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PubMed2001

Cholesteatoma: a morphologic study of stratum corneum lipids.

Two different lipid-retaining fixation techniques permitted electron microscopic visualization of both intra- and extracellular lipids in cholesteatoma epithelium obtained from 25 patients. An increased number of intracellular lipid-containing Odland bodies was demonstrated, with a maximum in the basal layer of the stratum granulosum, while the superior layer contained substantially fewer organelles than are found in normal skin. At the stratum granulosum/stratum corneum interface lipids secreted from Odland bodies were found in sac-like invaginations along the cell membrane but premature exocytosis was also frequently observed. In the intercellular spaces of the stratum corneum, multiple long sheets of lamellar structures interrupted by slits or pores enclosed the keratinized corneocytes. The intercellular spaces seemed narrow and an extracellular barrier was not found until well above the stratum granulosum/stratum corneum interface. A similar distribution of Odland bodies and structure of intercellular lipids can occur in several dermatoses, where the formation and maintenance of the cutaneous permeability barrier are defective.

Cell Count↗

PubMed1992

Germination of Trichophyton mentagrophytes on human stratum corneum in vitro.

The emergence of germ tubes from arthroconidia of Trichophyton mentagrophytes on stripped sheets of stratum corneum from different body areas was measured. Arthroconidia increased in size and started germination by 4 h at 37 degrees C. Germ tubes originated from a point on the arthroconidium surface mid-way between the points of attachment to adjacent conidia. With further incubation arthroconidial germination increased and germ tubes extended across the stratum corneum. Histological staining of transverse sections of infected stratum corneum showed hyphae penetrating longitudinally and perpendicularly through the thickness of the stratum corneum. By 7 days' incubation hyphae started to form arthroconidia thereby completing the vegetative growth cycle of the fungus. Scanning electron microscopy revealed penetration of corneocytes by germ tubes resulting in damage to the corneocyte surface.

Culture Techniques↗

PubMed1991

Functional analyses of the superficial stratum corneum in atopic xerosis.

Dermatologists universally recognize that the unaffected skin of patients with atopic dermatitis tends to be dry and slightly scaly. To characterize the functional properties of the superficial stratum corneum in atopic xerosis, we studied the forearms of 28 patients with atopic dermatitis, aged 14 to 30 years, and 18 age-matched controls, with the use of mainly noninvasive methods. Patients with atopic xerosis showed markedly higher transepidermal water loss and markedly lower skin surface hydration levels than did the controls. The corneocytes in atopic xerosis tended to desquamate in clumps of cell aggregates instead of as individual cells. They contained a substantially lower amount of water-soluble amino acids, which play a role in the water-retaining capacity of stratum corneum, than did those of controls. Although the number of stratum corneum cell layers in atopic xerosis (21 +/- 4) was substantially larger than that in controls (15 +/- 1), its turnover time (7 +/- 2 days) was appreciably shorter than that for controls (14 +/- 2 days). Like those noted in the skin with increased epidermal proliferation, the size of superficial corneocytes in patients with atopic xerosis was substantially smaller than in controls. Histopathologic examination revealed acanthotic epidermis, mild perivascular mononuclear cell infiltrate, and pigment incontinence. Atopic xerosis, the dry skin of patients with atopic dermatitis, shows various stratum corneum functional impairments, probably reflecting increased epidermal proliferation due to a low-level ongoing dermatitis.

Adolescent↗

PubMed1986

The water content of the stratum corneum in patients with atopic dermatitis. Measurement with the Corneometer CM 420.

The dry looking skin seen in many patients with atopic dermatitis reflects a defect in the epidermal barrier, the stratum corneum, as demonstrated by an increased transepidermal water loss (TEWL) and a decreased ability of the stratum corneum to bind water. The absolute amount of water within the stratum corneum is of importance both for barrier properties and for the clinical appearance of the skin. This water content was measured with a new instrument, the Corneometer CM 420, which takes advantage of the high dielectric constant of water. Forty patients with atopic dermatitis were studied--20 with dry skin and 20 with clinically normal skin on non-eczematous areas. The stratum corneum in dry skin was found to have a lower content of water than that in the clinically normal skin (p less than 0.01). Clinically normal skin in patients with atopic dermatitis did not differ significantly from normal control skin. An experiment was performed in vitro in an attempt to correlate the values obtained with the Corneometer to the absolute amount of water within the corneum.

Adolescent↗

PubMed1985

The stratum album centrale in the optic tectum of Cyprinus carpio.

The most outstanding characteristics of the stratum album centrale of the optic tectum of Cyprinus carpio were analyzed by light and electron microscopy, with special reference to the morphology and ultrastructure of the neurons with cell bodies in this stratum. Neurons belonging to the stratum album centrale itself are described, both vertical and horizontal in development, together with others which are found in this and the periventricular stratum. The possible involvement of this zone in the cytoarchitectural development of the tectal structure is discussed.

Animals↗

PubMed1981

Studies on structural lipids in the stratum corneum.

To determine the mode of existence of structural lipids in the stratum corneum, lipids induced in the thick horny cell layers of guinea pig skin by n-hexadecane treatment were analyzed. Total lipids in the stratum corneum were extracted by Folch's solution and the ratio of phospholipids to free cholesterol was 1:8. Lipids extracted by non-ionic surfactant treatment appeared to originate from both the cell surface and intercellular space of the stratum corneum and the ratio of free cholesterol to phospholipids in this lipid fraction was much higher than that in the total lipids of the stratum corneum extracted by Folch's solution.

Animals↗

PubMed1975

[Functional significance of the columnar structure of the stratum corneum and its occurrence on free autologous skin grafts].

The morphological presentation of the stratum corneum and simultaneously measurements of the alkali resistance and alkali neutralization time of the skin have been carried out in 26 guinea pigs. Whereas we could not demonstrate any association between the alkali neutralization time and the structure of the stratum corneum, a significantly better alkali resistance of the skin could be found when the columnar structure of the stratum corneum was most pronounced. The structure of the stratum corneum on full thickness skin autografts was also compared to that of normal skin in 26 animals. The columnar structure can be just as well pronounced on grafts as on normal skin. Significant differences between graft and normal skin could not be demonstrated but random samples showed that a disturbance in the columnar structure occurred more often in the grafts.

Alkalies↗

PubMed1994

Interlamellar lipid differences between normal and psoriatic stratum corneum.

Intercellular lipids of the stratum corneum are involved in permeability barrier integrity and function. In psoriasis, desquamation and permeability barrier homeostasis are modified; these observations are consistent with an alteration in stratum corneum lipid production. Therefore, in the present study, we determined and compared the total content of the three main intercellular lipids in psoriatic scales and normal human stratum corneum. Our results showed that the relative free fatty acid content decreased remarkably (46%) in psoriatic scales, compared with normal human stratum corneum. This decrease may reflect a general state of emergency of keratinocytes, in which free fatty acids can be employed.

Ceramides↗

PubMed1996

Effects of calcipotriol on stratum corneum barrier function, hydration and cell renewal in humans.

Calcipotriol, a vitamin D analogue utilized for psoriasis, has irritation as its most frequent reported adverse event. However, studies on its irritant properties in humans have produced conflicting data. This study evaluates the effect of calcipotriol on stratum corneum barrier function, hydration and cell turnover in healthy volunteers, compared with sodium lauryl sulphate (SLS) as a model irritant. Calcipotriol 0.005% ointment and 1% aqueous SLS solution were applied for 60 min once daily for 2 weeks (5 consecutive days weekly) on untreated and on dansyl-chloride-labelled skin. Irritant responses were documented by visual scoring and by measurement of the transepidermal water loss (TEWL) and stratum corneum hydration (electrical capacitance), until day 18. Stratum corneum turnover time (SCTT) was the time in days between staining (day 0) and the disappearance of dansyl fluorescence. SLS caused more erythema, scaling, and a significant TEWL increase for 18 days. In contrast, calcipotriol induced erythema, and slightly but significantly increased TEWL on day 11 only, as compared with the vehicle control (P < 0.05). SLS, but not calcipotriol, caused skin dryness from day 4 to day 18. The shortest SCTT was obtained at SLS-exposed sites (11.2 +/- 0.7 days: mean +/- SD). Calcipotriol significantly shortened SCTT (16.3 +/- 1.1 days) when compared with its vehicle. Compared with the skin irritation induced by SLS, under these test conditions, calcipotriol is a far weaker irritant on normal human skin. In addition, calcipotriol accelerates stratum corneum turnover to a significantly greater extent than its vehicle.

Adult↗

PubMed1997

Studies on the antifungal activity of the new imidazole antimycotic lanoconazole in infected sites. Distribution in the skin and in vitro activity in the presence of stratum corneum.

To answer the question why topically applied lanoconazole (CAS 101530-10-3, NND-318) is so highly effective in the treatment of dermatomycoses in both animal models and human patients, the antifungal activity of lanoconazole in infected sites was investigated. 1. Distribution of lanoconazole in rat skin: The distribution of lanoconazole within the dorsal skin of rats was examined by measurement of radioactivity and microscopic autoradiography. 24 h after dermal application of 14C-lanoconazole cream formulation, 83% of the total radioactivity in the skin was recovered from the stratum corneum, and thereafter the radioactivity decreased gradually up to 96 h. Metabolite analysis showed that more than 94% of the extractable radioactivity was lanoconazole itself after 24 and 48 h. Microautoradiograms of the skin also supported the radioactivity distribution. 2. In vitro antifungal activity in stratum corneum-containing medium: Candida albicans TIMM 2640 was incubated for 10 days at 27 degrees C in a vitamin-supplemented yeast carbon base medium containing 5 mg/ml of human stratum corneum and different concentrations of lanoconazole or bifonazole (CAS 60628-96-8, reference agent). Compared with the control culture, lanoconazole strongly inhibited fungal growth in a concentration dependent manner at concentration above 0.1 microgram/ml, resulting in a reduction of viable cell recovery to less than 50% after 10 days. The inhibitory activity of bifonazole was clearly weaker than that of lanoconazole. At concentrations of 0.1-10 micrograms/ml lanoconazole reduced keratinolytic acid proteinase activity in the culture-supernate to 40-70% of the control value, while bifonazole showed 50% reduction of the activity at a concentration of 10 micrograms/ml. These results indicate that lanoconazole is mainly distributed and retained in the stratum corneum after topical application where it exerts strong antifungal activity.

Administration, Topical↗

PubMed1999

Altered lamellar body secretion and stratum corneum membrane structure in Netherton syndrome: differentiation from other infantile erythrodermas and pathogenic implications.

BACKGROUND: The infant with Netherton syndrome (NS) typically displays a generalized erythroderma covered by fine, translucent scales, which can be difficult to distinguish clinically from erythrodermic psoriasis, nonbullous congenital ichthyosiform erythroderma, or other infantile erythrodermas. Some infants with NS develop progressive hypernatremic dehydration, failure to thrive, and enteropathy. Such complications can be fatal. Diagnosis is typically delayed until the appearance of a pathognomonic hair shaft anomaly, trichorrhexis invaginata (bamboo hair). To facilitate the early diagnosis of NS, we obtained biopsy specimens from 7 patients with erythrodermic NS and compared their morphologic findings to those of 3 patients with erythrodermic psoriasis and 2 with congenital ichthyosiform erythroderma. Biopsy specimens were processed for light and electron microscopy using postfixation with osmium tetroxide and ruthenium tetroxide. OBSERVATION: In NS, and often in congenital ichthyosiform erythroderma and erythrodermic psoriasis, the stratum corneum layer was largely replaced by parakeratotic cells. A distinctive feature--premature secretion of lamellar body contents--occurred only in NS. Furthermore, lamellar body-derived extracellular lamellae and stratum corneum lipid membranes were separated extensively by foci of electron-dense material. Finally, transformation of lamellar body-derived lamellae into mature lamellar membrane structures was disturbed in NS. CONCLUSIONS: Premature lamellar body secretion and foci of electron-dense material in the intercellular spaces of stratum corneum, features not observed in other erythrodermic disorders, appear to be frequent and relatively specific markers for NS. These ultrastructural features could permit the early diagnosis of NS before the appearance of the hair shaft abnormality. These abnormalities could explain the impaired permeability barrier in NS, and account for hypernatremia and dehydration in infants with NS.

Child, Preschool↗

PubMed1998

Stratum corneum, corneodesmosomes and ex vivo percutaneous penetration.

The stratum corneum is composed of cornified keratinocytes, joined together with corneodesmosomes and embedded in the relatively hydrophobic intercellular substance. Formation of this horny layer and its constant desquamation are fundamental processes leading to the establishment of an efficient epidermal barrier. We examined structural changes occurring in the stratum corneum ex vivo, in order to better understand the mechanisms regulating corneocyte desquamation at the epidermal surface and influencing percutaneous penetration of exogenous substances. Morphologic modifications were induced by occlusion, increasing the tissue hydration, or by application of propylene glycol, a hydrophilic solvent of small molecular size. Distribution of the major epidermal antigens, markers of terminal differentiation, was studied immunohistochemically and showed no modification related to the tissue alteration. Skin samples were fixed in paraformaldehyde and either postfixed in OsO4 and embedded in Epon or postfixed in RuO4 and embedded in epoxy and acrylic resins. Structural composition and spatial organization of the elements present in the intercorneocyte spaces were evaluated ultrastructurally, with special attention paid to the fate of corneodesmosomes. Our results suggest that the spontaneous organization of lipids excreted into the intercellular spaces and constitution of the lamellar multilayers in the lower stratum corneum are at the origin of partition of the intercellular compartment to the hydrophobic and hydrophilic domains. The latter, compatible with the proteinic contents, seem to be displaced by the hydrophobic components undergoing reorganization, towards the invariable hydrophilic foci represented by corneodesmosomes. This mechanism may be involved in the delivery of proteolytic enzymes, thus contributing to the progressive degradation of corneodesmosomal proteins.

Desmosomes↗

PubMed2004

Properties of horizontal axo-axonic cells in stratum oriens of the hippocampal CA1 area of rats in vitro.

Local-circuit gamma-aminobutyric acid (GABA)ergic interneurons constitute a diverse population of cells, which remain poorly defined into functionally distinct subclasses. Traditionally, dendritic and axonal arbors have been used to describe cell classes. In the present report, we characterize a set of hippocampal interneurons, horizontal axo-axonic cells, located in stratum oriens. They displayed the pattern of axonal arborization characteristic of axo-axonic cells with radially aligned rows of boutons making synapses exclusively on axon initial segments of pyramidal cells, as shown by electron microscopy. However, in contrast to previously described axo-axonic cells, which have radial dendrites spanning all layers, the dendrites of the horizontal axo-axonic cells were restricted to stratum oriens and ran parallel with the layers for several hundred micrometers. Single action potentials elicited by depolarizing current steps in these cells were often followed by a fast- and medium-duration afterhyperpolarization, distinguishing them from fast-spiking interneurons. In two out of four cells, trains of action potentials showed prominent early spike frequency adaptation and a characteristic "accommodative hump." Excitatory postsynaptic potentials (EPSPs) could be evoked by stimuli delivered to stratum oriens. Paired recordings unequivocally confirmed direct synaptic inputs from CA1 pyramidal cells. The kinetics of the EPSPs were fast (rise time 1.7 +/- 0.6 ms, mean +/- SD, n = 3; decay time constant 19.3 +/- 2.4 ms). They showed paired-pulse depression with inter-stimulus intervals of 10-50 ms. One pair showed a reciprocal connection establishing a direct feedback loop. The axo-axonic cell-evoked inhibitory postsynaptic potentials (IPSPs) were reliable (failure rate approximately 10%). Our data show that the laminar distribution of the dendrites of axo-axonic cells can vary, suggesting distinct synaptic inputs. However, this remains to be shown directly, and we cannot exclude the possibility that all axo-axonic cells may gather similar synaptic input, leaving them as one distinct class of interneuron.

Action Potentials↗

PubMed2005

Extracellular diffusion is fast and isotropic in the stratum radiatum of hippocampal CA1 region in rat brain slices.

Molecular transport in brain extracellular space (ECS) is hindered by the structure of the tissue. Diffusion analysis of small extracellular markers quantifies tissue hindrance, expressed as tortuosity lambda = (D/D*)(1/2), where D is the free diffusion coefficient and D* is the effective diffusion coefficient in tissue. In healthy brain, lambda is approximately 1.6, but the nature of this parameter is poorly understood. We report that the stratum radiatum of the hippocampal CA1 region in vitro, previously shown to be anisotropic (i.e., different along the x-, y-, and z-axes) in in vivo study, is isotropic like somatosensory neocortex but has a reduced lambda. Diffusion of fluorophore-labeled dextran (f-dex, M(r) 3,000) and tetramethylammonium (TMA(+), M(r) 74) was measured in rat brain slices (400 mum) using integrative optical imaging (IOI) and real-time iontophoresis (RTI), respectively. In the stratum radiatum, diffusion of f-dex was similar along the x-, y-, and z-axes (lambda(x), lambda(y); lambda(z) were 1.55, 1.53, and 1.55), but the tortuosity was significantly lower than in the neocortex, where lambda = 1.81. This finding was confirmed by the RTI method, which measured lambda with TMA(+), a much smaller molecule, and determined volume fraction alpha, the proportion of tissue occupied by the ECS. In stratum radiatum, lambda(x), lambda(y), and lambda(z) were 1.47, 1.44, and 1.46, while in neocortex, lambda was 1.65. The ECS volume fraction was similar (0.24) in both regions. It is proposed that in the hippocampus, low lambda reflects a reduced occurrence of concave extracellular microdomains, referred to as dead spaces, which increase tortuosity by transient trapping of markers. Functionally, a low lambda may permit structural plasticity and facilitate extrasynaptic communication. It may also enhance the spread of neuroactive substances and thus contribute to the sensitivity of the hippocampal CA1 region to ischemia and epilepsy.

Animals↗

PubMed1987

Role of stratum corneum lipid fluidity in transdermal drug flux.

Fatty acids are effective penetration enhancers for the transdermal delivery of certain co-applied drugs. In order to assess the mechanism of enhancement, spectrometric, calorimetric, and flux techniques were used to study porcine stratum corneum following treatment with a series of cis- and trans-positional isomers of octadecenoic acid. Results obtained from spectrometric and calorimetric measurements show increased lipid fluidity following treatment of the stratum corneum with the cis monoenoic acids which have the site of unsaturation centrally located. Under similar conditions, these same cis monounsaturated acids resulted in enhancement of salicyclic acid flux through porcine skin. The striking parallelism between flux and fluidity measurements suggests that transdermal drug flux may be ultimately related to stratum corneum lipid structure.

Animals↗

PubMed1989

Water evaporation rates from a model of stratum corneum lipids.

Water evaporation rates were measured from thin samples of a model layered structure of stratum corneum lipids with 32% water. A model with only free fatty acids present gave the lowest evaporation rates, while a model with only oleic acid gave values approximately 50% higher. Using the total lipid spectrum of stratum corneum gave a structure with an evaporation rate between those mentioned above. The diffusion coefficients calculated were one to two orders of magnitude higher than those of stratum corneum, reflecting the influence of the proteinous part of the latter structure. A sample with only saturated fatty acids gave extremely high evaporation rates; in fact, they were of the same magnitude as those from an unprotected water surface.

Diffusion↗

PubMed1991

Lyotropic liquid crystals and the structural lipids of the stratum corneum.

Lipids were extracted from human stratum corneum and the remaining corneocytes were reaggregated with different lyotropic liquid crystals. Water transport through the reaggregated stratum corneum was determined using a diffusion chamber according to Smith and Blank. The permeability constant for the reaggregated stratum corneum with natural lipids was 25-40% lower than that with the surfactant liquid crystals, but there was no significant difference between different liquid crystals.

Adult↗

PubMedDate not supplied

Assessment of stratum-covariate interactions in Cox's proportional hazards regression model.

We assess stratum (e.g. treatment) interactions with covariates and with the baseline hazard function in the proportional hazards (PH) regression model for lifetime data. We consider models incorporating stratum interactions both with and without stratification of the risk sets in the likelihood function, and describe likelihood ratio statistics for tests of the presence of these interactions. We also present step-down methods for building reduced models which include stratum-specific parameters corresponding to covariates which interact with treatment. We apply PH models with such interactions to a clinical trial of DES in the treatment of prostate cancer to determine optimal treatment conditional on each patient's covariates.

Analysis of Variance↗