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Johanna A. Bouwstra - One of the best experts on this subject based on the ideXlab platform.
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applying a Vernix caseosa based formulation accelerates skin barrier repair by modulating lipid biosynthesis
Journal of Lipid Research, 2017Co-Authors: Walter Boiten, Tineke Berkers, Samira Absalah, Jeroen Van Smeden, A P M Lavrijsen, Johanna A. BouwstraAbstract:: Restoring the lipid homeostasis of the stratum corneum (SC) is a common strategy to enhance skin barrier function. Here, we used a ceramide containing Vernix caseosa (VC)-based formulation and were able to accelerate barrier recovery in healthy volunteers. The recovery was examined over 16 days by monitoring trans-epidermal water loss (TEWL) after barrier disruption by tape-stripping. Four skin sites were used to examine the effects of both treatment and barrier recovery. After 16 days, samples were harvested at these sites to examine the SC ceramide composition and lipid organization. Changes in ceramide profiles were identified using principal component analysis. After barrier recovery, the untreated sites showed increased levels of ceramide subclass AS and ceramides with a 34 total carbon-atom chain length, while the mean ceramide chain length was reduced. These changes were diminished by treatment with the studied formulation, which concurrently increased the formulated ceramides. Correlations were observed between SC lipid composition, lipid organization, and TEWL, and changes in the ceramide subclass composition suggest changes in the ceramide biosynthesis. These results suggest that VC-based formulations enhance skin barrier recovery and are attractive candidates to treat skin disorders with impaired barrier properties.
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Mimicking Vernix caseosa--preparation and characterization of synthetic biofilms.
International Journal of Pharmaceutics, 2009Co-Authors: Robert Rissmann, Marion H.m. Oudshoorn, Johanna A. Bouwstra, Maria Ponec, Raphaël Zwier, Wim E. HenninkAbstract:The multiple protecting and barrier-supporting properties of the creamy, white biofilm Vernix caseosa (VC) before and after birth suggest that a VC biomimetic could be an innovative barrier cream for barrier-deficient skin. The aim of this study was the rational design and preparation of synthetic biofilms mimicking the unique composition and properties of natural VC. Hexagonal, highly hydrated hyperbranched polyglycerol microgel particles (30 microm in diameter) were embedded in a synthetic lanolin-based lipid mixture using a micromixer. In these formulations, the water content of the particles (i.e. 50% and 80%), an additional lipid coating of the particles and different particle/lipid ratios were varied. Characterization with confocal laser scanning microscopy (CLSM) showed a homogeneous distribution of the labeled particles in the lipid matrix. Regarding structural appearance, particle density and distribution, the formulations with a high particle/lipid ratio (5:1) resembled native VC very closely. Comparable results between native VC and the synthetic formulations were obtained concerning water handling properties, thermotropic behavior while lower elasticity and lower viscosity were observed for the synthetic biofilms. The biofilm formulations were stable for at least 1 month at 4 degrees C. In conclusion, our formulations mimic natural VC very closely and are promising candidates for in vivo studies.
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Long periodicity phase in extracted lipids of Vernix caseosa obtained with equilibration at physiological temperature
Chemistry and physics of lipids, 2008Co-Authors: Robert Rissmann, Maria Ponec, Gert S. Gooris, Johanna A. BouwstraAbstract:Abstract The outermost layer of the skin, the stratum corneum (SC), comprises the main barrier function between body and environment. The SC features a highly structured lipid organization: a short periodicity phase and a long periodicity phase (LPP) with a repeat distance of 6 and 13 nm, respectively. Like SC, Vernix caseosa (VC), the creamy white skin-surface biofilm of the newborn, also contains barrier lipids, i.e. ceramides, cholesterol and free fatty acids. Aim of this study was to investigate whether isolated VC lipids also form the characteristic LPP. Several preparation methods were examined and only when the solution of the lipid mixture, isolated either from VC or SC, was dried under nitrogen at 37 °C and subsequently spread onto a support, the LPP was formed. When VC barrier lipids were first exposed to elevated temperatures and subsequently cooled down, the LPP was formed at around 34 °C, which is at a much lower temperature than observed with the lipids in SC. In conclusion, we showed for the first time that depending on the preparation method, (i) VC lipids also form the LPP and (ii) the LPP in VC lipids and SC lipids was obtained at a low equilibration temperature, mimicking the physiological condition.
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Development of a murine model to evaluate the effect of Vernix caseosa on skin barrier recovery.
Experimental dermatology, 2008Co-Authors: Marion H.m. Oudshoorn, Robert Rissmann, Wim E. Hennink, Maria Ponec, Dennis Van Der Coelen, Johanna A. BouwstraAbstract:The aim of this study was twofold, that is the generation of a reliable model for skin barrier disruption and repair and to evaluate recovery of damaged skin after application of Vernix caseosa (VC). VC was selected as its wound healing properties were suggested previously, but never clearly demonstrated. Five different levels of barrier disruption in mice, accomplished by tape-stripping, were evaluated. Disruption models such as moderate, severe #1 and #2 (transepidermal water loss (TEWL) of 31 +/- 2, 59 +/- 4 and 66 +/- 3 g/m(2)/h, respectively) showed complete recovery within 72 h. However, not all corneocytes were removed after tape-stripping. Additionally, models such as severe #3 and #4 (TEWL of 73 +/- 5 and 79 +/- 6 g/m(2)/h, respectively) with a more severe disruption were evaluated. After tape-stripping, all corneocytes were removed and the remaining epidermis was intact. However, model #3 still showed complete recovery within 72 h. With model #4, a crust was formed and almost complete recovery (approximately 90%) was obtained within only 8 days. The effect of VC application on recovery of disrupted skin was evaluated with model #3 and #4. Model #3 showed that application of VC predominantly influenced initial recovery and is therefore merely appropriate to study the effect of formulations in the initial recovery period. Topical application of VC on model #4 considerably increased initial and long-term recovery. Moreover, VC application promoted rapid formation of stratum corneum and prevented epidermal thickening. These observations not only confirm the ability of VC to enhance barrier recovery, but also suggest potential use of this treatment clinically.
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Lanolin-derived lipid mixtures mimic closely the lipid composition and organization of Vernix caseosa lipids
Biochimica et Biophysica Acta, 2008Co-Authors: Robert Rissmann, Marion H.m. Oudshoorn, Elise Kocks, Wim E. Hennink, Maria Ponec, Johanna A. BouwstraAbstract:Abstract The aim of the present study was to use semi-synthetic lipid mixtures to mimic the complex lipid composition, organization and thermotropic behaviour of Vernix caseosa (VC) lipids. As VC shows multiple protecting and barrier supporting properties before and after birth, it is suggested that a VC substitute could be an innovative barrier cream for barrier deficient skin. Lanolin was selected as the source of the branched chain sterol esters and wax esters — the main lipid classes of VC. Different lipid fractions were isolated from lanolin and subsequently mixed with squalene, triglycerides, cholesterol, ceramides and fatty acids to generate semi-synthetic lipid mixtures that mimic the lipid composition of VC, as established by high-performance thin-layer chromatography. Differential scanning calorimetry and Fourier transform infrared spectroscopy investigations revealed that triglycerides play an important role in the (lateral) lipid organization and thermotropic behaviour of the synthetic lipid mixtures. Excellent resemblance of VC lipids was obtained when adding unsaturated triglycerides. Moreover, these lipid mixtures showed similar long range ordering as VC. The optimal lipid mixture was evaluated on tape-stripped hairless mouse skin in vivo. The rate of barrier recovery was increased and comparable to VC lipid treatment.
Steven B. Hoath - One of the best experts on this subject based on the ideXlab platform.
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Epidermal barrier treatments based on Vernix caseosa.
Skin pharmacology and physiology, 2011Co-Authors: Marty O. Visscher, William L. Pickens, Angela A. Laruffa, Vivek Narendran, Namrata D. Barai, Steven B. HoathAbstract:Background/Aims: Premature infants lack the Vernix caseosa, have an incompetent stratum corneum (SC) barrier and are predisposed to infection. Use of topical agents to improve barrier function has had mixed outcomes. The aim was to determine the effect of Vernix versus common barrier creams on the rate and quality of the epidermal barrier repair following controlled wounding. Methods: Minor wounds were created with (1) laser ablation in the minipig and (2) tape stripping of mother’s volar skin as a model for premature skin. Native Vernix was applied to the mother’s tape-stripped skin. Treatments were no occlusion (NO), Vernix and a petrolatum-based cream (PBC) in the pig, and NO, Vernix, PBC, an oil-in-water cream (OWC), a semipermeable film (SP) and full occlusion (FO) in adults. Results: Outcomes for both trials were barrier recovery and skin hydration (moisture accumulation rate, MAT), initial hydration, erythema and dryness in adults. Vernix and PBC produced greater barrier repair than NO in the pig. SP produced greater recovery than NO and FO in adults. Vernix yielded greater recovery than FO and was similar to PBC, OWC and NO. Vernix had a directionally higher MAT than OWC and directionally higher initial hydration than NO. Conclusions: The findings suggest that Vernix-based topical creams would be effective for the treatment of epidermal wounds and show promise to augment SC repair and maturation in infants.
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Neonatal skin maturation--Vernix caseosa and free amino acids.
Pediatric dermatology, 2011Co-Authors: Marty O. Visscher, William L. Pickens, R. Randall Wickett, Radhika Subhash Utturkar, Angela A. Laruffa, Marisa Robinson, Vivek Narendran, Steven B. HoathAbstract:Neonatal skin hydration decreases rapidly postnatally and then increases, indicating adaptive changes in stratum corneum water handling properties. Transition from high to low humidity at birth may initiate filaggrin proteolysis to free amino acids. Neonatal skin with Vernix caseosa retained is more hydrated than skin with Vernix removed. This study examines the potential roles of free amino acids and Vernix in postnatal adaptation of infant stratum corneum in vivo. Specifically, the ontogeny of free amino acid generation in neonatal stratum corneum and the role of Vernix caseosa in postnatal adaptation were examined using high performance liquid chromatography. Free amino acids were quantified for infant skin samples collected at (i) birth and 1 month and (ii) birth and 24 hours after Vernix caseosa retention or removal and compared to neonatal foreskin, Vernix caseosa, and adult stratum corneum using t-tests, analysis of variance, or univariate procedures. Free amino acids were extremely low at birth, significantly higher 1 month later but lower than in adults. Vernix caseosa retention led to significantly higher free amino acids 24 hours after birth compared to infants with Vernix caseosa removed, and it paralleled the higher stratum corneum hydration of Vernix caseosa-retained skin. Vernix caseosa contained free amino acids, with glutamic acid and histidine levels higher than in infants. Free amino acids in Vernix caseosa-retained skin appear to originate from Vernix caseosa. Free amino acids were lower in neonatal foreskin than adult forearm stratum corneum. Arginine was higher than citrulline at birth, but levels were comparable in older infants. The free amino acid increase at 1 month may be initiated by the humidity transition at birth and supports results in animals. The findings have implications for infant skin care practices.
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Effect of Vernix caseosa on the Penetration of Chymotryptic Enzyme: Potential Role in Epidermal Barrier Development
Pediatric research, 2007Co-Authors: Anyarporn Tansirikongkol, Marty O. Visscher, R. Randall Wickett, Steven B. HoathAbstract:The fetal epidermal barrier undergoes rapid develop- ment during late gestation despite conditions injurious to the skin postnatally, i.e. prolonged exposure to water (urine) and noxious substances such as pancreatic chymotrypsin. Nevertheless, at birth, term newborns have a superb epidermal barrier. Concomitant with formation of the stratum corneum in utero, Vernix caseosa forms a natural multifunctional cream separating the skin surface from the amniotic fluid with possible unique barrier properties. Therefore, we investigated the effect of native Vernix, synthetic Vernix, and Desitin ® on penetration of chymotrypsin, a proteolytic enzyme present in both developing epidermis and meconium. -Chymotrypsin penetration through test materials was conducted in vitro using a modified Franz diffusion cell. The presence of -chymotrypsin in Vernix and a possible inhibitory effect of Vernix on -chymotrypsin activity were investigated. Vernix films significantly impeded chymotrypsin pen- etration compared with controls during 24-h exposure experiments. -Chymotryptic activity in Vernix was undetectable, and Vernix showed no endogenous inhibition of such activity. Both synthetic Vernix and Desitin ® significantly impeded -chymotrypsin penetra- tion compared with controls during 9-h exposure experiments. With respect to the developing epidermal barrier, these results are consis- tent with the hypothesis that Vernix films retain endogenous (epider- mal) chymotrypsin while preventing exposure to exogenous (pancre- atic) chymotrypsin. (Pediatr Res 62: 49-53, 2007)
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New Insights into Ultrastructure, Lipid Composition and Organization of Vernix caseosa
The Journal of investigative dermatology, 2006Co-Authors: Robert Rissmann, Steven B. Hoath, Maria Ponec, Hendrik W.w. Groenink, Arij Weerheim, Johanna A. BouwstraAbstract:The upper layer of the epidermis, the stratum corneum (SC), is very important for skin barrier function. During the last trimester of gestation, the SC of the fetus is protected by a cheesy, white biofilm called Vernix caseosa (VC). VC consists of water-containing corneocytes embedded in a lipid matrix and the basic structure shows certain similarities with the SC. This study aimed to characterize VC, with the main focus on an integral analysis of free and (to the corneocytes) bound lipids, on the lipid organization, and on ultrastructure. Free lipids of VC show a wide distribution in polarity; nonpolar lipids such as sterol esters and triglycerides predominate, having a chain length of up to 32 carbon atoms. The profile of fatty acids, ω -hydroxyacids and ω -hydroxyceramides – representing the bound lipids of VC – shows high similarity to that of SC. Morphological studies revealed the presence of highly hydrated corneocytes embedded in lipids, the latter being occasionally accumulated as lipid pools. Freeze fracture electron microscopy showed smooth surfaces of corneocytes and a heterogeneous appearance of intercellular lipids. The results suggest a lower degree of ordering of VC lipids as compared to the SC. A small-angle X-ray diffraction study showed similar results.
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The biology of Vernix caseosa
International journal of cosmetic science, 2006Co-Authors: Steven B. Hoath, William L. Pickens, Marty O. VisscherAbstract:Synopsis The biology and physical properties of the uniquely human skin cream ‘Vernix caseosa’ are discussed. This material coats the foetal skin surface during the last trimester of gestation and provides multiple beneficial functions for the foetus and newborn infant. Vernix has a complex structure similar to stratum corneum but lacks lipid lamellae and is more plastic due to the absence of desmosomal constraints. In utero, Vernix is made in part by foetal sebaceous glands, interacts with pulmonary surfactant, detaches into the amniotic fluid, and is swallowed by the foetus. At the time of birth, Vernix has a remarkably constant water content approximating 80%. Postnatally, Vernix is simultaneously a cleanser, a moisturizer, an antiinfective, and an anti-oxidant. Vernix facilitates acid mantle development and supports normal bacterial colonization. Its hydrated cellular structure and unusual lipid composition provide a ‘best’ solution for the needs of the foetus and newborn, not least of which is the attraction of caregivers. Vernix is an important natural biomaterial of potential interest to cosmetic scientists, and other disciplines involved in product development and therapies targeting the complex interface between the stratum corneum and a changing terrestrial environment.
Robert Rissmann - One of the best experts on this subject based on the ideXlab platform.
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Mimicking Vernix caseosa--preparation and characterization of synthetic biofilms.
International Journal of Pharmaceutics, 2009Co-Authors: Robert Rissmann, Marion H.m. Oudshoorn, Johanna A. Bouwstra, Maria Ponec, Raphaël Zwier, Wim E. HenninkAbstract:The multiple protecting and barrier-supporting properties of the creamy, white biofilm Vernix caseosa (VC) before and after birth suggest that a VC biomimetic could be an innovative barrier cream for barrier-deficient skin. The aim of this study was the rational design and preparation of synthetic biofilms mimicking the unique composition and properties of natural VC. Hexagonal, highly hydrated hyperbranched polyglycerol microgel particles (30 microm in diameter) were embedded in a synthetic lanolin-based lipid mixture using a micromixer. In these formulations, the water content of the particles (i.e. 50% and 80%), an additional lipid coating of the particles and different particle/lipid ratios were varied. Characterization with confocal laser scanning microscopy (CLSM) showed a homogeneous distribution of the labeled particles in the lipid matrix. Regarding structural appearance, particle density and distribution, the formulations with a high particle/lipid ratio (5:1) resembled native VC very closely. Comparable results between native VC and the synthetic formulations were obtained concerning water handling properties, thermotropic behavior while lower elasticity and lower viscosity were observed for the synthetic biofilms. The biofilm formulations were stable for at least 1 month at 4 degrees C. In conclusion, our formulations mimic natural VC very closely and are promising candidates for in vivo studies.
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Long periodicity phase in extracted lipids of Vernix caseosa obtained with equilibration at physiological temperature
Chemistry and physics of lipids, 2008Co-Authors: Robert Rissmann, Maria Ponec, Gert S. Gooris, Johanna A. BouwstraAbstract:Abstract The outermost layer of the skin, the stratum corneum (SC), comprises the main barrier function between body and environment. The SC features a highly structured lipid organization: a short periodicity phase and a long periodicity phase (LPP) with a repeat distance of 6 and 13 nm, respectively. Like SC, Vernix caseosa (VC), the creamy white skin-surface biofilm of the newborn, also contains barrier lipids, i.e. ceramides, cholesterol and free fatty acids. Aim of this study was to investigate whether isolated VC lipids also form the characteristic LPP. Several preparation methods were examined and only when the solution of the lipid mixture, isolated either from VC or SC, was dried under nitrogen at 37 °C and subsequently spread onto a support, the LPP was formed. When VC barrier lipids were first exposed to elevated temperatures and subsequently cooled down, the LPP was formed at around 34 °C, which is at a much lower temperature than observed with the lipids in SC. In conclusion, we showed for the first time that depending on the preparation method, (i) VC lipids also form the LPP and (ii) the LPP in VC lipids and SC lipids was obtained at a low equilibration temperature, mimicking the physiological condition.
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Development of a murine model to evaluate the effect of Vernix caseosa on skin barrier recovery.
Experimental dermatology, 2008Co-Authors: Marion H.m. Oudshoorn, Robert Rissmann, Wim E. Hennink, Maria Ponec, Dennis Van Der Coelen, Johanna A. BouwstraAbstract:The aim of this study was twofold, that is the generation of a reliable model for skin barrier disruption and repair and to evaluate recovery of damaged skin after application of Vernix caseosa (VC). VC was selected as its wound healing properties were suggested previously, but never clearly demonstrated. Five different levels of barrier disruption in mice, accomplished by tape-stripping, were evaluated. Disruption models such as moderate, severe #1 and #2 (transepidermal water loss (TEWL) of 31 +/- 2, 59 +/- 4 and 66 +/- 3 g/m(2)/h, respectively) showed complete recovery within 72 h. However, not all corneocytes were removed after tape-stripping. Additionally, models such as severe #3 and #4 (TEWL of 73 +/- 5 and 79 +/- 6 g/m(2)/h, respectively) with a more severe disruption were evaluated. After tape-stripping, all corneocytes were removed and the remaining epidermis was intact. However, model #3 still showed complete recovery within 72 h. With model #4, a crust was formed and almost complete recovery (approximately 90%) was obtained within only 8 days. The effect of VC application on recovery of disrupted skin was evaluated with model #3 and #4. Model #3 showed that application of VC predominantly influenced initial recovery and is therefore merely appropriate to study the effect of formulations in the initial recovery period. Topical application of VC on model #4 considerably increased initial and long-term recovery. Moreover, VC application promoted rapid formation of stratum corneum and prevented epidermal thickening. These observations not only confirm the ability of VC to enhance barrier recovery, but also suggest potential use of this treatment clinically.
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Lanolin-derived lipid mixtures mimic closely the lipid composition and organization of Vernix caseosa lipids
Biochimica et Biophysica Acta, 2008Co-Authors: Robert Rissmann, Marion H.m. Oudshoorn, Elise Kocks, Wim E. Hennink, Maria Ponec, Johanna A. BouwstraAbstract:Abstract The aim of the present study was to use semi-synthetic lipid mixtures to mimic the complex lipid composition, organization and thermotropic behaviour of Vernix caseosa (VC) lipids. As VC shows multiple protecting and barrier supporting properties before and after birth, it is suggested that a VC substitute could be an innovative barrier cream for barrier deficient skin. Lanolin was selected as the source of the branched chain sterol esters and wax esters — the main lipid classes of VC. Different lipid fractions were isolated from lanolin and subsequently mixed with squalene, triglycerides, cholesterol, ceramides and fatty acids to generate semi-synthetic lipid mixtures that mimic the lipid composition of VC, as established by high-performance thin-layer chromatography. Differential scanning calorimetry and Fourier transform infrared spectroscopy investigations revealed that triglycerides play an important role in the (lateral) lipid organization and thermotropic behaviour of the synthetic lipid mixtures. Excellent resemblance of VC lipids was obtained when adding unsaturated triglycerides. Moreover, these lipid mixtures showed similar long range ordering as VC. The optimal lipid mixture was evaluated on tape-stripped hairless mouse skin in vivo. The rate of barrier recovery was increased and comparable to VC lipid treatment.
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Temperature-induced changes in structural and physicochemical properties of Vernix caseosa.
The Journal of investigative dermatology, 2007Co-Authors: Robert Rissmann, Marion H.m. Oudshoorn, Wim E. Hennink, Maria Ponec, Hendrik W.w. Groenink, Gert S. Gooris, Johanna A. BouwstraAbstract:The skin of the third trimester fetus and early newborn exhibits a complex, multifunctional, highly hydrated but viscous skin-surface biofilm called Vernix caseosa (VC). During birth, VC undergoes a substantial change from an aqueous and warm surrounding into a gaseous and colder environment postnatally. The aim of this study was to investigate the structural and physicochemical changes in VC, which accompany physiologically relevant variations in environment parameters, such as temperature and humidity. A remarkable difference was observed in water release and uptake properties: dehydration and rehydration processes take place two to four times faster at 37°C than at room temperature (RT). The dehydration was irreversible; rehydration was only possible to a final weight of 55% (37°C) and 46% (RT) of the pre-desiccation weight. Differential scanning calorimetry showed two different overlapping phase transitions within physiological temperature range. Investigation of the lipid organization by Fourier transform infrared spectroscopy and small-angle X-ray diffraction revealed a more disordered state of lipids at 37°C than at RT, which might explain the faster dehydration and rehydration process at 37°C as well as the changes in thermotropic rheological behavior. In conclusion, we demonstrated that VC properties adjust to the fundamental change from the intrauterine to the post-natal environment.
Josef Cvačka - One of the best experts on this subject based on the ideXlab platform.
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Analysis of (O-acyl) alpha- and omega-hydroxy fatty acids in Vernix caseosa by high-performance liquid chromatography-Orbitrap mass spectrometry
Analytical and Bioanalytical Chemistry, 2020Co-Authors: Aneta Vavrušová, Vladimír Vrkoslav, Richard Plavka, Zuzana Bosáková, Josef CvačkaAbstract:Fatty acid esters of long-chain hydroxy fatty acids or ( O -acyl)-hydroxy fatty acids (OAHFAs) were identified for the first time in Vernix caseosa and characterized using chromatography and mass spectrometry. OAHFAs were isolated from the total lipid extract by a two-step semipreparative TLC. The general structure of OAHFAs was established using high-resolution and tandem mass spectrometry of intact lipids and their transesterification and derivatization products. Two isomeric lipid classes were identified: O -acyl esters of ω-hydroxy fatty acids (ωOAHFA) and O -acyl esters of α-hydroxy fatty acids (αOAHFAs). To the best of our knowledge, αOAHFAs have never been detected in any biological sample before. Chromatographic separation and identification of OAHFAs species were achieved using non-aqueous reversed-phase HPLC coupled to electrospray ionization hybrid linear ion trap-Orbitrap mass spectrometry. The lipid species were detected as deprotonated molecules, and their structures were elucidated using data-dependent fragmentation in the negative ion mode. More than 400 OAHFAs were identified in this way. The most abundant ωOAHFAs species were 28:0/ ω -18:2, 29:0/ ω -18:2, 30:0/ ω -18:2, 32:0/ ω -18:2, and 30:0/ ω -18:3, while αOAHFAs comprised saturated species 21:0/ α -24:0, 22:0/ α -24:0, 23:0/ α -24:0, 24:0/ α -24:0, and 26:0/ α -24:0. OAHFAs were estimated to account for approximately 0.04% of Vernix caseosa lipids. Graphical Abstract
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Nonhydroxylated 1-O-acylceramides in Vernix caseosa
Journal of lipid research, 2018Co-Authors: Eva Harazim, Vladimír Vrkoslav, Miloš Buděšínský, Petr Harazim, Martin Svoboda, Richard Plavka, Zuzana Bosáková, Josef CvačkaAbstract:Vernix caseosa, the waxy substance that coats the skin of newborn babies, has an extremely complex lipid composition. We have explored these lipids and identified nonhydroxylated 1-O-acylceramides (1-O-ENSs) as a new class of lipids in Vernix caseosa. These ceramides mostly contain saturated C11-C38 ester-linked (1-O) acyls, saturated C12-C39 amide-linked acyls, and C16-C24 sphingoid bases. Because their fatty acyl chains are frequently branched, numerous molecular species were separable and detectable by HPLC/MS: we found more than 2,300 molecular species, 972 of which were structurally characterized. The most abundant 1-O-ENSs contained straight-chain and branched fatty acyls with 20, 22, 24, or 26 carbons in the 1-O position, 24 or 26 carbons in the N position, and sphingosine. The 1-O-ENSs were isolated using multistep TLC and HPLC and they accounted for 1% of the total lipid extract. The molecular species of 1-O-ENSs were separated on a C18 HPLC column using an acetonitrile/propan-2-ol gradient and detected by APCI-MS, and the structures were elucidated by high-resolution and tandem MS. Medium-polarity 1-O-ENSs likely contribute to the cohesiveness and to the waterproofing and moisturizing properties of Vernix caseosa.
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cholesteryl esters of ω o acyl hydroxy fatty acids in Vernix caseosa
Journal of Lipid Research, 2017Co-Authors: Aneta Kalužikova, Eva Harazim, Vladimír Vrkoslav, Richard Plavka, Zuzana Bosáková, Michal Hoskovec, Milos Buděsinský, Josef CvačkaAbstract:: Cholesteryl esters of ω-(O-acyl)-hydroxy FAs (Chl-ωOAHFAs) were identified for the first time in Vernix caseosa and characterized using chromatography and MS. Chl-ωOAHFAs were isolated using adsorption chromatography on silica gel and magnesium hydroxide. Their general structure was established using high-resolution and tandem MS of intact lipids, and products of their transesterification and derivatizations. Individual molecular species were characterized using nonaqueous reversed-phase HPLC coupled to atmospheric pressure chemical ionization. The analytes were detected as protonated molecules, and their structures were elucidated in the negative ion mode using controlled thermal decomposition and data-dependent fragmentation. About three hundred molecular species of Chl-ωOAHFAs were identified in this way. The most abundant Chl-ωOAHFAs contained 32:1 ω-hydroxy FA (ω-HFA) and 14:0, 15:0, 16:0, 16:1, and 18:1 FAs. The double bond in the 32:1 ω-HFA was in the n-7 and n-9 positions. Chl-ωOAHFAs are estimated to account for approximately 1-2% of Vernix caseosa lipids.
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Analysis of 1,2-diol diesters in Vernix caseosa by high-performance liquid chromatography - atmospheric pressure chemical ionization mass spectrometry.
Journal of chromatography. A, 2014Co-Authors: Lenka Šubčíková, Vladimír Vrkoslav, Richard Plavka, Radka Míková, Eva Háková, Antonín Doležal, Pavel Coufal, Michal Hoskovec, Tereza Čmelíková, Josef CvačkaAbstract:Abstract Fatty acid diesters of long-chain 1,2-diols (1,2-DDE), or type II wax diesters, were analyzed in the Vernix caseosa of a newborn girl. 1,2-DDE were isolated from the total lipid extract by the semipreparative TLC using plates coated with silica gel. Chromatographic separation of the 1,2-DDE molecular species was achieved on the non-aqueous reversed-phase HPLC with two Nova-Pak C18 columns connected in series (a total length of 45 cm) and using an acetonitrile–ethyl acetate gradient. 1,2-DDE eluted from the column in the order of their equivalent chain number. The analytes were detected as ammonium adducts by an ion-trap mass spectrometer equipped with an atmospheric pressure chemical ionization source. Their structures were elucidated using tandem mass spectrometry with MS, MS2 and MS3 steps in a data-dependent mode. More than two thousand molecular species of 1,2-DDE were identified in 141 chromatographic peaks. The most abundant 1,2-DDE were monounsaturated lipids consisting of a C22 diol and a C18:1 fatty acid together with C16:0, C14:0 or C15:0 fatty acids. The positions of double bonds were characterized by the fragmentation of [M+C3H5N]+ formed in the ion source.
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Newborn Boys and Girls Differ in the Lipid Composition of Vernix caseosa
PloS one, 2014Co-Authors: Radka Míková, Vladimír Vrkoslav, Richard Plavka, Robert Hanus, Eva Háková, Zuzana Hábová, Antonín Doležal, Pavel Coufal, Josef CvačkaAbstract:Vernix caseosa protects the skin of a human fetus during the last trimester of pregnancy and of a newborn after the delivery. Besides its cellular and proteinaceous components, an important constituent and functional agent is a complex lipid fraction, implicated in a multitude of salubrious effects of Vernix caseosa. Little is known about how the chemical composition of Vernix caseosa lipids is affected by various biological characteristics of the baby, such as the gestational age, birth weight, and, last but not least, the gender of the newborn. This study reports on the chemical variability of lipids contained in the Vernix caseosa of twenty newborn girls and boys and shows that the quantitative patterns of the lipids are sex-specific. The specificity of lipids was investigated at the level of fatty acids in the total lipid extracts and intact lipids of several neutral lipid classes. Hydrocarbons, wax esters, cholesteryl esters, diol diesters and triacylglycerols were isolated using optimized semipreparative thin-layer chromatography, and the molecular species within each class were characterized using matrix-assisted laser desorption/ionization mass spectrometry. Statistical evaluation revealed significant quantitative sex-related differences in the lipid composition of Vernix caseosa among the newborns, pronounced in the two lipid classes associated with the activity of sebaceous glands. Higher proportions of wax esters and triacylglycerols with longer hydrocarbon chains were observed in newborn girls.
Marty O. Visscher - One of the best experts on this subject based on the ideXlab platform.
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Epidermal barrier treatments based on Vernix caseosa.
Skin pharmacology and physiology, 2011Co-Authors: Marty O. Visscher, William L. Pickens, Angela A. Laruffa, Vivek Narendran, Namrata D. Barai, Steven B. HoathAbstract:Background/Aims: Premature infants lack the Vernix caseosa, have an incompetent stratum corneum (SC) barrier and are predisposed to infection. Use of topical agents to improve barrier function has had mixed outcomes. The aim was to determine the effect of Vernix versus common barrier creams on the rate and quality of the epidermal barrier repair following controlled wounding. Methods: Minor wounds were created with (1) laser ablation in the minipig and (2) tape stripping of mother’s volar skin as a model for premature skin. Native Vernix was applied to the mother’s tape-stripped skin. Treatments were no occlusion (NO), Vernix and a petrolatum-based cream (PBC) in the pig, and NO, Vernix, PBC, an oil-in-water cream (OWC), a semipermeable film (SP) and full occlusion (FO) in adults. Results: Outcomes for both trials were barrier recovery and skin hydration (moisture accumulation rate, MAT), initial hydration, erythema and dryness in adults. Vernix and PBC produced greater barrier repair than NO in the pig. SP produced greater recovery than NO and FO in adults. Vernix yielded greater recovery than FO and was similar to PBC, OWC and NO. Vernix had a directionally higher MAT than OWC and directionally higher initial hydration than NO. Conclusions: The findings suggest that Vernix-based topical creams would be effective for the treatment of epidermal wounds and show promise to augment SC repair and maturation in infants.
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Neonatal skin maturation--Vernix caseosa and free amino acids.
Pediatric dermatology, 2011Co-Authors: Marty O. Visscher, William L. Pickens, R. Randall Wickett, Radhika Subhash Utturkar, Angela A. Laruffa, Marisa Robinson, Vivek Narendran, Steven B. HoathAbstract:Neonatal skin hydration decreases rapidly postnatally and then increases, indicating adaptive changes in stratum corneum water handling properties. Transition from high to low humidity at birth may initiate filaggrin proteolysis to free amino acids. Neonatal skin with Vernix caseosa retained is more hydrated than skin with Vernix removed. This study examines the potential roles of free amino acids and Vernix in postnatal adaptation of infant stratum corneum in vivo. Specifically, the ontogeny of free amino acid generation in neonatal stratum corneum and the role of Vernix caseosa in postnatal adaptation were examined using high performance liquid chromatography. Free amino acids were quantified for infant skin samples collected at (i) birth and 1 month and (ii) birth and 24 hours after Vernix caseosa retention or removal and compared to neonatal foreskin, Vernix caseosa, and adult stratum corneum using t-tests, analysis of variance, or univariate procedures. Free amino acids were extremely low at birth, significantly higher 1 month later but lower than in adults. Vernix caseosa retention led to significantly higher free amino acids 24 hours after birth compared to infants with Vernix caseosa removed, and it paralleled the higher stratum corneum hydration of Vernix caseosa-retained skin. Vernix caseosa contained free amino acids, with glutamic acid and histidine levels higher than in infants. Free amino acids in Vernix caseosa-retained skin appear to originate from Vernix caseosa. Free amino acids were lower in neonatal foreskin than adult forearm stratum corneum. Arginine was higher than citrulline at birth, but levels were comparable in older infants. The free amino acid increase at 1 month may be initiated by the humidity transition at birth and supports results in animals. The findings have implications for infant skin care practices.
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j cosmet sci 158 651 662 november december 2007 water handling properties of Vernix caseosa and a synthetic analogue
International Journal of Cosmetic Science, 2008Co-Authors: A. Tansirikongkol, Marty O. Visscher, Randall R WickettAbstract:Accepted for publication May 14, 2007 Synopsis A naturally occurring barrier cream, Vernix caseosa, is the viscous material synthesized by the sebaceous glands in the late gestational human fetus. Vernix functions as a moisturizer by increasing the skin hydration and water-holding capacity of treated skin. Vernix films are semi-permeable, i.e., in the range that facilitates barrier repair. Antioxidant, disinfectant, and skin cleansing functions are also present. Premature infants have a markedly immature epidermal barrier and the excessive water loss can lead to fluid and electrolyte imbalances, along with high evaporative heat loss. Application of petrolatum-based, low-water creams on these infants has decreased TEWL and improved the skin condition. However, in infants of 500–750 g, this treatment was associated with an increased incidence of late-onset nosocomial infection, and questions regarding efficacy and safety have been raised. The water-handling properties, semi-permeability and multi-functionality, suggest that application of Vernix may promote the development and restoration of premature or other compromised skin. The present study focuses on the development of barrier creams to simulate the water-handling properties of native Vernix. Barrier creams were prepared as high-water-phase emulsions containing various lipid mixtures. Several stable creams with high water content exhibited slow water release and water vapor transport rates in the range to facilitate barrier repair. The results showed the importance of emulsion type in preventing water release. Preparations with Vernix-like lipids demonstrated water release profiles closer to the native Vernix benchmark than those with conventional lipids. The work resulted in a synthetic Vernix barrier cream prototype for evaluation on skin and to which additional functionality, e.g., anti-infective and antioxidant activity, could be added. J. Cosmet. Sci., 58, 663–666 (November/December 2007) Abstracts International Journal of Cosmetic Science, Vol. 29, No. 4, 2007* J. Cosmet. Sci., 58, 667–668 (November/December 2007) Abstracts Journal of the Polish Society of Cosmetic Science, “Wiadomości PTK” Vol. 10, No 2, 2007* J. Cosmet. Sci., 58, 669–678 (November/December 2007) Author Index To Volume 58 J. Cosmet. Sci., 58, 679–685 (November/December 2007) Subject Index To Volume 58
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J. Cosmet. Sci., 158, 651–662 (November/December 2007) Water‐handling properties of Vernix caseosa and a synthetic analogue
International Journal of Cosmetic Science, 2008Co-Authors: A. Tansirikongkol, Marty O. Visscher, R. Randall WickettAbstract:Accepted for publication May 14, 2007 Synopsis A naturally occurring barrier cream, Vernix caseosa, is the viscous material synthesized by the sebaceous glands in the late gestational human fetus. Vernix functions as a moisturizer by increasing the skin hydration and water-holding capacity of treated skin. Vernix films are semi-permeable, i.e., in the range that facilitates barrier repair. Antioxidant, disinfectant, and skin cleansing functions are also present. Premature infants have a markedly immature epidermal barrier and the excessive water loss can lead to fluid and electrolyte imbalances, along with high evaporative heat loss. Application of petrolatum-based, low-water creams on these infants has decreased TEWL and improved the skin condition. However, in infants of 500–750 g, this treatment was associated with an increased incidence of late-onset nosocomial infection, and questions regarding efficacy and safety have been raised. The water-handling properties, semi-permeability and multi-functionality, suggest that application of Vernix may promote the development and restoration of premature or other compromised skin. The present study focuses on the development of barrier creams to simulate the water-handling properties of native Vernix. Barrier creams were prepared as high-water-phase emulsions containing various lipid mixtures. Several stable creams with high water content exhibited slow water release and water vapor transport rates in the range to facilitate barrier repair. The results showed the importance of emulsion type in preventing water release. Preparations with Vernix-like lipids demonstrated water release profiles closer to the native Vernix benchmark than those with conventional lipids. The work resulted in a synthetic Vernix barrier cream prototype for evaluation on skin and to which additional functionality, e.g., anti-infective and antioxidant activity, could be added. J. Cosmet. Sci., 58, 663–666 (November/December 2007) Abstracts International Journal of Cosmetic Science, Vol. 29, No. 4, 2007* J. Cosmet. Sci., 58, 667–668 (November/December 2007) Abstracts Journal of the Polish Society of Cosmetic Science, “Wiadomości PTK” Vol. 10, No 2, 2007* J. Cosmet. Sci., 58, 669–678 (November/December 2007) Author Index To Volume 58 J. Cosmet. Sci., 58, 679–685 (November/December 2007) Subject Index To Volume 58
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Effect of Vernix caseosa on the Penetration of Chymotryptic Enzyme: Potential Role in Epidermal Barrier Development
Pediatric research, 2007Co-Authors: Anyarporn Tansirikongkol, Marty O. Visscher, R. Randall Wickett, Steven B. HoathAbstract:The fetal epidermal barrier undergoes rapid develop- ment during late gestation despite conditions injurious to the skin postnatally, i.e. prolonged exposure to water (urine) and noxious substances such as pancreatic chymotrypsin. Nevertheless, at birth, term newborns have a superb epidermal barrier. Concomitant with formation of the stratum corneum in utero, Vernix caseosa forms a natural multifunctional cream separating the skin surface from the amniotic fluid with possible unique barrier properties. Therefore, we investigated the effect of native Vernix, synthetic Vernix, and Desitin ® on penetration of chymotrypsin, a proteolytic enzyme present in both developing epidermis and meconium. -Chymotrypsin penetration through test materials was conducted in vitro using a modified Franz diffusion cell. The presence of -chymotrypsin in Vernix and a possible inhibitory effect of Vernix on -chymotrypsin activity were investigated. Vernix films significantly impeded chymotrypsin pen- etration compared with controls during 24-h exposure experiments. -Chymotryptic activity in Vernix was undetectable, and Vernix showed no endogenous inhibition of such activity. Both synthetic Vernix and Desitin ® significantly impeded -chymotrypsin penetra- tion compared with controls during 9-h exposure experiments. With respect to the developing epidermal barrier, these results are consis- tent with the hypothesis that Vernix films retain endogenous (epider- mal) chymotrypsin while preventing exposure to exogenous (pancre- atic) chymotrypsin. (Pediatr Res 62: 49-53, 2007)
