A study of the combination of triamcinolone and 5-fluorouracil in modulating keloid fibroblasts in vitro.

BACKGROUND: Preliminary clinical trials suggest a superior effect when steroids and 5-fluorouracil are injected together for the intralesional therapy of keloids. In addition, it has been proposed that low-dose 5-fluorouracil may have advantages over conventional high dosages. We explored the molecular basis for the potential synergy involved in the combined treatment with triamcinolone and 5-fluorouracil. METHODS: The effects of triamcinolone alone or in combination with low-dose 5-fluorouracil on cell proliferation, cell-cycle progression, apoptosis and regulation of p53, p21, type I collagen (Col-1), vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1) and matrix metalloproteinase-2 (MMP-2) production in primary cultured keloid fibroblasts were examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), flow cytometric and Western blotting assays. RESULTS: Triamcinolone suppressed cell proliferation and induced G1 cell-cycle arrest but not apoptosis. By contrast, 5-fluorouracil induced G2 cell-cycle arrest and apoptosis that may be associated with p53 activation and p21 up-regulation. The modulation of Col-1, VEGF, TGF-beta1 and MMP-2 expression by triamcinolone and 5-fluorouracil alone or their combination varied between individual cell lines; the trend is to promote a reduction in Col-1 and TGF-beta1 but up-regulation of MMP-2 expression. 5-Fluorouracil played a predominant role in the combined treatment leading to more significant cell proliferation inhibition, apoptosis, Col-1 suppression and MMP-2 induction (p < 0.05). CONCLUSIONS: Our data provide the molecular-based evidence for the observed clinical benefits of adding 5-fluorouracil to a steroid injection for improved scar regression and reduced recurrence of keloids. We expect fewer undesirable side effects in the combined treatment when the lower therapeutic dose of the individual drugs is to be used.

Antimicrobial activities of silver dressings: an in vitro comparison.

A range of silver-coated or -impregnated dressings are now commercially available for use but comparative data on their antimicrobial efficacies are limited. The antibacterial activities of five commercially available silver-coated/impregnated dressings were compared against nine common burn-wound pathogens, namely methicillin-sensitive and -resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Proteus vulgaris, Acinetobacter baumannii and a multi-drug-efflux-positive Acinetobacter baumannii (BM4454), using a broth culture method. The rapidity and extent of killing of these pathogens under in vitro conditions were evaluated. All five silver-impregnated dressings investigated exerted bactericidal activity, particularly against Gram-negative bacteria, including Enterobacter species, Proteus species and E. coli. The spectrum and rapidity of action, however, ranged widely for different dressings. Acticoat and Contreet had a broad spectrum of bactericidal activities against both Gram-positive and -negative bacteria. Contreet was characterized by a very rapid bactericidal action and achieved a reduction of > or =10,000 c.f.u. ml(-1) in the first 30 min for Enterobacter cloacae, Proteus vulgaris, Pseudomonas aeruginosa and Acinetobacter baumanii. Other dressings demonstrated a narrower range of bactericidal activities. Understanding the characteristics of these dressings may enable them to be targeted more appropriately according to the specific requirements for use of a particular dressing, as in for prophylaxis in skin grafting or for an infected wound with MRSA.