The determination of stratum corneum thickness - An alternative approach

Department of Pharmacy & Pharmacology, University of Bath, Bath, UK.
European Journal of Pharmaceutics and Biopharmaceutics (Impact Factor: 3.38). 03/2008; 69(3):861-70. DOI: 10.1016/j.ejpb.2008.02.002
Source: PubMed


The individual thickness of the stratum corneum is required to normalise drug permeation profiles in dermato-pharmacokinetic studies. The thickness is often estimated using tape-stripping combined with transepidermal water loss measurements. A linear transformation of Fick's first law is used to relate the progressively thinner barrier with the corresponding increase in transepidermal water loss and to estimate the thickness by linear regression. However, the data from an important subset of subjects are poorly fitted to this linear model. This is typically due to the removal of loose outer layers of stratum corneum, which do not contribute significantly to barrier function. This work proposes two alternative non-linear models. All three models were used to fit data from 31 in vivo tape-stripping experiments and their outcomes and goodness-of-fit compared. The results suggest that the linear model may overestimate the stratum corneum thickness and is open to subjectivity regarding the selection of data points to be fitted. The non-linear models satisfactorily fitted all the data, including all data points. No significant differences were found between the thicknesses derived from the two non-linear models. However, the analysis of the goodness-of-fit of the models to the data suggests a preference for a baseline-corrected approach.

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Available from: Sandra Wiedersberg, Sep 29, 2015
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    • "At the tissue level, the two organs at major risk from UV light are the skin and the eye [15]–[18]. The key skin cells at risk from UV exposure, such as basal cells and melanocytes, are located within the epidermis below the stratum corneum which is a 5 to 20 µm thick layer of dead non-nucleated cells [28]. Given its very limited penetration (half-value thickness ∼0.3 µm, as discussed above), ∼200-nm light will thus have minimal ability to penetrate the stratum corneum and reach the underlying key skin cells such as basal cells or melanocytes. "
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    ABSTRACT: 0.5% to 10% of clean surgeries result in surgical-site infections, and attempts to reduce this rate have had limited success. Germicidal UV lamps, with a broad wavelength spectrum from 200 to 400 nm are an effective bactericidal option against drug-resistant and drug-sensitive bacteria, but represent a health hazard to patient and staff. By contrast, because of its limited penetration, ∼200 nm far-UVC light is predicted to be effective in killing bacteria, but without the human health hazards to skin and eyes associated with conventional germicidal UV exposure. The aim of this work was to test the biophysically-based hypothesis that ∼200 nm UV light is significantly cytotoxic to bacteria, but minimally cytotoxic or mutagenic to human cells either isolated or within tissues. A Kr-Br excimer lamp was used, which produces 207-nm UV light, with a filter to remove higher-wavelength components. Comparisons were made with results from a conventional broad spectrum 254-nm UV germicidal lamp. First, cell inactivation vs. UV fluence data were generated for methicillin-resistant S. aureus (MRSA) bacteria and also for normal human fibroblasts. Second, yields of the main UV-associated pre-mutagenic DNA lesions (cyclobutane pyrimidine dimers and 6-4 photoproducts) were measured, for both UV radiations incident on 3-D human skin tissue. We found that 207-nm UV light kills MRSA efficiently but, unlike conventional germicidal UV lamps, produces little cell killing in human cells. In a 3-D human skin model, 207-nm UV light produced almost no pre-mutagenic UV-associated DNA lesions, in contrast to significant yields induced by a conventional germicidal UV lamp. As predicted based on biophysical considerations, 207-nm light kills bacteria efficiently but does not appear to be significantly cytotoxic or mutagenic to human cells. Used appropriately, 207-nm light may have the potential for safely and inexpensively reducing surgical-site infection rates, including those of drug-resistant origin.
    PLoS ONE 10/2013; 8(10):e76968. DOI:10.1371/journal.pone.0076968 · 3.23 Impact Factor
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    • "Total volume reduction of a keratinocyte during its passage through the SG R 0.46 ± 10 [49] Viable sublayer heights above the BM for human epidermis z 1 28 ± 17 µm [4] [12] [50] z 2 83 ± 20 µm [4] [12] [50] z 3 115 ± 3 µm [12] [50] Viable sublayer heights above the BM for murine epidermis z 1 20 µm [24] z 2 60 µm [24] z 3 90 µm [24] Table 1: Parameter values used in numerical solutions throughout this paper. Justification is provided in Appendix A. thereby giving expressions for the cell and ECF velocities in the viable epidermis. "
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    ABSTRACT: A distinct calcium profile is strongly implicated in regulating the multi-layered structure of the epidermis. However, the mechanisms that govern the regulation of this calcium profile are currently unclear. It clearly depends on the relatively impermeable barrier of the stratum corneum (passive regulation) but may also depend on calcium exchanges between keratinocytes and extracellular fluid (active regulation). Using a mathematical model that treats the viable sublayers of unwounded human and murine epidermis as porous media and assumes that their calcium profiles are passively regulated, we demonstrate that these profiles are also actively regulated. To obtain this result, we found that diffusion governs extracellular calcium motion in the viable epidermis and hence intracellular calcium is the main source of the epidermal calcium profile. Then, by comparison with experimental calcium profiles and combination with a hypothesised cell velocity distribution in the viable epidermis, we found that the net influx of calcium ions into keratinocytes from extracellular fluid may be constant and positive throughout the stratum basale and stratum spinosum, and that there is a net outflux of these ions in the stratum granulosum. Hence, the calcium exchange between keratinocytes and extracellular fluid differs distinctly between the stratum granulosum and the underlying sublayers, and these differences actively regulate the epidermal calcium profile. Our results also indicate that plasma membrane dysfunction may be an early event during keratinocyte disintegration in the stratum granulosum.
    Journal of Theoretical Biology 02/2012; 301:112-21. DOI:10.1016/j.jtbi.2012.02.017 · 2.12 Impact Factor
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