PubMed Health⌕ Search

Biomedical subjects

G K Menon

Publications and source records attributed to G K Menon.

At least 19 recordsLinked to original sources
PubMed2002

Postnatal ecdysis establishes the permeability barrier in snake skin: new insights into barrier lipid structures.

A competent barrier to transepidermal water loss (TEWL) is essential for terrestrial life. In various vertebrates, epidermal water barriers composed of lipids prevent excessive TEWL, which varies inversely with habitat aridity. Little is known, however, about the mechanisms and regulation of permeability relative to natal transition from the 'aqueous' environments of gestation to the 'aerial' environments of terrestrial neonates. We investigated newly hatched California king snakes Lampropeltis getula to test the hypothesis that the first ecdysis is important for establishing the barrier to TEWL. We found that skin resistance to TEWL increases twofold following the first postnatal ecdysis, corresponding with a roughly twofold increase in thickness and deposition of lamellar lipids in the mesos layer, the site of the skin permeability barrier in snakes. In addition, novel observations on lipid inclusions within the alpha layer of epidermis suggest that this layer has functional similarities with avian epidermis. It appears that emergence of the integument from embryonic fluids, and its subsequent pan-body replacement following contact with air, are essential for completion of barrier competence in the newborn. These conditions provide a potentially useful model for investigations on the mechanism of barrier formation. We also found that hatchling snakes are transiently endothermic, with skin temperatures elevated by approximately 0.6 degrees C above ambient air temperature during the period of barrier formation. Behaviourally, hatchlings showed a higher tendency to seek humid microenvironments before the first ecdysis than after. The degree of water movement across the integument might explain the switch from reclusive to dispersive behaviours associated with postnatal ecdysis in snakes.

Aging↗
PubMed2001

Basis of occlusive therapy in psoriasis: correcting defects in permeability barrier and calcium gradient.

BACKGROUND: Although occlusive dressings have great potential in the management of psoriasis vulgaris, the therapeutic mechanism is not completely understood. Occlusion artificially restores and corrects the defective barrier in psoriasis plaques. Additionally, occlusion is know to normalize the epidermal calcium gradients in hyperproliferative murine skin models. METHODS: To investigate the basis of the therapeutic effect of occlusion on psoriatic plaques, we investigated the ultrastructural morphology of intercorneocyte lipid layers, lamellar bodies, and calcium gradient in chronic plaque-type psoriasis after occlusion with a water vapor-impermeable membrane. The specimens were processed for electron microscopy using: (i) ruthenium tetroxide postfixation; and (ii) ion-capture cytochemistry for calcium localization. RESULTS: Occlusion for 7 days resulted in a nearly mature pattern of intercellular multilamellar structures, re-establishment of the near-normal epidermal calcium gradient, and disappearance of calcium precipitates from the stratum corneum interstices. CONCLUSIONS: The normalization of the permeability barrier and epidermal calcium gradient may play important roles in the therapeutic effects of occlusive dressings in chronic plaque-type psoriasis.

Calcium↗
PubMed1998

The secretory granular cell: the outermost granular cell as a specialized secretory cell.

The contents of epidermal lamellar bodies (LB) are delivered selectively to the intercellular spaces at the stratum granulosum (SG)-stratum corneum (SC) interface. We assessed the subcellular basis for LB secretion first by confocal microscopy, following labeling with Nile red or NBD-ceramide, which reveals a tubulo-reticular membrane system within the apical cytosol of the outermost SG cell layer under basal conditions, changing to a more peripheral staining pattern when secretion is stimulated. Ultrastructural study demonstrates that this network is composed of a widely disbursed trans-Golgi-like network (TGN), associated with arrays of contiguous LB, and deep invaginations of the SG-SC interface. Under basal conditions, limited fusion of apically directed LB leads to deep, interconnected invaginations of the apical plasma membrane, resulting in the formation of an extensive, honeycomb extension of the SG-SC interface. Still deeper invaginations and more extensive organelle fusion develop after the epidermis is acutely permeabilized by either acetone treatment, sonophoresis, or iontophoresis. Finally, nascent LB appear to bud off cisternae of the TGN, a process that appears to accelerate after barrier disruption. The deep invaginations of the SG-SC interface; the wide distribution of the TGN within the apical cytosol; the association of nascent LB with the TGN; and the rapid fusion of LB with these invaginations, deep within the cytosol, account for (i) the polarized secretion of LB from the apex of the outermost SG cell, and (ii) the rapid LB-secretory response to barrier perturbations. Finally, our results point to the outermost SG cell as a uniquely specialized secretory cell. We propose the term "secretory granulocyte" to encompass the specialized features of these cells.

4-Chloro-7-nitrobenzofurazan↗
PubMed1997

Mode of action of glycolic acid on human stratum corneum: ultrastructural and functional evaluation of the epidermal barrier.

Alpha-hydroxy acids (AHA) such as glycolic acid have recently been used extensively in cosmetic and dermatological formulas. In low concentration (2-5%) glycolic acid is believed to facilitate progressive weakening of cohesion of the intercellular material of the stratum corneum (SC), resulting in uniform exfoliation of its outermost layers (the stratum disjunctum). Since thinning of the SC as well as changes of intercellular lipids could theoretically compromise the barrier functions of the skin, we investigated the mode of AHA action on the SC to determine whether enhanced desquamation compromises the barrier structures of the SC and changes transepidermal water loss (TEWL) values. Electron microscopy of the epidermis biopsied from the volar forearm of human volunteers after 3 weeks of treatment with a 4% glycolic acid formulation twice daily was employed to evaluate 1) epidermal morphology and thickness of the SC, (2) the lamellar body and SC lipid bilayer organization, and (3) desquamative events based on degradation of desmosomes. TEWL values and SC hydration were recorded prior to and at the end of the study. Electron microscopy revealed no ultrastructural changes in the nucleated layers of the epidermis. The lamellar body (LB) secretory system in the stratum granulosum (SG), and intercellular lipid lamellae in the SC in both vehicle- and glycolic acid-treated samples were comparable to normal human SC. Within the SC, enhanced desmosomal breakdown, promoting loss of cohesion and desquamation, was restricted to the stratum disjunctum while desmosomes of the stratum compactum were unaffected. Treated areas displayed histologically, a more compact appearing SC. TEWL values remained unchanged in glycolic acid- and vehicle-treated skin. Our findings indicate that the barrier structures of the SC are not disrupted by glycolic acid formulations at the concentration used. One of the mechanism of action of AHA on the SC seemed to be a "targeted" desmosomal (corneosomal) action without compromising the barrier structures of the skin.

Adult↗
PubMed1997

Morphologic basis for a pore-pathway in mammalian stratum corneum.

Although prior morphologic studies have shown that both polar and nonpolar materials permeate across the stratum corneum (SC) via a paracellular route, the actual pathway through these heterogeneous domains is unknown. We applied hydrophilic and hydrophobic tracers in vivo to murine skin under basal conditions and/or after permeation enhancement with occlusion, vehicle enhancers, a lipid synthesis inhibitor, sonophoresis, and iontophoresis. Ruthenium tetroxide, ruthenium red plus osmium tetroxide, in situ precipitation with osmium vapor, and microwave postfixation methods were used to visualize penetration pathways. Tracers invariably localized to discrete lacunar domains embedded within the extracellular lamellar membrane system, regardless of their polarity or the enhancement method. Moreover, while the lacunar domains remained discontinuous under basal conditions, they appeared to gain structural continuity with permeation enhancement. These results indicate that extracellular lacunar domains comprise a pore pathway for penetration of polar and nonpolar molecules across the SC.

1-Butanol↗
PubMed1996

Ultrastructural organization of avian stratum corneum lipids as the basis for facultative cutaneous waterproofing.

The ultrastructure of naked neck epidermis from the ostrich (Struthio camelus) and ventral apterium from watered, and water-deprived, Zebra finches (Taeniopygia [Poephila] guttata castanotis) is presented. The form and distribution of the fully differentiated products of the lipid-enriched multigranular bodies are compared in biopsies post-fixed with osmium tetroxide or ruthenium tetroxide. The fine structure of ostrich epidermis suggests it is a relatively poor barrier to cutaneous water loss (CWL). The fine structure from watered, and 16-hr water-deprived Zebra finches, considered in conjunction with measurements of CWL, confirms previous reports of "facultative waterproofing," and emphasizes the rapidity of tissue response to dehydration. The seemingly counterintuitive facts that one xerophilic avian species, the ostrich, lacks a "good barrier" to CWL, whereas another, the Zebra finch, is capable of forming a good barrier, but does not always express this capability, are discussed. An explanation of these data in comparison to mammals centers on the dual roles of the integument of homeotherms in thermoregulation and conserving body water. It is concluded that birds, whose homeothermic control depends so much on CWL, cannot possess a permanent "good barrier," as such would compromise the heat loss mechanism. Facultative waterproofing (also documented in lizards) protects the organism against sudden reductions in water availability. In birds, and probably in snakes and lizards, facultative waterproofing involves qualitative changes in epidermal cell differentiation. Possible control mechanisms are discussed.

Animals↗
PubMed1995

Cutaneous barrier function after cold exposure in hairless mice: a model to demonstrate how cold interferes with barrier homeostasis among workers in the fish-processing industry.

Dry skin and eczema only seldomly occur in workers in the Danish fish-processing industry (FPI) during work, when their fingers and palms have a low skin surface temperature, low transepidermal water loss (TEWL), and a high capacitance. However, shortly after work, when the skin temperature has become normal, TEWL levels increase to above normal, and capacitance decreases to below normal, followed by the development of dry skin or chapping, which subsequently revert to normal over a period of hours. These observations suggest that workers in the FPI may have a defect in skin barrier function, which is, however, masked by a low skin temperature, resulting in misleadingly low TEWL levels during work. To test this hypothesis, we disrupted the permeability barrier in hairless mice with topical acetone, and exposed the treated skin to ice for 3.5 h. Although TEWL rates immediately after cold exposure were low, suggesting normal barrier recovery, TEWL increased to levels slightly above pre-cold exposure levels (i.e. levels just after the barrier was disrupted with acetone) when the skin temperature reverted to normal (> or = 15 min). The changes in TEWL were paralleled by equivalent changes in percutaneous penetration of the electron-dense tracer lanthanum nitrate. This indicates that cold masks a defective barrier, and inhibits barrier repair. After a few hours at ambient temperatures, normal barrier recovery was observed. Electron microscopy revealed empty or partially empty lamellar bodies during the first 30 min post-cold exposure. After 1 h the majority of nascent LBs displayed normal morphology. Moreover, histochemical studies showed a delayed reappearance of stratum corneum intercellular lipids following cold exposure. These results demonstrate that cold exposure prevents barrier recovery after acetone disruption, and provide an explanation for the occupational dermatosis observed in the fish-processing industry and related occupations.

Acetone↗
PubMed1994

Selective obliteration of the epidermal calcium gradient leads to enhanced lamellar body secretion.

The epidermal permeability barrier is formed by lipids delivered to the intercellular spaces through the secretion of lamellar bodies. Prior studies have shown that the rate of lamellar body secretion appears to be regulated by the extracellular calcium content of the upper epidermis, which is altered following permeability barrier disruption. To determine directly whether changes in extracellular calcium content in the upper epidermis versus disruption of the barrier regulate lamellar body secretion, we experimentally manipulated the Ca++ content of the upper epidermis by sonophoresis of aqueous solutions containing physiologic Ca++ (and K+) versus ion-free solutions across hairless mouse stratum corneum. Sonophoresis at 15 MHz did not alter barrier function, but in the absence of Ca++ the extracellular calcium content of the outer epidermis, as revealed by ion capture cytochemistry, was displaced downward toward the basal layer and dermis. In contrast, following sonophoresis of Ca(++)-containing solutions, the extracellular Ca++ gradient became obscured by excess Ca++ in the cytosol at all levels of the epidermis. These changes in the extracellular calcium content lead, in turn, to accelerated lamellar body secretion (with low Ca++), or basal rates of lamellar body secretion (with normal Ca++). These results demonstrate that the epidermal extracellular calcium content in the upper epidermis can be manipulated by sonophoresis without prior barrier disruption, and that changes in the Ca++ gradient induce lamellar body secretion, independent of barrier disruption.

Animals↗
PubMed1994

Integrity of the permeability barrier is crucial for maintenance of the epidermal calcium gradient.

Prior studies have demonstrated a Ca2+ gradient within the epidermis, with the highest concentration in the outer nucleated layers, disappearance of the Ca2+ gradient when the permeability barrier is acutely disrupted, and reappearance of the Ca2+ gradient in parallel with barrier repair, and disruption of the gradient in psoriasis. These observations suggest that integrity of the permeability barrier may maintain the epidermal Ca2+ gradient. To determine further whether a functional barrier is crucial for maintaining the Ca2+ gradient, we examined Ca2+ distribution by ion-capture cytochemistry in essential-fatty-acid-deficient (EFAD) and topical-lovastatin-treated mice, which display a chronic barrier abnormality. In both models, loss of the Ca2+ gradient occurred due to increased cytosolic Ca2+ in the lower epidermis, which normally displays a paucity of Ca2+. Moreover, artificial barrier restoration for 48 h with a water vapour-impermeable wrap normalized the Ca2+ distribution pattern. Acute barrier disruption also leads to the loss of the Ca2+ gradient, but in contrast with the chronic models, loss of the gradient was due to decreased Ca2+ in the upper epidermis. Occlusion with a vapour-impermeable wrap blocked restoration of the Ca2+ gradient after acute barrier disruption. These results demonstrate that chronic barrier disruption increases Ca2+ in the epidermis, and blockade of water flux normalizes Ca2+ distribution, whereas acute barrier disruption leads to loss of Ca2+, and blockade of water flux prevents the return of Ca2+. We conclude: (i) that the epidermal Ca2+ reservoir is derived from the movement of fluids and Ca2+ across the basement membrane, and (ii) that the integrity of the permeability barrier maintains the epidermal Ca2+ gradient.

Acetone↗
PubMed1994

High-frequency sonophoresis: permeation pathways and structural basis for enhanced permeability.

The mechanism of stratum corneum (SC) permeabilization by ultrasound (sonophoresis) is unknown. We studied here permeation pathways, and SC intercellular structural organization following applications of high-frequency sonophoresis to hairless mouse skin. Ruthenium tetroxide post-fixation and tracer solutions of LaNO3 and FITC-dextrans were employed to examine SC lamellar bilayers, lamellar body morphology and subcellular permeation pathways. Sonophoresis disrupted the compact organization of SC bilayers and LB-derived contents at the stratum granulosum (SG)-SC interface, leading to domain separation between 0 and 20 h, reverting by 48 h. Post-sonophoresis, tracers traversed the SC via lacunae within the lamellar bilayers, and via lamellae in sites that displayed domain separation. These studies provide insights about the penetration pathways, permeabilizing mechanisms, and kinetics of sonophoresis on the epidermis.

Animals↗
PubMed1994

Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease.

Hydrolysis of glucosylceramide by beta-glucocerebrosidase results in ceramide, a critical component of the intercellular lamellae that mediate the epidermal permeability barrier. A subset of type 2 Gaucher patients displays ichthyosiform skin abnormalities, as do transgenic Gaucher mice homozygous for a null allele. To investigate the relationship between glucocerebrosidase deficiency and epidermal permeability barrier function, we compared the stratum corneum (SC) ultrastructure, lipid content, and barrier function of Gaucher mice to carrier and normal mice, and to hairless mice treated topically with bromoconduritol B epoxide (BrCBE), an irreversible inhibitor of glucocerebrosidase. Both Gaucher mice and BrCBE-treated mice revealed abnormal, incompletely processed, lamellar body-derived sheets throughout the SC interstices, while transgenic carrier mice displayed normal bilayers. The SC of a severely affected type 2 Gaucher's disease infant revealed similarly abnormal ultrastructure. Furthermore, the Gaucher mice demonstrated markedly elevated transepidermal water loss (4.2 +/- 0.6 vs < 0.10 g/m2 per h). The electron-dense tracer, colloidal lanthanum, percolated between the incompletely processed lamellar body-derived sheets in the SC interstices of Gaucher mice only, demonstrating altered permeability barrier function. Gaucher and BrCBE-treated mice showed < 1% and < 5% of normal epidermal glucocerebrosidase activity, respectively, and the epidermis/SC of Gaucher mice demonstrated elevated glucosylceramide (5- to 10-fold), with diminished ceramide content. Thus, the skin changes observed in Gaucher mice and infants may result from the formation of incompetent intercellular lamellar bilayers due to a decreased hydrolysis of glucosylceramide to ceramide. Glucocerebrosidase therefore appears necessary for the generation of membranes of sufficient functional competence for epidermal barrier function.

Animals↗
PubMed1994

Permeability barrier requirements regulate epidermal beta-glucocerebrosidase.

The intercellular spaces of the outermost layers of the epidermis (stratum corneum, SC) of terrestrial mammals contain a mixture of lipids, enriched in ceramides that are critical for the epidermal permeability barrier. Whereas glucosylceramides (GlcCer) are synthesized in abundance in the epidermis, they disappear coincident with an increase of ceramides (Cer) in the SC. Hence, hydrolysis of GlcCer to Cer by beta-glucocerebrosidase (GlcCer'ase), may be required for permeability barrier homeostasis. We determined first whether modulations in epidermal GlcCer'ase activity and mRNA levels occur in response to barrier disruption; and second, how GlcCer'ase inhibitors influence barrier function and SC membrane ultrastructure. Barrier disruption significantly increased epidermal GlcCer'ase mRNA levels, with a 2.8-fold increase over untreated control levels at 8 h (P < 0.01). GlcCer'ase activity was increased in whole epidermis (34%; P < 0.02) 24 h after barrier disruption. Localization of GlcCer'ase activity showed an increase (33%; P < 0.05) in the outer epidermis (SC and stratum granulosum), without a change in lower epidermal activity (stratum spinosum and stratum basale). Furthermore, a single topical application of the GlcCer'ase inhibitor, bromoconduritol-B-epoxide (BrCBE), inhibited enzyme activity (98%) and significantly delayed permeability barrier recovery after acetone treatment. In addition, BrCBE treatment disrupted SC intercellular lamellar bilayers, without evidence of cellular toxicity. These results indicate that epidermal processing of GlcCer to Cer by GlcCer'ase is required for barrier homeostasis, and that this important enzymatic step is regulated by barrier requirements.

Acetone↗
PubMed1993

Localization and quantitation of calcium pools and calcium binding sites in cultured human keratinocytes.

Calcium plays a crucial role in regulating the growth and differentiation of cultured keratinocytes. However, the mechanism(s) of this regulation is not clear. Prior studies have shown that intracellular free calcium (Cai) increases with keratinocyte differentiation. In this study, in order to evaluate the role of cytosolic free calcium and organelle-bound calcium in keratinocyte differentiation, we quantitated and localized calcium pools in keratinocytes, utilizing the fluorescence probe indo-1 and ion-capture cytochemistry, respectively. Cai of undifferentiated keratinocytes was 80-120 nM, whereas Cai of differentiated keratinocytes was 200-300 nM depending on the extent of differentiation. The Cai of individual cells in an undifferentiated colony was heterogeneous (60-160 nM) with larger cells displaying higher Cai. Heterogeneity also was observed in the intracellular calcium-containing precipitates in the different layers of stratifying keratinocyte cultures using the cytochemical technique. Calcium precipitates were abundant in the lower cell layers, progressively decreasing apically, with the uppermost layer devoid of precipitates. Calcium-containing precipitates appeared as fine-to-coarse electron-dense granules on the plasma membrane, within the cytosol, mitochondria, nucleus, and vacuolar organelles. Whereas ionomycin in the presence of extracellular calcium increased the amount of intracellular calcium precipitates, EGTA removed calcium precipitates from organelles. Unlike intact epidermis, keratinocytes displayed no extracellular calcium reservoirs. Putative calcium binding sites, visualized by trivalent lanthanum (La) binding, were abundant on cell membranes and desmosomes of basaloid cells, but decreased in the upper cell layers. These studies revealed differences in the distribution of free ionic calcium (as determined by the fluorescence technique) and organelle-bound calcium (as determined by the cytochemical technique). Striking differences were also observed in calcium localization between intact epidermis and cultured epidermal cells. The localization pattern of calcium in cultured keratinocytes may reflect the hyperproliferative state of these cells, as in psoriatic epidermis, and/or the absence of a normal permeability barrier in these submerged cultures.

Binding Sites↗
PubMed1993

Barrier function regulates epidermal lipid and DNA synthesis.

The stratum corneum, the permeability barrier between the internal milieu and the environment, is composed of fibrous protein-enriched corneocytes and a lipid-enriched intercellular matrix. The lipids are a mixture of sphingolipids, cholesterol and free fatty acids, which form intercellular membrane bilayers. Lipid synthesis occurs in the keratinocytes in all nucleated layers of the epidermis, and the newly synthesized lipids are delivered by lamellar bodies to the interstices of the stratum corneum during epidermal differentiation. Disruption of barrier function by topical acetone treatment results in an increase in the synthesis of free fatty acids, sphingolipids and cholesterol in the living layers of the epidermis, leading to barrier repair. Cholesterol and sphingolipid synthesis are regulated by the rate-limiting enzymes HMG CoA reductase and serine palmitoyl transferase (SPT), respectively. Acute barrier disruption leads to an increase in both enzymes, but with a different time curve: increase in HMG CoA reductase activity begins at 1.5 h, whereas the increase in SPT activity occurs 6 h after barrier impairment. Topical application of HMG CoA reductase or SPT inhibitors after acetone treatment delays barrier repair, providing further evidence for a role of cholesterol and sphingolipids in epidermal barrier function. Repeated application of lovastatin to untreated skin results in disturbed barrier function accompanied by increased DNA synthesis and epidermal hyperplasia. Therefore, we have examined the specific relationship between barrier function and epidermal DNA synthesis. After acute and chronic disturbances not only lipid, but also DNA synthesis, is stimulated. Thus, stimulation of DNA synthesis leading to epidermal hyperplasia may be a second mechanism by which the epidermis repairs defects in barrier function. The link between barrier function and both lipid and DNA synthesis is supported further by occlusion studies. Artificial barrier repair by latex occlusion prevents an increase in both lipid and DNA synthesis. In addition, increased epidermal lipid and DNA synthesis in essential fatty-acid deficiency can be reversed by topical applications of the n-6 unsaturated fatty acids, linoleic or columbinic acid. These studies may be of relevance in understanding the pathogenesis of hyperproliferative skin diseases, such as ichthyosis, psoriasis, atopic dermatitis, and irritant contact dermatitis.

Animals↗
PubMed1993

Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function.

The interstices of the mammalian stratum corneum contain lipids in a system of continuous membrane bilayers critical for the epidermal permeability barrier. During the transition from inner to outer stratum corneum, the content of polar lipids including glucosylceramides, decreases while ceramide content increases. We investigated whether inhibition of glucosylceramide hydrolysis would alter epidermal permeability barrier function. Daily topical applications of bromoconduritol B epoxide (BrCBE) to intact murine skin selectively inhibited beta-glucocerebrosidase, increased glucosylceramide content of stratum corneum with ceramide content remaining largely unchanged, and caused a progressive, reversible decrease in barrier function. Histochemistry of inhibitor-treated epidermis revealed persistence of periodic acid-Schiff-positive staining in stratum corneum cell membranes, consistent with retention of hexose moieties. Electron microscopy of inhibitor-treated samples revealed no evidence of toxicity or changes in the epidermal lipid delivery system. However, immature membrane structures persisted in the intercellular spaces throughout the stratum corneum, with reappearance of mature membrane structures progressing outward from the lower stratum corneum upon termination of BrCBE. Finally, the induced barrier abnormality was not reversed by coapplications of ceramide. These data demonstrate that glucosylceramide hydrolysis is important in the formation of the epidermal permeability barrier, and suggest that accumulation of glucosylceramides in stratum corneum intercellular membrane domains leads to abnormal barrier function.

Administration, Topical↗
PubMed1993

Glucocorticoids accelerate fetal maturation of the epidermal permeability barrier in the rat.

The cutaneous permeability barrier to systemic water loss is mediated by hydrophobic lipids forming membrane bilayers within the intercellular domains of the stratum corneum (SC). The barrier emerges during day 20 of gestation in the fetal rat and is correlated with increasing SC thickness and increasing SC lipid content, the appearance of well-formed lamellar bodies in the epidermis, and the presence of lamellar unit structures throughout the SC. Because glucocorticoids accelerate lung lamellar body and surfactant maturation in man and experimental animals, these studies were undertaken to determine whether maternal glucocorticoid treatment accelerates maturation of the epidermal lamellar body secretory system. Maternal rats were injected with betamethasone or saline (control) on days 16-18, and pups were delivered prematurely on day 19. Whereas control pups exhibited immature barriers to transepidermal water loss (8.16 +/- 0.52 mg/cm2 per h), glucocorticoid-treated pups exhibited competent barriers (0.74 +/- 0.14 mg/cm2 per h; P < 0.001). Glucocorticoid treatment also: (a) accelerated maturation of lamellar body and SC membrane ultrastructure; (b) increased SC total lipid content twofold; and (c) increased cholesterol and polar ceramide content three- to sixfold. Thus, glucocorticoids accelerate the functional, morphological, and lipid biochemical maturation of the permeability barrier in the fetal rat.

Animals↗
PubMed1993

Preservation of permeability barrier ontogenesis in the intrauterine growth-retarded fetal rat.

The epidermal permeability barrier is provided by intercellular lipids forming multiple membrane bilayers in the stratum corneum. In the fetal rat, the barrier to transepidermal water loss forms during the 20th d of gestation and is accompanied by 1) increasing stratum corneum thickness; 2) increasing stratum corneum lipid content, particularly nonpolar ceramide and cholesterol content; and 3) the formation of lamellar unit structures throughout the stratum corneum interstices. In this report, we demonstrate that among pups of 20 d gestational age increasing barrier competence is correlated with increasing fetal weight. It has been previously demonstrated that fetal rats subjected to intrauterine growth retardation (IUGR) exhibit a thinner stratum corneum and decreased content of differentiation-specific epidermal structural proteins. To determine whether IUGR fetal rats also exhibit immaturity of barrier function and the barrier membrane system, maternal rats underwent unilateral uterine vessel ligation on d 17 or 18 of gestation and IUGR and control littermates were harvested on d 20, 21, or 22 of gestation for determination of transepidermal water loss. Despite significant somatic growth retardation and a thinner stratum corneum, barrier function in IUGR fetal rats did not significantly differ from that in control littermates at any gestational age. In both IUGR and control fetal rat epidermis at 21 d gestational age, lipids were deposited in a membrane pattern as visualized by nile red fluorescence microscopy and formed lamellar unit membrane structures throughout the stratum corneum intercellular domains as observed by electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗