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Biomedical subjects

A V Rawlings

Publications and source records attributed to A V Rawlings.

10 recordsLinked to original sources

Moisturization and skin barrier function.

Over the past decade, great progress has been made toward elucidating the structure and function of the stratum corneum (SC), the outermost layer of the epidermis. SC cells (corneocytes) protect against desiccation and environmental challenge by regulating water flux and retention. Maintenance of an optimal level of hydration by the SC is largely dependent on several factors. First, intercellular lamellar lipids, organized predominantly in an orthorhombic gel phase, provide an effective barrier to the passage of water through the tissue. Secondly, the diffusion path length also retards water loss, since water must traverse the tortuous path created by the SC layers and corneocyte envelopes. Thirdly, and equally important, is natural moisturizing factor (NMF), a complex mixture of low-molecular-weight, water-soluble compounds first formed within the corneocytes by degradation of the histidine-rich protein known as filaggrin. Each maturation step leading to the formation of an effective moisture barrier--including corneocyte strengthening, lipid processing, and NMF generation--is influenced by the level of SC hydration. These processes, as well as the final step of corneodesmolysis that mediates exfoliation, are often disturbed upon environmental challenge, resulting in dry, flaky skin conditions. The present paper reviews our current understanding of the biology of the SC, particularly its homeostatic mechanisms of hydration.

Epidermis↗

Moisturizer technology versus clinical performance.

The principles of humectancy, emolliency, and occlusion, all central to stratum corneum (SC) maintenance, continue to drive the development of novel moisturizing technologies. Humectants promote water retention within the SC, whereas occlusives generally minimize water loss to the external environment. The complementary occlusive activity of emollients contributes to SC hydration as well. Moisturization technologies, ranging from face care to hand and body care, vary in the types and levels of humectants, emollients (including lipids), and occlusives; accordingly, their therapeutic effects differ as well. Emulsification of these components into a single formulation-the technologies of which are as varied as their individual components-is thought to enhance the aesthetics of the moisturizer and its overall moisturization efficiency. The present article reviews the current approaches to SC moisturization, increasingly viewed as critical to its structural and functional integrity, and to fundamental skin care.

Dermatologic Agents↗

Broad specificity alkaline proteases efficiently reduce the visual scaling associated with soap-induced xerosis.

In xerotic skin, the proteolysis of desmosomes is reduced leading to the accumulation of corneocytes on the surface of the skin. The effect of proteases applied topically to soap-induced xerotic skin was evaluated using a five-point visual scale. The visual scaling associated with soap-induced xerosis could be ameliorated by the topical application of exogenous protease. Bovine pancreatic chymotrypsin, papain, and a bacterial protease from Bacillus licheniformis were all capable of facilitating the reduction in visual scaling in a short time. Alcalase and Optimase, both broad specificity alkaline bacterial proteases, were the most weight-efficient at delivering this clinical effect. The reduction in scaling could be achieved either by occluded application of an aqueous enzyme solution or by a two-step unoccluded application first of an aqueous enzyme solution followed by a commercial moisturizer. Morphological and immunological analysis of bacterial enzyme-treated skin revealed that topically applied protease specifically induced the degradation of the desmosomes thereby promoting desquamation. These results indicate that topical application of protease can significantly and rapidly reduce the visual scaling associated with soap-induced xerosis by promoting desmosome degradation within the corneocyte clumps.

Administration, Topical↗

Effect of lactic acid isomers on keratinocyte ceramide synthesis, stratum corneum lipid levels and stratum corneum barrier function.

Alpha-hydroxy acids are effective agents for the treatment of skin xerosis and it is known that, following treatment with lotions containing D,L-lactic acid, the stratum corneum prevents xerosis more effectively. To date, the relative efficacy of the different isomers of lactic acid has not been evaluated and the mode of action of lactic acid in improving stratum corneum resilience is not known. The objective of the present studies was to determine the effects of lactic acid isomers on keratinocyte ceramide biosynthesis, stratum corneum barrier function and the resistance of the stratum corneum to the appearance of skin xerosis. In vitro, lactic acid enhanced the production of ceramides by keratinocytes. L-Lactic acid was more effective than the D isomer (300% increase vs 100% increase). Carbon label from lactic acid was incorporated into all keratinocyte lipid species and a greater incorporation of label into ceramides was achieved with L-lactate than with D-lactate. In vivo, lactic acid increased the levels of stratum corneum ceramides. Whereas, lotions containing L-lactic acid resulted in the greatest increase (48% increase) followed by D,L-lactic acid (25% increase), D-lactic acid had no effect on stratum corneum ceramide levels. The increases in stratum corneum ceramide levels following lactic acid treatment also led to improvements in stratum corneum barrier function, measured by transepidermal water loss following a challenge to the skin with SLS and in the regression phase of a moisturization efficacy study. Significant improvements in barrier function and resistance to the appearance of skin xerosis were observed following L-lactic acid and D,L-lactic acid, but not following D-lactic acid treatment. From these results we believe that lactic acid, particularly the L isomer, stimulates ceramide biosynthesis leading to increased stratum corneum ceramide levels which results in superior lipid barrier and a more effective resistance against xerosis.

Adult↗

Synergy between vitamin D precursor 25-hydroxyvitamin D and short chain ceramides on keratinocyte proliferation and differentiation.

The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25D), and its analogs induce normal human keratinocyte differentiation and are used for the treatment of psoriasis. Long-term topical use of 1,25D, however, causes hypercalcemia. The precursor of 1,25D, 25-hydroxyvitamin D3 (25D) is converted to 1,25D in the keratinocyte in a regulated manner. The action of 1,25D is reported to be mediated, at least in part, by cellular ceramides in the leukemia cell line, HL-60 cells. Therefore, in this study we evaluated the synergy between 25D and short chain cell permeable ceramides (SCC) or synthetic analogs of ceramides on keratinocyte growth and differentiation in vitro. C2 ceramide (acetyl sphingosine) synergistically enhanced the growth inhibitory effect of 25D and 1,25D in a concentration-dependent manner. Short chain analogs of ceramide-like compounds, neoceramides and pseudoceramides, also inhibited keratinocyte proliferation and acted in synergy with 25D and 1,25D. SCC alone increased transglutaminase and cornified envelope levels. 25D potentiated this prodifferentiating effect of SCC. Twenty-four-hour preincubation with SCC did not alter 25D or 1,25D uptake into keratinocytes. These studies demonstrate a synergy between vitamin D metabolites and ceramides in human keratinocytes and indicate the potential of using 25D as an effective and safer alternative to deliver 1,25D benefits to the epidermis.

Calcifediol↗

Structural and thermotropic properties of synthetic C16:0 (palmitoyl) ceramide: effect of hydration.

Differential scanning calorimetry (DSC) and X-ray diffraction techniques have been used to investigate the structure and thermotropic properties of synthetic, non-hydroxy fatty acid (16:0) ceramide (NFA(C16)CER) as a function of hydration. Anhydrous NFA(C16)CER shows a single, broad endothermic transition at 95.4 degrees C (delta H = 10.4 kcal/mol). On hydration, a broad exothermic transition appears at approximately 50-70 degrees C while the main endothermic transition decreases to 90.0 degrees C (delta H = 13.8 kcal/mol). The enthalpy of the exothermic transition increases with hydration to a maximum value, delta H = 4.8 kcal/mol. This polymorphic phase behavior depends on the low temperature incubation time and prior cooling rate. X-ray diffraction of fully hydrated NFA(C16)CER at 26 degrees C, shows a well-ordered lamellar phase with a bilayer periodicity d = 46.9 A. At 68 degrees C, above the first exothermic transition, X-ray diffraction shows again a lamellar phase with reduced bilayer periodicity d = 41.8 A and an increased number of both lamellar and wide-angle reflections indicative of enhanced layer and chain packing order, respectively. At 90.0 degrees C, above the main transition, the diffraction pattern shows a broad, intense reflection at 29.9 A and a diffuse reflection at 4.6 A, indicative of a melted chain phase. On cooling, NFA(C16)CER exhibits polymorphic phase behavior involving the conversion of the melted chain phase to a metastable bilayer phase. On heating, this metastable phase undergoes an exothermic transition to a stable bilayer phase; on further heating, NFA(C16)CER converts endothermically to the melted-chain phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry, Differential Scanning↗

Physical properties of ceramides: effect of fatty acid hydroxylation.

The structural and thermotropic properties of alpha-hydroxy fatty acid (HFA) and non-hydroxy fatty acid (NFA) ceramides (CER) have been studied using differential scanning calorimetry (DSC) and X-ray diffraction techniques. The DSC of anhydrous HFA-CER shows a single, sharp reversible transition at 95.6 degrees C (delta H = 15.3 kcal/mol). At intermediate hydrations HFA-CER exhibited more complex behavior but at maximum hydration only a single reversible transition is observed at 80.0 degrees C (delta H = 8.5 kcal/mol). X-ray diffraction of hydrated (74% water) HFA-CER at 20 degrees C shows a lamellar structure with a bilayer periodicity d = 60.7 Angstrum; a single wide angle reflection at 4.2 Angstrum is characteristic of hexagonal chain packing. Above the main transition temperature at 91 degrees C, a hexagonal (HII) phase is observed. In contrast, DSC of anhydrous NFA-CER demonstrates two thermal transitions at 81.3 degrees C (delta H = 6.8 kcal/mol) and 85.9 degrees C (delta H = 3.5 kcal/mol). With increasing hydration, both transitions shift towards lower temperatures; at maximum hydration, on heating, the endothermic transitions occur at 72.7 degrees C (delta H = 9.8 kcal/mol) and 81.1 degrees C (delta H = 4.0 kcal/mol). On cooling, there is hysteresis of both transitions. X-ray diffraction of NFA-CER (80% water) at 20 degrees C shows a well-ordered lamellar structure with a bilayer periodicity d = 58.6 Angstrum and three wide-angle reflections at 4.6 Angstrum, 4.2 Angstrum, and 3.8 Angstrum. At 77 degrees C (between the two transitions), again a lamellar structure exists with reduced bilayer periodicity d = 53.1 Angstrum and four wide-angle reflections at 4.6 Angstrum, 4.2 Angstrum, and 3.8 Angstrum are observed. Above the second transition, only a single low angle reflection at 30.0 Angstrum is observed; a diffuse reflection at 4.6 Angstrum is indicative of a melted chain phase. Thus, HFA-CER exhibits a simple phase behavior involving the reversible conversion of a gel phase to a hexagonal phase (L beta-->HII). However, NFA-CER shows a more complex polymorphic phase behavior involving two gel phases.

Calorimetry, Differential Scanning↗

Interference by pro-apolipoprotein A-I in apolipoprotein E phenotyping using chemical precipitation procedures.

Lipoproteins of density, d less than 1.063, isolated by polyanion-cation precipitation methods, gave isoelectric focussing patterns of apolipoprotein E isoforms by rod-gel electrophoresis which differed from the corresponding patterns obtained from ultracentrifugally-derived very low density lipoproteins. The differences were sporadic and variable but the most common effect was an increased frequency of the E3 isoform. Two-dimensional analyses involving sodium dodecyl sulphate-polyacrylamide gel electrophoresis and immunoelectrophoresis against anti-apolipoprotein A-I indicated that contamination of precipitated lipoproteins with pro-apolipoprotein A-I was responsible for this phenomenon. It is suggested that two-dimensional techniques should be applied for definitive phenotyping if precipitated lipoproteins are used as source material.

Apolipoprotein A-I↗