Guselkumab treatment normalizes the stratum corneum ceramide profile and alleviates barrier dysfunction in psoriasis:results of a randomized controlled trial

The epidermal inflammation associated with psoriasis drives skin barrier perturbations. The skin barrier is primarily located in stratum corneum (SC). Its function depends on the SC lipid matrix of which ceramides constitute important components. Changes in the ceramide profile directly correlate to barrier function. In this study, we characterized the dynamics of the barrier function and ceramide profile of psoriatic skin during anti-Interleukin-23 therapy with guselkumab. We conducted a double-blind, randomized controlled trial in which 26 mild-to-severe plaque psoriasis patients were randomization 3:1–100 mg guselkumab or placebo for 16 weeks and barrier dynamics monitored throughout. Barrier function was measured by trans-epidermal water loss measurements. Untargeted ceramide profiling was performed using liquid chromatography-mass spectrometry after SC was harvested using tape-stripping. The barrier function and ceramide profile of lesional skin normalized to that of controls during treatment with guselkumab, but not placebo. This resulted in significant differences compared to placebo at the end of the treatment. Changes in the lesional ceramide profile during treatment correlated with barrier function and target lesion severity. Nonlesional skin remained similar throughout treatment. Guselkumab therapy restored the skin barrier in psoriasis. Concomitant correlations between skin barrier function, the ceramide profile, and disease severity demonstrate their interdependency.</p

On the nitrogen-induced lattice expansion of a non-stainless austenitic steel, Invar 36®, under triode plasma nitriding

Chromium, as a strong nitride-forming element, is widely regarded to be an “essential” ingredient for the formation of a nitrogen-expanded lattice in thermochemical nitrogen diffusion treatments of austenitic (stainless) steels. In this article, a proprietary “chrome-free” austenitic iron-nickel alloy, Invar® 36 (Fe-36Ni, in wt pct), is characterized after triode plasma nitriding (TPN) treatments at 400 °C to 450 °C and compared with a “stainless” austenitic counterpart RA 330® (Fe-19Cr-35Ni, in wt pct) treated under equivalent nitriding conditions. Cr does indeed appear to play a pivotal role in colossal nitrogen supersaturation (and hence anisotropic lattice expansion and superior surface hardening) of austenitic steel under low-temperature (≤ 450 °C) nitrogen diffusion. Nevertheless, this work reveals that nitrogen-induced lattice expansion occurs below the nitride-containing surface layer in Invar 36 alloy after TPN treatment, implying that Cr is not a necessity for the nitrogen-interstitial induced lattice expansion phenomenon to occur, also suggesting another type of γN