Journal Article

Xen36, Xen 36, Staphylococcus aureus Xen36, IVIS

Most animal studies indicate that early irrigation and debridement reduce infection after an open fracture. Unfortunately, these studies often do not involve antibiotics. Clinical studies indicate that the timing of initial debridement does not affect the rate of infection but these studies are observational and fraught with confounding variables. The purpose of this study was to control these variables using an animal model incorporating systemic antibiotics and surgical treatment. We used a rat femur model with a defect which was contaminated with Staphylococcus aureus and treated with a three-day course of systemic cefazolin (5 mg/kg 12-hourly) and debridement and irrigation, both of which were initiated independently at two, six and 24 hour time points. After 14 days the bone and hardware were harvested for separate microbiological analysis. No animal that received antibiotics and surgery two hours after injury had detectable bacteria. When antibiotics were started at two hours, a delay in surgical treatment from two to six hours significantly increased the development of infection (p = 0.047). However, delaying surgery to 24 hours increase the rate of infection, but not significantly (p = 0.054). The timing of antibiotics had a more significant effect on the proportion of positive samples than earlier surgery. Delaying antibiotics to six or 24 hours had a profoundly detrimental effect on the infection rate regardless of the timing of surgery. These findings are consistent with the concept that bacteria progress from a vulnerable planktonic form to a treatment-resistant biofilm.

Journal Article

IVIS, Xenogen, Xen30, Xen5, Xen41

Bacterial biofilms are resistant to conventional antimicrobial agents. Prior in vitro studies have shown that electrical current (EC) enhances the activities of aminoglycosides, quinolones, and oxytetracycline against Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus epidermidis, Escherichia coli, and Streptococcus gordonii. This phenomenon, known as the bioelectric effect, has been only partially defined. The purpose of this work was to study the in vitro bioelectric effect on the activities of 11 antimicrobial agents representing a variety of different classes against P. aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and S. epidermidis. An eight-channel current generator/controller and eight chambers delivering a continuous flow of fresh medium with or without antimicrobial agents and/or EC to biofilm-coated coupons were used. No significant decreases in the numbers of log10 CFU/cm2 were seen after exposure to antimicrobial agents alone, with the exception of a 4.57-log-unit reduction for S. epidermidis and trimethoprim-sulfamethoxazole. We detected a statistically significant bioelectric effect when vancomycin plus 2,000 microamperes EC were used against MRSA biofilms (P = 0.04) and when daptomycin and erythromycin were used in combination with 200 or 2,000 microamperes EC against S. epidermidis biofilms (P = 0.02 and 0.0004, respectively). The results of these experiments indicate that the enhancement of the activity of antimicrobial agents against biofilm organisms by EC is not a generalizable phenomenon across microorganisms and antimicrobial agents.

Journal Article

LnCaP-luc2, Prostate Cancer, IVIS, *Gene Silencing; *Gold; Metal Nanoparticles/*chemistry/ultrastructure; Microscopy, Electron, Transmission; Polylysine/chemistry; RNA, Small Interfering/*genetics

Small interfering RNA (siRNA) has been widely proposed to treat various diseases by silencing genes, but its delivery remains a challenge. A well controlled assembly approach is applied to prepare a protease-assisted nanodelivery system. Protease-degradable poly-L-lysine (PLL) and siRNA are fabricated onto gold nanoparticles (AuNPs), by alternating the charged polyelectrolytes. In this study, up to 4 layers of PLL and 3 layers of siRNA (sR3P) are coated. Due to the slow degradation of PLL, the incorporated siRNA is released gradually and shows extended gene-silencing effects. Importantly, the inhibition effect in cells is found to correlate with the number of siRNA layers.

Journal Article

Animals; Anti-Bacterial Agents; Bioware; Colony Count, Microbial; Disease Models, Animal; Female; Foreign Bodies; Humans; Mice; Mice, Inbred BALB C; Ofloxacin; Polymers; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus aureus; Xen29

OBJECTIVES To assess support discs, comprising polyethylene terephthalate (PET), coated with different polymer/levofloxacin combinations for antimicrobial activity in an animal model of infection, in order to explore the use of specific polymer coatings incorporating levofloxacin as a means of reducing device-related infections. METHODS Aliphatic polyester-polyurethanes containing different ratios of poly(lactic acid) diol and poly(caprolactone) diol were prepared, blended with levofloxacin and then used to coat support discs. The in vitro levofloxacin release profiles from these discs were measured in aqueous solution. Mice were surgically implanted with the coated discs placed subcutaneously and infection was initiated by injection of 10(6) cfu of Staphylococcus aureus into the subcutaneous pocket containing the implant. After 5, 10, 20 and 30 days, the discs were removed, and the number of bacteria adhering to the implant and the residual antimicrobial activity of the discs were determined. RESULTS In vitro, the release of levofloxacin from the coated discs occurred at a constant rate and then reached a plateau at different timepoints, depending on the polymer preparation used. In vivo, none of the discs coated with polymer blends containing levofloxacin was colonized by S. aureus, whereas 94% of the discs coated with polymer alone were infected. All discs coated with levofloxacin-blended polymers displayed residual antimicrobial activity for at least 20 days post-implantation. CONCLUSIONS Bioerodable polyester-polyurethane polymer coatings containing levofloxacin can prevent bacterial colonization of implants in an intra-operative model of device-related infections.

Journal Article

soft tissue sarcoma; radiotherapy; cell proliferation; apoptosis

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