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Sample records for mice disc degeneration

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

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

    2012-09-01

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

  2. Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2.

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    Bedore, Jake; Sha, Wei; McCann, Matthew R; Liu, Shangxi; Leask, Andrew; Séguin, Cheryle A

    2013-10-01

    Currently, our ability to treat intervertebral disc (IVD) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including CCN2, during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in IVD tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific CCN2 deletion. Expression of CCN proteins was assessed in IVD tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of CCN2 in notochord-derived tissues, we generated notochord-specific CCN2-null mice to assess the impact on the IVD structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), IVD health was assessed. Loss of the CCN2 gene in notochord-derived cells disrupted the formation of IVDs in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. CCN2-knockout mice also had altered expression of CCN1 (Cyr61) and CCN3 (Nov). Mirroring its role during early development, notochord-specific CCN2 deletion accelerated age-associated degeneration of IVDs. Using a notochord-specific gene targeting strategy, this study demonstrates that CCN2 expression by nucleus pulposus cells is essential to the regulation of IVD development and age-associated tissue maintenance. The ability of CCN2 to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration. Copyright © 2013 by the American College of Rheumatology.

  3. Intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bergknut, N.

    2011-01-01

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

  4. Intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bergknut, Niklas

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

  5. Disc degeneration: current surgical options

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    C Schizas

    2010-10-01

    Full Text Available Chronic low back pain attributed to lumbar disc degeneration poses a serious challenge to physicians. Surgery may be indicated in selected cases following failure of appropriate conservative treatment. For decades, the only surgical option has been spinal fusion, but its results have been inconsistent. Some prospective trials show superiority over usual conservative measures while others fail to demonstrate its advantages. In an effort to improve results of fusion and to decrease the incidence of adjacent segment degeneration, total disc replacement techniques have been introduced and studied extensively. Short-term results have shown superiority over some fusion techniques. Mid-term results however tend to show that this approach yields results equivalent to those of spinal fusion. Nucleus replacement has gained some popularity initially, but evidence on its efficacy is scarce. Dynamic stabilisation, a technique involving less rigid implants than in spinal fusion and performed without the need for bone grafting, represents another surgical option. Evidence again is lacking on its superiority over other surgical strategies and conservative measures. Insertion of interspinous devices posteriorly, aiming at redistributing loads and relieving pain, has been used as an adjunct to disc removal surgery for disc herniation. To date however, there is no clear evidence on their efficacy. Minimally invasive intradiscal thermocoagulation techniques have also been tried, but evidence of their effectiveness is questioned. Surgery using novel biological solutions may be the future of discogenic pain treatment. Collaboration between clinicians and basic scientists in this multidisciplinary field will undoubtedly shape the future of treating symptomatic disc degeneration.

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

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    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

  7. Magnetic resonance imaging of intervertebral disc degeneration

    International Nuclear Information System (INIS)

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

    1993-01-01

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

  8. Magnetic resonance imaging of intervertebral disc degeneration

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

    1993-02-01

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

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

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    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.

  10. Notochord Cells in Intervertebral Disc Development and Degeneration

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    McCann, Matthew R.; Séguin, Cheryle A.

    2016-01-01

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

  11. Notochord Cells in Intervertebral Disc Development and Degeneration

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    Matthew R. McCann

    2016-01-01

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

  12. New treatment strategies for canine intervertebral disc degeneration

    NARCIS (Netherlands)

    Smolders, L.A.

    2013-01-01

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

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

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    S Capossela

    2014-04-01

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

  14. Gender difference in genetic association between IL1A variant and early lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Kjær, Per; Sorensen, Joan S

    2012-01-01

    The purpose of the present study was to analyze the associations between specific genetic markers and early disc degeneration (DD) or early disc degeneration progression (DDP) defined by magnetic resonance imaging (MRI)....

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

    NARCIS (Netherlands)

    Alini, M.; Eisenstein, S.M.; Ito, K.; Little, C.; Kettler, A.A.; Masuda, K.; Melrose, J.; Ralphs, J.; Stokes, I.; Wilke, H.J.

    2008-01-01

    Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo

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

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    Takashi Ohnishi

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

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

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

    2012-02-01

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

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

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    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.

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

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

    2017-01-01

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

  20. Degeneration and height of cervical discs classified from MRI compared with precise height measurements from radiographs

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    Kolstad, Frode [National Centre of Spinal Disorders, Norwegian University of Science and Technology, University Hospital of Trondheim, 7006 Trondheim (Norway)]. E-mail: frode.kolstad@medisin.ntnu.no; Myhr, Gunnar [Department of Radiology, University Hospital of Trondheim, 7006 Trondheim (Norway); Kvistad, Kjell Arne [Department of Radiology, University Hospital of Trondheim, 7006 Trondheim (Norway); Nygaard, Oystein P. [National Centre of Spinal Disorders, Norwegian University of Science and Technology, University Hospital of Trondheim, 7006 Trondheim (Norway); Leivseth, Gunnar [Department of Neuromedicine, Faculty of Medicine, Norwegian University of Science and Technology, University Hospital of Trondheim, 7006 Trondheim (Norway)

    2005-09-01

    Study design: Descriptive study comparing MRI classifications with measurements from radiographs. Objectives: 1.Define the relationship between MRI classified cervical disc degeneration and objectively measured disc height. 2.Assess the level of inter- and intra-observer errors using MRI in defining cervical disc degeneration. Summary of background data: Cervical spine degeneration has been defined radiologically by loss of disc height, decreased disc and bone marrow signal intensity and disc protrusion/herniation on MRI. The intra- and inter-observer error using MRI in defining cervical degeneration influences data interpretation. Few previous studies have addressed this source of error. The relation and time sequence between cervical disc degeneration classified by MRI and cervical disc height decrease measured from radiographs is unclear. Methods: The MRI classification of degeneration was based on nucleus signal, prolaps identification and bone marrow signal. Two neuro-radiologists evaluated the MR-images independently in a blinded fashion. The radiographic disc height measurements were done by a new computer-assisted method compensating for image distortion and permitting comparison with normal level-, age- and gender-appropriate disc height. Results/conclusions: 1.Progressing disc degeneration classified from MRI is on average significantly associated with a decrease of disc height as measured from radiographs. Within each MRI defined category of degeneration measured disc heights, however, scatter in a wide range. 2.The inter-observer agreement between two neuro-radiologists in both defining degeneration and disc height by MRI was only moderate. Studies addressing questions related to cervical disc degeneration should take this into consideration.

  1. Degeneration and height of cervical discs classified from MRI compared with precise height measurements from radiographs

    International Nuclear Information System (INIS)

    Kolstad, Frode; Myhr, Gunnar; Kvistad, Kjell Arne; Nygaard, Oystein P.; Leivseth, Gunnar

    2005-01-01

    Study design: Descriptive study comparing MRI classifications with measurements from radiographs. Objectives: 1.Define the relationship between MRI classified cervical disc degeneration and objectively measured disc height. 2.Assess the level of inter- and intra-observer errors using MRI in defining cervical disc degeneration. Summary of background data: Cervical spine degeneration has been defined radiologically by loss of disc height, decreased disc and bone marrow signal intensity and disc protrusion/herniation on MRI. The intra- and inter-observer error using MRI in defining cervical degeneration influences data interpretation. Few previous studies have addressed this source of error. The relation and time sequence between cervical disc degeneration classified by MRI and cervical disc height decrease measured from radiographs is unclear. Methods: The MRI classification of degeneration was based on nucleus signal, prolaps identification and bone marrow signal. Two neuro-radiologists evaluated the MR-images independently in a blinded fashion. The radiographic disc height measurements were done by a new computer-assisted method compensating for image distortion and permitting comparison with normal level-, age- and gender-appropriate disc height. Results/conclusions: 1.Progressing disc degeneration classified from MRI is on average significantly associated with a decrease of disc height as measured from radiographs. Within each MRI defined category of degeneration measured disc heights, however, scatter in a wide range. 2.The inter-observer agreement between two neuro-radiologists in both defining degeneration and disc height by MRI was only moderate. Studies addressing questions related to cervical disc degeneration should take this into consideration

  2. Effect of Interbody Fusion on the Remaining Discs of the Lumbar Spine in Subjects with Disc Degeneration.

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    Ryu, Robert; Techy, Fernando; Varadarajan, Ravikumar; Amirouche, Farid

    2016-02-01

    To study effects (stress loads) of lumbar fusion on the remaining segments (adjacent or not) of the lumbar spine in the setting of degenerated adjacent discs. A lumbar spine finite element model was built and validated. The full model of the lumbar spine was a parametric finite element model of segments L 1-5 . Numerous hypothetical combinations of one-level lumbar spine fusion and one-level disc degeneration were created. These models were subjected to 10 Nm flexion and extension moments and the stresses on the endplates and consequently on the intervertebral lumbar discs measured. These values were compared to the stresses on healthy lumbar spine discs under the same load and fusion scenarios. Increased stress at endplates was observed only in the settings of L4-5 fusion and L3-4 disc degeneration (8% stress elevation at L2,3 in flexion or extension, and 25% elevation at L3,4 in flexion only). All other combinations showed less endplate stress than did the control model. For fusion at L3-4 and degeneration at L4-5 , the stresses in the endplates at the adjacent level inferior to the fused disc decreased for both loading disc height reductions. Stresses in flexion decreased after fusion by 29.5% and 25.8% for degeneration I and II, respectively. Results for extension were similar. For fusion at L2-3 and degeneration at L4-5 , stresses in the endplates decreased more markedly at the degenerated (30%), than at the fused level (14%) in the presence of 25% disc height reduction and 10 Nm flexion, whereas in extension stresses decreased more at the fused (24.3%) than the degenerated level (5.86%). For fusion at L3-4 and degeneration at L2-3 , there were no increases in endplate stress in any scenario. For fusion at L4-5 and degeneration at L3-4 , progression of degeneration from I to II had a significant effect only in flexion. A dramatic increase in stress was noted in the endplates of the degenerated disc (L3-4 ) in flexion for degeneration II. Stresses are greater

  3. Mechanical deformation and glycosaminoglycan content changes in a rabbit annular puncture disc degeneration model.

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    Chan, Deva D; Khan, Safdar N; Ye, Xiaojing; Curtiss, Shane B; Gupta, Munish C; Klineberg, Eric O; Neu, Corey P

    2011-08-15

    Evaluation of degenerated intervertebral discs from a rabbit annular puncture model by using specialized magnetic resonance imaging (MRI) techniques, including displacement encoding with stimulated echoes and a fast-spin echo (DENSE-FSE) acquisition and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). To evaluate a rabbit disc degeneration model by using various MRI techniques. To determine the displacements and strains, spin-lattice relaxation time (T1), and glycosaminoglycan (GAG) distribution of degenerated discs as compared to normal and adjacent level discs. Annular puncture of the intervertebral disc produces disc degeneration in rabbits. DENSE-FSE has been previously demonstrated in articular cartilage for the measurement of soft tissue displacements and strains. MRI also can measure the T1 of tissue, and dGEMRIC can quantify GAG concentration in cartilage. METHODS.: In eight New Zealand white rabbits, the annulus fibrosis of a lumbar disc was punctured. After 4 weeks, the punctured and cranially adjacent motion segments were isolated for MRI and histology. MRI was used to estimate the disc volume and map T1. DENSE-FSE was used to determine displacements for the estimation of strains. dGEMRIC was then used to determine GAG distributions. Histology and standard MRI indicated degeneration in punctured discs. Disc volume increased significantly at 4 weeks after the puncture. Displacement of the nucleus pulposus was distinct from that of the annulus fibrosis in most untreated discs but not in punctured discs. T1 was significantly higher and GAG concentration significantly lower in punctured discs compared with untreated adjacent level discs. Noninvasive and quantitative MRI techniques can be used to evaluate the mechanical and biochemical changes that occur with animal models of disc degeneration. DENSE-FSE, dGEMRIC, and similar techniques have potential for evaluating the progression of disc degeneration and the efficacy of treatments.

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

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

    2013-03-15

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

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

    2009-01-01

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

  8. A computational study of intervertebral disc degeneration in relation to changes in regional tissue composition and disc nutrition

    OpenAIRE

    Ruiz Wills, Carlos

    2015-01-01

    Up to 85% of the world population suffers from low back pain, a clinical condition often related to the intervertebral disc (IVD) degeneration (DD). Altered disc cell nutrition affects cell viability and can generate catabolic cascades that degrade the extracellular matrix (ECM). Also, a major degenerative biochemical change in the disc is the proteoglycan (PG) loss, which affects the osmotic pressure and hydration that is critical for cell nutrition. However, the relationship between biochem...

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

    Directory of Open Access Journals (Sweden)

    Delio Eulalio Martins

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

  10. Genetic susceptibility of intervertebral disc degeneration among young Finnish adults

    Directory of Open Access Journals (Sweden)

    Kelempisioti Anthi

    2011-11-01

    Full Text Available Abstract Background Disc degeneration (DD is a common condition that progresses with aging. Although the events leading to DD are not well understood, a significant genetic influence has been found. This study was undertaken to assess the association between relevant candidate gene polymorphisms and moderate DD in a well-defined and characterized cohort of young adults. Focusing on young age can be valuable in determining genetic predisposition to DD. Methods We investigated the associations of existing candidate genes for DD among 538 young adults with a mean age of 19 belonging to the 1986 Northern Finland Birth Cohort. Nineteen single nucleotide polymorphisms (SNP in 16 genes were genotyped. We evaluated lumbar DD using the modified Pfirrmann classification and a 1.5-T magnetic resonance scanner for imaging. Results Of the 538 individuals studied, 46% had no degeneration, while 54% had DD and 51% of these had moderate DD. The risk of DD was significantly higher in subjects with an allele G of IL6 SNPs rs1800795 (OR 1.45, 95% CI 1.07-1.96 and rs1800797 (OR 1.37, 95% CI 1.02-1.85 in the additive inheritance model. The role of IL6 was further supported by the haplotype analysis, which resulted in an association between the GGG haplotype (SNPs rs1800797, rs1800796 and rs1800795 and DD with an OR of 1.51 (95% CI 1.11-2.04. In addition, we observed an association between DD and two other polymorphisms, SKT rs16924573 (OR 0.27 95% CI 0.07-0.96 and CILP rs2073711 in women (OR 2.04, 95% CI 1.07-3.89. Conclusion Our results indicate that IL6, SKT and CILP are involved in the etiology of DD among young adults.

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

    Science.gov (United States)

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

    2009-03-01

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

  12. The non-invasive investigation of lumbar disc degeneration in patients with chronic low back pain

    International Nuclear Information System (INIS)

    Buirski, G.

    1989-01-01

    The painful degenerate disc is a recognised cause of low back pain. Magnetic Resonance Imaging (MRI) has now replaced discography in the non-invasive assessment of disk degeneration. However, the prohibitive capital expense of MRI and the small number of MR units in Australia produce limitations in clinical access. In contrast, Computed Tomography (CT) is readily available and is performed in most patients prior to MRI referral. This prospective study was undertaken to determine whether preliminary CT could offer any information about disc degeneration and so reduce the demand on a MRI scanner. 30 consecutive patients were studied all of whom had both CT and MRI examinations. Of a total 107 discs examined by both techniques, MRI was able to identify 37 degenerate discs. Conclusive evidence of degeneration (i.e. the presence of intervertebral gas) was only seen in 3 discs at CT (1 patient). Of the 29 posterior disc bulges found on CT, all were both bulging and degenerate on MRI. Indications for MRI based on the CT findings are recommended. Using these criteria, 13% (4 patients) of this study group could have avoided an expensive and unnecessary MR investigation. A useful algorithm for the investigation and assessment of patients with chronic low back pain is discussed. 8 refs., 5 figs., 1 tab

  13. Angiogenesis in the degeneration of the lumbar intervertebral disc

    OpenAIRE

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    João W Silveira

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  16. Functional disability of occupational-related lumbar disc degeneration: Evaluation by magnetic resonance imaging with surgical correlation

    Directory of Open Access Journals (Sweden)

    Alsiagy A. Salama

    2017-03-01

    Conclusion: Disability of occupational-related lumbar disc degeneration is a grave health problem between construction workers. MR imaging is a reliable tool for grading nerve root compromise in disc degeneration. Nerve root compromise is a significant factor to explain pain than the morphologic extension of disc material outside the intervertebral space.

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

    Science.gov (United States)

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

    2014-01-01

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

  18. Degeneration of the cervical disc: histology compared with radiography and magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Christe, A.; Vock, P. [University of Berne, Department of Radiology, Inselspital, Berne (Switzerland); Laeubli, R.; Berlemann, U. [University of Berne, Department of Orthopaedic Surgery, Inselspital, Berne (Switzerland); Guzman, R.; Schroth, G. [University of Berne, Department of Neuroradiology, Inselspital, Berne (Switzerland); Moore, R.J. [Institute of Medical and Veterinary Science, Adelaide (Australia); Loevblad, K.O. [University of Berne, Department of Neuroradiology, Inselspital, Berne (Switzerland); Geneva University Hospital, Neuroradiology SRRI, Geneva 14 (Switzerland)

    2005-10-01

    Decisions about the treatment of neck pain are largely made on the basis of information gained from plain X-rays and magnetic resonance imaging (MRI), which are used routinely as part of preliminary investigation. We performed a descriptive cadaveric study to compare histology with radiography and MRI. We correlated plain radiography, disc height [Farfan index (FI)] and MRI findings with histology to assess the ability of radiology to detect significant pathologic lesions. The study included 52 motion segments from nine subjects over the age of 50, who underwent routine hospital autopsy. Disc degeneration was assessed by histology, radiography, disc height (FI: anterior disc height plus posterior disc height divided by anterioposterior diameter) and MRI using established grading systems. Most of the discs were classified radiologically as grade 1 (19/52), grade 2 (13/52), grade 3 (9/52) or grade 4 (3/52). Eight of the discs were graded as normal. The distribution of MRI grades was grade 0 (9/36), grade 1 (9/36), grade 2 (7/36), grade 3 (8/36) and grade 4 (3/36). Half of the discs (26/52) showed advanced (grade 4) degeneration histologically. FI correlated with histological grade (P=0.013), MRI grade (P=0.02) and radiological grade (P<0.001) of degeneration. Radiological and histological grade of degeneration showed a weak correlation (r=0.3, P=0.033). MRI correlated with overall histological grade (r=0.41, P=0.015, n=34). Histological features (e.g., tears, rim lesions, prolapse of nucleus material) were poorly recognised by MRI, which had a sensitivity for disc material prolapse and annulus tears of less than 40%. Our study showed that discs from patients over 50 years are histologically severely degenerated; however, these changes may not be detected by conventional radiography and MRI. (orig.)

  19. Degeneration of the cervical disc: histology compared with radiography and magnetic resonance imaging

    International Nuclear Information System (INIS)

    Christe, A.; Vock, P.; Laeubli, R.; Berlemann, U.; Guzman, R.; Schroth, G.; Moore, R.J.; Loevblad, K.O.

    2005-01-01

    Decisions about the treatment of neck pain are largely made on the basis of information gained from plain X-rays and magnetic resonance imaging (MRI), which are used routinely as part of preliminary investigation. We performed a descriptive cadaveric study to compare histology with radiography and MRI. We correlated plain radiography, disc height [Farfan index (FI)] and MRI findings with histology to assess the ability of radiology to detect significant pathologic lesions. The study included 52 motion segments from nine subjects over the age of 50, who underwent routine hospital autopsy. Disc degeneration was assessed by histology, radiography, disc height (FI: anterior disc height plus posterior disc height divided by anterioposterior diameter) and MRI using established grading systems. Most of the discs were classified radiologically as grade 1 (19/52), grade 2 (13/52), grade 3 (9/52) or grade 4 (3/52). Eight of the discs were graded as normal. The distribution of MRI grades was grade 0 (9/36), grade 1 (9/36), grade 2 (7/36), grade 3 (8/36) and grade 4 (3/36). Half of the discs (26/52) showed advanced (grade 4) degeneration histologically. FI correlated with histological grade (P=0.013), MRI grade (P=0.02) and radiological grade (P<0.001) of degeneration. Radiological and histological grade of degeneration showed a weak correlation (r=0.3, P=0.033). MRI correlated with overall histological grade (r=0.41, P=0.015, n=34). Histological features (e.g., tears, rim lesions, prolapse of nucleus material) were poorly recognised by MRI, which had a sensitivity for disc material prolapse and annulus tears of less than 40%. Our study showed that discs from patients over 50 years are histologically severely degenerated; however, these changes may not be detected by conventional radiography and MRI. (orig.)

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Josemberg da Silva Baptista

    2015-06-01

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

  2. Quantitative analysis of disc degeneration using axial T2 mapping in a percutaneous annular puncture model in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Chai, Jee Won; Kim, Su Jin [Dept. of Radiology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Kang, Heung Sik; Lee, Joon Woo [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Hong, Sung Hwan [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-02-15

    To evaluate T2 relaxation time change using axial T2 mapping in a rabbit degenerated disc model and determine the most correlated variable with histologic score among T2 relaxation time, disc height index, and Pfirrmann grade. Degenerated disc model was made in 4 lumbar discs of 11 rabbits (n = 44) by percutaneous annular puncture with various severities of an injury. Lumbar spine lateral radiograph, MR T2 sagittal scan and MR axial T2 mapping were obtained at baseline and 2 weeks and 4 weeks after the injury in 7 rabbits and at baseline and 2 weeks, 4 weeks, and 6 weeks after the injury in 4 rabbits. Generalized estimating equations were used for a longitudinal analysis of changes in T2 relaxation time in degenerated disc model. T2 relaxation time, disc height index and Pfirrmann grade were correlated with the histologic scoring of disc degeneration using Spearman's rho test. There was a significant difference in T2 relaxation time between uninjured and injured discs after annular puncture. Progressive decrease in T2 relaxation time was observed in injured discs throughout the study period. Lower T2 relaxation time was observed in the more severely injured discs. T2 relaxation time showed the strongest inverse correlation with the histologic score among the variables investigated (r = -0.811, p < 0.001). T2 relaxation time measured with axial T2 mapping in degenerated discs is a potential method to assess disc degeneration.

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

    Directory of Open Access Journals (Sweden)

    KS Emanuel

    2015-06-01

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

  4. Correlation of radiographic and MRI parameters to morphological and biochemical assessment of intervertebral disc degeneration

    OpenAIRE

    Benneker, Lorin M.; Heini, Paul F.; Anderson, Suzanne E.; Alini, Mauro; Ito, Keita

    2004-01-01

    Degenerative disc disease (DDD) is a common finding in MRI scans and X-rays. However, their correlation to morphological and biochemical changes is not well established. In this study, radiological and MRI parameters of DDD were assessed and compared with morphological and biochemical findings of disc degeneration. Thirty-nine human lumbar discs (L1–S1), age 19–86 years, were harvested from eight cadavers. Within 48 h postmortem, MRIs in various spin-echo sequences and biplanar radiographs of...

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

    NARCIS (Netherlands)

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

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

  6. Does elite swimming accelerate lumbar intervertebral disc degeneration and increase low back pain?

    DEFF Research Database (Denmark)

    Folkvardsen, Steffen; Magnussen, Erland; Karppinen, Jaro

    2016-01-01

    PURPOSE: The aim was to elucidate elite swimming's possible influence on lumbar disc degeneration (DD) and low back pain (LBP). METHODS: Lumbar spine MRI was performed on a group of elite swimmers and compared to a matched Finnish population-based no-sport group. RESULTS: One hundred elite swimmers...

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

    Science.gov (United States)

    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 menopause, postmenopausal women had a significant tendency to develop more severe disc degeneration than their age-matched men (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.

  8. Observations on morphologic changes in the aging and degenerating human disc: Secondary collagen alterations

    Directory of Open Access Journals (Sweden)

    Hanley Edward N

    2002-03-01

    Full Text Available Abstract Background In the annulus, collagen fibers that make up the lamellae have a wavy, planar crimped pattern. This crimping plays a role in disc biomechanical function by allowing collagen fibers to stretch during compression. The relationship between morphologic changes in the aging/degenerating disc and collagen crimping have not been explored. Methods Ultrastructural studies were performed on annulus tissue from 29 control (normal donors (aged newborn to 79 years and surgical specimens from 49 patients (aged 16 to 77 years. Light microscopy and specialized image analysis to visualize crimping was performed on additional control and surgical specimens. Human intervertebral disc tissue from the annulus was obtained in a prospective morphologic study of the annulus. Studies were approved by the authors' Human Subjects Institutional Review Board. Results Three types of morphologic changes were found to alter the crimping morphology of collagen: 1 encircling layers of unusual matrix disrupted the lamellar collagen architecture; 2 collagen fibers were reduced in amount, and 3 collagen was absent in regions with focal matrix loss. Conclusions Although proteoglycan loss is well recognized as playing a role in the decreased shock absorber function of the aging/degenerating disc, collagen changes have received little attention. This study suggests that important stretch responses of collagen made possible by collagen crimping may be markedly altered by morphologic changes during aging/degeneration and may contribute to the early tissue changes involved in annular tears.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

    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.

  12. MRI histogram analysis enables objective and continuous classification of intervertebral disc degeneration.

    Science.gov (United States)

    Waldenberg, Christian; Hebelka, Hanna; Brisby, Helena; Lagerstrand, Kerstin Magdalena

    2018-05-01

    Magnetic resonance imaging (MRI) is the best diagnostic imaging method for low back pain. However, the technique is currently not utilized in its full capacity, often failing to depict painful intervertebral discs (IVDs), potentially due to the rough degeneration classification system used clinically today. MR image histograms, which reflect the IVD heterogeneity, may offer sensitive imaging biomarkers for IVD degeneration classification. This study investigates the feasibility of using histogram analysis as means of objective and continuous grading of IVD degeneration. Forty-nine IVDs in ten low back pain patients (six males, 25-69 years) were examined with MRI (T2-weighted images and T2-maps). Each IVD was semi-automatically segmented on three mid-sagittal slices. Histogram features of the IVD were extracted from the defined regions of interest and correlated to Pfirrmann grade. Both T2-weighted images and T2-maps displayed similar histogram features. Histograms of well-hydrated IVDs displayed two separate peaks, representing annulus fibrosus and nucleus pulposus. Degenerated IVDs displayed decreased peak separation, where the separation was shown to correlate strongly with Pfirrmann grade (P histogram appearances. Histogram features correlated well with IVD degeneration, suggesting that IVD histogram analysis is a suitable tool for objective and continuous IVD degeneration classification. As histogram analysis revealed IVD heterogeneity, it may be a clinical tool for characterization of regional IVD degeneration effects. To elucidate the usefulness of histogram analysis in patient management, IVD histogram features between asymptomatic and symptomatic individuals needs to be compared.

  13. Diffusion-Weighted MRI Assessment of Adjacent Disc Degeneration After Thoracolumbar Vertebral Fractures

    Energy Technology Data Exchange (ETDEWEB)

    Noriega, David C., E-mail: dcnoriega1970@gmail.com [Valladolid University Hospital, Spine Department (Spain); Marcia, Stefano, E-mail: stemarcia@gmail.com [SS. Trinità Hospital ASL 8 Cagliari, Department of Radiology (Italy); Ardura, Francisco, E-mail: fardura@ono.com [Valladolid University Hospital, Spine Department (Spain); Lite, Israel Sanchez, E-mail: israelslite@hotmail.com [Valladolid University Hospital, Radiology Department (Spain); Marras, Mariangela, E-mail: mariangela.marrasmd@gmail.com [Azienda Ospedaliero Brotzu (A.O.B.), Department of Radiology (Italy); Saba, Luca, E-mail: lucasaba@tiscali.it [Azienda Ospedaliero Universitaria (A.O.U.), Department of Radiology (Italy)

    2016-09-15

    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 the 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.

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

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  16. Hyaluronic Acid (HA)-Polyethylene glycol (PEG) as injectable hydrogel for intervertebral disc degeneration patients therapy

    Science.gov (United States)

    Putri Kwarta, Cityta; Widiyanti, Prihartini; Siswanto

    2017-05-01

    Chronic Low Back Pain (CLBP) is one health problem that is often encountered in a community. Inject-able hydrogels are the newest way to restore the disc thickness and hydration caused by disc degeneration by means of minimally invasive surgery. Thus, polymers can be combined to improve the characteristic properties of inject-able hydrogels, leading to use of Hyaluronic Acid (a natural polymer) and Polyethylene glycol (PEG) with Horse Radish Peroxide (HRP) cross linker enzymes. The swelling test results, which approaches were the ideal disc values, were sampled with variation of enzyme concentrations of 0.25 µmol/min/mL. The enzyme concentrations were 33.95%. The degradation test proved that the sample degradation increased along with the decrease of the HRP enzyme concentration. The results of the cytotoxicity assay with MTT assay method showed that all samples resulted in the 90% of living cells are not toxic. In vitro injection, models demonstrated that higher concentration of the enzymes was less state of gel which would rupture when released from the agarose gel. The functional group characterization shows the cross linking bonding in sample with enzyme adding. The conclusion of this study is PEG-HA-HRP enzyme are safe polymer composites which have a potential to be applied as an injectable hydrogel for intervertebral disc degeneration.

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

    Directory of Open Access Journals (Sweden)

    MP Grant

    2016-07-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  20. Relationship of modic type 1 change with disc degeneration: a prospective MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Luoma, Katariina [Helsinki University Central Hospital, Helsinki and Uudenmaa District University Hospitals, Helsinki (Finland)]|[Peijas Hospital, Helsinki University Central Hospitals, Department of Radiology, Vantaa (Finland); Vehmas, Tapio [Institute of Occupational Health, Helsinki (Finland); Groenblad, Mats; Kaeaepae, Eeva [Helsinki and Uudenmaa District University Hospitals, Helsinki University Central Hospital, Department of Physical Medicine and Rehabilitation, Helsinki (Finland); Kerttula, Liisa [Helsinki University Central Hospital, Helsinki and Uudenmaa District University Hospitals, Helsinki (Finland)

    2009-03-15

    The objective was to study the natural course of Modic type 1 change (M1) in relation to lumbar disc degeneration. Twenty-four chronic low back pain (LBP) patients with M1 on lumbar spine were selected from 1,015 patients with magnetic resonance imaging from a follow-up study lasting for 18-74 months. Exclusion criteria were any other specific back disorder, age {>=}60 years, or a recent spine operation. The association between the development of M1 and degenerative disc changes was studied using multivariate modeling (complex samples logistic regression). At baseline, 20 of 28 (71%) disc spaces with M1 had a decreased disc height (DH) and 16 of 28 (57%) a dark nucleus pulposus, but ten of 28 (36%) a very dark annulus fibrosus and a paradoxically bright nucleus pulposus albeit decreased DH. During follow-up, DH decreased in 13 of 28 (46%) and signal intensity of nucleus pulposus (DSI) in eight of 28 (29%) disc spaces with M1, but it increased in four (14%) discs. In those without M1, only few changes occurred. The larger the M1, the more likely was the DH low or decreased further. Both the presence and changes in M1 were associated with a decrease in DH and changes in DSI and bulges. The degenerative process in discs with adjacent M1 seems to be accelerated and leads to advanced and deforming changes with special morphologic features. M1 may be a sign of a pathologic degenerative process in the discovertebral unit. (orig.)

  1. Relationship of modic type 1 change with disc degeneration: a prospective MRI study

    International Nuclear Information System (INIS)

    Luoma, Katariina; Vehmas, Tapio; Groenblad, Mats; Kaeaepae, Eeva; Kerttula, Liisa

    2009-01-01

    The objective was to study the natural course of Modic type 1 change (M1) in relation to lumbar disc degeneration. Twenty-four chronic low back pain (LBP) patients with M1 on lumbar spine were selected from 1,015 patients with magnetic resonance imaging from a follow-up study lasting for 18-74 months. Exclusion criteria were any other specific back disorder, age ≥60 years, or a recent spine operation. The association between the development of M1 and degenerative disc changes was studied using multivariate modeling (complex samples logistic regression). At baseline, 20 of 28 (71%) disc spaces with M1 had a decreased disc height (DH) and 16 of 28 (57%) a dark nucleus pulposus, but ten of 28 (36%) a very dark annulus fibrosus and a paradoxically bright nucleus pulposus albeit decreased DH. During follow-up, DH decreased in 13 of 28 (46%) and signal intensity of nucleus pulposus (DSI) in eight of 28 (29%) disc spaces with M1, but it increased in four (14%) discs. In those without M1, only few changes occurred. The larger the M1, the more likely was the DH low or decreased further. Both the presence and changes in M1 were associated with a decrease in DH and changes in DSI and bulges. The degenerative process in discs with adjacent M1 seems to be accelerated and leads to advanced and deforming changes with special morphologic features. M1 may be a sign of a pathologic degenerative process in the discovertebral unit. (orig.)

  2. REHABILITATION THERAPY VERSUS DRUG THERAPY IN PATIENTS WITH LUMBAR DISC DEGENERATION

    Directory of Open Access Journals (Sweden)

    BROSCATEAN, Emanuela-Flavia

    2013-12-01

    Full Text Available Lumbar disc degeneration is a disorder whose clinical manifestations are represented by episodic pain in the lumbar spine, without lumbar blockage and minor muscle contraction. Because lumbalgia caused by lumbar disc degeneration is not always very high intensity pain, the easiest to apply treatment is drug therapy. The aim of this study was to analyze the potential role of rehabilitation treatment in the recovery of patients and the prevention of complications compared to drug therapy alone. The study included 28 patients (17 women and 11 men aged between 23-60 years, assigned to two groups: 20 patients who received rehabilitation treatment (consisting of massage, kinesiotherapy, hydrokinesiotherapy, electrotherapy and medication and 8 patients who received drug treatment consisting of anti-inflammatory and analgesic drugs. The treatment duration was 10 days. For the evaluation of pain, the visual analogue scale was used, for the degree of disability, the Oswestry questionnaire, and for joint mobility and muscle strength, articular and muscular testing. At the end of treatment, the study group compared to the control group had a statistically significant result for pain (p=0.001, as well as for the Oswestry score (p=0.030. The mean age of the patients was 35.51±3.026, which shows an increased incidence among young adults. A possible connection between the development of the disease in women and age less than 45 years was also investigated, but the result was not statistically significant, p=0.22. Our data suggest the fact that rehabilitation treatment plays an important role in the reduction of pain and the improvement of the quality of life of patients with lumbar disc degeneration by decreasing the degree of disability. In the future, it can be proposed to monitor patients with lumbar disc degeneration over a longer time period in order to see the effects of kinetic rehabilitation programs in relation to the delay of chronicization. As

  3. Stem-cell treatment in disc degeneration: What is the evidence?

    Directory of Open Access Journals (Sweden)

    Manuela Peletti-Figueiró

    2013-01-01

    Full Text Available To review the potential role of stem cells in treating degenerative disc disease of the intervertebral disc (IVD. A review was performed of articles from the Medline database concerning stem cells and degenerative disc disease (DDD. To discuss the data, the papers were classified as: review, in vitro, experimental, and clinical. The currently available treatments were basically for symptom reduction, not to revert the IVD degenerative process. The use of mesenchymal stem cells (MSC is being proposed as an option of treatment for DDD. In vitro studies have shown that the MSC are able to differentiate into NP cells and that the MSC also reduce the inflammatory levels of the degenerated IVD. Besides, experimental studies demonstrated that the MSC remained viable when injected into the IVD, and that they were able to regenerate partially from the degenerated IVD and its structure. The few clinical studies found in the literature presented diverging results. The use of MSC is being widely studied and shows promising results for the treatment of DDD. Although many advances are being achieved in studies in vitro and experimental, there is a lack of clinical studies to prove the role of MSC in DDD management.

  4. Histological, magnetic resonance imaging, and discographic findings on cervical disc degeneration in cadaver spines. A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Maruyama, Yuichiro [Juntendo Univ., Tokyo (Japan). School of Medicine

    1995-11-01

    A total of 210 cervical intervertebral discs were taken at autopsy from 36 cadavers, and underwent both magnetic resonance imaging (MRI) and discography to compare their diagnostic efficacies for investigating degenerative changes in the cervical spine. The age of the subjects had ranged from 43 to 92 years with an average of 68.1 years. Following the autopsy, MRI and discography were performed on the excised cervical spinal column, and the specimen was then prepared for histological examination. The findings were compared with those of the lumbar spine that had previously been reported by Yasuma et al. on 1238 lumbar discs from 197 cadavers ranging in age from 11 to 92 years. The results were as follows: Low intensity in the T2-weighted MRI was well correlated with histological degeneration in the cervical disc. The rate of appearance of the posterior protrusion of the cervical disc on the MRI was in accordance with the degree of histological disc degeneration, but it did not always correspond with histological posterior protrusion. There was a remarkably high incidence for false-positive posterior protrusion on the MRI, which should be kept in mind on reading the MRI. In the comparison of the MRI with the discography, a certain positive correlation was found as for disc degeneration, but not in complete accordance. There was a considerable difference in the patterns of degeneration and in posterior protrusion of the discs between the cervical spine and the lumbar spine. The posterior protrusion in the cervical disc was more likely related to horizontal fissure and hyalinization of the posterior annulus, while posterior protrusion in the lumbar disc was often related to reversed orientation of the bundles and myxomatous degeneration of the posterior annulus. This difference was attributed to the difference in the mechanical properties of the cervical and lumbar spines. (author).

  5. Histological, magnetic resonance imaging, and discographic findings on cervical disc degeneration in cadaver spines. A comparative study

    International Nuclear Information System (INIS)

    Maruyama, Yuichiro

    1995-01-01

    A total of 210 cervical intervertebral discs were taken at autopsy from 36 cadavers, and underwent both magnetic resonance imaging (MRI) and discography to compare their diagnostic efficacies for investigating degenerative changes in the cervical spine. The age of the subjects had ranged from 43 to 92 years with an average of 68.1 years. Following the autopsy, MRI and discography were performed on the excised cervical spinal column, and the specimen was then prepared for histological examination. The findings were compared with those of the lumbar spine that had previously been reported by Yasuma et al. on 1238 lumbar discs from 197 cadavers ranging in age from 11 to 92 years. The results were as follows: Low intensity in the T2-weighted MRI was well correlated with histological degeneration in the cervical disc. The rate of appearance of the posterior protrusion of the cervical disc on the MRI was in accordance with the degree of histological disc degeneration, but it did not always correspond with histological posterior protrusion. There was a remarkably high incidence for false-positive posterior protrusion on the MRI, which should be kept in mind on reading the MRI. In the comparison of the MRI with the discography, a certain positive correlation was found as for disc degeneration, but not in complete accordance. There was a considerable difference in the patterns of degeneration and in posterior protrusion of the discs between the cervical spine and the lumbar spine. The posterior protrusion in the cervical disc was more likely related to horizontal fissure and hyalinization of the posterior annulus, while posterior protrusion in the lumbar disc was often related to reversed orientation of the bundles and myxomatous degeneration of the posterior annulus. This difference was attributed to the difference in the mechanical properties of the cervical and lumbar spines. (author)

  6. Propofol causes neuronal degeneration in neonatal mice and long ...

    African Journals Online (AJOL)

    Propofol causes neuronal degeneration in neonatal mice and long-term ... of 2.5 and 5.0 mg/kg (treatment group) or normal saline (control) on postnatal day 7. ... PO2, glucose and lactate), among which decreased blood glucose might be ...

  7. Disc degeneration and chronic low back pain: an association which becomes nonsignificant when endplate changes and disc contour are taken into account

    International Nuclear Information System (INIS)

    Kovacs, Francisco M.; Arana, Estanislao; Royuela, Ana; Estremera, Ana; Amengual, Guillermo; Sarasibar, Helena; Martinez, Carmen; Asenjo, Beatriz; Galarraga, Isabel; Alonso, Ana; Casillas, Carlos; Muriel, Alfonso; Abraira, Victor

    2014-01-01

    The objective of this study was to assess the association between severe disc degeneration (DD) and low back pain (LBP). A case-control study was conducted with 304 subjects, aged 35-50, recruited in routine clinical practice across six hospitals; 240 cases (chronic LBP patients with a median pain duration of 46 months) and 64 controls (asymptomatic subjects without any lifetime history of significant LBP). The following variables were assessed once, using previously validated methods: gender, age, body mass index (BMI), lifetime smoking exposure, degree of physical activity, severity of LBP, disability, and findings on magnetic resonance (MRI) (disc degeneration, Modic changes (MC), disc protrusion/hernia, annular tears, spinal stenosis, and spondylolisthesis). Radiologists who interpreted MRI were blinded to the subjects' characteristics. A multivariate logistic regression model assessed the association between severe DD and chronic LBP, adjusting for gender, age, BMI, physical activity, MC, disc protrusion/hernia, and spinal stenosis. Severe DD at ≥1 level was found in 46.9 % of the controls and 65.8 % of the cases. Crude odds ratio (95 % CI), for suffering chronic LBP when having severe DD, was 2.06 (1.05; 4.06). After adjusting for ''MC'' and ''disc protrusion/hernia,'' it was 1.81 (0.81; 4.05). The association between severe DD and LBP ceases to be significant when adjusted for MC and disc protrusion/hernia. These results do not support that DD as a major cause of chronic LBP. (orig.)

  8. Spondylolisthesis adjacent to a cervical disc arthroplasty does not increase the risk of adjacent level degeneration.

    Science.gov (United States)

    Kieser, David Christopher; Cawley, Derek Thomas; Roscop, Cecile; Mazas, Simon; Coudert, Pierre; Boissiere, Louis; Obeid, Ibrahim; Vital, Jean-Marc; Pointillart, Vincent; Gille, Olivier

    2018-03-31

    To understand whether a spondylolisthesis in the sub-axial spine cranial to a cervical disc arthroplasty (CDA) construes a risk of adjacent level disease (ALD). A retrospective review of 164 patients with a minimum 5-year follow-up of a cervical disc arthroplasty was performed. Multi-level surgeries, including hybrid procedures, were included. Multiple implant types were included. The two inter-vertebral discs (IVD) cranial of the CDA were monitored for evidence of radiologic degeneration using the Kettler criteria. The rate of ALD in CDA found in this series was 17.8%, with most affecting the immediately adjacent IVD (27.4 and 7.6%, respectively p = 0.000). Pre-operative mild spondylolisthesis adjacent to a planned CDA was not found to be a risk factor for ALD within 5 years. Those with a degenerative spondylolisthesis are at higher risk of ALD (33%) than those with a non-degenerative cause for their spondylolisthesis (11%). Post-operative CDA alignment, ROM or induced spondylolisthesis do not affect the rate of ALD in those with an adjacent spondylolisthesis. Patients with ALD experience significantly worse 5-year pain and functional outcomes than those unaffected by ALD. A pre-operatively identified mild spondylolisthesis in the sub-axial spine cranially adjacent to a planned CDA is not a risk factor for ALD within 5 years. These slides can be retrieved under Electronic Supplementary Material.

  9. Familial history, age and smoking are important risk factors for disc degeneration disease in Arabic pedigrees

    International Nuclear Information System (INIS)

    Livshits, Gregory; Cohen, Zvi; Higla, Orabi; Yakovenko, Konstantin

    2001-01-01

    The present study used computed tomography imaging to evaluate the extent and pattern of the intergenerational transmission of spinal disc degeneration disease (DDD) in complex pedigrees. Contribution of a number of the potential covariates was also studied using univariate and multivariate logistic regression analysis, as well as two types of complex segregation analysis models. Among 161 individuals studied, DDD was diagnosed in 60 individuals. The number of protruded discs varied from 1 to 4, mostly in lumbar or lumbosacral regions. The average age at onset of the disease was similar for both women (36.0 years) and men (34.8 years). The proportion of the individuals affected by the DDD status of their parents ranged from 10% in families of two healthy parents to 55.5% of two affected parents (p < 0.01). The results of the logistic regression analyses and complex segregation analysis were qualitatively the same: DDD status of parents, age and smoking were the main risk factors for disc herniation in the Arabic families we examined. All analyses showed a predominating role of the family history as a risk factor for DDD in offsprings. It showed, for example, four times higher risk at age 50 for individuals with two affected parents vs. those who have two non-affected parents. However, the results of models-fitting genetic analysis, did not confirm a monogenic Mendelian pattern of inheritance

  10. Neuronal degeneration in autonomic nervous system of Dystonia musculorum mice

    Directory of Open Access Journals (Sweden)

    Liu Kang-Jen

    2011-01-01

    Full Text Available Abstract Background Dystonia musculorum (dt is an autosomal recessive hereditary neuropathy with a characteristic uncoordinated movement and is caused by a defect in the bullous pemphigoid antigen 1 (BPAG1 gene. The neural isoform of BPAG1 is expressed in various neurons, including those in the central and peripheral nerve systems of mice. However, most previous studies on neuronal degeneration in BPAG1-deficient mice focused on peripheral sensory neurons and only limited investigation of the autonomic system has been conducted. Methods In this study, patterns of nerve innervation in cutaneous and iridial tissues were examined using general neuronal marker protein gene product 9.5 via immunohistochemistry. To perform quantitative analysis of the autonomic neuronal number, neurons within the lumbar sympathetic and parasympathetic ciliary ganglia were calculated. In addition, autonomic neurons were cultured from embryonic dt/dt mutants to elucidate degenerative patterns in vitro. Distribution patterns of neuronal intermediate filaments in cultured autonomic neurons were thoroughly studied under immunocytochemistry and conventional electron microscopy. Results Our immunohistochemistry results indicate that peripheral sensory nerves and autonomic innervation of sweat glands and irises dominated degeneration in dt/dt mice. Quantitative results confirmed that the number of neurons was significantly decreased in the lumbar sympathetic ganglia as well as in the parasympathetic ciliary ganglia of dt/dt mice compared with those of wild-type mice. We also observed that the neuronal intermediate filaments were aggregated abnormally in cultured autonomic neurons from dt/dt embryos. Conclusions These results suggest that a deficiency in the cytoskeletal linker BPAG1 is responsible for dominant sensory nerve degeneration and severe autonomic degeneration in dt/dt mice. Additionally, abnormally aggregated neuronal intermediate filaments may participate in

  11. Matrix metalloproteinase-3, vitamin D receptor gene polymorphisms, and occupational risk factors in lumbar disc degeneration.

    Science.gov (United States)

    Zawilla, N H; Darweesh, H; Mansour, N; Helal, S; Taha, F M; Awadallah, M; El Shazly, R

    2014-06-01

    Lumbar disc degeneration (LDD) is a process that begins early in life, contributing to the development of low back pain. LDD is a consequence of a variety of factors, and its etiology remains poorly understood. Objectives to investigate occupational and genetic risk factors inducing lumbar disc degeneration, and to evaluate the possible association of genetic polymorphisms of matrix metalloproteinase 3 (MMP-3) and vitamin D receptor (VDR) with the severity of LDD in an Egyptian population. A case control study involving 84 LDD and 60 controls was carried out. Five types of work related factors were investigated by questionnaire, complete neurological examination for all subjects and MRI for the cases. Polymerase chain reaction and restriction fragment length polymorphism methods were applied to detect polymorphisms in MMP-3 Promoter (-1,171 6A/5A) (rs 731236) and VDR-Apa (rs 35068180). We found that family history, back injury, smoking, high level of sitting, bending/twisting, physical workload, lifting, whole body vibration, mutant allele 5A of MMP-3 and mutant allele T of VDR were significantly associated with LDD (OR = 2.9, 3.1, 2.1, 11.1, 15.9, 11.7, 8.2, 12.6, 2.5 and 3.1 respectively, p < 0.05). Cases that carry allele 5A and/or allele T were associated with LDD severity. LDD is closely associated in occurrence and severity with occupational, environmental risk factors and susceptibility genes namely MMP-3, and VDR (ApaI). This study throws light on the importance of screening for early detection of susceptible individuals and disease prevention.

  12. Quantitative evaluation of lumbar intervertebral disc degeneration by axial T2* mapping.

    Science.gov (United States)

    Huang, Leitao; Liu, Yuan; Ding, Yi; Wu, Xia; Zhang, Ning; Lai, Qi; Zeng, Xianjun; Wan, Zongmiao; Dai, Min; Zhang, Bin

    2017-12-01

    To quantitatively evaluate the clinical value and demonstrate the potential benefits of biochemical axial T2* mapping-based grading of early stages of degenerative disc disease (DDD) using 3.0-T magnetic resonance imaging (MRI) in a clinical setting.Fifty patients with low back pain and 20 healthy volunteers (control) underwent standard MRI protocols including axial T2* mapping. All the intervertebral discs (IVDs) were classified morphologically. Lumbar IVDs were graded using Pfirrmann score (I to IV). The T2* values of the anterior annulus fibrosus (AF), posterior AF, and nucleus pulposus (NP) of each lumbar IVD were measured. The differences between groups were analyzed regarding specific T2* pattern at different regions of interest.The T2* values of the NP and posterior AF in the patient group were significantly lower than those in the control group (P T2* value of the anterior AF was not significantly different between the patients and the controls (P > .05). The mean T2*values of the lumbar IVD in the patient group were significantly lower, especially the posterior AF, followed by the NP, and finally, the anterior AF. In the anterior AF, comparison of grade I with grade III and grade I with grade IV showed statistically significant differences (P = .07 and P = .08, respectively). Similarly, in the NP, comparison of grade I with grade III, grade I with grade IV, grade II with grade III, and grade II with grade IV showed statistically significant differences (P T2 values decreased linearly with increasing degeneration based on the Pfirrmann scoring system (ρ T2* value can signify early degenerative IVD diseases. Hence, T2* mapping can be used as a diagnostic tool for quantitative assessment of IVD degeneration. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  13. Quantitative evaluation of lumbar intervertebral disc degeneration by axial T2∗ mapping

    Science.gov (United States)

    Huang, Leitao; Liu, Yuan; Ding, Yi; Wu, Xia; Zhang, Ning; Lai, Qi; Zeng, Xianjun; Wan, Zongmiao; Dai, Min; Zhang, Bin

    2017-01-01

    Abstract To quantitatively evaluate the clinical value and demonstrate the potential benefits of biochemical axial T2∗ mapping-based grading of early stages of degenerative disc disease (DDD) using 3.0-T magnetic resonance imaging (MRI) in a clinical setting. Fifty patients with low back pain and 20 healthy volunteers (control) underwent standard MRI protocols including axial T2∗ mapping. All the intervertebral discs (IVDs) were classified morphologically. Lumbar IVDs were graded using Pfirrmann score (I to IV). The T2∗ values of the anterior annulus fibrosus (AF), posterior AF, and nucleus pulposus (NP) of each lumbar IVD were measured. The differences between groups were analyzed regarding specific T2∗ pattern at different regions of interest. The T2∗ values of the NP and posterior AF in the patient group were significantly lower than those in the control group (P T2∗ value of the anterior AF was not significantly different between the patients and the controls (P > .05). The mean T2∗values of the lumbar IVD in the patient group were significantly lower, especially the posterior AF, followed by the NP, and finally, the anterior AF. In the anterior AF, comparison of grade I with grade III and grade I with grade IV showed statistically significant differences (P = .07 and P = .08, respectively). Similarly, in the NP, comparison of grade I with grade III, grade I with grade IV, grade II with grade III, and grade II with grade IV showed statistically significant differences (P T2∗ values decreased linearly with increasing degeneration based on the Pfirrmann scoring system (ρ T2∗ value can signify early degenerative IVD diseases. Hence, T2∗ mapping can be used as a diagnostic tool for quantitative assessment of IVD degeneration. PMID:29390547

  14. Posteriorly directed shear loads and disc degeneration affect the torsional stiffness of spinal motion segments; a biomechanical modeling study

    NARCIS (Netherlands)

    Homminga, Jasper Johan; Lehr, A.M.; Meijer, Gerdine; Janssen, M.M.A.; Schlösser, T.P.C.; Verkerke, Gijsbertus Jacob; Castelein, R.M.

    2013-01-01

    Objective. To analyze the effects of posterior shear loads, disc degeneration, and the combination of both on spinal torsion stiffness. Summary of Background Data. Scoliosis is a 3-dimensional deformity of the spine that presents itself mainly in adolescent girls and elderly patients. Our concept of

  15. Nucleoplasty as a therapeutic option for lumbar disc degeneration related pain: a retrospective study of 396 cases

    Directory of Open Access Journals (Sweden)

    José Lourenço Kallás

    2013-01-01

    Full Text Available OBJECTIVES: To make a retrospective analysis and evaluate a clinical response to the control of disc degeneration related pain of 396 patients submitted to percutaneous lumbar nucleoplasty; and to make a record of visual analogical scale (VAS up to a three-year follow-up after the surgical procedure. METHODS: Analysis of VAS score in 396 patients with lumbar disc degeneration related pain, according to anamnesis, clinical examination and magnetic resonance imaging (MRI, without improvement of previous clinical treatment, submitted to percutaneous nucleoplasty. RESULTS: A total of 26% of the patients presented 100% remission of pain or paresthesia, of whom 75% showed at least 50% of pain improvement. The median VAS pain improvement was about 67%. CONCLUSIONS: The median VAS improvement in inferior disc levels was higher than four points. The VAS showed improvement of the pain and paresthesia up to a three-year follow up after the surgical procedure.

  16. Prevalence and pattern of radiographic intervertebral disc degeneration in Vietnamese: a population-based study.

    Science.gov (United States)

    Ho-Pham, Lan T; Lai, Thai Q; Mai, Linh D; Doan, Minh C; Pham, Hoa N; Nguyen, Tuan V

    2015-06-01

    Intervertebral disc degeneration (IDD) is one of the most common skeletal disorders, yet few data are available in Asian populations. We sought to assess the prevalence and pattern of radiographic IDD in a Vietnamese population. This population-based cross-sectional investigation involved 170 men and 488 women aged ≥40 years, who were randomly sampled from the Ho Chi Minh City (Vietnam). Anthropometric data, clinical history and self-reported back and neck pain were ascertained by a questionnaire. Plain radiographs (from the cervical spine, thoracic spine to the lumbar spine) were examined for the presence of disc space narrowing and/or osteophytosis using the Kellgren-Lawrence (KL) grading system. The presence of radiographic IDD was defined if the KL grade was 2 or greater in at least one disc. The prevalence of radiographic IDD was 62.4% (n = 106) in men and 54.7% (n = 267) in women. The most frequently affected site was the lumbar spine with prevalence being 50.6 and 43.2% in men and women, respectively. The prevalence of IDD increased with advancing age: 18.8% among those aged 40-49 years, and increased to 83.4% in those aged ≥60 years. Self-reported neck pain and lower back pain were found in 30 and 44% of individuals, respectively. There was no statistically significant association between self-reported neck pain and cervical spine OA. These data suggest that radiographic IDD is highly prevalent in the Vietnamese population, and that self-reported back pain is not a sensitive indicator of IDD.

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

    Science.gov (United States)

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

    2016-11-17

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

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

    International Nuclear Information System (INIS)

    Shang Tiesong; Wang Yunzhao

    2002-01-01

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

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

    Science.gov (United States)

    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 osteoarthritis entered the regression model, however, greater spine BMD was associated with greater facet joint osteoarthritis (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.

  20. Disc degeneration and chronic low back pain: an association which becomes nonsignificant when endplate changes and disc contour are taken into account

    Energy Technology Data Exchange (ETDEWEB)

    Kovacs, Francisco M. [Fundacion Kovacs, Departamento Cientifico, Palma de Mallorca (Spain); Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Arana, Estanislao [Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Fundacion Instituto Valenciano de Oncologia, Servicio de Radiologia, Valencia (Spain); Royuela, Ana [CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid (Spain); Hospital Ramon y Cajal, Unidad de Bioestadistica Clinica, IRYCIS, Madrid (Spain); Estremera, Ana; Amengual, Guillermo; Sarasibar, Helena; Martinez, Carmen [Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Hospital Son Llatzer, Palma de Mallorca (Spain); Asenjo, Beatriz [Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Hospital Carlos Haya, Malaga (Spain); Galarraga, Isabel [Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Hospital de Manacor, Manacor, Mallorca (Spain); Alonso, Ana [Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Fundacion Jimenez Diaz, Madrid (Spain); Casillas, Carlos [Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Instituto de Traumatologia Union de Mutuas, Castellon (Spain); Muriel, Alfonso; Abraira, Victor [Hospital Ramon y Cajal, Unidad de Bioestadistica Clinica, IRYCIS, Madrid (Spain); CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid (Spain)

    2014-01-15

    The objective of this study was to assess the association between severe disc degeneration (DD) and low back pain (LBP). A case-control study was conducted with 304 subjects, aged 35-50, recruited in routine clinical practice across six hospitals; 240 cases (chronic LBP patients with a median pain duration of 46 months) and 64 controls (asymptomatic subjects without any lifetime history of significant LBP). The following variables were assessed once, using previously validated methods: gender, age, body mass index (BMI), lifetime smoking exposure, degree of physical activity, severity of LBP, disability, and findings on magnetic resonance (MRI) (disc degeneration, Modic changes (MC), disc protrusion/hernia, annular tears, spinal stenosis, and spondylolisthesis). Radiologists who interpreted MRI were blinded to the subjects' characteristics. A multivariate logistic regression model assessed the association between severe DD and chronic LBP, adjusting for gender, age, BMI, physical activity, MC, disc protrusion/hernia, and spinal stenosis. Severe DD at ≥1 level was found in 46.9 % of the controls and 65.8 % of the cases. Crude odds ratio (95 % CI), for suffering chronic LBP when having severe DD, was 2.06 (1.05; 4.06). After adjusting for ''MC'' and ''disc protrusion/hernia,'' it was 1.81 (0.81; 4.05). The association between severe DD and LBP ceases to be significant when adjusted for MC and disc protrusion/hernia. These results do not support that DD as a major cause of chronic LBP. (orig.)

  1. Evaluation of Lumbar Intervertebral Disc Degeneration Using T1ρ and T2 Magnetic Resonance Imaging in a Rabbit Disc Injury Model.

    Science.gov (United States)

    Ishikawa, Tetsuhiro; Watanabe, Atsuya; Kamoda, Hiroto; Miyagi, Masayuki; Inoue, Gen; Takahashi, Kazuhisa; Ohtori, Seiji

    2018-04-01

    An in vivo histologic and magnetic resonance imaging (MRI) study of lumbar intervertebral disc (IVD) degeneration was conducted. To clarify the sensitivity and efficacy of T1ρ/T2 mapping for IVD degeneration, the correlation between T1ρ/T2 mapping and degenerative grades and histological findings in the lumbar IVD were investigated. The early signs of IVD degeneration are proteoglycan loss, dehydration, and collagen degradation. Recently, several quantitative MRI techniques have been developed; T2 mapping can be used to evaluate hydration and collagen fiber integrity within cartilaginous tissue, and T1ρ mapping can be used to evaluate hydration and proteoglycan content. Using New Zealand White rabbits, annular punctures of the IVD were made 10 times at L2/3, 5 times at L3/4, and one time at L4/5 using an 18-gauge needle (n=6) or a 21-gauge needle (n=6). At 4 and 8 weeks post-surgery, MRI was performed including T1ρ and T2 mapping. The degree of IVD degeneration was macroscopically assessed using the Thompson grading system. All specimens were cut for hematoxylin and eosin, safranin-O, and toluidine blue staining. Disc degeneration became more severe as the number of punctures increased and when the larger needle was used. T1ρ and T2 values were significantly different between grade 1 and grade 3 IVDs, grade 1 and grade 4 IVDs, grade 2 and grade 3 IVDs, and grade 2 and grade 4 IVDs ( p T2 quantitative MRI could detect these small differences. Our results suggest that T1ρ and T2 mapping are sensitive to degenerative changes of lumbar IVDs and that T1ρ mapping can be used as a clinical tool to identify early IVD degeneration.

  2. The Effect of Electroacupuncture on the Extracellular Matrix Synthesis and Degradation in a Rabbit Model of Disc Degeneration

    Directory of Open Access Journals (Sweden)

    Guo-fu Huang

    2014-01-01

    Full Text Available The present study was aimed at determining if the electroacupuncture (EA is able to protect degenerated disc in vivo. New Zealand white rabbits (n=40 were used for the study. The rabbits were randomly assigned to four groups. EA intervention was applied to one of the four groups. Magnetic resonance imaging and Pfirrmann’s classification were obtained for each group to evaluate EA treatment on the intervertebral disc degeneration. Discs were analyzed using immunofluorescence for the labeling of collagens 1 and 2, bone morphogenetic protein-2 (BMP-2, matrix metalloproteinase-13 (MMP-13, and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1. For protein expression analysis, western blot was used for biglycan and decorin. Outcomes indicated that EA intervention decreased the grades compared with the compressed disc. Immunofluorescence analysis showed a significant increase of collagens 1 and 2, TIMP-1, and BMP-2 positive cells, in contrast to MMP-13 after EA treatment for 28 days. The protein expression showed a sign of regeneration that decorin and biglycan were upregulated. It was concluded that EA contributed to the extracellular matrix (ECM anabolic processes and increased the ECM components. MMPs and their inhibitors involved in the mechanism of EA intervention on ECM decreased disc. It kept a dynamic balance between ECM synthesis and degradation.

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

    Science.gov (United States)

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

    2017-12-01

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

  4. Correlation of matrix metalloproteinase-3 expression with patient age, magnetic resonance imaging and histopathological grade in lumbar disc degeneration.

    Science.gov (United States)

    Canbay, Suat; Turhan, Nesrin; Bozkurt, Melih; Arda, Kemal; Caglar, Sukru

    2013-01-01

    The purpose of the present study is to analyze the expression of matrix metalloproteinase-3 (MMP-3), magnetic resonance imaging (MRI) grading and histopathological alterations of the intervertebral disc (IVD) for correlations with each other and with the age, gender and low back pain duration of the patients who had undergone operations for lumbar disc herniation (LDH). Forty-two patients were admitted to our clinic with signs of LDH and underwent surgery for LDH at 48 IVD levels. In all cases, specimens for histological and immunohistochemical analyses were removed from the IVD space. Lumbar IVD degeneration on MRI of the 48 IVDs from which surgical specimens had been obtained was classified into five grades using the Pfirrmann classification. In the degenerated IVD, the expression of MMP-3, MRI grading and histopathological alterations of the IVD displayed significant correlation. Increased age is closely related with aforementioned alterations. There was no correlation between MMP-3 expression and age, gender and duration of the pain. For evaluating and treating IVD degeneration, MRI is a good and non-invasive diagnostic tool to determine the severity of degeneration. MMP-3 may be a therapeutic target of the degenerated IVD.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Makino, Hiroto; Seki, Shoji; Yahara, Yasuhito; Shiozawa, Shunichi; Aikawa, Yukihiko; Motomura, Hiraku; Nogami, Makiko; Watanabe, Kenta; Sainoh, Takeshi; Ito, Hisakatsu; Tsumaki, Noriyuki; Kawaguchi, Yoshiharu; Yamazaki, Mitsuaki; Kimura, Tomoatsu

    2017-12-05

    Intervertebral disc (IVD) degeneration is a major cause of low back pain. The transcription factor c-Fos/Activator Protein-1 (AP-1) controls the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) that contribute to the pathogenesis IVD degeneration. We investigated the effects of inhibition of c-Fos/AP-1 on IVD degeneration and associated pain. A selective inhibitor, T-5224, significantly suppressed the interleukin-1β-induced up-regulation of Mmp-3, Mmp-13 and Adamts-5 transcription in human nucleus pulposus cells and in a mouse explant culture model of IVD degeneration. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of disc height, T2-magnetic resonance imaging (MRI) findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain and that T-5224 may serve as a drug for the prevention of IVD degeneration.

  7. The impact of generalized joint laxity (GJL) on the posterior neck pain, cervical disc herniation, and cervical disc degeneration in the cervical spine.

    Science.gov (United States)

    Lee, Sun-Mi; Oh, Su Chan; Yeom, Jin S; Shin, Ji-Hoon; Park, Sam-Guk; Shin, Duk-Seop; Ahn, Myun-Whan; Lee, Gun Woo

    2016-12-01

    Generalized joint laxity (GJL) can have a negative impact on lumbar spine pathology, including low back pain, disc degeneration, and disc herniation, but the relationship between GJL and cervical spine conditions remains unknown. To investigate the relationship between GJL and cervical spine conditions, including the prevalence of posterior neck pain (PNP), cervical disc herniation (CDH), and cervical disc degeneration (CDD), in a young, active population. Retrospective 1:2 matched cohort (case-control) study from prospectively collected data PATIENT SAMPLE: Of a total of 1853 individuals reviewed, 73 individuals with GJL (study group, gruop A) and 146 without GJL (control group, Group B) were included in the study according to a 1:2 case-control matched design for age, sex, and body mass index. The primary outcome measure was the prevalence and intensity of PNP at enrollment based on a visual analogue scale score for pain. The secondary outcome measures were (1) clinical outcomes as measured with the neck disability index (NDI) and 12-item short form health survey (SF-12) at enrollment, and (2) radiological outcomes of CDH and CDD at enrollment. We compared baseline data between groups. Descriptive statistical analyses were performed to compare the 2 groups in terms of the outcome measures. The prevalence and intensity of PNP were significantly greater in group A (patients with GJL) than in group B (patients without GJL) (prevalence: p=.02; intensity: p=.001). Clinical outcomes as measured with NDI and SF-12 did not differ significantly between groups. For radiologic outcomes, the prevalence of CDD was significantly greater in group A than in group B (p=.04), whereas the prevalence of CDH did not differ significantly between groups (p=.91). The current study revealed that GJL was closely related to the prevalence and intensity of PNP, suggesting that GJL may be a causative factor for PNP. In addition, GJL may contribute to the occurrence of CDD, but not CDH. Spine

  8. Are the determinants of vertebral endplate changes and severe disc degeneration in the lumbar spine the same? A magnetic resonance imaging study in middle-aged male workers

    Directory of Open Access Journals (Sweden)

    Korpelainen Raija

    2008-04-01

    Full Text Available Abstract Background Modic changes are bone marrow lesions visible in magnetic resonance imaging (MRI, and they are assumed to be associated with symptomatic intervertebral disc disease, especially changes located at L5-S1. Only limited information exists about the determinants of Modic changes. The objective of this study was to evaluate the determinants of vertebral endplate (Modic changes, and whether they are similar for Modic changes and severe disc degeneration focusing on L5-S1 level. Methods 228 middle-aged male workers (159 train engineers and 69 sedentary factory workers from northern Finland underwent sagittal T1- and T2-weighted MRI. Modic changes and disc degeneration were analyzed from the scans. The participants responded to a questionnaire including items of occupational history and lifestyle factors. Logistic regression analysis was used to evaluate the associations between selected determinants (age, lifetime exercise, weight-related factors, fat percentage, smoking, alcohol use, lifetime whole-body vibration and Modic type I and II changes, and severe disc degeneration (= grade V on Pfirrmann's classification. Results The prevalences of the Modic changes and severe disc degeneration were similar in the occupational groups. Age was significantly associated with all degenerative changes. In the age-adjusted analyses, only weight-related determinants (BMI, waist circumference were associated with type II changes. Exposure to whole-body vibration, besides age, was the only significant determinant for severe disc degeneration. In the multivariate model, BMI was associated with type II changes at L5-S1 (OR 2.75 per one SD = 3 unit increment in BMI, and vibration exposure with severe disc degeneration at L5-S1 (OR 1.08 per one SD = 11-year increment in vibration exposure. Conclusion Besides age, weight-related factors seem important in the pathogenesis of Modic changes, whereas whole-body vibration was the only significant determinant

  9. Oxygen-induced retinopathy in mice with retinal photoreceptor cell degeneration.

    Science.gov (United States)

    Zhang, Qian; Zhang, Zuo-Ming

    2014-04-25

    It is reported that retinal neovascularization seems to rarely co-exist with retinitis pigmentosa in patients and in some mouse models; however, it is not widely acknowledged as a universal phenomenon in all strains of all animal species. We aimed to further explore this phenomenon with an oxygen-induced retinopathy model in mice with retinal photoreceptor cell degeneration. Oxygen-induced retinopathy of colored and albino mice with rapid retinal degeneration were compared to homologous wild-type mice. The retinas were analyzed using high-molecular-weight FITC-dextran stained flat-mount preparation, hematoxylin and eosin (H&E) stained cross-sections, an immunohistochemical test for vascular endothelial growth factor (VEGF) distribution and Western blotting for VEGF expression after exposure to hyperoxia between postnatal days 17 (P17) and 21. Leakage and areas of non-perfusion of the retinal blood vessels were alleviated in the retinal degeneration mice. The number of preretinal vascular endothelial cell nuclei in the retinal degeneration mice was smaller than that in the homologous wild-type mice after exposure to hyperoxia (Poxygen-induced retinopathy was positively correlated with the VEGF expression level. However, the VEGF expression level was lower in the retinal degeneration mice. Proliferative retinopathy occurred in mice with rapid retinal degeneration, but retinal photoreceptor cell degeneration could partially restrain the retinal neovascularization in this rapid retinal degeneration mouse model. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Early UV emission from disc-originated matter (DOM) in Type Ia supernovae in the double-degenerate scenario

    Science.gov (United States)

    Levanon, Naveh; Soker, Noam

    2017-09-01

    We show that the blue and UV excess emission in the first few days of some Type Ia supernovae (SNe Ia) can be accounted in the double-degenerate (DD) scenario by the collision of the SN ejecta with circumstellar matter that was blown by the accretion disc formed during the merger process of the two white dwarfs (WDs). We assume that in cases of excess early light, the disc blows the circumstellar matter, that we term disc-originated matter (DOM), hours to days before explosion. To perform our analysis, we first provide a model-based definition for early excess light, replacing the definition of excess light relative to a power-law fit to the rising luminosity. We then examine the light curves of the SNe Ia iPTF14atg and SN 2012cg, and find that the collision of the ejecta with a DOM in the frame of the DD scenario can account for their early excess emission. Thus, early excess light does not necessarily imply the presence of a stellar companion in the frame of the single-degenerate scenario. Our findings further increase the variety of phenomena that the DD scenario can account for, and emphasize the need to consider all different SN Ia scenarios when interpreting observations.

  11. Computer aided vertebral visualization and analysis: a methodology using the sand rat, a small animal model of disc degeneration

    Directory of Open Access Journals (Sweden)

    Hanley Edward N

    2003-03-01

    Full Text Available Abstract Background The purpose of this study is to present an automated system that analyzes digitized x-ray images of small animal spines identifying the effects of disc degeneration. The age-related disc and spine degeneration that occurs in the sand rat (Psammomys obesus has previously been documented radiologically; selected representative radiographs with age-related changes were used here to develop computer-assisted vertebral visualization/analysis techniques. Techniques presented here have the potential to produce quantitative algorithms that create more accurate and informative measurements in a time efficient manner. Methods Signal and image processing techniques were applied to digitized spine x-ray images the spine was segmented, and orientation and curvature determined. The image was segmented based on orientation changes of the spine; edge detection was performed to define vertebral boundaries. Once vertebrae were identified, a number of measures were introduced and calculated to retrieve information on the vertebral separation/orientation and sclerosis. Results A method is described which produces computer-generated quantitative measurements of vertebrae and disc spaces. Six sand rat spine radiographs illustrate applications of this technique. Results showed that this method can successfully automate calculation and analysis of vertebral length, vertebral spacing, vertebral angle, and can score sclerosis. Techniques also provide quantitative means to explore the relation between age and vertebral shape. Conclusions This method provides a computationally efficient system to analyze spinal changes during aging. Techniques can be used to automate the quantitative processing of vertebral radiographic images and may be applicable to human and other animal radiologic models of the aging/degenerating spine.

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

    Directory of Open Access Journals (Sweden)

    Ismail Ismail

    2006-12-01

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

  13. Upper thoracic-spine disc degeneration in patients with cervical pain.

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    Arana, Estanislao; Martí-Bonmatí, Luis; Mollá, Enrique; Costa, Salvador

    2004-01-01

    To study the relationship of upper thoracic spine degenerative disc contour changes on MR imaging in patients with neck pain. The relation between upper thoracic and cervical spine degenerative disc disease is not well established. One hundred and fifty-six patients referred with cervical pain were studied. There were 73 women and 77 men with a mean age of 48.6 +/- 14.6 years (range, 19 to 83 years). All MR studies were performed with a large 23-cm FOV covering at least from the body of T4 to the clivus. Discs were coded as normal, protrusion/bulge or extrusion. Degenerative thoracic disc contour changes were observed in 13.4% of patients with cervical pain. T2-3 was the most commonly affected level of the upper thoracic spine, with 15 bulge/protrusions and one extrusion. Upper degenerative thoracic disc contour changes presented in older patients than the cervical levels (Student-Newman-Keuls test, P < 0.001). Degenerative disc contour changes at the C7-T1, T1-2, T2-3 and T3-4 levels were significantly correlated ( P = 0.001), but unrelated to any other disc disease, patient's gender or age. Degenerative cervical disc disease was closely related together ( P < 0.001), but not with any thoracic disc. A statistically significant relation was found within the upper thoracic discs, reflecting common pathoanatomical changes. The absence of relation to cervical segments is probably due to differences in their pathomechanisms.

  14. Upper thoracic-spine disc degeneration in patients with cervical pain

    Energy Technology Data Exchange (ETDEWEB)

    Arana, Estanislao; Marti-Bonmati, Luis; Costa, Salvador [Department of Radiology, Clinica Quiron, Avda Blasco Ibanez 14, 46010, Valencia (Spain); Molla, Enrique [Department of Radiology, Clinica Quiron, Avda Blasco Ibanez 14, 46010, Valencia (Spain); Department of Morphological Sciences, University of Valencia, Valencia (Spain)

    2004-01-01

    To study the relationship of upper thoracic spine degenerative disc contour changes on MR imaging in patients with neck pain. The relation between upper thoracic and cervical spine degenerative disc disease is not well established. One hundred and fifty-six patients referred with cervical pain were studied. There were 73 women and 77 men with a mean age of 48.6{+-}14.6 years (range, 19 to 83 years). All MR studies were performed with a large 23-cm FOV covering at least from the body of T4 to the clivus. Discs were coded as normal, protrusion/bulge or extrusion. Degenerative thoracic disc contour changes were observed in 13.4% of patients with cervical pain. T2-3 was the most commonly affected level of the upper thoracic spine, with 15 bulge/protrusions and one extrusion. Upper degenerative thoracic disc contour changes presented in older patients than the cervical levels (Student-Newman-Keuls test, P<0.001). Degenerative disc contour changes at the C7-T1, T1-2, T2-3 and T3-4 levels were significantly correlated (P=0.001), but unrelated to any other disc disease, patient's gender or age. Degenerative cervical disc disease was closely related together (P<0.001), but not with any thoracic disc. A statistically significant relation was found within the upper thoracic discs, reflecting common pathoanatomical changes. The absence of relation to cervical segments is probably due to differences in their pathomechanisms. (orig.)

  15. Upper thoracic-spine disc degeneration in patients with cervical pain

    International Nuclear Information System (INIS)

    Arana, Estanislao; Marti-Bonmati, Luis; Costa, Salvador; Molla, Enrique

    2004-01-01

    To study the relationship of upper thoracic spine degenerative disc contour changes on MR imaging in patients with neck pain. The relation between upper thoracic and cervical spine degenerative disc disease is not well established. One hundred and fifty-six patients referred with cervical pain were studied. There were 73 women and 77 men with a mean age of 48.6±14.6 years (range, 19 to 83 years). All MR studies were performed with a large 23-cm FOV covering at least from the body of T4 to the clivus. Discs were coded as normal, protrusion/bulge or extrusion. Degenerative thoracic disc contour changes were observed in 13.4% of patients with cervical pain. T2-3 was the most commonly affected level of the upper thoracic spine, with 15 bulge/protrusions and one extrusion. Upper degenerative thoracic disc contour changes presented in older patients than the cervical levels (Student-Newman-Keuls test, P<0.001). Degenerative disc contour changes at the C7-T1, T1-2, T2-3 and T3-4 levels were significantly correlated (P=0.001), but unrelated to any other disc disease, patient's gender or age. Degenerative cervical disc disease was closely related together (P<0.001), but not with any thoracic disc. A statistically significant relation was found within the upper thoracic discs, reflecting common pathoanatomical changes. The absence of relation to cervical segments is probably due to differences in their pathomechanisms. (orig.)

  16. Ultrashort time-to-echo MRI of the cartilaginous endplate: technique and association with intervertebral disc degeneration

    International Nuclear Information System (INIS)

    Law, Travis; Anthony, Marina-Portia; Kim, Mina; Khong, Pek-Lan; Chan, Queenie; Samartzis, Dino

    2013-01-01

    The purpose of this study was to report the feasibility of the ultrashort time-to-echo (UTE) MRI technique to assess cartilaginous endplate (CEP) defects in humans in vivo and to assess their relationship with intervertebral disc (IVD) degeneration. Nine volunteer subjects (mean age=43.9 years; range=22–61 years) were recruited, representing 54 IVDs and 108 CEPs. The subjects underwent T2-weighted and UTE MRI to assess for the presence and severity of IVD degeneration, and for the presence of CEP defects, respectively, from T12 to S1. IVD degeneration was graded according to the Schneiderman et al. classification on T2-weighted MRI. CEP defects were defined on UTE MRI as discontinuity of high signal over four consecutive images and were independently assessed by two observers. Thirty-seven out of 108 (34.3%) CEPs had defects, which mainly occurred at T12/L1, L1/L2 and L4/L5 (P=0.008). Multivariate logistic regression revealed that lower body mass index (P=0.009) and younger (P=0.034) individuals had a decreased likelihood of having CEP defects. A statistically significant association was found to exist between the presence of CEP defects and IVD degeneration (P=0.036). A higher prevalence of degenerated IVDs with CEP defects was found at L4/5 and L5/S1, while degenerated IVDs with no CEP defects were found throughout the whole lumbar region. Mean IVD degeneration scores of the L4/5 and L5/S1 levels with CEP defects were higher in comparison with those with no CEP defects. Our study demonstrates the feasibility of using UTE MRI in humans in vivo to assess the integrity of the CEP. A statistically significant association was found to exist between the presence of CEP defects and IVD degeneration. In the lower lumbar region, more severe degeneration was found to occur in the IVDs with CEP defects than in those without defects.

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

    Science.gov (United States)

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

    2016-09-15

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

  18. Effect of Lumbar Disc Degeneration and Low-Back Pain on the Lumbar Lordosis in Supine and Standing

    DEFF Research Database (Denmark)

    Hansen, Bjarke B; Bendix, Tom; Grindsted, Jacob

    2015-01-01

    STUDY DESIGN: Cross-sectional study. OBJECTIVE: To examine the influence of low-back pain (LBP) and lumbar disc degeneration (LDD) on the lumbar lordosis in weight-bearing positional magnetic resonance imaging (pMRI). SUMMARY OF BACKGROUND DATA: The lumbar lordosis increases with a change...... of position from supine to standing and is known as an essential contributor to dynamic changes. However, the lordosis may be affected by disc degeneration and pain. METHODS: Patients with LBP >40 on a 0 to 100 mm Visual Analog Scale (VAS) both during activity and rest and a sex and age-decade matching...... control group without LBP were scanned in the supine and standing position in a 0.25-T open MRI unit. LDD was graded using Pfirrmann's grading-scale. Subsequently, the L2-to-S1 lumbar lordosis angle (LA) was measured. RESULTS: Thirty-eight patients with an average VAS of 58 (±13.8) mm during rest and 75...

  19. Longitudinal Comparison of Enzyme- and Laser-Treated Intervertebral Disc by MRI, X-Ray, and Histological Analyses Reveals Discrepancies in the Progression of Disc Degeneration: A Rabbit Study

    Directory of Open Access Journals (Sweden)

    Marion Fusellier

    2016-01-01

    Full Text Available Regenerative medicine is considered an attractive prospect for the treatment of intervertebral disc (IVD degeneration. To assess the efficacy of the regenerative approach, animal models of IVD degeneration are needed. Among these animal models, chemonucleolysis based on the enzymatic degradation of the Nucleus Pulposus (NP is often used, but this technique remains far from the natural physiopathological process of IVD degeneration. Recently, we developed an innovative animal model of IVD degeneration based on the use of a laser beam. In the present study, this laser model was compared with the chemonucleolysis model in a longitudinal study in rabbits. The effects of the treatments were studied by MRI (T2-weighted signal intensity (T2wsi, radiography (IVD height index, and histology (NP area and Boos’ scoring. The results showed that both treatments induced a degeneration of the IVD with a decrease in IVD height and T2wsi as well as NP area and an increase in Boos’ scoring. The enzyme treatment leads to a rapid and acute process of IVD degeneration. Conversely, laser radiation induced more progressive and less pronounced degeneration. It can be concluded that laser treatment provides an instrumental in vivo model of slowly evolving IVD degenerative disease that can be of preclinical relevance for assessing new prophylactic biological treatments of disc degeneration.

  20. Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan

    Science.gov (United States)

    Watanabe, Hideto; Nakata, Ken; Kimata, Koji; Nakanishi, Isao; Yamada, Yoshihiko

    1997-01-01

    Mouse cartilage matrix deficiency (cmd) is an autosomal recessive disorder caused by a genetic defect of aggrecan, a large chondroitin sulfate proteoglycan in cartilage. The homozygotes (−/−) are characterized by cleft palate and short limbs, tail, and snout. They die just after birth because of respiratory failure, and the heterozygotes (+/−) appear normal at birth. Here we report that the heterozygotes show dwarfism and develop spinal misalignment with age. Within 19 months of age, they exhibit spastic gait caused by misalignment of the cervical spine and die because of starvation. Histological examination revealed a high incidence of herniation and degeneration of vertebral discs. Electron microscopy showed a degeneration of disc chondrocytes in the heterozygotes. These findings may facilitate the identification of mutations in humans predisposed to spinal degeneration. PMID:9192671

  1. Is the transport of a gadolinium-based contrast agent decreased in a degenerated or aged disc? A post contrast MRI study.

    Directory of Open Access Journals (Sweden)

    Marta Tibiletti

    Full Text Available A post contrast magnetic resonance imaging study has been performed in a wide population of low back pain patients to investigate which radiological and phenotypic characteristics influence the penetration of the contrast agent in lumbar discs in vivo. 37 patients affected by different pathologies (disc herniation, spondylolisthesis, foraminal stenosis, central canal stenosis were enrolled in the study. The selected population included 26 male and 11 female subjects, with a mean age of 42.4 ± 9.3 years (range 18-60. Magnetic resonance images of the lumbar spine were obtained with a 1.5 T scanner (Avanto, Siemens, Erlangen, Germany with a phased-array back coil. A paramagnetic non-ionic contrast agent was injected with a dose of 0.4 ml/kg. T1-weighted magnetic resonance images were subsequently acquired at 5 time points, 5 and 10 minutes, 2, 4 and 6 hours after injection. Endplates presented clear enhancement already 5 minutes after injection, and showed an increase in the next 2 hours followed by a decrease. At 5 and 10 minutes, virtually no contrast medium was present inside the intervertebral disc; afterwards, enhancement significantly increased. Highly degenerated discs showed higher enhancement in comparison with low and medium degenerated discs. Discs classified as Pfirrmann 5 showed a statistically significant higher enhancement than Pfirrmann 1, 2 and 3 at all time points but the first one, possibly due to vascularization. Disc height collapse and Modic changes significantly increased enhancement. Presence of endplate defects did not show any significant influence on post contrast enhancement, but the lack of a clear classification of endplate defects as seen on magnetic resonance scans may be shadowing some effects. In conclusion, disc height, high level of degeneration and presence of Modic changes are factors which increase post contrast enhancement in the intervertebral disc. The effect of age could not be demonstrated.

  2. Progression, incidence, and risk factors for intervertebral disc degeneration in a longitudinal population-based cohort: the Wakayama Spine Study.

    Science.gov (United States)

    Teraguchi, M; Yoshimura, N; Hashizume, H; Yamada, H; Oka, H; Minamide, A; Nagata, K; Ishimoto, Y; Kagotani, R; Kawaguchi, H; Tanaka, S; Akune, T; Nakamura, K; Muraki, S; Yoshida, M

    2017-07-01

    The present study examined the progression, incidence, and risk factors for intervertebral disc degeneration (DD) throughout the lumbar spine using magnetic resonance imaging (MRI) in a large population-based cohort. We followed up 617 subjects for more than 4 years as part of the Wakayama Spine Study. 1) "Progression of DD" in each of the entire, upper (L1/2 to L3/4) and lower (L4/5 and L5/S1) lumbar spine was defined as Pfirrmann grade progression at follow-up in at least one disc in the affected region. 2) "Incidence of DD" in each of these regions was defined if all discs were grade 3 or lower (white disc) at baseline, and at least one disc had progressed to grade 4 or higher (black disc) at follow-up. Logistic regression analyses were used to determine the risk factors for progression and incidence of DD. DD progression and incidence in the entire lumbar spine were 52.0% and 31.6% in men, and 60.4% and 44.7% in women, respectively. Women was associated with DD progression in the upper lumbar spine (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.18-2.42). Aging was associated with the incidence of DD in each region (entire: OR = 1.14, CI = 1.06-1.14; upper: OR = 1.10, CI = 1.05-1.15; lower: OR = 1.11, CI = 1.05-1.19). Diabetes mellitus (DM) was associated with the incidence of DD in the upper lumbar spine (OR = 6.83, CI = 1.07-133.7). This 4-year longitudinal study is the first to demonstrate DD progression and incidence in the lumbar spine and their risk factors in a large population-based cohort. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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

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

    2017-07-25

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

  4. Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration

    International Nuclear Information System (INIS)

    Kang, Liang; Hu, Jia; Weng, Yuxiong; Jia, Jie; Zhang, Yukun

    2017-01-01

    Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptional activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity. - Highlights: • SIRT6 expression is decreased in degenerative nucleus pulposus (NP) tissues. • SIRT6 overexpression lowers IL-1β-induced matrix degradation of NP. • SIRT6 inhibition induces matrix degradation of NP. • SIRT6 prevents matrix degradation of NP via the NF-κB signaling pathway.

  5. Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Liang [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Hu, Jia [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Weng, Yuxiong [Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Jia, Jie [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Zhang, Yukun, E-mail: zhangyukuncom@126.com [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

    2017-03-15

    Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptional activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity. - Highlights: • SIRT6 expression is decreased in degenerative nucleus pulposus (NP) tissues. • SIRT6 overexpression lowers IL-1β-induced matrix degradation of NP. • SIRT6 inhibition induces matrix degradation of NP. • SIRT6 prevents matrix degradation of NP via the NF-κB signaling pathway.

  6. Análise radiológica da degeneração discal experimental em coelhos Radiological analysis of experimental disc degeneration in rabbits

    Directory of Open Access Journals (Sweden)

    Emiliano Vialle

    2009-01-01

    Full Text Available OBJETIVO: Validar a avaliação radiográfica da degeneração discal experimental em coelhos. MÉTODOS: Os discos intervertebrais lombares de coelhos New Zealand foram puncionados três vezes com uma agulha 18G com profundidade limitada de 5mm, através de abordagem lateral. Foram realizadas radiografias seriadas pré e pós-operatórias imediatas, e depois de quatro, oito e 12 semanas do procedimento, com posterior análise da altura discal, formação de osteófito, esclerose da placa vertebral e presença de degeneração discal. A análise estatística dos dados foi validada pelo coeficiente de concordância Kappa, com intervalo de confiança (IC de 95%. RESULTADOS: Observou-se diminuição significativa do espaço discal nas radiografias em AP após 12 semanas de pós-operatório, com Kappa = 0,489 para IC 95% (0,25-0,72 com p OBJECTIVE: To validate radiographic evaluation of a rabbit model for disc degeneration. METHODS: Lumbar intervertebral discs of New Zealand rabbits were stabbed three times with a 18G needle at a limited depth of 5mm, through lateral approach. Serial radiographic images were taken on the early pre-and postoperative periods, and after four, eight and 12 weeks of the procedure, with subsequent analysis of disc height, osteophyte formation, endplate sclerosis, and presence of disc degeneration. The statistical analysis of data was validated by the Kappa coefficient, with a confidence interval (CI of 95%. RESULTS: A significant reduction of disc space was found on AP X-ray images after 12 postoperative weeks, with Kappa = 0.489 for CI 95% (0.25-0.72 with p < 0.001. X-ray signs of disc degeneration also presented Kappa = 0.63 for CI 95% (0.39-0.86 with p < 0.001. The remaining assessed criteria showed positive results, but with a lower Kappa value. CONCLUSION: The disc degeneration model using rabbits as proposed in this study was shown to be feasible, with positive X-ray correlation between pre- and postoperative images

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

    Science.gov (United States)

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

    2015-11-01

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

  8. The Pfirrmann classification of lumbar intervertebral disc degeneration: an independent inter- and intra-observer agreement assessment.

    Science.gov (United States)

    Urrutia, Julio; Besa, Pablo; Campos, Mauricio; Cikutovic, Pablo; Cabezon, Mario; Molina, Marcelo; Cruz, Juan Pablo

    2016-09-01

    Grading inter-vertebral disc degeneration (IDD) is important in the evaluation of many degenerative conditions, including patients with low back pain. Magnetic resonance imaging (MRI) is considered the best imaging instrument to evaluate IDD. The Pfirrmann classification is commonly used to grade IDD; the authors describing this classification showed an adequate agreement using it; however, there has been a paucity of independent agreement studies using this grading system. The aim of this study was to perform an independent inter- and intra-observer agreement study using the Pfirrmann classification. T2-weighted sagittal images of 79 patients consecutively studied with lumbar spine MRI were classified using the Pfirrmann grading system by six evaluators (three spine surgeons and three radiologists). After a 6-week interval, the 79 cases were presented to the same evaluators in a random sequence for repeat evaluation. The intra-class correlation coefficient (ICC) and the weighted kappa (wκ) were used to determine the inter- and intra-observer agreement. The inter-observer agreement was excellent, with an ICC = 0.94 (0.93-0.95) and wκ = 0.83 (0.74-0.91). There were no differences between spine surgeons and radiologists. Likewise, there were no differences in agreement evaluating the different lumbar discs. Most differences among observers were only of one grade. Intra-observer agreement was also excellent with ICC = 0.86 (0.83-0.89) and wκ = 0.89 (0.85-0.93). In this independent study, the Pfirrmann classification demonstrated an adequate agreement among different observers and by the same observer on separate occasions. Furthermore, it allows communication between radiologists and spine surgeons.

  9. Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs.

    Science.gov (United States)

    Zhu, Jun; Tang, Haoyu; Zhang, Zhenhua; Zhang, Yong; Qiu, Chengfeng; Zhang, Ling; Huang, Pinge; Li, Feng

    2017-02-01

    Intervertebral disc (IVD) degeneration is a common disease that represents a significant cause of socio-economic problems. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. Kaempferol has been reported to exert protective effects against both osteoporosis and obesity. This study explored the effect of kaempferol on BMSCs differentiation and inflammation. The results demonstrated that kaempferol did not show any cytotoxicity at concentrations of 20, 60 and 100μM. Kaempferol enhanced cell viability by counteracting the lipopolysaccharide (LPS)-induced cell apoptosis and increasing cell proliferation. Western blot analysis of mitosis-associated nuclear antigen (Ki67) and proliferation cell nuclear antigen (PCNA) further confirmed the increased effect of kaempferol on LPS-induced decreased viability of BMSCs. Besides, kaempferol elevated LPS-induced reduced level of chondrogenic markers (SOX-9, Collagen II and Aggrecan), decreased the level of matrix-degrading enzymes, i.e., matrix metalloprotease (MMP)-3 and MMP-13, suggesting the osteogenesis of BMSC under kaempferol treatment. On the other hand, kaempferol enhanced LPS-induced decreased expression of lipid catabolism-related genes, i.e., carnitine palmitoyl transferase-1 (CPT-1). Kaempferol also suppressed the expression of lipid anabolism-related genes, i.e., peroxisome proliferators-activated receptor-γ (PPAR-γ). The Oil red O staining further convinced the inhibition effect of kaempferol on BMSCs adipogenesis. In addition, kaempferol alleviated inflammatory by reducing the level of pro-inflammatory cytokines (i.e., interleukin (IL)-6) and increasing anti-inflammatory cytokine (IL-10) via inhibiting the nucleus translocation of nuclear transcription factor (NF)-κB p65. Taken together, our research indicated that kaempferol may serve as a novel target for treatment of IVD degeneration. Copyright © 2016 Elsevier B.V. All rights

  10. Progressive Retinal Degeneration and Accumulation of Autofluorescent Lipopigments in Progranulin Deficient Mice

    Science.gov (United States)

    Hafler, Brian P.; Klein, Zoe A.; Zhou, Z. Jimmy; Strittmatter, Stephen M.

    2014-01-01

    Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn−/− mice develop degenerative pathology similar to features of human CLN11. PMID:25234724

  11. Lumbar paraspinal muscle fat infiltration is independently associated with sex, age, and inter-vertebral disc degeneration in symptomatic patients.

    Science.gov (United States)

    Urrutia, Julio; Besa, Pablo; Lobos, Daniel; Campos, Mauricio; Arrieta, Cristobal; Andia, Marcelo; Uribe, Sergio

    2018-01-29

    To determine the association of paraspinal muscles and psoas relative cross-sectional area (RCSA) and fat signal fraction (FSF) with sex, age, and intervertebral disc degeneration (IDD) in symptomatic patients. We retrospectively evaluated 80 adult patients with spinal symptoms using T2-weighted magnetic resonance images. We determined RCSA and FSF of the paraspinal muscles (erector spinae and multifidus) and psoas from L1-L2 to L5-S1; we determined IDD using the Pfirrmann classification. We compared differences in muscle RCSA and FSF based on sex and IDD, and we correlated age and IDD with RCSA and FSF. Using multivariate linear regression analyses, we determined the impact of sex, age, and IDD on RCSA and FSF. Men exhibited larger psoas RCSA but not larger paraspinal muscles RCSA than women. Women had larger FSF in the paraspinal muscles and psoas. Increasing IDD was associated with larger FSF if ≥2 Pfirrmann grades were observed. IDD correlated with FSF of the paraspinal muscles, and age correlated with FSF of the paraspinal muscles and psoas. IDD was less consistently correlated with RCSA, but age correlated negatively with RCSA of all three muscles. Linear regression analyses demonstrated that sex, age, and IDD were each independently associated with FSF of the paraspinal muscles; additionally, sex and age, but not IDD, were associated with psoas FSF. RCSA was less consistently influenced by these three variables. Sex, age, and IDD are independently associated with paraspinal muscles FSF; only sex and age influence psoas FSF.

  12. Effect of Lumbar Disc Degeneration and Low-Back Pain on the Lumbar Lordosis in Supine and Standing: A Cross-Sectional MRI Study.

    Science.gov (United States)

    Hansen, Bjarke B; Bendix, Tom; Grindsted, Jacob; Bliddal, Henning; Christensen, Robin; Hansen, Philip; Riis, Robert G C; Boesen, Mikael

    2015-11-01

    Cross-sectional study. To examine the influence of low-back pain (LBP) and lumbar disc degeneration (LDD) on the lumbar lordosis in weight-bearing positional magnetic resonance imaging (pMRI). The lumbar lordosis increases with a change of position from supine to standing and is known as an essential contributor to dynamic changes. However, the lordosis may be affected by disc degeneration and pain. Patients with LBP >40 on a 0 to 100 mm Visual Analog Scale (VAS) both during activity and rest and a sex and age-decade matching control group without LBP were scanned in the supine and standing position in a 0.25-T open MRI unit. LDD was graded using Pfirrmann's grading-scale. Subsequently, the L2-to-S1 lumbar lordosis angle (LA) was measured. Thirty-eight patients with an average VAS of 58 (±13.8) mm during rest and 75 (±5.0) mm during activities, and 38 healthy controls were included. MRI findings were common in both groups, whereas, the summation of the Pfirrmann's grades (LDD-score) was significantly higher in the patients [(MD 1.44; 95% confidence intervals (CI) 0.80 to 2.10; P lordosis between the positions may be independent of pain. Decreasing lordosis change seems to be associated with age-related increasing disc degeneration in healthy individuals. 2.

  13. Transgenic Mice Over-Expressing RBP4 Have RBP4-Dependent and Light-Independent Retinal Degeneration.

    Science.gov (United States)

    Du, Mei; Phelps, Eric; Balangue, Michael J; Dockins, Aaron; Moiseyev, Gennadiy; Shin, Younghwa; Kane, Shelley; Otalora, Laura; Ma, Jian-Xing; Farjo, Rafal; Farjo, Krysten M

    2017-08-01

    Transgenic mice overexpressing serum retinol-binding protein (RBP4-Tg) develop progressive retinal degeneration, characterized by microglia activation, yet the precise mechanisms underlying retinal degeneration are unclear. Previous studies showed RBP4-Tg mice have normal ocular retinoid levels, suggesting that degeneration is independent of the retinoid visual cycle or light exposure. The present study addresses whether retinal degeneration is light-dependent and RBP4-dependent by testing the effects of dark-rearing and pharmacological lowering of serum RBP4 levels, respectively. RBP4-Tg mice reared on normal mouse chow in normal cyclic light conditions were directly compared to RBP4-Tg mice exposed to chow supplemented with the RBP4-lowering compound A1120 or dark-rearing conditions. Quantitative retinal histological analysis was conducted to assess retinal degeneration, and electroretinography (ERG) and optokinetic tracking (OKT) tests were performed to assess retinal and visual function. Ocular retinoids and bis-retinoid A2E were quantified. Dark-rearing RBP4-Tg mice effectively reduced ocular bis-retinoid A2E levels, but had no significant effect on retinal degeneration or dysfunction in RBP4-Tg mice, demonstrating that retinal degeneration is light-independent. A1120 treatment lowered serum RBP4 levels similar to wild-type mice, and prevented structural retinal degeneration. However, A1120 treatment did not prevent retinal dysfunction in RBP4-Tg mice. Moreover, RBP4-Tg mice on A1120 diet had significant worsening of OKT response and loss of cone photoreceptors compared to RBP4-Tg mice on normal chow. This may be related to the very significant reduction in retinyl ester levels in the retina of mice on A1120-supplemented diet. Retinal degeneration in RBP4-Tg mice is RBP4-dependent and light-independent.

  14. Moderate Light-Induced Degeneration of Rod Photoreceptors with Delayed Transducin Translocation in shaker1 Mice

    Science.gov (United States)

    Zallocchi, Marisa; Wang, Wei-Min; Delimont, Duane; Cosgrove, Dominic

    2011-01-01

    Purpose. Usher syndrome is characterized by congenital deafness associated with retinitis pigmentosa (RP). Mutations in the myosin VIIa gene (MYO7A) cause a common and severe subtype of Usher syndrome (USH1B). Shaker1 mice have mutant MYO7A. They are deaf and have vestibular dysfunction but do not develop photoreceptor degeneration. The goal of this study was to investigate abnormalities of photoreceptors in shaker1 mice. Methods. Immunocytochemistry and hydroethidine-based detection of intracellular superoxide production were used. Photoreceptor cell densities under various conditions of light/dark exposures were evaluated. Results. In shaker1 mice, the rod transducin translocation is delayed because of a shift of its light activation threshold to a higher level. Even moderate light exposure can induce oxidative damage and significant rod degeneration in shaker1 mice. Shaker1 mice reared under a moderate light/dark cycle develop severe retinal degeneration in less than 6 months. Conclusions. These findings show that, contrary to earlier studies, shaker1 mice possess a robust retinal phenotype that may link to defective rod protein translocation. Importantly, USH1B animal models are likely vulnerable to light-induced photoreceptor damage, even under moderate light. PMID:21447681

  15. Predictive factors associated with neck pain in patients with cervical disc degeneration

    Science.gov (United States)

    Kong, Lingde; Tian, Weifeng; Cao, Peng; Wang, Haonan; Zhang, Bing; Shen, Yong

    2017-01-01

    Abstract The predictive factors associated with neck pain remain unclear. We conducted a cross-sectional study to assess predictive factors, especially Modic changes (MCs), associated with the intensity and duration of neck pain in patients with cervical disc degenerative disease. We retrospectively reviewed patients in our hospital from January 2013 to December 2016. Severe neck pain (SNP) and persistent neck pain (PNP) were the 2 main outcomes, and were assessed based on the numerical rating scale (NRS). Basic data, and also imaging data, were collected and analyzed as potential predictive factors. Univariate analysis and multiple logistic regression analysis were performed to assess the predictive factors for neck pain. In all, 381 patients (193 males and 188 females) with cervical degenerative disease were included in our study. The number of patients with SNP and PNP were 94 (24.67%) and 109 (28.61%), respectively. The NRS of neck pain in patients with type 1 MCs was significantly higher than type 2 MCs (4.8 ± 0.9 vs 3.9 ± 1.1; P = .004). The multivariate logistic analysis showed that kyphosis curvature (odds ratio [OR] 1.082, 95% confidence interval [CI] 1.044–1.112), spondylolisthesis (OR 1.339, 95% CI 1.226–1.462), and annular tear (OR 1.188, 95% CI 1.021–1.382) were factors associated with SNP, whereas kyphosis curvature (OR 1.568, 95% CI 1.022–2.394), spondylolisthesis (OR 1.486, 95% CI 1.082–2.041), and MCs (OR 1.152, 95% CI 1.074–1.234) were associated with PNP. We concluded that kyphosis curvature, spondylolisthesis, and annular tear are associated with SNP, whereas kyphosis curvature, spondylolisthesis, and MCs are associated with PNP. This study supports the view that MCs can lead to a long duration of neck pain. PMID:29069048

  16. Progressive hearing loss and degeneration of hair cell stereocilia in taperin gene knockout mice

    International Nuclear Information System (INIS)

    Chen, Mo; Wang, Qin; Zhu, Gang-Hua; Hu, Peng; Zhou, Yuan; Wang, Tian; Lai, Ruo-Sha; Xiao, Zi-An; Xie, Ding-Hua

    2016-01-01

    The TPRN gene encodes taperin, which is prominently present at the taper region of hair cell stereocilia. Mutations in TPRN have been reported to cause autosomal recessive nonsyndromic deafness 79(DFNB 79). To investigate the role of taperin in pathogenesis of hearing loss, we generated TPRN knockout mice using TALEN technique. Sanger sequencing confirmed an 11 bp deletion at nucleotide 177–187 in exon 1 of TPRN, which results in a truncated form of taperin protein. Heterozygous TPRN +/− mice showed apparently normal auditory phenotypes to their wide-type (WT) littermates. Homozygous TPRN −/− mice exhibited progressive sensorineural hearing loss as reflected by auditory brainstem response to both click and tone burst stimuli at postnatal days 15 (P15), 30 (P30), and 60 (P60). Alex Fluor-594 phalloidin labeling showed no obvious difference in hair cell numbers in the cochlea between TPRN −/− mice and WT mice under light microscope. However, scanning electronic microscopy revealed progressive degeneration of inner hair cell stereocilia, from apparently normal at postnatal days 3 (P3) to scattered absence at P15 and further to substantial loss at P30. The outer hair cell stereocilia also showed progressive degeneration, though much less severe, Collectively, we conclude that taperin plays an important role in maintenance of hair cell stereocilia. Establishment of TPRN knockout mice enables further investigation into the function of this gene. - Highlights: • TPRN −/− mice were generated using TALEN technique. • TPRN −/− mice presented progressive hearing loss. • WT and TPRN −/− mice showed no difference in hair cell numbers. • TPRN −/− mice showed progressive degeneration of hair cell stereocilia.

  17. Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

    Directory of Open Access Journals (Sweden)

    Shanshan Huang

    2015-10-01

    Full Text Available In polyglutamine (polyQ diseases, large polyQ repeats cause juvenile cases with different symptoms than those of adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knockin mouse models of spinal cerebellar ataxia-17 (SCA17, we found that a large polyQ (105 glutamines in the TATA-box-binding protein (TBP preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases.

  18. Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

    Science.gov (United States)

    Huang, Shanshan; Yang, Su; Guo, Jifeng; Yan, Sen; Gaertig, Marta A.; Li, Shihua; Li, Xiao-Jiang

    2015-01-01

    SUMMARY In polyglutamine (polyQ) diseases, large polyQ repeats cause juvenile cases with different symptoms than adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knock-in mouse models of spinal cerebellar ataxia-17 (SCA17), we found that a large polyQ (105 glutamines) in the TATA box-binding protein (TBP) preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases. PMID:26387956

  19. 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.

    Science.gov (United States)

    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

  20. Quantitative T2 magnetic resonance imaging compared to morphological grading of the early cervical intervertebral disc degeneration: an evaluation approach in asymptomatic young adults.

    Directory of Open Access Journals (Sweden)

    Chun Chen

    Full Text Available OBJECTIVE: The objective of this study was to evaluate the efficacy of quantitative T2 magnetic resonance imaging (MRI for quantifying early cervical intervertebral disc (IVD degeneration in asymptomatic young adults by correlating the T2 value with Pfirrmann grade, sex, and anatomic level. METHODS: Seventy asymptomatic young subjects (34 men and 36 women; mean age, 22.80±2.11 yr; range, 18-25 years underwent 3.0-T MRI to obtain morphological data (one T1-fast spin echo (FSE and three-plane T2-FSE, used to assign a Pfirrmann grade (I-V and for T2 mapping (multi-echo spin echo. T2 values in the nucleus pulposus (NP, n = 350 and anulus fibrosus (AF, n = 700 were obtained. Differences in T2 values between sexes and anatomic level were evaluated, and linear correlation analysis of T2 values versus degenerative grade was conducted. FINDINGS: Cervical IVDs of healthy young adults were commonly determined to be at Pfirrmann grades I and II. T2 values of NPs were significantly higher than those of AF at all anatomic levels (P0.05. T2 values decreased linearly with degenerative grade. Linear correlation analysis revealed a strong negative association between the Pfirrmann grade and the T2 values of the NP (P = 0.000 but not the T2 values of the AF (P = 0.854. However, non-degenerated discs (Pfirrmann grades I and II showed a wide range of T2 relaxation time. T2 values according to disc degeneration level classification were as follows: grade I (>62.03 ms, grade II (54.60-62.03 ms, grade III (<54.60 ms. CONCLUSIONS: T2 quantitation provides a more sensitive and robust approach for detecting and characterizing the early stage of cervical IVD degeneration and to create a reliable quantitative in healthy young adults.

  1. Quantitative T2 magnetic resonance imaging compared to morphological grading of the early cervical intervertebral disc degeneration: an evaluation approach in asymptomatic young adults.

    Science.gov (United States)

    Chen, Chun; Huang, Minghua; Han, Zhihua; Shao, Lixin; Xie, Yan; Wu, Jianhong; Zhang, Yan; Xin, Hongkui; Ren, Aijun; Guo, Yong; Wang, Deli; He, Qing; Ruan, Dike

    2014-01-01

    The objective of this study was to evaluate the efficacy of quantitative T2 magnetic resonance imaging (MRI) for quantifying early cervical intervertebral disc (IVD) degeneration in asymptomatic young adults by correlating the T2 value with Pfirrmann grade, sex, and anatomic level. Seventy asymptomatic young subjects (34 men and 36 women; mean age, 22.80±2.11 yr; range, 18-25 years) underwent 3.0-T MRI to obtain morphological data (one T1-fast spin echo (FSE) and three-plane T2-FSE, used to assign a Pfirrmann grade (I-V)) and for T2 mapping (multi-echo spin echo). T2 values in the nucleus pulposus (NP, n = 350) and anulus fibrosus (AF, n = 700) were obtained. Differences in T2 values between sexes and anatomic level were evaluated, and linear correlation analysis of T2 values versus degenerative grade was conducted. Cervical IVDs of healthy young adults were commonly determined to be at Pfirrmann grades I and II. T2 values of NPs were significantly higher than those of AF at all anatomic levels (P0.05). T2 values decreased linearly with degenerative grade. Linear correlation analysis revealed a strong negative association between the Pfirrmann grade and the T2 values of the NP (P = 0.000) but not the T2 values of the AF (P = 0.854). However, non-degenerated discs (Pfirrmann grades I and II) showed a wide range of T2 relaxation time. T2 values according to disc degeneration level classification were as follows: grade I (>62.03 ms), grade II (54.60-62.03 ms), grade III (T2 quantitation provides a more sensitive and robust approach for detecting and characterizing the early stage of cervical IVD degeneration and to create a reliable quantitative in healthy young adults.

  2. 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.

    Science.gov (United States)

    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

  3. TMJ degeneration in SAMP8 mice is accompanied by deranged Ihh signaling.

    Science.gov (United States)

    Ishizuka, Y; Shibukawa, Y; Nagayama, M; Decker, R; Kinumatsu, T; Saito, A; Pacifici, M; Koyama, E

    2014-03-01

    The temporomandibular joint (TMJ) functions as a load-bearing diarthrodial joint during mastication, and its continuous use and stress can lead to degeneration over age. Using senescence-accelerated (SAMP8) mice that develop early osteoarthritis-like changes in synovial joints at high frequency, we analyzed possible molecular mechanisms of TMJ degeneration and tested whether and how malocclusion may accelerate it. Condylar articular cartilage in young SAMP8 mice displayed early-onset osteoarthritic changes that included reductions in superficial/chondroprogenitor cell number, proteoglycan/collagen content, and Indian hedgehog (Ihh)-expressing chondrocytes. Following malocclusion induced by tooth milling, the SAMP8 condyles became morphologically defective, displayed even lower proteoglycan levels, and underwent abnormal chondrocyte maturation compared with malocclusion-treated condyles in wild-type mice. Malocclusion also induced faster progression of pathologic changes with increasing age in SAMP8 condyles as indicated by decreased PCNA-positive proliferating chondroprogenitors and increased TUNEL-positive apoptotic cells. These changes were accompanied by steeper reductions in Ihh signaling and by expression of matrix metalloproteinase 13 at the chondro-osseous junction in SAMP8 articular cartilage. In sum, we show for the first time that precocious TMJ degeneration in SAMP8 mice is accompanied by--and possibly attributable to--altered Ihh signaling and that occlusal dysfunction accelerates progression toward degenerative TMJ disease in this model.

  4. Effect of pharmacologically induced retinal degeneration on retinal autofluorescence lifetimes in mice.

    Science.gov (United States)

    Dysli, Chantal; Dysli, Muriel; Zinkernagel, Martin S; Enzmann, Volker

    2016-12-01

    Fluorescence lifetime imaging ophthalmoscopy (FLIO) was used to investigate retinal autofluorescence lifetimes in mouse models of pharmacologically induced retinal degeneration over time. Sodium iodate (NaIO 3 , 35 mg/kg intravenously) was used to induce retinal pigment epithelium (RPE) degeneration with subsequent loss of photoreceptors (PR) whereas N-methyl-N-nitrosourea (MNU, 45 mg/kg intraperitoneally) was employed for degeneration of the photoreceptor cell layer alone. All mice were measured at day 3, 7, 14, and 28 after the respective injection of NaIO 3 , MNU or NaCl (control). Fluorescence lifetime imaging was performed using a fluorescence lifetime imaging ophthalmoscope (Heidelberg Engineering, Heidelberg, Germany). Fluorescence was excited at 473 nm and fluorescence lifetimes were measured in a short and a long spectral channel (498-560 nm and 560-720 nm). Corresponding optical coherence tomography (OCT) images were consecutively acquired and histology was performed at the end of the experiments. Segmentation of OCT images and histology verified the cell type-specific degeneration process over time. Retinal autofluorescence lifetimes increased from day 3 to day 28 in mice after NaIO 3 treatment. Finally, at day 28, fluorescence lifetimes were prolonged by 8% in the short and 61% in the long spectral channel compared to control animals (p = 0.21 and p = 0.004, respectively). In mice after MNU treatment, the mean retinal autofluorescence lifetimes were already decreased at day 3 and retinal lifetimes were finally shortened by 27% in the short and 51% in the long spectral channel at day 28 (p = 0.0028). In conclusion, degeneration of the RPE with subsequent photoreceptor degeneration by NaIO 3 lead to longer mean fluorescence lifetimes of the retina compared to control mice, whereas during specific degeneration of the photoreceptor layer induced by MNU shorter lifetimes were measured. Therefore, short retinal fluorescence lifetimes may originate

  5. In vitro assessment of biomaterial-induced remodeling of subchondral and cancellous bone for the early intervention of joint degeneration with focus on the spinal disc

    Science.gov (United States)

    McCanless, Jonathan D.

    Osteoarthritis-associated pain of the spinal disc, knee, and hip derives from degeneration of cartilagenous tissues in these joints. Traditional therapies have focused on these cartilage (and disc specific nucleus pulposus) changes as a means of treatment through tissue grafting, regenerative synthetic implants, non-regenerative space filling implants, arthroplasty, and arthrodesis. Although such approaches may seem apparent upon initial consideration of joint degeneration, tissue pathology has shown changes in the underlying bone and vascular bed precede the onset of cartilaginous changes. It is hypothesized that these changes precedent joint degeneration and as such may provide a route for early prevention. The current work proposes an injectable biomaterial-based therapy within these subchondral and cancellous bone regions as a means of preventing or reversing osteoarthritis. Two human concentrated platelet releasate-containing alginate hydrogel/beta-tricalcium phosphate composites have been developed for this potential biomaterial application. The undertaking of assessing these materials through bench-, in vitro, and ex vivo work is described herein. These studies showed the capability of the biomaterials to initiate a wound healing response in monocytes, angiogenic and differentiation behavior in immature endothelial cells, and early osteochondral differentiation in mesenchymal stem cells. These cellular activities are associated with fracture healing and endochondral bone formation, demonstrating the potential of the biomaterials to induce osseous and vascular tissue remodeling underlying osteoarthritic joints as a novel therapy for a disease with rapidly growing healthcare costs.

  6. [Presbycusis: neural degeneration and aging on the auditory receptor of C57/BL6J mice].

    Science.gov (United States)

    Castillo, E; Carricondo, F; Bartolomé, M V; Vicente-Torres, A; Poch Broto, J; Gil-Loyzaga, P

    2006-11-01

    Presbycusis is a progressive hearing impairment associated with aging, characterized by hearing loss and a degeneration of cochlear structures. In this paper we analyze the effects of aging on the auditory system of C57/BL6J mice, with electrophysiological and morphological studies. With this aim the auditory potentials of mice aging 1, 3, 6, 9, 12, 15, 18, 21 and 24 months were recorded, and then the morphology of the cochleal were analyzed. Auditory potentials revealed an increase in wave latencies, as well as a decrease in their amplitudes during aging. Morphological results showed a total Corti's organ degeneration, being replaced by a flat epithelial layer, and a total absence of hair cells.

  7. Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice.

    Science.gov (United States)

    Wang, Yanhe; Yin, Zhiyuan; Gao, Lixiong; Sun, Dayu; Hu, Xisu; Xue, Langyue; Dai, Jiaman; Zeng, YuXiao; Chen, Siyu; Pan, Boju; Chen, Min; Xie, Jing; Xu, Haiwei

    2017-01-01

    Retinitis pigmentosa (RP) is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1) mice. The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells. Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP. © 2017 The Author(s). Published by S. Karger AG, Basel.

  8. Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice

    Directory of Open Access Journals (Sweden)

    Yanhe Wang

    2017-11-01

    Full Text Available Background/Aims: Retinitis pigmentosa (RP is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. Methods: Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1 mice. Results: The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells. Conclusions: Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP.

  9. Ubiquitin–Synaptobrevin Fusion Protein Causes Degeneration of Presynaptic Motor Terminals in Mice

    Science.gov (United States)

    Liu, Yun; Li, Hongqiao; Sugiura, Yoshie; Han, Weiping; Gallardo, Gilbert; Khvotchev, Mikhail; Zhang, Yinan; Kavalali, Ege T.; Südhof, Thomas C.

    2015-01-01

    Protein aggregates containing ubiquitin (Ub) are commonly observed in neurodegenerative disorders, implicating the involvement of the ubiquitin proteasome system (UPS) in their pathogenesis. Here, we aimed to generate a mouse model for monitoring UPS function using a green fluorescent protein (GFP)-based substrate that carries a “noncleavable” N-terminal ubiquitin moiety (UbG76V). We engineered transgenic mice expressing a fusion protein, consisting of the following: (1) UbG76V, GFP, and a synaptic vesicle protein synaptobrevin-2 (UbG76V-GFP-Syb2); (2) GFP-Syb2; or (3) UbG76V-GFP-Syntaxin1, all under the control of a neuron-specific Thy-1 promoter. As expected, UbG76V-GFP-Syb2, GFP-Syb2, and UbG76V-GFP-Sytaxin1 were highly expressed in neurons, such as motoneurons and motor nerve terminals of the neuromuscular junction (NMJ). Surprisingly, UbG76V-GFP-Syb2 mice developed progressive adult-onset degeneration of motor nerve terminals, whereas GFP-Syb2 and UbG76V-GFP-Syntaxin1 mice were normal. The degeneration of nerve terminals in UbG76V-GFP-Syb2 mice was preceded by a progressive impairment of synaptic transmission at the NMJs. Biochemical analyses demonstrated that UbG76V-GFP-Syb2 interacted with SNAP-25 and Syntaxin1, the SNARE partners of synaptobrevin. Ultrastructural analyses revealed a marked reduction in synaptic vesicle density, accompanying an accumulation of tubulovesicular structures at presynaptic nerve terminals. These morphological defects were largely restricted to motor nerve terminals, as the ultrastructure of motoneuron somata appeared to be normal at the stages when synaptic nerve terminals degenerated. Furthermore, synaptic vesicle endocytosis and membrane trafficking were impaired in UbG76V-GFP-Syb2 mice. These findings indicate that UbG76V-GFP-Syb2 may compete with endogenous synaptobrevin, acting as a gain-of-function mutation that impedes SNARE function, resulting in the depletion of synaptic vesicles and degeneration of the nerve

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

    OpenAIRE

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

    2004-01-01

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

  11. BMI1 loss delays photoreceptor degeneration in Rd1 mice. Bmi1 loss and neuroprotection in Rd1 mice.

    Science.gov (United States)

    Zencak, Dusan; Crippa, Sylvain V; Tekaya, Meriem; Tanger, Ellen; Schorderet, Daniel E; Munier, Francis L; van Lohuizen, Maarten; Arsenijevic, Yvan

    2006-01-01

    Retinitis pigmentosa (RP) is a heterogeneous group of genetic disorders leading to blindness, which remain untreatable at present. Rd1 mice represent a recognized model of RP, and so far only GDNF treatment provided a slight delay in the retinal degeneration in these mice. Bmi1, a transcriptional repressor, has recently been shown to be essential for neural stem cell (NSC) renewal in the brain, with an increased appearance of glial cells in vivo in Bmi1 knockout (Bmi1-/-) mice. One of the roles of glial cells is to sustain neuronal function and survival. In the view of a role of the retinal Miller glia as a source of neural protection in the retina, the increased astrocytic population in the Bmi1-/- brain led us to investigate the effect of Bmi1 loss in Rd1 mice. We observed an increase of Müller glial cells in Rd1-Bmi1-/- retinas compared to Rd1. Moreover, Rd1-Bmi1-/- mice showed 7-8 rows of photoreceptors at 30 days of age (P30), while in Rd1 littermates there was a complete disruption of the outer nuclear layer (ONL). Preliminary ERG results showed a responsiveness of Rd1-Bmi1-/- mice in scotopic vision at P35. In conclusion, Bmi1 loss prevented, or rescued, photoreceptors from degeneration to an unanticipated extent in Rd1 mice. In this chapter, we will first provide a brief review of our work on the cortical NSCs and introduce the Bmi1 oncogene, thus offering a rational to our observations on the retina.

  12. DNA damage preceding dopamine neuron degeneration in A53T human α-synuclein transgenic mice.

    Science.gov (United States)

    Wang, Degui; Yu, Tianyu; Liu, Yongqiang; Yan, Jun; Guo, Yingli; Jing, Yuhong; Yang, Xuguang; Song, Yanfeng; Tian, Yingxia

    2016-12-02

    Defective DNA repair has been linked with age-associated neurodegenerative disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by genetic and environmental factors. Whether damages to nuclear DNA contribute to neurodegeneration of PD still remain obscure. in this study we aim to explore whether nuclear DNA damage induce dopamine neuron degeneration in A53T human α-Synuclein over expressed mouse model. We investigated the effects of X-ray irradiation on A53T-α-Syn MEFs and A53T-α-Syn transgene mice. Our results indicate that A53T-α-Syn MEFs show a prolonged DNA damage repair process and senescense phenotype. DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice and decrease the number of nigrostriatal dopaminergic neurons. Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice

    Directory of Open Access Journals (Sweden)

    Hernán H. Dieguez

    2018-02-01

    Full Text Available Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age

  14. Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice.

    Science.gov (United States)

    Dieguez, Hernán H; Romeo, Horacio E; González Fleitas, María F; Aranda, Marcos L; Milne, Georgia A; Rosenstein, Ruth E; Dorfman, Damián

    2018-02-07

    Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy) on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and

  15. DNA damage preceding dopamine neuron degeneration in A53T human α-synuclein transgenic mice

    International Nuclear Information System (INIS)

    Wang, Degui; Yu, Tianyu; Liu, Yongqiang; Yan, Jun; Guo, Yingli; Jing, Yuhong; Yang, Xuguang; Song, Yanfeng; Tian, Yingxia

    2016-01-01

    Defective DNA repair has been linked with age-associated neurodegenerative disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by genetic and environmental factors. Whether damages to nuclear DNA contribute to neurodegeneration of PD still remain obscure. in this study we aim to explore whether nuclear DNA damage induce dopamine neuron degeneration in A53T human α-Synuclein over expressed mouse model. We investigated the effects of X-ray irradiation on A53T-α-Syn MEFs and A53T-α-Syn transgene mice. Our results indicate that A53T-α-Syn MEFs show a prolonged DNA damage repair process and senescense phenotype. DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice and decrease the number of nigrostriatal dopaminergic neurons. Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages. - Highlights: • This study explore contribution of DNA damage to neurodegeneration in Parkinson's disease mice. • A53T-α-Syn MEF cells show a prolonged DNA damage repair process and senescense phenotype. • DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice. • DNA damage decrease the number of nigrostriatal dopaminergic neurons. • Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages.

  16. Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration

    DEFF Research Database (Denmark)

    Laursen, Bettina; Mørk, Arne; Plath, Niels

    2013-01-01

    (BFCD) in 3 months old male Tg2576 mice to co-express cholinergic degeneration with Aβ overexpression as these characteristics constitutes key hallmarks of AD. At 9 months, SAP lesioned Tg2576 mice were cognitively impaired in two spatial paradigms addressing working memory and mid to long-term memory...

  17. Comprehensive behavioral analysis of ENU-induced Disc1-Q31L and -L100P mutant mice

    Directory of Open Access Journals (Sweden)

    Shoji Hirotaka

    2012-02-01

    Full Text Available Abstract Background Disrupted-in-Schizophrenia 1 (DISC1 is considered to be a candidate susceptibility gene for psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. A recent study reported that N-ethyl-N-nitrosourea (ENU-induced mutations in exon 2 of the mouse Disc1 gene, which resulted in the amino acid exchange of Q31L and L100P, caused an increase in depression-like behavior in 31 L mutant mice and schizophrenia-like behavior in 100P mutant mice; thus, these are potential animal models of psychiatric disorders. However, remaining heterozygous mutations that possibly occur in flanking genes other than Disc1 itself might induce behavioral abnormalities in the mutant mice. Here, to confirm the effects of Disc1-Q31L and Disc1-L100P mutations on behavioral phenotypes and to investigate the behaviors of the mutant mice in more detail, the mutant lines were backcrossed to C57BL/6JJcl through an additional two generations and the behaviors were analyzed using a comprehensive behavioral test battery. Results Contrary to expectations, 31 L mutant mice showed no significant behavioral differences when compared with wild-type control mice in any of the behavioral tests, including the Porsolt forced swim and tail suspension tests, commonly used tests for depression-like behavior. Also, 100P mutant mice exhibited no differences in almost all of the behavioral tests, including the prepulse inhibition test for measuring sensorimotor gating, which is known to be impaired in schizophrenia patients; however, 100P mutant mice showed higher locomotor activity compared with wild-type control mice in the light/dark transition test. Conclusions Although these results are partially consistent with the previous study in that there was hyperactivity in 100P mutant mice, the vast majority of the results are inconsistent with those of the previous study; this discrepancy may be explained by differences in the genetic background of the

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  19. NADPH Oxidase Contributes to Photoreceptor Degeneration in Constitutively Active RAC1 Mice

    Science.gov (United States)

    Song, Hongman; Vijayasarathy, Camasamudram; Zeng, Yong; Marangoni, Dario; Bush, Ronald A.; Wu, Zhijian; Sieving, Paul A.

    2016-01-01

    Purpose The active form of small GTPase RAC1 is required for activation of NADPH oxidase (NOX), which in turn generates reactive oxygen species (ROS) in nonphagocytic cells. We explored whether NOX-induced oxidative stress contributes to rod degeneration in retinas expressing constitutively active (CA) RAC1. Methods Transgenic (Tg)–CA-RAC1 mice were given apocynin (10 mg/kg, intraperitoneal), a NOX inhibitor, or vehicle daily for up to 13 weeks. Superoxide production and oxidative damage were assessed by dihydroethidium staining and by protein carbonyls and malondialdehyde levels, respectively. Outer nuclear layer (ONL) cells were counted and electroretinogram (ERG) amplitudes measured in Tg-CA-RAC1 mice. Outer nuclear layer cells were counted in wild-type (WT) mice after transfer of CA-Rac1 gene by subretinal injection of AAV8-pOpsin-CA Rac1-GFP. Results Transgenic-CA-RAC1 retinas had significantly fewer photoreceptor cells and more apoptotic ONL cells than WT controls from postnatal week (Pw) 3 to Pw13. Superoxide accumulation and protein and lipid oxidation were increased in Tg-CA-RAC1 retinas and were reduced in mice treated with apocynin. Apocynin reduced the loss of photoreceptors and increased the rod ERG a- and b-wave amplitudes when compared with vehicle-injected transgenic controls. Photoreceptor loss was also observed in regions of adult WT retina transduced with AAV8-pOpsin-CA Rac1-GFP but not in neighboring regions that were not transduced or in AAV8-pOpsin-GFP–transduced retinas. Conclusions Constitutively active RAC1 promotes photoreceptor cell death by oxidative damage that occurs, at least partially, through NOX-induced ROS. Reactive oxygen species are likely involved in multiple forms of retinal degenerations, and our results support investigating RAC1 inhibition as a therapeutic approach that targets this disease pathway. PMID:27233035

  20. Course of Sodium Iodate-Induced Retinal Degeneration in Albino and Pigmented Mice.

    Science.gov (United States)

    Chowers, Guy; Cohen, Matan; Marks-Ohana, Devora; Stika, Shelly; Eijzenberg, Ayala; Banin, Eyal; Obolensky, Alexey

    2017-04-01

    To characterize the course of sodium iodate (SI)-induced retinal degeneration in young adult albino and pigmented mice. Single intraperitoneal (IP) injections of SI (25, 50, and 100 mg/kg) were performed in 7- to 8-week-old BALB/c and C57Bl/6J mice. Retinal function and structure was assessed at baseline, 24 hours, 3 days, 1, 2, 3, and 4 weeks postinjection by optokinetic tracking response, ERG, optical coherence tomography (OCT), and histologic and immunohistochemical techniques. The 50 mg/kg SI dosage was selected after dose ranging due to consistent retinal effects and lack of systemic toxicity. Time-dependent deterioration in retinal function and morphology was consistently observed between 1 and 4 weeks in all measured parameters. These include reduction of ERG responses, thinning of retinal layers as observed by OCT and histology, and loss of RPE nuclei. Immunohistochemistry revealed rapid RPE disorganization with loss of tight junctions and markedly reduced expression of RPE65 and rod opsin, accompanied by mislocalization of cone opsins. Earlier time points displayed variable results, including partial recovery of visual acuity at 1 week and supranormal ERG cone responses at 24 hours, suggesting possible limitations of early intervention and assessment in the SI model. A single IP injection of 50 mg/kg SI leads to severe RPE injury followed by vision impairment, dysfunction, and loss of photoreceptors in both BALB/c and C57Bl/6J mice. This easily induced and reproducible noninherited model may serve as a useful tool for seeking and evaluating novel therapeutic modalities for the treatment of retinal degenerations caused by primary failure of the RPE.

  1. ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model.

    Science.gov (United States)

    Miyazaki, Shingo; Diwan, Ashish D; Kato, Kenji; Cheng, Kevin; Bae, Won C; Sun, Yang; Yamada, Junichi; Muehleman, Carol; Lenz, Mary E; Inoue, Nozomu; Sah, Robert L; Kawakami, Mamoru; Masuda, Koichi

    2018-04-01

    To elucidate the effects of growth differentiation factor-6 (GDF6) on: (i) gene expression of inflammatory/pain-related molecules and structural integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii) sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia (DRGs) in the rat xenograft radiculopathy model. Forty-six adolescent rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 µg) was injected into the nucleus pulposus (NP) of punctured discs and followed for 4 weeks for gene expression analysis and 12 weeks for structural analyses. For pain assessment, eight rabbits were sacrificed at 4 weeks post-injection and NP tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically. In GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, prostaglandin-endoperoxide synthase 2, and nerve growth factor were significantly lower than those in the PBS group. GDF6 injections resulted in partial restoration of disc height and improvement of MRI disc degeneration grades with statistical significance in rabbit structural analyses. Allodynia induced by xenograft transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced by GDF6 injection. Staining intensities for ionized calcium-binding adaptor molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were significantly lower than those of the PBS group. GDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.

  2. Effects of single injection of local anesthetic agents on intervertebral disc degeneration: ex vivo and long-term in vivo experimental study.

    Directory of Open Access Journals (Sweden)

    Koji Iwasaki

    Full Text Available Analgesic discography (discoblock can be used to diagnose or treat discogenic low back pain by injecting a small amount of local anesthetics. However, recent in vitro studies have revealed cytotoxic effects of local anesthetics on intervertebral disc (IVD cells. Here we aimed to investigate the deteriorative effects of lidocaine and bupivacaine on rabbit IVDs using an organotypic culture model and an in vivo long-term follow-up model.For the organotypic culture model, rabbit IVDs were harvested and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine or 0.5% bupivacaine. Nucleus pulposus (NP cell death was measured using confocal microscopy. Histological and TUNEL assays were performed. For in vivo study, each local anesthetic was injected into rabbit lumbar IVDs under a fluoroscope. Six or 12 months after the injection, each IVD was prepared for magnetic resonance imaging (MRI and histological analysis.In the organotypic culture model, both anesthetic agents induced time-dependent NP cell death; when compared with injected saline solution, significant effects were detected within 7 days. Compared with the saline group, TUNEL-positive NP cells were significantly increased in the bupivacaine group. In the in vivo study, MRI analysis did not show any significant difference. Histological analysis revealed that IVD degeneration occurred to a significantly level in the saline- and local anesthetics-injected groups compared with the untreated control or puncture-only groups. However, there was no significant difference between the saline and anesthetic agents groups.In the in vivo model using healthy IVDs, there was no strong evidence to suggest that discoblock with local anesthetics has the potential of inducing IVD degeneration other than the initial mechanical damage of the pressurized injection. Further studies should be performed to investigate the deteriorative effects of the local injection of analgesic agents

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

    Science.gov (United States)

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

    2017-08-01

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

  4. Dynamics of oligodendrocyte responses to anterograde axonal (Wallerian) and terminal degeneration in normal and TNF-transgenic mice

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Fenger, Christina; Nielsen, Helle H

    2004-01-01

    degeneration and lesion-induced axonal sprouting in the hippocampal dentate gyrus in TNF-transgenic mice with the response in genetically normal mice. Transectioning of the entorhino-dentate perforant path axonal projection increased hippocampal TNF mRNA expression in both types of mice, but to significantly...... larger levels in the TNF-transgenics. At 5 days after axonal transection, numbers of oligodendrocytes and myelin basic protein (MBP) mRNA expression in the denervated dentate gyrus in TNF-transgenic mice had increased to the same extent as in nontransgenic littermates. At this time, transgenics showed...

  5. Normal myogenic cells from newborn mice restore normal histology to degenerating muscles of the mdx mouse

    International Nuclear Information System (INIS)

    Morgan, J.E.; Hoffman, E.P.; Partridge, T.A.

    1990-01-01

    Dystrophin deficiency in skeletal muscle of the x-linked dystrophic (mdx) mouse can be partially remedied by implantation of normal muscle precursor cells (mpc). However, it is difficult to determine whether this biochemical rescue results in any improvement in the structure or function of the treated muscle, because the vigorous regeneration of mdx muscle more than compensates for the degeneration. By using x-ray irradiation to prevent mpc proliferation, it is possible to study loss of mdx muscle fibers without the complicating effect of simultaneous fiber regeneration. Thus, improvements in fiber survival resulting from any potential therapy can be detected easily. Here, we have implanted normal mpc, obtained from newborn mice, into such preirradiated mdx muscles, finding that it is far more extensively permeated and replaced by implanted mpc than is nonirradiated mdx muscle; this is evident both from analysis of glucose-6-phosphate isomerase isoenzyme markers and from immunoblots and immunostaining of dystrophin in the treated muscles. Incorporation of normal mpc markedly reduces the loss of muscle fibers and the deterioration of muscle structure which otherwise occurs in irradiated mdx muscles. Surprisingly, the regenerated fibers are largely peripherally nucleated, whereas regenerated mouse skeletal muscle fibers are normally centrally nucleated. We attribute this regeneration of apparently normal muscle to the tendency of newborn mouse mpc to recapitulate their neonatal ontogeny, even when grafted into 3-wk-old degenerating muscle

  6. Fungiform Taste Bud Degeneration in C57BL/6J Mice Following Chorda-Lingual Nerve Transection

    OpenAIRE

    Guagliardo, Nick A.; Hill, David L.

    2007-01-01

    Taste buds are dependent on innervation for normal morphology and function. Fungiform taste bud degeneration after chorda tympani nerve injury has been well documented in rats, hamsters, and gerbils. The current study examines fungiform taste bud distribution and structure in adult C57BL/6J mice from both intact taste systems and after unilateral chorda-lingual nerve transection. Fungiform taste buds were visualized and measured with the aid of cytokeratin 8. In control mice, taste buds were ...

  7. Role of LncRNA TUG1 in intervertebral disc degeneration and nucleus pulposus cells via regulating Wnt/β-catenin signaling pathway.

    Science.gov (United States)

    Chen, Jiang; Jia, Yu-Song; Liu, Gen-Zhe; Sun, Qi; Zhang, Fan; Ma, Sheng; Wang, Yong-Jun

    2017-09-23

    To investigate the role of TUG1 in intervertebral disc degeneration (IDD) and human nucleus pulposus cells (NPCs) via regulating Wnt/β-catenin pathway. The study collected nucleus pulposus (NP) tissue samples from 30 patients with lumbar disc herniation (LDH) (Case group) and 18 patients with lumbar spine trauma (Control group). NPCs induced by TNF-α in vitro were divided into Blank, Vector, TUG1, TUG1-siRNA, XAV-939, TUG1 + XAV-939 groups. qRT-PCR was used to detect the expression of TUG1 and ECM-related genes, Western blot to determine the expression of Wnt/β-catenin pathway and apoptosis-related proteins, and ELISA to measure the expression of ECM-related proteins. The apoptosis was detected by TUNEL and Annexin V-FITC/PI double-staining. The proliferation and senescence were tested by CCK-8 and SA-β-gal staining respectively. TUG1 was upregulated in patients with IDD, which was positively related to Wnt and β-catenin. Besides, TUG1, Wnt1 and β-catenin were greatly increased in the NPCs after TNF-α induction. Compared with the Blank group, TUG1-siRNA and XAV-939 can appreciably down-regulate the expressions of Wnt1, β-catenin, Caspase-3, Bax, MMP3 and ADAMTS5, up-regulate the expression of Bcl-2, Aggrecan and COL2A1, inhibit the apoptosis and senescence, and promote cell proliferation; however, the TUG1 group had the completely opposite results. Silencing TUG1 may not only protect human NPCs from TNF-α-induced apoptosis and senescence, but also promote cell proliferation by blocking Wnt/β-catenin pathway, which provides a theoretical basis for the clinical treatment of IDD. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Plasma vitamin D and osteo-cartilaginous markers in Italian males affected by intervertebral disc degeneration: Focus on seasonal and pathological trend of type II collagen degradation.

    Science.gov (United States)

    Brayda-Bruno, Marco; Viganò, Marco; Cauci, Sabina; Vitale, Jacopo A; de Girolamo, Laura; De Luca, Paola; Lombardi, Giovanni; Banfi, Giuseppe; Colombini, Alessandra

    2017-08-01

    To evaluate plasma vitamin D and cross-linked C-telopeptides of type I (CTx-I) and type II (CTx-II) collagen concentrations in males with lumbar intervertebral disc degeneration (IVD) compared to healthy controls. Improved knowledge might suggest to optimize the vitamin D status of IVD patients and contribute to clarify mechanisms of cartilage degradation. 79 Italian males with lumbar IVD assessed by Magnetic Resonance Imaging (MRI) and 79 age, sex and BMI-matched healthy controls were enrolled. Plasma 25hydroxyvitamin D (25(OH)D), CTx-I and CTx-II were measured by immunoassays. Circannual seasonality, correlation between biomarkers concentrations and clinical variables were assessed. Overall subjects 25(OH)D and CTx-II showed month rhythmicity with acrophase in August/September and October/November, and nadir in February/March and April/May, respectively. An inverse correlation between 25(OH)D and CTx-I, and a direct correlation between CTx-II and CTx-I were observed. IVD patients, particularly with osteochondrosis, showed higher CTx-II than healthy controls. Month of sampling may affect plasma 25(OH)D and CTx-II concentrations. The correlation between CTx-I and CTx-II suggests an interplay between the osteo-cartilaginous endplate and the fibro-cartilaginous disc. The results of this study highlighted that osteochondrosis associates with increased cartilaginous catabolism. Vitamin D supplementation seems more necessary in winter for lumbar IVD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Intermittent Fasting Applied in Combination with Rotenone Treatment Exacerbates Dopamine Neurons Degeneration in Mice

    Directory of Open Access Journals (Sweden)

    Giuseppe Tatulli

    2018-01-01

    Full Text Available Intermittent fasting (IF was suggested to be a powerful nutritional strategy to prevent the onset of age-related neurodegenerative diseases associated with compromised brain bioenergetics. Whether the application of IF in combination with a mitochondrial insult could buffer the neurodegenerative process has never been explored yet. Herein, we defined the effects of IF in C57BL/6J mice treated once per 24 h with rotenone (Rot for 28 days. Rot is a neurotoxin that inhibits the mitochondrial complex I and causes dopamine neurons degeneration, thus reproducing the neurodegenerative process observed in Parkinson’s disease (PD. IF (24 h alternate-day fasting was applied alone or in concomitance with Rot treatment (Rot/IF. IF and Rot/IF groups showed the same degree of weight loss when compared to control and Rot groups. An accelerating rotarod test revealed that only Rot/IF mice have a decreased ability to sustain the test at the higher speeds. Rot/IF group showed a more marked decrease of dopaminergic neurons and increase in alpha-synuclein (α-syn accumulation with respect to Rot group in the substantia nigra (SN. Through lipidomics and metabolomics analyses, we found that in the SN of Rot/IF mice a significant elevation of excitatory amino acids, inflammatory lysophospholipids and sphingolipids occurred. Collectively, our data suggest that, when applied in combination with neurotoxin exposure, IF does not exert neuroprotective effects but rather exacerbate neuronal death by increasing the levels of excitatory amino acids and inflammatory lipids in association with altered brain membrane composition.

  10. Intermittent Fasting Applied in Combination with Rotenone Treatment Exacerbates Dopamine Neurons Degeneration in Mice.

    Science.gov (United States)

    Tatulli, Giuseppe; Mitro, Nico; Cannata, Stefano M; Audano, Matteo; Caruso, Donatella; D'Arcangelo, Giovanna; Lettieri-Barbato, Daniele; Aquilano, Katia

    2018-01-01

    Intermittent fasting (IF) was suggested to be a powerful nutritional strategy to prevent the onset of age-related neurodegenerative diseases associated with compromised brain bioenergetics. Whether the application of IF in combination with a mitochondrial insult could buffer the neurodegenerative process has never been explored yet. Herein, we defined the effects of IF in C57BL/6J mice treated once per 24 h with rotenone (Rot) for 28 days. Rot is a neurotoxin that inhibits the mitochondrial complex I and causes dopamine neurons degeneration, thus reproducing the neurodegenerative process observed in Parkinson's disease (PD). IF (24 h alternate-day fasting) was applied alone or in concomitance with Rot treatment (Rot/IF). IF and Rot/IF groups showed the same degree of weight loss when compared to control and Rot groups. An accelerating rotarod test revealed that only Rot/IF mice have a decreased ability to sustain the test at the higher speeds. Rot/IF group showed a more marked decrease of dopaminergic neurons and increase in alpha-synuclein (α-syn) accumulation with respect to Rot group in the substantia nigra (SN). Through lipidomics and metabolomics analyses, we found that in the SN of Rot/IF mice a significant elevation of excitatory amino acids, inflammatory lysophospholipids and sphingolipids occurred. Collectively, our data suggest that, when applied in combination with neurotoxin exposure, IF does not exert neuroprotective effects but rather exacerbate neuronal death by increasing the levels of excitatory amino acids and inflammatory lipids in association with altered brain membrane composition.

  11. Fungiform taste bud degeneration in C57BL/6J mice following chorda-lingual nerve transection.

    Science.gov (United States)

    Guagliardo, Nick A; Hill, David L

    2007-09-10

    Taste buds are dependent on innervation for normal morphology and function. Fungiform taste bud degeneration after chorda tympani nerve injury has been well documented in rats, hamsters, and gerbils. The current study examines fungiform taste bud distribution and structure in adult C57BL/6J mice from both intact taste systems and after unilateral chorda-lingual nerve transection. Fungiform taste buds were visualized and measured with the aid of cytokeratin 8. In control mice, taste buds were smaller and more abundant on the anterior tip (taste buds were smaller and fewer on the side of the tongue ipsilateral to the transection and continued to decrease in both size and number until 15 days posttransection. Degenerating fungiform taste buds were smaller due to a loss of taste bud cells rather than changes in taste bud morphology. While almost all taste buds disappeared in more posterior fungiform papillae by 15 days posttransection, the anterior tip of the tongue retained nearly half of its taste buds compared to intact mice. Surviving taste buds could not be explained by an apparent innervation from the remaining intact nerves. Contralateral effects of nerve transection were also observed; taste buds were larger due to an increase in the number of taste bud cells. These data are the first to characterize adult mouse fungiform taste buds and subsequent degeneration after unilateral nerve transection. They provide the basis for more mechanistic studies in which genetically engineered mice can be used. (c) 2007 Wiley-Liss, Inc.

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Science.gov (United States)

    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

  14. All-optical recording and stimulation of retinal neurons in vivo in retinal degeneration mice

    Science.gov (United States)

    Strazzeri, Jennifer M.; Williams, David R.; Merigan, William H.

    2018-01-01

    Here we demonstrate the application of a method that could accelerate the development of novel therapies by allowing direct and repeatable visualization of cellular function in the living eye, to study loss of vision in animal models of retinal disease, as well as evaluate the time course of retinal function following therapeutic intervention. We use high-resolution adaptive optics scanning light ophthalmoscopy to image fluorescence from the calcium sensor GCaMP6s. In mice with photoreceptor degeneration (rd10), we measured restored visual responses in ganglion cell layer neurons expressing the red-shifted channelrhodopsin ChrimsonR over a six-week period following significant loss of visual responses. Combining a fluorescent calcium sensor, a channelrhodopsin, and adaptive optics enables all-optical stimulation and recording of retinal neurons in the living eye. Because the retina is an accessible portal to the central nervous system, our method also provides a novel non-invasive method of dissecting neuronal processing in the brain. PMID:29596518

  15. Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice.

    Science.gov (United States)

    Meira, Lisiane B; Moroski-Erkul, Catherine A; Green, Stephanie L; Calvo, Jennifer A; Bronson, Roderick T; Shah, Dharini; Samson, Leona D

    2009-01-20

    Vision loss affects >3 million Americans and many more people worldwide. Although predisposing genes have been identified their link to known environmental factors is unclear. In wild-type animals DNA alkylating agents induce photoreceptor apoptosis and severe retinal degeneration. Alkylation-induced retinal degeneration is totally suppressed in the absence of the DNA repair protein alkyladenine DNA glycosylase (Aag) in both differentiating and postmitotic retinas. Moreover, transgenic expression of Aag activity restores the alkylation sensitivity of photoreceptors in Aag null animals. Aag heterozygotes display an intermediate level of retinal degeneration, demonstrating haploinsufficiency and underscoring that Aag expression confers a dominant retinal degeneration phenotype.

  16. Fatores genéticos e ambientais envolvidos na degeneração do disco intervertebral Genetic and environmental factors involved on intervertebral disc degeneration

    Directory of Open Access Journals (Sweden)

    Francine Teresa Brioni Nunes

    2007-01-01

    Full Text Available A etiologia da degeneração do disco intervertebral (DDI ainda não está totalmente esclarecida. O gene do receptor da vitamina D (VDR tem sido apontado como um dos possíveis envolvidos no surgimento das discopatias. Por outro lado, este estudo relaciona pela primeira vez, a participação dos genes das glutatião transferases M1 e T1 (GSTT1 e GSTM1, responsáveis pela inativação dos componentes do cigarro, na DDI. Foi extraído DNA de leucócitos de 66 pacientes e 88 controles, pareados por gênero e idade. O polimorfismo VDR-FokI foi amplificado por reação em cadeia da polimerase (PCR seguido de restrição com a enzima FokI. Os polimorfismos das GSTT1/M1 foram determinados por meio da PCR multiplex. A história familial e a gravidade da doença se destacaram nos pacientes portadores do alelo f do gene VDR-FokI (P=0,000 e 0,0012, respectivamente. A idade de surgimento da doença mostrou-se precoce nos indivíduos com genótipo _/f (média de 26 anos. Foi encontrada associação do polimorfismo FokI com a degeneração precoce e gravidade da DDI, sendo que o hábito de fumar também interferiu nesse processo, independente da presença ou não do genótipo favorável para GSTT1/M1.The etiology of intervertebral disc degeneration (IDD has not been fully clarified yet. Vitamin D receptor’s gene (VDR has been suggested as one of the potential entities involved in disc pathologies onset. On the other hand, this study correlates, for the first time, glutathione transferases M1 and T1 genes (GSTT1 and GSTM1 participation, which are responsible for cigarette components’ inactivation, in IDD. DNA was extracted from leukocytes of 66 patients and 88 controls, paired by gender and age. The VDR-Fokl polymorphism was amplified by polymerase chain reaction (PCR followed by restriction with Fokl enzyme. GSTT1/M1 polymorphisms were determined by means of PCR multiplex. Family history and disease severity were highlighted in patients carrying the f

  17. Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia.

    Science.gov (United States)

    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.

  18. Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Lu, Kang; Li, Hai-Yin; Yang, Kuang; Wu, Jun-Long; Cai, Xiao-Wei; Zhou, Yue; Li, Chang-Qing

    2017-05-10

    The stem cell-based therapies for intervertebral disc degeneration have been widely studied. However, the mechanisms of mesenchymal stem cells interacting with intervertebral disc cells, such as nucleus pulposus cells (NPCs), remain unknown. Exosomes as a vital paracrine mechanism in cell-cell communication have been highly focused on. The purpose of this study was to detect the role of exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) and NPCs in their interaction with corresponding cells. The exosomes secreted by BM-MSCs and NPCs were purified by differential centrifugation and identified by transmission electron microscope and immunoblot analysis of exosomal marker proteins. Fluorescence confocal microscopy was used to examine the uptake of exosomes by recipient cells. The effects of NPC exosomes on the migration and differentiation of BM-MSCs were determined by transwell migration assays and quantitative RT-PCR analysis of NPC phenotypic genes. Western blot analysis was performed to examine proteins such as aggrecan, sox-9, collagen II and hif-1α in the induced BM-MSCs. Proliferation and the gene expression profile of NPCs induced by BM-MSC exosomes were measured by Cell Counting Kit-8 and qRT-PCR analysis, respectively. Both the NPCs and BM-MSCs secreted exosomes, and these exosomes underwent uptake by the corresponding cells. NPC-derived exosomes promoted BM-MSC migration and induced BM-MSC differentiation to a nucleus pulposus-like phenotype. BM-MSC-derived exosomes promoted NPC proliferation and healthier extracellular matrix production in the degenerate NPCs. Our study indicates that the exosomes act as an important vehicle in information exchange between BM-MSCs and NPCs. Given a variety of functions and multiple advantages, exosomes alone or loaded with specific genes and drugs would be an appropriate option in a cell-free therapy strategy for intervertebral disc degeneration.

  19. The severity of retinal degeneration in Rp1h gene-targeted mice is dependent on genetic background.

    Science.gov (United States)

    Liu, Qin; Saveliev, Alexei; Pierce, Eric A

    2009-04-01

    The severity of disease in patients with retinitis pigmentosa (RP) can vary significantly, even among patients with the same primary mutations. It is hypothesized that modifier genes play important roles in determining the severity of RP, including the retinitis pigmentosa 1 (RP1) form of disease. To investigate the basis of variation in disease expression for RP1 disease, the authors generated congenic mice with a gene-targeted retinitis pigmentosa 1 homolog (Rp1h) allele (Rp1h(tm1Eap)) on several different genetic backgrounds and analyzed their retinal phenotypes. The Rp1h(tm1Eap) allele was placed onto the C57BL/6J, DBA1/J, and A/J backgrounds. Retinal function of the resultant congenic mice was evaluated using electroretinographic analyses. Retinal structure and ultrastructure were evaluated using light and electron microscopy. Rp1h protein location was determined with immunofluorescence microscopy. Analysis of the retinal phenotype of incipient congenic (N6) B6.129S-Rp1h(+/tm1Eap), DBA.129S(B6)-Rp1h(+/tm1Eap), and A.129S(B6)-Rp1h(+/tm1Eap) mice at 1 year of age showed retinal degeneration only in the A.129S(B6)-Rp1h(+/tm1Eap) mice. Further analyses revealed that the photoreceptors of the fully congenic A.129S(B6)-Rp1h(+/tm1Eap) mice show evidence of degeneration at 6 months of age and are almost completely lost by 18 months of age. In contrast, the photoreceptor cells in the fully congenic B6.129S-Rp1h(+/tm1Eap) mice remain healthy up to 18 months. The severity of the retinal degeneration caused by the Rp1h(tm1Eap) allele is notably dependent on genetic background. The development and characterization of the B6.129S-Rp1h(+/tm1Eap) and A.129S(B6)-Rp1h(+/tm1Eap) congenic mouse lines will facilitate identification of sequence alterations in genes that modify the severity of RP1 disease.

  20. Qualitative grading of disc degeneration by magnetic resonance in the lumbar and cervical spine: lack of correlation with histology in surgical cases.

    Science.gov (United States)

    Davies, B M; Atkinson, R A; Ludwinski, F; Freemont, A J; Hoyland, J A; Gnanalingham, K K

    2016-08-01

    Clinically, magnetic resonance (MR) imaging is the most effective non-invasive tool for assessing IVD degeneration. Histological examination of the IVD provides a more detailed assessment of the pathological changes at a tissue level. However, very few reports have studied the relationship between these techniques. Identifying a relationship may allow more detailed staging of IVD degeneration, of importance in targeting future regenerative therapies. To investigate the relationship between MR and histological grading of IVD degeneration in the cervical and lumbar spine in patients undergoing discectomy. Lumbar (N = 99) and cervical (N = 106) IVD samples were obtained from adult patients undergoing discectomy surgery for symptomatic IVD herniation and graded to ascertain a histological grade of degeneration. The pre-operative MR images from these patients were graded for the degree of IVD (MR grade) and vertebral end-plate degeneration (Modic Changes, MC). The relationship between histological and MR grades of degeneration were studied. In lumbar and cervical IVD the majority of samples (93%) exhibited moderate levels of degeneration (ie MR grades 3-4) on pre-operative MR scans. Histologically, most specimens displayed moderate to severe grades of degeneration in lumbar (99%) and cervical spine (93%). MR grade was weakly correlated with patient age in lumbar and cervical study groups. MR and histological grades of IVD degeneration did not correlate in lumbar or cervical study groups. MC were more common in the lumbar than cervical spine (e.g. 39 versus 20% grade 2 changes; p < 0.05), but failed to correlate with MR or histological grades for degeneration. In this surgical series, the resected IVD tissue displayed moderate to severe degeneration, but there is no correlation between MR and histological grades using a qualitative classification system. There remains a need for a quantitative, non-invasive, pre-clinical measure of IVD degeneration that

  1. Cholinergic degeneration is associated with increased plaque deposition and cognitive impairment in APPswe/PS1dE9 mice

    DEFF Research Database (Denmark)

    Laursen, Bettina; Mørk, Arne; Plath, Niels

    2013-01-01

    mice was not due to a more extensive cholinergic degeneration since the reduction in choline acetyltransferase activity was similar following SAP treatment in APP/PS1 mice and Wt. Interestingly, plaque load was significantly increased in SAP treated APP/PS1 mice relative to sham lesioned APP/PS1 mice....... Additionally, APP/PS1 mice treated with SAP showed a tendency towards an increased level of soluble and insoluble Aß1-40 and Aß1-42 measured in brain tissue homogenate. Our results suggest that the combination of cholinergic degeneration and Aß overexpression in the APP/PS1 mouse model results in cognitive...... decline and accelerated plaque burden. SAP treated APP/PS1 mice might thus constitute an improved model of Alzheimer's disease-like neuropathology and cognitive deficits compared to the conventional APP/PS1 model without selective removal of basal forebrain cholinergic neurons....

  2. Degeneration of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits following Mid-Cervical Spinal Contusion in Mice

    Science.gov (United States)

    Nicaise, Charles; Putatunda, Rajarshi; Hala, Tamara J.; Regan, Kathleen A.; Frank, David M.; Brion, Jean-Pierre; Leroy, Karelle; Pochet, Roland; Wright, Megan C.

    2012-01-01

    Abstract A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle of inspiration. Contusion-type trauma to the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron–diaphragm circuitry. We have generated a mouse model of cervical contusion SCI that unilaterally targets both C4 and C5 levels, the location of the phrenic motor neuron pool, and have examined histological and functional outcomes for up to 6 weeks post-injury. We report that phrenic motor neuron loss in cervical spinal cord, phrenic nerve axonal degeneration, and denervation at diaphragm neuromuscular junctions (NMJ) resulted in compromised ipsilateral diaphragm function, as demonstrated by persistent reduction in diaphragm compound muscle action potential amplitudes following phrenic nerve stimulation and abnormalities in spontaneous diaphragm electromyography (EMG) recordings. This injury paradigm is reproducible, does not require ventilatory assistance, and provides proof-of-principle that generation of unilateral cervical contusion is a feasible strategy for modeling diaphragmatic/respiratory deficits in mice. This study and its accompanying analyses pave the way for using transgenic mouse technology to explore the function of specific genes in the pathophysiology of phrenic motor neuron degeneration and respiratory dysfunction following cervical SCI. PMID:23176637

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

    Science.gov (United States)

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

    2012-01-01

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

  4. DKK1 mediated inhibition of Wnt signaling in postnatal mice leads to loss of TEC progenitors and thymic degeneration.

    Directory of Open Access Journals (Sweden)

    Masako Osada

    2010-02-01

    Full Text Available Thymic epithelial cell (TEC microenvironments are essential for the recruitment of T cell precursors from the bone marrow, as well as the subsequent expansion and selection of thymocytes resulting in a mature self-tolerant T cell repertoire. The molecular mechanisms, which control both the initial development and subsequent maintenance of these critical microenvironments, are poorly defined. Wnt signaling has been shown to be important to the development of several epithelial tissues and organs. Regulation of Wnt signaling has also been shown to impact both early thymocyte and thymic epithelial development. However, early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of canonical Wnt signaling in the maintenance of TECs in the postnatal thymus.Here we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice, results in rapid thymic degeneration characterized by a loss of DeltaNP63(+ Foxn1(+ and Aire(+ TECs, loss of K5K8DP TECs thought to represent or contain an immature TEC progenitor, decreased TEC proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments.Taken together, the results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at counteracting age associated thymic involution or the premature thymic

  5. Histological and reference system for the analysis of mouse intervertebral disc.

    Science.gov (United States)

    Tam, Vivian; Chan, Wilson C W; Leung, Victor Y L; Cheah, Kathryn S E; Cheung, Kenneth M C; Sakai, Daisuke; McCann, Matthew R; Bedore, Jake; Séguin, Cheryle A; Chan, Danny

    2018-01-01

    A new scoring system based on histo-morphology of mouse intervertebral disc (IVD) was established to assess changes in different mouse models of IVD degeneration and repair. IVDs from mouse strains of different ages, transgenic mice, or models of artificially induced IVD degeneration were assessed. Morphological features consistently observed in normal, and early/later stages of degeneration were categorized into a scoring system focused on nucleus pulposus (NP) and annulus fibrosus (AF) changes. "Normal NP" exhibited a highly cellularized cell mass that decreased with natural ageing and in disc degeneration. "Normal AF" consisted of distinct concentric lamellar structures, which was disrupted in severe degeneration. NP/AF clefts indicated more severe changes. Consistent scores were obtained between experienced and new users. Altogether, our scoring system effectively differentiated IVD changes in various strains of wild-type and genetically modified mice and in induced models of IVD degeneration, and is applicable from the post-natal stage to the aged mouse. This scoring tool and reference resource addresses a pressing need in the field for studying IVD changes and cross-study comparisons in mice, and facilitates a means to normalize mouse IVD assessment between different laboratories. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:233-243, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. Deficient Mechanical Activation of Anabolic Transcripts and Post-Traumatic Cartilage Degeneration in Matrilin-1 Knockout Mice.

    Directory of Open Access Journals (Sweden)

    Yupeng Chen

    Full Text Available Matrilin-1 (Matn1, a cartilage-specific peri-cellular and extracellular matrix (ECM protein, has been hypothesized to regulate ECM interactions and transmit mechanical signals in cartilage. Since Matn1 knock-out (Matn1-/- mice exhibit a normal skeleton, its function in vivo is unclear. In this study, we found that the anabolic Acan and Col2a transcript levels were significantly higher in wildtype (Matn1+/+ mouse cartilage than that of MATN1-/- mice in vivo. However, such difference was not observed between Matn1+/+ and MATN1-/- chondrocytes cultured under stationary conditions in vitro. Cyclic loading significantly stimulated Acan and Col2a transcript levels in Matn1+/+ but not in MATN1-/- chondrocytes. This suggests that, while Matn1+/+ chondrocytes increase their anabolic gene expression in response to mechanical loading, the MATN1-/- chondrocytes fail to do so because of the deficiency in mechanotransduction. We also found that altered elastic modulus of cartilage matrix in Matn1-/- mice, suggesting the mechanotransduction has changed due to the deficiency of Matn1. To understand the impact of such deficiency on joint disease, mechanical loading was altered in vivo by destabilization of medial meniscus. While Matn1+/+ mice exhibited superficial fissures and clefts consistent with mechanical damage to the articular joint, Matn1-/- mice presented more severe cartilage lesions characterized by proteoglycan loss and disorganization of cells and ECM. This suggests that Matn1 deficiency affects pathogenesis of post-traumatic osteoarthritis by failing to up-regulate anabolic gene expression. This is the first demonstration of Matn1 function in vivo, which suggests its protective role in cartilage degeneration under altered mechanical environment.

  7. Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice.

    Science.gov (United States)

    Miyazaki, Kazunori; Masamoto, Kazuto; Morimoto, Nobutoshi; Kurata, Tomoko; Mimoto, Takahumi; Obata, Takayuki; Kanno, Iwao; Abe, Koji

    2012-03-01

    The exact mechanism of selective motor neuron death in amyotrophic lateral sclerosis (ALS) remains still unclear. In the present study, we performed in vivo capillary imaging, directly measured spinal blood flow (SBF) and glucose metabolism, and analyzed whether if a possible flow-metabolism coupling is disturbed in motor neuron degeneration of ALS model mice. In vivo capillary imaging showed progressive decrease of capillary diameter, capillary density, and red blood cell speed during the disease course. Spinal blood flow was progressively decreased in the anterior gray matter (GM) from presymptomatic stage to 0.80-fold of wild-type (WT) mice, 0.61 at early-symptomatic, and 0.49 at end stage of the disease. Local spinal glucose utilization (LSGU) was transiently increased to 1.19-fold in anterior GM at presymptomatic stage, which in turn progressively decreased to 0.84 and 0.60 at early-symptomatic and end stage of the disease. The LSGU/SBF ratio representing flow-metabolism uncoupling (FMU) preceded the sequential pathological changes in the spinal cord of ALS mice and was preferentially found in the affected region of ALS. The present study suggests that this early and progressive FMU could profoundly involve in the whole disease process as a vascular factor of ALS pathology, and could also be a potential target for therapeutic intervention of ALS.

  8. Expression of wild-type Rp1 protein in Rp1 knock-in mice rescues the retinal degeneration phenotype.

    Directory of Open Access Journals (Sweden)

    Qin Liu

    Full Text Available Mutations in the retinitis pigmentosa 1 (RP1 gene are a common cause of autosomal dominant retinitis pigmentosa (adRP, and have also been found to cause autosomal recessive RP (arRP in a few families. The 33 dominant mutations and 6 recessive RP1 mutations identified to date are all nonsense or frameshift mutations, and almost exclusively (38 out of 39 are located in the 4(th and final exon of RP1. To better understand the underlying disease mechanisms of and help develop therapeutic strategies for RP1 disease, we performed a series of human genetic and animal studies using gene targeted and transgenic mice. Here we report that a frameshift mutation in the 3(rd exon of RP1 (c.686delC; p.P229QfsX35 found in a patient with recessive RP1 disease causes RP in the homozygous state, whereas the heterozygous carriers are unaffected, confirming that haploinsufficiency is not the causative mechanism for RP1 disease. We then generated Rp1 knock-in mice with a nonsense Q662X mutation in exon 4, as well as Rp1 transgenic mice carrying a wild-type BAC Rp1 transgene. The Rp1-Q662X allele produces a truncated Rp1 protein, and homozygous Rp1-Q662X mice experience a progressive photoreceptor degeneration characterized disorganization of photoreceptor outer segments. This phenotype could be prevented by expression of a normal amount of Rp1 protein from the BAC transgene without removal of the mutant Rp1-Q662X protein. Over-expression of Rp1 protein in additional BAC Rp1 transgenic lines resulted in retinal degeneration. These findings suggest that the truncated Rp1-Q662X protein does not exert a toxic gain-of-function effect. These results also imply that in principle gene augmentation therapy could be beneficial for both recessive and dominant RP1 patients, but the levels of RP1 protein delivered for therapy will have to be carefully controlled.

  9. GLYX-13 Ameliorates Schizophrenia-Like Phenotype Induced by MK-801 in Mice: Role of Hippocampal NR2B and DISC1

    Science.gov (United States)

    Zhou, Dongsheng; Lv, Dan; Wang, Zhen; Zhang, Yanhua; Chen, Zhongming; Wang, Chuang

    2018-01-01

    Background: Evidence supports that the hypofunction of N-methyl-D-aspartate receptor (NMDAR) and downregulation of disrupted-in-schizophrenia 1 (DISC1) contribute to the pathophysiology of schizophrenia. N-Methyl D-aspartate receptor subtype 2B (NR2B)-containing NMDAR are associated with cognitive dysfunction in schizophrenia. GLYX-13 is an NMDAR glycine-site functional partial agonist and cognitive enhancer that does not induce psychotomimetic side effects. However, it remains unclear whether NR2B plays a critical role in the GLYX-13-induced alleviation of schizophrenia-like behaviors in mice. Methods: The effect of GLYX-13 was tested by observing changes in locomotor activity, novel object recognition ability, and prepulse inhibition (PPI) induced by dizocilpine (known as MK-801) in mice. Lentivirus-mediated NR2B knockdown in the hippocampus was assessed to confirm the role of NR2B in GLYX-13 pathophysiology, using Western blots and immunohistochemistry. Results: The systemic administration of GLYX-13 (0.5 and 1 mg/kg, i.p.) ameliorates MK-801 (0.5 mg/kg, i.p.)-induced hyperlocomotion, deficits in memory, and PPI in mice. Additionally, GLYX-13 normalized the MK-801-induced alterations in signaling molecules, including NR2B and DISC1 in the hippocampus. Furthermore, we found that NR2B knockdown produced memory and PPI deficits without any changes in locomotor activity. Notably, DISC1 levels significantly decreased by NR2B knockdown. However, the effective dose of GLYX-13 did not alleviate the memory and PPI dysfunctions or downregulation of DISC1 induced by NR2B knockdown. Conclusion: Our results suggest GLYX-13 as a candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may account for the molecular mechanisms of GLYX-13. PMID:29695955

  10. Different effects of valproic acid on photoreceptor loss in Rd1 and Rd10 retinal degeneration mice.

    Science.gov (United States)

    Mitton, Kenneth P; Guzman, Alvaro E; Deshpande, Mrinalini; Byrd, David; DeLooff, Camryn; Mkoyan, Kristina; Zlojutro, Paul; Wallace, Adrianne; Metcalf, Brandon; Laux, Kirsten; Sotzen, Jason; Tran, Trung

    2014-01-01

    The histone-deacetylase inhibitor activity of valproic acid (VPA) was discovered after VPA's adoption as an anticonvulsant. This generated speculation for VPA's potential to increase the expression of neuroprotective genes. Clinical trials for retinitis pigmentosa (RP) are currently active, testing VPA's potential to reduce photoreceptor loss; however, we lack information regarding the effects of VPA on available mammalian models of retinal degeneration, nor do we know if retinal gene expression is perturbed by VPA in a predictable way. Thus, we examined the effects of systemic VPA on neurotrophic factor and Nrl-related gene expression in the mouse retina and compared VPA's effects on the rate of photoreceptor loss in two strains of mice, Pde6b(rd1/rd1) and Pde6b(rd10/rd10) . The expression of Bdnf, Gdnf, Cntf, and Fgf2 was measured by quantitative PCR after single and multiple doses of VPA (intraperitoneal) in wild-type and Pde6b(rd1/rd1) mice. Pde6b(rd1/rd1) mice were treated with daily doses of VPA during the period of rapid photoreceptor loss. Pde6b(rd10/rd10) mice were also treated with systemic VPA to compare in a partial loss-of-function model. Retinal morphology was assessed by virtual microscopy or spectral-domain optical coherence tomography (SD-OCT). Full-field and focal electroretinography (ERG) analysis were employed with Pde6b(rd10/rd10) mice to measure retinal function. In wild-type postnatal mice, a single VPA dose increased the expression of Bdnf and Gdnf in the neural retina after 18 h, while the expression of Cntf was reduced by 70%. Daily dosing of wild-type mice from postnatal day P17 to P28 resulted in smaller increases in Bdnf and Gdnf expression, normal Cntf expression, and reduced Fgf2 expression (25%). Nrl gene expression was decreased by 50%, while Crx gene expression was not affected. Rod-specific expression of Mef2c and Nr2e3 was decreased substantially by VPA treatment, while Rhodopsin and Pde6b gene expression was normal at P28. Daily

  11. Edaravone Prevents Retinal Degeneration in Adult Mice Following Optic Nerve Injury.

    Science.gov (United States)

    Akiyama, Goichi; Azuchi, Yuriko; Guo, Xiaoli; Noro, Takahiko; Kimura, Atsuko; Harada, Chikako; Namekata, Kazuhiko; Harada, Takayuki

    2017-09-01

    To assess the therapeutic potential of edaravone, a free radical scavenger that is used for the treatment of acute brain infarction and amyotrophic lateral sclerosis, in a mouse model of optic nerve injury (ONI). Two microliters of edaravone (7.2 mM) or vehicle were injected intraocularly 3 minutes after ONI. Optical coherence tomography, retrograde labeling of retinal ganglion cells (RGCs), histopathology, and immunohistochemical analyses of phosphorylated apoptosis signal-regulating kinase-1 (ASK1) and p38 mitogen-activated protein kinase (MAPK) in the retina were performed after ONI. Reactive oxygen species (ROS) levels were assessed with a CellROX Green Reagent. Edaravone ameliorated ONI-induced ROS production, RGC death, and inner retinal degeneration. Also, activation of the ASK1-p38 MAPK pathway that induces RGC death following ONI was suppressed with edaravone treatment. The results of this study suggest that intraocular administration of edaravone may be a useful treatment for posttraumatic complications.

  12. Imaging retinal degeneration in mice by combining Fourier domain optical coherence tomography and fluorescent scanning laser ophthalmoscopy

    Science.gov (United States)

    Hossein-Javaheri, Nima; Molday, Laurie L.; Xu, Jing; Molday, Robert S.; Sarunic, Marinko V.

    2009-02-01

    Visualization of the internal structures of the retina is critical for clinical diagnosis and monitoring of pathology as well as for medical research investigating the root causes of retinal degeneration. Optical Coherence Tomography (OCT) is emerging as the preferred technique for non-contact sub-surface depth-resolved imaging of the retina. The high resolution cross sectional images acquired in vivo by OCT can be compared to histology to visually delineate the retinal layers. The recent demonstration of the significant sensitivity increase obtained through use of Fourier domain (FD) detection with OCT has been used to facilitate high speed scanning for volumetric reconstruction of the retina in software. The images acquired by OCT are purely structural, relying on refractive index differences in the tissue for contrast, and do not provide information on the molecular content of the sample. We have constructed a FDOCT prototype and combined it with a fluorescent Scanning Laser Ophthalmoscope (fSLO) to permit real time alignment of the field of view on the retina. The alignment of the FDOCT system to the specimen is crucial for the registration of measurements taken throughout longitudinal studies. In addition, fluorescence detection has been integrated with the SLO to enable the en face localization of a molecular contrast signal, which is important for retinal angiography, and also for detection of autofluorescence associated with some forms of retinal degeneration, for example autofluorescence lipofuscin accumulations are associated with Stargardt's Macular Dystrophy. The integrated FD OCT/fSLO system was investigated for imaging the retina of the mice in vivo.

  13. Parametric T2 and T2* mapping techniques to visualize intervertebral disc degeneration in patients with low back pain: initial results on the clinical use of 3.0 Tesla MRI

    International Nuclear Information System (INIS)

    Welsch, Goetz Hannes; Trattnig, Siegfried; Goed, Sabine; Stelzeneder, David; Paternostro-Sluga, Tatjana; Bohndorf, Klaus; Mamisch, Tallal Charles

    2011-01-01

    To assess, compare and correlate quantitative T2 and T2* relaxation time measurements of intervertebral discs (IVDs) in patients suffering from low back pain, with respect to the IVD degeneration as assessed by the morphological Pfirrmann Score. Special focus was on the spatial variation of T2 and T2* between the annulus fibrosus (AF) and the nucleus pulposus (NP). Thirty patients (mean age: 38.1 ± 9.1 years; 20 female, 10 male) suffering from low back pain were included. Morphological (sagittal T1-FSE, sagittal and axial T2-FSE) and biochemical (sagittal T2- and T2* mapping) MRI was performed at 3 Tesla covering IVDs L1-L2 to L5-S1. All IVDs were morphologically classified using the Pfirrmann score. Region-of-interest (ROI) analysis was performed on midsagittal T2 and T2* maps at five ROIs from anterior to posterior to obtain information on spatial variation between the AF and the NP. Statistical analysis-of-variance and Pearson correlation was performed. The spatial variation as an increase in T2 and T2* values from the AF to the NP was highest at Pfirmann grade I and declined at higher Pfirmann grades II-IV (p < 0.05). With increased IVD degeneration, T2 and T2* revealed a clear differences in the NP, whereas T2* was additionally able to depict changes in the posterior AF. Correlation between T2 and T2* showed a medium Pearson's correlation (0.210 to 0.356 [p < 0.001]). The clear differentiation of IVD degeneration and the possible quantification by means of T2 and fast T2* mapping may provide a new tool for follow-up therapy protocols in patients with low back pain. (orig.)

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  15. Early Involvement of Immune/Inflammatory Response Genes in Retinal Degeneration in DBA/2J Mice

    Directory of Open Access Journals (Sweden)

    W. Fan

    2010-01-01

    Full Text Available Purpose The DBA/2J (D2 mouse carries mutations in two of its genes, Tyrp1 and Gpnmb. These alterations result in the development of an immune response in the iris, leading to iris atrophy and pigment dispersion. The development of elevated intraocular pressure (IOP in this model of glaucoma is considered to be a significant factor leading to the death of retinal ganglion cells (RGCs. Changes in gene expression in the retina have already been correlated with the appearance of elevated IOP in the D2 mouse. The purpose of the present study was to determine if any changes in gene expression occur prior to the development of IOP. Methods The IOP was measured monthly using a rebound tonometer in D2 and age-matched C57/BL6 (B6 mice (normal controls. D2 animals with normal IOP at 2 and 4 M were used. In addition, mice at the age of 6–7 M were included to look for any trends in gene expression that might develop during the progression of the disease. Separate RNA samples were prepared from each of three individual retinas for each age, and gene expression profiles were determined with the aid of mouse oligonucleotide arrays (Agilent. A subset of genes was examined with the aid of real-time PCR. Immunocytochemistry was used to visualize changes in the retina for some of the gene-products. Results Four hundred and thirteen oligonucleotide probes were differentially expressed in the retinas of 4 M versus 2 M old D2 mice. The most significantly up-regulated genes (181 were associated with immune responses including interferon signaling, the complement system and the antigen presentation pathway, whereas the down-regulated genes (232 were linked to pathways related to cell death and known neurological diseases/disorders. These particular changes were not revealed in the age-matched B6 mice. By 6 M, when IOP started to increase in many of the D2 mice, more robust changes of these same genes were observed. Changes in the levels of selected genes

  16. Early Involvement of Immune/Inflammatory Response Genes in Retinal Degeneration in DBA/2J Mice

    Directory of Open Access Journals (Sweden)

    W. Fan

    2010-03-01

    Full Text Available Purpose: The DBA/2J (D2 mouse carries mutations in two of its genes, Tyrp1 and Gpnmb. These alterations result in the development of an immune response in the iris, leading to iris atrophy and pigment dispersion. The development of elevated intraocular pressure (IOP in this model of glaucoma is considered to be a significant factor leading to the death of retinal ganglion cells (RGCs. Changes in gene expression in the retina have already been correlated with the appearance of elevated IOP in the D2 mouse. The purpose of the present study was to determine if any changes in gene expression occur prior to the development of IOP. Methods: The IOP was measured monthly using a rebound tonometer in D2 and age-matched C57/BL6 (B6 mice (normal controls. D2 animals with normal IOP at 2 and 4 M were used. In addition, mice at the age of 6–7 M were included to look for any trends in gene expression that might develop during the progression of the disease. Separate RNA samples were prepared from each of three individual retinas for each age, and gene expression profiles were determined with the aid of mouse oligonucleotide arrays (Agilent. A subset of genes was examined with the aid of real-time PCR. Immunocytochemistry was used to visualize changes in the retina for some of the gene-products. Results: Four hundred and thirteen oligonucleotide probes were differentially expressed in the retinas of 4 M versus 2 M old D2 mice. The most significantly up-regulated genes (181 were associated with immune responses including interferon signaling, the complement system and the antigen presentation pathway, whereas the down-regulated genes (232 were linked to pathways related to cell death and known neurological diseases/disorders. These particular changes were not revealed in the age-matched B6 mice. By 6 M, when IOP started to increase in many of the D2 mice, more robust changes of these same genes were observed. Changes in the levels of selected genes

  17. Chronic exposure of mutant DISC1 mice to lead produces sex-dependent abnormalities consistent with schizophrenia and related mental disorders: a gene-environment interaction study.

    Science.gov (United States)

    Abazyan, Bagrat; Dziedzic, Jenifer; Hua, Kegang; Abazyan, Sofya; Yang, Chunxia; Mori, Susumu; Pletnikov, Mikhail V; Guilarte, Tomas R

    2014-05-01

    The glutamatergic hypothesis of schizophrenia suggests that hypoactivity of the N-methyl-D-aspartate receptor (NMDAR) is an important factor in the pathophysiology of schizophrenia and related mental disorders. The environmental neurotoxicant, lead (Pb(2+)), is a potent and selective antagonist of the NMDAR. Recent human studies have suggested an association between prenatal Pb(2+) exposure and the increased likelihood of schizophrenia later in life, possibly via interacting with genetic risk factors. In order to test this hypothesis, we examined the neurobehavioral consequences of interaction between Pb(2+) exposure and mutant disrupted in schizophrenia 1 (mDISC1), a risk factor for major psychiatric disorders. Mutant DISC1 and control mice born by the same dams were raised and maintained on a regular diet or a diet containing moderate levels of Pb(2+). Chronic, lifelong exposure of mDISC1 mice to Pb(2+) was not associated with gross developmental abnormalities but produced sex-dependent hyperactivity, exaggerated responses to the NMDAR antagonist, MK-801, mildly impaired prepulse inhibition of the acoustic startle, and enlarged lateral ventricles. Together, these findings support the hypothesis that environmental toxins could contribute to the pathogenesis of mental disease in susceptible individuals.

  18. Suppressed retinal degeneration in aged wild type and APPswe/PS1ΔE9 mice by bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Yue Yang

    Full Text Available Alzheimer's disease (AD is an age-related condition characterized by accumulation of neurotoxic amyloid β peptides (Aβ in brain and retina. Because bone marrow transplantation (BMT results in decreased cerebral Aβ in experimental AD, we hypothesized that BMT would mitigate retinal neurotoxicity through decreased retinal Aβ. To test this, we performed BMT in APPswe/PS1ΔE9 double transgenic mice using green fluorescent protein expressing wild type (wt mice as marrow donors. We first examined retinas from control, non-transplanted, aged AD mice and found a two-fold increase in microglia compared with wt mice, prominent inner retinal Aβ and paired helical filament-tau, and decreased retinal ganglion cell layer neurons. BMT resulted in near complete replacement of host retinal microglia with BMT-derived cells and normalized total AD retinal microglia to non-transplanted wt levels. Aβ and paired helical filament-tau were reduced (61.0% and 44.1% respectively in BMT-recipient AD mice, which had 20.8% more retinal ganglion cell layer neurons than non-transplanted AD controls. Interestingly, aged wt BMT recipients also had significantly more neurons (25.4% compared with non-transplanted aged wt controls. Quantitation of retinal ganglion cell layer neurons in young mice confirmed age-related retinal degeneration was mitigated by BMT. We found increased MHC class II expression in BMT-derived microglia and decreased oxidative damage in retinal ganglion cell layer neurons. Thus, BMT is neuroprotective in age-related as well as AD-related retinal degeneration, and may be a result of alterations in innate immune function and oxidative stress in BMT recipient mice.

  19. Deletion of the Thyroid Hormone-Activating Type 2 Deiodinase Rescues Cone Photoreceptor Degeneration but Not Deafness in Mice Lacking Type 3 Deiodinase.

    Science.gov (United States)

    Ng, Lily; Liu, Hong; St Germain, Donald L; Hernandez, Arturo; Forrest, Douglas

    2017-06-01

    Type 2 deiodinase amplifies and type 3 deiodinase depletes levels of the active form of thyroid hormone, triiodothyronine. Given the opposing activities of these enzymes, we tested the hypothesis that they counteract each other's developmental functions by investigating whether deletion of type 2 deiodinase (encoded by Dio2) modifies sensory phenotypes in type 3 deiodinase-deficient (Dio3-/-) mice. Dio3-/- mice display degeneration of retinal cones, the photoreceptors that mediate daylight and color vision. In Dio2-/- mice, cone function was largely normal but deletion of Dio2 in Dio3-/- mice markedly recovered cone numbers and electroretinogram responses, suggesting counterbalancing roles for both enzymes in cone survival. Both Dio3-/- and Dio2-/- strains exhibit deafness with cochlear abnormalities. In Dio3-/-;Dio2-/- mice, deafness was exacerbated rather than alleviated, suggesting unevenly balanced actions by these enzymes during auditory development. Dio3-/- mice also exhibit an atrophic thyroid gland, low thyroxine, and high triiodothyronine levels, but this phenotype was ameliorated in Dio3-/-;Dio2-/- mice, indicating counterbalancing roles for the enzymes in determining the thyroid hormone status. The results suggest that the composite action of these two enzymes is a critical determinant in visual and auditory development and in setting the systemic thyroid hormone status.

  20. Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF in a rat model.

    Science.gov (United States)

    Hu, Yuan; Tang, Jin-Shu; Hou, Shu-Xun; Shi, Xiu-Xiu; Qin, Jiang; Zhang, Tie-Song; Wang, Xiao-Jing

    2017-11-01

    Curcumin is a natural product with antimutagenic, antitumor, antioxidant and neuroprotective properties. However, to the best of our knowledge, curcumin has yet to be investigated for the treatment of lumbar intervertebral disc degeneration LIDD). The aim of the present study was to investigate whether curcumin can alleviate LIDD through regulating the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, transforming growth factor (TGF)‑β1/2, matrix metalloproteinase (MMP)‑9 and brain‑derived neurotrophic factor (BDNF) in a rat model of LIDD. The results of the present study suggest that pretreatment with curcumin can prevent the development of LIDD in rats. It was revealed that treatment with curcumin significantly reduced interleukin (IL)‑1β and IL‑6, iNOS, COX‑2 and MMP‑9 levels in rats with LIDD. In addition, treatment with curcumin reduced the mRNA expression levels of TGF‑β1 and TGF‑β2, whereas it increased the mRNA expression levels of BDNF in rats with LIDD. In conclusion, the present findings indicate that curcumin may exert protective effects on LIDD development, exerting its action through the regulation of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF.

  1. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP and signi...... is cyclic: exacerbations relieved by asymptomatic periods. New imaging modalities, including the combination of MR imaging and multiplanar 3-D CT scans, have broadened our awareness of possible pain-generating degenerative processes of the lumbar spine other than disc degeneration....

  2. Predictive factors associated with neck pain in patients with cervical disc degeneration: A cross-sectional study focusing on Modic changes.

    Science.gov (United States)

    Kong, Lingde; Tian, Weifeng; Cao, Peng; Wang, Haonan; Zhang, Bing; Shen, Yong

    2017-10-01

    The predictive factors associated with neck pain remain unclear. We conducted a cross-sectional study to assess predictive factors, especially Modic changes (MCs), associated with the intensity and duration of neck pain in patients with cervical disc degenerative disease.We retrospectively reviewed patients in our hospital from January 2013 to December 2016. Severe neck pain (SNP) and persistent neck pain (PNP) were the 2 main outcomes, and were assessed based on the numerical rating scale (NRS). Basic data, and also imaging data, were collected and analyzed as potential predictive factors. Univariate analysis and multiple logistic regression analysis were performed to assess the predictive factors for neck pain.In all, 381 patients (193 males and 188 females) with cervical degenerative disease were included in our study. The number of patients with SNP and PNP were 94 (24.67%) and 109 (28.61%), respectively. The NRS of neck pain in patients with type 1 MCs was significantly higher than type 2 MCs (4.8 ± 0.9 vs 3.9 ± 1.1; P = .004). The multivariate logistic analysis showed that kyphosis curvature (odds ratio [OR] 1.082, 95% confidence interval [CI] 1.044-1.112), spondylolisthesis (OR 1.339, 95% CI 1.226-1.462), and annular tear (OR 1.188, 95% CI 1.021-1.382) were factors associated with SNP, whereas kyphosis curvature (OR 1.568, 95% CI 1.022-2.394), spondylolisthesis (OR 1.486, 95% CI 1.082-2.041), and MCs (OR 1.152, 95% CI 1.074-1.234) were associated with PNP.We concluded that kyphosis curvature, spondylolisthesis, and annular tear are associated with SNP, whereas kyphosis curvature, spondylolisthesis, and MCs are associated with PNP. This study supports the view that MCs can lead to a long duration of neck pain.

  3. Activation of liver X receptor delayed the retinal degeneration of rd1 mice through modulation of the immunological function of glia.

    Science.gov (United States)

    He, Xiao; Sun, Dayu; Chen, Siyu; Xu, Haiwei

    2017-05-09

    Retinal degeneration (RD), including retinitis pigmentosa (RP), is an inherited eye disease characterized by progressive degeneration of photoreceptors. Recently, immune cells, including microglia, Müller cells and astrocytes, in degenerative retina are demonstrated to play key roles in the development of RD and can be used as potential therapeutic targets. Liver X receptors (LXRs) are important immuno-inflammatory response transcription factors that have been reported to be a new potential therapeutic drug target for neurodegenerative diseases. However, the potential therapeutic utility of LXRs for RP has not been evaluated. In the present study, Pde6β (rd1) mice received intraperitoneal injections of T0901317 (T0, 50 mg/kg/d) or vehicle (2% DMSO) for 7 days with age-matched C57/BL6 mice as controls. The effect of T0 was examined by quantitating photoreceptor apoptosis, microglial density and the expression of inflammatory mediators; the underlying mechanisms were then explored with a microarray assay. T0 markedly delayed apoptosis of the photoreceptors, partially through suppressing the activation of microglia and the gliosis of Müller cells, and decreased the expression levels of IL-6, iNOS, COX-2 and ENG in rd1 mice; as a result, the visual function of T0-treated rd1 mice measured with electroretinograms (ERG) was preserved for a longer time than that of vehicle-treated rd1 mice. The microarray assay showed that the Janus kinase/Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway was significantly affected in the retina of rd1 mice with T0 treatment. Our data suggested that T0 modulated the immunologic function of glia cells in the degenerative retina through the JAK3/STAT pathway and delayed the apoptosis of photoreceptors.

  4. Primary immune system responders to nucleus pulposus cells: evidence for immune response in disc herniation

    Directory of Open Access Journals (Sweden)

    K Murai

    2010-01-01

    Full Text Available Although intervertebral disc herniation and associated sciatica is a common disease, its molecular pathogenesis is not well understood. Immune responses are thought to be involved. This study provides direct evidence that even non-degenerated nucleus pulposus (NP cells elicit immune responses. An in vitro colony forming inhibition assay demonstrated the suppressive effects of autologous spleen cells on NP cells and an in vitro cytotoxicity assay showed the positive cytotoxic effects of natural killer (NK cells and macrophages on NP cells. Non-degenerated rat NP tissues transplanted into wild type rats and immune-deficient mice demonstrated a significantly higher NP cell survival rate in immune-deficient mice. Immunohistochemical staining showed the presence of macrophages and NK cells in the transplanted NP tissues. These results suggest that even non-degenerated autologous NP cells are recognized by macrophages and NK cells, which may have an immunological function in the early phase of disc herniation. These findings contribute to understanding resorption and the inflammatory reaction to disc herniation.

  5. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    and significant relationships between radiological findings and subjective symptoms have both been notoriously difficult to identify. The lack of consensus on clinical criteria and radiological definitions has hampered the undertaking of properly executed epidemiological studies. The natural history of LBP...... is cyclic: exacerbations relieved by asymptomatic periods. New imaging modalities, including the combination of MR imaging and multiplanar 3-D CT scans, have broadened our awareness of possible pain-generating degenerative processes of the lumbar spine other than disc degeneration....

  6. Lipoprotein(A) with An Intact Lysine Binding Site Protects the Retina From an Age-Related Macular Degeneration Phenotype in Mice (An American Ophthalmological Society Thesis)

    Science.gov (United States)

    Handa, James T.; Tagami, Mizuki; Ebrahimi, Katayoon; Leibundgut, Gregor; Janiak, Anna; Witztum, Joseph L.; Tsimikas, Sotirios

    2015-01-01

    Purpose: To test the hypothesis that the accumulation of oxidized phospholipids (OxPL) in the macula is toxic to the retina unless neutralized by a variety of mechanisms, including binding by lipoprotein(a) [Lp(a)], which is composed of apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apoB). Methods: Human maculas and eyes from two Lp(a) transgenic murine models were subjected to morphologic, ultrastructural, and immunohistochemical analysis. “Wild-type Lp(a)” mice, which express human apoB-100 and apo(a) that contains oxidized phospholipid, and “mutant LBS− Lp(a)” mice with a defective apo(a) lysine binding site (LBS) for oxidized phospholipid binding, were fed a chow or high-fat diet for 2 to 12 months. Oxidized phospholipid–containing lipoproteins were detected by immunoreactivity to E06, a murine monoclonal antibody binding to the phosphocholine headgroup of oxidized, but not native, phospholipids. Results: Oxidized phospholipids, apo(a), and apoB accumulate in maculas, including drusen, of age-related macular degeneration (AMD) samples and age-matched controls. Lp(a) mice fed a high-fat diet developed age-related changes. However, mutant LBS− Lp(a) mice fed a high-fat diet developed retinal pigment epithelial cell degeneration and drusen. These changes were associated with increased OxPL, decreased antioxidant defenses, increased complement, and decreased complement regulators. Conclusions: Human maculas accumulate Lp(a) and OxPL. Mutant LBS− Lp(a) mice, lacking the ability to bind E06-detectable oxidized phospholipid, develop AMD-like changes. The ability of Lp(a) to bind E06-detectable OxPL may play a protective role in AMD. PMID:26538774

  7. Anterior cervical discectomy with fusion in patients with cervical disc degeneration: a prospective outcome study of 258 patients (181 fused with autologous bone graft and 77 fused with a PEEK cage)

    Science.gov (United States)

    2010-01-01

    Background Anterior cervical discectomy with fusion (ACDF) is challenging with respect to both patient selection and choice of surgical procedure. The aim of this study was to evaluate the clinical outcome of ACDF, with respect to both patient selection and choice of surgical procedure: fusion with an autologous iliac crest graft (AICG) versus fusion with an artificial cage made of polyetheretherketone (PEEK). Methods This was a non-randomized prospective single-center outcome study of 258 patients who underwent ACDF for cervical disc degeneration (CDD). Fusion was attained with either tricortical AICG or PEEK cages without additional anterior plating, with treatment selected at surgeon's discretion. Radicular pain, neck-pain, headache and patient satisfaction with the treatment were scored using the visual analogue scale (VAS). Results The median age was 47.5 (28.3-82.8) years, and 44% of patients were female. 59% had single-level ACDF, 40% had two level ACDF and 1% had three-level ACDF. Of the patients, 181 were fused with AICG and 77 with a PEEK-cage. After surgery, the patients showed a significant reduction in radicular pain (ΔVAS = 3.05), neck pain (ΔVAS = 2.30) and headache (ΔVAS = 0.55). Six months after surgery, 48% of patients had returned to work: however 24% were still receiving workers' compensation. Using univariate and multivariate analyses we found that high preoperative pain intensity was significantly associated with a decrease in pain intensity after surgery, for all three pain categories. There were no significant correlations between pain relief and the following patient characteristics: fusion method (AICG or PEEK-cage), sex, age, number of levels fused, disc level fused, previous neck surgery (except for neck pain), previous neck trauma, or preoperative symptom duration. Two hundred out of the 256 (78%) patients evaluated the surgical result as successful. Only 27/256 (11%) classified the surgical result as a failure. Patient satisfaction

  8. Anterior cervical discectomy with fusion in patients with cervical disc degeneration: a prospective outcome study of 258 patients (181 fused with autologous bone graft and 77 fused with a PEEK cage

    Directory of Open Access Journals (Sweden)

    Roenning Paal

    2010-03-01

    Full Text Available Abstract Background Anterior cervical discectomy with fusion (ACDF is challenging with respect to both patient selection and choice of surgical procedure. The aim of this study was to evaluate the clinical outcome of ACDF, with respect to both patient selection and choice of surgical procedure: fusion with an autologous iliac crest graft (AICG versus fusion with an artificial cage made of polyetheretherketone (PEEK. Methods This was a non-randomized prospective single-center outcome study of 258 patients who underwent ACDF for cervical disc degeneration (CDD. Fusion was attained with either tricortical AICG or PEEK cages without additional anterior plating, with treatment selected at surgeon's discretion. Radicular pain, neck-pain, headache and patient satisfaction with the treatment were scored using the visual analogue scale (VAS. Results The median age was 47.5 (28.3-82.8 years, and 44% of patients were female. 59% had single-level ACDF, 40% had two level ACDF and 1% had three-level ACDF. Of the patients, 181 were fused with AICG and 77 with a PEEK-cage. After surgery, the patients showed a significant reduction in radicular pain (ΔVAS = 3.05, neck pain (ΔVAS = 2.30 and headache (ΔVAS = 0.55. Six months after surgery, 48% of patients had returned to work: however 24% were still receiving workers' compensation. Using univariate and multivariate analyses we found that high preoperative pain intensity was significantly associated with a decrease in pain intensity after surgery, for all three pain categories. There were no significant correlations between pain relief and the following patient characteristics: fusion method (AICG or PEEK-cage, sex, age, number of levels fused, disc level fused, previous neck surgery (except for neck pain, previous neck trauma, or preoperative symptom duration. Two hundred out of the 256 (78% patients evaluated the surgical result as successful. Only 27/256 (11% classified the surgical result as a failure

  9. Nuclei pulposi formation from the embryonic notochord occurs normally in GDF-5-deficient mice.

    Science.gov (United States)

    Maier, Jennifer A; Harfe, Brian D

    2011-11-15

    The transition of the mouse embryonic notochord into nuclei pulposi was determined ("fate mapped") in vivo in growth and differentiating factor-5 (GDF-5)-null mice using the Shhcre and R26R alleles. To determine whether abnormal nuclei pulposi formation from the embryonic notochord was responsible for defects present in adult nuclei pulposi of Gdf-5-null mice. The development, maintenance, and degeneration of the intervertebral disc are not understood. Previously, we demonstrated that all cells in the adult nucleus pulposus of normal mice are derived from the embryonic notochord. Gdf-5-null mice have been reported to contain intervertebral discs in which the nucleus pulposus is abnormal. It is currently unclear if disc defects in Gdf-5-null mice arise during the formation of nuclei pulposi from the notochord during embryogenesis or result from progressive postnatal degeneration of nuclei pulposi. Gdf-5 messenger RNA expression was examined in the discs of wild-type embryos by RNA in situ hybridization to determine when and where this gene was expressed. To examine nucleus pulposus formation in Gdf-5-null mice, intervertebral discs in which embryonic notochord cells were marked were analyzed in newborn and 24-week-old mice. Our Gdf-5 messenger RNA in situ experiments determined that this gene is localized to the annulus fibrosus and not the nucleus pulposus in mouse embryos. Notochord fate-mapping experiments revealed that notochord cells in Gdf-5-null mice correctly form nuclei pulposi. Our data suggest that the defects reported in the nucleus pulposus of adult Gdf-5-null mice do not result from abnormal patterning of the embryonic notochord. The use of mouse alleles to mark cells that produce all cell types that reside in the adult nucleus pulposus will allow for a detailed examination of disc formation in other mouse mutants that have been reported to contain disc defects.

  10. Grafted c-kit+/SSEA1- eye-wall progenitor cells delay retinal degeneration in mice by regulating neural plasticity and forming new graft-to-host synapses.

    Science.gov (United States)

    Chen, Xi; Chen, Zehua; Li, Zhengya; Zhao, Chen; Zeng, Yuxiao; Zou, Ting; Fu, Caiyun; Liu, Xiaoli; Xu, Haiwei; Yin, Zheng Qin

    2016-12-30

    Despite diverse pathogenesis, the common pathological change observed in age-related macular degeneration and in most hereditary retinal degeneration (RD) diseases is photoreceptor loss. Photoreceptor replacement by cell transplantation may be a feasible treatment for RD. The major obstacles to clinical translation of stem cell-based cell therapy in RD remain the difficulty of obtaining sufficient quantities of appropriate and safe donor cells and the poor integration of grafted stem cell-derived photoreceptors into the remaining retinal circuitry. Eye-wall c-kit + /stage-specific embryonic antigen 1 (SSEA1) - cells were isolated via fluorescence-activated cell sorting, and their self-renewal and differentiation potential were detected by immunochemistry and flow cytometry in vitro. After labeling with quantum nanocrystal dots and transplantation into the subretinal space of rd1 RD mice, differentiation and synapse formation by daughter cells of the eye-wall c-kit + /SSEA1 - cells were evaluated by immunochemistry and western blotting. Morphological changes of the inner retina of rd1 mice after cell transplantation were demonstrated by immunochemistry. Retinal function of rd1 mice that received cell grafts was tested via flash electroretinograms and the light/dark transition test. Eye-wall c-kit + /SSEA1 - cells were self-renewing and clonogenic, and they retained their proliferative potential through more than 20 passages. Additionally, eye-wall c-kit + /SSEA1 - cells were capable of differentiating into multiple retinal cell types including photoreceptors, bipolar cells, horizontal cells, amacrine cells, Müller cells, and retinal pigment epithelium cells and of transdifferentiating into smooth muscle cells and endothelial cells in vitro. The levels of synaptophysin and postsynaptic density-95 in the retinas of eye-wall c-kit + /SSEA1 - cell-transplanted rd1 mice were significantly increased at 4 weeks post transplantation. The c-kit + /SSEA1 - cells were

  11. Artificial Disc Replacement

    Science.gov (United States)

    ... Spondylolisthesis BLOG FIND A SPECIALIST Treatments Artificial Disc Replacement (ADR) Patient Education Committee Jamie Baisden The disc ... Disc An artificial disc (also called a disc replacement, disc prosthesis or spine arthroplasty device) is a ...

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

    Science.gov (United States)

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

    2015-03-01

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

  13. Increased Oocyte Degeneration and Follicular Atresia during the Estrous Cycle in Anti-Müllerian Hormone Null Mice

    NARCIS (Netherlands)

    Visser, Jenny A.; Durlinger, Alexandra L.L.; Peters, Isolde J.J.; Heuvel, Edwin R. van den; Rose, Ursula M.; Kramer, Piet; Jong, Frank H. de; Themmen, Axel P.N.

    2007-01-01

    Anti-Müllerian hormone (AMH) plays an important role in folliculogenesis. AMH null mice display an increased recruitment of primordial follicles. Nevertheless, these mice do not have proportionally more preovulatory follicles. Therefore, AMH null mice provide an interesting genetic model to study

  14. Cfh genotype interacts with dietary glycemic index to modulate age-related macular degeneration-like features in mice

    Science.gov (United States)

    Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide. Genetics and diet contribute to the relative risk for developing AMD, but their interactions are poorly understood. Genetic variations in Complement Factor H (CFH), and dietary glycemic index (GI) are major ris...

  15. MR findings of degenerative changes of nucleus pulposus in lumbar spine: sequential changes after disc herniation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Joon [Choong-Ang Gil Hospital, Seoul (Korea, Republic of); Cha, Yoo Mi; Hwang, Hee Young [College of Medicine, Dankook University, Chenoan (Korea, Republic of)

    1994-04-15

    To evaluate the relationship between MR changes of the nucleus pulposus and the time interval after traumatic disc herniation. T2-weighted MR images of 132 patients with back pain and/or sciatica were reviewed. The changes of signal intensity, central cleft and height of the nucleus pulposus were used as criteria of disc degeneration and they were graded as normal, mild, moderate and severe degree of degeneration. Putting these criteria together we provided integrated grade of degeneration of the nucleus pulposus(grade 0-3). To get the preliminary data for normal and age-related disc degeneration, we measured the disc height by age groups and disc levels and analyzed the relationship between the age of the patients and the signal intensity, cleft and height in normal disc levels of the 132 patients. In 68 patients of 88 levels disc herniation, we analyzed the relationship between symptom duration and the degree of degeneration. Among these 68 patients we selected 14 patients(16 levels) who were under 30 years of age and had history of recent trauma to minimize data distortion from age related degeneration and ambiguity of initiation point of degeneration. In this group we analyzed the relationship between the time period after traumatic disc herniation and the degree of degeneration. The age of the patient had close relationship with the grade of signal intensity, central cleft, and disc height and grade of degeneration of the nucleus pulposus in normal discs. In 88 levels of herniated discs, the duration of symptom and degree of degeneration showed moderate correlation. In 14 patients of disc herniation who were under 30 years old and had trauma history in recent 2 years, grade 1 disc degeneration occurred in average 3.7 months after trauma. Although it was difficult to proceed statistical analysis in the last group because of small patients number, the degree of degeneration of nucleus pulposus had close relationship with the duration after traumas or duration of

  16. MR findings of degenerative changes of nucleus pulposus in lumbar spine: sequential changes after disc herniation

    International Nuclear Information System (INIS)

    Kim, Sang Joon; Cha, Yoo Mi; Hwang, Hee Young

    1994-01-01

    To evaluate the relationship between MR changes of the nucleus pulposus and the time interval after traumatic disc herniation. T2-weighted MR images of 132 patients with back pain and/or sciatica were reviewed. The changes of signal intensity, central cleft and height of the nucleus pulposus were used as criteria of disc degeneration and they were graded as normal, mild, moderate and severe degree of degeneration. Putting these criteria together we provided integrated grade of degeneration of the nucleus pulposus(grade 0-3). To get the preliminary data for normal and age-related disc degeneration, we measured the disc height by age groups and disc levels and analyzed the relationship between the age of the patients and the signal intensity, cleft and height in normal disc levels of the 132 patients. In 68 patients of 88 levels disc herniation, we analyzed the relationship between symptom duration and the degree of degeneration. Among these 68 patients we selected 14 patients(16 levels) who were under 30 years of age and had history of recent trauma to minimize data distortion from age related degeneration and ambiguity of initiation point of degeneration. In this group we analyzed the relationship between the time period after traumatic disc herniation and the degree of degeneration. The age of the patient had close relationship with the grade of signal intensity, central cleft, and disc height and grade of degeneration of the nucleus pulposus in normal discs. In 88 levels of herniated discs, the duration of symptom and degree of degeneration showed moderate correlation. In 14 patients of disc herniation who were under 30 years old and had trauma history in recent 2 years, grade 1 disc degeneration occurred in average 3.7 months after trauma. Although it was difficult to proceed statistical analysis in the last group because of small patients number, the degree of degeneration of nucleus pulposus had close relationship with the duration after traumas or duration of

  17. Retina image–based optic disc segmentation

    Directory of Open Access Journals (Sweden)

    Ching-Lin Wang

    2016-05-01

    Full Text Available The change of optic disc can be used to diagnose many eye diseases, such as glaucoma, diabetic retinopathy and macular degeneration. Moreover, retinal blood vessel pattern is unique for human beings even for identical twins. It is a highly stable pattern in biometric identification. Since optic disc is the beginning of the optic nerve and main blood vessels in retina, it can be used as a reference point of identification. Therefore, optic disc segmentation is an important technique for developing a human identity recognition system and eye disease diagnostic system. This article hence presents an optic disc segmentation method to extract the optic disc from a retina image. The experimental results show that the optic disc segmentation method can give impressive results in segmenting the optic disc from a retina image.

  18. Physical Limitations to Tissue Engineering of Intervertabral Disc Cells

    OpenAIRE

    Kobayashi, Shigeru; Baba, Hisatoshi; Takeno, Kenichi; Miyazaki, Tsuyoshi; Meir, Adam; Urban, Jill

    2010-01-01

    There is increasing interest in the using biological methods to repair degenerate discs. Biological repair depends on the disc maintaining a population of viable and active cells. Adequate nutrition of the disc influences the outcome of such therapies and, hence, must be considered to be a crucial parameter. Therefore, it is very important to maintain an appropriate physicochemical environment to achieve successful disc repair by biological methods and tissue engineering procedures.

  19. Loss of Function of P2X7 Receptor Scavenger Activity in Aging Mice: A Novel Model for Investigating the Early Pathogenesis of Age-Related Macular Degeneration.

    Science.gov (United States)

    Vessey, Kirstan A; Gu, Ben J; Jobling, Andrew I; Phipps, Joanna A; Greferath, Ursula; Tran, Mai X; Dixon, Michael A; Baird, Paul N; Guymer, Robyn H; Wiley, James S; Fletcher, Erica L

    2017-08-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible, severe vision loss in Western countries. Recently, we identified a novel pathway involving P2X7 receptor scavenger function expressed on ocular immune cells as a risk factor for advanced AMD. In this study, we investigate the effect of loss of P2X7 receptor function on retinal structure and function during aging. P2X7-null and wild-type C57bl6J mice were investigated at 4, 12, and 18 months of age for macrophage phagocytosis activity, ocular histological changes, and retinal function. Phagocytosis activity of blood-borne macrophages decreased with age at 18 months in the wild-type mouse. Lack of P2X7 receptor function reduced phagocytosis at all ages compared to wild-type mice. At 12 months of age, P2X7-null mice had thickening of Bruchs membrane and retinal pigment epithelium dysfunction. By 18 months of age, P2X7-null mice displayed phenotypic characteristics consistent with early AMD, including Bruchs membrane thickening, retinal pigment epithelium cell loss, retinal functional deficits, and signs of subretinal inflammation. Our present study shows that loss of function of the P2X7 receptor in mice induces retinal changes representing characteristics of early AMD, providing a valuable model for investigating the role of scavenger receptor function and the immune system in the development of this age-related disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Using Patient-Specific Induced Pluripotent Stem Cells and Wild-Type Mice to Develop a Gene Augmentation-Based Strategy to Treat CLN3-Associated Retinal Degeneration.

    Science.gov (United States)

    Wiley, Luke A; Burnight, Erin R; Drack, Arlene V; Banach, Bailey B; Ochoa, Dalyz; Cranston, Cathryn M; Madumba, Robert A; East, Jade S; Mullins, Robert F; Stone, Edwin M; Tucker, Budd A

    2016-10-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL) is a childhood neurodegenerative disease with early-onset, severe central vision loss. Affected children develop seizures and CNS degeneration accompanied by severe motor and cognitive deficits. There is no cure for JNCL, and patients usually die during the second or third decade of life. In this study, independent lines of induced pluripotent stem cells (iPSCs) were generated from two patients with molecularly confirmed mutations in CLN3, the gene mutated in JNCL. Clinical-grade adeno-associated adenovirus serotype 2 (AAV2) carrying the full-length coding sequence of human CLN3 was generated in a U.S. Food and Drug Administration-registered cGMP facility. AAV2-CLN3 was efficacious in restoring full-length CLN3 transcript and protein in patient-specific fibroblasts and iPSC-derived retinal neurons. When injected into the subretinal space of wild-type mice, purified AAV2-CLN3 did not show any evidence of retinal toxicity. This study provides proof-of-principle for initiation of a clinical trial using AAV-mediated gene augmentation for the treatment of children with CLN3-associated retinal degeneration.

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

    Science.gov (United States)

    Liang, Hang; Deng, Xiangyu; Shao, Zengwu

    2017-10-01

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

  2. Influence of degenerative changes of intervertebral disc

    Directory of Open Access Journals (Sweden)

    WANG Yi

    2012-04-01

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

  3. Striatonigral Degeneration

    Science.gov (United States)

    ... See More About Research The NINDS supports and conducts research on disorders of the brain and nervous system such as striatonigral degeneration. This research ... Publications Definition Striatonigral ...

  4. Peripheral motor axons of SOD1(G127X) mutant mice are susceptible to activity-dependent degeneration

    DEFF Research Database (Denmark)

    Alvarez Herrero, Susana; Calin, A; Graffmo, K S

    2013-01-01

    -onset, fast-progression SOD1(G127X) mouse model of amyotrophic lateral sclerosis to long-lasting, high-frequency repetitive activity. Tibial nerves were stimulated at ankle in 7 to 8-month-old SOD1(G127X) mice when they were clinically indistinguishable from wild-type (WT) mice. The evoked compound muscle......-concentrations. It is possible that in SOD1(G127X) there is inadequate energy-dependent Na(+)/K(+) pumping, which may lead to a lethal Na(+) overload....

  5. Local intra-articular injection of resveratrol delays cartilage degeneration in C57BL/6 mice by inducing autophagy via AMPK/mTOR pathway.

    Science.gov (United States)

    Qin, Na; Wei, Liwei; Li, Wuyin; Yang, Wei; Cai, Litao; Qian, Zhuang; Wu, Shufang

    2017-07-01

    Autophagy is an essential cellular homeostasis mechanism that was found to be compromised in aging and osteoarthritis (OA) cartilage. Previous studies showed that resveratrol can effectively regulate autophagy in other cells. The purpose of this study was to determine whether the chondroprotective effect of resveratrol was related to chondrocyte autophagy and to elucidate underlying mechanisms. OA model was induced by destabilization of the medial meniscus (DMM) in 10-week-old male mice. OA mice were treated with resveratrol with/without 3-MA for 8 weeks beginning 4 weeks after surgery. The local intra-articular injection of resveratrol delayed articular cartilage degradation in DMM-induced OA by OARSI scoring systems and Safranin O-fast green. Resveratrol treatment increased Unc-51-like kinase1, Beclin1, microtubule-associated protein light chain 3, hypoxia inducible factor-1α, phosphorylated AMPK, collagen-2A1, Aggrecan expressions, but decreased hypoxia inducible factor-2α, phosphorylated mTOR, matrix metalloproteinases13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 expressions. The effects of resveratrol were obviously blunted by 3-MA except HIF and AMPK. These findings indicate that resveratrol intra-articular injection delayed articular cartilage degeneration and promoted chondrocyte autophagy in an experimental model of surgical DMM-induced OA, in part via balancing HIF-1α and HIF-2α expressions and thereby regulating AMPK/mTOR signaling pathway. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  6. Dihydrotestosterone ameliorates degeneration in muscle, axons and motoneurons and improves motor function in amyotrophic lateral sclerosis model mice.

    Directory of Open Access Journals (Sweden)

    Young-Eun Yoo

    Full Text Available Amyotrophic lateral sclerosis (ALS is a lethal disease characterized by a progressive loss of motoneurons. The clinical symptoms include skeletal muscle weakness and atrophy, which impairs motor performance and eventually leads to respiratory failure. We tested whether dihydrotestosterone (DHT, which has both anabolic effects on muscle and neuroprotective effects on axons and motoneurons, can ameliorate clinical symptoms in ALS. A silastic tube containing DHT crystals was implanted subcutaneously in SOD1-G93A mice at early symptomatic age when decreases in body weight and grip-strength were observed as compared to wild-type mice. DHT-treated SOD1-G93A mice demonstrated ameliorated muscle atrophy and increased body weight, which was associated with stronger grip-strength. DHT treatment increased the expression of insulin-like growth factor-1 in muscle, which can exert myotrophic as well as neurotrophic effects through retrograde transport. DHT treatment attenuated neuromuscular junction denervation, and axonal and motoneuron loss. DHT-treated SOD1-G93A mice demonstrated improvement in motor behavior as assessed by rota-rod and gait analyses, and an increased lifespan. Application of DHT is a relatively simple and non-invasive procedure, which may be translated into therapy to improve the quality of life for ALS patients.

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

    Science.gov (United States)

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

    2005-12-01

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

  8. Accumulation of Misfolded SOD1 in Dorsal Root Ganglion Degenerating Proprioceptive Sensory Neurons of Transgenic Mice with Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Javier Sábado

    2014-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is an adult-onset progressive neurodegenerative disease affecting upper and lower motoneurons (MNs. Although the motor phenotype is a hallmark for ALS, there is increasing evidence that systems other than the efferent MN system can be involved. Mutations of superoxide dismutase 1 (SOD1 gene cause a proportion of familial forms of this disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a noncell autonomous manner, as evidenced in studies using transgenic mouse models. Here, we used the SOD1G93A mouse model for ALS to detect, by means of conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated neurotoxicity extended to neuronal types other than MNs. We report that large dorsal root ganglion (DRG proprioceptive neurons accumulate misfolded SOD1 and suffer a degenerative process involving the inflammatory recruitment of macrophagic cells. Degenerating sensory axons were also detected in association with activated microglial cells in the spinal cord dorsal horn of diseased animals. As large proprioceptive DRG neurons project monosynaptically to ventral horn MNs, we hypothesise that a prion-like mechanism may be responsible for the transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory neurons.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Valdeci Manoel de Oliveira

    2007-01-01

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

  11. Cerebellar Degeneration

    Science.gov (United States)

    ... FARA) National Ataxia Foundation (NAF) National Multiple Sclerosis Society See all related organizations Publications Degeneración cerebelosa Order NINDS Publications Definition Cerebellar degeneration is a process in which neurons ( ...

  12. Macular degeneration

    Science.gov (United States)

    The macula is the part of the retina that distinguishes fine details at the center of the field of vision. Macular degeneration results from a partial breakdown of the insulating layer between the retina and the choroid layer of ...

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

    Science.gov (United States)

    2017-09-14

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

  14. Burned-out discs stop hurting: fact or fiction?

    DEFF Research Database (Denmark)

    Bendix, Tom; Kjær, Per; Korsholm, Lars

    2008-01-01

      STUDY DESIGN: Cross-sectional study of a general-population sample. OBJECTIVE: The aim was to test the hypothesis that moderate disc degeneration (DD) is stronger associated with low back pain (LBP) than severe degeneration, and also to identify a possible dose-response relationship between num...

  15. Disc defect classification for optical disc drives

    NARCIS (Netherlands)

    Helvoirt, van J.; Leenknegt, G.A.L.; Steinbuch, M.; Goossens, H.J.

    2005-01-01

    Optical disc drives are subject to various disturbances and faults. A special type of fault is the so-called disc defect. In this paper we present an approach for disc defect classification. It is based on hierarchical clustering of measured signals that are affected by disc defects. The

  16. Influence of osmotic pressure changes on the opening of existing cracks in 2 intervertebral disc models

    NARCIS (Netherlands)

    Wognum, Silvia; Huyghe, Jacques M.; Baaijens, Frank P. T.

    2006-01-01

    An experimental hydrogel model and a numerical mixture model were used to investigate why the disc herniates while osmotic pressure is decreasing. To investigate the influence of decreasing osmotic pressure on the opening of cracks in the disc. In the degeneration process, the disc changes structure

  17. Regional disc change in segmental hypoplasia of the lumbosacral vertebral bodies: MR findings

    International Nuclear Information System (INIS)

    Kim, Sung Kyu; Lee Seung Ro; Moon, Won Jin; Park, Dong Woo; Hahm, Chang Kok

    2000-01-01

    To classify types of vertebral hypoplasia and to investigate the prevalence and patterns of associated disc degeneration. Defining vertebral hypoplasia as occurring when the AP diameter of a lower vertebral body is smaller than that of an upper ones, we retrospectively reviewed the MR images obtained in 34 cases of this condition involving young adults. Two major types and two subtypes, a total of four different entities were classified as follows; type I: hypoplasia involving a single vertebral body; type II: hypoplasia involving serial lower segmental vertebral bodies; subtype a: hypoplastic body located anteriorly along the anterior spinal line; subtype b: hypoplastic body located posteriorly along the posterior spinal line. We also investigated each type of vertebral hypoplasia and patterns of associated disc changes. Three different types were observed. In type IIa (n=3D29), posterior disc occurred in 8/29 cases, diffuse degeneration in 21/29 patients, and posterior disc herniation in all. All type Ia cases (3/3) showed diffuse disc degeneration at both upper and lower disc levels, with posterior disc herniation, while both type IIb cases (2/2) showed diffuse disc degeneration, with bidirectional disc herniation. By identifying the exact patterns of vertebral hypoplasia, we were able to predict which portion of the disc was likely to degenerate. (author)

  18. Nucleoplasty as a therapeutic option for lumbar disc degeneration related pain: a retrospective study of 396 cases Nucleoplastia como opção terapêutica para dor relacionada à degeneração do disco lombar: um estudo retrospectivo de 396 casos

    Directory of Open Access Journals (Sweden)

    José Lourenço Kallás

    2013-01-01

    Full Text Available OBJECTIVES: To make a retrospective analysis and evaluate a clinical response to the control of disc degeneration related pain of 396 patients submitted to percutaneous lumbar nucleoplasty; and to make a record of visual analogical scale (VAS up to a three-year follow-up after the surgical procedure. METHODS: Analysis of VAS score in 396 patients with lumbar disc degeneration related pain, according to anamnesis, clinical examination and magnetic resonance imaging (MRI, without improvement of previous clinical treatment, submitted to percutaneous nucleoplasty. RESULTS: A total of 26% of the patients presented 100% remission of pain or paresthesia, of whom 75% showed at least 50% of pain improvement. The median VAS pain improvement was about 67%. CONCLUSIONS: The median VAS improvement in inferior disc levels was higher than four points. The VAS showed improvement of the pain and paresthesia up to a three-year follow up after the surgical procedure.OBJETIVOS: Analisar retrospectivamente a resposta clínica no controle da dor relacionada à degeneração discal em 396 pacientes submetidos à nucleoplastia percutânea lombar; e fazer um registro da escala analógica visual (EAV com seguimento de três anos após a cirurgia. MÉTODOS: Análise da EAV de 396 pacientes com diagnóstico de hérnia de disco, de acordo com anamnese, exame clínico e imagens por meio de ressonância magnética (RM, sendo que nenhum deles apresentou melhora com tratamento clínico prévio. Estes pacientes foram submetidos à nucleoplastia percutânea. O estudo utilizou, para avaliação, o registro de escala analógica visual (EAV durante seguimento de até três anos após o procedimento cirúrgico. RESULTADOS: Um total de 26% apresentou 100% de remissão da dor ou parestesia; 75% apresentaram pelo menos 50% de melhora da dor. A mediana da EAV de melhora da dor foi de aproximadamente 67%. CONCLUSÕES: Houve melhora da EAV, com mediana maior do que quatro pontos nos

  19. Radiological assessment of loss of disc height during acute and chronic degenerative lumbar disc alterations

    International Nuclear Information System (INIS)

    Zoellner, J.; Sancaktaroglu, T.; Nafe, B.; Eysel, P.; Loew, R.

    2001-01-01

    Aim of the study: A loss of disc height with increasing segmental mobility is an important reason for low back pain. The measurement of hyaluronic acid content of the nucleus pulposus prolaps shows a difference between acute (group 1) and chronic (group 2) disc degeneration. The purpose of the present investigation was to determine the decreasing of disc height between these two groups and the no-symptomatic segments of these patients. Methods: 20 human lateral preoperative X-ray measurements according to Frobin et al. were taken; group 1 with 7 patients (mean age 41 years) and group 2 with 13 patients (mean age 44 years). Results: There was a significant tendency (p=0.091) to a reduction of disc height in group 2 between symptomatic and asymptomatic discs. Conclusion: The used method is not suitable to answer the present question conclusively. (orig.) [de

  20. Thoracic spine disc-related abnormalities: longitudinal MR imaging assessment

    Energy Technology Data Exchange (ETDEWEB)

    Girard, Charles J.; Schweitzer, Mark E.; Morrison, William B.; Parellada, Joan A. [TJUH Radiology, Philadelphia, Pennsylvania (United States); Carrino, J.A. [Department of Radiology ASB-1, Harvard Medical School, Brigham and Women' s Hospital, L1, Room 002B, 75 Francis Street, MA 02115, Boston (United States)

    2004-04-01

    To describe and characterize the temporal changes in disc-related disorders of the thoracic spine using MR imaging. A retrospective longitudinal cohort study was carried out of 40 patients with two sequential thoracic spine MR images at variable intervals. The images were assessed for baseline presence of, new incidence of and changes in disc herniation, degenerative disc disease, endplate marrow signal alteration and Schmorl nodes. The range of follow-up was 4-149 weeks. Baseline presence was: disc herniation, 10% (49/480); degenerative disc disease, 14% (66/480); endplate marrow signal alteration, 2.3% (11/480); Schmorl nodes 9.6% (46/480). Most pre-existing lesions tended to remain unchanged. Herniations showed the most change, tending to improve in 27%. New incidence was: disc herniation, 1.5% (7/480), degenerative disc disease, 2% (10/480); endplate marrow signal alteration, 1.6% (8/480); Schmorl nodes, 2.1% (10/480). Disc degeneration was first visible at an 11-week interval and once established almost never changed over many weeks to months. Endplate signal alterations (Modic changes) were uncommon. Schmorl nodes show no change from baseline for up to 2 1/2 years. All findings predominated in the lower intervertebral levels from T6 to T10. The most prevalent thoracic spine disc-related findings are degeneration and herniation. Disc herniations predominate in the lower segments and are a dynamic phenomenon. Disc degeneration can be rapidly evolving but tends to remain unchanged after occurrence. Endplate marrow signal changes were an uncommon manifestation of thoracic disc disease. Schmorl nodes showed the least change over time. (orig.)

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

    OpenAIRE

    Mwale F.; Roughley P.; Antoniou J.

    2004-01-01

    Tissue engineering of intervertebral discs (IVD) using mesenchymal stem cells (MSCs) induced to differentiate into a disc-cell phenotype has been considered as an alternative treatment for disc degeneration. However, since there is no unique marker characteristic of discs and since hyaline cartilage and immature nucleus pulposus (NP) possess similar macromolecules in their extracellular matrix, it is currently difficult to recognize MSC conversion to a disc cell. This study was performed to c...

  2. Cells and Biomaterials for Intervertebral Disc Regeneration

    CERN Document Server

    Grad, Sibylle

    2010-01-01

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

  3. The comparative study of lumbar disc disruption with MRI and CT discography

    International Nuclear Information System (INIS)

    Chen Xingcan; Liu Naifang; Li Xiaohong; Xu Wengen; Zou Qing; Yang Yonghong

    2005-01-01

    Objective: To compare MRI with CT discography (CTD) for diagnostic assessment of lumbar disc disruption. Methods: Paired comparative examination in 16 patients with chronic lower back pain without radicular pain and no disc herniation was conducted using CT or MRI. The standard of CTD classification and positive disc was formulated and the correlation between the induced lower back pain and dosage used in CTD was observed. Results: For a total of 21 discs in the 16 patients, CTD showed the disc as type 2 in 12 discs and type 5 in 1 disc with 13 positive discs, while MRI only showed the high-intensity zone of posterior annulus in 6 discs as the indirect sign of disc disruption and disc degeneration in 7 discs. Conclusion: CTD was the only method for showing the direct sign of disc disruption. The induced lower back pain was related with the type of disc disruption. MRI can show some of the indirect signs of disc disruption and CTD can show the direct sign of disc disruption. (authors)

  4. Cervical disc arthroplasty: Pros and cons.

    Science.gov (United States)

    Moatz, Bradley; Tortolani, P Justin

    2012-01-01

    Cervical disc arthroplasty has emerged as a promising potential alternative to anterior cervical discectomy and fusion (ACDF) in appropriately selected patients. Despite a history of excellent outcomes after ACDF, the question as to whether a fusion leads to adjacent segment degeneration remains unanswered. Numerous US investigational device exemption trials comparing cervical arthroplasty to fusion have been conducted to answer this question. This study reviews the current research regarding cervical athroplasty, and emphasizes both the pros and cons of arthroplasty as compared with ACDF. Early clinical outcomes show that cervical arthroplasty is as effective as the standard ACDF. However, this new technology is also associated with an expanding list of novel complications. Although there is no definitive evidence that cervical disc replacement reduces the incidence of adjacent segment degeneration, it does show other advantages; for example, faster return to work, and reduced need for postoperative bracing.

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Jeremy Alsup

    2017-10-01

    The Translational Potential of this Article: 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.

  7. Spectroscopic Parameters of Lumbar Intervertebral Disc Material

    Science.gov (United States)

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

    2009-06-01

    needle can give additional information of needle position, assuring the needle tip is directed into intervertebral disc material. Spectroscopic analysis of intervertebral disc removed during open surgery, creates background for further investigation on intervertebral disc degeneration spectral classification.

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-02-01

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

  10. Can magnetic resonance imaging accurately predict concordant pain provocation during provocative disc injection?

    International Nuclear Information System (INIS)

    Kang, Chang Ho; Kim, Yun Hwan; Kim, Jung Hyuk; Chung, Kyoo Byung; Sung, Deuk Jae; Lee, Sang-Heon; Derby, Richard

    2009-01-01

    To correlate magnetic resonance (MR) image findings with pain response by provocation discography in patients with discogenic low back pain, with an emphasis on the combination analysis of a high intensity zone (HIZ) and disc contour abnormalities. Sixty-two patients (aged 17-68 years) with axial low back pain that was likely to be disc related underwent lumbar discography (178 discs tested). The MR images were evaluated for disc degeneration, disc contour abnormalities, HIZ, and endplate abnormalities. Based on the combination of an HIZ and disc contour abnormalities, four classes were determined: (1) normal or bulging disc without HIZ; (2) normal or bulging disc with HIZ; (3) disc protrusion without HIZ; (4) disc protrusion with HIZ. These MR image findings and a new combined MR classification were analyzed in the base of concordant pain determined by discography. Disc protrusion with HIZ [sensitivity 45.5%; specificity 97.8%; positive predictive value (PPV), 87.0%] correlated significantly with concordant pain provocation (P < 0.01). A normal or bulging disc with HIZ was not associated with reproduction of pain. Disc degeneration (sensitivity 95.4%; specificity 38.8%; PPV 33.9%), disc protrusion (sensitivity 68.2%; specificity 80.6%; PPV 53.6%), and HIZ (sensitivity 56.8%; specificity 83.6%; PPV 53.2%) were not helpful in the identification of a disc with concordant pain. The proposed MR classification is useful to predict a disc with concordant pain. Disc protrusion with HIZ on MR imaging predicted positive discography in patients with discogenic low back pain. (orig.)

  11. Radially truncated galactic discs

    NARCIS (Netherlands)

    Grijs, R. de; Kregel, M.; Wesson, K H

    2000-01-01

    Abstract: We present the first results of a systematic analysis of radially truncatedexponential discs for four galaxies of a sample of disc-dominated edge-onspiral galaxies. Edge-on galaxies are very useful for the study of truncatedgalactic discs, since we can follow their light distributions out

  12. Mechanical design criteria for intervertebral disc tissue engineering.

    Science.gov (United States)

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

    2010-04-19

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

  13. The distribution and degeneration pattern of the cone opsins in rd11 mice%rd11小鼠视锥细胞变性过程中视蛋白的变化特点

    Institute of Scientific and Technical Information of China (English)

    韩娟娟; 戴旭锋; 戚艳; 张华; 庞继景

    2014-01-01

    -视蛋白更为明显.随着鼠龄的增长,rd11小鼠M-视蛋白变性从视神经周围区向鼻下方,再向颞上方逐渐进展,而S-视蛋白变性由颞上方向鼻下方逐渐进展.%Background The retinal degeneration 11 (rd11) mouse is a newly discovered naturally occurring recessive animal model with lysophosphatidylcholine acyltransferase 1 (Lpcatl) mutation.Previous studies showed that the photoreceptor cells are characterized by typical rod-cone degeneration pattern in rd1 1 mice,while cone degeneration pattern in rd11 mice is unclcar.Objective Using immunofluorescence staining techniques with retinal wholemount,we aim to clarify the degeneration patterns of cone-function related M-opsin or S-opsin in different ages of rd1 1 mice.Methods A total of thirty rd1 1 and C57BL/6J mice at postnatal (P) day 14,28,42 (five in each age group) were sacrificed and retinal wholemounts were prepared.Immunohistochemistry was performed to identify the expression of M-opsin or S-opsin in retinal wholemounts,which were photographed with a fluorescent microscope.Cone opsins were compared between rd1 1 retinas and age-matched normal C57BL/6J retinas by manually counting the opsin positive cone cells in different quadrants of the retinas.Results The number of M-opsin or S-opsin positive fluorescent dots in each quadrant was similar at all ages of normal C57BL/6J retina.M-opsin positive fluorescent dots in dorsal/temporal,ventral/temporal,dorsal/nasal and ventral/nasal quadrants of rdl 1 retina at P28 were (414±32),(300± 8),(324 ± 22) and (250± 20)/0.037 mm2,which were lower than the age-matched normal C57BL/6J mice (t =4.114,15.225,7.505,17.990,all at P<0.05).At the same time the S-opsin positive fluorescent dots in P28 rd11 were (8 ±4),(175 ± 16),(74 ± 13) and (315 ±20)/0.037 mm2,with significant decrease in comparison with those in the age-matched normal C57BL/6J mice (t =8.555,17.076,21.637,13.498,all at P<0.05).With the development of retinal degeneration

  14. Trends analysis of surgical procedures for cervical degenerative disc disease and myelopathy in patients with tobacco use disorder.

    Science.gov (United States)

    Grisdela, Phillip; Buser, Zorica; D'Oro, Anthony; Paholpak, Permsak; Liu, John C; Wang, Jeffrey C

    2017-09-01

    This study defined the incidence and trends of surgeries performed for patients with cervical disc degeneration with and without tobacco use disorder (TUD). This study utilized the Humana Inc. database between 2007 and 2013 to identify patients with cervical disc degeneration with or without myelopathy. International Classification of Diseases, ninth revision (ICD-9) and Current Procedural Terminology (CPT) codes determined the initial diagnosis of disc degeneration, myelopathy status and TUD, whether patients received surgery, and TUD status at surgery. The prevalence of disc degeneration with myelopathy increased by 32.8% between 2007 and 2013, while disc disease with myelopathy and TUD increased by 91.6%. For patients without myelopathy, the prevalence of disc degeneration alone increased by 65.4%, and disc degeneration with myelopathy increased by 148.7%. Of myelopathy patients, 1717 (6.4%) had TUD and 1024 (59.6%) received surgery, compared to 6508 patients without TUD (26.1%). For patients without myelopathy, 11,337 (3.5%) had TUD and 787 (6.9%) underwent surgery, compared to 9716 patients (3%) without TUD. Of surgical patients, 781 (76.3%) with myelopathy and TUD still had a TUD diagnosis at surgery, and 542 (68.9%) of patients without myelopathy still had a TUD diagnosis at surgery. The prevalence of degenerative disc disease and TUD has increased more than disc disease alone. Patients with TUD were more likely to get surgery, and to have surgeries earlier than patients without TUD. Patients with TUD at the time of the diagnosis of their disc degeneration likely still had a TUD diagnosis at the time of surgery.

  15. The Time Course of Deafness and Retinal Degeneration in a Kunming Mouse Model for Usher Syndrome.

    Science.gov (United States)

    Yao, Lu; Zhang, Lei; Qi, Lin-Song; Liu, Wei; An, Jing; Wang, Bin; Xue, Jun-Hui; Zhang, Zuo-Ming

    2016-01-01

    Usher syndrome is a group of autosomal recessive diseases characterized by congenital deafness and retinitis pigmentosa. In a mouse model for Usher syndrome, KMush/ush, discovered in our laboratory, we measured the phenotypes, characterized the architecture and morphology of the retina, and quantified the level of expression of pde6b and ush2a between postnatal (P) days 7, and 56. Electroretinograms and auditory brainstem response were used to measure visual and auditory phenotypes. Fundus photography and light microscopy were used to measure the architecture and morphology of the retina. Quantitative real-time PCR was used to measure the expression levels of mRNA. KMush/ush mice had low amplitudes and no obvious waveforms of Electroretinograms after P14 compared with controls. Thresholds of auditory brainstem response in our model were higher than those of controls after P14. By P21, the retinal vessels of KMush/ush mice were attenuated and their optic discs had a waxy pallor. The retinas of KMush/ush mice atrophied and the choroidal vessels were clearly visible. Notably, the architecture of each retinal layer was not different as compared with control mice at P7, while the outer nuclear layer (ONL) and other retinal layers of KMush/ush mice were attenuated significantly between P14 and P21. ONL cells were barely seen in KMush/ush mice at P56. As compared with control mice, the expression of pde6b and ush2a in KMush/ush mice declined significantly after P7. This study is a first step toward characterizing the progression of disease in our mouse model. Future studies using this model may provide insights about the etiology of the disease and the relationships between genotypes and phenotypes providing a valuable resource that could contribute to the foundation of knowledge necessary to develop therapies to prevent the retinal degeneration in patients with Usher Syndrome.

  16. The Time Course of Deafness and Retinal Degeneration in a Kunming Mouse Model for Usher Syndrome.

    Directory of Open Access Journals (Sweden)

    Lu Yao

    Full Text Available Usher syndrome is a group of autosomal recessive diseases characterized by congenital deafness and retinitis pigmentosa. In a mouse model for Usher syndrome, KMush/ush, discovered in our laboratory, we measured the phenotypes, characterized the architecture and morphology of the retina, and quantified the level of expression of pde6b and ush2a between postnatal (P days 7, and 56. Electroretinograms and auditory brainstem response were used to measure visual and auditory phenotypes. Fundus photography and light microscopy were used to measure the architecture and morphology of the retina. Quantitative real-time PCR was used to measure the expression levels of mRNA. KMush/ush mice had low amplitudes and no obvious waveforms of Electroretinograms after P14 compared with controls. Thresholds of auditory brainstem response in our model were higher than those of controls after P14. By P21, the retinal vessels of KMush/ush mice were attenuated and their optic discs had a waxy pallor. The retinas of KMush/ush mice atrophied and the choroidal vessels were clearly visible. Notably, the architecture of each retinal layer was not different as compared with control mice at P7, while the outer nuclear layer (ONL and other retinal layers of KMush/ush mice were attenuated significantly between P14 and P21. ONL cells were barely seen in KMush/ush mice at P56. As compared with control mice, the expression of pde6b and ush2a in KMush/ush mice declined significantly after P7. This study is a first step toward characterizing the progression of disease in our mouse model. Future studies using this model may provide insights about the etiology of the disease and the relationships between genotypes and phenotypes providing a valuable resource that could contribute to the foundation of knowledge necessary to develop therapies to prevent the retinal degeneration in patients with Usher Syndrome.

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

    Science.gov (United States)

    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.

  18. Cockayne syndrome group B (Csb) and group a (Csa) deficiencies predispose to hearing loss and cochlear hair cell degeneration in mice.

    Science.gov (United States)

    Nagtegaal, A Paul; Rainey, Robert N; van der Pluijm, Ingrid; Brandt, Renata M C; van der Horst, Gijsbertus T J; Borst, J Gerard G; Segil, Neil

    2015-03-11

    Sensory hair cells in the cochlea, like most neuronal populations that are postmitotic, terminally differentiated, and non-regenerating, depend on robust mechanisms of self-renewal for lifelong survival. We report that hair cell homeostasis requires a specific sub-branch of the DNA damage nucleotide excision repair pathway, termed transcription-coupled repair (TCR). Cockayne syndrome (CS), caused by defects in TCR, is a rare DNA repair disorder with a broad clinical spectrum that includes sensorineural hearing loss. We tested hearing and analyzed the cellular integrity of the organ of Corti in two mouse models of this disease with mutations in the Csb gene (CSB(m/m) mice) and Csa gene (Csa(-/-) mice), respectively. Csb(m/m) and Csa(-/-) mice manifested progressive hearing loss, as measured by an increase in auditory brainstem response thresholds. In contrast to wild-type mice, mutant mice showed reduced or absent otoacoustic emissions, suggesting cochlear outer hair cell impairment. Hearing loss in Csb(m/m) and Csa(-/-) mice correlated with progressive hair cell loss in the base of the organ of Corti, starting between 6 and 13 weeks of age, which increased by 16 weeks of age in a basal-to-apical gradient, with outer hair cells more severely affected than inner hair cells. Our data indicate that the hearing loss observed in CS patients is reproduced in mouse models of this disease. We hypothesize that accumulating DNA damage, secondary to the loss of TCR, contributes to susceptibility to hearing loss. Copyright © 2015 the authors 0270-6474/15/354280-07$15.00/0.

  19. Superluminous accretion discs

    Energy Technology Data Exchange (ETDEWEB)

    Sikora, M [Cambridge Univ. (UK). Inst. of Astronomy; Polska Akademia Nauk, Warsaw. Centrum Astronomiczne)

    1981-07-01

    Upper limits are computed for the total luminosities and collimation of radiation from thick, radiation supported accretion discs around black holes. Numerical results are obtained for the 'extreme' discs with rsub(out) = 10/sup 3/ GMsub(BH)/c/sup 2/, the angular momentum of the black hole being Jsub(BH) = 0.998 GMsub(BH)/c. The high luminosity (L approximately 8.5 Lsub(Edd)) and substantial collimation of radiation found for these discs indicate that such discs can explain both the high luminosities of quasars and similar objects and may produce some of the observed beams and jets.

  20. Macular degeneration (image)

    Science.gov (United States)

    ... macula in the back of the eye. The macula is important for clear central vision, allowing an individual to see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2006-08-01

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

  3. Instability of warped discs

    Science.gov (United States)

    Doǧan, S.; Nixon, C. J.; King, A. R.; Pringle, J. E.

    2018-05-01

    Accretion discs are generally warped. If a warp in a disc is too large, the disc can `break' apart into two or more distinct planes, with only tenuous connections between them. Further, if an initially planar disc is subject to a strong differential precession, then it can be torn apart into discrete annuli that precess effectively independently. In previous investigations, torque-balance formulae have been used to predict where and when the disc breaks into distinct parts. In this work, focusing on discs with Keplerian rotation and where the shearing motions driving the radial communication of the warp are damped locally by turbulence (the `diffusive' regime), we investigate the stability of warped discs to determine the precise criterion for an isolated warped disc to break. We find and solve the dispersion relation, which, in general, yields three roots. We provide a comprehensive analysis of this viscous-warp instability and the emergent growth rates and their dependence on disc parameters. The physics of the instability can be understood as a combination of (1) a term that would generally encapsulate the classical Lightman-Eardley instability in planar discs (given by ∂(νΣ)/∂Σ < 0) but is here modified by the warp to include ∂(ν1|ψ|)/∂|ψ| < 0, and (2) a similar condition acting on the diffusion of the warp amplitude given in simplified form by ∂(ν2|ψ|)/∂|ψ| < 0. We discuss our findings in the context of discs with an imposed precession, and comment on the implications for different astrophysical systems.

  4. Stem-cell treatment in disc degeneration: What is the evidence? Células madre en el tratamiento de degeneración de disco: ¿Cual es la evidencia? Células tronco no tratamento de doença degenerativa discal: Qual é a evidência?

    Directory of Open Access Journals (Sweden)

    Manuela Peletti-Figueiró

    2013-01-01

    Full Text Available To review the potential role of stem cells in treating degenerative disc disease of the intervertebral disc (IVD. A review was performed of articles from the Medline database concerning stem cells and degenerative disc disease (DDD. To discuss the data, the papers were classified as: review, in vitro, experimental, and clinical. The currently available treatments were basically for symptom reduction, not to revert the IVD degenerative process. The use of mesenchymal stem cells (MSC is being proposed as an option of treatment for DDD. In vitro studies have shown that the MSC are able to differentiate into NP cells and that the MSC also reduce the inflammatory levels of the degenerated IVD. Besides, experimental studies demonstrated that the MSC remained viable when injected into the IVD, and that they were able to regenerate partially from the degenerated IVD and its structure. The few clinical studies found in the literature presented diverging results. The use of MSC is being widely studied and shows promising results for the treatment of DDD. Although many advances are being achieved in studies in vitro and experimental, there is a lack of clinical studies to prove the role of MSC in DDD management.Revisar el papel potencial de las células madre en el tratamiento de la enfermedad degenerativa del disco intervertebral (IVD. Se realizó una revisión de los artículos de la base de datos Medline sobre células madre y la enfermedad degenerativa del disco (DDD. Para fines de discusión de los datos, los trabajos se dividieron en: revisión, in vitro, experimentales y clínicos. Los tratamientos disponibles actualmente enfocan básicamente la reducción de los síntomas, y no la reversión del proceso degenerativo del IVD. El uso de células madre mesenquimales (MSC se propone como una opción de tratamiento para DDD. Estudios in vitro demostraron que las MSC son capaces de diferenciarse en células NP y que las MSC también reducen los niveles

  5. MR imaging of degenerative disc disease

    International Nuclear Information System (INIS)

    Farshad-Amacker, Nadja A.; Farshad, Mazda; Winklehner, Anna; Andreisek, Gustav

    2015-01-01

    Highlights: • This systematic literature review summarizes the current knowledge on MR imaging in degenerative disc disease. • Different classification systems for segmental spine degeneration are summarized. • It outlines the diagnostic limitations of MR imaging. - Abstract: Magnet resonance imaging (MRI) is the most commonly used imaging modality for diagnosis of degenerative disc disease (DDD). Lack of precise observations and documentation of aspects within the complex entity of DDD might partially be the cause of poor correlation of radiographic findings to clinical symptoms. This literature review summarizes the current knowledge on MRI in DDD and outlines the diagnostic limitations. The review further sensitizes the reader toward awareness of potentially untended aspects of DDD and the interaction of DDD and endplate changes. A summary of the available classifications for DDD is provided

  6. MR imaging of degenerative disc disease

    Energy Technology Data Exchange (ETDEWEB)

    Farshad-Amacker, Nadja A., E-mail: nadja.farshad@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital of Zurich, Zurich (Switzerland); Farshad, Mazda [Department of Orthopaedic Surgery, Balgrist University Hospital, Zurich (Switzerland); Winklehner, Anna; Andreisek, Gustav [Institute of Diagnostic and Interventional Radiology, University Hospital of Zurich, Zurich (Switzerland)

    2015-09-15

    Highlights: • This systematic literature review summarizes the current knowledge on MR imaging in degenerative disc disease. • Different classification systems for segmental spine degeneration are summarized. • It outlines the diagnostic limitations of MR imaging. - Abstract: Magnet resonance imaging (MRI) is the most commonly used imaging modality for diagnosis of degenerative disc disease (DDD). Lack of precise observations and documentation of aspects within the complex entity of DDD might partially be the cause of poor correlation of radiographic findings to clinical symptoms. This literature review summarizes the current knowledge on MRI in DDD and outlines the diagnostic limitations. The review further sensitizes the reader toward awareness of potentially untended aspects of DDD and the interaction of DDD and endplate changes. A summary of the available classifications for DDD is provided.

  7. Adjacent Lumbar Disc Herniation after Lumbar Short Spinal Fusion

    Directory of Open Access Journals (Sweden)

    Koshi Ninomiya

    2014-01-01

    Full Text Available A 70-year-old outpatient presented with a chief complaint of sudden left leg motor weakness and sensory disturbance. He had undergone L4/5 posterior interbody fusion with L3–5 posterior fusions for spondylolisthesis 3 years prior, and the screws were removed 1 year later. He has been followed up for 3 years, and there had been no adjacent segment problems before this presentation. Lumbar magnetic resonance imaging (MRI showed a large L2/3 disc hernia descending to the L3/4 level. Compared to the initial MRI, this hernia occurred in an “intact” disc among multilevel severely degenerated discs. Right leg paresis and bladder dysfunction appeared a few days after admission. Microscopic lumbar disc herniotomy was performed. The right leg motor weakness improved just after the operation, but the moderate left leg motor weakness and difficulty in urination persisted.

  8. Disc operational system

    International Nuclear Information System (INIS)

    Veretenov, V.Yu.; Volkov, A.I.; Gurevich, M.I.; Kozik, V.S.; Pod'yachev, E.I.; Shapiro, M.L.

    1974-01-01

    A disc operational system is proposed, which is based on the file structure and designed for use in a BESM-6 computer with the software system comprising a dispatcher DD-73 and a monitor 'Dubna'. The main distinguishing feature of the disc operational system is the decentralization of the file system. Each disc package is an independent file unaffected by the state of the other disc packages. The use of several disc packages is allowed. The above feature of the disc operational system makes it possible to simplify the language of communication with the system, to give the user the opportunity of controlling the file quite independently, and to simplify the maintenance of the discs by the computer personnel. One and the same disc can be simultaneously addressed by all problems in the processor (both mathematical and service). A single file, however, may be used in the recording mode by only one problem. The description presented is the instruction for users. It also describes special possibilities open to the system programmers [ru

  9. Intratracheal Seal Disc

    DEFF Research Database (Denmark)

    Christiansen, Karen J; Moeslund, Niels; Lauridsen, Henrik

    2017-01-01

    . The device consisted of an intratracheal silicone seal disc fixated by a cord through the stoma to an external part. At day 14, computed tomography (CT) was performed before the device was extracted. With the pulling of a cord, the disc unraveled into a thin thread and was extracted through the stoma. At day...

  10. Investigation of intervertebral disc degeneration using multivariate FTIR spectroscopic imaging

    NARCIS (Netherlands)

    Mader, Kerstin T.; Peeters, Mirte; Detiger, Suzanne E. L.; Helder, Marco N.; Smit, Theo H.; Le Maitre, Christine L.; Sammon, Chris

    2016-01-01

    Traditionally tissue samples are analysed using protein or enzyme specific stains on serial sections to build up a picture of the distribution of components contained within them. In this study we investigated the potential of multivariate curve resolution-alternating least squares (MCR-ALS) to

  11. Double rupture disc experience

    International Nuclear Information System (INIS)

    1979-01-01

    Result of these observations, comparisons and evaluations can be summarized in the following list of concerns regarding the use of double rupture discs coupled to the liquid space of a steam generator that is subjected to a large leak sodium water reaction event. Single rupture disc show delayed collapse characteristics in LLTR Series I and double disc assemblies are presumed to be more complex with additional delay before opening to give pressure relief. Delayed failure increases pressures in the IHTS and must be adequately covered by design requirements. With CRBR design, the first disc may fail only partially reducing the loading on the second disc with the result that relief performance may not meet requirements

  12. Confiabilidade de um método de análise histológica da degeneração discal experimental em coelhos Confiabilidad de un método para el análisis histológico de la degeneración discal experimental en conejos Reliability of a method for histological analysis of experimental disc degeneration in rabbits

    Directory of Open Access Journals (Sweden)

    Emiliano Neves Vialle

    2011-01-01

    Zealand fueron sometidos a procedimiento de inducción de la degeneración discal a través de punción directa de tres discos intervertebrales (DIV consecutivos con aguja 18G bajo anestesia. Al fin de dos meses, se colectó la columna vertebral completa de cada conejo y se procedió a la preparación de las piezas para análisis histológico de los discos intervertebrales (Experimentales y Controles, siendo coloreadas por el método hematoxilina-eosina. Las láminas histológicas fueron evaluadas cuanto a ocurrencia de degeneración a través del análisis de los siguientes criterios: presencia de vasos sanguíneos; presencia de protrusión del núcleo pulposo (NP a través del anillo fibroso (AF; y rotura de las fibras del AF. RESULTADOS: Al final de los procesos de eutanasia, remoción y preparación histológica de la columna, se obtuvieron 60 DIV viables para evaluación de degeneración. De este total, 25 piezas eran de DIV experimentales y 35 piezas de DIV control. La presencia de vaso sanguíneo fue observada en 18 de los 25 DIV degenerados, con concordancia de Kappa = 0,95 entre los observadores. La presencia de la extrusión del NP fue identificada en 19 de los 25 DIV experimentales, con concordancia de Kappa = 0,78 entre los observadores. Con relación a la rotura de las fibras del AF, se puede identificar la positividad en 24 de los 25 DIV degenerados, con concordancia entre los observadores de Kappa = 0,65. CONCLUSIÓN: Este modelo de evaluación histológica de la degeneración experimental del DIV se mostró viable, con alto grado de concordancia entre los observadores en la identificación de la degeneración discal.OBJECTIVE: To validate a method for histological evaluation of disc degeneration in rabbits based on the reliability of interobserver analysis. METHODS: Thirteen New Zealand white rabbits underwent a procedure to induce disc degeneration through direct puncture of three consecutive intervertebral discs (IVD with an 18G needle under anesthesia

  13. Optic disc oedema

    DEFF Research Database (Denmark)

    Nielsen, Marianne Kromann; Hamann, Steffen

    2014-01-01

    Optic disc oedema describes the nonspecific, localized swelling of the optic nerve head regardless of aetiology. Therefore, differentiating among the various aetiologies depends on a thorough history and knowledge of the clinical characteristics of the underlying conditions. Papilloedema strictly...... refers to optic disc oedema as a consequence of elevated intracranial pressure. It is usually a bilateral condition and visual function is preserved until late. Optic disc oedema caused by an anterior optic neuropathy is usually unilateral and accompanied by the loss of visual function....

  14. Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer’s disease or corticobasal degeneration brains

    Science.gov (United States)

    Boluda, Susana; Iba, Michiyo; Zhang, Bin; Raible, Kevin M.; Lee, Virginia M-Y.; Trojanowski, John Q.

    2015-01-01

    Filamentous tau pathologies are hallmark lesions of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and corticobasal degeneration (CBD) which show cell type-specific and topographically distinct tau inclusions. Growing evidence supports templated transmission of tauopathies through functionally interconnected neuroanatomical pathways suggesting that different self-propagating strains of pathological tau could account for the diverse manifestations of neurodegenerative tauopathies. Here, we describe the rapid and distinct cell type-specific spread of pathological tau following intracerebral injections of CBD or AD brain extracts enriched in pathological tau (designated CBD-Tau and AD-Tau, respectively) in young human mutant P301S tau transgenic (Tg) mice (line PS19) ~6–9 months before they show onset of mutant tau transgene-induced tau pathology. At 1 month post-injection of CBD-Tau, tau inclusions developed predominantly in oligodendrocytes of the fimbria and white matter near the injection sites with infrequent intraneuronal tau aggregates. In contrast, injections of AD-Tau in young PS19 mice induced tau pathology predominantly in neuronal perikarya with little or no oligodendrocyte involvement 1 month post-injection. With longer post-injection survival intervals of up to 6 months, CBD-Tau- and AD-Tau-induced tau pathology spread to different brain regions distant from the injection sites while maintaining the cell type-specific pattern noted above. Finally, CA3 neuron loss was detected 3 months post-injection of AD-Tau but not CBD-Tau. Thus, AD-Tau and CBD-Tau represent specific pathological tau strains that spread differentially and may underlie distinct clinical and pathological features of these two tauopathies. Hence, these strains could become targets to develop disease-modifying therapies for CBD and AD. PMID:25534024

  15. Effect of whole-body vibration and insulin-like growth factor-I on muscle paralysis-induced bone degeneration after botulinum toxin injection in mice.

    Science.gov (United States)

    Niehoff, Anja; Lechner, Philipp; Ratiu, Oana; Reuter, Sven; Hamann, Nina; Brüggemann, Gert-Peter; Schönau, Eckhard; Bloch, Wilhelm; Beccard, Ralf

    2014-04-01

    Botulinum toxin A (BTX)-induced muscle paralysis results in pronounced bone degradation with substantial bone loss. We hypothesized that whole-body vibration (WBV) and insulin-like growth factor-I (IGF-I) treatment can counteract paralysis-induced bone degradation following BTX injections by activation of the protein kinase B (Akt) signaling pathway. Female C57BL/6 mice (n = 60, 16 weeks) were assigned into six groups (n = 10 each): SHAM, BTX, BTX+WBV, BTX+IGF-I, BTX+WBV+IGF-I, and a baseline group, which was killed at the beginning of the study. Mice received a BTX (1.0 U/0.1 mL) or saline (SHAM) injection in the right hind limb. The BTX+IGF-I and BTX+WBV+IGF-I groups obtained daily subcutaneous injections of human IGF-I (1 μg/day). The BTX+WBV and BTX+WBV+IGF-I groups underwent WBV (25 Hz, 2.1 g, 0.83 mm) for 30 min/day, 5 days/week for 4 weeks. Femora were scanned by pQCT, and mechanical properties were determined. On tibial sections TRAP staining, static histomorphometry, and immunohistochemical staining against Akt, phospho-Akt, IGF-IR (IGF-I receptor), and phospho-IGF-IR were conducted. BTX injection decreased trabecular and cortical bone mineral density. The WBV and WBV+IGF-I groups showed no difference in trabecular bone mineral density compared to the SHAM group. The phospho-IGF-IR and phospho-Akt stainings were not differentially altered in the injected hind limbs between groups. We found that high-frequency, low-magnitude WBV can counteract paralysis-induced bone loss following BTX injections, while we could not detect any effect of treatment with IGF-I.

  16. Herniated Cervical Disc

    Science.gov (United States)

    ... are sometimes prescribed for more severe arm and neck pain because of their very powerful anti-inflammatory effect. ... caused by a herniated cervical disc. However, some neck pain may persist. Most patients respond well to discectomy; ...

  17. Imbalanced Protein Expression Patterns of Anabolic, Catabolic, Anti-Catabolic and Inflammatory Cytokines in Degenerative Cervical Disc Cells: New Indications for Gene Therapeutic Treatments of Cervical Disc Diseases

    Science.gov (United States)

    Mern, Demissew S.; Beierfuß, Anja; Fontana, Johann; Thomé, Claudius; Hegewald, Aldemar A.

    2014-01-01

    Degenerative disc disease (DDD) of the cervical spine is common after middle age and can cause loss of disc height with painful nerve impingement, bone and joint inflammation. Despite the clinical importance of these problems, in current publications the pathology of cervical disc degeneration has been studied merely from a morphologic view point using magnetic resonance imaging (MRI), without addressing the issue of biological treatment approaches. So far a wide range of endogenously expressed bioactive factors in degenerative cervical disc cells has not yet been investigated, despite its importance for gene therapeutic approaches. Although degenerative lumbar disc cells have been targeted by different biological treatment approaches, the quantities of disc cells and the concentrations of gene therapeutic factors used in animal models differ extremely. These indicate lack of experimentally acquired data regarding disc cell proliferation and levels of target proteins. Therefore, we analysed proliferation and endogenous expression levels of anabolic, catabolic, ant-catabolic, inflammatory cytokines and matrix proteins of degenerative cervical disc cells in three-dimensional cultures. Preoperative MRI grading of cervical discs was used, then grade III and IV nucleus pulposus (NP) tissues were isolated from 15 patients, operated due to cervical disc herniation. NP cells were cultured for four weeks with low-glucose in collagen I scaffold. Their proliferation rates were analysed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Their protein expression levels of 28 therapeutic targets were analysed using enzyme-linked immunosorbent assay. During progressive grades of degeneration NP cell proliferation rates were similar. Significantly decreased aggrecan and collagen II expressions (P<0.0001) were accompanied by accumulations of selective catabolic and inflammatory cytokines (disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix

  18. LUMBOSACRAL TRANSITIONAL ANATOMY TYPES AND DISC DEGENERATIVE CHANGES

    Directory of Open Access Journals (Sweden)

    Chabukovska Radulovska Jasminka

    2014-07-01

    Full Text Available Background and purpose: The relationship between presence of lumbo sacral transitional vertebra (LSTV and disc degenerative changes is unclear. The aim of the study was to examine the relation between different types of LSTV and disc degenerative changes at the transitional and the adjacent cephalad segment. Material and methods: Sixty-three patients (mean age 51.48 ± 13.51 out of 200 adults with low back pain who performed MRI examination of the lumbo sacral spine, classified as positive for LSTV, were included in the study. Annular tears, disc degeneration according to Phirmann classification and disc herniations were evaluated and graded at transitional and adjacent cephalad level. Results: The severity of disc degeneration at the transitional level and the adjacent level correlated with the types of LSTV. Severe disc degenerative changes were most frequent in articulated connection LSTV types and incombined LSTV type at the transitional level and in osseus connection LSTV types at the adjacent cephalad level. These changes were more frequent in unilateral articulated connection LSTV subtype (64% vs 54%; and in unilateral osseus connection LSTV subtype (25% vs no patients at transitional level, and in bilateral osseus connection LSTV subtype (100% vs 50% at the level above. High prevalence of disc herniations was observed in articulated connection LSTV types as well as in unilateral osseus connection LSTV subtype at transitional and the adjacent cephalad level. At the transitional level higher prevalence of disc herniations was characteristic for unilateral articulated connection LSTV sub type (46%vs 41% and for unilateral osseus connection LSTV subtype (50% vs no patients. At the adjacent level higher prevalence of disc herniations was observed in bilateral articulated connection LSTV subtype (38% vs 27% and in bilateral osseus connection LSTV subtype (50% vs 25%. Conclusions: The compact osseus connection (osseus bridging vs articular

  19. Lumbosacral transitional anatomy types and disc degenerative changes

    Directory of Open Access Journals (Sweden)

    Chabukovska-Radulovska Jasminka

    2014-07-01

    Full Text Available Background and purpose: The relationship between presence of lumbosacral transitional vertebra (LSTV and disc degenerative changes is unclear. The aim of the study was to examine the relation between different types of LSTV and disc degenerative changes at the transitional and the adjacent cephalad segment. Material and methods: Sixty-three patients (mean age 51.48 ± 13.51 out of200 adults with low back pain who performed MRI examination of the lumbosacral spine, classified as positive for LSTV, were included in the study. Annular tears, disc degeneration according to Phirmann classification and disc herniations were evaluated and graded at transitional and adjacent cephalad level. Results: The severity of disc degeneration at the transitional level and the adjacent level correlated with the types of LSTV. Severe disc degenerative changes were most frequent in articulated connection LSTV types and in combined LSTV type at the transitional level and in osseus connection LSTV types at the adjacent cephalad level. These changes were more frequent in unilateral articulated connection LSTV subtype (64% vs 54%; and in unilateral osseus connection LSTV subtype (25% vs no patients at transitional level, and in bilateral osseus connection LSTV subtype (100% vs 50% at the level above. High prevalence of disc herniations was observed in articulated connection LSTV types as well as in unilateral osseus connection LSTV subtype at transitional and the adjacent cephalad level. At the transitional level higher prevalence of disc herniations was characteristic for unilateral articulated connection LSTV subtype (46%vs 41% and for unilateral osseus connection LSTV subtype (50% vs no patients. At the adjacent level higher prevalence of disc herniations was observed in bilateral articulated connection LSTV subtype (38% vs 27% and in bilateral osseus connection LSTV subtype (50% vs 25%. Conclusions: The compact osseus connection (osseus bridging vs articular

  20. Regulation of CTL responses to MHC-restricted class I peptide of the gp70 tumour antigen by splenic parenchymal CD4+ T cells in mice failing immunotherapy with DISC-mGM-CSF.

    Science.gov (United States)

    Ahmad, Murrium; Rees, Robert C; McArdle, Stephanie E; Li, Geng; Mian, Shahid; Entwisle, Claire; Loudon, Peter; Ali, Selman A

    2005-07-20

    Direct intratumour injection of the disabled infectious single-cycle-herpes simplex virus-encoding murine granulocyte/macrophage colony-stimulating factor (DISC-HSV-mGM-CSF) into established colon carcinoma CT26 tumours induced complete tumour rejection in up to 70% of treated animals (regressors), while the remaining mice developed progressive tumours (progressors). This murine Balb/c model was used to dissect the cellular mechanisms involved in tumour regression or progression following immunotherapy. CTLs were generated by coculturing lymphocytes and parenchymal cells from the same spleens of individual regressor or progressor animals in the presence of the relevant AH-1 peptide derived from the gp70 tumour-associated antigens expressed by CT26 tumours. Tumour regression was correlated with potent CTL responses, spleen weight and cytokine (IFN-gamma) production. Conversely, progressor splenocytes exhibited weak to no CTL activity and poor IFN-gamma production, concomitant with the presence of a suppressor cell population in the progressor splenic parenchymal cell fraction. Further fractionation of this parenchymal subpopulation demonstrated that cells inhibitory to the activation of AH-1-specific CTLs, restimulated in vitro with peptide, were present in the nonadherent parenchymal fraction. In vitro depletion of progressor parenchymal CD3+/CD4+ T cells restored the CTL response of the cocultured splenocytes (regressor lymphocytes and progressor parenchymal cells) and decreased the production of IL-10, suggesting that CD3+CD4+ T lymphocytes present in the parenchymal fraction regulated the CTL response to AH-1. We examined the cellular responses associated with tumour rejection and progression, identifying regulatory pathways associated with failure to respond to immunotherapy. Copyright 2005 Wiley-Liss, Inc.

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

    Science.gov (United States)

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

    2018-04-19

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  4. Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease

    Science.gov (United States)

    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

  5. Can Exercise Positively Influence the Intervertebral Disc?

    Science.gov (United States)

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

    2016-04-01

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

  6. A potential role for cell-based therapeutics in the treatment of intervertebral disc herniation

    OpenAIRE

    Ganey, Timothy M.; Meisel, Hans

    2002-01-01

    Lower back pain and disc degeneration negatively affect quality of life and impose an enormous financial burden. An extensive body of scientific work has evolved that characterizes the disc, demonstrating spinal anatomy and morphology that contribute to risk and likely promote failure. Ultimately, matrix failure is responsible for mechanical failure, which in turn results in spinal compromise anatomically and subsequent pain. One intervening approach to breaking this sequence has been to repo...

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  8. Foxa1 and Foxa2 are required for formation of the intervertebral discs.

    Directory of Open Access Journals (Sweden)

    Jennifer A Maier

    Full Text Available The intervertebral disc (IVD is composed of 3 main structures, the collagenous annulus fibrosus (AF, which surrounds the gel-like nucleus pulposus (NP, and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreER(T2, we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1(-/-;Foxa2(c/c;ShhcreER(T2 double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord.

  9. Foxa1 and Foxa2 Are Required for Formation of the Intervertebral Discs

    Science.gov (United States)

    Maier, Jennifer A.; Lo, YinTing; Harfe, Brian D.

    2013-01-01

    The intervertebral disc (IVD) is composed of 3 main structures, the collagenous annulus fibrosus (AF), which surrounds the gel-like nucleus pulposus (NP), and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreERT2), we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1−/−;Foxa2c/c;ShhcreERT2 double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord. PMID:23383217

  10. The Galactic stellar disc

    International Nuclear Information System (INIS)

    Feltzing, S; Bensby, T

    2008-01-01

    The study of the Milky Way stellar discs in the context of galaxy formation is discussed. In particular, we explore the properties of the Milky Way disc using a new sample of about 550 dwarf stars for which we have recently obtained elemental abundances and ages based on high-resolution spectroscopy. For all the stars we also have full kinematic information as well as information about their stellar orbits. We confirm results from previous studies that the thin and the thick discs have distinct abundance patterns. But we also explore a larger range of orbital parameters than what has been possible in our previous studies. Several new results are presented. We find that stars that reach high above the Galactic plane and have eccentric orbits show remarkably tight abundance trends. This implies that these stars formed out of well-mixed gas that had been homogenized over large volumes. We find some evidence that suggest that the event that most likely caused the heating of this stellar population happened a few billion years ago. Through a simple, kinematic exploration of stars with super-solar [Fe/H], we show that the solar neighbourhood contains metal-rich, high velocity stars that are very likely associated with the thick disc. Additionally, the HR1614 moving group and the Hercules and Arcturus stellar streams are discussed and it is concluded that, probably, a large fraction of the groups and streams so far identified in the disc are the result of evolution and interactions within the stellar disc rather than being dissolved stellar clusters or engulfed dwarf galaxies.

  11. Isolated Optic Disc Tuberculosis

    Science.gov (United States)

    Mansour, Ahmad M.; Tabbara, Khalid F.; Tabbarah, Zuhair

    2015-01-01

    We present a healthy male subject who developed progressive visual loss in the left eye initially diagnosed as optic neuritis. Upon suspicion of infectious etiology, testing was positive for tuberculosis. There were no signs or symptoms of active systemic tuberculosis infection. The patient responded swiftly to antimycobacterial therapy with return of vision and resolution of disc swelling. Positive purified protein derivative skin test, negative chest radiograph, negative systemic workup, negative workup for other causes of unilateral optic neuritis and quick response to mycobacterial therapy reaffirm the entity of isolated optic disc tuberculosis similar to isolated choroidal tuberculosis without systemic manifestation. PMID:26483675

  12. Isolated Optic Disc Tuberculosis

    Directory of Open Access Journals (Sweden)

    Ahmad M. Mansour

    2015-09-01

    Full Text Available We present a healthy male subject who developed progressive visual loss in the left eye initially diagnosed as optic neuritis. Upon suspicion of infectious etiology, testing was positive for tuberculosis. There were no signs or symptoms of active systemic tuberculosis infection. The patient responded swiftly to antimycobacterial therapy with return of vision and resolution of disc swelling. Positive purified protein derivative skin test, negative chest radiograph, negative systemic workup, negative workup for other causes of unilateral optic neuritis and quick response to mycobacterial therapy reaffirm the entity of isolated optic disc tuberculosis similar to isolated choroidal tuberculosis without systemic manifestation.

  13. Hybrid testing of lumbar CHARITE discs versus fusions.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  15. Degenerate nonlinear diffusion equations

    CERN Document Server

    Favini, Angelo

    2012-01-01

    The aim of these notes is to include in a uniform presentation style several topics related to the theory of degenerate nonlinear diffusion equations, treated in the mathematical framework of evolution equations with multivalued m-accretive operators in Hilbert spaces. The problems concern nonlinear parabolic equations involving two cases of degeneracy. More precisely, one case is due to the vanishing of the time derivative coefficient and the other is provided by the vanishing of the diffusion coefficient on subsets of positive measure of the domain. From the mathematical point of view the results presented in these notes can be considered as general results in the theory of degenerate nonlinear diffusion equations. However, this work does not seek to present an exhaustive study of degenerate diffusion equations, but rather to emphasize some rigorous and efficient techniques for approaching various problems involving degenerate nonlinear diffusion equations, such as well-posedness, periodic solutions, asympt...

  16. Degenerative disc disease as a cause of back pain in the thalassaemic population: a case-control study using MRI and plain radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Desigan, S.; Hall-Craggs, M.A.; Ho, C.-P. [Department of Imaging, University College London Hospitals NHS Foundation Trust, London (United Kingdom); Eliahoo, J. [University College London Hospitals NHS Trust, Research and Development Directorate, London (United Kingdom); Porter, J.B. [University College Hospital, Department of Haematology, University College London Hospitals NHS Trust, London (United Kingdom)

    2006-02-15

    The aim of this study was to test our observation that back pain in thalassemic patients could be caused by premature and extensive lumbar degenerative disc disease, when compared to non-thalassemic patients with back pain. Sixteen thalassemic patients with their sex- and age-matched controls were recruited into the study, 12 with thalassemia major, and 4 with thalassemia intermedia. Both the thalassemia patients and control subjects suffered from back pain, which was subjective rather than measured/pain scored. All subjects underwent magnetic resonance (MR) imaging of the lumbar spine, and 11 of the cases and 8 controls had lumbar spine radiographs. Each lumbar disc was scored for radiographic appearances and MR features of disc degeneration and disc protrusion. Proportion values for these parameters and median scores were derived at each disc level, and were analyzed and compared. There was a statistically-significant difference between proportion values of cases and controls for the MR features (P value=0.01, n=16) and the radiographic features (P value=0.01, n=11 cases, n=8 controls) of disc degeneration. The median disc level scores for the thalassemic group were uniformly high across all lumbar discs, and at all levels except at L 4/5. The control group conversely demonstrated a predilection for disc degeneration at L4/5 level. The distribution of lumbar disc degeneration in thalassemic patients with back pain is more extensive, severe and multi-level in nature compared to matched controls, and disc degeneration should be considered as a significant cause of back pain in this population group. (orig.)

  17. Degenerative disc disease as a cause of back pain in the thalassaemic population: a case-control study using MRI and plain radiographs

    International Nuclear Information System (INIS)

    Desigan, S.; Hall-Craggs, M.A.; Ho, C.-P.; Eliahoo, J.; Porter, J.B.

    2006-01-01

    The aim of this study was to test our observation that back pain in thalassemic patients could be caused by premature and extensive lumbar degenerative disc disease, when compared to non-thalassemic patients with back pain. Sixteen thalassemic patients with their sex- and age-matched controls were recruited into the study, 12 with thalassemia major, and 4 with thalassemia intermedia. Both the thalassemia patients and control subjects suffered from back pain, which was subjective rather than measured/pain scored. All subjects underwent magnetic resonance (MR) imaging of the lumbar spine, and 11 of the cases and 8 controls had lumbar spine radiographs. Each lumbar disc was scored for radiographic appearances and MR features of disc degeneration and disc protrusion. Proportion values for these parameters and median scores were derived at each disc level, and were analyzed and compared. There was a statistically-significant difference between proportion values of cases and controls for the MR features (P value=0.01, n=16) and the radiographic features (P value=0.01, n=11 cases, n=8 controls) of disc degeneration. The median disc level scores for the thalassemic group were uniformly high across all lumbar discs, and at all levels except at L 4/5. The control group conversely demonstrated a predilection for disc degeneration at L4/5 level. The distribution of lumbar disc degeneration in thalassemic patients with back pain is more extensive, severe and multi-level in nature compared to matched controls, and disc degeneration should be considered as a significant cause of back pain in this population group. (orig.)

  18. Tracing Planets in Circumstellar Discs

    Directory of Open Access Journals (Sweden)

    Uribe Ana L.

    2013-04-01

    Full Text Available Planets are assumed to form in circumstellar discs around young stellar objects. The additional gravitational potential of a planet perturbs the disc and leads to characteristic structures, i.e. spiral waves and gaps, in the disc density profile. We perform a large-scale parameter study on the observability of these planet-induced structures in circumstellar discs in the (submm wavelength range for the Atacama Large (SubMillimeter Array (ALMA. On the basis of hydrodynamical and magneto-hydrodynamical simulations of star-disc-planet models we calculate the disc temperature structure and (submm images of these systems. These are used to derive simulated ALMA maps. Because appropriate objects are frequent in the Taurus-Auriga region, we focus on a distance of 140 pc and a declination of ≈ 20°. The explored range of star-disc-planet configurations consists of six hydrodynamical simulations (including magnetic fields and different planet masses, nine disc sizes with outer radii ranging from 9 AU to 225 AU, 15 total disc masses in the range between 2.67·10-7 M⊙ and 4.10·10-2 M⊙, six different central stars and two different grain size distributions, resulting in 10 000 disc models. At almost all scales and in particular down to a scale of a few AU, ALMA is able to trace disc structures induced by planet-disc interaction or the influence of magnetic fields in the wavelength range between 0.4...2.0 mm. In most cases, the optimum angular resolution is limited by the sensitivity of ALMA. However, within the range of typical masses of protoplane tary discs (0.1 M⊙...0.001 M⊙ the disc mass has a minor impact on the observability. At the distance of 140 pc it is possible to resolve discs down to 2.67·10-6 M⊙ and trace gaps in discs with 2.67·10-4 M⊙ with a signal-to-noise ratio greater than three. In general, it is more likely to trace planet-induced gaps in magneto-hydrodynamical disc models, because gaps are wider in the presence of

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marie Klauser

    2012-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-11-15

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

  2. Lumbar internal disc derangement in patients with chronic low back pain: diagnostic value of the MR imaging findings as compared with provoked discography as the standard

    International Nuclear Information System (INIS)

    Park, Hyeon Seon; Park, Jee Young; Lee, Sang Ho; Ahn, Yong; Lee, Sang Yeun

    2006-01-01

    The aim of this study was to evaluate the diagnostic value of the MR imaging findings with provoked discography used as the standard for painful lumbar disc derangement. Two hundred patients (412 discs), (age rang: 21-77 year), with chronic low back pain underwent MRI and provoked discography. We evaluated the MRI T2-WI findings such as disc degeneration, high-Intensity zones and endplate abnormalities. Subsequently, provocative discography was independently performed with using MR imaging, and a painful disc was defined when moderate to severe and concordant pain was provoked. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the MRI findings with using provoked discography as the standard. 400 discs showed abnormal findings such as disc degeneration, HIZ and endplate abnormalities on the T2-WI images. 12 discs showed normal finding. HIZ or endplate abnormalities were always combined with disc degeneration. The prevalence of each findings were disc degeneration (400 discs: 97.1%), HIZ (111 discs: 26.9%), type I endplate abnormalities (34 discs: 8.3%), type II endplate abnormalities (75 discs: 18.2%), the combined findings of HIZ and type I endplate abnormalities (2 discs: 0.5%) and the combined findings of HIZ and type II endplate abnormalities (7 discs: 1.7%). The disc degeneration showed high sensitivity (99.5%) and low specificity (5.0%), so only the NPV (91.7%) was significant, and not the PPV (47.8%). Each findings of HIZ (sensitivity, 36.5%, specificity, 81.4%; PPV, 63.18%; NPV, 59.5%), type I endplate abnormalities (11.0%, 94.1%, 61.8% and 54.8%, respectively), type II endplate abnormalities (19.8%, 83.2%, 50.7% and 54.3%, respectively), the combined findings of HIZ and type I endplate abnormalities (0.5%, 99.6%, 50.0% and 53.4%, respectively) and the combined findings of HIZ and type II endplate abnormalities (26.0%, 99.1%, 71.4% and 53.8%, respectively) show high specificity, but low

  3. Lumbar internal disc derangement in patients with chronic low back pain: diagnostic value of the MR imaging findings as compared with provoked discography as the standard

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyeon Seon; Park, Jee Young; Lee, Sang Ho; Ahn, Yong [Wooridul spine Hospital, Seoul (Korea, Republic of); Lee, Sang Yeun [Puchon Daesung Hospital, Puchon (Korea, Republic of)

    2006-04-15

    The aim of this study was to evaluate the diagnostic value of the MR imaging findings with provoked discography used as the standard for painful lumbar disc derangement. Two hundred patients (412 discs), (age rang: 21-77 year), with chronic low back pain underwent MRI and provoked discography. We evaluated the MRI T2-WI findings such as disc degeneration, high-Intensity zones and endplate abnormalities. Subsequently, provocative discography was independently performed with using MR imaging, and a painful disc was defined when moderate to severe and concordant pain was provoked. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the MRI findings with using provoked discography as the standard. 400 discs showed abnormal findings such as disc degeneration, HIZ and endplate abnormalities on the T2-WI images. 12 discs showed normal finding. HIZ or endplate abnormalities were always combined with disc degeneration. The prevalence of each findings were disc degeneration (400 discs: 97.1%), HIZ (111 discs: 26.9%), type I endplate abnormalities (34 discs: 8.3%), type II endplate abnormalities (75 discs: 18.2%), the combined findings of HIZ and type I endplate abnormalities (2 discs: 0.5%) and the combined findings of HIZ and type II endplate abnormalities (7 discs: 1.7%). The disc degeneration showed high sensitivity (99.5%) and low specificity (5.0%), so only the NPV (91.7%) was significant, and not the PPV (47.8%). Each findings of HIZ (sensitivity, 36.5%, specificity, 81.4%; PPV, 63.18%; NPV, 59.5%), type I endplate abnormalities (11.0%, 94.1%, 61.8% and 54.8%, respectively), type II endplate abnormalities (19.8%, 83.2%, 50.7% and 54.3%, respectively), the combined findings of HIZ and type I endplate abnormalities (0.5%, 99.6%, 50.0% and 53.4%, respectively) and the combined findings of HIZ and type II endplate abnormalities (26.0%, 99.1%, 71.4% and 53.8%, respectively) show high specificity, but low

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  5. Nearby stars of the Galactic disc and halo - IV

    Science.gov (United States)

    Fuhrmann, Klaus

    2008-02-01

    The Milky Way Galaxy has an age of about 13 billion years. Solar-type stars evolve all the long way to the realm of degenerate objects on essentially this time-scale. This, as well as the particular advantage that the Sun offers through reliable differential spectroscopic analyses, render these stars the ideal tracers for the fossil record of our parent spiral. Astrophysics is a science that is known to be notoriously plagued by selection effects. The present work - with a major focus in this fourth contribution on model atmosphere analyses of spectroscopic binaries and multiple star systems - aims at a volume-complete sample of about 300 nearby F-, G-, and K-type stars that particularly avoids any kinematical or chemical pre-selection from the outset. It thereby provides an unbiased record of the local stellar populations - the ancient thick disc and the much younger thin disc. On this base, the detailed individual scrutiny of the long-lived stars of both populations unveils the thick disc as a single-burst component with a local normalization of no less than 20 per cent. This enormous fraction, combined with its much larger scaleheight, implies a mass for the thick disc that is comparable to that of the thin disc. On account of its completely different mass-to-light ratio the thick disc thereby becomes the dark side of the Milky Way, an ideal major source for baryonic dark matter. This massive, ancient population consequently challenges any gradual build-up scenario for our parent spiral. Even more, on the supposition that the Galaxy is not unusual, the thick disc - as it emerges from this unbiased spectroscopic work - particularly challenges the hierarchical cold-dark-matter-dominated formation picture for spiral galaxies in general.

  6. Biomechanical analysis of the camelid cervical intervertebral disc

    Directory of Open Access Journals (Sweden)

    Dean K. Stolworthy

    2015-01-01

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

  7. Wave disc engine apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Muller, Norbert; Piechna, Janusz; Sun, Guangwei; Parraga, Pablo-Francisco

    2018-01-02

    A wave disc engine apparatus is provided. A further aspect employs a constricted nozzle in a wave rotor channel. A further aspect provides a sharp bend between an inlet and an outlet in a fluid pathway of a wave rotor, with the bend being spaced away from a peripheral edge of the wave rotor. A radial wave rotor for generating electricity in an automotive vehicle is disclosed in yet another aspect.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  9. Changes seen on magnetic resonance imaging in the intervertebral disc space after chemonucleosis: a hypothesis concerning regeneration of the disc after chemonucleosis

    International Nuclear Information System (INIS)

    Kato, F.; Mimatsu, K.; Kawakami, N.; Miura, T.

    1992-01-01

    Measurements of the intervertebral disc space were made by magnetic resonance imaging and plain film examinations over a period of 2 years in 26 patients who had undergone chemonucleolysis. The height of the posterior portion of the disc decreased after 3 months and never recovered; the height of the anterior portion also decreased but recovered slightly over the same period. The angle of lordosis and the range of motion in the treated segment were decreased, but recovered. Marked decrease in signal from the disc was observed after 2 weeks which did not recover till 2 years after chemonucleolysis. We suspect that the disc degenerated markedly after chemonucleolysis and changed into a type of scar tissue, maturation of which could stabilize the affected segment. (orig.)

  10. Changes seen on magnetic resonance imaging in the intervertebral disc space after chemonucleosis: a hypothesis concerning regeneration of the disc after chemonucleosis

    Energy Technology Data Exchange (ETDEWEB)

    Kato, F; Mimatsu, K; Kawakami, N; Miura, T [Dept. of Orthopaedic Surgery, School of Medicine, Nagoya Univ. (Japan)

    1992-08-01

    Measurements of the intervertebral disc space were made by magnetic resonance imaging and plain film examinations over a period of 2 years in 26 patients who had undergone chemonucleolysis. The height of the posterior portion of the disc decreased after 3 months and never recovered; the height of the anterior portion also decreased but recovered slightly over the same period. The angle of lordosis and the range of motion in the treated segment were decreased, but recovered. Marked decrease in signal from the disc was observed after 2 weeks which did not recover till 2 years after chemonucleolysis. We suspect that the disc degenerated markedly after chemonucleolysis and changed into a type of scar tissue, maturation of which could stabilize the affected segment. (orig.).

  11. Accretion discs around neutron stars

    International Nuclear Information System (INIS)

    Pringle, J.E.

    1982-01-01

    If the central object in the disc is a neutron star, then we do not need the disc itself to produce the X-rays. In other words, the disc structure itself is not important as long as it plays the role of depositing matter on the neutron star at a sufficient rate to produce the X-ray flux. Similarly, in the outer disc regions, the main disc luminosity comes from absorption and reradiation of X-ray photons and not from the intrinsic, viscously-produced, local energy production rate. These two points indicate why in the compact binary X-ray sources confrontation between disc theory and observations is not generally practicable. For this reason I will divide my talk into two parts: one on observational discs in which I discuss what observational evidence there is for discs in the compact X-ray sources and what the evidence can tell the theorist about disc behaviour, and the other on theoretical discs where I consider in what ways theoretical arguments can put limits or cast doubt on some of the empirical models put forward to explain the observations. (orig.)

  12. Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.

    Science.gov (United States)

    Tran, Cassie M; Shapiro, Irving M; Risbud, Makarand V

    2013-08-08

    Connective tissue growth factor (CCN2/CTGF) plays an important role in extracellular matrix synthesis, especially in skeletal tissues such as cartilage, bone, and the intervertebral disc. As a result there is a growing interest in examining the function and regulation of this important molecule in the disc. This review discusses the regulation of CCN2 by TGF-β and hypoxia, two critical determinants that characterize the disc microenvironment, and discusses known functions of CCN2 in the disc. The almost ubiquitous regulation of CCN2 by TGF-β, including that seen in the disc, emphasizes the importance of the TGF-β-CCN2 relationship, especially in terms of extracellular matrix synthesis. Likewise, the unique cross-talk between CCN2 and HIF-1 in the disc highlights the tissue and niche specific mode of regulation. Taken together the current literature supports an anabolic role for CCN2 in the disc and its involvement in the maintenance of tissue homeostasis during both health and disease. Further studies of CCN2 in this tissue may reveal valuable targets for the biological therapy of disc degeneration. © 2013 Elsevier B.V. All rights reserved.

  13. CT discography for cervical soft disc hernia

    Energy Technology Data Exchange (ETDEWEB)

    Iwasa, Kenichi; Mizutani, Shigeru; Morimoto, Hiroyuki; Yamada, Hidehito; Iwasa, Satoru

    1985-03-01

    In this study the effectiveness of computed tomographic discography (CTD) in diagnosing cervical soft disc hernia was evaluated. Twenty-five intervertebral discs of 15 cases with cervical soft disc hernia were examined with a discography and then a CT scan. Results of the CT scan were as follows: three discs were protruded, 12 discs were prolapsed, 6 discs were extruded, and 4 discs were sequestrated. The findings were helpful in determining the location of soft disc hernias between the median and posterolateral discs. They were also valuable in classifying types of hernias and surgical approaches.

  14. CT discography for cervical soft disc hernia

    International Nuclear Information System (INIS)

    Iwasa, Kenichi; Mizutani, Shigeru; Morimoto, Hiroyuki; Yamada, Hidehito; Iwasa, Satoru

    1985-01-01

    In this study the effectiveness of computed tomographic discography (CTD) in diagnosing cervical soft disc hernia was evaluated. Twenty-five interververtebral discs of 15 cases with cervical soft disc hernia were examined with a discography and then a CT scan. Results of the CT scan were as follows: three discs were protruded, 12 discs were prolapsed, 6 discs were extruded, and 4 discs were sequestrated. The findings were helpful in determining the location of soft disc hernians between the median and posterolateral discs. They were also valuable in classifying types of hernians and surgical aproaches. (author)

  15. On Degenerate Partial Differential Equations

    OpenAIRE

    Chen, Gui-Qiang G.

    2010-01-01

    Some of recent developments, including recent results, ideas, techniques, and approaches, in the study of degenerate partial differential equations are surveyed and analyzed. Several examples of nonlinear degenerate, even mixed, partial differential equations, are presented, which arise naturally in some longstanding, fundamental problems in fluid mechanics and differential geometry. The solution to these fundamental problems greatly requires a deep understanding of nonlinear degenerate parti...

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

    Science.gov (United States)

    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

  17. [Surgical treatment of thoracic disc herniation].

    Science.gov (United States)

    Hrabálek, L; Kalita, O; Langová, K

    2010-08-01

    The aim of this study was to compare the efficiency of different surgical approaches to thoracic disc herniation, and to show the role of segmental fusion and selection of an appropriate microsurgical decompression technique for the successful outcome of surgery. A group of 27 patients, 10 men and 17 women, between 31 and 70 years (average age, 49.33 years) were included in this prospective study. They underwent surgery for thoracic degeneration disc disease in the period from June 1994 to August 2008. In all patients, the severity of myelopathy was assessed using the grading Frankel system and JOA score, axial and radicular pain intensity was evaluated with VAS and ODI rating systems. The diagnosis was established on the basis of thoracic spine radiography, thoracic spine MRI and a CT scan of the segment. A total of 30 thoracic segments, in the range of Th4/Th5 to Th12/L1, were indicated for surgery. Localisation of the hernia was medial at 19 segments, mediolateral at three and lateral at eight segments. Soft disc herniation was found in 17 cases and hard disc protrusion at the remaining 13 segments. Surgery for significant myelopathy was carried out in 23 patients and for pain in four patients. According to the surgical procedure used, the patients were allocated to two groups: group A comprised 10 patients treated without disc replacement through a laminectomy or a costotransversectomy exposure, and group B consisted of 17 patients undergo- ing intersomatic fusion via a thoracotomy. Clinical and radiographic examinations were made at regular intervals for at least 1 year of follow-up. The results of clinical assessment, including JOA scores, JOA Recovery Rate, VAS scores at rest and after exercise and ODI, were statistically analysed for each group and compared. There was a statistically significant difference in JOA evaluation of myelopathy between the groups in group A, the mean JOA score declined from 7.9 to 7.0, i.e., -0.9 point, while in group B it

  18. A potential role for cell-based therapeutics in the treatment of intervertebral disc herniation.

    Science.gov (United States)

    Ganey, Timothy M; Meisel, Hans Joerg

    2002-10-01

    Lower back pain and disc degeneration negatively affect quality of life and impose an enormous financial burden. An extensive body of scientific work has evolved that characterizes the disc, demonstrating spinal anatomy and morphology that contribute to risk and likely promote failure. Ultimately, matrix failure is responsible for mechanical failure, which in turn results in spinal compromise anatomically and subsequent pain. One intervening approach to breaking this sequence has been to repopulate the anatomy with autologous disc chondrocytes--cells capable of restoring the matrix and retaining the mechanical balance by which the disc functions. This strategy has been implemented both in patients and in animal models, and early results, although preliminary, support the premise as a positive approach.

  19. Gravitating discs around black holes

    International Nuclear Information System (INIS)

    Karas, V; Hure, J-M; Semerak, O

    2004-01-01

    Fluid discs and tori around black holes are discussed within different approaches and with the emphasis on the role of disc gravity. First reviewed are the prospects of investigating the gravitational field of a black hole-disc system using analytical solutions of stationary, axially symmetric Einstein equations. Then, more detailed considerations are focused to the middle and outer parts of extended disc-like configurations where relativistic effects are small and the Newtonian description is adequate. Within general relativity, only a static case has been analysed in detail. Results are often very inspiring. However, simplifying assumptions must be imposed: ad hoc profiles of the disc density are commonly assumed and the effects of frame-dragging are completely lacking. Astrophysical discs (e.g. accretion discs in active galactic nuclei) typically extend far beyond the relativistic domain and are fairly diluted. However, self-gravity is still essential for their structure and evolution, as well as for their radiation emission and the impact on the surrounding environment. For example, a nuclear star cluster in a galactic centre may bear various imprints of mutual star-disc interactions, which can be recognized in observational properties, such as the relation between the central mass and stellar velocity dispersion. (topical review)

  20. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP and signi......Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP...... and significant relationships between radiological findings and subjective symptoms have both been notoriously difficult to identify. The lack of consensus on clinical criteria and radiological definitions has hampered the undertaking of properly executed epidemiological studies. The natural history of LBP...

  1. Quantum degenerate systems

    Energy Technology Data Exchange (ETDEWEB)

    Micheli, Fiorenza de [Centro de Estudios Cientificos, Arturo Prat 514, Valdivia (Chile); Instituto de Fisica, Pontificia Universidad Catolica de Valparaiso, Casilla 4059, Valparaiso (Chile); Zanelli, Jorge [Centro de Estudios Cientificos, Arturo Prat 514, Valdivia (Chile); Universidad Andres Bello, Av. Republica 440, Santiago (Chile)

    2012-10-15

    A degenerate dynamical system is characterized by a symplectic structure whose rank is not constant throughout phase space. Its phase space is divided into causally disconnected, nonoverlapping regions in each of which the rank of the symplectic matrix is constant, and there are no classical orbits connecting two different regions. Here the question of whether this classical disconnectedness survives quantization is addressed. Our conclusion is that in irreducible degenerate systems-in which the degeneracy cannot be eliminated by redefining variables in the action-the disconnectedness is maintained in the quantum theory: there is no quantum tunnelling across degeneracy surfaces. This shows that the degeneracy surfaces are boundaries separating distinct physical systems, not only classically, but in the quantum realm as well. The relevance of this feature for gravitation and Chern-Simons theories in higher dimensions cannot be overstated.

  2. Unilateral Acute Anterior Ischemic Optic Neuropathy in a Patient with an Already Established Diagnosis of Bilateral Optic Disc Drusen

    Directory of Open Access Journals (Sweden)

    Ziya Ayhan

    2015-01-01

    Full Text Available Optic disc drusen (ODD are calcific deposits that form in the optic nerve head secondary to abnormalities in axonal metabolism and degeneration. Anterior ischemic optic neuropathy, central retinal artery, and vein occlusion are among the rare vascular complications of disc drusen. We reported the clinical course of a 51-year-old patient with a unilateral acute nonarteritic anterior ischemic optic neuropathy (NAION who received the diagnosis of bilateral optic disc drusen five years earlier and thereby reiterated the association of ODD and acute NAION.

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

    Directory of Open Access Journals (Sweden)

    Yue JJ

    2016-05-01

    Full Text Available James J Yue,1 Rolando Garcia Jr,2 Larry E Miller3 1Department of Orthopaedic Surgery, Yale School of Medicine, New Haven, CT, 2Orthopedic Care Center, Miami, FL, 3Miller Scientific Consulting, Inc., Asheville, NC, USA Abstract: 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. Keywords: activL® Artificial Disc, artificial disc, degenerative disc disease, discogenic, implant, lumbar, motion preservation, pain

  4. An ex vivo study on immunohistochemical localization of MMP-7 and MMP-9 in temporomandibular joint discs with internal derangement

    Directory of Open Access Journals (Sweden)

    C. Loreto

    2013-04-01

    Full Text Available Internal derangement (ID is among the most common disorders of the temporomandibular joint (TMJ. Previous research by our group highlighted a correlation between apoptosis and TMJ ID. Metalloproteinases (MMP-7 and -9 have been shown to play an important role in extracellular matrix ECM homeostasis and, through it, in joint disc remodelling. The immunohistochemical expression of MMP-7 and -9 was investigated in discs from patients with TMJ ID and from healthy donors and compared with the degree of histological tissue degeneration. The collagen fibre arrangement in pathological discs exhibited varying degrees of disruption. New vessels were consistently detected; endothelial cells from these vessels were immunolabelled with both MMP-7 and MMP-9. More or less intense MMP-7 and MMP-9 immunolabelling was detected in the cytoplasm of disc cells from all patients. MMP-7 and MMP-9 immunostaining was significantly different between pathological and normal discs and correlated with the extent of histopathological degeneration. MMP-7 and MMP-9 upregulation in discs from patients with TMJ ID demonstrates their involvement in disc damage in this disorder. A greater understanding of these processes could help identify ways to curb MMP overproduction without affecting their tissue remodelling action. The design of specific inhibitors for these MMPs would not only help to gain insights into the biological roles of MMPs, but would also aid in developing therapeutic interventions for diseases associated with abnormal ECM degradation.

  5. An intervertebral disc whole organ culture system to investigate proinflammatory and degenerative disc disease condition.

    Science.gov (United States)

    Lang, Gernot; Liu, Yishan; Geries, Janna; Zhou, Zhiyu; Kubosch, David; Südkamp, Norbert; Richards, R Geoff; Alini, Mauro; Grad, Sibylle; Li, Zhen

    2018-04-01

    The aim of this study was to compare the effect of different disease initiators of degenerative disc disease (DDD) within an intervertebral disc (IVD) organ culture system and to understand the interplay between inflammation and degeneration in the early stage of DDD. Bovine caudal IVDs were cultured within a bioreactor for up to 11 days. Control group was cultured under physiological loading (0.02-0.2 MPa; 0.2 Hz; 2 hr/day) and high glucose (4.5 g/L) medium. Detrimental loading (0.32-0.5 MPa, 5 Hz; 2 hr/day) and low glucose (2 g/L) medium were applied to mimic the condition of abnormal mechanical stress and limited nutrition supply. Tumour necrosis factor alpha (TNF-α) was injected into the nucleus pulposus (100 ng per IVD) as a proinflammatory trigger. TNF-α combined with detrimental loading and low glucose medium up-regulated interleukin 1β (IL-1β), IL-6, and IL-8 gene expression in disc tissue, nitric oxide, and IL-8 release from IVD, which indicate a proinflammatory effect. The combined initiators up-regulated matrix metalloproteinase 1 gene expression, down-regulated gene expression of Type I collagen in annulus fibrosus and Type II collagen in nucleus pulposus, and reduced the cell viability. Furthermore, the combined initiators induced a degradative effect, as indicated by markedly higher glycosaminoglycan release into conditioned medium. The combination of detrimental dynamic loading, nutrient deficiency, and TNF-α intradiscal injection can synergistically simulate the proinflammatory and degenerative disease condition within DDD. This model will be of high interest to screen therapeutic agents in further preclinical studies for early intervention and treatment of DDD. Copyright © 2018 John Wiley & Sons, Ltd.

  6. Chronic ingestion of advanced glycation end products induces degenerative spinal changes and hypertrophy in aging pre-diabetic mice.

    Science.gov (United States)

    Illien-Jünger, Svenja; Lu, Young; Qureshi, Sheeraz A; Hecht, Andrew C; Cai, Weijing; Vlassara, Helen; Striker, Gary E; Iatridis, James C

    2015-01-01

    Intervertebral disc (IVD) degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs), cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG)) on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+) or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG). dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions.

  7. Chronic ingestion of advanced glycation end products induces degenerative spinal changes and hypertrophy in aging pre-diabetic mice.

    Directory of Open Access Journals (Sweden)

    Svenja Illien-Jünger

    Full Text Available Intervertebral disc (IVD degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs, cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+ or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG. dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions.

  8. Double-disc gate valve

    International Nuclear Information System (INIS)

    Wheatley, S.J.

    1979-01-01

    The invention relates to an improvement in a conventional double-disc gate valve having a vertically movable gate assembly including a wedge, spreaders slidably engaged therewith, a valve disc carried by the spreaders. When the gate assembly is lowered to a selected point in the valve casing, the valve discs are moved transversely outward to close inlet and outlet ports in the casing. The valve includes hold-down means for guiding the disc-and-spreader assemblies as they are moved transversely outward and inward. If such valves are operated at relatively high differential pressures, they sometimes jam during opening. Such jamming has been a problem for many years in gate valves used in gaseous diffusion plants for the separation of uranium isotopes. The invention is based on the finding that the above-mentioned jamming results when the outlet disc tilts about its horizontal axis in a certain way during opening of the valve. In accordance with the invention, tilting of the outlet disc is maintained at a tolerable value by providing the disc with a rigid downwardly extending member and by providing the casing with a stop for limiting inward arcuate movement of the member to a preselected value during opening of the valve

  9. Helicoid peripapillary chorioretinal degeneration complicated by choroidal neovascularization.

    Science.gov (United States)

    Triantafylla, Magdalini; Panos, Georgios D; Dardabounis, Doukas; Nanos, Panagiotis; Konstantinidis, Aristeidis

    2016-02-15

    Helicoid peripapillary chorioretinal degeneration (HPCD) is a hereditary disease of the fundus that is characterized by atrophic chorioretinal areas that appear early in life and expand gradually from the optic disc towards the macula and the periphery. We describe the case of an elderly man with a known diagnosis of HPCD who developed choroidal neovascular membrane (CNV) in both eyes during the course of the disease. The patient was treated with intravitreal injection of ranibizumab, to which he had excellent response. The CNV subsided with 2 injections in the right eye and 1 in the left. Two years after the initial diagnosis of CNV in the right eye, visual acuity was 5/10 OD and 9/10 OS. Helicoid peripapillary chorioretinal degeneration is rarely complicated by CNV as the fundus lacks the trigger factors that would sustain this process. Although rare, HPCD complicated by CNV can be seen bilaterally, but responds well to few ranibizumab injections.

  10. Radiation treatment for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Tomoko; Mandai, Michiko; Honjo, Megumi; Matsuda, Naoko; Miyamoto, Hideki; Takahashi, Masayo; Ogura, Yuichiro; Sasai, Keisuke [Kyoto Univ. (Japan). Faculty of Medicine

    1996-11-01

    Fifteen eyes of age-related macular degeneration were treated by low-dose radiation. All the affected eyes had subfoveal neovascular membrane. Seventeen nontreated eyes with similar macular lesion served as control. Radiation was performed using photon beam at 6MV. Each eye received daily dose of 2 Gy for 5 consecutive days. When evaluated 9 to 12 months after treatment, the size of neovascular membrane had decreased in 47% of treated eyes and 7% of control eyes. The visual acuity improved by 2 lines or more in 13% of treated eyes and in none of control eyes. When the initial neovascular membrane was less than 1.5 disc diameter in size, the visual acuity had improved or remained stationary in 90% of treated eyes and in 36% of control eyes. The findings show the potential beneficial effect of radiation for age-related macular degeneration. (author)

  11. Are galaxy discs optically thick?

    International Nuclear Information System (INIS)

    Disney, Michael; Davies, Jonathan; Phillipps, Steven

    1989-01-01

    We re-examine the classical optical evidence for the low optical depths traditionally assigned to spiral discs and argue that it is highly model-dependent and unconvincing. In particular, layered models with a physically thin but optically thick dust layer behave like optically thin discs. The opposite hypotheses, that such discs are optically thick is then examined in the light of modern evidence. We find it to be consistent with the near-infrared and IRAS observations, with the surface brightnesses, with the HI and CO column densities and with the Hα measurements. (author)

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

    Science.gov (United States)

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

    2011-03-01

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

  13. Relationship between facet tropism and facet joint degeneration in the sub-axial cervical spine

    Directory of Open Access Journals (Sweden)

    Xin Rong

    2017-02-01

    Full Text Available Abstract Background Facet tropism is the angular asymmetry between the left and right facet joint orientation. Although debatable, facet tropism was suggested to be associated with disc degeneration, facet degeneration and degenerative spondylolisthesis in the lumbar spine. The purpose of this study was to explore the relationship between facet tropism and facet degeneration in the sub-axial cervical spine. Methods A total of 200 patients with cervical spondylosis were retrospectively analyzed. Facet degeneration was categorized into 4 grade: grade I, normal; grade II, degenerative changes including joint space narrowing, cyst formation, small osteophytes (3 mm without fusion of the joint; grade IV, bony fusion of the facet joints. Facet orientations and facet tropisms with respect to the transverse, sagittal and coronal plane were calculated from the reconstructed cervical spine, which was based on the axial CT scan images. The paired facet joints were then categorized into three types: symmetric, moderated tropism and severe tropism. Univariate and multivariate analysis were performed to evaluate the relationship between any demographic and anatomical factor and facet degeneration. Results The mean age of enrolled patients was 46.23 years old (ranging from 30 to 64 years old. There were 114 males and 86 females. The degrees of facet degeneration varied according to cervical levels and ages. Degenerated facet joints were most common at C2-C3 level and more common in patients above 50 years old. The facet orientations were also different from level to level. By univariate analysis, genders, ages, cervical levels, facet orientations and facet tropisms were all significantly different between the normal facets and degenerated facets. However, results from multivariate logistic regression suggested only age and facet tropism with respect to the sagittal plane were related to facet degeneration. Conclusion Facet degeneration were more common at

  14. Disc piezoelectric ceramic transformers.

    Science.gov (United States)

    Erhart, Jirií; Půlpán, Petr; Doleček, Roman; Psota, Pavel; Lédl, Vít

    2013-08-01

    In this contribution, we present our study on disc-shaped and homogeneously poled piezoelectric ceramic transformers working in planar-extensional vibration modes. Transformers are designed with electrodes divided into wedge, axisymmetrical ring-dot, moonie, smile, or yin-yang segments. Transformation ratio, efficiency, and input and output impedances were measured for low-power signals. Transformer efficiency and transformation ratio were measured as a function of frequency and impedance load in the secondary circuit. Optimum impedance for the maximum efficiency has been found. Maximum efficiency and no-load transformation ratio can reach almost 100% and 52 for the fundamental resonance of ring-dot transformers and 98% and 67 for the second resonance of 2-segment wedge transformers. Maximum efficiency was reached at optimum impedance, which is in the range from 500 Ω to 10 kΩ, depending on the electrode pattern and size. Fundamental vibration mode and its overtones were further studied using frequency-modulated digital holographic interferometry and by the finite element method. Complementary information has been obtained by the infrared camera visualization of surface temperature profiles at higher driving power.

  15. Genetic Alterations in Intervertebral Disc Disease

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    Nikolay L. Martirosyan

    2016-11-01

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

  16. Disc Golf: Teaching a Lifetime Activity

    Science.gov (United States)

    Eastham, Susan L.

    2015-01-01

    Disc golf is a lifetime activity that can be enjoyed by students of varying skill levels and abilities. Disc golf follows the principles of ball golf but is generally easier for students to play and enjoy success. The object of disc golf is similar to ball golf and involves throwing a disc from the teeing area to the target in as few throws as…

  17. Degenerate band edge laser

    Science.gov (United States)

    Veysi, Mehdi; Othman, Mohamed A. K.; Figotin, Alexander; Capolino, Filippo

    2018-05-01

    We propose a class of lasers based on a fourth-order exceptional point of degeneracy (EPD) referred to as the degenerate band edge (DBE). EPDs have been found in parity-time-symmetric photonic structures that require loss and/or gain; here we show that the DBE is a different kind of EPD since it occurs in periodic structures that are lossless and gainless. Because of this property, a small level of gain is sufficient to induce single-frequency lasing based on a synchronous operation of four degenerate Floquet-Bloch eigenwaves. This lasing scheme constitutes a light-matter interaction mechanism that leads also to a unique scaling law of the laser threshold with the inverse of the fifth power of the laser-cavity length. The DBE laser has the lowest lasing threshold in comparison to a regular band edge laser and to a conventional laser in cavities with the same loaded quality (Q ) factor and length. In particular, even without mirror reflectors the DBE laser exhibits a lasing threshold which is an order of magnitude lower than that of a uniform cavity laser of the same length and with very high mirror reflectivity. Importantly, this novel DBE lasing regime enforces mode selectivity and coherent single-frequency operation even for pumping rates well beyond the lasing threshold, in contrast to the multifrequency nature of conventional uniform cavity lasers.

  18. Reprodutibilidade intra e interobservadores da classificação de hipersinal facetário lombar e correlação com a degeneração discal para ressonância magnética Reproducibilidad intra e inter observadores de la clasificación de hiperseñal facetaria lumbar y correlación con la degeneración discal para resonancia magnética Intraobserver and interobserver reproducibility of lumbar facet hypersignal rating and correlation with disc degeneration by magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    André Evaristo Marcondes César

    2011-01-01

    la relación entre la artrosis facetaria y la degeneración del disco. RESULTADOS: Fueran evaluados y clasificados 205 discos lumbares y sus facetas articulares por los cuatro examinadores con las informaciones analizadas por la Prueba de Cronbach y el Análisis de Correlación de Spearman, con resultados estadísticamente elevados, confirmando buena relación inter e intra observadores para la "clasificación de hiperseñal facetaria" . No fue observada relación estadísticamente significativa entre artrosis facetaria y degeneración discal. CONCLUSIÓN: Fueran obtenidos resultados suficientes para asegurar que hay buena relación inter y intra observadores para la "Clasificación de hiperseñal facetaria" . No fue verificada relación estadísticamente significativa entre artrosis facetaria y degeneración discal.OBJECTIVE: To assess intraobserver and interobserver reproducibility of lumbar facet hypersignal rating and to assess the correlation with disc degeneration. METHODS: Retrospective study of magnetic resonance imaging of 41 patients (18 male and 23 female, with mean age of 48 years and three months (range 26-84 years. Three independent orthopaedic spine surgeons and one radiologist reviewed the images to assess and quantify the presence of lumbar facet hypersignal. Later, the relation between facet arthrosis and disc degeneration was evaluated. RESULTS: 205 lumbar discs and facets were assessed and rated by four independent observers, the records were analyzed by Cronbach test and Spearman correlation analysis with high statistical outcomes which confirm a good interobserver and intraobserver relation for lumbar facet hypersignal rating. No statistical difference between facet arthrosis and disc degeneration was verified. CONCLUSION: Sufficient outcomes were obtained to confirm the existence of good interobserver and intraobserver relation for lumbar facet hypersignal rating. No statistical difference between facet arthrosis and disc degeneration was

  19. Spontaneous oscillatory rhythms in the degenerating mouse retina modulate retinal ganglion cell responses to electrical stimulation

    Directory of Open Access Journals (Sweden)

    Yong Sook eGoo

    2016-01-01

    Full Text Available Characterization of the electrical activity of the retina in the animal models of retinal degeneration has been carried out in part to understand the progression of retinal degenerative diseases like age-related macular degeneration (AMD and retinitis pigmentosa (RP, but also to determine optimum stimulus paradigms for use with retinal prosthetic devices. The models most studied in this regard have been the two lines of mice deficient in the β-subunit of phosphodiesterase (rd1 and rd10 mice, where the degenerating retinas exhibit characteristic spontaneous hyperactivity and oscillatory local field potentials (LFPs. Additionally, there is a robust ~10 Hz rhythmic burst of retinal ganglion cell (RGC spikes on the trough of the oscillatory LFP. In rd1 mice, the rhythmic burst of RGC spikes is always phase-locked with the oscillatory LFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, the frequency of the oscillatory rhythm changes according to postnatal age, suggesting that this rhythm might be a marker of the stage of degeneration. Furthermore when a biphasic current stimulus is applied to rd10 mice degenerate retina, distinct RGC response patterns that correlate with the stage of degeneration emerge. This review also considers the significance of these response properties.

  20. Lumbar disc excision through fenestration

    Directory of Open Access Journals (Sweden)

    Sangwan S

    2006-01-01

    Full Text Available Background : Lumbar disc herniation often causes sciatica. Many different techniques have been advocated with the aim of least possible damage to other structures while dealing with prolapsed disc surgically in the properly selected and indicated cases. Methods : Twenty six patients with clinical symptoms and signs of prolapsed lumbar intervertebral disc having radiological correlation by MRI study were subjected to disc excision by interlaminar fenestration method. Results : The assessment at follow-up showed excellent results in 17 patients, good in 6 patients, fair in 2 patients and poor in 1 patient. The mean preoperative and postoperative Visual Analogue Scores were 9.34 ±0.84 and 2.19 ±0.84 on scale of 0-10 respectively. These were statistically significant (p value< 0.001, paired t test. No significant complications were recorded. Conclusion : Procedures of interlaminar fenestration and open disc excision under direct vision offers sufficient adequate exposure for lumbar disc excision with a smaller incision, lesser morbidity, shorter convalescence, early return to work and comparable overall results in the centers where recent laser and endoscopy facilities are not available.

  1. Death Receptor 6 Promotes Wallerian Degeneration in Peripheral Axons.

    Science.gov (United States)

    Gamage, Kanchana K; Cheng, Irene; Park, Rachel E; Karim, Mardeen S; Edamura, Kazusa; Hughes, Christopher; Spano, Anthony J; Erisir, Alev; Deppmann, Christopher D

    2017-03-20

    Axon degeneration during development is required to sculpt a functional nervous system and is also a hallmark of pathological insult, such as injury [1, 2]. Despite similar morphological characteristics, very little overlap in molecular mechanisms has been reported between pathological and developmental degeneration [3-5]. In the peripheral nervous system (PNS), developmental axon pruning relies on receptor-mediated extrinsic degeneration mechanisms to determine which axons are maintained or degenerated [5-7]. Receptors have not been implicated in Wallerian axon degeneration; instead, axon autonomous, intrinsic mechanisms are thought to be the primary driver for this type of axon disintegration [8-10]. Here we survey the role of neuronally expressed, paralogous tumor necrosis factor receptor super family (TNFRSF) members in Wallerian degeneration. We find that an orphan receptor, death receptor 6 (DR6), is required to drive axon degeneration after axotomy in sympathetic and sensory neurons cultured in microfluidic devices. We sought to validate these in vitro findings in vivo using a transected sciatic nerve model. Consistent with the in vitro findings, DR6 -/- animals displayed preserved axons up to 4 weeks after injury. In contrast to phenotypes observed in Wld s and Sarm1 -/- mice, preserved axons in DR6 -/- animals display profound myelin remodeling. This indicates that deterioration of axons and myelin after axotomy are mechanistically distinct processes. Finally, we find that JNK signaling after injury requires DR6, suggesting a link between this novel extrinsic pathway and the axon autonomous, intrinsic pathways that have become established for Wallerian degeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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

  3. Clinical evaluation of CT discography in the diagnosis of lumbar disc herniation

    International Nuclear Information System (INIS)

    Maehara, Tadayuki; Katsumata, Yasushi; Noda, Masanobu; Tanaka, Mariko; Shirouzu, Ichirou

    1988-01-01

    The CT discographic findings of 56 discs in 43 patients with low-back and/or leg pain were evaluated mainly from the clinical standpoint including pain provocation during the injection of the contrast material, correlation between the type of the herniation and symptoms and clinical course after the examination. The clinical value of CT discography is controversial, but it is well recognized that CT discography is the diagnostic method of choice for equivocal situations as patients showing negative myelography and significant symptoms and for the preoperative evaluation of patient thought to have the extreme lateral disc herniation. Exact provoked pain response was noted in 72 % of 43 pathologic discs and almost all discs especially in patients showing positive SLR test at less than 70 deg. So this pain response seems to provide additional information indicating the true pathologic disc level. Sciatic pain in the legs was much more frequently seen in the paramedian or lateral type herniation, but there was no relation between low-back pain and central type herniation. Majority of either type of disc herniation showed both low-back and leg pains. This suggests that clinical symptoms are based on not only disc herniation but also disc degeneration itself. We injected steroid (4 mg of Decadron) and local anesthetic (1 ml of 1 % Carbocain) into the disc after the examination for the purpose of improving the clinical symptoms as the first attempt. Definite improvement of various degree was noted in 56 % of total 43 cases after the procedure and CT discography was thought to be a valuable method of diagnosis in proper indications despite risky needle puncture. (author)

  4. Second order degenerate elliptic equations

    International Nuclear Information System (INIS)

    Duong Minh Duc.

    1988-08-01

    Using an improved Sobolev inequality we study a class of elliptic operators which is degenerate inside the domain and strongly degenerate near the boundary of the domain. Our results are applicable to the L 2 -boundary value problem and the mixed boundary problem. (author). 18 refs

  5. Evolution of viscous discs. 3. Giant discs in symbiotic stars

    Energy Technology Data Exchange (ETDEWEB)

    Bath, G T [Oxford Univ. (UK). Dept. of Astrophysics; Pringle, J E [Cambridge Univ. (UK). Inst. of Astronomy

    1982-10-01

    The structure of time-dependent accretion discs in giant binaries with separation of the order of 10/sup 13/ cm is examined. Radiative ..cap alpha..-viscosity discs with ..cap alpha.. of order unity accreting on to main-sequence stars at accretion rates which generate luminosities greater than a giant companion decay on time-scales of the same order as the binary period, unlike those in dwarf nova binaries which decay on time-scales 100 times longer than the binary period. This results from the lower gravitational potential and consequent larger disc thickness (relative to the radius) of luminous 'giant' discs accreting at high accretion rates. The eruptions of the symbiotic binary C I Cygni are modelled by an ..cap alpha.. = 1 disc with outer radius 8.5 x 10/sup 12/ cm and a sequence of five mass-transfer bursts at rates between 1.5 x 10/sup 21/ and 4 x 10/sup 22/g s/sup -1/.

  6. Double Degenerate Stars

    International Nuclear Information System (INIS)

    Xin-Lian, Luo; Hua, Bai; Lei, Zhao

    2008-01-01

    Regardless of the formation mechanism, an exotic object, the double degenerate star (DDS), is introduced and investigated, which is composed of baryonic matter and some unknown fermion dark matter. Different from the simple white dwarfs (WDs), there is additional gravitational force provided by the unknown fermion component inside DDSs, which may strongly affect the structure and the stability of such kind of objects. Many possible and strange observational phenomena connecting with them are concisely discussed. Similar to the normal WD, this object can also experience thermonuclear explosion as type Ia supernova explosion when DDS's mass exceeds the maximum mass that can be supported by electron degeneracy pressure. However, since the total mass of baryonic matter can be much lower than that of WD at Chandrasekhar mass limit, the peak luminosity should be much dimmer than what we expect before, which may throw a slight shadow on the standard candle of SN Ia in the research of cosmology. (general)

  7. Adjacent segment degeneration after lumbar spinal fusion: the impact of anterior column support: a randomized clinical trial with an eight- to thirteen-year magnetic resonance imaging follow-up.

    Science.gov (United States)

    Videbaek, Tina S; Egund, Niels; Christensen, Finn B; Grethe Jurik, Anne; Bünger, Cody E

    2010-10-15

    Randomized controlled trial. To analyze long-term adjacent segment degeneration (ASD) after lumbar fusion on magnetic resonance imaging and compare randomization groups with and without anterior column support. ASD can be a long-term complication after fusion. The prevalence and the cause of ASD are not well documented, but ASD are one of the main arguments for introducing the use of motion-preserving techniques as an alternative to fusion. Anterior lumbar interbody fusion combined with posterolateral lumbar fusion (ALIF+PLF) has been proved superior to posterolateral fusion alone regarding outcome and cost-effectiveness. Between 1996 and 1999, 148 patients with severe chronic low back pain were randomly selected for ALIF+PLF or for PLF alone. Ninety-five patients participated. ASD was examined on magnetic resonance imaging with regard to disc degeneration, disc herniation, stenosis, and endplate changes. Disc heights on radiographs taken at index surgery and at long-term follow-up were compared. Outcome was assessed by validated questionnaires. The follow-up rate was 76%. ASD was similar between randomization groups. In the total cohort, endplate changes were seen in 26% of the participants and correlated significantly with the presence of disc degeneration and disc herniation. Disc degeneration and dorsal disc herniation were the parameters registered most frequently and were significantly more pronounced at the first adjacent level than at the second and the third adjacent levels. Patients without disc height reduction over time were significantly younger than patients with disc height reduction. Disc degeneration and stenosis correlated significantly with outcome at the first adjacent level. The cause of the superior outcome in the group with anterior support is still unclear. Compared with the findings reported in the literature, the prevalence of ASD is likely to be in concordance with the expected changes in a nonoperated symptomatic population and therefore

  8. A minimally invasive in-fiber Bragg grating sensor for intervertebral disc pressure measurements

    International Nuclear Information System (INIS)

    Dennison, Christopher R; Wild, Peter M; Wilson, David R; Cripton, Peter A

    2008-01-01

    We present an in-fiber Bragg grating (FBG) based intervertebral disc (IVD) pressure sensor that has pressure sensitivity seven times greater than that of a bare fiber, and a major diameter and sensing area of only 400 µm and 0.03 mm 2 , respectively. This is the only optical, the smallest and the most mechanically compliant disc pressure sensor reported in the literature. This is also an improvement over other FBG pressure sensors that achieve increased sensitivity through mechanical amplification schemes, usually resulting in major diameters and sensing lengths of many millimeters. Sensor sensitivity is predicted using numerical models, and the predicted sensitivity is verified through experimental calibrations. The sensor is validated by conducting IVD pressure measurements in porcine discs and comparing the FBG measurements to those obtained using the current standard sensor for IVD pressure. The predicted sensitivity of the FBG sensor matched with that measured experimentally. IVD pressure measurements showed excellent repeatability and agreement with those obtained from the standard sensor. Unlike the current larger sensors, the FBG sensor could be used in discs with small disc height (i.e. cervical or degenerated discs). Therefore, there is potential to conduct new measurements that could lead to new understanding of the biomechanics

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Masamitsu Tanaka

    2010-08-01

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

  11. [Lattice degeneration of the retina].

    Science.gov (United States)

    Boĭko, E V; Suetov, A A; Mal'tsev, D S

    2014-01-01

    Lattice degeneration of the retina is a clinically important type of peripheral retinal dystrophies due to its participation in the pathogenesis of rhegmatogenous retinal detachment. In spite of extensive epidemiological, morphological, and clinical data, the question on causes of this particular type of retinal dystrophies currently remains debatable. Existing hypotheses on pathogenesis of retinal structural changes in lattice degeneration explain it to a certain extent. In clinical ophthalmology it is necessary to pay close attention to this kind of degenerations and distinguish between cases requiring preventive treatment and those requiring monitoring.

  12. Vertebral osteomyelitis without disc involvement

    Energy Technology Data Exchange (ETDEWEB)

    Kamani, I.; Syed, I.; Saifuddin, A. E-mail: asaifuddin@aol.com; Green, R.; MacSweeney, F

    2004-10-01

    Vertebral osteomyelitis is most commonly due to pyogenic or granulomatous infection and typically results in the combined involvement of the intervertebral disc and adjacent vertebral bodies. Non-infective causes include the related conditions of chronic recurrent multifocal osteomyelitis (CRMO) and SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. Occasionally, these conditions may present purely within the vertebral body, resulting in various combinations of vertebral marrow oedema and sclerosis, destructive lesions of the vertebral body and pathological vertebral collapse, thus mimicking neoplastic disease. This review illustrates the imaging features of vertebral osteomyelitis without disc involvement, with emphasis on magnetic resonance imaging (MRI) findings.

  13. [Tapeto-retinal degeneration combined with incomplete general albinism (author's transl)].

    Science.gov (United States)

    Ivandić, T

    1975-05-01

    Report on a family, which presented the rare autosomal dominant transmitted, incomplete general albinism associated with autosomal recessive inherited, diffuse tapeto-retinal degeneration "sine pigmento". hypopigmentation of skin, eyebrows and hair, blue iris and fundus albinoticus with hypoplasia of the macula. In 3 cases additionally appeared: waxy pallor of optic disc, vascular narrowing, reflexless hypoplastic macula, pigmentless periphery, acquired blue-yellow blindness, concentric limitation of the visual field, reduced darkadaptation, abolished electroretinogram and myopic astigmatism.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  16. Macular degeneration - age-related

    Science.gov (United States)

    ... AMD occurs when the blood vessels under the macula become thin and brittle. Small yellow deposits, called drusen, form. Almost all people with macular degeneration start with the dry form. Wet AMD occurs ...

  17. Computed tomography of Wallerian degeneration

    International Nuclear Information System (INIS)

    Uchino, Akira; Maeda, Fumihiko

    1986-01-01

    CT findings of wallerian degeneration of the pyramidal tract at the midbrain (atrophy of cerebral peduncle following cerebrovascular accident) were studied in 34 patients (44 CT scans) with old cerebrovascular accidents. Severe atrophy of cerebral peduncle was noted when the ipsilateral motor cortex was involved. However, when the posterior limb of the internal capsule was involved, atrophy of the ipsilateral cerebral peduncle was mild. In this series, the shortest interval between cerebrovascular accident and wallerian degeneration was 8 month. (author)

  18. What Is Age-Related Macular Degeneration?

    Science.gov (United States)

    ... Eye Health / Eye Health A-Z Age-Related Macular Degeneration Sections What Is Macular Degeneration? How is AMD ... What Does Macular Degeneration Look Like? What Is Macular Degeneration? Leer en Español: ¿Qué es la degeneración macular ...

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

    Science.gov (United States)

    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

  20. CT morphometry of adult thoracic intervertebral discs.

    Science.gov (United States)

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

    2015-10-01

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

  1. Digoxin-induced retinal degeneration depends on rhodopsin.

    Science.gov (United States)

    Landfried, Britta; Samardzija, Marijana; Barben, Maya; Schori, Christian; Klee, Katrin; Storti, Federica; Grimm, Christian

    2017-03-16

    Na,K-ATPases are energy consuming ion pumps that are required for maintaining ion homeostasis in most cells. In the retina, Na,K-ATPases are especially important to sustain the dark current in photoreceptor cells needed for rapid hyperpolarization of rods and cones in light. Cardiac glycosides like digoxin inhibit the activity of Na,K-ATPases by targeting their catalytic alpha subunits. This leads to a disturbed ion balance, which can affect cellular function and survival. Here we show that the treatment of wild-type mice with digoxin leads to severe retinal degeneration and loss of vision. Digoxin induced cell death specifically in photoreceptor cells with no or only minor effects in other retinal cell types. Photoreceptor-specific cytotoxicity depended on the presence of bleachable rhodopsin. Photoreceptors of Rpe65 knockouts, which have no measurable rhodopsin and photoreceptors of Rpe65 R91W mice that have treatment. Similarly, cones in the all-cone retina of Nrl knockout mice were also not affected. Digoxin induced expression of several genes involved in stress signaling and inflammation. It also activated proteins such as ERK1/2, AKT, STAT1, STAT3 and CASP1 during a period of up to 10 days after treatment. Activation of signaling genes and proteins, as well as the dependency on bleachable rhodopsin resembles mechanisms of light-induced photoreceptor degeneration. Digoxin-mediated photoreceptor cell death may thus be used as an inducible model system to study molecular mechanisms of retinal degeneration.

  2. Thermochemical modelling of brown dwarf discs

    NARCIS (Netherlands)

    Greenwood, A. J.; Kamp, I.; Waters, L. B. F. M.; Woitke, P.; Thi, W.-F.; Rab, Ch.; Aresu, G.; Spaans, M.

    The physical properties of brown dwarf discs, in terms of their shapes and sizes, are still largely unexplored by observations. ALMA has by far the best capabilities to observe these discs in sub-mm CO lines and dust continuum, while also spatially resolving some discs. To what extent brown dwarf

  3. CT findings of lumbar intervertebral disc: II. Disc herniation (HNP)

    International Nuclear Information System (INIS)

    Yang, W. J.; Lee, J. M.; Bahk, Y. W.

    1984-01-01

    In lumbar region the epidural fat pad is relatively abundant so that CT can provides sufficient information in diagnosis of lumbar HNP. Many authors have reported on the CT findings of HNP such as focal nodular protrusion of the posterior disc margin, obliteration of epidural fat pad, impingement of dural sac and nerve root, swelling of nerve root, soft tissue density in the spinal canal and calcification of disc. However there was so previous report describing incidence and reliability of the findings. It is the purpose of the present study to survey the frequency, reliability, and limitation of these CT findings. The clinical material was consisted of 30 operatively proven cases of HNP of the lumbar spine. Each lumbar CT scan was reviewed retrospectively and the findings were analysed by two radiologists independently. There were 20 males and 10 females and the mean age was 36.7 years. Involvement of L4-S5 level was 2.3 times more frequent than that of L5-S1 level. Of 30 cases, 22 were unilateral posterolateral types and 8 cases central or unilateral far lateral types. CT findings observed were nodular protrusion of the posterior margin of the disc, obliteration of epidural fat pad, impingement of dural sac or nerve root, soft tissue density in the spinal canal and calcification in the posterior portion of the protruded disc, in order of decreasing frequency. The conclusions are follows: 1. Nodular protrusion of the posterior disc margin accompanied by obliteration of epidural fat pad was observed in every case. The former findings was designated as direct sign and the latter indirect. 2. Obliteration of the epidural fat appears to be significant in lateral recesses especially when it occurs unilaterally. This was not true, however, in the centrally located fat pad. 3. Impingement of the dural sac and nerve root were observed in 90% and 67%, respectively, and were very helpful in establishing HNP diagnosis when the direct and indirect signs were equivocal

  4. Autophagy Is a Protective Response to the Oxidative Damage to Endplate Chondrocytes in Intervertebral Disc: Implications for the Treatment of Degenerative Lumbar Disc

    Directory of Open Access Journals (Sweden)

    Ke Chen

    2017-01-01

    Full Text Available Low back pain (LBP is the leading cause of disability in the elderly. Intervertebral disc degeneration (IDD was considered as the main cause for LBP. Degeneration of cartilaginous endplate was a crucial harmful factor during the initiation and development of IDD. Oxidative stress was implicated in IDD. However, the underlying molecular mechanism for the degeneration of cartilaginous endplate remains elusive. Herein, we found that oxidative stress could induce apoptosis and autophagy in endplate chondrocytes evidenced by western blot analysis, flow cytometry, immunofluorescence staining, GFP-LC3B transfection, and MDC staining. In addition, we also found that the apoptosis of endplate chondrocytes was significantly increased after the inhibition of autophagy by bafilomycin A1 shown by flow cytometry. Furthermore, mTOR pathway upstream autophagy was greatly suppressed suggested by western blot assay. In conclusion, our study strongly revealed that oxidative stress could increase autophagy and apoptosis of endplate chondrocytes in intervertebral disc. The increase of autophagy activity could prevent endplate chondrocytes from apoptosis. The autophagy in endplate chondrocytes induced by oxidative stress was mTOR dependent. These findings might shed some new lights on the mechanism for IDD and provide new strategies for the treatments of IDD.

  5. Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease: A Systematic Review of Animal Studies and Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    David Oehme

    2015-01-01

    Full Text Available Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. Advances in regenerative medicine and cell-based therapies, particularly the transplantation of mesenchymal stem cells and intervertebral disc chondrocytes, have led to the publication of numerous studies and clinical trials utilising these biological therapies to treat degenerative spinal conditions, often reporting favourable outcomes. Stem cell mediated disc regeneration may bridge the gap between the two current alternatives for patients with low back pain, often inadequate pain management at one end and invasive surgery at the other. Through cartilage formation and disc regeneration or via modification of pain pathways stem cells are well suited to enhance spinal surgery practice. This paper will systematically review the current status of basic science studies, preclinical and clinical trials utilising cell-based therapies to repair the degenerate intervertebral disc. The mechanism of action of transplanted cells, as well as the limitations of published studies, will be discussed.

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

    Science.gov (United States)

    Mwale, F; Roughley, P; Antoniou, J

    2004-12-15

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

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

    Directory of Open Access Journals (Sweden)

    Mwale F.

    2004-12-01

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

  8. Axonal degeneration stimulates the formation of NG2+ cells and oligodendrocytes in the mouse

    DEFF Research Database (Denmark)

    Nielsen, Helle Hvilsted; Ladeby, Rune; Drøjdahl, Nina

    2006-01-01

    the response of the NG2+ cells to the different components of demyelinating pathology, we investigated the response of adult NG2+ cells to axonal degeneration in the absence of primary myelin or oligodendrocyte pathology. Axonal degeneration was induced in the hippocampal dentate gyrus of adult mice...... by transection of the entorhino-dentate perforant path projection. The acutely induced degeneration of axons and terminals resulted in a prompt response of NG2+ cells, consisting of morphological transformation, cellular proliferation, and upregulation of NG2 expression days 2-3 after surgery. This was followed...

  9. Sensitivity of quantitative UTE MRI to the biomechanical property of the temporomandibular joint disc

    International Nuclear Information System (INIS)

    Bae, Won C.; Biswas, Reni; Statum, Sheronda; Sah, Robert L.; Chung, Christine B.

    2014-01-01

    To quantify MR properties of discs from cadaveric human temporomandibular joints (TMJ) using quantitative conventional and ultrashort time-to-echo magnetic resonance imaging (UTE MRI) techniques and to corroborate regional variation in the MR properties with that of biomechanical indentation stiffness. This study was exempt from the institutional review board approval. Cadaveric (four donors, two females, 74 ± 10.7 years) TMJs were sliced (n = 14 slices total) sagittally and imaged using quantitative techniques of conventional spin echo T2 (SE T2), UTE T2*, and UTE T1rho. The discs were then subjected to biomechanical indentation testing, which is performed by compressing the tissue with the blunt end of a small solid cylinder. Regional variations in MR and indentation stiffness were correlated. TMJ of a healthy volunteer was also imaged to show in vivo feasibility. Using the ME SE T2 and the UTE T1rho techniques, a significant (each p 2 = 0.42) than SE T2 (R 2 = 0.19) or UTE T2* (R 2 = 0.02, p = 0.1) techniques. The UTE T1rho technique, applicable in vivo, facilitated quantitative evaluation of TMJ discs and showed a high sensitivity to biomechanical softening of the TMJ discs. With additional work, the technique may become a useful surrogate measure for loss of biomechanical integrity of TMJ discs reflecting degeneration. (orig.)

  10. Lumbar Disc Herniation in a Patient With Congenital Vertebral Body Anomaly: A Case Report

    Science.gov (United States)

    Atabey, Cem; Topuz, Ali Kivanc; Velioğlu, Murat; Demircan, Mehmet Nusret

    2014-01-01

    Lumbar disc herniation is characterized with low back and leg pain resulting from the degenerated lumbar disc compressing the spinal nerve root. The etiology of degenerative spine is related to age, smoking, microtrauma, obesity, disorders of familial collagen structure, occupational and sports-related physical activity. However, disc herniations induced by congenital lumbar vertebral anomalies are rarely seen. Vertebral fusion defect is one of the causes of congenital anomalies. The pathogenesis of embryological corpus vertebral fusion anomaly is not fully known. In this paper, a 30-year-old patient who had the complaints of low back and right leg pain after falling from a height is presented. She had right L5-S1 disc herniation that had developed on the basis of S1 vertebra corpus fusion anomaly in Lumbar computed tomography. This case has been discussed in the light of literature based on evaluations of Lumbar Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). This case is unique in that it is the first case with development of lumbar disc herniation associated with S1 vertebral corpus fusion anomaly. Congenital malformations with unusual clinical presentation after trauma should be evaluated through advanced radiological imaging techniques. PMID:25620987

  11. Correlação entre as classificações de Pfirrmann e Modic na degeneração do disco intervertebral lombar Correspondencia entre las clasificaciones de Pfirrmann y Modic en la degeneración del disco intervertebral lumbar Correlation between Pfirrmann and Modic classifications in the degeneration of lumbar intervertebral disc

    Directory of Open Access Journals (Sweden)

    Marcio Squassoni Leite

    2010-12-01

    con Pfirrmann tipo V, y el 36,4% de las alteraciones Modic 1 fueron por igual entre Pfirrmann tipo IV y V. Se encontró una asociación estadísticamente significativa entre los cambios de Modic y Pfirrmann (pOBJECTIVE: to correlate the changes found in the lumbar magnetic resonance imaging according to Modic and Pfirrmann classifications. METHODS: lumbar spine resonances of 54 outpatients were selected (23 men and 31 women, who were already under investigation because of their comorbidity. According to their degree of Pfirrmann classification, 264 intervertebral discs (L1 to S1 were classified. The presence of signal abnormalities of the vertebral body was recorded as Modic classification. The χ2 mwas applied, adopting significance levels below 0.05 (a=5%. RESULTS: The mean age studied was of 48.4 years (26-77 years. A higher prevalence of Pfirrmann type IV (31.1% was observed. In 88.3% of the sample, Modic was absent, and also Modic 3; 60% of Modic 2 was related to Pfirrmann type V, and 36.4% of Modic 1 was equally distributed among Pfirrmann type IV and V. Statistically significant association between Modic changes and Pfirrmann (p<0.001 was found. CONCLUSION: there was a clear association between the classifications studied, comparing the stages of Pfirrmann (IV and V with Modic type 1 and 2.

  12. Adolescent cannabis exposure interacts with mutant DISC1 to produce impaired adult emotional memory.

    Science.gov (United States)

    Ballinger, Michael D; Saito, Atsushi; Abazyan, Bagrat; Taniguchi, Yu; Huang, Ching-Hsun; Ito, Koki; Zhu, Xiaolei; Segal, Hadar; Jaaro-Peled, Hanna; Sawa, Akira; Mackie, Ken; Pletnikov, Mikhail V; Kamiya, Atsushi

    2015-10-01

    Cannabis is an increasingly popular and controversial drug used worldwide. Cannabis use often begins during adolescence, a highly susceptible period for environmental stimuli to alter functional and structural organization of the developing brain. Given that adolescence is a critical time for the emergence of mental illnesses before full-onset in early adulthood, it is particularly important to investigate how genetic insults and adolescent cannabis exposure interact to affect brain development and function. Here we show for the first time that a perturbation in disrupted in schizophrenia 1 (DISC1) exacerbates the response to adolescent exposure to delta-9-tetrahydrocannabinol (Δ(9)-THC), a major psychoactive ingredient of cannabis, consistent with the concept that gene-environment interaction may contribute to the pathophysiology of psychiatric conditions. We found that chronic adolescent treatment with Δ(9)-THC exacerbates deficits in fear-associated memory in adult mice that express a putative dominant-negative mutant of DISC1 (DN-DISC1). Synaptic expression of cannabinoid receptor 1 (CB1R) is down-regulated in the prefrontal cortex, hippocampus, and amygdala, critical brain regions for fear-associated memory, by either expression of DN-DISC1 or adolescent Δ(9)-THC treatment. Notably, elevation of c-Fos expression evoked by context-dependent fear memory retrieval is impaired in these brain regions in DN-DISC1 mice. We also found a synergistic reduction of c-Fos expression induced by cue-dependent fear memory retrieval in DN-DISC1 with adolescent Δ(9)-THC exposure. These results suggest that alteration of CB1R-mediated signaling in DN-DISC1 mice may underlie susceptibility to detrimental effects of adolescent cannabis exposure on adult behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. MR imaging findings of a sequestered disc in the lumbar spine: a comparison with an extruded disc

    International Nuclear Information System (INIS)

    Sim, Su Youn; Park, Ji Seon; Ryu, Kyung Nam; Jin, Wook

    2007-01-01

    To compare the MR findings of a sequestered disc with an extruded disc. MR images of 28 patients with a sequestered disc and 18 patients with an extruded disc were retrospectively reviewed. Patients with sequestered discs were divided into two groups whether definite separation from the parent disc was or was not seen. In the latter group (definite separation not seen) and the extruded disc group of patients, the signal intensities of the herniated discs were compared with the signal intensities of the parent discs and were evaluated on T1-and T2-weighted images. We also assessed the presence of a notch within the herniated disc. In the sequestered disc group of patients (28 discs), only 5 discs (18%) showed obvious separation from the parent disc. Among the remaining 23 discs with indefinite separation, the notch was visible in 14 discs (61%) and 9 discs (39%) had no notch. In the extruded disc group (18 discs), the notch was visible in 2 (11%) discs and the difference between the two groups was statistically significant (ρ 0.0002). The signal intensities of the herniated discs on T1-weighted images were isointense in both the sequestered and extruded discs. The difference of incidence of high signal intensities on T2-weighted images was not statistically significant (ρ = 0.125). It is necessary to consider the possibility of the presence of a sequestered disc when a herniated disc material shows a notch

  14. Rapid glutamate receptor 2 trafficking during retinal degeneration

    Directory of Open Access Journals (Sweden)

    Lin Yanhua

    2012-02-01

    Full Text Available Abstract Background Retinal degenerations, such as age-related macular degeneration (AMD and retinitis pigmentosa (RP, are characterized by photoreceptor loss and anomalous remodeling of the surviving retina that corrupts visual processing and poses a barrier to late-stage therapeutic interventions in particular. However, the molecular events associated with retinal remodeling remain largely unknown. Given our prior evidence of ionotropic glutamate receptor (iGluR reprogramming in retinal degenerations, we hypothesized that the edited glutamate receptor 2 (GluR2 subunit and its trafficking may be modulated in retinal degenerations. Results Adult albino Balb/C mice were exposed to intense light for 24 h to induce light-induced retinal degeneration (LIRD. We found that prior to the onset of photoreceptor loss, protein levels of GluR2 and related trafficking proteins, including glutamate receptor-interacting protein 1 (GRIP1 and postsynaptic density protein 95 (PSD-95, were rapidly increased. LIRD triggered neuritogenesis in photoreceptor survival regions, where GluR2 and its trafficking proteins were expressed in the anomalous dendrites. Immunoprecipitation analysis showed interaction between KIF3A and GRIP1 as well as PSD-95, suggesting that KIF3A may mediate transport of GluR2 and its trafficking proteins to the novel dendrites. However, in areas of photoreceptor loss, GluR2 along with its trafficking proteins nearly vanished in retracted retinal neurites. Conclusions All together, LIRD rapidly triggers GluR2 plasticity, which is a potential mechanism behind functionally phenotypic revisions of retinal neurons and neuritogenesis during retinal degenerations.

  15. The PANDA Endcap Disc DIRC

    Science.gov (United States)

    Föhl, K.; Ali, A.; Belias, A.; Dzhygadlo, R.; Gerhardt, A.; Götzen, K.; Kalicy, G.; Krebs, M.; Lehmann, D.; Nerling, F.; Patsyuk, M.; Peters, K.; Schepers, G.; Schmitt, L.; Schwarz, C.; Schwiening, J.; Traxler, M.; Böhm, M.; Eyrich, W.; Lehmann, A.; Pfaffinger, M.; Uhlig, F.; Düren, M.; Etzelmüller, E.; Hayrapetyan, A.; Kreutzfeld, K.; Merle, O.; Rieke, J.; Schmidt, M.; Wasem, T.; Achenbach, P.; Cardinali, M.; Hoek, M.; Lauth, W.; Schlimme, S.; Sfienti, C.; Thiel, M.

    2018-02-01

    Positively identifying charged kaons in the PANDA forward endcap solid angle range can be achieved with the Endcap Disc DIRC, allowing kaon-pion separation from 1 up to 4 GeV/c with a separation power of at least 3 standard deviations. Design, performance, and components of this DIRC are given, including the recently introduced TOFPET-ASIC based read-out. Results of a prototype operated in a test beam at DESY in 2016 are shown.

  16. Intervertebral disc disease in dogs - Part 2: Comparison of clinical, magnetic resonance imaging, and histological findings in 74 surgically treated dogs

    NARCIS (Netherlands)

    Kranenburg, H.C.; Grinwis, G.C.M.; Bergknut, N.; Gahrmann, Ninke; Voorhout, G.; Hazewinkel, H.A.W.

    The relationship between intervertebral disc (IVD) disease and IVD degeneration remains unclear. The aim of the present study was to compare the clinical severity of IVD herniation (IVDH), determined with a neurological grading system, with findings of magnetic resonance imaging (MRI) and

  17. Normal modes of Bardeen discs

    International Nuclear Information System (INIS)

    Verdaguer, E.

    1983-01-01

    The short wavelength normal modes of self-gravitating rotating polytropic discs in the Bardeen approximation are studied. The discs' oscillations can be seen in terms of two types of modes: the p-modes whose driving forces are pressure forces and the r-modes driven by Coriolis forces. As a consequence of differential rotation coupling between the two takes place and some mixed modes appear, their properties can be studied under the assumption of weak coupling and it is seen that they avoid the crossing of the p- and r-modes. The short wavelength analysis provides a basis for the classification of the modes, which can be made by using the properties of their phase diagrams. The classification is applied to the large wavelength modes of differentially rotating discs with strong coupling and to a uniformly rotating sequence with no coupling, which have been calculated in previous papers. Many of the physical properties and qualitative features of these modes are revealed by the analysis. (author)

  18. Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy.

    Science.gov (United States)

    Lee, Yun-Sil; Lehar, Adam; Sebald, Suzanne; Liu, Min; Swaggart, Kayleigh A; Talbot, C Conover; Pytel, Peter; Barton, Elisabeth R; McNally, Elizabeth M; Lee, Se-Jin

    2015-10-15

    Myostatin is a secreted signaling molecule that normally acts to limit muscle growth. As a result, there is extensive effort directed at developing drugs capable of targeting myostatin to treat patients with muscle loss. One potential concern with this therapeutic approach in patients with muscle degenerative diseases like muscular dystrophy is that inducing hypertrophy may increase stress on dystrophic fibers, thereby accelerating disease progression. To investigate this possibility, we examined the effect of blocking the myostatin pathway in dysferlin-deficient (Dysf(-/-)) mice, in which membrane repair is compromised, either by transgenic expression of follistatin in skeletal muscle or by systemic administration of the soluble form of the activin type IIB receptor (ACVR2B/Fc). Here, we show that myostatin inhibition by follistatin transgene expression in Dysf(-/-) mice results in early improvement in histopathology but ultimately exacerbates muscle degeneration; this effect was not observed in dystrophin-deficient (mdx) mice, suggesting that accelerated degeneration induced by follistatin transgene expression is specific to mice lacking dysferlin. Dysf(-/-) mice injected with ACVR2B/Fc showed significant increases in muscle mass and amelioration of fibrotic changes normally seen in 8-month-old Dysf(-/-) mice. Despite these potentially beneficial effects, ACVR2B/Fc treatment caused increases in serum CK levels in some Dysf(-/-) mice, indicating possible muscle damage induced by hypertrophy. These findings suggest that depending on the disease context, inducing muscle hypertrophy by myostatin blockade may have detrimental effects, which need to be weighed against the potential gains in muscle growth and decreased fibrosis. © The Author 2015. Published by Oxford University Press.

  19. Dynamic Stabilisation in the Treatment of Degenerative Disc Disease with Modic Changes

    Directory of Open Access Journals (Sweden)

    Olcay Eser

    2013-01-01

    Full Text Available Objective. Posterior dynamic stabilization is an effective alternative to fusion in the treatment of chronic instability and degenerative disc disease (DDD of the lumbar spine. This study was undertaken to investigate the efficacy of dynamic stabilization in chronic degenerative disc disease with Modic types 1 and 2. Modic types 1 and 2 degeneration can be painful. Classic approach in such cases is spine fusion. We operated 88 DDD patients with Modic types 1 and 2 via posterior dynamic stabilization. Good results were obtained after 2 years of followup. Methods. A total of 88 DDD patients with Modic types 1 and 2 were selected for this study. The patients were included in the study between 2004 and 2010. All of them were examined with lumbar anteroposterior (AP and lateral X-rays. Lordosis of the lumbar spine, segmental lordosis, and ratio of the height of the intervertebral disc spaces (IVSs were measured preoperatively and at 3, 12, and 24 months after surgery. Magnetic resonance imaging (MRI analysis was carried out, and according to the data obtained, the grade of disc degeneration was classified. The quality of life and pain scores were evaluated by visual analog scale (VAS score and Oswestry Disability Index (ODI preoperatively and at 3, 12, and 24 months after surgery. Appropriate statistical method was chosen. Results. The mean 3- and 12-month postoperative IVS ratio was significantly greater than that of the preoperative group (P0.05. Furthermore, the mean preoperative and 1 and 2 postoperative angles of lumbar lordosis and segmental lordosis were not significantly different (P>0.05. The mean VAS score and ODI, 3, 12, and 24 months after surgery, decreased significantly, when compared with the preoperative scores in the groups (P=0.000. Conclusion. Dynamic stabilization in chronic degenerative disc disease with Modic types 1 and 2 was effective.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2014-10-01

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

  2. Internal disc derangement in patients with low back pain: correlation of MR imaging and provocative discography and CT discography

    International Nuclear Information System (INIS)

    Chung, Hye Won; Cheon, Jung Eun; Hong, Sung Hwan; Kang, Heung Sik; Lee, Ji Ho; Oh, Joo Han; Jeon, Pyoung

    2004-01-01

    The aim of this study was to correlate the MR imaging abnormalities of the lumbar intervertebral discs, with emphasis being placed on the high intensity zone (HIZ) with the use of discography for pain provocation and disc morphologic evaluation of the disc. Consecutive patients with low back pain unresponsive to conservative treatment, and who were being considered for spinal fusion had MRI performed, and this was followed by lumbar discography. The MR imaging, discography and CT discography (CTD) were evaluated for all of the 19 patients. Forty-three lumbar discs in 19 patients were included in this study. The findings of MR and CTD images were evaluated retrospectively with the professional opinion and agreement of two radiologists. MR images were assessed for the presence or absence of decreased T2-wighted signal intensity, decreased disc height, annular bulging, HIZ on T2-weighted images and disc herniation. The results of pain provocation were graded as 0, nonconcordant pain; 1, definite pain, but only as part of the symptom complex; 2, concordant pain. The morphology of CTD was analyzed for presence or absence of disc degeneration, radial tearing and extravasation of the contrast agent. The presence of radial tearing was defined as contrast extension to the outer third of the annulus. The prevalence of all MR abnormalities was calculated, and the data were compared with disc morphologic characteristics and the pain response on provocative discography. We used the chi-square test to analyze the results. Grade 1 and 2 discogenic pain was observed in 8 (19%) and 12 disc levels (28%), respectively. All of the seven non-degenerated discs on MR had no pain response. The decreased SI on T2-weighted image, annular bulging and HIZ were significantly correlated with discogenic pain. Extravasation of contrast media had good correlation with annular bulging and disc herniation on MRI. Radial tearing on CT discography correlated significantly with HIZ. The HIZ was

  3. A mouse model for degeneration of the spiral ligament.

    Science.gov (United States)

    Kada, Shinpei; Nakagawa, Takayuki; Ito, Juichi

    2009-06-01

    Previous studies have indicated the importance of the spiral ligament (SL) in the pathogenesis of sensorineural hearing loss. The aim of this study was to establish a mouse model for SL degeneration as the basis for the development of new strategies for SL regeneration. We injected 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase, at various concentrations into the posterior semicircular canal of adult C57BL/6 mice. Saline-injected animals were used as controls. Auditory function was monitored by measurements of auditory brain stem responses (ABRs). On postoperative day 14, cochlear specimens were obtained after the measurement of the endocochlear potential (EP). Animals that were injected with 5 or 10 mM 3-NP showed a massive elevation of ABR thresholds along with extensive degeneration of the cochleae. Cochleae injected with 1 mM 3-NP exhibited selective degeneration of the SL fibrocytes but alterations in EP levels and ABR thresholds were not of sufficient magnitude to allow for testing functional recovery after therapeutic interventions. Animals injected with 3 mM 3-NP showed a reduction of around 50% in the EP along with a significant loss of SL fibrocytes, although degeneration of spiral ganglion neurons and hair cells was still present in certain regions. These findings indicate that cochleae injected with 3 mM 3-NP may be useful in investigations designed to test the feasibility of new therapeutic manipulations for functional SL regeneration.

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

    Directory of Open Access Journals (Sweden)

    Mohsen Sheykhhasan

    2017-02-01

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

  5. Proto-planetary disc evolution and dispersal

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    C Mauth

    2009-10-01

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

  7. Temporal Analyses of the Response of Intervertebral Disc Cells and Mesenchymal Stem Cells to Nutrient Deprivation

    Directory of Open Access Journals (Sweden)

    Sarah A. Turner

    2016-01-01

    Full Text Available Much emphasis has been placed recently on the repair of degenerate discs using implanted cells, such as disc cells or bone marrow derived mesenchymal stem cells (MSCs. This study examines the temporal response of bovine and human nucleus pulposus (NP cells and MSCs cultured in monolayer following exposure to altered levels of glucose (0, 3.15, and 4.5 g/L and foetal bovine serum (0, 10, and 20% using an automated time-lapse imaging system. NP cells were also exposed to the cell death inducers, hydrogen peroxide and staurosporine, in comparison to serum starvation. We have demonstrated that human NP cells show an initial “shock” response to reduced nutrition (glucose. However, as time progresses, NP cells supplemented with serum recover with minimal evidence of cell death. Human NP cells show no evidence of proliferation in response to nutrient supplementation, whereas MSCs showed greater response to increased nutrition. When specifically inducing NP cell death with hydrogen peroxide and staurosporine, as expected, the cell number declined. These results support the concept that implanted NP cells or MSCs may be capable of survival in the nutrient-poor environment of the degenerate human disc, which has important clinical implications for the development of IVD cell therapies.

  8. Age-Related Macular Degeneration.

    Science.gov (United States)

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice.

    Directory of Open Access Journals (Sweden)

    Yan Gong

    Full Text Available The mouse model of laser-induced choroidal neovascularization (CNV has been used in studies of the exudative form of age-related macular degeneration using both the conventional slit lamp and a new image-guided laser system. A standardized protocol is needed for consistent results using this model, which has been lacking. We optimized details of laser-induced CNV using the image-guided laser photocoagulation system. Four lesions with similar size were consistently applied per eye at approximately double the disc diameter away from the optic nerve, using different laser power levels, and mice of various ages and genders. After 7 days, the mice were sacrificed and retinal pigment epithelium/choroid/sclera was flat-mounted, stained with Isolectin B4, and imaged. Quantification of the area of the laser-induced lesions was performed using an established and constant threshold. Exclusion criteria are described that were necessary for reliable data analysis of the laser-induced CNV lesions. The CNV lesion area was proportional to the laser power levels. Mice at 12-16 weeks of age developed more severe CNV than those at 6-8 weeks of age, and the gender difference was only significant in mice at 12-16 weeks of age, but not in those at 6-8 weeks of age. Dietary intake of omega-3 long-chain polyunsaturated fatty acid reduced laser-induced CNV in mice. Taken together, laser-induced CNV lesions can be easily and consistently applied using the image-guided laser platform. Mice at 6-8 weeks of age are ideal for the laser-induced CNV model.

  10. Degenerated differential pair with controllable transconductance

    NARCIS (Netherlands)

    Mensink, Clemens; Mensink, Clemens H.J.; Nauta, Bram

    1998-01-01

    A differential pair with input transistors and provided with a variable degeneration resistor. The degeneration resistor comprises a series arrangement of two branches of coupled resistors which are shunted in mutually corresponding points by respective control transistors whose gates are

  11. Biomaterials for intervertebral disc regeneration and repair.

    Science.gov (United States)

    Bowles, Robert D; Setton, Lori A

    2017-06-01

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

  12. Development of rupture discs for the FBTR

    International Nuclear Information System (INIS)

    Chetal, S.C.; Raju, C.; Anandkumar, V.; Seetharaman, V.; Rajan, K.K.

    1984-01-01

    Rupture discs are required as a safety device for protecting the secondary sodium circuit and its components against high pressure surges due to accidental water steam leaks in sodium heated steam generator and the consequent sodium water reaction. For identical reasons, rupture discs are also required on the vessels used for decontamination of sodium components. Reverse buckling knife blade concept with austenitic stainless steel disc has been developed for the rupture disc assemblies required for Fast Breeder Test Reactor (FBTR). Hydroforming process without any die has been used for disc fabrication. One rupture disc assembly required for steam generator is undergoing sodium endurance test and has accumulated 4,500 hours. The present status of development work as demonstrated by room temperature experimental results as well as the scope for future work are discussed. (author)

  13. Physiological pattern of lumbar disc height

    International Nuclear Information System (INIS)

    Biggemann, M.; Frobin, W.; Brinckmann, P.

    1997-01-01

    Purpose of this study is to present a new method of quantifying objectively the height of all discs in lateral radiographs of the lumbar spine and of analysing the normal craniocaudal sequence pattern of lumbar disc heights. Methods: The new parameter is the ventrally measured disc height corrected for the dependence on the angle of lordosis by normalisation to mean angles observed in the erect posture of healthy persons. To eliminate radiographic magnification, the corrected ventral height is related to the mean depth of the cranially adjoining vertebra. In this manner lumbar disc heights were objectively measured in young, mature and healthy persons (146 males and 65 females). The craniocaudal sequence pattern was analysed by mean values from all persons and by height differences of adjoining discs in each individual lumbar spine. Results: Mean normative values demonstrated an increase in disc height between L1/L2 and L4/L5 and a constant or decreasing disc height between L4/L5 and L5/S1. However, this 'physiological sequence of disc height in the statistical mean' was observed in only 36% of normal males and 55% of normal females. Conclusion: The radiological pattern of the 'physiological sequence of lumbar disc height' leads to a relevant portion of false positive pathological results especially at L4/L5. An increase of disc height from L4/L5 to L5/S1 may be normal. The recognition of decreased disc height should be based on an abrupt change in the heights of adjoining discs and not on a deviation from a craniocaudal sequence pattern. (orig.) [de

  14. Molecular Therapy for Degenerative Disc Disease: Clues from Secretome Analysis of the Notochordal Cell-Rich Nucleus Pulposus

    Science.gov (United States)

    Matta, Ajay; Karim, M. Zia; Isenman, David E.; Erwin, W. Mark

    2017-01-01

    Degenerative disc disease (DDD) is associated with spinal pain often leading to long-term disability. However, the non-chondrodystrophic canine intervertebral disc is protected from the development of DDD, ostensibly due to its retention of notochordal cells (NC) in the nucleus pulposus (NP). In this study, we hypothesized that secretome analysis of the NC-rich NP will lead to the identification of key proteins that delay the onset of DDD. Using mass-spectrometry, we identified 303 proteins including components of TGFβ- and Wnt-signaling, anti-angiogeneic factors and proteins that inhibit axonal ingrowth in the bioactive fractions of serum free, notochordal cell derived conditioned medium (NCCM). Ingenuity Pathway Analysis revealed TGFβ1 and CTGF as major hubs in protein interaction networks. In vitro treatment with TGFβ1 and CTGF promoted the synthesis of healthy extra-cellular matrix proteins, increased cell proliferation and reduced cell death in human degenerative disc NP cells. A single intra-discal injection of recombinant TGFβ1 and CTGF proteins in a pre-clinical rat-tail disc injury model restored the NC and stem cell rich NP. In conclusion, we demonstrate the potential of TGFβ1 and CTGF to mitigate the progression of disc degeneration and the potential use of these molecules in a molecular therapy to treat the degenerative disc. PMID:28358123

  15. Debris disc constraints on planetesimal formation

    Science.gov (United States)

    Krivov, Alexander V.; Ide, Aljoscha; Löhne, Torsten; Johansen, Anders; Blum, Jürgen

    2018-02-01

    Two basic routes for planetesimal formation have been proposed over the last decades. One is a classical `slow-growth' scenario. Another one is particle concentration models, in which small pebbles are concentrated locally and then collapse gravitationally to form planetesimals. Both types of models make certain predictions for the size spectrum and internal structure of newly born planetesimals. We use these predictions as input to simulate collisional evolution of debris discs left after the gas dispersal. The debris disc emission as a function of a system's age computed in these simulations is compared with several Spitzer and Herschel debris disc surveys around A-type stars. We confirm that the observed brightness evolution for the majority of discs can be reproduced by classical models. Further, we find that it is equally consistent with the size distribution of planetesimals predicted by particle concentration models - provided the objects are loosely bound `pebble piles' as these models also predict. Regardless of the assumed planetesimal formation mechanism, explaining the brightest debris discs in the samples uncovers a `disc mass problem'. To reproduce such discs by collisional simulations, a total mass of planetesimals of up to ˜1000 Earth masses is required, which exceeds the total mass of solids available in the protoplanetary progenitors of debris discs. This may indicate that stirring was delayed in some of the bright discs, that giant impacts occurred recently in some of them, that some systems may be younger than previously thought or that non-collisional processes contribute significantly to the dust production.

  16. Temporomandibular joint fibrocartilage degeneration from unilateral dental splints.

    Science.gov (United States)

    Henderson, Sarah E; Lowe, Jesse R; Tudares, Mauro A; Gold, Michael S; Almarza, Alejandro J

    2015-01-01

    The objective of this study was to determine the extent to which altered loading in the temporomandibular joint (TMJ), as might be associated with a malocclusion, drives degeneration of articulating surfaces in the TMJ. We therefore sought to quantify the effects of altered joint loading on the mechanical properties and biochemical content and distribution of TMJ fibrocartilage in the rabbit. Altered TMJ loading was induced with a 1mm splint placed unilaterally over the maxillary and mandibular molars for 6 weeks. At that time, TMJ fibrocartilage was assessed by compression testing, biochemical content (collagen, glycosaminoglycan (GAG), DNA) and distribution (histology), for both the TMJ disc and the condylar fibrocartilage. There were no changes in the TMJ disc for any of the parameters tested. The condylar fibrocartilage from the splinted animals was significantly stiffer and the DNA content was significantly lower than that in control animals. There was significant remodeling in the condylar fibrocartilage layers as manifested by a change in GAG and collagen II distribution and a loss of defined cell layers. A connection between the compressive properties of TMJ condylar fibrocartilage after 6 weeks of splinting and the changes in histology was observed. These results suggest a change in joint loading leads to condylar damage, which may contribute to pain associated with at least some forms of TMJ disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Association of endothelin-1 expression and cartilaginous endplate degeneration in humans.

    Directory of Open Access Journals (Sweden)

    Wei Yuan

    Full Text Available BACKGROUND: Inflammatory cytokines are involved in intervertebral disc (IVD degeneration. Endothelin-1 (ET-1, a 21-amino-acid cytokine implicated with cartilage degradation, is secreted by vascular endothelial cells and also by many other cell types. The expression of ET-1 in human IVD cartilage endplate (CEP and its role in disc degeneration have not been explored. METHODS AND FINDINGS: The expression of ET-1 in degenerated CEP was analyzed by immunohistochemical staining and Western blotting; ET-1 was demonstrated in cartilaginous endplate cells (CECs by immunofluorescent staining. The ET-1 mRNA expression and protein production by CECs stimulated by tumor necrosis factor alpha (TNF-α, a pro-inflammatory cytokine, were determined by real-time PCR analysis and Western blotting, respectively. The matrix metalloprotease-1 (MMP-1, MMP-13 and tissue inhibitor of metalloproteases-1 (TIMP-1 levels in the supernatant of cultured CECs treated with ET-1 were determined using enzyme-linked immunosorbent assays. Nitric oxide (NO release and nitric oxide synthase (NOS activity were measured using a spectrophotometric assay. The apoptosis of CECs by ET-1 was measured by an Annexin V-FITC detection assay. The production of ET-1 in degenerated cartilage endplate was significantly higher than normal CEP. The results showed that ET-1 was expressed by CECs and modulated by TNF-α in a dose-dependent manner. ET-1 increased production of MMP-1 and MMP-13, decreased TIMP-1 production, and induced NO and NOS release by cultured CECs. The direct stimulation of CECs by ET-1 did not promote cell apoptosis. CONCLUSION: The study results suggest that ET-1 played a pivotal role in human CEP degeneration, and may be a new target for development of therapies for this condition.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  20. Decreased Expression of DREAM Promotes the Degeneration of Retinal Neurons

    Science.gov (United States)

    Chintala, Shravan; Cheng, Mei; Zhang, Xiao

    2015-01-01

    The intrinsic mechanisms that promote the degeneration of retinal ganglion cells (RGCs) following the activation of N-Methyl-D-aspartic acid-type glutamate receptors (NMDARs) are unclear. In this study, we have investigated the role of downstream regulatory element antagonist modulator (DREAM) in NMDA-mediated degeneration of the retina. NMDA, phosphate-buffered saline (PBS), and MK801 were injected into the vitreous humor of C57BL/6 mice. At 12, 24, and 48 hours after injection, expression of DREAM in the retina was determined by immunohistochemistry, western blot analysis, and electrophoretic mobility-shift assay (EMSA). Apoptotic death of cells in the retina was determined by terminal deoxynucleotidyl transferace dUTP nick end labeling (TUNEL) assays. Degeneration of RGCs in cross sections and in whole mount retinas was determined by using antibodies against Tuj1 and Brn3a respectively. Degeneration of amacrine cells and bipolar cells was determined by using antibodies against calretinin and protein kinase C (PKC)-alpha respectively. DREAM was expressed constitutively in RGCs, amacrine cells, bipolar cells, as well as in the inner plexiform layer (IPL). NMDA promoted a progressive decrease in DREAM levels in all three cell types over time, and at 48 h after NMDA-treatment very low DREAM levels were evident in the IPL only. DREAM expression in retinal nuclear proteins was decreased progressively after NMDA-treatment, and correlated with its decreased binding to the c-fos-DRE oligonucleotides. A decrease in DREAM expression correlated significantly with apoptotic death of RGCs, amacrine cells and bipolar cells. Treatment of eyes with NMDA antagonist MK801, restored DREAM expression to almost normal levels in the retina, and significantly decreased NMDA-mediated apoptotic death of RGCs, amacrine cells, and bipolar cells. Results presented in this study show for the first time that down-regulation of DREAM promotes the degeneration of RGCs, amacrine cells, and

  1. Biochemical imaging of cervical intervertebral discs with glycosaminoglycan chemical exchange saturation transfer magnetic resonance imaging: feasibility and initial results

    International Nuclear Information System (INIS)

    Schleich, Christoph; Mueller-Lutz, Anja; Zimmermann, Lisa; Boos, Johannes; Wittsack, Hans-Joerg; Antoch, Gerald; Miese, Falk; Schmitt, Benjamin

    2016-01-01

    To evaluate glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging at 3T in the assessment of the GAG content of cervical IVDs in healthy volunteers. Forty-two cervical intervertebral discs of seven healthy volunteers (four females, three males; mean age: 21.4 ± 1.4 years; range: 19-24 years) were examined at a 3T MRI scanner in this prospective study. The MRI protocol comprised standard morphological, sagittal T2 weighted (T2w) images to assess the magnetic resonance imaging (MRI) based grading system for cervical intervertebral disc degeneration (IVD) and biochemical imaging with gagCEST to calculate a region-of-interest analysis of nucleus pulposus (NP) and annulus fibrosus (AF). GagCEST of cervical IVDs was technically successful at 3T with significant higher gagCEST values in NP compared to AF (1.17 % ± 1.03 % vs. 0.79 % ± 1.75 %; p = 0.005). We found topological differences of gagCEST values of the cervical spine with significant higher gagCEST effects in lower IVDs (r = 1; p = 0). We could demonstrate a significant, negative correlation between gagCEST values and cervical disc degeneration of NP (r = -0.360; p = 0.019). Non-degenerated IVDs had significantly higher gagCEST effects compared to degenerated IVDs in NP (1.76 % ± 0.92 % vs. 0.52 % ± 1.17 %; p < 0.001). Biochemical imaging of cervical IVDs is feasible at 3T. GagCEST analysis demonstrated a topological GAG distribution of the cervical spine. The depletion of GAG in the NP with increasing level of morphological degeneration can be assessed using gagCEST imaging. (orig.)

  2. Local models of astrophysical discs

    Science.gov (United States)

    Latter, Henrik N.; Papaloizou, John

    2017-12-01

    Local models of gaseous accretion discs have been successfully employed for decades to describe an assortment of small-scale phenomena, from instabilities and turbulence, to dust dynamics and planet formation. For the most part, they have been derived in a physically motivated but essentially ad hoc fashion, with some of the mathematical assumptions never made explicit nor checked for consistency. This approach is susceptible to error, and it is easy to derive local models that support spurious instabilities or fail to conserve key quantities. In this paper we present rigorous derivations, based on an asympototic ordering, and formulate a hierarchy of local models (incompressible, Boussinesq and compressible), making clear which is best suited for a particular flow or phenomenon, while spelling out explicitly the assumptions and approximations of each. We also discuss the merits of the anelastic approximation, emphasizing that anelastic systems struggle to conserve energy unless strong restrictions are imposed on the flow. The problems encountered by the anelastic approximation are exacerbated by the disc's differential rotation, but also attend non-rotating systems such as stellar interiors. We conclude with a defence of local models and their continued utility in astrophysical research.

  3. Optic Disc Drusen in Children

    DEFF Research Database (Denmark)

    Malmqvist, Lasse; Li, Xiao Qiang; Eckmann, Christina L

    2017-01-01

    diameter and fetal birth and pubertal parameters are associated with the presence of ODD. METHODS: This observational, longitudinal population-based birth cohort study, with a nested case-control, included 1,406 children. Eye examinations were performed when the children were between 11 and 12 years of age....... Assessment was performed of optical coherence tomography (OCT) scans from 1,304 children with gradable enhanced depth imaging scans of the optic disc. RESULTS: ODD in one or both eyes were found in 13 (1.0%) of all children. All but one of the cases were found in children with scleral canal diameter...... in the lowest quartile (1,182-1,399 μm) in the nested case-control study. Children with ODD had a mean disc diameter of 1,339 μm (interquartile range, 30 μm), whereas it was 1,508 μm (interquartile range, 196 μm) in the 130 controls without ODD (P

  4. Radiological assessment of loss of disc height during acute and chronic degenerative lumbar disc alterations; Radiologische Beurteilung der segmentalen Hoehenabnahme bei akuten und chronisch degenerativen lumbalen Bandscheibenveraenderungen

    Energy Technology Data Exchange (ETDEWEB)

    Zoellner, J.; Sancaktaroglu, T.; Nafe, B.; Eysel, P. [Orthopaedische Universitaetsklinik Mainz (Germany); Loew, R. [Radiologische Universitaetsklinik Mainz (Germany)

    2001-03-01

    Aim of the study: A loss of disc height with increasing segmental mobility is an important reason for low back pain. The measurement of hyaluronic acid content of the nucleus pulposus prolaps shows a difference between acute (group 1) and chronic (group 2) disc degeneration. The purpose of the present investigation was to determine the decreasing of disc height between these two groups and the no-symptomatic segments of these patients. Methods: 20 human lateral preoperative X-ray measurements according to Frobin et al. were taken; group 1 with 7 patients (mean age 41 years) and group 2 with 13 patients (mean age 44 years). Results: There was a significant tendency (p=0.091) to a reduction of disc height in group 2 between symptomatic and asymptomatic discs. Conclusion: The used method is not suitable to answer the present question conclusively. (orig.) [German] Ziel: Die segmentale Hoehenabnahme der Bandscheibe mit nachfolgender Instabilitaet im Rahmen von degenerativen lumbalen Bandscheibenerkrankungen hat eine wesentliche klinische Bedeutung. In einer vorgeschalteten Untersuchung konnte ueber die Bestimmung des Hyaluronsaeuregehaltes von Nucleus pulposus-Material der Grad der Bandscheibendegeneration beurteilt werden. Die Frage ist, ob hier ein praeoperativ radiologisch nachweisbarer Hoehenunterschied zwischen den akuten (Gruppe 1) und den chronischen (Gruppe 2) Bandscheibenvorfaellen im Vergleich zu den klinisch nicht betroffenen Bandscheibensegmenten der Patienten besteht? Methode: Es wurden 20 konsekutive praeoperative seitliche Roentgenaufnahmen der Lendenwirbelsaeule nach der Methode von Frobin et al. vermessen. Diese bestanden aus einer ersten Gruppe (7 Patienten) mit einem durchschnittlichen Alter von 41 Jahren und einer zweiten Gruppe (13 Patienten) mit einem durchschnittlichen Alter von 44 Jahren. Ergebnisse: Die Ergebnisse der Untersuchung zeigten lediglich in der 2. Gruppe mit einer chronischen Bandscheibendegeneration eine Tendenz zur Abhaengigkeit (p

  5. Effect of total lumbar disc replacement on lumbosacral lordosis.

    Science.gov (United States)

    Kasliwal, Manish K; Deutsch, Harel

    2012-10-01

    Original article : To study effect of lumbar disc replacement on lumbosacral lordosis. There has been a growing interest in total disc replacement (TDR) for back pain with the rising concern of adjacent segment degeneration. Lumbar fusion surgery has been shown to lead to decrease in lumbar lordosis, which may account for postfusion pain resulting in less acceptable clinical outcome after successful fusion. TDR has recently emerged as an alternative treatment for back pain. There have been very few studies reporting lumbar sagittal outcome after TDR. Retrospective study of radiographic data of 17 patients who underwent TDR for single level degenerative disc disease at the author's institution was carried out. Study included measurement of preoperative and postoperative segmental and global lumbar lordosis and angle of lordosis. Patients age varied from 19 to 54 (mean, 35) years. Follow-up ranged from 12 to 24 months. TDR was performed at L4-5 level in 3 patients and L5-S1 level in 14 patients. The average values for segmental lordosis, global lordosis, and angle of lordosis at the operated level before and after surgery were 17.3, 49.7, and 8.6 degrees and 21.6, 54, and 9.5 degrees, respectively. There was a trend toward significant (P=0.02) and near significant (P=0.057) increase in segmental and global lordosis, respectively after TDR. Although prosthesis increased angle of lordosis at the level implanted in majority of the patients, the difference in preoperative and postoperative angle of lordosis was not significant (P=0.438). In addition, there was no correlation between the angle of implant of chosen and postoperative angle of lordosis at the operated level. The effect of TDR on sagittal balance appears favorable with an increase in global and segmental lumbar lordosis after single level TDR for degenerative disc disease. The degree of postoperative angle of lordosis was not affected by the angle of implant chosen at the operated level and varied

  6. Minimum weight design of inhomogeneous rotating discs

    International Nuclear Information System (INIS)

    Jahed, Hamid; Farshi, Behrooz; Bidabadi, Jalal

    2005-01-01

    There are numerous applications for gas turbine discs in the aerospace industry such as in turbojet engines. These discs normally work under high temperatures while subjected to high angular velocities. Minimizing the weight of such items in aerospace applications results in benefits such as low dead weights and lower costs. High speed of rotation causes large centrifugal forces in a disc and simultaneous application of high temperatures reduces disc material strength. Thus, the latter effects tend to increase deformations of the disc under the applied loads. In order to obtain a reliable disc analysis and arrive at the corresponding correct stress distribution, solutions should consider changes in material properties due to the temperature field throughout the disc. To achieve this goal, an inhomogeneous disc model with variable thickness is considered. Using the variable material properties method, stresses are obtained for the disc under rotation and a steady temperature field. In this paper this is done by modelling the rotating disc as a series of rings of different but constant properties. The optimum disc profile is arrived at by sequentially proportioning the thicknesses of each ring to satisfy the stress requirements. This method vis-a-vis a mathematical programming procedure for optimization shows several advantages. Firstly, it is simple iterative proportioning in each design cycle not requiring involved mathematical operations. Secondly, due to its simplicity it alleviates the necessity of certain simplifications that are common in so-called rigorous mathematical procedures. The results obtained, compared to those published in the literature show agreement and superiority. A further advantage of the proposed method is the independence of the end results from the initially assumed point in the iterative design routine, unlike most methods published so far

  7. Pediatric Lumbar Disc Herniation: A Review of Manifestations, Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    Kaveh Haddadi

    2016-01-01

    Full Text Available Lumbar disc herniation (LDH is a public complaint among adults with degenerated lumbar intervertebral discs. However, its incidence in childhood and adolescence is abundant. This dissimilarity designates that children are distant from being just little adults. Findings recommended that pediatric LDH is, in numerous ways, dissimilar from that in adults. The occurrence, the etiological and the diagnostic topographies of pediatric LDH have been entirely described in the text, while the features concerning the treatment have not been yet studied in details. It was confirmed that pediatric patients respond to conventional management less positively as matched with adults. Also, the consequences of the operation continued to be acceptable for at least 10 years after the first surgery, even though it seems to decline somewhat. The purpose of the current review is to offer a comparative view on the management of pediatric LDH.

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

    Science.gov (United States)

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

    2015-05-01

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

  9. Diapause formation and downregulation of insulin-like signaling via DAF-16/FOXO delays axonal degeneration and neuronal loss.

    Directory of Open Access Journals (Sweden)

    Andrea Calixto

    Full Text Available Axonal degeneration is a key event in the pathogenesis of neurodegenerative conditions. We show here that mec-4d triggered axonal degeneration of Caenorhabditis elegans neurons and mammalian axons share mechanistical similarities, as both are rescued by inhibition of calcium increase, mitochondrial dysfunction, and NMNAT overexpression. We then explore whether reactive oxygen species (ROS participate in axonal degeneration and neuronal demise. C. elegans dauers have enhanced anti-ROS systems, and dauer mec-4d worms are completely protected from axonal degeneration and neuronal loss. Mechanistically, downregulation of the Insulin/IGF-1-like signaling (IIS pathway protects neurons from degenerating in a DAF-16/FOXO-dependent manner and is related to superoxide dismutase and catalase-increased expression. Caloric restriction and systemic antioxidant treatment, which decrease oxidative damage, protect C. elegans axons from mec-4d-mediated degeneration and delay Wallerian degeneration in mice. In summary, we show that the IIS pathway is essential in maintaining neuronal homeostasis under pro-degenerative stimuli and identify ROS as a key intermediate of neuronal degeneration in vivo. Since axonal degeneration represents an early pathological event in neurodegeneration, our work identifies potential targets for therapeutic intervention in several conditions characterized by axonal loss and functional impairment.

  10. Light and inherited retinal degeneration

    OpenAIRE

    Paskowitz, D M; LaVail, M M; Duncan, J L

    2006-01-01

    Light deprivation has long been considered a potential treatment for patients with inherited retinal degenerative diseases, but no therapeutic benefit has been demonstrated to date. In the few clinical studies that have addressed this issue, the underlying mutations were unknown. Our rapidly expanding knowledge of the genes and mechanisms involved in retinal degeneration have made it possible to reconsider the potential value of light restriction in specific genetic contexts. This review summ...

  11. An Unconventional Approach To Reducing Retinal Degeneration After Traumatic Ocular Injury

    Science.gov (United States)

    2016-07-01

    regulating drugs – currently not purposed to treat retinal damage – may serve to ameliorate retinal degeneration in mice who have experienced blast...to buy a set for for our experiments going forward). A parallel experiments of SNR experiments with red vs green dye (data not shown), moreover

  12. Why do intervertebral discs degenerate ? Presentation of the European research project EURODISC.

    NARCIS (Netherlands)

    Neidlinger-Wilke, C.; Urban, J.; Roberts, S.; Maroudas, A.; Sivan, S.; Kletsas, D.; Videman, T.; Battie, M.; Huyghe, J.M.R.J.

    2006-01-01

    Back pain is a very common burden that almost everybody experiences at least once in his lifetime. It leads to considerable loss of productivity in the working population, which together with direct health and benefit costs, make it one of the expensive health problems in the western world. The

  13. Degenerate Hopf bifurcation in a self-exciting Faraday disc dynamo

    Indian Academy of Sciences (India)

    Weiquan Pan

    2017-05-31

    May 31, 2017 ... Recently, self-exciting Faraday disk dynamo is also a topic of con- cern [16–20]. ..... Hopf bifurcation. (a) Projected on the x–z plane and (b) pro- ... Key Lab of Com- plex System Optimization and Big Data Processing. (No.

  14. A Simulation Model of Focus and Radial Servos in Compact Disc Players with Disc Surface Defects

    DEFF Research Database (Denmark)

    Odgaard, Peter Fogh; Stoustrup, Jakob; Andersen, Palle

    2004-01-01

    Compact Disc players have been on the market in more than two decades.As a consequence most of the control servo problems have been solved. A large remaining problem to solve is the handling of Compact Discs with severe surface defects like scratches and fingerprints. This paper introduces a method...... for making the design of controllers handling surface defects easier. A simulation model of Compact Disc players playing discs with surface defects is presented. The main novel element in the model is a model of the surface defects. That model is based on data from discs with surface defects. This model...

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

    African Journals Online (AJOL)

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

  16. The evolution of stellar exponential discs

    NARCIS (Netherlands)

    Ferguson, AMN; Clarke, CJ

    2001-01-01

    Models of disc galaxies which invoke viscosity-driven radial flows have long been known to provide a natural explanation for the origin of stellar exponential discs, under the assumption that the star formation and viscous time-scales are comparable. We present models which invoke simultaneous star

  17. Feature Based Control of Compact Disc Players

    DEFF Research Database (Denmark)

    Odgaard, Peter Fogh

    Two servo control loops are used to keep the Optical Pick-up Unit focused and radially on the information track of the Compact Disc. These control servos have problems handling surface faults on the Compact Disc. In this Ph.D thesis a method is proposed to improve the handling of these surface...

  18. Robust control of a compact disc mechanism

    NARCIS (Netherlands)

    Steinbuch, M.; Schootstra, G.; Bosgra, O.H.; Levine, W.S.

    1995-01-01

    A compact disc (CD) player is an optical decoding device that reproduces high-quality audio from a digitally coded signal recorded as a spiral-shaped track on a reflective disc. Apart from the audio application, other optical data systems (CD-ROM, optical data drive) and combined audio/video

  19. Computing Decoupled Residuals for Compact Disc Players

    DEFF Research Database (Denmark)

    Odgaard, Peter Fogh; Stoustrup, Jakob; Andersen, Palle

    2006-01-01

    a pair of residuals generated by Compact Disc Player. However, these residuals depend on the performance of position servos in the Compact Disc Player. In other publications of the same authors a pair of decoupled residuals is derived. However, the computation of these alternative residuals has been...

  20. Use NASA GES DISC Data in ArcGIS

    Science.gov (United States)

    Yang, Wenli; Pham, Long B.; Kempler, Steve

    2015-01-01

    This presentation describes GIS relevant data at NASA Goddard Earth Sciences Data and Information Services Center (GES DISC), GES DISC Services and Support for GIS Users, and use cases of GES DISC data in ArcGIS.

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

    Science.gov (United States)

    1982-08-01

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

  2. The formation of planets by disc fragmentation

    Directory of Open Access Journals (Sweden)

    Stamatellos Dimitris

    2013-04-01

    Full Text Available I discuss the role that disc fragmentation plays in the formation of gas giant and terrestrial planets, and how this relates to the formation of brown dwarfs and low-mass stars, and ultimately to the process of star formation. Protostellar discs may fragment, if they are massive enough and can cool fast enough, but most of the objects that form by fragmentation are brown dwarfs. It may be possible that planets also form, if the mass growth of a proto-fragment is stopped (e.g. if this fragment is ejected from the disc, or suppressed and even reversed (e.g by tidal stripping. I will discuss if it is possible to distinguish whether a planet has formed by disc fragmentation or core accretion, and mention of a few examples of observed exoplanets that are suggestive of formation by disc fragmentation.

  3. T1 hyperintense disc in alkaptonuria.

    Science.gov (United States)

    Sag, Alan A; Silbergleit, Richard; Olson, Rick E; Wilson, Jon; Krishnan, Anant

    2012-10-01

    Case report. To report a rare case of alkaptonuria presenting as a T1-hyperintense disc herniation. A 46-year-old man without previous diagnosis of alkaptonuria underwent evaluation for progressive back pain revealing a T1-hyperintense disc herniation at the L3-L4 level. Discectomy recovered a blackened disc that was pathologically confirmed to be nucleus pulposus with alkaptonuric involvement. The differential diagnosis of a T1-hyperintense, T2-hypointense disc on magnetic resonance imaging is discussed, with emphasis on the pathophysiology of alkaptonuria. A single patient is reported. Pathologically proven patient presentation with radiological and pathological images. We report a rare case of alkaptonuria presenting as a T1-hyperintense disc herniation.

  4. Animal models of age related macular degeneration

    Science.gov (United States)

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  5. The Mobi-C cervical disc for one-level and two-level cervical disc replacement: a review of the literature

    Directory of Open Access Journals (Sweden)

    Alvin MD

    2014-11-01

    Full Text Available Matthew D Alvin,1,2 Thomas E Mroz1,3,41Cleveland Clinic Center for Spine Health, Cleveland Clinic, Cleveland, OH, USA; 2Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA; 4Department of Neurological Surgery, Cleveland Clinic, Cleveland, OH, USABackground: Cervical disc arthroplasty (CDA is a novel motion-preserving procedure that is an alternative to fusion. The Mobi-C disc prosthesis, one of many Food and Drug Administration (FDA-approved devices for CDA, is the only FDA-approved prosthesis for two-level CDA. Hence, it may allow for improved outcomes compared with multilevel fusion procedures.Purpose: To critically assess the available literature on CDA with the Mobi-C prosthesis, with a focus on two-level CDA.Methods: All clinical articles involving the Mobi-C disc prosthesis for CDA through September 1, 2014 were identified on Medline. Any paper that presented Mobi-C CDA clinical results was included. Study design, sample size, length of follow-up, use of statistical analysis, quality of life outcome scores, conflict of interest, and complications were recorded.Results: Fifteen studies were included that investigated Mobi-C CDA, only one of which was a level Ib randomized control trial. All studies included showed non-inferiority of one-level Mobi-C CDA to one-level anterior cervical discectomy and fusion (ACDF. Only one study analyzed outcomes of one-level versus two-level Mobi-C CDA, and only one study analyzed two-level Mobi-C CDA versus two-level ACDF. In comparison with other cervical disc prostheses, the Mobi-C prosthesis is associated with higher rates of heterotopic ossification (HO. Studies with conflicts of interest reported lower rates of HO. Adjacent segment degeneration or disease, along with other complications, were not assessed in most studies.Conclusion: One-level Mobi-C CDA is non-inferior, but not superior, to one-level ACDF for patients

  6. Intervertebral Disc Characteristic on Progressive Neurological Deficit

    Directory of Open Access Journals (Sweden)

    Farid Yudoyono

    2017-09-01

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

  7. Deep-down ionization of protoplanetary discs

    Science.gov (United States)

    Glassgold, A. E.; Lizano, S.; Galli, D.

    2017-12-01

    The possible occurrence of dead zones in protoplanetary discs subject to the magneto-rotational instability highlights the importance of disc ionization. We present a closed-form theory for the deep-down ionization by X-rays at depths below the disc surface dominated by far-ultraviolet radiation. Simple analytic solutions are given for the major ion classes, electrons, atomic ions, molecular ions and negatively charged grains. In addition to the formation of molecular ions by X-ray ionization of H2 and their destruction by dissociative recombination, several key processes that operate in this region are included, e.g. charge exchange of molecular ions and neutral atoms and destruction of ions by grains. Over much of the inner disc, the vertical decrease in ionization with depth into the disc is described by simple power laws, which can easily be included in more detailed modelling of magnetized discs. The new ionization theory is used to illustrate the non-ideal magnetohydrodynamic effects of Ohmic, Hall and Ambipolar diffusion for a magnetic model of a T Tauri star disc using the appropriate Elsasser numbers.

  8. Lattice degeneration of the retina.

    Science.gov (United States)

    Byer, N E

    1979-01-01

    Lattice degeneration of the retina is the most important of all clinically distinct entities that effect the peripheral fundus and are related to retinal detachment. The purpose of this review is to survey the extensive literature, to evaluate the many diverse opinions on this subject, and to correlate and summarize all the known facts regarding this disease entity. The disease is fully defined and described, both clinically and histologically. Some aspects of the disease are still poorly understood, and some remain controversial, especially in the area of management. For this reason, the indications for treatment are discussed under eight subsections, with a view toward providing practical guidelines for recommendations in management.

  9. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  10. DISC1 and striatal volume: a potential risk phenotype for mental illness

    Directory of Open Access Journals (Sweden)

    M. Mallar eChakravarty

    2012-06-01

    Full Text Available Disrupted-in-schizophrenia 1 was originally discovered in a large Scottish family with abnormally high rates of severe mental illness, including schizophrenia, bipolar disorder, and depression. An accumulating body of evidence from genetic, postmortem, and animal data supports a role for DISC1 in different forms of mental illness. DISC1 may play an important role in determining structure and function of several brain regions. One brain region of particular importance for several mental disorders is the striatum, and DISC1 mutant mice have demonstrated an increase in dopamine (D2 receptors in this structure. However, association between DISC1 functional polymorphisms and striatal structure have not been examined in humans to our knowledge. We, therefore hypothesized that there would be a relationship between human striatal volume and DISC1 genotype, specifically in the Leu607Phe (rs6675281 and Ser704Cys (rs821618 single nucleotide polymorphisms. We tested our hypothesis by automatically identifying the striatum in fifty-four healthy volunteers recruited for this study. We also performed an exploratory analysis of cortical thickness, cortical surface area, and structure volume. Our results demonstrate that Phe allele carriers have larger striatal volume bilaterally (left striatum: p=0.017; right striatum: p=0.016. From the exploratory analyses we found that Phe carriers also had larger right hemisphere volumes and right occipital lobe surface area (p=0.014 compared to LeuLeu homozygotes (p=0.0074. However, these exploratory findings do not survive a conservative correction for multiple comparisons. Our findings demonstrate that a functional DISC1 variant influences striatal volumes. Taken together with animal data that this gene influences D2 receptor levels in striatum, a key risk pathway for mental illnesses such as schizophrenia and bipolar disorder may be conferred via DISC1’s effects on the striatum .

  11. Likelihood inference for unions of interacting discs

    DEFF Research Database (Denmark)

    Møller, Jesper; Helisova, K.

    2010-01-01

    This is probably the first paper which discusses likelihood inference for a random set using a germ-grain model, where the individual grains are unobservable, edge effects occur and other complications appear. We consider the case where the grains form a disc process modelled by a marked point...... process, where the germs are the centres and the marks are the associated radii of the discs. We propose to use a recent parametric class of interacting disc process models, where the minimal sufficient statistic depends on various geometric properties of the random set, and the density is specified......-based maximum likelihood inference and the effect of specifying different reference Poisson models....

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

    Science.gov (United States)

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

    2018-05-21

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

  13. Automatic Detection of Optic Disc in Retinal Image by Using Keypoint Detection, Texture Analysis, and Visual Dictionary Techniques

    Directory of Open Access Journals (Sweden)

    Kemal Akyol

    2016-01-01

    Full Text Available With the advances in the computer field, methods and techniques in automatic image processing and analysis provide the opportunity to detect automatically the change and degeneration in retinal images. Localization of the optic disc is extremely important for determining the hard exudate lesions or neovascularization, which is the later phase of diabetic retinopathy, in computer aided eye disease diagnosis systems. Whereas optic disc detection is fairly an easy process in normal retinal images, detecting this region in the retinal image which is diabetic retinopathy disease may be difficult. Sometimes information related to optic disc and hard exudate information may be the same in terms of machine learning. We presented a novel approach for efficient and accurate localization of optic disc in retinal images having noise and other lesions. This approach is comprised of five main steps which are image processing, keypoint extraction, texture analysis, visual dictionary, and classifier techniques. We tested our proposed technique on 3 public datasets and obtained quantitative results. Experimental results show that an average optic disc detection accuracy of 94.38%, 95.00%, and 90.00% is achieved, respectively, on the following public datasets: DIARETDB1, DRIVE, and ROC.

  14. Risk factors for adjacent segment degeneration after surgical correction of degenerative lumbar scoliosis

    Directory of Open Access Journals (Sweden)

    Kee-yong Ha

    2013-01-01

    Full Text Available Background: Degenerative lumbar scoliosis surgery can lead to development of adjacent segment degeneration (ASD after lumbar or thoracolumbar fusion. Its incidence, risk factors, morbidity and correlation between radiological and clinical symptoms of ASD have no consensus. We evaluated the correlation between the occurrence of radiologic adjacent segment disease and certain imperative parameters. Materials and Methods: 98 patients who had undergone surgical correction and lumbar/thoracolumbar fusion with pedicle screw instrumentation for degenerative lumbar scoliosis with a minimum 5 year followup were included in the study. We evaluated the correlation between the occurrence of radiologic adjacent segment disease and imperative patient parameters like age at operation, sex, body mass index (BMI, medical comorbidities and bone mineral density (BMD. The radiological parameters taken into consideration were Cobb′s angle, angle type, lumbar lordosis, pelvic incidence, intercristal line, preoperative existence of an ASD on plain radiograph and magnetic resonance imaging (MRI and surgical parameters were number of the fusion level, decompression level, floating OP (interlumbar fusion excluding L5-S1 level and posterolateral lumbar interbody fusion (PLIF. Clinical outcomes were assessed with the Visual Analogue Score (VAS and Oswestry Disability Index (ODI. Results: ASD was present in 44 (44.9% patients at an average period of 48.0 months (range 6-98 months. Factors related to occurrence of ASD were preoperative existence of disc degeneration (as revealed by MRI and age at operation ( P = 0.0001, 0.0364. There were no statistically significant differences between radiological adjacent segment degeneration and clinical results (VAS, P = 0.446; ODI, P = 0.531. Conclusions: Patients over the age of 65 years and with preoperative disc degeneration (as revealed by plain radiograph and MRI were at a higher risk of developing ASD.

  15. Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Kuboyama, Tomoharu; Hirotsu, Keisuke; Arai, Tetsuya; Yamasaki, Hiroo; Tohda, Chihiro

    2017-01-01

    Memory impairments in Alzheimer's disease (AD) occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia ; PR) is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract) was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ) plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.

  16. Sensitivity of quantitative UTE MRI to the biomechanical property of the temporomandibular joint disc

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Won C.; Biswas, Reni; Statum, Sheronda [University of California-San Diego, Department of Radiology, San Diego, CA (United States); Sah, Robert L. [University of California-San Diego, Department of Bioengineering, La Jolla, CA (United States); Chung, Christine B. [University of California-San Diego, Department of Radiology, San Diego, CA (United States); VA San Diego Healthcare System, Department of Radiology, San Diego, CA (United States)

    2014-09-15

    To quantify MR properties of discs from cadaveric human temporomandibular joints (TMJ) using quantitative conventional and ultrashort time-to-echo magnetic resonance imaging (UTE MRI) techniques and to corroborate regional variation in the MR properties with that of biomechanical indentation stiffness. This study was exempt from the institutional review board approval. Cadaveric (four donors, two females, 74 ± 10.7 years) TMJs were sliced (n = 14 slices total) sagittally and imaged using quantitative techniques of conventional spin echo T2 (SE T2), UTE T2*, and UTE T1rho. The discs were then subjected to biomechanical indentation testing, which is performed by compressing the tissue with the blunt end of a small solid cylinder. Regional variations in MR and indentation stiffness were correlated. TMJ of a healthy volunteer was also imaged to show in vivo feasibility. Using the ME SE T2 and the UTE T1rho techniques, a significant (each p < 0.0001) inverse relation between MR and indentation stiffness properties was observed for the data in the lower range of stiffness. However, the strength of correlation was significantly higher (p < 0.05) for UTE T1rho (R{sup 2} = 0.42) than SE T2 (R{sup 2} = 0.19) or UTE T2* (R{sup 2} = 0.02, p = 0.1) techniques. The UTE T1rho technique, applicable in vivo, facilitated quantitative evaluation of TMJ discs and showed a high sensitivity to biomechanical softening of the TMJ discs. With additional work, the technique may become a useful surrogate measure for loss of biomechanical integrity of TMJ discs reflecting degeneration. (orig.)

  17. PARP inhibitors protect against sex- and AAG-dependent alkylation-induced neural degeneration.

    Science.gov (United States)

    Allocca, Mariacarmela; Corrigan, Joshua J; Fake, Kimberly R; Calvo, Jennifer A; Samson, Leona D

    2017-09-15

    Alkylating agents are commonly used to treat cancer. Although base excision repair (BER) is a major pathway for repairing DNA alkylation damage, under certain conditions, the initiation of BER produces toxic repair intermediates that damage healthy tissues. The initiation of BER by the alkyladenine DNA glycosylase (AAG, a.k.a. MPG) can mediate alkylation-induced cytotoxicity in specific cells in the retina and cerebellum of male mice. Cytotoxicity in both wild-type and Aag -transgenic ( AagTg ) mice is abrogated in the absence of Poly(ADP-ribose) polymerase-1 (PARP1). Here, we tested whether PARP inhibitors can also prevent alkylation-induced retinal and cerebellar degeneration in male and female WT and AagTg mice. Importantly, we found that WT mice display sex-dependent alkylation-induced retinal damage (but not cerebellar damage), with WT males being more sensitive than females. Accordingly, estradiol treatment protects males against alkylation-induced retinal degeneration. In AagTg male and female mice, the alkylation-induced tissue damage in both the retina and cerebellum is exacerbated and the sex difference in the retina is abolished. PARP inhibitors, much like Parp1 gene deletion, protect against alkylation-induced AAG-dependent neuronal degeneration in WT and AagTg mice, regardless of the gender, but their efficacy in preventing alkylation-induced neuronal degeneration depends on PARP inhibitor characteristics and doses. The recent surge in the use of PARP inhibitors in combination with cancer chemotherapeutic alkylating agents might represent a powerful tool for obtaining increased therapeutic efficacy while avoiding the collateral effects of alkylating agents in healthy tissues.

  18. Development and degeneration of cone bipolar cells are independent of cone photoreceptors in a mouse model of retinitis pigmentosa.

    Directory of Open Access Journals (Sweden)

    Miao Chen

    Full Text Available Retinal photoreceptors die during retinal synaptogenesis in a portion of retinal degeneration. Whether cone bipolar cells establish regular retinal mosaics and mature morphologies, and resist degeneration are not completely understood. To explore these issues, we backcrossed a transgenic mouse expressing enhanced green fluorescent protein (EGFP in one subset of cone bipolar cells (type 7 into rd1 mice, a classic mouse model of retinal degeneration, to examine the development and survival of cone bipolar cells in a background of retinal degeneration. Our data revealed that both the development and degeneration of cone bipolar cells are independent of the normal activity of cone photoreceptors. We found that type 7 cone bipolar cells achieved a uniform tiling of the retinal surface and developed normal dendritic and axonal arbors without the influence of cone photoreceptor innervation. On the other hand, degeneration of type 7 cone bipolar cells, contrary to our belief of central-to-peripheral progression, was spatially uniform across the retina independent of the spatiotemporal pattern of cone degeneration. The results have important implications for the design of more effective therapies to restore vision in retinal degeneration.

  19. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    Science.gov (United States)

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  20. Serum levels of lipid metabolites in age-related macular degeneration

    OpenAIRE

    Orban, Tivadar; Johnson, William M.; Dong, Zhiqian; Maeda, Tadao; Maeda, Akiko; Sakai, Tsutomu; Tsuneoka, Hiroshi; Mieyal, John J.; Palczewski, Krzysztof

    2015-01-01

    Age-related macular degeneration (AMD) is a neurodegenerative disease that causes adult-onset blindness. There are 2 forms of this progressive disease: wet and dry. Currently there is no cure for AMD, but several treatment options have started to emerge making early detection critical for therapeutic success. Analysis of the eyes of Abca4−/−Rdh8−/− mice that display light-induced retinal degeneration indicates that 11-cis-retinal and docosahexaenoic acid (DHA) levels were significantly decrea...

  1. Thermal analysis on motorcycle disc brake geometry

    Science.gov (United States)

    W. M. Zurin W., S.; Talib, R. J.; Ismail, N. I.

    2017-08-01

    Braking is a phase of slowing and stop the movement of motorcycle. During braking, the frictional heat was generated and the energy was ideally should be faster dissipated to surrounding to prevent the built up of the excessive temperature which may lead to brake fluid vaporization, thermoelastic deformation at the contact surface, material degradation and failure. In this paper, solid and ventilated type of motorcycle disc brake are being analyse using Computational Fluid Dynamic (CFD) software. The main focus of the analysis is the thermal behaviour during braking for solid and ventilated disc brake. A comparison between both geometries is being discussed to determine the better braking performance in term of temperature distribution. It is found that ventilated disc brake is having better braking performance in terms of heat transfer compare to solid disc.

  2. Hydrodynamic forces on two moving discs

    Directory of Open Access Journals (Sweden)

    Burton D.A.

    2004-01-01

    Full Text Available We give a detailed presentation of a flexible method for constructing explicit expressions of irrotational and incompressible fluid flows around two rigid circular moving discs. We also discuss how such expressions can be used to compute the fluid-induced forces and torques on the discs in terms of Killing drives. Conformal mapping techniques are used to identify a meromorphic function on an annular region in C with a flow around two circular discs by a Mobius transformation. First order poles in the annular region correspond to vortices outside of the two discs. Inflows are incorporated by putting a second order pole at the point in the annulus that corresponds to infinity.

  3. Locally prepared antibiotic sensitivity discs: a substitute for imported ...

    African Journals Online (AJOL)

    Zones of inhibition were compared with those obtained from commercial antibiotic discs. Results obtained showed that discs prepared locally from antibiotic tablets, performed comparably with commercially obtained discs. There was no significant statistical difference between the two tested discs. We therefore recommend ...

  4. Optic Disc Pit with Sectorial Retinitis Pigmentosa

    OpenAIRE

    Balikoglu-Yilmaz, Melike; Taskapili, Muhittin; Yilmaz, Tolga; Teke, Mehmet Yasin

    2013-01-01

    Sectorial retinitis pigmentosa (RP) and optic disc pit (ODP) are rare clinical conditions. We present a 40-year-old woman with a history of mild night blindness and decreased vision in the right eye for about 5 years. Fundus examination revealed retinal pigmentary changes in the superior and inferotemporal sectors covering the macula and reduced arterial calibre and ODP at the temporal edge of the optic disc. In addition, fundus autofluorescence, spectral-domain optical coherence tomography, ...

  5. The lowest surface brightness disc galaxy known

    International Nuclear Information System (INIS)

    Davies, J.I.; Phillipps, S.; Disney, M.J.

    1988-01-01

    The discovery of a galaxy with a prominent bulge and a dominant extremely low surface brightness disc component is reported. The profile of this galaxy is very similar to the recently discovered giant low surface brightness galaxy Malin 1. The disc central surface brightness is found to be ∼ 26.4 Rμ, some 1.5 mag fainter than Malin 1 and thus by far the lowest yet observed. (author)

  6. Spontaneous Resolution of Optic Disc Pit Maculopathy

    OpenAIRE

    Tripathy, Koushik

    2017-01-01

    I read with interest the article reporting spontaneous resolution of optic disc pit maculopathy in a boy.1 Though the presence of an optic disc pit and associated macular involvement is undoubted in the presented case, the provided optical coherence tomography (OCT) does not clearly show typical intraretinal schisis (Figure 1B)1 at multiple retinal levels which may communicate with the pit. Instead, it shows a sub-internal limiting membrane (sub-ILM) cavity. Such cavities are known to occur f...

  7. Archival-grade optical disc design and international standards

    Science.gov (United States)

    Fujii, Toru; Kojyo, Shinichi; Endo, Akihisa; Kodaira, Takuo; Mori, Fumi; Shimizu, Atsuo

    2015-09-01

    Optical discs currently on the market exhibit large variations in life span among discs, making them unsuitable for certain business applications. To assess and potentially mitigate this problem, we performed accelerated degradation testing under standard ISO conditions, determined the probable disc failure mechanisms, and identified the essential criteria necessary for a stable disc composition. With these criteria as necessary conditions, we analyzed the physical and chemical changes that occur in the disc components, on the basis of which we determined technological measures to reduce these degradation processes. By applying these measures to disc fabrication, we were able to develop highly stable optical discs.

  8. Dopamine induces soluble α-synuclein oligomers and nigrostriatal degeneration.

    Science.gov (United States)

    Mor, Danielle E; Tsika, Elpida; Mazzulli, Joseph R; Gould, Neal S; Kim, Hanna; Daniels, Malcolm J; Doshi, Shachee; Gupta, Preetika; Grossman, Jennifer L; Tan, Victor X; Kalb, Robert G; Caldwell, Kim A; Caldwell, Guy A; Wolfe, John H; Ischiropoulos, Harry

    2017-11-01

    Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated both dopamine levels and α-synuclein expression. Nigrally targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine levels without damaging neurons in non-transgenic mice. In contrast, raising dopamine levels in mice expressing human A53T mutant α-synuclein induced progressive nigrostriatal degeneration and reduced locomotion. Dopamine elevation in A53T mice increased levels of potentially toxic α-synuclein oligomers, resulting in conformationally and functionally modified species. Moreover, in genetically tractable Caenorhabditis elegans models, expression of α-synuclein mutated at the site of interaction with dopamine prevented dopamine-induced toxicity. These data suggest that a unique mechanism links two cardinal features of PD: dopaminergic cell death and α-synuclein aggregation.

  9. Genetics of Frontotemporal Lobar Degeneration

    Directory of Open Access Journals (Sweden)

    Daniela eGalimberti

    2012-04-01

    Full Text Available Frontotemporal Lobar Degeneration (FTLD is the most frequent neurodegenerative disorder with a presenile onset. It presents with a spectrum of clinical manifestations, ranging from behavioural and executive impairment to language disorders and motor dysfunction. Familial aggregation is frequently reported in FTLD, and about 10% of cases have an autosomal dominant transmission. Microtubule Associated Protein Tau gene (MAPT mutations have been the first ones identified and are generally associated with early onset behavioural variant Frontotemporal Dementia (bvFTD phenotype. More recently, progranulin gene (GRN mutations were recognized in association with familial form of FTLD. In addition, other genes are linked to rare cases of familial FTLD. Lastly, a number of genetic risk factors for sporadic forms have also been identified.

  10. Frontotemporal Degeneration in a Child.

    Science.gov (United States)

    Terrill, Tyler; Pascual, Juan M

    2017-07-01

    There is a predilection for the frontal and temporal lobes in certain cases of dementia in the adult, leading to the syndrome of frontotemporal dementia. However, this syndrome has seemed to elude the developing brain until now. We describe an example of apparently selective neurodegeneration of the frontal and temporal regions during development associated with some of the clinical, magnetic resonance imaging, and fludeoxyglucose positron emission tomography (FDG PET) scan features of canonical frontotemporal dementia in the adult. This patient does not have any of the common frontotemporal dementia-causing mutations or known progressive brain disorders of children. This patient illustrates that symptomatic, selective, and progressive vulnerability of the frontal and temporal lobes is not restricted to adulthood, expanding the phenotype of frontotemporal degeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Naturalness of nearly degenerate neutrinos

    International Nuclear Information System (INIS)

    Casas, J.A.; Espinosa, J.R.; Ibarra, A.; Navarro, I.

    1999-01-01

    If neutrinos are to play a relevant cosmological role, they must be essentially degenerate. We study whether radiative corrections can or cannot be responsible for the small mass splittings, in agreement with all the available experimental data. We perform an exhaustive exploration of the bimaximal mixing scenario, finding that (i) the vacuum oscillations solution to the solar neutrino problem is always excluded; (ii) if the mass matrix is produced by a see-saw mechanism, there are large regions of the parameter space consistent with the large angle MSW solution, providing a natural origin for the Δm sol 2 atm 2 hierarchy; (iii) the bimaximal structure becomes then stable under radiative corrections. We also provide analytical expressions for the mass splittings and mixing angles and present a particularly simple see-saw ansatz consistent with all observations

  12. Eigenstate Thermalization for Degenerate Observables

    Science.gov (United States)

    Anza, Fabio; Gogolin, Christian; Huber, Marcus

    2018-04-01

    Under unitary time evolution, expectation values of physically reasonable observables often evolve towards the predictions of equilibrium statistical mechanics. The eigenstate thermalization hypothesis (ETH) states that this is also true already for individual energy eigenstates. Here we aim at elucidating the emergence of the ETH for observables that can realistically be measured due to their high degeneracy, such as local, extensive, or macroscopic observables. We bisect this problem into two parts, a condition on the relative overlaps and one on the relative phases between the eigenbases of the observable and Hamiltonian. We show that the relative overlaps are unbiased for highly degenerate observables and demonstrate that unless relative phases conspire to cumulative effects, this makes such observables verify the ETH. Through this we elucidate potential pathways towards proofs of thermalization.

  13. In-vivo Intervertebral Disc Characterization using Magnetic Resonance Spectroscopy and T1ρ Imaging: Association with Discography and Oswestry Disability Index and SF-36

    Science.gov (United States)

    Zuo, Jin; Joseph, Gabby B.; Li, Xiaojuan; Link, Thomas M.; Hu, Serena S.; Berven, Sigurd H.; Kurhanewitz, John; Majumdar, Sharmila

    2011-01-01

    Study Design An in vivo study of intervertebral disc degeneration using quantitative MRI and MRS. Objective To quantify water and proteoglycan (PG) content in the intervertebral disc using in vivo magnetic resonance spectroscopy (MRS), and to evaluate the relationship between MRS- quantified water/PG content, T1ρ, Pfirrmann score, clinical self-assessment, and discography. Summary of Background Data Previous in vitro studies have investigated the relationship between MRS-quantified water/PG content, and degenerative grade using cadaveric intervertebral discs. T1ρ has been shown to relate to Pfirmann grade and clinical self-assessment. However, the associations between MRS-quantified water/PG content, MR imaging-based T1ρ, self-assessment of health status and clinical response to discography have not been studied in vivo. Methods MRS and MR imaging were performed in 26 patients (70 discs) with symptomatic intervertebral degenerative disc (IVDD) and 23 controls (41 discs). Patients underwent evaluation of intervertebral discs with provocative discography. All subjects completed the SF-36 Health Survey and Oswestry Disability Index questionnaires. Results The water/PG peak area ratio was significantly elevated in a) patients (compared to controls) and in b) discs with positive discography (compared to negative discography). MR T1ρ exhibited similar trends. A significant association was found between T1ρ and normalized PG content (R2 = 0.61, p 0.05). The water/PG peak area ratio, normalized water, normalized PG, and Pfirrmann grade were significantly associated with patient self-assessment of disability and physical composite score, while disc height was not. Conclusion This study demonstrated a relationship between in vivo MRS spectroscopy (water content, PG content), imaging parameters (T1ρ, Pfirrmann Grade), discography results, and clinical self-assessment, suggesting that MRS-quantified water, PG and MR T1ρ relaxation time may potentially serve as

  14. In vivo intervertebral disc characterization using magnetic resonance spectroscopy and T1ρ imaging: association with discography and Oswestry Disability Index and Short Form-36 Health Survey.

    Science.gov (United States)

    Zuo, Jin; Joseph, Gabby B; Li, Xiaojuan; Link, Thomas M; Hu, Serena S; Berven, Sigurd H; Kurhanewitz, John; Majumdar, Sharmila

    2012-02-01

    An in vivo study of intervertebral disc degeneration by using quantitative magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). To quantify water and proteoglycan (PG) content in the intervertebral disc by using in vivo MRS and to evaluate the relationship between MRS-quantified water/PG content, T1ρ, Pfirrmann score, clinical self-assessment, and discography. Previous in vitro studies have investigated the relationship between MRS-quantified water/PG content and degenerative grade by using cadaveric intervertebral discs. T1ρ has been shown to relate to Pfirrmann grade and clinical self-assessment. However, the associations between MRS-quantified water/PG content, MRI-based T1ρ, self-assessment of health status, and clinical response to discography have not been studied in vivo. MRS and MRI were performed in 26 patients (70 discs) with symptomatic intervertebral degenerative disc (IVDD) and 23 controls (41 discs). Patients underwent evaluation of intervertebral discs with provocative discography. All subjects completed the Short Form-36 Health Survey and Oswestry Disability Index questionnaires. The water/PG peak area ratio was significantly elevated in (a) patients (compared with controls) and in (b) discs with positive discography (compared with negative discography). Magnetic resonance (MR) T1ρ exhibited similar trends. A significant association was found between T1ρ and normalized PG content (R = 0.61, P 0.05). The water/PG peak area ratio, normalized water, normalized PG, and Pfirrmann grade were significantly associated with patient self-assessment of disability and physical composite score, while disc height was not. This study demonstrated a relationship between in vivo MRS spectroscopy (water content and PG content), imaging parameters (T1ρ and Pfirrmann grade), discography results, and clinical self-assessment, suggesting that MRS-quantified water, PG, and MR T1ρ relaxation time may potentially serve as biomarkers of

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

    Science.gov (United States)

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

    2015-03-18

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

  16. Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics

    Directory of Open Access Journals (Sweden)

    LM Benneker

    2014-05-01

    Full Text Available Intervertebral disc (IVD degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encouraging results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium "Where Science meets Clinics", sponsored by the AO Foundation and held in Davos, Switzerland, from September 5-7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imaging methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neuro-genesis. Discogenic pain, originating from "black discs" or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.

  17. Metallothionein 1+2 protect the CNS during neuroglial degeneration induced by 6-aminonicotinamide

    DEFF Research Database (Denmark)

    Penkowa, Milena; Giralt, Mercedes; Camats, Jordi

    2002-01-01

    6-Aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of gray matter astrocytes. Metallothionein 1+2 (MT-1+2) are neuroprotective factors in the central nervous system (CNS), and to determine the roles for MT after 6-AN, we have examined transgenic mice overexpressing MT-1...... (NITT), and the number of terminal deoxynucleotidyl transferase [TdT]-mediated deoxyuridine triphosphate [dUTP]-digoxigenin nick end labeling-positive (TUNEL+), caspase-3+ apoptotic cells were significantly increased in the brainstem of normal mice after 6-AN. In the TgMTI* mice, the 6-AN-induced tissue...... damage was decreased in comparison to control mice, and they showed significantly reduced numbers of recruited macrophages and T lymphocytes, and a drastic reduction of oxidative stress and apoptotic cell death. In addition, the accompanying reactive astrogliosis was increased in the transgenic mice...

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

    Science.gov (United States)

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

    2017-01-01

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

  19. Cervical disc hernia operations through posterior laminoforaminotomy.

    Science.gov (United States)

    Yolas, Coskun; Ozdemir, Nuriye Guzin; Okay, Hilmi Onder; Kanat, Ayhan; Senol, Mehmet; Atci, Ibrahim Burak; Yilmaz, Hakan; Coban, Mustafa Kemal; Yuksel, Mehmet Onur; Kahraman, Umit

    2016-01-01

    The most common used technique for posterolateral cervical disc herniations is anterior approach. However, posterior cervical laminotoforaminomy can provide excellent results in appropriately selected patients with foraminal stenosis in either soft disc prolapse or cervical spondylosis. The purpose of this study was to present the clinical outcomes following posterior laminoforaminotomy in patients with radiculopathy. We retrospectively evaluated 35 patients diagnosed with posterolateral cervical disc herniation and cervical spondylosis with foraminal stenosis causing radiculopathy operated by the posterior cervical keyhole laminoforaminotomy between the years 2010 and 2015. The file records and the radiographic images of the 35 patients were assessed retrospectively. The mean age was 46.4 years (range: 34-66 years). Of the patients, 19 were males and 16 were females. In all of the patients, the neurologic deficit observed was radiculopathy. The posterolaterally localized disc herniations and the osteophytic structures were on the left side in 18 cases and on the right in 17 cases. In 10 of the patients, the disc level was at C5-6, in 18 at C6-7, in 2 at C3-4, in 2 at C4-5, in 1 at C7-T1, in 1 patient at both C5-6 and C6-7, and in 1 at both C4-5 and C5-6. In 14 of these 35 patients, both osteophytic structures and protruded disc herniation were present. Intervertebral foramen stenosis was present in all of the patients with osteophytes. Postoperatively, in 31 patients the complaints were relieved completely and four patients had complaints of neck pain and paresthesia radiating to the arm (the success of operation was 88.5%). On control examinations, there was no finding of instability or cervical kyphosis. Posterior cervical laminoforaminotomy is an alternative appropriate choice in both cervical soft disc herniations and cervical stenosis.

  20. Cervical disc hernia operations through posterior laminoforaminotomy

    Directory of Open Access Journals (Sweden)

    Coskun Yolas

    2016-01-01

    Full Text Available Objective: The most common used technique for posterolateral cervical disc herniations is anterior approach. However, posterior cervical laminotoforaminomy can provide excellent results in appropriately selected patients with foraminal stenosis in either soft disc prolapse or cervical spondylosis. The purpose of this study was to present the clinical outcomes following posterior laminoforaminotomy in patients with radiculopathy. Materials and Methods: We retrospectively evaluated 35 patients diagnosed with posterolateral cervical disc herniation and cervical spondylosis with foraminal stenosis causing radiculopathy operated by the posterior cervical keyhole laminoforaminotomy between the years 2010 and 2015. Results: The file records and the radiographic images of the 35 patients were assessed retrospectively. The mean age was 46.4 years (range: 34-66 years. Of the patients, 19 were males and 16 were females. In all of the patients, the neurologic deficit observed was radiculopathy. The posterolaterally localized disc herniations and the osteophytic structures were on the left side in 18 cases and on the right in 17 cases. In 10 of the patients, the disc level was at C5-6, in 18 at C6-7, in 2 at C3-4, in 2 at C4-5, in 1 at C7-T1, in 1 patient at both C5-6 and C6-7, and in 1 at both C4-5 and C5-6. In 14 of these 35 patients, both osteophytic structures and protruded disc herniation were present. Intervertebral foramen stenosis was present in all of the patients with osteophytes. Postoperatively, in 31 patients the complaints were relieved completely and four patients had complaints of neck pain and paresthesia radiating to the arm (the success of operation was 88.5%. On control examinations, there was no finding of instability or cervical kyphosis. Conclusion: Posterior cervical laminoforaminotomy is an alternative appropriate choice in both cervical soft disc herniations and cervical stenosis.

  1. Only marginal alignment of disc galaxies

    Science.gov (United States)

    Andrae, René; Jahnke, Knud

    2011-12-01

    Testing theories of angular-momentum acquisition of rotationally supported disc galaxies is the key to understanding the formation of this type of galaxies. The tidal-torque theory aims to explain this acquisition process in a cosmological framework and predicts positive autocorrelations of angular-momentum orientation and spiral-arm handedness, i.e. alignment of disc galaxies, on short distance scales of 1 Mpc h-1. This disc alignment can also cause systematic effects in weak-lensing measurements. Previous observations claimed discovering these correlations but are overly optimistic in the reported level of statistical significance of the detections. Errors in redshift, ellipticity and morphological classifications were not taken into account, although they have a significant impact. We explain how to rigorously propagate all the important errors through the estimation process. Analysing disc galaxies in the Sloan Digital Sky Survey (SDSS) data base, we find that positive autocorrelations of spiral-arm handedness and angular-momentum orientations on distance scales of 1 Mpc h-1 are plausible but not statistically significant. Current data appear not good enough to constrain parameters of theory. This result agrees with a simple hypothesis test in the Local Group, where we also find no evidence for disc alignment. Moreover, we demonstrate that ellipticity estimates based on second moments are strongly biased by galactic bulges even for Scd galaxies, thereby corrupting correlation estimates and overestimating the impact of disc alignment on weak-lensing studies. Finally, we discuss the potential of future sky surveys. We argue that photometric redshifts have too large errors, i.e. PanSTARRS and LSST cannot be used. Conversely, the EUCLID project will not cover the relevant redshift regime. We also discuss the potentials and problems of front-edge classifications of galaxy discs in order to improve the autocorrelation estimates of angular-momentum orientation.

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

    Science.gov (United States)

    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.

  3. DZ Chamaeleontis: a bona fide photoevaporating disc

    Science.gov (United States)

    Canovas, H.; Montesinos, B.; Schreiber, M. R.; Cieza, L. A.; Eiroa, C.; Meeus, G.; de Boer, J.; Ménard, F.; Wahhaj, Z.; Riviere-Marichalar, P.; Olofsson, J.; Garufi, A.; Rebollido, I.; van Holstein, R. G.; Caceres, C.; Hardy, A.; Villaver, E.

    2018-02-01

    Context. DZ Cha is a weak-lined T Tauri star (WTTS) surrounded by a bright protoplanetary disc with evidence of inner disc clearing. Its narrow Hα line and infrared spectral energy distribution suggest that DZ Cha may be a photoevaporating disc. Aims: We aim to analyse the DZ Cha star + disc system to identify the mechanism driving the evolution of this object. Methods: We have analysed three epochs of high resolution optical spectroscopy, photometry from the UV up to the sub-mm regime, infrared spectroscopy, and J-band imaging polarimetry observations of DZ Cha. Results: Combining our analysis with previous studies we find no signatures of accretion in the Hα line profile in nine epochs covering a time baseline of 20 yr. The optical spectra are dominated by chromospheric emission lines, but they also show emission from the forbidden lines [SII] 4068 and [OI] 6300Å that indicate a disc outflow. The polarized images reveal a dust depleted cavity of 7 au in radius and two spiral-like features, and we derive a disc dust mass limit of Mdust 80 MJup) companions are detected down to 0.̋07 ( 8 au, projected). Conclusions: The negligible accretion rate, small cavity, and forbidden line emission strongly suggests that DZ Cha is currently at the initial stages of disc clearing by photoevaporation. At this point the inner disc has drained and the inner wall of the truncated outer disc is directly exposed to the stellar radiation. We argue that other mechanisms like planet formation or binarity cannot explain the observed properties of DZ Cha. The scarcity of objects like this one is in line with the dispersal timescale (≲105 yr) predicted by this theory. DZ Cha is therefore an ideal target to study the initial stages of photoevaporation. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programme 097.C-0536. Based on data obtained from the ESO Science Archive Facility under request number 250112.

  4. Cervical Lordosis Actually Increases With Aging and Progressive Degeneration in Spinal Deformity Patients.

    Science.gov (United States)

    Kim, Han Jo; Lenke, Lawrence G; Oshima, Yasushi; Chuntarapas, Tapanut; Mesfin, Addisu; Hershman, Stuart; Fogelson, Jeremy L; Riew, K Daniel

    2014-09-01

    Retrospective. The authors hypothesized that cervical lordosis (CL) would decrease with aging and increasing degeneration. It is theorized that with age and degeneration, the cervical spine loses lordosis and becomes progressively more kyphotic; however, no studies support these conclusions in patients with various spinal deformities. The authors performed a radiographic analysis of asymptomatic adults (referring to their cervical spine) of varying ages, with differing forms of spinal deformity to the thoracic/lumbar spine to see how cervical lordosis changes with increasing age. A total of 104 total spine EOS X-rays of adult (aged >18 years) spinal deformity patients without documented neck pain, prior neck surgery, or cervical deformity were reviewed. The researchers only reviewed EOS X-rays because they allow complete visualization from occiput to feet. Cervical lordosis, standard Cobb measurements, sagittal balance parameters, and cervical degeneration were quantified radiographically by the method previously described by Gore et al. Statistical analysis was performed with 1-way analysis of variance to compare significant differences between groups aged 60 years as well as changes in sagittal balance. A p-value 60 years, respectively; p 60 years, respectively; p < .01), with the highest degeneration at the C5-6 and C6-7 disc spaces (3.7 ± 3.3 and 3.2 ± 2.9, respectively; p < .01). This increase did not correlate with the increase in CL seen with aging (r = 0.02; p = .84). Cervical lordosis increased with aging in adult spinal deformity patients. There was no relationship between cervical degeneration and lordosis despite the strong relationship seen between increasing CL in older age groups. Copyright © 2014 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

  5. INJURIES IN DISC GOLF - A DESCRIPTIVE CROSS-SECTIONAL STUDY

    DEFF Research Database (Denmark)

    Rahbek, Martin Amadeus; Nielsen, Rasmus Oestergaard

    2016-01-01

    BACKGROUND: Disc golf is rapidly increasing in popularity and more than two million people are estimated to regularly participate in disc golf activities. Despite this popularity, the epidemiology of injuries in disc golf remains under reported. PURPOSE: The purpose of the present study...... was to investigate the prevalence and anatomic distribution of injuries acquired through disc-golf participation in Danish disc golf players. METHODS: The study was a cross-sectional study conducted on Danish disc-golf players. In May 2015, invitations to complete a web-based questionnaire were spread online via...... social media, and around disc-golf courses in Denmark. The questionnaire included questions regarding disc-golf participation and the characteristics of injuries acquired through disc golf participation. The data was analyzed descriptively. RESULTS: An injury prevalence of 13.3% (95% CI: 6.7% to 19...

  6. MRI findings of traumatic cervical disc herniation

    International Nuclear Information System (INIS)

    Tanaka, Hisato; Kasahara, Takaki; Akiyama, Nanae

    2011-01-01

    In general practice, disc hernia is increasingly being questioned about its relation with traffic injuries. In this study, we examined the image findings of cervical disc herniation for findings indicative of traumatic hernia. In 2008, we examined 35 cases of cervical disc herniation at our hospital by MRI. The patients were divided into two groups; patients with trauma history (19 cases) and those without (16 cases), and their images were compared. Disc herniation in the trauma group showed high intensity at T2, with some of the patients in this group also indicating continuous high intensity of the internal and herniated discs. Traumatic force was found to cause swelling under the laryngeal soft tissue. Cases with further flexion injury showed interspinous ligament hemorrhage. These findings strongly suggest the involvement of injury. But given that some younger patients in the non-trauma group also show high intensity at T2*, attention must be paid not to confuse swelling below the larynx with inflammation of the longus colli muscle. (author)

  7. Active galactic nucleus outflows in galaxy discs

    Science.gov (United States)

    Hartwig, Tilman; Volonteri, Marta; Dashyan, Gohar

    2018-05-01

    Galactic outflows, driven by active galactic nuclei (AGNs), play a crucial role in galaxy formation and in the self-regulated growth of supermassive black holes (BHs). AGN feedback couples to and affects gas, rather than stars, and in many, if not most, gas-rich galaxies cold gas is rotationally supported and settles in a disc. We present a 2D analytical model for AGN-driven outflows in a gaseous disc and demonstrate the main improvements, compared to existing 1D solutions. We find significant differences for the outflow dynamics and wind efficiency. The outflow is energy-driven due to inefficient cooling up to a certain AGN luminosity (˜1043 erg s-1 in our fiducial model), above which the outflow remains momentum-driven in the disc up to galactic scales. We reproduce results of 3D simulations that gas is preferentially ejected perpendicular to the disc and find that the fraction of ejected interstellar medium is lower than in 1D models. The recovery time of gas in the disc, defined as the free-fall time from the radius to which the AGN pushes the ISM at most, is remarkably short, of the order 1 Myr. This indicates that AGN-driven winds cannot suppress BH growth for long. Without the inclusion of supernova feedback, we find a scaling of the BH mass with the halo velocity dispersion of MBH ∝ σ4.8.

  8. Frontotemporal lobar degeneration: current perspectives

    Directory of Open Access Journals (Sweden)

    Riedl L

    2014-02-01

    Full Text Available Lina Riedl,1 Ian R Mackenzie,2 Hans Förstl,1 Alexander Kurz,1 Janine Diehl-Schmid1 1Center for Cognitive Disorders, Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; 2Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada Abstract: The term frontotemporal lobar degeneration (FTLD refers to a group of progressive brain diseases, which preferentially involve the frontal and temporal lobes. Depending on the primary site of atrophy, the clinical manifestation is dominated by behavior alterations or impairment of language. The onset of symptoms usually occurs before the age of 60 years, and the mean survival from diagnosis varies between 3 and 10 years. The prevalence is estimated at 15 per 100,000 in the population aged between 45 and 65 years, which is similar to the prevalence of Alzheimer's disease in this age group. There are two major clinical subtypes, behavioral-variant frontotemporal dementia and primary progressive aphasia. The neuropathology underlying the clinical syndromes is also heterogeneous. A common feature is the accumulation of certain neuronal proteins. Of these, the microtubule-associated protein tau (MAPT, the transactive response DNA-binding protein, and the fused in sarcoma protein are most important. Approximately 10% to 30% of FTLD shows an autosomal dominant pattern of inheritance, with mutations in the genes for MAPT, progranulin (GRN, and in the chromosome 9 open reading frame 72 (C9orf72 accounting for more than 80% of familial cases. Although significant advances have been made in recent years regarding diagnostic criteria, clinical assessment instruments, neuropsychological tests, cerebrospinal fluid biomarkers, and brain imaging techniques, the clinical diagnosis remains a challenge. To date, there is no specific pharmacological treatment for FTLD. Some evidence has been provided for serotonin reuptake

  9. Motor axon excitability during Wallerian degeneration

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez, Susana; Krarup, Christian

    2008-01-01

    Axonal loss and degeneration are major factors in determining long-term outcome in patients with peripheral nerve dis