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      1. Author :
        Bisland, Stuart K; Chien, Claudia; Wilson, Brian C; Burch, Shane
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Photochemical & photobiological sciences: Official journal of the European Photochemistry Association and the European Society for Photobiology
      6. Products :
      7. Volume :
        5
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Aminolevulinic Acid; Animals; Biofilms; Bioware; Cell Survival; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Implants, Experimental; Light; Luminescent Measurements; Methylene Blue; Osteomyelitis; Photochemotherapy; Photosensitizing Agents; Rats; Rats, Sprague-Dawley; Staphylococcus aureus; Xen29
      12. Abstract :
        Osteomyelitis can lead to severe morbidity and even death resulting from an acute or chronic inflammation of the bone and contiguous structures due to fungal or bacterial infection. Incidence approximates 1 in 1000 neonates and 1 in 5000 children in the United States annually and increases up to 0.36% and 16% in adults with diabetes or sickle cell anaemia, respectively. Current regimens of treatment include antibiotics and/or surgery. However, the increasing number of antibiotic resistant pathogens suggests that alternate strategies are required. We are investigating photodynamic therapy (PDT) as one such alternate treatment for osteomyelitis using a bioluminescent strain of biofilm-producing staphylococcus aureus (S. aureus) grown onto kirschner wires (K-wire). S. aureus-coated K-wires were exposed to methylene blue (MB) or 5-aminolevulinic acid (ALA)-mediated PDT either in vitro or following implant into the tibial medullary cavity of Sprague-Dawley rats. The progression of S. aureus biofilm was monitored non-invasively using bioluminescence and expressed as a percentage of the signal for each sample immediately prior to treatment. S. aureus infections were subject to PDT 10 days post inoculation. Treatment comprised administration of ALA (300 mg kg(-1)) intraperitoneally followed 4 h later by light (635 +/- 10 nm; 75 J cm(-2)) delivered transcutaneously via an optical fiber placed onto the tibia and resulted in significant delay in bacterial growth. In vitro, MB and ALA displayed similar cell kill with > or =4 log(10) cell kill. In vivo, ALA-mediated PDT inhibited biofilm implants in bone. These results confirm that MB or ALA-mediated PDT have potential to treat S. aureus cultures grown in vitro or in vivo using an animal model of osteomyelitis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16395425
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9054
      1. Author :
        Figg, William D; Li, Haiqing; Sissung, Tristan; Retter, Avi; Wu, Shenhong; Gulley, James L; Arlen, Phil; Wright, John J; Parnes, Howard; Fedenko, Kathy; Latham, Lea; Steinberg, Seth M; Jones, Elizabeth; Chen, Clara; Dahut, William
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        BJU international
      6. Products :
      7. Volume :
        99
      8. Issue :
        5
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Aged; Androgens; Animals; Antineoplastic Combined Chemotherapy Protocols; Aryl Hydrocarbon Hydroxylases; Bioware; Cytochrome P-450 Enzyme System; Estramustine; Genotype; Humans; Male; Mice; Mice, Nude; Middle Aged; PC-3M-luc; Prostatic Neoplasms; Survival Analysis; Taxoids; Thalidomide; Treatment Outcome
      12. Abstract :
        OBJECTIVE To evaluate the combination of docetaxel plus estramustine (which prolongs survival in patients with androgen-independent prostate cancer, AIPC), and thalidomide (that also adds to docetaxel activity), both pre-clinically and clinically in AIPC. PATIENTS, MATERIALS AND METHODS In the pre-clinical evaluation we injected PC3 cells subcutaneously into severely combined immunodeficient mice and started treatment after the tumour volume reached 50 mm3. We also evaluated the combination using luciferase-labelled PC3M-luc-C6 cells in nude mice. We enrolled 20 patients with metastatic progressive AIPC into a phase II clinical trial to evaluate this combination. Docetaxel (30 mg/m2) was administered every week, for 3 of 4 weeks. The dose of thalidomide was 200 mg/day and estramustine was given three times a day at 1, 2, 3, 8, 9, 10, 15, 16 and 17 days. RESULTS In the mice, thalidomide with docetaxel plus estramustine reduced tumour volume by 88% at 17 days vs the control treatment (p=0.001). The combination of docetaxel, estramustine and thalidomide nearly eradicated the signal from the luciferase-expressing PC3M cells in the metastasis model. Clinically, the progression-free time was 7.2 months with this combination; 18 of 20 patients had a decline of half or more in prostate-specific antigen level and two of 10 patients with soft-tissue lesions had a partial response on computed tomography. There were 24 grade 3 and two grade 4 complications associated with this combination. There was a statistically significant association between overall survival and the CYP1B1*3 genotype (P=0.013). CONCLUSION Docetaxel-based chemotherapy is now regarded as a standard regimen for metastatic AIPC. The combination of estramustine, docetaxel and thalidomide is an advantageous treatment in pre-clinical models of prostate cancer and is a safe, tolerable and active regimen in patients with AIPC.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17437439
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8970
      1. Author :
        Leszczynska, K.; Namiot, A.; Cruz, K.; Byfield, F. J.; Won, E.; Mendez, G.; Sokolowski, W.; Savage, P. B.; Bucki, R.; Janmey, P. A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Appl Microbiol
      6. Products :
      7. Volume :
        110
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen5, Xen 5, Pseudomonas aeruginosa Xen 5, Anti-Bacterial Agents/administration & dosage/*pharmacology/therapeutic; use; Antimicrobial Cationic Peptides/chemistry; Biofilms/drug effects; Cholic Acid/chemistry; Cystic Fibrosis/microbiology; Hemolysis/drug effects; Humans; *Poloxamer; Pseudomonas Infections/drug therapy; Pseudomonas aeruginosa/drug effects/growth & development; Skin Diseases, Bacterial/drug therapy; Staphylococcus aureus/drug effects; Steroids/administration & dosage/*pharmacology/therapeutic use; *Surface-Active Agents
      12. Abstract :
        AIMS: Ceragenin CSA-13 is a synthetic mimic of cationic antibacterial peptides, with facial amphiphilic morphology reproduced using a cholic acid scaffold. Previous data have shown that this molecule displays broad-spectrum antibacterial activity, which decreases in the presence of blood plasma. However, at higher concentrations, CSA-13 can cause lysis of erythrocytes. This study was designed to assess in vitro antibacterial and haemolytic activity of CSA-13 in the presence of pluronic F-127. METHODS AND RESULTS: CSA-13 bactericidal activity against clinical strains of bacteria associated with topical infections and in an experimental setting relevant to their pathophysiological environment, such as various epithelial tissue fluids and the airway sputum of patients suffering from cystic fibrosis (CF), was evaluated using minimum inhibitory and minimum bactericidal concentration (MIC/MBC) measurements and bacterial killing assays. We found that in the presence of pluronic F-127, CSA-13 antibacterial activity was only slightly decreased, but CSA-13 haemolytic activity was significantly inhibited. CSA-13 exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, including methicillin-resistant strains, Pseudomonas aeruginosa present in CF sputa, and biofilms formed by different Gram (+) and Gram (-) bacteria. CSA-13 bactericidal action is partially compromised in the presence of plasma, but is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid. The synergistic action of CSA-13, determined by the use of a standard checkerboard assay, reveals an increase in CSA-13 antibacterial activity in the presence of host defence molecules such as the cathelicidin LL-37 peptide, lysozyme, lactoferrin and secretory phospholipase A (sPLA). CONCLUSION: These results suggest that CSA-13 may be useful to prevent and treat topical infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Combined application of CSA-13 with pluronic F-127 may be beneficial by reducing CSA-13 toxicity.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20961363
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10389
      1. Author :
        Lee, H. L.; Chen, C. C.; Baasov, T.; Ron, Y.; Dougherty, J. P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Mol Ther
      6. Products :
      7. Volume :
        19
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        RediJect Coelenterazine h, XenoLight
      12. Abstract :
        Cells have developed a mechanism to discriminate between premature termination codons (PTCs) and normal stop codons during translation, sparking vigorous research to develop drugs promoting readthrough at PTCs to treat genetic disorders caused by PTCs. It was posed that this concept could also be applied to regulated gene therapy protocols by incorporating a PTC into a therapeutic gene, so active protein would only be made after administration of a readthrough agent. The strengths of the system are highlighted here by results demonstrating: (i) background expression levels were reduced to 0.01% to 0.0005% of wild type in unselected mass populations of cells depending upon the specific stop codon utilized and its position within the gene; (ii) expression levels responded well to multiple “On” and “Off” regulation cycles in vivo in human xenograft systems; (iii) the level of induction approached three logs using aminoglycoside activators including NB54, a newly synthesized aminoglycoside with significantly reduced toxicity; and (iv) expression levels could be appreciably altered when employing different promoters in a variety of cell types. These results strongly support the contention that this system should have important clinical applications when tight control of gene expression is required.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21587212
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10422
      1. Author :
        Kadioglu, A.; Brewin, H.; Hartel, T.; Brittan, J. L.; Klein, M.; Hammerschmidt, S.; Jenkinson, H. F.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Mol Oral Microbiol
      6. Products :
      7. Volume :
        25
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen10, Xen 10, Streptococcus pneumoniae Xen10, IVIS, Animals; Bacterial Adhesion; Bacterial Processes; Bacterial Proteins/*physiology; *Carrier State; Colony Count, Microbial; Female; Host-Pathogen Interactions; Lung/microbiology; Meningitis, Pneumococcal/microbiology; Mice; Models, Animal; Mutation; Nasopharynx/*microbiology; Pneumonia, Pneumococcal/complications; Sepsis/*microbiology; Streptococcus pneumoniae/*pathogenicity; Virulence Factors/physiology
      12. Abstract :
        Summary The pneumococcal cell surface protein PavA is a virulence factor associated with adherence and invasion in vitro. In this study we show in vivo that PavA is necessary for Streptococcus pneumoniae D39 colonization of the murine upper respiratory tract in a long-term carriage model, with PavA-deficient pneumococci being quickly cleared from nasopharyngeal tissue. In a pneumonia model, pavA mutants were not cleared from the lungs of infected mice and persisted to cause chronic infection, whereas wild-type pneumococci caused systemic infection. Hence, under the experimental conditions, PavA-deficient pneumococci appeared to be unable to seed from lung tissue into blood, although they survived in blood when administered intravenously. In a meningitis model of infection, levels of PavA-deficient pneumococci in blood and brain following intercisternal injection were significantly lower than wild type. Taken collectively these results suggest that PavA is involved in successful colonization of mucosal surfaces and in translocation of pneumococci across host barriers. Pneumococcal sepsis is a major cause of mortality worldwide so identification of factors such as PavA that are necessary for carriage and for translocation from tissue to blood is of clinical and therapeutic importance.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20331793
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10400
      1. Author :
        Joh, E. H.; Hollenbaugh, J. A.; Kim, B.; Kim, D. H.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        7
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        A549-luc-C8, A549-luc, IVIS, Bioware
      12. Abstract :
        While pharmacological inhibition of Akt kinase has been regarded as a promising anti-cancer strategy, most of the Akt inhibitors that have been developed are enzymatic inhibitors that target the kinase active site of Akt. Another key cellular regulatory event for Akt activation is the translocation of Akt kinase to the cell membrane from the cytoplasm, which is accomplished through the pleckstrin homology (PH) domain of Akt. However, compounds specifically interacting with the PH domain of Akt to inhibit Akt activation are currently limited. Here we identified a compound, lancemaside A (LAN-A), which specifically binds to the PH domain of Akt kinase. First, our mass spectra analysis of cellular Akt kinase isolated from cells treated with LAN-A revealed that LAN-A specifically binds to the PH domain of cellular Akt kinase. Second, we observed that LAN-A inhibits the translocation of Akt kinase to the membrane and thus Akt activation, as examined by the phosphorylation of various downstream targets of Akt such as GSK3beta, mTOR and BAD. Third, in a co-cultured cell model containing human lung epithelial cancer cells (A549) and normal human primary lung fibroblasts, LAN-A specifically restricts the growth of the A549 cells. LAN-A also displayed anti-proliferative effects on various human cancer cell lines. Finally, in the A549-luciferase mouse transplant model, LAN-A effectively inhibited A549 cell growth with little evident cytotoxicity. Indeed, the therapeutic index of LAN-A in this mouse model was >250, supporting that LAN-A is a potential lead compound for PH domain targeting as a safe anti-cancer Akt inhibitor.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23189201
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10524
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Brazilian dental journal
      6. Products :
      7. Volume :
        18
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Colony Count, Microbial; Cuspid; Dental Pulp Cavity; Disinfectants; Drug Combinations; Genetic Engineering; Humans; Hydrogen peroxide; Incisor; Luminescent Measurements; Luminescent Proteins; Maxilla; Pseudomonas aeruginosa; Root Canal Irrigants; Root Canal Preparation; Sensitivity and Specificity; Sodium Hypochlorite; Xen5
      12. Abstract :
        Microbial infection plays an important role in the development of pulp necrosis and formation of periapical lesions. In vitro and in vivo research in this field, traditionally microbiological culture methods using paper point sampling and quantitative culture, faces difficulties in completely removing bacteria from the root canal system and analyzing sequential procedures. This study employed genetically engineered bioluminescent bacteria and a light-sensitive imaging system to allow real-time visualization of the infection. Ten extracted teeth incubated with P. aeruginosa were treated by mechanical instrumentation with K-files (#30 K-file, #35 K-file and #40 K-file) and chemical irrigation with sodium hypochlorite and hydrogen peroxide. Irrigation alone reduced the contamination in 18%; the first chemomechanical sequence (instrumentation with a #30 K-file + irrigation) provided 41% of reduction; the second sequence (#35 K-file + irrigation) achieved 62%; and the complete therapy (#30 K-file + #35 K-file + #40 K-file + irrigation) achieved 93% of bacterial reduction. These results suggest that the endodontic treatment is dependent on the association of a chemical and mechanical approaches and that root canal enlargement improves bacterial reduction probably because the irrigation has more access to the apical third.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18176710
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9998
      1. Author :
        Curbelo, J; Moulton, K; Willard, S
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Theriogenology
      6. Products :
      7. Volume :
        73
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Cattle; Escherichia coli; Female; Genitalia, Female; Optical Phenomena; Photons; Xen14
      12. Abstract :
        The objectives of this study were to (1) characterize the photonic properties of Escherichia coli-Xen14 and (2) conduct photonic imaging of E. coli-Xen14 within bovine reproductive tract segments (RTS) ex vivo (Bos indicus). E. coli-Xen14 was grown for 24h in Luria Bertani medium (LB), with or without kanamycin (KAN). Every 24h, for an 8-d interval, inoculums were imaged and photonic emissions (PE) collected. Inoculums were subcultured and plated daily to determine the colony forming units (CFU) and ratio of photon emitters to nonemitters. In the second objective, abattoir-derived bovine reproductive tracts (n=9) were separated into posterior and anterior vagina, cervix, uterine body, and uterine horns. Two concentrations (3.2x10(8) and 3.2x10(6) CFU/200microL for relative [High] and [Low], respectively) of E. coli-Xen14 were placed in translucent tubes for detection of PE through RTS. The CFU did not differ (P=0.31) over time with or without KAN presence; they remained stable with 99.93% and 99.98% photon emitters, respectively. However, PE were lower (P<0.0001) in cultures containing KAN than in those containing no KAN (629.8+/-117.7 vs. 3012.0+/-423.5 relative lights units per second [RLU/sec], respectively). On average, the percentage of PE between RTS, for both concentrations, was higher (P<0.05) in the uterine body. In summary, E. coli-Xen14 remained stable with respect to the proportions of photon emitters with or without KAN (used to selectively culture E. coli-Xen14). However, KAN presence suppressed photonic activity. The ability to detect PE through various segments of the reproductive tract demonstrated the feasibility of monitoring the presence of E. coli-Xen14 in the bovine reproductive tract ex vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19819541
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        10004
      1. Author :
        Curbelo, J.; Moulton, K.; Willard, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Theriogenology
      6. Products :
      7. Volume :
        73
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen14, Xen 14, E. coli Xen14, IVIS, Animals; Cattle; Escherichia coli/*cytology/isolation & purification/physiology; Female; Genitalia, Female/*microbiology; Optical Phenomena; *Photons
      12. Abstract :
        The objectives of this study were to (1) characterize the photonic properties of Escherichia coli-Xen14 and (2) conduct photonic imaging of E. coli-Xen14 within bovine reproductive tract segments (RTS) ex vivo (Bos indicus). E. coli-Xen14 was grown for 24h in Luria Bertani medium (LB), with or without kanamycin (KAN). Every 24h, for an 8-d interval, inoculums were imaged and photonic emissions (PE) collected. Inoculums were subcultured and plated daily to determine the colony forming units (CFU) and ratio of photon emitters to nonemitters. In the second objective, abattoir-derived bovine reproductive tracts (n=9) were separated into posterior and anterior vagina, cervix, uterine body, and uterine horns. Two concentrations (3.2x10(8) and 3.2x10(6) CFU/200microL for relative [High] and [Low], respectively) of E. coli-Xen14 were placed in translucent tubes for detection of PE through RTS. The CFU did not differ (P=0.31) over time with or without KAN presence; they remained stable with 99.93% and 99.98% photon emitters, respectively. However, PE were lower (P<0.0001) in cultures containing KAN than in those containing no KAN (629.8+/-117.7 vs. 3012.0+/-423.5 relative lights units per second [RLU/sec], respectively). On average, the percentage of PE between RTS, for both concentrations, was higher (P<0.05) in the uterine body. In summary, E. coli-Xen14 remained stable with respect to the proportions of photon emitters with or without KAN (used to selectively culture E. coli-Xen14). However, KAN presence suppressed photonic activity. The ability to detect PE through various segments of the reproductive tract demonstrated the feasibility of monitoring the presence of E. coli-Xen14 in the bovine reproductive tract ex vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19819541
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10391
      1. Author :
        Lu, Z.; Dai, T.; Huang, L.; Kurup, D. B.; Tegos, G. P.; Jahnke, A.; Wharton, T.; Hamblin, M. R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Nanomedicine (Lond)
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen5, Xen 5, Pseudomonas aeruginosa Xen 5, Animals; Fullerenes/*chemistry; Male; Mice; Mice, Inbred BALB C; Photochemotherapy/*methods; Photosensitizing Agents/*chemistry; Pseudomonas Infections/*drug therapy; Pseudomonas aeruginosa/drug effects; Wound Infection/*drug therapy
      12. Abstract :
        AIMS: Fullerenes are under intensive study for potential biomedical applications. We have previously reported that a C60 fullerene functionalized with three dimethylpyrrolidinium groups (BF6) is a highly active broad-spectrum antimicrobial photosensitizer in vitro when combined with white-light illumination. We asked whether this high degree of in vitro activity would translate into an in vivo therapeutic effect in two potentially lethal mouse models of infected wounds. MATERIALS & METHODS: We used stable bioluminescent bacteria and a low light imaging system to follow the progress of the infection noninvasively in real time. An excisional wound on the mouse back was contaminated with one of two bioluminescent Gram-negative species, Proteus mirabilis (2.5 x 10(7) cells) and Pseudomonas aeruginosa (5 x 10(6) cells). A solution of BF6 was placed into the wound followed by delivery of up to 180 J/cm(2) of broadband white light (400-700 nm). RESULTS: In both cases there was a light-dose-dependent reduction of bioluminescence from the wound not observed in control groups (light alone or BF6 alone). Fullerene-mediated photodynamic therapy of mice infected with P. mirabilis led to 82% survival compared with 8% survival without treatment (p < 0.001). Photodynamic therapy of mice infected with highly virulent P. aeruginosa did not lead to survival, but when photodynamic therapy was combined with a suboptimal dose of the antibiotic tobramycin (6 mg/kg for 1 day) there was a synergistic therapeutic effect with a survival of 60% compared with a survival of 20% with tobramycin alone (p < 0.01). CONCLUSION: These data suggest that cationic fullerenes have clinical potential as an antimicrobial photosensitizer for superficial infections where red light is not needed to penetrate tissue.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21143031
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10390
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