Explore the vast range of titles available.

Hyaluronic acid (HA) is a major component of the skin, contributing to tissue hydration and biomechanical properties. As HA content in the skin decreases with age, formulas containing HA are widely used in cosmetics and HA injections in aesthetic procedures to reduce the signs of aging. To prove the beneficial effects of these treatments, efficient quantification of HA levels in the skin is necessary, but remains difficult. A new analytical method has been developed based on matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to quantify HA content in cross sections of human skin explants. A standardized and reproducible chemical entity (3 dimeric motifs or 6-mer) quantifiable by MALDI-MSI was produced by enzymatic hydrolysis using a specific hyaluronidase (H1136) in HA solution. This enzymatic digestion was carried out on skin sections before laser desorption, enabling the detection of HA. Histological coloration allowed us to localize the epidermis and the dermis on skin sections and, by comparison with the MALDI molecular image, to calculate the relative HA concentrations in these tissue areas. Skin explants were treated topically using a formula containing HA or its placebo, and the HA distribution profiles were compared with those obtained from untreated explants. A significant increase in HA was shown in each skin layer following topical application of the formula containing HA versus placebo and untreated samples (average of 126±40% and 92±40%, respectively). The MALDI-MSI technique enabled the quantification and localization of all HA macromolecules (endogenous and exogenous) on skin sections and could be useful for determining the efficacy of new cosmetic products designed to fight the signs of aging.

Introduction Amorolfine 5% lacquer is an established topical treatment for fungal infection of the nails. The success of topical therapy for onychomycosis depends on whether the permeated drug concentration in the deep nail bed is retained above the effective antifungal minimum inhibitory concentration (MIC). We compared the penetration profile of amorolfine and a new topical formula of terbinafine in human mycotic toenails using matrix-assisted laser desorption ionization mass spectrometry imaging–Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging. Methods Amorolfine 5% lacquer and terbinafine 7.8% lacquer were applied to mycotic nails ( n  = 17); nail sections were prepared, and MALDI-FTICR analysis was performed. Based on the MICs of amorolfine and terbinafine needed to kill 90% (MIC 90 ) of Trichophyton rubrum , the fold differences between the MIC 90 and the antifungal concentrations in the nails (the multiplicity of the MIC 90 ) were calculated overall and for the keratin-unbound fractions. Results Both amorolfine and terbinafine penetrated the entire thickness of the nail. The mean concentration across the entire nail section 3 h following terbinafine treatment was 1414 μg/g of tissue (equivalent to 4.9 mM) compared with 780 μg/g (2.5 mM) following amorolfine treatment (not significantly different; p  = 0.878). The median multiplicity of the MIC 90 was significantly higher in amorolfine- than terbinafine-treated nails overall (191 vs. 48; p  = 0.010) and for the keratin-unbound fractions only (7.4 vs. 0.8; p  = 0.002). Conclusion In this ex vivo study, MALDI-FTICR demonstrated that, although amorolfine 5% and terbinafine 7.8% had similar distribution profiles, both penetrating from the surface to the nail bed, the concentration of amorolfine in the nail was significantly higher than that of terbinafine relative to their respective MIC 90 values. Clinical studies are required to determine whether these effects translate to a clinical difference in treatment success.

Introduction Onychomycosis is a fungal infection of the nails that can be challenging to treat. Here, matrix-assisted laser desorption ionization–Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging was applied to the quantitative analysis of the penetration profile of the antifungal compound, amorolfine, in human mycotic toenails. The amorolfine profile was compared with those of three other antifungals, ciclopirox, naftifine, and tioconazole. Methods Antifungal compounds (amorolfine 5% lacquer, ciclopirox 8% lacquer, naftifine 1% solution, and tioconazole 28% solution) were applied to mycotic nails ( n  = 42). Nail sections were prepared, and MALDI-FTICR analysis was performed on the sections at a spatial resolution of 70 μm to compare the distribution profiles. Based on the minimum inhibitory concentrations of the four test compounds needed to kill 90% (MIC 90 ) of the fungal organism, Trichophyton rubrum , the fold differences between the MIC 90 and the antifungal concentrations in the nails (termed the multiplicity of the MIC 90 ) were calculated for each. Results The penetration profiles indicated higher concentrations of amorolfine and ciclopirox in the deeper layers of the nails 3 h after treatment, compared with naftifine and tioconazole. The mean concentrations across the entire nail sections at 3 h were significantly different among the four antifungals: amorolfine, 2.46 mM; ciclopirox, 0.95 mM; naftifine, 0.63 mM; and tioconazole, 1.36 mM ( p  = 0.016; n  = 8 per compound). The median multiplicity of the MIC 90 at 3 h was 191-fold for amorolfine, tenfold for ciclopirox, 52-fold for naftifine, and 208-fold for tioconazole. Conclusion In this study, MALDI-FTICR was successfully applied to the quantitative analysis of antifungal distribution in human mycotic nails. The findings suggest that amorolfine penetrates deeper layers of the nail and accumulates at concentrations far exceeding the MIC needed to exert antimycotic activity.

IntroductionInflammatory bowel diseases (IBDs) are chronic immune driven intestinal disorders with marked metabolic alteration. Mass spectrometry imaging (MSI) enables the direct visualization of biomolecules within tissues and facilitates the study of metabolic changes. Integrating multiple spatial information sources is a promising approach for discovering new biomarkers and understanding biochemical alteration within the context of the disease.ObjectiveThis study evaluates the metabolomic changes in gut tissue samples from a preclinical model of spontaneous colitis, the HLA-B27/hβ2m transgenic rat, to uncover disease biomarkers.MethodsWe applied MSI to study the biochemical profile of bowel samples from HLA-B27/hβ2m transgenic and WT control rats in an unbiased manner. Statistical comparison was used to identify discriminative features. Some features were annotated using LC-MS/MS. The significance of these discriminative features was evaluated based on their distribution within histological layers and the presence of immune infiltration.ResultsWe identified spatially resolved changes in the metabolomic pattern of HLA-B27+ samples compared to WT controls. Out of the 275 discriminative features identified, 83 were annotated as metabolites. Two functional groups of discriminative metabolites were discussed as markers of gut barrier impairment and immune cell infiltration.ConclusionMS imaging’s spatial dimension provides insights into disease mechanisms through the identification of spatially resolved biomarkers.