Journal Title
Title of Journal: Pharm Res
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Abbravation: Pharmaceutical Research
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Authors: A Baraldi S A Jones S Guesné M J Traynor W J McAuley M B Brown S Murdan
Publish Date: 2014/11/22
Volume: 32, Issue: 5, Pages: 1626-1633
Abstract
The mechanical properties of the human nail were characterised using a Lloyd tensile strength tester The nail’s density was determined via pycnometry and the nail’s ultrastructure by electron microscopy Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying water and rhodamine uptakeChronic in vivo nail plate infection increased human nailplate thickness healthy 049 ± 015 mm diseased 120 ± 067 mm but reduced its tensile strength healthy 637 ± 134 MPa diseased 417 ± 50 MPa and density healthy 134 ± 001 g/cm3 diseased 129 ± 000 g/cm3 Onchomycosis caused cellcell separation without disrupting the nail disulfide bonds or desmosomes The diseased and healthy nails showed equivalent water uptake profiles but the rhodamine penetration was 4fold higher in the diseased nails using a PBS vehicle and 3 fold higher in an ethanol/PBS vehicleOnychomycosis refers to the infection of the nail unit by fungi It constitutes 40 of all reported nail disorders 1 Responsible fungi include dermatophytes most frequently Trichophyton rubrum Trichophyton interdigitale and Trichophyton mentagrophytes moulds Scytalidium spp Scopulariopsis spp Fusarium spp Acremonium spp Onychocola canadensis and yeasts Candida spp 2 Onychomycosis may be treated by both oral and topical routes with topical treatment reducing the risks of hepatotoxic side effects associated with some systemic antifungals However topical medication appears to provide relatively low cure rates typically up to 30 and relatively long treatment times 12 months or longer 3 One reason for the low cure rates of topical therapy is thought to be the inability of active agents to penetrate the nail plate but the studies that propose this generally use healthy tissue to study chemical penetration and there remains a need to conduct such studies in the presence of the disease 4 5 6The onychomycotic nail is visually very different to the healthy nail Clinically it presents as a thickened crumbling barrier in advanced disease These properties have been previously characterized qualitatively using electron microscopy 7 8 9 10 11 and are thought to be caused by enzymatic tissue degradation by keratinolytic proteinases that are released by the invading organisms during an onychomycotic episode 12 13 14 15 16 17 The keratinolysis which occurs during the infection is also thought to be accompanied by sulfitolysis which results according to the data generated in hair samples in the breakage of disulfide bonds 18 However to date the thickness the density the sulfur bonding and barrier properties of diseased nails have not been quantified Therefore a strong link between onychomycotic induced nail plate changes and nail plate barrier properties has not yet been establishedThe aim of this investigation was to understand how onychomycosisinduced structural changes influenced nail plate barrier function To achieve this aim structural surface morphology cell layer integrity cellcell linkages nail thickness density mechanical tensile strength elasticity fracture strain and chemical properties disulfide bonds of healthy and diseased human nails were studied This data was interpreted alongside a comparison of rhodamine B uptake 19 20 21 22 and nail hydration characterisation in healthy and infected nails in order to try and determine how the invading organisms altered the passage of chemicals into the tissue
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