A dissolved oxygen dressing: a pilot study in an ischemic skin flap model.

OBJECTIVES: To determine if skin flap failure rates could be improved with the use of a dissolved oxygen wound dressing in a porcine model. METHODS: Full-thickness skin flaps (4 × 16 cm) were raised on pigs. Flaps were randomly assigned after surgery to experimental treatment with a dissolved oxygen dressing (treatment group) or a hydrogel dressing (control group). Flaps were evaluated daily for 14 days. Skin flaps that failed any one of four key clinical outcomes were considered failures. Histological parameters (including skin and subcutaneous necrosis, inflammation, ischemia, fibrosis, and bacterial load) were compared by a blinded histopathologist. RESULTS: Sixteen full-thickness skin flaps were raised on four pigs. All animals survived surgery and all incisions were evaluable. Clinical flap failure was observed in six (75%) control-treated wounds and in two (25%) dissolved oxygen-treated wounds. Histological evaluation demonstrated no significant differences in the proximal 75% of the flaps. There were significant differences in a number of histological parameters in the distal 25% in favor of the dissolved oxygen dressing. CONCLUSIONS: Flaps treated with a dissolved oxygen dressing had fewer clinical failures and improved histological profiles compared with control-treated flaps, suggesting that increasing local oxygen supply may improve the local wound healing environment.

Topically delivered dissolved oxygen reduces inflammation and positively influences structural proteins in healthy intact human skin.

BACKGROUND: As oxygen is essential for wound healing and there is limited diffusion across the stratum corneum into the epidermis, we wanted to evaluate whether the topical delivery of a total dissolved oxygen in dressing form on intact human subject skin would improve clinical and histologic skin functioning. AIMS: Fifty normal, healthy subjects completed a pilot clinical evaluation to assess the efficacy and tolerability of a dissolved oxygen dressing (OxygeneSys™-Continuous) to improve the health and appearance of intact skin. METHODS: Clinical analysis was performed on 50 subjects; histological and gene expression analysis was performed on 12 of the 50 subjects to assess the effect of the dissolved oxygen dressing. RESULTS: Clinical data demonstrate that the dressing is well tolerated, and several measures of skin health and integrity showed improvements compared with a control dressing site. Skin hydration measurements showed a statistically significant increase in skin hydration at 0-4, 4-8, and 0-8 weeks (P < 0.05 at each time point). The blinded clinical investigator's grading of desquamation, roughness, and skin texture show significant decreases from baseline to the 8-week time point (P < 0.05). The dressings were removed prior to the blinded clinical investigator's grading. These data were supported by the histological and gene expression studies, which showed a general reduction in inflammatory response markers and transcription products (IL-6, IL-8, TNF-alpha, MMP-1, and MMP-12), while facilitating a general increase in structural skin proteins (collagen I, elastin, and filaggrin). Additionally, p53 signals from biopsy samples support the clinical investigator's observations of no safety concerns. CONCLUSION: The data from this study demonstrate that the dressing has no deleterious effects and stimulates beneficial effects on intact, nonwounded skin.

Topical dissolved oxygen penetrates skin: model and method.

BACKGROUND: It has been commonly perceived that skin receives its oxygen supply from the internal circulation. However, recent investigations have shown that a significant amount of oxygen may enter skin from the external overlying surface. A method has been developed for measuring the transcutaneous penetration of human skin by oxygen as described herein. This method was used to determine both the depth and magnitude of penetration of skin by topically applied oxygen. MATERIAL AND METHODS: An apparatus consisting of human skin samples interposed between a topical oxygen source and a fluid filled chamber that registered changes in dissolved oxygen. Viable human skin samples of variable thicknesses with and without epidermis were used to evaluate the depth and magnitude of oxygen penetration from either topical dissolved oxygen (TDO) or topical gaseous oxygen (TGO) devices. RESULTS AND CONCLUSION: This model effectively demonstrates transcutaneous penetration of topically applied oxygen. Topically applied dissolved oxygen penetrates through >700 microm of human skin. Topically applied oxygen penetrates better though dermis than epidermis, and TDO devices deliver oxygen more effectively than TGO devices.

Nicotinic stimulation modulates tyrosine hydroxylase mRNA half-life and protein binding to the 3'UTR in a manner that requires transcription.

Tyrosine hydroxylase (TH) expression increases in adrenal chromaffin cells treated with the nicotinic agonist, dimethylphenylpiperazinium (DMPP; 1 microM). We are using this response as a model of the changes in TH level that occur during increased cholinergic neural activity. Here we report a 4-fold increase in TH mRNA half-life in DMPP-treated cells chromaffin cells that is apparent when using a pulse-chase analysis to measure TH mRNA half-life. No increase is apparent using actinomycin D to measure half-life, indicating a requirement for ongoing transcription. Characterization of protein binding to the TH 3'UTR responsible for stabilization using labeled TH 3'UTR probes and electro-mobility shift assays shows the presence of two complexes both of which are increased by DMPP-treatment. The faster migrating complex (FMC) increases 2.5-fold and the slower migrating complex (SMC) increases 1.5-fold. Both changes are prevented by actinomycin D. Characterization of the protein binding to the TH UTR probes indicates SMC is disrupted by polyribonucleotides, poly (A) and poly (U), while binding to FMC is reduced by poly (CU). Separation of UV crosslinked RNA-protein complexes on SDS polyacrylamide gels shows FMC to contain a single protein whereas SMC contains three proteins. Northwesterns yielded similar results. Comparison of DMPP-induced protein binding with the poly C binding protein (PCBP) involved in hypoxia induced rat PC12 TH mRNA stability indicates none of the bovine UTR binding proteins are the PCBP. Thus, nicotinic stimulation produces a transcription-dependent increase in TH mRNA half-life that is mediated by previously unrecognized TH mRNA binding proteins.