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      1. Author :
        Liu, W. F.; Ma, M.; Bratlie, K. M.; Dang, T. T.; Langer, R.; Anderson, D. G.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        32
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        ProSense, IVIS, Animals; Biocompatible Materials/*adverse effects; Cells, Cultured; Free Radicals/metabolism; Immunohistochemistry; Male; Mice; Prostheses and Implants/*adverse effects; Reactive Oxygen Species/*metabolism
      12. Abstract :
        The non-specific host response to implanted biomaterials is often a key challenge of medical device design. To evaluate biocompatibility, measuring the release of reactive oxygen species (ROS) produced by inflammatory cells in response to biomaterial surfaces is a well-established method. However, the detection of ROS in response to materials implanted in vivo has not yet been demonstrated. Here, we develop a bioluminescence whole animal imaging approach to observe ROS released in response to subcutaneously-implanted materials in live animals. We compared the real-time generation of ROS in response to two representative materials, polystyrene and alginate, over the course of 28 days. High levels of ROS were observed near polystyrene, but not alginate implants, and persisted throughout the course of 28 days. Histological analysis revealed that high levels of ROS correlated not only with the presence of phagocytic cells at early timepoints, but also fibrosis at later timepoints, suggesting that ROS may be involved in both the acute and chronic phase of the foreign body response. These data are the first in vivo demonstration of ROS generation in response to implanted materials, and describe a novel technique to evaluate the host response.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21146868
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10428
      1. Author :
        Derwall, M.; Malhotra, R.; Lai, C. S.; Beppu, Y.; Aikawa, E.; Seehra, J. S.; Zapol, W. M.; Bloch, K. D.; Yu, P. B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Arterioscler Thromb Vasc Biol
      6. Products :
      7. Volume :
        32
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Anti-Inflammatory Agents/pharmacology; Antioxidants/pharmacology; Atherosclerosis/etiology/genetics/metabolism/pathology/*prevention & control; Bone Morphogenetic Protein Receptors, Type I/metabolism; Bone Morphogenetic Proteins/*antagonists & inhibitors/metabolism; Cardiovascular Agents/*pharmacology; Cholesterol, LDL/blood; Diet, High-Fat; Disease Models, Animal; Endothelial Cells/drug effects/metabolism; Fatty Liver/etiology/metabolism/prevention & control; Female; Hep G2 Cells; Humans; Lipoproteins, LDL/metabolism; Liver/drug effects/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Pyrazoles/*pharmacology; Pyrimidines/*pharmacology; Reactive Oxygen Species/metabolism; Receptors, LDL/deficiency/genetics; Recombinant Fusion Proteins/metabolism; Signal Transduction/*drug effects; Time Factors; Vascular Calcification/etiology/genetics/metabolism/pathology/*prevention &; control
      12. Abstract :
        OBJECTIVE: The expression of bone morphogenetic proteins (BMPs) is enhanced in human atherosclerotic and calcific vascular lesions. Although genetic gain- and loss-of-function experiments in mice have supported a causal role of BMP signaling in atherosclerosis and vascular calcification, it remains uncertain whether BMP signaling might be targeted pharmacologically to ameliorate both of these processes. METHODS AND RESULTS: We tested the impact of pharmacological BMP inhibition on atherosclerosis and calcification in LDL receptor-deficient (LDLR-/-) mice. LDLR-/- mice fed a high-fat diet developed abundant vascular calcification within 20 weeks. Prolonged treatment of LDLR-/- mice with the small molecule BMP inhibitor LDN-193189 was well-tolerated and potently inhibited development of atheroma, as well as associated vascular inflammation, osteogenic activity, and calcification. Administration of recombinant BMP antagonist ALK3-Fc replicated the antiatherosclerotic and anti-inflammatory effects of LDN-193189. Treatment of human aortic endothelial cells with LDN-193189 or ALK3-Fc abrogated the production of reactive oxygen species induced by oxidized LDL, a known early event in atherogenesis. Unexpectedly, treatment of mice with LDN-193189 lowered LDL serum cholesterol by 35% and markedly decreased hepatosteatosis without inhibiting HMG-CoA reductase activity. Treatment with BMP2 increased, whereas LDN-193189 or ALK3-Fc inhibited apolipoprotein B100 secretion in HepG2 cells, suggesting that BMP signaling contributes to the regulation of cholesterol biosynthesis. CONCLUSION: These results definitively implicate BMP signaling in atherosclerosis and calcification, while uncovering a previously unidentified role for BMP signaling in LDL cholesterol metabolism. BMP inhibition may be helpful in the treatment of atherosclerosis and associated vascular calcification.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22223731
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10469
      1. Author :
        Krespi, Y. P.; Kizhner, V.; Nistico, L.; Hall-Stoodley, L.; Stoodley, P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Am J Otolaryngol
      6. Products :
      7. Volume :
        32
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen31, Xen 31, MRSA, S. aureus, IVIS, Bioluminescence, Biofilms/drug effects/*radiation effects; Ciprofloxacin/*pharmacology; Culture Media; High-Energy Shock Waves; Humans; *Laser Therapy, Low-Level; Methicillin-Resistant Staphylococcus aureus/*growth &; development/physiology/*radiation effects; Microbial Sensitivity Tests; Reference Values; Sensitivity and Specificity; Spectroscopy, Near-Infrared; Staphylococcal Infections/drug therapy
      12. Abstract :
        OBJECTIVE: The aim of the study was to study the efficacy of 2 different lasers in vitro, in disrupting biofilm and killing planktonic pathogenic bacteria. MATERIALS AND METHODS: Biofilms of a stable bioluminescent of Staphylococcus aureus Xen 31 were grown in a 96-well microtiter plate for 3 days. The study included 7 arms: (a) control; (b) ciprofloxacin (3 mg/L, the established minimum inhibitory concentration [MIC]) alone; (c) shock wave (SW) laser alone; (d) near-infrared (NIR) laser alone; (e) SW laser and ciprofloxacin; (f) SW and NIR lasers; (g) SW, NIR lasers, and ciprofloxacin. The results were evaluated with an in vivo imaging system (IVIS) biophotonic system (for live bacteria) and optical density (OD) for total bacteria. RESULTS: Without antibiotics, there was a 43% reduction in OD (P < .05) caused by the combination of SW and NIR suggesting that biofilm had been disrupted. There was an 88% reduction (P < .05) in live biofilm. Ciprofloxacin alone resulted in a decrease of 28% of total live cells (biofilm remaining attached) and 58% of biofilm cells (both P > .05). Ciprofloxacin in combination with SW and SW + NIR lasers caused a decrease of more than 60% in total live biomass and more than 80% of biofilm cells, which was significantly greater than ciprofloxacin alone (P < .05). CONCLUSIONS: We have demonstrated an effective nonpharmacologic treatment method for methicillin-resistant Staphylococcus aureus (MRSA) biofilm disruption and killing using 2 different lasers. The preferred treatment sequence is a SW laser disruption of biofilm followed by NIR laser illumination. Treatment optimization of biofilm is possible with the addition of ciprofloxacin in concentrations consistent with planktonic MIC.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20434806
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10554
      1. Author :
        Goergen, C.J.; Azuma, J.; Barr, K.N.; Magdefessel, L.; Kallop, D.Y.; Gogineni, A.; Grewall, A.; Weimer, R.M.; Connolly, A.J.; Dalman, R.L.; Taylor, C.A.; Tsao, P.S.; Greve, J.M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Arteriosclerosis, Thrombosis, and Vascular Biology
      6. Products :
      7. Volume :
        31
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Aaa; abdominal aortic aneurysm; FX Pro Kodak molecular Imaging System; ImageJ software; in vivo imaging; jugular vein injection; mice; MMPSense 680; ProSense 750; tail vein injection; thoracic aorta; vascular
      12. Abstract :
        <AbstractText Label=“OBJECTIVE” NlmCategory=“OBJECTIVE”>To quantitatively compare aortic curvature and motion with resulting aneurysm location, direction of expansion, and pathophysiological features in experimental abdominal aortic aneurysms (AAAs).</AbstractText> <AbstractText Label=“METHODS AND RESULTS” NlmCategory=“RESULTS”>MRI was performed at 4.7 T with the following parameters: (1) 3D acquisition for vessel geometry and (2) 2D cardiac-gated acquisition to quantify luminal motion. Male 24-week-old mice were imaged before and after AAA formation induced by angiotensin II (AngII)-filled osmotic pump implantation or infusion of elastase. AngII-induced AAAs formed near the location of maximum abdominal aortic curvature, and the leftward direction of expansion was correlated with the direction of suprarenal aortic motion. Elastase-induced AAAs formed in a region of low vessel curvature and had no repeatable direction of expansion. AngII significantly increased mean blood pressure (22.7 mm Hg, P<0.05), whereas both models showed a significant 2-fold decrease in aortic cyclic strain (P<0.05). Differences in patterns of elastin degradation and localization of fluorescent signal from protease-activated probes were also observed.</AbstractText> <AbstractText Label=“CONCLUSIONS” NlmCategory=“CONCLUSIONS”>The direction of AngII aneurysm expansion correlated with the direction of motion, medial elastin dissection, and adventitial remodeling. Anterior infrarenal aortic motion correlated with medial elastin degradation in elastase-induced aneurysms. Results from both models suggest a relationship between aneurysm pathological features and aortic geometry and motion.</AbstractText>
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21071686
      14. Call Number :
        PKI @ user @ 8450
      15. Serial :
        4803
      1. Author :
        Ranganath, Sudhir H; Fu, Yilong; Arifin, Davis Y; Kee, Irene; Zheng, Lin; Lee, How-Sung; Chow, Pierce K-H; Wang, Chi-Hwa
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        31
      8. Issue :
        19
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antineoplastic Agents; Bioware; Brain Neoplasms; Cell Line, Tumor; Drug Implants; Glioblastoma; Male; Metabolic Clearance Rate; Mice; Mice, Inbred BALB C; Nanostructures; Paclitaxel; Treatment Outcome; U-87 MG-luc2
      12. Abstract :
        Pharmacokinetics and therapeutic efficacy of submicron/nanoscale, intracranial implants were evaluated for treating malignant glioblastoma in mice. 9.1% (w/w) paclitaxel-loaded polylactide-co-glycolide (PLGA) nanofiber discs (F3) were fabricated and characterized for morphology and size distribution. Along with F3, three other formulations, 9.1% (w/w) paclitaxel-loaded PLGA submicron-fiber discs (F2), 16.7% (w/w) paclitaxel-loaded PLGA microspheres entrapped in hydrogel matrices (H80 and M80) were intracranially implanted in BALB/c mice and the coronal brain sections were analyzed for bio-distribution of paclitaxel on 14, 28 and 42 days post-implantation. BALB/c nude mice with intracranial human glioblastoma (U87 MG-luc2) were used in the therapeutic efficacy study. Animals were randomized to intracranial implantation of F3 and H80 with paclitaxel dose of 10mg/kg, placebo F3, placebo H80, weekly intratumoral injection of Taxol (10mg/kg) or no treatment and the treatment response was analyzed by bioluminescence imaging and histological (H&E, Ki-67) examinations. Enhanced, therapeutic paclitaxel penetration (approximately 1 microm) in the mouse brain up to 5mm from the implant site even after 42 days post-implantation from F3 and H80 was confirmed and deduced to be diffusion/elimination controlled. F3 and H80 demonstrated significant (approximately 30 fold) tumor inhibition and significantly low tumor proliferation index after 41 days of treatment in comparison to sham and placebo controls. The submicron/nanoscale implants are able to demonstrate optimal paclitaxel pharmacokinetics in the brain/tumor with significant tumor inhibition in a glioblastoma xenograft model in mice and hence could be potentially useful to treat highly recurrent GBM.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20350766
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8942
      1. Author :
        Sjollema, Jelmer; Sharma, Prashant K; Dijkstra, Rene J B; van Dam, Gooitzen M; van der Mei, Henny C; Engelsman, Anton F; Busscher, Henk J
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        31
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Infective Agents; Bacteria; Bacterial Infections; Biocompatible Materials; Biofilms; Bioware; Coated Materials, Biocompatible; Fluorescent Dyes; Humans; Image Enhancement; Light; Luminescent Measurements; Luminescent Proteins; Microscopy, Fluorescence; Prosthesis-Related Infections; Sensitivity and Specificity; Xen29
      12. Abstract :
        This review presents the current state of Bioluminescence and Fluorescent Imaging technologies (BLI and FLI) as applied to Biomaterial-Associated Infections (BAI). BLI offers the opportunity to observe the in vivo course of BAI in small animals without the need to sacrifice animals at different time points after the onset of infection. BLI is highly dependent on the bacterial cell metabolism which makes BLI a strong reporter of viable bacterial presence. Fluorescent sources are generally more stable than bioluminescent ones and specifically targeted, which renders the combination of BLI and FLI a promising tool for imaging BAI. The sensitivity and spatial resolution of both imaging tools are, however, dependent on the imaging system used and the tissue characteristics, which makes the interpretation of images, in terms of the location and shape of the illuminating source, difficult. Tomographic reconstruction of the luminescent source is possible in the most modern instruments, enabling exact localization of a colonized implant material, spreading of infecting organisms in surrounding tissue and immunological tissue reactions. BLI studies on BAI have successfully distinguished between different biomaterials with respect to the development and clearance of BAI in vivo, simultaneously reducing animal use and experimental variation. It is anticipated that bio-optical imaging will become an indispensable technology for the in vivo evaluation of antimicrobial coatings.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19969345
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9038
      1. Author :
        Sjollema, J.; Sharma, P. K.; Dijkstra, R. J.; van Dam, G. M.; van der Mei, H. C.; Engelsman, A. F.; Busscher, H. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        31
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen14, Xen 14, E. coli Xen14, IVIS, Animals; Anti-Infective Agents/*pharmacology/therapeutic use; Bacteria/*drug effects/pathogenicity; Bacterial Infections/drug therapy/*etiology; Biocompatible Materials/*adverse effects/chemistry; Biofilms; Coated Materials, Biocompatible/chemistry; Fluorescent Dyes/chemistry/metabolism; Humans; Image Enhancement/methods; Light; Luminescent Measurements/instrumentation/*methods; Luminescent Proteins/metabolism; Microscopy, Fluorescence/instrumentation/*methods; Prosthesis-Related Infections/drug therapy/microbiology; Sensitivity and Specificity
      12. Abstract :
        This review presents the current state of Bioluminescence and Fluorescent Imaging technologies (BLI and FLI) as applied to Biomaterial-Associated Infections (BAI). BLI offers the opportunity to observe the in vivo course of BAI in small animals without the need to sacrifice animals at different time points after the onset of infection. BLI is highly dependent on the bacterial cell metabolism which makes BLI a strong reporter of viable bacterial presence. Fluorescent sources are generally more stable than bioluminescent ones and specifically targeted, which renders the combination of BLI and FLI a promising tool for imaging BAI. The sensitivity and spatial resolution of both imaging tools are, however, dependent on the imaging system used and the tissue characteristics, which makes the interpretation of images, in terms of the location and shape of the illuminating source, difficult. Tomographic reconstruction of the luminescent source is possible in the most modern instruments, enabling exact localization of a colonized implant material, spreading of infecting organisms in surrounding tissue and immunological tissue reactions. BLI studies on BAI have successfully distinguished between different biomaterials with respect to the development and clearance of BAI in vivo, simultaneously reducing animal use and experimental variation. It is anticipated that bio-optical imaging will become an indispensable technology for the in vivo evaluation of antimicrobial coatings.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19969345
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10397
      1. Author :
        Kwong, G. A.; von Maltzahn, G.; Murugappan, G.; Abudayyeh, O.; Mo, S.; Papayannopoulos, I. A.; Sverdlov, D. Y.; Liu, S. B.; Warren, A. D.; Popov, Y.; Schuppan, D.; Bhatia, S. N.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nat Biotechnol
      6. Products :
      7. Volume :
        31
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        VivoTag, IVIS, Vivotag
      12. Abstract :
        Biomarkers are becoming increasingly important in the clinical management of complex diseases, yet our ability to discover new biomarkers remains limited by our dependence on endogenous molecules. Here we describe the development of exogenously administered 'synthetic biomarkers' composed of mass-encoded peptides conjugated to nanoparticles that leverage intrinsic features of human disease and physiology for noninvasive urinary monitoring. These protease-sensitive agents perform three functions in vivo: they target sites of disease, sample dysregulated protease activities and emit mass-encoded reporters into host urine for multiplexed detection by mass spectrometry. Using mouse models of liver fibrosis and cancer, we show that these agents can noninvasively monitor liver fibrosis and resolution without the need for invasive core biopsies and substantially improve early detection of cancer compared with current clinically used blood biomarkers. This approach of engineering synthetic biomarkers for multiplexed urinary monitoring should be broadly amenable to additional pathophysiological processes and point-of-care diagnostics.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23242163
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10567
      1. Author :
        Fogal, Valentina; Richardson, Adam D; Karmali, Priya P; Scheffler, Immo E; Smith, Jeffrey W; Ruoslahti, Erkki
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Molecular and cellular biology
      6. Products :
      7. Volume :
        30
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Carbon; Carrier Proteins; Cell Death; Cell Line, Tumor; Cell Proliferation; Cell Survival; Electron Transport Complex I; Gene Knockdown Techniques; Humans; Mass Spectrometry; MDA-MB-231-D3H2LN cells; Mice; Mitochondria; Mitochondrial Proteins; Neoplasm Metastasis; Neoplasms; Oxidative Phosphorylation; Protein Biosynthesis; Protein Stability; Rotenone
      12. Abstract :
        p32/gC1qR/C1QBP/HABP1 is a mitochondrial/cell surface protein overexpressed in certain cancer cells. Here we show that knocking down p32 expression in human cancer cells strongly shifts their metabolism from oxidative phosphorylation (OXPHOS) to glycolysis. The p32 knockdown cells exhibited reduced synthesis of the mitochondrial-DNA-encoded OXPHOS polypeptides and were less tumorigenic in vivo. Expression of exogenous p32 in the knockdown cells restored the wild-type cellular phenotype and tumorigenicity. Increased glucose consumption and lactate production, known as the Warburg effect, are almost universal hallmarks of solid tumors and are thought to favor tumor growth. However, here we show that a protein regularly overexpressed in some cancers is capable of promoting OXPHOS. Our results indicate that high levels of glycolysis, in the absence of adequate OXPHOS, may not be as beneficial for tumor growth as generally thought and suggest that tumor cells use p32 to regulate the balance between OXPHOS and glycolysis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20100866
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8952
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