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      1. Author :
        Emmett, M. S.; Lanati, S.; Dunn, D. B.; Stone, O. A.; Bates, D. O.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Microcirculation
      6. Products :
      7. Volume :
        18
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc,
      12. Abstract :
        OBJECTIVE: To determine whether chemotactic-metastasis, the preferential growth of melanomas towards areas of high lymphatic density, is CCL21/CCR7 dependent in vivo. Lymphatic endothelial cells (LECs) produce the chemokine CCL21. Metastatic melanoma cells express CCR7, its receptor, and exhibit chemotactic-metastasis, whereby metastatic cells recognise and grow towards areas of higher lymphatic density. METHODS: We used two in vivo models of directional growth towards depots of LECs of melanoma cells over-expressing CCR7. Injected LEC were tracked by intravital fluorescence microscopy, and melanoma growth by bioluminescence. RESULTS: Over-expression of the chemokine receptor CCR7 enables non-metastatic tumor cells to recognise and grow towards LECs (3.9 fold compared with control), but not blood endothelial cells (0.9 fold), in vitro and in vivo in the absence of increased lymphatic clearance. Chemotactic metastasis was inhibited by a CCL21 neutralising antibody (4-17% of control). Furthermore, CCR7 expression in mouse B16 melanomas resulted in in-transit metastasis (50-100% of mice) that was less often seen with control tumors (0-50%) in vivo. CONCLUSION: These results suggest that recognition of LEC by tumors expressing receptors for lymphatic specific ligands contributes towards the identification and invasion of lymphatics by melanoma cells and provides further evidence for a chemotactic metastasis model of tumor spread.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21166932
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10355
      1. Author :
        Stangenberg L, Ellson C, Cortez-Retamozo V, Ortiz-Lopez A, Yuan H, Blois J, Smith RA, Yaffe MB, Weissleder R, Benoist C, Mathis D, Josephson L and Mahmood U
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Arthritis and Rheumatism
      6. Products :
      7. Volume :
        60
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        Physiology
      11. Keywords :
        ProSense; AngioSense; arthritis; in vivo imaging
      12. Abstract :
        OBJECTIVE: To test a novel self-activating viridin (SAV) prodrug that slowly releases wortmannin, a potent phosphoinositide 3-kinase inhibitor, in a model of antibody-mediated inflammatory arthritis.

        METHODS: The SAV prodrug was administered to K/BxN mice or to C57BL/6 (B6) mice that had been injected with K/BxN serum. Ankle thickness was measured, and histologic changes were scored after a 10-day disease course (serum-transfer arthritis). Protease activity was measured by a near-infrared imaging approach using a cleavable cathepsin-selective probe. Further near-infrared imaging techniques were used to analyze early changes in vascular permeability after serum injection, as well as neutrophil-endothelial cell interactions. Neutrophil functions were assessed using an oxidative burst assay as well as a degranulation assay.

        RESULTS: SAV prevented ankle swelling in mice with serum-transfer arthritis in a dose-dependent manner. It also markedly reduced the extent of other features of arthritis, such as protease activity and histology scores for inflammation and joint erosion. Moreover, SAV was an effective therapeutic agent. The underlying mechanisms for the antiinflammatory activity were manifold. Endothelial permeability after serum injection was reduced, as was firm neutrophil attachment to endothelial cells. Endothelial cell activation by tumor necrosis factor alpha was impeded by SAV, as measured by the expression of vascular cell adhesion molecule. Crucial neutrophil functions, such as generation of reactive oxygen species and degranulation of protease-laden vesicles, were decreased by SAV administration.

        CONCLUSION: A novel SAV prodrug proved strongly antiinflammatory in a murine model of antibody-induced inflammatory arthritis. Its activity could be attributed, at least in part, to the inhibition of neutrophil and endothelial cell functions.
      13. URL :
        http://onlinelibrary.wiley.com/doi/10.1002/art.24704/abstract
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4528
      1. Author :
        Evans, L.; Williams, A.S.; Hayes, A.J.; Jones, S.A.; Nowell, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Arthritis and Rheumatism
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Apo866; Arthritis; In vivo; Living Image software; MMPSense 750 FAST; Xenogen Caliper IVIS 200
      12. Abstract :
        OBJECTIVE: Using APO866, studies assessed the ability of Pre-B-cell colony-Enhancing Factor (PBEF) to regulate inflammatory and degradative processes in fibroblasts and collagen-induced arthritis. METHODS: ELISAs were used to examine regulation of metalloproteinases and chemokine expression by HFF fibroblasts. PBEF was further examined in the collagen-induced arthritis model using APO866. Disease activity was assessed using radiography, histology, in vivo imaging and quantitative PCR (qPCR). RESULTS: In vitro activation of fibroblasts with PBEF promoted MMP-3, CCL-2 and CXCL-8 expression, an effect inhibited by APO866. Early intervention with APO866 in collagen-induced arthritis inhibited both synovial inflammation, including chemokine-directed leukocyte infiltration, and the systemic marker of inflammation, serum hyaluronic acid. Blockade of degenerative processes by APO866 was further illustrated by the reduced expression of MMP-3 and MMP-13 in joint extracts and reduction of the systemic marker of cartilage erosion, serum cartilage oligomeric matrix protein (COMP). Radiology showed that APO866 protected against bone erosion, whilst qPCR demonstrated inhibition of RANKL expression. APO866 treatment in established disease (clinical score >=5) reduced synovial inflammation, cartilage destruction and halted bone erosion. MMP-3, CCL-2 and RANKL activity, as assessed by in vivo imaging with MMPSense750 and qPCR were reduced in treated animals. qPCR of synovial explants from animals with CIA showed that APO866 inhibited MMP-3, CCL-2 and RANKL production, a result that was reversed with nicotinamide mononucleotide (NMN) CONCLUSIONS: These data confirm PBEF to be an important regulator of inflammation, cartilage catabolism and bone erosion, and highlights APO866 as a promising therapy for targeting PBEF activity in inflammatory arthritis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21400478
      14. Call Number :
        PKI @ user @ 8551
      15. Serial :
        4800
      1. Author :
        Nejadnik, M Reza; Engelsman, Anton F; Saldarriaga Fernandez, Isabel C; Busscher, Henk J; Norde, Willem; van der Mei, Henny C
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        The Journal of antimicrobial chemotherapy
      6. Products :
      7. Volume :
        62
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Bacterial Agents; Bioware; Colony Count, Microbial; Mice; Mice, Inbred BALB C; Polymers; Prostheses and Implants; Rifampin; Silicone Elastomers; Staphylococcus aureus; Vancomycin; Xen29
      12. Abstract :
        OBJECTIVES Curing biomaterial-associated infection (BAI) frequently includes antibiotic treatment, implant removal and re-implantation. However, revision implants are at a greater risk of infection as they may attract bacteria from their infected surroundings. Polymer brush-coatings attract low numbers of bacteria, but the virtue of polymer brush-coatings in vivo has seldom been investigated. Here, we determine the possible benefits of polymer brush-coated versus pristine silicone rubber in revision surgery, using a murine model. METHODS BAI was induced in 26 mice by subcutaneous implantation of silicone rubber discs with a biofilm of Staphylococcus aureus Xen29. During the development of BAI, half of the mice received rifampicin/vancomycin treatment. After 5 days, the infected discs were removed from all mice, and either a polymer brush-coated or pristine silicone rubber disc was re-implanted. Revision discs were explanted after 5 days, and the number of cfu cultured from the discs and the surrounding tissue was determined. RESULTS None of the polymer brush-coated discs after antibiotic treatment appeared colonized by staphylococci, whereas 83% of the pristine silicone rubber discs were re-infected. Polymer brush-coated discs also showed reduced colonization rates in the absence of antibiotic treatment when compared with pristine silicone rubber discs. Tissue surrounding the discs was culture-positive in all cases. CONCLUSIONS Polymer brush-coatings are less prone to re-infection than pristine silicone rubber when used in revision surgery, i.e. when implanted in a subcutaneous pocket infected by a staphylococcal BAI. Antibiotic pre-treatment during the development of BAI hardly had any effect in preventing the colonization of pristine silicone rubber.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18812426
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9045
      1. Author :
        Hart, Emily; Azzopardi, Kristy; Taing, Heng; Graichen, Florian; Jeffery, Justine; Mayadunne, Roshan; Wickramaratna, Malsha; O'Shea, Mike; Nijagal, Brunda; Watkinson, Rebecca; O'Leary, Stephen; Finnin, Barrie; Tait, Russell; Robins-Browne, Roy
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        The Journal of antimicrobial chemotherapy
      6. Products :
      7. Volume :
        65
      8. Issue :
        5
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Bacterial Agents; Bioware; Colony Count, Microbial; Disease Models, Animal; Female; Foreign Bodies; Humans; Mice; Mice, Inbred BALB C; Ofloxacin; Polymers; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus aureus; Xen29
      12. Abstract :
        OBJECTIVES To assess support discs, comprising polyethylene terephthalate (PET), coated with different polymer/levofloxacin combinations for antimicrobial activity in an animal model of infection, in order to explore the use of specific polymer coatings incorporating levofloxacin as a means of reducing device-related infections. METHODS Aliphatic polyester-polyurethanes containing different ratios of poly(lactic acid) diol and poly(caprolactone) diol were prepared, blended with levofloxacin and then used to coat support discs. The in vitro levofloxacin release profiles from these discs were measured in aqueous solution. Mice were surgically implanted with the coated discs placed subcutaneously and infection was initiated by injection of 10(6) cfu of Staphylococcus aureus into the subcutaneous pocket containing the implant. After 5, 10, 20 and 30 days, the discs were removed, and the number of bacteria adhering to the implant and the residual antimicrobial activity of the discs were determined. RESULTS In vitro, the release of levofloxacin from the coated discs occurred at a constant rate and then reached a plateau at different timepoints, depending on the polymer preparation used. In vivo, none of the discs coated with polymer blends containing levofloxacin was colonized by S. aureus, whereas 94% of the discs coated with polymer alone were infected. All discs coated with levofloxacin-blended polymers displayed residual antimicrobial activity for at least 20 days post-implantation. CONCLUSIONS Bioerodable polyester-polyurethane polymer coatings containing levofloxacin can prevent bacterial colonization of implants in an intra-operative model of device-related infections.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20233779
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9035
      1. Author :
        Yu, Jun; Wu, Jenny; Francis, Kevin P; Purchio, Tony F; Kadurugamuwa, Jagath L
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        The Journal of antimicrobial chemotherapy
      6. Products :
      7. Volume :
        55
      8. Issue :
        4
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Bacterial Agents; Biofilms; Bioware; Drug Resistance, Bacterial; Mice; Mutation; Rifampin; Staphylococcus aureus; Xen29
      12. Abstract :
        OBJECTIVES To investigate in vivo fitness of rifampicin-resistant Staphylococcus aureus mutants in a mouse biofilm model using bioluminescence imaging. MATERIALS AND METHODS S. aureus was engineered with a luciferase operon to emit bioluminescence that can be detected in vivo using an IVIS imaging system. Two rifampicin-resistant strains of S. aureus that were previously isolated from animals undergoing rifampicin treatment, S464P (resistant to low concentrations of rifampicin) and H481Y (resistant to high concentrations of rifampicin), were characterized and then compared with their parental strain for in vivo fitness to form biofilm infections in the absence of rifampicin. RESULTS The mutant S464P showed better adaptation to in vivo growth than either the parental strain or H481Y without selective pressure. Six days after implanting pre-colonized catheters, bioluminescent signals were seen from 100% of the catheters coated by the mutant S464P. In comparison, only 83% and 61% of the catheters coated by the parental strain and H481Y, respectively, maintained a signal in vivo. Rifampicin treatment of S464P biofilms in vivo resulted in a slight decline, but earlier rebound in bioluminescence from these catheters compared with the parental signal, whereas rifampicin had no affect on bioluminescence in mice infected with mutant H481Y. CONCLUSIONS The mutant with low-level rifampicin resistance appears to be better adapted to in vivo growth than the mutant that has high-level rifampicin resistance. Moreover, the former mutant may actually have a slight competitive advantage over the rifampicin-susceptible strain (parental), raising awareness for the occurrence of such strains in clinical environments.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/15743898
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9055
      1. Author :
        Lorenz, U.; Schafer, T.; Ohlsen, K.; Tiurbe, G. C.; Buhler, C.; Germer, C. T.; Kellersmann, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Eur J Vasc Endovasc Surg
      6. Products :
      7. Volume :
        41
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29, Acetates; Animals; *Biofilms; Bioprosthesis; Blood Vessel Prosthesis/*microbiology; Cattle; Colony Count, Microbial; Luminescent Measurements/*methods; Mice; Microbial Viability; Pericardium; *Photons; Polyesters; Polytetrafluoroethylene; Prospective Studies; Prosthesis-Related Infections/*diagnosis; Random Allocation; Silver Compounds; Staphylococcus aureus/isolation & purification/*physiology
      12. Abstract :
        OBJECTIVES: Biophotonic imaging was compared to standard enumeration method both for counting Staphylococcus aureus in biofilm and bacterial susceptibility tests of different graft materials. DESIGN: Prospective, randomized, controlled animal study. MATERIAL AND METHODS: Five types of vascular grafts were placed subcutaneously in 35 mice and challenged with bioluminescent S. aureus. The mice were divided into equal groups as follows: group A (polyester), group B (polytetrafluoroethylene), group C and D (two types of silver acetate-coated polyester) and group E (bovine pericardium). Controls were given only the bacteria. The bioluminescence signal of S. aureus, able to predict number of viable bacteria in biofilm without any manipulation, was measured at different time points. Five days postinfection, regular cultures of adherent bacteria on grafts were obtained. Comparative analyses between bioluminescence activity and culture enumeration were performed. RESULTS: The number of viable bacteria on silver-coated prostheses was the slightest, indicating superior bacterial resistance. The density of bacteria on polytetrafluoroethylene and polyester was comparable, with a non-significant advantage for polytetrafluoroethylene. Moreover, bioluminescence detected the number of viable S. aureus in biofilm more exactly compared to enumeration of bacteria. CONCLUSION: Bioluminescence imaging can be considered a useful tool to characterize susceptibility of any graft material to bacterial biofilm prior to implantation.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20943422
      14. Call Number :
        PKI @ kd.modi @ 12
      15. Serial :
        10453
      1. Author :
        Wen, D.; Qing, L.; Harrison, G.; Golub, E.; Akintoye, S. O.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Oral Dis
      6. Products :
      7. Volume :
        17
      8. Issue :
        N/A
      9. Page Numbers :
        427-32
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Maestro, Animals; Bone Density Conservation Agents/administration & dosage/*pharmacokinetics; Bone and Bones/*metabolism; Calcium/metabolism; Chelating Agents; Decalcification Technique; Diphosphonates/administration & dosage/*pharmacokinetics; Durapatite/metabolism; Edetic Acid; Female; Femur/metabolism; Fibula/metabolism; Fluorescent Dyes/diagnostic use; Fluorometry; Humerus/metabolism; Injections, Intravenous; Mandible/metabolism; Models, Animal; Radius/metabolism; Rats; Rats, Nude; Spectrophotometry, Atomic; Tibia/metabolism; Tissue Distribution; Ulna/metabolism
      12. Abstract :
        OBJECTIVES: Bisphosphonates commonly used to treat osteoporosis, Paget's disease, multiple myeloma, hypercalcemia of malignancy and osteolytic lesions of cancer metastasis have been associated with bisphosphonate-associated jaw osteonecrosis (BJON). The underlying pathogenesis of BJON is unclear, but disproportionate bisphosphonate concentration in the jaw has been proposed as one potential etiological factor. This study tested the hypothesis that skeletal biodistribution of intravenous bisphosphonate is anatomic site-dependent in a rat model system. MATERIALS AND METHODS: Fluorescently labeled pamidronate was injected intravenously in athymic rats of equal weights followed by in vivo whole body fluorimetry, ex vivo optical imaging of oral, axial, and appendicular bones and ethylenediaminetetraacetic acid bone decalcification to assess hydroxyapatite-bound bisphosphonate. RESULTS: Bisphosphonate uptake and bisphosphonate released per unit calcium were similar in oral and appendicular bones but lower than those in axial bones. Hydroxyapatite-bound bisphosphonate liberated by sequential acid decalcification was the highest in oral, relative to axial and appendicular bones (P < 0.05). CONCLUSIONS: This study demonstrates regional differences in uptake and release of bisphosphonate from oral, axial, and appendicular bones of immune deficient rats.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21122034
      14. Call Number :
        PKI @ kd.modi @ 11
      15. Serial :
        10467
      1. Author :
        Rahul Anil Sheth; Rabi Upadhyay; Lars Stangenberg; Rucha Sheth; Ralph Weissleder; Umar Mahmood
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Gynecologic Oncology
      6. Products :
      7. Volume :
        112
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        Ovarian cancer; Molecular imaging; Intraoperative imaging; Fluorescence imaging
      12. Abstract :
        OBJECTIVES: Cytoreductive surgery is a cornerstone of therapy in metastatic ovarian cancer. While conventional white light (WL) inspection detects many obvious tumor foci, careful histologic comparison has shown considerable miss rates for smaller foci. The goal of this study was to compare tumor detection using WL versus near infrared (NIR) imaging with a protease activatable probe, as well as to evaluate the ability to quantify NIR fluorescence using a novel quantitative optical imaging system.

        METHODS: A murine model for peritoneal carcinomatosis was generated and metastatic foci were imaged using WL and NIR imaging following the i.v. administration of the protease activatable probe ProSense750. The presence of tumor was confirmed by histology. Additionally, the ability to account for variations in fluorescence signal intensity due to changes in distance between the catheter and target lesion during laparoscopic procedures was evaluated.

        RESULTS: NIR imaging with a ProSense750 significantly improved upon the target-to-background ratios (TBRs) of tumor foci in comparison to WL imaging (minimum improvement was approximately 3.5 fold). Based on 52 histologically validated samples, the sensitivity for WL imaging was 69%, while the sensitivity for NIR imaging was 100%. The effects of intraoperative distance changes upon fluorescence intensity were corrected in realtime, resulting in a decrease from 89% to 5% in signal variance during fluorescence laparoscopy.

        CONCLUSIONS: With its molecular specificity, low background autofluorescence, high TBRs, and quantitative signal, optical imaging with NIR protease activatable probes greatly improves upon the intraoperative detection of ovarian cancer metastases.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19135233?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4497
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