Atopic dermatitis is a common skin disease of unknown etiology with an impaired permeability barrier function. To learn more about the molecular pathology in lesional skin, we analyzed levels of free extractable as well as protein-bound barrier lipids in the epidermis of atopic dermatitis subjects. The amount of protein-bound omega-hydroxyceramides in healthy epidermis comprised 46-53 wt% of total protein-bound lipids, whereas this percentage was decreased to 23-28 wt% in nonlesional areas and even down to 10-25 wt% in affected atopic skin areas of the subjects. Furthermore, the partial amount of free extractable very long chain fatty acids with more than 24 carbon atoms was reduced in affected regions down to 25 wt% and in nonlesional regions of the atopic dermatitis subjects down to 40 wt% compared to healthy controls. This "hydrocarbon chain length deficiency" regarding the barrier lipids in atopic skin was supported by metabolic labeling studies with [14C]-serine in cultured epidermis. The biosynthesis of free glucosylceramides and free ceramides was remarkably decreased in affected skin areas of the atopic subjects compared to healthy control subjects. Especially affected were the de novo syntheses of ceramide 4 (i.e., ceramide EOH, consisting of a very long chain N-acyl omega-hydroxy fatty acid esterified with linoleic acid and 6-hydroxysphingosine as sphingoid base) and ceramide 3 (ceramide NP, consisting of a nonhydroxy N-acyl fatty acid and phytosphingosine). In conclusion, this study revealed that the lesional epidermis in atopic dermatitis has considerable deficiencies within main barrier lipid components, which may contribute to the severely damaged permeability barrier.
Due to the major improvement of quality of life and quick onset of improvement together with the high acceptance by the patients Xamiol(®) gel may be regarded as the topical treatment of choice for scalp psoriasis.
matrix of likely sample size based on these values ranged from 44 to 193 per group. Based on this DPP, a sample of 120 per group was selected as the sample size that would deliver clinically meaningful results. ConClusions: A DPP is useful in late phase research to define appropriate sample size where no data exist. It is important to note that DPP methods do not require significance testing, but the benefit is no need for a correction for multiple comparisons at the time of the final analysis.
This chapter discusses enzymatically inactive proteins that play a part in two areas of endosomal-lysosomal membrane lipid metabolism. Some are involved in binding and transfer processes that assist lysosomal sphingolipid catabolism and others appear to regulate cholesterol transport from these acidic compartments back to the plasma membrane and the endoplasmic reticulum (ER). These activator-mediated processes are of physiological relevance since defects in activator function can lead to fatal human diseases.
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