Effect of dexamethasone prodrug on inflamed temporomandibular joints in juvenile rats

Introduction: Juvenile idiopathic arthritis (JIA) often causes inflammation of the temporomandibular joint (TMJ) and has been treated with both systemic and intra-articular steroids, with concerns about effects on growing bones. In this study, we evaluated the impact of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting potential applied systemically or directly to the TMJ. Methods: Joint inflammation was initiated by injecting two doses of complete Freund’s adjuvant (CFA) at 1-month intervals into the right TMJs of 24 growing Sprague–Dawley male rats (controls on left side). Four additional rats were not manipulated. With the second CFA injection, animals received (1) 5 mg of P-DEX intra-articularly (n = 9), (2) 15 mg of P-DEX into the tail vein (n = 7), or (3) nothing in addition to CFA (n = 8). The rats were killed 28 days later and measured by radiography for ramus height (condylar superior to gonion inferior [CsGoInf]), by micro-computed tomography for condylar width (CW) and bone volume/standardized condylar volume (BV/CV), and by histology for retrodiscal inflammatory cells. Inflammation targeting of systemic P-DEX was confirmed by IVIS infrared dye imaging. Inflammation and bone growth were compared between groups using analysis of variance and Pearson’s correlations. Results: CFA caused a significant reduction in CsGoInf (p \u3c 0.05), but neither route of P-DEX administration had an effect on CsGoInf or CW at CFA injection sites. BV/CV was significantly reduced in both inflamed and control condyles as a result of either steroid application (p \u3c 0.05). The inflammatory infiltrate was overwhelmingly lymphocytic, comprising 16.4 ± 1.3 % of the field in CFA alone vs. 2; p = 0.009), but not in the group that received intra-articular P-DEX (8.8 ± 1.2 mm2). Conclusions: High-dose systemic administration of inflammation-targeting P-DEX is more effective than an intra-articular injection in reducing TMJ inflammation, but both routes may affect TMJ bone density

Effect of dexamethasone prodrug on inflamed temporomandibular joints in juvenile rats

Introduction: Juvenile idiopathic arthritis (JIA) often causes inflammation of the temporomandibular joint (TMJ) and has been treated with both systemic and intra-articular steroids, with concerns about effects on growing bones. In this study, we evaluated the impact of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting potential applied systemically or directly to the TMJ. Methods: Joint inflammation was initiated by injecting two doses of complete Freund’s adjuvant (CFA) at 1-month intervals into the right TMJs of 24 growing Sprague–Dawley male rats (controls on left side). Four additional rats were not manipulated. With the second CFA injection, animals received (1) 5 mg of P-DEX intra-articularly (n = 9), (2) 15 mg of P-DEX into the tail vein (n = 7), or (3) nothing in addition to CFA (n = 8). The rats were killed 28 days later and measured by radiography for ramus height (condylar superior to gonion inferior [CsGoInf]), by micro-computed tomography for condylar width (CW) and bone volume/standardized condylar volume (BV/CV), and by histology for retrodiscal inflammatory cells. Inflammation targeting of systemic P-DEX was confirmed by IVIS infrared dye imaging. Inflammation and bone growth were compared between groups using analysis of variance and Pearson’s correlations. Results: CFA caused a significant reduction in CsGoInf (p \u3c 0.05), but neither route of P-DEX administration had an effect on CsGoInf or CW at CFA injection sites. BV/CV was significantly reduced in both inflamed and control condyles as a result of either steroid application (p \u3c 0.05). The inflammatory infiltrate was overwhelmingly lymphocytic, comprising 16.4 ± 1.3 % of the field in CFA alone vs. 2; p = 0.009), but not in the group that received intra-articular P-DEX (8.8 ± 1.2 mm2). Conclusions: High-dose systemic administration of inflammation-targeting P-DEX is more effective than an intra-articular injection in reducing TMJ inflammation, but both routes may affect TMJ bone density

Effect of dexamethasone prodrug on inflamed temporomandibular joints in juvenile rats.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) often causes inflammation of the temporomandibular joint (TMJ) and has been treated with both systemic and intra-articular steroids, with concerns about effects on growing bones. In this study, we evaluated the impact of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting potential applied systemically or directly to the TMJ. METHODS: Joint inflammation was initiated by injecting two doses of complete Freund\u27s adjuvant (CFA) at 1-month intervals into the right TMJs of 24 growing Sprague-Dawley male rats (controls on left side). Four additional rats were not manipulated. With the second CFA injection, animals received (1) 5 mg of P-DEX intra-articularly (n = 9), (2) 15 mg of P-DEX into the tail vein (n = 7), or (3) nothing in addition to CFA (n = 8). The rats were killed 28 days later and measured by radiography for ramus height (condylar superior to gonion inferior [CsGoInf]), by micro-computed tomography for condylar width (CW) and bone volume/standardized condylar volume (BV/CV), and by histology for retrodiscal inflammatory cells. Inflammation targeting of systemic P-DEX was confirmed by IVIS infrared dye imaging. Inflammation and bone growth were compared between groups using analysis of variance and Pearson\u27s correlations. RESULTS: CFA caused a significant reduction in CsGoInf (p \u3c 0.05), but neither route of P-DEX administration had an effect on CsGoInf or CW at CFA injection sites. BV/CV was significantly reduced in both inflamed and control condyles as a result of either steroid application (p \u3c 0.05). The inflammatory infiltrate was overwhelmingly lymphocytic, comprising 16.4 ± 1.3 % of the field in CFA alone vs. CONCLUSIONS: High-dose systemic administration of inflammation-targeting P-DEX is more effective than an intra-articular injection in reducing TMJ inflammation, but both routes may affect TMJ bone density

Growth factor release from a chemically modified elastomeric poly(1,8‐octanediol‐co‐citrate) thin film promotes angiogenesis in vivo

The ultimate success of in vivo organ formation utilizing ex vivo expanded “starter” tissues relies heavily upon the level of vascularization provided by either endogenous or artificial induction of angiogenic or vasculogenic events. To facilitate proangiogenic outcomes and promote tissue growth, an elastomeric scaffold previously shown to be instrumental in the urinary bladder regenerative process was modified to release proangiogenic growth factors. Carboxylic acid groups on poly(1,8‐octanediol‐co‐citrate) films (POCfs) were modified with heparan sulfate creating a heparan binding POCf (HBPOCf). Release of proangiogenic growth factors vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and insulin‐like growth factor 1 (IGF‐1) from HBPOCfs demonstrated an approximate threefold increase over controls during a 30‐day time course in vitro . Atomic force microscopy demonstrated significant topological differences between films. Subcutaneous implantation of POCf alone, HBPOCf, POCf‐VEGF, and HBPOCf‐VEGF within the dorsa of nude rats yielded increased vascular growth in HBPOCf‐VEGF constructs. Vessel quantification studies revealed that POCfs alone contained 41.1 ± 4.1 vessels/mm 2 , while HBPOCf, POCf‐VEGF, and HBPOCF‐VEGF contained 41.7 ± 2.6, 76.3 ± 9.4, and 167.72 ± 15.3 vessels/mm 2 , respectively. Presence of increased vessel growth was demonstrated by CD31 and vWF immunostaining in HBPOCf‐VEGF implanted areas. Data demonstrate that elastomeric POCfs can be chemically modified and possess the ability to promote angiogenesis in vivo . © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90248/1/33306_ftp.pd

Green Propellant Infusion Mission Program Development and Technology Maturation

The NASA Space Technology Mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) Technology Demonstration Mission (TDM) is comprised of a cross-cutting team of domestic spacecraft propulsion and storable green propellant technology experts. This TDM is led by Ball Aerospace & Technologies Corp. (BATC), who will use their BCP- 100 spacecraft to carry a propulsion system payload consisting of one 22 N thruster for primary divert (DeltaV) maneuvers and four 1 N thrusters for attitude control, in a flight demonstration of the AF-M315E technology. The GPIM project has technology infusion team members from all three major market sectors: Industry, NASA, and the Department of Defense (DoD). The GPIM project team includes BATC, includes Aerojet Rocketdyne (AR), Air Force Research Laboratory, Aerospace Systems Directorate, Edwards AFB (AFRL), NASA Glenn Research Center (GRC), NASA Kennedy Space Center (KSC), and NASA Goddard Space Flight Center (GSFC). STMD programmatic and technology oversight is provided by NASA Marshall Space Flight Center. The GPIM project shall fly an operational AF-M315E green propulsion subsystem on a Ball-built BCP-100 spacecraft

Discrimination of fresh frozen non-tumour and tumour brain tissue using spectrochemical analyses and a classification model

Introduction: In order for brain tumours to be successfully treated, maximal resection is beneficial. A method to detect infiltrative tumour edges intraoperatively, improving on current methods would be clinically useful. Vibrational spectroscopy offers the potential to provide a handheld, reagent-free method for tumour detection. Purpose: This study was designed to determine the ability of both Raman and Fourier-transform infrared (FTIR) spectroscopy towards differentiating between normal brain tissue, glioma or meningioma. Method: Unfixed brain tissue, which had previously only been frozen, comprising normal, glioma or meningioma tissue was placed onto calcium fluoride slides for analysis using Raman and attenuated total reflection (ATR)-FTIR spectroscopy. Matched haematoxylin and eosin slides were used to confirm tumour areas. Analyses were then conducted to generate a classification model. Results: This study demonstrates the ability of both Raman and ATR-FTIR spectroscopy to discriminate tumour from non-tumour fresh frozen brain tissue with 94% and 97.2% of cases correctly classified, with sensitivities of 98.8% and 100%, respectively. This decreases when spectroscopy is used to determine tumour type. Conclusion: The study demonstrates the ability of both Raman and ATR-FTIR spectroscopy to detect tumour tissue from non-tumour brain tissue with a high degree of accuracy. This demonstrates the ability of spectroscopy when targeted for a cancer diagnosis. However, further improvement would be required for a classification model to determine tumour type using this technology, in order to make this tool clinically viable

Particle export from the upper ocean over the continental shelf of the west Antarctic Peninsula: A long-term record, 1992–2007

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 55 (2008): 2118-2131, doi:10.1016/j.dsr2.2008.04.028.Includes supplemental materialsWe report on results of a long-term (1993-2007) time series sediment trap moored at 170 m to the west of the Antarctic Peninsula in the mid-continental shelf region (350 m depth; 64º30’ S, 66º00’ W). This is a region characterized by late spring-summer diatom blooms, moderately high seasonal primary productivity (50-150 mmol C m-2 d-1 in December-February) and high phytoplankton and krill biomass in the seasonal sea ice zone. The mass flux ranged from near 0 to over 1 g m-2 d-1 and was near 0 to >30% organic carbon (mean 8%). Sedimentation from the upper ocean as estimated by the trap collections at 170 m exhibited strong seasonality with high fluxes (1-10 mmol C m-2 d-1) in November-March following ice retreat and very low fluxes (<0.001 mmol C m-2 d-1) during the Austral winter and under sea ice cover. An average of 85% of the annual export of 212 mmol C m-2 occurred during the seasonal peak flux episodes. Over the trap record, the annual peak flux episode has tended to occur later in the Austral summer, advancing by about 40 days since 1993. The time-integrated sedimentation during the peak flux episode was <1 – 50% of the SeaWiFS-estimated primary production (mean 4%) at the trap site over the period 1998-2006. The elemental composition of material captured in the traps had an average C:N:P of 212:28:1, greater than the canonical Redfield values. High C:P ratios (400- 600) corresponded with the annual flux peak, indicating preferential loss of P from the sinking particles in the summer, ice-free period. The composition of the exported material more closely approximated the Redfield composition during the low-flux, winter period.This research was supported by NSF Grants OPP 9011927, 9632763 and 0217282 for the Palmer Long Term Ecological Research project

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population

Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population