Suchergebnisse

Combating antimicrobial resistance is one of the most serious public health challenges facing society today. The development of new antibiotics or alternative techniques that can help combat antimicrobial resistance is being prioritised by many governments and stakeholders across the globe. Antimicrobial photodynamic therapy is one such technique that has received considerable attention but is limited by the inability of light to penetrate through human tissue, reducing its effectiveness when used to treat deep-seated infections. The related technique sonodynamic therapy (SDT) has the potential to overcome this limitation given the ability of low-intensity ultrasound to penetrate human tissue. In this study, a Rose Bengal–antimicrobial peptide conjugate was prepared for use in antimicrobial SDT (ASDT). When Staphylococcus aureus and Pseudomonas aeruginosa planktonic cultures were treated with the conjugate and subsequently exposed to ultrasound, 5 log and 7 log reductions, respectively, in bacterial numbers were observed. The conjugate also displayed improved uptake by bacterial cells compared with a mammalian cell line (P ≤ 0.01), whilst pre-treatment of a P. aeruginosa biofilm with ultrasound resulted in a 2.6-fold improvement in sensitiser diffusion (P ≤ 0.01). A preliminary in vivo experiment involving ASDT treatment of P. aeruginosa-infected wounds in mice demonstrated that ultrasound irradiation of conjugate-treated wounds affects a substantial reduction in bacterial burden. Combined, the results obtained from this study highlight ASDT as a targeted broad-spectrum novel modality with potential for the treatment of deep-seated bacterial infections.

Low-level laser (light) therapy (LLLT) has been clinically applied around the world for a spectrum of disorders requiring healing, regeneration and prevention of tissue death. One area that is attracting growing interest in this scope is the use of transcranial LLLT to treat stroke and traumatic brain injury (TBI). We developed a mouse model of severe TBI induced by controlled cortical impact and explored the effect of different treatment schedules. Adult male BALB/c mice were divided into 3 broad groups (a) sham-TBI sham-treatment, (b) real-TBI sham-treatment, and (c) real-TBI active-treatment. Mice received active-treatment (transcranial LLLT by continuous wave 810 nm laser, 25 mW/cm[superscript 2], 18 J/cm[superscript 2], spot diameter 1 cm) while sham-treatment was immobilization only, delivered either as a single treatment at 4 hours post TBI, as 3 daily treatments commencing at 4 hours post TBI or as 14 daily treatments. Mice were sacrificed at 0, 4, 7, 14 and 28 days post-TBI for histology or histomorphometry, and injected with bromodeoxyuridine (BrdU) at days 21–27 to allow identification of proliferating cells. Mice with severe TBI treated with 1-laser Tx (and to a greater extent 3-laser Tx) had significant improvements in neurological severity score (NSS), and wire-grip and motion test (WGMT). However 14-laser Tx provided no benefit over TBI-sham control. Mice receiving 1- and 3-laser Tx had smaller lesion size at 28-days (although the size increased over 4 weeks in all TBI-groups) and less Fluoro-Jade staining for degenerating neurons (at 14 days) than in TBI control and 14-laser Tx groups. There were more BrdU-positive cells in the lesion in 1- and 3-laser groups suggesting LLLT may increase neurogenesis. Transcranial NIR laser may provide benefit in cases of acute TBI provided the optimum treatment regimen is employed. ; National Institutes of Health (U.S.) (Grant R01AI050875) ; Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006) ; United States. Dept. of Defense. Congressionally Directed Medical Research Programs (W81XWH-09-1-0514) ; United States. Air Force Office of Scientific Research. Military Photomedicine Program (FA9550-11-1-0331)