Science.gov

Sample records for advanced disc degeneration

  1. Biomechanics of Disc Degeneration

    PubMed Central

    Palepu, V.; Kodigudla, M.; Goel, V. K.

    2012-01-01

    Disc degeneration and associated disorders are among the most debated topics in the orthopedic literature over the past few decades. These may be attributed to interrelated mechanical, biochemical, and environmental factors. The treatment options vary from conservative approaches to surgery, depending on the severity of degeneration and response to conservative therapies. Spinal fusion is considered to be the “gold standard” in surgical methods till date. However, the association of adjacent level degeneration has led to the evolution of motion preservation technologies like spinal arthroplasty and posterior dynamic stabilization systems. These new technologies are aimed to address pain and preserve motion while maintaining a proper load sharing among various spinal elements. This paper provides an elaborative biomechanical review of the technologies aimed to address the disc degeneration and reiterates the point that biomechanical efficacy followed by long-term clinical success will allow these nonfusion technologies as alternatives to fusion, at least in certain patient population. PMID:22745914

  2. Cell therapy for the degenerating intervertebral disc.

    PubMed

    Tong, Wei; Lu, Zhouyu; Qin, Ling; Mauck, Robert L; Smith, Harvey E; Smith, Lachlan J; Malhotra, Neil R; Heyworth, Martin F; Caldera, Franklin; Enomoto-Iwamoto, Motomi; Zhang, Yejia

    2017-03-01

    Spinal conditions related to intervertebral disc (IVD) degeneration cost billions of dollars in the US annually. Despite the prevalence and soaring cost, there is no specific treatment that restores the physiological function of the diseased IVD. Thus, it is vital to develop new treatment strategies to repair the degenerating IVD. Persons with IVD degeneration without back pain or radicular leg pain often do not require any intervention. Only patients with severe back pain related to the IVD degeneration or biomechanical instability are likely candidates for cell therapy. The IVD progressively degenerates with age in humans, and strategies to repair the IVD depend on the stage of degeneration. Cell therapy and cell-based gene therapy aim to address moderate disc degeneration; advanced stage disease may require surgery. Studies involving autologous, allogeneic, and xenogeneic cells have all shown good survival of these cells in the IVD, confirming that the disc niche is an immunologically privileged site, permitting long-term survival of transplanted cells. All of the animal studies reviewed here reported some improvement in disc structure, and 2 studies showed attenuation of local inflammation. Among the 50 studies reviewed, 25 used some type of scaffold, and cell leakage is a consistently noted problem, though some studies showed reduced cell leakage. Hydrogel scaffolds may prevent cell leakage and provide biomechanical support until cells can become established matrix producers. However, these gels need to be optimized to prevent this leakage. Many animal models have been leveraged in this research space. Rabbit is the most frequently used model (28 of 50), followed by rat, pig, and dog. Sheep and goat IVDs resemble those of humans in size and in the absence of notochordal cells. Despite this advantage, there were only 2 sheep and 1 goat studies of 50 studies in this cohort. It is also unclear if a study in large animals is needed before clinical trials since

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2013-01-01

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

  5. Genetic Factors in Intervertebral Disc Degeneration

    PubMed Central

    Feng, Yi; Egan, Brian; Wang, Jinxi

    2016-01-01

    Low back pain (LBP) is a major cause of disability and imposes huge economic burdens on human society worldwide. Among many factors responsible for LBP, intervertebral disc degeneration (IDD) is the most common disorder and is a target for intervention. The etiology of IDD is complex and its mechanism is still not completely understood. Many factors such as aging, spine deformities and diseases, spine injuries, and genetic factors are involved in the pathogenesis of IDD. In this review, we will focus on the recent advances in studies on the most promising and extensively examined genetic factors associated with IDD in humans. A number of genetic defects have been correlated with structural and functional changes within the intervertebral disc (IVD), which may compromise the disc’s mechanical properties and metabolic activities. These genetic and proteomic studies have begun to shed light on the molecular basis of IDD, suggesting that genetic factors are important contributors to the onset and progression of IDD. By continuing to improve our understanding of the molecular mechanisms of IDD, specific early diagnosis and more effective treatments for this disabling disease will be possible in the future. PMID:27617275

  6. Decellularized allogeneic intervertebral disc: natural biomaterials for regenerating disc degeneration

    PubMed Central

    Hu, Zhijun; Chen, Kai; Shan, Zhi; Chen, Shuai; Wang, Jiying; Mo, Jian; Ma, Jianjun; Xu, Wenbing; Qin, An; Fan, Shunwu

    2016-01-01

    Intervertebral disc degeneration is associated with back pain and disc herniation. This study established a modified protocol for intervertebral disc (IVD) decellularization and prepared its extracellular matrix (ECM). By culturing mesenchymal stem cells (MSCs)(3, 7, 14 and 21 days) and human degenerative IVD cells (7 days) in the ECM, implanting it subcutaneously in rabbit and injecting ECM microparticles into degenerative disc, the biological safety and efficacy of decellularized IVD was evaluated both in vitro and in vivo. Here, we demonstrated that cellular components can be removed completely after decellularization and maximally retain the structure and biomechanics of native IVD. We revealed that allogeneic ECM did not evoke any apparent inflammatory reaction in vivo and no cytotoxicity was found in vitro. Moreover, IVD ECM can induce differentiation of MSCs into IVD-like cells in vitro. Furthermore, allogeneic ECM microparticles are effective on the treatment of rabbit disc degeneration in vivo. In conclusion, our study developed an optimized method for IVD decellularization and we proved decellularized IVD is safe and effective for the treatment of degenerated disc diseases. PMID:26933821

  7. Biological treatment strategies for disc degeneration: potentials and shortcomings

    PubMed Central

    Nerlich, Andreas G.; Boos, Norbert

    2006-01-01

    Recent advances in molecular biology, cell biology and material sciences have opened a new emerging field of techniques for the treatment of musculoskeletal disorders. These new treatment modalities aim for biological repair of the affected tissues by introducing cell-based tissue replacements, genetic modifications of resident cells or a combination thereof. So far, these techniques have been successfully applied to various tissues such as bone and cartilage. However, application of these treatment modalities to cure intervertebral disc degeneration is in its very early stages and mostly limited to experimental studies in vitro or in animal studies. We will discuss the potential and possible shortcomings of current approaches to biologically cure disc degeneration by gene therapy or tissue engineering. Despite the increasing number of studies examining the therapeutic potential of biological treatment strategies, a practicable solution to routinely cure disc degeneration might not be available in the near future. However, knowledge gained from these attempts might be applied in a foreseeable future to cure the low back pain that often accompanies disc degeneration and therefore be beneficial for the patient. PMID:16983559

  8. Inflammation in intervertebral disc degeneration and regeneration

    PubMed Central

    Molinos, Maria; Almeida, Catarina R.; Caldeira, Joana; Cunha, Carla; Gonçalves, Raquel M.; Barbosa, Mário A.

    2015-01-01

    Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players. PMID:25673296

  9. Intervertebral disc degeneration: evidence for two distinct phenotypes

    PubMed Central

    Adams, Michael A; Dolan, Patricia

    2012-01-01

    We review the evidence that there are two types of disc degeneration. ‘Endplate-driven’ disc degeneration involves endplate defects and inwards collapse of the annulus, has a high heritability, mostly affects discs in the upper lumbar and thoracic spine, often starts to develop before age 30 years, usually leads to moderate back pain, and is associated with compressive injuries such as a fall on the buttocks. ‘Annulus-driven’ disc degeneration involves a radial fissure and/or a disc prolapse, has a low heritability, mostly affects discs in the lower lumbar spine, develops progressively after age 30 years, usually leads to severe back pain and sciatica, and is associated with repetitive bending and lifting. The structural defects which initiate the two processes both act to decompress the disc nucleus, making it less likely that the other defect could occur subsequently, and in this sense the two disc degeneration phenotypes can be viewed as distinct. PMID:22881295

  10. Notochord Cells in Intervertebral Disc Development and Degeneration

    PubMed Central

    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. Cell transplantation in lumbar spine disc degeneration disease.

    PubMed

    Hohaus, C; Ganey, T M; Minkus, Y; Meisel, H J

    2008-12-01

    Low back pain is an extremely common symptom, affecting nearly three-quarters of the population sometime in their life. Given that disc herniation is thought to be an extension of progressive disc degeneration that attends the normal aging process, seeking an effective therapy that staves off disc degeneration has been considered a logical attempt to reduce back pain. The most apparent cellular and biochemical changes attributable to degeneration include a decrease in cell density in the disc that is accompanied by a reduction in synthesis of cartilage-specific extracellular matrix components. With this in mind, one therapeutic strategy would be to replace, regenerate, or augment the intervertebral disc cell population, with a goal of correcting matrix insufficiencies and restoring normal segment biomechanics. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. We designed an animal study using the dog as our model to investigate this hypothesis by transplantation of autologous disc-derived chondrocytes into degenerated intervertebral discs. As a result we demonstrated that disc cells remained viable after transplantation; transplanted disc cells produced an extracellular matrix that contained components similar to normal intervertebral disc tissue; a statistically significant correlation between transplanting cells and retention of disc height could displayed. Following these results the Euro Disc Randomized Trial was initiated to embrace a representative patient group with persistent symptoms that had not responded to conservative treatment where an indication for surgical treatment was given. In the interim analyses we evaluated that patients who received autologous disc cell transplantation had greater pain reduction at 2 years compared with patients who did not receive cells following their discectomy surgery and discs in patients that

  12. RADIOLOGICAL ANALYSIS OF EXPERIMENTAL DISC DEGENERATION IN RABBITS

    PubMed Central

    Vialle, Emiliano; Vialle, Luiz Roberto; Arruda, André de Oliveira; Riet, Ricardo Nascimento; Krieger, Antônio Bernardo de Queiroz

    2015-01-01

    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, validating the potential to induce disc degeneration in this animal model for future studies. PMID:27022512

  13. Lumbar intervertebral disc degeneration and related factors in Korean firefighters

    PubMed Central

    Jang, Tae-Won; Ahn, Yeon-Soon; Byun, Junsu; Lee, Jong-In; Kim, Kun-Hyung; Kim, Youngki; Song, Han-Soo; Lee, Chul-Gab; Kwon, Young-Jun; Yoon, Jin-Ha; Jeong, Kyoungsook

    2016-01-01

    Objectives The job of firefighting can cause lumbar burden and low back pain. This study aimed to identify the association between age and lumbar intervertebral disc degeneration and whether the association differs between field and administrative (non-field) firefighters. Methods Subjects were selected using a stratified random sampling method. Firefighters were stratified by geographic area, gender, age and type of job. First, 25 fire stations were randomly sampled considering regional distribution. Then firefighters were stratified by gender, age and their job and randomly selected among the strata. A questionnaire survey and MRI scans were performed, and then four radiologists used Pfirrmann classification methods to determine the grade of lumbar intervertebral disc degeneration. Results Pfirrmann grade increased with lumbar intervertebral disc level. Analysis of covariance showed that age was significantly associated with lumbar intervertebral disc degeneration (p<0.05). The value of β (parameter estimate) was positive at all lumbar intervertebral disc levels and was higher in the field group than in the administrative group at each level. In logistic regression analysis, type of job was statistically significant only with regard to the L4–5 intervertebral disc (OR 3.498, 95% CI 1.241 to 9.860). Conclusions Lumbar intervertebral disc degeneration is associated with age, and field work such as firefighting, emergency and rescue may accelerate degeneration in the L4–5 intervertebral disc. The effects of field work on lumbar intervertebral disc degeneration were not clear in discs other than at the level L4–5. PMID:27354080

  14. Progranulin Knockout Accelerates Intervertebral Disc Degeneration in Aging Mice

    PubMed Central

    Zhao, Yun-peng; Tian, Qing-yun; Liu, Ben; Cuellar, Jason; Richbourgh, Brendon; Jia, Tang-hong; Liu, Chuan-ju

    2015-01-01

    Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-κB signaling and β-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases. PMID:25777988

  15. Disc in Flames: Roles of TNF-α and IL-1β in Intervertebral Disc Degeneration

    PubMed Central

    Johnson, Zariel I.; Schoepflin, Zachary R.; Choi, Hyowon; Shapiro, Irving M.; Risbud, Makarand V.

    2016-01-01

    The intervertebral disc is an important mechanical structure that allows range of motion of the spinal column. Degeneration of the intervertebral disc, incited by aging, traumatic insult, genetic predisposition, or other factors, is often defined by functional and structural changes in the tissue, including excessive breakdown of the extracellular matrix, increased disc cell senescence and death, and compromised biomechanical function of the tissue. Intervertebral disc degeneration is strongly correlated with low back pain, which is a highly prevalent and costly condition, significantly contributing to loss in productivity and health care costs. Disc degeneration is a chronic, progressive condition, and current therapies are limited and often focused on symptomatic pain relief rather than curtailing the progression of the disease. Inflammatory processes, exacerbated by cytokines TNF-α and IL-1β are believed to be key mediators of disc degeneration and low back pain. In this review, we describe the contributions of TNF-α and IL-1β to changes seen during disc degeneration at the cellular and tissue level, new evidence suggesting a link between infection of the spine and low back pain, and the emerging therapeutic modalities aimed at combating these processes. PMID:26388614

  16. Histological Identification of Propionibacterium acnes in Nonpyogenic Degenerated Intervertebral Discs

    PubMed Central

    Yuan, Ye; Zhou, Zezhu; Jiao, Yucheng; Zheng, Yuehuan; Lin, Yazhou; Xiao, Jiaqi

    2017-01-01

    Purpose. Low-virulence anaerobic bacteria, especially the Propionibacterium acnes (P. acnes), have been thought to be a new pathogeny for a series of disc diseases. However, until now, there has been no histological evidence to confirm this link. The purpose of this study was to confirm the presence of P. acnes in nonpyogenic intervertebral discs via histological observation. Method. Degenerated intervertebral discs were harvested from 76 patients with low back pain and/or sciatica but without any symptoms of discitis or spondylodiscitis. The samples were cultured under anaerobic conditions and then examined using 16S rDNA PCR to screen for P. acnes. Samples found to be positive for P. acnes were stained with hematoxylin-eosin (HE) and modified Brown-Brenn staining and observed under a microscope. Results. Here, 16 intervertebral discs were found to be positive for P. acnes via 16S rDNA PCR and the prevalence was 21.05% (16/76). Among them, 7 samples had visible microbes stained with HE and modified Brown-Brenn staining. Morphological examination showed the bacteria to be Gram-positive and rod-shaped, so they were considered P. acnes. Conclusion. P. acnes is capable of colonizing some degenerated intervertebral discs without causing discitis, and its presence could be further confirmed by histological evidence. Targeting these bacteria may be a promising therapy method for some disc diseases.

  17. Angiogenesis in the degeneration of the lumbar intervertebral disc

    PubMed Central

    David, Gh; Iencean, SM; Mohan, A

    2010-01-01

    The goal of the study is to show the histological and biochemical changes that indicate the angiogenesis of the intervertebral disc in lumbar intervertebral disc hernia and the existence of epidemiological correlations between these changes and the risk factors of lumbar intervertebral disc hernia, as well as the patient's quality of life (QOL). We have studied 50 patients aged between 18 and 73 years old, who have undergone lumbar intervertebral disc hernia surgery, making fibroblast growth factor and vascular endothelial growth factor level measurements, as elements in the process of appreciating the disc angiogenesis. Also, pre–surgery and post–surgery QOL has been measured, as well as the intensity of the pain syndrome. We have identified factors capable of stimulating vascular endothelial growth (VEGF, FGF–2) for the examined disc material, but histological examination did not show angiogenesis. The process of angiogenesis at the degenerated intervertebral disc level affects the patient's quality of life both pre and postoperatively, and may be a predictive factor for the post–operative results. Patients can prevent the appearance of angiogenesis type degenerative processes of the intervertebral disc by avoiding angiogenesis correlated factors (weight control, physical effort, and smoking). PMID:20968201

  18. ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

    PubMed Central

    Yang, Minghui; Lan, Minghong; Liu, Chang; Zhang, Yang; Huang, Bo

    2017-01-01

    Excessive reactive oxygen species (ROS) generation in degenerative intervertebral disc (IVD) indicates the contribution of oxidative stress to IVD degeneration (IDD), giving a novel insight into the pathogenesis of IDD. ROS are crucial intermediators in the signaling network of disc cells. They regulate the matrix metabolism, proinflammatory phenotype, apoptosis, autophagy, and senescence of disc cells. Oxidative stress not only reinforces matrix degradation and inflammation, but also promotes the decrease in the number of viable and functional cells in the microenvironment of IVDs. Moreover, ROS modify matrix proteins in IVDs to cause oxidative damage of disc extracellular matrix, impairing the mechanical function of IVDs. Consequently, the progression of IDD is accelerated. Therefore, a therapeutic strategy targeting oxidative stress would provide a novel perspective for IDD treatment. Various antioxidants have been proposed as effective drugs for IDD treatment. Antioxidant supplementation suppresses ROS production in disc cells to promote the matrix synthesis of disc cells and to prevent disc cells from death and senescence in vitro. However, there is not enough in vivo evidence to support the efficiency of antioxidant supplementation to retard the process of IDD. Further investigations based on in vivo and clinical studies will be required to develop effective antioxidative therapies for IDD. PMID:28392887

  19. Role of Cytokines in Intervertebral Disc Degeneration: Pain and Disc-content

    PubMed Central

    Risbud, Makarand V.; Shapiro, Irving. M

    2014-01-01

    Degeneration of the intervertebral disc is the major contributor to back/neck and radicular pain. It is characterized by an elevation in levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1 α/β, IL-6 and IL-17 secreted by the disc cells themselves; these cytokines promote matrix degradation, chemokine production and changes in cell phenotype. The resulting imbalance between catabolic and anabolic responses leads to degeneration, as well as herniation and radicular pain. Release of chemokines from degenerating discs promote infiltration and activation of T and B cells, macrophages, neutrophils, and mast cells further amplifying the inflammatory cascade. Immunocyte migration into the disc is accompanied by the appearance of microvasculature and nerve fibers arising from the dorsal root ganglion (DRG). In this inflammatory milieu, neurogenic factors in particular nerve growth factor (NGF) and brain-derive neurotrophic factor (BDNF) generated by disc and immune cells induce expression of pain associated cation channels in DRGs. Depolarization of these channels is likely to promote discogenic and radicular pain and reinforce the cytokine-mediated degenerative cascade. Taken together, the enhanced understanding of the contribution of cytokines and immune cells to catabolic and nociceptive processes provide new targets for treating symptomatic disc disease. PMID:24166242

  20. Menopause causes vertebral endplate degeneration and decrease in nutrient diffusion to the intervertebral discs.

    PubMed

    Wang, Yi-Xiang J; Griffith, James F

    2011-07-01

    The vasculature in the outer annulus supplies only the periphery of the disc so that nutrition to the bulk of the disc, including all the inner annulus and nucleus pulposus, is derived from the vertebral epiphyseal end arteries where nutrients diffuse across the cartilaginous endplate to reach the disc. In this regard the vertebral endplate plays an important role in disc nutrition. Compromise of diffusion of nutrients to the disc cells may play a large part in the progression or even initiation of disc degeneration. Increasing evidence suggests that estrogen deficiency also influence the severity of disc degeneration in post-menopausal females. Structural disorganization of the vertebral endplate occurs with disc degeneration, with the most common endplate changes observed clinically being Schmorl's node. Schmorl's node is more commonly seen in post-menopausal women than younger women. Osteosclerosis, osteonecrosis and fibrosis associated with Schmorl's nodes can impede nutrient diffusion into the disc as well as removal of metabolites from the disc. We hypothesize that menopause negatively affects vertebral endplate quality and induces endplate degeneration. This endplate degeneration decreases nutrients diffusion from vertebral body into discs, and also impedes removal of metabolites, leads to further disc degeneration. To confirm our hypothesis, a cross-sectional post-contrast MRI study can be performed in pre-menopausal and post-menopausal women. If the hypothesis is confirmed, then low dose hormone replacement treatment may retard disc degeneration in post menopausal women and thereby limit the consequences associated with disc degeneration such as low back pain.

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

    NASA Astrophysics Data System (ADS)

    Ghouchani, Azadeh; Ravari, Mohammad; Mahmoudi, Farid

    2011-10-01

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

  2. A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic

    PubMed Central

    Ghosh, Peter

    2016-01-01

    Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored. PMID:27314030

  3. Protective effect of ligustrazine on lumbar intervertebral disc degeneration of rats induced by prolonged upright posture.

    PubMed

    Liang, Qian-Qian; Ding, Dao-Fang; Xi, Zhi-Jie; Chen, Yan; Li, Chen-Guang; Liu, Shu-Fen; Lu, Sheng; Zhao, Yong-Jian; Shi, Qi; Wang, Yong-Jun

    2014-01-01

    Most chronic low back pain is the result of degeneration of the lumbar intervertebral disc. Ligustrazine, an alkaloid from Chuanxiong, reportedly is able to relieve pain, suppress inflammation, and treat osteoarthritis and it has the protective effect on cartilage and chondrocytes. Therefore, we asked whether ligustrazine could reduce intervertebral disc degeneration. To determine the effect of ligustrazine on disc degeneration, we applied a rat model. The intervertebral disc degeneration of the rats was induced by prolonged upright posture. We found that pretreatment with ligustrazine for 1 month recovered the structural distortion of the degenerative disc; inhibited the expression of type X collagen, matrix metalloproteinase (MMP)-13, and MMP3; upregulated type II collagen; and decreased IL-1 β , cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) expression. In conclusion, ligustrazine is a promising agent for treating lumbar intervertebral disc degeneration disease.

  4. Clinical Impact of Sagittal Spinopelvic Parameters on Disc Degeneration in Young Adults.

    PubMed

    Oh, Young-Min; Eun, Jong-Pil

    2015-10-01

    The sagittal balance plays an important role in the determination of shear and compressive forces applied on the anterior (vertebral bodies and intervertebral discs) and posterior (facet joints) elements of the lumbar vertebral column. Many studies have also examined the effect of structural changes in the disc on the biomechanical characteristics of the spinal segment. Nevertheless, the relationship between sagittal balance and the degree of disc degeneration has not been extensively explored. Thus, here we investigated the relationships between various sagittal spinopelvic parameters and the degree of disc degeneration in young adults.A total of 278 young adult male patients were included in this study (age range: 18-24 years old). Multiple sagittal spinopelvic parameters, including pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), sacral inclination (SI), lumbosacral angle (LSA), and sacral table angle (STA), were measured from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. To assess the pain intensity of each patient, the visual analogue scale (VAS) score for low back pain (LBP) was obtained from all the patients. Finally, the relationships between these spinopelvic parameters and the degree of disc degeneration in young adults were analyzed. Also, we performed multiple logistic regression study.Out of all the spinopelvic parameters measured in this study, a low STA and a low SI were the only significant risk factors that were associated with disc degeneration in young adults. It means that patients with disc degeneration tend to have more severe sacral kyphosis and vertical sacrum.We found that patients with disc degeneration showed a lower SI and lower STA compared with patients without disc degeneration in young adults. Therefore, we suggest that the patients with disc degeneration tend to have more vertical sacrum, more sacral kyphosis

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

    PubMed Central

    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. PMID:23532265

  6. Landscape of RNAs in human lumbar disc degeneration

    PubMed Central

    Pei, Yan-Jun; Wu, Zhi-Gang; Yu, Yang; Yang, Yong-Feng; Liu, Xu; Che, Lu; Ma, Chi-Jiao; Xie, Yan-Ke; Hu, Qing-Jie; Wan, Zhong-Yuan; Wang, Hai-Qiang

    2016-01-01

    Accumulating evidence indicates noncoding RNAs (ncRNAs) fine-tune gene expression with mysterious machinery. We conducted a combination of mRNA, miRNA, circRNA, LncRNA microarray analyses on 10 adults' lumbar discs. Moreover, we performed additional global exploration on RNA interacting machinery in terms of in silico computational pipeline. Here we show the landscape of RNAs in human lumbar discs. In general, the RNA-abundant landscape comprises 14,635 mRNAs (37.93%), 2,059 miRNAs (5.34%), 18,995 LncRNAs (49.23%) and 2,894 (7.5%) circRNAs. Chromosome 1 contributes for RNA transcription at most (10%). Bi-directional transcription contributes evenly for RNA biogenesis, in terms of 5′ to 3′ and 3′ to 5′. Despite the majority of circRNAs are exonic, antisense (1.49%), intergenic (0.035%), intragenic (1.69%), and intronic (6.29%) circRNAs should not be ignored. A single miRNA could interact with a multitude of circRNAs. Notably, CDR1as or ciRS-7 harbors 66 consecutive binding sites for miR-7-5p (previous miR-7), evidencing our pipeline. The majority of binding sites are perfect-matched (78.95%). Collectively, global landscape of RNAs sheds novel insights on RNA interacting mechanisms in human intervertebral disc degeneration. PMID:27542248

  7. Association between apparent diffusion coefficient and intervertebral disc degeneration in patients with ankylosing spondylitis

    PubMed Central

    Resorlu, Mustafa; Gokmen, Ferhat; Resorlu, Hatice; Adam, Gurhan; Akbal, Ayla; Cevizci, Sibel; Sariyildirim, Abdullah; Savas, Yilmaz; Guven, Mustafa; Aras, Adem Bozkurt

    2015-01-01

    Purpose: To assess the relation between ankylosing spondylitis (AS) and degenerative disc disease emerging in association with various intrinsic and extrinsic factors and to evaluate the correlation between degree of degeneration in intervertebral discs and apparent diffusion coefficient (ADC) values. Methods: Thirty-five patients with AS and a control group of 35 patients were included in the study. Three hundred fifty intervertebral discs were assessed in terms of degeneration by analyzing signal intensities and morphologies on T2 weighted series of a 1.5 Tesla magnetic resonance scanner. ADC values were determined in diffusion weighted images (DWI) using a “b value of 500 s/mm2”. Patients in the AS and control groups were compared in terms of intervertebral disc degeneration, and association between degree of degeneration and ADC values was analyzed. Results: The mean of total degeneration degrees for five lumbar intervertebral discs was significantly higher in the patients with AS compared to the control group (16.77±4.67 vs 13.00±4.08, respectively; P=0.001). When intervertebral discs were analyzed separately, disc degeneration was again significantly higher in patients with AS compared to the control group, with the exception of L5-S1. Age, cholesterol level, triglyceride level, duration of disease and BASFI index were significantly associated with degree of degeneration in patients with AS. A negative correlation was determined between disc degeneration and ADC value. Conclusion: AS is a risk factor for degenerative disc disease due to its systemic effects, the fact it leads to posture impairment and its inflammatory effects on the vertebrae. A decrease in ADC values is observed as degeneration worsens in degenerative disc disease. PMID:25785119

  8. Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies.

    PubMed

    Wang, S Z; Rui, Y F; Lu, J; Wang, C

    2014-10-01

    Intervertebral disc degeneration (IDD) is a chronic, complex process associated with low back pain; mechanisms of its occurrence have not yet been fully elucidated. Its process is not only accompanied by morphological changes, but also by systematic changes in its histological and biochemical properties. Many cellular and molecular mechanisms have been reported to be related with IDD and to reverse degenerative trends, abnormal conditions of the living cells and altered cell phenotypes would need to be restored. Promising biological therapeutic strategies still rely on injection of active substances, gene therapy and cell transplantation. With advanced study of tissue engineering protocols based on cell therapy, combined use of seeding cells, bio-active substances and bio-compatible materials, are promising for IDD regeneration. Recently reported progenitor cells within discs themselves also hold prospects for future IDD studies. This article describes the background of IDD, current understanding and implications of potential therapeutic strategies.

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

    PubMed Central

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

    2005-01-01

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

  10. Simulation of the Progression of Intervertebral Disc Degeneration due to Decreased Nutrition Supply

    PubMed Central

    Gu, Weiyong; Zhu, Qiaoqiao; Gao, Xin; Brown, Mark D.

    2014-01-01

    Study Design Simulate the progression of human disc degeneration. Objective The objective of this study was to quantitatively analyze and simulate the changes in cell density, nutrition level, proteoglycan content, water content, and volume change during human disc degeneration using a numerical method. Summary of Background Data Understanding the etiology and progression of intervertebral disc (IVD) degeneration is crucial for developing effective treatment strategies for IVD-degeneration related diseases. During tissue degeneration, the disc undergoes losses of cell viability and activities, changes in extracellular matrix composition and structure, and compromise of the tissue-level integrity and function, which is significantly influenced by the inter-coupled biological, chemical, electrical, and mechanical signals in the disc. Characterizing these signals in human discs in vivo is difficult. Methods A realistic 3D finite element model of the human IVD was developed based on biomechano-electrochemical continuum mixture theory. The theoretical framework and the constitutive relationships were all biophysics based. All the material properties were obtained from experimental results. The cell-mediated disc degeneration process caused by lowered nutrition levels at disc boundaries was simulated and validated by comparing with experimental results. Results Cell density reached equilibrium state in 30 days after reduced nutrition supply at the disc boundary, while the proteoglycan (PG) and water contents reached a new equilibrium state in 55 years. The simulated results for the distributions of PG and water contents within the disc were consistent with the results measured in the literature, except for the distribution of PG content in the sagittal direction. Conclusions Poor nutrition supply has a long-term effect on disc degeneration. PMID:25188596

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    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

  13. Evidence for an Important Role of Smad-7 in Intervertebral Disc Degeneration

    PubMed Central

    Li, Bo; Su, Yi-Jun; Zheng, Xin-Feng; Yang, Yue-Hua; Jiang, Sheng-Dan

    2015-01-01

    Smad-7 inhibited the transforming growth factor beta (TGF-β)-induced proteoglycan synthesis in chondrocytes and completely antagonized the effect of TGF-β on the proliferation of the cells. The aim of this study was to evaluate the contribution of Smad-7 to the pathophysiology of disc degeneration by determining the expression of Smad-7 in the degenerative intervertebral discs and its effect on the extracellular matrix metabolism of disc cells. Instability of the lumbar spine produced by imbalanced dynamic and static forces was used to induce intervertebral disc degeneration in rats. The expression of Smad-7 was assessed by the immunohistochemical method. Disc cell apoptosis was detected by in situ TUNEL staining. The effect of Smad-7 overexpression on the matrix metabolism of disc cells was analyzed in vitro by real-time polymerase chain reaction (PCR) and Western blotting. Finally, intradiscal injection of the Smad-7 overexpression lentivirus was performed to evaluate the in vivo effect of Smad-7 on disc degeneration. Radiographic and histomorphological examinations showed that lumbar disc degeneration became more and more severe in the rats with induced instability. Immunohistochemical observation demonstrated increasing protein expression of Smad-7 in the degenerative discs. A significantly positive correlation was found between Smad-7 expression and the degree of disc degeneration and between Smad-7 expression and disc cell apoptosis. Overexpression of Smad-7 in disc cells inhibited the expression of TGF-β1, collagen type-I, collagen type-II, and aggrecan and promoted the expression of MMP-13, but did not change the expression of ADAMTS-5. The in vivo findings illustrated that intradiscal injection of lentivirus vector with Smad-7 overexpression accelerated the progress of disc degeneration. In conclusion, Smad-7 was highly expressed in the degenerative discs. Overexpression of Smad-7 weakened the protective role of TGF-β and accelerated the progress of

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

    PubMed Central

    Ohnishi, Takashi; Sudo, Hideki; Iwasaki, Koji; Tsujimoto, Takeru; Ito, Yoichi M.; Iwasaki, Norimasa

    2016-01-01

    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. PMID:27482708

  15. Effect of disc degeneration on the muscle recruitment pattern in upright posture: a computational analysis.

    PubMed

    Kim, Young Eun; Choi, Hae Won

    2015-01-01

    Based on the sensor driving control mechanism model, the effect of disc degeneration on the trunk muscle recruitment (TMR) pattern was analysed in erect standing posture. A previously developed computational model was used for this analysis, with modifications incorporating the T12-L1 motion segment and additional muscle fascicles. To generate disc degeneration at three different levels (L3-L4, L4-L5, or L5-S1), the material properties of the ground matrix of the annulus and bulk modulus of the nucleus were reduced. The finite element method combined with an optimization technique was applied to calculate the muscle forces. Minimization of deviations in the averaged tensile stress in the annulus fibres at the outermost layer in the five discs was selected for muscle force calculations. The results indicated that the disc degeneration noticeably increased the activation of the superficial muscle (IT and R) even though there was no clear change in the longissimus thoracis. Unlike some of the superficial muscles, activation in the deep muscles (multifidus (ML, MS, MT), LL and Q) was decreased. The change in TMR pattern generated an intervertebral disc angle difference and nucleus pressure increased in the upper level. These differences are expected to be functional in that they reduce the stress at the degenerated disc by changing the muscle activation, which slows down the progress of disc degeneration.

  16. Protective Effects of Cannabidiol on Lesion-Induced Intervertebral Disc Degeneration

    PubMed Central

    Silveira, João W.; Issy, Ana Carolina; Castania, Vitor A.; Salmon, Carlos E. G.; Nogueira-Barbosa, Marcello H.; Guimarães, Francisco S.; Defino, Helton L. A.; Bel, Elaine Del

    2014-01-01

    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. PMID:25517414

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

    PubMed

    Silveira, João W; Issy, Ana Carolina; Castania, Vitor A; Salmon, Carlos E G; Nogueira-Barbosa, Marcello H; Guimarães, Francisco S; Defino, Helton L A; Del Bel, Elaine

    2014-01-01

    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.

  18. Intervertebral Disc Degeneration and Ectopic Bone Formation in Apolipoprotein E Knockout Mice

    PubMed Central

    Zhang, Dawei; Jin, Li; Reames, Davis L.; Shen, Francis H.; Shimer, Adam L.; Li, Xudong

    2012-01-01

    Cardiovascular risk factors are known to be associated with intervertebral disc degeneration, but the underlying mechanism is still unclear. ApoE knockout (KO) mouse is a well-established model for arthrosclerosis. We hypothesize that ApoE may involve in maintaining disc health and ApoE KO mouse develops early disc degeneration. Discs of ApoE KO and wild-type (WT) mice were characterized with histological/immunological, biochemical, and real time RT-PCR assays. A comparison of the extracellular matrix production was also performed in disc cells. We demonstrated that ApoE was highly expressed in the endplates of WT discs and ectopic bone formed in the endplates of ApoE KO discs. Glycosaminoglycan content was decreased in both ApoE KO annulus fibrosus (AF) and nucleus pulpsous (NP) cells. Collagen levels were increased in AF and decreased in NP cells. Matrix metalloproteinases-3, 9, and 13 expression was increased which may partially explain the impaired matrix production. We also found increased collagen I, II, aggrecan and biglycan mRNA expressions in AF cells but decreased in NP cells. Apoptosis was increased in the ApoE KO NP tissue. These results suggest early disc degeneration changes in ApoE KO mice. ApoE, plus its importance to cardiovascular disease, may play a critical role in disc integrity and function. PMID:22915292

  19. 1980 Volvo award in basic science. Proteoglycans in experimental intervertebral disc degeneration.

    PubMed

    Lipson, S J; Muir, H

    1981-01-01

    An animal model of intervertebral disc degeneration induced surgically by ventral nuclear herniation in the rabbit produces morphologic changes of disc degeneration. Histologic characteristics and proteoglycan changes have been studied at various times after herniation. After injury, there was metaplasia into fibrocartilage originating from the cells along the margins of the annular wound, with proliferation of cells changing almost the entire disc space into fibrocartilage. A vertebral osteophyte occurred through an endochondral ossification sequence. Aggregating proteoglycans had two periods of repletion in the early course of degeneration. The water content of the disc was rapidly but only transiently restored in the first two days after herniation, whilst the changes in the total proteoglycan content of the disc paralleled these changes. Hyaluronic acid content decreased rapidly after herniation, but the size of the proteoglycan monomers did not change with degeneration. It is suggested that loss of confined fluid mechanics signals an abortive repair attempt rather than that of biochemical changes in proteoglycans initiate disc degeneration.

  20. Sitting versus standing: does the intradiscal pressure cause disc degeneration or low back pain?

    PubMed

    Claus, Andrew; Hides, Julie; Moseley, G Lorimer; Hodges, Paul

    2008-08-01

    Studies of lumbar intradiscal pressure (IDP) in standing and upright sitting have mostly reported higher pressures in sitting. It was assumed clinically that flexion of the lumbar spine in sitting relative to standing, caused higher IDP, disc degeneration or rupture, and low back pain. IDP indicates axial compressive load upon a non-degenerate disc, but provides little or no indication of shear, axial rotation or bending. This review is presented in two main parts. First, in vivo IDP data in standing and upright sitting for non-degenerate discs are comprehensively reviewed. As methodology, results and interpretations varied between IDP studies, in vivo studies measuring spinal shrinkage and spinal internal-fixator loads to infer axial compressive load to the discs are also reviewed. When data are considered together, it is clear that IDP is often similar in standing and sitting. Secondly, clinical assumptions related to IDP in sitting are considered in light of basic and epidemiologic studies. Current studies indicate that IDP in sitting is unlikely to pose a threat to non-degenerate discs, and sitting is no worse than standing for disc degeneration or low back pain incidence. If sitting is a greater threat for development of low back pain than standing, the mechanism is unlikely to be raised IDP.

  1. A Novel Catechol-O-Methyltransferase Variant Associated with Human Disc Degeneration

    PubMed Central

    Gruber, Helen E.; Sha, Wei; Brouwer, Cory R.; Steuerwald, Nury; Hoelscher, Gretchen L.; Hanley, Edward N. Jr.

    2014-01-01

    Background: Disc degeneration and its associated low back pain are a major health care concern causing disability with a prominent role in this country's medical, social and economic structure. Low back pain is devastating and influences the quality of life for millions. Low back pain lifetime prevalence approximates 80% with an estimated direct cost burden of $86 billion per year. Back pain patients incur higher costs, greater health care utilization, and greater work loss than patients without back pain. Methods: Research was performed following approval of our Institutional Review Board. DNA was isolated, processed and amplified using routine techniques. Amplified DNA was hybridized to Affymetrix Genome-Wide Human SNP Arrays. Quality control and genotyping analysis were performed using Affymetrix Genotyping Console. The Birdseed v2 algorithm was used for genotyping analysis. 2589 SNPs were selected a priori to enter statistical analysis using lotistic regression in SAS. Results: Our objective was to search for novel single nucleotide polymorphisms (SNPs) associated with disc degeneration. Four SNPs were found to have a significant relationship to disc degeneration; three are novel. Rs165656, a new SNP found to be associated with disc degeneration, was in catechol-O-methyltransferase (COMT), a gene with well-recognized pain involvement, especially in female subjects (p=0.01). Analysis confirmed the previously association between COMT SNP rs4633 and disc degeneration. We also report two novel disc degeneration-related SNPs (rs2095019 and rs470859) located in intergenic regions upstream to thrombospondin 2. Conclusions: Findings contribute to the challenging field of disc degeneration and pain, and are important in light of the high clinical relevance of low back pain and the need for improved understanding of its fundamental basis. PMID:24904231

  2. MRI quantification of human spine cartilage endplate geometry: Comparison with age, degeneration, level, and disc geometry.

    PubMed

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

    2016-08-01

    Geometry is an important indicator of disc mechanical function and degeneration. While the geometry and associated degenerative changes in the nucleus pulposus and the annulus fibrosus are well-defined, the geometry of the cartilage endplate (CEP) and its relationship to disc degeneration are unknown. The objectives of this study were to quantify CEP geometry in three dimensions using an MRI FLASH imaging sequence and evaluate relationships between CEP geometry and age, degeneration, spinal level, and overall disc geometry. To do so, we assessed the MRI-based measurements for accuracy and repeatability. Next, we measured CEP geometry across a larger sample set and correlated CEP geometric parameters to age, disc degeneration, level, and disc geometry. The MRI-based measures resulted in thicknesses (0.3-1 mm) that are comparable to prior measurements of CEP thickness. CEP thickness was greatest at the anterior/posterior (A/P) margins and smallest in the center. The CEP A/P thickness, axial area, and lateral width decreased with age but were not related to disc degeneration. Age-related, but not degeneration-related, changes in geometry suggest that the CEP may not follow the progression of disc degeneration. Ultimately, if the CEP undergoes significant geometric changes with aging and if these can be related to low back pain, a clinically feasible translation of the FLASH MRI-based measurement of CEP geometry presented in this study may prove a useful diagnostic tool. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1410-1417, 2016.

  3. Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: Biochemical rationale and case report

    PubMed Central

    van Blitterswijk, Wim J; van de Nes, Jos CM; Wuisman, Paul IJM

    2003-01-01

    Background Glucosamine and chondroitin sulfate preparations are widely used as food supplements against osteoarthritis, but critics are skeptical about their efficacy, because of the lack of convincing clinical trials and a reasonable scientific rationale for the use of these nutraceuticals. Most trials were on osteoarthritis of the knee, while virtually no documentation exists on spinal disc degeneration. The purpose of this article is to highlight the potential of these food additives against cartilage degeneration in general, and against symptomatic spinal disc degeneration in particular, as is illustrated by a case report. The water content of the intervertebral disc is a reliable measure of its degeneration/ regeneration status, and can be objectively determined by Magnetic Resonance Imaging (MRI) signals. Case presentation Oral intake of glucosamine and chondroitin sulfate for two years associated with disk recovery (brightening of MRI signal) in a case of symptomatic spinal disc degeneration. We provide a biochemical explanation for the possible efficacy of these nutraceuticals. They are bioavailable to cartilage chondrocytes, may stimulate the biosynthesis and inhibit the breakdown of their extracellular matrix proteoglycans. Conclusion The case suggests that long-term glucosamine and chondroitin sulfate intake may counteract symptomatic spinal disc degeneration, particularly at an early stage. However, definite proof requires well-conducted clinical trials with these food supplements, in which disc de-/regeneration can be objectively determined by MRI. A number of biochemical reasons (that mechanistically need to be further resolved) explain why these agents may have cartilage structure- and symptom-modifying effects, suggesting their therapeutic efficacy against osteoarthritis in general. PMID:12797867

  4. Stem Cell Therapies for Intervertebral Disc Degeneration: Immune Privilege Reinforcement by Fas/FasL Regulating Machinery.

    PubMed

    Ma, Chi-Jiao; Liu, Xu; Che, Lu; Liu, Zhi-Heng; Samartzis, Dino; Wang, Hai-Qiang

    2015-01-01

    As a main contributing factor to low back pain, intervertebral disc degeneration (IDD) is the fundamental basis for various debilitating spinal diseases. The pros and cons of current treatment modalities necessitate biological treatment strategies targeting for reversing or altering the degeneration process in terms of molecules or genes. The advances in stem cell research facilitate the studies aiming for possible clinical application of stem cell therapies for IDD. Human NP cells are versatile with cell morphology full of variety, capable of synthesizing extracellular matrix components, engulfing substances by autophagy and phagocytosis, mitochondrial vacuolization indicating dysfunction, expressing Fas and FasL as significant omens of immune privileged sites. Human discs belong to immune privilege organs with functional FasL expression, which can interact with invasive immune cells by Fas-FasL regulatory machinery. IDD is characterized by decreased expression level of FasL with dysfunctional FasL, which in turn unbalances the interaction between NP cells and immune cells. Certain modulation factors might play a role in the process, such as miR-155. Accumulating evidence indicates that Fas-FasL network expresses in a variety of stem cells. Given the expression of functional FasL and insensitive Fas in stem cells (we term as FasL privilege), transplantation of stem cells into the disc may regenerate the degenerative disc by not only differentiating into NP-like cells, increasing extracellular matrix, but also reinforce immune privilege via interaction with immune cells by Fas-FasL network.

  5. Effects of Tobacco Smoking on the Degeneration of the Intervertebral Disc: A Finite Element Study

    PubMed Central

    Elmasry, Shady; Asfour, Shihab; de Rivero Vaccari, Juan Pablo; Travascio, Francesco

    2015-01-01

    Tobacco smoking is associated with numerous pathological conditions. Compelling experimental evidence associates smoking to the degeneration of the intervertebral disc (IVD). In particular, it has been shown that nicotine down-regulates both the proliferation rate and glycosaminoglycan (GAG) biosynthesis of disc cells. Moreover, tobacco smoking causes the constriction of the vascular network surrounding the IVD, thus reducing the exchange of nutrients and anabolic agents from the blood vessels to the disc. It has been hypothesized that both nicotine presence in the IVD and the reduced solute exchange are responsible for the degeneration of the disc due to tobacco smoking, but their effects on tissue homeostasis have never been quantified. In this study, a previously presented computational model describing the homeostasis of the IVD was deployed to investigate the effects of impaired solute supply and nicotine-mediated down-regulation of cell proliferation and biosynthetic activity on the health of the disc. We found that the nicotine-mediated down-regulation of cell anabolism mostly affected the GAG concentration at the cartilage endplate, reducing it up to 65% of the value attained in normal physiological conditions. In contrast, the reduction of solutes exchange between blood vessels and disc tissue mostly affected the nucleus pulposus, whose cell density and GAG levels were reduced up to 50% of their normal physiological levels. The effectiveness of quitting smoking on the regeneration of a degenerated IVD was also investigated, and showed to have limited benefit on the health of the disc. A cell-based therapy in conjunction with smoke cessation provided significant improvements in disc health, suggesting that, besides quitting smoking, additional treatments should be implemented in the attempt to recover the health of an IVD degenerated by tobacco smoking. PMID:26301590

  6. Correlation between T2∗ (T2 star) relaxation time and cervical intervertebral disc degeneration

    PubMed Central

    Huang, Minghua; Guo, Yong; Ye, Qiong; Chen, Lei; Zhou, Kai; Wang, Qingjun; Shao, Lixin; Shi, Qinglei; Chen, Chun

    2016-01-01

    Abstract Purpose: To demonstrate the potential benefits of T2∗ relaxation time of intervertebral discs (IVDs) regarding the detection and grading of degenerative disc disease using 3.0-T magnetic resonance imaging (MRI) in a clinical setting. Materials and Methods: Cervical sagittal T2-weighted, T2∗ relaxation MRI was performed at 3.0-T in 61 subjects, covering discs C2–3 to C6–7. All discs were morphologically assessed based on the Pfirrmann grade, and regions of interests (ROIs) were drawn over the T2∗ mapping. Receiver operating characteristic (ROC) analysis was performed among grades to determine the cut-off values. Results: Cervical intervertebral discs (IVDs) of patients were commonly determined to be at Pfirrmann grades III to V. The nucleus pulposus (NP) values did not differ significantly between sexes at the same anatomic level (P > 0.05). In the NP, the T2∗ values tended to decrease with increasing grade (P < 0.000), and a significant difference was found in the T2 values between grades I to V (P < 0.05). T2∗ values based on disc degeneration level classification were as follows: grade I (>30 milliseconds), grade II (24.55–29.99 milliseconds), grade III (21.65–24.54 milliseconds), grade IV (18.35–21.64 milliseconds), and grade V (<18.34 milliseconds). Conclusion: Our standardized method of region-specific quantitative T2∗ relaxation time evaluation seems capable of characterizing different degrees of disc degeneration quantitatively. The T2∗ values obtained in these cervical IVDs may serve as baseline values for future T2∗ measurements in both healthy and degenerated cervical discs. PMID:27893652

  7. Endplate degeneration may be the origination of the vacuum phenomenon in intervertebral discs.

    PubMed

    Li, Fang-Cai; Zhang, Ning; Chen, Wei-Shan; Chen, Qi-Xin

    2010-08-01

    The intravertebral vacuum phenomenon (VP) is usually associated with degenerative disc disease, which could be related to the low back pain. Various theories related to the pathogenesis of VP have been proposed, but these theories have not been critically examined and remain hypothetical. In this article, we review the possible role of endplate degeneration in the pathogenesis of VP, and discuss several pathways possibly linked to them. Due to the endplate calcification and activated cytokines, the transport pathway of the nutrition for the intervertebral disc was blocked, resulting in the metabolic unbalance and decrease of the synthesis of matrix structural proteins. It could promote the matrix decomposition, causing the decrease of the quantity of matrix and the changes of stress distribution in intervertebral disc. As a result, the structure of intervertebral discs became increasingly unstable. While compression happened, the intravertebral cleft could occur and be gradually filled with gas, which may cause low back pain and aggravate the intervertebral discs degeneration. As outlined above, we hypothesize that endplate degeneration might be the origination of the vacuum phenomenon.

  8. A novel approach for the annulus needle puncture model of intervertebral disc degeneration in rabbits

    PubMed Central

    Lei, Tao; Zhang, Yuan; Zhou, Qiang; Luo, Xiaoji; Tang, Ke; Chen, Rongsheng; Yu, Chang; Quan, Zhengxue

    2017-01-01

    Objective: To create the rabbit animal model of intervertebral disc (IVD) degeneration by the annulus needle puncture technique through a novel transabdominal approach. Methods: Thirteen New Zealand White rabbits underwent annular puncture at the L3/4, L4/5, and L5/6 discs through a transabdominal approach. For a longitudinal study to assess changes in disc height over time, serial X-rays, T2-weighted magnetic resonance imaging (MRI) (T2WI), and T2 mapping MRI were performed pre-operation and at 2, 4, and 6 weeks after puncture. Three rabbits were randomly selected for histological evaluation at 4 weeks post-operation. In addition, the remaining rabbits underwent a second surgery at 6 weeks after puncture. Results: All rabbits underwent the initial and second surgeries successfully without nerve-related complications. The operations had no significant effects on the rabbit body weight, and partial mild intra-abdominal adhesions were found in only 1 rabbit. The punctured discs were confirmed to be those of interest post-surgery and displayed progressive degeneration in disc height index (%), T2WI, and T2 relaxation time over time. At 4 weeks after puncture, a histological analysis revealed notochordal cell loss from the nucleus pulposus, fibrocartilage filling the nucleus pulposus space, and annulus fibrosus disorganization. Conclusion: The annular needle puncture model established through a transabdominal approach, which demonstrates better visualization, exact identification, consistent degeneration degrees and minimal complications, is radiologically and histologically consistent with human IVD degeneration. T2 mapping MRI can quantitatively discriminate between grades of mild degeneration. PMID:28386320

  9. 3D finite element analysis of nutrient distributions and cell viability in the intervertebral disc: effects of deformation and degeneration.

    PubMed

    Jackson, Alicia R; Huang, Chun-Yuh C; Brown, Mark D; Gu, Wei Yong

    2011-09-01

    The intervertebral disc (IVD) receives important nutrients, such as glucose, from surrounding blood vessels. Poor nutritional supply is believed to play a key role in disc degeneration. Several investigators have presented finite element models of the IVD to investigate disc nutrition; however, none has predicted nutrient levels and cell viability in the disc with a realistic 3D geometry and tissue properties coupled to mechanical deformation. Understanding how degeneration and loading affect nutrition and cell viability is necessary for elucidating the mechanisms of disc degeneration and low back pain. The objective of this study was to analyze the effects of disc degeneration and static deformation on glucose distributions and cell viability in the IVD using finite element analysis. A realistic 3D finite element model of the IVD was developed based on mechano-electrochemical mixture theory. In the model, the cellular metabolic activities and viability were related to nutrient concentrations, and transport properties of nutrients were dependent on tissue deformation. The effects of disc degeneration and mechanical compression on glucose concentrations and cell density distributions in the IVD were investigated. To examine effects of disc degeneration, tissue properties were altered to reflect those of degenerated tissue, including reduced water content, fixed charge density, height, and endplate permeability. Two mechanical loading conditions were also investigated: a reference (undeformed) case and a 10% static deformation case. In general, nutrient levels decreased moving away from the nutritional supply at the disc periphery. Minimum glucose levels were at the interface between the nucleus and annulus regions of the disc. Deformation caused a 6.2% decrease in the minimum glucose concentration in the normal IVD, while degeneration resulted in an 80% decrease. Although cell density was not affected in the undeformed normal disc, there was a decrease in cell

  10. Lack of association between lumbar disc degeneration and osteophyte formation in elderly japanese women with back pain.

    PubMed

    Oishi, Y; Shimizu, K; Katoh, T; Nakao, H; Yamaura, M; Furuko, T; Narusawa, K; Nakamura, T

    2003-04-01

    Our study was designed to assess the contributions of the physical and constitutional factors to osteophyte formation, disc degeneration, and bone mineral density (BMD) in lumbar vertebrae of elderly postmenopausal women. A total of 126 Japanese women with back pain, aged over 60 years, were invited to participate in the study. Then 80 subjects with a full set of data for physical examinations, radiographs, MRI, and DXA were examined. TaqI polymorphism of vitamin D receptor (VDR) gene was examined in 60 subjects. Prevalence rates of osteophytes (on radiographs) and disc degeneration (on MRI) were 61 and 68%, respectively. Body weight and BMI correlated significantly with anteroposterior (AP) and lateral (LAT) BMD (r = 0.354 for weight, r = 0.347 for BMI) and mean osteophyte area (r = 0.557 for weight, r = 0.486 for BMI), and body weight also correlated with number of discs with osteophytes. However, these did not correlate with the disc area or the number of degenerated discs. Stepwise regression analysis revealed that body weight and LAT-BMD values independently related to the osteophyte area. Disc area (r = 0.386 for AP view) and osteophyte area (r = 0.384 for AP view) significantly correlated with BMD. However, disc area and osteophyte area did not correlate with each other (r = 0.056). The proportion of degenerated discs was higher in the lower lumbar discs, but not the proportion of discs with osteophytes. Frequencies of T and t alleles of VDR did not correlate with disc degeneration, osteophyte formation, or osteoporosis. Our data showed that increases in osteophyte formation and BMD in the lumbar vertebrae are influenced by body weight and BMI, but did not correlate with disc area, which correlated inversely with BMD. Disc degeneration and osteophyte formation seem to represent two different factors that affect lumbar spine in elderly women.

  11. Disc Degeneration Assessed by Quantitative T2* (T2 star) Correlated with Functional Lumbar Mechanics

    PubMed Central

    Ellingson, Arin M.; Mehta, Hitesh; Polly, David W.; Ellermann, Jutta; Nuckley, David J.

    2013-01-01

    Study Design Experimental correlation study design to quantify features of disc health, including signal intensity and distinction between the annulus fibrosus (AF) and nucleus pulposus (NP), with T2* magnetic resonance imaging (MRI) and correlate with the functional mechanics in corresponding motion segments. Objective Establish the relationship between disc health assessed by quantitative T2* MRI and functional lumbar mechanics. Summary of Background Data Degeneration leads to altered biochemistry in the disc, affecting the mechanical competence. Clinical routine MRI sequences are not adequate in detecting early changes in degeneration and fails to correlate with pain or improve patient stratification. Quantitative T2* relaxation time mapping probes biochemical features and may offer more sensitivity in assessing disc degeneration. Methods Cadaveric lumbar spines were imaged using quantitative T2* mapping, as well as conventional T2-weighted MRI sequences. Discs were graded by the Pfirrmann scale and features of disc health, including signal intensity (T2* Intensity Area) and distinction between the AF and NP (Transition Zone Slope), were quantified by T2*. Each motion segment was subjected to pure moment bending to determine range of motion (ROM), neutral zone (NZ), and bending stiffness. Results T2* Intensity Area and Transition Zone Slope were significantly correlated with flexion ROM (p=0.015; p=0.002), ratio of NZ/ROM (p=0.010; p=0.028), and stiffness (p=0.044; p=0.026), as well as lateral bending NZ/ROM (p=0.005; p=0.010) and stiffness (p=0.022; p=0.029). T2* Intensity Area was also correlated with LB ROM (p=0.023). Pfirrmann grade was only correlated with lateral bending NZ/ROM (p=0.001) and stiffness (p=0.007). Conclusions T2* mapping is a sensitive quantitative method capable of detecting changes associated with disc degeneration. Features of disc health quantified with T2* predicted altered functional mechanics of the lumbar spine better than

  12. The Effects of Platelet-Rich Plasma on Halting the Progression in Porcine Intervertebral Disc Degeneration.

    PubMed

    Cho, Hongsik; Holt, David C; Smith, Richard; Kim, Song-Ja; Gardocki, Raymond J; Hasty, Karen A

    2016-02-01

    Disc degeneration and the subsequent herniation and/or rupture of the intervertebral disc (IVD) are due to a failure of the extracellular matrix of the annulus to contain the contents of the nucleus. This results from inadequate maintenance of the matrix components as well as the proteolytic activity of matrix metalloproteinases (MMPs) that degrade matrix molecules. Arresting progression of disc degeneration in the annulus holds greater clinical potential at this point than prevention of its onset in the nucleus. Therefore, in this study, we have therapeutic aims that would decrease levels of the cytokines and growth factors that indirectly lead to disc degeneration via stimulating MMP and increase levels of several beneficial growth factors, such as transforming growth factor-β, with the addition of platelet-rich plasma (PRP) that would stimulate cell growth and matrix synthesis. For this study, we attempted to address these imbalances of metabolism by using tumor necrosis factor-α treated annulus fibrosus cells isolated from porcine IVD tissue and incubating the cells in a growth factor rich environment with PRP. These results indicate that the PRP in vitro increased the production of the major matrix components (type II collagen and aggrecan) and decreased the inhibitory collagenase MMP-1. This application will address a therapeutic approach for intervening early in the degenerative process.

  13. Reliable Magnetic Resonance Imaging Based Grading System for Cervical Intervertebral Disc Degeneration

    PubMed Central

    Chen, Antonia F.; Kang, James D.; Lee, Joon Y.

    2016-01-01

    Study Design Observational. Purpose To develop a simple and comprehensive grading system for cervical discs that precisely, consistently and meaningfully presents radiologic and morphologic data. Overview of Literature The Thompson grading system is commonly used to classify the severity of degenerative lumbar discs on magnetic resonance imaging (MRI). Inherent differences in the morphological and physiological characteristics of cervical discs have hindered development of precise classification systems. Other grading systems have been developed for degenerating cervical discs, but their versatility and feasibility in the clinical setting is suboptimal. Methods MRIs of 46 human cervical discs were de-identified and displayed in PowerPoint format. Each slide depicted a single disc with a normal (grade 0) disc displayed in the top right corner for reference. The presentation was given to 25 physicians comprising attending spine surgeons, spine fellows, orthopaedic residents, and two attending musculoskeletal radiologists. The grading system included Grade 0 (normal height compared to C2–3, mid cleft still visible), grade 1 (dark disc, normal height), grade 2 (collapsed disc, few osteophytes), and grade 3 (collapsed disc, many osteophytes). The ease of use of the system was gauged in the participants and the interobserver reliability was calculated. Results The intraclass correlation coefficient for interobserver reliability was 0.87, and 0.94 for intraobserver reliability, indicating excellent reliability. Ninety-five percent and 85 percent of the clinicians judged the grading system to be clinically feasible and useful in daily practice, respectively. Conclusions The grading system is easy to use, has excellent reliability, and can be used for precise and consistent clinician communication. PMID:26949461

  14. 1991 Volvo Award in clinical sciences. Smoking and lumbar intervertebral disc degeneration: an MRI study of identical twins.

    PubMed

    Battié, M C; Videman, T; Gill, K; Moneta, G B; Nyman, R; Kaprio, J; Koskenvuo, M

    1991-09-01

    The primary objective of this study was to determine whether disc degeneration, as assessed through magnetic resonance imaging, is greater in smokers than in nonsmokers. To control for the maximum number of potentially confounding variables, pairs of identical twins highly discordant for cigarette smoking were selected as study subjects. Data analyses revealed 18% greater mean disc degeneration scores in the lumbar spines of smokers as compared with nonsmokers. The effect was present across the entire lumbar spine, implicating a mechanism acting systemically. This investigation demonstrates the efficiency of using carefully selected controls in studying conditions of multifactorial etiology, such as disc degeneration.

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

    SciTech Connect

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

    2013-03-29

    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

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

    PubMed

    Gruber, H E; Hanley, E N

    2009-06-01

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

  17. Degeneration of the intervertebral disc with new approaches for treating low back pain.

    PubMed

    Le Maitre, C L; Binch, A L; Thorpe, A A; Hughes, S P

    2015-03-01

    This review paper discusses the process of disc degeneration and the current understanding of cellular degradation in patients who present with low back pain. The role of surgical treatment for low back pain is analysed with emphasis on the proven value of spinal fusion. The interesting and novel developments of stem cell research in the treatment of low back pain are presented with special emphasis on the importance of the cartilaginous end plate and the role of IL-1 in future treatment modalities.

  18. Comparative Role of Disc Degeneration and Ligament Failure on Functional Mechanics of the Lumbar Spine

    PubMed Central

    Ellingson, Arin M.; Shaw, Miranda N.; Giambini, Hugo; An, Kai-Nan

    2015-01-01

    Understanding spinal kinematics is essential for distinguishing between pathological conditions of spine disorders, which ultimately lead to low back pain. It’s of high importance to understand how changes in mechanical properties affect the response of the lumbar spine, specifically in an effort to differentiate those associated with disc degeneration from ligamentous changes, allowing for more precise treatment strategies. To do this the goals of this study were twofold: 1) develop and validate a finite element (FE) model of the lumbar spine and 2) systematically alter the properties of the intervertebral disc and ligaments to define respective roles in functional mechanics. A three-dimensional non-linear FE model of the lumbar spine (L3-Sacrum) was developed and validated for pure moment bending. Disc degeneration and sequential ligament failure was modeled. Intersegmental range of motion (ROM) and bending stiffness was measured. The prediction of the FE model to moment loading in all three planes of bending showed very good agreement, where global and intersegmental ROM and bending stiffness of the model fell within one standard deviation of the in vitro results. Degeneration decreased ROM for all directions. Stiffness increased for all directions except axial rotation, where it initially increased then decreased for moderate and severe degeneration, respectively. Incremental ligament failure produced increased ROM and decreased stiffness. This effect was much more pronounced for all directions except lateral bending, which is minimally impacted by ligaments. These results indicate that lateral bending may be more apt to detect the subtle changes associated with degeneration, without being masked by associated changes of surrounding stabilizing structures. PMID:26404463

  19. MSC response to pH levels found in degenerating intervertebral discs

    SciTech Connect

    Wuertz, Karin Godburn, Karolyn; Iatridis, James C.

    2009-02-20

    Painful degenerative disc disease is a major health problem and for successful tissue regeneration, MSCs must endure and thrive in a harsh disc microenvironment that includes matrix acidity as a critical factor. MSCs were isolated from bone marrow of Sprague-Dawley rats from two different age groups (<1 month, n = 6 and 4-5 months, n = 6) and cultured under four different pH conditions representative of the healthy, mildly or severely degenerated intervertebral disc (pH 7.4, 7.1, 6.8, and 6.5) for 5 days. Acidity caused an inhibition of aggrecan, collagen-1, and TIMP-3 expression, as well as a decrease in proliferation and viability and was associated with a change in cell morphology. Ageing had generally minor effects but young MSCs maintained greater mRNA expression levels. As acidic pH levels are typical of increasingly degenerated discs, our findings demonstrate the importance of early interventions and predifferentiation when planning to use MSCs for reparative treatments.

  20. Effects of psoralen on chondrocyte degeneration in lumbar intervertebral disc of rats.

    PubMed

    Yang, Libin; Sun, Xiaohui; Geng, Xiaolin

    2015-03-01

    Discuss the internal mechanism of delaying degeneration of lumber intervertebral disc. The cartilage of lumbar intervertebral disc of SD rats was selected in vitro, then cultured by tissue explant method, and identified by HE staining, toluidine blue staining and immunofluorescence. The optimal concentration of psoralen was screened by cell proliferation assay and RT-PCR method. The cells in third generation with good growth situation is selected and placed in 6-well plate at concentration of 1×10(5)/well and its expression was tested. Compared to concentration of 0, the mRNA expression of Col2al (Collagen Ⅱ) secreted by was up regulated chondrocyte of lumbar intervertebral disc at the concentration of 12.5 and 25μM (P<0.0 or P<0.01). The aggrecan mRNA of psoralen group was higher than blank control group (P<0.01); compared with IL-1β induced group, the mRNA expression of Col2al was significantly increased but the mRNA expression of ADAMTS-5 was significantly decreased in psoralen group (P<0.01). These findings suggest that, psoralen can remit the degeneration of lumbar intervertebral disc induced by IL-1β to some extent, and affect the related factors of IL-1β signaling pathway.

  1. The Involvement of Protease Nexin-1 (PN1) in the Pathogenesis of Intervertebral Disc (IVD) Degeneration

    PubMed Central

    Wu, Xinghuo; Liu, Wei; Duan, Zhenfeng; Gao, Yong; Li, Shuai; Wang, Kun; Song, Yu; Shao, Zengwu; Yang, Shuhua; Yang, Cao

    2016-01-01

    Protease nexin-1 (PN-1) is a serine protease inhibitor belonging to the serpin superfamily. This study was undertaken to investigate the regulatory role of PN-1 in the pathogenesis of intervertebral disk (IVD) degeneration. Expression of PN-1 was detected in human IVD tissue of varying grades. Expression of both PN-1 mRNA and protein was significantly decreased in degenerated IVD, and the expression levels of PN-1 were correlated with the grade of disc degeneration. Moreover, a decrease in PN-1 expression in primary NP cells was confirmed. On induction by IL-1β, the expression of PN-1 in NP cells was decreased at day 7, 14, and 21, as shown by western blot analysis and immunofluorescence staining. PN-1 administration decreased IL-1β-induced MMPs and ADAMTS production and the loss of Agg and Col II in NP cell cultures through the ERK1/2/NF-kB signaling pathway. The changes in PN-1 expression are involved in the pathogenesis of IVD degeneration. Our findings indicate that PN-1 administration could antagonize IL-1β-induced MMPs and ADAMTS, potentially preventing degeneration of IVD tissue. This study also revealed new insights into the regulation of PN-1 expression via the ERK1/2/NF-kB signaling pathway and the role of PN-1 in the pathogenesis of IVD degeneration. PMID:27460424

  2. Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration.

    PubMed

    Nasto, Luigi A; Robinson, Andria R; Ngo, Kevin; Clauson, Cheryl L; Dong, Qing; St Croix, Claudette; Sowa, Gwendolyn; Pola, Enrico; Robbins, Paul D; Kang, James; Niedernhofer, Laura J; Wipf, Peter; Vo, Nam V

    2013-07-01

    Oxidative damage is a well-established driver of aging. Evidence of oxidative stress exists in aged and degenerated discs, but it is unclear how it affects disc metabolism. In this study, we first determined whether oxidative stress negatively impacts disc matrix metabolism using disc organotypic and cell cultures. Mouse disc organotypic culture grown at atmospheric oxygen (20% O(2)) exhibited perturbed disc matrix homeostasis, including reduced proteoglycan synthesis and enhanced expression of matrix metalloproteinases, compared to discs grown at low oxygen levels (5% O(2)). Human disc cells grown at 20% O(2) showed increased levels of mitochondrial-derived superoxide anions and perturbed matrix homeostasis. Treatment of disc cells with the mitochondria-targeted reactive oxygen species (ROS) scavenger XJB-5-131 blunted the adverse effects caused by 20% O(2). Importantly, we demonstrated that treatment of accelerated aging Ercc1(-/Δ) mice, previously established to be a useful in vivo model to study age-related intervertebral disc degeneration (IDD), also resulted in improved disc total glycosaminoglycan content and proteoglycan synthesis. This demonstrates that mitochondrial-derived ROS contributes to age-associated IDD in Ercc1(-/Δ) mice. Collectively, these data provide strong experimental evidence that mitochondrial-derived ROS play a causal role in driving changes linked to aging-related IDD and a potentially important role for radical scavengers in preventing IDD.

  3. Reconstitution of degenerated ovine lumbar discs by STRO-3-positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate.

    PubMed

    Oehme, David; Ghosh, Peter; Goldschlager, Tony; Itescu, Silviu; Shimon, Susan; Wu, Jiehua; McDonald, Courtney; Troupis, John M; Rosenfeld, Jeffrey V; Jenkin, Graham

    2016-05-01

    OBJECTIVE Disc degeneration and associated low-back pain are major causes of suffering and disability. The authors examined the potential of mesenchymal precursor cells (MPCs), when formulated with pentosan polysulfate (PPS), to ameliorate disc degeneration in an ovine model. METHODS Twenty-four sheep had annular incisions made at L2-3, L3-4, and L4-5 to induce degeneration. Twelve weeks after injury, the nucleus pulposus of a degenerated disc in each animal was injected with ProFreeze and PPS formulated with either a low dose (0.1 million MPCs) or a high dose (0.5 million MPCs) of cells. The 2 adjacent injured discs in each spine were either injected with PPS and ProFreeze (PPS control) or not injected (nil-injected control). The adjacent noninjured L1-2 and L5-6 discs served as noninjured control discs. Disc height indices (DHIs) were obtained at baseline, before injection, and at planned death. After necropsy, 24 weeks after injection, the spines were subjected to MRI and morphological, histological, and biochemical analyses. RESULTS Twelve weeks after the annular injury, all the injured discs exhibited a significant reduction in mean DHI (low-dose group 17.19%; high-dose group 18.01% [p < 0.01]). Twenty-four weeks after injections, the discs injected with the low-dose MPC+PPS formulation recovered disc height, and their mean DHI was significantly greater than the DHI of PPS- and nil-injected discs (p < 0.001). Although the mean Pfirrmann MRI disc degeneration score for the low-dose MPC+PPS-injected discs was lower than that for the nil- and PPS-injected discs, the differences were not significant. The disc morphology scores for the nil- and PPS-injected discs were significantly higher than the normal control disc scores (p < 0.005), whereas the low-dose MPC+PPS-injected disc scores were not significantly different from those of the normal controls. The mean glycosaminoglycan content of the nuclei pulposus of the low-dose MPC+PPS-injected discs was significantly

  4. Effect of calcitonin pretreatment on naturally occurring intervertebral disc degeneration in guinea pig

    PubMed Central

    Jiang, Xiaohua; Tian, Faming; Wang, Wenya; Yan, Jinyin; Liu, Huanjiang; Liu, Binbin; Song, Huiping; Zhang, Yingze; Shen, Yong; Zhang, Liu

    2015-01-01

    Introduction: Our previous study suggested protective effects of calcitonin (CT) on experimental osteoarthritis. The aim of the present study was to provide evidence of whether CT pretreatment could prevent naturally occurring intervertebral disc degeneration in guinea pigs. Methods: Forty-two 3 months old female guinea pigs were randomly assigned into 2 groups as follows: Twenty-four were treated by normal saline as control group and sacrificed at 3, 6, 9 and 12 months of age (6 animals at each time point), the other 18 were received salmon CT (8 ug/kg/day, everyday) treatment at 3 months of age and sacrificed at the age of 6, 9 and 12 months respectively. Van Gieson stain and the histological score were used to identify the histological changes of the lumbar intervertebral discs. The disc height and vertebral body height were measured. Immunohistochemistry measurements for glycosaminoglycan, type II collagen, and matrix metalloprotease (MMP)-1 expressions were performed. Bone quality and microstructural changes in the L3-6 lumbar vertebral bodies were assessed by bone mineral density (BMD), micro-CT analysis and biomechanical testing. Results: Histological analysis indicated significantly higher disc degeneration scores in 9-month-old guinea pigs in comparison with younger animals, and grew higher with increasing age. CT treatment significantly reduced the histological score, and increased the disc height and the ratio to vertebral body height in 12 months old animals, as well as upregulated the glycosaminoglycan, type II collagen and inhibited the MMP-1 expression. Micro-CT analysis showed decreased percent bone volume (BV/TV) and increased trabecular separation (Tb.Sp), structural model index (SMI) in 12 months old animals in comparison with the younger animals. Markedly increased BV/TV and decreased Tb.Sp were observed in CT treated animals when compared with control animals. The biomechanical properties including maximum load, maximum stress, yield stress and

  5. High Prevalence of Disc Degeneration and Spondylolysis in the Lumbar Spine of Professional Beach Volleyball Players

    PubMed Central

    Külling, Fabrice A.; Florianz, Hannes; Reepschläger, Bastian; Gasser, Johann; Jost, Bernhard; Lajtai, Georg

    2014-01-01

    Background: Beach volleyball is an intensive sport with high impact on the lumbar spine. Low back pain (LBP) is frequent among elite players. Increased prevalence of pathological changes on magnetic resonance imaging (MRI) in the lumbar spine of elite athletes has been reported. Hypothesis: There is an increased prevalence of disc degeneration and spondylolysis in the MRI of the lumbar spine of professional beach volleyball players. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Twenty-nine fully competitive professional male volleyball players (mean age, 28 years) completed outcomes questionnaires and underwent a complete clinical examination and an MRI of their lumbar spine. Results: Whereas 86% of players suffered from LBP during their career, the incidence of LBP in the last 4 weeks was 35%. Pain rated using a visual analog scale (VAS) averaged 3 points (range, 0-8). Twenty-three of 29 players (79%) had at least 1 degenerated disc of Pfirrmann grade ≥3. The most affected spinal levels were L4-5 in 14 (48%) and L5-S1 in 15 players (52%); both levels were involved in 5 players (17%). Six of 29 (21%) players showed a spondylolysis grade 4 according to the Hollenburg classification; there was evidence of spondylolisthesis in 2 players. There was no significant correlation between LBP and MRI abnormalities. Conclusion: In the lumbar spine MRI of professional beach volleyball players, the prevalence of disc degeneration is 79%. Spondylolysis (21%) is up to 3 times higher compared with the normal population. Abnormal MRI findings did not correlate with LBP, thus MRIs have to be interpreted with caution. PMID:26535316

  6. Role of biomechanics on intervertebral disc degeneration and regenerative therapies: What needs repairing in the disc and what are promising biomaterials for its repair?

    PubMed Central

    Iatridis, James C.; Nicoll, Steven B.; Michalek, Arthur J.; Walter, Benjamin A.; Gupta, Michelle S.

    2013-01-01

    Background Context Degeneration and injuries of the intervertebral disc result in large alterations in biomechanical behaviors. Repair strategies using biomaterials can be optimized based on biomechanical and biological requirements. Purpose To review current literature on 1) effects of degeneration, simulated degeneration, and injury on biomechanics of the intervertebral disc with special attention paid to needle puncture injuries which are a pathway for diagnostics and regenerative therapies; and 2) promising biomaterials for disc repair with a focus on how those biomaterials may promote biomechanical repair. Study Design/Setting A narrative review to evaluate the role of biomechanics on disc degeneration and regenerative therapies with a focus on what biomechanical properties need to be repaired and how to evaluate and accomplish such repairs using biomaterials. Model systems for screening of such repair strategies are also briefly described. Methods Papers were selected from two main Pubmed searches using keywords: intervertebral AND biomechanics (1823 articles) and intervertebral AND biomaterials (361 articles). Additional keywords (injury, needle puncture, nucleus pressurization, biomaterials, hydrogel, sealant, tissue engineering) were used to narrow articles to the topics most relevant to this review. Results Degeneration and acute disc injuries have the capacity to influence nucleus pulposus pressurization and annulus fibrosus integrity, which are necessary for effective disc function, and therefore, require repair. Needle injection injuries are of particular clinical relevance with potential to influence disc biomechanics, cellularity, and metabolism, yet these effects are localized or small, and more research is required to evaluate and reduce potential clinical morbidity using such techniques. NP replacement strategies, such as hydrogels, are required to restore NP pressurization or lost volume. AF repair strategies, including crosslinked hydrogels

  7. A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype.

    PubMed

    Hirata, Hiroaki; Yurube, Takashi; Kakutani, Kenichiro; Maeno, Koichiro; Takada, Toru; Yamamoto, Junya; Kurakawa, Takuto; Akisue, Toshihiro; Kuroda, Ryosuke; Kurosaka, Masahiro; Nishida, Kotaro

    2014-03-01

    The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types-notochordal cells (NCs) and non-notochordal chondrocyte-like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI-positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, identified as NCs. The proportion of TUNEL-positive cells, which predominantly comprised non-NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2α-1 mRNA levels were down-regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration.

  8. Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo

    PubMed Central

    Chen, Deheng; Xia, Dongdong; Pan, Zongyou; Xu, Daoliang; Zhou, Yifei; Wu, Yaosen; Cai, Ningyu; Tang, Qian; Wang, Chenggui; Yan, Meijun; Zhang, Jing Jie; Zhou, Kailiang; Wang, Quan; Feng, Yongzeng; Wang, Xiangyang; Xu, Huazi; Zhang, Xiaolei; Tian, Naifeng

    2016-01-01

    Intervertebral disc degeneration (IDD) is a complicated process that involves both cellular apoptosis and senescence. Metformin has been reported to stimulate autophagy, whereas autophagy is shown to protect against apoptosis and senescence. Therefore, we hypothesize that metformin may have therapeutic effect on IDD through autophagy stimulation. The effect of metformin on IDD was investigated both in vitro and in vivo. Our study showed that metformin attenuated cellular apoptosis and senescence induced by tert-butyl hydroperoxide in nucleus pulposus cells. Autophagy, as well as its upstream regulator AMPK, was activated by metformin in nucleus pulposus cells in a dose- and time-dependent manner. Inhibition of autophagy by 3-MA partially abolished the protective effect of metformin against nucleus pulposus cells' apoptosis and senescence, indicating that autophagy was involved in the protective effect of metformin on IDD. In addition, metformin was shown to promote the expression of anabolic genes such as Col2a1 and Acan expression while inhibiting the expression of catabolic genes such as Mmp3 and Adamts5 in nucleus pulposus cells. In vivo study illustrated that metformin treatment could ameliorate IDD in a puncture-induced rat model. Thus, our study showed that metformin could protect nucleus pulposus cells against apoptosis and senescence via autophagy stimulation and ameliorate disc degeneration in vivo, revealing its potential to be a therapeutic agent for IDD. PMID:27787519

  9. [Correlation between shape and direction of small articular surface in lower lumbar vertebrae and degeneration of intervertebral disc].

    PubMed

    Tan, L; Bai, X; Li, D

    1997-01-01

    To assess the possible correlation between the shape and the direction of the small articular surface in the lower lumbar vertebrae and the degeneration of the intervertebral disc, we investigated with computed tomography (CT) and evaluated with statistics the small articular surface and the transverse interface-joint angle (TIFA) of the L4-5 and the L5-S1 in 152 cases who had normal or degenerative discs verified through CT, MRI or operation. The small articular surface was found arc in 69.1% of the L4-5 and in 23.0% of the L5-S1. The TIFA of the L4-5 was less than that of the L5-S1. There was no correlation between the ratio of degeneration of the intervertebral disc at the L4-5 and the TIFA of the L4-5 and the L5-S1, but the ratio of degeneration of the intervertebral disc at the L5-S1 had postive correlation with the TIFA of the L4-5, negative correlation with the TIFA of the L5-S1, and particular correlation with the TIFA of the L5-S1 and L4-5. These results suggest that the shape and direction of the lower lumbar facet joint are related to the lumbar degeneration of intervertebral disc and the causes of degeneration at the L4-5 disc differ from those at the L5-S1 disc in biomechanics.

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

    PubMed

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

    2017-12-01

    A sample of 512 Chinese was studied and we observed that greater disc degeneration on MRI was associated with greater spine DXA BMD. Yet, this association may be confounded by facet joint osteoarthritis. BMD may not be a risk factor for lumbar disc degeneration in Chinese.

  11. Notochordal cell disappearance and modes of apoptotic cell death in a rat tail static compression-induced disc degeneration model

    PubMed Central

    2014-01-01

    Introduction The intervertebral disc has a complex structure originating developmentally from both the mesenchyme and notochord. Notochordal cells disappear during adolescence, which is also when human discs begin to show degenerative signs. During degeneration later in life, disc cells decline because of apoptosis. Although many animal models have been developed to simulate human disc degeneration, few studies have explored the long-term changes in cell population and phenotype. Our objective was to elucidate the time-dependent notochordal cell disappearance and apoptotic cell death in a rat tail static compression-induced disc degeneration model. Methods Twenty-four 12-week-old male Sprague–Dawley rat tails were instrumented with an Ilizarov-type device and loaded statically at 1.3 MPa for up to 56 days. Loaded and distal-unloaded discs were harvested. Changes in cell number and phenotype were assessed with histomorphology and immunofluorescence. Apoptosis involvement was determined with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and immunohistochemistry. Results The number of disc nucleus pulposus and annulus fibrosus cells decreased with the loading period; particularly, the decrease was notable at day 7 in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, indicating notochordal origin. Subsequently, the proportion of cells positive for TUNEL and cleaved caspase-3, markers of apoptosis induction, increased from day 7 through day 56. Although the percentage of cells immunopositive for cleaved caspase-8, a marker of apoptosis initiation through the death-receptor pathway, increased only at day 7, the percentage of cells immunopositive for cleaved caspase-9 and p53-regulated apoptosis-inducing protein 1 (p53AIP1), markers of apoptosis initiation through the p53-mediated mitochondrial pathway, increased from day 7 through day 56. The percentage of cells immunopositive for B-cell lymphoma 2 (Bcl-2) and silent

  12. lncRNAs: novel players in intervertebral disc degeneration and osteoarthritis.

    PubMed

    Chen, Wen-Kang; Yu, Xiao-Hua; Yang, Wei; Wang, Cheng; He, Wen-Si; Yan, Yi-Guo; Zhang, Jian; Wang, Wen-Jun

    2017-02-01

    The term long non-coding RNA (lncRNA) refers to a group of RNAs with length more than 200 nucleotides, limited protein-coding potential, and having widespread biological functions, including regulation of transcriptional patterns and protein activity, formation of endogenous small interfering RNAs (siRNAs) and natural microRNA (miRNA) sponges. Intervertebral disc degeneration (IDD) and osteoarthritis (OA) are the most common chronic, prevalent and age-related degenerative musculoskeletal disorders. Numbers of lncRNAs are differentially expressed in human degenerative nucleus pulposus tissue and OA cartilage. Moreover, some lncRNAs have been shown to be involved in multiple pathological processes during OA, including extracellular matrix (ECM) degradation, inflammatory responses, apoptosis and angiogenesis. In this review, we summarize current knowledge concerning lncRNAs, from their biogenesis, classification and biological functions to molecular mechanisms and therapeutic potential in IDD and OA.

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

    PubMed

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

    2015-01-01

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

  14. Oestrogen and parathyroid hormone alleviate lumbar intervertebral disc degeneration in ovariectomized rats and enhance Wnt/β-catenin pathway activity

    PubMed Central

    Jia, Haobo; Ma, Jianxiong; Lv, Jianwei; Ma, Xinlong; Xu, Weiguo; Yang, Yang; Tian, Aixian; Wang, Ying; Sun, Lei; Xu, Liyan; Fu, Lin; Zhao, Jie

    2016-01-01

    To investigate the mitigation effect and mechanism of oestrogen and PTH on disc degeneration in rats after ovariectomy, as well as on Wnt/β-catenin pathway activity, thirty 3-month-old rats were ovariectomized and divided into three groups. Ten additional rats were used as controls. Eight weeks later, the rats were administered oestrogen or PTH for 12 weeks, and then discs were collected for tests. Results showed that nucleus pulposus cells in the Sham group were mostly notochord cells, while in the OVX group, cells gradually developed into chondrocyte-like cells. Oestrogen or PTH could partly recover the notochord cell number. After ovariectomy, the endplate roughened and endplate porosity decreased. After oestrogen or PTH treatment, the smoothness and porosity of endplate recovered. Compared with the Sham group, Aggrecan, Col2a and Wnt/β-catenin pathway expression in OVX group decreased, and either oestrogen or PTH treatment improved their expression. The biomechanical properties of intervertebral disc significantly changed after ovariectomy, and oestrogen or PTH treatment partly recovered them. Disc degeneration occurred with low oestrogen, and the underlying mechanisms involve nutrition supply disorders, cell type changes and decreased Wnt/β-catenin pathway activity. Oestrogen and PTH can retard disc degeneration in OVX rats and enhance Wnt/β-catenin pathway activity in nucleus pulposus. PMID:27279629

  15. The Effect of Discectomy and the Dependence on Degeneration of Human Intervertebral Disc Strain in Axial Compression

    PubMed Central

    O’Connell, Grace D.; Malhotra, Neil R.; Vresilovic, Edward J; Elliott, Dawn M.

    2011-01-01

    Study Design Biomechanics of human intervertebral discs before and after nucleotomy. Objective To noninvasively quantify the effect of nucleotomy on internal strains under axial compression in flexion, neutral, and extension positions, and to determine whether the change in strains depended on degeneration. Summary of Background Data Herniation and discectomy may accelerate the progression of disc degeneration. Removal of NP tissue has resulted in altered disc mechanics in vitro, including in a decrease in internal pressure and an increase in the deformations at physiologically relevant strains. We recently presented a technique to quantify internal disc strains using magnetic resonance imaging. Methods Degeneration was quantitatively assessed by the T1ρ relaxation in the nucleus pulposus (NP). Samples were prepared from human levels L3-L4 and/or L4-L5. A 1000N compressive load was applied while in the MR scanner. Nucleotomy was performed by removing 2g of NP through the posterior-lateral AF. The discs were rehydrated, reimaged and retested. The analyzed parameters include axial deformation, AF radial bulge and strains. Results The axial deformation was more compressive following nucleotomy. In the neutral position, the axial deformation following nucleotomy correlated with degeneration (as quantified by T1ρ in the NP), with minimal alteration in nondegenerated discs. Nucleotomy altered the radial displacements and strains in the neutral position, such that the inner AF radial bulge decreased and the radial strains were more tensile in the lateral AF and less tensile in the posterior AF. In the bending loading positions the radial strains were not affected by nucleotomy. Conclusions Nucleotomy alters the internal radial and axial AF strains in the neutral position, which may leave the AF vulnerable to damage and microfractures. In bending, the effects of nucleotomy were minimal; likely due to more of the applied load being directed over the AF. Some of the

  16. Elevated interleukin-6 expression levels are associated with intervertebral disc degeneration

    PubMed Central

    DENG, XIAO; ZHAO, FENG; KANG, BAOLIN; ZHANG, XIN

    2016-01-01

    The present study aimed to investigate whether serum interleukin-6 (IL-6) expression levels were associated with the onset and progression of intervertebral disc degeneration (IDD). A comprehensive meta-analysis of the scientific literature from numerous electronic databases was performed, in order to obtain published studies associated with the topic of interest. Relevant case-control studies that had previously assessed a correlation between IL-6 expression levels and IDD were identified using predetermined inclusion and exclusion criteria. The STATA version 12.0 software was used for statistical analysis of the extracted data. A total of 112 studies were initially retrieved, with eight studies meeting the inclusion criteria. These contained a total of 392 subjects, of which 263 were patients with IDD and 129 were healthy controls. A meta-analysis of the eight studies demonstrated that serum IL-6 protein expression levels may be associated with IDD, and this was irrespective of IDD subtype (bulging, protrusion, or sequestration). Notably, serum expression levels of the IL-6 protein were upregulated in intervertebral disc (IVD) protrusion tissue, as compared with normal IVD tissue; thus suggesting that IL-6 may have an important role in the pathophysiological process of IDD. PMID:27073460

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

    PubMed Central

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

    2016-01-01

    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. PMID:27853274

  18. MyD88-dependent Toll-like receptor 4 signal pathway in intervertebral disc degeneration

    PubMed Central

    Qin, Chuqiang; Zhang, Bo; Zhang, Liang; Zhang, Zhi; Wang, Le; Tang, Long; Li, Shuangqing; Yang, Yixi; Yang, Fuguo; Zhang, Ping; Yang, Bo

    2016-01-01

    Lower back pain (LBP) is a common and remitting problem. One of the primary causes of LBP is thought to be degeneration of the intervertebral disc (IVD). The aim of the present study was to investigate the role of the myeloid differentiation primary-response protein 88 (MyD88)-dependent Toll-like receptor 4 (TLR4) signal pathway in the mechanism of IVD degeneration. IVD nucleus pulposus cells isolated and cultured from the lumbar vertebrae of Wistar rats were stimulated by various doses of lipopolysaccharide (LPS; 0.1, 1, 10 and 100 µg/ml) to simulate IVD degeneration. Cells were rinsed and cultured in serum-free Dulbecco's modified Eagle's medium/F12. Reverse transcription-quantitative polymerase chain reaction was used to determine the levels of TLR4, MyD88, tumor necrosis factor α (TNFα), and interleukin-1β (IL-1β) mRNA expression after 1, 3, 6, 9 and 12 h of incubation. Additionally, western blot and enzyme-linked immunosorbent assay analyses were used to determine the levels of TLR4, MyD88, TNFα, and IL-1β protein expression after 24, 48 and 72 h of incubation. The levels of TLR4, MyD88, TNFα and IL-1β mRNA all increased in the cells stimulated by 10 µg/ml LPS at 3, 6 and 9 h (all P<0.001). Furthermore, the levels of TLR4, MyD88, TNFα and IL-1β protein all increased at 24, 48 and 72 h (all P<0.001). Additionally, the mRNA and protein levels of TLR4, MyD88, TNFα and IL-1β increased significantly in the cells stimulated by 1, 10 and 100 µg/ml LPS compared with the control group, and reached a peak in the 10 µg/ml LPS group (all P<0.001). These results suggest that the MyD88-dependent TLR4 signal pathway is a target pathway in IVD degeneration. This pathway is time phase- and dose-dependent, and when activated can lead to the release of inflammatory factors that participate in IVD degeneration. PMID:27446251

  19. Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor.

    PubMed

    Tolonen, Jukka; Grönblad, Mats; Vanharanta, Heikki; Virri, Johanna; Guyer, Richard D; Rytömaa, Tapio; Karaharju, Erkki O

    2006-05-01

    Degenerated intervertebral disc has lost its normal architecture, and there are changes both in the nuclear and annular parts of the disc. Changes in cell shape, especially in the annulus fibrosus, have been reported. During degeneration the cells become more rounded, chondrocyte-like, whereas in the normal condition annular cells are more spindle shaped. These chondrocyte-like cells, often forming clusters, affect extracellular matrix turnover. In previous studies transforming growth factor beta (TGFbeta) -1 and -2, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) have been highlighted in herniated intervertebral disc tissue. In the present study the same growth factors are analysed immunohistochemically in degenerated intervertebral disc tissue. Disc material was obtained from 16 discs operated for painful degenerative disc disease. Discs were classified according to the Dallas Discogram Description. Different disc regions were analysed in parallel. As normal control disc tissue material from eight organ donors was used. Polyclonal antibodies against different growth factors and TGFbeta receptor type II were used, and the immunoreaction was detected by the avidin biotin complex method. All studied degenerated discs showed immunoreactivity for TGFbeta receptor type II and bFGF. Fifteen of 16 discs were immunopositive for TGFbeta-1 and -2, respectively, and none showed immunoreaction for PDGF. Immunopositivity was located in blood vessels and in disc cells. In the nucleus pulposus the immunoreaction was located almost exclusively in chondrocyte-like disc cells, whereas in the annular region this reaction was either in chondrocyte-like disc cells, often forming clusters, or in fibroblast-like disc cells. Chondrocyte-like disc cells were especially prevalent in the posterior disrupted area. In the anterior area of the annulus fibrosus the distribution was more even between these two cell types. bFGF was expressed in the anterior annulus

  20. Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation.

    PubMed

    Vadalà, Gianluca; Sowa, Gwendolyn; Hubert, Mark; Gilbertson, Lars G; Denaro, Vincenzo; Kang, James D

    2012-05-01

    Recent studies have shown that mesenchymal stem cell (MSC)-based therapy might be an effective approach for the treatment of intervertebral disc degeneration (IDD). However, many unanswered questions remain before clinical translation, such as the most effective stem cell type, a reliable transplantation method, including the carrier choice, and the fate of stem cells after misdirected delivery, among others. The objective of the study was to evaluate the fate and effect of allogenic bone marrow MSCs after transplantation into an IDD model. The L2-3, L3-4 and L4-5 intervertebral discs (IVDs) of four rabbits were stabbed to create IDD. Rabbit MSCs were expanded in vitro and in part transduced with retrovirus/eGFP. After 3 weeks, 1 × 10(5) MSCs were injected into the IVDs. The rabbits were followed by X-ray and MRI 3 and 9 weeks after injection. Then the animals were sacrificed and the spines analysed histologically. MRI showed no signs of regeneration. X-ray and gross anatomy inspection demonstrated large anterolateral osteophytes. Histological analysis showed that the osteophytes were composed of mineralized tissue surrounded by chondrocytes, with the labelled MSCs among the osteophyte-forming cells. The labelled MSCs were not found in the nucleus. Inflammatory cells were not observed in any injected IVDs. These results raise concern that MSCs can migrate out of the nucleus and undesirable bone formation may occur. While cause cannot be inferred from this study, the presence of MSCs in the osteophytes suggests a potential side-effect with this approach. IVD regeneration strategies need to focus on cell carrier systems and annulus-sealing technologies to avoid pitfalls.

  1. The Relation Between Sacral Angle and Vertical Angle of Sacral Curvature and Lumbar Disc Degeneration

    PubMed Central

    Ghasemi, Ahmad; Haddadi, Kaveh; Khoshakhlagh, Mohammad; Ganjeh, Hamid Reza

    2016-01-01

    Abstract The purpose of this study is to determine the reliability and validity of a goniometric measurement of the vertical angle of the sacrum and sacral angle (SA), and their relationships to lumbar degeneration. A herniated lumbar disc is one of the most frequent medical issues. Investigators in a number of studies have reported associated risk factors for prevalent disc degeneration. Atypical lumbosacral angles and curvature are thought to contribute to the degradation of the spine by many researchers. This study analyzed 360 patients referred to our clinic from 2013 to 2015 due to low back pain. A cross-sectional case–control study was designed in order to compare the sagittal alignment of the lumbosacral area in 3 groups of patients suffering from LBP. A total 120 patients were in a control group with a normal lumbar magnetic resonance imaging (MRI), 120 patients had lumbar disk herniation (LDH), and 120 patients had spinal stenosis. From the sagittal plan of lumbar MRI, SA and vertical angle of sacral curvature (VASC) were determined and then analyzed. The means of VASC in these groups were: 38.98 (SD: 6.36 ± 0.58), 40.89 (SD: 7.69 ± 0.69), and 40.54 (SD: 7.13 ± 0.92), respectively (P = 0.089). Moreover, studies of SA in 3 groups showed that the means of SA were: 39.30 (SD: 6.69 ± 0.63), 40.52 (SD: 7.47 ± 0.65), and 35.63 (SD: 6.07 ± 0.79), respectively. Relation between SA and spinal stenosis was just statistically significant (P ≤ 0.05). One significant limitation of our study is the lack of standing MRI for increased accuracy of measurement. However, we were reluctant to give patients needless exposure to radiation from conventional X-ray, and instead used MRI scans. We did not find any significant correlation between the VASC and LDH in lumbar MRI. Also, SA is not an independent risk factor for LDH in men and women. We suggested that there are several biomechanical factors involved in LDH. PMID:26871821

  2. Advancing the cellular and molecular therapy for intervertebral disc disease.

    PubMed

    Sakai, Daisuke; Grad, Sibylle

    2015-04-01

    The healthy intervertebral disc (IVD) fulfils the essential function of load absorption, while maintaining multi-axial flexibility of the spine. The interrelated tissues of the IVD, the annulus fibrosus, the nucleus pulposus, and the cartilaginous endplate, are characterised by their specific niche, implying avascularity, hypoxia, acidic environment, low nutrition, and low cellularity. Anabolic and catabolic factors balance a slow physiological turnover of extracellular matrix synthesis and breakdown. Deviations in mechanical load, nutrient supply, cellular activity, matrix composition and metabolism may initiate a cascade ultimately leading to tissue dehydration, fibrosis, nerve and vessel ingrowth, disc height loss and disc herniation. Spinal instability, inflammation and neural sensitisation are sources of back pain, a worldwide leading burden that is challenging to cure. In this review, advances in cell and molecular therapy, including mobilisation and activation of endogenous progenitor cells, progenitor cell homing, and targeted delivery of cells, genes, or bioactive factors are discussed.

  3. Herb formula "Fufangqishe-Pill" prevents upright posture-induced intervertebral disc degeneration at the lumbar in rats.

    PubMed

    Liang, Qian-Qian; Xi, Zhi-Jie; Bian, Qin; Cui, Xue-Jun; Li, Chen-Guang; Hou, Wei; Shi, Qi; Wang, Yong-Jun

    2010-01-01

    Degeneration of the lumbar spine plays an important role in most chronic low back pain. Prevention of lumbar intervertebral disc (IVD) degeneration is therefore a high research priority. Both our previous multicenter clinical trials and pharmacological research showed that Fufangqishe-Pill (FFQSP), a newly patented traditional Chinese medicine, could effectively relieve the symptoms of neck pain and prevent cervical degeneration. To clarify the effect of FFQSP on lumbar IVD degeneration, we applied a lumbar IVD degeneration rat model induced by prolonged upright posture. Pretreatment of FFQSP for one month prevented the histological changes indicating IVD disorganization; increased type II-collagen level, decreased type X-collagen protein level, and increased Col2alpha1 mRNA expression at all time points; and decreased Col10alpha1, matrix metalloproteinase (MMP)-3, MMP13, and Interleukin (IL)-1beta mRNA expression induced by upright posture for 7 and 9 months. These results suggest that FFQSP prevents lumbar IVD degeneration induced by upright posture. FFQSP is a promising medicine for lumbar IVD degeneration disease.

  4. The Effects of Age, Gender, Ethnicity, and Spinal Level on the Rate of Intervertebral Disc Degeneration. A review of 1712 Intervertebral Discs

    PubMed Central

    Siemionow, Krzysztof; An, Howard; Masuda, Koichi; Andersson, Gunnar; Cs-Szabo, Gabriella

    2010-01-01

    Study Design A gross anatomical and magnetic resonance imaging (MRI) study of intervertebral disc (IVD) degeneration in fresh cadaveric lumbar spines. Objective The purpose of this study was to find the rate of IVD degeneration. Summary of Background Data Age, sex, race, and lumbar level are among some of the factors that play a role in IVD degeneration. The rate at which IVDs degenerate is unknown. Methods Complete lumbar spine segments (T11/12 to S1) were received within 24 hours of death. The nucleus pulposus, annulus fibrosus, cartilaginous and bony end-plate, and the peripheral verterbral body were assessed with MRI and IVD degeneration was graded by two observers from grade 1(nondegenerated) to grade 5(severely degenerated) based on a scale developed by Tanaka et al. The specimens were then sectioned and gross anatomical evaluation was performed according to Thompson et al. Results 433 donors and 1712 IVDs were analyzed. There were 366 Caucasians, 47 Africans, 16 Hispanics, 4 Asian. There were 306 males and 127 females. The age range was 14–81 years, (average 60.5+/−11.3). For donors greater than age 40, the L5/S1 IVD degenerated at a significantly faster rate of 0.043/year compared to 0.031, 0.034, 0.033, 0.027 for L12, L23, L34, L45, respectively. For donors younger than 40, L5/S1 IVD degenerated at a significantly faster rate of 0.141/year compared to 0.033,0.021, 0.031, 0.050 for L12, L23, L34, L45, respectively. Multiple regression analysis revealed that gender had no significant effect on IVD degeneration whereas African ethnicity was associated with lower Thompson score at L12, L23, L34, L45 when compared to Caucasians. Conclusions The relatively early degeneration at L5-S1 in all races and lower Thompson grade in donors of African ethnicity needs further investigation. Factors such as sagittal alignment, facet joint arthritis, and genetics potentially play a role in IVD degeneration. PMID:21217432

  5. Interleukin 1 Polymorphisms Contribute to Intervertebral Disc Degeneration Risk: A Meta-Analysis

    PubMed Central

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

    2016-01-01

    Objective We performed a meta-analysis to assess association between interleukin 1 (IL-1) polymorphisms and the risk of Intervertebral Disc Degeneration (IDD). Background A series of studies have investigated the association between common single nucleotide polymorphisms in IL-1 and IDD risk; however, the overall results are inconclusive. Methods Two independent investigators conducted a systematic search for relevant available studies. Allele frequencies were extracted from each study. The association between the IL-1α (+889C/T) or IL-1β (+3954C/T) polymorphism and IDD risk was measured by odds ratios (OR) with 95% confidence intervals (95% CI). Results Five and six studies, respectively, were ultimately included in the meta-analysis for the IL-1α (+889C/T) and IL-1β (+3954C/T) polymorphism. The combined results showed that the IL-1α (+889C/T) polymorphism was significantly associated with increased susceptibility to IDD, particularly in Caucasians (TT versus CC: OR = 2.95, 95% CI: 1.45, 6.04; Pheterogeneity = 0.82; TT versus CC/CT: OR = 2.29, 95% CI: 1.18, 4.47; Pheterogeneity = 0.20). In contrast, the IL-1β (+3954C/T) polymorphism showed a trend towards increased risk in Caucasians but no association in Asians. Conclusion This meta-analysis suggested that the IL-1α (+889C/T) polymorphism is significantly associated with risk of IDD, especially in Caucasian populations. PMID:27253397

  6. Genome-Wide Identification of Long Noncoding RNAs in Human Intervertebral Disc Degeneration by RNA Sequencing

    PubMed Central

    Zhao, Bo; Lu, Minjuan; Wang, Dong; Li, Haopeng

    2016-01-01

    Long noncoding RNAs (lncRNAs) are emerging as crucial players in a myriad of biological processes. However, the precise mechanism and functions of most lncRNAs are poorly characterized. In this study, we presented genome-wide identification of lncRNAs in the patients with intervertebral disc degeneration (IDD) and spinal cord injury (control) using RNA sequencing (RNA-seq). A total of 124.6 million raw reads were yielded using Hiseq 2500 platform and approximately 88% clean reads could be aligned to human reference genome in both IDD and control groups. RNA-seq profiling indicated that 1,854 lncRNAs were differentially expressed (log2 fold change ≥ 1 or ≤−1, p < 0.05), in which 1,530 could potentially target 6,386 genes via cis-regulatory effects. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for these target genes suggested that lncRNAs were involved in diverse pathways, such as lysosome, focal adhesion, and MAPK signaling. In addition, a competing endogenous RNA (ceRNA) network was constructed for analyzing the function of lncRNAs. Further, quantitative real time PCR (qRT-PCR) was used to confirm the differentially expressed lncRNAs and ceRNA network. In conclusion, our results present the first global identification of lncRNAs in IDD and may provide candidate diagnostic biomarkers for IDD treatment. PMID:28097131

  7. Hydrogen sulfide protects against endoplasmic reticulum stress and mitochondrial injury in nucleus pulposus cells and ameliorates intervertebral disc degeneration.

    PubMed

    Xu, Daoliang; Jin, Haiming; Wen, Jianxia; Chen, Jiaoxiang; Chen, Deheng; Cai, Ningyu; Wang, Yongli; Wang, Jianle; Chen, Yu; Zhang, Xiaolei; Wang, Xiangyang

    2017-03-01

    It has been suggested that excessive apoptosis in intervertebral disc cells induced by inflammatory cytokines, such as interleukin (IL)-1β, is related to the process of intervertebral disc degeneration (IVDD). Hydrogen sulfide (H2S), a gaseous signaling molecule, has drawn attention for its anti-apoptosis role in various pathophysiological processes in degenerative diseases. To date, there has been no investigation of the correlation of H2S production and IVDD or of the effects of H2S on IL-1β-induced apoptosis in nucleus pulposus (NP) cells. Here, we found that the expression levels of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), two key enzymes in the generation of H2S, were significantly decreased in human degenerate NP tissues as well as in IL-1β-treated NP cells. NaHS (H2S donor) administration showed a protective effect by inhibiting the endoplasmic reticulum (ER) stress response and mitochondrial dysfunction induced by IL-1β stimulation in vitro, the effect was related to activation of the PI3K/Akt and ERK1/2 signaling pathways. Suppression of these pathways by specific inhibitors, LY294002 and PD98059, partially reduced the protective effect of NaHS. Moreover, in the percutaneous needle puncture disc degeneration rat tail model, disc degeneration was partially reversed by NaHS administration. Taken together, our results suggest that H2S plays a protective role in IVDD and the underlying mechanism involves PI3K/Akt and ERK1/2 signaling pathways-mediated suppression of ER stress and mitochondrial dysfunction in IL-1β-induced NP cells.

  8. TGFβ and BMP Dependent Cell Fate Changes Due to Loss of Filamin B Produces Disc Degeneration and Progressive Vertebral Fusions

    PubMed Central

    Zieba, Jennifer; Forlenza, Kimberly Nicole; Khatra, Jagteshwar Singh; Sarukhanov, Anna; Duran, Ivan; Rigueur, Diana; Lyons, Karen M.; Cohn, Daniel H.; Merrill, Amy E.; Krakow, Deborah

    2016-01-01

    Spondylocarpotarsal synostosis (SCT) is an autosomal recessive disorder characterized by progressive vertebral fusions and caused by loss of function mutations in Filamin B (FLNB). FLNB acts as a signaling scaffold by linking the actin cytoskleteon to signal transduction systems, yet the disease mechanisms for SCT remain unclear. Employing a Flnb knockout mouse, we found morphologic and molecular evidence that the intervertebral discs (IVDs) of Flnb–/–mice undergo rapid and progressive degeneration during postnatal development as a result of abnormal cell fate changes in the IVD, particularly the annulus fibrosus (AF). In Flnb–/–mice, the AF cells lose their typical fibroblast-like characteristics and acquire the molecular and phenotypic signature of hypertrophic chondrocytes. This change is characterized by hallmarks of endochondral-like ossification including alterations in collagen matrix, expression of Collagen X, increased apoptosis, and inappropriate ossification of the disc tissue. We show that conversion of the AF cells into chondrocytes is coincident with upregulated TGFβ signaling via Smad2/3 and BMP induced p38 signaling as well as sustained activation of canonical and noncanonical target genes p21 and Ctgf. These findings indicate that FLNB is involved in attenuation of TGFβ/BMP signaling and influences AF cell fate. Furthermore, we demonstrate that the IVD disruptions in Flnb–/–mice resemble aging degenerative discs and reveal new insights into the molecular causes of vertebral fusions and disc degeneration. PMID:27019229

  9. Vitamin D Receptor Gene, Matrix Metalloproteinase 3 Polymorphisms and the Risk of Intervertebral Disc Degeneration Susceptibility: Meta-Analysis

    PubMed Central

    Huang, Yongjing; Zhao, Shujie; Xu, Nanwei

    2016-01-01

    Several studies have evaluated the association between vitamin D receptor, matrix metalloproteinase 3 (MMP-3) polymorphisms and the risk of intervertebral disc degeneration susceptibility. The findings were inconsistent. This meta-analysis aimed to systematically assess the association between vitamin D receptor, MMP-3 polymorphisms and the risk of intervertebral disc degeneration susceptibility. A search of various databases was done covering all papers published until December 31th, 2014. Eight, 4, 3 studies were finally included that addressed the risk of intervertebral disc degeneration susceptibility and vitamin D receptor FokI (rs2228570), ApaI (rs7975232), and MMP-3 (rs731236) polymorphisms, respectively. FokI (f vs. F: summary odds ratio [OR], 1.13; 95% confidence interval [CI], 0.76–1.69; ff vs. FF: OR, 1.02; 95% CI, 0.59–1.77; ff vs. Ff/FF: OR, 1.05; 95% CI, 0.70–1.58), ApaI (a vs. A: OR, 0.73; 95% CI, 0.45–1.19; aa vs. AA: OR, 0.53; 95% CI, 0.22–1.25 p=0.14; aa vs. AA/Aa: OR, 0.69; 95% CI, 0.53–0.89) in the vitamin D receptor gene and MMP3 polymorphisms (5A vs. 6A: OR, 1.92; 95% CI, 0.77–4.80; 5A5A vs. 6A6A: OR, 2.17; 95% CI, 0.75–6.24; 5A5A vs. 5A6A/6A6A: OR, 1.58; 95% CI, 0.72–3.44) were not obviously associated with risk of intervertebral disc degeneration susceptibility. FokI, ApaI polymorphisms in the vitamin D receptor gene and MMP-3 polymorphism are not obvious risk factors for intervertebral disc degeneration susceptibility. PMID:27790329

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

    PubMed Central

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

    2016-01-01

    The aim of the current study was to use gene therapy to attenuate or reverse the degenerative process within the intervertabral disc. The effect of survivin gene therapy via lentiviral vector transfection on the course of intervertebral disc degeneration was investigated in the current study in an in vivo rabbit model. A total of 15 skeletally mature female New Zealand White rabbits were randomly divided into three groups: Punctured blank control group (group A, n=5), punctured empty vector control group (group B, n=5) and the treatment group (group C, n=5). Computed tomography-guided puncture was performed at the L3-L4 and L4-L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, a lentiviral vector (LV) carrying survivin was injected into the nucleus pulposus. The results demonstrated that through magnetic resonance imaging, histology, gene expression, protein content and apoptosis analyses, group A and B were observed to exhibit disc degeneration, which increased over time, and no significant difference was observed between the two groups (P>0.05). However, there was reduced disc degeneration in group C compared with the punctured control groups, and the difference was statistically significant (P<0.05). Overall, the results of the present study demonstrated that injection of the LV carrying survivin into punctured rabbit intervertebral discs acted to delay changes associated with the degeneration of the discs. Although data from animal models should be extrapolated to the human condition with caution, the present study suggests potential for the use of gene therapy to decelerate disc degeneration. PMID:27748828

  11. Metabolic Syndrome Components Are Associated with Intervertebral Disc Degeneration: The Wakayama Spine Study

    PubMed Central

    Teraguchi, Masatoshi; Yoshimura, Noriko; Hashizume, Hiroshi; Muraki, Shigeyuki; Yamada, Hiroshi; Oka, Hiroyuki; Minamide, Akihito; Ishimoto, Yuyu; Nagata, Keiji; Kagotani, Ryohei; Tanaka, Sakae; Kawaguchi, Hiroshi; Nakamura, Kozo; Akune, Toru; Yoshida, Munehito

    2016-01-01

    Objective The objective of the present study was to examine the associations between metabolic syndrome (MS) components, such as overweight (OW), hypertension (HT), dyslipidemia (DL), and impaired glucose tolerance (IGT), and intervertebral disc degeneration (DD). Design The present study included 928 participants (308 men, 620 women) of the 1,011 participants in the Wakayama Spine Study. DD on magnetic resonance imaging was classified according to the Pfirrmann system. OW, HT, DL, and IGT were assessed using the criteria of the Examination Committee of Criteria for MS in Japan. Results Multivariable logistic regression analysis revealed that OW was significantly associated with cervical, thoracic, and lumbar DD (cervical: odds ratio [OR], 1.28; 95% confidence interval [CI], 0.92–1.78; thoracic: OR, 1.75; 95% CI, 1.24–2.51; lumbar: OR, 1.87; 95% CI, 1.06–3.48). HT and IGT were significantly associated with thoracic DD (HT: OR, 1.54; 95% CI, 1.09–2.18; IGT: OR, 1.65; 95% CI, 1.12–2.48). Furthermore, subjects with 1 or more MS components had a higher OR for thoracic DD compared with those without MS components (vs. no component; 1 component: OR, 1.58; 95% CI, 1.03–2.42; 2 components: OR, 2.60; 95% CI, 1.62–4.20; ≥3 components: OR, 2.62; 95% CI, 1.42–5.00). Conclusion MS components were significantly associated with thoracic DD. Furthermore, accumulation of MS components significantly increased the OR for thoracic DD. These findings support the need for further studies of the effects of metabolic abnormality on DD. PMID:26840834

  12. T1ρ MRI and Discography Pressure as Novel Biomarkers for Disc Degeneration and Low Back Pain

    PubMed Central

    Borthakur, Arijitt; Maurer, Philip M.; Fenty, Matthew; Wang, Chenyang; Berger, Rachelle; Yoder, Jonathon; Balderston, Richard A.; Elliott, Dawn M.

    2012-01-01

    Study Design Prospective MRI study of LBP patients requiring discography as part of their routine clinical diagnoses and asymptomatic age-matched volunteers. Objective To determine whether T1ρ MRI and discography opening pressure are quantitative biomarkers of disc degeneration in LBP patients and in asymptomatic volunteers. Summary of Background Data Disc degenerative disease (DDD), a common cause of low back pain (LBP), is related to the patient’s prognosis and serves as a target for therapeutic interventions. However, there are few quantitative measures in the clinical setting. Discography opening pressure (OP) and T1ρ MRI are potential biomarkers of DDD related to biochemical composition the intervertebral disc (IVD). Methods The Institutional Review Board approved all experiments and informed consent was provided by each subject. Patients being treated for LBP (n=17, 68 levels, mean age 44±6 years, range 30–53) and control (CTL) subjects (n=11, 44 levels, mean age 43±17, range 22–76) underwent T1ρ and T2 MRI on a Siemens 3T Tim Trio clinical scanner. The LBP patients also received multi-level provocative discography before their MRI. Opening Pressure (OP) was recorded as the pressure when fluid first enters the nucleus of the IVD. Results T1ρ was significantly lower in the painful discs (55.3ms±3.0 ms, mean ± std. error) from control (92.0±4.9 ms, p<0.001) and non-painful discs (83.6±3.2 ms, p<0.001). Mean OP for the painful discs (11.8±1.0 psi, mean ± std. error) was significantly lower than non-painful discs (19.1±0.7 psi, p<0.001). Both T1ρ and OP correlated moderately with Pfirrmann degenerative grade. ROC area under the curve was 0.91 for T1ρ MRI and 0.84 for OP for predicting painful discs. Conclusions T1ρ and OP are quantitative measures of degeneration that are consistent across both control subjects and LBP patients. A significant and strong correlation exists between T1ρ values and in vivo OP measurements obtained by

  13. Development and Kinematic Verification of a Finite Element Model for the Lumbar Spine: Application to Disc Degeneration

    PubMed Central

    Ibarz, Elena; Herrera, Antonio

    2013-01-01

    The knowledge of the lumbar spine biomechanics is essential for clinical applications. Due to the difficulties to experiment on living people and the irregular results published, simulation based on finite elements (FE) has been developed, making it possible to adequately reproduce the biomechanics of the lumbar spine. A 3D FE model of the complete lumbar spine (vertebrae, discs, and ligaments) has been developed. To verify the model, radiological images (X-rays) were taken over a group of 25 healthy, male individuals with average age of 27.4 and average weight of 78.6 kg with the corresponding informed consent. A maximum angle of 34.40° is achieved in flexion and of 35.58° in extension with a flexion-extension angle of 69.98°. The radiological measurements were 33.94 ± 4.91°, 38.73 ± 4.29°, and 72.67°, respectively. In lateral bending, the maximum angles were 19.33° and 23.40 ± 2.39, respectively. In rotation a maximum angle of 9.96° was obtained. The model incorporates a precise geometrical characterization of several elements (vertebrae, discs, and ligaments), respecting anatomical features and being capable of reproducing a wide range of physiological movements. Application to disc degeneration (L5-S1) allows predicting the affection in the mobility of the different lumbar segments, by means of parametric studies for different ranges of degeneration. PMID:23509766

  14. Oxidative damage induces apoptosis and promotes calcification in disc cartilage endplate cell through ROS/MAPK/NF-κB pathway: Implications for disc degeneration.

    PubMed

    Han, Yingchao; Li, Xinhua; Yan, Meijun; Yang, Mingjie; Wang, Shanjin; Pan, Jie; Jun, Lili; Tan, Jun

    2017-03-23

    Cartilage endplate (CEP) cell calcification and apoptosis play a vital role in the intervertebral disc degeneration (IVDD). Oxidative stress is a key factor in inducing programmed cell death and cartilage calcification. However, the cell death and calcification of cartilage endplate cells under oxidative stress have never been described. The present study investigated the apoptosis and calcification in the cartilage endplate cell under oxidative stress induced by H2O2 to understand the underlying mechanism of IVDD. The cartilage endplate cells isolated from human lumbar discs were subjected to different concentrations of H2O2 for various time periods. The cell viability was determined by CCK-8 assay, whereas Western blot, immunofluorescence, and Alcian blue, Alizarin red, and Von Kossa staining evaluated the apoptosis and calcification. The level of mitochondria-specific reactive oxygen species (ROS) was quantified with an oxygen radical-sensitive probe-MitoSOX. The potential signaling pathways were investigated by Western blot after the addition of N-acetyl-l-cysteine (NAC). We found that the oxidative stress induced by H2O2 increased the apoptosis and subsequently the calcification in the cartilage endplate cells through the ROS/p38/ERK/p65 pathway. The apoptosis and the calcification of the cartilage endplate cells induced by H2O2 can be abolished by NAC. These results suggested that regulating the apoptosis and the calcification in the cartilage endplate cells under oxidative stress should be advantageous for the survival of cells and might delay the process of disc degeneration.

  15. Minimum 10-Year Follow-up Study of Anterior Lumbar Interbody Fusion for Degenerative Spondylolisthesis: Progressive Pattern of the Adjacent Disc Degeneration

    PubMed Central

    Yasuda, Taketoshi; Hori, Takeshi; Suzuki, Kayo; Kawaguchi, Yoshiharu

    2012-01-01

    Study Design Retrospective study. Purpose The aims of the current study are to evaluate the minimum 10-year follow-up clinical results of anterior lumbar interbody fusion (ALIF) for degenerative spondylolisthesis. Overview of Literature ALIF has been widely used as a treatment regimen in the management of lumbar spondylolisthesis. Still much controversy exists regarding the factors that affect the postoperative clinical outcomes. Methods The author performed a retrospective review of 20 patients with degenerative spondylolisthesis treated with ALIF (follow-up, 16.4 years). The clinical results were assessed by the Japanese Orthopaedic Association (JOA) score for low back pain, vertebral slip and disc height index on the radiographs. Results The mean preoperative JOA score was 7.1 ± 1.8 points (15-point-method). At 1 year, 5 years, and 10 years or more after surgery, the JOA scores were assessed as 12.4 ± 2.2 points, 12.7 ± 2.6 points, 12.0 ± 2.5 points, respectively (excluding the data of reoperated cases). The adjacent disc degeneration developed in all cases during the long-term follow-up. The progressive pattern of disc degeneration was divided into three types. Initially, disc degeneration occurred due to disc space narrowing. After that, the intervertebral discs showed segmental instability with translation at the upper level. But the lower discs showed osteophyte formation, and occasionally lead to the collapse or spontaneous union. Conclusions The clinical results of the long-term follow-up data after ALIF became worse due to the adjacent disc degeneration. The progressive pattern of disc degeneration was different according to the adjacent levels. PMID:22708014

  16. Characterization of in vivo effects of platelet-rich plasma and biodegradable gelatin hydrogel microspheres on degenerated intervertebral discs.

    PubMed

    Sawamura, Kazuhide; Ikeda, Takumi; Nagae, Masateru; Okamoto, Shin-ichi; Mikami, Yasuo; Hase, Hitoshi; Ikoma, Kazuya; Yamada, Tetsuya; Sakamoto, Hirotaka; Matsuda, Ken-ichi; Tabata, Yasuhiko; Kawata, Mitsuhiro; Kubo, Toshikazu

    2009-12-01

    We have previously shown that administration of platelet-rich plasma-impregnated gelatin hydrogel microspheres (PRP-GHMs) into a degenerated intervertebral disc (IVD) markedly suppresses progression of IVD degeneration. In the current study, we characterized the in vivo effects of PRP-GHM treatment in a degenerated IVD model in rabbit. On magnetic resonance images, the IVD height was significantly greater after treatment with PRP-GHMs compared with phosphate-buffered saline-impregnated GHMs, PRP without GHMs, and needle puncture only. Water content was also preserved in PRP-GHM-treated IVDs. Consistent with this observation, the mRNA expression of proteoglycan core protein and type II collagen was significantly higher after PRP-GHM treatment compared with other treatment groups. No proliferating cells were found in the nucleus pulposus and inner annulus fibrosus in any groups, but the number of apoptotic cells in the nucleus pulposus after PRP-GHM treatment was significantly lower than that after other treatments. These results provide an improved understanding of the therapeutic effects of PRP-GHM treatment of degenerated IVDs.

  17. Injectable microcryogels reinforced alginate encapsulation of mesenchymal stromal cells for leak-proof delivery and alleviation of canine disc degeneration.

    PubMed

    Zeng, Yang; Chen, Chun; Liu, Wei; Fu, Qinyouen; Han, Zhihua; Li, Yaqian; Feng, Siyu; Li, Xiaokang; Qi, Chunxiao; Wu, Jianhong; Wang, Deli; Corbett, Christopher; Chan, Barbara P; Ruan, Dike; Du, Yanan

    2015-08-01

    In situ crosslinked thermo-responsive hydrogel applied for minimally invasive treatment of intervertebral disc degeneration (IVDD) may not prevent extrusion of cell suspension from injection site due to high internal pressure of intervertebral disc (IVD), causing treatment failure or osteophyte formation. In this study, mesenchymal stromal cells (MSCs) were encapsulated in alginate precursor and loaded into previously developed macroporous PGEDA-derived microcryogels (PMs) to form three-dimensional (3D) microscale cellular niches, enabling non-thermo-responsive alginate hydrogel to be injectable. The PMs reinforced alginate hydrogel showed superior elasticity compared to alginate hydrogel alone and could well protect encapsulated cells through injection. Chondrogenic committed MSCs in the injectable microniches expressed higher level of nucleus pulposus (NP) cell markers compared to 2D cultured cells. In an ex vivo organ culture model, injection of MSCs-laden PMs into NP tissue prevented cell leakage, improved cell retention and survival compared to free cell injection. In canine IVDD models, alleviated degeneration was observed in MSCs-laden PMs treated group after six months which was superior to other treated groups. Our results provide in-depth demonstration of injectable alginate hydrogel reinforced by PMs as a leak-proof cell delivery system for augmented regenerative therapy of IVDD in canine models.

  18. Analysis of the Relationship between Ligamentum Flavum Thickening and Lumbar Segmental Instability, Disc Degeneration, and Facet Joint Osteoarthritis in Lumbar Spinal Stenosis

    PubMed Central

    Yoshiiwa, Toyomi; Notani, Naoki; Ishihara, Toshinobu; Kawano, Masanori; Tsumura, Hiroshi

    2016-01-01

    Study Design Cross-sectional study. Purpose To investigate the relationship between ligamentum flavum (LF) thickening and lumbar segmental instability and disc degeneration and facet joint osteoarthritis. Overview of Literature Posterior spinal structures, including LF thickness, play a major role in lumbar spinal canal stenosis pathogenesis. The cause of LF thickening is multifactorial and includes activity level, age, and mechanical stress. LF thickening pathogenesis is unknown. Methods We examined 419 patients who underwent computed tomography (CT) myelography and magnetic resonance imaging after complaints of clinical symptoms. To investigate LF hypertrophy, 57 patients whose lumbar vertebra had normal disc heights at L4–5 were selected to exclude LF buckling as a hypertrophy component. LF thickness, disc space widening angulation in flexion, segmental angulation, presence of a vacuum phenomenon, and lumbar lordosis at T12–S1 were investigated. Disc and facet degeneration were also evaluated. Facet joint orientation was measured via an axial CT scan. Results The mean LF thickness in all patients was 4.4±1.0 mm at L4–5. There was a significant correlation between LF thickness and disc degeneration; LF thickness significantly increased with severe disc degeneration and facet joint osteoarthritis. There was a tendency toward increased LF thickness in more sagittalized facet joints than in coronalized facet joints. Logistic regression analysis showed that LF thickening was influenced by segmental angulation and facet joint osteoarthritis. Patient age was associated with LF thickening. Conclusions LF hypertrophy development was associated with segmental instability and severe disc degeneration, severe facet joint osteoarthritis, and a sagittalized facet joint orientation. PMID:27994791

  19. 2D segmentation of intervertebral discs and its degree of degeneration from T2-weighted magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Castro-Mateos, Isaac; Pozo, José Maria; Lazary, Aron; Frangi, Alejandro F.

    2014-03-01

    Low back pain (LBP) is a disorder suffered by a large population around the world. A key factor causing this illness is Intervertebral Disc (IVD) degeneration, whose early diagnosis could help in preventing this widespread condition. Clinicians base their diagnosis on visual inspection of 2D slices of Magnetic Resonance (MR) images, which is subject to large interobserver variability. In this work, an automatic classification method is presented, which provides the Pfirrmann degree of degeneration from a mid-sagittal MR slice. The proposed method utilizes Active Contour Models, with a new geometrical energy, to achieve an initial segmentation, which is further improved using fuzzy C-means. Then, IVDs are classified according to their degree of degeneration. This classification is attained by employing Adaboost on five specific features: the mean and the variance of the probability map of the nucleus using two different approaches and the eccentricity of the fitting ellipse to the contour of the IVD. The classification method was evaluated using a cohort of 150 intervertebral discs assessed by three experts, resulting in a mean specificity (93%) and sensitivity (83%) similar to the one provided by every expert with respect to the most voted value. The segmentation accuracy was evaluated using the Dice Similarity Index (DSI) and Root Mean Square Error (RMSE) of the point-to-contour distance. The mean DSI ± 2 standard deviation was 91:7% ±5:6%, the mean RMSE was 0:82mm and the 95 percentile was 1:36mm. These results were found accurate when compared to the state-of-the-art.

  20. 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

    PubMed Central

    Colombier, Pauline; Lesoeur, Julie; Youl, Samy; Madec, Stéphane; Gauthier, Olivier; Hamel, Olivier; Guicheux, Jérôme; Clouet, Johann

    2016-01-01

    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. PMID:27247937

  1. Matrix stiffness promotes cartilage endplate chondrocyte calcification in disc degeneration via miR-20a targeting ANKH expression

    PubMed Central

    Liu, Ming-Han; Sun, Chao; Yao, Yuan; Fan, Xin; Liu, Huan; Cui, You-Hong; Bian, Xiu-Wu; Huang, Bo; Zhou, Yue

    2016-01-01

    The mechanical environment is crucial for intervertebral disc degeneration (IDD). However, the mechanisms underlying the regulation of cartilage endplate (CEP) calcification by altered matrix stiffness remain unclear. In this study, we found that matrix stiffness of CEP was positively correlated with the degree of IDD, and stiff matrix, which mimicked the severe degeneration of CEP, promoted inorganic phosphate-induced calcification in CEP chondrocytes. Co-expression analysis of the miRNA and mRNA profiles showed that increasing stiffness resulted in up-regulation of miR-20a and down-regulation of decreased ankylosis protein homolog (ANKH) during inorganic phosphate-induced calcification in CEP chondrocytes. Through a dual luciferase reporter assay, we confirmed that miR-20a directly targets 3′-untranslated regions of ANKH. The inhibition of miR-20a attenuated the calcium deposition and calcification-related gene expression, whereas the overexpression of miR-20a enhanced calcification in CEP chondrocytes on stiff matrix. The rescue of ANKH expression restored the decreased pyrophosphate efflux and inhibited calcification. In clinical samples, the levels of ANKH expression were inversely associated with the degeneration degree of CEP. Thus, our findings demonstrate that the miR-20a/ANKH axis mediates the stiff matrix- promoted CEP calcification, suggesting that miR-20a and ANKH are potential targets in restraining the progression of IDD. PMID:27142968

  2. 1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model.

    PubMed

    Osti, O L; Vernon-Roberts, B; Fraser, R D

    1990-08-01

    An animal model was developed to test the hypothesis that discrete peripheral tears within the anulus lead to secondary degenerative changes in other disc components. In 21 adult sheep, a cut was made in the left anterolateral anulus of three randomly selected lumbar discs. The cut was parallel and adjacent to the inferior end-plate, and had a controlled depth of 5 mm. This left the inner third of the anulus and the nucleus pulposus intact and closely reproduced the rim Lear lesion described by Schmorl. Animals were randomly allocated to different groups in relation to the length of time interval between operation and death, varying from 1 to 18 months. At death, the lumbar spine was cut into individual joint units and each disc sectioned into six parasagittal slabs. After observation of the slabs under the dissecting microscope, two of the six slabs, the one containing the anulus lesion and a contralateral, were processed for histology. The results of this study suggest that, despite the great care taken at operation to ensure that the inner anulus was left intact, progressive failure of the inner anulus was seen in all sheep and occurred in the majority of discs between 4 and 12 months after the operation. Although the outermost anulus showed the ability to heal, the defect induced by the cut led initially to deformation and bulging of the collagen bundles, and eventually to inner extension of the tear and complete failure. These findings suggest that discrete tears of the outer anulus may have a role in the formation of concentric clefts and in accelerating the development of radiating clefts. Peripheral tears of the anulus fibrosus therefore may play an important role in the degeneration of the intervertebral joint complex.

  3. Injection of human umbilical tissue–derived cells into the nucleus pulposus alters the course of intervertebral disc degeneration in vivo

    PubMed Central

    Leckie, Steven K.; Sowa, Gwendolyn A.; Bechara, Bernard P.; Hartman, Robert A.; Coelho, Joao Paulo; Witt, William T.; Dong, Qing D.; Bowman, Brent W.; Bell, Kevin M.; Vo, Nam V.; Kramer, Brian C.; Kang, James D.

    2016-01-01

    Background context Patients often present to spine clinic with evidence of intervertebral disc degeneration (IDD). If conservative management fails, a safe and effective injection directly into the disc might be preferable to the risks and morbidity of surgery. Purpose To determine whether injecting human umbilical tissue–derived cells (hUTC) into the nucleus pulposus (NP) might improve the course of IDD. Design Prospective, randomized, blinded placebo–controlled in vivo study. Patient sample Skeletally mature New Zealand white rabbits. Outcome measures Degree of IDD based on magnetic resonance imaging (MRI), biomechanics, and histology. Methods Thirty skeletally mature New Zealand white rabbits were used in a previously validated rabbit annulotomy model for IDD. Discs L2–L3, L3–L4, and L4–L5 were surgically exposed and punctured to induce degeneration and then 3 weeks later the same discs were injected with hUTC with or without a hydrogel carrier. Serial MRIs obtained at 0, 3, 6, and 12 weeks were analyzed for evidence of degeneration qualitatively and quantitatively via NP area and MRI Index. The rabbits were sacrificed at 12 weeks and discs L4–L5 were analyzed histologically. The L3–L4 discs were fixed to a robotic arm and subjected to uniaxial compression, and viscoelastic displacement curves were generated. Results Qualitatively, the MRIs demonstrated no evidence of degeneration in the control group over the course of 12 weeks. The punctured group yielded MRIs with the evidence of disc height loss and darkening, suggestive of degeneration. The three treatment groups (cells alone, carrier alone, or cells+carrier) generated MRIs with less qualitative evidence of degeneration than the punctured group. MRI Index and area for the cell and the cell+carrier groups were significantly distinct from the punctured group at 12 weeks. The carrier group generated MRI data that fell between control and punctured values but failed to reach a statistically

  4. A papain-induced disc degeneration model for the assessment of thermo-reversible hydrogel-cells therapeutic approach.

    PubMed

    Malonzo, C; Chan, S C W; Kabiri, A; Eglin, D; Grad, S; Bonél, H M; Benneker, L M; Gantenbein-Ritter, B

    2015-12-01

    Nucleus pulposus (NP) regeneration by the application of injectable cell-embedded hydrogels is an appealing approach for tissue engineering. We investigated a thermo-reversible hydrogel (TR-HG), based on a modified polysaccharide with a thermo-reversible polyamide [poly(N-isopropylacrylamide), pNIPAM], which is made to behave as a liquid at room temperature and hardens at > 32 °C. In order to test the hydrogel, a papain-induced bovine caudal disc degeneration model (PDDM), creating a cavity in the NP, was employed. Human mesenchymal stem cells (hMSCs) or autologous bovine NP cells (bNPCs) were seeded in TR-HG; hMSCs were additionally preconditioned with rhGDF-5 for 7 days. Then, TR-HG was reversed to a fluid and the cell suspension injected into the PDDM and kept under static loading for 7 days. Experimental design was: (D1) fresh disc control + PBS injection; (D2) PDDM + PBS injection; (D3) PDDM + TR-HG (material control); (D4) PDDM + TR-HG + bNPCs; (D5) PDDM + TR-HG + hMSCs. Magnetic resonance imaging performed before and after loading, on days 9 and 16, allowed imaging of the hydrogel-filled PDDM and assessment of disc height and volume changes. In gel-injected discs the NP region showed a major drop in volume and disc height during culture under static load. The RT-PCR results of injected hMSCs showed significant upregulation of ACAN, COL2A1, VCAN and SOX9 during culture in the disc cavity, whereas the gene expression profile of NP cells remained unchanged. The cell viability of injected cells (NPCs or hMSCs) was maintained at over 86% in 3D culture and dropped to ~72% after organ culture. Our results underline the need for load-bearing hydrogels that are also cyto-compatible.

  5. Lumbar intervertebral disc degeneration associated with axial and radiating low back pain in ageing SPARC-null mice.

    PubMed

    Millecamps, Magali; Tajerian, Maral; Naso, Lina; Sage, E Helene; Stone, Laura S

    2012-06-01

    Chronic low back pain (LBP) is a complex, multifactorial disorder with unclear underlying mechanisms. In humans and rodents, decreased expression of secreted protein acidic rich in cysteine (SPARC) is associated with intervertebral disc (IVD) degeneration and signs of LBP. The current study investigates the hypothesis that IVD degeneration is a risk factor for chronic LBP. SPARC-null and age-matched control mice ranging from 6 to 78 weeks of age were evaluated in this study. X-ray and histologic analysis revealed reduced IVD height, increased wedging, and signs of degeneration (bulging and herniation). Cutaneous sensitivity to cold, heat, and mechanical stimuli were used as measures of referred (low back and tail) and radiating pain (hind paw). Region specificity was assessed by measuring icilin- and capsaicin-evoked behaviour after subcutaneous injection into the hind paw or upper lip. Axial discomfort was measured by the tail suspension and grip force assays. Motor impairment was determined by the accelerating rotarod. Physical function was evaluated by voluntary activity after axial strain or during ambulation with forced lateral flexion. SPARC-null mice developed (1) region-specific, age-dependent hypersensitivity to cold, icilin, and capsaicin (hind paw only), (2) axial discomfort, (3) motor impairment, and (4) reduced physical function. Morphine (6 mg/kg, i.p.) reduced cutaneous sensitivity and alleviated axial discomfort in SPARC-null mice. Ageing SPARC-null mice mirror many aspects of the complex and challenging nature of LBP in humans and incorporate both anatomic and functional components of the disease. The current study supports the hypothesis that IVD degeneration is a risk factor for chronic LBP.

  6. Atomic Absorption Spectrometry Analysis of Trace Elements in Degenerated Intervertebral Disc Tissue

    PubMed Central

    Kubaszewski, Łukasz; Zioła-Frankowska, Anetta; Frankowski, Marcin; Nowakowski, Andrzej; Czabak-Garbacz, Róża; Kaczmarczyk, Jacek; Gasik, Robert

    2014-01-01

    Background Few studies have investigated trace elements (TE) in human intervertebral disc (IVD) tissue. Trace element presence can have diverse meanings: essential TE show the metabolic modalities of the tissue, while environmentally-related TE indicate pollution and tissue-specific absorption and accumulation. IVD is a highly specific compartment with impaired communication with adjacent bone. Analysis of TE in IVD provides new insights regarding tissue metabolism and IVD communication with other tissues. Material/Methods Thirty intervertebral discs were acquired from 22 patients during surgical treatment for degenerative disease. Atomic absorption spectrometry was used to evaluate the concentrations of Al, Cd, Pb, Cu, Ni, Mo, Mg, and Zn. Results Al, Pb, Cu, Mg, and Zn were detected in all samples. Pb was significantly positively correlated with age, and Ni concentration was weakly correlated with population count in the patient’s place of residence. Only Cu was observed in higher concentrations in IVD compared to in other tissues. Significant positive correlations were observed between the following pairs: Mg/Zn, Mg/Al, Mg/Pb, Zn/Al, Zn/Pb, and Al/Pb. Negative correlations were observed between Mg/Cd, Zn/Cd, Mg/Mo, and Mo/Pb. Conclusions This study is one of few to profile the elements in intervertebral discs in patients with degenerative changes. We report significant differences between trace element concentrations in intervertebral discs compared to in other tissues. Knowledge of the TE accumulation pattern is vital for better understanding intervertebral disc nutrition and metabolism. PMID:25366266

  7. Association of matrilin‐3 polymorphisms with spinal disc degeneration and osteoarthritis of the first carpometacarpal joint of the hand

    PubMed Central

    Min, J L; Meulenbelt, I; Riyazi, N; Kloppenburg, M; Houwing‐Duistermaat, J J; Seymour, A B; van Duijn, C M; Slagboom, P E

    2006-01-01

    Background Seven polymorphisms in the matrilin‐3(MATN3) gene were previously tested for genetic association with hand osteoarthritis in an Icelandic cohort. One of the variants, involving a conserved amino acid substitution (T303M; SNP5), was related to idiopathic hand osteoarthritis. Objectives To investigate SNP5 and two other promising polymorphisms (rs2242190; SNP3, rs8176070; SNP6) for association with radiographic and symptomatic hand osteoarthritis phenotypes, as well as other heritable phenotypes. Methods Polymorphisms were examined in two distinct cohorts of subjects: a population based sample from the Rotterdam study (n = 809), and affected siblings from the genetics, osteoarthrosis and progression (GARP) study (n = 382). Results The originally described association of T303M with the hand osteoarthritis phenotype was not observed in the populations studied. In the Rotterdam sample, however, carrying the T allele of T303M conferred an odds ratio of 2.9 (95% confidence interval (CI), 1.2 to 7.3; p = 0.02) for spinal disc degeneration. In the GARP study, carriers of the A allele of SNP6 had an odds ratio of 2.0 (95% CI, 1.3 to 3.1, p = 0.004) for osteoarthritis of the first carpometacarpal joint (CMC1) as compared with the Rotterdam sample as a control group. Subsequent haplotype analysis showed that a common haplotype, containing the risk allele of SNP6, conferred a significant risk in sibling pairs with CMC1 osteoarthritis (odds ratio = 1.7 (95% CI, 1.1 to 2.7, p = 0.02)). Conclusions These associations suggest that the MATN3 region also determines susceptibility to spinal disc degeneration and CMC1 osteoarthritis. PMID:16396979

  8. Heme oxygenase-1 attenuates IL-1β induced alteration of anabolic and catabolic activities in intervertebral disc degeneration

    PubMed Central

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

    2016-01-01

    Intervertebral disc degeneration (IDD) is characterized by disordered extracellular matrix (ECM) metabolism, implicating subdued anabolism and enhanced catabolic activities in the nucleus pulposus (NP) of discs. Pro-inflammatory cytokines such as interleukin-1β (IL-1β) are considered to be potent mediators of ECM breakdown. Hemeoxygenase-1 (HO-1) has been reported to participate in cellular anti-inflammatory processes. The purpose of this study was to investigate HO-1 modulation of ECM metabolism in human NP cells under IL-1β stimulation. Our results revealed that expression of HO-1 decreased considerably during IDD progression. Induction of HO-1 by cobalt protoporphyrin IX attenuated the inhibition of sulfate glycosaminoglycan and collagen type II (COL-II) synthesis and ameliorated the reduced expressions of aggrecan, COL-II, SOX-6 and SOX-9 mediated by IL-1β. Induction of HO-1 also reversed the effect of IL-1β on expression of the catabolic markers matrix metalloproteinases-1, 3, 9 and 13. This was combined with inhibition of the activation of mitogen-activated protein kinase signaling. These findings suggest that HO-1 might play a pivotal role in IDD, and that manipulating HO-1 expression might mitigate the impairment of ECM metabolism in NP, thus potentially offering a novel therapeutic approach to the treatment of IDD. PMID:26877238

  9. Enhancement of Lumbar Fusion and Alleviation of Adjacent Segment Disc Degeneration by Intermittent PTH(1-34) in Ovariectomized Rats.

    PubMed

    Zhou, Zhuang; Tian, Fa-Ming; Gou, Yu; Wang, Peng; Zhang, Heng; Song, Hui-Ping; Shen, Yong; Zhang, Ying-Ze; Zhang, Liu

    2016-04-01

    Osteoporosis, which is prevalent in postmenopausal or aged populations, is thought to be a contributing factor to adjacent segment disc degeneration (ASDD), and the incidence and extent of ASDD may be augmented by osteopenia. Parathyroid hormone (PTH) (1-34) has already been shown to be beneficial in osteoporosis, lumbar fusion and matrix homeostasis of intervertebral discs. However, whether PTH(1-34) has a reversing or retarding effect on ASDD in osteopenia has not been confirmed. In the present study, we evaluated the effects of intermittent PTH(1-34) on ASDD in an ovariectomized (OVX) rat model. One hundred 3-month-old female Sprague-Dawley rats underwent L4 -L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after OVX surgery. Control groups were established accordingly. PTH(1-34) was intermittently administered immediately after PLF surgery and lasted for 8 weeks using the following groups (n = 20) (V = vehicle): Sham+V, OVX+V, Sham+PLF+V, OVX+PLF+V, OVX+PLF+PTH. The fused segments showed clear evidence of eliminated motion on the fusion-segment based on manual palpation. Greater new bone formation in histology was observed in PTH-treated animals compared to the control group. The extent of ASDD was significantly increased by ovariotomy. Intermittent PTH(1-34) significantly alleviated ASDD by preserving disc height, microvessel density, relative area of vascular buds, endplate thickness and the relative area of endplate calcification. Moreover, protein expression results showed that PTH(1-34) not only inhibited matrix degradation by decreasing MMP-13, ADAMTS-4 and Col-I, but also promote matrix synthesis by increasing Col-II and Aggrecan. In conclusion, PTH(1-34), which effectively improves lumbar fusion and alleviates ASDD in ovariectomized rats, may be a potential candidate to ameliorate the prognosis of lumbar fusion in osteopenia.

  10. Interleukin-1 receptor antagonist delivered directly and by gene therapy inhibits matrix degradation in the intact degenerate human intervertebral disc: an in situ zymographic and gene therapy study

    PubMed Central

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

    2007-01-01

    Data implicate IL-1 in the altered matrix biology that characterizes human intervertebral disc (IVD) degeneration. In the current study we investigated the enzymic mechanism by which IL-1 induces matrix degradation in degeneration of the human IVD, and whether the IL-1 inhibitor IL-1 receptor antagonist (IL-1Ra) will inhibit degradation. A combination of in situ zymography (ISZ) and immunohistochemistry was used to examine the effects of IL-1 and IL-1Ra on matrix degradation and metal-dependent protease (MDP) expression in explants of non-degenerate and degenerate human IVDs. ISZ employed three substrates (gelatin, collagen, casein) and different challenges (IL-1β, IL-1Ra and enzyme inhibitors). Immunohistochemistry was undertaken for MDPs. In addition, IL-1Ra was introduced into degenerate IVD explants using genetically engineered constructs. The novel findings from this study are: IL-1Ra delivered directly onto explants of degenerate IVDs eliminates matrix degradation as assessed by multi-substrate ISZ; there is a direct relationship between matrix degradation assessed by ISZ and MDP expression defined by immunohistochemistry; single injections of IVD cells engineered to over-express IL-1Ra significantly inhibit MDP expression for two weeks. Our findings show that IL-1 is a key cytokine driving matrix degradation in the degenerate IVD. Furthermore, IL-1Ra delivered directly or by gene therapy inhibits IVD matrix degradation. IL-1Ra could be used therapeutically to inhibit degeneration of the IVD. PMID:17760968

  11. Bone architecture and disc degeneration in the lumbar spine of mice lacking GDF-8 (myostatin).

    PubMed

    Hamrick, Mark W; Pennington, Catherine; Byron, Craig D

    2003-11-01

    GDF-8, also known as myostatin, is a member of the transforming growth factor-beta superfamily of secreted growth and differentiation factors that is expressed in vertebrate skeletal muscle. Myostatin functions as a negative regulator of skeletal muscle growth and myostatin null mice show a doubling of muscle mass compared to normal mice. We describe here morphology of the lumbar spine in myostatin knockout (Mstn(-/-)) mice using histological and densitometric techniques. The Mstn(-/-) mice examined in this study weigh approximately 10% more than controls (p<0.001) but the iliopsoas muscle is over 50% larger in the knockout mice than in wild-type mice (p<0.001). Peripheral quantitative computed tomography (pQCT) data from the fifth lumbar vertebra show that mice lacking myostatin have approximately 50% greater trabecular bone mineral density (p=0.001) and significantly greater cortical bone mineral content than normal mice. Toluidine blue staining of the intervertebral disc between L4-L5 reveals loss of proteoglycan staining in the hyaline end plates and inner annulus fibrosus of the knockout mice. Loss of cartilage staining in the caudal end plate of L4 is due to ossification of the end plate in the myostatin-deficient animals. Results from this study suggest that increased muscle mass in mice lacking myostatin is associated with increased bone mass as well as degenerative changes in the intervertebral disc.

  12. Narrowing of lumbar spinal canal predicts chronic low back pain more accurately than intervertebral disc degeneration: a magnetic resonance imaging study in young Finnish male conscripts.

    PubMed

    Visuri, Tuomo; Ulaska, Jaana; Eskelin, Marja; Pulkkinen, Pekka

    2005-11-01

    The objective of this magnetic resonance imaging study was to evaluate the role of degenerative changes, developmental spinal stenosis, and compression of spinal nerve roots in chronic low back (CLBP) and radicular pain in Finnish conscripts. The degree of degeneration, protrusion, and herniation of the intervertebral discs and stenosis of the nerve root canals was evaluated, and the midsagittal diameter and cross-sectional area of the lumbar vertebrae canal were measured in 108 conscripts with CLBP and 90 asymptomatic controls. The midsagittal diameters at L1-L4 levels were significantly smaller in the patients with CLBP than in the controls. Moreover, degeneration of the L4/5 disc and protrusion or herniation of the L5/S1 disc and stenosis of the nerve root canals at level L5/S1 were more frequent among the CLBP patients. Multifactorial analysis of the magnetic resonance imaging findings provided a total explanatory rate of only 33%. Narrowing of the vertebral canal in the anteroposterior direction was more likely to produce CLBP and radiating pain than intervertebral disc degeneration or narrowing of the intervertebral nerve root canals.

  13. The elastic fibre network of the human lumbar anulus fibrosus: architecture, mechanical function and potential role in the progression of intervertebral disc degeneration

    PubMed Central

    Fazzalari, Nicola L.

    2009-01-01

    Elastic fibres are critical constituents of dynamic biological structures that functionally require elasticity and resilience. The network of elastic fibres in the anulus fibrosus of the intervertebral disc is extensive, however until recently, the majority of histological, biochemical and biomechanical studies have focussed on the roles of other extracellular matrix constituents such as collagens and proteoglycans. The resulting lack of detailed descriptions of elastic fibre network architecture and mechanical function has limited understanding of the potentially important contribution made by elastic fibres to healthy disc function and their possible roles in the progression of disc degeneration. In addition, it has made it difficult to postulate what the consequences of elastic fibre related disorders would be for intervertebral disc behaviour, and to develop treatments accordingly. In this paper, we review recent and historical studies which have examined both the structure and the function of the human lumbar anulus fibrosus elastic fibre network, provide a synergistic discussion in an attempt to clarify its potentially critical contribution both to normal intervertebral disc behaviour and the processes relating to its degeneration, and recommend critical areas for future research. PMID:19263091

  14. IL-21 Is Positively Associated with Intervertebral Disc Degeneration by Interaction with TNF-α Through the JAK-STAT Signaling Pathway.

    PubMed

    Chen, Bin; Liu, Yi; Zhang, YuanQiang; Li, JingKun; Cheng, KaiYuan; Cheng, Lei

    2017-04-01

    This study was conducted in order to investigate the function of IL-21 in intervertebral disc degeneration. The serum concentration of IL-21 in patients with lumbar disc herniation (LDH) was examined by ELISA. Immunohistochemistry and western blot analysis were performed to detect the expression of IL-21, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-7), and tumor necrosis factor alpha (TNF-α) in degenerated intervertebral disc (IVD) tissues of human and rat. Moreover, nucleus pulposus (NP) cells were treated with 0, 10, 100, and 1000 ng/mL of IL-21 cytokine with and without AG490. TNF-α, ADAMTS-7, and matrix metalloproteinases-13 (MMP-13) mRNA expression was determined by RT-PCR. The expression of signal transducers and activators of transcription, STAT-1, STAT-3, and STAT-5b, was detected by western blot. IL-21 concentration level is higher in the degenerated group and positively correlates with the visual analog score (VAS). IL-21, ADAMTS-7, and TNF-α can be detected in the degenerative NP tissues in both human and rat degenerated NP tissues. The mRNA expression of ADAMTS-7, TNF-α, and MMP-13 was enhanced after stimulation with IL-21. Compared to control, STAT-1, STAT-3, and STAT-5b expression was also enhanced after IL-21 treatment, with STAT-3 being the most significantly enhanced; furthermore, expression was significantly reduced after treatment with AG490. The mRNA expression of TNF-α was markedly reduced after treatment with AG490 compared to treatment with IL-21 only. IL-21 is involved in the pathological development of IVD degeneration and IL-21 could aggravate IVD degeneration by stimulating TNF-α through the STAT signaling pathway.

  15. Early stage disc degeneration does not have an appreciable affect on stiffness and load transfer following vertebroplasty and kyphoplasty

    PubMed Central

    Keller, Tony S.; Schizas, Constantin

    2008-01-01

    Vertebroplasty and kyphoplasty have been reported to alter the mechanical behavior of the treated and adjacent-level segments, and have been suggested to increase the risk for adjacent-level fractures. The intervertebral disc (IVD) plays an important role in the mechanical behavior of vertebral motion segments. Comparisons between normal and degenerative IVD motion segments following cement augmentation have yet to be reported. A microstructural finite element model of a degenerative IVD motion segment was constructed from micro-CT images. Microdamage within the vertebral body trabecular structure was used to simulate a slightly (I = 83.5% of intact stiffness), moderately (II = 57.8% of intact stiffness), and severely (III = 16.0% of intact stiffness) damaged motion segment. Six variable geometry single-segment cement repair strategies (models A–F) were studied at each damage level (I–III). IVD and bone stresses, and motion segment stiffness, were compared with the intact and baseline damage models (untreated), as well as, previous findings using normal IVD models with the same repair strategies. Overall, small differences were observed in motion segment stiffness and average stresses between the degenerative and normal disc repair models. We did however observe a reduction in endplate bulge and a redistribution in the microstructural tissue level stresses across both endplates and in the treated segment following early stage IVD degeneration. The cement augmentation strategy placing bone cement along the periphery of the vertebra (model E) proved to be the most advantageous in treating the degenerative IVD models by showing larger reductions in the average bone stresses (vertebral and endplate) as compared to the normal IVD models. Furthermore, only this repair strategy, and the complete cement fill strategy (model F), were able to restore the slightly damaged (I) motion segment stiffness above pre-damaged (intact) levels. Early stage IVD degeneration

  16. TGFβ regulates Galectin-3 expression through canonical Smad3 signaling pathway in nucleus pulposus cells: implications in intervertebral disc degeneration.

    PubMed

    Tian, Ye; Yuan, Wen; Li, Jun; Wang, Hua; Hunt, Maxwell G; Liu, Chao; Shapiro, Irving M; Risbud, Makarand V

    2016-03-01

    Galectin-3 is highly expressed in notochordal nucleus pulposus (NP) and thought to play important physiological roles; however, regulation of its expression remains largely unexplored. The aim of the study was to investigate if TGFβ regulates Galectin-3 expression in NP cells. TGFβ treatment resulted in decreased Galectin-3 expression. Bioinformatic analysis using JASPAR and MatInspector databases cross-referenced with published ChIP-Seq data showed nine locations of highly probable Smad3 binding in the LGALS3 proximal promoter. In NP cells, TGFβ treatment resulted in decreased activity of reporters harboring several 5' deletions of the proximal Galectin-3 promoter. While transfection of NP cells with constitutively active (CA)-ALK5 resulted in decreased promoter activity, DN-ALK5 blocked the suppressive effect of TGFβ on the promoter. The suppressive effect of Smad3 on the Galectin-3 promoter was confirmed using gain- and loss-of-function studies. Transfection with DN-Smad3 or Smad7 blocked TGFβ mediated suppression of promoter activity. We also measured Galectin-3 promoter activity in Smad3 null and wild type cells. Noteworthy, promoter activity was suppressed by TGFβ only in wild type cells. Likewise, stable silencing of Smad3 in NP cells using sh-Smad3 significantly blocked TGFβ-dependent decrease in Galectin-3 expression. Treatment of human NP cells isolated from tissues with different grades of degeneration showed that Galectin-3 expression was responsive to TGF-β-mediated suppression. Importantly, Galectin-3 synergized effects of TNF-α on inflammatory gene expression by NP cells. Together these studies suggest that TGFβ, through Smad3 controls Galectin-3 expression in NP cells and may have implications in the intervertebral disc degeneration.

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

    PubMed

    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.

  18. Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)

    ClinicalTrials.gov

    2017-03-01

    FTLD; Progressive Supranuclear Palsy (PSP); Frontotemporal Dementia (FTD); Corticobasal Degeneration (CBD); PPA Syndrome; Behavioral Variant Frontotemporal Dementia (bvFTD); Semantic Variant Primary Progressive Aphasia (svPPA); Nonfluent Variant Primary Progressive Aphasia (nfvPPA); FTD With Amyotrophic Lateral Sclerosis (FTD/ALS); Amyotrophic Lateral Sclerosis (ALS); Oligosymptomatic PSP (oPSP); Corticobasal Syndrome (CBS)

  19. Genetic polymorphisms of interleukin-1 alpha and the vitamin d receptor in mexican mestizo patients with intervertebral disc degeneration.

    PubMed

    Cervin Serrano, Salvador; González Villareal, Dalia; Aguilar-Medina, Maribel; Romero-Navarro, Jose Guillermo; Romero Quintana, Jose Geovanni; Arámbula Meraz, Eliakym; Osuna Ramírez, Ignacio; Picos-Cárdenas, Veronica; Granados, Julio; Estrada-García, Iris; Sánchez-Schmitz, Guzman; Ramos-Payán, Rosalío

    2014-01-01

    Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population.

  20. Genetic Polymorphisms of Interleukin-1 Alpha and the Vitamin D Receptor in Mexican Mestizo Patients with Intervertebral Disc Degeneration

    PubMed Central

    Cervin Serrano, Salvador; González Villareal, Dalia; Aguilar-Medina, Maribel; Romero-Navarro, Jose Guillermo; Romero Quintana, Jose Geovanni; Arámbula Meraz, Eliakym; Osuna Ramírez, Ignacio; Picos-Cárdenas, Veronica; Granados, Julio; Estrada-García, Iris; Sánchez-Schmitz, Guzman; Ramos-Payán, Rosalío

    2014-01-01

    Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population. PMID:25506053

  1. Degenerated intervertebral disc prolapse and its association of collagen I alpha 1 Spl gene polymorphism: A preliminary case control study of Indian population

    PubMed Central

    Anjankar, Shailendra D; Poornima, Subhadra; Raju, Subodh; Jaleel, MA; Bhiladvala, Dilnavaz; Hasan, Qurratulain

    2015-01-01

    Background: Degenerated disc disease (DDD) is a common disorder responsible for increased morbidity in a productive age group. Its etiology is multifactorial and genetic factors have been predominantly implicated. Disc prolapse results due to tear in the annulus, which is a fibrous structure composed largely of type I collagen. Functional polymorphism at the Sp1 site of the collagen I alpha 1 (COL1A1) gene has shown a positive association with DDD in Dutch and Greek populations. The purpose of this study was to assess COL1A1 Sp1 gene polymorphism in the Indian population. Materials and Methods: Fifty clinically and radiologically proven patients with disc prolapse requiring surgery were included as cases and 50 healthy, age-matched volunteers served as controls. After isolating DNA from their blood sample, genotyping for COL1A1 polymorphism (rs1800012) was performed and identified as GG, GT, and TT. Results: The mean age and body mass index in cases and controls were similar. 76% of the patients were males. The most common site of disc degeneration was L4–L5 (36%), followed by L5–S1 (34%). Homozygous–GG, heterozygous GT, and homozygous TT genotypes were seen in 38 (76%), 10 (20%) and 2 (4%) cases respectively, controls had similar percentage of genotypes as well. The alleles in cases and the control group showed no significant difference (P = 0.6744) and followed the Hardy–Weinberg Equilibrium in the study population. Conclusion: The COL1A1 (rs1800012) is in Hardy–Weinberg equilibrium in the present subset of Indian population. But taken as a single factor, it was not found to be associated with DDD in this preliminary study. Disc degeneration is multifactorial and also anticipated to be a result of multiple genes involvement and gene-gene interaction. PMID:26806964

  2. Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes

    PubMed Central

    Dissanayake, Poruwalage Harsha; Senarath, Upul; Wijayaratne, Lalith Sirimevan; Karunanayake, Aranjan Lional; Dissanayake, Vajira Harshadeva Weerabaddana

    2017-01-01

    Introduction Lumbar disc degeneration (LDD) is genetically determined and severity of LDD is associated with Modic changes. Aggrecan is a major proteoglycan in the intervertebral disc and end plate. Progressive reduction of aggrecan is a main feature of LDD and Modic changes. Objectives The study investigated the associations of single nucleotide variants (SNVs) of candidate genes in the aggrecan metabolic pathway with the severity of LDD and Modic changes. In-silico functional analysis of significant SNVs was also assessed. Methods A descriptive cross sectional study was carried out on 106 patients with chronic mechanical low back pain. T1, T2 sagittal lumbar MRI scans were used to assess the severity of LDD and Modic changes. 62 SNVs in ten candidate genes (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on Sequenom MassARRAY iPLEX platform. Multiple linear regression analysis was carried out using PLINK 1.9 in accordance with additive genetic model. In-silico functional analysis was carried out using Provean, SIFT, PolyPhen and Mutation Taster. Results Mean age was 52.42±9.42 years. 74 (69.8%) were females. The rs2856836, rs1304037, rs17561 and rs1800587 variants of the IL1A gene were associated with the severity of LDD and Modic changes. The rs41270041 variant of the ADAMTS4 gene and the rs226794 variant of the ADAMTS5 gene were associated with severity of LDD while the rs34884997 variant of the ADAMTS4 gene, the rs55933916 variant of the ADAMTS5 gene and the rs9862 variant of the TIMP3 gene were associated with severity of Modic changes. The rs17561 variant of the IL1A gene was predicted as pathogenic by the PolyPhen prediction tool. Conclusions SNVs of candidate genes in ACAN metabolic pathway are associated with severity of LDD and Modic changes in patients with chronic mechanical low back pain. Predictions of in-silico functional analysis of significant SNVs are inconsistent. PMID:28081267

  3. OPG rs2073617 polymorphism is associated with upregulated OPG protein expression and an increased risk of intervertebral disc degeneration

    PubMed Central

    Xue, Jing-Bo; Zhan, Xin-Li; Wang, Wen-Jun; Yan, Yi-Guo; Liu, Chong

    2016-01-01

    The present study aimed to investigate the associations between three distinct osteoprotegerin (OPG) gene polymorphisms and the risk of intervertebral disc degeneration (IDD). A total of 200 IDD patients and 200 healthy controls were recruited from the Department of Spine Surgery at the First Affiliated Hospital of the University of South China (Hengyang, China) between January 2013 and May 2014. The allele, genotype and haplotype frequency distributions of three OPG polymorphisms in the study and control populations were analyzed by polymerase chain reaction prior to restriction fragment length polymorphism or high resolution melting assays. In addition, serum OPG levels were measured via an ELISA. The genotype and allele frequencies of the OPG rs2073617 polymorphisms were significantly higher in the IDD patients, as compared with the control group (P<0.05). Furthermore, carriers of the C allele exhibited a higher risk of IDD, as compared with carriers of the T allele (P<0.001). Conversely, the genotype and allele frequencies of the two other gene polymorphisms, rs2073618 and rs3102735, showed no significant differences between the patients and controls (P>0.05). The serum OPG levels were significantly higher in IDD patients with TT, TC and CC genotypes at the OPG rs2073617 polymorphism, as compared with the control group (P<0.05). Logistic-regression analysis suggested that high serum levels of OPG were positively correlated with IDD risk, whereas the T-C-A, T-G-A and T-G-G haplotypes were negatively correlated with IDD risk (P<0.05). Furthermore, the G-T-G haplotype was associated with protection against IDD (P=0.008), whereas the G-C-G haplotype was associated with an elevated susceptibility to IDD (P=0.007). The results of the present study suggested that OPG rs2073617 polymorphisms and upregulated serum levels of OPG were associated with an increased risk of IDD, whereas the T-C-A, T-G-A and T-G-G haplotypes were protective factors for IDD. The results of the

  4. Mutation of a Drosophila gamma tubulin ring complex subunit encoded by discs degenerate-4 differentially disrupts centrosomal protein localization

    PubMed Central

    Barbosa, Vitor; Yamamoto, Rochele R.; Henderson, Daryl S.; Glover, David M.

    2000-01-01

    We have cloned the Drosophila gene discs degenerate-4 (dd4) and find that it encodes a component of the γ-tubulin ring complex (γTuRC) homologous to Spc98 of budding yeast. This provides the first opportunity to study decreased function of a member of the γ-tubulin ring complex, other than γ-tubulin itself, in a metazoan cell. γ-tubulin is no longer at the centrosomes but is dispersed throughout dd4 cells and yet bipolar metaphase spindles do form, although these have a dramatically decreased density of microtubules. Centrosomin (CNN) remains in broad discrete bodies but only at the focused poles of such spindles, whereas Asp (abnormal spindle protein) is always present at the presumptive minus ends of microtubules, whether or not they are focused. This is consistent with the proposed role of Asp in coordinating the nucleation of mitotic microtubule organizing centers. The centrosome associated protein CP190 is partially lost from the spindle poles in dd4 cells supporting a weak interaction with γ-tubulin, and the displaced protein accumulates in the vicinity of chromosomes. Electron microscopy indicates not only that the poles of dd4 cells have irregular amounts of pericentriolar material, but also that they can have abnormal centrioles. In six dd4 cells subjected to serial sectioning centrioles were missing from one of the two poles. This suggests that in addition to its role in nucleating cytoplasmic and spindle microtubules, the γTuRC is also essential to the structure of centrioles and the separation of centrosomes. PMID:11124805

  5. Cervical Total Disc Arthroplasty

    PubMed Central

    Basho, Rahul; Hood, Kenneth A.

    2012-01-01

    Symptomatic adjacent segment degeneration of the cervical spine remains problematic for patients and surgeons alike. Despite advances in surgical techniques and instrumentation, the solution remains elusive. Spurred by the success of total joint arthroplasty in hips and knees, surgeons and industry have turned to motion preservation devices in the cervical spine. By preserving motion at the diseased level, the hope is that adjacent segment degeneration can be prevented. Multiple cervical disc arthroplasty devices have come onto the market and completed Food and Drug Administration Investigational Device Exemption trials. Though some of the early results demonstrate equivalency of arthroplasty to fusion, compelling evidence of benefits in terms of symptomatic adjacent segment degeneration are lacking. In addition, non-industry-sponsored studies indicate that these devices are equivalent to fusion in terms of adjacent segment degeneration. Longer-term studies will eventually provide the definitive answer. PMID:24353955

  6. 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

    NASA Astrophysics Data System (ADS)

    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.

  7. Foveal-Sparing Scotomas in Advanced Dry Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Sunness, Janet S.; Rubin, Gary S.; Zuckerbrod, Abraham; Applegate, Carol A.

    2008-01-01

    Foveal-sparing scotomas are common in advanced dry macular degeneration (geographic atrophy). Foveal preservation may be present for a number of years. Despite good visual acuity, these patients have reduced reading rates. Magnification may not be effective if the text becomes too large to "fit" within the central spared area. (Contains 2 tables…

  8. The noncoding RNA linc-ADAMTS5 cooperates with RREB1 to protect from intervertebral disc degeneration through inhibiting ADAMTS5 expression.

    PubMed

    Wang, Kun; Song, Yu; Liu, Wei; Wu, Xinghuo; Zhang, Yukun; Li, Shuai; Kang, Liang; Tu, Ji; Zhao, Kangcheng; Hua, Wenbin; Yang, Cao

    2017-03-24

    Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneration. However, the mechanisms that regulate ADAMTS5 expression in nuclear pulposus (NP) cells remain largely unknown. Evidence suggests that intergenic transcription may be associated with genes that encode transcriptional regulators. Here, we identified a long intergenic noncoding RNA, linc-ADAMTS5, that was transcribed in the opposite direction of ADAMTS5. In this study, through mining computational algorithm programs, and public available data sets, we identified Ras responsive element binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells. RNA pull-down, RNA immunoprecipitation, in vitro binding assays, and gain- and loss-of-function studies indicated that a physical interaction between linc-ADAMTS5 and splicing factor proline/glutamine-rich (SFPQ) facilitated the recruitment of RREB1 to binding sites within the ADAMTS5 promoter to induce chromatin remodeling. This resulted in subdued ADAMTS5 levels in cultured NP cells involving histone deacetylases. In clinical NP tissues, linc-ADAMTS5 and RREB1 were correlated negatively with ADAMTS5 expression. Taken together, these results demonstrate that RREB1 cooperates with noncoding RNA linc-ADAMTS5 to inhibit ADAMTS5 expression, thereby affecting degeneration of the extracellular matrix of the intervertebral disc.

  9. Temporomandibular Joint Condylar Changes Following Maxillomandibular Advancement and Articular Disc Repositioning

    PubMed Central

    Goncalves, Joao Roberto; Wolford, Larry Miller; Cassano, Daniel Serra; da Porciuncula, Guilherme; Paniagua, Beatriz; Cevidanes, Lucia Helena

    2014-01-01

    Purpose To evaluate condylar changes 1 year after bimaxillary surgical advancement with or without articular disc repositioning using longitudinal quantitative measurements in 3-dimensional (3D) temporomandibular joint (TMJ) models. Methods Twenty-seven patients treated with maxillomandibular advancement (MMA) underwent cone-beam computed tomography before surgery immediately after surgery and at 1-year follow-up. All patients underwent magnetic resonance imaging before surgery to assess disc displacements. Ten patients without disc displacement received MMA only. Seventeen patients with articular disc displacement received MMA with simultaneous TMJ disc repositioning (MMA-Drep). Pre- and postsurgical 3D models were superimposed using a voxel-based registration on the cranial base. Results The location, direction, and magnitude of condylar changes were displayed and quantified by graphic semitransparent overlays and 3D color-coded surface distance maps. Rotational condylar displacements were similar in the 2 groups. Immediately after surgery, condylar translational displacements of at least 1.5 mm occurred in a posterior, superior, or mediolateral direction in patients treated with MMA, whereas patients treated with MMA-Drep presented more marked anterior, inferior, and mediolateral condylar displacements. One year after surgery, more than half the patients in the 2 groups presented condylar resorptive changes of at least 1.5 mm. Patients treated with MMA-Drep presented condylar bone apposition of at least 1.5 mm at the superior surface in 26.4%, the anterior surface in 23.4%, the posterior surface in 29.4%, the medial surface in 5.9%, or the lateral surface in 38.2%, whereas bone apposition was not observed in patients treated with MMA. Conclusions One year after surgery, condylar resorptive changes greater than 1.5 mm were observed in the 2 groups. Articular disc repositioning facilitated bone apposition in localized condylar regions in patients treated with MMA

  10. The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: a descriptive study in humans.

    PubMed

    Brisby, Helena; Papadimitriou, Nikolaos; Brantsing, Camilla; Bergh, Peter; Lindahl, Anders; Barreto Henriksson, Helena

    2013-03-01

    Low back pain is common and degenerated discs (DDs) are believed to be a major cause. In non-degenerated intervertebral discs (IVDs) presence of stem/progenitor cells was recently reported in different mammals (rabbit, rat, pig). Understanding processes of disc degeneration and regenerative mechanisms within DDs is important. The aim of the study was to examine the presence of local stem/progenitor cells in human DDs and if these cell populations could respond to paracrine stimulation in vitro. Tissue biopsies from the IVD region (L3-S1) were collected from 15 patients, age 34-69 years, undergoing surgery (spinal fusion) and mesenchymal stem cells (MSCs) (iliac crest) from 2 donors. Non-DD cells were collected from 1 donor (scoliosis) and chordoma tissue was obtained from (positive control, stem cell markers) 2 donors. The IVD biopsies were investigated for gene and protein expression of: OCT3/4, CD105, CD90, STRO-1, and NOTCH1. DD cell cultures (pellet mass) were performed with conditioned media from MSCs and non-degenerated IVD cells. Pellets were investigated after 7, 14, 28 days for the same stem cell markers as above. Gene expression of OCT3/4 and STRO-1 was detected in 13/15 patient samples, CD105 in 14/15 samples, and CD90 and NOTCH1 were detected 15/15 samples. Immunohistochemistry analysis supported findings on the protein level, in cells sparsely distributed in DDs tissues. DDs cell cultures displayed more undifferentiated appearance with increased expression of CD105, CD90, STRO-1, OCT3/4, NOTCH1, and JAGGED1, which was observed when cultured in conditioned cell culture media from MSCs compared to cell cultures cultured with conditioned media from non-DD cells. Expression of OCT3/4 (multipotency marker) and NOTCH1 (regulator of cell fate), MSC-markers, CD105, CD90, and STRO-1, indicate that primitive cell populations are present within DDs. Furthermore, the possibility to influence cells from DDs by paracrine signaling /soluble factors from MSCs and from

  11. A 20-year-old female with Hirayama disease complicated with dysplasia of the cervical vertebrae and degeneration of intervertebral discs

    PubMed Central

    Hashimoto, Masaya; Yoshioka, Masayuki; Sakimoto, Yoshihiro; Suzuki, Masahiko

    2012-01-01

    A 20-year-old female patient was presented with a 1-year history of progressive weakness of the left hand. Examination on admission showed atrophy of the muscles of the left forearm, cold paralysis and minipolymyoclonus. MR images of the cervical cord showed anterior transfer of the cervical cord on anterior flexion and cervical cord compression at the site of cervical kyphosis, confirming the diagnosis of Hirayama disease. Many features of the present case are unusual: the patient is a female (who are rarely afflicted by this disease), with cervical kyphosis and a history of exercise involving cervical vertebral loading, suggesting a potential involvement of the latter two factors in the disease onset. The findings suggest that cervical vertebral dysplasia and intervertebral disc degeneration may influence cervical kyphosis, and be involved in the onset of Hirayama disease. PMID:23144342

  12. Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs

    PubMed Central

    Schaaf, Rainer; Wälchli, Beat; Boos, Norbert

    2006-01-01

    While there is consensus in the literature that blood vessels are confined to the outer anulus fibrosus of normal adult intervertebral disc, debate continues whether there is a vascular in-growths into inner parts of the intervertebral disc during degeneration. We therefore tested the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. The specific endothelial cell marker CD 31 (PECAM) was used to immunohistochemically investigate 42 paraffin-embedded complete mid-sagittal human intervertebral disc sections of various ages (0–86 years) and varying extent of histomorphological degeneration. Additionally, 20 surgical disc samples from individuals (26–69 years) were included in this study. In discs of fetal to infantile age, blood vessels perforated the cartilaginous end plate and extended into the inner and outer anulus fibrosus, but not into the nucleus pulposus. In adolescents and adults, no blood vessels were seen except for the outer zone of the anulus fibrosus adjacent to the insertion to ligaments. The cartilaginous end plate remained free of vessels, except for areas with circumscribed destruction of the end plate. In advanced disc degeneration, no vessels were observed except for those few cases with complete, scar-like disc destruction. However, some rim lesions and occasionally major clefts were surrounded by a small network of capillary blood vessels extending into deeper zones of the anulus fibrosus. A subsequent morphometric analysis, revealed slightly “deeper” blood vessel extension in juvenile/adolescent discs when compared to young, mature and senile adult individuals with significantly “deeper” extension in the posterior than anterior anulus. The analysis of the surgical specimens showed that only sparse capillary blood vessels which did not extend into the nucleus pulposus even in major disc disruption. Our results show that vascular invasion deeper than the periphery was not observed during disc

  13. Anxiety and depression in patients with advanced macular degeneration: current perspectives

    PubMed Central

    Cimarolli, Verena R; Casten, Robin J; Rovner, Barry W; Heyl, Vera; Sörensen, Silvia; Horowitz, Amy

    2016-01-01

    Age-related macular degeneration (AMD) – despite advances in prevention and medical treatment options – remains prevalent among older adults, often resulting in functional losses that negatively affect the mental health of older adults. In particular, the prevalence of both anxiety and depression in patients with AMD is high. Along with medical treatment options, low vision rehabilitation and AMD-specific behavioral and self-management programs have been developed and have demonstrated effectiveness in improving the mental health of AMD patients. This article reviews the prevalence of anxiety and depression in patients with advanced AMD, discusses potential mechanisms accounting for the development of depression and anxiety in AMD patients, presents the state-of the-art of available interventions for addressing anxiety and depression in AMD patients, and delineates recommendations for eye care professionals regarding how to screen for these two prevalent mental health problems and how to facilitate appropriate treatment for patients with AMD. PMID:26766899

  14. Tissue Engineering a Biological Repair Strategy for Lumbar Disc Herniation

    PubMed Central

    O'Connell, Grace D.; Leach, J. Kent; Klineberg, Eric O.

    2015-01-01

    Abstract The intervertebral disc is a critical part of the intersegmental soft tissue of the spinal column, providing flexibility and mobility, while absorbing large complex loads. Spinal disease, including disc herniation and degeneration, may be a significant contributor to low back pain. Clinically, disc herniations are treated with both nonoperative and operative methods. Operative treatment for disc herniation includes removal of the herniated material when neural compression occurs. While this strategy may have short-term advantages over nonoperative methods, the remaining disc material is not addressed and surgery for mild degeneration may have limited long-term advantage over nonoperative methods. Furthermore, disc herniation and surgery significantly alter the mechanical function of the disc joint, which may contribute to progression of degeneration in surrounding tissues. We reviewed recent advances in tissue engineering and regenerative medicine strategies that may have a significant impact on disc herniation repair. Our review on tissue engineering strategies focuses on cell-based and inductive methods, each commonly combined with material-based approaches. An ideal clinically relevant biological repair strategy will significantly reduce pain and repair and restore flexibility and motion of the spine. PMID:26634189

  15. Clinical and radiological outcome of anterior–posterior fusion versus transforaminal lumbar interbody fusion for symptomatic disc degeneration: a retrospective comparative study of 133 patients

    PubMed Central

    Schwender, James D.; Safriel, Yair; Gilbert, Thomas J.; Mehbod, Amir A.; Denis, Francis; Transfeldt, Ensor E.; Wroblewski, Jill M.

    2009-01-01

    Abundant data are available for direct anterior/posterior spine fusion (APF) and some for transforaminal lumbar interbody fusion (TLIF), but only few studies from one institution compares the two techniques. One-hundred and thirty-three patients were retrospectively analyzed, 68 having APF and 65 having TLIF. All patients had symptomatic disc degeneration of the lumbar spine. Only those with one or two-level surgeries were included. Clinical chart and radiologic reviews were done, fusion solidity assessed, and functional outcomes determined by pre- and postoperative SF-36 and postoperative Oswestry Disability Index (ODI), and a satisfaction questionnaire. The minimum follow-up was 24 months. The mean operating room time and hospital length of stay were less in the TLIF group. The blood loss was slightly less in the TLIF group (409 vs. 480 cc.). Intra-operative complications were higher in the APF group, mostly due to vein lacerations in the anterior retroperitoneal approach. Postoperative complications were higher in the TLIF group due to graft material extruding against the nerve root or wound drainage. The pseudarthrosis rate was statistically equal (APF 17.6% and TLIF 23.1%) and was higher than most published reports. Significant improvements were noted in both groups for the SF-36 questionnaires. The mean ODI scores at follow-up were 33.5 for the APF and 39.5 for the TLIF group. The patient satisfaction rate was equal for the two groups. PMID:19125304

  16. Design and fabrication of 3D-printed anatomically shaped lumbar cage for intervertebral disc (IVD) degeneration treatment.

    PubMed

    Serra, T; Capelli, C; Toumpaniari, R; Orriss, I R; Leong, J J H; Dalgarno, K; Kalaskar, D M

    2016-07-19

    Spinal fusion is the gold standard surgical procedure for degenerative spinal conditions when conservative therapies have been unsuccessful in rehabilitation of patients. Novel strategies are required to improve biocompatibility and osseointegration of traditionally used materials for lumbar cages. Furthermore, new design and technologies are needed to bridge the gap due to the shortage of optimal implant sizes to fill the intervertebral disc defect. Within this context, additive manufacturing technology presents an excellent opportunity to fabricate ergonomic shape medical implants. The goal of this study is to design and manufacture a 3D-printed lumbar cage for lumbar interbody fusion. Optimisations of the proposed implant design and its printing parameters were achieved via in silico analysis. The final construct was characterised via scanning electron microscopy, contact angle, x-ray micro computed tomography (μCT), atomic force microscopy, and compressive test. Preliminary in vitro cell culture tests such as morphological assessment and metabolic activities were performed to access biocompatibility of 3D-printed constructs. Results of in silico analysis provided a useful platform to test preliminary cage design and to find an optimal value of filling density for 3D printing process. Surface characterisation confirmed a uniform coating of nHAp with nanoscale topography. Mechanical evaluation showed mechanical properties of final cage design similar to that of trabecular bone. Preliminary cell culture results showed promising results in terms of cell growth and activity confirming biocompatibility of constructs. Thus for the first time, design optimisation based on computational and experimental analysis combined with the 3D-printing technique for intervertebral fusion cage has been reported in a single study. 3D-printing is a promising technique for medical applications and this study paves the way for future development of customised implants in spinal

  17. Inhibitory Effects of Platelet-Rich Plasma on Intervertebral Disc Degeneration: A Preclinical Study in a Rabbit Model

    PubMed Central

    Gui, Keke; Ren, Weimin; Yu, Yonglin; Li, Xin; Dong, Jiachun; Yin, Wangping

    2015-01-01

    Background Platelet-rich plasma (PRP) contains multiple growth hormones that may stimulate tissue repair. This study aimed to assess the effects of PRP in a rabbit model of IDD (annulus fibrosus puncture). Material/Methods Thirty-six adult New Zealand white rabbits were randomly divided into 3 groups: 0.1 mL PRP (group A), 0.1 mL phosphate-buffered saline (group B), and control (group C) (n=12/group). Annulus fibrosus puncture was performed to establish L4/5 and L5/6 IDD models. Two and 4 weeks later, 6 rabbits from each group were given an IVD injection at L4/5 and L5/6. Two or 4 weeks after injection, rabbits were scanned with X-ray and MRI before being sacrificed. IVDs were collected for hematoxylin and eosin, Masson’s trichrome, and Safranin O staining, and type II collagen immunohistochemistry. Results Over time, IVD height and disc imaging signal intensity decreased gradually in groups B and C, but only slightly in group A (baseline: 100% for all groups; A: 95.9±4.2% at 4 weeks, 90.1±8.4 at 6 weeks; B: 75.3±5.7% at 4 weeks, 70.8±6.4% at 6 weeks; C: 74.7±5.5% at 4 weeks, 69.9±6.2% at 6 weeks; all P<0.001, P<0.01 between A vs. B and C). Degenerative histological changes in IVDs in groups B and C were more severe compared with group A. Conclusions Platelet-rich plasma interventions can effectively attenuate the IDD process in rabbits. PMID:25965093

  18. A risk score for the prediction of advanced age-related macular degeneration: Development and validation in 2 prospective cohorts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We aimed to develop an eye specific model which used readily available information to predict risk for advanced age-related macular degeneration (AMD). We used the Age-Related Eye Disease Study (AREDS) as our training dataset, which consisted of the 4,507 participants (contributing 1,185 affected v...

  19. Advanced Science/Event-based Data Service Framework at GES DISC

    NASA Astrophysics Data System (ADS)

    Shie, C. L.; Shen, S.; Kempler, S. J.

    2014-12-01

    The NASA Goddard Earth Sciences Data and Information Service Center (GES DISC) has provided numerous Earth science data, information, and services to various research communities and general publics for decades. To maintain an overall fine service including improving serving our users with advanced data services has been our primary goal. We are developing an advanced science/event-based data service framework. The framework aims to effectively provide users with a sophisticatedly integrated data package via user-friendly discovering and selecting a system-preset science/event topic (e.g., hurricane, volcano, etc.) from an in-developing knowledge database of the framework. A data recipe page related to the Hurricane topic has been developed to demo the concept. More showcases of various subjects such as Volcano, Dust Storm, and Forest Fire are also under development. This framework is in developing on top of existing data services at GES DISC, such as Mirador (data search engine), Giovanni (visualization), OPeNDAP, and data recipes. It also involves other data tools, such as Panoply, GrADS, IDL, etc. The Hurricane Sandy (Oct 22-31 2012) event is used here for a sample description. As Hurricane Sandy being selected as a user case, a table containing nine system-preset data variables (i.e., precipitation, winds, sea surface temperature, sea level pressure, air temperature, relative humidity, aerosols, soil moisture and surface runoff, and trace gases) linked to the respective data products with fine temporal and spatial resolutions from various in-house sources is provided. The "bundled" variable data can thus be readily downloaded through Mirador. The in-house Giovanni is accessible for users to acquire quick views of Level 3 (gridded) variables. For Level 2 (swath) or the Giovanni-unavailable Level 3 data, the system provides a link to data recipes that give a how-to guide to read and visualize the data using offline tools, such as Panoply, GrADS, or IDL.

  20. Tumor Necrosis Factor Gene Polymorphisms in Advanced Non-exudative Age-related Macular Degeneration

    PubMed Central

    Bonyadi, Mohammad Hossein Jabbarpoor; Bonyadi, Morteza; Ahmadieh, Hamid; Fotuhi, Nikoo; Shoeibi, Nasser; Saadat, Saeed; Yagubi, Zakieh

    2015-01-01

    Purpose: To investigate tumor necrosis factor (TNF)-α gene polymorphisms in advanced dry-type age-related macular degeneration (AMD) in a population from Northeastern Iran. Methods: In this case-control study, 50 patients with geographic macular atrophy and 73 gender-matched controls were enrolled. Genomic deoxyribonucleic acid (DNA) was extracted from the peripheral blood. Polymerase chain reaction was performed to analyze 2 candidate single nucleotide polymorphisms in the TNF-α gene, namely −1031 thymine (T)/cytosine (C) and −308 guanine (G)/adenine (A). Results: The distribution of the - 1031 T/C genotype was TT, 62%; TC, 36%; CC, 2% in the patients and TT, 60%; TC, 36%; CC, 4% in the controls (P = 0.94). Genotype analysis of TNF-α −308 also revealed no significant difference in distribution between patients (G, 78%; GA, 22%; AA, 0%) and controls (GG, 74%; GA, 23%; AA, 3%) (P = 0.51). None of the haplotypes nor alleles of studied TNF-α polymorphisms were significantly associated with advanced dry-type AMD. Conclusion: The findings of this study show that polymorphisms in the TNF-α gene, do not play an important role in dry-type AMD in the studied population. PMID:26425318

  1. Radiologic Evaluation of Degeneration in Isthmic and Degenerative Spondylolisthesis

    PubMed Central

    Jeong, Hyun-Yoon; Sohn, Hong-Moon; Park, Sang-Ha

    2013-01-01

    Study Design A cross-sectional imaging study. Purpose The objective was to assess the degree of degeneration and the associated factors through imaging studies of the lesion segment and the adjacent superior and inferior segments of isthmic and degenerative spondylolisthesis. Overview of Literature Few articles existed for degeneration and related factors in isthmic and degenerative spondylolisthesis. Methods The subjects were 95 patients diagnosed with spondylolisthesis. Simple plain radiographs including flexion and extension and magnetic resonance imaging were used to investigate the degree of translation, disc degeneration, high intensity zone (HIZ) lesion, Schmorl's node (SN) and Modic changes. Results Advanced disc degeneration, grade 5, was shown to be significant in the index segment of the isthmic type (p=0.034). Overall, type 2 Modic change was most common in both groups and also, it was observed more in the isthmus group, specifically, the index segment compared to the degenerative group (p=0.03). For the SN, compared to the degenerative type, the isthmus type had a significantly high occurrence in the index segment (p=0.04). For the HIZ lesions, the isthmus type had a higher occurrence than the degenerative type, especially in the upper segment (p=0.03). Conclusions Most advanced disc degeneration, fifth degree, SN and Modic change occurred more frequently in the lesions of the isthmus type. HIZ lesions were observed more in the isthmus type, especially in the segment superior to the lesion. PMID:23508359

  2. Stem cells sources for intervertebral disc regeneration

    PubMed Central

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-01-01

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  3. Molecular Mechanisms of Biological Aging in Intervertebral Discs

    PubMed Central

    Vo, Nam V.; Hartman, Robert A.; Patil, Prashanti R.; Risbud, Makarand V.; Kletsas, Dimitris; Iatridis, James C.; Hoyland, Judith A.; Le Maitre, Christine L.; Sowa, Gwendolyn A.; Kang, James D.

    2016-01-01

    Advanced age is the greatest risk factor for the majority of human ailments, including spine-related chronic disability and back pain, which stem from age-associated intervertebral disc degeneration (IDD). Given the rapid global rise in the aging population, understanding the biology of intervertebral disc aging in order to develop effective therapeutic interventions to combat the adverse effects of aging on disc health is now imperative. Fortunately, recent advances in aging research have begun to shed light on the basic biological process of aging. Here we review some of these insights and organize the complex process of disc aging into three different phases to guide research efforts to understand the biology of disc aging. The objective of this review is to provide an overview of the current knowledge and the recent progress made to elucidate specific molecular mechanisms underlying disc aging. In particular, studies over the last few years have uncovered cellular senescence and genomic instability as important drivers of disc aging. Supporting evidence comes from DNA repair-deficient animal models that show increased disc cellular senescence and accelerated disc aging. Additionally, stress-induced senescent cells have now been well documented to secrete catabolic factors, which can negatively impact the physiology of neighboring cells and ECM. These along with other molecular drivers of aging are reviewed in depth to shed crucial insights into the underlying mechanisms of age-related disc degeneration. We also highlight molecular targets for novel therapies and emerging candidate therapeutics that may mitigate age-associated IDD. PMID:26890203

  4. An organ culture system to model early degenerative changes of the intervertebral disc II: profiling global gene expression changes

    PubMed Central

    2013-01-01

    Introduction Despite many advances in our understanding of the molecular basis of disc degeneration, there remains a paucity of preclinical models which can be used to study the biochemical and molecular events that drive disc degeneration, and the effects of potential therapeutic interventions. The goal of this study is to characterize global gene expression changes in a disc organ culture system that mimics early nontraumatic disc degeneration. Methods To mimic a degenerative insult, rat intervertebral discs were cultured in the presence of TNF-α, IL-1β and serum-limiting conditions. Gene expression analysis was performed using a microarray to identify differential gene expression between experimental and control groups. Differential pattern of gene expression was confirmed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) or Western blot. Results Treatment resulted in significant changes in expression of more than 1,000 genes affecting many aspects of cell function including cellular movement, the cell cycle, cellular development, and cell death and proliferation. Many of the most highly upregulated and downregulated genes have known functions in disc degeneration and extracellular matrix hemostasis. Construction of gene networks based on known cellular pathways and expression data from our analysis demonstrated that the network associated with cell death, cell cycle regulation and DNA replication and repair was most heavily affected in this model of disc degeneration. Conclusions This rat organ culture model uses cytokine exposure to induce wide gene expression changes with the most affected genes having known reported functions in disc degeneration. We propose that this model is a valuable tool to study the etiology of disc degeneration and evaluate potential therapeutic treatments. PMID:24171898

  5. The Paracrine Effect of Degenerated Disc Cells on Healthy Human Nucleus Pulposus Cells Is Mediated by MAPK and NF-κB Pathways and Can Be Reduced by TGF-β1.

    PubMed

    Cai, Feng; Zhu, Lei; Wang, Feng; Shi, Rui; Xie, Xin-Hui; Hong, Xin; Wang, Xiao-Hu; Wu, Xiao-Tao

    2017-02-01

    Inflammation is thought to have a major role in the pathogenesis of disc degeneration. Studies have shown that nucleus pulposus cells (NPCs) respond to one or two specific cytokines by regulating cell proliferation or matrix synthesis. However, the effects of a cocktail of factors secreted by degenerated disc cells on transplanted exogenous healthy NPCs remain unknown. Concentrations of multiple cytokines in degenerated disc tissue-conditioned medium (dCM) were measured using enzyme-linked immunosorbent assay (ELISA). 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Ki67 immunofluorescence staining were used to evaluate the proliferation of cells in dCM. The function of exogenous NPCs cultured in dCM was evaluated by examining catabolic markers (ADAMTS-4, ADAMTS-5, MMP-1, MMP-3, and MMP-13), anabolic markers (TIMP-1, TIMP-2, and TIMP-3), and the extracellular matrix protein-aggrecan (ACAN) and collagen II (COL2)-expression with real time polymerase chain reaction (RT-PCR). Mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathway activation was observed using Western blotting. Finally, we examined the role of transforming growth factor (TGF)-β1 in reducing dCM-mediated exogenous NPC dysfunction. Levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, interferon-γ (IFN-γ), and prostaglandin E2 (PGE2) were higher and TGF-β1 levels were lower in dCM compared with the control medium. Treatment with dCM increased the proliferation of healthy NPCs. NPCs exhibited significantly higher expression of ADAMTS-4, ADAMTS-5, MMP-1, MMP-3, and MMP-13 and decreased TIMP-2, ACAN, and COL2 expression in the dCM group in a dose- and time-dependent manner. Treatment with dCM moderately increased TIMP-1 expression and had no effect on TIMP-3 mRNA levels. The MAPK and NF-κB pathways were implicated in dCM-mediated responses of healthy NPCs. TGF-β1 partially reversed the d

  6. Cost-Utility Analyses of Cataract Surgery in Advanced Age-Related Macular Degeneration

    PubMed Central

    Ma, Yingyan; Huang, Jiannan; Zhu, Bijun; Sun, Qian; Miao, Yuyu; Zou, Haidong

    2016-01-01

    ABSTRACT Purpose To explore the cost-utility of cataract surgery in patients with advanced age-related macular degeneration (AMD). Methods Patients who were diagnosed as having and treated for age-related cataract and with a history of advanced AMD at the Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, were included in the study. All of the participants underwent successful phacoemulsification with foldable posterior chamber intraocular lens implantation under retrobulbar anesthesia. Best-corrected visual acuity (BCVA) and utility value elicited by time trade-off method from patients at 3-month postoperative time were compared with those before surgery. Quality-adjusted life years (QALYs) gained in a lifetime were calculated at a 3% annual discounted rate. Costs per QALY gained were calculated using the bootstrap method, and probabilities of being cost-effective were presented using a cost-effectiveness acceptability curve. Sensitivity analyses were performed to test the robustness of the results. Results Mean logarithm of the minimum angle of resolution BCVA in the operated eye increased from 1.37 ± 0.5 (Snellen, 20/469) to 0.98 ± 0.25 (Snellen, 20/191) (p < 0.001); BCVA in the weighted average from both eyes (=75% better eye + 25% worse eye) was changed from 1.13 ± 0.22 (Snellen, 20/270) to 0.96 ± 0.17 (Snellen, 20/182) (p < 0.001). Utility values from both patients and doctors increased significantly after surgery (p < 0.001 and p = 0.007). Patients gained 1.17 QALYs by cataract surgery in their lifetime. The cost per QALY was 8835 Chinese yuan (CNY) (1400 U.S. dollars [USD]). It is cost-effective at the threshold of 115,062 CNY (18,235 USD) per QALY in China recommended by the World Health Organization. The cost per QALY varied from 7045 CNY (1116 USD) to 94,178 CNY (14,925 USD) in sensitivity analyses. Conclusions Visual acuity and quality of life assessed by utility value improved significantly after surgery

  7. MECHANICAL DESIGN CRITERIA FOR INTERVERTEBRAL DISC TISSUE ENGINEERING

    PubMed Central

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

    2009-01-01

    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 behaviour, 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 measures where functional equivalence was achieved, and others 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. PMID:20080239

  8. Investigation of intervertebral disc degeneration using multivariate FTIR spectroscopic imaging† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5fd00160a Click here for additional data file.

    PubMed Central

    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 deconvolute 2nd derivative spectra of Fourier transform infrared (FTIR) microscopic images measured in transflectance mode of goat and human paraffin embedded intervertebral disc (IVD) tissue sections, to see if this methodology can provide analogous information to that provided by immunohistochemical stains and bioassays but from a single section. MCR-ALS analysis of non-degenerate and enzymatically in vivo degenerated goat IVDs reveals five matrix components displaying distribution maps matching histological stains for collagen, elastin and proteoglycan (PG), as well as immunohistochemical stains for collagen type I and II. Interestingly, two components exhibiting characteristic spectral and distribution profiles of proteoglycans were found, and relative component/tissue maps of these components (labelled PG1 and PG2) showed distinct distributions in non-degenerate versus mildly degenerate goat samples. MCR-ALS analysis of human IVD sections resulted in comparable spectral profiles to those observed in the goat samples, highlighting the inter species transferability of the presented methodology. Multivariate FTIR image analysis of a set of 43 goat IVD sections allowed the extraction of semi-quantitative information from component/tissue gradients taken across the IVD width of collagen type I, collagen type II, PG1 and PG2. Regional component/tissue parameters were calculated and significant correlations were found between histological grades of degeneration and PG parameters (PG1: p = 0.0003, PG2: p < 0.0001); glycosaminoglycan (GAG) content and PGs (PG1: p = 0.0055, PG2: p = 0.0001); and MRI T2* measurements and PGs (PG1: p = 0.0021, PG2: p < 0.0001). Additionally

  9. Laser treatment of drusen to prevent progression to advanced age-related macular degeneration

    PubMed Central

    Virgili, Gianni; Michelessi, Manuele; Parodi, Maurizio B; Bacherini, Daniela; Evans, Jennifer R

    2016-01-01

    Background Drusen are amorphous yellowish deposits beneath the sensory retina. People with drusen, particularly large drusen, are at higher risk of developing age-related macular degeneration (AMD). The most common complication in AMD is choroidal neovascularisation (CNV), the growth of new blood vessels in the centre of the macula. The risk of CNV is higher among people who are already affected by CNV in one eye. It has been observed clinically that laser photocoagulation of drusen leads to their disappearance and may prevent the occurrence of advanced disease (CNV or geographic atrophy) associated with visual loss. Objectives To examine the effectiveness and adverse effects of laser photocoagulation of drusen in AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2015), EMBASE (January 1980 to August 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 August 2015. Selection criteria Randomised controlled trials (RCTs) of laser treatment of drusen in AMD in which laser treatment had been compared with no intervention or sham treatment. Two types of trials were included. Some trials studied one eye of each participant (unilateral studies); other studies recruited participants with bilateral drusen and randomised one eye to photocoagulation or control and the fellow eye to the other group. Data collection and analysis Two review authors independently

  10. The Advanced Glaucoma Intervention Study (AGIS): 10. Variability among academic glaucoma subspecialists in assessing optic disc notching.

    PubMed Central

    Gaasterland, D E; Blackwell, B; Dally, L G; Caprioli, J; Katz, L J; Ederer, F

    2001-01-01

    PURPOSE: An analysis of data from the Advanced Glaucoma Intervention Study (AGIS) has found eyes reported to have partial optic disc rim notching (not to the edge) at baseline to have less risk of subsequent visual field loss than eyes with no notching. Because this is counterintuitive and because classification of notching had not been defined in the AGIS protocol, we have assessed AGIS ophthalmologists interobserver and intraobserver agreement on notching. METHODS: Fourteen glaucoma subspecialists classified notching in 26 pairs of stereoscopic disc photographs of eyes with mild to severe glaucomatous optic neuropathy. They classified images as showing either no notching, notching not to the edge, or notching to the edge. Several hours later, 10 of them classified the same images a second time. RESULTS: In an analysis of interobserver agreement, of 26 stereoscopic images, a plurality of ophthalmologists classified notching as absent in 9 (35%), as present but not to the edge in 7 (27%), and as present and not to the edge in 10 (38%). All 14 ophthalmologists (100%) agreed on the classification of 7 (27%) of the images, and 13 of the 14 ophthalmologists (93%) agreed on the classification of 4 additional images (15%). Of these 11 images with at least 93% agreement, notching was reported as absent in 3 (27%) and to the edge in 8 (73%). In the remaining 15 images, there was substantial disagreement about whether notching was present and, if so, whether it was to the edge. In an analysis of intraobserver agreement, none of the 10 ophthalmologists who completed the viewing a second time classified all eyes exactly the same as the first time, though 5 ophthalmologists made 4 or fewer reclassifications. Overall, 80% of the original classifications were reproduced on second reading. Of the initial classifications that were not reproduced, slightly more than half were first classified as having notching not to the edge. CONCLUSION: Without definitions or examples of optic

  11. Advanced AC permanent magnet axial flux disc motor for electric passenger vehicle

    NASA Technical Reports Server (NTRS)

    Kliman, G. B.

    1982-01-01

    An ac permanent magnet axial flux disc motor was developed to operate with a thyristor load commutated inverter as part of an electric vehicle drive system. The motor was required to deliver 29.8 kW (40 hp) peak and 10.4 kW (14 hp) average with a maximum speed of 11,000 rpm. It was also required to run at leading power factor to commutate the inverter. Three motors were built.

  12. Imaging mass spectrometry of the visual system: Advancing the molecular understanding of retina degenerations.

    PubMed

    Bowrey, Hannah E; Anderson, David M; Pallitto, Patrick; Gutierrez, Danielle B; Fan, Jie; Crouch, Rosalie K; Schey, Kevin L; Ablonczy, Zsolt

    2016-04-01

    Visual sensation is fundamental for quality of life, and loss of vision to retinal degeneration is a debilitating condition. The eye is the only part of the central nervous system that can be noninvasively observed with optical imaging. In the clinics, various spectroscopic methods provide high spatial resolution images of the fundus and the developing degenerative lesions. However, the currently utilized tools are not specific enough to establish the molecular underpinnings of retinal diseases. In contrast, mass spectrometric imaging (MSI) is a powerful tool to identify molecularly specific disease indicators and classification markers. This technique is particularly well suited to the eye, where molecular information can be correlated with clinical data collected via noninvasive diagnostic imaging modalities. Recent studies during the last few recent years have uncovered a plethora of new spatially defined molecular information on several vision-threatening diseases, including age-related macular degeneration, Stargardt disease, glaucoma, cataract, as well as lipid disorders. Even though MS inside the eye cannot be performed noninvasively, by linking diagnostic and molecular information, these studies are the first step toward the development of smart ophthalmic diagnostic and surgical tools. Here, we provide an overview of current approaches applying MSI technology to ocular pathology.

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

    PubMed

    Yang, Zechuan; Li, Chunde; Sun, Haolin

    2016-03-01

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

  14. Paeoniflorin inhibits nucleus pulposus cell apoptosis by regulating the expression of Bcl-2 family proteins and caspase-9 in a rabbit model of intervertebral disc degeneration

    PubMed Central

    SHI, LIJUN; TENG, HONGLIN; ZHU, MINYU; LI, CHI; HUANG, KELUN; CHEN, BI; DAI, YUSEN; WANG, JING

    2015-01-01

    Apoptosis plays a key role in the pathogenesis of internal disc disruption (IDD); therefore, the inhibition of apoptosis may offer a novel approach for treating IDD diseases. The aim of the present study was to investigate the effects and the underlying mechanisms of paeoniflorin through the detection of relevant indicators in a rabbit model of IDD. In total, 144 rabbits were used in the study and divided into four groups (n=36 per group). Rabbits successfully modeled with IDD received an intragastric injection of 120 mg/kg·day paeoniflorin (high-dose group), 30 mg/kg·day paeoniflorin (low-dose group) or saline (model saline group), while rabbits without IDD were used as a normal control group. The apoptosis rate of disc nucleus pulposus cells was detected using flow cytometry. In addition, the expression levels of Bcl-2, Bax and caspase-9 in the disc tissues were detected using immunohistochemistry and western blot analysis prior to and following the treatment. The results indicated that the expression levels of Bax in the low- and high-dose paeoniflorin groups were significantly reduced, while the Bcl-2 expression levels were significantly increased when compared with the model saline group (P<0.01). In addition, the expression levels of cleaved caspase-3 and cleaved caspase-9 were reduced in the low- and high-dose paeoniflorin groups, as compared with the model saline group (P<0.05). Furthermore, the average apoptotic index of the high- and low-dose paeoniflorin groups was decreased when compared with the model saline group (P<0.05). In conclusion, paeoniflorin was demonstrated to inhibit the apoptosis of nucleus pulposus cells and the activation of caspase-3 and caspase-9 through the regulation of Bcl-2 family protein expression. These results provide an experimental basis for the future treatment of IDD with paeoniflorin. PMID:26170945

  15. Arrhythmogenic cardiomyopathy: a disease of intercalated discs.

    PubMed

    Calore, Martina; Lorenzon, Alessandra; De Bortoli, Marzia; Poloni, Giulia; Rampazzo, Alessandra

    2015-06-01

    Arrhythmogenic cardiomyopathy (ACM) is an acquired progressive disease having an age-related penetrance and showing clinical manifestations usually during adolescence and young adulthood. It is characterized clinically by a high incidence of severe ventricular tachyarrhythmias and sudden cardiac death and pathologically by degeneration of ventricular cardiomyocytes with replacement by fibro-fatty tissue. Whereas, in the past, the disease was considered to involve only the right ventricle, more recent clinical studies have established that the left ventricle is frequently involved. ACM is an inherited disease in up to 50% of cases, with predominantly an autosomal dominant pattern of transmission, although recessive inheritance has also been described. Since most of the pathogenic mutations have been identified in genes encoding desmosomal proteins, ACM is currently defined as a disease of desmosomes. However, on the basis of the most recent description of the intercalated disc organization and of the identification of a novel ACM gene encoding for an area composita protein, ACM can be considered as a disease of the intercalated disc, rather than only as a desmosomal disease. Despite increasing knowledge of the genetic basis of ACM, we are just beginning to understand early molecular events leading to cardiomyocyte degeneration, fibrosis and fibro-fatty substitution. This review summarizes recent advances in our comprehension of the link between the molecular genetics and pathogenesis of ACM and of the novel role of cardiac intercalated discs.

  16. Recent patents relating to diagnostic advances in age related macular degeneration (AMD).

    PubMed

    Cantsilieris, Stuart; Schache, Maria; Ashdown, M Luisa; Baird, Paul N

    2009-01-01

    Age Related Macular Degeneration (AMD) is a complex neurodegenerative disorder accounting for 50% of blind registrations in the western world. Its substantial impact on quality of life has been a main driver in research to understand its etiology, which up until recently was mostly unknown. In the last three years our understanding of the molecular pathology of AMD has increased dramatically with the identification of two major AMD loci comprising of, Complement Factor H (CFH) and a chromosome 10q26 locus consisting of the Heat Shock Serine Protease (HTRA1) and LOC387715 genes. These two loci have been described as associated with over 50% of disease in certain ethnicities. The rapid pace in our understanding of the complex biology of this disease has placed a large emphasis on gene patenting, especially with the licensing of the CFH and chromosome 10 patents to a private life science company called Optherion Inc. The patents discussed in this review highlight the important discoveries that have contributed to our understanding of AMD and provide valuable information as to where research in this area will be heading in the future.

  17. Advancing therapeutic strategies for inherited retinal degeneration: recommendations from the Monaciano Symposium.

    PubMed

    Thompson, Debra A; Ali, Robin R; Banin, Eyal; Branham, Kari E; Flannery, John G; Gamm, David M; Hauswirth, William W; Heckenlively, John R; Iannaccone, Alessandro; Jayasundera, K Thiran; Khan, Naheed W; Molday, Robert S; Pennesi, Mark E; Reh, Thomas A; Weleber, Richard G; Zacks, David N

    2015-02-09

    Although rare in the general population, retinal dystrophies occupy a central position in current efforts to develop innovative therapies for blinding diseases. This status derives, in part, from the unique biology, accessibility, and function of the retina, as well as from the synergy between molecular discoveries and transformative advances in functional assessment and retinal imaging. The combination of these factors has fueled remarkable progress in the field, while at the same time creating complex challenges for organizing collective efforts aimed at advancing translational research. The present position paper outlines recent progress in gene therapy and cell therapy for this group of disorders, and presents a set of recommendations for addressing the challenges remaining for the coming decade. It is hoped that the formulation of these recommendations will stimulate discussions among researchers, funding agencies, industry, and policy makers that will accelerate the development of safe and effective treatments for retinal dystrophies and related diseases.

  18. Advancing Therapeutic Strategies for Inherited Retinal Degeneration: Recommendations From the Monaciano Symposium

    PubMed Central

    Thompson, Debra A.; Ali, Robin R.; Banin, Eyal; Branham, Kari E.; Flannery, John G.; Gamm, David M.; Hauswirth, William W.; Heckenlively, John R.; Iannaccone, Alessandro; Jayasundera, K. Thiran; Khan, Naheed W.; Molday, Robert S.; Pennesi, Mark E.; Reh, Thomas A.; Weleber, Richard G.; Zacks, David N.

    2015-01-01

    Although rare in the general population, retinal dystrophies occupy a central position in current efforts to develop innovative therapies for blinding diseases. This status derives, in part, from the unique biology, accessibility, and function of the retina, as well as from the synergy between molecular discoveries and transformative advances in functional assessment and retinal imaging. The combination of these factors has fueled remarkable progress in the field, while at the same time creating complex challenges for organizing collective efforts aimed at advancing translational research. The present position paper outlines recent progress in gene therapy and cell therapy for this group of disorders, and presents a set of recommendations for addressing the challenges remaining for the coming decade. It is hoped that the formulation of these recommendations will stimulate discussions among researchers, funding agencies, industry, and policy makers that will accelerate the development of safe and effective treatments for retinal dystrophies and related diseases. PMID:25667399

  19. How genetic studies have advanced our understanding of age-related macular degeneration and their impact on patient care: a review.

    PubMed

    Baird, Paul N; Chakrabarti, Subhabrata

    2014-01-01

    The last 10 years have seen an unprecedented explosion in our knowledge regarding the genomic basis of age-related macular degeneration. This has come about through major advances in computing power, microfabrication of large numbers of molecular markers on chips and improved statistical algorithms for analysis. In tandem, it has become clear that age-related macular degeneration appears to be a multifactorial disease with influences from genetic and structural variants, as well as epigenetic involvement. The combination of these factors with known environmental determinants indicates the highly complex nature of this disease, but at the same time also offers insights into risk prediction and disease stratification through genotype profiling.

  20. LIM mineralization protein-1 suppresses TNF-α induced intervertebral disc degeneration by maintaining nucleus pulposus extracellular matrix production and inhibiting matrix metalloproteinases expression.

    PubMed

    Liu, Hui; Pan, Hehai; Yang, Hao; Wang, Jianru; Zhang, Kuibo; Li, Xiang; Wang, Hua; Ding, Wenbin; Li, Bingxue; Zheng, Zhaomin

    2015-03-01

    Imbalanced metabolism of Nucleus pulposus (NP) extracellular matrix (ECM) is closely correlated to Intervertebral Disc Degenerative Disease. LIM mineralization protein-1 (LMP-1) has been proven to induce sulfated glycosaminoglycan (sGAG) production in NP and have an anti-inflammatory effect in pre-osteoclast. However, whether it has any effect on the NP ECM production and degradation under inflammatory stimulation has not been studied. In the current study, a TNF-α induced cell model was established in vitro. Lentivirus encoding LMP-1 (LV-LMP-1) and short heparin LMP-1 (LV-shLMP-1) were constructed to overexpress and knockdown LMP-1 expression in NP cells. LMP-1 mRNA level was regulated in a dose-dependent manner after transfection. LV-LMP-1 increased whereas LV-shLMP-1 decreased collagen II, aggrecan, versican expression, and sGAG production. LV-LMP-1 abolished while LV-shLMP-1 aggravated TNF-α mediated down-regulation of the above matrix genes via ERK1/2 activation. Moreover, LV-LMP-1 abrogated TNF-α induced MMP-3 and MMP-13 expression via inhibiting p65 translocation and MMP-3 and MMP-13 promoter activity. These results indicated that LMP-1 had an ECM production maintenance effect under inflammatory stimulation. This effect was via up-regulation of matrix genes expression at least partially through ERK1/2 activation, and down-regulation of MMPs expression through NF-κB inhibition.

  1. Defense Advanced Research Projects Agency Properly Awarded Contracts for Disc-Rotor Research and Development

    DTIC Science & Technology

    2013-07-19

    Boeing. Contract Solicitation DARPA personnel properly issued BAA 06-15, “DARPA Tactical Technology Office ( TTO ),” to solicit proposals for advanced R...technology. The BAA 06-15 published on the Federal Business Opportunities website https://www.fedbizopps.gov, stated that DARPA TTO personnel would...submission. DARPA contracting personnel provided letters of “Discouraged” to 122 white papers submissions based on the relevance to the TTO mission

  2. Striatonigral Degeneration

    MedlinePlus

    ... disease, striatonigral degeneration is not responsive to levodopa. Dopamine and anticholinergics provide some benefit. Generally, treatment is ... disease, striatonigral degeneration is not responsive to levodopa. Dopamine and anticholinergics provide some benefit. Generally, treatment is ...

  3. Macular degeneration

    MedlinePlus Videos and Cool Tools

    ... at the center of the field of vision. Macular degeneration results from a partial breakdown of the insulating ... choroid layer of blood vessels behind the retina. Macular degeneration results in the loss of central vision only.

  4. 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)

    PubMed Central

    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

  5. Tension-free cuff repairs with excision of macroscopic tendon lesions and muscular advancement: results in a prospective series with limited fatty muscular degeneration.

    PubMed

    Goutallier, D; Postel, J M; Van Driessche, S; Godefroy, D; Radier, C

    2006-01-01

    Recurrent tears after rotator cuff repairs are frequent. These could be influenced by excessive tension on a degenerated tendinous stump and by fatty degeneration of the cuff muscles. The goal of this study was to evaluate the anatomic and functional results of tension-free cuff repairs with the excision of macroscopic tendon lesions in a series with limited muscular fatty degeneration of the infraspinatus and a global fatty degeneration index of rotator cuff muscles equal to or lower than 2. We studied 27 tears, comprising 13 cases involving both supraspinatus and infraspinatus tears, 13 cases with 3-tendon tears, and 1 case with only a supraspinatus tear. All shoulders were operated on through a transacromial approach easily repaired with 2 titanium screws with washers. To obtain a repair without tension, a single advancement was performed in 20 cases and a double advancement of both the supraspinatus and infraspinatus was done in 7 cases. The shoulders were evaluated clinically preoperatively and postoperatively with the non-weighted Constant score and anatomically with computed arthrotomography scans. The mean age at operation was 59.5 years, and the length of follow-up ranged from 1 to 4 years. Of the cuffs, 23 (85%) were watertight 1 year after surgery. No predictive factor of retear could be found. The functional improvement was statistically significant only for watertight cuffs, with an improvement of the Constant score from 57.8 to 75. The only predictive factor of functional outcome in this watertight group was the preoperative Constant score. Single and double advancements yielded similar functional results regardless of the extent of the initial tear, provided that the cuff was watertight at revision.

  6. Advanced glycation end products in degenerative nucleus pulposus with diabetes.

    PubMed

    Tsai, Tsung-Ting; Ho, Natalie Yi-Ju; Lin, Ying-Ting; Lai, Po-Liang; Fu, Tsai-Sheng; Niu, Chi-Chien; Chen, Lih-Huei; Chen, Wen-Jer; Pang, Jong-Hwei S

    2014-02-01

    Diabetes mellitus (DM) has been clinically proved as a risk factor of disc degeneration, and the accumulation of advanced glycation end products (AGEs) is known to be potentially involved in diabetes. The purpose of this study is to investigate the effect of AGEs in the degeneration process of diabetic nucleus pulposus (NP) in rats and humans. Diabetic NP cells from rat coccygeal discs were treated with different concentrations of AGEs (0, 50, and 100 µg/ml) for 3 days, and mRNA expressions of MMP-2 and RAGE were measured by real-time RT-PCR. In addition, conditioned medium from NP cells was used to analyze protein expression of MMP-2 activity and ERK by gelatin zymography and Western blot. These experiments were repeated using human intervertebral disc samples. The immunohistochemical expression of AGEs was significantly increased in diabetic discs. In response to AGEs, an increase of MMP-2, RAGE, and ERK at both mRNA and protein expression levels was observed in diabetic NP cells. The findings suggest that AGEs and DM are associated with disc degeneration in both species. Hyperglycemia in diabetes enhances the accumulation of AGEs in the NP and triggers disc degeneration.

  7. Intervertebral disc regeneration: from the degenerative cascade to molecular therapy and tissue engineering.

    PubMed

    Vadalà, Gianluca; Russo, Fabrizio; Di Martino, Alberto; Denaro, Vincenzo

    2015-06-01

    Low back pain is one of the major health problems in industrialized countries, as a leading source of disability in the working population. Intervertebral disc degeneration has been identified as its main cause, being a progressive process mainly characterized by alteration of extracellular matrix composition and water content. Many factors are involved in the degenerative cascade, such as anabolism/catabolism imbalance, reduction of nutrition supply and progressive cell loss. Currently available treatments are symptomatic, and surgical procedures consisting of disc removal are often necessary. Recent advances in our understanding of intervertebral disc biology led to an increased interest in the development of novel biological treatments aimed at disc regeneration. Growth factors, gene therapy, stem cell transplantation and biomaterials-based tissue engineering might support intervertebral disc regeneration by overcoming the limitation of the self-renewal mechanism. The aim of this paper is to overview the literature discussing the current status of our knowledge from the degenerative cascade of the intervertebral disc to the latest molecular, cell-based therapies and tissue-engineering strategies for disc regeneration.

  8. Peripheral Disc Margin Shape and Internal Disc Derangement: Imaging Correlation in Significantly Painful Discs Identified at Provocation Lumbar Discography

    PubMed Central

    Bartynski, W.S.; Rothfus, W.E.

    2012-01-01

    Summary Annular margin shape is used to characterize lumbar disc abnormality on CT/MR imaging studies. Abnormal discs also have internal derangement including annular degeneration and radial defects. The purpose of this study was to evaluate potential correlation between disc-margin shape and annular internal derangement on post-discogram CT in significantly painful discs encountered at provocation lumbar discography (PLD). Significantly painful discs were encountered at 126 levels in 86 patients (47 male, 39 female) studied by PLD where no prior surgery had been performed and response to intradiscal lidocaine after provocation resulted in either substantial/total relief or no improvement after lidocaine administration. Post-discogram CT and discogram imaging was evaluated for disc-margin characteristics (bulge/protrusion), features of disc internal derangement (radial annular defect [RD: radial tear/fissure/annular gap], annular degeneration) and presence/absence of discographic contrast leakage. In discs with focal protrusion, 50 of 63 (79%) demonstrated Grade 3 RD with 13 (21%) demonstrating severe degenerative change only. In discs with generalized-bulge-only, 48 of 63 (76%) demonstrated degenerative change only (primarily Dallas Grade 3) with 15 of 63 (24%) demonstrating a RD (Dallas Grade 3). Differences were highly statistically significant (p<0.001). Pain elimination with intra-discal lidocaine correlated with discographic contrast leakage (p<0.001). Disc-margin shape correlates with features of internal derangement in significantly painful discs encountered at PLD. Discs with focal protrusion typically demonstrate RD while generalized bulging discs typically demonstrated degenerative changes only (p<0.001). Disc-margin shape may provide an important imaging clue to the cause of chronic discogenic low back pain. PMID:22681741

  9. Hybrid cervical disc arthroplasty.

    PubMed

    Tu, Tsung-Hsi; Wu, Jau-Ching; Cheng, Henrich; Mummaneni, Praveen V

    2017-01-01

    For patients with multilevel cervical stenosis at nonadjacent segments, one of the traditional approaches has included a multilevel fusion of the abnormal segments as well as the intervening normal segment. In this video we demonstrate an alternative treatment plan with tailored use of a combination of anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) with an intervening skipped level. The authors present the case of a 72-year-old woman with myeloradiculopathy and a large disc herniation with facet joint degeneration at C3-4 and bulging disc at C5-6. After nonoperative treatment failed, she underwent a single-level ACDF at C3-4 and single-level arthroplasty at C5-6, which successfully relieved her symptoms. No intervention was performed at the normal intervening C4-5 segment. By using ACDF combined with arthroplasty, the authors have avoided a 3-level fusion for this patient and maintained the range of motion of 2 disc levels. The video can be found here: https://youtu.be/OrxcPUBvqLk .

  10. Kineflex (Centurion) Lumbar Disc Prosthesis: Insertion Technique and 2-Year Clinical Results in 100 Patients

    PubMed Central

    Weinberg, Ian R.; Sliwa, Karen; Sweet, Barry MBE; de Villiers, Malan

    2007-01-01

    Background The Kineflex lumbar disc is a mechanical, unconstrained, re-centering disc prosthesis developed in South Africa. The first implantation took place in October 2002. We present a single-center, prospective, longitudinal study of the first 100 patients treated with the Kineflex lumbar disc. Our objective was to evaluate the insertion technique, clinical outcomes, and patient satisfaction at 2 years postimplantation in 100 consecutive patients with 132 (68 single- and 32 2-level) Kineflex lumbar disc replacements. Methods We determined the exact central placement of all disc implants in the coronal and midsagittal planes. We measured clinical outcome with the Oswestry disability index (ODI), our own questionnaire, and the time needed to return to work. All patients received radiological and clinical follow-up assessments for 2 years after the index procedure. Results Forty-three patients were female. The mean age of the patients at operation was 44.9 years (range, 23–63 years). Postoperative hospitalization averaged 2.8 days (range, 2 to 8 days). All patients who were employed before surgery returned to work 31 ± 16.8 days after the operation. Fifty-six percent of operated disc levels had intervertebral disc heights of less than 5 mm. A 2-year clinical outcome was available for 98 of the 100 patients (58 excellent, 30 good, 7 fair, 3 poor). The ODI score improved from 47.8 ± 16.0 preoperatively to 14.2 ± 14.0 (P < .01) at 2 years. At 2 years, 95% of disc implants were radiologically in the ideal position. The insertion technique, with a released prosthetic mechanism for final placement, allowed ideal placement in the sagittal plane in 98% of discs. The radiographic placement accuracy achieved was equal in patients with preoperative intervertebral disc height below and above 5 mm. Conclusions Good short-term clinical results were achieved with the Kineflex disc in a heterogeneous patient group with a high number of patients with advanced disc

  11. FACET ORIENTATION AND TROPISM: ASSOCIATION WITH ACCELERATED DEGENERATION OF STABILIZING STRUCTURES IN LOWER LUMBAR SPINE.

    PubMed

    Jelec, Vjekoslav; Turner, Rajka; Franić, Miljenko; Korušić, Anđelko; Rotim, Krešimir

    2016-03-01

    The influence of facet orientation and tropism on the process of spinal degeneration has been extensively studied during the last few decades, but there are still many controversies and conflicting results in this field of research. The biomechanical cause of accelerated degeneration of stabilizing structures in lower lumbar spine lies within the combination of several factors, but two most important ones are compressive load and more coronal facet orientation that offers less resistance against torsional loading. Axial rotation of lower lumbar spine is undoubtedly associated with higher strain in disc annulus, and enhanced range of secondary rotational movements may be even more significant for the progression of annular degeneration. Accordingly, more pronounced facet tropism could be having part in faster progression of disc degeneration in lower lumbar spine, as indicated by a number of recent studies. More sagittal facet orientation in patients with a higher facet osteoarthritis score at lower lumbar segments is very likely related to arthritic remodeling commonly seen in other synovial joints. There is also a possibility that it could be associated with the adaptation to partial loss of lumbar lordosis, as both coincide with advanced age.

  12. Omics in Ophthalmology: Advances in Genomics and Precision Medicine for Leber Congenital Amaurosis and Age-Related Macular Degeneration.

    PubMed

    den Hollander, Anneke I

    2016-03-01

    The genomic revolution has had a huge impact on our understanding of the genetic defects and disease mechanisms underlying ophthalmic diseases. Two examples are discussed here. The first is Leber congenital amaurosis (LCA), a severe inherited retinal dystrophy leading to severe vision loss in children, and the second is age-related macular degeneration (AMD), the most common cause of vision loss in the elderly. Twenty years ago, the genetic causes of these diseases were unknown. Currently, more than 20 LCA genes have been identified, and genetic testing can now successfully identify the genetic defects in at least 75% of all LCA cases. Gene-specific treatments have entered the clinical trial phase for three LCA genes, and for seven LCA genes gene-specific therapies have been tested in model systems. Age-related macular degeneration is a multifactorial disease caused by a combination of genetic and environmental factors. Currently, more than 40 loci have been identified for AMD, accounting for 15%-65% of the total genetic contribution to AMD. Despite the progress that has been made so far, genetic testing is not yet recommended for AMD, but this may change if we move to clinical trials or treatments that are dependent on an individual's genotype. The identification of serum or plasma biomarkers using other "-omics" technologies may further improve predictive tests and our understanding of the disease mechanisms of AMD. Ultimately, it is anticipated that predictive tests will help to stratify patients for the most suitable therapy, which will enable the development of precision medicine, tailored to individual needs.

  13. Total disc replacement.

    PubMed

    Vital, J-M; Boissière, L

    2014-02-01

    Total disc replacement (TDR) (partial disc replacement will not be described) has been used in the lumbar spine since the 1980s, and more recently in the cervical spine. Although the biomechanical concepts are the same and both are inserted through an anterior approach, lumbar TDR is conventionally indicated for chronic low back pain, whereas cervical TDR is used for soft discal hernia resulting in cervicobrachial neuralgia. The insertion technique must be rigorous, with precise centering in the disc space, taking account of vascular anatomy, which is more complex in the lumbar region, particularly proximally to L5-S1. All of the numerous studies, including prospective randomized comparative trials, have demonstrated non-inferiority to fusion, or even short-term superiority regarding speed of improvement. The main implant-related complication is bridging heterotopic ossification with resulting loss of range of motion and increased rates of adjacent segment degeneration, although with an incidence lower than after arthrodesis. A sufficiently long follow-up, which has not yet been reached, will be necessary to establish definitively an advantage for TDR, particularly in the cervical spine.

  14. Solute transport in intervertebral disc: experiments and finite element modeling.

    PubMed

    Das, D B; Welling, A; Urban, J P G; Boubriak, O A

    2009-04-01

    Loss of nutrient supply to the human intervertebral disc (IVD) cells is thought to be a major cause of disc degeneration in humans. To address this issue, transport of molecules of different size have been analyzed by a combination of experimental and modeling studies. Solute transport has been compared for steady-state and transient diffusion of several different solutes with molecular masses in the range 3-70 kDa, injected into parts of the disc where degeneration is thought most likely to occur first and into the blood supply to the disc. Diffusion coefficients of fluorescently tagged dextran molecules of different molecular weights have been measured in vitro using the concentration gradient technique in thin specimens of disc outer annulus and nucleus pulposus. Diffusion coefficients were found to decrease with molecular weight following a nonlinear relationship. Diffusion coefficients changed more rapidly for solutes with molecular masses less than 10 kDa. Although unrealistic or painful, solutes injected directly into the disc achieve the largest disc coverage with concentrations that would be high enough to be of practical use. Although more practical, solutes injected into the blood supply do not penetrate to the central regions of the disc and their concentrations dissipate more rapidly. Injection into the disc would be the best method to get drugs or growth factors to regions of degeneration in IVDs quickly; else concentrations of solute must be kept at a high value for several hours in the blood supply to the discs.

  15. Leukocyte telomere length is associated with advanced age-related macular degeneration in the Han Chinese population.

    PubMed

    Weng, Xiaoling; Zhang, Hong; Kan, Mengyuan; Ye, Junyi; Liu, Fatao; Wang, Ting; Deng, Jiaying; Tan, Yanfang; He, Lin; Liu, Yun

    2015-09-01

    Telomeres located at the ends of chromosomes are involved in genomic stability and play a key role in various cancers and age-related diseases. Age-related macular degeneration (AMD) is a late-onset, age-associated progressive neurodegenerative disease, which includes the geographic atrophy (GA) subtype and the choroidal neovascularization (CNV) subtype. To better understand how leukocyte telomere length (LTL) is related to AMD, we conducted an association study in 197 AMD patients and 259 healthy controls using the established quantitative PCR technique. Logistic regression was performed to evaluate the association of LTL and AMD with the age-adjusted ratio of the telomere length to the copy number of a single-copy gene (T/S). Notably, we found a significant association between AMD and LTL (OR=2.24; 95% CI=1.68-3.07; P=0.0001) after adjusting for age and sex. Furthermore, the results showed a strongly significant association between the GA subtype and the LTL (OR=4.81; 95% CI=3.15-7.82; P=0.0001) after adjusting for age and sex. Our findings provide evidence of the role that LTL plays in the pathological mechanisms of AMD, mainly in the GA subgroup but not the CNV subgroup.

  16. Rare genetic variants in the CFI gene are associated with advanced age-related macular degeneration and commonly result in reduced serum factor I levels.

    PubMed

    Kavanagh, David; Yu, Yi; Schramm, Elizabeth C; Triebwasser, Michael; Wagner, Erin K; Raychaudhuri, Soumya; Daly, Mark J; Atkinson, John P; Seddon, Johanna M

    2015-07-01

    To assess a potential diagnostic and therapeutic biomarker for age-related macular degeneration (AMD), we sequenced the complement factor I gene (CFI) in 2266 individuals with AMD and 1400 without, identifying 231 individuals with rare genetic variants. We evaluated the functional impact by measuring circulating serum factor I (FI) protein levels in individuals with and without rare CFI variants. The burden of very rare (frequency <1/1000) variants in CFI was strongly associated with disease (P = 1.1 × 10(-8)). In addition, we examined eight coding variants with counts ≥5 and saw evidence for association with AMD in three variants. Individuals with advanced AMD carrying a rare CFI variant had lower mean FI compared with non-AMD subjects carrying a variant (P < 0.001). Further new evidence that FI levels drive AMD risk comes from analyses showing individuals with a CFI rare variant and low FI were more likely to have advanced AMD (P = 5.6 × 10(-5)). Controlling for covariates, low FI increased the risk of advanced AMD among those with a variant compared with individuals without advanced AMD with a rare CFI variant (OR 13.6, P = 1.6 × 10(-4)), and also compared with control individuals without a rare CFI variant (OR 19.0, P = 1.1 × 10(-5)). Thus, low FI levels are strongly associated with rare CFI variants and AMD. Enhancing FI activity may be therapeutic and measuring FI provides a screening tool for identifying patients who are most likely to benefit from complement inhibitory therapy.

  17. Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects.

    PubMed

    Danis, Ronald P; Lavine, Jeremy A; Domalpally, Amitha

    2015-01-01

    Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular degeneration (AMD). GA may be classified as drusen-related (drusen-associated GA) or neovascularization-related (neovascular-associated GA). Drusen-related GA remains a large public health concern due to the burden of blindness it produces, but pathophysiology of the condition is obscure and there are no proven treatment options. Genotyping, cell biology, and clinical imaging point to upregulation of parainflammatory pathways, oxidative stress, and choroidal sclerosis as contributors, among other factors. Onset and monitoring of progression is accomplished through clinical imaging instrumentation such as optical coherence tomography, photography, and autofluorescence, which are the tools most helpful in determining end points for clinical trials at present. A number of treatment approaches with diverse targets are in development at this time, some of which are in human clinical trials. Neovascular-associated GA is a consequence of RPE loss after development of neovascular AMD. The neovascular process leads to a plethora of cellular stresses such as ischemia, inflammation, and dramatic changes in cell environment that further taxes RPE cells already dysfunctional from drusen-associated changes. GA may therefore develop secondary to the neovascular process de novo or preexisting drusen-associated GA may continue to worsen with the development of neovascular AMD. Neovascular-associated GA is a prominent cause of continued vision loss in patients with otherwise successfully treated neovascular AMD. Clearly, treatment with vascular endothelial growth factor (VEGF) inhibitors early in the course of the neovascular disease is of great clinical benefit. However, there is a rationale and some suggestive evidence that anti-VEGF agents themselves could be toxic to RPE and enhance neovascular-associated GA. The increasing prevalence of legal blindness from this

  18. Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects

    PubMed Central

    Danis, Ronald P; Lavine, Jeremy A; Domalpally, Amitha

    2015-01-01

    Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular degeneration (AMD). GA may be classified as drusen-related (drusen-associated GA) or neovascularization-related (neovascular-associated GA). Drusen-related GA remains a large public health concern due to the burden of blindness it produces, but pathophysiology of the condition is obscure and there are no proven treatment options. Genotyping, cell biology, and clinical imaging point to upregulation of parainflammatory pathways, oxidative stress, and choroidal sclerosis as contributors, among other factors. Onset and monitoring of progression is accomplished through clinical imaging instrumentation such as optical coherence tomography, photography, and autofluorescence, which are the tools most helpful in determining end points for clinical trials at present. A number of treatment approaches with diverse targets are in development at this time, some of which are in human clinical trials. Neovascular-associated GA is a consequence of RPE loss after development of neovascular AMD. The neovascular process leads to a plethora of cellular stresses such as ischemia, inflammation, and dramatic changes in cell environment that further taxes RPE cells already dysfunctional from drusen-associated changes. GA may therefore develop secondary to the neovascular process de novo or preexisting drusen-associated GA may continue to worsen with the development of neovascular AMD. Neovascular-associated GA is a prominent cause of continued vision loss in patients with otherwise successfully treated neovascular AMD. Clearly, treatment with vascular endothelial growth factor (VEGF) inhibitors early in the course of the neovascular disease is of great clinical benefit. However, there is a rationale and some suggestive evidence that anti-VEGF agents themselves could be toxic to RPE and enhance neovascular-associated GA. The increasing prevalence of legal blindness from this

  19. Implications for a Stem Cell Regenerative Medicine Based Approach to Human Intervertebral Disk Degeneration

    PubMed Central

    Kraus, Petra; Lufkin, Thomas

    2017-01-01

    The human body develops from a single cell, the zygote, the product of the maternal oocyte and the paternal spermatozoon. That 1-cell zygote embryo will divide and eventually grow into an adult human which is comprised of ~3.7 × 1013 cells. The tens of trillions of cells in the adult human can be classified into approximately 200 different highly specialized cell types that make up all of the different tissues and organs of the human body. Regenerative medicine aims to replace or restore dysfunctional cells, tissues and organs with fully functional ones. One area receiving attention is regeneration of the intervertebral discs (IVDs), which are located between the vertebrae and function to give flexibility and support load to the spine. Degenerated discs are a major cause of lower back pain. Different stem cell based regenerative medicine approaches to cure disc degeneration are now available, including using autologous mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs) and even attempts at direct transdifferentiation of somatic cells. Here we discuss some of the recent advances, successes, drawbacks, and the failures of the above-mentioned approaches. PMID:28326305

  20. Implications for a Stem Cell Regenerative Medicine Based Approach to Human Intervertebral Disk Degeneration.

    PubMed

    Kraus, Petra; Lufkin, Thomas

    2017-01-01

    The human body develops from a single cell, the zygote, the product of the maternal oocyte and the paternal spermatozoon. That 1-cell zygote embryo will divide and eventually grow into an adult human which is comprised of ~3.7 × 10(13) cells. The tens of trillions of cells in the adult human can be classified into approximately 200 different highly specialized cell types that make up all of the different tissues and organs of the human body. Regenerative medicine aims to replace or restore dysfunctional cells, tissues and organs with fully functional ones. One area receiving attention is regeneration of the intervertebral discs (IVDs), which are located between the vertebrae and function to give flexibility and support load to the spine. Degenerated discs are a major cause of lower back pain. Different stem cell based regenerative medicine approaches to cure disc degeneration are now available, including using autologous mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs) and even attempts at direct transdifferentiation of somatic cells. Here we discuss some of the recent advances, successes, drawbacks, and the failures of the above-mentioned approaches.

  1. How Does Lumbar Degenerative Disc Disease Affect the Disc Deformation at the Cephalic Levels In Vivo?

    PubMed Central

    Wang, Shaobai; Xia, Qun; Passias, Peter; Li, Weishi; Wood, Kirkham; Li, Guoan

    2013-01-01

    Study Design Case-control study. Objective . To evaluate the effect of lumbar degenerative disc disease (DDD) on the disc deformation at the adjacent level and at the level one above the adjacent level during end ranges of lumbar motion. Summary of Background Data It has been reported that in patients with DDD, the intervertebral discs adjacent to the diseased levels have a greater tendency to degenerate. Although altered biomechanics have been suggested to be the causative factors, few data have been reported on the deformation characteristics of the adjacent discs in patients with DDD. Methods Ten symptomatic patients with discogenic low back pain between L4 and S1 and with healthy discs at the cephalic segments were involved. Eight healthy subjects recruited in our previous studies were used as a reference comparison. The in vivo kinematics of L3–L4 (the cephalic adjacent level to the degenerated discs) and L2–L3 (the level one above the adjacent level) lumbar discs of both groups were obtained using a combined magnetic resonance imaging and dual fluoroscopic imaging technique at functional postures. Deformation characteristics, in terms of areas of minimal deformation (defined as less than 5%), deformations at the center of the discs, and maximum tensile and shear deformations, were compared between the two groups at the two disc levels. Results In the patients with DDD, there were significantly smaller areas of minimal disc deformation at L3–L4 and L2–L3 than the healthy subjects (18% compared with 45% of the total disc area, on average). Both L2–L3 and L3–L4 discs underwent larger tensile and shear deformations in all postures than the healthy subjects. The maximum tensile deformations were higher by up to 23% (of the local disc height in standing) and the maximum shear deformations were higher by approximately 25% to 40% (of the local disc height in standing) compared with those of the healthy subjects. Conclusion Both the discs of the adjacent

  2. Striatopallidonigral degeneration

    PubMed Central

    Bell, W. E.; McCormick, W. F.

    1971-01-01

    A 15-year-old girl is described with a sporadic, progressive illness manifested by unilateral limb rigidity and dystonia. Obvious dysarthria and some intellectual decline also were noted. Neuropathological findings included gross discoloration and shrinkage of the pallida and, microscopically, profound neuronal loss and gliosis of the caudata and putamena, with less severe neuronal loss from the pallida and substantia nigra. The disease bears some similarities to striatonigral degeneration, but certain clinical and morphological differences justify its consideration as a separate syndrome. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:5565467

  3. Responsiveness of the National Eye Institute Visual Function Questionnaire to Progression to Advanced Age-Related Macular Degeneration, Vision Loss, and Lens Opacity

    PubMed Central

    2006-01-01

    Objective To describe the ability of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to detect meaningful change over time (responsiveness) to the primary Age-Related Eye Disease Study outcomes. Methods The 25-item NEI-VFQ plus appendix was administered at 2 visits at 1- to 4-year intervals to 4119 participants in the Age-Related Eye Disease Study. Events evaluated were progression to advanced age-related macular degeneration (AMD), visual acuity (VA) loss of at least 15 letters, and lens opacity progression. Responsiveness was measured by the t statistic, effect size (ES), responsiveness statistic, and area under the receiver operating characteristic curve. Variance components were used to estimate the contributions of events to variability of the NEI-VFQ score. Results Overall NEI-VFQ score was responsive to AMD progression (t = 14.0; P<.001; ES=0.81) and VA (t = 16.2; P<.001; ES=0.74). Mean changes ranged from 11 to 25 points for the subscales of general vision, near and distance activities, social functioning, mental health, role difficulties, dependency, and driving. The NEI-VFQ was unresponsive to lens opacity progression, although when the event occurred in the eye with the best vision at the first administration, the lens opacity ES was moderate for the color vision (ES = 0.62) and driving subscales (ES=0.66). Progression to advanced AMD and VA loss contributed significantly to the variation in the mean difference in overall VFQ score. Conclusions Changes in the NEI-VFQ overall and subscale scores of 10 points or more are associated with clinically significant changes in vision and AMD. This finding may assist the design of interventional studies of AMD and VA loss that include the NEI-VFQ as an outcome measure. PMID:16157800

  4. Macular degeneration (image)

    MedlinePlus

    Macular degeneration is a disease of the retina that affects the macula in the back of the eye. ... see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

  5. Wet Macular Degeneration

    MedlinePlus

    Wet macular degeneration Overview By Mayo Clinic Staff Wet macular degeneration is a chronic eye disease that causes blurred vision ... of the retina responsible for central vision. Wet macular degeneration is one of two types of age-related ...

  6. Dry Macular Degeneration

    MedlinePlus

    Dry macular degeneration Overview By Mayo Clinic Staff Dry macular degeneration is a common eye disorder among people over 65. ... vision in your direct line of sight. Dry macular degeneration may first develop in one eye and then ...

  7. Physiological Loading Can Restore the Proteoglycan Content in a Model of Early IVD Degeneration

    PubMed Central

    Gawri, Rahul; Moir, Janet; Ouellet, Jean; Beckman, Lorne; Steffen, Thomas; Roughley, Peter; Haglund, Lisbet

    2014-01-01

    A hallmark of early IVD degeneration is a decrease in proteoglycan content. Progression will eventually lead to matrix degradation, a decrease in weight bearing capacity and loss of disc height. In the final stages of IVD degradation, fissures appear in the annular ring allowing extrusion of the NP. It is crucial to understand the interplay between mechanobiology, disc composition and metabolism to be able to provide exercise recommendations to patients with early signs of disc degeneration. This study evaluates the effect of physiological loading compared to no loading on matrix homeostasis in bovine discs with induced degeneration. Bovine discs with trypsin-induced degeneration were cultured for 14 days in a bioreactor under dynamic loading with maintained metabolic activity. Chondroadherin abundance and structure was used to confirm that a functional matrix was preserved in the chosen loading environment. No change was observed in chondroadherin integrity and a non-significant increase in abundance was detected in trypsin-treated loaded discs compared to unloaded discs. The proteoglycan concentration in loaded trypsin-treated discs was significantly higher than in unloaded disc and the newly synthesised proteoglycans were of the same size range as those found in control samples. The proteoglycan showed an even distribution throughout the NP region, similar to that of control discs. Significantly more newly synthesised type II collagen was detected in trypsin-treated loaded discs compared to unloaded discs, demonstrating that physiological load not only stimulates aggrecan production, but also that of type II collagen. Taken together, this study shows that dynamic physiological load has the ability to repair the extracellular matrix depletion typical of early disc degeneration. PMID:24992586

  8. Frontotemporal Lobar Degeneration

    PubMed Central

    Rabinovici, Gil D.; Miller, Bruce L.

    2010-01-01

    Frontotemporal lobar degeneration (FTLD) is a clinically and pathologically heterogeneous syndrome, characterized by progressive decline in behaviour or language associated with degeneration of the frontal and anterior temporal lobes. While the seminal cases were described at the turn of the 20th century, FTLD has only recently been appreciated as a leading cause of dementia, particularly in patients presenting before the age of 65 years. Three distinct clinical variants of FTLD have been described: (i) behavioural-variant frontotemporal dementia, characterized by changes in behaviour and personality in association with frontal-predominant cortical degeneration; (ii) semantic dementia, a syndrome of progressive loss of knowledge about words and objects associated with anterior temporal neuronal loss; and (iii) progressive nonfluent aphasia, characterized by effortful language output, loss of grammar and motor speech deficits in the setting of left perisylvian cortical atrophy. The majority of pathologies associated with FTLD clinical syndromes include either tau-positive (FTLD-TAU) or TAR DNA-binding protein 43 (TDP-43)-positive (FTLD-TDP) inclusion bodies. FTLD overlaps clinically and pathologically with the atypical parkinsonian disorders corticobasal degeneration and progressive supranuclear palsy, and with amyotrophic lateral sclerosis. The majority of familial FTLD cases are caused by mutations in the genes encoding microtubule-associated protein tau (leading to FTLD-TAU) or progranulin (leading to FTLD-TDP). The clinical and pathologic heterogeneity of FTLD poses a significant diagnostic challenge, and in vivo prediction of underlying histopathology can be significantly improved by supplementing the clinical evaluation with genetic tests and emerging biological markers. Current pharmacotherapy for FTLD focuses on manipulating serotonergic or dopaminergic neurotransmitter systems to ameliorate behavioural or motor symptoms. However, recent advances in FTLD

  9. Progression Rate From Intermediate to Advanced Age-Related Macular Degeneration Is Correlated With the Number of Risk Alleles at the CFH Locus

    PubMed Central

    Sardell, Rebecca J.; Persad, Patrice J.; Pan, Samuel S.; Whitehead, Patrice; Adams, Larry D.; Laux, Reneé A.; Fortun, Jorge A.; Brantley, Milam A.; Kovach, Jaclyn L.; Schwartz, Stephen G.; Agarwal, Anita; Haines, Jonathan L.; Scott, William K.; Pericak-Vance, Margaret A.

    2016-01-01

    Purpose Progression rate of age-related macular degeneration (AMD) varies substantially, yet its association with genetic variation has not been widely examined. Methods We tested whether progression rate from intermediate AMD to geographic atrophy (GA) or choroidal neovascularization (CNV) was correlated with genotype at seven single nucleotide polymorphisms (SNPs) in the four genes most strongly associated with risk of advanced AMD. Cox proportional hazards survival models examined the association between progression time and SNP genotype while adjusting for age and sex and accounting for variable follow-up time, right censored data, and repeated measures (left and right eyes). Results Progression rate varied with the number of risk alleles at the CFH:rs10737680 but not the CFH:rs1061170 (Y402H) SNP; individuals with two risk alleles progressed faster than those with one allele (hazard ratio [HR] = 1.61, 95% confidence interval [CI] = 1.08–2.40, P < 0.02, n = 547 eyes), although this was not significant after Bonferroni correction. This signal was likely driven by an association at the correlated protective variant, CFH:rs6677604, which tags the CFHR1-3 deletion; individuals with at least one protective allele progressed more slowly. Considering GA and CNV separately showed that the effect of CFH:rs10737680 was stronger for progression to CNV. Conclusions Results support previous findings that AMD progression rate is influenced by CFH, and suggest that variants within CFH may have different effects on risk versus progression. However, since CFH:rs10737680 was not significant after Bonferroni correction and explained only a relatively small portion of variation in progression rate beyond that explained by age, we suggest that additional factors contribute to progression. PMID:27832277

  10. Intervertebral disc properties: challenges for biodevices.

    PubMed

    Costi, John J; Freeman, Brian J C; Elliott, Dawn M

    2011-05-01

    Intervertebral disc biodevices that employ motion-preservation strategies (e.g., nucleus replacement, total disc replacement and posterior stabilization devices) are currently in use or in development. However, their long-term performance is unknown and only a small number of randomized controlled trials have been conducted. In this article, we discuss the following biodevices: interbody cages, nuclear pulposus replacements, total disc replacements and posterior dynamic stabilization devices, as well as future biological treatments. These biodevices restore some function to the motion segment; however, contrary to expectations, the risk of adjacent-level degeneration does not appear to have been reduced. The short-term challenge is to replicate the complex biomechanical function of the motion segment (e.g., biphasic, viscoelastic behavior and nonlinearity) to improve the quality of motion and minimize adjacent level problems, while ensuring biodevice longevity for the younger, more active patient. Biological strategies for regeneration and repair of disc tissue are being developed and these offer exciting opportunities (and challenges) for the longer term. Responsible introduction and rigorous assessment of these new technologies are required. In this article, we will describe the properties of the disc, explore biodevices currently in use for the surgical treatment of low back pain (with an emphasis on lumbar total disc replacement) and discuss future directions for biological treatments. Finally, we will assess the challenges ahead for the next generation of biodevices designed to replace the disc.

  11. Automatic Detection of Optic Disc in Retinal Image by Using Keypoint Detection, Texture Analysis, and Visual Dictionary Techniques

    PubMed Central

    Bayır, Şafak

    2016-01-01

    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. PMID:27110272

  12. Automatic Detection of Optic Disc in Retinal Image by Using Keypoint Detection, Texture Analysis, and Visual Dictionary Techniques.

    PubMed

    Akyol, Kemal; Şen, Baha; Bayır, Şafak

    2016-01-01

    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.

  13. Redundant disc

    NASA Technical Reports Server (NTRS)

    Barack, W. N.; Domas, P. A.; Beekman, S. W. (Inventor)

    1978-01-01

    A rotatable disc is described that consists of parallel plates tightly joined together for rotation about a hub. Each plate is provided with several angularly projecting spaced lands. The lands of each plate are interposed in alternating relationship between the lands of the next adjacent plate. In this manner, circumferential displacement of adjacent sectors in any one plate is prevented in the event that a crack develops. Each plate is redundantly sized so that, in event of structural failure of one plate, the remaining plates support a proportionate share of the load of the failed plate. The plates are prevented from separating laterally through the inclusion of generally radially extending splines which are inserted to interlock cooperating, circumferentially adjacent lands.

  14. Dietary folate, B vitamins, genetic susceptibility and progression to advanced nonexudative age-related macular degeneration with geographic atrophy: a prospective cohort study12

    PubMed Central

    Silver, Rachel E; Rosner, Bernard; Seddon, Johanna M

    2016-01-01

    Background: There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but few studies have explored associations with folate and B vitamins. No effective therapeutic strategy for geographic atrophy (GA) is available, and prevention could be of great value. Objective: We investigated associations between dietary folate, B vitamins, and progression to GA and whether these associations might be modified by genetic susceptibility. Design: Among 2525 subjects (4663 eyes) in the Age-Related Eye Disease Study, 405 subjects (528 eyes) progressed to GA over 13 y. Folate and B vitamins were log transformed and calorie adjusted separately for men and women. Ten loci in 7 AMD genes [complement factor H, age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1, complement component 2, complement component 3, complement factor B, collagen type VIII α 1, and RAD51 paralog B] were examined. Survival analysis was used to assess associations between incident GA and dietary intake of folate and B vitamins. Interaction effects between these nutrients and genetic variation on AMD risk were also evaluated. Subjects with at least one eye free of advanced AMD at baseline were included in these analyses. Results: There was a reduced risk of progression to GA with increasing intake of thiamin, riboflavin, and folate after adjusting for age, sex, and total energy intake (P-trend = 0.01, 0.03, and 0.001, respectively). After adjustment for demographic, behavioral, ocular, and genetic covariates, trends remained statistically significant for folate (P-trend = 0.007) and were borderline for thiamin (P-trend = 0.05). Riboflavin did not retain statistical significance (P-trend = 0.20). Folate was significantly associated with lower risk of incident GA among subjects homozygous for the complement component 3 (C3) R102G rs2230199 nonrisk genotype (CC) (HR = 0.43; 95% CI: 0.27, 0.70; P = 0.0005) but not subjects carrying

  15. Cervical disc arthroplasty: Pros and cons

    PubMed Central

    Moatz, Bradley; Tortolani, P. Justin

    2012-01-01

    Background: 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. Methods: This study reviews the current research regarding cervical athroplasty, and emphasizes both the pros and cons of arthroplasty as compared with ACDF. Results: 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. Conclusion: 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. PMID:22905327

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  17. Age-related macular degeneration.

    PubMed

    Lim, Laurence S; Mitchell, Paul; Seddon, Johanna M; Holz, Frank G; Wong, Tien Y

    2012-05-05

    Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies.

  18. Mesenchymal stem cell tracking in the intervertebral disc

    PubMed Central

    Handley, Charles; Goldschlager, Tony; Oehme, David; Ghosh, Peter; Jenkin, Graham

    2015-01-01

    Low back pain is a common clinical problem, which leads to significant social, economic and public health costs. Intervertebral disc (IVD) degeneration is accepted as a common cause of low back pain. Initially, this is characterized by a loss of proteoglycans from the nucleus pulposus resulting in loss of tissue hydration and hydrostatic pressure. Conservative management, including analgesia and physiotherapy often fails and surgical treatment, such as spinal fusion, is required. Stem cells offer an exciting possible regenerative approach to IVD disease. Preclinical research has demonstrated promising biochemical, histological and radiological results in restoring degenerate IVDs. Cell tracking provides an opportunity to develop an in-depth understanding of stem cell survival, differentiation and migration, enabling optimization of stem cell treatment. Magnetic Resonance Imaging (MRI) is a non-invasive, non-ionizing imaging modality with high spatial resolution, ideally suited for stem cell tracking. Furthermore, novel MRI sequences have the potential to quantitatively assess IVD disease, providing an improved method to review response to biological treatment. Superparamagnetic iron oxide nanoparticles have been extensively researched for the purpose of cell tracking. These particles are biocompatible, non-toxic and act as excellent MRI contrast agents. This review will explore recent advances and issues in stem cell tracking and molecular imaging in relation to the IVD. PMID:25621106

  19. Validation of Sodium MRI of Intervertebral Disc

    PubMed Central

    Wang, Chenyang; McArdle, Erin; Fenty, Matthew; Witschey, Walter; Elliott, Mark; Sochor, Matthew; Reddy, Ravinder; Borthakur, Arijitt

    2009-01-01

    Study Design This study demonstrated the diagnostic potential of sodium MRI for non-invasive quantification of PG in the intervertebral discs. Objective To determine the existence of a linear correlation between intervertebral disc [Na] measured from sodium MRI and [PG] measurement from DMMB assay. Summary of Background Data Previous studies have shown the possibility of quantifying [Na] in vivo using sodium MRI, however none has shown a direct linear correlation between [Na] measured from sodium MRI and [PG]. Methods 3D sodium MRI images of bovine discs were acquired and converted into [Na] maps. Samples were systematically removed from the discs for DMMB assay. The removal locations were photographically recorded and applied to the [Na] maps to extract the [Na] measurements for comparison. In vivo sodium MRI scans were also carried out on a pair of symptomatic and asymptomatic subjects. Results The linear regression fit of [Na] versus [PG] data yielded a significant linear correlation coefficient of 0.71. The in vivo sodium MRI image of the symptomatic subject showed significant [Na] decrease when compared to that of the asymptomatic subject. Conclusion Sodium MRI's specificity for PG in the intervertebral discs makes it a promising diagnostic tool for the earlier phase of disc degeneration. PMID:20147881

  20. Macular Degeneration Partnership

    MedlinePlus

    ... Age Related Macular Degeneration) Partnership Listen AMD Month Public Service Announcement To raise awareness of AMD, the Macular Degeneration Partnership (MDP) is distributing a public service announcement (PSA) nationwide. Seen through the eyes of a ...

  1. Lumbar disc herniation: Is there an association between histological and magnetic resonance imaging findings?

    PubMed Central

    Majeed, Shiju A; Seshadrinath, N Arun Kumar; Binoy, Kavitha Ravi; Raji, Laila

    2016-01-01

    Background: Although validated radiological scoring systems and histological scoring system of surgically removed degenerated disc are used in assessment of progression of intervertebral disc degeneration, there have not been many studies that integrate these two aspects of assessments. The data available in this respect are very limited. This clinical study was designed to find the correlation between quantitative radiological score (Pfirmann grading system and Modic changes [MC]) and quantitative histological degeneration score (HDS). Materials and Methods: A cohort of 77 patients (45 males, 32 females; mean age of 38 years [range 18–58 years]) who presented with complaints of discogenic pain or radiculopathy at single level were assessed radiologically. They were graded according to the radiological pattern. The surgically excised disc specimen was graded according to HDS. The degree of radiological changes were correlated with the degree of histological changes. Results: Though the overall HDS (0–15) did not show statistically significant correlation with Pfirmann grading system, there were positive association found between mucoid degeneration, chondrocyte proliferation with the Pfirmann grading and mucoid degeneration, which were statistically significant. Female sex also had a higher association with instability pattern. Conclusion: The study shows that the Pfirmann grading system, MCs and HDS can reliably be used as scoring systems for assessing lumbar disc degeneration. The radiological assessment can be used as a noninvasive tool to assess the probable change in content rather than the microstructure of a disc undergoing degeneration. PMID:27293282

  2. Macular Degeneration: An Overview.

    ERIC Educational Resources Information Center

    Chalifoux, L. M.

    1991-01-01

    This article presents information on macular degeneration for professionals helping persons with this disease adjust to their visual loss. It covers types of macular degeneration, the etiology of the disease, and its treatment. Also considered are psychosocial problems and other difficulties that persons with age-related macular degeneration face.…

  3. Molecular Therapy for Disk Degeneration and Pain

    PubMed Central

    Mwale, Fackson

    2013-01-01

    The nucleus pulposus of the intervertebral disk contains high amounts of the proteoglycan aggrecan, which confers the disk with a remarkable ability to resist compression. Other molecules such as collagens and noncollagenous proteins in the extracellular matrix are also essential for function. During disk degeneration, aggrecan and other molecules are lost due to proteolysis. This can result in loss of disk height, which can ultimately lead to pain. Biological therapy of intervertebral disk degeneration aims at preventing or restoring primarily aggrecan content and other molecules using therapeutic molecules. The purpose of the article is to review recent advances in biological repair of degenerate disks and pain. PMID:24436869

  4. Apparent diffusion coefficient in normal and abnormal pattern of intervertebral lumbar discs: initial experience☆

    PubMed Central

    Niu, Gang; Yu, Xuewen; Yang, Jian; Wang, Rong; Zhang, Shaojuan; Guo, Youmin

    2011-01-01

    The aim of the present study was to compare the relationship of morphologically defined non-bulging/herniated, bulging and herniated intervertebral lumbar discs with quantitative apparent diffusion coefficient (ADC). Thirty-two healthy volunteers and 28 patients with back pain or sciatica were examined by MRI. All intervertebral lumbar discs from L1 to S1 were classified according to morphological abnormality and degenerated grades. The ADC values of nucleus pulposus (NP) were measured and recorded. The significant differences about mean ADC values of NP were found between non-bulging/herniated discs and bulging discs as well as herniated discs (P < 0.05), whereas there were no significant differences in ADC values between bulging and herniated discs (P > 0.05). Moreover, statistically significant relationship was found in the mean ADC values of NP between “non-bulging/herniated and non-degenerated discs” and “non-bulging/herniated degenerated discs” as well as herniated discs (P < 0.05). Linear regression analysis between ADC value and disc level revealed an inverse correlation (r = -0.18). The ADC map of the NP is a potentially useful tool for the quantitative assessment of componential and molecular alterations accompanied with lumbar disc abnormalities. PMID:23554690

  5. Turbine disc sealing assembly

    DOEpatents

    Diakunchak, Ihor S.

    2013-03-05

    A disc seal assembly for use in a turbine engine. The disc seal assembly includes a plurality of outwardly extending sealing flange members that define a plurality of fluid pockets. The sealing flange members define a labyrinth flow path therebetween to limit leakage between a hot gas path and a disc cavity in the turbine engine.

  6. Design concepts in lumbar total disc arthroplasty

    PubMed Central

    Bellini, Chiara M.; Zweig, Thomas; Ferguson, Stephen; Raimondi, Manuela T.; Lamartina, Claudio; Brayda-Bruno, Marco; Fornari, Maurizio

    2008-01-01

    The implantation of lumbar disc prostheses based on different design concepts is widely accepted. This paper reviews currently available literature studies on the biomechanics of TDA in the lumbar spine, and is targeted at the evaluation of possible relationships between the aims of TDA and the geometrical, mechanical and material properties of the various available disc prostheses. Both theoretical and experimental studies were analyzed, by a PUBMED search (performed in February 2007, revised in January 2008), focusing on single level TDA. Both semi-constrained and unconstrained lumbar discs seem to be able to restore nearly physiological IAR locations and ROM values. However, both increased and decreased ROM was stated in some papers, unrelated to the clinical outcome. Segmental lordosis alterations after TDA were reported in most cases, for both constrained and unconstrained disc prostheses. An increase in the load through the facet joints was documented, for both semi-constrained and unconstrained artificial discs, but with some contrasting results. Semi-constrained devices may be able to share a greater part of the load, thus protecting the surrounding biological structure from overloading and possible early degeneration, but may be more susceptible to wear. The next level of development will be the biomechanical integration of compression across the motion segment. All these findings need to be supported by long-term clinical outcome studies. PMID:18946684

  7. Intervertebral disc regeneration using platelet-rich plasma-containing bone marrow-derived mesenchymal stem cells: A preliminary investigation

    PubMed Central

    WANG, SHAN-ZHENG; JIN, JI-YANG; GUO, YU-DONG; MA, LIANG-YU; CHANG, QING; PENG, XIN-GUI; GUO, FANG-FANG; ZHANG, HAI-XIANG; HU, XIN-FENG; WANG, CHEN

    2016-01-01

    Platelet-rich plasma (PRP) is a promising strategy for intervertebral disc degeneration (IDD). However, the short half-life of growth factors released from PRP cannot continuously stimulate the degenerated discs. Thus, the present study hypothesized that the combined use of PRP and bone marrow-derived mesenchymal stem cells (BMSCs) may repair the early degenerated discs in the long term for their synergistic reparative effect. In the present study, following the induction of early IDD by annular puncture in rabbits, PRP was prepared and mixed with BMSCs (PRP-BMSC group) for injection into the early degenerated discs. As controls, phosphate-buffered saline (PBS; PBS group) and PRP (PRP group) were similarly injected. Rabbits without any intervention served as a control group. At 8 weeks following treatment, histological changes of the injected discs were assessed. Magnetic resonance imaging (MRI) was used to detect the T2-weighted signal intensity of the targeted discs at weeks 1, 2 and 8 following treatment. Annular puncture resulted in disc narrowing and decreased T2-weighted signal intensity. At weeks 1 and 3, MRI examinations showed regenerative changes in the PRP-BMSC group and PRP group, whereas the PBS group exhibited a continuous degenerative process of the discs. At 8 weeks post-injection, the PRP-BMSCs induced a statistically significant restoration of discs, as shown by MRI (PRP-BMSCs, vs.PRP and PBS; P<0.05), which was also confirmed by histological evaluations. Thus, compared with PRP, the administration of PRP-containing BMSCs resulted in a superior regenerative effect on the early degenerated discs, which may be a promising therapeutic strategy for the restoration of early degenerated discs. PMID:26956080

  8. Intervertebral disc replacement. Experimental study.

    PubMed

    Kostuik, J P

    1997-04-01

    Arthrodesis of the lumbosacral spine, although satisfactory for a majority of patients, has long term sequelae in 30% of patients. This is particularly true for adjacent segment degeneration. Numerous attempts at providing a mobile motion segment have been made in the past. The current status of the development of dynamic intervertebral prosthesis, including biomechanical and clinical data have been presented. The relevant material properties of plastics, ceramics, and metal are presented with the conclusion that metals currently present with the greatest longevity without undue fatigue and wear as many as 100,000,000 cycles (40 years use) as an alternative to spinal fusion. An analysis of the kinematics of the motion segment have resulted, together with the material properties in the development of a dynamic intervertebral disc for use in the lumbar spine. The disc resembles a normal motion segment. In motion stiffness and center of rotation, wear debris development in 1/300 equivalent to that of a total hip prosthesis for the same given time. Safety features include immediate screw fixation to prevent displacement, a wedge elastic (spring) shape, and a bony porous ingrowth surface. The prosthesis is constructed of cobalt chromium and titanium with minimal corrosive properties on long term testing.

  9. Simulating the sensitivity of cell nutritive environment to composition changes within the intervertebral disc

    NASA Astrophysics Data System (ADS)

    Wills, C. Ruiz; Malandrino, A.; van Rijsbergen, MM.; Lacroix, D.; Ito, K.; Noailly, J.

    2016-05-01

    Altered nutrition in the intervertebral disc affects cell viability and can generate catabolic cascades contributing to extracellular matrix (ECM) degradation. Such degradation is expected to affect couplings between disc mechanics and nutrition, contributing to accelerate degenerative processes. However, the relation of ECM changes to major biophysical events within the loaded disc remains unclear. A L4-L5 disc finite element model including the nucleus (NP), annulus (AF) and endplates was used and coupled to a transport-cell viability model. Solute concentrations and cell viability were evaluated along the mid-sagittal plane path. A design of experiment (DOE) was performed. DOE parameters corresponded to AF and NP biochemical tissue measurements in discs with different degeneration grades. Cell viability was not affected by any parameter combinations defined. Nonetheless, the initial water content was the parameter that affected the most the solute contents, especially glucose. Calculations showed that altered NP composition could negatively affect AF cell nutrition. Results suggested that AF and NP tissue degeneration are not critical to nutrition-related cell viability at early-stage of disc degeneration. However, small ECM degenerative changes may alter significantly disc nutrition under mechanical loads. Coupling disc mechano-transport simulations and enzyme expression studies could allow identifying spatiotemporal sequences related to tissue catabolism.

  10. Advanced glycation end products regulate anabolic and catabolic activities via NLRP3-inflammasome activation in human nucleus pulposus cells.

    PubMed

    Song, Yu; Wang, Yan; Zhang, Yukun; Geng, Wen; Liu, Wei; Gao, Yong; Li, Shuai; Wang, Kun; Wu, Xinghuo; Kang, Liang; Yang, Cao

    2017-02-22

    Intervertebral disc degeneration is widely recognized as a cause of lower back pain, neurological dysfunction and other musculoskeletal disorders. The major inflammatory cytokine IL-1β is associated with intervertebral disc degeneration; however, the molecular mechanisms that drive IL-1β production in the intervertebral disc, especially in nucleus pulposus (NP) cells, are unknown. In some tissues, advanced glycation end products (AGEs), which accumulate in NP tissues and promote its degeneration, increase oxidative stress and IL-1β secretion, resulting in disorders, such as obesity, diabetes mellitus and ageing. It remains unclear whether AGEs exhibit similar effects in NP cells. In this study, we observed significant activation of the NLRP3 inflammasome in NP tissues obtained from patients with degenerative disc disease compared to that with idiopathic scoliosis according to results detected by Western blot and immunofluorescence. Using NP cells established from healthy tissues, our in vitro study revealed that AGEs induced an inflammatory response in NP cells and a degenerative phenotype in a NLRP3-inflammasome-dependent manner related to the receptor for AGEs (RAGE)/NF-κB pathway and mitochondrial damage induced by mitochondrial reactive oxygen species (mtROS) generation, mitochondrial permeability transition pore (mPTP) activation and calcium mobilization. Among these signals, both RAGE and mitochondrial damage primed NLRP3 and pro-IL-1β activation as upstream signals of NF-κB activity, whereas mitochondrial damage was critical for the assembly of inflammasome components. These results revealed that accumulation of AGEs in NP tissue may initiate inflammation-related degeneration of the intervertebral disc via activation of the NLRP3 inflammasome.

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

    PubMed

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

    1998-02-01

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

  12. Goddard Earth Science Data and Information Center (GES DISC)

    NASA Technical Reports Server (NTRS)

    Kempler, Steve

    2016-01-01

    The GES DIS is one of 12 NASA Earth science data centers. The GES DISC vision is to enable researchers and educators maximize knowledge of the Earth by engaging in understanding their goals, and by leading the advancement of remote sensing information services in response to satisfying their goals. This presentation will describe the GES DISC approach, successes, challenges, and best practices.

  13. Complement inhibition in cynomolgus monkeys by anti-factor d antigen-binding fragment for the treatment of an advanced form of dry age-related macular degeneration.

    PubMed

    Loyet, Kelly M; Good, Jeremy; Davancaze, Teresa; Sturgeon, Lizette; Wang, Xiangdan; Yang, Jihong; Le, Kha N; Wong, Maureen; Hass, Philip E; van Lookeren Campagne, Menno; Haughney, Peter C; Morimoto, Alyssa; Damico-Beyer, Lisa A; DeForge, Laura E

    2014-12-01

    Anti-factor D (AFD; FCFD4514S, lampalizumab) is a humanized IgG Fab fragment directed against factor D (fD), a rate-limiting serine protease in the alternative complement pathway (AP). Evaluation of AFD as a potential intravitreal (IVT) therapeutic for dry age-related macular degeneration patients with geographic atrophy (GA) is ongoing. However, it is unclear whether IVT administration of AFD can affect systemic AP activation and potentially compromise host-immune responses. We characterized the pharmacologic properties of AFD and assessed the effects of AFD administered IVT (2 or 20 mg) or intravenous (0.2, 2, or 20 mg) on systemic complement activity in cynomolgus monkeys. For the IVT groups, serum AP activity was reduced for the 20 mg dose group between 2 and 6 hours postinjection. For the intravenous groups, AFD inhibited systemic AP activity for periods of time ranging from 5 minutes (0.2 mg group) to 3 hours (20 mg group). Interestingly, the concentrations of total serum fD increased up to 10-fold relative to predose levels following administration of AFD. Furthermore, AFD was found to inhibit systemic AP activity only when the molar concentration of AFD exceeded that of fD. This occurred in cynomolgus monkeys at serum AFD levels ≥2 µg/ml, a concentration 8-fold greater than the maximum serum concentration observed following a single 10 mg IVT dose in a clinical investigation in patients with GA. Based on these findings, the low levels of serum AFD resulting from IVT administration of a clinically relevant dose are not expected to appreciably affect systemic AP activity.

  14. Pellucid marginal corneal degeneration.

    PubMed

    Krachmer, J H

    1978-07-01

    Pellucid marginal degeneration of the cornea is a bilateral, clear, inferior, peripheral corneal-thinning disorder. Protrusion of the cornea occurs above a band of thinning, which is located 1 to 2 mm from the limbus and measures 1 to 2 mm in width. American ophthalmologists are generally not familiar with the condition because most of the literature concerning pellucid degeneration is European. Four cases are described. This condition is differentiated from other noninflammatory cornel-thinning disorders such as keratoconus, keratoglobus, keratotorus, and posterior keratoconus. It is also differentiated from peripheral corneal disorders associated with inflammation such as Terrien's peripheral corneal degeneration, Mooren's ulcers, and ulcers from connective tissue disease.

  15. Lumbosacral Sagittal Alignment in Association to Intervertebral Disc Diseases

    PubMed Central

    Maleki, Farid; Meybodi, Ali Tayebi; Mahdavi, Ali; Saberi, Hooshang

    2014-01-01

    Study Design A cross-sectional case-control study was designed to compare the sagittal alignment of lumbosacral regions in two groups of patients suffering from low back pain, one with intervertebral disc pathologies and one without. Purpose To evaluate the correlation between lumbosacral sagittal alignment and disc degeneration. Overview of Literature Changes in lumbar lordosis and pelvic parameters in degenerative disc lesions have been assessed in few studies. Overall, patients with discopathy were shown to have lower lumbar lordosis and more vertical sacral profiles. Methods From patients with intractable low back pain undergoing lumbosacral magnetic resonance imaging, 50 subjects with disc degeneration and 50 controls with normal scans were consecutively enrolled. A method was defined with anterior tangent-lines going through anterior bodies of L1 and S1 to measure global lumbosacral angle, incorporating both lumbar lordosis and sacral slope. Global lumbosacral angle using the proposed method and lumbar lordosis using Cobb's method were measured in both groups. Results Lumbar lordosis based on Cobb's method was lower in group with discopathy (20°-67°; mean, 40.48°±9.89°) than control group (30°-62°; mean, 44.96°±7.68°), although it was not statistically significant. The proposed global lumbosacral angle in subject group (53°-103°; mean, 76.5°±11.018°) was less than control group (52°-101°; mean, 80.18°±9.95°), with the difference being statistically significant (p=0.002). Conclusions Patients with intervertebral disc lesions seem to have more straightened lumbosacral profiles, but it has not been proven which comes first: disc degeneration or changes in sagittal alignment. Finding an answer to this dilemma demands more comprehensive long-term prospective studies. PMID:25558325

  16. Intervertebral disc magnetic resonance image: correlation with gross morphology and biochemical composition

    PubMed Central

    Bishop, Paul B

    1993-01-01

    The magnetic resonance image, gross morphology, and biochemical composition of the intervertebral disc nucleus pulposus (NP), anulus fibrosus (AF) and cartilaginous endplates (CEP) from two groups of three human lumbar spines were compared. Group I consisted of all healthy discs from young donors (Grade I) and group II was comprised of discs that had undergone degeneration and age-related changes (average Grade 4). The gross morphological changes in the individual disc tissues associated with ageing/degeneration were consistent with specific changes in the characteristics of the magnetic resonance image. In particular, the mid-nuclear band of decreased magnetic resonance signal intensity seen in Grade 4 discs was associated with the appearance of clefts and fissures as well as a region of mucinous infiltration. The results of the biochemical analysis suggest that the changes in signal intensity are not due merely to changes in water content, but are also associated with changes in proteoglycan content. The changes associated with ageing/degeneration in the magnetic resonance image of the disc were related to a decrease in the proteoglycan content of the AF and NP. The water content of the NP also decreased. There was no clear association between the biochemical composition of the CEP and the magnetic resonance image. These results demonstrate that magnetic resonance imaging is an effective technique for evaluating subtle morphological changes in the intervertebral disc tissues and may be a sensitive indicator of the proteoglycan content of the AF and NP. ImagesFigure 1Figure 2

  17. Double Degenerate Binary Systems

    SciTech Connect

    Yakut, K.

    2011-09-21

    In this study, angular momentum loss via gravitational radiation in double degenerate binary (DDB)systems (NS + NS, NS + WD, WD + WD, and AM CVn) is studied. Energy loss by gravitational waves has been estimated for each type of systems.

  18. Mesenchymal stem cells regulate mechanical properties of human degenerated nucleus pulposus cells through SDF-1/CXCR4/AKT axis.

    PubMed

    Liu, Ming-Han; Bian, Bai-Shi-Jiao; Cui, Xiang; Liu, Lan-Tao; Liu, Huan; Huang, Bo; Cui, You-Hong; Bian, Xiu-Wu; Zhou, Yue

    2016-08-01

    Transplantation of mesenchymal stem cells (MSCs) into the degenerated intervertebral disc (IVD) has shown promise for decelerating or arresting IVD degeneration. Cellular mechanical properties play crucial roles in regulating cell-matrix interactions, potentially reflecting specific changes that occur based on cellular phenotype and behavior. However, the effect of co-culturing of MSCs with nucleus pulposus cells (NPCs) on the mechanical properties of NPCs remains unknown. In our study, we demonstrated that co-culture of degenerated NPCs with MSCs resulted in significantly decreased mechanical moduli (elastic modulus, relaxed modulus, and instantaneous modulus) and increased biological activity (proliferation and expression of matrix genes) in degenerated NPCs, but not normal NPCs. SDF-1, CXCR4 ligand, was highly expressed in MSCs when co-cultured with degenerated NPCs. Inhibition of SDF-1 using CXCR4 antagonist AMD3100 or knocking-down CXCR4 in degenerated NPCs abolished the MSCs-induced decrease in the mechanical moduli and increased biological activity of degenerated NPCs, suggesting a crucial role for SDF-1/CXCR4 signaling. AKT and FAK inhibition attenuated the MSCs- or SDF-1-induced decrease in the mechanical moduli of degenerated NPCs. In conclusion, it was demonstrated in vitro that MSCs regulate the mechanical properties of degenerated NPCs through SDF-1/CXCR4/AKT signaling. These findings highlight a possible mechanical mechanism for MSCs-induced modulation with degenerated NPCs, which may be applicable to MSCs-based therapy for disc degeneration.

  19. 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

    PubMed Central

    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

  20. The effect of sustained compression on oxygen metabolic transport in the intervertebral disc decreases with degenerative changes.

    PubMed

    Malandrino, Andrea; Noailly, Jérôme; Lacroix, Damien

    2011-08-01

    Intervertebral disc metabolic transport is essential to the functional spine and provides the cells with the nutrients necessary to tissue maintenance. Disc degenerative changes alter the tissue mechanics, but interactions between mechanical loading and disc transport are still an open issue. A poromechanical finite element model of the human disc was coupled with oxygen and lactate transport models. Deformations and fluid flow were linked to transport predictions by including strain-dependent diffusion and advection. The two solute transport models were also coupled to account for cell metabolism. With this approach, the relevance of metabolic and mechano-transport couplings were assessed in the healthy disc under loading-recovery daily compression. Disc height, cell density and material degenerative changes were parametrically simulated to study their influence on the calculated solute concentrations. The effects of load frequency and amplitude were also studied in the healthy disc by considering short periods of cyclic compression. Results indicate that external loads influence the oxygen and lactate regional distributions within the disc when large volume changes modify diffusion distances and diffusivities, especially when healthy disc properties are simulated. Advection was negligible under both sustained and cyclic compression. Simulating degeneration, mechanical changes inhibited the mechanical effect on transport while disc height, fluid content, nucleus pressure and overall cell density reductions affected significantly transport predictions. For the healthy disc, nutrient concentration patterns depended mostly on the time of sustained compression and recovery. The relevant effect of cell density on the metabolic transport indicates the disturbance of cell number as a possible onset for disc degeneration via alteration of the metabolic balance. Results also suggest that healthy disc properties have a positive effect of loading on metabolic transport. Such

  1. Holographic optical disc

    NASA Astrophysics Data System (ADS)

    Zhou, Gan; An, Xin; Pu, Allen; Psaltis, Demetri; Mok, Fai H.

    1999-11-01

    The holographic disc is a high capacity, disk-based data storage device that can provide the performance for next generation mass data storage needs. With a projected capacity approaching 1 terabit on a single 12 cm platter, the holographic disc has the potential to become a highly efficient storage hardware for data warehousing applications. The high readout rate of holographic disc makes it especially suitable for generating multiple, high bandwidth data streams such as required for network server computers. Multimedia applications such as interactive video and HDTV can also potentially benefit from the high capacity and fast data access of holographic memory.

  2. Discal cyst associated with myxoid change and apoptosis of herniated disc materials: a case report.

    PubMed

    Okada, Kyoji; Saito, Hajime; Nishida, Jun; Miyakoshi, Naohisa; Takahashi, Shu; Nagasawa, Hiroyuki; Suzuki, Norio; Chida, Shuichi

    2007-01-01

    Discal cyst is a lumbar intraspinal cyst communicating with intervertebral disc, and previously reported series described the wall of these cysts as consisting of dense fibrous connective tissue. We report a 29-year-old Japanese male with discal cyst showing unusual histological features. Clinical symptoms in the current case as well as imaging features including discography were similar to those previously reported.However, the wall of the cyst consisted of disc material with myxoid degeneration. In addition, apoptosis of chondrocytes was diffusely observed in the herniated disc material. The current case was considered a histological variant of discal cyst. Myxoid degeneration of herniated disc material with diffuse apoptotic change of chondrocytes was probably associated with the formation of discal cyst.

  3. Disc replacement using Pro-Disc C versus fusion: a prospective randomised and controlled radiographic and clinical study

    PubMed Central

    Ahlhelm, F.; Pitzen, T.; Steudel, W. I.; Jung, J.; Shariat, K.; Steimer, O.; Bachelier, F.; Pape, D.

    2006-01-01

    Anterior cervical discectomy and fusion (ACDF) may be considered to be the gold standard for treatment of symptomatic degenerative disc disease within the cervical spine. However, fusion of the segment may result in progressive degeneration of the adjacent segments. Therefore, dynamic stabilization procedures have been introduced. Among these, artificial disc replacement by disc prosthesis seems to be promising. However, to be so, segmental motion must be preserved. This, again, is very difficult to judge and has not yet been proven. The aim of the current study was to first analyse the segmental motion following artificial disc replacement using a disc prosthesis. A second aim was to compare both segmental motion as well as clinical result to the current gold standard (ACDF). This is a prospective controlled study. Twenty-five patients with cervical disc herniation were enrolled and assigned to either study group (receiving a disc prosthesis) or control group (receiving ACDF, using a cage with bone graft and an anterior plate.) Radiostereometric analysis was used to quantify intervertebral motion immediately as well as 3, 6, 12 and 24 weeks postoperatively. Further, clinical results were judged using visual analogue scale and neuro-examination. Cervical spine segmental motion decreased over time in the presence of disc prosthesis or ACDF. However, the loss of segmental motion is significantly higher in the ACDF group, when looked at 3, 6, 12 and 24 weeks after surgery. We observed significant pain reduction in neck and arm postoperatively, without significant difference between both groups (P > 0.05). Cervical spine disc prosthesis preserves cervical spine segmental motion within the first 6 months after surgery. The clinical results are the same when compared to the early results following ACDF. PMID:17106665

  4. Bryan total disc arthroplasty: a replacement disc for cervical disc disease

    PubMed Central

    Wenger, Markus; Markwalder, Thomas-Marc

    2010-01-01

    Total disc arthroplasty is a new option in the treatment of cervical degenerative disc disease. Several types of cervical disc prostheses currently challenge the gold-standard discectomy and fusion procedures. This review describes the Bryan Cervical Disc System and presents the Bryan prosthesis, its indications, surgical technique, complications, and outcomes, as given in the literature. PMID:22915917

  5. Can Exercise Positively Influence the Intervertebral Disc?

    PubMed

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

    2016-04-01

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

  6. Evaluation of load transfer characteristics of a dynamic stabilization device on disc loading under compression.

    PubMed

    Zhang, Qing Hang; Zhou, Yuan Li; Petit, Dominique; Teo, Ee Chon

    2009-06-01

    In the current study, finite element analyses were conducted to examine the biomechanical capability of a newly design dynamic stabilization system, FlexPLUS, to restore the load transmission of degenerated intervertebral L4-L5 lumbar motion segment spine under compression. Detailed three-dimensional FE models of L4-L5 motion segment and the FlexPLUS were developed. Compressive loading up to 1000N was applied to the intact L4-L5 model, the L4-L5 models with slight and moderate degenerated disc, and the implanted L4-L5 model. Further more, the load transmission characteristics of Dynesys and a rigid rod was also simulated for comparison. The resultant load-displacement curves and the load transferred through annulus under various conditions were compared. The predicted axial displacement of L4 top surface against applied compressive force of the intact L4-L5 model agreed well with experimental data. The predicted results showed that degenerated disc has significant effect on the lumbar segment load bearing capacity. Not only the stiffness of the segment was greatly increased, the uniform nature of the disc stress distribution was also altered. The FlexPLUS can effectively reduce the disc loading of degenerated model. Although the non-uniform load distribution pattern through annulus was not improved, the overall stress magnitude was greatly reduced to the level of intact model for grade II degeneration.

  7. An In Vivo Model of Reduced Nucleus Pulposus Glycosaminoglycan Content in the Rat Lumbar Intervertebral Disc

    PubMed Central

    Boxberger, John I.; Auerbach, Joshua D.; Sen, Sounok; Elliott, Dawn M.

    2009-01-01

    Study Design An in vivo model resembling early stage disc degeneration in the rat lumbar spine. Objective Simulate the reduced glycosaminoglycan content and altered mechanics observed in intervertebral disc degeneration using a controlled injection of chondroitinase ABC (ChABC). Summary of Background Data Nucleus glycosaminoglycan reduction occurs early during disc degeneration; however, mechanisms through which degeneration progresses from this state are unknown. Animal models simulating this condition are essential for understanding disease progression and for development of therapies aimed at early intervention. Methods ChABC was injected into the nucleus pulposus, and discs were evaluated via micro-CT, mechanical testing, biochemical assays, and histology 4 and 12 weeks after injection. Results At 4 weeks, reductions in nucleus glycosaminoglycan level by 43%, average height by 12%, neutral zone modulus by 40%, and increases in range of motion by 40%, and creep strain by 25% were found. Neutral zone modulus and range of motion were correlated with nucleus glycosaminoglycan. At 12 weeks, recovery of some mechanical function was detected as range of motion and creep returned to control levels; however, this was not attributed to glycosaminoglycan restoration, because mechanics were no longer correlated with glycosaminoglycan. Conclusion An in vivo model simulating physiologic levels of glycosaminoglycan loss was created to aid in understanding the relationships between altered biochemistry, altered mechanics, and altered cellular function in degeneration. PMID:18197098

  8. Striatal degeneration in childhood.

    PubMed Central

    Erdohazi, M; Marshall, P

    1979-01-01

    The clinical features, and the radiological and neuropathological findings of 3 unrelated children with striatal degeneration are presented. In one case the father had recently developed choreiform movements while in the other two the family history was negative for neurological disorders. Two patients had juvenile onset of psychiatric symptoms, seizures, and rigidity. The 3rd child presented with focal seizures at 9 weeks of age. The neuropathological findings are virtually identical in all 3 cases. The classification of striatal degeneration in childhood is discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:434899

  9. Constitutive expression of cathepsin K in the human intervertebral disc: new insight into disc extracellular matrix remodeling via cathepsin K and receptor activator of nuclear factor-κB ligand

    PubMed Central

    2011-01-01

    Introduction Cathepsin K is a recently discovered cysteine protease which cleaves the triple helical domains of type I to II collagen. It has been shown to be up-regulated in synovial tissue from osteoarthritic and rheumatoid patients, and is a component in normal and nonarthritic cartilage, where it increases with aging. Studies on heart valve development have recently shown that receptor activator of nuclear factor-κB ligand (RANKL) acts during valve remodeling to promote cathepsin K expression. Since extracellular matrix remodeling is a critical component of disc structure and biomechanical function, we hypothesized that cathepsin K and RANKL may be present in the human intervertebral disc. Methods Studies were performed following approval of the authors' Human Subjects Institutional Review Board. Six annulus specimens from healthier Thompson grade I to II discs, and 12 specimens from more degenerate grade III to IV discs were utilized in microarray analysis of RANKL and cathepsin K gene expression. Immunohistochemistry was also performed on 15 additional disc specimens to assess the presence of RANKL and cathepsin K. Results Cathepsin K gene expression was significantly greater in more degenerated grade III to IV discs compared to healthier grade I to II discs (P = 0.001). RANKL was also identified with immunohistochemistry and molecular analyses. RANKL gene expression was also significantly greater in more degenerated discs compared to healthier ones (P = 0.0001). A significant linear positive correlation was identified between expression of cathepsin K and RANKL (r2 = 92.2; P < 0.0001). Conclusions Extracellular matrix remodeling is a key element of disc biology. Our use of an appropriate antibody and gene expression studies showed that cathepsin K is indeed present in the human intervertebral disc. Immunolocalization and molecular analyses also confirmed that RANKL is present in the human disc. Expression of RANKL was found to be significantly greater in

  10. Investigation of Product Performance of Al-Metal Matrix Composites Brake Disc using Finite Element Analysis

    NASA Astrophysics Data System (ADS)

    Fatchurrohman, N.; Marini, C. D.; Suraya, S.; Iqbal, AKM Asif

    2016-02-01

    The increasing demand of fuel efficiency and light weight components in automobile sectors have led to the development of advanced material parts with improved performance. A specific class of MMCs which has gained a lot of attention due to its potential is aluminium metal matrix composites (Al-MMCs). Product performance investigation of Al- MMCs is presented in this article, where an Al-MMCs brake disc is analyzed using finite element analysis. The objective is to identify the potentiality of replacing the conventional iron brake disc with Al-MMCs brake disc. The simulation results suggested that the MMCs brake disc provided better thermal and mechanical performance as compared to the conventional cast iron brake disc. Although, the Al-MMCs brake disc dissipated higher maximum temperature compared to cast iron brake disc's maximum temperature. The Al-MMCs brake disc showed a well distributed temperature than the cast iron brake disc. The high temperature developed at the ring of the disc and heat was dissipated in circumferential direction. Moreover, better thermal dissipation and conduction at brake disc rotor surface played a major influence on the stress. As a comparison, the maximum stress and strain of Al-MMCs brake disc was lower than that induced on the cast iron brake disc.

  11. Kraepelin and degeneration theory.

    PubMed

    Hoff, Paul

    2008-06-01

    Emil Kraepelin's contribution to the clinical and scientific field of psychiatry is recognized world-wide. In recent years, however, there have been a number of critical remarks on his acceptance of degeneration theory in particular and on his political opinion in general, which was said to have carried "overtones of proto-fascism" by Michael Shepherd [28]. The present paper discusses the theoretical cornerstones of Kraepelinian psychiatry with regard to their relevance for Kraepelin's attitude towards degeneration theory. This theory had gained wide influence not only in scientific, but also in philosophical and political circles in the last decades of the nineteenth century. There is no doubt that Kraepelin, on the one hand, accepted and implemented degeneration theory into the debate on etiology and pathogenesis of mental disorders. On the other hand, it is not appropriate to draw a simple and direct line from early versions of degeneration theory to the crimes of psychiatrists and politicians during the rule of national socialism. What we need, is a differentiated view, since this will be the only scientific one. Much research needs to be done here in the future, and such research will surely have a significant impact not only on the historical field, but also on the continuous debate about psychiatry, neuroscience and neurophilosophy.

  12. Frontotemporal Lobar Degeneration

    PubMed Central

    Josephs, Keith A.

    2009-01-01

    Synopsis Frontotemporal lobar degeneration (FTLD) is a syndromic diagnosis that encompasses at least three different variants. Imaging modalities are clinically useful in FTLD while pathology remains the gold standard for definitive diagnosis. To date three different genes have been identified that account for FTLD. PMID:17659185

  13. The origin of thick discs

    NASA Astrophysics Data System (ADS)

    Comerón, Sébastien

    2015-03-01

    Thick discs are defined to be disc-like components with a scale height larger than that of the classical discs. They are ubiquitous (Yoachim & Dalcanton 2006; Comerón et al. 2011a), they are made of mostly old and metal-poor stars and are most easily detected in close to edge-on galaxies. Their origin has been considered mysterious and several formation theories have been proposed: • The thick disc being formed secularly by thin disc stars heated by disc overdensities such as giant molecular clouds or spiral arms (Villumsen 1985, ApJ, 290, 75) and by stars moved outwards from their original orbits by radial migration mechanisms (Schönrich & Binney 2009). • The thick disc being formed by the heating of the thin disc by satellites (Quinn et al. 1993) and the tidal stripping of them (Abadi et al. 2003). • The thick disc being formed fast and already thick at high redshift in an highly unstable disc. Inside that thick disc, a thin disc would form afterwards as suggested by Elemgreen & Elmegreen (2006). • The thick disc being formed originally thick at high redshift by the merger of gas-rich protogalactic fragments and a thin disc forming afterwards within it (Brook et al. 2007). The first mechanism is a secular evolution mechanism. The time-scale of the second one is dependent on the merger history of the main galaxy. In the two last mechanisms, the thick disc forms already thick in a short time-scale at high redshift. Recent Milky Way studies, (see, e.g., Bovy et al. 2012), have shown indications that there is no discontinuity between the thin and the thick disc chemical and kinematic properties. Instead, those studies indicate the presence of a monotonic distribution of disc thicknesses. This would suggest a secular origin for the Milky Way thick disc. Studies in external galaxies (Yoachim & Dalcanton 2006; Comerón et al. 2011b), have shown that low-mass disc galaxies have thick disc relative masses much larger than those found in large-mass galaxies

  14. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2017-01-12

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  15. Transition of a herniated lumbar disc to lumbar discal cyst: A case report

    PubMed Central

    Bansil, Rohit; Hirano, Yoshitaka; Sakuma, Hideo; Watanabe, Kazuo

    2016-01-01

    Background: Another rare cause of lower back pain with radiculopathy is the discal cyst. It is believed to arise from degeneration of a herniated disc, although many other theories of its origin have been proposed. Here, we report a patient with lower back pain/radiculopathy attributed originally to a herniated lumbar disc, which transformed within 6 months into a discal cyst. Case Description: A 42-year-old male had a magnetic resonance (MR) documented herniated lumbar disc at the L4-5 level. It was managed conservatively for 6 months, after which symptoms recurred and progressed. The follow-up MR study revealed a discal cyst at the L4-5 without residual herniated disc. Of interest, the cyst communicated with the L4-5 intervertebral disc, which was herniated under the posterior longitudinal ligament and the disc space. During surgery, the cyst was completely removed, and his symptoms/signs resolved. Conclusion: A discal cyst develops as pathological sequelae of a degenerated herniated disc. Although rare, these lesions must be considered among the differential diagnoses in young patients with radicular back pain. MR study clearly documents these lesions, and surgical excision of the cyst is the treatment of choice. PMID:27843689

  16. Interobserver error in interpretation of the radiographs for degeneration of the lumbar spine.

    PubMed

    Madan, Sanjeev S; Rai, Am; Harley, John M

    2003-01-01

    We examined 114 segments in 23 patients' lumbar spine plain radiographs affected by disc degeneration. Two consultant orthopaedic surgeons, two consultant radiologists, and one spine nurse practitioner made independent observations on the radiographs. MRI scan films of the corresponding 114 segments were used as a gold standard. Kappa coefficients were used to evaluate the interobserver error, and the error between the independent observers and the MRI scanning reports. The systematic differences between the observers for the diagnosis of the disc degeneration at each segment level was recorded. There was significant interobserver error between the independent observers. The pairwise interobserver agreement ranged from fair to substantial on the plain radiograph observations [Weighted kappa coefficient, mean: 0.517 (CI=0.388-0.646)]. The pairwise interobserver agreement between the independent observers and the MRI scan ranged from fair to moderate [Weighted kappa coefficient, mean: 0.388 (CI=0.259-0.518)]. There is significant error in interpretation of the plain radiographs for the diagnosis of lumbar disc degeneration. MRI may be more accurate in the diagnosis of lumbar disc degeneration.

  17. Interobserver Error in Interpretation of the Radiographs for Degeneration of the Lumbar Spine

    PubMed Central

    Madan, Sanjeev S; Rai, Am; Harley, John M

    2003-01-01

    We examined 114 segments in 23 patients' lumbar spine plain radiographs affected by disc degeneration. Two consultant orthopaedic surgeons, two consultant radiologists, and one spine nurse practitioner made independent observations on the radiographs. MRI scan films of the corresponding 114 segments were used as a gold standard. Kappa coefficients were used to evaluate the interobserver error, and the error between the independent observers and the MRI scanning reports. The systematic differences between the observers for the diagnosis of the disc degeneration at each segment level was recorded. There was significant interobserver error between the independent observers. The pairwise interobserver agreement ranged from fair to substantial on the plain radiograph observations [Weighted kappa coefficient, mean: 0.517 (CI=0.388-0.646)]. The pairwise interobserver agreement between the independent observers and the MRI scan ranged from fair to moderate [Weighted kappa coefficient, mean: 0.388 (CI=0.259-0.518)]. There is significant error in interpretation of the plain radiographs for the diagnosis of lumbar disc degeneration. MRI may be more accurate in the diagnosis of lumbar disc degeneration. PMID:14575250

  18. Junctional disc herniation syndrome in post spinal fusion treated with endoscopic spine surgery.

    PubMed

    Chiu, John C; Clifford, Thomas; Princenthal, Robert; Shaw, Stephen

    2005-01-01

    Fusions of the cervical and lumbar spine are often followed within months or several years by protrusion of discs at the adjacent level or levels. Biomechanical alterations and mobility lost at the fused levels are thought to be transferring the stress to the adjacent segments or discs, which results in accelerated degeneration of the discs and causes disc protrusion. This post-spinal fusion "junctional disc herniation syndrome" (JDHS), or the post-spinal fusion "adjacent segment disease (ASD)" can occur from 15% to 52% of post-spinal fusion, in both superior and/or inferior adjacent levels. The ways in which endoscopic minimally invasive spinal discectomy procedure can be used to treat this JDHS and preserve spinal segmental motion are discussed herein. Also, case illustrations are presented.

  19. The Galactic stellar disc

    NASA Astrophysics Data System (ADS)

    Feltzing, S.; Bensby, T.

    2008-12-01

    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. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile. Also based on observations collected at the Nordic Optical Telescope on La Palma, Spain, and at the European Southern Observatories on La Silla and Paranal, Chile, Proposals no. 65.L-0019(B), 67.B-0108(B), 69.B-0277.

  20. Changes in disc status in the reducing and nonreducing anterior disc displacement of temporomandibular joint: a longitudinal retrospective study.

    PubMed

    Hu, Ying Kai; Yang, Chi; Xie, Qian Yang

    2016-09-27

    Treatment procedures for anterior disc displacement (ADD) of temporomandibular joint (TMJ) are far from reaching a consensus. The aim of the study was to evaluate disc status changes of anterior disc displacement with reduction (ADDWR) and without reduction (ADDWoR) comparatively, to get a better understanding of the disease progress without intervention. This longitudinal retrospective study included 217 joints in 165 patients, which were divided into ADDWR group and ADDWoR group based on magnetic resonance imaging (MRI) examination. The joints were assessed quantitatively for disc length and displacement distance at initial and follow-up visits. Disc morphology, which was classified in 5 types, was also evaluated. Paired t-test and Wilcoxon signed rank test were used to assess intra-group differences and independent t-test for inter-group differences. Moreover, analysis of covariance was applied to analyze influential factors for changes in disc length and displacement distance. According to our results, discs tended to become shorter, move further forward and distort more seriously in ADDWoR group than in ADDWR group after follow-up. Moreover, discs were prone to become shorter and more anteriorly displaced in teenagers, type I and III morphologies, advanced Wilkes stages, or those with joint effusion. Follow-up period seemed to be not critical.

  1. Changes in disc status in the reducing and nonreducing anterior disc displacement of temporomandibular joint: a longitudinal retrospective study

    PubMed Central

    Hu, Ying Kai; Yang, Chi; Xie, Qian Yang

    2016-01-01

    Treatment procedures for anterior disc displacement (ADD) of temporomandibular joint (TMJ) are far from reaching a consensus. The aim of the study was to evaluate disc status changes of anterior disc displacement with reduction (ADDWR) and without reduction (ADDWoR) comparatively, to get a better understanding of the disease progress without intervention. This longitudinal retrospective study included 217 joints in 165 patients, which were divided into ADDWR group and ADDWoR group based on magnetic resonance imaging (MRI) examination. The joints were assessed quantitatively for disc length and displacement distance at initial and follow-up visits. Disc morphology, which was classified in 5 types, was also evaluated. Paired t-test and Wilcoxon signed rank test were used to assess intra-group differences and independent t-test for inter-group differences. Moreover, analysis of covariance was applied to analyze influential factors for changes in disc length and displacement distance. According to our results, discs tended to become shorter, move further forward and distort more seriously in ADDWoR group than in ADDWR group after follow-up. Moreover, discs were prone to become shorter and more anteriorly displaced in teenagers, type I and III morphologies, advanced Wilkes stages, or those with joint effusion. Follow-up period seemed to be not critical. PMID:27671371

  2. A meta-model analysis of a finite element simulation for defining poroelastic properties of intervertebral discs.

    PubMed

    Nikkhoo, Mohammad; Hsu, Yu-Chun; Haghpanahi, Mohammad; Parnianpour, Mohamad; Wang, Jaw-Lin

    2013-06-01

    Finite element analysis is an effective tool to evaluate the material properties of living tissue. For an interactive optimization procedure, the finite element analysis usually needs many simulations to reach a reasonable solution. The meta-model analysis of finite element simulation can be used to reduce the computation of a structure with complex geometry or a material with composite constitutive equations. The intervertebral disc is a complex, heterogeneous, and hydrated porous structure. A poroelastic finite element model can be used to observe the fluid transferring, pressure deviation, and other properties within the disc. Defining reasonable poroelastic material properties of the anulus fibrosus and nucleus pulposus is critical for the quality of the simulation. We developed a material property updating protocol, which is basically a fitting algorithm consisted of finite element simulations and a quadratic response surface regression. This protocol was used to find the material properties, such as the hydraulic permeability, elastic modulus, and Poisson's ratio, of intact and degenerated porcine discs. The results showed that the in vitro disc experimental deformations were well fitted with limited finite element simulations and a quadratic response surface regression. The comparison of material properties of intact and degenerated discs showed that the hydraulic permeability significantly decreased but Poisson's ratio significantly increased for the degenerated discs. This study shows that the developed protocol is efficient and effective in defining material properties of a complex structure such as the intervertebral disc.

  3. How do accretion discs break?

    NASA Astrophysics Data System (ADS)

    Dogan, Suzan

    2016-07-01

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

  4. Revival of the Jumping Disc

    ERIC Educational Resources Information Center

    Ucke, C.; Schlichting, H-J.

    2009-01-01

    Snap discs made of bimetal have many technical applications as thermostats. Jumping discs are a toy version of such snap discs. Besides giving technical information, we describe physical investigations. We show especially how, through simple measurements and calculations, you can determine the initial speed ([approximately equal to]3.5 m…

  5. Tensile properties of the porcine temporomandibular joint disc.

    PubMed

    Detamore, Michael S; Athanasiou, Kyriacos A

    2003-08-01

    Despite the significant morbidity associated with the temporomandibular joint (TMJ), little is known about the pathophysiology of this complex joint. TMJ disc degeneration plays a central role in the progression of TMJ disorders, and therefore disc regeneration would be a crucial treatment modality. Unfortunately, scarce information about the structural and functional characteristics of the TMJ disc is available. The current study aims to provide a standard for the biomechanical behavior of the TMJ disc for future tissue engineering studies. The disc was loaded under uniaxial tension in two directions, mediolateral and anteroposterior, and in three locations per direction. In the mediolateral direction, the posterior band was 2.5 times stiffer, 2.4 times tougher (energy to maximum stress), and 2.2 times stronger than the anterior band, which was in turn 16 times stiffer and 5.7 times stronger than the intermediate zone. In the anteroposterior direction, the central and medial regions were 74% and 35% stiffer and 56% and 59% stronger than the lateral region, respectively, although similar to each other in strength and stiffness. There was no significant difference in toughness between regions in the anteroposterior direction. These results correlated qualitatively with collagen fiber orientation and fiber size obtained using polarized light microscopy.

  6. Cataracts and macular degeneration.

    PubMed

    Shoch, D

    1979-09-01

    The intraocular lens restores general vision and some degree of independence and mobility to patients with dense cataracts and macular degeneration. The patient, however, must be repeatedly warned that fine central vision, particularly reading, will not be possible after the surgery. An aphakic spectacle leaves such patients a narrow band of vision when superimposed over the macular lesion, and contact lenses are too small for the patient to manage insertion without help.

  7. The Teddy Bears' Disc.

    ERIC Educational Resources Information Center

    Laurillard, Diana

    1985-01-01

    Reports an evaluation of the Teddy Bear disc, an interactive videodisc developed at the Open University for a second-level course in metallurgy and materials technology. Findings from observation of students utilizing the videodisc are reviewed; successful design features and design problems are considered; and development costs are outlined. (MBR)

  8. Retinal remodeling in inherited photoreceptor degenerations.

    PubMed

    Marc, Robert E; Jones, Bryan W

    2003-10-01

    Photoreceptor degenerations initiated in rods or the retinal pigmented epithelium usually evoke secondary cone death and sensory deafferentation of the surviving neural retina. In the mature central nervous system, deafferentation evokes atrophy and connective re-patterning. It has been assumed that the neural retina does not remodel, and that it is a passive survivor. Screening of advanced stages of human and rodent retinal degenerations with computational molecular phenotyping has exposed a prolonged period of aggressive negative remodeling in which neurons migrate along aberrant glial columns and seals, restructuring the adult neural retina (1). Many neurons die, but survivors rewire the remnant inner plexiform layer (IPL), forming thousands of novel ectopic microneuromas in the remnant inner nuclear layer (INL). Bipolar and amacrine cells engage in new circuits that are most likely corruptive. Remodeling in human and rodent retinas emerges regardless of the molecular defects that initially trigger retinal degenerations. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, the exposure of intrinsic retinal remodeling by the removal of sensory control in retinal degenerations suggests that neuronal organization in the normal retina may be more plastic than previously believed.

  9. Intervertebral disk degeneration and emerging biologic treatments.

    PubMed

    Kepler, Christopher K; Anderson, D Greg; Tannoury, Chadi; Ponnappan, Ravi K

    2011-09-01

    Although understanding of the biologic basis of intervertebral disk (IVD) degeneration is rapidly advancing, the unique IVD environment presents challenges to the development and delivery of biologic treatments. Acceleration of cellular senescence and apoptosis in degenerative IVDs and the depletion of matrix proteins have prompted the development of treatments based on replacing IVD cells using various cell sources. However, this strategy has not been tested in animal models. IVD degeneration and associated pain have led to interest in pathologic innervation of the IVD and ultimately to the development of percutaneous devices to ablate afferent nerve endings in the posterior annulus. Degeneration leads to changes in the expression of matrix protein, cytokines, and proteinases. Injection of growth factors and mitogens may help overcome these degenerative changes in IVD phenotype, and these potential treatments are being explored in animal studies. Gene therapy is an elegant method to address changes in protein expression, but efforts to apply this technology to IVD degeneration are still at early stages.

  10. Propionibacterium acnes, Coagulase-Negative Staphylococcus, and the “Biofilm-like” Intervertebral Disc

    PubMed Central

    Coscia, Michael F.; Denys, Gerald A.; Wack, Matthew F.

    2016-01-01

    Study Design. Patients scheduled for spinal surgery were screened prospectively for a microbial presence associated with intervertebral disc specimens. Inclusion was limited to patients requiring surgery for any of five conditions: study patients with cervical spine intervertebral herniation (IVH), lumbar spine IVH, lumbar spine discogenic pain, and control patients with idiopathic scoliosis/Scheurermann's kyphosis or trauma/neuromuscular deformity. Exclusion criteria included ongoing systemic infection, abnormal pre-operative white cell counts, documented or suspected spinal infection, or previous surgery to the involved disc. Objective. The aim of this study was to test for an association between the presence of a bacterial entity in operated discs and a diagnosis of pathologic disc disease. Summary of Background Data. An association has been described between microbial colonization and progressive intervertebral disc degeneration in 36 herniation patients undergoing microdiscectomies. A total of 19 patients had positive cultures on long-term incubation, with Propionibacterium acnes present in 84% of discs. Materials and Methods. Discs were harvested during surgery, using strict sterile technique. Each disc was divided, with half the sample sealed in a sterile, commercially prepared anaerobic culture transport container, and half fixed in formalin. Live specimens were cultured for bacteria at a university-affiliated laboratory in a blinded fashion. Fixed pathologic specimens were gram-stained and read by a board-certified pathologist. Results. A total of 169 intervertebral discs from 87 patients were evaluated (46 males, 41 females). Positive cultures were noted in 76 of 169 discs (45%), with 34 discs positive for P. acnes and 30 discs positive for Staphylococcus. No pathologic evidence was seen of microorganisms, acute or chronic inflammation, or infection. Pooling the IVH and discogenic pain patients and contrasting them with control patients showed a

  11. A prospective morphological study of facet joint integrity following intervertebral disc replacement with the CHARITE Artificial Disc.

    PubMed

    Trouillier, Hans; Kern, P; Refior, H J; Müller-Gerbl, M

    2006-02-01

    In degenerative disc disease (DDD), increased loading in the posterior column increases facet joint subchondral bone density and may lead to facet joint degeneration. While spinal fusion is commonly used to treat patients with symptomatic DDD, increased stress at the levels adjacent to fusion may accelerate facet joint and adjacent segment degeneration. Artificial disc replacements have been developed as an alternative to fusion. In this prospective study, the effects of disc replacement with the CHARITE Artificial Disc on facet joint loading and integrity were evaluated. Thirteen patients aged <50 years with symptomatic DDD were recruited. Computed tomography (CT) osteoabsorptiometry was performed prior to the implantation of the CHARITE Artificial Disc and six months after. With this technique, increases or decreases in facet joint loading and integrity are indicated by corresponding changes in subchondral bone density. Changes in the distribution of load alter the distribution of the areas of maximum bone density. Clinical outcome was also assessed at pre-operative and 6 and 12 month post-operative visits using the Visual Analogue Scale back and leg pain scores, the Oswestry Disability Index and the Short Form-36 (SF-36) questionnaire. The height of the intervertebral space at the operated level was monitored by lateral X-ray. Subchondral bone density was evaluated in the facet joints of all 13 patients at the operated level, 12 patients at the level above the operated segment, and five patients at the level below the operated segment. Quantitative measurements revealed no significant increases (> or =3%) in subchondral bone density of the facet joints at any level in any patient. Significant decreases (> or =3%) in subchondral bone density were measured at the operated level in 10/13 patients, at the level above the operated segment in 6/12 patients, and at the level below the operated segment in 3/5 patients. There were no changes in the distribution of the

  12. Spine degeneration in a murine model of chronic human tobacco smokers

    PubMed Central

    Wang, Dong; Nasto, Luigi A; Roughley, Peter; Leme, Adriana S.; Houghton, McGarry; Usas, Arvydas; Sowa, Gwendolyn; Lee, Joon; Niedernhofer, Laura; Shapiro, Steven; Kang, James; Vo, Nam

    2012-01-01

    Objective To investigate the mechanisms by which chronic tobacco smoking promotes intervertebral disc degeneration (IDD) and vertebral degeneration in mice. Methods Three months old C57BL/6 mice were exposed to tobacco smoke by direct inhalation (5 cigarettes/day, 5 days/week for 6 months) to model long-term smoking in humans. Total disc proteoglycan content (DMMB assay), aggrecan proteolysis (immunobloting analysis), and cellular senescence (p16INK4a immunohistochemistry) were analyzed. Proteoglycan and collagen syntheses (35S-sulfate and 3H-proline incorporation, respectively) were measured using disc organotypic culture. Vertebral osteoporosity was measured by micro-computed tomography. Results Disc proteoglycan content of smoke-exposed mice was 63% of unexposed control, while new proteoglycan and collagen syntheses were 59% and 41% of those of untreated mice, respectively. Exposure to tobacco smoke dramatically increased metalloproteinase-mediated proteolysis of disc aggrecan within its interglobular domain (IGD). Cellular senescence was elevated two folds in discs of smoke-exposed mice. Smoke exposure increased vertebral endplate porosity, which closely correlates with IDD in humans. Conclusions These findings further support tobacco smoke as a contributor to spinal degeneration. Furthermore, the data provide a novel mechanistic insight, indicating that smoking-induced IDD is a result of both reduced PG synthesis and increased degradation of a key disc extracellular matrix protein, aggrecan. Cleavage of aggrecan IGD is extremely detrimental as this result in the loss of the entire glycosaminoglycan-attachment region of aggrecan, which is vital for attracting water necessary to counteract compressive forces. Our results suggest identification and inhibition of specific metalloproteinases responsible for smoke-induced aggrecanolysis as a potential therapeutic strategy to treat IDD. PMID:22531458

  13. Four-year results of a prospective single-arm study on 200 semi-constrained total cervical disc prostheses: clinical and radiographic outcome.

    PubMed

    Meisel, Hans-Jörg; Jurák, Lubomír; Antinheimo, Jussi; Arregui, Ricardo; Bruchmann, Bernhard; Čabraja, Mario; Caroli, Fabrizio; Kroppenstedt, Stefan; Kryl, Jan; Pohjola, Juha; Shackleford, Ian; Sola, Steffen; Stosberg, Peter; Stulik, Jan; Woiciechowsky, Christian; Suchomel, Petr

    2016-11-01

    OBJECTIVE Recent studies have described encouraging outcomes after cervical total disc replacement (cTDR), but there are also critical debates regarding the long-term effects of heterotopic ossification (HO) and the prevalence of adjacent-level degeneration. The aim in this paper was to provide 4-year clinical and radiographic outcome results on the activ C disc prosthesis. METHODS A total of 200 subjects underwent single-level activ C (Aesculap AG) implantation between C-3 and C-7 for the treatment of symptomatic degenerative disc disease. Clinical and radiographic assessments were performed preoperatively, intraoperatively, at discharge, and again at 6 weeks, 6 months, 1 year, 2 years, and 4 years. Radiographic evaluations were done by an independent core laboratory using a specific software for quantitative motion analysis. RESULTS Neck Disability Index (NDI) and visual analog scale (VAS) score for neck and arm pain decreased significantly from baseline to the 4-year follow-up. The mean improvement for NDI was 20, for VAS severity and frequency of neck pain 26.4 and 28, and for VAS severity and frequency of arm pain 30.7 and 35.1, respectively. The neurological situation improved for the majority of patients (86.4%); 76.1% of cases were asymptomatic. Subsequent surgical interventions were reported in 7% of the cases, including device removals in 3%. In 2.5% a subsidence greater than 3 mm was recorded; 1 of these cases also had a migration greater than 3 mm. No device displacement, expulsion, disassembly, loose or fractured device, osteolysis, or facet joint degeneration at the index level was observed. Segmental lordotic alignment changed from -2.4° preoperatively to -6.2° at 4 years, and postoperative height was maintained during the follow-up. Advanced HO (Grade III and IV) was present in 27.1% of the cases; 82.4% showed segmental mobility. A progression of radiographic adjacent-segment degeneration occurred in 28.2%, but only 4.5% required surgical

  14. Stem cell therapy for intervertebral disc regeneration: obstacles and solutions.

    PubMed

    Sakai, Daisuke; Andersson, Gunnar B J

    2015-04-01

    Intervertebral disc (IVD) degeneration is frequently associated with low back and neck pain, which accounts for disability worldwide. Despite the known outcomes of the IVD 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 IVD 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 conditions. Despite preliminary results showing positive effects of cell-injection strategies for IVD regeneration, detailed basic research on IVD cells and their niche indicates 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 research, both in the laboratory and in the clinic.

  15. Multi-center, Prospective, Randomized, Controlled Investigational Device Exemption Clinical Trial Comparing Mobi-C Cervical Artificial Disc to Anterior Discectomy and Fusion in the Treatment of Symptomatic Degenerative Disc Disease in the Cervical Spine

    PubMed Central

    Bae, Hyun W.; Davis, Reginald; Gaede, Steven; Hoffman, Greg; Kim, Kee; Nunley, Pierce D.; Peterson, Daniel; Rashbaum, Ralph; Stokes, John

    2014-01-01

    Background Anterior cervical discectomy and fusion (ACDF) is the gold standard for treating symptomatic cervical disc degeneration. Cervical total disc replacements (TDRs) have emerged as an alternative for some patients. The purpose of this study was to evaluate the safety and effectiveness of a new TDR device compared with ACDF for treating single-level cervical disc degeneration. Methods This was a prospective, randomized, controlled, multicenter Food and Drug Administration (FDA) regulated Investigational Device Exemption (IDE) study. A total of 245 patients were treated (164 TDR: 81 ACDF). The primary outcome measure was overall success based on improvement in Neck Disability Index (NDI), no subsequent surgical interventions, and no adverse events (AEs) classified as major complications. Secondary outcome measures included SF-12, visual analog scale (VAS) assessing neck and arm pain, patient satisfaction, radiographic range of motion, and adjacent level degeneration. Patients were evaluated preoperatively and postoperatively at 6 weeks, 3, 6, 12, 18, and 24 months. The hypothesis was that the TDR success rate was non-inferior to ACDF at 24 months. Results Overall success rates were 73.6% for TDR and 65.3% for ACDF, confirming non-inferiority (p < 0.0025). TDR demonstrated earlier improvements with significant differences in NDI scores at 6 weeks and 3 months, and VAS neck pain and SF-12 PCS scores at 6 weeks (p<0.05). Operative level range of motion in the TDR group was maintained throughout follow-up. Radiographic evidence of inferior adjacent segment degeneration was significantly greater with ACDF at 12 and 24 months (p < 0.05). AE rates were similar. Conclusions Mobi-C TDR is a safe and effective treatment for single-level disc degeneration, producing outcomes similar to ACDF with less adjacent segment degeneration. Level of Evidence: Level I. Clinical relevance: This study adds to the literature supporting cervical TDR as a viable option to ACDF in

  16. Mechanisms for mechanical damage in the intervertebral disc annulus fibrosus.

    PubMed

    Iatridis, J C James C; ap Gwynn, Iolo

    2004-08-01

    Intervertebral disc degeneration results in disorganization of the laminate structure of the annulus that may arise from mechanical microfailure. Failure mechanisms in the annulus were investigated using composite lamination theory and other analyses to calculate stresses in annulus layers, interlaminar shear stress, and the region of stress concentration around a fiber break. Scanning electron microscopy (SEM) was used to evaluate failure patterns in the annulus and evaluate novel structural features of the disc tissue. Stress concentrations in the annulus due to an isolated fiber break were localized to approximately 5 microm away from the break, and only considered a likely cause of annulus fibrosus failure (i.e., radial tears in the annulus) under extreme loading conditions or when collagen damage occurs over a relatively large region. Interlaminar shear stresses were calculated to be relatively large, to increase with layer thickness (as reported with degeneration), and were considered to be associated with propagation of circumferential tears in the annulus. SEM analysis of intervertebral disc annulus fibrosus tissue demonstrated a clear laminate structure, delamination, matrix cracking, and fiber failure. Novel structural features noted with SEM also included the presence of small tubules that appear to run along the length of collagen fibers in the annulus and a distinct collagenous structure representative of a pericellular matrix in the nucleus region.

  17. Age-related macular degeneration.

    PubMed

    Cheung, Lily K; Eaton, Angie

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease.

  18. Two Ultracool Degenerate Companions

    NASA Astrophysics Data System (ADS)

    Farihi, J.

    2005-07-01

    In the course of an extensive survey for low mass stellar and substellar companions to nearby white dwarfs, two extrememly cool degenerate objects have been discovered. GD 392B is one of only a few known white dwarfs with Teff⪉4000 K and exhibits collision induced absorption in the near infrared tep{far04}. GD 1400B is the second known L dwarf companion to a white dwarf and a possible brown dwarf (Farihi & Christopher 2004). Interested readers should consult the references for a complete description of these two cool objects.

  19. Expression of the two pore domain potassium channel TREK-1 in human intervertebral disc cells.

    PubMed

    Sharma, Pankaj; Hughes, Stephen; El Haj, Alicia; Maffulli, Nicola

    2012-07-01

    Potassium channels play a major role in intracellular homeostasis and regulation of cell volume. Intervertebral disc cells respond to mechanical loading in a complex manner. Mechanical loading may play a role in disc degeneration. Lumbar intervertebral disc samples from 5 patients (average age: 47 years, range: 25-64 years) were used for this study, investigating cells from the nucleus pulposus and the annulus fibrosus duplicate samples to determine RNA expression and protein expression. Analysis of mRNA expression by RT-PCR demonstrated that TREK 1 was expressed by nucleus pulposus (n=5) and annulus fibrosus (n=5) cells. Currently, TREK-1 is the only potassium channel known to be activated by intracellular acidosis, and responds to mechanical and chemical stimuli. Whilst the precise role of potassium channels in cellular homeostasis remains to be determined, TREK-1 may be important to protect disc cells against ischaemic damage, and subsequent disc degeneration, and may also play a role in effecting mechanotransduction. Further research is required to fully elucidate the role of the TREK-1 ion channel in intervertebral disc cells.

  20. LUMBAR DISC HERNIATION

    PubMed Central

    Vialle, Luis Roberto; Vialle, Emiliano Neves; Suárez Henao, Juan Esteban; Giraldo, Gustavo

    2015-01-01

    Lumbar disc herniation is the most common diagnosis among the degenerative abnormalities of the lumbar spine (affecting 2 to 3% of the population), and is the principal cause of spinal surgery among the adult population. The typical clinical picture includes initial lumbalgia, followed by progressive sciatica. The natural history of disc herniation is one of rapid resolution of the symptoms (four to six weeks). The initial treatment should be conservative, managed through medication and physiotherapy, sometimes associated with percutaneous nerve root block. Surgical treatment is indicated if pain control is unsuccessful, if there is a motor deficit greater than grade 3, if there is radicular pain associated with foraminal stenosis, or if cauda equina syndrome is present. The latter represents a medical emergency. A refined surgical technique, with removal of the extruded fragment and preservation of the ligamentum flavum, resolves the sciatic symptoms and reduces the risk of recurrence over the long term. PMID:27019834

  1. Mechanotransduction in intervertebral discs

    PubMed Central

    Tsai, Tsung-Ting; Cheng, Chao-Min; Chen, Chien-Fu; Lai, Po-Liang

    2014-01-01

    Mechanotransduction plays a critical role in intracellular functioning—it allows cells to translate external physical forces into internal biochemical activities, thereby affecting processes ranging from proliferation and apoptosis to gene expression and protein synthesis in a complex web of interactions and reactions. Accordingly, aberrant mechanotransduction can either lead to, or be a result of, a variety of diseases or degenerative states. In this review, we provide an overview of mechanotransduction in the context of intervertebral discs, with a focus on the latest methods of investigating mechanotransduction and the most recent findings regarding the means and effects of mechanotransduction in healthy and degenerative discs. We also provide some discussion of potential directions for future research and treatments. PMID:25267492

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

    PubMed

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

    2013-08-08

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

  3. Mechanosignaling activation of TGFβ maintains intervertebral disc homeostasis

    PubMed Central

    Bian, Qin; Ma, Lei; Jain, Amit; Crane, Janet L; Kebaish, Khaled; Wan, Mei; Zhang, Zhengdong; Edward Guo, X; Sponseller, Paul D; Séguin, Cheryle A; Riley, Lee H; Wang, Yongjun; Cao, Xu

    2017-01-01

    Intervertebral disc (IVD) degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal (NC) cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin αvβ6-mediated activation of transforming growth factor beta (TGFβ), decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease (DDD). Knockout of TGFβ type II receptor (TβRII) or integrin αv in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading. Administration of RGD peptide, TGFβ, and αvβ6-neutralizing antibodies attenuated IVD degeneration. Thus, integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD. PMID:28392965

  4. Translation of an engineered nanofibrous disc-like angle-ply structure for intervertebral disc replacement in a small animal model.

    PubMed

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

    2014-06-01

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

  5. Mechanics of Actuated Disc Cutting

    NASA Astrophysics Data System (ADS)

    Dehkhoda, Sevda; Detournay, Emmanuel

    2017-02-01

    This paper investigates the mechanics of an actuated disc cutter with the objective of determining the average forces acting on the disc as a function of the parameters characterizing its motion. The specific problem considered is that of a disc cutter revolving off-centrically at constant angular velocity around a secondary axis rigidly attached to a cartridge, which is moving at constant velocity and undercutting rock at a constant depth. This model represents an idealization of a technology that has been implemented in a number of hard rock mechanical excavators with the goal of reducing the average thrust force to be provided by the excavation equipment. By assuming perfect conformance of the rock with the actuated disc as well as a prescribed motion of the disc (perfectly rigid machine), the evolution of the contact surface between the disc and the rock during one actuation of the disc can be computed. Coupled with simple cutter/rock interaction models that embody either a ductile or a brittle mode of fragmentation, these kinematical considerations lead to an estimate of the average force on the cartridge and of the partitioning of the energy imparted by the disc to the rock between the actuation mechanism of the disc and the translation of the cartridge on which the actuated disc is attached.

  6. Polarimetric microlensing of circumstellar discs

    NASA Astrophysics Data System (ADS)

    Sajadian, Sedighe; Rahvar, Sohrab

    2015-12-01

    We study the benefits of polarimetry observations of microlensing events to detect and characterize circumstellar discs around the microlensed stars located at the Galactic bulge. These discs which are unresolvable from their host stars make a net polarization effect due to their projected elliptical shapes. Gravitational microlensing can magnify these signals and make them be resolved. The main aim of this work is to determine what extra information about these discs can be extracted from polarimetry observations of microlensing events in addition to those given by photometry ones. Hot discs which are closer to their host stars are more likely to be detected by microlensing, owing to more contributions in the total flux. By considering this kind of discs, we show that although the polarimetric efficiency for detecting discs is similar to the photometric observation, but polarimetry observations can help to constraint the disc geometrical parameters e.g. the disc inner radius and the lens trajectory with respect to the disc semimajor axis. On the other hand, the time-scale of polarimetric curves of these microlensing events generally increases while their photometric time-scale does not change. By performing a Monte Carlo simulation, we show that almost four optically thin discs around the Galactic bulge sources are detected (or even characterized) through photometry (or polarimetry) observations of high-magnification microlensing events during 10-yr monitoring of 150 million objects.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    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.

  9. Novel localized heating technique on centrifugal microfluidic disc with wireless temperature monitoring system.

    PubMed

    Joseph, Karunan; Ibrahim, Fatimah; Cho, Jongman

    2015-01-01

    Recent advances in the field of centrifugal microfluidic disc suggest the need for electrical interface in the disc to perform active biomedical assays. In this paper, we have demonstrated an active application powered by the energy harvested from the rotation of the centrifugal microfluidic disc. A novel integration of power harvester disc onto centrifugal microfluidic disc to perform localized heating technique is the main idea of our paper. The power harvester disc utilizing electromagnetic induction mechanism generates electrical energy from the rotation of the disc. This contributes to the heat generation by the embedded heater on the localized heating disc. The main characteristic observed in our experiment is the heating pattern in relative to the rotation of the disc. The heating pattern is monitored wirelessly with a digital temperature sensing system also embedded on the disc. Maximum temperature achieved is 82 °C at rotational speed of 2000 RPM. The technique proves to be effective for continuous heating without the need to stop the centrifugal motion of the disc.

  10. Rethinking Black Hole Accretion Discs

    NASA Astrophysics Data System (ADS)

    Salvesen, Greg

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

  11. Key emerging issues in progressive supranuclear palsy and corticobasal degeneration.

    PubMed

    Josephs, Keith A

    2015-03-01

    It has been approximately 50 years since neurologists were introduced to the entities, "progressive supranuclear palsy" and "corticobasal degeneration". Since the two seminal publications, there have been significant advancements in our understanding of these two neurodegenerative diseases, particularly the fact that both are associated with tau. Recent advances over the past 3 years that are notable to the field are discussed in this review that covers clinical diagnosis, pathological features, neuroimaging and CSF biomarkers, genetic associations and clinical trials related to progressive supranuclear palsy and corticobasal degeneration.

  12. Heat distribution in disc brake

    NASA Astrophysics Data System (ADS)

    Klimenda, Frantisek; Soukup, Josef; Kampo, Jan

    2016-06-01

    This article is deals by the thermal analysis of the disc brake with floating caliper. The issue is solved by numerically. The half 2D model is used for solution in program ADINA 8.8. Two brake discs without the ventilation are solved. One disc is made from cast iron and the second is made from stainless steel. Both materials are an isotropic. By acting the pressure force on the brake pads will be pressing the pads to the brake disc. Speed will be reduced (slowing down). On the contact surface generates the heat, which the disc and pads heats. In the next part of article is comparison the maximum temperature at the time of braking. The temperatures of both materials for brake disc (gray cast iron, stainless steel) are compares. The heat flux during braking for the both materials is shown.

  13. Enclosed rotary disc air pulser

    DOEpatents

    Olson, A. L.; Batcheller, Tom A.; Rindfleisch, J. A.; Morgan, John M.

    1989-01-01

    An enclosed rotary disc air pulser for use with a solvent extraction pulse olumn includes a housing having inlet, exhaust and pulse leg ports, a shaft mounted in the housing and adapted for axial rotation therein, first and second disc members secured to the shaft within the housing in spaced relation to each other to define a chamber therebetween, the chamber being in communication with the pulse leg port, the first disc member located adjacent the inlet port, the second disc member being located adjacent the exhaust port, each disc member having a milled out portion, the disc members positioned on the shaft so that as the shaft rotates, the milled out portions permit alternative cyclical communication between the inlet port and the chamber and the exhaust port and the chamber.

  14. Vertebral degenerative disc disease severity evaluation using random forest classification

    NASA Astrophysics Data System (ADS)

    Munoz, Hector E.; Yao, Jianhua; Burns, Joseph E.; Pham, Yasuyuki; Stieger, James; Summers, Ronald M.

    2014-03-01

    Degenerative disc disease (DDD) develops in the spine as vertebral discs degenerate and osseous excrescences or outgrowths naturally form to restabilize unstable segments of the spine. These osseous excrescences, or osteophytes, may progress or stabilize in size as the spine reaches a new equilibrium point. We have previously created a CAD system that detects DDD. This paper presents a new system to determine the severity of DDD of individual vertebral levels. This will be useful to monitor the progress of developing DDD, as rapid growth may indicate that there is a greater stabilization problem that should be addressed. The existing DDD CAD system extracts the spine from CT images and segments the cortical shell of individual levels with a dual-surface model. The cortical shell is unwrapped, and is analyzed to detect the hyperdense regions of DDD. Three radiologists scored the severity of DDD of each disc space of 46 CT scans. Radiologists' scores and features generated from CAD detections were used to train a random forest classifier. The classifier then assessed the severity of DDD at each vertebral disc level. The agreement between the computer severity score and the average radiologist's score had a quadratic weighted Cohen's kappa of 0.64.

  15. Analysis of cell viability in intervertebral disc: Effect of endplate permeability on cell population.

    PubMed

    Shirazi-Adl, A; Taheri, M; Urban, J P G

    2010-05-07

    Responsible for making and maintaining the extracellular matrix, the cells of intervertebral discs are supplied with essential nutrients by diffusion from the blood supply through mainly the cartilaginous endplates (CEPs) and disc tissue. Decrease in transport rate and increase in cellular activity may adversely disturb the intricate supply-demand balance leading ultimately to cell death and disc degeneration. The present numerical study aimed to introduce for the first time cell viability criteria into nonlinear coupled nutrition transport equations thereby evaluating the dynamic nutritional processes governing viable cell population and concentrations of oxygen, glucose and lactic acid in the disc as CEP exchange area dropped from a fully permeable condition to an almost impermeable one. A uniaxial model of an in vitro cell culture analogue of the disc is first employed to examine and validate cell viability criteria. An axisymmetric model of the disc with four distinct regions was subsequently used to investigate the survival of cells at different CEP exchange areas. In agreement with measurements, predictions of the diffusion chamber model demonstrated substantial cell death as essential nutrient concentrations fell to levels too low to support cells. Cells died away from the nutrient supply and at higher cell densities. In the disc model, the nucleus region being farthest away from supply sources was most affected; cell death initiated first as CEP exchange area dropped below approximately 40% and continued exponentially thereafter to depletion as CEP calcified further. In cases with loss of endplate permeability and/or disruptions therein, as well as changes in geometry and fall in diffusivity associated with fluid outflow, the nutrient concentrations could fall to levels inadequate to maintain cellular activity or viability, resulting in cell death and disc degeneration.

  16. Preparation of ormetoprim sulfadimethoxine medicated discs for disc diffusion assay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Romet (a blend of ormetoprim and sulfadimethoxine) is a typeA medicated article for the manufacture of medicated feed in the catfish industry. Recently, the commercial manufacture of ormetoprim–sulfadimethoxine susceptibility discs was discontinued. Ormetoprim–sulfadimethoxine discs were prepared at...

  17. Sizes of protoplanetary discs after star-disc encounters

    NASA Astrophysics Data System (ADS)

    Breslau, Andreas; Steinhausen, Manuel; Vincke, Kirsten; Pfalzner, Susanne

    2014-05-01

    Most stars do not form in isolation, but as part of a star cluster or association. These young stars are initially surrounded by protoplanetary discs. In these cluster environments tidal interactions with other cluster members can alter the disc properties. Besides the disc frequency, its mass, angular momentum, and energy, the disc's size is particularly prone to being changed by a passing star. So far the change in disc size has only been investigated for a small number of very specific encounters. Several studies investigated the effect of the cluster environment on the sizes of planetary systems like our own solar system, based on a generalisation of information from this limited sample. We performed numerical simulations covering the wide parameter space typical of young star clusters, to test the validity of this approach. Here the sizes of discs after encounters are presented, based on a size definition that is comparable to the one used in observational studies. We find that, except for encounters between equal-mass stars, the usually applied estimates are insufficient. They tend to severely overestimate the remaining disc size. We show that the disc size after an encounter can be described by a relatively simple dependence on the periastron distance and the mass ratio of the encounter partners. This knowledge allows us, for example, to pin down the types of encounter possibly responsible for the structure of today's solar system. Appendix A is available in electronic form at http://www.aanda.org

  18. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... of Low Vision Age-Related Macular Degeneration Vision Simulator AMD Pictures and Videos: What Does Macular Degeneration ... degeneration as part of the body's natural aging process. There are different kinds of macular problems, but ...

  19. Genetics Home Reference: Stargardt macular degeneration

    MedlinePlus

    ... Genetics Home Health Conditions Stargardt macular degeneration Stargardt macular degeneration Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Stargardt macular degeneration is a genetic eye disorder that causes progressive ...

  20. An Ex Vivo Study on Immunohistochemical Localization of MMP-7 and MMP-9 in Temporomandibular Joint Discs with Internal Derangement

    PubMed Central

    Loreto, C.; Leonardi, R.; Musumeci, G.; Pannone, G.; Castorina, S.

    2013-01-01

    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. PMID:23807291

  1. Calcification in the ovine intervertebral disc: a model of hydroxyapatite deposition disease

    PubMed Central

    Burkhardt, D.; Taylor, T. K. F.; Dillon, C. T.; Read, R.; Cake, M.; Little, C. B.

    2009-01-01

    The study design included a multidisciplinary examination of the mineral phase of ovine intervertebral disc calcifications. The objective of the study was to investigate the mineral phase and its mechanisms of formation/association with degeneration in a naturally occurring animal model of disc calcification. The aetiology of dystrophic disc calcification in adult humans is unknown, but occurs as a well-described clinical disorder with hydroxyapatite as the single mineral phase. Comparable but age-related pathology in the sheep could serve as a model for the human disorder. Lumbar intervertebral discs (n = 134) of adult sheep of age 6 years (n = 4), 8 years (n = 12) and 11 years (n = 2) were evaluated using radiography, morphology, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray powder diffraction, histology, immunohistology and proteoglycan analysis. Half of the 6-year, 84% of the 8-year and 86% of the 11-year-old discs had calcific deposits. These were not well delineated by plain radiography. They were either: (a) punctate deposits in the outer annulus, (b) diffuse deposits in the transitional zone or inner annulus fibrosus with occasional deposits in the nucleus, or (c) large deposits in the transitional zone extending variably into the nucleus. Their maximal incidence was in the lower lumbar discs (L4/5–L6/7) with no calcification seen in the lumbosacral or lower thoracic discs. All deposits were hydroxyapatite with large crystallite sizes (800–1,300 Å) compared to cortical bone (300–600 Å). No type X-collagen, osteopontin or osteonectin were detected in calcific deposits, although positive staining for bone sialoprotein was evident. Calcified discs had less proteoglycan of smaller hydrodynamic size than non-calcified discs. Disc calcification in ageing sheep is due to hydroxyapatite deposition. The variable, but large, crystal size and lack of protein markers indicate that this does not occur by

  2. Short Link N Stimulates Intervertebral Disc Repair in a Novel Long-Term Organ Culture Model that Includes the Bony Vertebrae.

    PubMed

    AlGarni, Nizar; Grant, Michael P; Epure, Laura M; Salem, Omar; Bokhari, Rakan; Antoniou, John; Mwale, Fackson

    2016-11-01

    Link N (DHLSDNYTLDHDRAIH) is a peptide that occurs naturally in the intervertebral discs (IVDs) and cartilage as a result of proteolytic cleavage of Link protein. Several studies have identified Link N as a growth factor capable of stimulating matrix synthesis in these tissues. We have recently discovered that annulus fibrosus cells can release an enzyme (possibly cathepsin K) that can further cleave Link N resulting in an eight amino acid peptide, we called short Link N (sLink N). Separately, we recently developed and validated an organ culture model that has the vertebrae attached (vIVDs; IVD with intact vertebrae). The aims of this study were (i) to examine if sLink N has the potential to repair early degenerate discs and (ii) to determine if this new model can be used to test potential drugs for disc repair. To determine if sLink N was able to stimulate repair of the degenerate disc, vIVDs with trypsin-induced degeneration (DG) were used. After 4 weeks of culture, the proteoglycan content measured as glycosaminoglycans was stimulated by sLink N in the degenerated discs, and the staining of proteoglycan was observed throughout the tissue irrespective of its proximity to the cells. The quantity of extractable type II collagen and aggrecan was also increased when the degenerate discs were treated with sLink N. Taken together, the results suggest that sLink N can increase key disc matrix molecules, namely type II collagen and aggrecan. Thus sLink N is an attractive peptide for tissue engineering and regeneration of the disc due to its anabolic effects. Finally, we show the feasibility of using the long-term whole organ culture system with adjacent intact vertebrae for studying the DG and regeneration of the IVD.

  3. Imaginal disc regeneration takes flight.

    PubMed

    Hariharan, Iswar K; Serras, Florenci

    2017-04-01

    Drosophila imaginal discs, the larval precursors of adult structures such as the wing and leg, are capable of regenerating after damage. During the course of regeneration, discs can sometimes generate structures that are appropriate for a different type of disc, a phenomenon termed transdetermination. Until recently, these phenomena were studied by physically fragmenting discs and then transplanting them into the abdomens of adult female flies. This field has experienced a renaissance following the development of genetic ablation systems that can damage precisely defined regions of the disc without the need for surgery. Together with more traditional approaches, these newer methods have generated many novel insights into wound healing, the mechanisms that drive regenerative growth, plasticity during regeneration and systemic effects of tissue damage and regeneration.

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  5. Intraoral micro-identification discs.

    PubMed

    Hansen, R W

    1991-12-01

    Intraoral micro-identification discs have recently been utilized to provide a more permanent method of personal identification. A wafer of plastic or metal with a surface area of 2.5 to 5 mm2 and carrying identifying numbers and/or letters (indicia) is bonded to the buccal enamel surface of the posterior teeth. Personal identification can occur after the I.D. disc is identified and the indicia is read. Reading of photoreduced indicia requires the aid of a microscope subsequent to the removal of the microdisc. In situ reading of disc indicia is possible using low power handheld magnifiers if the size of the indicia approximates 0.3 mm. Computerization is an integral part of non-custom alpha/numeric type designs, but a custom disc carries a name, address, and other specific information unique to the manufacturer. The use of a computer improves access to the database and it decreases the amount of data placed on the disc. Microdisc bases may be fabricated using a mylar type plastic or they may be manufactured from a stainless steel blank. Plastic discs are constructed with an internal sandwich containing the photo-reduced indicia. Metal discs are marked with a photochemical etch or engraved with a computer driven YAG laser. Attachment of the disc to the enamel surface is accomplished by conventional etching and bonding techniques and are typically bonded to the buccal surface of the maxillary first permanent molar or the second primary molar. Clear composite bonding material covers the disc so that salivary contamination does not result in degradation of the indicia. Orthodontic style discs with a mesh back carry laser written information that may be cemented with conventional orthodontic bonding cement. Standardization of the indicia and overall design is considered to be an important aspect of patient and professional acceptance.

  6. [Age related macular degeneration].

    PubMed

    Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.

  7. Three-lane and multilane signatures of planets in planetesimal discs

    NASA Astrophysics Data System (ADS)

    Demidova, Tatiana V.; Shevchenko, Ivan I.

    2016-11-01

    In massive numerical experiments we show that a planet embedded in a planetesimal disc induces a characteristic multilane `planetosignature' representing a pattern of several stellar-centric rings. If the planet's mass is large enough, the multilane signature degenerates to a three-lane one: then it consists of three rings, one bright co-orbital with the planet, and two dark gaps in the radial distribution of the particles. The gaps correspond to orbital resonances 2:1 and 1:2 with the planet. This theoretical prediction may explain recent ALMA observations of the disc of HL Tau.

  8. Frontotemporal lobar degeneration: current perspectives

    PubMed Central

    Riedl, Lina; Mackenzie, Ian R; Förstl, Hans; Kurz, Alexander; Diehl-Schmid, Janine

    2014-01-01

    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 inhibitors to reduce behavioral disturbances. No large-scale or high-quality studies have been conducted to determine the efficacy of non-pharmacological treatment approaches in FTLD. In view of the limited treatment options, caregiver education and support is currently the most important component of the clinical management. PMID:24600223

  9. Age-Related Macular Degeneration

    MedlinePlus

    ... version of this page please turn Javascript on. Age-related Macular Degeneration About AMD Click for more ... a leading cause of vision loss among people age 60 and older. It causes damage to the ...

  10. Double-disc gate valve

    DOEpatents

    Wheatley, Seth J.

    1979-01-01

    This invention relates to an improvement in a conventional double-disc gate valve having a vertically movable gate assembly including a wedge, spreaders slidably engaged therewtih, 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 separtion 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.

  11. Medical Information on Optical Disc*

    PubMed Central

    Schipma, Peter B.; Cichocki, Edward M.; Ziemer, Susan M.

    1987-01-01

    Optical discs may permit a revolutionary change in the distribution and use of medical information. A single compact disc, similar in size to that used for digital audio recording, can contain over 500 million characters of information that is accessible by a Personal Computer. These discs can be manufactured at a cost lower than that of print on paper, at reasonable volumes. Software can provide the health care professional with nearly instantaneous access to the information. Thus, for the first time, the opportunity exists to have large local medical information collections. This paper describes an application of this technology in the field of Oncology.

  12. Mitral disc-valve variance

    PubMed Central

    Berroya, Renato B.; Escano, Fernando B.

    1972-01-01

    This report deals with a rare complication of disc-valve prosthesis in the mitral area. A significant disc poppet and struts destruction of mitral Beall valve prostheses occurred 20 and 17 months after implantation. The resulting valve incompetence in the first case contributed to the death of the patient. The durability of Teflon prosthetic valves appears to be in question and this type of valve probably will be unacceptable if there is an increasing number of disc-valve variance in the future. Images PMID:5017573

  13. A Structurally and Functionally Biomimetic Biphasic Scaffold for Intervertebral Disc Tissue Engineering

    PubMed Central

    Choy, Andrew Tsz Hang; Chan, Barbara Pui

    2015-01-01

    Tissue engineering offers high hopes for the treatment of intervertebral disc (IVD) degeneration. Whereas scaffolds of the disc nucleus and annulus have been extensively studied, a truly biomimetic and mechanically functional biphasic scaffold using naturally occurring extracellular matrix is yet to be developed. Here, a biphasic scaffold was fabricated with collagen and glycosaminoglycans (GAGs), two of the most abundant extracellular matrix components in the IVD. Following fabrication, the scaffold was characterized and benchmarked against native disc. The biphasic scaffold was composed of a collagen-GAG co-precipitate making up the nucleus pulposus-like core, and this was encapsulated in multiple lamellae of photochemically crosslinked collagen membranes comprising the annulus fibrosus-like lamellae. On mechanical testing, the height of our engineered disc recovered by ~82-89% in an annulus-independent manner, when compared with the 99% recovery exhibited by native disc. The annulus-independent nature of disc height recovery suggests that the fluid replacement function of the engineered nucleus pulposus core might mimic this hitherto unique feature of native disc. Biphasic scaffolds comprised of 10 annulus fibrosus-like lamellae had the best overall mechanical performance among the various designs owing to their similarity to native disc in most aspects, including elastic compliance during creep and recovery, and viscous compliance during recovery. However, the dynamic mechanical performance (including dynamic stiffness and damping factor) of all the biphasic scaffolds was similar to that of the native discs. This study contributes to the rationalized design and development of a biomimetic and mechanically viable biphasic scaffold for IVD tissue engineering. PMID:26115332

  14. Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy

    PubMed Central

    Ruzicka, Filip; Schmitz, Jonathan E.; James, Garth A.; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Lipina, Radim; Ahmed, Fahad S.; Alamin, Todd F.; Anand, Neel; Baird, John C.; Bhatia, Nitin; Demir-Deviren, Sibel; Eastlack, Robert K.; Fisher, Steve; Garfin, Steven R.; Gogia, Jaspaul S.; Gokaslan, Ziya L.; Kuo, Calvin C.; Lee, Yu-Po; Mavrommatis, Konstantinos; Michu, Elleni; Noskova, Hana; Raz, Assaf; Sana, Jiri; Shamie, A. Nick; Stewart, Philip S.; Stonemetz, Jerry L.; Wang, Jeffrey C.; Witham, Timothy F.; Coscia, Michael F.; Birkenmaier, Christof; Fischetti, Vincent A.; Slaby, Ondrej

    2017-01-01

    Background In previous studies, Propionibacterium acnes was cultured from intervertebral disc tissue of ~25% of patients undergoing microdiscectomy, suggesting a possible link between chronic bacterial infection and disc degeneration. However, given the prominence of P. acnes as a skin commensal, such analyses often struggled to exclude the alternate possibility that these organisms represent perioperative microbiologic contamination. This investigation seeks to validate P. acnes prevalence in resected disc cultures, while providing microscopic evidence of P. acnes biofilm in the intervertebral discs. Methods Specimens from 368 patients undergoing microdiscectomy for disc herniation were divided into several fragments, one being homogenized, subjected to quantitative anaerobic culture, and assessed for bacterial growth, and a second fragment frozen for additional analyses. Colonies were identified by MALDI-TOF mass spectrometry and P. acnes phylotyping was conducted by multiplex PCR. For a sub-set of specimens, bacteria localization within the disc was assessed by microscopy using confocal laser scanning and FISH. Results Bacteria were cultured from 162 discs (44%), including 119 cases (32.3%) with P. acnes. In 89 cases, P. acnes was cultured exclusively; in 30 cases, it was isolated in combination with other bacteria (primarily coagulase-negative Staphylococcus spp.) Among positive specimens, the median P. acnes bacterial burden was 350 CFU/g (12 - ~20,000 CFU/g). Thirty-eight P. acnes isolates were subjected to molecular sub-typing, identifying 4 of 6 defined phylogroups: IA1, IB, IC, and II. Eight culture-positive specimens were evaluated by fluorescence microscopy and revealed P. acnes in situ. Notably, these bacteria demonstrated a biofilm distribution within the disc matrix. P. acnes bacteria were more prevalent in males than females (39% vs. 23%, p = 0.0013). Conclusions This study confirms that P. acnes is prevalent in herniated disc tissue. Moreover, it

  15. Design Issues in Video Disc Map Display.

    DTIC Science & Technology

    1984-10-01

    Tables: disc storage capacities under various conditions. Photos: map frames. Constanzo , D.J. (1984a), "The Potential for Video Disc Technology in...discs. Constanzo , D.J. (1984b), "Requirements and Specifications for Cartographic Video Discs", presented as a poster paper at the 1984 Army Science

  16. Enlivening Physics, a Local Video Disc Project.

    ERIC Educational Resources Information Center

    McInerney, M.

    1989-01-01

    Describes how to make and use an inexpensive video disc of physics demonstrations. Discusses the background, production of the disc, subject of the disc including angular momentum, "monkey and the hunter" experiment, Doppler shift, pressure of a constant volume of gas thermometer, and wave effects, and using the disc in classroom. (YP)

  17. Disc Golf: Teaching a Lifetime Activity

    ERIC Educational Resources Information Center

    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…

  18. P23H opsin knock-in mice reveal a novel step in retinal rod disc morphogenesis

    PubMed Central

    Sakami, Sanae; Kolesnikov, Alexander V.; Kefalov, Vladimir J.; Palczewski, Krzysztof

    2014-01-01

    Retinal rod photoreceptor cells have double membrane discs located in their outer segments (ROS) that are continuously formed proximally from connecting cilia (CC) and phagocytized distally by the retinal pigmented epithelium. The major component of these rod discs, the light-sensitive visual pigment rhodopsin (Rho), consists of an opsin protein linked to 11-cis-retinal. The P23H mutation of rod opsin (P23H opsin) is the most common cause of human blinding autosomal dominant retinitis pigmentosa (adRP). A mouse model of adRP with this mutation (RhoP23H/+) shows low levels of P23H opsin protein, partial misalignment of discs and progressive retinal degeneration. However, the impact of mutant P23H opsin on the formation of abnormal discs is unclear and it is still unknown whether this mutant pigment can mediate phototransduction. Using transretinal ERG recordings, we demonstrate that P23H mutant Rho can trigger phototransduction but RhoP23H/P23H rods are ∼17 000-fold less sensitive to light than Rho+/+ rods and produce abnormally fast photo-responses. By analyzing homozygous RhoP23H/P23H knock-in mice, we show that P23H opsin is transported to ciliary protrusions where it forms sagittally elongated discs. Transmission electron microscopy of postnatal day (PND) 14 RhoP23H/+ mouse retina revealed disordered sagittally oriented discs before the onset of retinal degeneration. Surprisingly, we also observed smaller, immature sagittally oriented discs in PND14 Rho+/− and Rho+/+ mice that were not seen in older animals. These findings provide fundamental insights into the pathogenesis of the P23H mutant opsin and reveal a novel early sagittally aligned disc formation step in normal ROS disc expansion. PMID:24214395

  19. Eclipse Mapping of Accretion Discs

    NASA Astrophysics Data System (ADS)

    Baptista, R.

    The eclipse mapping method is an inversion technique that makes use of the information contained in eclipse light curves to probe the structure, the spectrum and the time evolution of accretion discs. In this review I present the basics of the method and discuss its different implementations. I summarize the most important results obtained to date and discuss how they have helped to improve our understanding of accretion physics, from testing the theoretical radial brightness temperature distribution and measuring mass accretion rates to showing the evolution of the structure of a dwarf novae disc throughout its outburst cycle, from isolating the spectrum of a disc wind to revealing the geometry of disc spiral shocks. I end with an outline of the future prospects.

  20. Tissue engineering: A live disc

    NASA Astrophysics Data System (ADS)

    Hukins, David W. L.

    2005-12-01

    A material-cell hybrid device that mimics the anatomic shape of the intervertebral disc has been made and successfully implanted into mice to show that tissue engineering may, in the future, benefit sufferers from back pain.

  1. Disc Golf, a Growing Sport

    PubMed Central

    Nelson, Joseph T.; Jones, Richard E.; Runstrom, Michael; Hardy, Jolene

    2015-01-01

    Background Disc golf is a sport played much like traditional golf, but rather than using a ball and club, players throw flying discs with various throwing motions. It has been played by an estimated 8 to 12 million people in the United States. Like all sports, injuries sustained while playing disc golf are not uncommon. Although formalized in the 1970s, it has grown at a rapid pace; however, disc golf–related injuries have yet to be described in the medical literature. Purpose To describe the most common injuries incurred by disc golf players while comparing the different types of throwing styles. Study Design Descriptive epidemiology study. Methods The data in this study were collected from 883 disc golf players who responded to an online survey collected over a 1-month period. Respondents answered 49 questions related to demographics, experience, style of play, and injury details. Using a chi-square analysis, common injuries sustained in players using backhand and forehand throwing styles were compared. Results More than 81% of respondents stated that they had sustained an injury playing disc golf, including injuries to the elbow (n = 325), shoulder (n = 305), back (n = 218), and knee (n = 199). The injuries were most commonly described as a muscle strain (n = 241), sprain (n = 162), and tendinitis (n = 145). The type of throw primarily used by players varied, with 86.2% using backhand, 12.7% using forehand, and 1.1% using an overhead throw. Players using a forehand throw were more likely to sustain an elbow injury (P = .014). Many players (n = 115) stated they had undergone surgery due to a disc golf–related injury, with the most common surgeries including meniscal, shoulder, spine, and foot/ankle surgeries. Conclusion The majority of surveyed disc golfers sustained at least 1 injury while playing disc golf, with many requiring surgery. The types of injuries sustained by players varied by the types of throw primarily used. As the sport of disc golf continues

  2. Percutaneous diode laser disc nucleoplasty

    NASA Astrophysics Data System (ADS)

    Menchetti, P. P.; Longo, Leonardo

    2004-09-01

    The treatment of herniated disc disease (HNP) over the years involved different miniinvasive surgical options. The classical microsurgical approach has been substituted over the years both by endoscopic approach in which is possible to practice via endoscopy a laser thermo-discoplasty, both by percutaneous laser disc nucleoplasty. In the last ten years, the percutaneous laser disc nucleoplasty have been done worldwide in more than 40000 cases of HNP. Because water is the major component of the intervertebral disc, and in HNP pain is caused by the disc protrusion pressing against the nerve root, a 980 nm Diode laser introduced via a 22G needle under X-ray guidance and local anesthesia, vaporizes a small amount of nucleous polposus with a disc shrinkage and a relief of pressure on nerve root. Most patients get off the table pain free and are back to work in 5 to 7 days. Material and method: to date, 130 patients (155 cases) suffering for relevant symptoms therapy-resistant 6 months on average before consulting our department, have been treated. Eightyfour (72%) males and 46 (28%) females had a percutaneous laser disc nucleoplasty. The average age of patients operated was 48 years (22 - 69). The level of disc removal was L3/L4 in 12 cases, L4/L5 in 87 cases and L5/S1 in 56 cases. Two different levels were treated at the same time in 25 patients. Results: the success rate at a minimum follow-up of 6 months was 88% with a complication rate of 0.5%.

  3. A self-similar solution for thermal disc winds

    NASA Astrophysics Data System (ADS)

    Clarke, C. J.; Alexander, R. D.

    2016-08-01

    We derive a self-similar description for the 2D streamline topology and flow structure of an axisymmetric, thermally driven wind originating from a disc in which the density is a power-law function of radius. Our scale-free solution is strictly only valid in the absence of gravity or centrifugal support; comparison with 2D hydrodynamic simulations of winds from Keplerian discs however demonstrates that the scale-free solution is a good approximation also in the outer regions of such discs, and can provide a reasonable description even for launch radii well within the gravitational radius of the flow. Although other authors have considered the flow properties along streamlines whose geometry has been specified in advance, this is the first isothermal calculation in which the flow geometry and variation of flow variables along streamlines is determined self-consistently. It is found that the flow trajectory is very sensitive to the power-law index of radial density variation in the disc: the steeper the density gradient, the stronger is the curvature of streamlines close to the flow base that is required in order to maintain momentum balance perpendicular to the flow. Steeper disc density profiles are also associated with more rapid acceleration, and a faster fall-off of density, with height above the disc plane. The derivation of a set of simple governing equations for the flow structure of thermal winds from the outer regions of power-law discs offers the possibility of deriving flow observables without having to resort to hydrodynamical simulation.

  4. Prediction of glycosaminoglycan synthesis in intervertebral disc under mechanical loading.

    PubMed

    Gao, Xin; Zhu, Qiaoqiao; Gu, Weiyong

    2016-09-06

    The loss of glycosaminoglycan (GAG) content is a major biochemical change during intervertebral disc (IVD) degeneration. Abnormal mechanical loading is one of the major factors causing disc degeneration. In this study, a multiscale mathematical model was developed to quantify the effect of mechanical loading on GAG synthesis. This model was based on a recently developed cell volume dependent GAG synthesis theory that predicts the variation of GAG synthesis rate of a cell under the influence of mechanical stimuli, and the biphasic theory that describes the deformation of IVD under mechanical loading. The GAG synthesis (at the cell level) was coupled with the mechanical loading (at the tissue level) via a cell-matrix unit approach which established a relationship between the variation of cell dilatation and the local tissue dilatation. This multiscale mathematical model was used to predict the effect of static load (creep load) on GAG synthesis in bovine tail discs. The predicted results are in the range of experimental results. This model was also used to investigate the effect of static (0.2MPa) and diurnal loads (0.1/0.3MPa and 0.15/0.25MPa in 12/12 hours shift with an average of 0.2MPa over a cycle) on GAG synthesis. It was found that static load and diurnal loads have different effects on GAG synthesis in a diurnal cycle, and the diurnal load effects depend on the amplitude of the load. The model is important to understand the effect of mechanical loading at the tissue level on GAG synthesis at the cellular level, as well as to optimize the mechanical loading in growing engineered tissue.

  5. Ruptured disc after arthroscopic repositioning in the temporomandibular joint: a retrospective magnetic resonance imaging study.

    PubMed

    Li, Hui; Cai, Xieyi; Yang, Chi; Wang, Shaoyi; Huang, Linjian

    2014-07-01

    Our aim was to explore the incidence of rupture after arthroscopic repositioning of the disc of the temporomandibular joint (TMJ) by reviewing magnetic resonance images (MRI) of the TMJ taken before and after operation, and to investigate correlations retrospectively. We studied 247 patients with anterior disc displacement of the TMJ, and categorised them into 3 groups based on the postoperative MRI. The first group comprised those whose disc ruptured after repositioning, the second those who had a possible rupture of the disc after repositioning, and the third had no rupture of the disc after repositioning. Age, sex, duration of symptoms, maximum incisal mouth opening, whether the anterior disc displacement was unilateral or bilateral, and the Wilkes stage, were included in the analysis. The incidence of rupture (5/247) was 2%. Weak points at the intermediate zone of the disc were found in 4 of the 5 joints. The patients whose discs ruptured were significantly younger than the other 2 groups (p=0.001). There was no statistically significant difference in preoperative duration of symptoms and mouth opening among the groups. The proportions of unilateral and bilateral disc displacement (p=0.047) and Wilkes stage (p=0.027) differed among the 3 groups. The Wilkes stages was significantly more advanced in the ruptured group than in the other 2 groups (p=0.027) with 4/5 being bilateral. The weak point in the intermediate zone of the disc on MRI could be a sign of rupture. Teenagers and young adults with anterior disc displacement without reduction, particularly those in whom it is bilateral, are at a higher risk of a rupture after repositioning of the disc by arthroscopy.

  6. Intervertebral disc extrusion and spinal decompression in a binturong (Arctictis binturong).

    PubMed

    Spriggs, Maria; Arble, Jason; Myers, Gwen

    2007-03-01

    A 10-yr-old binturong (Arctictis binturong) developed an acute onset of hind limb paralysis. Neurological examination revealed sensorimotor paraplegia. Myelography and computed tomography demonstrated a ventrolateral extradural compression of the spinal cord centered over the L3-L4 intervertebral disc space. Spinal decompression was performed via hemilaminectomy and excision of degenerate nucleus pulposus, confirmed by histopathologic examination. The binturong regained slight motor function by day 8 postoperatively but succumbed to pancreatitis 19 days postoperatively.

  7. Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs

    PubMed Central

    Nasto, Luigi A.; Wang, Dong; Robinson, Andria R.; Clauson, Cheryl L.; Ngo, Kevin; Dong, Qing; Roughley, Peter; Epperly, Michael; Huq, Saiful M.; Pola, Enrico; Sowa, Gwendolyn; Robbins, Paul D.; Kang, James; Niedernhofer, Laura J.; Vo, Nam V.

    2013-01-01

    Intervertebral disc degeneration (IDD) is the leading cause of debilitating spinal disorders such as chronic lower back pain. Aging is the greatest risk factor for IDD. Previously, we demonstrated IDD in a murine model of a progeroid syndrome caused by reduced expression of a key DNA repair enzyme. This led us to hypothesize that DNA damage promotes IDD. To test our hypothesis, we chronically exposed adult wild-type (Wt) and DNA repair-deficient Ercc1−/Δ mice to the cancer therapeutic agent mechlorethamine (MEC) or ionization radiation (IR) to induce DNA damage and measured the impact on disc structure. Proteoglycan, a major structural matrix constituent of the disc, was reduced 3-5x in the discs of MEC- and IR-exposed animals compared to untreated controls. Expression of the protease ADAMTS4 and aggrecan proteolytic fragments were significantly increased. Additionally, new PG synthesis was reduced 2-3x in MEC- and IR-treated discs compared to untreated controls. Both cellular senescence and apoptosis were increased in discs of treated animals. The effects were more severe in the DNA repair-deficient Ercc1−/Δ mice than in Wt littermates. Local irradiation of the vertebra in Wt mice elicited a similar reduction in PG. These data demonstrate that genotoxic stress drives degenerative changes associated with IDD. PMID:23262094

  8. Developments in age-related macular degeneration: Diagnosis and treatment.

    PubMed

    Kaufman, Steven R

    2009-03-01

    Age-related macular degeneration (ARMD) is the leading cause of legal blindness of Americans over age 65 years. Severe loss of vision is usually due to exudative ARMD, of which there are about 200,000 new cases in the United States annually. Until recently, only a small fraction of patients benefited from treatment, but advances in the early diagnosis of the disease and major developments in therapy have substantially improved the prognosis of patients with ARMD. Because visual loss substantially reduces quality of life, effective management of ARMD will have increasing public health importance as the population ages. The American Academy of Ophthalmology recommends that people over age 65 years should have a comprehensive eye examination every 1 to 2 years to check for cataracts, macular degeneration, glaucoma, and other conditions. Those who complain of difficulty reading, driving at night, or adapting from sunlight to indoor lighting might have macular degeneration.

  9. Evolution of protoplanetary discs with magnetically driven disc winds

    NASA Astrophysics Data System (ADS)

    Suzuki, Takeru K.; Ogihara, Masahiro; Morbidelli, Alessandro; Crida, Aurélien; Guillot, Tristan

    2016-12-01

    Aims: We investigate the evolution of protoplanetary discs (PPDs) with magnetically driven disc winds and viscous heating. Methods: We considered an initially massive disc with 0.1 M⊙ to track the evolution from the early stage of PPDs. We solved the time evolution of surface density and temperature by taking into account viscous heating and the loss of mass and angular momentum by the disc winds within the framework of a standard α model for accretion discs. Our model parameters, turbulent viscosity, disc wind mass-loss, and disc wind torque, which were adopted from local magnetohydrodynamical simulations and constrained by the global energetics of the gravitational accretion, largely depends on the physical condition of PPDs, particularly on the evolution of the vertical magnetic flux in weakly ionized PPDs. Results: Although there are still uncertainties concerning the evolution of the vertical magnetic flux that remains, the surface densities show a large variety, depending on the combination of these three parameters, some of which are very different from the surface density expected from the standard accretion. When a PPD is in a wind-driven accretion state with the preserved vertical magnetic field, the radial dependence of the surface density can be positive in the inner region <1-10 au. The mass accretion rates are consistent with observations, even in the very low level of magnetohydrodynamical turbulence. Such a positive radial slope of the surface density strongly affects planet formation because it inhibits the inward drift or even causes the outward drift of pebble- to boulder-sized solid bodies, and it also slows down or even reversed the inward type-I migration of protoplanets. Conclusions: The variety of our calculated PPDs should yield a wide variety of exoplanet systems.

  10. Numerical exploration of the combined effect of nutrient supply, tissue condition and deformation in the intervertebral disc.

    PubMed

    Malandrino, Andrea; Noailly, Jérôme; Lacroix, Damien

    2014-04-11

    Novel strategies to heal discogenic low back pain could highly benefit from comprehensive biophysical studies that consider both mechanical and biological factors involved in intervertebral disc degeneration. A decrease in nutrient availability at the bone-disc interface has been indicated as a relevant risk factor and as a possible initiator of cell death processes. Mechanical behaviour of both healthy and degenerated discs could highly interact with cell death in these compromised situations. In the present study, a mechano-transport finite element model was used to investigate the nature of mechanical effects on cell death processes via load-induced metabolic transport variations. Cycles of static sustained compression were chosen to simulate daily human activity. Healthy and degenerated cases were simulated as well as a reduced supply of solutes and an increase in solute exchange area at the bone-disc interface. Results showed that a reduction in metabolite concentrations at the bone-disc boundaries induced cell death, even when the increased exchange area was simulated. Slight local mechanical enhancements of glucose in the disc centre were capable of decelerating cell death but occurred only with healthy mechanical properties. However, mechanical deformations were responsible for a worsening in terms of cell death in the inner annulus, a disadvantaged zone far from the boundary supply with both an increased cell demand and a strain-dependent decrease of diffusivity. Such adverse mechanical effects were more accentuated when degenerative properties were simulated. Overall, this study paves the way for the use of biophysical models for a more integrated understanding of intervertebral disc pathophysiology.

  11. Delivering mesenchymal stem cells in collagen microsphere carriers to rabbit degenerative disc: reduced risk of osteophyte formation.

    PubMed

    Li, Yuk Yin; Diao, Hua Jia; Chik, Tze Kit; Chow, Cin Ting; An, Xiao Meng; Leung, Victor; Cheung, Kenneth Man Chi; Chan, Barbara Pui

    2014-05-01

    Mesenchymal stem cells (MSCs) have the potential to treat early intervertebral disc (IVD) degeneration. However, during intradiscal injection, the vast majority of cells leaked out even in the presence of hydrogel carrier. Recent evidence suggests that annulus puncture is associated with cell leakage and contributes to osteophyte formation, an undesirable side effect. This suggests the significance of developing appropriate carriers for intradiscal delivery of MSCs. We previously developed a collagen microencapsulation platform, which entraps MSCs in a solid microsphere consisting of collagen nanofiber meshwork. These solid yet porous microspheres support MSC attachment, survival, proliferation, migration, differentiation, and matrix remodeling. Here we hypothesize that intradiscal injection of MSCs in collagen microspheres will outperform that of MSCs in saline in terms of better functional outcomes and reduced side effects. Specifically, we induced disc degeneration in rabbits and then intradiscally injected autologous MSCs, either packaged within collagen microspheres or directly suspended in saline, into different disc levels. Functional outcomes including hydration index and disc height were monitored regularly until 6 months. Upon sacrifice, the involved discs were harvested for histological, biochemical, and biomechanical evaluations. MSCs in collagen microspheres showed advantage over MSCs in saline in better maintaining the dynamic mechanical behavior but similar performance in hydration and disc height maintenance and matrix composition. More importantly, upon examination of gross appearance, radiograph, and histology of IVD, delivering MSCs in collagen microspheres significantly reduced the risk of osteophyte formation as compared to that in saline. This work demonstrates the significance of using cell carriers during intradiscal injection of MSCs in treating disc degeneration.

  12. Delivering Mesenchymal Stem Cells in Collagen Microsphere Carriers to Rabbit Degenerative Disc: Reduced Risk of Osteophyte Formation

    PubMed Central

    Li, Yuk Yin; Diao, Hua Jia; Chik, Tze Kit; Chow, Cin Ting; An, Xiao Meng; Leung, Victor; Cheung, Kenneth Man Chi

    2014-01-01

    Mesenchymal stem cells (MSCs) have the potential to treat early intervertebral disc (IVD) degeneration. However, during intradiscal injection, the vast majority of cells leaked out even in the presence of hydrogel carrier. Recent evidence suggests that annulus puncture is associated with cell leakage and contributes to osteophyte formation, an undesirable side effect. This suggests the significance of developing appropriate carriers for intradiscal delivery of MSCs. We previously developed a collagen microencapsulation platform, which entraps MSCs in a solid microsphere consisting of collagen nanofiber meshwork. These solid yet porous microspheres support MSC attachment, survival, proliferation, migration, differentiation, and matrix remodeling. Here we hypothesize that intradiscal injection of MSCs in collagen microspheres will outperform that of MSCs in saline in terms of better functional outcomes and reduced side effects. Specifically, we induced disc degeneration in rabbits and then intradiscally injected autologous MSCs, either packaged within collagen microspheres or directly suspended in saline, into different disc levels. Functional outcomes including hydration index and disc height were monitored regularly until 6 months. Upon sacrifice, the involved discs were harvested for histological, biochemical, and biomechanical evaluations. MSCs in collagen microspheres showed advantage over MSCs in saline in better maintaining the dynamic mechanical behavior but similar performance in hydration and disc height maintenance and matrix composition. More importantly, upon examination of gross appearance, radiograph, and histology of IVD, delivering MSCs in collagen microspheres significantly reduced the risk of osteophyte formation as compared to that in saline. This work demonstrates the significance of using cell carriers during intradiscal injection of MSCs in treating disc degeneration. PMID:24372278

  13. The use of a novel injectable hydrogel nucleus pulposus replacement in restoring the mechanical properties of cyclically fatigued porcine intervertebral discs.

    PubMed

    Balkovec, Christian; Vernengo, Jennifer; McGill, Stuart M

    2013-06-01

    Repeated flexion and extension of an intervertebral disc has been shown to affect the angular stiffness of spinal motion segments and is a barometer of the mechanical integrity of the disc. A degenerated disc that loses height causes higher levels of stress on the annulus and facet joints which may increase its level of degeneration; restoring disc height may therefore help to slow this degenerative cascade. Previous research has indicated that nucleus implants have the potential to improve the mechanical characteristics of a disc and an implant that is custom-fit to the intervertebral disc yields the best results with respect to decreasing annular degeneration. Two groups of porcine spinal motion segments were exposed to repeated flexion and extension. One group was then injected with a novel hydrogel while the other group was used as a control. Both groups were then exposed to another round of cyclic flexion and extension to examine the effect that the hydrogel had on restoring the original mechanics to the motion segments. Angular stiffness was restored to the group which received the hydrogel injection in addition to a significant improvement in specimen height. No significant changes were seen in the group which did not receive an injection. It would appear that use of the novel injectable hydrogel is able to restore angular stiffness to cyclically fatigued spinal motion segments. It is also important to note that continued repetition of the event causing specimen fatigue after performing hydrogel injection will result in an eventual return to the same fatigued state.

  14. Experimental Application of Bone Marrow Mesenchymal Stem Cells for the Repair of Intervertebral Disc Annulus Fibrosus

    PubMed Central

    Li, Xiaohe; Zhang, Yunfeng; Song, Bin; En, He; Gao, Shang; Zhang, Shaojie; Cai, Yongqiang; Li, Zhi-jun; Li, Cunbao; Wang, Weiping; Wang, Xin; Wang, Haiyan; Wang, Zhiqiang; Zhang, Qi; Ma, Jierong

    2016-01-01

    Background This study provides experimental results on the applicability of bone marrow mesenchymal stem cells (BMSCs) for the repair of intervertebral disc annulus fibrosus in rabbits. Material/Method Thirty healthy rabbits were randomized into an observation group (n=15) and a control group (n=15). Both groups underwent degeneration of intervertebral disc annulus fibrosus. The observation group was treated with a solution of BMSCs and dexamethasone sodium phosphate, while the control group was treated with dexamethasone sodium phosphate only. Results The two groups were compared for efficacy and pathological conditions after treatment. Both disc height index and level of type II collagen in nucleus pulposus were significantly higher in the observation group than in the control group at 2, 4, 8, and 12 weeks after degeneration (p<0.05 for all comparisons). The percentages of grade 0 and grade 1 were significantly higher in the observation group than in the control group (p<0.05 for both grade 0 and 1 comparisons), while the percentage of grade 4 and grade 5 were significantly lower in the observation group than in the control group (p<0.05 for both grade 4 and 5 comparisons). Conclusions BMSCs cultured in vitro can effectively repair intervertebral disc annulus fibrosus, which is of positive significance, and thus is clinically recommended. PMID:27857031

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

    PubMed Central

    2010-01-01

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

  16. Form and function of the intervertebral disc in health and disease: a morphological and stain comparison study

    PubMed Central

    Walter, B. A.; Torre, O. M.; Laudier, D.; Naidich, T. P.; Hecht, A. C.; Iatridis, J. C.

    2015-01-01

    Multiple histologic measurements are commonly used to assess degenerative changes in intervertebral disc (IVD) structure; however, there is no consensus on which stains offer the clearest visualization of specific areas within the IVD. The objective of this study was to compare multiple tinctorial stains, evaluate their ability to highlight structural features within the IVD, and investigate how they influence the capacity to implement a degeneration scoring system. Lumbar IVDs from seven human autopsy specimens were stained using six commonly used stains (Hematoxylin/Eosin, Toluidine Blue, Safranin-O/Fast Green, Extended FAST, modified Gomori’s Trichrome, and Picrosirius Red Alcian Blue). All IVDs were evaluated by three separate graders to independently determine which stains (i) were most effective at discerning different structural features within different regions of the IVDs and (ii) allowed for the most reproducible assessment of degeneration grade, as assessed via the Rutges histological scoring system (Rutges et al. A validated new histological classification for intervertebral disc degeneration. Osteoarthritis Cartilage, 21, 2039-47). Although Trichrome, XFAST and PR/AB stains were all effective at highlighting different regions of whole IVDs, we recommend the use of PR/AB because it had the highest degree of rater agreement on assigned degeneration grade, allowed greater resolution of degeneration grade, has an inferential relationship between color and composition, and allowed clear differentiation of the different regions and structural disruptions within the IVD. The use of a standard set of stains together with a histological grading scheme can aid in the characterization of structural changes in different regions of the IVD and may simplify comparisons across the field. This collection of human IVD histological images highlights how IVD degeneration is not a single disease but a composite of multiple processes such as aging, injury, repair, and

  17. Determination of the intervertebral disc space from CT images of the lumbar spine

    NASA Astrophysics Data System (ADS)

    Korez, Robert; Å tern, Darko; Likar, Boštjan; Pernuš, Franjo; Vrtovec, Tomaž

    2014-03-01

    Degenerative changes of the intervertebral disc are among the most common causes of low back pain, where for individuals with significant symptoms surgery may be needed. One of the interventions is the total disc replacement surgery, where the degenerated disc is replaced by 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 the determination of the intervertebral disc space from three-dimensional (3D) computed tomography (CT) images of the lumbar spine. The first step of the proposed method is the construction of a model of vertebral bodies in the lumbar spine. For this purpose, a chain of five elliptical cylinders is initialized in the 3D image and then deformed to resemble vertebral bodies by introducing 25 shape parameters. The parameters are obtained by aligning the chain to the vertebral bodies in the CT image according to image intensity and appearance information. The determination of the intervertebral disc space is finally achieved by finding the planes that fit the endplates of the obtained parametric 3D models, and placing points in the space between the planes of adjacent vertebrae that enable surface reconstruction of the intervertebral disc space. The morphometric analysis of images from 20 subjects yielded 11:3 +/- 2:6, 12:1 +/- 2:4, 12:8 +/- 2:0 and 12:9 +/- 2:7 cm3 in terms of L1-L2, L2-L3, L3-L4 and L4-L5 intervertebral disc space volume, respectively.

  18. Gravitoturbulence in magnetized protostellar discs

    NASA Astrophysics Data System (ADS)

    Riols, A.; Latter, H.

    2016-08-01

    Gravitational instability (GI) features in several aspects of protostellar disc evolution, most notably in angular momentum transport, fragmentation, and the outbursts exemplified by FU Ori and EX Lupi systems. The outer regions of protostellar discs may also be coupled to magnetic fields, which could then modify the development of GI. To understand the basic elements of their interaction, we perform local 2D ideal and resistive magnetohydrodynamics simulations with an imposed toroidal field. In the regime of moderate plasma beta, we find that the system supports a hot gravitoturbulent state, characterized by considerable magnetic energy and stress and a surprisingly large Toomre parameter Q ≳ 10. This result has potential implications for disc structure, vertical thickness, ionization, etc. Our simulations also reveal the existence of long-lived and dense `magnetic islands' or plasmoids. Lastly, we find that the presence of a magnetic field has little impact on the fragmentation criterion of the disc. Though our focus is on protostellar discs, some of our results may be relevant for the outer radii of AGN.

  19. The cellular memory disc of reprogrammed cells.

    PubMed

    Anjamrooz, Seyed Hadi

    2013-04-01

    The crucial facts underlying the low efficiency of cellular reprogramming are poorly understood. Cellular reprogramming occurs in nuclear transfer, induced pluripotent stem cell (iPSC) formation, cell fusion, and lineage-switching experiments. Despite these advances, there are three fundamental problems to be addressed: (1) the majority of cells cannot be reprogrammed, (2) the efficiency of reprogramming cells is usually low, and (3) the reprogrammed cells developed from a patient's own cells activate immune responses. These shortcomings present major obstacles for using reprogramming approaches in customised cell therapy. In this Perspective, the author synthesises past and present observations in the field of cellular reprogramming to propose a theoretical picture of the cellular memory disc. The current hypothesis is that all cells undergo an endogenous and exogenous holographic memorisation such that parts of the cellular memory dramatically decrease the efficiency of reprogramming cells, act like a barrier against reprogramming in the majority of cells, and activate immune responses. Accordingly, the focus of this review is mainly to describe the cellular memory disc (CMD). Based on the present theory, cellular memory includes three parts: a reprogramming-resistance memory (RRM), a switch-promoting memory (SPM) and a culture-induced memory (CIM). The cellular memory arises genetically, epigenetically and non-genetically and affects cellular behaviours. [corrected].

  20. Towards long term cultivation of Drosophila wing imaginal discs in vitro.

    PubMed

    Handke, Björn; Szabad, János; Lidsky, Peter V; Hafen, Ernst; Lehner, Christian F

    2014-01-01

    The wing imaginal disc of Drosophila melanogaster is a prominent experimental system for research on control of cell growth, proliferation and death, as well as on pattern formation and morphogenesis during organogenesis. The precise genetic methodology applicable in this system has facilitated conceptual advances of fundamental importance for developmental biology. Experimental accessibility and versatility would gain further if long term development of wing imaginal discs could be studied also in vitro. For example, culture systems would allow live imaging with maximal temporal and spatial resolution. However, as clearly demonstrated here, standard culture methods result in a rapid cell proliferation arrest within hours of cultivation of dissected wing imaginal discs. Analysis with established markers for cells in S- and M phase, as well as with RGB cell cycle tracker, a novel reporter transgene, revealed that in vitro cultivation interferes with cell cycle progression throughout interphase and not just exclusively during G1. Moreover, quantification of EGFP expression from an inducible transgene revealed rapid adverse effects of disc culture on basic cellular functions beyond cell cycle progression. Disc transplantation experiments confirmed that these detrimental consequences do not reflect fatal damage of imaginal discs during isolation, arguing clearly for a medium insufficiency. Alternative culture media were evaluated, including hemolymph, which surrounds imaginal discs during growth in situ. But isolated larval hemolymph was found to be even less adequate than current culture media, presumably as a result of conversion processes during hemolymph isolation or disc culture. The significance of prominent growth-regulating pathways during disc culture was analyzed, as well as effects of insulin and disc co-culture with larval tissues as potential sources of endocrine factors. Based on our analyses, we developed a culture protocol that prolongs cell

  1. Towards Long Term Cultivation of Drosophila Wing Imaginal Discs In Vitro

    PubMed Central

    Handke, Björn; Szabad, János; Lidsky, Peter V.; Hafen, Ernst; Lehner, Christian F.

    2014-01-01

    The wing imaginal disc of Drosophila melanogaster is a prominent experimental system for research on control of cell growth, proliferation and death, as well as on pattern formation and morphogenesis during organogenesis. The precise genetic methodology applicable in this system has facilitated conceptual advances of fundamental importance for developmental biology. Experimental accessibility and versatility would gain further if long term development of wing imaginal discs could be studied also in vitro. For example, culture systems would allow live imaging with maximal temporal and spatial resolution. However, as clearly demonstrated here, standard culture methods result in a rapid cell proliferation arrest within hours of cultivation of dissected wing imaginal discs. Analysis with established markers for cells in S- and M phase, as well as with RGB cell cycle tracker, a novel reporter transgene, revealed that in vitro cultivation interferes with cell cycle progression throughout interphase and not just exclusively during G1. Moreover, quantification of EGFP expression from an inducible transgene revealed rapid adverse effects of disc culture on basic cellular functions beyond cell cycle progression. Disc transplantation experiments confirmed that these detrimental consequences do not reflect fatal damage of imaginal discs during isolation, arguing clearly for a medium insufficiency. Alternative culture media were evaluated, including hemolymph, which surrounds imaginal discs during growth in situ. But isolated larval hemolymph was found to be even less adequate than current culture media, presumably as a result of conversion processes during hemolymph isolation or disc culture. The significance of prominent growth-regulating pathways during disc culture was analyzed, as well as effects of insulin and disc co-culture with larval tissues as potential sources of endocrine factors. Based on our analyses, we developed a culture protocol that prolongs cell

  2. Age-Related Macular Degeneration.

    PubMed

    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.

  3. Atomic gas in debris discs

    NASA Astrophysics Data System (ADS)

    Hales, Antonio S.; Barlow, M. J.; Crawford, I. A.; Casassus, S.

    2017-04-01

    We have conducted a search for optical circumstellar absorption lines in the spectra of 16 debris disc host stars. None of the stars in our sample showed signs of emission line activity in either Hα, Ca II or Na I, confirming their more evolved nature. Four stars were found to exhibit narrow absorption features near the cores of the photospheric Ca II and Na I D lines (when Na I D data were available). We analyse the characteristics of these spectral features to determine whether they are of circumstellar or interstellar origins. The strongest evidence for circumstellar gas is seen in the spectrum of HD 110058, which is known to host a debris disc observed close to edge-on. This is consistent with a recent ALMA detection of molecular gas in this debris disc, which shows many similarities to the β Pictoris system.

  4. Coevolution of binaries and circumbinary gaseous discs

    NASA Astrophysics Data System (ADS)

    Fleming, David P.; Quinn, Thomas R.

    2017-01-01

    The recent discoveries of circumbinary planets by Kepler raise questions for contemporary planet formation models. Understanding how these planets form requires characterizing their formation environment, the circumbinary protoplanetary disc and how the disc and binary interact and change as a result. The central binary excites resonances in the surrounding protoplanetary disc which drive evolution in both the binary orbital elements and in the disc. To probe how these interactions impact binary eccentricity and disc structure evolution, N-body smooth particle hydrodynamics simulations of gaseous protoplanetary discs surrounding binaries based on Kepler 38 were run for 104 binary periods for several initial binary eccentricities. We find that nearly circular binaries weakly couple to the disc via a parametric instability and excite disc eccentricity growth. Eccentric binaries strongly couple to the disc causing eccentricity growth for both the disc and binary. Discs around sufficiently eccentric binaries which strongly couple to the disc develop an m = 1 spiral wave launched from the 1:3 eccentric outer Lindblad resonance which corresponds to an alignment of gas particle longitude of periastrons. All systems display binary semimajor axis decay due to dissipation from the viscous disc.

  5. The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling.

    PubMed

    Luther, Pradeep K

    2009-01-01

    The Z-disc, appearing as a fine dense line forming sarcomere boundaries in striated muscles, when studied in detail reveals crosslinked filament arrays that transmit tension and house myriads of proteins with diverse functions. At the Z-disc the barbed ends of the antiparallel actin filaments from adjoining sarcomeres interdigitate and are crosslinked primarily by layers of alpha-actinin. The Z-disc is therefore the site of polarity reversal of the actin filaments, as needed to interact with the bipolar myosin filaments in successive sarcomeres. The layers of alpha-actinin determine the Z-disc width: fast fibres have narrow (approximately 30-50 nm) Z-discs and slow and cardiac fibres have wide (approximately 100 nm) Z-discs. Comprehensive reviews on the roles of the numerous proteins located at the Z-disc in signalling and disease have been published; the aim here is different, namely to review the advances in structural aspects of the Z-disc.

  6. Riboflavin crosslinked high-density collagen gel for the repair of annular defects in intervertebral discs: An in vivo study.

    PubMed

    Grunert, Peter; Borde, Brandon H; Towne, Sara B; Moriguchi, Yu; Hudson, Katherine D; Bonassar, Lawrence J; Härtl, Roger

    2015-10-01

    Open annular defects compromise the ability of the annulus fibrosus to contain nuclear tissue in the disc space, and therefore lead to disc herniation with subsequent degenerative changes to the entire intervertebral disc. This study reports the use of riboflavin crosslinked high-density collagen gel for the repair of annular defects in a needle-punctured rat-tail model. High-density collagen has increased stiffness and greater hydraulic permeability than conventional low-density gels; riboflavin crosslinking further increases these properties. This study found that treating annular defects with crosslinked high-density collagen inhibited the progression of disc degeneration over 18 weeks compared to untreated control discs. Histological sections of FITC-labeled collagen gel revealed an early tight attachment to host annular tissue. The gel was subsequently infiltrated by host fibroblasts which remodeled it into a fibrous cap that bridged the outer disrupted annular fibers and partially repaired the defect. This repair tissue enhanced retention of nucleus pulposus tissue, maintained physiological disc hydration, and preserved hydraulic permeability, according to MRI, histological, and mechanical assessments. Degenerative changes were partially reversed in treated discs, as indicated by an increase in nucleus pulposus size and hydration between weeks 5 and 18. The collagen gel appeared to work as an instant sealant and by enhancing the intrinsic healing capabilities of the host tissue.

  7. Disc-shaped ionic polymer metal composites for use in mechano-electrical applications

    NASA Astrophysics Data System (ADS)

    Tiwari, R.; Kim, K. J.

    2010-06-01

    Previously, mechano-electrical energy harvesting from IPMC has been studied in the conventional bender configuration. However, for mechano-electrical energy harvesting from uncontrolled or multi-directional vibration, there is a need to produce 2D and/or 3D IPMCs. In addition, the conventional bender configuration of IPMC may impose restriction on its application as an energy harvester. For these reasons, there is a need to advance the geometry of the IPMC. In this paper, a new configuration, a disc-type IPMC, is introduced. The disc IPMC was manufactured by hot pressing Nafion pellets. The voltage across the disc on deformation was extracted using two-electrode systems.

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

    PubMed Central

    Yu, Fei; Ma, Junxuan

    2017-01-01

    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. PMID:28321270

  9. Finite element analysis predicts experimental failure patterns in vertebral bodies loaded via intervertebral discs up to large deformation.

    PubMed

    Clouthier, Allison L; Hosseini, Hadi S; Maquer, Ghislain; Zysset, Philippe K

    2015-06-01

    Vertebral compression fractures are becoming increasingly common. Patient-specific nonlinear finite element (FE) models have shown promise in predicting yield strength and damage pattern but have not been experimentally validated for clinically relevant vertebral fractures, which involve loading through intervertebral discs with varying degrees of degeneration up to large compressive strains. Therefore, stepwise axial compression was applied in vitro on segments and performed in silico on their FE equivalents using a nonlocal damage-plastic model including densification at large compression for bone and a time-independent hyperelastic model for the disc. The ability of the nonlinear FE models to predict the failure pattern in large compression was evaluated for three boundary conditions: healthy and degenerated intervertebral discs and embedded endplates. Bone compaction and fracture patterns were predicted using the local volume change as an indicator and the best correspondence was obtained for the healthy intervertebral discs. These preliminary results show that nonlinear finite element models enable prediction of bone localisation and compaction. To the best of our knowledge, this is the first study to predict the collapse of osteoporotic vertebral bodies up to large compression using realistic loading via the intervertebral discs.

  10. Temporomandibular Joint Fibrocartilage Degeneration from Unilateral Dental Splints

    PubMed Central

    Henderson, Sarah E.; Lowe, Jesse R.; Tudares, Mauro A.; Gold, Michael S.; Almarza, Alejandro J.

    2014-01-01

    Objective 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 maloclussion, 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. Design Altered TMJ loading was induced with a 1 mm splint placed unilaterally over the maxillary and mandibular molars for six 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. Results 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. Conclusions 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. PMID:25247778

  11. Photoevaporating transitional discs and molecular cloud cores

    NASA Astrophysics Data System (ADS)

    Li, Min; Sui, Ning

    2017-04-01

    We investigate the evolution of photoevaporating protoplanetary discs including mass influx from molecular cloud cores. We examine the influence of cloud core properties on the formation and evolution of transitional discs. We use one-dimensional thin disc assumption and calculate the evolution of the protoplanetary disc. The effects of X-ray photoevaporation are also included. Our calculations suggest that most discs should experience the transitional disc phase within 10 Myr. The formation time of a gap and its initial location are functions of the properties of the cloud cores. In some circumstances, discs can open two gaps by photoevaporation alone. The two gaps form when the gas in the disc can expand to large radius and if the mass at large radius is sufficiently small. The surface density profile of the disc determines whether the two gaps can form. Since the structure of a disc is determined by the properties of a molecular cloud core, the core properties determine the formation of two gaps in the disc. We further find that even when the photoevaporation rate is reduced to 10 per cent of the standard value, two gaps can still form in the disc. The only difference is that the formation time is delayed.

  12. Lack of Relationship Between Occupational Workload and Microscopic Alterations in Lumbar Intervertebral Disc Disease

    PubMed Central

    Huschak, Gerald; Holzhausen, Hans-Jürgen; Beier, Andre; Meisel, Hans Jörg; Hoell, Thomas

    2014-01-01

    Objectives : The study investigated the impact of occupational workloads on disc surgery specimens. We report the relationship between workload and histological features. Methods : Specimens were collected prospectively from patients suffering from lumbar disc prolapse (n=90) or spinal osteochondrosis (n=19). Histomorphology and occupational workload data and histomorphological features were evaluated. Occupational data were collected in a structured, standardized patient interview assessing lifting and carrying loads. In this way the exposure was assessed for each test subject's entire working life up to surgery. Results : There was no association between cumulative workload and histological patterns. In a subgroup of patients with a workload period of 12 months prior to surgery a relevant formation of chondrocyte clusters (p=0.055) was apparent. Chondrocyte cluster formation was found in 83% (n=74) of the prolapse patients and in 58% (n=11) of the osteochondrosis patients (p=0.02). Fibrocyte mediated scar formation was found in 55% of the prolapse patients and in 45% of the spinal stenosis patients. Chondrocyte clusters and their de novo collagen matrix did not integrate biomechanically sufficient with collagen fibers of the disc. Disintegration of clusters from disc matrix and formation of intra-discal sequesters were observed. Conclusion : Matrix degeneration was common but displayed no relationship to occupational workload or other histological features. Scar formation was observed in every second specimen. Regenerative chondrocyte cluster proliferation was a common feature in disc specimens and tended to be associated in patients with a workload one year before surgery. PMID:25136392

  13. Mechanical Vibrations Reduce the Intervertebral Disc Swelling and Muscle Atrophy from Bed Rest

    NASA Technical Reports Server (NTRS)

    Holguin, Nilsson; Muir, Jesse; Evans, Harlan J.; Qin, Yi-Xian; Rubin, Clinton; Wagshul, Mark; Judex, Stefan

    2007-01-01

    Loss of functional weight bearing, such as experienced during space flight or bed rest (BR), distorts intervertebral disc (IVD) and muscle morphology. IVDs are avascular structures consisting of cells that may derive their nutrition and waste removal from the load induced fluid flow into and out of the disc. A diurnal cycle is produced by forces related to weight bearing and muscular activity, and comprised of a supine and erect posture over a 24 hr period. A diurnal cycle will include a disc volume change of approx. 10-13%. However, in space there are little or no diurnal changes because of the microgravity, which removes the gravitational load and compressive forces to the back muscles. The BR model and the etiology of the disc swelling and muscle atrophy could provide insight into those subjects confined to bed for chronic disease/injury and aging. We hypothesize that extremely low-magnitude, high frequency mechanical vibrations will abate the disc degeneration and muscle loss associated with long-term BR.

  14. Electromagnetic Levitation of a Disc

    ERIC Educational Resources Information Center

    Valle, R.; Neves, F.; de Andrade, R., Jr.; Stephan, R. M.

    2012-01-01

    This paper presents a teaching experiment that explores the levitation of a disc of ferromagnetic material in the presence of the magnetic field produced by a single electromagnet. In comparison to the classical experiment of the levitation of a sphere, the main advantage of the proposed laboratory bench is that the uniform magnetic field…

  15. Artificial Discs for Lumbar and Cervical Degenerative Disc Disease –Update

    PubMed Central

    2006-01-01

    Executive Summary Objective To assess the safety and efficacy of artificial disc replacement (ADR) technology for degenerative disc disease (DDD). Clinical Need Degenerative disc disease is the term used to describe the deterioration of 1 or more intervertebral discs of the spine. The prevalence of DDD is roughly described in proportion to age such that 40% of people aged 40 years have DDD, increasing to 80% among those aged 80 years or older. Low back pain is a common symptom of lumbar DDD; neck and arm pain are common symptoms of cervical DDD. Nonsurgical treatments can be used to relieve pain and minimize disability associated with DDD. However, it is estimated that about 10% to 20% of people with lumbar DDD and up to 30% with cervical DDD will be unresponsive to nonsurgical treatments. In these cases, surgical treatment is considered. Spinal fusion (arthrodesis) is the process of fusing or joining 2 bones and is considered the surgical gold standard for DDD. Artificial disc replacement is the replacement of the degenerated intervertebral disc with an artificial disc in people with DDD of the lumbar or cervical spine that has been unresponsive to nonsurgical treatments for at least 6 months. Unlike spinal fusion, ADR preserves movement of the spine, which is thought to reduce or prevent the development of adjacent segment degeneration. Additionally, a bone graft is not required for ADR, and this alleviates complications, including bone graft donor site pain and pseudoarthrosis. It is estimated that about 5% of patients who require surgery for DDD will be candidates for ADR. Review Strategy The Medical Advisory Secretariat conducted a computerized search of the literature published between 2003 and September 2005 to answer the following questions: What is the effectiveness of ADR in people with DDD of the lumbar or cervical regions of the spine compared with spinal fusion surgery? Does an artificial disc reduce the incidence of adjacent segment degeneration (ASD

  16. Congenital posterior atlas defect associated with anterior rachischisis and early cervical degenerative disc disease: a case study and review of the literature.

    PubMed

    Pasku, Dritan; Katonis, Pavlos; Karantanas, Apostolos; Hadjipavlou, Alexander

    2007-04-01

    A rare case of a wide congenital atlas defect is reported. A 25 year-old woman was admitted after complaints of radicular pain in the right arm. Radiographs incidentally revealed aplasia of the posterior arch of the atlas together with anterior rachischisis. A review of the literature is presented and a possible association with early disc degeneration is discussed.

  17. General Pathophysiology in Retinal Degeneration

    PubMed Central

    Wert, Katherine J.; Lin, Jonathan H.; Tsang, Stephen H.

    2015-01-01

    Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/ or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6β) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759

  18. Adjacent disc height reduction and clinical outcome after intradiscal cement leakage

    PubMed Central

    Shen, Minjie; Niu, Junjie; Zhou, Haifei; Meng, Qian; Gan, Minfeng

    2016-01-01

    Objective The purpose of this study is to evaluate the effect of intradiscal cement leakage on the height of adjacent cement-containing discs and the resulting clinical efficacy after kyphoplasty. Methods A total of 124 patients were included and classified into two groups: group A included 20 patients with intradiscal leakage, and group B contained 104 patients without intradiscal leakage. The mean follow-up time was 20.56±3.51 months. The height of the corresponding discs in both groups was measured using Farfan’s method. Clinical efficacy was assessed using the Visual Analog Scale and Oswestry Disability Index scores at each follow-up time. Results The anterior disc height, posterior disc height and Farfan Index significantly decreased in both groups at last follow-up. The disc height reduction was 9.19±2.89% in group A and 3.88±2.70% in group B, which was significantly different between the groups (P<0.01). The disc height reduction rate was 29.39±7.90% in group A and 12.75±8.18% in group B, which was also a statistically significant difference (P<0.01). The VAS and ODI scores improved significantly after surgery and maintained at last follow-up, and there was no statistically significant difference between Groups A and B. Conclusion Intradiscal cement leakage was associated with the degeneration of cement-containing disc but did not reduce the clinical efficacy at early stages. PMID:27909655

  19. Antitruncated stellar light profiles in the outer regions of STAGES spiral galaxies: bulge or disc related?

    NASA Astrophysics Data System (ADS)

    Maltby, David T.; Hoyos, Carlos; Gray, Meghan E.; Aragón-Salamanca, Alfonso; Wolf, Christian

    2012-03-01

    We present a comparison of azimuthally averaged radial surface brightness μ(r) profiles and analytical bulge-disc decompositions (de Vaucouleurs, r1/4 bulge plus exponential disc) for spiral galaxies using Hubble Space Telescope/Advanced Camera for Surveys V-band imaging from the Space Telescope A901/2 Galaxy Evolution Survey (STAGES). In the established classification scheme, antitruncated μ(r) profiles (Type III) have a broken exponential disc with a shallower region beyond the break radius rbrk. The excess light at large radii (r > rbrk) can either be caused by an outer exponential disc (Type III-d) or an extended spheroidal component (Type III-s). Using our comparisons, we determine the contribution of bulge light at r > rbrk for a large sample of 78 (barred/unbarred, Sa-Sd) spiral galaxies with outer disc antitruncations (?). In the majority of cases (˜85 per cent), evidence indicates that excess light at r > rbrk is related to an outer shallow disc (Type III-d). Here, the contribution of bulge light at r > rbrk is either negligible (˜70 per cent) or too little to explain the antitruncation (˜15 per cent). However in the latter cases, bulge light can affect the measured disc properties (e.g. μbrk, outer scalelength). In the remaining cases (˜15 per cent), light at r > rbrk is dominated by the bulge (Type III-s). Here, for most cases the bulge profile dominates at all radii and only occasionally (? galaxies, ˜5 per cent) extends beyond that of a dominant disc and explains the excess light at r > rbrk. We thus conclude that in the vast majority of cases antitruncated outer discs cannot be explained by bulge light and thus remain a pure disc phenomenon.

  20. Parainflammation, chronic inflammation, and age-related macular degeneration.

    PubMed

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration.

  1. [Optic disc granuloma secondary to sarcoidosis].

    PubMed

    Qu-Knafo, L; Auregan-Giocanti, A

    2017-02-01

    We report a case of optic disc granuloma due to sarcoidosis. A 64-year-old, caucasian female with a history of pulmonary sarcoidosis presented with a vision loss on her left eye. The ophthalmologic examination revealed a discrete optic disc infiltrate compatible with the diagnosis of optic disc granuloma. Fluorescein angiography showed diffusion and impregnation of the granuloma without vascularitis. The optical coherence tomography demonstrated a homogenous and isoreflective lesion at the optic disc. The patient recovered her visual acuity after systemic corticosteroid treatment. Isolated optic disc granuloma is a rare condition of ocular sarcoidosis.

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

    PubMed

    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

  3. Structural and Ultrastructural Analysis of the Cervical Discs of Young and Elderly Humans.

    PubMed

    Fontes, Ricardo Braganca de Vasconcellos; Baptista, Josemberg Silva; Rabbani, Said Rahnamaye; Traynelis, Vincent C; Liberti, Edson Aparecido

    2015-01-01

    Several studies describing the ultrastructure and extracellular matrix (ECM) of intervertebral discs (IVDs) involve animal models and specimens obtained from symptomatic individuals during surgery for degenerative disease or scoliosis, which may not necessarily correlate to changes secondary to normal aging in humans. These changes may also be segment-specific based on different load patterns throughout life. Our objective was to describe the ECM and collagen profile of cervical IVDs in young (G1 - <35 years) and elderly (G2 - >65 years) presumably-asymptomatic individuals. Thirty cervical discs per group were obtained during autopsies of presumably-asymptomatic individuals. IVDs were analyzed with MRI, a morphological grading scale, light microscopy, scanning electron microscopy (SEM) and immunohistochemistry (IHC) for collagen types I, II, III, IV, V, VI, IX and X. Macroscopic degenerative features such as loss of annulus-nucleus distinction and fissures were found in both groups and significantly more severe in G2 as expected. MRI could not detect all morphological changes when compared even with simple morphological inspection. The loose fibrocartilaginous G1 matrix was replaced by a denser ECM in G2 with predominantly cartilaginous characteristics, chondrocyte clusters and absent elastic fibers. SEM demonstrated persistence of an identifiable nucleus and Sharpey-type insertion of cervical annulus fibers even in highly-degenerated G2 specimens. All collagen types were detected in every disc sector except for collagen X, with the largest area stained by collagens II and IV. Collagen detection was significantly decreased in G2: although significant intradiscal differences were rare, changes may occur faster or earlier in the posterior annulus. These results demonstrate an extensive modification of the ECM with maintenance of basic ultrastructural features despite severe macroscopic degeneration. Collagen analysis supports there is not a "pathologic" collagen type

  4. An interpenetrating network composite for a regenerative spinal disc application.

    PubMed

    Chan, A H; Boughton, P C; Ruys, A J; Oyen, M L

    2017-01-01

    Severe degeneration of the intervertebral disc has an immensely debilitating effect on quality of life that has become a serious health and economic burden throughout the world. The disc plays an integral role in biomechanical movement and support within the spine. The emergence of tissue engineering endeavours to restore the structural characteristics and functionality of the native tissue. Hydrogels have been widely investigated as a candidate for regeneration of the gelatinous nucleus pulposus due to its architectural resemblance and fluid retention characteristics. However, hydrogels are often limited due to small compressive stiffness and tear resistance, leading to extrusion complications. Reinforcement of the hydrogel network using polymeric scaffolds may address these issues of inadequate mechanical properties and implant instability. This study investigates the potential of a carrageenan gel-infused polycaprolactone scaffold for nucleus pulposus tissue engineering. Mechanical properties were characterised using viscoelastic and poroelastic frameworks via microindentation. The incorporation of polymeric reinforcement within the gels increased material stiffness to that comparable to the native nucleus pulposus, however permeability was significantly greater than native values. A preliminary cell evaluation culturing NIH 3T3s over 21 days suggested the incorporation of polymeric networks also enhanced cellular proliferation compared to gels alone.

  5. Temporal Analyses of the Response of Intervertebral Disc Cells and Mesenchymal Stem Cells to Nutrient Deprivation

    PubMed Central

    Turner, Sarah A.; Wright, Karina T.; Jones, Philip N.; Balain, Birender; Roberts, Sally

    2016-01-01

    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. PMID:26977156

  6. Difference in Energy Metabolism of Annulus Fibrosus and Nucleus Pulposus Cells of the Intervertebral Disc

    PubMed Central

    Salvatierra, Jessica Czamanski; Yuan, Tai Yi; Fernando, Hanan; Castillo, Andre; Gu, Wei Yong; Cheung, Herman S.; Huant, C.-Y. Charles

    2011-01-01

    Low back pain is associated with intervertebral disc degeneration. One of the main signs of degeneration is the inability to maintain extracellular matrix integrity. Extracellular matrix synthesis is closely related to production of adenosine triphosphate (i.e. energy) of the cells. The intervertebral disc is composed of two major anatomical regions: annulus fibrosus and nucleus pulposus, which are structurally and compositionally different, indicating that their cellular metabolisms may also be distinct. The objective of this study was to investigate energy metabolism of annulus fibrosus and nucleus pulposus cells with and without dynamic compression, and examine differences between the two cell types. Porcine annulus and nucleus tissues were harvested and enzymatically digested. Cells were isolated and embedded into agarose constructs. Dynamically loaded samples were subjected to a sinusoidal displacement at 2 Hz and 15% strain for 4 h. Energy metabolism of cells was analyzed by measuring adenosine triphosphate content and release, glucose consumption, and lactate/nitric oxide production. A comparison of those measurements between annulus and nucleus cells was conducted. Annulus and nucleus cells exhibited different metabolic pathways. Nucleus cells had higher adenosine triphosphate content with and without dynamic loading, while annulus cells had higher lactate production and glucose consumption. Compression increased adenosine triphosphate release from both cell types and increased energy production of annulus cells. Dynamic loading affected energy metabolism of intervertebral disc cells, with the effect being greater in annulus cells. PMID:21625336

  7. [Age-related macular degeneration].

    PubMed

    Budzinskaia, M V

    2014-01-01

    The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy.

  8. Degeneration of a Nonrecombining Chromosome

    NASA Astrophysics Data System (ADS)

    Rice, William R.

    1994-01-01

    Comparative studies suggest that sex chromosomes begin as ordinary autosomes that happen to carry a major sex determining locus. Over evolutionary time the Y chromosome is selected to stop recombining with the X chromosome, perhaps in response to accumulation of alleles beneficial to the heterogametic but harmful to the homogametic sex. Population genetic theory predicts that a nonrecombining Y chromosome should degenerate. Here this prediction is tested by application of specific selection pressures to Drosophila melanogaster populations. Results demonstrate the decay of a nonrecombining, nascent Y chromosome and the capacity for recombination to ameliorate such decay.

  9. Age-related macular degeneration

    PubMed Central

    Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

    2011-01-01

    Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887

  10. Molecular Therapy for Degenerative Disc Disease: Clues from Secretome Analysis of the Notochordal Cell-Rich Nucleus Pulposus

    PubMed Central

    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

  11. Indications for Lumbar Total Disc Replacement: Selecting the Right Patient with the Right Indication for the Right Total Disc

    PubMed Central

    Guyer, Richard D.; Ohnmeiss, Donna D.

    2014-01-01

    Summary of Background Data As with any surgery, care should be taken to determine patient selection criteria for lumbar TDR based on safety and optimizing outcome. These goals may initially be addressed by analyzing biomechanical implant function and early clinical experience, ongoing evaluation is needed to refine indications. Objective The purpose of this work was to synthesize information published on general indications for lumbar TDR. A secondary objective was to determine if indications vary for different TDR designs. Methods A comprehensive literature search was conducted to identify lumbar TDR articles. Articles were reviewed and patient selection criteria and indications were synthesized. Results With respect to safety, there was good agreement in the literature to exclude patients with osteopenia/osteoporosis or fracture. Risk of injury to vascular structures due to the anterior approach was often addressed by excluding patients with previous abdominal surgery in the area of disc pathology or increased age. The literature was very consistent on the primary indication for TDR being painful disc degeneration unresponsive to at least 6 months of nonoperative care. Literature investigating the impact of previous spine surgery was mixed; however, prior surgery was not necessarily a contra-indication, provided the patient otherwise met selection criteria. The literature was mixed on setting a minimum preoperative disc height as a selection criterion. There were no publications investigating whether some patients are better/worse candidates for specific TDR designs. Based on the literature a proposal for patient selection criteria is offered. Conclusions Several TDR indications and contra-indications are widely accepted. No literature addresses particular TDR design being preferable for some patients. As with any spine surgery, ongoing evaluation of TDR outcomes will likely lead to more detailed general and device design specific indications. PMID:25694946

  12. Mathematical glimpse on the Y chromosome degeneration

    NASA Astrophysics Data System (ADS)

    Lobo, M. P.

    2006-04-01

    The Y chromosomes are genetically degenerate and do not recombine with their matching partners X. Non-recombination of XY pairs has been pointed out as the key factor for the degeneration of the Y chromosome. The aim here is to show that there is a mathematical asymmetry in sex chromosomes which leads to the degeneration of Y chromosomes even in the absence of XX and XY recombination. A model for sex-chromosome evolution in a stationary regime is proposed. The consequences of their asymmetry are analyzed and lead us to a couple of conclusions. First, Y chromosome degeneration shows up sqrt{2} more often than X chromosome degeneration. Second, if nature prohibits female mortalities from beeing exactly 50%, then Y chromosome degeneration is inevitable.

  13. Survivin is expressed in degenerated nucleus pulposus cells and is involved in proliferation and the prevention of apoptosis in vitro

    PubMed Central

    LIN, YAZHOU; YUE, BIN; XIANG, HONGFEI; LIU, YONG; MA, XUEXIAO; CHEN, BOHUA

    2016-01-01

    Survivin is a unique inhibitor of apoptosis, which is frequently present within degenerated human nucleus pulposus (NP) cells. Survivin has been extensively investigated using proliferation and apoptosis assays in tumor cells; however, studies conducted on survivin in degenerative NP cells remain limited to date. The aim of the present study was to investigate survivin expression and its effects on the proliferation and apoptosis of degenerated NP cells in vitro. The expression levels of survivin in the NP cells of patients (>45 years) with lumbar disc degenerative disease and the NP cells of patients (<25 years) with lumbar vertebra fracture were assessed by reverse transcription-quantitative polymerase chain reaction. The effects on in vitro proliferation and apoptosis were investigated through transfection with a specific small interfering (si)RNA. The results of the present study demonstrated that survivin was expressed in the degenerated NP cells, but was undetectable in normal NP cells at the mRNA level. Survivin suppression following transfection with a specific survivin-siRNA reduced the proliferation rate of NP cells and enhanced sensitization to pro-apoptotic stimuli. Therefore, survivin was shown to be expressed and exhibit an important role in the proliferation and prevention of apoptosis of degenerated NP cells. Studies on survivin in NP cells may aid in increasing the understanding of the complex processes underlying NP cell degeneration, and could provide fundamental information for gene therapy to inhibit this degeneration in vitro. PMID:26648308

  14. Proto-planetary disc evolution and dispersal

    NASA Astrophysics Data System (ADS)

    Rosotti, Giovanni Pietro

    2015-05-01

    Planets form from gas and dust discs in orbit around young stars. The timescale for planet formation is constrained by the lifetime of these discs. The properties of the formed planetary systems depend thus on the evolution and final dispersal of the discs, which is the main topic of this thesis. Observations reveal the existence of a class of discs called "transitional", which lack dust in their inner regions. They are thought to be the last stage before the complete disc dispersal, and hence they may provide the key to understanding the mechanisms behind disc evolution. X-ray photoevaporation and planet formation have been studied as possible physical mechanisms responsible for the final dispersal of discs. However up to now, these two phenomena have been studied separately, neglecting any possible feedback or interaction. In this thesis we have investigated what is the interplay between these two processes. We show that the presence of a giant planet in a photo-evaporating disc can significantly shorten its lifetime, by cutting the inner regions from the mass reservoir in the exterior of the disc. This mechanism produces transition discs that for a given mass accretion rate have larger holes than in models considering only X-ray photo-evaporation, constituting a possible route to the formation of accreting transition discs with large holes. These discs are found in observations and still constitute a puzzle for the theory. Inclusion of the phenomenon called "thermal sweeping", a violent instability that can destroy a whole disc in as little as 10 4 years, shows that the outer disc left can be very short-lived (depending on the X-ray luminosity of the star), possibly explaining why very few non accreting transition discs are observed. However the mechanism does not seem to be efficient enough to reconcile with observations. In this thesis we also show that X-ray photo-evaporation naturally explains the observed correlation between stellar masses and accretion

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

    PubMed Central

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

    2016-01-01

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

  16. [Pathogenesis of age-related macular degeneration].

    PubMed

    Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

    2009-01-01

    Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells.

  17. [Polish nomenclature of lumbar disc disease].

    PubMed

    Radło, Paweł; Smetkowski, Andrzej; Tesiorowski, Maciej

    2014-01-01

    Lumbar disc herniation is one of the most common damage of musculoskeletal system. The incidence of pain of lumbosacral spine is estimated approximately on 60-90% in general population, whereas the incidence of disc herniation in patients experiencing low back pain is about 91%. Despite the high incidence and uncomplicated pathogenesis of disc disease there is a problem with the nomenclature. In the vast majority of cases, the naming confusion stems from ignorance of the etiology of low back pain. Different terminologies: morphological, topographical, Radiological and Clinical are used interchangeably. In addition, diagnosis is presented in a variety of languages: Polish, English and Latin. Moreover, the medical and traditional language are used alternately. The authors found in Polish literature more, than 20 terms to describe lumbar disc herniation. All of these terms in the meaning of the authors are used to determine one pathology--mechanical damage to the intervertebral disc and moving the disc material beyond the anatomical area.

  18. Close-packing of growing discs

    SciTech Connect

    Bursill, L.A.; Xudong, F. . School of Physics)

    1988-12-01

    Spiral lattices are derived by allowing growing discs to aggregate under a close-packing rule. Both Fibonacci and Lucas numbers of visible spirals arise naturally, dependent only on the choice of growth centre. Both the rate of convergence towards an ideal spiral, and chirality, are determined by the initial placement of the first few discs (initial conditions). Thus the appearance of spiral packings is no more or less mysterious than the appearance of hexagonal packed arrays of equal discs.

  19. Accretion Discs Show Their True Colours

    NASA Astrophysics Data System (ADS)

    2008-07-01

    Quasars are the brilliant cores of remote galaxies, at the hearts of which lie supermassive black holes that can generate enough power to outshine the Sun a trillion times. These mighty power sources are fuelled by interstellar gas, thought to be sucked into the hole from a surrounding 'accretion disc'. A paper in this week's issue of the journal Nature, partly based on observations collected with ESO's Very Large Telescope, verifies a long-standing prediction about the intensely luminous radiation emitted by these accretion discs. Uncovering the disc ESO PR Photo 21/08 Uncovering the inner disc "Astronomers were puzzled by the fact that the best models of these discs couldn't quite be reconciled with some of the observations, in particular, with the fact that these discs did not appear as blue as they should be," explains lead-author Makoto Kishimoto. Such a discrepancy could be the signal that there was something very wrong with the models. With his colleagues, he investigated this discrepancy by studying the polarised light from six quasars. This enabled them to demonstrate that the disc spectrum is as blue as predicted. "The crucial observational difficulty here has been that the disc is surrounded by a much larger torus containing hot dust, whose light partly outshines that of the disc," says Kishimoto. "Because the light coming from the disc is scattered in the disc vicinity and thus polarised, by observing only polarised light from the quasars, one can uncover the buried light from the disc." In a similar way that a fisherman would wear polarised sunglasses to help get rid of the glare from the water surface and allow him to see more clearly under the water, the filter on the telescope allowed the astronomers to see beyond surrounding clouds of dust and gas to the blue colour of the disc in infrared light. The observations were done with the FORS and ISAAC instruments on one of the 8.2-m Unit Telescopes of ESO's Very Large Telescope, located in the Atacama

  20. The quiescent phase of galactic disc growth

    NASA Astrophysics Data System (ADS)

    Aumer, Michael; Binney, James; Schönrich, Ralph

    2016-07-01

    We perform a series of controlled N-body simulations of growing disc galaxies within non-growing, live dark matter haloes of varying mass and concentration. Our initial conditions include either a low-mass disc or a compact bulge. New stellar particles are continuously added on near-circular orbits to the existing disc, so spiral structure is continuously excited. To study the effect of combined spiral and giant molecular cloud (GMC) heating on the discs, we introduce massive, short-lived particles that sample a GMC mass function. An isothermal gas component is introduced for a subset of the models. We perform a resolution study and vary parameters governing the GMC population, the histories of star formation and radial scale growth. Models with GMCs and standard values for the disc mass and halo density provide the right level of self-gravity to explain the age-velocity dispersion relation of the solar neighbourhood (Snhd). GMC heating generates remarkably exponential vertical profiles with scaleheights that are radially constant and agree with observations of galactic thin discs. GMCs are also capable of significantly delaying bar formation. The amount of spiral-induced radial migration agrees with what is required for the metallicity distribution of the Snhd. However, in our standard models, the outward-migrating populations are not hot enough vertically to create thick discs. Thick discs can form in models with high baryon fractions, but the corresponding bars are too long, the young stellar populations too hot and the discs flare considerably.

  1. The cellular and molecular biology of the intervertebral disc: A clinician’s primer

    PubMed Central

    Erwin, W. Mark; Hood, Katherine E.

    2014-01-01

    Clinicians routinely encounter patients suffering from both degenerative and acute spinal pain, often as a consequence of pathology affecting the intervertebral disc (IVD). The IVD is a complex structure essential to spinal function and is subject to degenerative disease and injury. However, due to the complexity of spinal pain syndromes it is often difficult to determine the extent of the IVD’s contribution to the genesis of spinal pain. The location of the IVD is within close proximity to vital neural elements and may in the event of pathological change or injury compromise those structures. It is therefore important that clinicians performing manual therapy understand the cellular and molecular biology of the IVD as well as its clinical manifestation of degeneration/injury in order to safely manage and appreciate the role played by the disc in the development of mechanical spinal pain syndromes. PMID:25202152

  2. The cellular and molecular biology of the intervertebral disc: A clinician's primer.

    PubMed

    Erwin, W Mark; Hood, Katherine E

    2014-09-01

    Clinicians routinely encounter patients suffering from both degenerative and acute spinal pain, often as a consequence of pathology affecting the intervertebral disc (IVD). The IVD is a complex structure essential to spinal function and is subject to degenerative disease and injury. However, due to the complexity of spinal pain syndromes it is often difficult to determine the extent of the IVD's contribution to the genesis of spinal pain. The location of the IVD is within close proximity to vital neural elements and may in the event of pathological change or injury compromise those structures. It is therefore important that clinicians performing manual therapy understand the cellular and molecular biology of the IVD as well as its clinical manifestation of degeneration/injury in order to safely manage and appreciate the role played by the disc in the development of mechanical spinal pain syndromes.

  3. Circumplanetary discs around young giant planets: a comparison between core-accretion and disc instability

    NASA Astrophysics Data System (ADS)

    Szulágyi, J.; Mayer, L.; Quinn, T.

    2017-01-01

    Circumplanetary discs can be found around forming giant planets, regardless of whether core accretion or gravitational instability built the planet. We carried out state-of-the-art hydrodynamical simulations of the circumplanetary discs for both formation scenarios, using as similar initial conditions as possible to unveil possible intrinsic differences in the circumplanetary disc mass and temperature between the two formation mechanisms. We found that the circumplanetary discs' mass linearly scales with the circumstellar disc mass. Therefore, in an equally massive protoplanetary disc, the circumplanetary discs formed in the disc instability model can be only a factor of 8 more massive than their core-accretion counterparts. On the other hand, the bulk circumplanetary disc temperature differs by more than an order of magnitude between the two cases. The subdiscs around planets formed by gravitational instability have a characteristic temperature below 100 K, while the core-accretion circumplanetary discs are hot, with temperatures even greater than 1000 K when embedded in massive, optically thick protoplanetary discs. We explain how this difference can be understood as the natural result of the different formation mechanisms. We argue that the different temperatures should persist up to the point when a full-fledged gas giant forms via disc instability; hence, our result provides a convenient criterion for observations to distinguish between the two main formation scenarios by measuring the bulk temperature in the planet vicinity.

  4. Optic Disc - Fovea Distance, Axial Length and Parapapillary Zones. The Beijing Eye Study 2011

    PubMed Central

    Jonas, Rahul Arvo; Wang, Ya Xing; Yang, Hua; Li, Jian Jun; Xu, Liang; Panda-Jonas, Songhomitra; Jonas, Jost Bruno

    2015-01-01

    Purpose To measure the distance between the optic disc center and the fovea (DFD) and to assess its associations. Methods The population-based cross-sectional Beijing Eye Study 2011 included 3468 individuals aged 50+ years. The DFD was measured on fundus photographs. Results Readable fundus photographs were available for 2836 (81.8%) individuals. Mean DFD was 4.76 ± 0.34mm (median: 4.74 mm; range: 3.76–6.53mm). In multivariate analysis, longer DFD was associated with longer axial length (P<0.001; standardized correlation coefficient beta: 0.62), higher prevalence of axially high myopia (P<0.001; beta:0.06), shallower anterior chamber depth (P<0.001; beta:-0.18), thinner lens thickness (P = 0.004; beta: -0.06), smaller optic disc-fovea angle (P = 0.02; beta: -0.04), larger parapapillary alpha zone (P = 0.008; beta: 0.05), larger parapapillary beta/gamma zone (P<0.001; beta: 0.11), larger optic disc area (P<0.001; beta: 0.08), lower degree of cortical cataract (P = 0.002; beta: -0.08), and lower prevalence of age-related macular degeneration (P = 0.001; beta: -0.06). Bruch´s membrane opening-fovea distance (DFD minus disc radius minus parapapillary beta/gamma zone width) in non-glaucomatous eyes was not significantly (P = 0.60) related with axial length in emmetropic or axially myopic eyes (axial length ≥23.5 mm), while it increased significantly (P<0.001; r: 0.32) with longer axial length in eyes with an axial length of <23.5mm. Ratio of mean DFD to disc diameter was 2.65 ± 0.30. If the ratio of disc-fovea distance to disc diameter was considered constant and if the individual disc diameter was calculated as the individual disc-fovea distance divided by the constant factor of 2.65, the resulting calculated disc diameter differed from the directly measured disc diameter by 0.16 ±0.13 mm (median: 0.13 mm, range: 0.00–0.89 mm) or 8.9 ± 7.3% (median: 7.4%; range: 0.00–70%) of the measured disc diameter. Conclusions DFD (mean: 4.76mm) increases with longer

  5. Total Disc Replacement in Lumbar Degenerative Disc Diseases

    PubMed Central

    2015-01-01

    More than 10 years have passed since lumbar total disc replacement (LTDR) was introduced for the first time to the world market for the surgical management of lumbar degenerative disc disease (DDD). It seems like the right time to sum up the relevant results in order to understand where LTDR stands on now, and is heading forward to. The pathogenesis of DDD has been currently settled, but diagnosis and managements are still controversial. Fusion is recognized as golden standard of surgical managements but has various kinds of shortcomings. Lately, LTDR has been expected to replace fusion surgery. A great deal of LTDR reports has come out. Among them, more than 5-year follow-up prospective randomized controlled studies including USA IDE trials were expected to elucidate whether for LTDR to have therapeutic benefit compared to fusion. The results of these studies revealed that LTDR was not inferior to fusion. Most of clinical studies dealing with LTDR revealed that there was no strong evidence for preventive effect of LTDR against symptomatic degenerative changes of adjacent segment disease. LTDR does not have shortcomings associated with fusion. However, it has a potentiality of the new complications to occur, which surgeons have never experienced in fusion surgeries. Consequently, longer follow-up should be necessary as yet to confirm the maintenance of improved surgical outcome and to observe any very late complications. LTDR still may get a chance to establish itself as a substitute of fusion both nominally and virtually if it eases the concerns listed above. PMID:26713139

  6. Grain charging in protoplanetary discs

    NASA Astrophysics Data System (ADS)

    Ilgner, M.

    2012-02-01

    Context. Recent work identified a growth barrier for dust coagulation that originates in the electric repulsion between colliding particles. Depending on its charge state, dust material may have the potential to control key processes towards planet formation such as magnetohydrodynamic (MHD) turbulence and grain growth, which are coupled in a two-way process. Aims: We quantify the grain charging at different stages of disc evolution and differentiate between two very extreme cases: compact spherical grains and aggregates with fractal dimension Df = 2. Methods: Applying a simple chemical network that accounts for collisional charging of grains, we provide a semi-analytical solution. This allowed us to calculate the equilibrium population of grain charges and the ionisation fraction efficiently. The grain charging was evaluated for different dynamical environments ranging from static to non-stationary disc configurations. Results: The results show that the adsorption/desorption of neutral gas-phase heavy metals, such as magnesium, effects the charging state of grains. The greater the difference between the thermal velocities of the metal and the dominant molecular ion, the greater the change in the mean grain charge. Agglomerates have more negative excess charge on average than compact spherical particles of the same mass. The rise in the mean grain charge is proportional to N1/6 in the ion-dust limit. We find that grain charging in a non-stationary disc environment is expected to lead to similar results. Conclusions: The results indicate that the dust growth and settling in regions where the dust growth is limited by the so-called "electro-static barrier" do not prevent the dust material from remaining the dominant charge carrier.

  7. [Standardized terminology for disc disease].

    PubMed

    Sánchez Pérez, M; Gil Sierra, A; Sánchez Martín, A; Gallego Gómez, P; Pereira Boo, D

    2012-01-01

    This article reviews the terminology used to describe morphological alterations in the intervertebral discs. Radiologists must be able to communicate information about the type, location, and severity of these alterations to medical and surgical clinicians. It is crucial to use simple, standard, and unified terminology to ensure comprehension not only among radiologists but also with professionals from the different specialties for whom the radiology reports are written (fundamentally traumatologists and neurosurgeons). This terminology will help ensure a more accurate diagnosis and better patient management.

  8. Photoreceptor Cells Influence Retinal Vascular Degeneration in Mouse Models of Retinal Degeneration and Diabetes

    PubMed Central

    Liu, Haitao; Tang, Jie; Du, Yunpeng; Saadane, Aicha; Tonade, Deoye; Samuels, Ivy; Veenstra, Alex; Palczewski, Krzysztof; Kern, Timothy S.

    2016-01-01

    Purpose Loss of photoreceptor cells is associated with retinal vascular degeneration in retinitis pigmentosa, whereas the presence of photoreceptor cells is implicated in vascular degeneration in diabetic retinopathy. To investigate how both the absence and presence of photoreceptors could damage the retinal vasculature, we compared two mouse models of photoreceptor degeneration (opsin−/− and RhoP23H/P23H ) and control C57Bl/5J mice, each with and without diabetes. Methods Retinal thickness, superoxide, expression of inflammatory proteins, ERG and optokinetic responses, leukocyte cytotoxicity, and capillary degeneration were evaluated at 1 to 10 months of age using published methods. Results Retinal photoreceptor cells degenerated completely in the opsin mutants by 2 to 4 months of age, and visual function subsided correspondingly. Retinal capillary degeneration was substantial while photoreceptors were still present, but slowed after the photoreceptors degenerated. Diabetes did not further exacerbate capillary degeneration in these models of photoreceptor degeneration, but did cause capillary degeneration in wild-type animals. Photoreceptor cells, however, did not degenerate in wild-type diabetic mice, presumably because the stress responses in these cells were less than in the opsin mutants. Retinal superoxide and leukocyte damage to retinal endothelium contributed to the degeneration of retinal capillaries in diabetes, and leukocyte-mediated damage was increased in both opsin mutants during photoreceptor cell degeneration. Conclusions Photoreceptor cells affect the integrity of the retinal microvasculature. Deterioration of retinal capillaries in opsin mutants was appreciable while photoreceptor cells were present and stressed, but was less after photoreceptors degenerated. This finding proves relevant to diabetes, where persistent stress in photoreceptors likewise contributes to capillary degeneration. PMID:27548901

  9. Regularized degenerate multi-solitons

    NASA Astrophysics Data System (ADS)

    Correa, Francisco; Fring, Andreas

    2016-09-01

    We report complex {P}{T} -symmetric multi-soliton solutions to the Korteweg de-Vries equation that asymptotically contain one-soliton solutions, with each of them possessing the same amount of finite real energy. We demonstrate how these solutions originate from degenerate energy solutions of the Schrödinger equation. Technically this is achieved by the application of Darboux-Crum transformations involving Jordan states with suitable regularizing shifts. Alternatively they may be constructed from a limiting process within the context Hirota's direct method or on a nonlinear superposition obtained from multiple Bäcklund transformations. The proposed procedure is completely generic and also applicable to other types of nonlinear integrable systems.

  10. Degenerate doping of metallic anodes

    DOEpatents

    Friesen, Cody A; Zeller, Robert A; Johnson, Paul B; Switzer, Elise E

    2015-05-12

    Embodiments of the invention relate to an electrochemical cell comprising: (i) a fuel electrode comprising a metal fuel, (ii) a positive electrode, (iii) an ionically conductive medium, and (iv) a dopant; the electrodes being operable in a discharge mode wherein the metal fuel is oxidized at the fuel electrode and the dopant increases the conductivity of the metal fuel oxidation product. In an embodiment, the oxidation product comprises an oxide of the metal fuel which is doped degenerately. In an embodiment, the positive electrode is an air electrode that absorbs gaseous oxygen, wherein during discharge mode, oxygen is reduced at the air electrode. Embodiments of the invention also relate to methods of producing an electrode comprising a metal and a doped metal oxidation product.

  11. Neural reprogramming in retinal degenerations

    PubMed Central

    Marc, Robert E.; Jones, Bryan W.; Anderson, James R.; Kinard, Krista; Marshak, David W.; Wilson, John H.; Wensel, Theodore; Lucas, Robert J.

    2008-01-01

    Purpose Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. We sought to explore the functional expression of ionotropic (iGluR) and group III, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degenerations. Methods Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degenerations and a sample of human RP. Results After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, while amacrine and ganglion cells retain iGluR-mediated responsivity. Paradoxically, amacrine and ganglion cells show spontaneous iGluR signals in vivo even though bipolar cells lack glutamate-coupled depolarization mechanisms. Cone survival can rescue iGluR expression by OFF bipolar cells. In a case of human RP with cone sparing, iGluR signaling appeared intact, but the numbers of bipolar cells expressing functional iGluRs was double that of normal retina. Conclusions RP triggers permanent loss of bipolar cell glutamate receptor expression, though spontaneous iGluR-mediated signaling by amacrine and ganglion cells implies that such truncated bipolar cells still release glutamate in response to some non-glutamatergic depolarization. Focal cone-sparing can preserve iGluR display by nearby bipolar cells, which may facilitate late-RP photoreceptor transplant attempts. An instance of human RP provides evidence that rod bipolar cell dendrite switching likely triggers new gene expression patterns and may impair cone pathway function. PMID:17591910

  12. Exact propagators for some degenerate hyperbolic operators

    NASA Astrophysics Data System (ADS)

    Beals, Richard; Kannai, Yakar

    2006-10-01

    Exact propagators are obtained for the degenerate second order hyperbolic operators ∂2 t - t 2 l Δ x , l=1,2,..., by analytic continuation from the degenerate elliptic operators ∂2 t + t 2 l Δ x . The partial Fourier transforms are also obtained in closed form, leading to integral transform formulas for certain combinations of Bessel functions and modified Bessel functions.

  13. Stellar discs in Aquarius dark matter haloes

    NASA Astrophysics Data System (ADS)

    DeBuhr, Jackson; Ma, Chung-Pei; White, Simon D. M.

    2012-10-01

    We investigate the gravitational interactions between live stellar discs and their dark matter haloes, using Λ cold dark matter haloes similar in mass to that of the Milky Way taken from the Aquarius Project. We introduce the stellar discs by first allowing the haloes to respond to the influence of a growing rigid disc potential from z = 1.3 to 1.0. The rigid potential is then replaced with star particles which evolve self-consistently with the dark matter particles until z = 0.0. Regardless of the initial orientation of the disc, the inner parts of the haloes contract and change from prolate to oblate as the disc grows to its full size. When the disc's normal is initially aligned with the major axis of the halo at z = 1.3, the length of the major axis contracts and becomes the minor axis by z = 1.0. Six out of the eight discs in our main set of simulations form bars, and five of the six bars experience a buckling instability that results in a sudden jump in the vertical stellar velocity dispersion and an accompanying drop in the m = 2 Fourier amplitude of the disc surface density. The bars are not destroyed by the buckling but continue to grow until the present day. Bars are largely absent when the disc mass is reduced by a factor of 2 or more; the relative disc-to-halo mass is therefore a primary factor in bar formation and evolution. A subset of the discs is warped at the outskirts and contains prominent non-coplanar material with a ring-like structure. Many discs reorient by large angles between z = 1 and 0, following a coherent reorientation of their inner haloes. Larger reorientations produce more strongly warped discs, suggesting a tight link between the two phenomena. The origins of bars and warps appear independent: some discs with strong bars show little disturbances at the outskirts, while the discs with the weakest bars show severe warps.

  14. Adipose-Derived Stromal Cells Protect Intervertebral Disc Cells in Compression: Implications for Stem Cell Regenerative Disc Therapy

    PubMed Central

    Sun, Zhen; Luo, Beier; Liu, Zhi-Heng; Samartzis, Dino; Liu, Zhongyang; Gao, Bo; Huang, Liangliang; Luo, Zhuo-Jing

    2015-01-01

    Introduction: Abnormal biomechanics plays a role in intervertebral disc degeneration. Adipose-derived stromal cells (ADSCs) have been implicated in disc integrity; however, their role in the setting of mechanical stimuli upon the disc's nucleus pulposus (NP) remains unknown. As such, the present study aimed to evaluate the influence of ADSCs upon NP cells in compressive load culture. Methods: Human NP cells were cultured in compressive load at 3.0MPa for 48 hours with or without ADSCs co-culture (the ratio was 50:50). We used flow cytometry, live/dead staining and scanning electron microscopy (SEM) to evaluate cell death, and determined the expression of specific apoptotic pathways by characterizing the expression of activated caspases-3, -8 and -9. We further used real-time (RT-) PCR and immunostaining to determine the expression of the extracellular matrix (ECM), mediators of matrix degradation (e.g. MMPs, TIMPs and ADAMTSs), pro-inflammatory factors and NP cell phenotype markers. Results: ADSCs inhibited human NP cell apoptosis via suppression of activated caspase-9 and caspase-3. Furthermore, ADSCs protected NP cells from the degradative effects of compressive load by significantly up-regulating the expression of ECM genes (SOX9, COL2A1 and ACAN), tissue inhibitors of metalloproteinases (TIMPs) genes (TIMP-1 and TIMP-2) and cytokeratin 8 (CK8) protein expression. Alternatively, ADSCs showed protective effect by inhibiting compressive load mediated increase of matrix metalloproteinases (MMPs; MMP-3 and MMP-13), disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs; ADAMTS-1 and 5), and pro-inflammatory factors (IL-1beta, IL-6, TGF-beta1 and TNF-alpha). Conclusions: Our study is the first in vitro study assessing the impact of ADSCs on NP cells in an un-physiological mechanical stimulation culture environment. Our study noted that ADSCs protect compressive load induced NP cell death and degradation by inhibition of activated caspase-9 and -3

  15. Use NASA GES DISC Data in ArcGIS

    NASA Technical Reports Server (NTRS)

    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.

  16. Form and function of the intervertebral disc in health and disease: a morphological and stain comparison study.

    PubMed

    Walter, B A; Torre, O M; Laudier, D; Naidich, T P; Hecht, A C; Iatridis, J C

    2015-12-01

    Multiple histologic measurements are commonly used to assess degenerative changes in intervertebral disc (IVD) structure; however, there is no consensus on which stains offer the clearest visualization of specific areas within the IVD. The objective of this study was to compare multiple tinctorial stains, evaluate their ability to highlight structural features within the IVD, and investigate how they influence the capacity to implement a degeneration scoring system. Lumbar IVDs from seven human autopsy specimens were stained using six commonly used stains (Hematoxylin/Eosin, Toluidine Blue, Safranin-O/Fast Green, Extended FAST, modified Gomori's Trichrome, and Picrosirius Red Alcian Blue). All IVDs were evaluated by three separate graders to independently determine which stains (i) were most effective at discerning different structural features within different regions of the IVDs and (ii) allowed for the most reproducible assessment of degeneration grade, as assessed via the Rutges histological scoring system (Rutges et al. A validated new histological classification for intervertebral disc degeneration. Osteoarthritis Cartilage, 21, 2039-47). Although Trichrome, XFAST and PR/AB stains were all effective at highlighting different regions of whole IVDs, we recommend the use of PR/AB because it had the highest degree of rater agreement on assigned degeneration grade, allowed greater resolution of degeneration grade, has an inferential relationship between color and composition, and allowed clear differentiation of the different regions and structural disruptions within the IVD. The use of a standard set of stains together with a histological grading scheme can aid in the characterization of structural changes in different regions of the IVD and may simplify comparisons across the field. This collection of human IVD histological images highlights how IVD degeneration is not a single disease but a composite of multiple processes such as aging, injury, repair, and

  17. Cervical and lumbar pain and radiological degeneration among fighter pilots: a systematic review and meta-analysis.

    PubMed

    Shiri, Rahman; Frilander, Heikki; Sainio, Markku; Karvala, Kirsi; Sovelius, Roope; Vehmas, Tapio; Viikari-Juntura, Eira

    2015-02-01

    To assess the associations of acceleration force indicators (aircraft type and flight hours) with cervical and lumbar pain and radiological degeneration among fighter pilots. The PubMed, Embase, Scopus and Web of Science databases were searched until October 2013. Twenty-seven studies were included in the review and 20 in the meta-analysis. There were no differences in the prevalence of neck pain (pooled OR=1.07, 95% CI 0.87 to 1.33), cervical disc degeneration (OR=1.26, CI 0.81 to 1.96), low back pain (OR=0.80, CI 0.47 to 1.38) or lumbar disc degeneration (OR=0.87, CI 0.67 to 1.13) between fighter pilots and helicopter or transport/cargo pilots. Moreover, the prevalence of cervical (OR=1.14, CI 0.61 to 2.16) or lumbar (OR=1.05, CI 0.49 to 2.26) disc degeneration did not differ between fighter pilots and non-flying personnel. Most studies did not control their estimates for age and other potential confounders. Among high-performance aircraft pilots, exposure to the highest G-forces was associated with a higher prevalence of neck pain compared with exposure to lower G-forces (pooled OR=3.12, CI 2.08 to 4.67). The studies on the association between flight hours and neck pain reported inconsistent findings. Moreover, looking back over the shoulder (check six) was the most common posture associated with neck pain. Fighter pilots exposed to high G-forces may be at a greater risk for neck pain than those exposed to low G-forces. This finding should be confirmed with better control for confounding. Awkward neck posture may be an important factor in neck pain among fighter pilots.

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

    PubMed Central

    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. PMID:26617738

  19. Tissue engineering strategies to study cartilage development, degeneration and regeneration.

    PubMed

    Bhattacharjee, Maumita; Coburn, Jeannine; Centola, Matteo; Murab, Sumit; Barbero, Andrea; Kaplan, David L; Martin, Ivan; Ghosh, Sourabh

    2015-04-01

    Cartilage tissue engineering has primarily focused on the generation of grafts to repair cartilage defects due to traumatic injury and disease. However engineered cartilage tissues have also a strong scientific value as advanced 3D culture models. Here we first describe key aspects of embryonic chondrogenesis and possible cell sources/culture systems for in vitro cartilage generation. We then review how a tissue engineering approach has been and could be further exploited to investigate different aspects of cartilage development and degeneration. The generated knowledge is expected to inform new cartilage regeneration strategies, beyond a classical tissue engineering paradigm.

  20. Biomarkers to identify the pathological basis for frontotemporal lobar degeneration.

    PubMed

    Grossman, Murray

    2011-11-01

    Recent findings assessing the utility of biomarkers are reviewed that help identify the basis for disease in patients with frontotemporal lobar degeneration (FTLD) spectrum pathology. Biofluid studies identify about 15% of patients with FTLD due to a genetic mutation that is associated with the specific histopathologic features of TDP-43 or a tauopathy. Other genetically based risk factors and targeted proteomic searches of plasma and cerebrospinal fluid have suggested additional markers that may be useful in sporadic cases of FTLD. While progress has been made in developing biomarkers for FTLD, additional work is needed to extend these advances so that the histopathologic abnormality causing FTLD can be specified in an individual patient.

  1. Imaging geographic atrophy in age-related macular degeneration.

    PubMed

    Göbel, Arno P; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Brinkmann, Christian K; Holz, Frank G

    2011-01-01

    Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized.

  2. Structure formation through self-gravitational instability in degenerate and non-degenerate anisotropic magnetized plasma

    NASA Astrophysics Data System (ADS)

    Sharma, Prerana

    2017-04-01

    The self-gravitational instability is examined for non-degenerate and degenerate magnetized plasma. In the case of non-degenerate collisionless magnetized plasma the pressure is considered as anisotropic while in the case of degenerate situations it is taken as isotropic. The effect of finite Larmor radius correction of non-degenerate ions and viscous dissipation is taken into account in both the cases. Firstly in non-degenerate anisotropic plasma the conventional magnetohydrodynamic model is used to construct basic set of equations within the framework of modified Chew-Goldberger and Low theory. Secondly, in the case of degenerate isotropic plasma, which is considered to be composed of degenerate electrons and non-degenerate ions, the model equations are constructed using quantum magneto hydrodynamic model. The dynamics of degenerate particles are governed by Bohm and exchange potentials. The general dispersion relations are derived for both degenerate and non-degenerate situations separately using linearized perturbation equations. The results are discussed analytically and numerically for various modes of propagation. In case of non degenerate strongly magnetized plasma the effects of stress tensor anisotropy dominate over the influence of FLR effects while the FLR effects prevail in the weak magnetic field region. In case of isotropic degenerate plasma the implications of exchange parameter on the Jeans mass have been estimated and it is found that the increase in exchange parameter increases the limit of Jeans mass. The Jeans length and Jeans mass have been estimated for the white dwarf stars as LJ ≈ 2.1 × 10^{11} m and MJ ≈ 5 × 10^{39} kg respectively assist the existence of super Chandrasekhar white dwarfs.

  3. Spiral Waves in Accretion Discs - Theory

    NASA Astrophysics Data System (ADS)

    Boffin, H. M. J.

    Spirals shocks have been widely studied in the context of galactic dynamics and protostellar discs. They may however also play an important role in some classes of close binary stars, and more particularly in cataclysmic variables. In this paper, we review the physics of spirals waves in accretion discs, present the results of numerical simulations and consider whether theory can be reconcilied with observations.

  4. Circular plate capacitor with different discs

    NASA Astrophysics Data System (ADS)

    Paffuti, Giampiero; Cataldo, Enrico; Di Lieto, Alberto; Maccarrone, Francesco

    2016-10-01

    In this paper, we write a system of integral equations for a capacitor composed of two discs of different radii, generalizing Love's equation for equal discs. We compute the complete asymptotic form of the capacitance matrix for both large and small distances obtaining a generalization of Kirchhoff's formula for the latter case.

  5. 46 CFR 64.61 - Rupture disc.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Rupture disc. 64.61 Section 64.61 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Pressure Relief Devices and Vacuum Relief Devices for MPTs § 64.61 Rupture disc. If a rupture...

  6. 46 CFR 64.61 - Rupture disc.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Rupture disc. 64.61 Section 64.61 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Pressure Relief Devices and Vacuum Relief Devices for MPTs § 64.61 Rupture disc. If a rupture...

  7. 46 CFR 64.61 - Rupture disc.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Rupture disc. 64.61 Section 64.61 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Pressure Relief Devices and Vacuum Relief Devices for MPTs § 64.61 Rupture disc. If a rupture...

  8. 46 CFR 64.61 - Rupture disc.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Rupture disc. 64.61 Section 64.61 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Pressure Relief Devices and Vacuum Relief Devices for MPTs § 64.61 Rupture disc. If a rupture...

  9. 46 CFR 64.61 - Rupture disc.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Rupture disc. 64.61 Section 64.61 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Pressure Relief Devices and Vacuum Relief Devices for MPTs § 64.61 Rupture disc. If a rupture...

  10. The inner cavity of the circumnuclear disc

    NASA Astrophysics Data System (ADS)

    Blank, M.; Morris, M. R.; Frank, A.; Carroll-Nellenback, J. J.; Duschl, W. J.

    2016-06-01

    The circumnuclear disc (CND) orbiting the Galaxy's central black hole is a reservoir of material that can ultimately provide energy through accretion, or form stars in the presence of the black hole, as evidenced by the stellar cluster that is presently located at the CND's centre. In this paper, we report the results of a computational study of the dynamics of the CND. The results lead us to question two paradigms that are prevalent in previous research on the Galactic Centre. The first is that the disc's inner cavity is maintained by the interaction of the central stellar cluster's strong winds with the disc's inner rim, and secondly, that the presence of unstable clumps in the disc implies that the CND is a transient feature. Our simulations show that, in the absence of a magnetic field, the interaction of the wind with the inner disc rim actually leads to a filling of the inner cavity within a few orbital time-scales, contrary to previous expectations. However, including the effects of magnetic fields stabilizes the inner disc rim against rapid inward migration. Furthermore, this interaction causes instabilities that continuously create clumps that are individually unstable against tidal shearing. Thus the occurrence of such unstable clumps does not necessarily mean that the disc is itself a transient phenomenon. The next steps in this investigation are to explore the effect of the magnetorotational instability on the disc evolution and to test whether the results presented here persist for longer time-scales than those considered here.

  11. Rapid radiative clearing of protoplanetary discs

    NASA Astrophysics Data System (ADS)

    Haworth, Thomas J.; Clarke, Cathie J.; Owen, James E.

    2016-04-01

    The lack of observed transition discs with inner gas holes of radii greater than ˜50 au implies that protoplanetary discs dispersed from the inside out must remove gas from the outer regions rapidly. We investigate the role of photoevaporation in the final clearing of gas from low mass discs with inner holes. In particular, we study the so-called `thermal sweeping' mechanism which results in rapid clearing of the disc. Thermal sweeping was originally thought to arise when the radial and vertical pressure scalelengths at the X-ray heated inner edge of the disc match. We demonstrate that this criterion is not fundamental. Rather, thermal sweeping occurs when the pressure maximum at the inner edge of the dust heated disc falls below the maximum possible pressure of X-ray heated gas (which depends on the local X-ray flux). We derive new critical peak volume and surface density estimates for rapid radiative clearing which, in general, result in rapid dispersal happening less readily than in previous estimates. This less efficient clearing of discs by X-ray driven thermal sweeping leaves open the issue of what mechanism (e.g. far-ultraviolet heating) can clear gas from the outer disc sufficiently quickly to explain the non-detection of cold gas around weak line T Tauri stars.

  12. Age related macular degeneration and visual disability.

    PubMed

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

  13. About detection of precessing circumpulsar discs

    NASA Astrophysics Data System (ADS)

    Grimani, Catia

    2016-08-01

    Detections of circumpulsar discs and planetary systems through electromagnetic observations appear quite rare. In the case of PSR 1931+24 and B0656+14, the hypothesis of a precessing disc penetrating the pulsar light cylinder is found consistent with radio and gamma observations from these stars. Disc self-occultation and precession may affect electromagnetic measurements. We investigate here under which conditions gravitational waves generated by circumpulsar disc precession may be detected by the proposed second-generation space interferometers DECI-hertz Interferometer Gravitational Wave Observatory and Big Bang Observer. The characteristics of circumpulsar detectable precessing discs are estimated as a function of distance from the Solar system. Speculations on detection rates are presented.

  14. Lumbar Epidural Varix Mimicking Disc Herniation

    PubMed Central

    Bursalı, Adem; Guvenal, Ahmet Burak; Yaman, Onur

    2016-01-01

    Lumbar radiculopathy is generally caused by such well-recognized entity as lumbar disc herniation in neurosurgical practice; however rare pathologies such as thrombosed epidural varix may mimic them by causing radicular symptoms. In this case report, we present a 26-year-old man with the complaint of back and right leg pain who was operated for right L4–5 disc herniation. The lesion interpreted as an extruded disc herniation preoperatively was found to be a thrombosed epidural varix compressing the nerve root preoperatively. The nerve root was decompressed by shrinking the lesion with bipolar thermocoagulation and excision. The patient's complaints disappeared in the postoperative period. Thrombosed lumbar epidural varices may mimic lumbar disc herniations both radiologically and clinically. Therefore, must be kept in mind in the differential diagnosis of lumbar disc herniations. Microsurgical techniques are mandatory for the treatment of these pathologies and decompression with thermocoagulation and excision is an efficient method. PMID:27446525

  15. Strongly magnetized accretion discs require poloidal flux

    NASA Astrophysics Data System (ADS)

    Salvesen, Greg; Armitage, Philip J.; Simon, Jacob B.; Begelman, Mitchell C.

    2016-08-01

    Motivated by indirect observational evidence for strongly magnetized accretion discs around black holes, and the novel theoretical properties of such solutions, we investigate how a strong magnetization state can develop and persist. To this end, we perform local simulations of accretion discs with an initially purely toroidal magnetic field of equipartition strength. We demonstrate that discs with zero net vertical magnetic flux and realistic boundary conditions cannot sustain a strong toroidal field. However, a magnetic pressure-dominated disc can form from an initial configuration with a sufficient amount of net vertical flux and realistic boundary conditions. Our results suggest that poloidal flux is a necessary prerequisite for the sustainability of strongly magnetized accretion discs.

  16. Roentgenographic measurement of lumbar intervertebral disc height.

    PubMed

    Andersson, G B; Schultz, A; Nathan, A; Irstam, L

    1981-01-01

    The influences of differences in both intervertebral motion segment orientations and in reader judgments on measurements of the apparent intervertebral disc heights in lateral roentgenographs of the lumbar spine were examined. Forty-nine roentgenographs were obtained of nine discs that were titled laterally up to +/- 10 degrees, and rotated longitudinally up to +/- 20 degrees. Three orthopaedic surgeons and three radiologists measured disc heights from five of these roentgenographs, all using the same measurement method. The differences in apparent height that resulted from the orientation changes and differences in judgments among the six readers were considerable, usually of the order of one half of the nominal disc height. The results show that, while roentgenographic measurements can be used to estimate disc height, accurate measurements cannot readily be made from routine roentgenographs, and the interpretation should always be cautious.

  17. Link protein N-terminal peptide binds to bone morphogenetic protein (BMP) type II receptor and drives matrix protein expression in rabbit intervertebral disc cells.

    PubMed

    Wang, Zili; Weitzmann, M Neale; Sangadala, Sreedhara; Hutton, William C; Yoon, S Tim

    2013-09-27

    Intervertebral disc (IVD) degeneration and associated spinal disorders are leading sources of morbidity, and they can be responsible for chronic low back pain. Treatments for degenerative disc diseases continue to be a challenge. Intensive research is now focusing on promoting regeneration of degenerated discs by stimulating production of the disc matrix. Link protein N-terminal peptide (LPP) is a proteolytic fragment of link protein, an important cross-linker and stabilizer of the major structural components of cartilage, aggrecan and hyaluronan. In this study we investigated LPP action in rabbit primary intervertebral disc cells cultured ex vivo in a three-dimensional alginate matrix. Our data reveal that LPP promotes disc matrix production, which was evidenced by increased expression of the chondrocyte-specific transcription factor SOX9 and the extracellular matrix macromolecules aggrecan and collagen II. Using colocalization and pulldown studies we further document a noggin-insensitive direct peptide-protein association between LPP and BMP-RII. This association mediated Smad signaling that converges on BMP genes leading to expression of BMP-4 and BMP-7. Furthermore, through a cell-autonomous loop BMP-4 and BMP-7 intensified Smad1/5 signaling though a feedforward circuit involving BMP-RI, ultimately promoting expression of SOX9 and downstream aggrecan and collagen II genes. Our data define a complex regulatory signaling cascade initiated by LPP and suggest that LPP may be a useful therapeutic substitute for direct BMP administration to treat IVD degeneration and to ameliorate IVD-associated chronic low back pain.

  18. Link Protein N-terminal Peptide Binds to Bone Morphogenetic Protein (BMP) Type II Receptor and Drives Matrix Protein Expression in Rabbit Intervertebral Disc Cells*

    PubMed Central

    Wang, Zili; Weitzmann, M. Neale; Sangadala, Sreedhara; Hutton, William C.; Yoon, S. Tim

    2013-01-01

    Intervertebral disc (IVD) degeneration and associated spinal disorders are leading sources of morbidity, and they can be responsible for chronic low back pain. Treatments for degenerative disc diseases continue to be a challenge. Intensive research is now focusing on promoting regeneration of degenerated discs by stimulating production of the disc matrix. Link protein N-terminal peptide (LPP) is a proteolytic fragment of link protein, an important cross-linker and stabilizer of the major structural components of cartilage, aggrecan and hyaluronan. In this study we investigated LPP action in rabbit primary intervertebral disc cells cultured ex vivo in a three-dimensional alginate matrix. Our data reveal that LPP promotes disc matrix production, which was evidenced by increased expression of the chondrocyte-specific transcription factor SOX9 and the extracellular matrix macromolecules aggrecan and collagen II. Using colocalization and pulldown studies we further document a noggin-insensitive direct peptide-protein association between LPP and BMP-RII. This association mediated Smad signaling that converges on BMP genes leading to expression of BMP-4 and BMP-7. Furthermore, through a cell-autonomous loop BMP-4 and BMP-7 intensified Smad1/5 signaling though a feedforward circuit involving BMP-RI, ultimately promoting expression of SOX9 and downstream aggrecan and collagen II genes. Our data define a complex regulatory signaling cascade initiated by LPP and suggest that LPP may be a useful therapeutic substitute for direct BMP administration to treat IVD degeneration and to ameliorate IVD-associated chronic low back pain. PMID:23940040

  19. Interactive Visualization of a Thin Disc around a Schwarzschild Black Hole

    ERIC Educational Resources Information Center

    Muller, Thomas; Frauendiener, Jorg

    2012-01-01

    In a first course in general relativity, the Schwarzschild spacetime is the most discussed analytic solution to Einstein's field equations. Unfortunately, there is rarely enough time to study the optical consequences of the bending of light for some advanced examples. In this paper, we present how the visual appearance of a thin disc around a…

  20. The role of thermodynamics in disc fragmentation

    NASA Astrophysics Data System (ADS)

    Stamatellos, Dimitris; Whitworth, Anthony P.

    2009-12-01

    Thermodynamics play an important role in determining the way a protostellar disc fragments to form planets, brown dwarfs and low-mass stars. We explore the effect that different treatments of radiative transfer have in simulations of fragmenting discs. Three prescriptions for the radiative transfer are used: (i) the diffusion approximation of Stamatellos et al.; (ii) the barotropic equation of state (EOS) of Goodwin et al. and (iii) the barotropic EOS of Bate et al. The barotropic approximations capture the general evolution of the density and temperature at the centre of each proto-fragment but (i) they do not make any adjustments for particular circumstances of a proto-fragment forming in the disc and (ii) they do not take into account thermal inertia effects that are important for fast-forming proto-fragments in the outer disc region. As a result, the number of fragments formed in the disc and their properties are different, when a barotropic EOS is used. This is important not only for disc studies but also for simulations of collapsing turbulent clouds, as in many cases in such simulations stars form with discs that subsequently fragment. We also examine the difference in the way proto-fragments condense out in the disc at different distances from the central star using the diffusion approximation and following the collapse of each proto-fragment until the formation of the second core (ρ ~= 10-3gcm-3). We find that proto-fragments forming closer to the central star tend to form earlier and evolve faster from the first to the second core than proto-fragments forming in the outer disc region. The former have a large pool of material in the inner disc region that they can accrete from and grow in mass. The latter accrete more slowly and they are hotter because they generally form in a quick abrupt event.

  1. Molecular mechanisms of retinal ganglion cell degeneration in glaucoma and future prospects for cell body and axonal protection

    PubMed Central

    Munemasa, Yasunari; Kitaoka, Yasushi

    2013-01-01

    Glaucoma, which affects more than 70 million people worldwide, is a heterogeneous group of disorders with a resultant common denominator; optic neuropathy, eventually leading to irreversible blindness. The clinical manifestations of primary open-angle glaucoma (POAG), the most common subtype of glaucoma, include excavation of the optic disc and progressive loss of visual field. Axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies are observed in glaucoma, in which the reduction of intraocular pressure (IOP) is known to slow progression of the disease. A pattern of localized retinal nerve fiber layer (RNFL) defects in glaucoma patients indicates that axonal degeneration may precede RGC body death in this condition. The mechanisms of degeneration of neuronal cell bodies and their axons may differ. In this review, we addressed the molecular mechanisms of cell body death and axonal degeneration in glaucoma and proposed axonal protection in addition to cell body protection. The concept of axonal protection may become a new therapeutic strategy to prevent further axonal degeneration or revive dying axons in patients with preperimetric glaucoma. Further study will be needed to clarify whether the combination therapy of axonal protection and cell body protection will have greater protective effects in early or progressive glaucomatous optic neuropathy (GON). PMID:23316132

  2. A multi-component fiber-reinforced PHEMA-based hydrogel/HAPEX™ device for customized intervertebral disc prosthesis.

    PubMed

    Gloria, Antonio; De Santis, Roberto; Ambrosio, Luigi; Causa, Filippo; Tanner, K Elizabeth

    2011-05-01

    Spinal disease due to intervertebral disc degeneration represents a serious medical problem which affects many people worldwide. Disc arthroplasty may be considered the future ''gold standard'' of back pain treatment, even if problems related to available disc prostheses are considered. Hence, the aim of the present study was to improve the artificial disc technology by proposing the engineering of a pilot-scale device production process for a total multi-component intervertebral disc prosthesis. The device is made up of a poly(2-hydroxyethyl methacrylate)/poly(methyl methacrylate) (PHEMA/PMMA) (80/20 w/w) semi-interpenetrating polymer network (s-IPN) composite hydrogel reinforced with poly(ethylene terephthalate) (PET) fibers as annulus/nucleus substitute, and two hydroxyapatite-reinforced polyethylene composite (HAPEX™) endplates in order to anchor the multi-component device to the vertebral bodies. Static and dynamic-mechanical characterization show appropriate mechanical behavior. An example of engineering of a suitable pilot-scale device production process is also proposed in order to manufacture custom made implants.

  3. Modified gravitational instability of degenerate and non-degenerate dusty plasma

    NASA Astrophysics Data System (ADS)

    Jain, Shweta; Sharma, Prerana

    2016-09-01

    The gravitational instability of strongly coupled dusty plasma (SCDP) is studied considering degenerate and non-degenerate dusty plasma situations. The SCDP system is assumed to be composed of the electrons, ions, neutrals, and strongly coupled dust grains. First, in the high density regime, due to small interparticle distance, the electrons are considered degenerate, whereas the neutrals, dust grains, and ions are treated non-degenerate. In this case, the dynamics of inertialess electrons are managed by Fermi pressure and Bohm potential, while the inertialess ions are by only thermal pressure. Second, in the non-degenerate regime, both the electrons and ions are governed by the thermal pressure. The generalized hydrodynamic model and the normal mode analysis technique are employed to examine the low frequency waves and gravitational instability in both degenerate and non-degenerate cases. The general dispersion relation is discussed for a characteristic timescale which provides two regimes of frequency, i.e., hydrodynamic regime and kinetic regime. Analytical solutions reveal that the collisions reduce the growth rate and have a strong impact on structure formation in both degenerate and non-degenerate circumstances. Numerical estimation on the basis of observed parameters for the degenerate and non-degenerate cases is presented to show the effects of dust-neutral collisions and dust effective velocity in the presence of polarization force. The values of Jeans length and Jeans mass have been estimated for degenerate white dwarfs as Jeans length L J = 1.3 × 10 5 cm and Jeans mass M J = 0.75 × 10 - 3 M⊙ and for non-degenerate laboratory plasma Jeans length L J = 6.86 × 10 16 cm and Jeans mass M J = 0.68 × 10 10 M⊙. The stability of the SCDP system is discussed using the Routh-Hurwitz criterion.

  4. Total absorption by degenerate critical coupling

    SciTech Connect

    Piper, Jessica R. Liu, Victor; Fan, Shanhui

    2014-06-23

    We consider a mirror-symmetric resonator with two ports. We show that, when excited from a single port, complete absorption can be achieved through critical coupling to degenerate resonances with opposite symmetry. Moreover, any time two resonances with opposite symmetry are degenerate in frequency and absorption is always significantly enhanced. In contrast, when two resonances with the same symmetry are nearly degenerate, there is no absorption enhancement. We numerically demonstrate these effects using a graphene monolayer on top of a photonic crystal slab, illuminated from a single side in the near-infrared.

  5. Very Degenerate Higgsino Dark Matter

    NASA Astrophysics Data System (ADS)

    Chun, Eung Jin; Jung, Sunghoon; Park, Jong-Chul

    2017-01-01

    We present a study of the Very Degenerate Higgsino Dark Matter (DM), whose mass splitting between the lightest neutral and charged components is O(1) MeV, much smaller than radiative splitting of 355 MeV. The scenario is realized in the minimal supersymmetric standard model by small gaugino mixings. In contrast to the pure Higgsino DM with the radiative splitting only, various observable signatures with distinct features are induced. First of all, the very small mass splitting makes (a) sizable Sommerfeld enhancement and Ramsauer-Townsend (RT) suppression relevant to ˜1 TeV Higgsino DM, and (b) Sommerfeld-Ramsauer-Townsend effect saturate at lower velocities v/c ≲ 10-3. As a result, annihilation signals can be large enough to be observed from the galactic center and/or dwarf galaxies, while the relative signal sizes can vary depending on the locations of Sommerfeld peaks and RT dips. In addition, at collider experiments, stable chargino signatures can be searched for to probe the model in the future. DM direct detection signals, however, depend on the Wino mass; even no detectable signals can be induced if the Wino is heavier than about 10 TeV.

  6. Lumbar herniated disc: spontaneous regression

    PubMed Central

    Yüksel, Kasım Zafer

    2017-01-01

    Background Low back pain is a frequent condition that results in substantial disability and causes admission of patients to neurosurgery clinics. To evaluate and present the therapeutic outcomes in lumbar disc hernia (LDH) patients treated by means of a conservative approach, consisting of bed rest and medical therapy. Methods This retrospective cohort was carried out in the neurosurgery departments of hospitals in Kahramanmaraş city and 23 patients diagnosed with LDH at the levels of L3−L4, L4−L5 or L5−S1 were enrolled. Results The average age was 38.4 ± 8.0 and the chief complaint was low back pain and sciatica radiating to one or both lower extremities. Conservative treatment was administered. Neurological examination findings, durations of treatment and intervals until symptomatic recovery were recorded. Laségue tests and neurosensory examination revealed that mild neurological deficits existed in 16 of our patients. Previously, 5 patients had received physiotherapy and 7 patients had been on medical treatment. The number of patients with LDH at the level of L3−L4, L4−L5, and L5−S1 were 1, 13, and 9, respectively. All patients reported that they had benefit from medical treatment and bed rest, and radiologic improvement was observed simultaneously on MRI scans. The average duration until symptomatic recovery and/or regression of LDH symptoms was 13.6 ± 5.4 months (range: 5−22). Conclusions It should be kept in mind that lumbar disc hernias could regress with medical treatment and rest without surgery, and there should be an awareness that these patients could recover radiologically. This condition must be taken into account during decision making for surgical intervention in LDH patients devoid of indications for emergent surgery. PMID:28119770

  7. Zonal flow evolution and overstability in accretion discs

    NASA Astrophysics Data System (ADS)

    Vanon, R.; Ogilvie, G. I.

    2017-04-01

    This work presents a linear analytical calculation on the stability and evolution of a compressible, viscous self-gravitating (SG) Keplerian disc with both horizontal thermal diffusion and a constant cooling time-scale when an axisymmetric structure is present and freely evolving. The calculation makes use of the shearing sheet model and is carried out for a range of cooling times. Although the solutions to the inviscid problem with no cooling or diffusion are well known, it is non-trivial to predict the effect caused by the introduction of cooling and of small diffusivities; this work focuses on perturbations of intermediate wavelengths, therefore representing an extension to the classical stability analysis on thermal and viscous instabilities. For density wave modes, the analysis can be simplified by means of a regular perturbation analysis; considering both shear and thermal diffusivities, the system is found to be overstable for intermediate and long wavelengths for values of the Toomre parameter Q ≲ 2; a non-SG instability is also detected for wavelengths ≳18H, where H is the disc scale-height, as long as γ ≲ 1.305. The regular perturbation analysis does not, however, hold for the entropy and potential vorticity slow modes as their ideal growth rates are degenerate. To understand their evolution, equations for the axisymmetric structure's amplitudes in these two quantities are analytically derived and their instability regions obtained. The instability appears boosted by increasing the value of the adiabatic index and of the Prandtl number, while it is quenched by efficient cooling.

  8. Autologous adipose stem cells and polylactide discs in the replacement of the rabbit temporomandibular joint disc

    PubMed Central

    Ahtiainen, Katja; Mauno, Jari; Ellä, Ville; Hagström, Jaana; Lindqvist, Christian; Miettinen, Susanna; Ylikomi, Timo; Kellomäki, Minna; Seppänen, Riitta

    2013-01-01

    The temporomandibular joint (TMJ) disc lacks functional replacement after discectomy. We investigated tissue-engineered bilayer polylactide (PLA) discs and autologous adipose stem cells (ASCs) as a potential replacement for the TMJ disc. These ASC discs were pre-cultured either in control or in differentiation medium, including transforming growth factor (TGF)-β1 for one week. Prior to implantation, expression of fibrocartilaginous genes was measured by qRT-PCR. The control and differentiated ASC discs were implanted, respectively, in the right and left TMJs of rabbits for six (n = 5) and 12 months (n = 5). Thereafter, the excised TMJ areas were examined with cone beam computed tomography (CBCT) and histology. No signs of infection, inflammation or foreign body reactions were detected at histology, whereas chronic arthrosis and considerable condylar hypertrophy were observed in all operated joints at CBCT. The left condyle treated with the differentiated ASC discs appeared consistently smoother and more sclerotic than the right condyle. The ASC disc replacement resulted in dislocation and morphological changes in the rabbit TMJ. The ASC discs pre-treated with TGF-β1 enhanced the condylar integrity. While adverse tissue reactions were not shown, the authors suggest that with improved attachment and design, the PLA disc and biomaterial itself would hold potential for TMJ disc replacement. PMID:23720535

  9. Spontaneous Regression of Herniated Lumbar Disc with New Disc Protrusion in the Adjacent Level

    PubMed Central

    Gürcan, Serkan

    2016-01-01

    Spontaneous regression of herniated lumbar discs was reported occasionally. The mechanisms proposed for regression of disc herniation are still incomplete. This paper describes and discusses a case of spontaneous regression of herniated lumbar discs with a new disc protrusion in the adjacent level. A 41-year-old man was admitted with radiating pain and numbness in the left lower extremity with a left posterolateral disc extrusion at L5-S1 level. He was admitted to hospital with low back pain due to disc herniation caudally immigrating at L4-5 level three years ago. He refused the surgical intervention that was offered and was treated conservatively at that time. He had no neurological deficit and a history of spontaneous regression of the extruded lumbar disc; so, a conservative therapy, including bed rest, physical therapy, nonsteroidal anti-inflammatory drugs, and analgesics, was advised. In conclusion, herniated lumbar disc fragments may regress spontaneously. Reports are prone to advise conservative treatment for extruded or sequestrated lumbar disc herniations. However, these patients should be followed up closely; new herniation at adjacent/different level may occur. Furthermore, it is important to know which herniated disk should be removed and which should be treated conservatively, because disc herniation may cause serious complications as muscle weakness and cauda equine syndrome. PMID:27429818

  10. End Plate Disproportion and Degenerative Disc Disease: A Case-Control Study

    PubMed Central

    Poureisa, Masoud; Daghighi, Mohammad Hossein; Mesbahi, Sepideh; Hagigi, Amir

    2014-01-01

    Study Design Case-control. Purpose To determine whether a disproportion between two neighboring vertebral end plates is associated with degenerative disc disease. Overview of Literature Recently, it has been suggested that disproportion of the end plates of two adjacent vertebrae may increase the risk of disc herniation. Methods Magnetic resonance (MR) images (n=160) with evidence of grades I-II lumbar degenerative disc disease (modified Pfirrmann's classification) and normal MR images of the lumbar region (n=160) were reviewed. On midsagittal sections, the difference of anteroposterior diameter of upper and lower end plates neighboring a degenerated (in the case group) or normal (in the control group) intervertebral disc was calculated (difference of end plates [DEP]). Results Mean DEP was significantly higher in the case group at the L5-S1 level (2.73±0.23 mm vs. 2.21±0.12 mm, p=0.03). Differences were not statistically significant at L1-L2 (1.31±0.13 mm in the cases vs. 1.28±0.08 mm in the controls, p=0.78), L2-L3 (1.45±0.12 mm in the cases vs. 1.37±0.08 mm in the controls, p=0.58), L3-L4 (1.52±0.13 mm in the cases vs. 1.49±0.10 mm in the controls, p=0.88), and L4-L5 (2.15±0.21 mm in the cases vs. 2.04±0.20 mm in the controls, p=0.31) levels. The difference at the L5-S1 level did not remain significant after adjusting for body mass index (BMI), which was significantly higher in the patients. Conclusions End plate disproportion may be a significant, BMI-dependent risk factor for lumbar degenerative disc disease. PMID:25187856

  11. Differences in acoustic properties of intact and degenerated human patellar cartilage during compression.

    PubMed

    Kiviranta, Panu; Lammentausta, Eveliina; Töyräs, Juha; Nieminen, Heikki J; Julkunen, Petro; Kiviranta, Ilkka; Jurvelin, Jukka S

    2009-08-01

    Ultrasound indentation measurements have been shown to provide means to assess cartilage integrity and mechanical properties. To determine cartilage stiffness in the ultrasound indentation geometry, cartilage is compressed with an ultrasound transducer to determine the induced strain from the ultrasound signal using the time-of-flight principle. As the ultrasound speed in cartilage has been shown to vary during compression, the assumption of constant speed generates significant errors in the values of mechanical parameters. This variation in ultrasound speed has been investigated in intact cartilage, however, its existence and significance in degenerated tissue is unknown. In the present study, we investigate this issue with both intact and spontaneously degenerated human tissue. To accomplish this aim, we determined ultrasound speed and attenuation in human patellar cartilage (n=68) during mechanical loading. For reference, cartilage mechanical properties and proteoglycan, collagen and water contents were determined. The acoustic properties were related to the composition and mechanical properties of the samples. Ultrasound speed showed significant, site-dependent variation and it was significantly associated (r=0.79-0.81, p<0.01) with the mechanical properties of cartilage. The compression related decrease in ultrasound speed showed statistically significant variation between different stages of degeneration. Error simulations revealed that changes in ultrasound speed during 2% compression could generate errors up to 15% in the values of elastic moduli of samples with early degeneration, if determined with the ultrasound indentation technique. In samples with advanced degeneration, the error was significantly (p<0.05) smaller being 2% on average. As the compression related variation in ultrasound speed was lower in more degenerated samples, the mechanical parameters could be diagnosed more reliably in tissue showing advanced degeneration. The present results

  12. The Quiescent Growth Of Galactic Discs

    NASA Astrophysics Data System (ADS)

    Binney, James

    2016-09-01

    We use N-bodies to simulate the growth since redshift 2 of an isolated disc in a live halo. Giant molecular clouds (GMCs), The bar and spiral structure all play key roles in the evolution of the disc. Our GMCs are short-lived and have masses drawn from a mass spectrum. Their number density is related to the SFR. For the expected number densities and likely maximum masses of GMCs, they heat the disc very effectively at early times, and either postpone or cancel bar formation. They generate remarkably exponential vertical profiles. Spiral structure drives a level of radial migration that agrees well with that predicted by models of local chemical evolution. The radial patterns of star formation include different levels of inside-out growth. The radial scale length of the final disc is always greater than any of the scale lengths used for star formation and rather independent of the extent of inside-out growth. The only way to obtain a thick disc nearly as massive as those observed is to include in the initial conditions a massive, extended object that will be compressed into the present thick disc by the gravity of the thin disc.

  13. Constraining the double-degenerate scenario for Type Ia supernovae from merger ejected matter

    NASA Astrophysics Data System (ADS)

    Levanon, Naveh; Soker, Noam; García-Berro, Enrique

    2015-03-01

    We follow the mass expelled during the WD-WD merger process in a particular case of the double-degenerate (DD) scenario for Type Ia supernovae (SNe Ia), and find that the interaction of the SN ejecta with the resulting wind affects the early (first day) light-curve in a way that may be in conflict with some SN Ia observations, if the detonation occurs shortly after the merger, i.e. (103 s ≲ texp ≲ 1 d). The main source of the expelled mass is a disc-wind, or jets that are launched by the accretion disc around the more massive white dwarf (WD) during the viscous phase of the merger. This disc-originated matter will be shocked and heated by the SN ejecta from an explosion, leading to additional radiation in the early light-curve. This enhanced early radiation could then be interpreted as an explosion originating from a progenitor having an inferred radius of one solar radius or more, in conflict with observations of SN 2011fe.

  14. Chemical separation of disc components using RAVE

    NASA Astrophysics Data System (ADS)

    Wojno, Jennifer; Kordopatis, Georges; Steinmetz, Matthias; McMillan, Paul; Matijevič, Gal; Binney, James; Wyse, Rosemary F. G.; Boeche, Corrado; Just, Andreas; Grebel, Eva K.; Siebert, Arnaud; Bienaymé, Olivier; Gibson, Brad K.; Zwitter, Tomaž; Bland-Hawthorn, Joss; Navarro, Julio F.; Parker, Quentin A.; Reid, Warren; Seabroke, George; Watson, Fred

    2016-10-01

    We present evidence from the RAdial Velocity Experiment (RAVE) survey of chemically separated, kinematically distinct disc components in the solar neighbourhood. We apply probabilistic chemical selection criteria to separate our sample into α-low (`thin disc') and α-high (`thick disc') sequences. Using newly derived distances, which will be utilized in the upcoming RAVE DR5, we explore the kinematic trends as a function of metallicity for each of the disc components. For our α-low disc, we find a negative trend in the mean rotational velocity (Vφ) as a function of iron abundance ([Fe/H]). We measure a positive gradient ∂Vφ/∂[Fe/H] for the α-high disc, consistent with results from high-resolution surveys. We also find differences between the α-low and α-high discs in all three components of velocity dispersion. We discuss the implications of an α-low, metal-rich population originating from the inner Galaxy, where the orbits of these stars have been significantly altered by radial mixing mechanisms in order to bring them into the solar neighbourhood. The probabilistic separation we propose can be extended to other data sets for which the accuracy in [α/Fe] is not sufficient to disentangle the chemical disc components a priori. For such data sets which will also have significant overlap with Gaia DR1, we can therefore make full use of the improved parallax and proper motion data as it becomes available to investigate kinematic trends in these chemical disc components.

  15. Determination and comparison of specifics of nucleus pulposus cells of human intervertebral disc in alginate and chitosan–gelatin scaffolds

    PubMed Central

    Renani, Hamid Bahramian; Ghorbani, Masood; Beni, Batool Hashemibeni; Karimi, Z; Mirhosseini, MM; Zarkesh, H; Kabiri, A

    2012-01-01

    Introduction: Low back pain is a major economical and social problem nowadays. Intervertebral disc herniation and central degeneration of disc are two major reasons of low back pain that occur because of structural impairment of disc. The intervertebral disc contains three parts as follows : Annulus fibrosus, transitional region, and nucleus pulposus, which forms the central nucleus of the disc. The reduction of cell count and extracellular matrix, especially in nucleus pulposus, causes disc degeneration. Different scaffolds (natural and synthetic) have been used for tissue repairing and regeneration of the intervertebral disc in tissue engineering. Most scaffolds have biodegradable and biocompatible characteristics and also prepare a fine condition for proliferation and migration of cells. In this study, proliferation of NP cells of human intervertebral disc compromised in Chitosan-gelatin scaffold with alginate scaffold was studied. Materials and Methods: NP cells derived from nucleus pulposus by collagenase enzymatic hydrolysis. They were derived from patients who undergoing open surgery for discectomy in the Isfahan Alzahra hospital. Chitosan was blended with gelatin and glutaraldehyde was used for cross linking the two polymers. Then, alginate scaffold was prepared. Cellular suspension with 1 × 105 transferred to each scaffold and cultured for 21 days. Cell viability and proliferation investigated by trypan blue and (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Scanning electron microscope (SEM) was used to assert the porosity and to survey structure of scaffold. Results: MTT assay dem1onstrated that cell viability of third day had significant difference in contrast by first day in both scaffolds. Accordingly, there was a significant decreased in cellular viability from day 3 to 21. Results of the cell count showed a punctual elevation cell numbers for alginate scaffold but there was no similar result for chitosan

  16. Thermal Properties of Degenerate Relativistic Quantum Gases

    NASA Astrophysics Data System (ADS)

    Homorodean, Laurean

    We present the concentration-temperature phase diagram, characteristic functions, thermal equation of state and heat capacity at constant volume for degenerate ideal gases of relativistic fermions and bosons. The nonrelativistic and ultrarelativistic limits of these laws are also discussed.

  17. Macular Degeneration Prevention and Risk Factors

    MedlinePlus

    ... Degeneration Research National Glaucoma Research About Research Programs Leadership Partners Accountability Careers Grants Types of Grants Deadlines & ... Browse our A–Z index . About Research Programs Leadership Partners Accountability Careers Grants Types of Grants Deadlines & ...

  18. Hamiltonian structure for degenerate AKNS systems

    NASA Astrophysics Data System (ADS)

    Corona-Corona, Gulmaro

    1997-01-01

    There is a family of degenerate AKNS systems for which the full theory of generic AKNS systems does not directly extend. The linear space of potentials still has a natural Poisson structure, but the scattering method used by Beals and Sattinger to show complete integrability for the generic AKNS systems fails for the degenerate case. A Poisson structure is not induced on the scattering side as in the generic case. As a consequence, the problem of complete integrability for degenerate AKNS systems still is an open question. In addition, contrary to the generic case, the Lax pair gives flows for degenerate integrable systems that are nonlocal. In general, they do not exist, and they are no longer linear on the scattering side. Necessary conditions for their existence and for linear evolution in the scattering side are found.

  19. Hamiltonian Structure for Degenerate Akns Systems

    NASA Astrophysics Data System (ADS)

    Corona-Corona, Gulmaro

    1995-01-01

    There is a family of degenerate AKNS systems for which the full theory of generic AKNS systems does not directly extend. The linear space of potentials still has a natural Poisson structure. This is studied by the scattering method used by Richard Beals and D.H. Sattinger (Commun. Math. Phys. 138, 409-436, 1991) to show complete integrability for the generic AKNS systems. This method fails for the degenerate case since a Poisson structure is not induced on the scattering side as in the generic case. As a consequence, the problem of complete integrability for degenerate AKNS systems still is an open question. In addition, contrary to the generic case, the Lax pair gives flows for degenerate integrable systems that are nonlocal. In general they do not exist, and they are no longer linear on the scattering side. Necessary conditions for their existence and for linear evolution of the scattering side are found.

  20. Neural remodeling in retinal degeneration.

    PubMed

    Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica

    2003-09-01

    Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in

  1. Update on geographic atrophy in age-related macular degeneration.

    PubMed

    Biarnés, Marc; Monés, Jordi; Alonso, Jordi; Arias, Luis

    2011-07-01

    Age-related macular degeneration (AMD) is the main cause of legal blindness in older patients in developed countries, and geographic atrophy (GA) represents the advanced form of dry AMD. Although it accounts for one third of the cases of late AMD and is responsible for 20% of the cases of severe visual loss due to the disorder. GA currently lacks effective treatment, whereas antiangiogenic therapies have been shown to be successful in managing choroidal neovascularization, the other form of late AMD. Recent advances in GA epidemiology, etiology, genetics, and imaging techniques have renewed the interest in this entity, which is a cause of progressive visual loss even in treated patients with neovascular AMD. This knowledge has triggered many clinical trials targeting different molecules shown to be associated with the disease, and it is hoped that this research will translate into effective drugs for GA in the near future.

  2. Cordycepin inhibits LPS-induced inflammatory and matrix degradation in the intervertebral disc

    PubMed Central

    Mao, Lu; Han, Xiuguo; Zhang, Kai; Zhao, Changqing

    2016-01-01

    Cordycepin is a component of the extract obtained from Cordyceps militaris and has many biological activities, including anti-cancer, anti-metastatic and anti-inflammatory effects. Intervertebral disc degeneration (IDD) is a degenerative disease that is closely related to the inflammation of nucleus pulposus (NP) cells. The effect of cordycepin on NP cells in relation to inflammation and degeneration has not yet been studied. In our study, we used a rat NP cell culture and an intervertebral disc (IVD) organ culture model to examine the inhibitory effects of cordycepin on lipopolysaccharide (LPS)-induced gene expression and the production of matrix degradation enzymes (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5) and oxidative stress-associated factors (nitric oxide and PGE2). We found a protective effect of cordycepin on NP cells and IVDs against LPS-induced matrix degradation and macrophage infiltration. In addition, western blot and luciferase assay results demonstrated that pretreatment with cordycepin significantly suppressed the LPS-induced activation of the NF-κB pathway. Taken together, the results of our research suggest that cordycepin could exert anti-inflammatory and anti-degenerative effects on NP cells and IVDs by inhibiting the activation of the NF-κB pathway. Therefore, cordycepin may be a potential treatment for IDD in the future. PMID:27190710

  3. Effects of enzymatic digestion on compressive properties of rat intervertebral discs.

    PubMed

    Barbir, Ana; Michalek, Arthur J; Abbott, Rosalyn D; Iatridis, James C

    2010-04-19

    Enzymatic treatments were applied to rat motion segments to establish structure-function relationships and determine mechanical parameters most sensitive to simulated remodeling and degeneration. Rat caudal and lumbar disc biomechanical behaviors were evaluated to improve knowledge of their similarities and differences due to their frequent use during in vivo models. Caudal motion segments were assigned to four groups: soaked (control), genipin treated, elastase treated, and collagenase treated. Fresh lumbar and caudal discs were also compared. The mechanical protocol involved five force-controlled loading stages: equilibration, cyclic compression-tension, quasi-static compression, frequency sweep, and creep. Crosslinking was found to have the greatest effect on IVD properties at resting stress. Elastin's role was greatest in tension and at higher force conditions, where GAG content was also a contributing factor. Collagenase treatment caused tissue compaction, which impacted mechanical properties at both high and low force conditions. Equilibration creep and cyclic compression-tension tests were the mechanical tests most sensitive to alterations in specific matrix constituents. Caudal and lumbar motion segments had many similarities but biomechanical differences suggested some distinctions in collagenous structure and water transport characteristics in addition to the geometric differences. Results provide a basis for interpreting biomechanical changes observed in animal model studies of degeneration and remodeling, and underscore the need to maintain and/or repair collagen integrity in IVD health and disease.

  4. T1ρ magnetic resonance: basic physics principles and applications in knee and intervertebral disc imaging

    PubMed Central

    Zhang, Qinwei; Li, Xiaojuan; Chen, Weitian; Ahuja, Anil; Yuan, Jing

    2015-01-01

    T1ρ relaxation time provides a new contrast mechanism that differs from T1- and T2-weighted contrast, and is useful to study low-frequency motional processes and chemical exchange in biological tissues. T1ρ imaging can be performed in the forms of T1ρ-weighted image, T1ρ mapping and T1ρ dispersion. T1ρ imaging, particularly at low spin-lock frequency, is sensitive to B0 and B1 inhomogeneity. Various composite spin-lock pulses have been proposed to alleviate the influence of field inhomogeneity so as to reduce the banding-like spin-lock artifacts. T1ρ imaging could be specific absorption rate (SAR) intensive and time consuming. Efforts to address these issues and speed-up data acquisition are being explored to facilitate wider clinical applications. This paper reviews the T1ρ imaging’s basic physic principles, as well as its application for cartilage imaging and intervertebral disc imaging. Compared to more established T2 relaxation time, it has been shown that T1ρ provides more sensitive detection of proteoglycan (PG) loss at early stages of cartilage degeneration. T1ρ has also been shown to provide more sensitive evaluation of annulus fibrosis (AF) degeneration of the discs. PMID:26807369

  5. T1ρ magnetic resonance: basic physics principles and applications in knee and intervertebral disc imaging.

    PubMed

    Wáng, Yì-Xiáng J; Zhang, Qinwei; Li, Xiaojuan; Chen, Weitian; Ahuja, Anil; Yuan, Jing

    2015-12-01

    T1ρ relaxation time provides a new contrast mechanism that differs from T1- and T2-weighted contrast, and is useful to study low-frequency motional processes and chemical exchange in biological tissues. T1ρ imaging can be performed in the forms of T1ρ-weighted image, T1ρ mapping and T1ρ dispersion. T1ρ imaging, particularly at low spin-lock frequency, is sensitive to B0 and B1 inhomogeneity. Various composite spin-lock pulses have been proposed to alleviate the influence of field inhomogeneity so as to reduce the banding-like spin-lock artifacts. T1ρ imaging could be specific absorption rate (SAR) intensive and time consuming. Efforts to address these issues and speed-up data acquisition are being explored to facilitate wider clinical applications. This paper reviews the T1ρ imaging's basic physic principles, as well as its application for cartilage imaging and intervertebral disc imaging. Compared to more established T2 relaxation time, it has been shown that T1ρ provides more sensitive detection of proteoglycan (PG) loss at early stages of cartilage degeneration. T1ρ has also been shown to provide more sensitive evaluation of annulus fibrosis (AF) degeneration of the discs.

  6. 21 CFR 872.3970 - Interarticular disc prosthesis (interpositional implant).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Interarticular disc prosthesis (interpositional... disc prosthesis (interpositional implant). (a) Identification. An interarticular disc prosthesis... Food and Drug Administration on or before March 30, 1999, for any interarticular disc...

  7. 21 CFR 872.3970 - Interarticular disc prosthesis (interpositional implant).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Interarticular disc prosthesis (interpositional... disc prosthesis (interpositional implant). (a) Identification. An interarticular disc prosthesis... Food and Drug Administration on or before March 30, 1999, for any interarticular disc...

  8. 21 CFR 872.3970 - Interarticular disc prosthesis (interpositional implant).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Interarticular disc prosthesis (interpositional... disc prosthesis (interpositional implant). (a) Identification. An interarticular disc prosthesis... Food and Drug Administration on or before March 30, 1999, for any interarticular disc...

  9. Reading disc-based bioassays with standard computer drives.

    PubMed

    Yu, Hua-Zhong; Li, Yunchao; Ou, Lily M-L

    2013-02-19

    Traditional methods of disease diagnosis are both time-consuming and labor-intensive, and many tests require expensive instrumentation and trained professionals, which restricts their use to biomedical laboratories. Because patients can wait several days (even weeks) for the results, the consequences of delayed treatment could be disastrous. Therefore, affordable and simple point-of-care (POC) biosensor devices could fill a diagnostic niche in the clinic or even at home, as personal glucose meters do for diabetics. These devices would allow patients to check their own health conditions and enable physicians to make prompt treatment decisions, which could improve the chances for rapid recovery and cure. Compact discs (CDs) provide inexpensive substrate materials for the preparation of microarray biochips, and conventional computer drives/disc players can be adapted as precise optical reading devices for signal processing. Researchers can employ the polycarbonate (PC) base of a CD as an alternative substrate to glass slides or silicon wafers for the preparation of microanalytical devices. Using the characteristic optical phenomena occurring on the metal layer of a CD, researchers can develop biosensors based on advanced spectroscopic readout (interferometry or surface plasmon resonance). If researchers integrate microfluidic functions with CD mechanics, they can control fluid transfer through the spinning motion of the disc, leading to "lab-on-a-CD" devices. Over the last decade, our laboratory has focused on the construction of POC biosensor devices from off-the-shelf CDs or DVDs and standard computer drives. Besides the initial studies of the suitability of CDs for surface and materials chemistry research (fabrication of self-assembled monolayers and oxide nanostructures), we have demonstrated that an ordinary optical drive, without modification of either the hardware or the software driver, can function as the signal transducing element for reading disc

  10. Up-regulation of niacinamide in intervertebral disc aggrecan in vitro.

    PubMed

    Xiong, Xiaoqian; Yang, Shuhua; Shao, Zengwu; Liu, Xin; Zhan, Zirui; Duan, Deyu

    2006-01-01

    The regulatory effects of niacinamide (Nia) on intervertebral disc (IVD) aggrecan in vitro was investigated. Chiba's 10 ng/mL interleukin-1 (IL-1)-induced rabbit IVD degeneration model in vitro was established. 0.5, 0.25 and 0.05 mg/mL Nia was added to normal and degenerated IVDs for intervention. On the first and second week after intervention, safranin O-fast green staining intensity and glycosaminoglycan (GS) content were measured. The expression of aggrecan core protein was detected by RT-PCR. The results showed: (1) After treatment with 0.5 mg/mL Nia for one week, the GS content in nucleus pulposus (NP) was increased by 44.8% as compared with control group (P < 0 01); The GS content in IL-1 induction groups was increased with the increase of Nia concentrations: After treatment with 0.5 mg/mL for one week, the GS content in NP was increased by 68.3% as compared with control group (P < 0.01). After two weeks, GS content in NP and fibrous rings was still higher than in control group at the same period (P < 0.01) and untreated group (P < 0.01). (2) Safranin O-fast green staining revealed that with the increase of Nia concentrations, staining density in NP and fibrous rings was increased and histological structure damage to IVDs by IL-1beta was alleviated. (3) RT-PCR showed that the expression of core protein gene in IL-1beta-induced degenerated IVDS was increased with the increase of Nia concentrations. It was concluded that under conditions in vitro, Nia could up-regulate the expression of aggrecan in IVDs and protect IVDs from IL-1beta-induced degeneration at least partially, which offers a potential choice for IVD degeneration clinical therapy.

  11. Archival-grade optical disc design and international standards

    NASA Astrophysics Data System (ADS)

    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.

  12. Treatment of lumbar disc herniation by percutaneous laser disc decompression (PLDD) and modified PLDD

    NASA Astrophysics Data System (ADS)

    Chi, Xiao fei; Li, Hong zhi; Wu, Ru zhou; Sui, Yun xian

    2005-07-01

    Objective: To study the micro-invasive operative method and to compare the effect of treatment of PLDD and modified PLDD for Lumbar Disc Herniation. Method: Vaporized part of the nucleus pulposus in single or multiple point after acupuncture into lumbar disc, to reach the purpose of the decompression of the lumbar disc. Result: Among the 19 cases of the regular PLDD group, the excellent and good rate was 63.2%, and among the 40 cases of the modified PLDD group, the excellent and good rate was 82.5%. Conclusion: The modified PLDD has good effect on the treatment for lumbar disc herniation.

  13. Genetics Home Reference: intervertebral disc disease

    MedlinePlus

    ... link) National Institute of Neurological Disorders and Stroke: Low Back Pain Fact Sheet Educational Resources (8 links) American Association ... MalaCards: intervertebral disc disease Merck Manual Consumer Version: Low Back Pain Merck Manual Consumer Version: Neck Pain The Children's ...

  14. Dynamical modelling of galactic disc outskirts

    NASA Astrophysics Data System (ADS)

    Athanassoula, E.

    2017-03-01

    I review briefly some dynamical models of structures in the outer parts of disc galaxies, including models of polar rings, tidal tails and bridges. I then discuss the density distribution in the outer parts of discs. For this, I compare observations to results of a model in which the disc galaxy is in fact the remnant of a major merger, and find good agreement. This comparison includes radial profiles of the projected surface density and of stellar age, as well as time evolution of the break radius and of the inner and outer disc scale lengths. I also compare the radial projected surface density profiles of dynamically motivated mono-age populations and find that, compared to older populations, younger ones have flatter density profiles in the inner region and steeper in the outer one. The break radius, however, does not vary with stellar age, again in good agreement with observations.

  15. [Disc electrophoresis of collagen protein (author's transl)].

    PubMed

    Reitmayr, P; Verzár, F

    1975-01-01

    The composition of proteins extracted from tendon collagen is investigated by disc electrophoresis. No qualitative differences can be demonstrated between young and old collagen. The action of formaldehyde and methionine on the tendons has no effect on the electrophoretic picture.

  16. Cardiac pathology after valve replacement by disc prosthesis. A study of 61 necropsy patients.

    PubMed

    Roberts, W C; Fishbein, M C; Golden, A

    1975-05-01

    indicates that the poppet disc prosthesis is considerably traumatic to erythrocytes. Thus, this type of prosthesis is not an ideal substitute cardiac valve. It clots, despite anticoagulant therapy, it is intrinsically stenotic, portions of it, that is, the disc, degenerate, and it causes hemolysis to erythrocytes.

  17. Investigation of cryogenic rupture disc design

    NASA Technical Reports Server (NTRS)

    Keough, J. B.; Oldland, A. H.

    1973-01-01

    Rupture disc designs of both the active (command actuated) and passive (pressure ruptured) types were evaluated for performance characteristics at cryogenic temperatures and for capability to operate in a variety of cryogens, including gaseous and liquid fluorine. The test results, coupled with information from literature and industry searches, were used to establish a statement of design criteria and recommended practices for application of rupture discs to cryogenic rocket propellant feed and vent systems.

  18. Disc valve for sampling erosive process streams

    DOEpatents

    Mrochek, John E.; Dinsmore, Stanley R.; Chandler, Edward W.

    1986-01-01

    A four-port disc valve for sampling erosive, high temperature process streams. A rotatable disc defining opposed first and second sampling cavities rotates between fired faceplates defining flow passageways positioned to be alternatively in axial alignment with the first and second cavities. Silicon carbide inserts and liners composed of .alpha. silicon carbide are provided in the faceplates and in the sampling cavities to limit erosion while providing lubricity for a smooth and precise operation when used under harsh process conditions.

  19. Effect of Static Load on the Nucleus Pulposus of Rabbit Intervertebral Disc Motion Segment in an Organ Culture

    PubMed Central

    Feng, Min-Shan; Zhang, Ping; Yu, Jie

    2016-01-01

    The development of mechanically active culture systems helps in understanding of the role of mechanical stress in intervertebral disc (IVD) degeneration. Motion segment cultures facilitate the application and control of mechanical loads. The purpose of this study was to establish a culturing method for rabbit IVD motion segments to observe the effect of static load on the whole disc organ. Segments were cultured in custom-made apparatuses under a constant, compressive load (3 kg) for 2 weeks. Tissue integrity, matrix synthesis, and matrix gene expression profile were assessed and compared with fresh one. The results showed ex vivo culturing of samples gradually destroyed the morphology. Proteoglycan contents and gene expression were decreased and downregulated obviously. However, immunohistochemical staining intensity and collagen type II gene expression were significantly enhanced and upregulated. In contrast, these trends were reversed under constant compression. These results indicated short-term static load stimulated the synthesis of type II collagen; however, constant compression led to progressive degeneration and specifically to proteoglycan. Through this study a loading and organ-culturing system for ex vivo rabbit IVD motion segments was developed, which can be used to study the effects of mechanical stimulation on the biology of IVDs and the pathomechanics of IVD degeneration. PMID:27872846

  20. Management of advanced corneal ectasias.

    PubMed

    Maharana, Prafulla K; Dubey, Aditi; Jhanji, Vishal; Sharma, Namrata; Das, Sujata; Vajpayee, Rasik B

    2016-01-01

    Corneal ectasias include a group of disorders characterised by progressive thinning, bulging and distortion of the cornea. Keratoconus is the most common disease in this group. Other manifestations include pellucid marginal degeneration, Terrien's marginal degeneration, keratoglobus and ectasias following surgery. Advanced ectasias usually present with loss of vision due to high irregular astigmatism. Management of these disorders is difficult due to the peripheral location of ectasia and associated severe corneal thinning. Newer contact lenses such as scleral lenses are helpful in a selected group of patients. A majority of these cases requires surgical intervention. This review provides an update on the current treatment modalities available for management of advanced corneal ectasias.

  1. Hybrid Surgery Versus Anterior Cervical Discectomy and Fusion in Multilevel Cervical Disc Diseases

    PubMed Central

    Zhang, Jianfeng; Meng, Fanxin; Ding, Yan; Li, Jie; Han, Jian; Zhang, Xintao; Dong, Wei

    2016-01-01

    Abstract To investigate the outcomes and reliability of hybrid surgery (HS) versus anterior cervical discectomy and fusion (ACDF) for the treatment of multilevel cervical spondylosis and disc diseases. Hybrid surgery, combining cervical disc arthroplasty (CDA) with fusion, is a novel treatment to multilevel cervical degenerated disc disease in recent years. However, the effect and reliability of HS are still unclear compared with ACDF. To investigate the studies of HS versus ACDF in patients with multilevel cervical disease, electronic databases (Medline, Embase, Pubmed, Cochrane library, and Cochrane Central Register of Controlled Trials) were searched. Studies were included when they compared HS with ACDF and reported at least one of the following outcomes: functionality, neck pain, arm pain, cervical range of motion (ROM), quality of life, and incidence of complications. No language restrictions were used. Two authors independently assessed the methodological quality of included studies and extracted the relevant data. Seven clinical controlled trials were included in this study. Two trials were prospective and the other 5 were retrospective. The results of the meta-analysis indicated that HS achieved better recovery of NDI score (P = 0.038) and similar recovery of VAS score (P = 0.058) compared with ACDF at 2 years follow-up. Moreover, the total cervical ROM (C2–C7) after HS was preserved significantly more than the cervical ROM after ACDF (P = 0.000) at 2 years follow-up. Notably, the compensatory increase of the ROM of superior and inferior adjacent segments was significant in ACDF groups at 2-year follow-up (P < 0.01), compared with HS. The results demonstrate that HS provides equivalent outcomes and functional recovery for cervical disc diseases, and significantly better preservation of cervical ROM compared with ACDF in 2-year follow-up. This suggests the HS is an effective alternative invention for the treatment of multilevel cervical

  2. Intradural Migration of a Sequestrated Lumbar Disc Fragment Masquerading as a Spinal Intradural Tumor

    PubMed Central

    Kim, Hyeong-Suk; Park, Jung-Soo

    2012-01-01

    Intervertebral intradural lumbar disc herniation (ILDH) is a quite rare pathology, and isolated intradural lumbar disc herniation is even more rare. Magnetic resonance imaging (MRI) may not be able to reveal ILDHs, especially if MRI findings show an intact lumbar disc annulus and posterior longitudinal ligament. Here, we present an exceedingly rare case of an isolated IDLH that we initially misidentified as a spinal intradural tumor, in a 54-year-old man hospitalized with a 2-month history of back pain and right sciatica. Neurologic examination revealed a positive straight leg raise test on the right side, but he presented no other sensory, motor, or sphincter disturbances. A gadolinium-enhanced MRI revealed what we believed to be an intradural extramedullary tumor compressing the cauda equina leftward in the thecal sac, at the L2 vertebral level. The patient underwent total L2 laminectomy, and we extirpated the intradural mass under microscopic guidance. Histologic examination of the mass revealed a degenerated nucleus pulposus. PMID:23091677

  3. Inequality in leg length is important for the understanding of the pathophysiology of lumbar disc herniation

    PubMed Central

    Balik, Mehmet Sabri; Kanat, Ayhan; Erkut, Adem; Ozdemir, Bulent; Batcik, Osman Ersagun

    2016-01-01

    Objective: Inequality in leg length may lead to to abnormal transmission of load across the endplates and degeneration lumbar spine and the disc space. There has been no study focusing on lumbar disc herniation (LDH) and leg length discrepancy. This subject was investigated in this study. Materials and Methods: Consecutive adult patients with leg length discrepancy and low back pain (LBP) admitted to our department were respectivelly studied. Results: A total number of 39 subjects (31 women and eight men) with leg length discrepancy and LBP and 43 (25 females and 18 males) patients with LBP as a control group were tested. Occurrence of disc herniation is statistically different between patients with hip dysplasia and control groups (P < 0.05). Conclusion: The results of this study showed a statistically significant association between leg length discrepancy and occurrence of LDH. The changes of spine anatomy with leg length discrepancy in hip dysplastic patients are of importance in understanding the nature of LDH. PMID:27217654

  4. Temperature Distributions of the Lumbar Intervertebral Disc during Laser Annuloplasty : A Cadaveric Study

    PubMed Central

    Lee, Min Hyung; Hong, Jae Taek; Sung, Jae Hoon; Lee, Sang Won; Kim, Daniel H.

    2016-01-01

    Objective Low back pain, caused intervertebral disc degeneration has been treated by thermal annuloplasty procedure, which is a non-surgical treatement. The theoretical backgrounds of the annuloplasty are thermal destruct of nociceptor and denaturization of collagen fiber to induce contraction, to shrink annulus and thus enhancing stability. This study is about temperature and its distribution during thermal annuloplasty using 1414 nm Nd : YAG laser. Methods Thermal annuloplasty was performed on fresh human cadaveric lumbar spine with 20 intact intervertebral discs in a 37℃ circulating water bath using newly developed 1414 nm Nd : YAG laser. Five thermocouples were attached to different locations on the disc, and at the same time, temperature during annuloplasty was measured and analyzed. Results Thermal probe's temperature was higher in locations closer to laser fiber tip and on lateral locations, rather than the in depth locations. In accordance with the laser fiber tip and the depth, temperatures above 45.0℃ was measured in 3.0 mm depth which trigger nociceptive ablation in 16 levels (80%), in accordance with the laser fiber end tip and laterality, every measurement had above 45.0℃, and also was measured temperature over 60.0℃, which can trigger collagen denaturation at 16 levels (80%). Conclusion When thermal annuloplasty is needed in a selective lesion, annuloplasty using a 1414 nm Nd : YAG laser can be one of the treatment options. PMID:27847567

  5. Radio Monitoring of Protoplanetary Discs

    NASA Astrophysics Data System (ADS)

    Ubach, C.; Maddison, S. T.; Wright, C. M.; Wilner, D. J.; Lommen, D. J. P.; Koribalski, B.

    2017-01-01

    Protoplanetary disc systems observed at radio wavelengths often show excess emission above that expected from a simple extrapolation of thermal dust emission observed at short millimetre wavelengths. Monitoring the emission at radio wavelengths can be used to help disentangle the physical mechanisms responsible for this excess, including free-free emission from a wind or jet, and chromospheric emission associated with stellar activity. We present new results from a radio monitoring survey conducted with Australia Telescope Compact Array over the course of several years with observation intervals spanning days, months and years, where the flux variability of 11 T Tauri stars in the Chamaeleon and Lupus star forming regions was measured at 7 and 15 mm and 3 and 6 cm. Results show that for most sources are variable to some degree at 7 mm, indicating the presence of emission mechanisms other than thermal dust in some sources. Additionally, evidence of grain growth to cm-sized pebbles was found for some sources that also have signs of variable flux at 7 mm. We conclude that multiple processes contributing to the emission are common in T Tauri stars at 7 mm and beyond, and that a detection at a single epoch at radio wavelengths should not be used to determine all processes contributing to the emission.

  6. Circumplanetary disc or circumplanetary envelope?

    NASA Astrophysics Data System (ADS)

    Szulágyi, J.; Masset, F.; Lega, E.; Crida, A.; Morbidelli, A.; Guillot, T.

    2016-08-01

    We present three-dimensional simulations with nested meshes of the dynamics of the gas around a Jupiter mass planet with the JUPITER and FARGOCA codes. We implemented a radiative transfer module into the JUPITER code to account for realistic heating and cooling of the gas. We focus on the circumplanetary gas flow, determining its characteristics at very high resolution (80 per cent of Jupiter's diameter). In our nominal simulation where the temperature evolves freely by the radiative module and reaches 13000 K at the planet, a circumplanetary envelope was formed filling the entire Roche lobe. Because of our equation of state is simplified and probably overestimates the temperature, we also performed simulations with limited maximal temperatures in the planet region (1000, 1500, and 2000 K). In these fixed temperature cases circumplanetary discs (CPDs) were formed. This suggests that the capability to form a CPD is not simply linked to the mass of the planet and its ability to open a gap. Instead, the gas temperature at the planet's location, which depends on its accretion history, plays also fundamental role. The CPDs in the simulations are hot and cooling very slowly, they have very steep temperature and density profiles, and are strongly sub-Keplerian. Moreover, the CPDs are fed by a strong vertical influx, which shocks on the CPD surfaces creating a hot and luminous shock-front. In contrast, the pressure supported circumplanetary envelope is characterized by internal convection and almost stalled rotation.

  7. Minimally invasive photopolymerization in intervertebral disc tissue cavities

    NASA Astrophysics Data System (ADS)

    Schmocker, Andreas M.; Khoushabi, Azadeh; Gantenbein-Ritter, Benjamin; Chan, Samantha; Bonél, Harald Marcel; Bourban, Pierre-Etienne; Mânson, Jan Anders; Schizas, Constantin; Pioletti, Dominique; Moser, Christophe

    2014-03-01

    Photopolymerized hydrogels are commonly used for a broad range of biomedical applications. As long as the polymer volume is accessible, gels can easily be hardened using light illumination. However, in clinics, especially for minimally invasive surgery, it becomes highly challenging to control photopolymerization. The ratios between polymerizationvolume and radiating-surface-area are several orders of magnitude higher than for ex-vivo settings. Also tissue scattering occurs and influences the reaction. We developed a Monte Carlo model for photopolymerization, which takes into account the solid/liquid phase changes, moving solid/liquid-boundaries and refraction on these boundaries as well as tissue scattering in arbitrarily designable tissue cavities. The model provides a tool to tailor both the light probe and the scattering/absorption properties of the photopolymer for applications such as medical implants or tissue replacements. Based on the simulations, we have previously shown that by adding scattering additives to the liquid monomer, the photopolymerized volume was considerably increased. In this study, we have used bovine intervertebral disc cavities, as a model for spinal degeneration, to study photopolymerization in-vitro. The cavity is created by enzyme digestion. Using a custom designed probe, hydrogels were injected and photopolymerized. Magnetic resonance imaging (MRI) and visual inspection tools were employed to investigate the successful photopolymerization outcomes. The results provide insights for the development of novel endoscopic light-scattering polymerization probes paving the way for a new generation of implantable hydrogels.

  8. The role of disc self-gravity in circumbinary planet systems - I. Disc structure and evolution

    NASA Astrophysics Data System (ADS)

    Mutter, Matthew M.; Pierens, Arnaud; Nelson, Richard P.

    2017-03-01

    We present the results of two-dimensional hydrodynamic simulations of self-gravitating circumbinary discs around binaries whose parameters match those of the circumbinary planet-hosting systems Kepler-16, Kepler-34 and Kepler-35. Previous work has shown that non-self-gravitating discs in these systems form an eccentric precessing inner cavity due to tidal truncation by the binary, and planets which form at large radii migrate until stalling at this cavity. Whilst this scenario appears to provide a natural explanation for the observed orbital locations of the circumbinary planets, previous simulations have failed to match the observed planet orbital parameters. The aim of this work is to examine the role of self-gravity in modifying circumbinary disc structure as a function of disc mass, prior to considering the evolution of embedded circumbinary planets. In agreement with previous work, we find that for disc masses between one and five times the minimum mass solar nebula (MMSN), disc self-gravity affects modest changes in the structure and evolution of circumbinary discs. Increasing the disc mass to 10 or 20 MMSN leads to two dramatic changes in disc structure. First, the scale of the inner cavity shrinks substantially, bringing its outer edge closer to the binary. Secondly, in addition to the eccentric inner cavity, additional precessing eccentric ring-like features develop in the outer regions of the discs. If planet formation starts early in the disc lifetime, these changes will have a significant impact on the formation and evolution of planets and precursor material.

  9. Prospectives for Gene Therapy of Retinal Degenerations

    PubMed Central

    Thumann, Gabriele

    2012-01-01

    Retinal degenerations encompass a large number of diseases in which the retina and associated retinal pigment epithelial (RPE) cells progressively degenerate leading to severe visual disorders or blindness. Retinal degenerations can be divided into two groups, a group in which the defect has been linked to a specific gene and a second group that has a complex etiology that includes environmental and genetic influences. The first group encompasses a number of relatively rare diseases with the most prevalent being Retinitis pigmentosa that affects approximately 1 million individuals worldwide. Attempts have been made to correct the defective gene by transfecting the appropriate cells with the wild-type gene and while these attempts have been successful in animal models, human gene therapy for these inherited retinal degenerations has only begun recently and the results are promising. To the second group belong glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR). These retinal degenerations have a genetic component since they occur more often in families with affected probands but they are also linked to environmental factors, specifically elevated intraocular pressure, age and high blood sugar levels respectively. The economic and medical impact of these three diseases can be assessed by the number of individuals affected; AMD affects over 30 million, DR over 40 million and glaucoma over 65 million individuals worldwide. The basic defect in these diseases appears to be the relative lack of a neurogenic environment; the neovascularization that often accompanies these diseases has suggested that a decrease in pigment epithelium-derived factor (PEDF), at least in part, may be responsible for the neurodegeneration since PEDF is not only an effective neurogenic and neuroprotective agent but also a potent inhibitor of neovascularization. In the last few years inhibitors of vascularization, especially antibodies against vascular endothelial cell

  10. The high-throughput phenotyping of the viscoelastic behavior of whole mouse intervertebral discs using a novel method of dynamic mechanical testing.

    PubMed

    Liu, Jennifer W; Abraham, Adam C; Tang, Simon Y

    2015-07-16

    Intervertebral disc (IVD) degeneration is highly correlated with lower back pain, and thus understanding the mechanisms of IVD degeneration is critical for the treatment of this disease. Utilizing mouse models to probe the mechanisms of degeneration is especially attractive due to the ease of manipulating mouse models and the availability of transgenics. Yet characterizing the mechanical behavior of mice IVDs remain challenging due to their minute size (approximately 540 μm in height