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https://www.readbyqxmd.com/read/28544701/intradiscal-application-of-a-pcla-peg-pcla-hydrogel-loaded-with-celecoxib-for-the-treatment-of-back-pain-in-canines-what-s-in-it-for-humans
#1
Anna R Tellegen, Nicole Willems, Martijn Beukers, Guy C M Grinwis, Saskia G M Plomp, Clemens Bos, Maarten van Dijk, Mike de Leeuw, Laura B Creemers, Marianna A Tryfonidou, Björn P Meij
Chronic low back pain is a common clinical problem in both the human and canine population. Current pharmaceutical treatment often consists of oral anti-inflammatory drugs to alleviate pain. Novel treatments for degenerative disc diseases focus on local application of sustained released drug formulations. The aim of this study was to determine safety and feasibility of intradiscal application of a PCLA-PEG-PCLA hydrogel releasing celecoxib, a COX-2 inhibitor. Biocompatibility was evaluated after subcutaneous injection in mice and safety of intradiscal injection of the hydrogel was evaluated in experimental dogs with early spontaneous intervertebral disc (IVD) degeneration...
May 19, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28542104/reduced-spinal-cord-movement-with-the-straight-leg-raise-test-in-patients-with-lumbar-intervertebral-disc-herniation
#2
Marinko Rade, Janne Pesonen, Mervi Könönen, Jarkko Marttila, Michael Shacklock, Ritva Vanninen, Markku Kankaanpää, Olavi Airaksinen
STUDY DESIGN: Controlled radiological study. OBJECTIVE: To explore whether impairment of neural excursion during the straight leg raise test occurs in patients with sciatic symptoms secondary to lumbar intervertebral disc herniation (LIDH). SUMMARY OF BACKGROUND DATA: Earlier studies have shown that during the SLR test in asymptomatic volunteers tensile forces are consistently transmitted throughout the neural system and the thoracolumbar spinal cord slides distally...
May 25, 2017: Spine
https://www.readbyqxmd.com/read/28542098/comparison-of-oxygen-consumption-rates-of-nondegenerate-and-degenerate-human-ivd-cells
#3
Sarah E Cisewski, Yongren Wu, Brooke J Damon, Barton L Sachs, Michael J Kern, Hai Yao
STUDY DESIGN: In vitro measurements of the oxygen consumption rates (OCR) of human intervertebral disc (IVD) cells. OBJECTIVE: To determine the differences in the OCR of nondegenerate and degenerate human annulus fibrosus (AF), nucleus pulposus (NP), and cartilage endplate (CEP) cells at different glucose concentrations. SUMMARY OF BACKGROUND DATA: The avascular nature of the IVD creates a delicate balance between rate of nutrient transport through the matrix and rate of disc cell consumption necessary to maintain tissue health...
May 24, 2017: Spine
https://www.readbyqxmd.com/read/28535199/genotype-phenotype-correlation-in-patients-with-isovaleric-acidemia-comparative-structural-modelling-and-computational-analysis-of-novel-variants
#4
Osama K Zaki, George Priya Doss C, Salsabil A Ali, Ghadeer G Murad, Shaima A Elashi, Maryam Sa Ebnou, D Thirumal Kumar, Ola Khalifa, Radwa Gamal, Heba S A El Abd, Bilal N Nasr, Hatem Zayed
Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine metabolism. It is caused by a deficiency in the mitochondrial isovaleryl-CoA dehydrogenase (IVD) enzyme. In this study, we investigated eight patients with IVA. The patients diagnoses were confirmed by urinary organic acid analysis and the blood C5-Carnitine value. A molecular genetic analysis of the IVD gene revealed nine different variants: five were missense variants (c.1193G>A; p. R398Q, c.1207T>A; p. Y403N, c.872C>T; p...
May 23, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28527899/egfr-mutation-analysis-for-prospective-patient-selection-in-two-phase-ii-registration-studies-of-osimertinib
#5
Suzanne Jenkins, James Chih-Hsin Yang, Pasi A Jänne, Kenneth S Thress, Karen Yu, Rachel Hodge, Susie Weston, Simon Dearden, Sabina Patel, Mireille Cantarini, Frances A Shepherd
INTRODUCTION: Osimertinib is an oral, CNS active, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of EGFR T790M-positive advanced non-small cell lung cancer (NSCLC). Here we evaluate EGFR mutation frequencies in two Phase II studies of osimertinib (AURA extension and AURA2). METHODS: Patients with EGFR mutation-positive advanced NSCLC provided tumor samples following progression on their latest line of therapy for mandatory central T790M testing for study selection criteria...
May 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28526405/hypoxia-inducible-factor-l%C3%AE-mediates-aggrecan-and-collagen-%C3%AE-expression-via-notch1-signaling-in-nucleus-pulposus-cells-during-intervertebral-disc-degeneration
#6
Zhuochao Liu, Changwei Li, Xiangchao Meng, Yunting Bai, Jin Qi, Jun Wang, Qi Zhou, Weibin Zhang, Xingkai Zhang
Although hypoxia-inducible factor-lα (HIF-lα) has been reported to have an important role in the metabolism and synthesis of the extracellular matrix (ECM) of nucleus pulposus cells (NPCs), the underlying mechanism has not been fully clarified. Here, we show for the first time that NOTCH1 expression is decreased in NPs isolated from degenerated human intervertebral discs (IVDs), as well as in the NPs of NP-specific HIF-1α(-/-) mice. Our study reveals that overexpression of HIF-1α leads to increased expression of NOTCH1, the NOTCH1 ligand JAGGED1, and its target gene hairy and enhancer of split-1 (HES1), while also upregulating collagen Π and aggrecan expression in human NPCs...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28521616/a-10-gene-classifier-for-indeterminate-thyroid-nodules-development-and-multicenter-accuracy-study
#7
Hernan E Gonzalez, Jose R Martínez, Sergio Vargas, Antonieta Solar, Loreto Pamela Véliz, Francisco Cruz, Tatiana Arias, Soledad Loyola, Eleonora Horvath, Hernán Tala, Eufrosina Traipe, Manuel Meneses, Luis Marin, Nelson Wohllk, Rene Eduardo Diaz, Jesús Véliz, Pedro Pineda, Patricia Arroyo, Natalia Mena, Milagros Bracamonte, Giovanna Miranda, Elsa Bruce, Soledad Urra
BACKGROUND: In most of the world, diagnostic surgery remains as the most frequent approach for indeterminate thyroid cytology. Although several molecular tests are available for central-lab testing in the US, there are no available kits for local laboratory testing. The aim of this study was to develop a prototype in-vitro diagnostic (IVD) gene classifier for diagnosis of indeterminate thyroid cytology. METHODS: In a first stage, the expression of 18 genes was determined by qPCR in a broad histopathological spectrum of fresh tissue biopsies (114)...
May 18, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28515001/in-vitro-extracellular-matrix-accumulation-of-nasal-and-articular-chondrocytes-for-intervertebral-disc-repair
#8
S Vedicherla, C T Buckley
Chondrocyte based regenerative therapies for intervertebral disc repair such as Autologous Disc Cell Transplantation (ADCT, CODON) and allogeneic juvenile chondrocyte implantation (NuQu(®), ISTO Technologies) have demonstrated good outcomes in clinical trials. However concerns remain with the supply demand reconciliation and issues surrounding immunoreactivity which exist for allogeneic-type technologies. The use of stem cells is challenging due to high growth factor requirements, regulatory barriers and differentiation towards a stable phenotype...
May 8, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28507882/aquaporin-1-expression-in-herniated-human-lumbar-intervertebral-discs
#9
Haydn Hoffman, Aaron W Choi, Victor Chang, Jon Kimball, Alan S Verkman, Rubeen Virani, Brian Kim, Tianyi Niu, Daniel C Lu
STUDY DESIGN: Case series. OBJECTIVE: Intervertebral disc (IVD) degeneration is the cause of spondylosis. The pathogenesis is poorly understood, but disc dehydration often plays a role. In this study, we aim to identify and quantify aquaporin-1 (AQP1) in ex vivo human degenerated IVDs obtained intraoperatively and to investigate the relationship between AQP1 levels and magnetic resonance imaging (MRI) T2 intensity of the disc. METHODS: Ex vivo samples of nucleus pulposus (NP) tissue from lumbar IVDs were obtained from 18 consecutive patients who underwent surgery for disc herniation at L4/5 and L5/S1 level...
April 2017: Global Spine Journal
https://www.readbyqxmd.com/read/28505597/an-interpenetrating-network-strengthened-and-toughened-hydrogel-that-supports-cell-based-nucleus-pulposus-regeneration
#10
Yibo Gan, Pei Li, Liyuan Wang, Xiumei Mo, Lei Song, Yuan Xu, Chen Zhao, Bin Ouyang, Bing Tu, Lei Luo, Linyong Zhu, Shiwu Dong, Fuyou Li, Qiang Zhou
Hydrogel is a suitable scaffold for the nucleus pulposus (NP) regeneration. However, its unmatched mechanical properties lead to implant failure in late-stage disc degeneration because of structural failure and implant extrusion after long-term compression. In this study, we evaluated an interpenetrating network (IPN)-strengthened and toughened hydrogel for NP regeneration, using dextran and gelatin as the primary network while poly (ethylene glycol) as the secondary network. The aim of this study was to realize the NP regeneration using the hydrogel...
May 10, 2017: Biomaterials
https://www.readbyqxmd.com/read/28501720/characterization-and-restoration-of-degenerated-ivd-function-with-an-injectable-in-situ-gelling-alginate-hydrogel-an-in-vitro-and-ex-vivo-study
#11
Emily A Growney Kalaf, Meghana Pendyala, J Gary Bledsoe, Scott A Sell
Intervertebral disc (IVD) degeneration is a naturally, irreparable process that causes loss in IVD hydration, cellularity, and, mechanical stability. Invasive surgical attempts to ease back pain and, radiculopathy have shown to cause increased degeneration along the rest, of the spine. Due to its highly tunable mechanical and degradation, properties, alginate is a viable option for a less-invasive injectable, repair for IVD degeneration. This study centers on the characterization, of in situ gelling alginate and subsequent injection into enzymatically, degraded motion segments...
May 7, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28500957/design-synthesis-of-novel-oxazolone-triazinone-derivatives-and-their-biological-evaluation-as-cox-2-inhibitors
#12
Lamia W Mohamed, Osama M El-Badry, Afaf K El-Ansary, Ahmed Ismael
A new series of oxazolones and triazinones were designed and synthesized and evaluated against both COX-1 and COX-2 enzymes. Full structure elucidation of the new derivatives was performed using microanalyses, IR, 1H NMR, 13C NMR and mass spectra. Most of the derivatives showed good inhibitory activity against COX-2 enzyme specifically compounds IIIc, IIIe, IVd and IVg with IC50 values 0.024, 0.019, 0.011 and 0.014µM compared to celecoxib as reference drug with IC50 value of 0.05µM. Altogether, these results indicate that these derivatives can be effective anti-inflammatory agents...
April 24, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28499627/clinical-application-of-moskin-dosimeters-to-rectal-wall-in-vivo-dosimetry-in-gynecological-hdr-brachytherapy
#13
M Carrara, A Romanyukha, C Tenconi, D Mazzeo, A Cerrotta, M Borroni, D Cutajar, M Petasecca, M Lerch, J Bucci, A Richetti, S Presilla, C Fallai, G Gambarini, E Pignoli, A Rosenfeld
PURPOSE: Three MOSkins dosimeters were assembled over a rectal probe and used to perform in vivo dosimetry during HDR brachytherapy treatments of vaginal cancer. The purpose of this study was to verify the applicability of the developed tool to evaluate discrepancies between planned and measured doses to the rectal wall. MATERIALS AND METHODS: MOSkin dosimeters from the Centre for Medical Radiation Physics are particularly suitable for brachytherapy procedures for their ability to be easily incorporated into treatment instrumentation...
May 9, 2017: Physica Medica: PM
https://www.readbyqxmd.com/read/28499451/effects-of-annulus-defects-and-implantation-of-poly-lactic-co-glycolic-acid-plga-fibrin-gel-scaffolds-on-nerves-ingrowth-in-a-rabbit-model-of-annular-injury-disc-degeneration
#14
Long Xin, Weixing Xu, Leijun Yu, Shunwu Fan, Wei Wang, Fang Yu, Zhenbin Wang
BACKGROUND: Growth of nerve fibers has been shown to occur in a rabbit model of intravertebral disc degeneration (IVD) induced by needle puncture. As nerve growth may underlie the process of chronic pain in humans affected by disc degeneration, we sought to investigate the factors underlying nerve ingrowth in a minimally invasive annulotomy rabbit model of IVD by comparing the effects of empty disc defects with those of defects filled with poly(lactic-co-glycolic acid)/fibrin gel (PLGA) plugs...
May 12, 2017: Journal of Orthopaedic Surgery and Research
https://www.readbyqxmd.com/read/28498326/a-histopathological-scheme-for-the-quantitative-scoring-of-intervertebral-disc-degeneration-and-the-therapeutic-utility-of-adult-mesenchymal-stem-cells-for-intervertebral-disc-regeneration
#15
Cindy C Shu, Margaret M Smith, Susan M Smith, Andrew J Dart, Christopher B Little, James Melrose
The purpose of this study was to develop a quantitative histopathological scoring scheme to evaluate disc degeneration and regeneration using an ovine annular lesion model of experimental disc degeneration. Toluidine blue and Haematoxylin and Eosin (H&E) staining were used to evaluate cellular morphology: (i) disc structure/lesion morphology; (ii) proteoglycan depletion; (iii) cellular morphology; (iv) blood vessel in-growth; (v) cell influx into lesion; and (vi) cystic degeneration/chondroid metaplasia...
May 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28486045/in-vitro-generated-intervertebral-discs-towards-engineering-tissue-integration
#16
Jonathan Iu, Eric Massicotte, Shu-Qiu Li, Mark B Hurtig, Ehsan Toyserkani, J Paul Santerre, Rita Kandel
The intervertebral disc (IVD) is composed of nucleus pulposus (NP) surrounded by multilamellated annulus fibrosus (AF), and is located between the vertebral bodies. Current treatments for chronic neck or low back pain do not completely restore the functionality of degenerated IVDs. Thus developing biological disc replacements is an approach of great interest. Given the complex structure of the IVD, tissue engineering of the individual IVD components and then combining them together may be the only way to achieve this...
May 9, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28482118/autoantigens-adamtsl5-and-ll37-are-significantly-upregulated-in-active-psoriasis-and-localized-with-keratinocytes-dendritic-cells-and-other-leukocytes
#17
Judilyn Fuentes-Duculan, Kathleen M Bonifacio, Jason E Hawkes, Norma Kunjravia, Inna Cueto, Xuan Li, Juana Gonzalez, Sandra Garcet, James G Krueger
Psoriasis is a common immune-mediated disease that affects 2-4% of individuals in North America and Europe. In the past decade, advances in research have led to an improved understanding of immune pathways involved in the pathogenesis of psoriasis and has spurred the development of targeted therapeutics. Recently, three psoriasis autoantigens have been described: cathelicidin (LL37), a disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5), and lipid antigens generated by phospholipase A2 (PLA2) group IVD (PLA2G4D)...
May 8, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28475716/the-role-of-hypoxia-in-angiogenesis-and-extracellular-matrix-regulation-of-intervertebral-disc-cells-during-inflammatory-reactions
#18
Woo-Keun Kwon, Hong Joo Moon, Taek-Hyun Kwon, Youn-Kwan Park, Joo Han Kim
BACKGROUND: The intervertebral disc (IVD) is an avascular structure, and is therefore stable under hypoxic conditions. Previous studies have demonstrated that hypoxia might be related to symptomatic degenerative disc diseases (DDDs); however, the pathomechanism is still poorly understood. OBJECTIVE: To identify the effect of hypoxia on the production of inflammatory mediators, angiogenic factors, and extracellular matrix-regulating enzymes of IVD cells during inflammatory reactions...
May 5, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28473691/notochordal-and-nucleus-pulposus-marker-expression-is-maintained-by-sub-populations-of-adult-human-nucleus-pulposus-cells-through-aging-and-degeneration
#19
Stephen M Richardson, Francesca E Ludwinski, Kanna K Gnanalingham, Ross A Atkinson, Anthony J Freemont, Judith A Hoyland
The nucleus pulposus (NP) of the intervertebral disc (IVD) demonstrates substantial changes in cell and matrix composition with both ageing and degeneration. While recent transcriptomic profiling studies have helped define human NP cell phenotype, it remains unclear how expression of these markers is influenced by ageing or degeneration. Furthermore, cells of the NP are thought to derive from the notochord, although adult NP lacks identifiable notochordal (NC) cells. This study aimed to confirm expression of previously identified NP and NC marker genes in adult human NP cells from a range of ages and degenerate states...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28471866/newborn-congenital-cytomegalovirus-screening-based-on-clinical-manifestations-and-evaluation-of-dna-based-assays-for-in-vitro-diagnostics
#20
Tomoyuki Fujii, Akira Oka, Ichiro Morioka, Hiroyuki Moriuchi, Shin Koyano, Hideto Yamada, Shigeru Saito, Hiroshi Sameshima, Takeshi Nagamatsu, Shinya Tsuchida, Naoki Inoue
OBJECTIVES: To establish a strategy for congenital cytomegalovirus (cCMV) screening and to establish confirmatory assays approved as In Vitro diagnostics (IVD) by the regulatory authorities, we evaluated the clinical risks and performance of diagnostic assays developed by commercial companies, since cCMV infection has significant clinical consequences. STUDY DESIGN: Newborns with clinical manifestations considered to be consequences of cCMV infection (n=575) were screened for the presence of CMV DNA in urine specimens collected onto filter paper placed in their diapers using the PCR-based assay reported previously...
May 3, 2017: Pediatric Infectious Disease Journal
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