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      1. Author :
        Bucki, Robert; Leszczynska, Katarzyna; Byfield, Fitzroy J; Fein, David E; Won, Esther; Cruz, Katrina; Namiot, Andrzej; Kulakowska, Alina; Namiot, Zbigniew; Savage, Paul B; Diamond, Scott L; Janmey, Paul A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Antimicrobial agents and chemotherapy
      6. Products :
      7. Volume :
        54
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Bacterial Infections; Biofilms; Cathelicidins; Cattle; Cells, Cultured; Dexamethasone; Drug Design; Humans; Interleukins; Macrophages; Microbial Sensitivity Tests; Neutrophils; Phagocytosis; Pseudomonas aeruginosa; Receptors, Glucocorticoid; Spermine; Staphylococcus aureus; Xen5
      12. Abstract :
        The rising number of antibiotic-resistant bacterial strains represents an emerging health problem that has motivated efforts to develop new antibacterial agents. Endogenous cationic antibacterial peptides (CAPs) that are produced in tissues exposed to the external environment are one model for the design of novel antibacterial compounds. Here, we report evidence that disubstituted dexamethasone-spermine (D2S), a cationic corticosteroid derivative initially identified as a by-product of synthesis of dexamethasone-spermine (DS) for the purpose of improving cellular gene delivery, functions as an antibacterial peptide-mimicking molecule. This moiety exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa present in cystic fibrosis (CF) sputa, and Pseudomonas aeruginosa biofilm. Although compromised in the presence of plasma, D2S antibacterial activity resists the proteolytic activity of pepsin and is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage (BAL) fluid. D2S also enhances S. aureus susceptibility to antibiotics, such as amoxicillin (AMC), tetracycline (T), and amikacin (AN). Inhibition of interleukin-6 (IL-6) and IL-8 release from lipopolysaccharide (LPS)- or lipoteichoic acid (LTA)-treated neutrophils in the presence of D2S suggests that this molecule might also prevent systemic inflammation caused by bacterial wall products. D2S-mediated translocation of green fluorescent protein (GFP)-labeled glucocorticoid receptor (GR) in bovine aorta endothelial cells (BAECs) suggests that some of its anti-inflammatory activities involve engagement of glucocorticoid receptors. The combined antibacterial and anti-inflammatory activities of D2S suggest its potential as an alternative to natural CAPs in the prevention and treatment of some bacterial infections.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20308375
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9996
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Lasers in surgery and medicine
      6. Products :
      7. Volume :
        39
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Anti-Infective Agents; Biofilms; Dental Pulp Cavity; Dental Pulp Diseases; Endodontics; Humans; Luminescence; Photochemotherapy; Polyethyleneimine; Porphyrins; Proteus Infections; Proteus mirabilis; Pseudomonas aeruginosa; Pseudomonas Infections; Xen5; Xen44
      12. Abstract :
        BACKGROUND AND OBJECTIVE To compare the effectiveness of antimicrobial photodynamic therapy (PDT), standard endodontic treatment and the combined treatment to eliminate bacterial biofilms present in infected root canals. STUDY DESIGN/MATERIALS AND METHODS Ten single-rooted freshly extracted human teeth were inoculated with stable bioluminescent Gram-negative bacteria, Proteus mirabilis and Pseudomonas aeruginosa to form 3-day biofilms in prepared root canals. Bioluminescence imaging was used to serially quantify bacterial burdens. PDT employed a conjugate between polyethylenimine and chlorin(e6) as the photosensitizer (PS) and 660-nm diode laser light delivered into the root canal via a 200-micro fiber, and this was compared and combined with standard endodontic treatment using mechanical debridement and antiseptic irrigation. RESULTS Endodontic therapy alone reduced bacterial bioluminescence by 90% while PDT alone reduced bioluminescence by 95%. The combination reduced bioluminescence by >98%, and importantly the bacterial regrowth observed 24 hours after treatment was much less for the combination (P<0.0005) than for either single treatment. CONCLUSIONS Bioluminescence imaging is an efficient way to monitor endodontic therapy. Antimicrobial PDT may have a role to play in optimized endodontic therapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17066481
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9997
      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 :
        Sadikot, Ruxana T; Zeng, Heng; Yull, Fiona E; Li, Bo; Cheng, Dong-sheng; Kernodle, Douglas S; Jansen, E Duco; Contag, Christopher H; Segal, Brahm H; Holland, Steven M; Blackwell, Timothy S; Christman, John W
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2004
      5. Publication :
        Journal of immunology (Baltimore, Md.: 1950)
      6. Products :
      7. Volume :
        172
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Cells, Cultured; Dose-Response Relationship, Immunologic; Immunity, Innate; Lung; Macrophages; Membrane Glycoproteins; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; NADPH Oxidase; Neutrophil Infiltration; NF-kappa B; Phosphoproteins; Pneumonia, Bacterial; Pseudomonas Infections; Receptors, Cell Surface; Signal Transduction; Toll-Like Receptors; Xen5
      12. Abstract :
        We examined the role of redox signaling generated by NADPH oxidase in activation of NF-kappaB and host defense against Pseudomonas aeruginosa pneumonia. Using mice with an NF-kappaB-driven luciferase reporter construct (HIV-LTR/luciferase (HLL)), we found that intratracheal administration of P. aeruginosa resulted in a dose-dependent neutrophilic influx and activation of NF-kappaB. To determine the effects of reactive oxygen species generated by the NADPH oxidase system on activation of NF-kappaB, we crossbred mice deficient in p47(phox) with NF-kappaB reporter mice (p47(phox-/-)HLL). These p47(phox-/-)HLL mice were unable to activate NF-kappaB to the same degree as HLL mice with intact NADPH oxidase following P. aeruginosa infection. In addition, lung TNF-alpha levels were significantly lower in p47(phox-/-)HLL mice compared with HLL mice. Bacterial clearance was impaired in p47(phox-/-)HLL mice. In vitro studies using bone marrow-derived macrophages showed that Toll-like receptor 4 was necessary for NF-kappaB activation following treatment with P. aeruginosa. Additional studies with macrophages from p47(phox-/-) mice confirmed that redox signaling was necessary for maximal Toll-like receptor 4-dependent NF-kappaB activation in this model. These data indicate that the NADPH oxidase-dependent respiratory burst stimulated by Pseudomonas infection contributes to host defense by modulating redox-dependent signaling through the NF-kappaB pathway.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/14734763
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9999
      1. Author :
        Yang, Li; Johansson, Jan; Ridsdale, Ross; Willander, Hanna; Fitzen, Michael; Akinbi, Henry T; Weaver, Timothy E
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Journal of immunology (Baltimore, Md.: 1950)
      6. Products :
      7. Volume :
        184
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Hydrogen-Ion Concentration; Immunity, Innate; Klebsiella pneumoniae; Macrophages, Alveolar; Mice; Mice, Transgenic; Protein Precursors; Protein Structure, Tertiary; Proteolipids; Saposins; Staphylococcus aureus; Tissue Distribution; Xen5
      12. Abstract :
        Surfactant protein B (SP-B) proprotein contains three saposin-like protein (SAPLIP) domains: a SAPLIP domain corresponding to the mature SP-B peptide is essential for lung function and postnatal survival; the function of SAPLIP domains in the N-terminal (SP-BN) and C-terminal regions of the proprotein is not known. In the current study, SP-BN was detected in the supernatant of mouse bronchoalveolar lavage fluid (BALF) and in nonciliated bronchiolar cells, alveolar type II epithelial cells, and alveolar macrophages. rSP-BN indirectly promoted the uptake of bacteria by macrophage cell lines and directly killed bacteria at acidic pH, consistent with a lysosomal, antimicrobial function. Native SP-BN isolated from BALF also killed bacteria but only at acidic pH; the bactericidal activity of BALF at acidic pH was completely blocked by SP-BN Ab. Transgenic mice overexpressing SP-BN and mature SP-B peptide had significantly decreased bacterial burden and increased survival following intranasal inoculation with bacteria. These findings support the hypothesis that SP-BN contributes to innate host defense of the lung by supplementing the nonoxidant antimicrobial defenses of alveolar macrophages.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20007532
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9995
      1. Author :
        Srivastava, Amit; Henneke, Philipp; Visintin, Alberto; Morse, Sarah C; Martin, Victoria; Watkins, Claire; Paton, James C; Wessels, Michael R; Golenbock, Douglas T; Malley, Richard
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        Infection and immunity
      6. Products :
      7. Volume :
        73
      8. Issue :
        10
      9. Page Numbers :
        6479-6487
      10. Research Area :
        N/A
      11. Keywords :
        Amino Acid Chloromethyl Ketones; Animals; Apoptosis; Bacterial Proteins; Caspases; Lipopolysaccharides; Macrophages; Mice; Mice, Inbred Strains; Nasopharynx; Pneumococcal Infections; Streptococcus pneumoniae; Streptolysins; Xen10
      12. Abstract :
        Pneumolysin, the cholesterol-dependent cytolysin of Streptococcus pneumoniae, induces inflammatory and apoptotic events in mammalian cells. Toll-like receptor 4 (TLR4) confers resistance to pneumococcal infection via its interaction with pneumolysin, but the underlying mechanisms remain to be identified. In the present study, we found that pneumolysin-induced apoptosis is also mediated by TLR4 and confers protection against invasive disease. The interaction between TLR4 and pneumolysin is direct and specific; ligand-binding studies demonstrated that pneumolysin binds to TLR4 but not to TLR2. Involvement of TLR4 in pneumolysin-induced apoptosis was demonstrated in several complementary experiments. First, macrophages from wild-type mice were significantly more prone to pneumolysin-induced apoptosis than cells from TLR4-defective mice. In gain-of-function experiments, we found that epithelial cells expressing TLR4 and stimulated with pneumolysin were more likely to undergo apoptosis than cells expressing TLR2. A specific TLR4 antagonist, B1287, reduced pneumolysin-mediated apoptosis in wild-type cells. This apoptotic response was also partially caspase dependent as preincubation of cells with the pan-caspase inhibitor zVAD-fmk reduced pneumolysin-induced apoptosis. Finally, in a mouse model of pneumococcal infection, pneumolysin-producing pneumococci elicited significantly more upper respiratory tract cell apoptosis in wild-type mice than in TLR4-defective mice, and blocking apoptosis by administration of zVAD-fmk to wild-type mice resulted in a significant increase in mortality following nasopharyngeal pneumococcal exposure. Overall, our results strongly suggest that protection against pneumococcal disease is dependent on the TLR4-mediated enhancement of pneumolysin-induced apoptosis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16177320
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        10001
      1. Author :
        Orihuela, Carlos J; Gao, Geli; Francis, Kevin P; Yu, Jun; Tuomanen, Elaine I
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2004
      5. Publication :
        The Journal of infectious diseases
      6. Products :
      7. Volume :
        190
      8. Issue :
        9
      9. Page Numbers :
        1661-1669
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bacteremia; Bacterial Proteins; Cerebrospinal Fluid; Disease Models, Animal; Female; Lung; Meningitis, Pneumococcal; Mice; Mice, Inbred BALB C; Mutation; N-Acetylmuramoyl-L-alanine Amidase; Nasopharynx; Neuraminidase; Pneumococcal Infections; Pneumonia, Pneumococcal; Pyruvate Oxidase; Streptococcus pneumoniae; Streptolysins; Virulence Factors; Xen7
      12. Abstract :
        We assessed the ability of Streptococcus pneumoniae mutants deficient in either choline binding protein A (CbpA), pneumolysin (Pln), pyruvate oxidase (SpxB), autolysin (LytA), pneumococcal surface protein A, or neuraminidase A (NanA) to replicate in distinct anatomical sites and translocate from one site to the next. Intranasal, intratracheal, and intravenous models of disease were assessed in 4-week-old BALB/cJ mice by quantitation of bacterial titers in the relevant organs. Mice were also observed by use of real-time bioluminescent imaging (BLI). BLI allowed visualization of the bacteria in sites not tested by sampling. All mutants were created in D39 Xen7, a fully virulent derivative of capsular type 2 strain D39 that contains an optimized luxABCDE cassette. NanA, SpxB, and, to a lesser extent, CbpA contributed to prolonged nasopharyngeal colonization, whereas CbpA and NanA contributed to the transition to the lower respiratory tract. Once lung infection was established, Pln, SpxB, and LytA contributed to bacterial replication in the lungs and translocation to the bloodstream. In the bloodstream, only Pln and LytA were required for high-titer replication, whereas CbpA was required for invasion of the cerebrospinal fluid. We conclude that transitions between body sites require virulence determinants distinct from those involved in organ-specific replication.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/15478073
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        10002
      1. Author :
        Min, Jung-Joon; Nguyen, Vu H.; Gambhir, Sanjiv S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Nuclear Medicine and Molecular Imaging
      6. Products :
      7. Volume :
        44
      8. Issue :
        1
      9. Page Numbers :
        15-24
      10. Research Area :
        N/A
      11. Keywords :
        Cancer; Cardiology; Gene delivery vector; Gene Therapy; Imaging / Radiology; Molecular Imaging; Nuclear Medicine; Oncology; Orthopedics; Xen26
      12. Abstract :
        Cancer persists as one of the most devastating diseases in the world. Problems including metastasis and tumor resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of present clinical treatments. To overcome these limitations, cancer gene therapy has been developed over the last two decades for a broad spectrum of applications, from gene replacement and knockdown to vaccination, each with different requirements for gene delivery. So far, a number of genes and delivery vectors have been investigated, and significant progress has been made with several gene therapy modalities in clinical trials. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications. However, both have limitations and risks that restrict gene therapy applications, including the complexity of production, limited packaging capacity, and unfavorable immunological features. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents such as bacteria, bacteriophages, and bacteria-like particles. Recently, many molecular imaging techniques for safe, repeated, and high-resolution in vivo imaging of gene expression have been employed to assess vector-mediated gene expression in living subjects. In this review, molecular imaging techniques for monitoring biological gene delivery vehicles are described, and the specific use of these methods at different steps is illustrated. Linking molecular imaging to gene therapy will eventually help to develop novel gene delivery vehicles for preclinical study and support the development of future human applications.
      13. URL :
        http://link.springer.com/article/10.1007/s13139-009-0006-3
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        10003
      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