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  • 1
    Digitale Medien
    Digitale Medien
    Oxford, UK; Malden, USA : Blackwell Science Ltd/Inc.
    Wound repair and regeneration 12 (2004), S. 0 
    ISSN: 1524-475X
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Topical prophylaxis against wound infection by an agent that is active against multi-resistant bacteria does not generate resistance and is rapidly cidal would be of great clinical benefit. Peptides of the innate immune system have long been known to protect a wide range of organisms from attack by bacterial and fungal pathogens. Helix BioMedix Inc. has developed a short bioactive peptide antimicrobial modeled after these peptides. HB-50 is an amphipathic cationic alpha-helical peptide that has broad spectrum activity and is rapidly microbicidal. These attributes make HB-50 an ideal candidate for wound infection prophylaxis. In vitro studies have demonstrated HB-50 to be active against both gram-positive and gram-negative bacteria killing 5–7 log orders of bacteria within minutes. In addition, this peptide has potent activity against Vancomycin and Mupirocin resistant S. aureus. Preliminary testing of the peptide in a rat abraded skin infection model has shown the peptide’s effectiveness in preventing wound infection while not inhibiting wound healing. Additionally, the HB-50 sequence has been specifically developed to be cost effective to manufacture and therefore is well suited for use as a topical antimicrobial agent.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Oxford, UK; Malden, USA : Blackwell Science Ltd/Inc.
    Wound repair and regeneration 12 (2004), S. 0 
    ISSN: 1524-475X
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Peptides of the innate immune system play a vital role in the protection and repair of almost all biological systems. Such peptides have been implicated in a range of activities associated with prevention of disease and modulation of innate immunity. HB107 is a derivative of one such peptide, Cecropin B, that has demonstrated efficacy in enhancing wound healing in both burn and incision animal models. HB107 has been evaluated for efficacy in a mouse incision model and for safety and efficacy in a pig burn wound model. Topical application of the peptide gives RE50(time needed for 50% re-epithelialization) values of 10.28 days for 500 ug/mL and 12.72 days for 100 ug/mL compared to control 16.45 days. Additionally the peptide was well tolerated in terms of safety both topically and in an IV acute toxicity mouse model with no adverse effects observed. HB107 not only demonstrated efficacy and safety, but due to being a relatively short synthetic peptide, costs significantly less to manufacture than the current approved therapies.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1524-475X
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Antimicrobial peptides are essential to innate host defense as effectors of pathogen clearance and can modify host cell behaviors to promote wound repair. While these two functions appear interrelated, it is unclear whether the ability to aid in wound repair requires inherent antimicrobial function. We hypothesized that the influence of antimicrobial peptides on wound repair is not dependent on antimicrobial function. To explore this, we analyzed the microbial killing activity of peptide fragments and correlated this with the ability to influence wound repair in mice. HB-107, a peptide lacking antimicrobial activity and originally derived from the antimicrobial cecropin B, showed up to 64 percent improvement in wound repair compared to scrambled peptide and vehicle controls, an effect comparable to treatment with recombinant human platelet-derived growth factor-BB (formulated as RegranexTM). Wounds treated with HB-107 showed keratinocyte hyperplasia and increased leukocyte infiltration. Furthermore, HB-107 stimulated interleukin-8 secretion from cultured endothelial cells, an effect that may explain the increase in leukocyte migration. These findings confirm that antimicrobial peptides can function as effectors of cutaneous wound repair. Moreover, this study furthers our understanding of antimicrobial peptides by showing that their wound repair properties can be independent of antimicrobial function.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1365-2958
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Biologie , Medizin
    Notizen: The Y. enterocolitica O:8 (YeO8) O-antigen repeat units consist of five sugar residues: N-acetyl-d-galactosamine (GalNAc), d-galactose (Gal), d-mannose (Man), l-fucose (Fuc), and 6-deoxy-d-gulose (6d-Gul). The nucleotide sequence of the O-antigen gene cluster of the YeO8 strain 8081-c was determined. Altogether, 18 open reading frames (ORFs) were identified and shown to be essential for O-antigen biosynthesis. We previously characterized the 3′-end of the O-antigen gene cluster and identified four genes: two for GDP-Man biosynthesis, one for UDP-Gal biosynthesis, and one for O-antigen polymerase. Based on sequence similarity, Tn5-insertion phenotypes and chemical analysis, the 14 new genes were assigned the following functions: four genes are involved in the biosynthesis of CDP-6d-Gul and two in GDP-Fuc biosynthesis. Five gene products were assigned sugar transferase functions and one gene product was similar to Wzx, the O-antigen flippase. Two genes remained unassigned. By genetic complementation we also showed that YeO8 O-antigen biosynthesis was dependent on N-acetyl-glucosaminyl:undecaprenylphosphate transferase (GlcNAc transferase), the WecA (formerly known as Rfe) protein. Data obtained from chemical-composition analysis suggest that in addition to being GlcNAc transferase, WecA may also function as a GalNAc transferase. Using a restriction-deficient derivative of Y. enterocolitica O:8 strain 8081, a rough mutant, designated 8081-R2, was isolated. 8081-R2 was complemented in trans with a cloned O-antigen gene cluster restoring surface O-antigen expression. The virulence of the wild-type strain and that of the complemented strain were significantly higher (approx. 100-fold) than that of the rough mutant in an orally infected mouse model, showing that YeO8 O-antigen is a virulence factor.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1365-2958
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Biologie , Medizin
    Notizen: The Yersinia enterocolitica O:3 lipopotysaccharide O-antigen is a homopotymer of 6-deoxy-L-altrose. The cloned rfb region was sequenced, and 10 open reading frames were identified. Transposon mutagenesis, deletion analysis and transcomplementatton experiments showed that eight of the genes, organized into two operons, rfbABC and rfbDEFGH, are essential for 0-antigen synthesis. Functional tandem promoters were identified upstream of both operons. Of the deduced polypeptides RfbA, RfbF and RfbG were similar to Salmonella proteins involved in the dTDP-l-rhamnose biosynthesis. Rhamnose and 6-deoxy-l-altrose are C3-epimers suggesting that analogous pathways function in their biosynthesis. RfbD and RfbE were similar to capsular polysaccharide export proteins, e.g. KpsM and KpsT of Escherichia coli. This and transposon mutagenesis showed that RfbD and RfbE function as O-antigen exporters.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1365-2958
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Biologie , Medizin
    Notizen: Lipopolysaccharide (LPS) is a glycolipid present in the outer membrane of all Gram-negative bacteria, and it is one of the signature molecules recognized by the receptors of the innate immune system. In addition to its lipid A portion (the endotoxin), its O-chain polysaccharide (the O-antigen) plays a critical role in the bacterium–host interplay and, in a number of bacterial pathogens, it is a virulence factor. We present evidence that, in Yersinia enterocolitica serotype O:8, a complex signalling network regulates O-antigen expression in response to temperature. Northern blotting and reporter fusion analyses indicated that temperature regulates the O-antigen expression at the transcriptional level. Promoter cloning showed that the O-antigen gene cluster contains two transcriptional units under the control of promoters Pwb1 and Pwb2. The activity of both promoters is under temperature regulation and is repressed in bacteria grown at 37°C. We demonstrate that the RosA/RosB efflux pump/potassium antiporter system and Wzz, the O-antigen chain length determinant, are indirectly involved in the regulation mainly affecting the activity of promoter Pwb2. The rosAB transcription, under the control of Pros, is activated at 37°C, and Pwb2 is repressed through the signals generated by the RosAB system activation, i.e. decreased [K+] and increased [H+]. The wzz transcription is under the control of Pwb2, and we show that, at 37°C, overexpression of Wzz downregulates slightly the Pwb1 and Pwb2 activities and more strongly the Pros activity, with the net result that more O-antigen is produced. Finally, we demonstrate that overexpression of Wzz causes membrane stress that activates the CpxAR two-component signal transduction system.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1572-901X
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary Two novel charge-transfer (CT) heteropoly complexes, (C8H12N2)5H7PMo12O40 (1) and (C8H12N2)3H3-PMo12O40·5H2O (2), prepared by reacting p-Me2NC6H4NH2 with the four-electron heteropoly blue H7PMo12O40·12H2O and heteropoly acid H3PMo12O40· xH2O, respectively, were characterized by elemental analysis, and u.v., i.r., XPS and e.s.r. spectroscopies. A sizable electron-transfer interaction occurs within the product molecules and the heteropoly anions retain their Keggin structure. Their third-order optical non-linearity coefficients were measured using the Z-scan technique at a concentration of 4.68 × 10−6 mol dm−3 for (1) and 2.79 × 10−6 mol dm−3 for (2), with I 0 = 2.38 × 1013 w m−2 and λ = 532nm. The ¦χ(3)¦ for (1) is 2.61 × 10−10 esu and ¦χ(3)¦ for (2) is 1.05 × 10−10 esu.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1572-901X
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The new complex alpha-H6P2W18O62middot 6phen middot 10H2O, consisting of the heteropolytungstophosphate α-H6P2W18 O62middotxH2O and organic substrate 1,10-phenanthroline (phen) has been synthesized and spectroscopically characterized. There appears to be a sizeable electron-transfer interaction between the electron-rich aromatic organic moiety and the inorganic acid, both in the solid state and in solution, and this interaction is thought to be responsible for the formation of the title compound, which exhibits second-order and third-order nonlinear optical responses of Isample2 omega=0.6IKDP2 omega and χ(3)=3.35*10-11esu, respectively.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 129 (1996), S. 137-142 
    ISSN: 0009-2940
    Schlagwort(e): Rhenium complexes ; Thiourea ; Clusters ; Chemistry ; Inorganic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: The reactions of Re2(CO)9(NCMe) and Re3(CO)10-(CH3CN)2(μ-H)3 with S=C(NEt2)N(H)(p-tolyl) have yielded the new compounds Re2(CO)9[S=C(NEt2)N(H)(p-tolyl)] (1) and Re3(CO)10(μ-SC(NEt2)N(H)(p-tolyl)](μ-H)3 (2) in 89% and 98% yields, respectively. Compounds 1 and 2 were characterized by single-crystal X-ray diffraction analyses. Compound 1 contains an S-coordinated S = C(NEt2)N(H)(p-tolyl) ligand terminally coordinated in an equatorial coordination site on one of the rhenium atoms. Compound 2 contains the first example of an S-coordinated bridging thiourea grouping. When solutions of 1 were heated to 97°C, it was transformed to the new compound {Re(CO)3[μ-SC(N-p-tolyl)(NEt2)]}2 (3) plus Re2(CO)10. Compound 3 is a centro-symmetrical dimer of the unit Re(CO)3[SC(N-p-tolyl)(NEt2)] in which the sulfur atom bridges the two rhenium atoms. The tolyl-substituted nitrogen atoms are coordinated to the rhenium atoms to form two Re-S-C-N rings.
    Zusätzliches Material: 3 Ill.
    Materialart: Digitale Medien
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  • 10
    ISSN: 0009-2940
    Schlagwort(e): Platinum ; Ruthenium ; Cluster anions ; Phosphanes ; Chemistry ; Inorganic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: The reactions of [Pt3Ru6(CO)21(μ-H)3(μ3-H)] (1) with PMe3 and PPh3 have produced the salts [Pt(PR3)3H]-[Pt3Ru6(CO)21(μ3-H)(μ-H)2], 5a and 5d, R = Me and Ph in the yields 9% and 22%, respectively. By contrast the reaction of 1 with PPh3 in the presence of Me3NO has yielded the phosphane-substituted derivative [Pt3Ru6(CO)20(PPh3)μ-H)3(μ3-H)] }(6) in 22% yield. Compounds 5a and 6 were characterized by single crystal X-ray diffraction analysis. Compounds 5a and 5d are salts of the anion [Pt3Ru6(CO)21(μ3-H)(μ-H)2]-. The anion contains a layer segregated Ru3Pt3Ru3 structure similar to that of 1 with two bridging hydride ligands on one Ru3 triangle and one semi-triply bridging hydride ligand on the other. The cation [Pt(PR3)3H]+ was evidently formed by the abstraction of platinum from other molecules of 1. Compound 6 is a PPh3 derivative of the parent 1 that also contains the layer segregated stacking of Ru3 and Pt3 triangles. The PPh3 ligand is coordinated to one of the ruthenium atoms in an axial position.
    Zusätzliches Material: 3 Ill.
    Materialart: Digitale Medien
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