamante, Sebastian; Marinacci, Federico; Pakmor, Rüdiger; Simpson, Christine M.; Springel, Volker; Frenk, Carlos S.

    2017-12-01

    We characterize the contribution from accreted material to the galactic discs of the Auriga Project, a set of high-resolution magnetohydrodynamic cosmological simulations of late-type galaxies performed with the moving-mesh code AREPO. Our goal is to explore whether a significant accreted (or ex situ) stellar component in the Milky Way disc could be hidden within the near-circular orbit population, which is strongly dominated by stars born in situ. One-third of our models shows a significant ex situ disc but this fraction would be larger if constraints on orbital circularity were relaxed. Most of the ex situ material (≳50 per cent) comes from single massive satellites (>6 × 1010 M⊙). These satellites are accreted with a wide range of infall times and inclination angles (up to 85°). Ex situ discs are thicker, older and more metal poor than their in situ counterparts. They show a flat median age profile, which differs from the negative gradient observed in the in situ component. As a result, the likelihood of identifying an ex situ disc in samples of old stars on near-circular orbits increases towards the outskirts of the disc. We show three examples that, in addition to ex situ discs, have a strongly rotating dark matter component. Interestingly, two of these ex situ stellar discs show an orbital circularity distribution that is consistent with that of the in situ disc. Thus, they would not be detected in typical kinematic studies.

  20. Dominant negative DISC1 mutant mice display specific social behaviour deficits and aberration in BDNF and cannabinoid receptor expression.

    PubMed

    Kaminitz, Ayelet; Barzilay, Ran; Segal, Hadar; Taler, Michal; Offen, Daniel; Gil-Ad, Irit; Mechoulam, Raphael; Weizman, Abraham

    2014-01-01

    OBJECTIVES. Disrupted in schizophrenia 1 (DISC1) is considered the most prominent candidate gene for schizophrenia. In this study, we aimed to characterize behavioural and brain biochemical traits in a mouse expressing a dominant negative DISC1mutant (DN-DISC1). DN-DISC1 mice underwent behavioural tests to evaluate object recognition, social preference and social novelty seeking. ELISA was conducted on brain tissue to evaluate BDNF levels. Western blot was employed to measure BDNF receptor (TrkB) and cannabinoid receptor CB1. The mutant DISC1 mice displayed deficits in preference to social novelty while both social preference and object recognition were intact. Biochemical analysis of prefrontal cortex and hippocampus revealed a modest reduction in cortical TrkB protein levels of male mice while no differences in BDNF levels were observed. We found sex dependent differences in the expression of cannabinoid-1 receptors. We describe novel behavioural and biochemical abnormalities in the DN-DISC1 mouse model of schizophrenia. The data shows for the first time a possible link between DISC1 mutation and the cannabinoid system.

  1. Forming Disc Galaxies In Major Mergers: Radial Density Profiles And Angular Momentum

    NASA Astrophysics Data System (ADS)

    Peschken, Nicolas; Athanassoula, E.; Rodionov, S. A.; Lambert, J. C.

    2017-06-01

    In Athanassoula et al. (2016), we used high resolution N-body hydrodynamical simulations to model the major merger between two disc galaxies with a hot gaseous halo each, and showed that the remnant is a spiral galaxy. The two discs are destroyed by the collision, but after the merger, accretion from the surrounding gaseous halo allows the building of a new disc in the remnant galaxy. In Peschken et al. (2017), we used these simulations to study the radial surface density profiles of the remnant galaxies with downbending profiles (type II), i.e. composed of an inner and an outer exponential disc separated by a break. We analyzed the effect of angular momentum on these profiles, and found that the inner and outer disc scalelengths, as well as the break radius, all increase linearly with the total angular momentum of the initial merging system. Following the angular momentum redistribution in our simulations, we find that the disc angular momentum is acquired via accretion from the gaseous halo. Furthermore, high angular momentum systems give more angular momentum to their discs, which affects directly their radial density profile.

  2. DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212.

    PubMed

    Kim, Ju Young; Duan, Xin; Liu, Cindy Y; Jang, Mi-Hyeon; Guo, Junjie U; Pow-anpongkul, Nattapol; Kang, Eunchai; Song, Hongjun; Ming, Guo-li

    2009-09-24

    Disrupted-in-schizophrenia 1 (DISC1), a susceptibility gene for major mental illnesses, regulates multiple aspects of embryonic and adult neurogenesis. Here, we show that DISC1 suppression in newborn neurons of the adult hippocampus leads to overactivated signaling of AKT, another schizophrenia susceptibility gene. Mechanistically, DISC1 directly interacts with KIAA1212, an AKT binding partner that enhances AKT signaling in the absence of DISC1, and DISC1 binding to KIAA1212 prevents AKT activation in vitro. Functionally, multiple genetic manipulations to enhance AKT signaling in adult-born neurons in vivo exhibit similar defects as DISC1 suppression in neuronal development that can be rescued by pharmacological inhibition of mammalian target of rapamycin (mTOR), an AKT downstream effector. Our study identifies the AKT-mTOR signaling pathway as a critical DISC1 target in regulating neuronal development and provides a framework for understanding how multiple susceptibility genes may functionally converge onto a common pathway in contributing to the etiology of certain psychiatric disorders.

  3. METABOLIC EFFECTS OF ANGULATION, COMPRESSION AND REDUCED MOBILITY ON ANNULUS FIBROSIS IN A MODEL OF ALTERED MECHANICAL ENVIRONMENT IN SCOLIOSIS

    PubMed Central

    Stokes, Ian A.F.; McBride, Carole; Aronsson, David D.; Roughley, Peter J.

    2013-01-01

    Study Design Comparison of disc tissue from rat tails in six groups having different mechanical conditions imposed. Objectives To identify disc annulus changes associated with the supposed altered biomechanical environment in a spine with scoliosis deformity using an immature rat model that produces disc narrowing and wedging. Background Intervertebral discs become wedged and narrowed in a scoliosis curve, probably due in part to altered biomechanical environment. Methods Tail discs of 5-week-old immature Sprague-Dawley rats were subjected to an altered mechanical environment using an external apparatus applying permutations of loading and deformity for 5 weeks. Four groups of rats (A) 15 degrees Angulation, (B) Angulation with 0.1 MPa Compression, (C) 0.1 MPa Compression, and (R) Reduced mobility, together with a sham and a control group were studied. Disc height changes and matrix composition (water, DNA, GAG and HA content) were measured after 5 weeks, and proline and sulphate incorporation and mRNA expression were measured at 5 days and 5 weeks. Results After 5 weeks, disc space was significantly narrowed relative to internal controls in all four intervention groups. Water content and cellularity (DNA content) were not different at interventional levels relative to internal controls and not different between the concave and convex sides of the angulated discs. There was increased GAG content in compressed tissue (in Groups B and C), as expected, and compression resulted in a decrease in hyaluronic acid size. Slightly increased incorporation of tritiated-proline into the concave side of angulated discs and compressed discs was observed. Asymmetries of gene expression in Groups A and B, and some group-wise differences, did not identify consistent patterns associating the discs’ responses to mechanical alterations. Conclusions Intervertebral discs in this model underwent substantial narrowing after 5 weeks, with minimal alteration in tissue composition and minimal evidence of metabolic changes. PMID:27927288

  4. Biological intervertebral disc replacement: an in vivo model and comparison of two surgical techniques to approach the rat caudal disc

    PubMed Central

    Gebhard, Harry; James, Andrew R.; Bowles, Robby D.; Dyke, Jonathan P.; Saleh, Tatianna; Doty, Stephen P.; Bonassar, Lawrence J.; Härtl, Roger

    2011-01-01

    Study design: Prospective randomized animal study. Objective: To determine a surgical technique for reproducible and functional intervertebral disc replacement in an orthotopic animal model. Methods: The caudal 3/4 intervertebral disc (IVD) of the rat tail was approached by two surgical techniques: blunt dissection, stripping and retracting (Technique 1) or incising and repairing (Technique 2) the dorsal longitudinal tendons. The intervertebral disc was dissected and removed, and then either discarded or reinserted. Outcome measures were perioperative complications, spontaneous tail movement, 7T MRI (T1- and T2-sequences for measurement of disc space height (DSH) and disc hydration). Microcomputed tomographic imaging (micro CT) was additionally performed postmortem. Results: No vascular injuries occurred and no systemic or local infections were observed over the course of 1 month. Tail movements were maintained. With tendon retraction (Technique 1) gross loss of DSH occurred with both discectomy and reinsertion. Tendon division (Technique 2) maintained DSH with IVD reinsertion but not without. The DSH was demonstrated on MRI measurement. A new scoring system to assess IVD appearances was described. Conclusions: The rat tail model, with a tendon dividing surgical technique, can function as an orthotopic animal model for IVD research. Mechanical stimulation is maintained by preserved tail movements. 7T MRI is a feasible modality for longitudinal monitoring for the rat caudal disc. PMID:22956934

  5. A flickering study of nova-like systems KR Aur and UU Aqr

    NASA Astrophysics Data System (ADS)

    Dobrotka, A.; Mineshige, S.; Casares, J.

    2012-03-01

    We present a study of the flickering activity in two nova-like systems, KR Aur and UU Aqr. We applied a statistical model of flickering simulations in accretion discs based on turbulent angular momentum transport between two adjacent rings with an exponential distribution of the turbulence dimension scale. The model is based on a steady-state disc model, which is satisfied in the case of hot ionized discs of nova-like cataclysmic variables. Our model successfully fits the observed power-density spectrum of KR Aur with the disc parameter α= 0.10-0.40 and an inner-disc truncation radius in the range Rin= 0.88-1.67 × 109 cm. The exact values depend on the mass-transfer rate in the sense that α decreases and Rin increases with mass-transfer rate. In any case, the inner-disc radius found for KR Aur is considerably smaller than those for quiescent dwarf novae, as predicted by the disc instability model. On the other hand, our simulations fail to reproduce the power-density spectrum of UU Aqr. A tantalizing explanation involves the possible presence of spiral waves, which are expected in UU Aqr because of its low mass ratio but not in KR Aur. In general our model predicts the observed concentration of flickering in the central disc. We explain this by the radial dependence of the angular-momentum gradient.

  6. Rock deformation equations and application to the study on slantingly installed disc cutter

    NASA Astrophysics Data System (ADS)

    Zhang, Zhao-Huang; Meng, Liang; Sun, Fei

    2014-08-01

    At present the mechanical model of the interaction between a disc cutter and rock mainly concerns indentation experiment, linear cutting experiment and tunnel boring machine (TBM) on-site data. This is not in line with the actual rock-breaking movement of the disc cutter and impedes to some extent the research on the rock-breaking mechanism, wear mechanism and design theory. Therefore, our study focuses on the interaction between the slantingly installed disc cutter and rock, developing a model in accordance with the actual rock-breaking movement. Displacement equations are established through an analysis of the velocity vector at the rock-breaking point of the disc cutter blade; the functional relationship between the displacement parameters at the rock-breaking point and its rectangular coordinates is established through an analysis of micro-displacement vectors at the rock-breaking point, thus leading to the geometric equations of rock deformation caused by the slantingly installed disc cutter. Considering the basically linear relationship between the cutting force of disc cutters and the rock deformation before and after the leap break of rock, we express the constitutive relations of rock deformation as generalized Hooke's law and analyze the effect of the slanting installation angle of disc cutters on the rock-breaking force. This will, as we hope, make groundbreaking contributions to the development of the design theory and installation practice of TBM.

  7. Effects of A Novel Disc Formulation on Dry Mouth Symptoms and Enamel Remineralization in Patients With Hyposalivation: An In Vivo Study.

    PubMed

    Ho, Jessica; Firmalino, Miracle Vania; Anbarani, Afarin Golabgir; Takesh, Thair; Epstein, Joel; Wilder-Smith, Petra

    2017-02-01

    The goal of this study was to identify the in vivo effects in patients with hyposalivation of a novel slowly dissolving adhering test disc upon on enamel remineralization, oral biofilm, salivary production, pH and buffering, gingival health, and on self-evaluation of oral well-being. Five subjects with xerostomia wore custom made retainers carrying 5 demineralized enamel chips for periods of 1 week each. In 1 study arm, subjects used the test agent plus oral hygiene self-care; in the other they used oral hygiene self-care only, with a 1 week washout in between arms. The treatment sequence was randomized. Before and after each study arm Plaque Index (PI), Gingival Index (GI) and Sulcus Bleeding Index (mSBI) were recorded. Clinical plaque staining was quantified using digital image analysis. Saliva production, pH and buffering capacity were recorded. Subjects completed a self-evaluation questionnaire for oral comfort. Enamel samples underwent standardized Knoop microhardness testing to quantify mineralization status. Plaque presence and clinical Plaque Indices decreased significantly with test agent use (p<0.05). Five-minute saliva production almost doubled 10 and 40 minutes after oral test disc insertion (significant, p<0.05). Salivary pH buffering improved in 4/5 subjects with disc use. All demineralized tooth samples re-hardened intraorally (p>0.05). The discs favorably impacted eating problems and dental sensitivity. Subjects were positive about disc flavor and mouth feel. Using established in vivo techniques, the effects of a novel product in xerostomic patients were evaluated and quantified. The adhering disc facilitated eating, reduced dental sensitivity, improved saliva production and buffering capacity, reduced plaque, and alleviated xerostomia symptoms. Xerostomia management is challenging. A novel dry mouth disc was effective in alleviating dry mouth symptoms.

  8. Morphological Features and Important Parameters of Large Optic Discs for Diagnosing Glaucoma

    PubMed Central

    Okimoto, Satoshi; Yamashita, Keiko; Shibata, Tetsuo; Kiuchi, Yoshiaki

    2015-01-01

    Purpose To compare the optic disc parameters of glaucomatous eyes to those of non-glaucomatous eyes with large discs. Methods We studied 225 consecutive eyes with large optic discs (>2.82 mm2): 91 eyes with glaucoma and 134 eyes without glaucoma. An eye was diagnosed with glaucoma when visual field defects were detected by the Humphrey Field Analyzer. All of the Heidelberg Retina Tomograph II (HRT II) parameters were compared between the non-glaucomatous and glaucomatous eyes. A logistic regression analysis of the HRT II parameters was used to establish a new formula for diagnosing glaucoma, and the sensitivity and specificity of the Moorfields Regression Analysis (MRA) was compared to the findings made by our analyses. Results The mean disc area was 3.44±0.50 mm2 in the non-glaucomatous group and 3.40±0.52 mm2 in the glaucoma group. The cup area, cup volume, cup-to-disc area ratio, linear cup/disc ratio, mean cup depth, and the maximum cup depth were significantly larger in glaucomatous eyes than in the non-glaucomatous eyes. The rim area, rim volume, cup shape measurement, mean retinal nerve fiber layer (RNFL) thickness, and RFNL cross-sectional area were significantly smaller in glaucomatous eyes than in non-glaucomatous eyes. The cup-to-disc area ratio, the height variation contour (HVC), and the RNFL cross-sectional area were important parameters for diagnosing the early stage glaucoma, and the cup-to-disc area ratio and cup volume were useful for diagnosing advanced stage glaucoma in eyes with a large optic disc. The new formula had higher sensitivity and specificity for diagnosing glaucoma than MRA. Conclusions The cup-to-disc area ratio, HVC, RNFL cross-sectional area, and cup volume were important parameters for diagnosing glaucoma in eyes with a large optic disc. The important disc parameters to diagnose glaucoma depend on the stage of glaucoma in patients with large discs. PMID:25798580

  9. Optical Coherence Tomography Angiography of Optic Disc Perfusion in Glaucoma

    PubMed Central

    Jia, Yali; Wei, Eric; Wang, Xiaogang; Zhang, Xinbo; Morrison, John C.; Parikh, Mansi; Lombardi, Lori H.; Gattey, Devin M.; Armour, Rebecca L.; Edmunds, Beth; Kraus, Martin F.; Fujimoto, James G.; Huang, David

    2014-01-01

    Purpose To compare optic disc perfusion between normal and glaucoma subjects using optical coherence tomography (OCT) angiography and detect optic disc perfusion changes in glaucoma. Design Observational, cross-sectional study. Participants Twenty-four normal subjects and 11 glaucoma patients were included. Methods One eye of each subject was scanned by a high-speed 1050 nm wavelength swept-source OCT instrument. The split-spectrum amplitude-decorrelation angiography algorithm (SSADA) was used to compute three-dimensional optic disc angiography. A disc flow index was computed from four registered scans. Confocal scanning laser ophthalmoscopy (cSLO) was used to measure disc rim area, and stereo photography was used to evaluate cup/disc ratios. Wide field OCT scans over the discs were used to measure retinal nerve fiber layer (NFL) thickness. Main Outcome Measurements Variability was assessed by coefficient of variation (CV). Diagnostic accuracy was assessed by sensitivity and specificity. Comparisons between glaucoma and normal groups were analyzed by Wilcoxon rank-sum test. Correlations between disc flow index, structural assessments, and visual field (VF) parameters were assessed by linear regression. Results In normal discs, a dense microvascular network was visible on OCT angiography. This network was visibly attenuated in glaucoma subjects. The intra-visit repeatability, inter-visit reproducibility, and normal population variability of the optic disc flow index were 1.2%, 4.2%, and 5.0% CV respectively. The disc flow index was reduced by 25% in the glaucoma group (p = 0.003). Sensitivity and specificity were both 100% using an optimized cutoff. The flow index was highly correlated with VF pattern standard deviation (R2 = 0.752, p = 0.001). These correlations were significant even after accounting for age, cup/disc area ratio, NFL, and rim area. Conclusions OCT angiography, generated by the new SSADA algorithm, repeatably measures optic disc perfusion. OCT angiography could be useful in the evaluation of glaucoma and glaucoma progression. PMID:24629312

  10. Effect of ceramic thickness and cement shade on the final shade after bonding using the 3D master system: a laboratory study.

    PubMed

    Montero, Javier; Gómez-Polo, Cristina

    2016-06-01

    The final color of a ceramic restoration is influenced by both the ceramic thickness and the cement shade. This study aims to evaluate the color stability according to the 3D Master System of e.max ceramic discs after bonding with different shades of luting agents. A total of 120 e.max.Press 2M1 HT ceramic discs (60 discs of 1-mm thick and 60 discs of 0.5 mm thick) and three different values of Variolink Veneer cement were used (-3, 0, +3) for the cementation process. An Easyshade compact device was used to measure color shade tabs, according to the 3D Master System, on the discs both before and after the cementation protocols. Bivariate and multivariate analyses were carried out with the spss v.21. After bonding with the different luting agents, only 30% remained as 2M1: specifically, 22% of the thinner discs and 37.3% of the thicker discs. In general, the effect of bonding increased the value and the chroma of the shade to a significant extent. Regression analyses revealed that the most significant predictor for all color parameters was cement shade, the thinner disc group bonded with -3 cement being the most unstable subgroup. According to the 3D Master System, the shade of the luting agent was the main predictor of the final color. However, the final color seems to be somewhat unpredictable, at least according to the modulating factors evaluated in the present study.

  11. Clinical evaluation of disc battery ingestion in children.

    PubMed

    Mirshemirani, AliReza; Khaleghnejad-Tabari, Ahmad; Kouranloo, Jaefar; Sadeghian, Naser; Rouzrokh, Mohsen; Roshanzamir, Fatolah; Razavi, Sajad; Sayary, Ali Akbar; Imanzadeh, Farid

    2012-04-01

    BACKGROUND The purpose of this study was to evaluate the characteristics, management, and outcomes of disc battery ingestion in children. METHODS We reviewed the medical records of children admitted to Mofid Children's Hospital due to disc battery ingestion from January 2006 to January 2010. Clear history, clinical symptoms and results of imaging studies revealed diagnosis of disc battery ingestion in suspected patients. The clinical data reviewed included age, gender, clinical manifestation, radiologic findings, location of disc battery, duration of ingestion, endoscopic results and surgical treatment. RESULTS We found 22 cases (11 males and 11 females) of disc battery ingestion with a mean age of 4.3 years (range: 9 months to 12 years). Common symptoms were vomiting, cough, dysphagia, and dyspnea. The mean duration of ingestion was 2.7 days (4 hours to 1.5 months). A total of 19 patients had histories of disc battery ingestion, but three cases referred with the above symptoms, and the batteries were accidentally found by x-ray. Only three cases had batteries impacted in the esophagus. Twelve batteries were removed endoscopically, 6 batteries spontaneously passed through the gastrointestinal (GI) tract within 5 to 7 days, and 4 patients underwent surgery due to complications: 3 due to tracheo-esophageal fistula (TEF) and 1 due to intestinal perforation. There was no mortality in our study. CONCLUSION Most cases of disc battery ingestion run uneventful courses, but some may be complicated. If the battery lodges in the esophagus, emergency endoscopic management is necessary. However, once in the stomach, it will usually pass through the GI tract.

  12. A Small Disc Area Is a Risk Factor for Visual Field Loss Progression in Primary Open-Angle Glaucoma: The Glaucoma Stereo Analysis Study.

    PubMed

    Kitaoka, Yasushi; Tanito, Masaki; Yokoyama, Yu; Nitta, Koji; Katai, Maki; Omodaka, Kazuko; Nakazawa, Toru

    2018-01-01

    The Glaucoma Stereo Analysis Study, a cross-sectional multicenter collaborative study, used a stereo fundus camera (nonmyd WX) to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients. We compared the associations of each parameter between the visual field loss progression group and no-progression group. The study included 187 eyes of 187 patients with primary open-angle glaucoma or normal-tension glaucoma. We divided the mean deviation (MD) slope values of all patients into the progression group (<-0.3 dB/year) and no-progression group (≧-0.3 dB/year). ONH morphological parameters were calculated with prototype analysis software. The correlations between glaucomatous visual field progression and patient characteristics or each ONH parameter were analyzed with Spearman's rank correlation coefficient. The MD slope averages in the progression group and no-progression group were -0.58 ± 0.28 dB/year and 0.05 ± 0.26 dB/year, respectively. Among disc parameters, vertical disc width (diameter), disc area, cup area, and cup volume in the progression group were significantly less than those in the no-progression group. Logistic regression analysis revealed a significant association between the visual field progression and disc area (odds ratio 0.49/mm 2 disc area). A smaller disc area may be associated with more rapid glaucomatous visual field progression.

  13. High-energy radiation from collisions of high-velocity clouds and the Galactic disc

    NASA Astrophysics Data System (ADS)

    del Valle, Maria V.; Müller, A. L.; Romero, G. E.

    2018-04-01

    High-velocity clouds (HVCs) are interstellar clouds of atomic hydrogen that do not follow normal Galactic rotation and have velocities of a several hundred kilometres per second. A considerable number of these clouds are falling down towards the Galactic disc. HVCs form large and massive complexes, so if they collide with the disc a great amount of energy would be released into the interstellar medium. The cloud-disc interaction produces two shocks: one propagates through the cloud and the other through the disc. The properties of these shocks depend mainly on the cloud velocity and the disc-cloud density ratio. In this work, we study the conditions necessary for these shocks to accelerate particles by diffusive shock acceleration and we study the non-thermal radiation that is produced. We analyse particle acceleration in both the cloud and disc shocks. Solving a time-dependent two-dimensional transport equation for both relativistic electrons and protons, we obtain particle distributions and non-thermal spectral energy distributions. In a shocked cloud, significant synchrotron radio emission is produced along with soft gamma rays. In the case of acceleration in the shocked disc, the non-thermal radiation is stronger; the gamma rays, of leptonic origin, might be detectable with current instruments. A large number of protons are injected into the Galactic interstellar medium, and locally exceed the cosmic ray background. We conclude that under adequate conditions the contribution from HVC-disc collisions to the galactic population of relativistic particles and the associated extended non-thermal radiation might be important.

  14. Origin of chemically distinct discs in the Auriga cosmological simulations

    NASA Astrophysics Data System (ADS)

    Grand, Robert J. J.; Bustamante, Sebastián; Gómez, Facundo A.; Kawata, Daisuke; Marinacci, Federico; Pakmor, Rüdiger; Rix, Hans-Walter; Simpson, Christine M.; Sparre, Martin; Springel, Volker

    2018-03-01

    The stellar disc of the Milky Way shows complex spatial and abundance structure that is central to understanding the key physical mechanisms responsible for shaping our Galaxy. In this study, we use six very high resolution cosmological zoom-in simulations of Milky Way-sized haloes to study the prevalence and formation of chemically distinct disc components. We find that our simulations develop a clearly bimodal distribution in the [α/Fe]-[Fe/H] plane. We find two main pathways to creating this dichotomy, which operate in different regions of the galaxies: (a) an early (z > 1) and intense high-[α/Fe] star formation phase in the inner region (R ≲ 5 kpc) induced by gas-rich mergers, followed by more quiescent low-[α/Fe] star formation; and (b) an early phase of high-[α/Fe] star formation in the outer disc followed by a shrinking of the gas disc owing to a temporarily lowered gas accretion rate, after which disc growth resumes. In process (b), a double-peaked star formation history around the time and radius of disc shrinking accentuates the dichotomy. If the early star formation phase is prolonged (rather than short and intense), chemical evolution proceeds as per process (a) in the inner region, but the dichotomy is less clear. In the outer region, the dichotomy is only evident if the first intense phase of star formation covers a large enough radial range before disc shrinking occurs; otherwise, the outer disc consists of only low-[α/Fe] sequence stars. We discuss the implication that both processes occurred in the Milky Way.

  15. Magnetic Resonance Imaging (MRI) Evaluation for Anterior Disc Displacement of the Temporomandibular Joint.

    PubMed

    Yang, Zhongjun; Wang, Mingguo; Ma, Yingwei; Lai, Qingguo; Tong, Dongdong; Zhang, Fenghe; Dong, Lili

    2017-02-08

    BACKGROUND Magnetic resonance imaging (MRI) is the criterion standard imaging technique for visualization of the temporomandibular joint (TMJ) region, and is currently considered the optimum modality for comprehensive evaluation in patients with temporomandibular joint disorder (TMD). This study was aimed at finding the value of MRI in pre-clinical diagnosis of TMJ disc displacement. MATERIAL AND METHODS Patients primarily diagnosed as having anterior disc displacement by clinical symptoms and X-ray were selected in the present study. MRI was used to evaluate surrounding anatomical structures and position, as well as morphological and signal intensity change between patients and normal controls. RESULTS Posterior band position was significantly different between the patient group and control group. At the maximum opened-mouth position, the location of disc intermediate zone returned to normal. At closed-mouth position, the thickness of anterior and middle, but not posterior, band increased. The motion range of the condyle in the anterior disc displacement without reduction (ADDWR) patient group was significantly less than the value in the anterior disc displacement with reduction (ADDR) patient group and the control group. Whether at closed-mouth position or maximum opened-mouth position, the exudate volume in the patient group was greater than in the normal group. CONCLUSIONS MRI can be successfully used to evaluate multiple morphological changes at different mouth positions of normal volunteers and patients. The disc-condyle relationship can serve as an important indicator in assessing anterior disc displacement, and can be used to distinguish disc displacement with or without reduction.

  16. Magnetic Resonance Imaging (MRI) Evaluation for Anterior Disc Displacement of the Temporomandibular Joint

    PubMed Central

    Yang, Zhongjun; Wang, Mingguo; Ma, Yingwei; Lai, Qingguo; Tong, Dongdong; Zhang, Fenghe; Dong, Lili

    2017-01-01

    Background Magnetic resonance imaging (MRI) is the criterion standard imaging technique for visualization of the temporomandibular joint (TMJ) region, and is currently considered the optimum modality for comprehensive evaluation in patients with temporomandibular joint disorder (TMD). This study was aimed at finding the value of MRI in pre-clinical diagnosis of TMJ disc displacement. Material/Methods Patients primarily diagnosed as having anterior disc displacement by clinical symptoms and X-ray were selected in the present study. MRI was used to evaluate surrounding anatomical structures and position, as well as morphological and signal intensity change between patients and normal controls. Results Posterior band position was significantly different between the patient group and control group. At the maximum opened-mouth position, the location of disc intermediate zone returned to normal. At closed-mouth position, the thickness of anterior and middle, but not posterior, band increased. The motion range of the condyle in the anterior disc displacement without reduction (ADDWR) patient group was significantly less than the value in the anterior disc displacement with reduction (ADDR) patient group and the control group. Whether at closed-mouth position or maximum opened-mouth position, the exudate volume in the patient group was greater than in the normal group. Conclusions MRI can be successfully used to evaluate multiple morphological changes at different mouth positions of normal volunteers and patients. The disc-condyle relationship can serve as an important indicator in assessing anterior disc displacement, and can be used to distinguish disc displacement with or without reduction. PMID:28176754

  17. Lumbar spine intervertebral disc gene delivery: a pilot study in lewis rats.

    PubMed

    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.

  18. The effects of dynamic loading on the intervertebral disc.

    PubMed

    Chan, Samantha C W; Ferguson, Stephen J; Gantenbein-Ritter, Benjamin

    2011-11-01

    Loading is important to maintain the balance of matrix turnover in the intervertebral disc (IVD). Daily cyclic diurnal assists in the transport of large soluble factors across the IVD and its surrounding circulation and applies direct and indirect stimulus to disc cells. Acute mechanical injury and accumulated overloading, however, could induce disc degeneration. Recently, there is more information available on how cyclic loading, especially axial compression and hydrostatic pressure, affects IVD cell biology. This review summarises recent studies on the response of the IVD and stem cells to applied cyclic compression and hydrostatic pressure. These studies investigate the possible role of loading in the initiation and progression of disc degeneration as well as quantifying a physiological loading condition for the study of disc degeneration biological therapy. Subsequently, a possible physiological/beneficial loading range is proposed. This physiological/beneficial loading could provide insight into how to design loading regimes in specific system for the testing of various biological therapies such as cell therapy, chemical therapy or tissue engineering constructs to achieve a better final outcome. In addition, the parameter space of 'physiological' loading may also be an important factor for the differentiation of stem cells towards most ideally 'discogenic' cells for tissue engineering purpose.

  19. Fabrication and Demonstration of Mercury Disc-Well Probes for Stripping-Based Cyclic Voltammetry Scanning Electrochemical Microscopy.

    PubMed

    Barton, Zachary J; Rodríguez-López, Joaquín

    2017-03-07

    Scanning electrochemical microscopy (SECM) is a rising technique for the study of energy storage materials. Hg-based probes allow the extension of SECM investigations to ionic processes, but the risk of irreversible Hg amalgam saturation limits their operation to rapid timescales and dilute analyte solutions. Here, we report a novel fabrication protocol for Hg disc-well ultramicroelectrodes (UMEs), which retain access to stripping information but are less susceptible to amalgam saturation than traditional Hg sphere-caps or thin-films. The amalgamation and stripping behaviors of Hg disc-well UMEs are compared to those of traditional Hg sphere-cap UMEs and corroborated with data from finite element simulations. The improved protection against amalgam saturation allows Hg disc-wells to operate safely in highly concentrated environments at long timescales. The utility of the probes for bulk measurements extends also to SECM studies, where the disc geometry facilitates small tip-substrate gaps and improves both spatial and temporal resolution. Because they can carry out slow, high-resolution anodic stripping voltammetry approaches and imaging in concentrated solutions, Hg disc-well electrodes fill a new analytical niche for studies of ionic reactivity and are a valuable addition to the electrochemical toolbox.

  20. Evidence for the concurrent growth of thick discs and central mass concentrations from S4G imaging

    NASA Astrophysics Data System (ADS)

    Comerón, S.; Elmegreen, B. G.; Salo, H.; Laurikainen, E.; Holwerda, B. W.; Knapen, J. H.

    2014-11-01

    We have produced 3.6 μm + 4.5 μm vertically integrated radial luminosity profiles of 69 edge-on galaxies from the Spitzer Survey of Stellar Structure in Galaxies (S4G). We decomposed the luminosity profiles into a disc and a central mass concentration (CMC). These fits, combined with thin/thick disc decompositions from our previous studies, allow us to estimate the masses of the CMCs, the thick discs, and the thin discs (ℳCMC, ℳT, and ℳT). We obtained atomic disc masses (ℳg) from the literature. We then consider the CMC and the thick disc to be dynamically hot components and the thin disc and the gas disc to be dynamically cold components. We find that the ratio between the mass of the hot components and that of the cold components, (ℳCMC + ℳT)/(ℳt + ℳg), does not depend on the total galaxy mass as described by circular velocities (vc). We also find that the higher the vc, the more concentrated the hot component of a galaxy. We suggest that our results are compatible with having CMCs and thick discs built in a short and early high star forming intensity phase. These components were born thick because of the large scale height of the turbulent gas disc in which they originated. Our results indicate that the ratio between the star forming rate in the former phase and that of the formation of the thin disc is of the order of 10, but the value depends on the duration of the high star forming intensity phase. Appendix A is available in electronic form at http://www.aanda.org

  1. Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia.

    PubMed

    Rampino, Antonio; Walker, Rosie May; Torrance, Helen Scott; Anderson, Susan Maguire; Fazio, Leonardo; Di Giorgio, Annabella; Taurisano, Paolo; Gelao, Barbara; Romano, Raffaella; Masellis, Rita; Ursini, Gianluca; Caforio, Grazia; Blasi, Giuseppe; Millar, J Kirsty; Porteous, David John; Thomson, Pippa Ann; Bertolino, Alessandro; Evans, Kathryn Louise

    2014-01-01

    Cognitive dysfunction is central to the schizophrenia phenotype. Genetic and functional studies have implicated Disrupted-in-Schizophrenia 1 (DISC1), a leading candidate gene for schizophrenia and related psychiatric conditions, in cognitive function. Altered expression of DISC1 and DISC1-interactors has been identified in schizophrenia. Dysregulated expression of DISC1-interactome genes might, therefore, contribute to schizophrenia susceptibility via disruption of molecular systems required for normal cognitive function. Here, the blood RNA expression levels of DISC1 and DISC1-interacting proteins were measured in 63 control subjects. Cognitive function was assessed using neuropsychiatric tests and functional magnetic resonance imaging was used to assess the activity of prefrontal cortical regions during the N-back working memory task, which is abnormal in schizophrenia. Pairwise correlations between gene expression levels and the relationship between gene expression levels and cognitive function and N-back-elicited brain activity were assessed. Finally, the expression levels of DISC1, AKAP9, FEZ1, NDEL1 and PCM1 were compared between 63 controls and 69 schizophrenic subjects. We found that DISC1-interactome genes showed correlated expression in the blood of healthy individuals. The expression levels of several interactome members were correlated with cognitive performance and N-back-elicited activity in the prefrontal cortex. In addition, DISC1 and NDEL1 showed decreased expression in schizophrenic subjects compared to healthy controls. Our findings highlight the importance of the coordinated expression of DISC1-interactome genes for normal cognitive function and suggest that dysregulated DISC1 and NDEL1 expression might, in part, contribute to susceptibility for schizophrenia via disruption of prefrontal cortex-dependent cognitive functions.

  2. Expression of DISC1-Interactome Members Correlates with Cognitive Phenotypes Related to Schizophrenia

    PubMed Central

    Rampino, Antonio; Walker, Rosie May; Torrance, Helen Scott; Anderson, Susan Maguire; Fazio, Leonardo; Di Giorgio, Annabella; Taurisano, Paolo; Gelao, Barbara; Romano, Raffaella; Masellis, Rita; Ursini, Gianluca; Caforio, Grazia; Blasi, Giuseppe; Millar, J. Kirsty; Porteous, David John; Thomson, Pippa Ann; Bertolino, Alessandro; Evans, Kathryn Louise

    2014-01-01

    Cognitive dysfunction is central to the schizophrenia phenotype. Genetic and functional studies have implicated Disrupted-in-Schizophrenia 1 (DISC1), a leading candidate gene for schizophrenia and related psychiatric conditions, in cognitive function. Altered expression of DISC1 and DISC1-interactors has been identified in schizophrenia. Dysregulated expression of DISC1-interactome genes might, therefore, contribute to schizophrenia susceptibility via disruption of molecular systems required for normal cognitive function. Here, the blood RNA expression levels of DISC1 and DISC1-interacting proteins were measured in 63 control subjects. Cognitive function was assessed using neuropsychiatric tests and functional magnetic resonance imaging was used to assess the activity of prefrontal cortical regions during the N-back working memory task, which is abnormal in schizophrenia. Pairwise correlations between gene expression levels and the relationship between gene expression levels and cognitive function and N-back-elicited brain activity were assessed. Finally, the expression levels of DISC1, AKAP9, FEZ1, NDEL1 and PCM1 were compared between 63 controls and 69 schizophrenic subjects. We found that DISC1-interactome genes showed correlated expression in the blood of healthy individuals. The expression levels of several interactome members were correlated with cognitive performance and N-back-elicited activity in the prefrontal cortex. In addition, DISC1 and NDEL1 showed decreased expression in schizophrenic subjects compared to healthy controls. Our findings highlight the importance of the coordinated expression of DISC1-interactome genes for normal cognitive function and suggest that dysregulated DISC1 and NDEL1 expression might, in part, contribute to susceptibility for schizophrenia via disruption of prefrontal cortex-dependent cognitive functions. PMID:24940743

  3. Modelling and observations of molecules in discs around young stars

    NASA Astrophysics Data System (ADS)

    Ilee, John David

    2013-04-01

    This thesis contains a study of molecules within circumstellar discs around young stars. Firstly, the chemistry of a disc around a young, Class 0 protostar is modelled. Such discs are thought to be massive, and thus experience gravitational instabilities, which produce spiral density waves. These affect the chemistry in three ways; by desorbing molecules from dust grains, by providing extra energy for new reactions to take place, and by mixing the internal structure of the disc to provide a rich chemistry near the midplane. Secondly, high resolution near-infrared spectra of 20 massive young stellar objects are presented. The objects display CO first overtone bandhead emission, which is excited in the conditions expected within circumstellar discs. The emission is modelled using a simple analytic model of a Keplerian disc, and good fits are found to all spectra. On average, the discs correspond to being geometrically thin, spread across a wide range of inclinations. The discs are located within the dust sublimation radius, providing strong evidence that the CO emission originates in small gaseous discs, supporting the scenario in which massive stars form via disc accretion. Finally, medium resolution near-infrared spectra of 5 Herbig Ae/Be stars are presented. The spectra cover both CO bandhead and Br gamma emission. Accretion rates are derived from the measuring the Br gamma emission and through modelling the CO emission, however these accretion rates are found to be inconsistent. High resolution archival data of one of the targets is presented, and it is shown that this CO disc model is unable to fit the high resolution data. Therefore, it is concluded that to properly fit CO spectra, high resolution data are needed, and that previously published information determined from low resolution spectra should be treated with caution.

  4. A RCT comparing 7-year clinical outcomes of one level symptomatic cervical disc disease (SCDD) following ProDisc-C total disc arthroplasty (TDA) versus anterior cervical discectomy and fusion (ACDF).

    PubMed

    Loumeau, Thomas P; Darden, Bruce V; Kesman, Thomas J; Odum, Susan M; Van Doren, Bryce A; Laxer, Eric B; Murrey, Daniel B

    2016-07-01

    The objective of this trial was to compare the safety and efficacy of TDA using the ProDisc-C implant to ACDF in patients with single-level SCDD between C3 and C7. We report on the single-site results from a larger multicenter trial of 13 sites using an approved US Food and Drug Administration protocol (prospective, randomized controlled non-inferiority design). Patients were randomized one-to-one to either the ProDisc-C device or ACDF. All enrollees were evaluated pre- and post-operatively at regular intervals through month 84. Visual Analog Scale (VAS) for neck and arm pain/intensity, Neck Disability Index (NDI), Short-Form 36 (SF-36), and satisfaction were assessed. Twenty-two patients were randomized to each arm of the study. Nineteen additional patients received the ProDisc-C via continued access. NDI improved with the ProDisc-C more than with ACDF. Total range of motion was maintained with the ProDisc-C, but diminished with ACDF. Neck and arm pain improved more in the ProDisc-C than ACDF group. Patient satisfaction remained higher in the ProDisc-C group at 7 years. SF-36 scores were higher in the TDA group than ACDF group at 7 years; the difference was not clinically significant. Six additional operations (two at the same level; four at an adjacent level) were performed in the ACDF, but none in the ProDisc-C group. The ProDisc-C implant appears to be safe and effective for the treatment of SCDD. Patients with the implant retained motion at the involved segment and had a lower reoperation rate than those with an ACDF.

  5. The Gas Content Of Protoplanetary Herbig Ae/be Discs As Seen With Herschel

    NASA Astrophysics Data System (ADS)

    Meeus, Gwendolyn; Herschel OTKP, GASPS; Dent, B.

    2011-09-01

    The mechanisms determining planet formation are not (yet) well-understood. Primordial protoplanetary discs consist 99% out of gas, and only 1% out of dust. With time, those discs are believed to evolve from a flaring geometry into a flat geometry, as the initially small dust grains grow to larger sizes and settle towards the mid-plane. In the mean time, the gas will disperse, until so little is left that giant planets no longer can form. As an important piece of the puzzle of planet formation, it is important to understand the influence of the gas heating/cooling processes on the young disc structure, its chemical composition and finally how fast gas gets dispersed. In this talk, we study the protoplanetary discs around Herbig Ae/Be stars, young objects of intermediate mass, in the context of its gas content. We present Herschel PACS spectroscopic observations for a sample that was obtained within the GASPS (Gas in Protoplanetary Systems) Open Time Key Project, concentrating on the detection and characterisation of emission lines of the [OI], [CII], and CO, tracing the disc between 5 and 500 AU. We look for correlations between the observed line fluxes and stellar properties such as effective temperature, Halpha emission, accretion rates and UV flux, as well as the disc properties: degree of flaring, presence and strength of PAH emission and disc mass. We will present a few cases to show how simultaneous modeling (using the thermo-chemical disc code ProDiMo) of the atomic fine structure lines and both molecular lines can constrain the disc gas mass, once the disc structure is derived. Finally, we compare our gas line observations with those of young debris disc stars, for which the HAEBE stars are thought to be progenitors.

  6. System modeling with the DISC framework: evidence from safety-critical domains.

    PubMed

    Reiman, Teemu; Pietikäinen, Elina; Oedewald, Pia; Gotcheva, Nadezhda

    2012-01-01

    The objective of this paper is to illustrate the development and application of the Design for Integrated Safety Culture (DISC) framework for system modeling by evaluating organizational potential for safety in nuclear and healthcare domains. The DISC framework includes criteria for good safety culture and a description of functions that the organization needs to implement in order to orient the organization toward the criteria. Three case studies will be used to illustrate the utilization of the DISC framework in practice.

  7. Drosophila wing imaginal discs respond to mechanical injury via slow InsP3R-mediated intercellular calcium waves

    NASA Astrophysics Data System (ADS)

    Restrepo, Simon; Basler, Konrad

    2016-08-01

    Calcium signalling is a highly versatile cellular communication system that modulates basic functions such as cell contractility, essential steps of animal development such as fertilization and higher-order processes such as memory. We probed the function of calcium signalling in Drosophila wing imaginal discs through a combination of ex vivo and in vivo imaging and genetic analysis. Here we discover that wing discs display slow, long-range intercellular calcium waves (ICWs) when mechanically stressed in vivo or cultured ex vivo. These slow imaginal disc intercellular calcium waves (SIDICs) are mediated by the inositol-3-phosphate receptor, the endoplasmic reticulum (ER) calcium pump SERCA and the key gap junction component Inx2. The knockdown of genes required for SIDIC formation and propagation negatively affects wing disc recovery after mechanical injury. Our results reveal a role for ICWs in wing disc homoeostasis and highlight the utility of the wing disc as a model for calcium signalling studies.

  8. Birth weight and optic nerve head parameters.

    PubMed

    Samarawickrama, Chameen; Huynh, Son C; Liew, Gerald; Burlutsky, George; Mitchell, Paul

    2009-06-01

    To assess the relationship of birth weight, birth length, and head circumference as proxy markers of intrauterine growth, cup/disc ratio, and other optic disc parameters measured using optical coherence tomography (OCT). Population-based cross sectional analysis. The Sydney Childhood Eye Study examined 2353 primarily 12-year-old children from 21 randomly selected secondary schools during 2003 to 2005. Of 2353 children examined, 2134 (90.7%) had OCT scans (Zeiss Stratus OCT, Carl Zeiss Meditec, Dublin, CA) and are included in this study. The "fast" optic disc scan protocol was used. Birth weight, birth length, and head circumference were ascertained from health records. Height and weight were measured using standardized protocols, body mass index (BMI) was defined as weight (kilograms)/ height squared (meters), and sociodemographic information was collected in a questionnaire completed by parents. Low birth weight was defined as birth weight

  9. Lumbar Disc Screening Using Back Pain Questionnaires: Oswestry Low Back Pain Score, Aberdeen Low Back Pain Scale, and Acute Low Back Pain Screening Questionnaire

    PubMed Central

    Kim, Do Yeon; Oh, Chang Hyun; Park, Hyung Chun; Park, Chong Oon

    2012-01-01

    Objective To evaluate the usefulness of back pain questionnaires for lumbar disc screening among Korean young males. Methods We carried out a survey for lumbar disc screening through back pain questionnaires among the volunteers with or without back pain. Three types of back pain questionnaire (Oswestry Low Back Pain Score, Aberdeen Low Back Pain Scale, and Acute Low Back Pain Screeing Questionnaire) were randomly assigned to the examinees. The authors reviewed lumbar imaging studies (simple lumbar radiographs, lumbar computed tomography, and magnetic resolutional images), and the severity of lumbar disc herniation was categorized according to the guidelines issued by the Korean military directorate. We calculated the relationship between the back pain questionnaire scores and the severity of lumbar disc herniation. Results The scores of back pain questionnaires increased according to the severity of lumbar disc herniation. But, the range of scores was very vague, so it is less predictable to detect lumbar disc herniation using only back pain questionnaires. The sensitivity between the back pain questionnaires and the presence of lumbar disc herniation was low (16-64%). Conclusion Screening of lumbar disc herniation using only back pain questionnaires has limited value. PMID:25983807

  10. Line-driven ablation of circumstellar discs - I. Optically thin decretion discs of classical Oe/Be stars.

    PubMed

    Kee, Nathaniel Dylan; Owocki, Stanley; Sundqvist, J O

    2016-05-21

    The extreme luminosities of massive, hot OB stars drive strong stellar winds through line-scattering of the star's UV continuum radiation. For OB stars with an orbiting circumstellar disc, we explore here the effect of such line-scattering in driving an ablation of material from the disc's surface layers, with initial focus on the marginally optically thin decretion discs of classical Oe and Be stars. For this we apply a multidimensional radiation-hydrodynamics code that assumes simple optically thin ray tracing for the stellar continuum, but uses a multiray Sobolev treatment of the line transfer; this fully accounts for the efficient driving by non-radial rays, due to desaturation of line-absorption by velocity gradients associated with the Keplerian shear in the disc. Results show a dense, intermediate-speed surface ablation, consistent with the strong, blueshifted absorption of UV wind lines seen in Be shell stars that are observed from near the disc plane. A key overall result is that, after an initial adjustment to the introduction of the disc, the asymptotic disc destruction rate is typically just an order-unity factor times the stellar wind mass-loss rate. For optically thin Be discs, this leads to a disc destruction time of order months to years, consistent with observationally inferred disc decay times. The much stronger radiative forces of O stars reduce this time to order days, making it more difficult for decretion processes to sustain a disc in earlier spectral types, and so providing a natural explanation for the relative rarity of Oe stars in the Galaxy. Moreover, the decrease in line-driving at lower metallicity implies both a reduction in the winds that help spin-down stars from near-critical rotation, and a reduction in the ablation of any decretion disc; together these provide a natural explanation for the higher fraction of classical Be stars, as well as the presence of Oe stars, in the lower metallicity Magellanic Clouds. We conclude with a discussion of future extensions to study line-driven ablation of denser, optically thick, accretion discs of pre-main-sequence massive stars.

  11. Line-driven ablation of circumstellar discs – I. Optically thin decretion discs of classical Oe/Be stars

    PubMed Central

    Kee, Nathaniel Dylan; Owocki, Stanley; Sundqvist, J. O.

    2016-01-01

    The extreme luminosities of massive, hot OB stars drive strong stellar winds through line-scattering of the star's UV continuum radiation. For OB stars with an orbiting circumstellar disc, we explore here the effect of such line-scattering in driving an ablation of material from the disc's surface layers, with initial focus on the marginally optically thin decretion discs of classical Oe and Be stars. For this we apply a multidimensional radiation-hydrodynamics code that assumes simple optically thin ray tracing for the stellar continuum, but uses a multiray Sobolev treatment of the line transfer; this fully accounts for the efficient driving by non-radial rays, due to desaturation of line-absorption by velocity gradients associated with the Keplerian shear in the disc. Results show a dense, intermediate-speed surface ablation, consistent with the strong, blueshifted absorption of UV wind lines seen in Be shell stars that are observed from near the disc plane. A key overall result is that, after an initial adjustment to the introduction of the disc, the asymptotic disc destruction rate is typically just an order-unity factor times the stellar wind mass-loss rate. For optically thin Be discs, this leads to a disc destruction time of order months to years, consistent with observationally inferred disc decay times. The much stronger radiative forces of O stars reduce this time to order days, making it more difficult for decretion processes to sustain a disc in earlier spectral types, and so providing a natural explanation for the relative rarity of Oe stars in the Galaxy. Moreover, the decrease in line-driving at lower metallicity implies both a reduction in the winds that help spin-down stars from near-critical rotation, and a reduction in the ablation of any decretion disc; together these provide a natural explanation for the higher fraction of classical Be stars, as well as the presence of Oe stars, in the lower metallicity Magellanic Clouds. We conclude with a discussion of future extensions to study line-driven ablation of denser, optically thick, accretion discs of pre-main-sequence massive stars. PMID:27346978

  12. Secular evolution of eccentricity in protoplanetary discs with gap-opening planets

    NASA Astrophysics Data System (ADS)

    Teyssandier, Jean; Ogilvie, Gordon I.

    2017-06-01

    We explore the evolution of the eccentricity of an accretion disc perturbed by an embedded planet whose mass is sufficient to open a large gap in the disc. Various methods for representing the orbit-averaged motion of an eccentric disc are discussed. We characterize the linear instability that leads to the growth of eccentricity by means of hydrodynamical simulations. We numerically recover the known result that eccentricity growth in the disc is possible when the planet-to-star mass ratio exceeds 3 × 10-3. For mass ratios larger than this threshold, the precession rates and growth rates derived from simulations, as well as the shape of the eccentric mode, compare well with the predictions of a linear theory of eccentric discs. We study mechanisms by which the eccentricity growth eventually saturates into a non-linear regime.

  13. Comparative Activity of Pradofloxacin, Enrofloxacin, and Azithromycin against Bartonella henselae Isolates Collected from Cats and a Human ▿

    PubMed Central

    Biswas, Silpak; Maggi, Ricardo G.; Papich, Mark G.; Keil, Daniel; Breitschwerdt, Edward B.

    2010-01-01

    Using Bartonella henselae isolates from cats and a human, the activity of pradofloxacin was compared with those of enrofloxacin and azithromycin. By Etest and disc diffusion assay, pradofloxacin showed greater antimicrobial activity than did other antibiotics. We conclude that pradofloxacin may prove useful for the treatment of B. henselae infections. PMID:20007401

  14. Impact of Cosmological Satellites on Stellar Discs: Dissecting One Satellite at a Time

    NASA Astrophysics Data System (ADS)

    Hu, Shaoran; Sijacki, Debora

    2018-05-01

    Within the standard hierarchical structure formation scenario, Milky Way-mass dark matter haloes have hundreds of dark matter subhaloes with mass ≳ 108 M⊙. Over the lifetime of a galactic disc a fraction of these may pass close to the central region and interact with the disc. We extract the properties of subhaloes, such as their mass and trajectories, from a realistic cosmological simulation to study their potential effect on stellar discs. We find that massive subhalo impacts can generate disc heating, rings, bars, warps, lopsidedness as wells as spiral structures in the disc. Specifically, strong counter-rotating single-armed spiral structures form each time a massive subhalo passes through the disc. Such single-armed spirals wind up relatively quickly (over 1 - 2 Gyrs) and are generally followed by co-rotating two-armed spiral structures that both develop and wind up more slowly. In our simulations self-gravity in the disc is not very strong and these spiral structures are found to be kinematic density waves. We demonstrate that there is a clear link between each spiral mode in the disc and a given subhalo that caused it, and by changing the mass of the subhalo we can modulate the strength of the spirals. Furthermore, we find that the majority of subhaloes interact with the disc impulsively, such that the strength of spirals generated by subhaloes is proportional to the total torque they exert. We conclude that only a handful of encounters with massive subhaloes is sufficient for re-generating and sustaining spiral structures in discs over their entire lifetime.

  15. The role of disc self-gravity in circumbinary planet systems - II. Planet evolution

    NASA Astrophysics Data System (ADS)

    Mutter, Matthew M.; Pierens, Arnaud; Nelson, Richard P.

    2017-08-01

    We present the results of hydrodynamic simulations examining migration and growth of planets embedded in self-gravitating circumbinary discs. The binary star parameters are chosen to mimic those of the Kepler-16, -34 and -35 systems; the aim of this study is to examine the role of disc mass in determining the stopping locations of migrating planets at the edge of the cavity created by the central binary. Disc self-gravity can cause significant shrinkage of the cavity for disc masses in excess of 5-10 × the minimum mass solar nebula model. Planets forming early in the disc lifetime can migrate through the disc and stall at locations closer to the central star than is normally the case for lower mass discs, resulting in closer agreement between simulated and observed orbital architecture. The presence of a planet orbiting in the cavity of a massive disc can prevent the cavity size from expanding to the size of a lower mass disc. As the disc mass reduces over long time-scales, this indicates that circumbinary planet systems retain memory of their initial conditions. Our simulations produce planetary orbits in good agreement with Keper-16b without the need for self-gravity; Kepler-34 analogue systems produce wide and highly eccentric cavities, and self-gravity improves the agreement between simulations and data. Kepler-35b is more difficult to explain in detail due to its relatively low mass, which results in the simulated stopping location being at a larger radius than that observed.

  16. Determination of self attenuation coefficient and relative TL efficiency of CaSO 4 :Dy, LiF:Mg,Cu,P and LiF:Mg,Ti TLDs - An alternate approach

    NASA Astrophysics Data System (ADS)

    Bakshi, A. K.; Chatterjee, S.; Palani Selvam, T.; Joshi, V. J.; Chougaonkar, M. P.

    2011-10-01

    Self attenuation of TL and relative TL efficiency of polytetra fluoro ethylene (PTFE) embedded CaSO 4:Dy disc, LiF:Mg,Ti (MTS) disc and LiF:Mg,Cu,P (MCP-N) chip were determined in the present study for photons of energy 10-34 keV. The relative TL efficiency was determined using an alternative approach in which ratio of experimental response and corrected theoretical response was used instead of measuring the absolute TL emission in photon counting mode. For CaSO 4:Dy disc, it was found that with increasing the proportion of CaSO 4:Dy phosphor in the disc, the light attenuation coefficient increases. The light attenuation coefficient of MTS disc and MCP-N chip was found to be 23.4 and 45.5 cm -1, respectively. The relative TL efficiency in the photon energy range of 10-34 keV for MTS discs and MCP-N chips, evaluated in the present study matches well with the reported values in the literature.

  17. A qualitative study of the cultural appropriateness of the Diagnostic Interview Schedule for Children (DISC-IV) in South Africa

    PubMed Central

    Skinner, Donald; Serekoane, Motsaathebe; Ross, Michael W.

    2012-01-01

    Background The Diagnostic Interview Schedule for Children (DISC-IV) has been designed for use by trained laypersons. It therefore shows great promise for use in developing countries such as South Africa, where there is a lack of clinically trained and skilled professionals at the primary care level. Against this background, the aim of the current study was to investigate the sociocultural appropriateness of the DISC-IV for use with Sesotho families in South Africa. Methods Qualitative methodology of expert review and contextualized content analyses were used. Ten Sesotho-speaking clinicians were recruited through a snowball sampling technique to the review the DISC through expert review reports. Results Several themes emerged, including the structure of the DISC-IV, its computerized nature, Americanisms, problems in interpretation due to the adversity children live under, language problems, the effect of rural settings and education level, and cultural norms regarding psychiatric symptoms, gender, the experience of time, the expression of emotion, and family structure. Conclusion Recommendations for the sociocultural adaptation and translation of the DISC into Sesotho are made. PMID:20526764

  18. Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia.

    PubMed

    Kim, Ju Young; Liu, Cindy Y; Zhang, Fengyu; Duan, Xin; Wen, Zhexing; Song, Juan; Feighery, Emer; Lu, Bai; Rujescu, Dan; St Clair, David; Christian, Kimberly; Callicott, Joseph H; Weinberger, Daniel R; Song, Hongjun; Ming, Guo-li

    2012-03-02

    How extrinsic stimuli and intrinsic factors interact to regulate continuous neurogenesis in the postnatal mammalian brain is unknown. Here we show that regulation of dendritic development of newborn neurons by Disrupted-in-Schizophrenia 1 (DISC1) during adult hippocampal neurogenesis requires neurotransmitter GABA-induced, NKCC1-dependent depolarization through a convergence onto the AKT-mTOR pathway. In contrast, DISC1 fails to modulate early-postnatal hippocampal neurogenesis when conversion of GABA-induced depolarization to hyperpolarization is accelerated. Extending the period of GABA-induced depolarization or maternal deprivation stress restores DISC1-dependent dendritic regulation through mTOR pathway during early-postnatal hippocampal neurogenesis. Furthermore, DISC1 and NKCC1 interact epistatically to affect risk for schizophrenia in two independent case control studies. Our study uncovers an interplay between intrinsic DISC1 and extrinsic GABA signaling, two schizophrenia susceptibility pathways, in controlling neurogenesis and suggests critical roles of developmental tempo and experience in manifesting the impact of susceptibility genes on neuronal development and risk for mental disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. [Biomechanical analysis of different ProDisc-C arthroplasty design parameters after implanted: a numerical sensitivity study based on finite element method].

    PubMed

    Tang, Qiaohong; Mo, Zhongjun; Yao, Jie; Li, Qi; Du, Chenfei; Wang, Lizhen; Fan, Yubo

    2014-12-01

    This study was aimed to estimate the effect of different ProDisc-C arthroplasty designs after it was implanted to C5-C6 cervicalspine. Finite element (FE) model of intact C5-C6 segments including the vertebrae and disc was developed and validated. Ball-and-socket artificial disc prosthesis model (ProDisc-C, Synthes) was implanted into the validated FE model and the curvature of the ProDisc-C prosthesis was varied. All models were loaded with compressed force 74 N and the pure moment of 1.8 Nm along flexion-extension and bilateral bending and axial torsion separately. The results indicated that the variation in the curvature of ball and socket configuration would influence the range of motion in flexion/extension, while there were not apparently differences under other conditions of loads. The method increasing the curvature will solve the stress concentration of the polyethylene, but it will also bring adverse outcomes, such as facet joint force increasing and ligament tension increasing. Therefore, the design of artificial discs should be considered comprehensively to reserve the range of motion as well as to avoid the adverse problems, so as not to affect the long-term clinical results.

  20. Low rate loading-induced convection enhances net transport into the intervertebral disc in vivo.

    PubMed

    Gullbrand, Sarah E; Peterson, Joshua; Mastropolo, Rosemarie; Roberts, Timothy T; Lawrence, James P; Glennon, Joseph C; DiRisio, Darryl J; Ledet, Eric H

    2015-05-01

    The intervertebral disc primarily relies on trans-endplate diffusion for the uptake of nutrients and the clearance of byproducts. In degenerative discs, diffusion is often diminished by endplate sclerosis and reduced proteoglycan content. Mechanical loading-induced convection has the potential to augment diffusion and enhance net transport into the disc. The ability of convection to augment disc transport is controversial and has not been demonstrated in vivo. To determine if loading-induced convection can enhance small molecule transport into the intervertebral disc in vivo. Net transport was quantified via postcontrast enhanced magnetic resonance imaging (MRI) into the discs of the New Zealand white rabbit lumbar spine subjected to in vivo cyclic low rate loading. Animals were administered the MRI contrast agent gadodiamide intravenously and subjected to in vivo low rate loading (0.5 Hz, 200 N) via a custom external loading apparatus for either 2.5, 5, 10, 15, or 20 minutes. Animals were then euthanized and the lumbar spines imaged using postcontrast enhanced MRI. The T1 constants in the nucleus, annulus, and cartilage endplates were quantified as a measure of gadodiamide transport into the loaded discs compared with the adjacent unloaded discs. Microcomputed tomography was used to quantify subchondral bone density. Low rate loading caused the rapid uptake and clearance of gadodiamide in the nucleus compared with unloaded discs, which exhibited a slower rate of uptake. Relative to unloaded discs, low rate loading caused a maximum increase in transport into the nucleus of 16.8% after 5 minutes of loading. Low rate loading increased the concentration of gadodiamide in the cartilage endplates at each time point compared with unloaded levels. Results from this study indicate that forced convection accelerated small molecule uptake and clearance in the disc induced by low rate mechanical loading. Low rate loading may, therefore, be therapeutic to the disc as it may enhance the nutrient uptake and waste product clearance. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Biomechanical analysis of disc pressure and facet contact force after simulated two-level cervical surgeries (fusion and arthroplasty) and hybrid surgery.

    PubMed

    Park, Jon; Shin, Jun Jae; Lim, Jesse

    2014-12-01

    The objective of this study was designed to compare 2-level cervical disc surgery (2-level anterior cervical discectomy and fusion [ACDF] or disc arthroplasty) and hybrid surgery (ACDF/arthroplasty) in terms of postoperative adjacent-level intradiscal pressure (IDP) and facet contact force (FCF). Twenty-four cadaveric cervical spines (C3-T2) were tested in various modes, including extension, flexion, and bilateral axial rotation, to compare adjacent-level IDP and FCF after specified treatments as follows: 1) C5-C6 arthroplasty using ProDisc-C (Synthes Spine, West Chester, Pennsylvania, USA) and C6-C7 ACDF, 2) C5-C6 ACDF and C6-C7 arthroplasty using ProDisc-C, 3) 2-level C5-C6/C6-C7 disc arthroplasties, and 4) 2-level C5-C6/C6-C7 ACDF. IDPs were recorded at anterior, central, and posterior disc portions. After 2-level cervical arthrodesis (ACDF), IDP increased significantly at the anterior annulus of distal adjacent-level disc during flexion and axial rotation and at the center of proximal adjacent-level disc during flexion. In contrast, after cervical specified treatments, including disc arthroplasty (2-level disc arthroplasties and hybrid surgery), IDP decreased significantly at the anterior annulus of distal adjacent-level disc during flexion and extension and was unchanged at the center of proximal adjacent-level disc during flexion. Two-level cervical arthrodesis also tended to adversely impact facet loads, increasing distal rather than proximal adjacent-level FCF. Both hybrid surgery and 2-level arthroplasties seem to offer significant advantages over 2-level arthrodesis by reducing IDP at adjacent levels and approximating FCF of an intact spine. These findings suggest that cervical arthroplasties and hybrid surgery are an alternative to reduce IDP and facet loads at adjacent levels. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Molecules in Protoplanetary HAEBE discs as seen with Herschel.

    NASA Astrophysics Data System (ADS)

    Meeus, G.

    2011-05-01

    The discovery of planets around other stars has revealed that planet formation is ubiquitous. However, the mechanisms determining planet formation are not (yet) well-understood. Primordial protoplanetary discs consist 99% out of gas, and only 1% out of dust. With time, those discs are believed to evolve from a flaring geometry into a flat geometry, as the initially small dust grains grow to larger sizes and settle towards the mid-plane. In the mean time, the gas will disperse, until so little is left that giant planets no longer can form. It is thus important to understand the chemical composition of the disc and the influence of the gas heating/cooling processes on the disc structure, and finally how gas gets dispersed as a pieces of the puzzle of planet formation. In this contribution, we study the protoplanetary discs around Herbig Ae/Be stars, young objects of intermediate mass, in the context of gas chemistry. We present Herschel PACS spectroscopic observations for a sample that was obtained within the GASPS (Gas in Protoplanetary Systems) Open Time Key Project, concentrating on the detection and characterisation of emission lines of the molecules H20, CO and CH+ (besides [OI] and [CII]), tracing the disc between 5 and 500 AU. We look for correlations between the observed line fluxes and stellar properties such as effective temperature, Halpha emission, accretion rates and UV flux, as well as the disc properties: degree of flaring, presence and strength of PAH emission and disc mass. We will present a few cases to show how simultaneous modeling (using the thermo-chemical disc code ProDiMo) of the atomic fine structure lines and both Space Telescope and ground-based molecular lines can constrain the disc gas mass, once the disc structure is derived (here with the radiative transfer code MCFost). Finally, we compare our gas line observations with those of young debris disc stars, for which the HAEBE stars are thought to be progenitors.

  3. Correlation between MRI evidence of degenerative condylar surface changes, induction of articular disc displacement and pathological joint sounds in the temporomandibular joint.

    PubMed

    Honda, Kosuke; Natsumi, Yoshiko; Urade, Masahiro

    2008-12-01

    The relationship of bony changes in the condylar surfaces in articular disc displacement without reduction in temporomandibular joint (TMJ) was investigated using diagnostic imaging. The study also evaluated whether the bony changes in the condylar surfaces limit disc and condyle motion, and produce pathological joint sounds. Thirty-seven joints in 28 patients diagnosed with degenerative bony changes in the condylar surfaces radiographically and anterior disc displacement without reduction using magnetic resonance imaging (MRI) were studied. The bony changes were assessed by radiographic examination and classified into two types: pathological bone changes (PBCs) including erosion, osteophyte formation and deformity, and adaptive bone changes (ABCs) including flattening and concavity. MRI was performed on the TMJ to examine the configuration and position of the discs. Joint sounds in the TMJ were determined using electrovibratograghy with a joint vibration analysis. The articular disc motion to the condyle in the PBC group was smaller than in the ABC group irrespective of the configuration of the disc, even though there were no significant differences between the two types of bony changes in the disc position during jaw closing. The joint vibration analysis of the TMJ showed that joint sounds with a higher frequency were observed in the PBC group than in the ABC group. High energy levels needed to produce the higher frequencies (over 300 Hz) were observed only in the PBC group.

  4. Reduced Nucleus Pulposus Glycosaminoglycan Content Alters Intervertebral Disc Dynamic Viscoelastic Mechanics

    PubMed Central

    Boxberger, John I.; Orlansky, Amy S.; Sen, Sounok; Elliott, Dawn M.

    2009-01-01

    The intervertebral disc functions over a range of dynamic loading regimes including axial loads applied across a spectrum of frequencies at varying compressive loads. Biochemical changes occurring in early degeneration, including reduced nucleus pulposus glycosaminoglycan content, may alter disc mechanical behavior and thus may contribute to the progression of degeneration. The objective of this study was to determine disc dynamic viscoelastic properties under several equilibrium loads and loading frequencies, and further, to determine how reduced nucleus glycosaminglycan content alters dynamic mechanics. We hypothesized (1) that dynamic stiffness would be elevated with increasing equilibrium load and increasing frequency, (2) that the disc would behave more elastically at higher frequencies, and finally, (3) that dynamic stiffness would be reduced at low equilibrium loads under all frequencies due to nucleus glycosaminoglycan loss. We mechanically tested control and chondroitinase-ABC injected rat lumbar motion segments at several equilibrium loads using oscillatory loading at frequencies ranging from 0.05 to 5 Hz. The rat lumbar disc behaved non-linearly with higher dynamic stiffness at elevated compressive loads irrespective of frequency. Phase angle was not affected by equilibrium load, although it decreased as frequency was increased. Reduced glycosaminoglycan decreased dynamic stiffness at low loads but not at high equilibrium loads and led to increased phase angle at all loads and frequencies. The findings of this study demonstrate the effect of equilibrium load and loading frequencies on dynamic disc mechanics and indicate possible mechanical mechanisms through which disc degeneration can progress. PMID:19539936

  5. NIHAO VI. The hidden discs of simulated galaxies

    NASA Astrophysics Data System (ADS)

    Obreja, Aura; Stinson, Gregory S.; Dutton, Aaron A.; Macciò, Andrea V.; Wang, Liang; Kang, Xi

    2016-06-01

    Detailed studies of galaxy formation require clear definitions of the structural components of galaxies. Precisely defined components also enable better comparisons between observations and simulations. We use a subsample of 18 cosmological zoom-in simulations from the Numerical Investigation of a Hundred Astrophysical Objects (NIHAO) project to derive a robust method for defining stellar kinematic discs in galaxies. Our method uses Gaussian Mixture Models in a 3D space of dynamical variables. The NIHAO galaxies have the right stellar mass for their halo mass, and their angular momenta and Sérsic indices match observations. While the photometric disc-to-total ratios are close to 1 for all the simulated galaxies, the kinematic ratios are around ˜0.5. Thus, exponential structure does not imply a cold kinematic disc. Above M* ˜ 109.5 M⊙, the decomposition leads to thin discs and spheroids that have clearly different properties, in terms of angular momentum, rotational support, ellipticity, [Fe/H] and [O/Fe]. At M* ≲ 109.5 M⊙, the decomposition selects discs and spheroids with less distinct properties. At these low masses, both the discs and spheroids have exponential profiles with high minor-to-major axes ratios, I.e. thickened discs.

  6. Effects of cryogenic treatment on the wear properties of brake discs

    NASA Astrophysics Data System (ADS)

    Nadig, D. S.; Shivakumar, P.; Anoop, S.; Chinmay, Kulkarni; Divine, P. V.; Harsha, H. P.

    2017-02-01

    Disc brakes are invariably used in all the automobiles either to reduce the rotational speed of the wheel or to hold the vehicle stationary. During the braking action, the kinetic energy is converted into heat which can result in high temperatures resulting in fading of brake effects. Brake discs produced out of martensite stainless steel (SS410) are expected to exhibit high wear resistance properties with low value of coefficient of friction. These factors increase the useful life of the brake discs with minimal possibilities of brake fade. To study the effects of cryogenic treatment on the wear behaviour, two types of brake discs were cryotreated at 98K for 8 and 24 hours in a specially developed cryotreatment system using liquid nitrogen. Wear properties of the untreated and cryotreated test specimens were experimentally determined using the pin on disc type tribometer (ASTM G99-95). Similarly, the Rockwell hardness (HRC) of the specimens were tested in a hardness tester in accordance with ASTM E18. In this paper, the effects of cryotreatment on the wear and hardness properties of untreated and cryotreated brake discs are presented. Results indicate enhancement of wear properties and hardness after cryogenic treatment compared with the normal brakes discs.

  7. Growth of carbon nanotubes in arc plasma treated graphite disc: microstructural characterization and electrical conductivity study

    NASA Astrophysics Data System (ADS)

    Nayak, B. B.; Sahu, R. K.; Dash, T.; Pradhan, S.

    2018-03-01

    Circular graphite discs were treated in arc plasma by varying arcing time. Analysis of the plasma treated discs by field emission scanning electron microscope revealed globular grain morphologies on the surfaces, but when the same were observed at higher magnification and higher resolution under transmission electron microscope, growth of multiwall carbon nanotubes of around 2 nm diameter was clearly seen. In situ growth of carbon nanotube bundles/bunches consisting of around 0.7 nm tube diameter was marked in the case of 6 min treated disc surface. Both the untreated and the plasma treated graphite discs were characterized by X-ray diffraction, energy dispersive spectra of X-ray, X-ray photoelectron spectroscopy, transmission electron microscopy, micro Raman spectroscopy and BET surface area measurement. From Raman spectra, BET surface area and microstructure observed in transmission electron microscope, growth of several layers of graphene was identified. Four-point probe measurements for electrical resistivity/conductivity of the graphite discs treated under different plasma conditions showed significant increase in conductivity values over that of untreated graphite conductivity value and the best result, i.e., around eightfold increase in conductivity, was observed in the case of 6 min plasma treated sample exhibiting carbon nanotube bundles/bunches grown on disc surface. By comparing the microstructures of the untreated and plasma treated graphite discs, the electrical conductivity increase in graphite disc is attributed to carbon nanotubes (including bundles/bunches) growth on disc surface by plasma treatment.

  8. Runaway gas accretion and gap opening versus type I migration

    NASA Astrophysics Data System (ADS)

    Crida, A.; Bitsch, B.

    2017-03-01

    Growing planets interact with their natal protoplanetary disc, which exerts a torque onto them allowing them to migrate in the disc. Small mass planets do not affect the gas profile and migrate in the fast type-I migration. Although type-I migration can be directed outwards for planets smaller than 20 - 30M⊕ in some regions of the disc, planets above this mass should be lost into the central star long before the disc disperses. Massive planets push away material from their orbit and open a gap. They subsequently migrate in the slower, type II migration, which could save them from migrating all the way to the star. Hence, growing giant planets can be saved if and only if they can reach the gap opening mass, because this extends their migration timescale, allowing them to eventually survive at large orbits until the disc itself disperses. However, most of the previous studies only measured the torques on planets with fixed masses and orbits to determine the migration rate. Additionally, the transition between type-I and type-II migration itself is not well studied, especially when taking the growth mechanism of rapid gas accretion from the surrounding disc into account. Here we use isothermal 2D disc simulations with FARGO-2D1D to study the migration behaviour of gas accreting protoplanets in discs. We find that migrating giant planets always open gaps in the disc. We further show analytically and numerically that in the runaway gas accretion regime, the growth time-scale is comparable to the type-I migration time-scale, indicating that growing planets will reach gap opening masses before migrating all the way to the central star in type-I migration if the disc is not extremely viscous and/or thick. An accretion rate limited to the radial gas flow in the disc, in contrast, is not fast enough. When gas accretion by the planet is taken into account, the gap opening process is accelerated because the planet accretes material originating from its horseshoe region. This allows an accreting planet to transition to type-II migration before being lost even if gas fails to be provided for a rapid enough growth and the classical gap opening mass is not reached.

  9. A novel finite element model of the ovine lumbar intervertebral disc with anisotropic hyperelastic material properties

    PubMed Central

    Galbusera, Fabio; Jonas, René; Schlager, Benedikt; Wilke, Hans-Joachim; Villa, Tomaso

    2017-01-01

    The Ovine spine is an accepted model to investigate the biomechanical behaviour of the human lumbar one. Indeed, the use of animal models for in vitro studies is necessary to investigate the mechanical behaviour of biological tissue, but needs to be reduced for ethical and social reasons. The aim of this study was to create a finite element model of the lumbar intervertebral disc of the sheep that may help to refine the understanding of parallel in vitro experiments and that can be used to predict when mechanical failure occurs. Anisotropic hyperelastic material properties were assigned to the annulus fibrosus and factorial optimization analyses were performed to find out the optimal parameters of the ground substance and of the collagen fibers. For the ground substance of the annulus fibrosus the investigation was based on experimental data taken from the literature, while for the collagen fibers tensile tests on annulus specimens were conducted. Flexibility analysis in flexion-extension, lateral bending and axial rotation were conducted. Different material properties for the anterior, lateral and posterior regions of the annulus were found. The posterior part resulted the stiffest region in compression whereas the anterior one the stiffest region in tension. Since the flexibility outcomes were in a good agreement with the literature data, we considered this model suitable to be used in conjunction with in vitro and in vivo tests to investigate the mechanical behaviour of the ovine lumbar disc. PMID:28472100

  10. Effects of Tobacco Smoking on the Degeneration of the Intervertebral Disc: A Finite Element Study

    PubMed Central

    Elmasry, Shady; Asfour, Shihab; de Rivero Vaccari, Juan Pablo; Travascio, Francesco

    2015-01-01

    Tobacco smoking is associated with numerous pathological conditions. Compelling experimental evidence associates smoking to the degeneration of the intervertebral disc (IVD). In particular, it has been shown that nicotine down-regulates both the proliferation rate and glycosaminoglycan (GAG) biosynthesis of disc cells. Moreover, tobacco smoking causes the constriction of the vascular network surrounding the IVD, thus reducing the exchange of nutrients and anabolic agents from the blood vessels to the disc. It has been hypothesized that both nicotine presence in the IVD and the reduced solute exchange are responsible for the degeneration of the disc due to tobacco smoking, but their effects on tissue homeostasis have never been quantified. In this study, a previously presented computational model describing the homeostasis of the IVD was deployed to investigate the effects of impaired solute supply and nicotine-mediated down-regulation of cell proliferation and biosynthetic activity on the health of the disc. We found that the nicotine-mediated down-regulation of cell anabolism mostly affected the GAG concentration at the cartilage endplate, reducing it up to 65% of the value attained in normal physiological conditions. In contrast, the reduction of solutes exchange between blood vessels and disc tissue mostly affected the nucleus pulposus, whose cell density and GAG levels were reduced up to 50% of their normal physiological levels. The effectiveness of quitting smoking on the regeneration of a degenerated IVD was also investigated, and showed to have limited benefit on the health of the disc. A cell-based therapy in conjunction with smoke cessation provided significant improvements in disc health, suggesting that, besides quitting smoking, additional treatments should be implemented in the attempt to recover the health of an IVD degenerated by tobacco smoking. PMID:26301590

  11. Role of Retinal Nerve Fiber Layer Thickness and Optic Disk Measurement by OCT on Early Diagnosis of Glaucoma.

    PubMed

    Hua, Zanmei; Fang, Qiuyun; Sha, Xiangyin; Yang, Ruiming; Hong, Zuopeng

    2015-03-01

    Glaucoma is an eye disease that can lead to irreversible optic nerve damage and cause blindness. Optical coherence tomography (OCT) allows an early diagnosis of glaucoma by the measurements of the retinal nerve fiber and optic disc parameters. A retrospective study was designed to analyze the effects of the measurement of the retinal nerve fiber layer (RNFL) thickness and the optic disc tomography by spectral-domain OCT on the early diagnosis of suspected glaucoma and primary open angle glaucoma (POAG). This was a clinical case-control study. The RNFL thickness around the optic disc and optic disk tomographic parameters of the control (n = 51, 98 eyes), suspected glaucoma (n = 81, 146 eyes), and POAG groups (n = 55, 106 eyes) were measured by OCT. The parameters included superior, inferior, nasal and temporal mean RNFL thickness, disc area (DA), cup area (CA), rim area (RA), disc volume (DV), cup volume (CV), rim volume (RV), cup/disc area ratio (CA/DA), rim/disc area ratio (RA/DA), cup/disc volume ratio (CV/DV) and rim/disc volume ratio (RV/DV). Superior, nasal, and mean RNFL parameters, DA, CA,RA, DV, CV, CA/DA, RA/DA, CV/DV and RV/DV significantly differed among three groups by single-factorial ANOVA. Inferior and temporal RNFL thickness significantly differed between the control and POAG groups. No significant difference was observed in RV among three groups. In the POAG group, the maximum area under the ROC curve (AROC) of mean RNFL thickness was 0.845. The maximum AROC of optic disk parameters was RA/DA (0.998), followed by CA/DA (0.997). The AROC of CA, RA, CV, and DV were all > 0.900. OCT may serve as a useful diagnostic modality in distinguishing suspected glaucoma from POAG.

  12. High-resolution ultrasonography in assessing temporomandibular joint disc position.

    PubMed

    Talmaceanu, Daniel; Lenghel, Lavinia Manuela; Bolog, Nicolae; Popa Stanila, Roxana; Buduru, Smaranda; Leucuta, Daniel Corneliu; Rotar, Horatiu; Baciut, Mihaela; Baciut, Grigore

    2018-02-04

    The purpose of this study was to determine the diagnostic value of high-resolution ultrasonography (US) in temporomandibular joint (TMJ) disc displacements. A number of 74 patients (148 TMJs) with signs and symptoms of TMJ disorders, according to the Research Diagnostic Criteria for Temporomandibular Disorders, were included in this study. All patients received US and magnetic resonance imaging (MRI) of both TMJs 1 to 5 days after the clinical examination. MRI examinations were performed using 1.5 T MRI equipment (Siemens Avanto, Siemens, Erlangen). Ultrasonographic examination was performed on a Hitachi EUB 8500 (Hitachi Medical Corp., Tokyo, Japan) scanner with L 54 M6.5-13 MHz linear transducer. MRI depicted 68 (45.95%) normal joints, 47 (31.76%) with disc displacement with reduction, 33 (22.3%) with disc displacement without reduction and 34 (22.97%) with degenerative changes. US detected 78 (52.7%) normal joints, 37 (25%) with disc displacement with reduction, 33 (22.3%) with disc displacement without reduction and 21 (14.19%) with degenerative changes. Compared to MRI, US showed a sensitivity of 93.1%, specificity of 87.88%, accuracy of 90.32%, a positive predictive value of 87.1% and a negative predictive value of 93.55% for overall diagnosis of disc displacement. The Youden index was 0.81. Based on our results, high-resolution ultrasonography showed high sensitivity, specificity and accuracy in the diagnosis of TMJ disc displacement. It could be a valuable imaging technique in assessing TMJ disc position. The diagnostic value of high-resolution ultrasonography depends strictly on the examiner's skills and on the equipment used.

  13. Influence of height, weight, and body mass index on optic disc parameters.

    PubMed

    Zheng, Yingfeng; Cheung, Carol Y L; Wong, Tien Y; Mitchell, Paul; Aung, Tin

    2010-06-01

    To examine the influence of body height, body weight, and body mass index (BMI) on optic disc parameters in a population-based study. The Singapore Malay Eye Study examined 3280 persons of Malay ethnicity, aged 40 to 80 years, of whom 2329 (71.0%) had reliable retinal scanning confocal laser tomography images for analyses. Intraocular pressure (IOP) was ascertained by Goldmann applanation tonometry. Body height and weight were measured with standardized protocols; BMI was calculated as weight (kilograms)/height squared (meters). Sociodemographic information was collected in an interviewer-administered questionnaire. In univariate analyses, body height, weight, and BMI were significantly associated with optic cup area, rim area, and cup-to-disc area ratio (all with P < 0.05) but none of the anthropometric parameters was significantly associated with optic disc area (all with P > 0.05). In multiple regression analyses after adjustment for age, sex, optic disc size, axial length, education, family income, and IOP, each SD increase in body height was associated with a 0.042-mm(2) decrease in optic rim area and a 0.020 increase in optic cup-to-disc area ratio; each SD decrease in body weight was associated with a 0.013-mm(2) decrease in optic rim area and a 0.010 increase in optic cup-to-disc ratio; and each SD decrease in BMI was associated with a 0.021-mm(2) decrease in optic rim area and a 0.010 increase in optic cup-to-disc ratio. Persons who are taller or have lower BMI have a smaller neuroretinal rim area and a larger optic cup-to-disc area ratio.

  14. Asymmetrical and smaller size of trunk muscles in combat sports athletes with lumbar intervertebral disc degeneration.

    PubMed

    Iwai, Kazunori; Koyama, Koji; Okada, Takashi; Nakazato, Koichi; Takahashi, Ray; Matsumoto, Shingo; Yamamoto, Yosuke; Hiranuma, Kenji

    2016-01-01

    Lumbar intervertebral disc degeneration (LDD) frequently occurs in athletes. Associations between LDD and trunk muscles still remain unclear. This study examined whether there is an association between the prevalence of LDD and the symmetry and size of the cross-sectional areas (CSAs) of the trunk muscles in combat sports athletes. Participants in this study were 151 collegiate male combat sports athletes. A total of 755 lumbar intervertebral discs from L1-2 to L5-S1 in 151 athletes were assessed using magnetic resonance imaging (MRI) and a comprehensive grading system of LDD (grades I-V). All 151 athletes were divided into 2 groups: LDD and non-LDD. CSAs of trunk muscles at the L3-4 disc level were measured using MRI. Sixty-nine athletes had LDD at 1 or more disc levels (45.7 %). The LDD grade for the lower 2 disc levels was significantly higher than that for the other disc levels (p < 0.001). The CSAs of the left and right sides in trunk muscles were significantly asymmetrical, independent of the LDD which was prevalent in the disc levels (obliques: p = 0.040; quadratus lumborum: p < 0.001). The relative CSAs of trunk muscles to their body weight in the LDD group were significantly smaller than those in the non-LDD group (rectus abdominis: p = 0.011; obliques: p = 0.024; quadratus lumborum: p = 0.006; lumbar erector spinae plus multifidus: p = 0.001). This study suggests that the prevalence of LDD is associated with asymmetrical and relatively smaller CSAs of trunk muscles in combat sports athletes.

  15. Affective, anxiety, and substance-related disorders in patients undergoing herniated disc surgery.

    PubMed

    Zieger, Margrit; Luppa, Melanie; Matschinger, Herbert; Meisel, Hans J; Günther, Lutz; Meixensberger, Jürgen; Toussaint, René; Angermeyer, Matthias C; König, Hans-Helmut; Riedel-Heller, Steffi G

    2011-11-01

    At present only a small number of studies have investigated psychiatric comorbidity in disc surgery patients. Objectives of this study are (1) to examine the prevalence rate of comorbid affective, anxiety, and substance-related disorders in nucleotomy patients in comparison to the German general population and (2) to investigate associations between psychiatric comorbidity and socio-demographic and illness-related characteristics. The study refers to 349 consecutive disc surgery patients (response rate 87%) between the age of 18 and 55 years. The final study sample consists of 239 lumbar and 66 cervical nucleotomy patients. Face-to-face interviews were conducted approximately 3.45 days (SD 3.170) after disc surgery, during hospital stay. Psychiatric comorbidity was assessed by means of the Composite International Diagnostic Interview (CIDI-DIA-X). The corresponding data of the German general population were derived from the German National Health Interview and Examination Survey (GHS). 12-Month prevalence rates of any affective, anxiety or substance-related disorders range between 33.7% in cervical and 23.5% in lumbar disc surgery patients. Four-week prevalence rates of any affective, anxiety or substance disorder vary between 13.2% in cervical and 14.0% in lumbar nucleotomy patients. Disc surgery patients suffer more often from affective disorders and illicit substance abuse than the general population. Significant associations were found between psychiatric comorbidity and gender, as well as pain intensity. Disc surgery patients show a higher risk to suffer from mental disorders than the general population. The assessment of psychiatric distress and the assistance by mental health professionals should be considered during hospital and rehabilitation treatment.

  16. Evaluation of orthognathic surgery on articular disc position and temporomandibular joint symptoms in skeletal class II patients: A Magnetic Resonance Imaging study.

    PubMed

    Firoozei, Gholamreza; Shahnaseri, Shirin; Momeni, Hasan; Soltani, Parisa

    2017-08-01

    The purpose of orthognathic surgery is to correct facial deformity and dental malocclusion and to obtain normal orofacial function. However, there are controversies of whether orthognathic surgery might have any negative influence on temporomandibular (TM) joint. The purpose of this study was to evaluate the influence of orthognathic surgery on articular disc position and temporomandibular joint symptoms of skeletal CI II patients by means of magnetic resonance imaging. For this purpose, fifteen patients with skeletal CI II malocclusion, aged 19-32 years (mean 23 years), 10 women and 5 men, from the Isfahan Department of Oral and Maxillofacial Surgery were studied. All received LeFort I and bilateral sagittal split osteotomy (BSSO) osteotomies and all patients received pre- and post-surgical orthodontic treatment. Magnetic resonance imaging was performed 1 day preoperatively and 3 month postoperatively. Descriptive statistics and Wilcoxon and Mc-Nemar tests were used for statistical analysis. P <0.05 was considered significant. Disc position ranged between 4.25 and 8.09 prior to surgery (mean=5.74±1.21). After surgery disc position range was 4.36 to 7.40 (mean=5.65±1.06). Statistical analysis proved that although TM disc tended to move anteriorly after BSSO surgery, this difference was not statistically significant ( p value<0.05). The findings of the present study revealed that orthognathic surgery does not alter the disc and condyle relationship. Therefore, it has minimal effects on intact and functional TM joint. Key words: Orthognathic surgery, skeletal class 2, magnetic resonance imaging, temporomandibular disc.

  17. Bundle Data Approach at GES DISC Targeting Natural Hazards

    NASA Technical Reports Server (NTRS)

    Shie, Chung-Lin; Shen, Suhung; Kempler, Steven J.

    2015-01-01

    Severe natural phenomena such as hurricane, volcano, blizzard, flood and drought have the potential to cause immeasurable property damages, great socioeconomic impact, and tragic loss of human life. From searching to assessing the Big, i.e., massive and heterogeneous scientific data (particularly, satellite and model products) in order to investigate those natural hazards, it has, however, become a daunting task for Earth scientists and applications researchers, especially during recent decades. The NASA Goddard Earth Sciences Data and Information Service Center (GES DISC) has served Big Earth science data, and the pertinent valuable information and services to the aforementioned users of diverse communities for years. In order to help and guide our users to online readily (i.e., with a minimum effort) acquire their requested data from our enormous resource at GES DISC for studying their targeted hazard event, we have thus initiated a Bundle Data approach in 2014, first targeting the hurricane event topic. We have recently worked on new topics such as volcano and blizzard. The bundle data of a specific hazard event is basically a sophisticated integrated data package consisting of a series of proper datasets containing a group of relevant (knowledge--based) data variables readily accessible to users via a system-prearranged table linking those data variables to the proper datasets (URLs). This online approach has been developed by utilizing a few existing data services such as Mirador as search engine; Giovanni for visualization; and OPeNDAP for data access, etc. The online Data Cookbook site at GES DISC is the current host for the bundle data. We are now also planning on developing an Automated Virtual Collection Framework that shall eventually accommodate the bundle data, as well as further improve our management in Big Data.

  18. Lumbar intervertebral disc allograft transplantation: long-term mobility and impact on the adjacent segments.

    PubMed

    Huang, Yong-Can; Xiao, Jun; Lu, William W; Leung, Victor Y L; Hu, Yong; Luk, Keith D K

    2017-03-01

    Fresh-frozen intervertebral disc (IVD) allograft transplantation has been successfully performed in the human cervical spine. Whether this non-fusion technology could truly decrease adjacent segment disease is still unknown. This study evaluated the long-term mobility of the IVD-transplanted segment and the impact on the adjacent spinal segments in a goat model. Twelve goats were used. IVD allograft transplantation was performed at lumbar L4/L5 in 5 goats; the other 7 goats were used as the untreated control (5) and for the supply of allografts (2). Post-operation lateral radiographs of the lumbar spine in the neutral, full-flexion and full-extension positions were taken at 1, 3, 6, 9 and 12 months. Disc height (DH) of the allograft and the adjacent levels was calculated and range of motion (ROM) was measured using the Cobb's method. The anatomy of the adjacent discs was observed histologically. DH of the transplanted segment was decreased significantly after 3 months but no further reduction was recorded until the final follow-up. No obvious alteration was seen in the ROM of the transplanted segment at different time points with the ROM at 12 months being comparable to that of the untreated control. The DH and ROM in the adjacent segments were well maintained during the whole observation period. At post-operative 12 months, the ROM of the adjacent levels was similar to that of the untreated control and the anatomical morphology was well preserved. Lumbar IVD allograft transplantation in goats could restore the segmental mobility and did not negatively affect the adjacent segments after 12 months.

  19. Pathogenesis of lumbar spine disease in mucopolysaccharidosis VII

    PubMed Central

    Smith, Lachlan J; Baldo, Guilherme; Wu, Susan; Liu, Yuli; Whyte, Michael P; Giugliani, Roberto; Elliott, Dawn M; Haskins, Mark E; Ponder, Katherine P

    2012-01-01

    Mucopolysaccharidosis type VII (MPS VII) is characterized by deficient β-glucuronidase (GUSB) activity, which leads to accumulation of chondroitin, heparan and dermatan sulfate glycosaminoglycans (GAGs), and multisystemic disease. MPS VII patients can develop kypho-scoliotic deformity and spinal cord compression due to disease of intervertebral discs, vertebral bodies, and associated tissues. We have previously demonstrated in MPS VII dogs that intervertebral discs degenerate, vertebral bodies have irregular surfaces, and vertebral body epiphyses have reduced calcification, but the pathophysiological mechanisms underlying these changes are unclear. We hypothesized that some of these manifestations could be due to upregulation of destructive proteases, possibly via the binding of GAGs to Toll-like receptor 4 (TLR4), as has been proposed for other tissues in MPS models. In this study, the annulus fibrosus of the intervertebral disc of 6 month-old MPS VII dogs had cathepsin B and K activities that were 117- and 2-fold normal, respectively, which were associated with elevations in mRNA levels for cathepsins as well as TLR4. The epiphyses of MPS VII dogs had a marked elevation in mRNA for the cartilage-associated gene collagen II, consistent with a developmental delay in the conversion of the cartilage to bone in this region. A spine from a human patient with MPS VII exhibited similar increased cartilage in the vertebral bodies adjacent to the end plates, disorganization of the intervertebral discs, and irregular vertebral end plate morphology. These data suggest that the pathogenesis of destructive changes in the spine in MPS VII may involve upregulation of cathepsins. Inhibition of destructive proteases, such as cathepsins, might reduce spine disease in patients with MPS VII or related disorders. PMID:22513347

  20. "Bundle Data" Approach at GES DISC Targeting Natural Hazards

    NASA Astrophysics Data System (ADS)

    Shie, C. L.; Shen, S.; Kempler, S. J.

    2015-12-01

    Severe natural phenomena such as hurricane, volcano, blizzard, flood and drought have the potential to cause immeasurable property damages, great socioeconomic impact, and tragic loss of human life. From searching to assessing the "Big", i.e., massive and heterogeneous scientific data (particularly, satellite and model products) in order to investigate those natural hazards, it has, however, become a daunting task for Earth scientists and applications researchers, especially during recent decades. The NASA Goddard Earth Sciences Data and Information Service Center (GES DISC) has served "Big" Earth science data, and the pertinent valuable information and services to the aforementioned users of diverse communities for years. In order to help and guide our users to online readily (i.e., with a minimum effort) acquire their requested data from our enormous resource at GES DISC for studying their targeted hazard/event, we have thus initiated a "Bundle Data" approach in 2014, first targeting the hurricane event/topic. We have recently worked on new topics such as volcano and blizzard. The "bundle data" of a specific hazard/event is basically a sophisticated integrated data package consisting of a series of proper datasets containing a group of relevant ("knowledge-based") data variables readily accessible to users via a system-prearranged table linking those data variables to the proper datasets (URLs). This online approach has been developed by utilizing a few existing data services such as Mirador as search engine; Giovanni for visualization; and OPeNDAP for data access, etc. The online "Data Cookbook" site at GES DISC is the current host for the "bundle data". We are now also planning on developing an "Automated Virtual Collection Framework" that shall eventually accommodate the "bundle data", as well as further improve our management in "Big Data".

  1. Ceramic (Feldspathic & IPS Empress II) vs. laboratory composite (Gradia) veneers; a comparison between their shear bond strength to enamel; an in vitro study.

    PubMed

    Nikzad, S; Azari, Abbas; Dehgan, S

    2010-07-01

    Patient demand for aesthetic dentistry is steadily growing. Laminates and free metal restorations have evolved in an attempt to overcome the invasiveness nature of full veneer restorations. Although many different materials have been used for making these restorations, there is no single material that fits best for all purposes. Two groups of ceramic material (Feldspathic and IPS Empress II) and one group of laboratory composite (Gradia) discs (10 discs in each group; 4 mm in diameter and 2 mm in thickness) were prepared according to the manufacturer's instruction. The surface of ceramic discs were etched and silanized. In Gradia group, liquid primer was applied on composite surfaces. Thirty freshly extracted sound human molars and premolars were randomly divided into three groups. The enamel surface of each tooth was slightly flattened (0.3 mm) on the buccal or lingual side and then primed and cemented to the prepared discs with the aid of a dental surveyor. The finishing specimens were thermocycled between 5 degrees C and 55 degrees C for 2500 cycles and then prepared for shear bond strength testing. The resulting data were analyzed by one-way anova and Tukey HSD test. The fractured surfaces of each specimen were inspected by means of stereomicroscope and SEM. There is significant difference between the bond strength of materials tested. The mean bond strengths obtained with Feldspathic ceramic, IPS Empress II and Gradia were 33.10 +/- 4.31 MPa, 26.04 +/- 7.61 MPa and 14.42 +/- 5.82 MPa, respectively. The fracture pattern was mainly mixed for ceramic groups. More scientific evidence needed for standardization of bonding protocols.

  2. Preflight, In-Flight, and Postflight Imaging of the Cervical and Lumbar Spine in Astronauts.

    PubMed

    Harrison, Michael F; Garcia, Kathleen M; Sargsyan, Ashot E; Ebert, Douglas; Riascos-Castaneda, Roy F; Dulchavsky, Scott A

    2018-01-01

    Back pain is a common complaint during spaceflight that is commonly attributed to intervertebral disc swelling in microgravity. Ultrasound (US) represents the only imaging modality on the International Space Station (ISS) to assess its etiology. The present study investigated: 1) The agreement and correlation of spinal US assessments as compared to results of pre- and postflight MRI studies; and 2) the trend in intervertebral disc characteristics over the course of spaceflight to ISS. Seven ISS astronauts underwent pre- and postflight US examinations that included anterior disc height and anterior intervertebral angles with comparison to pre- and postflight MRI results. In-flight US images were analyzed for changes in disc height and angle. Statistical analysis included repeated measures ANOVA with Bonferroni post hoc analysis, Bland-Altman plots, and Pearson correlation. Bland-Altman plots revealed significant disagreement between disc heights and angles for MRI and US measurements while significant Pearson correlations were found in MRI and US measurements for lumbar disc height (r2 = 0.83) and angle (r2 = 0.89), but not for cervical disc height (r2 = 0.26) or angle (r2 = 0.02). Changes in anterior intervertebral disc angle-initially increases followed by decreases-were observed in the lumbar and cervical spine over the course of the long-duration mission. The cervical spine demonstrated a loss of total disc height during in-flight assessments (∼0.5 cm). Significant disagreement but significant correlation was noted between US and MRI measurements of disc height and angle. Consistency in imaging modality is important for trending measurements and more research related to US technique is required.Harrison MF, Garcia KM, Sargsyan AE, Ebert D, Riascos-Castaneda RF, Dulchavsky SA. Preflight, in-flight, and postflight imaging of the cervical and lumbar spine in astronauts. Aerosp Med Hum Perform. 2018; 89(1):32-40.

  3. Quantification of disc displacement in internal derangement of the temporomandibular joint using magnetic resonance imaging.

    PubMed

    Arayasantiparb, Raweewan; Tsuchimochi, Makoto

    2010-02-01

    Many measures have been developed to determine the extent of disc displacement in internal derangements of the temporomandibular joint (TMJ) using magnetic resonance imaging. The purpose of this study was to develop a quantitative method of analyzing disc position and to evaluate the positions of the disc in internal derangements of the TMJ (group 1, with reduction; group 2, without reduction). Magnetic resonance images of 150 TMJs in 20 healthy volunteers and 55 patients with internal derangements were evaluated. The anatomical points of interest of the TMJ, including the anterior (DA) and posterior (DP) points of the disc, were marked on parasagittal magnetic resonance images of the TMJ disc taken in both the closed- and the open-mouth positions. All points were recorded using an x-y coordinate system, with reference to a referral line. In the closed-mouth position, the DP in patients in group 1 was situated in a more-anterior direction than the DP in volunteers. The DP in group 2 was located further anterior and inferior than the DP in group 1. However, the position of the DA did not differ between group 1 and group 2. In the open-mouth position, the DP was displaced anteroinferiorly to a greater extent in group 2 than in group 1 (one-way ANOVA, followed by Scheffe's test; P < 0.0001). The distance between the disc points in the closed- and open-mouth positions was also evaluated. Comparison of the disc point position in the closed- and open-mouth positions in symptomatic and asymptomatic displaced TMJ discs revealed no significant difference. In conclusion, most of our results quantitatively support previously reported findings in imaging, surgical, and histopathological studies of TMJ internal derangement. We suggest that our measure of disc position of the TMJ would be useful to assess the status and response to treatment of internal derangements of the TMJ.

  4. Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy.

    PubMed

    Capoor, Manu N; Ruzicka, Filip; Schmitz, Jonathan E; James, Garth A; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Lipina, Radim; Ahmed, Fahad S; Alamin, Todd F; Anand, Neel; Baird, John C; Bhatia, Nitin; Demir-Deviren, Sibel; Eastlack, Robert K; Fisher, Steve; Garfin, Steven R; Gogia, Jaspaul S; Gokaslan, Ziya L; Kuo, Calvin C; Lee, Yu-Po; Mavrommatis, Konstantinos; Michu, Elleni; Noskova, Hana; Raz, Assaf; Sana, Jiri; Shamie, A Nick; Stewart, Philip S; Stonemetz, Jerry L; Wang, Jeffrey C; Witham, Timothy F; Coscia, Michael F; Birkenmaier, Christof; Fischetti, Vincent A; Slaby, Ondrej

    2017-01-01

    In previous studies, Propionibacterium acnes was cultured from intervertebral disc tissue of ~25% of patients undergoing microdiscectomy, suggesting a possible link between chronic bacterial infection and disc degeneration. However, given the prominence of P. acnes as a skin commensal, such analyses often struggled to exclude the alternate possibility that these organisms represent perioperative microbiologic contamination. This investigation seeks to validate P. acnes prevalence in resected disc cultures, while providing microscopic evidence of P. acnes biofilm in the intervertebral discs. Specimens from 368 patients undergoing microdiscectomy for disc herniation were divided into several fragments, one being homogenized, subjected to quantitative anaerobic culture, and assessed for bacterial growth, and a second fragment frozen for additional analyses. Colonies were identified by MALDI-TOF mass spectrometry and P. acnes phylotyping was conducted by multiplex PCR. For a sub-set of specimens, bacteria localization within the disc was assessed by microscopy using confocal laser scanning and FISH. Bacteria were cultured from 162 discs (44%), including 119 cases (32.3%) with P. acnes. In 89 cases, P. acnes was cultured exclusively; in 30 cases, it was isolated in combination with other bacteria (primarily coagulase-negative Staphylococcus spp.) Among positive specimens, the median P. acnes bacterial burden was 350 CFU/g (12 - ~20,000 CFU/g). Thirty-eight P. acnes isolates were subjected to molecular sub-typing, identifying 4 of 6 defined phylogroups: IA1, IB, IC, and II. Eight culture-positive specimens were evaluated by fluorescence microscopy and revealed P. acnes in situ. Notably, these bacteria demonstrated a biofilm distribution within the disc matrix. P. acnes bacteria were more prevalent in males than females (39% vs. 23%, p = 0.0013). This study confirms that P. acnes is prevalent in herniated disc tissue. Moreover, it provides the first visual evidence of P. acnes biofilms within such specimens, consistent with infection rather than microbiologic contamination.

  5. A disc inside the bipolar planetary nebula M2-9

    NASA Astrophysics Data System (ADS)

    Lykou, F.; Chesneau, O.; Zijlstra, A. A.; Castro-Carrizo, A.; Lagadec, E.; Balick, B.; Smith, N.

    2011-03-01

    Aims: Bipolarity in proto-planetary and planetary nebulae is associated with events occurring in or around their cores. Past infrared observations have revealed the presence of dusty structures around the cores, many in the form of discs. Characterising those dusty discs provides invaluable constraints on the physical processes that govern the final mass expulsion of intermediate mass stars. We focus this study on the famous M2-9 bipolar nebula, where the moving lighthouse beam pattern indicates the presence of a wide binary. The compact and dense dusty core in the centre of the nebula can be studied by means of optical interferometry. Methods: M2-9 was observed with VLTI/MIDI at 39-47 m baselines with the UT2-UT3 and UT3-UT4 baseline configurations. These observations are interpreted using a dust radiative transfer Monte Carlo code. Results: A disc-like structure is detected perpendicular to the lobes, and a good fit is found with a stratified disc model composed of amorphous silicates. The disc is compact, 25 × 35 mas at 8 μm and 37 × 46 mas at 13 μm. For the adopted distance of 1.2 kpc, the inner rim of the disc is ~15 AU. The mass represents a few percent of the mass found in the lobes. The compactness of the disc puts strong constraints on the binary content of the system, given an estimated orbital period 90-120 yr. We derive masses of the binary components between 0.6-1.0 M⊙ for a white dwarf and 0.6-1.4 M⊙ for an evolved star. We present different scenarios on the geometric structure of the disc accounting for the interactions of the binary system, which includes an accretion disc as well. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile, ESO N: 079.D-146.

  6. Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy

    PubMed Central

    Ruzicka, Filip; Schmitz, Jonathan E.; James, Garth A.; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Lipina, Radim; Ahmed, Fahad S.; Alamin, Todd F.; Anand, Neel; Baird, John C.; Bhatia, Nitin; Demir-Deviren, Sibel; Eastlack, Robert K.; Fisher, Steve; Garfin, Steven R.; Gogia, Jaspaul S.; Gokaslan, Ziya L.; Kuo, Calvin C.; Lee, Yu-Po; Mavrommatis, Konstantinos; Michu, Elleni; Noskova, Hana; Raz, Assaf; Sana, Jiri; Shamie, A. Nick; Stewart, Philip S.; Stonemetz, Jerry L.; Wang, Jeffrey C.; Witham, Timothy F.; Coscia, Michael F.; Birkenmaier, Christof; Fischetti, Vincent A.; Slaby, Ondrej

    2017-01-01

    Background In previous studies, Propionibacterium acnes was cultured from intervertebral disc tissue of ~25% of patients undergoing microdiscectomy, suggesting a possible link between chronic bacterial infection and disc degeneration. However, given the prominence of P. acnes as a skin commensal, such analyses often struggled to exclude the alternate possibility that these organisms represent perioperative microbiologic contamination. This investigation seeks to validate P. acnes prevalence in resected disc cultures, while providing microscopic evidence of P. acnes biofilm in the intervertebral discs. Methods Specimens from 368 patients undergoing microdiscectomy for disc herniation were divided into several fragments, one being homogenized, subjected to quantitative anaerobic culture, and assessed for bacterial growth, and a second fragment frozen for additional analyses. Colonies were identified by MALDI-TOF mass spectrometry and P. acnes phylotyping was conducted by multiplex PCR. For a sub-set of specimens, bacteria localization within the disc was assessed by microscopy using confocal laser scanning and FISH. Results Bacteria were cultured from 162 discs (44%), including 119 cases (32.3%) with P. acnes. In 89 cases, P. acnes was cultured exclusively; in 30 cases, it was isolated in combination with other bacteria (primarily coagulase-negative Staphylococcus spp.) Among positive specimens, the median P. acnes bacterial burden was 350 CFU/g (12 - ~20,000 CFU/g). Thirty-eight P. acnes isolates were subjected to molecular sub-typing, identifying 4 of 6 defined phylogroups: IA1, IB, IC, and II. Eight culture-positive specimens were evaluated by fluorescence microscopy and revealed P. acnes in situ. Notably, these bacteria demonstrated a biofilm distribution within the disc matrix. P. acnes bacteria were more prevalent in males than females (39% vs. 23%, p = 0.0013). Conclusions This study confirms that P. acnes is prevalent in herniated disc tissue. Moreover, it provides the first visual evidence of P. acnes biofilms within such specimens, consistent with infection rather than microbiologic contamination. PMID:28369127

  7. [Expression of integrin alpha5 and actin in the cells of intervertebral disc under cyclic hydrostatic pressure in vitro].

    PubMed

    Yu, Sheng-ji; Qiu, Gui-xing; Burton, Yang; Sandra, Roth; Cari, Whyne; Albert, Yee

    2005-12-15

    To investigate the expression of integrin alpha5 and actin in the cells of intervertebral disc under cyclic hydrostatic pressure in vitro. The porcine lumbar intervertebral disc cells were isolated and cultured in vitro, and the cells underwent cyclic hydrostatic loading. After that, the expression of integrin alpha5 and actin in intervertebral disc cells were studied by means of morphology observing, Western blot and immunohistochemistry staining. The morphology of intervertebral disc cells were changed into smaller and flatten shape, and the expression of integrin alpha5 and actin were decreased after loading. The expression of integrin alpha5 decreases under cyclic hydrostatic pressure, and the actin is affected at the same time when signals are transferred into the cells by integrin alpha5. That may be one of the important mechanisms of the mechanotransduction in the cells of intervertebral disc.

  8. DISC1 genetics, biology and psychiatric illness

    PubMed Central

    THOMSON, Pippa A.; MALAVASI, Elise L.V.; GRÜNEWALD, Ellen; SOARES, Dinesh C.; BORKOWSKA, Malgorzata; MILLAR, J. Kirsty

    2012-01-01

    Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain. PMID:23550053

  9. ERIC on Compact Disc (CD-ROM). A Case Study.

    ERIC Educational Resources Information Center

    Brandhorst, Ted

    ORI, Inc., and SilverPlatter, Inc., have joined together in a joint venture to offer the ERIC database to the public on compact laser disc (CD-ROM). Data from both "Resources in Education" (RIE) and "Current Index to Journals in Education" (CIJE) will be offered on a single disc from January 1983 to the present (with the disc…

  10. The bulge-disc decomposed evolution of massive galaxies at 1 < z < 3 in CANDELS

    NASA Astrophysics Data System (ADS)

    Bruce, V. A.; Dunlop, J. S.; McLure, R. J.; Cirasuolo, M.; Buitrago, F.; Bowler, R. A. A.; Targett, T. A.; Bell, E. F.; McIntosh, D. H.; Dekel, A.; Faber, S. M.; Ferguson, H. C.; Grogin, N. A.; Hartley, W.; Kocevski, D. D.; Koekemoer, A. M.; Koo, D. C.; McGrath, E. J.

    2014-10-01

    We present the results of a new and improved study of the morphological and spectral evolution of massive galaxies over the redshift range 1 < z < 3. Our analysis is based on a bulge-disc decomposition of 396 galaxies with M* > 1011 M⊙ uncovered from the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) Wide Field Camera 3 (WFC3)/IR imaging within the Cosmological Evolution Survey (COSMOS) and UKIRT Infrared Deep Sky Survey (UKIDSS) UDS survey fields. We find that, by modelling the H160 image of each galaxy with a combination of a de Vaucouleurs bulge (Sérsic index n = 4) and an exponential disc (n = 1), we can then lock all derived morphological parameters for the bulge and disc components, and successfully reproduce the shorter-wavelength J125, i814, v606 HST images simply by floating the magnitudes of the two components. This then yields sub-divided four-band HST photometry for the bulge and disc components which, with no additional priors, is well described by spectrophotometric models of galaxy evolution. Armed with this information, we are able to properly determine the masses and star formation rates for the bulge and disc components, and find that: (i) from z = 3 to 1 the galaxies move from disc dominated to increasingly bulge dominated, but very few galaxies are pure bulges/ellipticals by z = 1; (ii) while most passive galaxies are bulge dominated, and most star-forming galaxies disc dominated, 18 ± 5 per cent of passive galaxies are disc dominated, and 11 ± 3 per cent of star-forming galaxies are bulge dominated, a result which needs to be explained by any model purporting to connect star formation quenching with morphological transformations; (iii) there exists a small but significant population of pure passive discs, which are generally flatter than their star-forming counterparts (whose axial ratio distribution peaks at b/a ≃ 0.7); (iv) flatter/larger discs re-emerge at the highest star formation rates, consistent with recent studies of sub-mm galaxies, and with the concept of a maximum surface density for star formation activity.

  11. Topographic optic disc analysis by Heidelberg retinal tomography in ocular Behçet's disease

    PubMed Central

    Berker, Nilufer; Elgin, Ufuk; Ozdal, Pinar; Batman, Aygen; Soykan, Emel; Ozkan, Seyhan S

    2007-01-01

    Aim To compare the topographic characteristics of the optic discs in patients with severe and mild ocular Behçet's disease by using Heidelberg retinal tomographaphy (HRT). Methods This prospective study included 47 eyes of 47 patients with ocular BD who were being followed‐up at the Uveitis Clinic of the Ankara Ulucanlar Eye Research Hospital, Ankara, Turkey. The patients were divided into two groups. Group 1 consisted of 21 eyes with mild uveitis, and group 2 consisted of 26 eyes with severe uveitis. All patients underwent topographic optic disc analysis by HRT II, and the quantitative optic disc parameters of both groups were compared by non‐parametric Mann‐Whitney U test. Results The mean cup volume, rim volume, cup area, disc area and cup depth in group 1 were found to be statistically significantly greater than those in group 2 (p<0.0001, p = 0.03, p = 0.021, p = 0.01 and p = 0.017, respectively), while the difference between the mean cup‐to‐disc ratios in group 1 and group 2 were found to be statistically insignificant (p = 0.148). Conclusion A relationship was found between the severity of ocular BD and optic disc topography determined by HRT. In eyes with smaller optic discs, uveitis was observed to have a more severe course with more frequent relapses than those with larger discs. PMID:17475703

  12. Topographic optic disc analysis by Heidelberg retinal tomography in ocular Behcet's disease.

    PubMed

    Berker, Nilufer; Elgin, Ufuk; Ozdal, Pinar; Batman, Aygen; Soykan, Emel; Ozkan, Seyhan S

    2007-09-01

    To compare the topographic characteristics of the optic discs in patients with severe and mild ocular Behçet's disease by using Heidelberg retinal tomographaphy (HRT). This prospective study included 47 eyes of 47 patients with ocular BD who were being followed-up at the Uveitis Clinic of the Ankara Ulucanlar Eye Research Hospital, Ankara, Turkey. The patients were divided into two groups. Group 1 consisted of 21 eyes with mild uveitis, and group 2 consisted of 26 eyes with severe uveitis. All patients underwent topographic optic disc analysis by HRT II, and the quantitative optic disc parameters of both groups were compared by non-parametric Mann-Whitney U test. The mean cup volume, rim volume, cup area, disc area and cup depth in group 1 were found to be statistically significantly greater than those in group 2 (p<0.0001, p = 0.03, p = 0.021, p = 0.01 and p = 0.017, respectively), while the difference between the mean cup-to-disc ratios in group 1 and group 2 were found to be statistically insignificant (p = 0.148). A relationship was found between the severity of ocular BD and optic disc topography determined by HRT. In eyes with smaller optic discs, uveitis was observed to have a more severe course with more frequent relapses than those with larger discs.

  13. Disruption of circumstellar discs by large-scale stellar magnetic fields

    NASA Astrophysics Data System (ADS)

    ud-Doula, Asif; Owocki, Stanley P.; Kee, Nathaniel Dylan

    2018-05-01

    Spectropolarimetric surveys reveal that 8-10% of OBA stars harbor large-scale magnetic fields, but thus far no such fields have been detected in any classical Be stars. Motivated by this, we present here MHD simulations for how a pre-existing Keplerian disc - like that inferred to form from decretion of material from rapidly rotating Be stars - can be disrupted by a rotation-aligned stellar dipole field. For characteristic stellar and disc parameters of a near-critically rotating B2e star, we find that a polar surface field strength of just 10 G can significantly disrupt the disc, while a field of 100 G, near the observational upper limit inferred for most Be stars, completely destroys the disc over just a few days. Our parameter study shows that the efficacy of this magnetic disruption of a disc scales with the characteristic plasma beta (defined as the ratio between thermal and magnetic pressure) in the disc, but is surprisingly insensitive to other variations, e.g. in stellar rotation speed, or the mass loss rate of the star's radiatively driven wind. The disc disruption seen here for even a modest field strength suggests that the presumed formation of such Be discs by decretion of material from the star would likely be strongly inhibited by such fields; this provides an attractive explanation for why no large-scale fields are detected from such Be stars.

  14. Composition of early planetary atmospheres - II. Coupled Dust and chemical evolution in protoplanetary discs

    NASA Astrophysics Data System (ADS)

    Cridland, A. J.; Pudritz, Ralph E.; Birnstiel, Tilman; Cleeves, L. Ilsedore; Bergin, Edwin A.

    2017-08-01

    We present the next step in a series of papers devoted to connecting the composition of the atmospheres of forming planets with the chemistry of their natal evolving protoplanetary discs. The model presented here computes the coupled chemical and dust evolution of the disc and the formation of three planets per disc model. Our three canonical planet traps produce a Jupiter near 1 AU, a Hot Jupiter and a Super-Earth. We study the dependence of the final orbital radius, mass, and atmospheric chemistry of planets forming in disc models with initial disc masses that vary by 0.02 M⊙ above and below our fiducial model (M_{disc,0} = 0.1 M_{⊙}). We compute C/O and C/N for the atmospheres formed in our three models and find that C/Oplanet ˜ C/O_{disc}, which does not vary strongly between different planets formed in our model. The nitrogen content of atmospheres can vary in planets that grow in different disc models. These differences are related to the formation history of the planet, the time and location that the planet accretes its atmosphere, and are encoded in the bulk abundance of NH3. These results suggest that future observations of atmospheric NH3 and an estimation of the planetary C/O and C/N can inform the formation history of particular planetary systems.

  15. Planetesimal formation in self-gravitating discs - dust trapping by vortices

    NASA Astrophysics Data System (ADS)

    Gibbons, P. G.; Mamatsashvili, G. R.; Rice, W. K. M.

    2015-11-01

    The mechanism through which metre-sized boulders grow to km-sized planetesimals in protoplanetary discs is a subject of active research, since it is critical for planet formation. To avoid spiralling into the protostar due to aerodynamic drag, objects must rapidly grow from cm-sized pebbles, which are tightly coupled to the gas, to large boulders of 1-100 m in diameter. It is already well known that overdensities in the gaseous component of the disc provide potential sites for the collection of solids, and that significant density structures in the gaseous component of the disc (e.g. spiral density waves) can trap solids efficiently enough for the solid component of the disc to undergo further gravitational collapse due to their own self-gravity. In this work, we employ the PENCIL CODE to conduct local shearing sheet simulations of massive self-gravitating protoplanetary discs, to study the effect of anticyclonic transient vortices, or eddies, on the evolution of solids in these discs. We find that these types of structures are extremely efficient at concentrating small and intermediate-sized dust particles with friction times comparable to, or less than, the local orbital period of the disc. This can lead to significant over-densities in the solid component of the disc, with density enhancements comparable to, and even higher, than those within spiral density waves; increasing the rate of gravitational collapse of solids into bound structures.

  16. On the energy dissipation rate at the inner edge of circumbinary discs

    NASA Astrophysics Data System (ADS)

    Terquem, Caroline; Papaloizou, John C. B.

    2017-01-01

    We study, by means of numerical simulations and analysis, the details of the accretion process from a disc on to a binary system. We show that energy is dissipated at the edge of a circumbinary disc and this is associated with the tidal torque that maintains the cavity: angular momentum is transferred from the binary to the disc through the action of compressional shocks and viscous friction. These shocks can be viewed as being produced by fluid elements that drift into the cavity and, before being accreted, are accelerated on to trajectories that send them back to impact the disc. The rate of energy dissipation is approximately equal to the product of potential energy per unit mass at the disc's inner edge and the accretion rate, estimated from the disc parameters just beyond the cavity edge, that would occur without the binary. For very thin discs, the actual accretion rate on to the binary may be significantly less. We calculate the energy emitted by a circumbinary disc taking into account energy dissipation at the inner edge and also irradiation arising there from reprocessing of light from the stars. We find that, for tight PMS binaries, the SED is dominated by emission from the inner edge at wavelengths between 1-4 and 10 μm. This may apply to systems like CoRoT 223992193 and V1481 Ori.

  17. Oscillations of Static Discs around Schwarzschild Black Holes: Effect of Self-Gravitation

    NASA Astrophysics Data System (ADS)

    Semerák, Oldřich; Žáček, Miroslav

    2000-12-01

    The oscillations of accretion-disc matter about roughly circular motion may produce a quasi-periodic variation in the observed signal (Ipser 1996, AAA 65.067.047). They were studied theoretically on non-gravitating, test discs, in a pseudo-Newtonian manner as well as in general relativity, both in static and in stationary fields. The present paper shows how the radial profiles of oscillation frequencies can be modified by the self-gravity of the disc. Exact superpositions of a Schwarzschild black hole with the Lemos and Letelier (1994, AAA 61.067.077) annular discs (static thin discs obtained by inversion of the first Morgan-Morgan solution) are considered to be simple (static) models of an accretion system. Both the epicyclic and perpendicular frequencies are plotted against the Schwarzschild radius, the circumferential radius, and the proper distance from the horizon. The curves indicate that in the innermost parts more massive discs are more stable with respect to horizontal perturbations, whereas they are less stable with respect to vertical perturbations. In the case of a sequence of discs interpretable as counter-rotating particles on stable time-like circular geodesics and having their inner rims just on marginally stable circular orbits, oscillations of the inner parts get faster with increasing disc mass; the maximum of the epicyclic frequency, important for trapping of the low-frequency modes near the inner radius, moves to smaller radii and becomes somewhat higher.

  18. Limits on the location of planetesimal formation in self-gravitating protostellar discs

    NASA Astrophysics Data System (ADS)

    Clarke, C. J.; Lodato, G.

    2009-09-01

    In this Letter, we show that if planetesimals form in spiral features in self-gravitating discs, as previously suggested by the idealized simulations of Rice et al., then in realistic protostellar discs, this process will be restricted to the outer regions of the disc (i.e. at radii in excess of several tens of au). This restriction relates to the requirement that dust has to be concentrated in spiral features on a time-scale that is less than the (roughly dynamical) lifetime of such features, and that such rapid accumulation requires spiral features whose fractional amplitude is not much less than unity. This in turn requires that the cooling time-scale of the gas is relatively short, which restricts the process to the outer disc. We point out that the efficient conversion of a large fraction of the primordial dust in the disc into planetesimals could rescue this material from the well-known problem of rapid inward migration at an approximate metre-size scale and that in principle the collisional evolution of these objects could help to resupply small dust to the protostellar disc. We also point out the possible implications of this scenario for the location of planetesimal belts inferred in debris discs around main sequence stars, but stress that further dynamical studies are required in order to establish whether the disc retains a memory of the initial site of planetesimal creation.

  19. A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection

    PubMed Central

    Choi, K. Yeon; Root, Matthew

    2016-01-01

    ABSTRACT Congenital cytomegalovirus (CMV) infection is a leading cause of mental retardation and deafness in newborns. The guinea pig is the only small animal model for congenital CMV infection. A novel CMV vaccine was investigated as an intervention strategy against congenital guinea pig cytomegalovirus (GPCMV) infection. In this disabled infectious single-cycle (DISC) vaccine strategy, a GPCMV mutant virus was used that lacked the ability to express an essential capsid gene (the UL85 homolog GP85) except when grown on a complementing cell line. In vaccinated animals, the GP85 mutant virus (GP85 DISC) induced an antibody response to important glycoprotein complexes considered neutralizing target antigens (gB, gH/gL/gO, and gM/gN). The vaccine also generated a T cell response to the pp65 homolog (GP83), determined via a newly established guinea pig gamma interferon enzyme-linked immunosorbent spot assay. In a congenital infection protection study, GP85 DISC-vaccinated animals and a nonvaccinated control group were challenged during pregnancy with wild-type GPCMV (105 PFU). The pregnant animals carried the pups to term, and viral loads in target organs of pups were analyzed. Based on live pup births in the vaccinated and control groups (94.1% versus 63.6%), the vaccine was successful in reducing mortality (P = 0.0002). Additionally, pups from the vaccinated group had reduced CMV transmission, with 23.5% infected target organs versus 75.9% in the control group. Overall, these preliminary studies indicate that a DISC CMV vaccine strategy has the ability to induce an immune response similar to that of natural virus infection but has the increased safety of a non-replication-competent virus, which makes this approach attractive as a CMV vaccine strategy. IMPORTANCE Congenital CMV infection is a leading cause of mental retardation and deafness in newborns. An effective vaccine against CMV remains an elusive goal despite over 50 years of CMV research. The guinea pig, with a placenta structure similar to that in humans, is the only small animal model for congenital CMV infection and recapitulates disease symptoms (e.g., deafness) in newborn pups. In this report, a novel vaccine strategy against congenital guinea pig cytomegalovirus (GPCMV) infection was developed, characterized, and tested for efficacy. This disabled infectious single-cycle (DISC) vaccine strategy induced a neutralizing antibody or a T cell response to important target antigens. In a congenital infection protection study, animals were protected against CMV in comparison to the nonvaccinated group (52% reduction of transmission). This novel vaccine was more effective than previously tested gB-based vaccines and most other strategies involving live virus vaccines. Overall, the DISC vaccine is a safe and promising approach against congenital CMV infection. PMID:27334585

  20. Control of lysosomal biogenesis and Notch-dependent tissue patterning by components of the TFEB-V-ATPase axis in Drosophila melanogaster.

    PubMed

    Tognon, Emiliana; Kobia, Francis; Busi, Ilaria; Fumagalli, Arianna; De Masi, Federico; Vaccari, Thomas

    2016-01-01

    In vertebrates, TFEB (transcription factor EB) and MITF (microphthalmia-associated transcription factor) family of basic Helix-Loop-Helix (bHLH) transcription factors regulates both lysosomal function and organ development. However, it is not clear whether these 2 processes are interconnected. Here, we show that Mitf, the single TFEB and MITF ortholog in Drosophila, controls expression of vacuolar-type H(+)-ATPase pump (V-ATPase) subunits. Remarkably, we also find that expression of Vha16-1 and Vha13, encoding 2 key components of V-ATPase, is patterned in the wing imaginal disc. In particular, Vha16-1 expression follows differentiation of proneural regions of the disc. These regions, which will form sensory organs in the adult, appear to possess a distinctive endolysosomal compartment and Notch (N) localization. Modulation of Mitf activity in the disc in vivo alters endolysosomal function and disrupts proneural patterning. Similar to our findings in Drosophila, in human breast epithelial cells we observe that impairment of the Vha16-1 human ortholog ATP6V0C changes the size and function of the endolysosomal compartment and that depletion of TFEB reduces ligand-independent N signaling activity. Our data suggest that lysosomal-associated functions regulated by the TFEB-V-ATPase axis might play a conserved role in shaping cell fate.

  1. Growth-inhibiting effects of seco-tanapartholides identified in Artemisia princeps var. orientalis whole plant on human intestinal bacteria.

    PubMed

    Cho, S-H; Na, Y-E; Ahn, Y-J

    2003-01-01

    The present work aimed at isolating antibacterial constituents from the whole plant of Artemisia princeps var. orientalis active towards nine human intestinal bacteria. The growth-inhibiting activities of materials derived from the Artemisia whole plant towards test bacteria were examined using an impregnated paper disc method. The biologically active constituents of the Artemisia whole plant were characterized as the sesquiterpene lactones seco-tanapartholides A and B by spectroscopic analysis. In a test using 1 mg per disc, seco-tanapartholides A and B produced a clear inhibitory effect against Clostridium perfringens, Bacteroides fragilis and Staphylococcus aureus. These compounds did not affect the growth of test lactic acid-producing bacteria (Bifidobacterium adolescentis, Bif. breve, Lactobacillus acidophilus and Lact. casei) and Escherichia coli, whereas weak growth inhibition towards Bif. bifidum was observed. At 0.5 mg per disc, seco-tanapartholides A and B exhibited moderate growth inhibition towards Cl. perfringens but weak growth inhibition towards Bact. fragilis and Staph. aureus. Inhibitory action of seco-tanapartholides A and B towards specific bacteria without any adverse effects on lactic acid-producing bacteria may be an indication of at least one of the pharmacological actions of A. princeps var. orientalis whole plant. These naturally occurring Artemisia whole plant-derived materials could be useful as a new preventive agent against various diseases caused by harmful intestinal bacteria such as clostridia.

  2. Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation

    PubMed Central

    Liao, Zhenhua; Fogel, Guy R.; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

    2015-01-01

    Background The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. Material/Methods Eighteen human cadaveric spines (C2–T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3–4 ACDR+C4–6 ACDF+C6–7ACDR; hybrid C3–5ACDF+C5–6ACDR+C6–7ACDR; hybrid C3–4ACDR+C4–5ACDR+C5–7ACDF); and 4-level fusion. Results Four-level fusion resulted in significant decrease in the C3–C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. Conclusions Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion. PMID:26694835

  3. Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation.

    PubMed

    Liao, Zhenhua; Fogel, Guy R; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

    2015-12-23

    BACKGROUND The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. MATERIAL AND METHODS Eighteen human cadaveric spines (C2-T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3-4 ACDR+C4-6 ACDF+C6-7ACDR; hybrid C3-5ACDF+C5-6ACDR+C6-7ACDR; hybrid C3-4ACDR+C4-5ACDR+C5-7ACDF); and 4-level fusion. RESULTS Four-level fusion resulted in significant decrease in the C3-C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. CONCLUSIONS Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion.

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

    PubMed

    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 < 0.001; for 3-7 cell monoclonal cell nests: groups DG vs. DB vs. C: 2.4 ± 1, 3.9 ± 1, 2.2 ± 1.1, respectively; p intervention x nest size  = 0.006) were found in the IVDs of patients in group DB. This in vivo study suggests that chondrotoxic effects occur in IVD cells after the intradiscal injection of 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.

  5. Finite Element Analysis of the Effect of Epidural Adhesions.

    PubMed

    Lee, Nam; Ji, Gyu Yeul; Yi, Seong; Yoon, Do Heum; Shin, Dong Ah; Kim, Keung Nyun; Ha, Yoon; Oh, Chang Hyun

    2016-07-01

    It is well documented that epidural adhesion is associated with spinal pain. However, the underlying mechanism of spinal pain generation by epidural adhesion has not yet been elucidated. To elucidate the underlying mechanism of spinal pain generation by epidural adhesion using a two-dimensional (2D) non-linear finite element (FE) analysis. A finite element analysis. A two-dimensional nonlinear FE model of the herniated lumbar disc on L4/5 with epidural adhesion. A two-dimensional nonlinear FE model of the lumbar spine was developed, consisting of intervertebral discs, dura, spinal nerve, and lamina. The annulus fibrosus and nucleus pulpous were modeled as hyperelastic using the Mooney-Rivlin equation. The FE mesh was generated and analyzed using Abaqus (ABAQUS 6.13.; Hibbitt, Karlsson & Sorenson, Inc., Providence, RI, USA). Epidural adhesion was simulated as rough contact, in which no slip occurred once two surfaces were in contact, between the dura mater and posterior annulus fibrosus. The FE model of adhesion showed significant stress concentration in the spinal nerves, especially on the dorsal root ganglion (DRG). The stress concentration was caused by the lack of adaptive displacement between the dura mater and posterior annulus fibrosus. The peak von Mises stress was higher in the epidural adhesion model (Adhesion, 0.67 vs. Control, 0.46). In the control model, adaptive displacement was observed with decreased stress in the spinal nerve and DRG (with adhesion, 2.59 vs. without adhesion, 3.58, P < 0.00). This study used a 2D non-linear FE model, which simplifies the 3D nature of the human intervertebral disc. In addition, this 2D non-linear FE model has not yet been validated. The current study clearly demonstrated that epidural adhesion causes significantly increased stress in the spinal nerves, especially at the DRG. We believe that the increased stress on the spinal nerve might elicit more pain under similar magnitudes of lumbar disc protrusion.

  6. Revolution evolution: tracing angular momentum during star and planetary system formation

    NASA Astrophysics Data System (ADS)

    Davies, Claire Louise

    2015-04-01

    Stars form via the gravitational collapse of molecular clouds during which time the protostellar object contracts by over seven orders of magnitude. If all the angular momentum present in the natal cloud was conserved during collapse, stars would approach rotational velocities rapid enough to tear themselves apart within just a few Myr. In contrast to this, observations of pre-main sequence rotation rates are relatively slow (∼ 1 - 15 days) indicating that significant quantities of angular momentum must be removed from the star. I use observations of fully convective pre-main sequence stars in two well-studied, nearby regions of star formation (namely the Orion Nebula Cluster and Taurus-Auriga) to determine the removal rate of stellar angular momentum. I find the accretion disc-hosting stars to be rotating at a slower rate and contain less specific angular momentum than the disc-less stars. I interpret this as indicating a period of accretion disc-regulated angular momentum evolution followed by near-constant rotational evolution following disc dispersal. Furthermore, assuming that the age spread inferred from the Hertzsprung-Russell diagram constructed for the star forming region is real, I find that the removal rate of angular momentum during the accretion-disc hosting phase to be more rapid than that expected from simple disc-locking theory whereby contraction occurs at a fixed rotation period. This indicates a more efficient process of angular momentum removal must operate, most likely in the form of an accretion-driven stellar wind or outflow emanating from the star-disc interaction. The initial circumstellar envelope that surrounds a protostellar object during the earliest stages of star formation is rotationally flattened into a disc as the star contracts. An effective viscosity, present within the disc, enables the disc to evolve: mass accretes inwards through the disc and onto the star while momentum migrates outwards, forcing the outer regions of the disc to expand. I used spatially resolved submillimetre detections of the dust and gas components of protoplanetary discs, gathered from the literature, to measure the radial extent of discs around low-mass pre-main sequence stars of ∼ 1-10 Myr and probe their viscous evolution. I find no clear observational evidence for the radial expansion of the dust component. However, I find tentative evidence for the expansion ofthe gas component. This suggests that the evolution of the gas and dust components of protoplanetary discs are likely governed by different astrophysical processes. Observations of jets and outflows emanating from protostars and pre-main sequence stars highlight that it may also be possible to remove angular momentum from the circumstellar material. Using the sample of spatially resolved protoplanetary discs, I find no evidence for angular momentum removal during disc evolution. I also use the spatially resolved debris discs from the Submillimetre Common-User Bolometer Array-2 Observations of Nearby Stars survey to constrain the amount of angular momentum retained within planetary systems. This sample is compared to the protoplanetary disc angular momenta and to the angular momentum contained within pre-stellar cores. I find that significant quantities of angular momentum must be removed during disc formation and disc dispersal. This likely occurs via magnetic braking during the formation of the disc, via the launching of a disc or photo-evaporative wind, and/or via ejection of planetary material following dynamical interactions.

  7. A Novel, Minimally-Invasive Approach to Repair Degenerative Disk Disease in an Ovine Model Using Injectable Polymethyl-Methacrylate and Bovine Collagen (PMMA/BC)

    PubMed Central

    Feldman, Erica; Narayan, Anisha; Taylor, William

    2016-01-01

    Background : The natural, inflammatory repair processes of an injured intervertebral degenerative disc can propagate further injury and destruction. While there are many different treatment modalities of the pain related to degenerative disc disease, none are actually reparative in nature. Treatment strategies to repair a degenerative disc without inducing a destructive inflammatory milieu have been elusive.  Purpose: The purpose of this experiment is to discover the feasibility of reconstructing an injured intervertebral disc using an injected, inert polymer as the foundation for endogenous collagen growth. Study Design: In this ovine model of six subjects in total, we introduce a modality where a large inert polymer, polymethyl methacrylate (PMMA), in conjunction bovine collagen (BC) is injected into the intervertebral disc. Following six months of observation, histologic specimens were evaluated macroscopically and microscopically for evidence of a benefit of the injectable PMMA/BC. Methods: We obtained six merino sheep for this study. Concentric injuries were made to four of their lumbar intervertebral discs. Two of those levels were treated with a percutaneous injection of 0.3 cc of PMMA/BC. The remaining lumbar levels were left untreated and were our controls. After six months, all subjects were sacrificed. Their four levels were extracted and were examined macroscopically and microscopically. Results: All subjects tolerated the lumbar injury and percutaneous injection of PMMA/BC well. After the six month interval, all subjects have demonstrated an intact architecture of their lumbar disc height at the macroscopic and microscopic level. Microscopically, there was no evidence of external migration of the PMMA/BC microspheres, nor was there any evidence of an inflammatory response by its presence. Notably, the PMMA/BC microspheres were well-incorporated into the concentric disc tears and had undergone endogenous collagen formation in its environment. Treatment levels were revealing for maintenance of disc height without evidence of an ongoing degeneration. The controlled levels were revealing for continued disc degeneration with loss of disc height and evolving injury at the level of the concentric tear. Conclusions: This ovine model demonstrates a novel and promising technique for prevention and arrest of lumbar intervertebral disc degeneration. PMID:27630802

  8. Catalase purification from rat liver with iron-chelated poly(hydroxyethyl methacrylate-N-methacryloyl-(l)-glutamic acid) cryogel discs.

    PubMed

    Göktürk, Ilgım; Perçin, Işık; Denizli, Adil

    2016-08-17

    In this study, iron-chelated poly(hydroxyethyl methacrylate-N-methacryloyl-(l)-glutamic acid) (PHEMAGA/Fe(3+)) cryogel discs were prepared. The PHEMAGA/Fe(3+) cryogel discs were characterized by elemental analysis, scanning electron microscopy, Fourier transform infrared spectroscopy, swelling tests, and surface area measurements. The PHEMAGA/Fe(3+) cryogel discs had large pores ranging from 10 to 100 µm with a swelling degree of 9.36 g H2O/g cryogel. Effects of pH, temperature, initial catalase concentration, and flow rate on adsorption capacity of the PHEMAGA/Fe(3+) cryogel discs were investigated. Maximum catalase adsorption capacity (62.6 mg/g) was obtained at pH 7.0, 25°C, and 3 mg/ml initial catalase concentration. The PHEMAGA/Fe(3+) cryogel discs were also tested for the purification of catalase from rat liver. After tissue homogenization, purification of catalase was performed using the PHEMAGA/Fe(3+) cryogel discs and catalase was obtained with a yield of 54.34 and 16.67 purification fold.

  9. The Causal Connection Between Disc and Power-Law Variability in Hard State Black Hole X-Ray Binaries

    NASA Technical Reports Server (NTRS)

    Uttley, P.; Wilkinson, T.; Cassatella, P.; Wilms, J.; Pottschimdt, K.; Hanke, M.; Boeck, M.

    2010-01-01

    We use the XMM-Newton EPIC-pn instrument in timing mode to extend spectral time-lag studies of hard state black hole X-ray binaries into the soft X-ray band. \\Ve show that variations of the disc blackbody emission substantially lead variations in the power-law emission, by tenths of a second on variability time-scales of seconds or longer. The large lags cannot be explained by Compton scattering but are consistent with time-delays due to viscous propagation of mass accretion fluctuations in the disc. However, on time-scales less than a second the disc lags the power-law variations by a few ms, consistent with the disc variations being dominated by X-ray heating by the power-law, with the short lag corresponding to the light-travel time between the power-law emitting region and the disc. Our results indicate that instabilities in the accretion disc are responsible for continuum variability on time-scales of seconds or longer and probably also on shorter time-scales.

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

    PubMed

    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.

  11. Prevalence of Propionibacterium acnes in Intervertebral Discs of Patients Undergoing Lumbar Microdiscectomy: A Prospective Cross-Sectional Study

    PubMed Central

    Capoor, Manu N.; Ruzicka, Filip; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Schmitz, Jonathan E.; Hermanova, Marketa; Sana, Jiri; Michu, Elleni; Baird, John C.; Ahmed, Fahad S.; Maca, Karel; Lipina, Radim; Alamin, Todd F.; Coscia, Michael F.; Stonemetz, Jerry L.; Witham, Timothy; Ehrlich, Garth D.; Gokaslan, Ziya L.; Mavrommatis, Konstantinos; Birkenmaier, Christof; Fischetti, Vincent A.; Slaby, Ondrej

    2016-01-01

    Background The relationship between intervertebral disc degeneration and chronic infection by Propionibacterium acnes is controversial with contradictory evidence available in the literature. Previous studies investigating these relationships were under-powered and fraught with methodical differences; moreover, they have not taken into consideration P. acnes’ ability to form biofilms or attempted to quantitate the bioburden with regard to determining bacterial counts/genome equivalents as criteria to differentiate true infection from contamination. The aim of this prospective cross-sectional study was to determine the prevalence of P. acnes in patients undergoing lumbar disc microdiscectomy. Methods and Findings The sample consisted of 290 adult patients undergoing lumbar microdiscectomy for symptomatic lumbar disc herniation. An intraoperative biopsy and pre-operative clinical data were taken in all cases. One biopsy fragment was homogenized and used for quantitative anaerobic culture and a second was frozen and used for real-time PCR-based quantification of P. acnes genomes. P. acnes was identified in 115 cases (40%), coagulase-negative staphylococci in 31 cases (11%) and alpha-hemolytic streptococci in 8 cases (3%). P. acnes counts ranged from 100 to 9000 CFU/ml with a median of 400 CFU/ml. The prevalence of intervertebral discs with abundant P. acnes (≥ 1x103 CFU/ml) was 11% (39 cases). There was significant correlation between the bacterial counts obtained by culture and the number of P. acnes genomes detected by real-time PCR (r = 0.4363, p<0.0001). Conclusions In a large series of patients, the prevalence of discs with abundant P. acnes was 11%. We believe, disc tissue homogenization releases P. acnes from the biofilm so that they can then potentially be cultured, reducing the rate of false-negative cultures. Further, quantification study revealing significant bioburden based on both culture and real-time PCR minimize the likelihood that observed findings are due to contamination and supports the hypothesis P. acnes acts as a pathogen in these cases of degenerative disc disease. PMID:27536784

  12. Prevalence of Propionibacterium acnes in Intervertebral Discs of Patients Undergoing Lumbar Microdiscectomy: A Prospective Cross-Sectional Study.

    PubMed

    Capoor, Manu N; Ruzicka, Filip; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Schmitz, Jonathan E; Hermanova, Marketa; Sana, Jiri; Michu, Elleni; Baird, John C; Ahmed, Fahad S; Maca, Karel; Lipina, Radim; Alamin, Todd F; Coscia, Michael F; Stonemetz, Jerry L; Witham, Timothy; Ehrlich, Garth D; Gokaslan, Ziya L; Mavrommatis, Konstantinos; Birkenmaier, Christof; Fischetti, Vincent A; Slaby, Ondrej

    2016-01-01

    The relationship between intervertebral disc degeneration and chronic infection by Propionibacterium acnes is controversial with contradictory evidence available in the literature. Previous studies investigating these relationships were under-powered and fraught with methodical differences; moreover, they have not taken into consideration P. acnes' ability to form biofilms or attempted to quantitate the bioburden with regard to determining bacterial counts/genome equivalents as criteria to differentiate true infection from contamination. The aim of this prospective cross-sectional study was to determine the prevalence of P. acnes in patients undergoing lumbar disc microdiscectomy. The sample consisted of 290 adult patients undergoing lumbar microdiscectomy for symptomatic lumbar disc herniation. An intraoperative biopsy and pre-operative clinical data were taken in all cases. One biopsy fragment was homogenized and used for quantitative anaerobic culture and a second was frozen and used for real-time PCR-based quantification of P. acnes genomes. P. acnes was identified in 115 cases (40%), coagulase-negative staphylococci in 31 cases (11%) and alpha-hemolytic streptococci in 8 cases (3%). P. acnes counts ranged from 100 to 9000 CFU/ml with a median of 400 CFU/ml. The prevalence of intervertebral discs with abundant P. acnes (≥ 1x103 CFU/ml) was 11% (39 cases). There was significant correlation between the bacterial counts obtained by culture and the number of P. acnes genomes detected by real-time PCR (r = 0.4363, p<0.0001). In a large series of patients, the prevalence of discs with abundant P. acnes was 11%. We believe, disc tissue homogenization releases P. acnes from the biofilm so that they can then potentially be cultured, reducing the rate of false-negative cultures. Further, quantification study revealing significant bioburden based on both culture and real-time PCR minimize the likelihood that observed findings are due to contamination and supports the hypothesis P. acnes acts as a pathogen in these cases of degenerative disc disease.

  13. Regulation of CCN2/CTGF Expression in the Nucleus Pulposus of the Intervertebral Disc: Role of Smad and AP1 Signaling

    PubMed Central

    Tran, Cassie M.; Markova, Dessislava; Smith, Harvey E.; Susarla, Bala; Ponnappan, Ravi Kumar; Anderson, D Greg; Symes, Aviva; Shapiro, Irving M.; Risbud, Makarand V.

    2011-01-01

    Objective To investigate TGFβ regulation of CTGF expression in cells of the nucleus pulposus. Methods Real Time RT-PCR and Western blot analysis was used to measure CTGF expression in the nucleus pulposus. Transfections were used to measure the effect of Smad2/3/7 and AP1on TGFβ mediated CTGF promoter activity. Results CTGF expression was lower in the neonatal disc compared with the skeletally mature rat disc. An increase in CTGF expression and promoter activity was observed in nucleus pulposus cells after TGFβ treatment. Deletion analysis indicated that promoter constructs lacking smad and AP1 motifs were unresponsive to treatment. Analysis showed that full-length Smad3 and the Smad3-MH2 domain alone increased CTGF activity. Further evidence of Smad3 and AP1 involvement was seen when DN-Smad3, SiRNA-Smad3, smad7 and DN-AP1 suppressed TGFβ mediated activation of the CTGF promoter. When either Smad3 or AP1 sites were mutated, CTGF promoter induction by TGFβ was suppressed. We also observed a decrease in expression of CTGF in discs of Smad3 null mice compared to the wild type. Analysis of human nucleus pulposus indicated a trend of increasing CTGF and TGFβ expression in the degenerate state. Conclusion TGFβ, through Smad3 and AP1, serves as a positive regulator of CTGF expression in the nucleus pulposus. We propose that CTGF is a part of the limited reparative response of the degenerate disc. PMID:20222112

  14. Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

    PubMed Central

    Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

    2014-01-01

    Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM. PMID:26069692

  15. Studies on proteinograms in dermatorphytes by disc electrophoresis. Part 2: Protein bands of keratinophilic fungi

    NASA Technical Reports Server (NTRS)

    Danev, P.; Balabanov, V.; Friedrich, E.

    1983-01-01

    Disc electrophoresis studies on keratinophili fungi demonstrated corresponding proteinograms in morphologically homogeneous strains of the same species, but different in different species of one and the same genus.

  16. Using improved technology for filter paper-based blood collection to survey wild Sika deer for antibodies to hepatitis E virus.

    PubMed

    Yu, Claro; Zimmerman, Carl; Stone, Roger; Engle, Ronald E; Elkins, William; Nardone, Glenn A; Emerson, Suzanne U; Purcell, Robert H

    2007-06-01

    Recent reports from Japan implicated wild Sika deer (Cervus nippon) in the zoonotic transmission of hepatitis E to humans. Seroprevalence studies were performed to determine if imported feral populations of Sika deer in Maryland and Virginia posed a similar risk of transmitting hepatitis E virus (HEV). Hunters collected blood on filter paper discs from freshly killed deer. The discs were desiccated and delivered to a collection point. The dried filters were weighed to estimate the amount of blood absorbed and were eluted and collected in one tube via a novel extraction system. The procedure was quantified and validated with negative and positive serum and blood samples obtained from domestic Sika deer before and after immunization with HEV recombinant capsid protein, respectively. None of the 155 tested samples contained antibody to HEV, suggesting that Sika deer in these populations, unlike those in Japan, do not pose a significant zoonotic threat for hepatitis E. However, the new method developed for collecting and eluting the samples should prove useful for field studies of many other pathogens.

  17. The contribution of collagen fibers to the mechanical compressive properties of the temporomandibular joint disc.

    PubMed

    Fazaeli, S; Ghazanfari, S; Everts, V; Smit, T H; Koolstra, J H

    2016-07-01

    The Temporomandibular Joint (TMJ) disc is a fibrocartilaginous structure located between the mandibular condyle and the temporal bone, facilitating smooth movements of the jaw. The load-bearing properties of its anisotropic collagenous network have been well characterized under tensile loading conditions. However, recently it has also been speculated that the collagen fibers may contribute dominantly in reinforcing the disc under compression. Therefore, in this study, the structural-functional role of collagen fibers in mechanical compressive properties of TMJ disc was investigated. Intact porcine TMJ discs were enzymatically digested with collagenase to disrupt the collagenous network of the cartilage. The digested and non-digested articular discs were analyzed mechanically, biochemically and histologically in five various regions. These tests included: (1) cyclic compression tests, (2) biochemical quantification of collagen and glycosaminoglycan (GAG) content and (3) visualization of collagen fibers' alignment by polarized light microscopy (PLM). The instantaneous compressive moduli of the articular discs were reduced by as much as 50-90% depending on the region after the collagenase treatment. The energy dissipation properties of the digested discs showed a similar tendency. Biochemical analysis of the digested samples demonstrated an average of 14% and 35% loss in collagen and GAG, respectively. Despite the low reduction of collagen content the PLM images showed considerable perturbation of the collagenous network of the TMJ disc. The results indicated that even mild disruption of collagen fibers can lead to substantial mechanical softening of TMJ disc undermining its reinforcement and mechanical stability under compression. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  18. CO bandhead emission of massive young stellar objects: determining disc properties

    NASA Astrophysics Data System (ADS)

    Ilee, J. D.; Wheelwright, H. E.; Oudmaijer, R. D.; de Wit, W. J.; Maud, L. T.; Hoare, M. G.; Lumsden, S. L.; Moore, T. J. T.; Urquhart, J. S.; Mottram, J. C.

    2013-03-01

    Massive stars play an important role in many areas of astrophysics, but numerous details regarding their formation remain unclear. In this paper we present and analyse high-resolution (R ˜ 30 000) near-infrared 2.3 μm spectra of 20 massive young stellar objects (MYSOs) from the Red MSX Source (RMS) data base, in the largest such study of CO first overtone bandhead emission to date. We fit the emission under the assumption it originates from a circumstellar disc in Keplerian rotation. We explore three approaches to modelling the physical conditions within the disc - a disc heated mainly via irradiation from the central star, a disc heated mainly via viscosity, and a disc in which the temperature and density are described analytically. We find that the models described by heating mechanisms are inappropriate because they do not provide good fits to the CO emission spectra. We therefore restrict our analysis to the analytic model, and obtain good fits to all objects that possess sufficiently strong CO emission, suggesting circumstellar discs are the source of this emission. On average, the temperature and density structure of the discs correspond to geometrically thin discs, spread across a wide range of inclinations. Essentially all the discs are located within the dust sublimation radius, providing strong evidence that the CO emission originates close to the central protostar, on astronomical unit scales. In addition, we show that the objects in our sample appear no different to the general population of MYSOs in the RMS data base, based on their near- and mid-infrared colours. The combination of observations of a large sample of MYSOs with CO bandhead emission and our detailed modelling provide compelling evidence of the presence of small-scale gaseous discs around such objects, supporting the scenario in which massive stars form via disc accretion.

  19. Noninvasive Assessment of Biochemical and Mechanical Properties of Lumbar Discs Through Quantitative Magnetic Resonance Imaging in Asymptomatic Volunteers.

    PubMed

    Foltz, Mary H; Kage, Craig C; Johnson, Casey P; Ellingson, Arin M

    2017-11-01

    Intervertebral disc degeneration is a prevalent phenomenon associated with back pain. It is of critical clinical interest to discriminate disc health and identify early stages of degeneration. Traditional clinical T2-weighted magnetic resonance imaging (MRI), assessed using the Pfirrmann classification system, is subjective and fails to adequately capture initial degenerative changes. Emerging quantitative MRI techniques offer a solution. Specifically, T2* mapping images water mobility in the macromolecular network, and our preliminary ex vivo work shows high predictability of the disc's glycosaminoglycan content (s-GAG) and residual mechanics. The present study expands upon this work to predict the biochemical and biomechanical properties in vivo and assess their relationship with both age and Pfirrmann grade. Eleven asymptomatic subjects (range: 18-62 yrs) were enrolled and imaged using a 3T MRI scanner. T2-weighted images (Pfirrmann grade) and quantitative T2* maps (predict s-GAG and residual stress) were acquired. Surface maps based on the distribution of these properties were generated and integrated to quantify the surface volume. Correlational analyses were conducted to establish the relationship between each metric of disc health derived from the quantitative T2* maps with both age and Pfirrmann grade, where an inverse trend was observed. Furthermore, the nucleus pulposus (NP) signal in conjunction with volumetric surface maps provided the ability to discern differences during initial stages of disc degeneration. This study highlights the ability of T2* mapping to noninvasively assess the s-GAG content, residual stress, and distributions throughout the entire disc, which may provide a powerful diagnostic tool for disc health assessment.

  20. Antipredator behaviours of a spider mite in response to cues of dangerous and harmless predators.

    PubMed

    Dias, Cleide Rosa; Bernardo, Ana Maria Guimarães; Mencalha, Jussara; Freitas, Caelum Woods Carvalho; Sarmento, Renato Almeida; Pallini, Angelo; Janssen, Arne

    2016-07-01

    Prey are known to invest in costly antipredator behaviour when perceiving cues of dangerous, but not of relatively harmless predators. Whereas most studies investigate one type of antipredator behaviour, we studied several types (changes in oviposition, in escape and avoidance behaviour) in the spider mite Tetranychus evansi in response to cues from two predatory mites. The predator Phytoseiulus longipes is considered a dangerous predator for T. evansi, whereas Phytoseiulus macropilis has a low predation rate on this prey, thus is a much less dangerous predator. Spider mite females oviposited less on leaf disc halves with predator cues than on clean disc halves, independent of the predator species. On entire leaf discs, they laid fewer eggs in the presence of cues of the dangerous predator than on clean discs, but not in the presence of cues of the harmless predator. Furthermore, the spider mites escaped more often from discs with cues of the dangerous predator than from discs without predator cues, but they did not escape more from discs with cues of the harmless predator. The spider mites did not avoid plants with conspecifics and predators. We conclude that the spider mites displayed several different antipredator responses to the same predator species, and that some of these antipredator responses were stronger with cues of dangerous predators than with cues of harmless predators.

  1. A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for Intervertebral Disc Regeneration

    PubMed Central

    Shu, Cindy C.; Smith, Margaret M.; Smith, Susan M.; Dart, Andrew J.; Little, Christopher B.; Melrose, James

    2017-01-01

    The purpose of this study was to develop a quantitative histopathological scoring scheme to evaluate disc degeneration and regeneration using an ovine annular lesion model of experimental disc degeneration. Toluidine blue and Haematoxylin and Eosin (H&E) staining were used to evaluate cellular morphology: (i) disc structure/lesion morphology; (ii) proteoglycan depletion; (iii) cellular morphology; (iv) blood vessel in-growth; (v) cell influx into lesion; and (vi) cystic degeneration/chondroid metaplasia. Three study groups were examined: 5 × 5 mm lesion; 6 × 20 mm lesion; and 6 × 20 mm lesion plus mesenchymal stem cell (MSC) treatment. Lumbar intervertebral discs (IVDs) were scored under categories (i–vi) to provide a cumulative score, which underwent statistical analysis using STATA software. Focal proteoglycan depletion was associated with 5 × 5 mm annular rim lesions, bifurcations, annular delamellation, concentric and radial annular tears and an early influx of blood vessels and cells around remodeling lesions but the inner lesion did not heal. Similar features in 6 × 20 mm lesions occurred over a 3–6-month post operative period. MSCs induced a strong recovery in discal pathology with a reduction in cumulative histopathology degeneracy score from 15.2 to 2.7 (p = 0.001) over a three-month recovery period but no recovery in carrier injected discs. PMID:28498326

  2. Three-dimensional disc-satellite interaction: torques, migration, and observational signatures

    NASA Astrophysics Data System (ADS)

    Arzamasskiy, Lev; Zhu, Zhaohuan; Stone, James M.

    2018-04-01

    The interaction of a satellite with a gaseous disc results in the excitation of spiral density waves, which remove angular momentum from the orbit. In addition, if the orbit is not coplanar with the disc, three-dimensional effects will excite bending and eccentricity waves. We perform three-dimensional hydrodynamic simulations to study nonlinear disc-satellite interaction in inviscid protoplanetary discs for a variety of orbital inclinations from 0° to 180°. It is well known that three-dimensional effects are important even for zero inclination. In this work, we (1) show that for planets with small inclinations (as in the Solar system), effects such as the total torque and migration rate strongly depend on the inclination and are significantly different (about 2.5 times smaller) from the two-dimensional case, (2) give formulae for the migration rate, inclination damping, and precession rate of planets with different inclination angles in disc with different scale heights, and (3) present the observational signatures of a planet on an inclined orbit with respect to the protoplanetary disc. For misaligned planets, we find good agreement with linear theory in the limit of small inclinations, and with dynamical friction estimates for intermediate inclinations. We find that in the latter case, the dynamical friction force is not parallel to the relative planetary velocity. Overall, the derived formulae will be important for studying exoplanets with obliquity.

  3. A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for Intervertebral Disc Regeneration.

    PubMed

    Shu, Cindy C; Smith, Margaret M; Smith, Susan M; Dart, Andrew J; Little, Christopher B; Melrose, James

    2017-05-12

    The purpose of this study was to develop a quantitative histopathological scoring scheme to evaluate disc degeneration and regeneration using an ovine annular lesion model of experimental disc degeneration. Toluidine blue and Haematoxylin and Eosin (H&E) staining were used to evaluate cellular morphology: (i) disc structure/lesion morphology; (ii) proteoglycan depletion; (iii) cellular morphology; (iv) blood vessel in-growth; (v) cell influx into lesion; and (vi) cystic degeneration/chondroid metaplasia. Three study groups were examined: 5 × 5 mm lesion; 6 × 20 mm lesion; and 6 × 20 mm lesion plus mesenchymal stem cell (MSC) treatment. Lumbar intervertebral discs (IVDs) were scored under categories (i-vi) to provide a cumulative score, which underwent statistical analysis using STATA software. Focal proteoglycan depletion was associated with 5 × 5 mm annular rim lesions, bifurcations, annular delamellation, concentric and radial annular tears and an early influx of blood vessels and cells around remodeling lesions but the inner lesion did not heal. Similar features in 6 × 20 mm lesions occurred over a 3-6-month post operative period. MSCs induced a strong recovery in discal pathology with a reduction in cumulative histopathology degeneracy score from 15.2 to 2.7 ( p = 0.001) over a three-month recovery period but no recovery in carrier injected discs.

  4. Effect of desensitizing agents on dentin permeability.

    PubMed

    Ishihata, Hiroshi; Kanehira, Masafumi; Nagai, Tomoko; Finger, Werner J; Shimauchi, Hidetoshi; Komatsu, Masashi

    2009-06-01

    To investigate the in vitro efficacy of two dentin desensitizing products at reducing liquid permeability through human dentin discs. The tested hypothesis was that the products, in spite of different chemical mechanisms were not different at reducing or eliminating flow through dentin discs. Dentin slices (1 mm thick) were prepared from 16 extracted human third molars and their permeability was indirectly recorded in a split chamber model, using a chemiluminescence technique, after EDTA treatment (control), after soaking with albumin, and after desensitizer application. Two products were studied: MS Coat, a self-curing resin-containing oxalate product, and Gluma Desensitizer, a glutaraldehyde/HEMA-based agent without initiator. The dentin slices were mounted between an upper chamber, filled with an aqueous solution of 1% potassium ferricyanide and 0.3% hydrogen peroxide, and a lower chamber filled with 1% sodium hydroxide solution and 0.02% luminol. The upper solution was pressurized, and upon contact with the luminol solution a photochemical signal was generated and recorded as a measure of permeability throughout two consecutive pressurizing cycles at 2.5 and 13 kPa (26 and 133 cm H2O), respectively. The permeability of the control and albumin-soaked samples was similarly high. After application of the desensitizing agents, dentin permeability was reduced to virtually zero at both pressure levels (P < 0.001).

  5. The clinical study of percutaneous disc decompression of treating herniation of cervical disc with Nd:YAG laser

    NASA Astrophysics Data System (ADS)

    Zhang, Dianxue; Cheng, Hefu; Wang, Jindong

    2005-07-01

    Objective: The possibility of PLDD (percutaneous laser disc decompression) and an ideal non-operative method which is long everlasting effect for PLDD was investigated. Methods: 159 patients of Cervical Disc Herniation with PLDD were studied. All the herniated discs were irradiated with 10­15J/S Nd:YAG laser quantum through optical-fiber under the supervision of C-arm X-ray. Results: All the patients were followed and reexamined CT or MRI after one to six months of PLDD. The result of cured (67.92%), excellent (24.53%), moderation (5.66%), non-effect (1.88%) was got. The excellent rate was 88.24%. The effective rate was 97.65%. Non-effective rate was 2.35%. Conclusion: When irradiated with Nd:YAG laser, the nucleus pulposus was vapouring, charring and coagulating. The volume and inner-pressure of the disc decreased. So the symptoms and signs improved. The main value of this methods were micro-damage, non-operation, no bleeding, no bone injury, good therapy effect, quick recovery, lesser pain, safety and excellent long everlasting effect. It is an ideal non-operative method of treating PLDD.

  6. The rotation of discs around neutron stars: dependence on the Hall diffusion

    NASA Astrophysics Data System (ADS)

    Faghei, Kazem; Salehi, Fatemeh

    2018-01-01

    In this paper, we study the dynamics of a geometrically thin, steady and axisymmetric accretion disc surrounding a rotating and magnetized star. The magnetic field lines of star penetrate inside the accretion disc and are twisted due to the differential rotation between the magnetized star and the disc. We apply the Hall diffusion effect in the accreting plasma, because of the Hall diffusion plays an important role in both fully ionized plasma and weakly ionized medium. In the current research, we show that the Hall diffusion is also an important mechanism in accreting plasma around neutron stars. For the typical system parameter values associated with the accreting X-ray binary pulsar, the angular velocity of the inner regions of disc departs outstandingly from Keplerian angular velocity, due to coupling between the magnetic field of neutron star and the rotating plasma of disc. We found that the Hall diffusion is very important in inner disc and increases the coupling between the magnetic field of neutron star and accreting plasma. On the other word, the rotational velocity of inner disc significantly decreases in the presence of the Hall diffusion. Moreover, the solutions imply that the fastness parameter decreases and the angular velocity transition zone becomes broad for the accreting plasma including the Hall diffusion.

  7. Disc immuno-immobilization method for simultaneous typing and isolation of Salmonella flagellar phases.

    PubMed

    Mohit, B

    1968-07-01

    Salmonella organisms of an unknown serotype are inoculated in the center of a motility agar plate, and paper discs impregnated with antiflagellar antisera are placed in the periphery of the plate. The plate is incubated at room temperature overnight. During this time, the bacteria spread in a widening circle toward the discs, while the antiserum from each disc, in turn, diffuses centrifugally. When the motile organisms encounter an antiserum reacting with their flagella, they are immobilized. A semicircular line of immobilization is noted around the reactive antiserum disc. Eleven different Salmonella isolates were typed in duplicate by a standard method and by the immuno-immobilization method. Results obtained by the two methods were essentially identical. Simultaneously, single phases were isolated from the zone between the immobilization line and its antiserum disc. Isolates from this region were of the phase not immobilized by the antiserum disc. The dried discs, prepared in tris(hydroxymethyl)aminomethane buffer and stored at 4 C, were stable for at least 5 months. The method can be used for the study of relatedness of surface antigens of motile, growing bacteria, thus circumventing the need for solubilization of these antigens. The results obtained can be interpreted in a similar fashion to the "identity"-"nonidentity" lines of the Ochterlony double-diffusion technique for soluble antigens.

  8. Wnt signaling activates Shh signaling in early postnatal intervertebral discs, and re-activates Shh signaling in old discs in the mouse.

    PubMed

    Winkler, Tamara; Mahoney, Eric J; Sinner, Debora; Wylie, Christopher C; Dahia, Chitra Lekha

    2014-01-01

    Intervertebral discs (IVDs) are strong fibrocartilaginous joints that connect adjacent vertebrae of the spine. As discs age they become prone to failure, with neurological consequences that are often severe. Surgical repair of discs treats the result of the disease, which affects as many as one in seven people, rather than its cause. An ideal solution would be to repair degenerating discs using the mechanisms of their normal differentiation. However, these mechanisms are poorly understood. Using the mouse as a model, we previously showed that Shh signaling produced by nucleus pulposus cells activates the expression of differentiation markers, and cell proliferation, in the postnatal IVD. In the present study, we show that canonical Wnt signaling is required for the expression of Shh signaling targets in the IVD. We also show that Shh and canonical Wnt signaling pathways are down-regulated in adult IVDs. Furthermore, this down-regulation is reversible, since re-activation of the Wnt or Shh pathways in older discs can re-activate molecular markers of the IVD that are lost with age. These data suggest that biological treatments targeting Wnt and Shh signaling pathways may be feasible as a therapeutic for degenerative disc disease.

  9. A simple framework for modelling the dependence of bulk Comptonization by turbulence on accretion disc parameters

    NASA Astrophysics Data System (ADS)

    Kaufman, J.; Blaes, O. M.; Hirose, S.

    2018-06-01

    Warm Comptonization models for the soft X-ray excess in active galactic nuclei (AGN) do not self-consistently explain the relationship between the Comptonizing medium and the underlying accretion disc. Because of this, they cannot directly connect the fitted Comptonization temperatures and optical depths to accretion disc parameters. Since bulk velocities exceed thermal velocities in highly radiation pressure dominated discs, in these systems bulk Comptonization by turbulence may provide a physical basis in the disc itself for warm Comptonization models. We model the dependence of bulk Comptonization on fundamental accretion disc parameters, such as mass, luminosity, radius, spin, inner boundary condition, and α. In addition to constraining warm Comptonization models, our model can help distinguish contributions from bulk Comptonization to the soft X-ray excess from those due to other physical mechanisms, such as absorption and reflection. By linking the time variability of bulk Comptonization to fluctuations in the disc vertical structure due to magnetorotational instability (MRI) turbulence, our results show that observations of the soft X-ray excess can be used to study disc turbulence in the radiation pressure dominated regime. Because our model connects bulk Comptonization to 1D vertical structure temperature profiles in a physically intuitive way, it will be useful for understanding this effect in future simulations run in new regimes.

  10. Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus

    PubMed Central

    van den Akker, Guus G. H.; Surtel, Don A. M.; Cremers, Andy; Richardson, Stephen M.; Hoyland, Judith A.; van Rhijn, Lodewijk W.

    2016-01-01

    Introduction Loss of annulus fibrosus (AF) integrity predisposes to disc herniation and is associated with IVD degeneration. Successful implementation of biomedical intervention therapy requires in-depth knowledge of IVD cell biology. We recently generated unique clonal human nucleus pulposus (NP) cell lines. Recurring functional cellular phenotypes from independent donors provided pivotal evidence for cell heterogeneity in the mature human NP. In this study we aimed to generate and characterize immortal cell lines for the human AF from matched donors. Methods Non-degenerate healthy disc material was obtained as surplus surgical material. AF cells were immortalized by simian virus Large T antigen (SV40LTAg) and human telomerase (hTERT) expression. Early passage cells and immortalized cell clones were characterized based on marker gene expression under standardized culturing and in the presence of Transforming Growth factor β (TGFβ). Results The AF-specific expression signature included COL1A1, COL5A1, COL12A1, SFRP2 and was largely maintained in immortal AF cell lines. Remarkably, TGFβ induced rapid 3D sheet formation in a subgroup of AF clones. This phenotype was associated with inherent differences in Procollagen type I processing and maturation, and correlated with differential mRNA expression of Prolyl 4-hydroxylase alpha polypeptide 1 and 3 (P4HA1,3) and Lysyl oxidase (LOX) between clones and differential P4HA3 protein expression between AF cells in histological sections. Conclusion We report for the first time the generation of representative human AF cell lines. Gene expression profile analysis and functional comparison of AF clones revealed variation between immortalized cells and suggests phenotypic heterogeneity in the human AF. Future characterization of AF cellular (sub-)populations aims to combine identification of additional specific AF marker genes and their biological relevance. Ultimately this knowledge will contribute to clinical application of cell-based technology in IVD repair. PMID:26794306

  11. Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus.

    PubMed

    van den Akker, Guus G H; Surtel, Don A M; Cremers, Andy; Richardson, Stephen M; Hoyland, Judith A; van Rhijn, Lodewijk W; Voncken, Jan Willem; Welting, Tim J M

    2016-01-01

    Loss of annulus fibrosus (AF) integrity predisposes to disc herniation and is associated with IVD degeneration. Successful implementation of biomedical intervention therapy requires in-depth knowledge of IVD cell biology. We recently generated unique clonal human nucleus pulposus (NP) cell lines. Recurring functional cellular phenotypes from independent donors provided pivotal evidence for cell heterogeneity in the mature human NP. In this study we aimed to generate and characterize immortal cell lines for the human AF from matched donors. Non-degenerate healthy disc material was obtained as surplus surgical material. AF cells were immortalized by simian virus Large T antigen (SV40LTAg) and human telomerase (hTERT) expression. Early passage cells and immortalized cell clones were characterized based on marker gene expression under standardized culturing and in the presence of Transforming Growth factor β (TGFβ). The AF-specific expression signature included COL1A1, COL5A1, COL12A1, SFRP2 and was largely maintained in immortal AF cell lines. Remarkably, TGFβ induced rapid 3D sheet formation in a subgroup of AF clones. This phenotype was associated with inherent differences in Procollagen type I processing and maturation, and correlated with differential mRNA expression of Prolyl 4-hydroxylase alpha polypeptide 1 and 3 (P4HA1,3) and Lysyl oxidase (LOX) between clones and differential P4HA3 protein expression between AF cells in histological sections. We report for the first time the generation of representative human AF cell lines. Gene expression profile analysis and functional comparison of AF clones revealed variation between immortalized cells and suggests phenotypic heterogeneity in the human AF. Future characterization of AF cellular (sub-)populations aims to combine identification of additional specific AF marker genes and their biological relevance. Ultimately this knowledge will contribute to clinical application of cell-based technology in IVD repair.

  12. Reoperation After Cervical Disc Arthroplasty Versus Anterior Cervical Discectomy and Fusion: A Meta-analysis.

    PubMed

    Zhong, Zhao-Ming; Zhu, Shi-Yuan; Zhuang, Jing-Shen; Wu, Qian; Chen, Jian-Ting

    2016-05-01

    Anterior cervical discectomy and fusion is a standard surgical treatment for cervical radiculopathy and myelopathy, but reoperations sometimes are performed to treat complications of fusion such as pseudarthrosis and adjacent-segment degeneration. A cervical disc arthroplasty is designed to preserve motion and avoid the shortcomings of fusion. Available evidence suggests that a cervical disc arthroplasty can provide pain relief and functional improvements similar or superior to an anterior cervical discectomy and fusion. However, there is controversy regarding whether a cervical disc arthroplasty can reduce the frequency of reoperations. We performed a meta-analysis of randomized controlled trials (RCTs) to compare cervical disc arthroplasty with anterior cervical discectomy and fusion regarding (1) the overall frequency of reoperation at the index and adjacent levels; (2) the frequency of reoperation at the index level; and (3) the frequency of reoperation at the adjacent levels. PubMed, EMBASE, and the Cochrane Register of Controlled Trials databases were searched to identify RCTs comparing cervical disc arthroplasty with anterior cervical discectomy and fusion and reporting the frequency of reoperation. We also manually searched the reference lists of articles and reviews for possible relevant studies. Twelve RCTs with a total of 3234 randomized patients were included. Eight types of disc prostheses were used in the included studies. In the anterior cervical discectomy and fusion group, autograft was used in one study and allograft in 11 studies. Nine of 12 studies were industry sponsored. Pooled risk ratio (RR) and associated 95% CI were calculated for the frequency of reoperation using random-effects or fixed-effects models depending on the heterogeneity of the included studies. A funnel plot suggested the possible presence of publication bias in the available pool of studies; that is, the shape of the plot suggests that smaller negative or no-difference studies may have been performed but have not been published, and so were not identified and included in this meta-analysis. The overall frequency of reoperation at the index and adjacent levels was lower in the cervical disc arthroplasty group (6%; 108/1762) than in the anterior cervical discectomy and fusion group (12%; 171/1472) (RR, 0.54; 95% CI, 0.36-0.80; p = 0.002). Subgroup analyses were performed according to secondary surgical level. Compared with anterior cervical discectomy and fusion, cervical disc arthroplasty was associated with fewer reoperations at the index level (RR, 0.50; 95% CI, 0.37-0.68; p < 0.001) and adjacent levels (RR, 0.52; 95% CI, 0.37-0.74; p < 0.001). Cervical disc arthroplasty is associated with fewer reoperations than anterior cervical discectomy and fusion, indicating that it is a safe and effective alternative to fusion for cervical radiculopathy and myelopathy. However, because of some limitations, these findings should be interpreted with caution. Additional studies are needed. Level I, therapeutic study.

  13. Regulation of molecular clock oscillations and phagocytic activity via muscarinic Ca2+ signaling in human retinal pigment epithelial cells

    PubMed Central

    Ikarashi, Rina; Akechi, Honami; Kanda, Yuzuki; Ahmad, Alsawaf; Takeuchi, Kouhei; Morioka, Eri; Sugiyama, Takashi; Ebisawa, Takashi; Ikeda, Masaaki; Ikeda, Masayuki

    2017-01-01

    Vertebrate eyes are known to contain circadian clocks, however, the intracellular mechanisms regulating the retinal clockwork remain largely unknown. To address this, we generated a cell line (hRPE-YC) from human retinal pigmental epithelium, which stably co-expressed reporters for molecular clock oscillations (Bmal1-luciferase) and intracellular Ca2+ concentrations (YC3.6). The hRPE-YC cells demonstrated circadian rhythms in Bmal1 transcription. Also, these cells represented circadian rhythms in Ca2+-spiking frequencies, which were canceled by dominant-negative Bmal1 transfections. The muscarinic agonist carbachol, but not photic stimulation, phase-shifted Bmal1 transcriptional rhythms with a type-1 phase response curve. This is consistent with significant M3 muscarinic receptor expression and little photo-sensor (Cry2 and Opn4) expression in these cells. Moreover, forskolin phase-shifted Bmal1 transcriptional rhythm with a type-0 phase response curve, in accordance with long-lasting CREB phosphorylation levels after forskolin exposure. Interestingly, the hRPE-YC cells demonstrated apparent circadian rhythms in phagocytic activities, which were abolished by carbachol or dominant-negative Bmal1 transfection. Because phagocytosis in RPE cells determines photoreceptor disc shedding, molecular clock oscillations and cytosolic Ca2+ signaling may be the driving forces for disc-shedding rhythms known in various vertebrates. In conclusion, the present study provides a cellular model to understand molecular and intracellular signaling mechanisms underlying human retinal circadian clocks. PMID:28276525

  14. The course and prognostic factors of symptomatic cervical disc herniation with radiculopathy: a systematic review of the literature.

    PubMed

    Wong, Jessica J; Côté, Pierre; Quesnele, Jairus J; Stern, Paula J; Mior, Silvano A

    2014-08-01

    Cervical spine disc herniation is a disabling source of cervical radiculopathy. However, little is known about its course and prognosis. Understanding the course and prognosis of symptomatic cervical disc herniation is necessary to guide patients' expectations and assist clinicians in managing patients. To describe the natural history, clinical course, and prognostic factors of symptomatic cervical disc herniations with radiculopathy. Systematic review of the literature and best evidence synthesis. A systematic search of MEDLINE, EMBASE, CINAHL, SportsDiscus, and the Cochrane Central Register of Controlled Trials from inception to 2013 was conducted to retrieve eligible articles. Eligible articles were critically appraised using the Scottish Intercollegiate Guidelines Network criteria. The results from articles with low risk of bias were analyzed using best evidence synthesis principles. We identified 1,221 articles. Of those, eight articles were eligible and three were accepted as having a low risk of bias. Two studies pertained to course and one study pertained to prognosis. Most patients with symptomatic cervical disc herniations with radiculopathy initially present with intense pain and moderate levels of disability. However, substantial improvements tend to occur within the first 4 to 6 months post-onset. Time to complete recovery ranged from 24 to 36 months in, approximately, 83% of patients. Patients with a workers' compensation claim appeared to have a poorer prognosis. Our best evidence synthesis describes the best available evidence on the course and prognosis of cervical disc herniations with radiculopathy. Most patients with symptomatic cervical spine disc herniation with radiculopathy recover. Possible recurrences and time to complete recovery need to be further studied. More studies are also needed to understand the prognostic factors for this condition. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Biological treatment strategies for disc degeneration: potentials and shortcomings

    PubMed Central

    Nerlich, Andreas G.; Boos, Norbert

    2006-01-01

    Recent advances in molecular biology, cell biology and material sciences have opened a new emerging field of techniques for the treatment of musculoskeletal disorders. These new treatment modalities aim for biological repair of the affected tissues by introducing cell-based tissue replacements, genetic modifications of resident cells or a combination thereof. So far, these techniques have been successfully applied to various tissues such as bone and cartilage. However, application of these treatment modalities to cure intervertebral disc degeneration is in its very early stages and mostly limited to experimental studies in vitro or in animal studies. We will discuss the potential and possible shortcomings of current approaches to biologically cure disc degeneration by gene therapy or tissue engineering. Despite the increasing number of studies examining the therapeutic potential of biological treatment strategies, a practicable solution to routinely cure disc degeneration might not be available in the near future. However, knowledge gained from these attempts might be applied in a foreseeable future to cure the low back pain that often accompanies disc degeneration and therefore be beneficial for the patient. PMID:16983559

  16. Spinal disabilities in military and civil aviators.

    PubMed

    Taneja, Narinder

    2008-12-01

    The purpose of this study was to analyze the nature and cause of spinal disabilities among military and civil aircrew in India. Studies suggest that military aircrew may be more prone than nonaviators to develop spinal disabilities. An in-depth analysis of such disabilities can enable policy makers to develop data-driven preventive health programs. Extensive literature search did not reveal even a single study focusing on spinal disabilities in symptomatic aircrew. A case record of each aircrew is maintained at the Institute of Aerospace Medicine, Indian Air Force, Bangalore, India These records were accessed for all aircrew evaluated for spinal disabilities from the year 2000 to 2006. The total data comprises of 239 military and 11 civil aircrew. Most of the military aircrew were from the fighter stream. The spectrum of causes for spinal disabilities ranged from ejection, aircraft accidents to road traffic accidents, and falls. Degenerative disc disease was the leading cause in helicopter and transport pilots, whereas fractures were the predominant category in fighter pilots. A total of 153 vertebral fractures and 190 intervertebral discs were involved. There were significant differences in the age and distribution of this aircrew. Spinal disabilities assume significance for variety of reasons. Firstly, a large number of spinal disabilities caused by vehicular trauma are preventable. Second, they generally entail a prolonged course of recovery. Third, they can result in loss of trained human resources, especially when the individual cannot return to his or her original workspace. This study provides insights into the nature of spinal disabilities in civil and military aviation. Ejection and aircraft accidents remain the leading cause of vertebral fractures. Disc degenerative disease is a cause of concern. Physical conditioning and regular physical exercise may possibly minimize spinal disabilities in susceptible aircrew.

  17. Artificial Cervical Vertebra and Intervertebral Complex Replacement through the Anterior Approach in Animal Model: A Biomechanical and In Vivo Evaluation of a Successful Goat Model

    PubMed Central

    Qin, Jie; He, Xijing; Wang, Dong; Qi, Peng; Guo, Lei; Huang, Sihua; Cai, Xuan; Li, Haopeng; Wang, Rui

    2012-01-01

    This was an in vitro and in vivo study to develop a novel artificial cervical vertebra and intervertebral complex (ACVC) joint in a goat model to provide a new method for treating degenerative disc disease in the cervical spine. The objectives of this study were to test the safety, validity, and effectiveness of ACVC by goat model and to provide preclinical data for a clinical trial in humans in future. We designed the ACVC based on the radiological and anatomical data on goat and human cervical spines, established an animal model by implanting the ACVC into goat cervical spines in vitro prior to in vivo implantation through the anterior approach, and evaluated clinical, radiological, biomechanical parameters after implantation. The X-ray radiological data revealed similarities between goat and human intervertebral angles at the levels of C2-3, C3-4, and C4-5, and between goat and human lordosis angles at the levels of C3-4 and C4-5. In the in vivo implantation, the goats successfully endured the entire experimental procedure and recovered well after the surgery. The radiological results showed that there was no dislocation of the ACVC and that the ACVC successfully restored the intervertebral disc height after the surgery. The biomechanical data showed that there was no significant difference in range of motion (ROM) or neural zone (NZ) between the control group and the ACVC group in flexion-extension and lateral bending before or after the fatigue test. The ROM and NZ of the ACVC group were greater than those of the control group for rotation. In conclusion, the goat provides an excellent animal model for the biomechanical study of the cervical spine. The ACVC is able to provide instant stability after surgery and to preserve normal motion in the cervical spine. PMID:23300816

  18. Experimental study using ER-YAG laser in discs: changes in glycosaminoglycan content and synthesis in discs

    NASA Astrophysics Data System (ADS)

    Maehara, Kazuyuki; Nakai, Sadaaki; Naga, Kumi; Nishimoto, Seiji

    2004-09-01

    Changes in discs after Er-Yag laser irradiation are scarcely reported. We made an experimental study using white rabbits and Er-Yag laser. Under general anesthesia, Er-Yag laser was irradiated into lumbar discs. Three or 8 weeks after irradiation, rabbits were sacrificed, and these discs were extracted. The quantitative analysis of the glycosaminoglycan content in the annulus fibrosus, and the incorporation of 35S-sulfate in chondroitin 4 sulfate were measured. The results showed, the increased incorporation of 35S-sulfate in chondroitin 4 sulfate and chondroitin 6 sulfates in groups of laser irradiation may indicate Er-Yag laser irradiation in nucleus pulposus, accelerated glycosaminoglycan production, in the annulus fibrosus. But no difference of unsaturated isomers of chondroitin 4 sulfate, and chondroitin 6 sulfate, and no difference of saturated isomer of keratan sulfate indicate, the influence of Er-Yag laser irradiation was not so high, as to bring the quantitative changes of matrix of annulus fibrosus in term of 8 weeks.

  19. Bifurcation and response analysis of a nonlinear flexible rotating disc immersed in bounded compressible fluid

    NASA Astrophysics Data System (ADS)

    Remigius, W. Dheelibun; Sarkar, Sunetra; Gupta, Sayan

    2017-03-01

    Use of heavy gases in centrifugal compressors for enhanced oil extraction have made the impellers susceptible to failures through acousto-elastic instabilities. This study focusses on understanding the dynamical behavior of such systems by considering the effects of the bounded fluid housed in a casing on a rotating disc. First, a mathematical model is developed that incorporates the interaction between the rotating impeller - modelled as a flexible disc - and the bounded compressible fluid medium in which it is immersed. The nonlinear effects arising due to large deformations of the disc have been included in the formulation so as to capture the post flutter behavior. A bifurcation analysis is carried out with the disc rotational speed as the bifurcation parameter to investigate the dynamical behavior of the coupled system and estimate the stability boundaries. Parametric studies reveal that the relative strengths of the various dissipation mechanisms in the coupled system play a significant role that affect the bifurcation route and the post flutter behavior in the acousto-elastic system.

  20. Skelemins: cytoskeletal proteins located at the periphery of M-discs in mammalian striated muscle

    PubMed Central

    1987-01-01

    The cytoskeletons of mammalian striated and smooth muscles contain a pair of high molecular weight (HMW) polypeptides of 220,000 and 200,000 mol wt, each with isoelectric points of about 5 (Price, M. G., 1984, Am. J. Physiol., 246:H566-572) in a molar ratio of 1:1:20 with desmin. The HMW polypeptides of mammalian muscle have been named "skelemins," because they are in the insoluble cytoskeletons of striated muscle and are at the M-discs. I have used two-dimensional peptide mapping to show that the two skelemin polypeptides are closely related to each another. Polyclonal antibodies directed against skelemins were used to demonstrate that they are immunologically distinct from talin, fodrin, myosin heavy chain, synemin, microtubule-associated proteins, and numerous other proteins of similar molecular weight, and are not oligomers of other muscle proteins. Skelemins appear not to be proteolytic products of larger proteins, as shown by immunoautoradiography on 3% polyacrylamide gels. Skelemins are predominantly cytoskeletal, with little extractable from myofibrils by various salt solutions. Human, bovine, and rat cardiac, skeletal, and smooth muscles, but not chicken muscles, contain proteins cross- reacting with anti-skelemin antibodies. Skelemins are localized by immunofluorescence at the M-lines of cardiac and skeletal muscle, in 0.4-micron-wide smooth striations. Cross sections reveal that skelemins are located at the periphery of the M-discs. Skelemins are seen in threads linking isolated myofibrils at the M-discs. There is sufficient skelemin in striated muscle to wrap around the M-disc about three times, if the skelemin molecules are laid end to end, assuming a length- to-weight ratio similar to M-line protein and other elongated proteins. The results indicate that skelemins form linked rings around the periphery of the myofibrillar M-discs. These cytoskeletal rings may play a role in the maintenance of the structural integrity of striated muscle throughout cycles of contraction and relaxation. PMID:3553209

  1. LIDT-DD: A new self-consistent debris disc model that includes radiation pressure and couples dynamical and collisional evolution

    NASA Astrophysics Data System (ADS)

    Kral, Q.; Thébault, P.; Charnoz, S.

    2013-10-01

    Context. In most current debris disc models, the dynamical and the collisional evolutions are studied separately with N-body and statistical codes, respectively, because of stringent computational constraints. In particular, incorporating collisional effects (especially destructive collisions) into an N-body scheme has proven a very arduous task because of the exponential increase of particles it would imply. Aims: We present here LIDT-DD, the first code able to mix both approaches in a fully self-consistent way. Our aim is for it to be generic enough to be applied to any astrophysical case where we expect dynamics and collisions to be deeply interlocked with one another: planets in discs, violent massive breakups, destabilized planetesimal belts, bright exozodiacal discs, etc. Methods: The code takes its basic architecture from the LIDT3D algorithm for protoplanetary discs, but has been strongly modified and updated to handle the very constraining specificities of debris disc physics: high-velocity fragmenting collisions, radiation-pressure affected orbits, absence of gas that never relaxes initial conditions, etc. It has a 3D Lagrangian-Eulerian structure, where grains of a given size at a given location in a disc are grouped into super-particles or tracers whose orbits are evolved with an N-body code and whose mutual collisions are individually tracked and treated using a particle-in-a-box prescription designed to handle fragmenting impacts. To cope with the wide range of possible dynamics for same-sized particles at any given location in the disc, and in order not to lose important dynamical information, tracers are sorted and regrouped into dynamical families depending on their orbits. A complex reassignment routine that searches for redundant tracers in each family and reassignes them where they are needed, prevents the number of tracers from diverging. Results: The LIDT-DD code has been successfully tested on simplified cases for which robust results have been obtained in past studies: we retrieve the classical features of particle size distributions in unperturbed discs and the outer radial density profiles in ~r-1.5 outside narrow collisionally active rings as well as the depletion of small grains in dynamically cold discs. The potential of the new code is illustrated with the test case of the violent breakup of a massive planetesimal within a debris disc. Preliminary results show that we are able for the first time to quantify the timescale over which the signature of such massive break-ups can be detected. In addition to studying such violent transient events, the main potential future applications of the code are planet and disc interactions, and more generally, any configurations where dynamics and collisions are expected to be intricately connected.

  2. U.S. Army weapon systems human-computer interface style guide. Version 2

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Avery, L.W.; O`Mara, P.A.; Shepard, A.P.

    1997-12-31

    A stated goal of the US Army has been the standardization of the human computer interfaces (HCIs) of its system. Some of the tools being used to accomplish this standardization are HCI design guidelines and style guides. Currently, the Army is employing a number of HCI design guidance documents. While these style guides provide good guidance for the command, control, communications, computers, and intelligence (C4I) domain, they do not necessarily represent the more unique requirements of the Army`s real time and near-real time (RT/NRT) weapon systems. The Office of the Director of Information for Command, Control, Communications, and Computers (DISC4),more » in conjunction with the Weapon Systems Technical Architecture Working Group (WSTAWG), recognized this need as part of their activities to revise the Army Technical Architecture (ATA), now termed the Joint Technical Architecture-Army (JTA-A). To address this need, DISC4 tasked the Pacific Northwest National Laboratory (PNNL) to develop an Army weapon systems unique HCI style guide, which resulted in the US Army Weapon Systems Human-Computer Interface (WSHCI) Style Guide Version 1. Based on feedback from the user community, DISC4 further tasked PNNL to revise Version 1 and publish Version 2. The intent was to update some of the research and incorporate some enhancements. This document provides that revision. The purpose of this document is to provide HCI design guidance for the RT/NRT Army system domain across the weapon systems subdomains of ground, aviation, missile, and soldier systems. Each subdomain should customize and extend this guidance by developing their domain-specific style guides, which will be used to guide the development of future systems within their subdomains.« less

  3. Cervical Disc Deformation During Flexion–Extension in Asymptomatic Controls and Single-Level Arthrodesis Patients

    PubMed Central

    Anderst, William; Donaldson, William; Lee, Joon; Kang, James

    2016-01-01

    The aim of this study was to characterize cervical disc deformation in asymptomatic subjects and single-level arthrodesis patients during in vivo functional motion. A validated model-based tracking technique determined vertebral motion from biplane radiographs collected during dynamic flexion–extension. Level-dependent differences in disc compression–distraction and shear deformation were identified within the anterior and posterior annulus (PA) and the nucleus of 20 asymptomatic subjects and 15 arthrodesis patients using a mixed-model statistical analysis. In asymptomatic subjects, disc compression and shear deformation per degree of flexion–extension progressively decreased from C23 to C67. The anterior and PA experienced compression–distraction deformation of up to 20%, while the nucleus region was compressed between 0% (C67) and 12% (C23). Peak shear deformation ranged from 16% (at C67) to 33% (at C45). In the C5–C6 arthrodesis group, C45 discs were significantly less compressed than in the control group in all disc regions (all p ≤ 0.026). In the C6–C7 arthrodesis group, C56 discs were significantly less compressed than the control group in the nucleus (p = 0.023) and PA (p = 0.014), but not the anterior annulus (AA; p = 0.137). These results indicate in vivo disc deformation is level-dependent, and single-level anterior arthrodesis alters the compression–distraction deformation in the disc immediately superior to the arthrodesis. PMID:23861160

  4. Size and density sorting of dust grains in SPH simulations of protoplanetary discs

    NASA Astrophysics Data System (ADS)

    Pignatale, F. C.; Gonzalez, J.-F.; Cuello, Nicolas; Bourdon, Bernard; Fitoussi, Caroline

    2017-07-01

    The size and density of dust grains determine their response to gas drag in protoplanetary discs. Aerodynamical (size × density) sorting is one of the proposed mechanisms to explain the grain properties and chemical fractionation of chondrites. However, the efficiency of aerodynamical sorting and the location in the disc in which it could occur are still unknown. Although the effects of grain sizes and growth in discs have been widely studied, a simultaneous analysis including dust composition is missing. In this work, we present the dynamical evolution and growth of multicomponent dust in a protoplanetary disc using a 3D, two-fluid (gas+dust) smoothed particle hydrodynamics code. We find that the dust vertical settling is characterized by two phases: a density-driven phase that leads to a vertical chemical sorting of dust and a size-driven phase that enhances the amount of lighter material in the mid-plane. We also see an efficient radial chemical sorting of the dust at large scales. We find that dust particles are aerodynamically sorted in the inner disc. The disc becomes sub-solar in its Fe/Si ratio on the surface since the early stage of evolution but sub-solar Fe/Si can be also found in the outer disc-mid-plane at late stages. Aggregates in the disc mimic the physical and chemical properties of chondrites, suggesting that aerodynamical sorting played an important role in determining their final structure.

  5. Bulge Growth Through Disc Instabilities in High-Redshift Galaxies

    NASA Astrophysics Data System (ADS)

    Bournaud, Frédéric

    The role of disc instabilities, such as bars and spiral arms, and the associated resonances, in growing bulges in the inner regions of disc galaxies have long been studied in the low-redshift nearby Universe. There it has long been probed observationally, in particular through peanut-shaped bulges (Chap. 14 10.1007/978-3-319-19378-6_14"). This secular growth of bulges in modern disc galaxies is driven by weak, non-axisymmetric instabilities: it mostly produces pseudobulges at slow rates and with long star-formation timescales. Disc instabilities at high redshift (z > 1) in moderate-mass to massive galaxies (1010 to a few 1011 M⊙ of stars) are very different from those found in modern spiral galaxies. High-redshift discs are globally unstable and fragment into giant clumps containing 108-9 M⊙ of gas and stars each, which results in highly irregular galaxy morphologies. The clumps and other features associated to the violent instability drive disc evolution and bulge growth through various mechanisms on short timescales. The giant clumps can migrate inward and coalesce into the bulge in a few 108 years. The instability in the very turbulent media drives intense gas inflows toward the bulge and nuclear region. Thick discs and supermassive black holes can grow concurrently as a result of the violent instability. This chapter reviews the properties of high-redshift disc instabilities, the evolution of giant clumps and other features associated to the instability, and the resulting growth of bulges and associated sub-galactic components.

  6. Electromagnetic versus Lense-Thirring alignment of black hole accretion discs

    NASA Astrophysics Data System (ADS)

    Polko, Peter; McKinney, Jonathan C.

    2017-01-01

    Accretion discs and black holes (BHs) have angular momenta that are generally misaligned, which can lead to warped discs and bends in any jets produced. We examine whether a disc that is misaligned at large radii can be aligned more efficiently by the torque of a Blandford-Znajek (BZ) jet than by Lense-Thirring (LT) precession. To obtain a strong result, we will assume that these torques maximally align the disc, rather than cause precession, or disc tearing. We consider several disc states that include radiatively inefficient thick discs, radiatively efficient thin discs, and super-Eddington accretion discs. The magnetic field strength of the BZ jet is chosen as either from standard equipartition arguments or from magnetically arrested disc (MAD) simulations. We show that standard thin accretion discs can reach spin-disc alignment out to large radii long before LT would play a role, due to the slow infall time that gives even a weak BZ jet time to align the disc. We show that geometrically thick radiatively inefficient discs and super-Eddington discs in the MAD state reach spin-disc alignment near the BH when density profiles are shallow as in magnetohydrodynamical simulations, while the BZ jet aligns discs with steep density profiles (as in advection-dominated accretion flows) out to larger radii. Our results imply that the BZ jet torque should affect the cosmological evolution of BH spin magnitude and direction, spin measurements in active galactic nuclei and X-ray binaries, and the interpretations for Event Horizon Telescope observations of discs or jets in strong-field gravity regimes.

  7. An annulus fibrosus closure device based on a biodegradable shape-memory polymer network.

    PubMed

    Sharifi, Shahriar; van Kooten, Theo G; Kranenburg, Hendrik-Jan C; Meij, Björn P; Behl, Marc; Lendlein, Andreas; Grijpma, Dirk W

    2013-11-01

    Injuries to the intervertebral disc caused by degeneration or trauma often lead to tearing of the annulus fibrosus (AF) and extrusion of the nucleus pulposus (NP). This can compress nerves and cause lower back pain. In this study, the characteristics of poly(D,L-lactide-co-trimethylene carbonate) networks with shape-memory properties have been evaluated in order to prepare biodegradable AF closure devices that can be implanted minimally invasively. Four different macromers with (D,L-lactide) to trimethylene carbonate (DLLA:TMC) molar ratios of 80:20, 70:30, 60:40 and 40:60 with terminal methacrylate groups and molecular weights of approximately 30 kg mol(-1) were used to prepare the networks by photo-crosslinking. The mechanical properties of the samples and their shape-memory properties were determined at temperatures of 0 °C and 40 °C by tensile tests- and cyclic, thermo-mechanical measurements. At 40 °C all networks showed rubber-like behavior and were flexible with elastic modulus values of 1.7-2.5 MPa, which is in the range of the modulus values of human annulus fibrosus tissue. The shape-memory characteristics of the networks were excellent with values of the shape-fixity and the shape-recovery ratio higher than 98 and 95%, respectively. The switching temperatures were between 10 and 39 °C. In vitro culture and qualitative immunocytochemistry of human annulus fibrosus cells on shape-memory films with DLLA:TMC molar ratios of 60:40 showed very good ability of the networks to support the adhesion and growth of human AF cells. When the polymer network films were coated by adsorption of fibronectin, cell attachment, cell spreading, and extracellular matrix production was further improved. Annulus fibrosus closure devices were prepared from these AF cell-compatible materials by photo-polymerizing the reactive precursors in a mold. Insertion of the multifunctional implant in the disc of a cadaveric canine spine showed that these shape-memory devices could be implanted through a small slit and to some extent deploy self-sufficiently within the disc cavity. © 2013 Elsevier Ltd. All rights reserved.

  8. Vertebral body or intervertebral disc wedging: which contributes more to thoracolumbar kyphosis in ankylosing spondylitis patients?: A retrospective study.

    PubMed

    Liu, Hao; Qian, Bang-Ping; Qiu, Yong; Wang, Yan; Wang, Bin; Yu, Yang; Zhu, Ze-Zhang

    2016-09-01

    Both vertebral body wedging and disc wedging are found in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis. However, their relative contribution to thoracolumbar kyphosis is not fully understood. The objective of this study was to compare different contributions of vertebral and disc wedging to the thoracolumbar kyphosis in AS patients, and to analyze the relationship between the apical vertebral wedging angle and thoracolumbar kyphosis.From October 2009 to October 2013, a total of 59 consecutive AS patients with thoracolumbar kyphosis with a mean age of 38.1 years were recruited in this study. Based on global kyphosis (GK), 26 patients with GK < 70° were assigned to group A, and the other 33 patients with GK ≥ 70° were included in group B. Each GK was divided into disc wedge angles and vertebral wedge angles. The wedging angle of each disc and vertebra comprising the thoracolumbar kyphosis was measured, and the proportion of the wedging angle to the GK was calculated accordingly. Intergroup and intragroup comparisons were subsequently performed to investigate the different contributions of disc and vertebra to the GK. The correlation between the apical vertebral wedging angle and GK was calculated by Pearson correlation analysis. The duration of disease and sex were also recorded in this study.With respect to the mean disease duration, significant difference was observed between the two groups (P < 0.01). The wedging angle and wedging percentage of discs were significantly higher than those of vertebrae in group A (34.8° ± 2.5° vs 26.7° ± 2.7°, P < 0.01 and 56.6% vs 43.4%, P < 0.01), whereas disc wedging and disc wedging percentage were significantly lower than vertebrae in group B (37.6° ± 7.0° vs 50.1° ± 5.1°, P < 0.01 and 42.7% vs 57.3%, P < 0.01). The wedging of vertebrae was significantly higher in group B than in group A (50.1° ± 5.1° vs 26.7° ± 2.7°, P < 0.01). Additionally, correlation analysis revealed a significant correlation between the apical vertebral wedging angle and GK (R = 0.850, P = 0.001).Various disc and vertebral wedging exist in thoracolumbar kyphosis secondary to AS. The discs wedging contributes more to the thoracolumbar kyphosis in patients with GK < 70° than vertebral wedging, whereas vertebral wedging is more conducive to the thoracolumbar kyphosis in patients with GK ≥ 70°, indicating different biomechanical pathogenesis in varied severity of thoracolumbar kyphosis secondary to AS.

  9. Prize of the best thesis 2015: Study of debris discs through state-of-the-art numerical modelling

    NASA Astrophysics Data System (ADS)

    Kral, Q.; Thébault, P.

    2015-12-01

    This proceeding summarises the thesis entitled ``Study of debris discs with a new generation numerical model'' by Quentin Kral, for which he obtained the prize of the best thesis in 2015. The thesis brought major contributions to the field of debris disc modelling. The main achievement is to have created, almost ex-nihilo, the first truly self-consistent numerical model able to simultaneously follow the coupled collisional and dynamical evolutions of debris discs. Such a code has been thought as being the ``Holy Grail'' of disc modellers for the past decade, and while several codes with partial dynamics/collisions coupling have been presented, the code developed in this thesis, called ``LIDT-DD'' is the first to achieve a full coupling. The LIDT-DD model, which is the first of a new-generation of fully self-consistent debris disc models is able to handle both planetesimals and dust and create new fragments after each collision. The main idea of LIDT-DD development was to merge into one code two approaches that were so far used separately in disc modelling, that is, an N-body algorithm to investigate the dynamics, and a statistical scheme to explore the collisional evolution. This complex scheme is not straightforward to develop as there are major difficulties to overcome: 1) collisions in debris discs are highly destructive and produce clouds of small fragments after each single impact, 2) the smallest (and most numerous) of these fragments have a strongly size-dependent dynamics because of the radiation pressure, and 3) the dust usually observed in discs is precisely these smallest grains. These extreme constraints had so far prevented all previous attempts at developing self-consistent disc models to succeed. The thesis contains many examples of the use of LIDT-DD that are not yet published but the case of the collision between two asteroid-like bodies is studied in detail. In particular, LIDT-DD is able to predict the different stages that should be observed after such massive collisions that happen mainly in the latest stages of planetary formation. Some giant impact signatures and observability predictions for VLT/SPHERE and JWST/MIRI are given. JWST should be able to detect many of such impacts and would enable to see on-going planetary formation in dozens of planetary systems.

  10. Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease

    PubMed Central

    Than, Khoi D.; Rahman, Shayan U.; Wang, Lin; Khan, Adam; Kyere, Kwaku A.; Than, Tracey T.; Miyata, Yoshinari; Park, Yoon-Shin; La Marca, Frank; Kim, Hyungjin M.; Zhang, Huina; Park, Paul; Lin, Chia-Ying

    2014-01-01

    BACKGROUND CONTEXT A large percentage of back pain can be attributed to degeneration of the intervertebral disc (IVD). Bone morphogenetic protein-2 (BMP-2) is known to play an important role in chondrogenesis of the IVD. Simvastatin is known to up-regulate expression of BMP-2. Thus, we hypothesized that intradiscal injection of simvastatin in a rat model of degenerative disc disease (DDD) would result in retardation of DDD. PURPOSE To develop a novel conservative treatment for DDD and related discogenic back pain. STUDY DESIGN/SETTING Laboratory investigation. METHODS Disc injury was induced in 272 rats via 21-gauge needle puncture. After 6 weeks, injured discs were treated with simvastatin in a saline or hydrogel carrier. Rats were sacrificed at predetermined time points. Outcome measures assessed were radiologic, histologic, and genetic. Radiologically, the MRI index (number of pixels multiplied by corresponding image densities) was determined. Histologically, disc spaces were read by 3 blinded scorers employing a previously described histological grading scale. Genetically, nuclei pulposi were harvested and polymerase chain reaction was run to determine relative levels of aggrecan, collagen type II, and BMP-2 gene expression. This project was supported by Grant No. R01 AR056649 from NIAMS/NIH. There are no other financial conflicts of interest to report. RESULTS Radiologically, discs treated with 5 mg/mL simvastatin in hydrogel or saline demonstrated MRI indices that were normal through 8 weeks post-treatment, although this was more sustained when delivered in hydrogel. Histologically, discs treated with 5 mg/mL simvastatin in hydrogel demonstrated improved grades in comparison to discs treated at higher doses. Genetically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated higher gene expression of aggrecan and collagen type II than control. CONCLUSIONS Degenerate discs treated with 5 mg/mL simvastatin in a hydrogel carrier demonstrated radiographic and histologic features resembling normal, non-injured IVDs. In addition, gene expression of aggrecan and collagen type II (important constituents of the IVD extracellular matrix) was up-regulated in treated discs. Injection of simvastatin into degenerate IVDs may result in retardation of disc degeneration and represents a promising investigational therapy for conservative treatment of DDD. PMID:24291703

  11. Phenotype variations affect genetic association studies of degenerative disc disease: conclusions of analysis of genetic association of 58 single nucleotide polymorphisms with highly specific phenotypes for disc degeneration in 332 subjects.

    PubMed

    Rajasekaran, S; Kanna, Rishi Mugesh; Senthil, Natesan; Raveendran, Muthuraja; Cheung, Kenneth M C; Chan, Danny; Subramaniam, Sakthikanal; Shetty, Ajoy Prasad

    2013-10-01

    Although the influence of genetics on the process of disc degeneration is well recognized, in recently published studies, there is a wide variation in the race and selection criteria for such study populations. More importantly, the radiographic features of disc degeneration that are selected to represent the disc degeneration phenotype are variable in these studies. The study presented here evaluates the association between single nucleotide polymorphisms (SNPs) of candidate genes and three distinct radiographic features that can be defined as the degenerative disc disease (DDD) phenotype. The study objectives were to examine the allelic diversity of 58 SNPs related to 35 candidate genes related to lumbar DDD, to evaluate the association in a hitherto unevaluated ethnic Indian population that represents more than one-sixth of the world population, and to analyze how genetic associations can vary in the same study subjects with the choice of phenotype. A cross-sectional, case-control study of an ethnic Indian population was carried out. Fifty-eight SNPs in 35 potential candidate genes were evaluated in 342 subjects and the associations were analyzed against three highly specific markers for DDD, namely disc degeneration by Pfirrmann grading, end-plate damage evaluated by total end-plate damage score, and annular tears evaluated by disc herniations and hyperintense zones. Genotyping of cases and controls was performed on a genome-wide SNP array to identify potential associated disease loci. The results from the genome-wide SNP array were then used to facilitate SNP selection and genotype validation was conducted using Sequenom-based genotyping. Eleven of the 58 SNPs provided evidence of association with one of the phenotypes. For annular tears, rs1042631 SNP of AGC1 and rs467691 SNP of ADAMTS5 were highly significantly associated (p<.01) and SNPs in NGFB, IL1B, IL18RAP, and MMP10 were also significantly associated (p<.05). The rs4076018 SNP of NGFB was highly significant (p<.01) and rs2292657 SNP of GLI1 was significantly (p<.05) correlated to disc degeneration. For end-plate damage, the rs2252070 SNP of MMP 13 showed a significant association (p<.05). Previously associated genes such as COL 9, SKT, CHST 3, CILP, IGFR, SOXp, BMP, MMP 2-12, ADH2, IL1RN, and COX2 were not significantly associated and new associations (NGFB and GLI1) were identified. The validity of all the associations was found to be phenotype dependent. For the first time, genetic associations with DDD have been performed in an Indian population. Apart from identifying new associations, the highlight of the study was that in the same study population with DDD, SNP associations completely changed when different radiographic features were used to define the DDD phenotype. Our study results therefore indicate that standardization of the phenotypes chosen to study the genetics of disc degeneration is essential and should be strongly considered before planning genetic association studies. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Slow deformation of intervertebral discs.

    PubMed

    Broberg, K B

    1993-01-01

    Intervertebral discs exhibit pronounced time-dependent deformations when subjected to load variations. These deformations are caused by fluid flow to and from the disc and by viscoelastic deformation of annulus fibres. The fluid flow is caused by differences between mechanical and osmotic pressure. A mechanical model of lumbar disc functions allows one to calculate both the extent of fluid flow and its implications for disc height as well as the role played by viscoelastic deformation of annulus fibres. From such calculations changes in body height are estimated. Experimental results already documented in the literature offer bases for the determination of the parameters involved. Body height variations are studied, both those related to normal diurnal rhythmicity and those related to somewhat exceptional circumstances. The normal diurnal fluid flow is found to be about +/- 40% of the disc fluid content late in the evening. Viscoelastic deformation of annulus fibres contributes approximately one quarter of the height change obtained after several hours normal activity, but dominates during the first hour.

  13. Planet signatures and Size Segregation in Debris Discs

    NASA Astrophysics Data System (ADS)

    Thébault, Philippe

    2014-01-01

    The response of a debris disc to a planetary perturber is the result of the complex interplay between gravitational effects, grain collisions and stellar radiation pressure (Stark & Kuchner (2009). We investigate to what extent this response can depart from the pure gravitational case when including grain collisional production and radiation pressure. We use the DyCoSS code (Thébault (2012), designed to study the coupled effect of collisions and dynamics for systems at steady state with one perturbing body. We focus on two outcomes: the 2D surface density profile of the disc+planet system, and the way the Particle Size Distribution (PSD) is spatially segregated within the disc. We consider two set-ups: 1) a narrow ring with an exterior ``shepherding'' planet, and 2) an extended disc in which a planet is embedded. For each case, the planet mass and orbit are explored as free parameters, and an unperturbed ``no-planet'' case is also considered. Another parameter is the disc's collisional activity, as parameterized by its optical depth τ.

  14. Fine structures of embryonic discs of in vivo post-hatching porcine blastocysts at the pre-primitive streak stage.

    PubMed

    Xia, P; Liu, Z; Qin, P

    2011-04-01

    To date, reports about the ultrastructure of porcine embryonic discs have not shown details of the primitive streak. The main objective of this study was to examine the ultrastructure of interior and exterior embryonic discs in porcine in vivo blastocysts with diameters of 1, 3 and 9 mm using scanning electron microscopy and transmission electron microscopy. For the first time, we revealed the ultrastructure of the unusual group of cells in the pre-primitive streak area of embryonic discs. The cells were 1-2 μm in diameter, had high electron density and contained abundant, free ribosomes and endoplasmic reticulum. These primitive streak cells could represent original embryonic stem cells or represent a stem cell niche. The results also showed three types of cells on the exterior surface of the embryonic discs. Moreover, our results provided morphological evidence of condensed nuclei in the smooth cells on the surface of the embryonic disc. © 2010 Blackwell Verlag GmbH.

  15. Three-Dimensional Numerical Hydrodynamical Simulation of Low/hard and High/soft States in Accretion Discs of Microquasars and Quasars on Base of Undefined Precession

    NASA Astrophysics Data System (ADS)

    Nazarenko, V. V.; Nazarenko, S. V.

    In this study, the models of slaved precession of accretion disc and donors radiation-driven wind were performed using three-dimensional numerical astrophysical methods by the example of microquasar Cyg X-1. As is shown, in the course of precession of the accretion disc blown by the donor's wind the states with high and low temperature (low and high mass accretion rate, respectively) start being generated in the centre of disc. Our computations of disc precession performed on base of undefined precession that means each point of rotation axis of accretion disc makes unclosed difficult curve instead of a circle as it is in case of definite precession. In this case, the transition between states of high and low temperature takes place irregularly and not depend on precession period. The duration of transition between these both states is less than intervals of states on several orders of magnitudes.

  16. Black Hole with Wobbling Disk Artist Concept

    NASA Image and Video Library

    2016-07-12

    This artist's impression depicts the accretion disc surrounding a black hole, in which the inner region of the disc precesses. "Precession" means that the orbit of material surrounding the black hole changes orientation around the central object. In these three views, the precessing inner disc shines high-energy radiation that strikes the matter in the surrounding accretion disc. This causes the iron atoms in that disc to emit X-rays, depicted as the glow on the accretion disc to the right (in view a), to the front (in view b) and to the left (in view c) (see Figure 1). In a study published in July 2016, astronomers used data from ESA's XMM-Newton X-ray Observatory and NASA's NuSTAR telescope to measure this "wobble" in X-ray emission from excited iron atoms. Scientists interpreted this as evidence for the Lense-Thirring effect -- a name for the precession phenomenon -- in the strong gravitational field of a black hole. http://photojournal.jpl.nasa.gov/catalog/PIA20697

  17. Examination of electromagnetic powers with the example of a uc(Faraday) disc dynamo

    NASA Astrophysics Data System (ADS)

    Reich, Felix A.; Müller, Wolfgang H.

    2018-03-01

    This paper studies the mathematical form of electromagnetic powers and their influence on the balance of energy by using the example of a uc(Faraday) disc. First, two forms of energy (and balances thereof) are discussed. These employ different forms of powers, which can be distinguished w.r.t. their physical origins and their interpretations in context with the notions of supply and production. The stationary uc(Faraday) disc experiment is modeled following the description by Kovetz (Electromagnetic theory, Oxford University Press, Oxford, 2000). Concepts for formulating the electromagnetic field equations for the rotating disc are discussed, and the corresponding approximate analytical solutions are presented. Based on the obtained electromagnetic fields, the powers of the disc are analyzed for a stationary process. The conversion of mechanical power to heating and electromagnetic powering of an external resistor is explained. The paper concludes with the computation of the time evolution of the angular velocity for a magnetically induced breaking process of the disc.

  18. Neurological complications of lumbar artificial disc replacement and comparison of clinical results with those related to lumbar arthrodesis in the literature: results of a multicenter, prospective, randomized investigational device exemption study of Charité intervertebral disc. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004.

    PubMed

    Geisler, Fred H; Blumenthal, Scott L; Guyer, Richard D; McAfee, Paul C; Regan, John J; Johnson, J Patrick; Mullin, Bradford

    2004-09-01

    Arthrodesis is the gold standard for surgical treatment of lumbar degenerative disc disease (DDD). Solid fusion, however, can cause stress and increased motion in the segments adjacent to the fused level. This may initiate and/or accelerate the adjacent-segment disease process. Artificial discs are designed to restore and maintain normal motion of the lumbar intervertebral segment. Restoring and maintaining normal motion of the segment reduces stresses and loads on adjacent level segments. A US Food and Drug Administration Investigational Device Exemptions multicentered study of the Charité artificial disc was completed. The control group consisted of individuals who underwent anterior lumbar interbody fusion involving BAK cages and iliac crest bone graft. This is the first report of Class I data in which a lumbar artificial disc is compared with lumbar fusion. Of 304 individuals enrolled in the study, 205 were randomized to the Charité disc-treated group and 99 to the BAK fusion-treated (control) group. Neurological status was equivalent between the two groups at 6, 12, and 24 months postoperatively. The number of patients with major, minor, or other neurological complications was equivalent. There was a greater incidence of both major and minor complications in the BAK fusion group at 0 to 42 days postoperatively. Compared with data reported in the lumbar fusion literature, the Charité disc-treated patients had equivalent or better mean changes in visual analog scale and Oswestry Disability Index scores. The Charité artificial disc is safe and effective for the treatment of single-level lumbar DDD, resulting in no higher incidence of neurological complications compared with BAK-assisted fusion and leading to equivalent or better outcomes compared with those obtained in the control group and those reported in the lumbar fusion literature.

  19. Diagnosis of sustainable collaboration in health promotion – a case study

    PubMed Central

    Leurs, Mariken TW; Mur-Veeman, Ingrid M; van der Sar, Rosalie; Schaalma, Herman P; de Vries, Nanne K

    2008-01-01

    Background Collaborations are important to health promotion in addressing multi-party problems. Interest in collaborative processes in health promotion is rising, but still lacks monitoring instruments. The authors developed the DIagnosis of Sustainable Collaboration (DISC) model to enable comprehensive monitoring of public health collaboratives. The model focuses on opportunities and impediments for collaborative change, based on evidence from interorganizational collaboration, organizational behavior and planned organizational change. To illustrate and assess the DISC-model, the 2003/2004 application of the model to the Dutch whole-school health promotion collaboration is described. Methods The study combined quantitative research, using a cross-sectional survey, with qualitative research using the personal interview methodology and document analysis. A DISC-based survey was sent to 55 stakeholders in whole-school health promotion in one Dutch region. The survey consisted of 22 scales with 3 to 8 items. Only scales with a reliability score of 0.60 were accepted. The analysis provided for comparisons between stakeholders from education, public service and public health. The survey was followed by approaching 14 stakeholders for a semi-structured DISC-based interview. As the interviews were timed after the survey, the interviews were used to clarify unexpected and unclear outcomes of the survey as well. Additionally, a DISC-based document analysis was conducted including minutes of meetings, project descriptions and correspondence with schools and municipalities. Results Response of the survey was 77% and of the interviews 86%. Significant differences between respondents of different domains were found for the following scales: organizational characteristics scale, the change strategies, network development, project management, willingness to commit and innovative actions and adaptations. The interviews provided a more specific picture of the state of the art of the studied collaboration regarding the DISC-constructs. Conclusion The DISC-model is more than just the sum of the different parameters provided in the literature on interorganizational collaboration, organization change, networking and setting-approaches. Monitoring a collaboration based on the DISC-model yields insight into windows of opportunity and current impediments for collaborative change. DISC-based monitoring is a promising strategy enabling project managers and social entrepreneurs to plan change management strategies systematically. PMID:18992132

  20. Effect of race, age, and axial length on optic nerve head parameters and retinal nerve fiber layer thickness measured by Cirrus HD-OCT.

    PubMed

    Knight, O'Rese J; Girkin, Christopher A; Budenz, Donald L; Durbin, Mary K; Feuer, William J

    2012-03-01

    To determine the effect of race, demographic, and ocular variables on optic nerve head and retinal nerve fiber layer (RNFL) thickness measurements using spectral-domain optical coherence tomography. In a cross-sectional observational study, 284 normal subjects aged 18 to 84 years were evaluated at 7 sites using Cirrus HD-OCT. Disc area, rim area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and average, temporal, superior, nasal, and inferior RNFL thicknesses were calculated. The main outcome measures were associations between Cirrus HD-OCT optic nerve head and RNFL measurements and age, sex, and race. The 284 subjects self-identified as being of European (122), Chinese (63), African (51), or Hispanic (35) descent. After adjusting for the effect of age, there was a statistically significant difference among racial groups for all optic nerve head and RNFL parameters (all P ≤ .005) except rim area (P = .22). Rim area, average cup-disc ratio, vertical cup-disc ratio, and cup volume were moderately associated with disc area (r(2) = 0.15, 0.33, 0.33, and 0.37, respectively). After a linear adjustment for disc area, there was no statistically significant difference among racial groups for any optic nerve head parameter. Individuals of European descent had thinner RNFL measurements except in the temporal quadrant. There are racial differences in optic disc area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and RNFL thickness as measured by Cirrus HD-OCT. These differences should be considered when using Cirrus HD-OCT to assess for glaucomatous damage in differing population groups.

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