Infections of vascular prostheses are still a major risk in surgery. The current work presents an in vitro evaluation of novel slow release antibiotic coatings based on new gentamicin fatty acid ...salts for polytetrafluoroethylene grafts. These grafts were coated with gentamicin sodium dodecyl sulfate, gentamicin laurate and gentamicin palmitate. Drug release kinetics, anti-infective characteristics, biocompatibility and haemocompatibility of developed coatings were compared to commercially available gelatin sealed PTFE grafts (SEALPTFE™) and knitted silver coated Dacron
®
grafts (InterGard
®
). Each gentamicin fatty acid coating showed a continuous drug release in the first eight hours followed by a low continuous release. Grafts coated with gentamicin fatty acids reduced bacterial growth even beyond pathologically relevant high concentrations. Cytotoxicity levels depending on drug formulation bringing up gentamicin palmitate as the most promising biocompatible coating. Thrombelastography studies, ELISA assays and an amidolytic substrate assay confirmed haemocompatibility of developed gentamicin fatty acid coatings comparable to commercially available grafts.
Implant-associated infections are a challenging problem in surgery. Bacteria in biofilms are difficult to treat as they are less susceptible to antibiotics or antiseptics which require high drug ...concentrations at the site of infection. We present a novel strategy to concentrate high antibiotic doses systemically at the target site using newly developed antibiotic-functionalized nanoparticles directed by a magnetic drug-targeting system. The important and effective antibiotic gentamicin served as antimicrobial substance and was ionically or covalently attached to magnetic nanoparticles. Subsequently, the particles were characterized thoroughly. Anti-infective properties with regard to Staphylococcus aureus and the degree of cytotoxicity concerning human umbilical vein endothelial cells were determined. The enrichment of the magnetic nanoparticles at the surface of model tubes in circulatory experiments was investigated. We describe a promising technique for the loading of magnetic nanoparticles to treat systemic infections. Gentamicin-coated magnetic nanoparticles reduced bacterial growth even beyond pathologically relevant concentrations within 24 h. Excellent concentration independent biocompatibility was found for the nanoparticles themselves and we demonstrate that the magnetic nanoparticles can be navigated and concentrated on surfaces of model implants using a permanent magnetic field.
Wound infection is a complication feared in surgery. The aim of this study was to develop new anti-infective coatings of surgical sutures and to compare the anti-microbial effectiveness and ...biocompatibility to the well-established Vicryl Plus
®
. Synthetic absorbable PGA
surgical sutures were coated with three different chlorhexidine concentrations and two different octenidine concentrations in combination with palmitic acid and lauric acid. Drug-release kinetics lasting 96 h were studied in phosphate-buffered saline at 37°C. Anti-infective characteristics
were determined by measuring the change in optical density of Staphylococcus aureus suspensions charged with coated sutures over time. Microorganisms adsorbed at the surface of coated sutures were assessed on blood agar plates and coated sutures eluted for 24 h were placed on bacterial
lawns cultured on Mueller-Hinton plates to prove retained anti-microbial potency. A cell proliferation assay was performed to assess the degree of cytotoxicity. Anti-infective characteristics and biocompatibility were compared to Vicryl Plus
®
. A coating technology for
slow-release drug-delivery systems on surgical sutures could be developed. All coatings showed a continuous drug release within 96 h. Individual chlorhexidine and octenidine coated sutures showed superior anti-infective characteristics but inferior biocompatibility in comparison to Vicryl
Plus
®
. We conclude that the developed anti-infective suture coatings consisting of lipid-based drug-delivery systems in combination with antiseptics are highly effective against bacterial colonization in vitro; however, drug doses have to be adjusted to improve biocompatibility.
Dendritic cells (DCs) involved in proinflammatory immune responses derive mainly from peripheral monocytes, and the cells subsequently mature and migrate into the inflammatory micromilieu. Here we ...report that suppressing of 15-lipoxygenase-1 led to a substantial reduction in DC spreading and podosome formation in vitro. The surface expression of CD83 was significantly lower in both sh-15-lipoxygenase-1 (15-LOX-1)-transduced cells and DCs cultivated in the presence of a novel specific 15-LOX-1 inhibitor. The T-cell response against tetanus-pulsed DCs was only affected to a minor extent on inhibition of 15-LOX-1. In contrast, endocytosis and migration ability of DCs were significantly suppressed on 15-LOX-1 inhibition. The expression of 15-LOX-1 in DCs was also demonstrated in affected human skin in atopic and contact dermatitis, showing that the enzyme is indeed expressed in inflammatory diseases in vivo. This study demonstrated that inhibiting 15-LOX-1 led to an impaired podosome formation in DCs, and consequently suppressed antigen uptake and migration capacity. These results indicated that 15-LOX-1 is a potential target for inhibiting the trafficking of DCs to lymphoid organs and inflamed tissues and decreasing the inflammatory response attenuating symptoms of certain immunologic and inflammatory disorders such as dermatitis.-Han, H., Liang, X., Ekberg, M., Kritikou, J. S., Brunnström, Å., Pelcman, B., Matl, M., Miao, X., Andersson, M., Yuan, X., Schain, F., Parvin, S., Melin, E., Sjöberg, J., Xu, D., Westerberg, L. S., Björkholm, M., Claesson, H.-E. Human 15-lipoxygenase-1 is a regulator of dendritic-cell spreading and podosome formation.
The Heidelberg heavy ion cooler storage ring TSR Bisoffi, G.; Blum, M.; Friedrich, A. ...
Proceedings of the 1989 IEEE Particle Accelerator Conference, . 'Accelerator Science and Technology,
1989
Conference Proceeding
Commissioning of the Heidelberg Test Storage Ring (TSR) started in May 1988. The TSR is a low-energy cooler storage ring for heavy ions with energies up to 30 MeV/amu at a charge-to-mass ratio ...1/A=0.5. Phase space cooling for coasting beams as well as for bunched beams is routinely done by electron cooling. As the ring is fed by a tandem linac combination, stored intensities of up to 1*10/sup 10/ particles are obtained by combined stacking into transversal and longitudinal phase space (multiturn injection and RF stacking). This stacking method gives 800 times the number of stored ions compared to single-turn injection. Cooling oxygen and carbon beams resulted in a typical emittance of 0.3 pi mm-mrad and a momentum spread of Delta p/p=10/sup -4/. The equilibrium was mainly determined by intrabeam scattering, and the heating in the residual gas was mainly determined by multiple scattering. An overall increase of phase space density by six orders of magnitude was observed, similar to cooling results at proton machines. Results on the first year of operation with heavy ions at the TSR are reported.< >
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