Human skin volatiles: a review.

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Dormont, Laurent; Bessière, Jean-Marie; Cohuet, Anna

2013-05-01

Odors emitted by human skin are of great interest to biologists in many fields; applications range from forensic studies to diagnostic tools, the design of perfumes and deodorants, and the ecology of blood-sucking insect vectors of human disease. Numerous studies have investigated the chemical composition of skin odors, and various sampling methods have been used for this purpose. The literature shows that the chemical profile of skin volatiles varies greatly among studies, and the use of different sampling procedures is probably responsible for some of these variations. To our knowledge, this is the first review focused on human skin volatile compounds. We detail the different sampling techniques, each with its own set of advantages and disadvantages, which have been used for the collection of skin odors from different parts of the human body. We present the main skin volatile compounds found in these studies, with particular emphasis on the most frequently studied body regions, axillae, hands, and feet. We propose future directions for promising experimental studies on odors from human skin, particularly in relation to the chemical ecology of blood-sucking insects.

Characterization of the fetal blood transcriptome and proteome in maternal anti-fetal rejection: evidence of a distinct and novel type of human fetal systemic inflammatory response.

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Lee, Joonho; Romero, Roberto; Chaiworapongsa, Tinnakorn; Dong, Zhong; Tarca, Adi L; Xu, Yi; Chiang, Po Jen; Kusanovic, Juan Pedro; Hassan, Sonia S; Yeo, Lami; Yoon, Bo Hyun; Than, Nandor Gabor; Kim, Chong Jai

2013-10-01

The human fetus is able to mount a systemic inflammatory response when exposed to microorganisms. This stereotypic response has been termed the 'fetal inflammatory response syndrome' (FIRS), defined as an elevation of fetal plasma interleukin-6 (IL-6). FIRS is frequently observed in patients whose preterm deliveries are associated with intra-amniotic infection, acute inflammatory lesions of the placenta, and a high rate of neonatal morbidity. Recently, a novel form of fetal systemic inflammation, characterized by an elevation of fetal plasma CXCL10, has been identified in patients with placental lesions consistent with 'maternal anti-fetal rejection'. These lesions include chronic chorioamnionitis, plasma cell deciduitis, and villitis of unknown etiology. In addition, positivity for human leukocyte antigen (HLA) panel-reactive antibodies (PRA) in maternal sera can also be used to increase the index of suspicion for maternal anti-fetal rejection. The purpose of this study was to determine (i) the frequency of pathologic lesions consistent with maternal anti-fetal rejection in term and spontaneous preterm births; (ii) the fetal serum concentration of CXCL10 in patients with and without evidence of maternal anti-fetal rejection; and (iii) the fetal blood transcriptome and proteome in cases with a fetal inflammatory response associated with maternal anti-fetal rejection. Maternal and fetal sera were obtained from normal term (n = 150) and spontaneous preterm births (n = 150). A fetal inflammatory response associated with maternal anti-fetal rejection was diagnosed when the patients met two or more of the following criteria: (i) presence of chronic placental inflammation; (ii) ≥80% of maternal HLA class I PRA positivity; and (iii) fetal serum CXCL10 concentration >75th percentile. Maternal HLA PRA was analyzed by flow cytometry. The concentrations of fetal CXCL10 and IL-6 were determined by ELISA. Transcriptome analysis was undertaken after the extraction of total RNA

Retinoic Acid signalling and the control of meiotic entry in the human fetal gonad.

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Andrew J Childs

Full Text Available The development of mammalian fetal germ cells along oogenic or spermatogenic fate trajectories is dictated by signals from the surrounding gonadal environment. Germ cells in the fetal testis enter mitotic arrest, whilst those in the fetal ovary undergo sex-specific entry into meiosis, the initiation of which is thought to be mediated by selective exposure of fetal ovarian germ cells to mesonephros-derived retinoic acid (RA. Aspects of this model are hard to reconcile with the spatiotemporal pattern of germ cell differentiation in the human fetal ovary, however. We have therefore examined the expression of components of the RA synthesis, metabolism and signalling pathways, and their downstream effectors and inhibitors in germ cells around the time of the initiation of meiosis in the human fetal gonad. Expression of the three RA-synthesising enzymes, ALDH1A1, 2 and 3 in the fetal ovary and testis was equal to or greater than that in the mesonephros at 8-9 weeks gestation, indicating an intrinsic capacity within the gonad to synthesise RA. Using immunohistochemistry to detect RA receptors RARα, β and RXRα, we find germ cells to be the predominant target of RA signalling in the fetal human ovary, but also reveal widespread receptor nuclear localization indicative of signalling in the testis, suggesting that human fetal testicular germ cells are not efficiently shielded from RA by the action of the RA-metabolising enzyme CYP26B1. Consistent with this, expression of CYP26B1 was greater in the human fetal ovary than testis, although the sexually-dimorphic expression patterns of the germ cell-intrinsic regulators of meiotic initiation, STRA8 and NANOS2, appear conserved. Finally, we demonstrate that RA induces a two-fold increase in STRA8 expression in cultures of human fetal testis, but is not sufficient to cause widespread meiosis-associated gene expression. Together, these data indicate that while local production of RA within the fetal ovary may

Retinoic Acid Signalling and the Control of Meiotic Entry in the Human Fetal Gonad

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Kinnell, Hazel L.; Anderson, Richard A.; Saunders, Philippa T. K.

2011-01-01

The development of mammalian fetal germ cells along oogenic or spermatogenic fate trajectories is dictated by signals from the surrounding gonadal environment. Germ cells in the fetal testis enter mitotic arrest, whilst those in the fetal ovary undergo sex-specific entry into meiosis, the initiation of which is thought to be mediated by selective exposure of fetal ovarian germ cells to mesonephros-derived retinoic acid (RA). Aspects of this model are hard to reconcile with the spatiotemporal pattern of germ cell differentiation in the human fetal ovary, however. We have therefore examined the expression of components of the RA synthesis, metabolism and signalling pathways, and their downstream effectors and inhibitors in germ cells around the time of the initiation of meiosis in the human fetal gonad. Expression of the three RA-synthesising enzymes, ALDH1A1, 2 and 3 in the fetal ovary and testis was equal to or greater than that in the mesonephros at 8–9 weeks gestation, indicating an intrinsic capacity within the gonad to synthesise RA. Using immunohistochemistry to detect RA receptors RARα, β and RXRα, we find germ cells to be the predominant target of RA signalling in the fetal human ovary, but also reveal widespread receptor nuclear localization indicative of signalling in the testis, suggesting that human fetal testicular germ cells are not efficiently shielded from RA by the action of the RA-metabolising enzyme CYP26B1. Consistent with this, expression of CYP26B1 was greater in the human fetal ovary than testis, although the sexually-dimorphic expression patterns of the germ cell-intrinsic regulators of meiotic initiation, STRA8 and NANOS2, appear conserved. Finally, we demonstrate that RA induces a two-fold increase in STRA8 expression in cultures of human fetal testis, but is not sufficient to cause widespread meiosis-associated gene expression. Together, these data indicate that while local production of RA within the fetal ovary may be important in

Distinct functional programming of human fetal and adult monocytes.

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Krow-Lucal, Elisabeth R; Kim, Charles C; Burt, Trevor D; McCune, Joseph M

2014-03-20

Preterm birth affects 1 out of 9 infants in the United States and is the leading cause of long-term neurologic handicap and infant mortality, accounting for 35% of all infant deaths in 2008. Although cytokines including interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-6, and IL-1 are produced in response to in utero infection and are strongly associated with preterm labor, little is known about how human fetal immune cells respond to these cytokines. We demonstrate that fetal and adult CD14(+)CD16(-) classical monocytes are distinct in terms of basal transcriptional profiles and in phosphorylation of signal transducers and activators of transcription (STATs) in response to cytokines. Fetal monocytes phosphorylate canonical and noncanonical STATs and respond more strongly to IFN-γ, IL-6, and IL-4 than adult monocytes. We demonstrate a higher ratio of SOCS3 to IL-6 receptor in adult monocytes than in fetal monocytes, potentially explaining differences in STAT phosphorylation. Additionally, IFN-γ signaling results in upregulation of antigen presentation and costimulatory machinery in adult, but not fetal, monocytes. These findings represent the first evidence that primary human fetal and adult monocytes are functionally distinct, potentially explaining how these cells respond differentially to cytokines implicated in development, in utero infections, and the pathogenesis of preterm labor.

Elastin hydrolysate derived from fish enhances proliferation of human skin fibroblasts and elastin synthesis in human skin fibroblasts and improves the skin conditions.

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Shiratsuchi, Eri; Nakaba, Misako; Yamada, Michio

2016-03-30

Recent studies have shown that certain peptides significantly improve skin conditions, such as skin elasticity and the moisture content of the skin of healthy woman. This study aimed to investigate the effects of elastin hydrolysate on human skin. Proliferation and elastin synthesis were evaluated in human skin fibroblasts exposed to elastin hydrolysate and proryl-glycine (Pro-Gly), which is present in human blood after elastin hydrolysate ingestion. We also performed an ingestion test with elastin hydrolysate in humans and evaluated skin condition. Elastin hydrolysate and Pro-Gly enhanced the proliferation of fibroblasts and elastin synthesis. Maximal proliferation response was observed at 25 ng mL(-1) Pro-Gly. Ingestion of elastin hydrolysate improved skin condition, such as elasticity, number of wrinkles, and blood flow. Elasticity improved by 4% in the elastin hydrolysate group compared with 2% in the placebo group. Therefore, elastin hydrolysate activates human skin fibroblasts and has beneficial effects on skin conditions. © 2015 Society of Chemical Industry.

Characterization of a Cryopreserved Split-Thickness Human Skin Allograft-TheraSkin.

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Landsman, Adam; Rosines, Eran; Houck, Amanda; Murchison, Angela; Jones, Alyce; Qin, Xiaofei; Chen, Silvia; Landsman, Arnold R

2016-09-01

The purpose of this study was to examine the characteristics of a cryopreserved split-thickness skin allograft produced from donated human skin and compare it with fresh, unprocessed human split-thickness skin. Cutaneous wound healing is a complex and organized process, where the body re-establishes the integrity of the injured tissue. However, chronic wounds, such as diabetic or venous stasis ulcers, are difficult to manage and often require advanced biologics to facilitate healing. An ideal wound care product is able to directly influence wound healing by introducing biocompatible extracellular matrices, growth factors, and viable cells to the wound bed. TheraSkin (processed by LifeNet Health, Virginia Beach, Virginia, and distributed by Soluble Systems, Newport News, Virginia) is a minimally manipulated, cryopreserved split-thickness human skin allograft, which contains natural extracellular matrices, native growth factors, and viable cells. The authors characterized TheraSkin in terms of the collagen and growth factor composition using ELISA, percentage of apoptotic cells using TUNEL analysis, and cellular viability using alamarBlue assay (Thermo Fisher Scientific, Waltham, Massachusetts), and compared these characteristics with fresh, unprocessed human split-thickness skin. It was found that the amount of the type I and type III collagen, as well as the ratio of type I to type III collagen in TheraSkin, is equivalent to fresh unprocessed human split-thickness skin. Similar quantities of vascular endothelial growth factor, insulinlike growth factor 1, fibroblast growth factor 2, and transforming growth factor β1 were detected in TheraSkin and fresh human skin. The average percent of apoptotic cells was 34.3% and 3.1% for TheraSkin and fresh skin, respectively. Cellular viability was demonstrated in both TheraSkin and fresh skin.

Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

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Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

2010-10-01

In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular

Dissecting human cerebral organoids and fetal neocortex using single-cell RNAseq

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Treutlein, Barbara

Cerebral organoids - three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells - have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures.

Human reconstructed skin xenografts on mice to model skin physiology.

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Salgado, Giorgiana; Ng, Yi Zhen; Koh, Li Fang; Goh, Christabelle S M; Common, John E

Xenograft models to study skin physiology have been popular for scientific use since the 1970s, with various developments and improvements to the techniques over the decades. Xenograft models are particularly useful and sought after due to the lack of clinically relevant animal models in predicting drug effectiveness in humans. Such predictions could in turn boost the process of drug discovery, since novel drug compounds have an estimated 8% chance of FDA approval despite years of rigorous preclinical testing and evaluation, albeit mostly in non-human models. In the case of skin research, the mouse persists as the most popular animal model of choice, despite its well-known anatomical differences with human skin. Differences in skin biology are especially evident when trying to dissect more complex skin conditions, such as psoriasis and eczema, where interactions between the immune system, epidermis and the environment likely occur. While the use of animal models are still considered the gold standard for systemic toxicity studies under controlled environments, there are now alternative models that have been approved for certain applications. To overcome the biological limitations of the mouse model, research efforts have also focused on "humanizing" the mice model to better recapitulate human skin physiology. In this review, we outline the different approaches undertaken thus far to study skin biology using human tissue xenografts in mice and the technical challenges involved. We also describe more recent developments to generate humanized multi-tissue compartment mice that carry both a functioning human immune system and skin xenografts. Such composite animal models provide promising opportunities to study drugs, disease and differentiation with greater clinical relevance. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Anti-inflammatory Elafin in human fetal membranes.

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Stalberg, Cecilia; Noda, Nathalia; Polettini, Jossimara; Jacobsson, Bo; Menon, Ramkumar

2017-02-01

Elafin is a low molecular weight protein with antileukoproteinase, anti-inflammatory, antibacterial and immunomodulating properties. The profile of Elafin in fetal membranes is not well characterized. This study determined the changes in Elafin expression and concentration in human fetal membrane from patients with preterm prelabor rupture of membranes (PPROM) and in vitro in response to intra-amniotic polymicrobial pathogens. Elafin messenger RNA (mRNA) expressions were studied in fetal membranes from PPROM, normal term as well as in normal term not in labor membranes in an organ explant system treated (24 h) with lipopolysaccharide (LPS), using quantitative reverse transcription-polymerase chain reaction (RT-PCR). Enzyme-linked immunosorbent assay (ELISA) measured Elafin concentrations in culture supernatants from tissues treated with LPS and polybacterial combinations of heat-inactivated Mycoplasma hominis (MH), Ureaplasma urealyticum (UU) and Gardnerella vaginalis (GV). Elafin mRNA expression in fetal membranes from women with PPROM was significantly higher compared to women who delivered at term after normal pregnancy (5.09±3.50 vs. 11.71±2.21; Pmembranes showed a significantly increased Elafin m-RNA expression (Pmembranes also showed no changes in Elafin protein concentrations compared to untreated controls. Higher Elafin expression in PPROM fetal membranes suggests a host response to an inflammatory pathology. However, lack of Elafin response to LPS and polymicrobial treatment is indicative of the minimal anti-inflammatory impact of this molecule in fetal membranes.

Human fetal anatomy: MR imaging.

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Weinreb, J C; Lowe, T; Cohen, J M; Kutler, M

1985-12-01

Twenty-four pregnant women carrying 26 fetuses (two sets of twins) were imaged with magnetic resonance (MR) imaging at 0.35 T following sonographic evaluation. Each study was retrospectively evaluated to determine which of 33 normal fetal structures were visible on the images and which imaging parameters were most useful for depicting fetal anatomy. Fetal motion degraded fetal images in all but two cases, both with oligohydramnios and in the third trimester of gestation. Nevertheless, many fetal structures were identifiable, particularly in the third trimester. Visualization of fetal anatomy improved with intravenous maternal sedation in five cases. Relatively T1-weighted images occasionally offered the advantage of less image degradation owing to fetal motion and improved contrast between different fetal structures. More T2 weighting was believed to be advantageous in one case for outlining the fetal head and in one case for delineation of the brain. In many cases, structures were similarly identifiable (though with different signal intensities) regardless of the parameters selected. The authors conclude that MR imaging of many fetal structures is currently unsatisfactory and is probably of limited value, particularly in the first and second trimesters. However, the relative frequency and detail with which the fetal head and liver can be depicted indicate that these may be areas for further investigation, and the potential utility of imaging fetal fat warrants further investigation.

Myocardial bridges of the coronary arteries in the human fetal heart.

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Cakmak, Yusuf Ozgür; Cavdar, Safiye; Yalin, Aymelek; Yener, Nuran; Ozdogmus, Omer

2010-09-01

During the last century, many investigators reported on myocardial bridges in the adult human heart. In the present study, 39 human fetal hearts (the mean gestastional age was 30 weeks) were studied for myocardial bridging, and the results were correlated with adult data. Among the 39 (27 male and 12 female) fetal hearts studied, 26 bridges were observed on 18 fetal hearts (46.2%). Ten of the bridges had one myocardial bridge, whereas double myocardial bridges were observed in eight fetal hearts. The most frequent myocardial bridges were observed on the left anterior descending artery (LAD), which had 13 bridges (50%). Eight (30.7%) myocardial bridges were on the diagonal artery, and on the posterior descending artery there were five (19.3%). Myocardial bridges were not observed on the circumflex artery. The data presented in this study may provide potentially useful information for the preoperative evaluation of the newborn and may have a clinical implication for sudden fetal death.

Skin friction: a novel approach to measuring in vivo human skin

OpenAIRE

Veijgen, N.K.

2013-01-01

The human skin plays an important role in people’s lives. It is in constant interaction with the environment, clothing and consumer products. This thesis discusses one of the parameters in the interaction between the human skin in vivo and other materials: skin friction. The thesis is divided into three parts. The first part is an introduction to skin friction and to current knowledge on skin friction. The second part presents the RevoltST, the tribometer that was specially developed for skin...

Histochemical and radioautographic studies of normal human fetal colon

International Nuclear Information System (INIS)

Lev, R.; Orlic, D.; New York Medical Coll., N.Y.

1974-01-01

Twenty fetal and infant colons ranging from 10 weeks in utero to 20 months postpartum, and 12 adult human colons were examined using histochemical techniques in conjunction with in vitro radioautography using Na 2 35 SO 4 as a sulfomucin precursor. Only the sulfated components of mucus in fetal goblet cells was found to differ significantly from adult colonic mucins. In the fetus sulfomucin staining was much weaker than in the adult, and was more intense in the left colon which is the reverse of the adult pattern. Sulfomucin was concentrated in the crypts throughout the fetal colon whereas in the adult right colon it predominated in the surface cells. As in the adult, saponification liberated carboxyl groups, possibly belonging to sialic acid, and vicinal hydroxyl groups from fetal mucins suggesting that this procedure hydrolyses an ester linkage between these 2 reactive groups. During the middle trimester of fetal life the colon possesses villi whose constituent cells display alkaline phosphatase in their surface coat. These and other morphological and histochemical similarities to fetal small intestine suggest that the fetal colon may have a limited capacity to absorb materials contained within swallowed amniotic fluid during this period. (orig.) [de

Preparation of Artificial Skin that Mimics Human Skin Surface and Mechanical Properties.

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Shimizu, Rana; Nonomura, Yoshimune

2018-01-01

We have developed an artificial skin that mimics the morphological and mechanical properties of human skin. The artificial skin comprises a polyurethane block possessing a microscopically rough surface. We evaluated the tactile sensations when skin-care cream was applied to the artificial skin. Many subjects perceived smooth, moist, and soft feels during the application process. Cluster analysis showed that these characteristic tactile feels are similar to those when skin-care cream is applied to real human skin. Contact angle analysis showed that an oil droplet spread smoothly on the artificial skin surface, which occurred because there were many grooves several hundred micrometers in width on the skin surface. In addition, when the skin-care cream was applied, the change in frictional force during the dynamic friction process increased. These wetting and frictional properties are important factors controlling the similarity of artificial skin to real human skin.

Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing.

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Zheng, Zhong; Zhang, Xinli; Dang, Catherine; Beanes, Steven; Chang, Grace X; Chen, Yao; Li, Chen-Shuang; Lee, Kevin S; Ting, Kang; Soo, Chia

2016-11-01

In contrast to adult and late-gestation fetal skin wounds, which heal with scar, early-gestation fetal skin wounds display a remarkable capacity to heal scarlessly. Although the underlying mechanism of this transition from fetal-type scarless healing to adult-type healing with scar has been actively investigated for decades, in utero restoration of scarless healing in late-gestation fetal wounds has not been reported. In this study, using loss- and gain-of-function rodent fetal wound models, we identified that fibromodulin (Fm) is essential for fetal-type scarless wound healing. In particular, we found that loss of Fm can eliminate the ability of early-gestation fetal rodents to heal without scar. Meanwhile, administration of fibromodulin protein (FM) alone was capable of restoring scarless healing in late-gestation rat fetal wounds, which naturally heal with scar, as characterized by dermal appendage restoration and organized collagen architectures that were virtually indistinguishable from those in age-matched unwounded skin. High Fm levels correlated with decreased transforming growth factor (TGF)-β1 expression and scarless repair, while low Fm levels correlated with increased TGF-β1 expression and scar formation. This study represents the first successful in utero attempt to induce scarless repair in late-gestation fetal wounds by using a single protein, Fm, and highlights the crucial role that the FM-TGF-β1 nexus plays in fetal-type scarless skin repair. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Diffusion of [2-14C]diazepam across hairless mouse skin and human skin

International Nuclear Information System (INIS)

Koch, R.L.; Palicharla, P.; Groves, M.J.

1987-01-01

The objectives of this study were to investigate the absorption of diazepam applied topically to the hairless mouse in vivo and to determine the diffusion of diazepam across isolated hairless mouse skin and human skin. [ 14 C]Diazepam was readily absorbed after topical administration to the intact hairless mouse, a total of 75.8% of the 14 C-label applied being recovered in urine and feces. Diazepam was found to diffuse across human and hairless mouse skin unchanged in experiments with twin-chambered diffusion cells. The variation in diffusion rate or the flux for both human and mouse tissues was greater among specimens than between duplicate or triplicate trials for a single specimen. Fluxes for mouse skin (stratum corneum, epidermis, and dermis) were greater than for human skin (stratum corneum and epidermis): 0.35-0.61 microgram/cm2/h for mouse skin vs 0.24-0.42 microgram/cm2/h for human skin. The permeability coefficients for mouse skin ranged from 1.4-2.4 X 10(-2)cm/h compared with 0.8-1.4 X 10(-2)cm/h for human skin. Although human stratum corneum is almost twice the thickness of that of the hairless mouse, the diffusion coefficients for human skin were 3-12 times greater (0.76-3.31 X 10(-6) cm2/h for human skin vs 0.12-0.27 X 10(-6) cm2/h for hairless mouse) because of a shorter lag time for diffusion across human skin. These differences between the diffusion coefficients and diffusion rates (or permeability coefficients) suggest that the presence of the dermis may present some barrier properties. In vitro the dermis may require complete saturation before the diazepam can be detected in the receiving chamber

Discovery and Characterization of piRNAs in the Human Fetal Ovary

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Zev Williams

2015-10-01

Full Text Available Piwi-interacting RNAs (piRNAs, a class of 26- to 32-nt non-coding RNAs (ncRNAs, function in germline development, transposon silencing, and epigenetic regulation. We performed deep sequencing and annotation of untreated and periodate-treated small RNA cDNA libraries from human fetal and adult germline and reference somatic tissues. This revealed abundant piRNAs originating from 150 piRNA-encoding genes, including some exhibiting gender-specific expression, in fetal ovary and adult testis—developmental periods coinciding with mitotic cell divisions expanding fetal germ cells prior to meiotic divisions. The absence of reads mapping uniquely to annotated piRNA genes demonstrated their paucity in fetal testis and adult ovary and absence in somatic tissues. We curated human piRNA-expressing regions and defined their precise borders and observed piRNA-guided cleavage of transcripts antisense to some piRNA-producing genes. This study provides insights into sex-specific mammalian piRNA expression and function and serves as a reference for human piRNA analysis and annotation.

Human age and skin physiology shape diversity and abundance of Archaea on skin.

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Moissl-Eichinger, Christine; Probst, Alexander J; Birarda, Giovanni; Auerbach, Anna; Koskinen, Kaisa; Wolf, Peter; Holman, Hoi-Ying N

2017-06-22

The human skin microbiome acts as an important barrier protecting our body from pathogens and other environmental influences. Recent investigations have provided evidence that Archaea are a constant but highly variable component of the human skin microbiome, yet factors that determine their abundance changes are unknown. Here, we tested the hypothesis that the abundance of archaea on human skin is influenced by human age and skin physiology by quantitative PCR of 51 different skin samples taken from human subjects of various age. Our results reveal that archaea are more abundant in human subjects either older than 60 years or younger than 12 years as compared to middle-aged human subjects. These results, together with results obtained from spectroscopy analysis, allowed us gain first insights into a potential link of lower sebum levels and lipid content and thus reduced skin moisture with an increase in archaeal signatures. Amplicon sequencing of selected samples revealed the prevalence of specific eury- and mainly thaumarchaeal taxa, represented by a core archaeome of the human skin.

Skin friction: a novel approach to measuring in vivo human skin

NARCIS (Netherlands)

Veijgen, N.K.

2013-01-01

The human skin plays an important role in people’s lives. It is in constant interaction with the environment, clothing and consumer products. This thesis discusses one of the parameters in the interaction between the human skin in vivo and other materials: skin friction. The thesis is divided into

Electroosmotic pore transport in human skin.

Science.gov (United States)

Uitto, Olivia D; White, Henry S

2003-04-01

To determine the pathways and origin of electroosmotic flow in human skin. Iontophoretic transport of acetaminophen in full thickness human cadaver skin was visualized and quantified by scanning electrochemical microscopy. Electroosmotic flow in the shunt pathways of full thickness skin was compared to flow in the pores of excised stratum corneum and a synthetic membrane pore. The penetration of rhodamine 6G into pore structures was investigated by laser scanning confocal microscopy. Electroosmotic transport is observed in shunt pathways in full thickness human skin (e.g., hair follicles and sweat glands), but not in pore openings of freestanding stratum corneum. Absolute values of the diffusive and iontophoretic pore fluxes of acetaminophen in full thickness human skin are also reported. Rhodamine 6G is observed to penetrate to significant depths (approximately 200 microm) along pore pathways. Iontophoresis in human cadaver skin induces localized electroosmotic flow along pore shunt paths. Electroosmotic forces arise from the passage of current through negatively charged mesoor nanoscale pores (e.g., gap functions) within cellular regions that define the pore structure beneath the stratum corneum.

Assessment of fetal activity concentration and fetal dose for selected radionuclides based on animal and human data

International Nuclear Information System (INIS)

Roedler, H.D.

1987-01-01

Biokinetic data of selected radionuclide compounds from investigations in man and animal were taken from literature references with the purpose to provide a basis for a comparative assessment of fetal and adult radiation doses after intake or administration of radionuclides. The following ratios of fetal to adult doses were derived from human data: 0.5 for caesium 137 and total body, 2.3 for iron 59 and liver, 0.06 - 0.3 - 1.1 for iodine 131 and thyroid, and 0.1 - 0.3 for strontium 90 and bone. The ratios of activity concentrations in fetal and adult tissues are of considerable variability - up to three orders of magnitude. Further studies on fetal and adult biokinetics specifically designed for comparative dose assessment are indispensable. 106 refs.; 6 tabs

Programmed Fetal Membrane Senescence and Exosome-Mediated Signaling: A Mechanism Associated With Timing of Human Parturition

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Ramkumar Menon

2017-08-01

Full Text Available Human parturition is an inflammatory process that involves both fetal and maternal compartments. The precise immune cell interactions have not been well delineated in human uterine tissues during parturition, but insights into human labor initiation have been informed by studies in animal models. Unfortunately, the timing of parturition relative to fetal maturation varies among viviparous species—indicative of different phylogenetic clocks and alarms—but what is clear is that important common pathways must converge to control the birth process. Herein, we hypothesize a novel signaling mechanism initiated by human fetal membrane aging and senescence-associated inflammation. Programmed events of fetal membrane aging coincide with fetal growth and organ maturation. Mechanistically, senescence involves in telomere shortening and activation of p38 mitogen-activated signaling kinase resulting in aging-associated phenotypic transition. Senescent tissues release inflammatory signals that are propagated via exosomes to cause functional changes in maternal uterine tissues. In vitro, oxidative stress causes increased release of inflammatory mediators (senescence-associated secretory phenotype and damage-associated molecular pattern markers that can be packaged inside the exosomes. These exosomes traverse through tissues layers, reach maternal tissues to increase overall inflammatory load transitioning them from a quiescent to active state. Animal model studies have shown that fetal exosomes can travel from fetal to the maternal side. Thus, aging fetal membranes and membrane-derived exosomes cargo fetal signals to the uterus and cervix and may trigger parturition. This review highlights a novel hypothesis in human parturition research based on data from ongoing research using human fetal membrane model system.

In-vitro percutaneous absorption of losartan potassium in human skin and prediction of human skin permeability

Directory of Open Access Journals (Sweden)

Petkar K.C.

2007-05-01

Full Text Available This study describes the feasibility of transdermal controlled administration of Losartan potassium (LP across human cadaver skin. Study also defines the influence of capsaicin, sex and site of application on permeation characteristics and determined an appropriate animal model for human skin permeability. The permeation of LP of various formulations was studied using Keshary-Chein diffusion cell. Optimized controlled formulation (without capsaicin released 42.17% (±1.85 of LP in 12 hr whereas treatment formulation (with capsaicin 0.028 % w/v released 48.94% (±1.71 of LP with significant difference on null hypothesis. Influence of sex showed statistically significant difference for permeation of LP through male and female rats, as well as male and female mice across both the abdominal and dorsal sides of the skin (p<0.05. Similarly statistically significant differences were noted for permeation of LP across male and female mice abdomen-dorsal, but not for male rat abdomen-dorsal and female rat abdomen-dorsal. Furthermore, in-vitro permeation of LP across human skin was compared with the permeation across rat and mice skins. Male rat and male mice dorsal skin was found to have closer permeability characteristics to human than other skin membranes, but the Factor of Difference values were < 3 for all membranes which were used suggesting the membranes are good models for human skin permeability. In conclusion simple transdermal adhesive patches formulations incorporating high molecular weight of LP can deliver a dose in-vivo and proposed model skin membranes can be utilized for future pharmacokineic and toxicokinetic studies as well as metabolism studies of LP

An ex vivo human skin model for studying skin barrier repair.

Science.gov (United States)

Danso, Mogbekeloluwa O; Berkers, Tineke; Mieremet, Arnout; Hausil, Farzia; Bouwstra, Joke A

2015-01-01

In the studies described in this study, we introduce a novel ex vivo human skin barrier repair model. To develop this, we removed the upper layer of the skin, the stratum corneum (SC) by a reproducible cyanoacrylate stripping technique. After stripping the explants, they were cultured in vitro to allow the regeneration of the SC. We selected two culture temperatures 32 °C and 37 °C and a period of either 4 or 8 days. After 8 days of culture, the explant generated SC at a similar thickness compared to native human SC. At 37 °C, the early and late epidermal differentiation programmes were executed comparably to native human skin with the exception of the barrier protein involucrin. At 32 °C, early differentiation was delayed, but the terminal differentiation proteins were expressed as in stripped explants cultured at 37 °C. Regarding the barrier properties, the SC lateral lipid organization was mainly hexagonal in the regenerated SC, whereas the lipids in native human SC adopt a more dense orthorhombic organization. In addition, the ceramide levels were higher in the cultured explants at 32 °C and 37 °C than in native human SC. In conclusion, we selected the stripped ex vivo skin model cultured at 37 °C as a candidate model to study skin barrier repair because epidermal and SC characteristics mimic more closely the native human skin than the ex vivo skin model cultured at 32 °C. Potentially, this model can be used for testing formulations for skin barrier repair. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fetal responses to induced maternal relaxation during pregnancy

OpenAIRE

DiPietro, Janet A.; Costigan, Kathleen A.; Nelson, Priscilla; Gurewitsch, Edith D.; Laudenslager, Mark L.

2007-01-01

Fetal responses to induced maternal relaxation during the 32nd week of pregnancy were recorded in 100 maternal-fetal pairs using a digitized data collection system. The 18-minute guided imagery relaxation manipulation generated significant changes in maternal heart rate, skin conductance, respiration period, and respiratory sinus arrhythmia. Significant alterations in fetal neurobehavior were observed, including decreased fetal heart rate (FHR), increased FHR variability, suppression of fetal...

Detection and partial characterization of a midlamina lucida-hemidesmosome-associated antigen (19-DEJ-1) present within human skin

DEFF Research Database (Denmark)

Fine, J D; Horiguchi, Y; Jester, J

1989-01-01

, esophagus, cervix, and cornea, and BMs surrounding smooth muscle in medium-sized vessels, placenta, uterus, and esophagus. When 16 human fetal skins (aged 54-142 gestational days) were examined, the antigen was first detected at 81 days. Using immunoperoxidase and immunogold staining techniques, indirect......A murine anti-human monoclonal antibody (19-DEJ-1) has been produced that binds to basement membranes (BMs) of the dermoepidermal junction and arrector pili muscles but not to either dermal glandular or vascular BMs. 19-DEJ-1 also recognizes BMs underneath epithelia of buccal mucosa, tongue......-specific proteoglycan that is present within BMs along the epithelial-connective tissue interface and around smooth muscle in skin and other selected organs. Its unique ultrastructural localization suggests the possibility that 19-DEJ-1 may recognize an antigenic epitope of either anchoring filaments or alternatively...

Immunohistochemical distribution of regulatory peptides in the human fetal adenohypophysis

Science.gov (United States)

Reyes, R; Valladares, F; Gutiérrez, R; González, M; Bello, A R

2008-01-01

We have studied here the cellular distribution of several regulatory peptides in hormone-producing cells of the human pituitary during the fetal period. Immunohistochemistry was used to show the expression of several regulatory peptides, namely Angiotensin-II, Neurotensin and Galanin, at successive gestational stages and their co-localization with hormones in the human fetal adenohypophysis. Somatotrophs, gonadotrophs and thyrotrophs were differentiated earliest. At gestational week 9, Angiotensin-II immunoreactivity was co-localized only with growth hormone immunoreactivity in somatotrophs, one of the first hormone-producing cells to differentiate. This co-localization remained until week 37. Neurotensin immunoreactivity was present in gonadotrophs and thyrotrophs in week 23, after FSH and TSH hormone differentiation. Galanin immunoreactivity was present in all hormone-producing cell types except corticotrophs. The different pro-opiomelanocortin-derived peptides were detected at different stages of gestation and adrenocorticotrophic hormone immunoreaction was the last to be detected. Our results show an interesting relationship between regulatory peptides and hormones during human fetal development, which could imply that these peptides play a regulatory role in the development of pituitary function. PMID:18510508

Mathematical models of human cerebellar development in the fetal period.

Science.gov (United States)

Dudek, Krzysztof; Nowakowska-Kotas, Marta; Kędzia, Alicja

2018-04-01

The evaluation of cerebellar growth in the fetal period forms a part of a widely used examination to identify any features of abnormalities in early stages of human development. It is well known that the development of anatomical structures, including the cerebellum, does not always follow a linear model of growth. The aim of the study was to analyse a variety of mathematical models of human cerebellar development in fetal life to determine their adequacy. The study comprised 101 fetuses (48 males and 53 females) between the 15th and 28th weeks of fetal life. The cerebellum was exposed and measurements of the vermis and hemispheres were performed, together with statistical analyses. The mathematical model parameters of fetal growth were assessed for crown-rump length (CRL) increases, transverse cerebellar diameter and ventrodorsal dimensions of the cerebellar vermis in the transverse plane, and rostrocaudal dimensions of the cerebellar vermis and hemispheres in the frontal plane. A variety of mathematical models were applied, including linear and non-linear functions. Taking into consideration the variance between models and measurements, as well as correlation parameters, the exponential and Gompertz models proved to be the most suitable for modelling cerebellar growth in the second and third trimesters of pregnancy. However, the linear model gave a satisfactory approximation of cerebellar growth, especially in older fetuses. The proposed models of fetal cerebellar growth constructed on the basis of anatomical examination and objective mathematical calculations could be useful in the estimation of fetal development. © 2018 Anatomical Society.

Quaternary structure and spin state of human fetal methemoglobin

International Nuclear Information System (INIS)

Chevion, M.; Navok, T.; Ilan, Y.A.; Czapski, G.

1981-01-01

Using the pulse-radiolysis technique, solutions of fetal human methemoglobin were irradiated in order to reduce a single heme-iron within the protein tetramers. The valence-hybrids thus formed ere reacted wjth oxygen. Kinetics of the reactions were studied. The effects of p and inositol-hexaphosphate (IHP) were examined. The kinetics of the ligation of oxygen to stripped valence-hybrids showed a single-phase behaviour at the pH range 7-9. As the pH was lowered below 6.5, a second slower phase became apparent. This slow phase consisted of approximately 50% at pH 5.8. In the presence of IHP above pH 7.4, the kinetics of oxygen-binding was of a single-phase. As the pH was lowered a transition to a second, slower phase was noticed. Below pH 7 the slower phase was the only detectable one. The analysis of the relative contribution of the faster phase to the total reaction, as a function of the pH, showed a typical sigmoidal transition curve characterized by a pK = 7.2 and a Hill parameter n = 3.06. On this basis it is concluded that stripped, fetal human methemoglobin resides in an R quaternary structure while the presence of IHP stabilizes the T structure at pH below 7.2. The switch between the high spin aquomet- and the low spin hydroxymet-derivatives of adult and fetal human hemoglobins was studied optically in detail. These switches were found to be only slightly affected by IHP, and exhibited very low cooperativity (pK = 8.04; n = 1.1 and pK = 8.10; n = 1.3 for adult methemoglobin when stripped and in the presence of IHP, respectively; pK = 8.18; n = 1.11 and pK = 8.21; n = 1.28 for fetal methemoglobin when stripped and in the presence of IHP, respectively). These findings lead to the conclusion that the transition between quaternary structures in either human or fetal methemoglobins is not coupled to the switch of the spin state of the ferric heme. (author)

Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

Science.gov (United States)

Kim, K H; Patel, L; Tobet, S A; King, J C; Rubin, B S; Stopa, E G

1999-05-01

Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode. Copyright 1999 Elsevier Science B.V.

Reconstruction of living bilayer human skin equivalent utilizing human fibrin as a scaffold.

Science.gov (United States)

Mazlyzam, A L; Aminuddin, B S; Fuzina, N H; Norhayati, M M; Fauziah, O; Isa, M R; Saim, L; Ruszymah, B H I

2007-05-01

Our aim of this study was to develop a new methodology for constructing a bilayer human skin equivalent to create a more clinical compliance skin graft composite for the treatment of various skin defects. We utilized human plasma derived fibrin as the scaffold for the development of a living bilayer human skin equivalent: fibrin-fibroblast and fibrin-keratinocyte (B-FF/FK SE). Skin cells from six consented patients were culture-expanded to passage 1. For B-FF/FK SE formation, human fibroblasts were embedded in human fibrin matrix and subsequently another layer of human keratinocytes in human fibrin matrix was stacked on top. The B-FF/FK SE was then transplanted to athymic mice model for 4 weeks to evaluate its regeneration and clinical performance. The in vivo B-FF/FK SE has similar properties as native human skin by histological analysis and expression of basal Keratin 14 gene in the epidermal layer and Collagen type I gene in the dermal layer. Electron microscopy analysis of in vivo B-FF/FK SE showed well-formed and continuous epidermal-dermal junction. We have successfully developed a technique to engineer living bilayer human skin equivalent using human fibrin matrix. The utilization of culture-expanded human skin cells and fibrin matrix from human blood will allow a fully autologous human skin equivalent construction.

Fetal- and uterine-specific antigens in human amniotic fluid.

Science.gov (United States)

Sutcliffe, R G; Brock, D J; Nicholson, L V; Dunn, E

1978-09-01

Removal of the major maternal serum proteins from second trimester amniotic fluid by antibody affinity chromatography revealed various soluble tissue antigens, of which two were fetal-specific skin proteins and another, of alpha2-mobility, was specific to the uterus, and was therefore designated alpha-uterine protein (AUP). These proteins could not be detected in maternal serum by antibody-antigen crossed electrophoresis. The concentration of AUP in amniotic fluid reached a maximum between 10 and 20 weeks of gestation, suggesting that there is an influx of uterine protein into the amniotic fluid at this stage of pregnancy.

Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

Science.gov (United States)

Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

2009-10-01

Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

Maternal exercise, season and sex modify the human fetal circadian rhythm.

Science.gov (United States)

Sletten, Julie; Cornelissen, Germaine; Assmus, Jørg; Kiserud, Torvid; Albrechtsen, Susanne; Kessler, Jörg

2018-05-13

The knowledge on circadian rhythmicity is rapidly expanding. We aimed to define the longitudinal development of the circadian heart rate rhythm in the human fetus in an unrestricted, out-of-hospital setting, and to examine the effects of maternal physical activity, season and fetal sex. We recruited 48 women with low-risk singleton pregnancies. Using a portable monitor for continuous fetal electrocardiography, fetal heart rate recordings were obtained around gestational weeks 24, 28, 32 and 36. Circadian rhythmicity in fetal heart rate and fetal heart rate variation was detected by cosinor analysis; developmental trends were calculated by population-mean cosinor and multilevel analysis. For the fetal heart rate and fetal heart rate variation, a significant circadian rhythm was present in 122/123 (99.2%) and 116/121 (95.9%) of the individual recordings, respectively. The rhythms were best described by combining cosine waves with periods of 24 and 8 hours. With increasing gestational age, the magnitude of the fetal heart rate rhythm increased, and the peak of the fetal heart rate variation rhythm shifted from a mean of 14:25 (24 weeks) to 20:52 (36 weeks). With advancing gestation, the rhythm-adjusted mean value of the fetal heart rate decreased linearly in females (prhythm diversity was found in male fetuses, during higher maternal physical activity and during the summer season. The dynamic development of the fetal circadian heart rate rhythm during the second half of pregnancy is modified by fetal sex, maternal physical activity and season. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Isolation of Human Skin Dendritic Cell Subsets.

Science.gov (United States)

Gunawan, Merry; Jardine, Laura; Haniffa, Muzlifah

2016-01-01

Dendritic cells (DCs) are specialized leukocytes with antigen-processing and antigen-presenting functions. DCs can be divided into distinct subsets by anatomical location, phenotype and function. In human, the two most accessible tissues to study leukocytes are peripheral blood and skin. DCs are rare in human peripheral blood (skin covering an average total surface area of 1.8 m(2) has approximately tenfold more DCs than the average 5 L of total blood volume (Wang et al., J Invest Dermatol 134:965-974, 2014). DCs migrate spontaneously from skin explants cultured ex vivo, which provide an easy method of cell isolation (Larsen et al., J Exp Med 172:1483-1493, 1990; Lenz et al., J Clin Invest 92:2587-2596, 1993; Nestle et al., J Immunol 151:6535-6545, 1993). These factors led to the extensive use of skin DCs as the "prototype" migratory DCs in human studies. In this chapter, we detail the protocols to isolate DCs and resident macrophages from human skin. We also provide a multiparameter flow cytometry gating strategy to identify human skin DCs and to distinguish them from macrophages.

Proteolytic processing of anti-Müllerian hormone differs between human fetal testes and adult ovaries

DEFF Research Database (Denmark)

Mamsen, L S; Petersen, T S; Jeppesen, J V

2015-01-01

and specificity of a panel of five novel high-affinity AMH monoclonal antibodies. Two recognize the mature C-terminal form of AMH, whereas three recognize the active pro-mature form of AMH in human tissue. The antibodies were tested on fetal male testicular and mesonephric tissue aged 8-19 weeks post conception...... (pc), fetal male serum aged 16-26 weeks pc and human immature GCs by immunofluorescence, immunohistochemistry, ELISA and western blotting. The active pro-mature forms of AMH were expressed in both Sertoli cells from human fetal testis and human immature GCs. In contrast, the mature C-terminal form...... of AMH was hardly detected in Sertoli cells, but was readily detected in GCs. This particular form was also located to the nucleus in GCs, whereas the other investigated AMH forms remained in the cytoplasm. Interestingly, the distribution of the AMH forms in the fetal serum of boys showed...

Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches

Energy Technology Data Exchange (ETDEWEB)

Muczynski, V. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Cravedi, J.P. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Lehraiki, A.; Levacher, C.; Moison, D.; Lecureuil, C.; Messiaen, S. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Perdu, E. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Frydman, R. [Service de Gynécologie-Obstétrique, Hôpital A. Béclère, Université Paris Sud F-92141 Clamart (France); Habert, R. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); and others

2012-05-15

The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10{sup −5} M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes. Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation and cultured in the presence or not of 10{sup −5} M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with {sup 14}C-MEHP. A 10{sup −5} M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo. This study suggests that this 10{sup −5} M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells. -- Highlights: ► 10{sup −5} M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.

Black and white human skin differences

DEFF Research Database (Denmark)

Andersen, Klaus Ejner; Maibach, H I

1979-01-01

This review of black and white human skin differences emphasizes the alleged importance of factors other than the obvious, i.e., skin color. Physicochemical differences and differences in susceptibility to irritants and allergens suggest a more resistant black than white skin. Differences appear...

A radiographic study of the human fetal spine

International Nuclear Information System (INIS)

Bagnall, K.M.; Harris, P.F.; Jones, P.R.M.

1979-01-01

Regression equations are presented which describe the growth in length of the various regions of the vertebral column in the human fetus. From 8 weeks on the thoracic is always the longest region and the sacral the shortest, while the lumbar region is longer than the cervical. From the regression equations predictions of fetal vertebral length can be made from fetal age: this should be useful in obstetric practice when diagnostic ultrasound techniques are being employed for the diagnosis of growth disorders and skeletal abnormalities. A different development pattern emerges when average 'vertebral units' for each region are compared. The lumbar vertebrae are always the largest with the thoracic, cervical and sacral vertebrae being progressively smaller. (author)

Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models.

Science.gov (United States)

Oesch, F; Fabian, E; Guth, K; Landsiedel, R

2014-12-01

The exposure of the skin to medical drugs, skin care products, cosmetics, and other chemicals renders information on xenobiotic-metabolizing enzymes (XME) in the skin highly interesting. Since the use of freshly excised human skin for experimental investigations meets with ethical and practical limitations, information on XME in models comes in the focus including non-human mammalian species and in vitro skin models. This review attempts to summarize the information available in the open scientific literature on XME in the skin of human, rat, mouse, guinea pig, and pig as well as human primary skin cells, human cell lines, and reconstructed human skin models. The most salient outcome is that much more research on cutaneous XME is needed for solid metabolism-dependent efficacy and safety predictions, and the cutaneous metabolism comparisons have to be viewed with caution. Keeping this fully in mind at least with respect to some cutaneous XME, some models may tentatively be considered to approximate reasonable closeness to human skin. For dermal absorption and for skin irritation among many contributing XME, esterase activity is of special importance, which in pig skin, some human cell lines, and reconstructed skin models appears reasonably close to human skin. With respect to genotoxicity and sensitization, activating XME are not yet judgeable, but reactive metabolite-reducing XME in primary human keratinocytes and several reconstructed human skin models appear reasonably close to human skin. For a more detailed delineation and discussion of the severe limitations see the "Overview and Conclusions" section in the end of this review.

Development of human skin equivalents to unravel the impaired skin barrier in atopic dermatitis skin

NARCIS (Netherlands)

Eweje, M.O.

2016-01-01

The studies in this thesis describes the barrier defects in Atopic Dermatitis (AD) skin and various techniques to develop AD Human Skin Equivalents (HSEs) which can be used to better understand the role of several factors in the pathogenesis of AD skin. The results described show that Inflammation

The Role of Carotenoids in Human Skin

Directory of Open Access Journals (Sweden)

Theognosia Vergou

2011-12-01

Full Text Available The human skin, as the boundary organ between the human body and the environment, is under the constant influence of free radicals (FR, both from the outside in and from the inside out. Carotenoids are known to be powerful antioxidant substances playing an essential role in the reactions of neutralization of FR (mainly reactive oxygen species ROS. Carotenoid molecules present in the tissue are capable of neutralizing several attacks of FR, especially ROS, and are then destroyed. Human skin contains carotenoids, such as α-, γ-, β-carotene, lutein, zeaxanthin, lycopene and their isomers, which serve the living cells as a protection against oxidation. Recent studies have reported the possibility to investigate carotenoids in human skin quickly and non-invasively by spectroscopic means. Results obtained from in-vivo studies on human skin have shown that carotenoids are vital components of the antioxidative protective system of the human skin and could serve as marker substances for the overall antioxidative status. Reflecting the nutritional and stress situation of volunteers, carotenoids must be administered by means of antioxidant-rich products, e.g., in the form of fruit and vegetables. Carotenoids are degraded by stress factors of any type, inter alia, sun radiation, contact with environmental hazards, illness, etc. The kinetics of the accumulation and degradation of carotenoids in the skin have been investigated.

Age-related changes in the proteoglycans of human skin. Specific cleavage of decorin to yield a major catabolic fragment in adult skin.

Science.gov (United States)

Carrino, David A; Onnerfjord, Patrik; Sandy, John D; Cs-Szabo, Gabriella; Scott, Paul G; Sorrell, J Michael; Heinegård, Dick; Caplan, Arnold I

2003-05-09

Dramatic changes occur in skin as a function of age, including changes in morphology, physiology, and mechanical properties. Changes in extracellular matrix molecules also occur, and these changes likely contribute to the overall age-related changes in the physical properties of skin. The major proteoglycans detected in extracts of human skin are decorin and versican. In addition, adult human skin contains a truncated form of decorin, whereas fetal skin contains virtually undetectable levels of this truncated decorin. Analysis of this molecule, herein referred to as decorunt, indicates that it is a catabolic fragment of decorin rather than a splice variant. With antibody probes to the core protein, decorunt is found to lack the carboxyl-terminal portion of decorin. Further analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry shows that the carboxyl terminus of decorunt is at Phe(170) of decorin. This result indicates that decorunt represents the amino-terminal 43% of the mature decorin molecule. Such a structure is inconsistent with alternative splicing of decorin and suggests that decorunt is a catabolic fragment of decorin. A neoepitope antiserum, anti-VRKVTF, was generated against the carboxyl terminus of decorunt. This antiserum does not recognize intact decorin in any skin proteoglycan sample tested on immunoblots but recognizes every sample of decorunt tested. The results with anti-VRKVTF confirm the identification of the carboxyl terminus of decorunt. Analysis of collagen binding by surface plasmon resonance indicates that the affinity of decorunt for type I collagen is 100-fold less than that of decorin. This observation correlates with the structural analysis of decorunt, in that it lacks regions of decorin previously shown to be important for interaction with type I collagen. The detection of a catabolic fragment of decorin suggests the existence of a specific catabolic pathway for this proteoglycan. Because of the

Volumetric Visualization of Human Skin

Science.gov (United States)

Kawai, Toshiyuki; Kurioka, Yoshihiro

We propose a modeling and rendering technique of human skin, which can provide realistic color, gloss and translucency for various applications in computer graphics. Our method is based on volumetric representation of the structure inside of the skin. Our model consists of the stratum corneum and three layers of pigments. The stratum corneum has also layered structure in which the incident light is reflected, refracted and diffused. Each layer of pigment has carotene, melanin or hemoglobin. The density distributions of pigments which define the color of each layer can be supplied as one of the voxel values. Surface normals of upper-side voxels are fluctuated to produce bumps and lines on the skin. We apply ray tracing approach to this model to obtain the rendered image. Multiple scattering in the stratum corneum, reflective and absorptive spectrum of pigments are considered. We also consider Fresnel term to calculate the specular component for glossy surface of skin. Some examples of rendered images are shown, which can successfully visualize a human skin.

ABSORPTION-SPECTRA OF HUMAN FETAL AND ADULT OXYHEMOGLOBIN, DE-OXYHEMOGLOBIN, CARBOXYHEMOGLOBIN, AND METHEMOGLOBIN

NARCIS (Netherlands)

ZIJLSTRA, WG; MEEUWSENVANDERROEST, WP

We determined the millimolar absorptivities of the four clinically relevant derivatives of fetal and adult human hemoglobin in the visible and near-infrared spectral range (450-1000 nm). As expected, spectral absorption curves of similar shape were found, but the small differences between fetal and

Cellular and Molecular Effect of MEHP Involving LXRα in Human Fetal Testis and Ovary

OpenAIRE

Muczynski, Vincent; Lecureuil, Charlotte; Messiaen, Sébastien; Guerquin, Marie-Justine; N’Tumba-Byn, Thierry; Moison, Delphine; Hodroj, Wassim; Benjelloun, Hinde; Baijer, Jan; Livera, Gabriel; Frydman, René; Benachi, Alexandra; Habert, René; Rouiller-Fabre, Virginie

2012-01-01

Background Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro. Methodology/Principal Findings Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10−4M...

Altered Decorin and Smad Expression in Human Fetal Membranes in PPROM1

Science.gov (United States)

Horgan, Casie E.; Roumimper, Hailey; Tucker, Richard; Lechner, Beatrice E.

2014-01-01

ABSTRACT Humans with Ehlers-Danlos syndrome, a subtype of which is caused by abnormal decorin expression, are at increased risk of preterm birth due to preterm premature rupture of fetal membranes (PPROM). In the mouse model, the absence of decorin leads to fetal membrane abnormalities, preterm birth, and dysregulation of decorin's downstream pathway components, including the transcription factor p-Smad-2. However, the role of decorin and p-Smad-2 in idiopathic human PPROM is unknown. Fetal membranes from 20–25 pregnancies per group were obtained as a cross-sectional sample of births at one institution between January 2010 and December 2012. The groups were term, preterm without PPROM, and preterm with PPROM. Immunohistochemical analysis of fetal membranes was performed for decorin and p-Smad-2 using localization and quantification assessment. Decorin expression is developmentally regulated in fetal membranes and is decreased in preterm birth with PPROM compared to preterm birth without PPROM. In preterm with PPROM samples, the presence of infection is associated with significant decorin downregulation compared to preterm with PPROM samples without infection. The preterm with PPROM group exhibited decreased p-Smad-2 staining compared to both the term controls and the preterm-without-PPROM group. Our findings suggest that dysregulation of decorin and its downstream pathway component p-Smad-2 occurs in fetal membranes during the second trimester in pathological pregnancies, thus supporting a role for decorin and p-Smad-2 in the pathophysiology of fetal membranes and adverse pregnancy outcomes. These findings may lead to the discovery of new targets for the diagnosis and treatment of PPROM. PMID:25232019

Maturation of the human fetal startle response: Evidence for sex-specific maturation of the human fetus1

Science.gov (United States)

Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A.; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M.; Sandman, Curt A.

2009-01-01

Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks’ GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks’ GA, females however, presented with a mature FHR startle response by 31 weeks’ GA. The results indicate that there are different rates of maturation in the male and female fetus that may have implications for sex-specific programming influences. PMID:19726143

Neurogenic inflammation in human and rodent skin

DEFF Research Database (Denmark)

Schmelz, M; Petersen, Lars Jelstrup

2001-01-01

The combination of vasodilation and protein extravasation following activation of nociceptors has been termed "neurogenic inflammation." In contrast to rodents, no neurogenic protein extravasation can be elicited in healthy human skin. Dermal microdialysis has considerably increased our knowledge...... about neurogenic inflammation in human skin, including the involvement of mast cells.......The combination of vasodilation and protein extravasation following activation of nociceptors has been termed "neurogenic inflammation." In contrast to rodents, no neurogenic protein extravasation can be elicited in healthy human skin. Dermal microdialysis has considerably increased our knowledge...

Characterization of SLC transporters in human skin

Directory of Open Access Journals (Sweden)

Marion Alriquet

2015-03-01

Full Text Available Most identified drug transporters belong to the ATP-binding Cassette (ABC and Solute Carrier (SLC families. Recent research indicates that some of these transporters play an important role in the absorption, distribution and excretion of drugs, and are involved in clinically relevant drug-drug interactions for systemic drugs. However, very little is known about the role of drug transporters in human skin in the disposition of topically applied drugs and their involvement in drug-drug interactions. The aim of this work was to compare the expression in human skin (vs human hepatocytes and kidney of SLC transporters included in the EMA guidance as the most likely clinical sources of drug interactions. The expression of SLC transporters in human tissues was analyzed by quantitative RT-PCR. Modulation of SLC47A1 and SLC47A2 (MATE1 and MATE2 expression was analyzed after treatment of human skin in organ-culture with rifampicin and UV irradiation. The expression of SLCO2B1 (OATPB, SLCO3A1 (OATPD, SLCO4A1 (OATPE, SLC47A1 and SLC47A2 (MATE1 and MATE2 was detected in human skin, OATPE and MATE1 being the most expressed. OATPE is about 70 times more expressed in human skin than in human hepatocytes. Moreover, the expression of SLC47A1 and SLC47A2 was down-regulated after treatment with rifampicin or after exposure to UV light. The present findings demonstrate that SLCO4A1 (OATPE and SLC47A1 (MATE1 are highly expressed in human skin and suggest the involvement of SLC transporters in the disposition of topically applied drugs.

Chromosome 11-linked determinant controls fetal globin expression and the fetal-to-adult globin switch

International Nuclear Information System (INIS)

Melis, M.; Demopulos, G.; Najfeld, V.; Zhang, J.W.; Brice, M.; Papayannopoulou, T.; Stamatoyannopoulos, G.

1987-01-01

Hybrids formed by fusing mouse erythroleukemia (MEL) cells with human fetal erythroid cells produce human fetal globin, but they switch to adult globin production as culture time advances. To obtain information on the chromosomal assignment of the elements that control γ-to-β switching, the authors analyzed the chromosomal composition of hybrids producing exclusively or predominantly human fetal globin and hybrids producing only adult human globin. No human chromosome was consistently present in hybrids expressing fetal globin and consistently absent in hybrids expressing adult globin. Subcloning experiments demonstrated identical chromosomal compositions in subclones displaying the fetal globin program and those that had switched to expression of the adult globin program. These data indicate that retention of only one human chromosome -- i.e., chromosome 11 -- is sufficient for expression of human fetal globin and the subsequent γ-to-β switch. The results suggest that the γ-to-β switch is controlled either cis to the β-globin locus of by a trans-acting mechanism, the genes of which reside on human chromosome 11

Three-Dimensional In Vitro Skin and Skin Cancer Models Based on Human Fibroblast-Derived Matrix.

Science.gov (United States)

Berning, Manuel; Prätzel-Wunder, Silke; Bickenbach, Jackie R; Boukamp, Petra

2015-09-01

Three-dimensional in vitro skin and skin cancer models help to dissect epidermal-dermal and tumor-stroma interactions. In the model presented here, normal human dermal fibroblasts isolated from adult skin self-assembled into dermal equivalents with their specific fibroblast-derived matrix (fdmDE) over 4 weeks. The fdmDE represented a complex human extracellular matrix that was stabilized by its own heterogeneous collagen fiber meshwork, largely resembling a human dermal in vivo architecture. Complemented with normal human epidermal keratinocytes, the skin equivalent (fdmSE) thereof favored the establishment of a well-stratified and differentiated epidermis and importantly allowed epidermal regeneration in vitro for at least 24 weeks. Moreover, the fdmDE could be used to study the features of cutaneous skin cancer. Complementing fdmDE with HaCaT cells in different stages of malignancy or tumor-derived cutaneous squamous cell carcinoma cell lines, the resulting skin cancer equivalents (fdmSCEs) recapitulated the respective degree of tumorigenicity. In addition, the fdmSCE invasion phenotypes correlated with their individual degree of tissue organization, disturbance in basement membrane organization, and presence of matrix metalloproteinases. Together, fdmDE-based models are well suited for long-term regeneration of normal human epidermis and, as they recapitulate tumor-specific growth, differentiation, and invasion profiles of cutaneous skin cancer cells, also provide an excellent human in vitro skin cancer model.

The isolated perfused human skin flap model: A missing link in skin penetration studies?

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Ternullo, Selenia; de Weerd, Louis; Flaten, Gøril Eide; Holsæter, Ann Mari; Škalko-Basnet, Nataša

2017-01-01

Development of effective (trans)dermal drug delivery systems requires reliable skin models to evaluate skin drug penetration. The isolated perfused human skin flap remains metabolically active tissue for up to 6h during in vitro perfusion. We introduce the isolated perfused human skin flap as a close-to-in vivo skin penetration model. To validate the model's ability to evaluate skin drug penetration the solutions of a hydrophilic (calcein) and a lipophilic (rhodamine) fluorescence marker were applied. The skin flaps were perfused with modified Krebs-Henseleit buffer (pH7.4). Infrared technology was used to monitor perfusion and to select a well-perfused skin area for administration of the markers. Flap perfusion and physiological parameters were maintained constant during the 6h experiments and the amount of markers in the perfusate was determined. Calcein was detected in the perfusate, whereas rhodamine was not detectable. Confocal images of skin cross-sections shoved that calcein was uniformly distributed through the skin, whereas rhodamine accumulated in the stratum corneum. For comparison, the penetration of both markers was evaluated on ex vivo human skin, pig skin and cellophane membrane. The proposed perfused flap model enabled us to distinguish between the penetrations of the two markers and could be a promising close-to-in vivo tool in skin penetration studies and optimization of formulations destined for skin administration. Copyright © 2016 Elsevier B.V. All rights reserved.

IL-27 induces a pro-inflammatory response in human fetal membranes mediating preterm birth.

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Yin, Nanlin; Wang, Hanbing; Zhang, Hua; Ge, Huisheng; Tan, Bing; Yuan, Yu; Luo, Xiaofang; Olson, David M; Baker, Philip N; Qi, Hongbo

2017-09-01

Inflammation at the maternal-fetal interface has been shown to be involved in the pathogenesis of preterm birth. Interleukin 27 (IL-27), a heterodimeric cytokine, is known to mediate an inflammatory response in some pregnancy complications. In this study, we aimed to determine whether IL-27 could induce an inflammatory reaction at the maternal-fetal interface that would mediate the onset of preterm birth. We found elevated expression of IL-27 in human peripheral serum and elevated expression of its specific receptor (wsx-1) on fetal membranes in cases of preterm birth. Moreover, the release of inflammatory markers (CXCL10, IFN-γ, MCP-1, IL-6, IL-1β and TNF-α), especially CXCL10, was markedly augmented upon stimulation of IL-27 in the fetal membranes. Additionally, IL-27 and IFN-γ cooperated to amplify the expression of CXCL10 in the fetal membranes. Moreover, the production of CXCL10 was increased in IL-27-treated fetal membrane through JNK, PI3K or Erk signaling pathways. Finally, MMP2 and MMP9 were activated by IL-27 in human fetal membranes, which may be related to the onset of preterm premature rupture of membranes (pPROM). In conclusion, for the first time, we reported that the aberrant expression of IL-27 could mediate an excessive inflammatory response in fetal membranes through the JNK, PI3K or Erk signaling pathways, which contributes to preterm birth. Copyright © 2017 Elsevier B.V. All rights reserved.

The skin immune system (SIS): distribution and immunophenotype of lymphocyte subpopulations in normal human skin

NARCIS (Netherlands)

Bos, J. D.; Zonneveld, I.; Das, P. K.; Krieg, S. R.; van der Loos, C. M.; Kapsenberg, M. L.

1987-01-01

The complexity of immune response-associated cells present in normal human skin was recently redefined as the skin immune system (SIS). In the present study, the exact immunophenotypes of lymphocyte subpopulations with their localizations in normal human skin were determined quantitatively. B cells

Advanced haptic sensor for measuring human skin conditions

Science.gov (United States)

Tsuchimi, Daisuke; Okuyama, Takeshi; Tanaka, Mami

2010-01-01

This paper is concerned with the development of a tactile sensor using PVDF (Polyvinylidene Fluoride) film as a sensory receptor of the sensor to evaluate softness, smoothness, and stickiness of human skin. Tactile sense is the most important sense in the sensation receptor of the human body along with eyesight, and we can examine skin condition quickly using these sense. But, its subjectivity and ambiguity make it difficult to quantify skin conditions. Therefore, development of measurement device which can evaluate skin conditions easily and objectively is demanded by dermatologists, cosmetic industries, and so on. In this paper, an advanced haptic sensor system that can measure multiple information of skin condition in various parts of human body is developed. The applications of the sensor system to evaluate softness, smoothness, and stickiness of skin are investigated through two experiments.

Materials used to simulate physical properties of human skin.

Science.gov (United States)

Dąbrowska, A K; Rotaru, G-M; Derler, S; Spano, F; Camenzind, M; Annaheim, S; Stämpfli, R; Schmid, M; Rossi, R M

2016-02-01

For many applications in research, material development and testing, physical skin models are preferable to the use of human skin, because more reliable and reproducible results can be obtained. This article gives an overview of materials applied to model physical properties of human skin to encourage multidisciplinary approaches for more realistic testing and improved understanding of skin-material interactions. The literature databases Web of Science, PubMed and Google Scholar were searched using the terms 'skin model', 'skin phantom', 'skin equivalent', 'synthetic skin', 'skin substitute', 'artificial skin', 'skin replica', and 'skin model substrate.' Articles addressing material developments or measurements that include the replication of skin properties or behaviour were analysed. It was found that the most common materials used to simulate skin are liquid suspensions, gelatinous substances, elastomers, epoxy resins, metals and textiles. Nano- and micro-fillers can be incorporated in the skin models to tune their physical properties. While numerous physical skin models have been reported, most developments are research field-specific and based on trial-and-error methods. As the complexity of advanced measurement techniques increases, new interdisciplinary approaches are needed in future to achieve refined models which realistically simulate multiple properties of human skin. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fetal magnetic resonance imaging and human genetics

International Nuclear Information System (INIS)

Hengstschlaeger, Markus

2006-01-01

The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data

Fetal magnetic resonance imaging and human genetics

Energy Technology Data Exchange (ETDEWEB)

Hengstschlaeger, Markus [Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)]. E-mail: markus.hengstschlaeger@meduniwien.ac.at

2006-02-15

The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data.

Evaluation of dermal-epidermal skin equivalents ('composite-skin') of human keratinocytes in a collagen-glycosaminoglycan matrix(Integra artificial skin).

Science.gov (United States)

Kremer, M; Lang, E; Berger, A C

2000-09-01

Integra artificial skin (Integra LifeSciences Corp., Plainsboro, NJ, USA) is a dermal template consisting of bovine collagen, chondroitin-6-sulphate and a silastic membrane manufactured as Integra. This product has gained widespread use in the clinical treatment of third degree burn wounds and full thickness skin defects of different aetiologies. The product was designed to significantly reduce the time needed to achieve final wound closure in the treatment of major burn wounds, to optimise the sparse autologous donor skin resources and to improve the durable mechanical quality of the skin substitute. The clinical procedure requires two stages. The first step creates a self neodermis, the second creates a self epidermis on the neodermis. However, it is desirable to cover major burn wounds early in a single step by a skin substitute consisting of a dermal equivalent seeded in vitro with autologous keratinocytes ('composite-skin') out of which a full thickness skin develops in vivo.The goal of this experimental study was to develop a method to integrate human keratinocytes in homogeneous distribution and depth into Integra Artificial Skin. The seeded cell-matrix composites were grafted onto athymic mice in order to evaluate their potential to reconstitute a human epidermis in vivo. We were able to demonstrate that the inoculated human keratinocytes reproducibly displayed a homogeneous pattern of distribution, adherence, proliferation and confluence. The cell-matrix composites grafted in this model exhibited good wound adherence, complete healing, minor wound contraction and had the potential to reconstitute an elastic, functional and durable human skin. Histologically we were able to show that the inoculated human keratinocytes in vivo colonised the matrix in a histomorphologically characteristic epidermal pattern (keratomorula, keratinocyte bubbling) and developed a persisting, stratified, keratinising epidermis which immunohistologically proved to be of human

Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

Science.gov (United States)

Ganguli, Kriston; Collado, Maria Carmen; Rautava, Jaana; Lu, Lei; Satokari, Reetta; von Ossowski, Ingemar; Reunanen, Justus; de Vos, Willem M.; Palva, Airi; Isolauri, Erika; Salminen, Seppo; Walker, W. Allan; Rautava, Samuli

2015-01-01

Background Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models. Methods TNF-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR. Results Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression. Conclusion The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human intestinal epithelial cells and directly modulates intestinal epithelial cell innate immune gene expression. PMID:25580735

Human skin penetration of silver nanoparticles through intact and damaged skin

International Nuclear Information System (INIS)

Larese, Francesca Filon; D'Agostin, Flavia; Crosera, Matteo; Adami, Gianpiero; Renzi, Nadia; Bovenzi, Massimo; Maina, Giovanni

2009-01-01

There is a growing interest on nanoparticle safety for topical use. The benefits of nanoparticles have been shown in several scientific fields, but little is known about their potential to penetrate the skin. This study aims at evaluating in vitro skin penetration of silver nanoparticles. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. Physiological solution was used as receiving phase and 70 μg/cm 2 of silver nanoparticles coated with polyvinylpirrolidone dispersed in synthetic sweat were applied as donor phase to the outer surface of the skin for 24 h. The receptor fluid measurements were performed by electro thermal atomic absorption spectroscopy (ETAAS). Human skin penetration was also determined by using transmission electron microscope (TEM) to verify the location of silver nanoparticles in exposed membranes. Median silver concentrations of 0.46 ng cm -2 (range -2 (range 0.43-11.6) were found in the receiving solutions of cells where the nanoparticles solution was applied on intact skin (eight cells) and on damaged skin (eight cells), respectively. Twenty-four hours silver flux permeation in damaged skin was 0.62 ± 0.2 ng cm -2 with a lag time <1 h. Our experimental data showed that silver nanoparticles absorption through intact and damaged skin was very low but detectable, and that in case of damaged skin it was possible an increasing permeation of silver applied as nanoparticles. Moreover, silver nanoparticles could be detected in the stratum corneum and the outermost surface of the epidermis by electron microscopy. We demonstrated for the first time that silver applied as nanoparticles coated with polyvinylpirrolidone is able to permeate the damaged skin in an in vitro diffusion cell system

Human skin wetness perception: psychophysical and neurophysiological bases

Science.gov (United States)

Filingeri, Davide; Havenith, George

2015-01-01

The ability to perceive thermal changes in the surrounding environment is critical for survival. However, sensing temperature is not the only factor among the cutaneous sensations to contribute to thermoregulatory responses in humans. Sensing skin wetness (i.e. hygrosensation) is also critical both for behavioral and autonomic adaptations. Although much has been done to define the biophysical role of skin wetness in contributing to thermal homeostasis, little is known on the neurophysiological mechanisms underpinning the ability to sense skin wetness. Humans are not provided with skin humidity receptors (i.e., hygroreceptors) and psychophysical studies have identified potential sensory cues (i.e. thermal and mechanosensory) which could contribute to sensing wetness. Recently, a neurophysiological model of human wetness sensitivity has been developed. In helping clarifying the peripheral and central neural mechanisms involved in sensing skin wetness, this model has provided evidence for the existence of a specific human hygrosensation strategy, which is underpinned by perceptual learning via sensory experience. Remarkably, this strategy seems to be shared by other hygroreceptor-lacking animals. However, questions remain on whether these sensory mechanisms are underpinned by specific neuromolecular pathways in humans. Although the first study on human wetness perception dates back to more than 100 years, it is surprising that the neurophysiological bases of such an important sensory feature have only recently started to be unveiled. Hence, to provide an overview of the current knowledge on human hygrosensation, along with potential directions for future research, this review will examine the psychophysical and neurophysiological bases of human skin wetness perception. PMID:27227008

BMP signaling in the human fetal ovary is developmentally regulated and promotes primordial germ cell apoptosis.

Science.gov (United States)

Childs, Andrew J; Kinnell, Hazel L; Collins, Craig S; Hogg, Kirsten; Bayne, Rosemary A L; Green, Samira J; McNeilly, Alan S; Anderson, Richard A

2010-08-01

Primordial germ cells (PGCs) are the embryonic precursors of gametes in the adult organism, and their development, differentiation, and survival are regulated by a combination of growth factors collectively known as the germ cell niche. Although many candidate niche components have been identified through studies on mouse PGCs, the growth factor composition of the human PGC niche has not been studied extensively. Here we report a detailed analysis of the expression of components of the bone morphogenetic protein (BMP) signaling apparatus in the human fetal ovary, from postmigratory PGC proliferation to the onset of primordial follicle formation. We find developmentally regulated and reciprocal patterns of expression of BMP2 and BMP4 and identify germ cells to be the exclusive targets of ovarian BMP signaling. By establishing long-term cultures of human fetal ovaries in which PGCs are retained within their physiological niche, we find that BMP4 negatively regulates postmigratory PGC numbers in the human fetal ovary by promoting PGC apoptosis. Finally, we report expression of both muscle segment homeobox (MSX)1 and MSX2 in the human fetal ovary and reveal a selective upregulation of MSX2 expression in human fetal ovary in response to BMP4, suggesting this gene may act as a downstream effector of BMP-induced apoptosis in the ovary, as in other systems. These data reveal for the first time growth factor regulation of human PGC development in a physiologically relevant context and have significant implications for the development of cultures systems for the in vitro maturation of germ cells, and their derivation from pluripotent stem cells.

Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

Science.gov (United States)

Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

2016-08-01

Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models.

Science.gov (United States)

Oesch, F; Fabian, E; Landsiedel, Robert

2018-06-18

Studies on the metabolic fate of medical drugs, skin care products, cosmetics and other chemicals intentionally or accidently applied to the human skin have become increasingly important in order to ascertain pharmacological effectiveness and to avoid toxicities. The use of freshly excised human skin for experimental investigations meets with ethical and practical limitations. Hence information on xenobiotic-metabolizing enzymes (XME) in the experimental systems available for pertinent studies compared with native human skin has become crucial. This review collects available information of which-taken with great caution because of the still very limited data-the most salient points are: in the skin of all animal species and skin-derived in vitro systems considered in this review cytochrome P450 (CYP)-dependent monooxygenase activities (largely responsible for initiating xenobiotica metabolism in the organ which provides most of the xenobiotica metabolism of the mammalian organism, the liver) are very low to undetectable. Quite likely other oxidative enzymes [e.g. flavin monooxygenase, COX (cooxidation by prostaglandin synthase)] will turn out to be much more important for the oxidative xenobiotic metabolism in the skin. Moreover, conjugating enzyme activities such as glutathione transferases and glucuronosyltransferases are much higher than the oxidative CYP activities. Since these conjugating enzymes are predominantly detoxifying, the skin appears to be predominantly protected against CYP-generated reactive metabolites. The following recommendations for the use of experimental animal species or human skin in vitro models may tentatively be derived from the information available to date: for dermal absorption and for skin irritation esterase activity is of special importance which in pig skin, some human cell lines and reconstructed skin models appears reasonably close to native human skin. With respect to genotoxicity and sensitization reactive

Fetal alcohol exposure and development of the integument

Directory of Open Access Journals (Sweden)

Longhurst WD

2016-05-01

Full Text Available William D Longhurst,1 Jordan Ernst,2 Larry Burd3 1Center for Emergency Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA; 2University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA; 3Department of Pediatrics, North Dakota Fetal Alcohol Syndrome Center, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA Background: The physiology of fetal alcohol exposure changes across gestation. Early in pregnancy placental, fetal, and amniotic fluid concentrations of alcohol exposure are equivalent. Beginning in mid-pregnancy, the maturing fetal epidermis adds keratins which decrease permeability resulting in development of a barrier between fetal circulation and the amniotic fluid. Barrier function development is essential for viability in late pregnancy and in the extra-uterine environment. In this paper we provide a selected review of the effects of barrier function on fetal alcohol exposure. Methods: We utilized a search of PubMed and Google for all years in all languages for MeSH on Demand terms: alcohol drinking, amnion, amniotic fluid, epidermis, ethanol, female, fetal development, fetus, humans, keratins, permeability, and pregnancy. We also reviewed the reference lists of relevant papers and hand-searched reference lists of textbooks for additional references. Results: By 30 gestational weeks, development of barrier function alters the pathophysiology of ethanol dispersion between the fetus and amniotic fluid. Firstly, increases in the effectiveness of barrier function decreases the rate of diffusion of alcohol from fetal circulation across fetal skin into the amniotic fluid. This reduces the volume of alcohol entering the amniotic fluid. Secondly, barrier function increases the duration of fetal exposure by decreasing the rate of alcohol diffusion from amniotic fluid back into fetal circulation. Ethanol is then transported into

Multivariate Models for Prediction of Human Skin Sensitization ...

Science.gov (United States)

One of the lnteragency Coordinating Committee on the Validation of Alternative Method's (ICCVAM) top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary to produce skin sensitization suggests that no single alternative method will replace the currently accepted animal tests. ICCVAM is evaluating an integrated approach to testing and assessment based on the adverse outcome pathway for skin sensitization that uses machine learning approaches to predict human skin sensitization hazard. We combined data from three in chemico or in vitro assays - the direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT) and KeratinoSens TM assay - six physicochemical properties and an in silico read-across prediction of skin sensitization hazard into 12 variable groups. The variable groups were evaluated using two machine learning approaches , logistic regression and support vector machine, to predict human skin sensitization hazard. Models were trained on 72 substances and tested on an external set of 24 substances. The six models (three logistic regression and three support vector machine) with the highest accuracy (92%) used: (1) DPRA, h-CLAT and read-across; (2) DPRA, h-CLAT, read-across and KeratinoSens; or (3) DPRA, h-CLAT, read-across, KeratinoSens and log P. The models performed better at predicting human skin sensitization hazard than the murine

Modelling glucose and water dynamics in human skin

NARCIS (Netherlands)

Groenendaal, W.; Schmidt, K.H.; Basum, von G.; Riel, van N.A.W.; Hilbers, P.A.J.

2008-01-01

Background: Glucose is heterogeneously distributed in the different physiological compartments in the human skin. Therefore, for the development of a noninvasive measurement method, both a good quantification of the different compartments of human skin and an understanding of glucose transport

Comparison of the biological features between human fetal hepatocyte and immortalized L-02 hepatocyte in vitro

International Nuclear Information System (INIS)

Kong Weiwei; Teng Gaojun

2004-01-01

Objective: To evaluate the feasibilities of the potential donors in liver cell transplantation using the human fetal hepatocytes and immortalized L-02 hepatocytes by comparing their biological features. Methods: Human fetal hepatocytes were isolated from aborted fetal livers (gestational ages from 14 w to 24 w) by an improved two-stage perfusion method and cultured in a conditioned medium without any growth factors. α-fetal protein (AFP) and albumin (ALB) were detected by radioimmunoassay (RIA) and cytokeratin-19 (CK-19 ) was identified by cellular immunochemistry study. Immortalized L-02 hepatocytes were cultured in the same condition and the characteristic proteins were detected by the same methods. Results: The viability of human fetal hepatocytes was approximately 95% using the perfusion method, and the maximum survival time of the cultured hepatocytes was 3 weeks. The expression of AFP, ALB, and CK19 was detected at the same time, especially during Day 3 to Day 7 in the culture. By comparison, the proliferation ability of L-02 hepatocyte was greater, although with a lower level of ALB secretion. The expression of AFP and CK19 was not detected. Furthermore, during the long culture, L-02 hepatocytes may undergo a morphologic change and fail to express ALB. Conclusion: Human fetal hepatocyte may be a practical donor for hepatocyte transplantation with its high-level protein expression and potential bi-differentiation ability. In view of the absent expression of ALB and the morphologic change in culture, although with better proliferation, L-02 hepatocyte seems not useful for hepatocyte transplantation

Immortalization of Human Fetal Hepatocyte by Ectopic Expression of Human Telomerase Reverse Transcriptase, Human Papilloma Virus (E7) and Simian Virus 40 Large T (SV40 T) Antigen Towards Bioartificial Liver Support.

Science.gov (United States)

Giri, Shibashish; Bader, Augustinus

2014-09-01

Generation of genetically stable and non-tumoric immortalization cell line from primary cells would be enormously useful for research and therapeutic purposes, but progress towards this goal has so far been limited. It is now universal acceptance that immortalization of human fetal hepatocytes based on recent advances of telomerase biology and oncogene, lead to unlimited population doubling could be the possible source for bioartificial liver device. Immortalization of human fetal hepatocytes cell line by ectopic expression of human telomerase reverse transcriptase (hTERT), human papilloma virus gene (E7) and simian virus 40 large T (SV40 T) antigens is main goal of present study. We used an inducible system containing human telomerase and E7, both of which are cloned into responder constructs controlled by doxycycline transactivator. We characterized the immortalized human fetal hepatocyte cells by analysis of green fluorescent cells (GFP) positive cells using flow cytometry (FACs) cell sorting and morphology, proliferative rate and antigen expression by immunohistochemical analysis. In addition to we analysized lactate formation, glucose consumption, albumin secretion and urea production of immortalized human fetal hepatocyte cells. After 25 attempts for transfection of adult primary hepatocytes by human telomerase and E7 to immortalize them, none of the transfection systems resulted in the production of a stable, proliferating cell line. Although the transfection efficiency was more than 70% on the first day, the vast majority of the transfected hepatocytes lost their signal within the first 5-7 days. The remaining transfected hepatocytes persisted for 2-4 weeks and divided one or two times without forming a clone. After 10 attempts of transfection human fetal hepatocytes using the same transfection system, we obtained one stable human fetal hepatocytes cell line which was able albumin secretion urea production and glucose consumption. We established a

Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues

International Nuclear Information System (INIS)

Prody, C.A.; Zevin-Sonkin, D.; Gnatt, A.; Goldberg, O.; Soreq, H.

1987-01-01

To study the primary structure and regulation of human cholinesterases, oligodeoxynucleotide probes were prepared according to a consensus peptide sequence present in the active site of both human serum pseudocholinesterase and Torpedo electric organ true acetylcholinesterase. Using these probes, the authors isolated several cDNA clones from λgt10 libraries of fetal brain and liver origins. These include 2.4-kilobase cDNA clones that code for a polypeptide containing a putative signal peptide and the N-terminal, active site, and C-terminal peptides of human BtChoEase, suggesting that they code either for BtChoEase itself or for a very similar but distinct fetal form of cholinesterase. In RNA blots of poly(A) + RNA from the cholinesterase-producing fetal brain and liver, these cDNAs hybridized with a single 2.5-kilobase band. Blot hybridization to human genomic DNA revealed that these fetal BtChoEase cDNA clones hybridize with DNA fragments of the total length of 17.5 kilobases, and signal intensities indicated that these sequences are not present in many copies. Both the cDNA-encoded protein and its nucleotide sequence display striking homology to parallel sequences published for Torpedo AcChoEase. These finding demonstrate extensive homologies between the fetal BtChoEase encoded by these clones and other cholinesterases of various forms and species

Fetal abdominal magnetic resonance imaging

International Nuclear Information System (INIS)

Brugger, Peter C.; Prayer, Daniela

2006-01-01

This review deals with the in vivo magnetic resonance imaging (MRI) appearance of the human fetal abdomen. Imaging findings are correlated with current knowledge of human fetal anatomy and physiology, which are crucial to understand and interpret fetal abdominal MRI scans. As fetal MRI covers a period of more than 20 weeks, which is characterized not only by organ growth, but also by changes and maturation of organ function, a different MR appearance of the fetal abdomen results. This not only applies to the fetal intestines, but also to the fetal liver, spleen, and adrenal glands. Choosing the appropriate sequences, various aspects of age-related and organ-specific function can be visualized with fetal MRI, as these are mirrored by changes in signal intensities. Knowledge of normal development is essential to delineate normal from pathological findings in the respective developmental stages

Fetal abdominal magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Brugger, Peter C. [Center of Anatomy and Cell Biology, Integrative Morphology Group, Medical University of Vienna, Waehringerstrasse 13, 1090 Vienna (Austria)]. E-mail: peter.brugger@meduniwien.ac.at; Prayer, Daniela [Department of Radiology, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna (Austria)

2006-02-15

This review deals with the in vivo magnetic resonance imaging (MRI) appearance of the human fetal abdomen. Imaging findings are correlated with current knowledge of human fetal anatomy and physiology, which are crucial to understand and interpret fetal abdominal MRI scans. As fetal MRI covers a period of more than 20 weeks, which is characterized not only by organ growth, but also by changes and maturation of organ function, a different MR appearance of the fetal abdomen results. This not only applies to the fetal intestines, but also to the fetal liver, spleen, and adrenal glands. Choosing the appropriate sequences, various aspects of age-related and organ-specific function can be visualized with fetal MRI, as these are mirrored by changes in signal intensities. Knowledge of normal development is essential to delineate normal from pathological findings in the respective developmental stages.

Immune Cell-Supplemented Human Skin Model for Studying Fungal Infections.

Science.gov (United States)

Kühbacher, Andreas; Sohn, Kai; Burger-Kentischer, Anke; Rupp, Steffen

2017-01-01

Human skin is a niche for various fungal species which either colonize the surface of this tissue as commensals or, primarily under conditions of immunosuppression, invade the skin and cause infection. Here we present a method for generation of a human in vitro skin model supplemented with immune cells of choice. This model represents a complex yet amenable tool to study molecular mechanisms of host-fungi interactions at human skin.

Quality system and audit of human skin allografts

International Nuclear Information System (INIS)

Van Baare, J.

1999-01-01

Allograft skin has long been recognised as an important resource in the management of bum wounds. The important issue in skin banking is fust to guarantee safety of human cadaveric donor skin. Second, the quality of the allografts should be assured. The Euro Skin Bank, established in 1976, is located in The Netherlands. Not only in The Netherlands, but in many other (European) countries no specific regulation exists for tissue banking. With respect to skin banking in The Netherlands the Euro Skin Bank requested the government what regulations should be applied on their activities. It was stated in 1994 that human allografl skin should be regarded as a phan-naceutical drug, a magistral preparation. The Euro Skin Bank should therefore be subjected to the guidelines given for the Good Laboraton, Practices and Good Manufacturing Practices to process allogmft skin. Nevertheless, it was in the opinion of the Euro Skin Bank that regulating human tissue as a pharmaceutical drug was not sufficient e.g. no specific regulations for serologic testing of the tissue donor is given, which should be one of the most important issues in tissue banking. Recently the government has published new legislation for tissue banks in The Netherlands: on July I st, 1998, a new legislation was enforced concerning organ and tissue donation and on November I st, 1998, quality requirements for organ and tissue banks are published. The European Community discussed the possibility to bring all animal and human tissues under the Medical Device Directive (MDD). Soon it was proposed not to incorporate viable hw-nan tissue into the MDD. Last year all human tissue was excluded from the MDD. Lack of European regulations has been resulted in national laws, e.g. in The Netherlands, Germany and France. Possibly there might be a more significant role for the European Association of Tissue Banks in the near future for European legislation on tissue banking. In order to have a standard quality system wmch is

Fetal responses to induced maternal relaxation during pregnancy.

Science.gov (United States)

DiPietro, Janet A; Costigan, Kathleen A; Nelson, Priscilla; Gurewitsch, Edith D; Laudenslager, Mark L

2008-01-01

Fetal responses to induced maternal relaxation during the 32nd week of pregnancy were recorded in 100 maternal-fetal pairs using a digitized data collection system. The 18-min guided imagery relaxation manipulation generated significant changes in maternal heart rate, skin conductance, respiration period, and respiratory sinus arrhythmia. Significant alterations in fetal neurobehavior were observed, including decreased fetal heart rate (FHR), increased FHR variability, suppression of fetal motor activity (FM), and increased FM-FHR coupling. Attribution of the two fetal cardiac responses to the guided imagery procedure itself, as opposed to simple rest or recumbency, is tempered by the observed pattern of response. Evaluation of correspondence between changes within individual maternal-fetal pairs revealed significant associations between maternal autonomic measures and fetal cardiac patterns, lower umbilical and uterine artery resistance and increased FHR variability, and declining salivary cortisol and FM activity. Potential mechanisms that may mediate the observed results are discussed.

Utilization of reconstructed cultured human skin models as an alternative skin for permeation studies of chemical compounds

OpenAIRE

Kano, Satoshi; 藤堂, 浩明; 杉江, 謙一; 藤本, 英哲; 中田, 圭一; 徳留, 嘉寛; 橋本, フミ惠; 杉林, 堅次

2010-01-01

Two reconstructed human skin models, EpiskinSM and EpiDermTM, have been approved as alternative membranes for skin corrosive/irritation experiments due to their close correlation with animal skin. Such reconstructed human skin models were evaluated as alternative membranes for skin permeation experiments. Seven drugs with different lipophilicities and almost the same molecular weight were used as test penetrants. Relationships were investigated between permeability coefficients (P values) of ...

[The clinical use of cryopreserved human skin allografts for transplantation].

Science.gov (United States)

Martínez-Flores, Francisco; Chacón-Gómez, María; Madinaveitia-Villanueva, Juan Antonio; Barrera-Lopez, Araceli; Aguirre-Cruz, Lucinda; Querevalu-Murillo, Walter

2015-01-01

The biological recovery of human skin allografts is the gold standard for preservation in Skin Banks. However, there is no worldwide consensus about specific allocation criteria for preserved human skin allografts with living cells. A report is presented on the results of 5 years of experience of using human skin allografts in burned patient in the Skin and Tissue Bank at the "Instituto Nacional de Rehabilitacion" The human skin allografts were obtained from multi-organ donors. processed and preserved at -80 °C for 12 months. Allocation criteria were performed according to blood type match, clinical history, and burned body surface. Up to now, the Skin and Tissue Bank at 'Instituto Nacional de Rehabilitacion" has processed and recovered 125,000 cm(2) of human skin allografts. It has performed 34 surgical implants on 21 burned patients. The average of burn body surface was 59.2%. More than two-thirds (67.7%) of recipients of skin allografts were matched of the same to type blood of the donor, and 66.6% survived after 126 days hospital stay. It is proposed to consider recipient's blood group as allocation criteria to assign tissue; and use human skin allografts on patiens affected with burns over 30% of body surface (according the "rule of the 9"). Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Evaluation of a Silicone Membrane as an Alternative to Human Skin for Determining Skin Permeation Parameters of Chemical Compounds.

Science.gov (United States)

Uchida, Takashi; Yakumaru, Masafumi; Nishioka, Keisuke; Higashi, Yoshihiro; Sano, Tomohiko; Todo, Hiroaki; Sugibayashi, Kenji

2016-01-01

We evaluated the effectiveness of a silicone membrane as an alternative to human skin using the skin permeation parameters of chemical compounds. An in vitro permeation study using 15 model compounds was conducted, and permeation parameters comprising permeability coefficient (P), diffusion parameter (DL(-2)), and partition parameter (KL) were calculated from each permeation profile. Significant correlations were obtained in log P, log DL(-2), and log KL values between the silicone membrane and human skin. DL(-2) values of model compounds, except flurbiprofen, in the silicone membrane were independent of the lipophilicity of the model compounds and were 100-fold higher than those in human skin. For antipyrine and caffeine, which are hydrophilic, KL values in the silicone membrane were 100-fold lower than those in human skin, and P values, calculated as the product of a DL(-2) and KL, were similar. For lipophilic compounds, such as n-butyl paraben and flurbiprofen, KL values for silicone were similar to or 10-fold higher than those in human skin, and P values for silicone were 100-fold higher than those in human skin. Furthermore, for amphiphilic compounds with log Ko/w values from 0.5 to 3.5, KL values in the silicone membrane were 10-fold lower than those in human skin, and P values for silicone were 10-fold higher than those in human skin. The silicone membrane was useful as a human skin alternative in an in vitro skin permeation study. However, depending on the lipophilicity of the model compounds, some parameters may be over- or underestimated.

DNA damage and repair in human skin in situ

International Nuclear Information System (INIS)

Sutherland, B.M.; Gange, R.W.; Freeman, S.E.; Sutherland, J.C.

1987-01-01

Understanding the molecular and cellular origins of sunlight-induced skin cancers in man requires knowledge of the damages inflicted on human skin during sunlight exposure, as well as the ability of cells in skin to repair or circumvent such damage. Although repair has been studied extensively in procaryotic and eucaryotic cells - including human cells in culture - there are important differences between repair by human skin cells in culture and human skin in situ: quantitative differences in rates of repair, as well as qualitative differences, including the presence or absence of repair mechanisms. Quantitation of DNA damage and repair in human skin required the development of new approaches for measuring damage at low levels in nanogram quantities of non-radioactive DNA. The method allows for analysis of multiple samples and the resulting data should be related to behavior of the DNA molecules by analytic expressions. Furthermore, it should be possible to assay a variety of lesions using the same methodology. The development of new analysis methods, new technology, and new biochemical probes for the study of DNA damage and repair are described. 28 refs., 4 figs

DNA damage and repair in human skin in situ

Energy Technology Data Exchange (ETDEWEB)

Sutherland, B.M.; Gange, R.W.; Freeman, S.E.; Sutherland, J.C.

1987-01-01

Understanding the molecular and cellular origins of sunlight-induced skin cancers in man requires knowledge of the damages inflicted on human skin during sunlight exposure, as well as the ability of cells in skin to repair or circumvent such damage. Although repair has been studied extensively in procaryotic and eucaryotic cells - including human cells in culture - there are important differences between repair by human skin cells in culture and human skin in situ: quantitative differences in rates of repair, as well as qualitative differences, including the presence or absence of repair mechanisms. Quantitation of DNA damage and repair in human skin required the development of new approaches for measuring damage at low levels in nanogram quantities of non-radioactive DNA. The method allows for analysis of multiple samples and the resulting data should be related to behavior of the DNA molecules by analytic expressions. Furthermore, it should be possible to assay a variety of lesions using the same methodology. The development of new analysis methods, new technology, and new biochemical probes for the study of DNA damage and repair are described. 28 refs., 4 figs.

Assessment of penetration of quantum dots through in vitro and in vivo human skin using the human skin equivalent model and the tape stripping method

International Nuclear Information System (INIS)

Jeong, Sang Hoon; Kim, Jae Hwan; Yi, Sang Min; Lee, Jung Pyo; Kim, Jin Ho; Sohn, Kyung Hee; Park, Kui Lea; Kim, Meyoung-Kon; Son, Sang Wook

2010-01-01

Quantum dots (QDs) are rapidly emerging as an important class of nanoparticles (NPs) with potential applications in medicine. However, little is known about penetration of QDs through human skin. This study investigated skin penetration of QDs in both in vivo and in vitro human skin. Using the tape stripping method, this study demonstrates for the first time that QDs can actually penetrate through the stratum corneum (SC) of human skin. Transmission electron microscope (TEM) and energy diverse X-ray (EDX) analysis showed accumulation of QDs in the SC of a human skin equivalent model (HSEM) after dermal exposure to QDs. These findings suggest possible transdermal absorption of QDs after dermal exposure over a relatively long period of time.

Skin and the non-human human

DEFF Research Database (Denmark)

Rösing, Lilian Munk

2013-01-01

The article puts forward an aesthetic and psychoanalytic analysis of Titian's painting, The Flaying of Marsyas, arguing that the painting is a reflection on the human subject as a being constituted by skin and by a core of non-humanity. The analysis is partly an answer to Melanie Hart's (2007) ar...... of the 'Muselmann', and Anton Ehrenzweig's psychoanalytic theory of artistic creation. Whereas Hart is focusing on form and colour, I also turn my attention towards the texture of the painting....

Skin Sensitive Difference of Human Body Sections under Clothing-Smirnov Test of Skin Surface Temperatures' Dynamic Changing

Institute of Scientific and Technical Information of China (English)

LI Jun; WU Hai-yan; WANG Yun-yi

2004-01-01

Skin sensitive difference of human body sections under clothing is the theoretic foundation of thermal insulation clothing design.By a new method of researching on clothing comfort perception,the skin temperature live changing procedure of human body sections affected by the same cold stimulation is inspected.Furthermore with the Smirnov test the skin temperatures dynamic changing patterns of main human body sections are obtained.

In vitro dermal absorption of pyrethroid pesticides in human and rat skin

International Nuclear Information System (INIS)

Hughes, Michael F.; Edwards, Brenda C.

2010-01-01

Dermal exposure to pyrethroid pesticides can occur during manufacture and application. This study examined the in vitro dermal absorption of pyrethroids using rat and human skin. Dermatomed skin from adult male Long Evans rats or human cadavers was mounted in flow-through diffusion cells, and radiolabeled bifenthrin, deltamethrin or cis-permethrin was applied in acetone to the skin. Fractions of receptor fluid were collected every 4 h. At 24 h, the skins were washed with soap and water to remove unabsorbed chemical. The skin was then solubilized. Two additional experiments were performed after washing the skin; the first was tape-stripping the skin and the second was the collection of receptor fluid for an additional 24 h. Receptor fluid, skin washes, tape strips and skin were analyzed for radioactivity. For rat skin, the wash removed 53-71% of the dose and 26-43% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid ranged from 1 to 5%. For human skin, the wash removed 71-83% of the dose and 14-25% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid was 1-2%. Tape-stripping removed 50-56% and 79-95% of the dose in rat and human skin, respectively, after the wash. From 24-48 h, 1-3% and about 1% of the dose diffused into the receptor fluid of rat and human skin, respectively. The pyrethroids bifenthrin, deltamethrin and cis-permethrin penetrated rat and human skin following dermal application in vitro. However, a skin wash removed 50% or more of the dose from rat and human skin. Rat skin was more permeable to the pyrethroids than human skin. Of the dose in skin, 50% or more was removed by tape-stripping, suggesting that permeation of pyrethroids into viable tissue could be impeded. The percentage of the dose absorbed into the receptor fluid was considerably less than the dose in rat and human skin. Therefore, consideration of the skin type used and fractions analyzed are important when using

Development of human skin equivalents mimicking skin aging : contrast between papillary and reticular fibroblasts as a lead

NARCIS (Netherlands)

Janson, D.

2017-01-01

This thesis describes the development of human skin equivalents that show characteristics of skin aging. The type of skin equivalent used was a fibroblast derived matrix equivalent, in which the dermal compartment is generated by fibroblasts and thus is fully of human origin. Two strategies are

Multivariate Models for Prediction of Human Skin Sensitization Hazard

Science.gov (United States)

Strickland, Judy; Zang, Qingda; Paris, Michael; Lehmann, David M.; Allen, David; Choksi, Neepa; Matheson, Joanna; Jacobs, Abigail; Casey, Warren; Kleinstreuer, Nicole

2016-01-01

One of ICCVAM’s top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary to produce skin sensitization suggests that no single alternative method will replace the currently accepted animal tests. ICCVAM is evaluating an integrated approach to testing and assessment based on the adverse outcome pathway for skin sensitization that uses machine learning approaches to predict human skin sensitization hazard. We combined data from three in chemico or in vitro assays—the direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT), and KeratinoSens™ assay—six physicochemical properties, and an in silico read-across prediction of skin sensitization hazard into 12 variable groups. The variable groups were evaluated using two machine learning approaches, logistic regression (LR) and support vector machine (SVM), to predict human skin sensitization hazard. Models were trained on 72 substances and tested on an external set of 24 substances. The six models (three LR and three SVM) with the highest accuracy (92%) used: (1) DPRA, h-CLAT, and read-across; (2) DPRA, h-CLAT, read-across, and KeratinoSens; or (3) DPRA, h-CLAT, read-across, KeratinoSens, and log P. The models performed better at predicting human skin sensitization hazard than the murine local lymph node assay (accuracy = 88%), any of the alternative methods alone (accuracy = 63–79%), or test batteries combining data from the individual methods (accuracy = 75%). These results suggest that computational methods are promising tools to effectively identify potential human skin sensitizers without animal testing. PMID:27480324

First genomic survey of human skin fungal diversity

Science.gov (United States)

Fungal infections of the skin affect 29 million people in the United States. In the first study of human fungal skin diversity, National Institutes of Health researchers sequenced the DNA of fungi that thrive at different skin sites of healthy adults to d

Design of a light stimulator for fetal and neonatal magnetoencephalography

International Nuclear Information System (INIS)

Wilson, J D; Adams, A J; Murphy, P; Eswaran, H; Preissl, H

2009-01-01

The design, safety analysis and performance of a fetal visual stimulation system suitable for fetal and neonatal magnetoencephalography studies are presented. The issue of fetal, neonatal and maternal safety is considered and the maximum permissible exposure is computed for the maternal skin and the adult eye. The risk for neonatal eye exposure is examined. It is demonstrated that the fetus, neonate and mother are not at risk. (note)

Recent advances in the prenatal interrogation of the human fetal genome.

Science.gov (United States)

Hui, Lisa; Bianchi, Diana W

2013-02-01

The amount of genetic and genomic information obtainable from the human fetus during pregnancy is accelerating at an unprecedented rate. Two themes have dominated recent technological advances in prenatal diagnosis: interrogation of the fetal genome in increasingly high resolution and the development of non-invasive methods of fetal testing using cell-free DNA in maternal plasma. These two areas of advancement have now converged with several recent reports of non-invasive assessment of the entire fetal genome from maternal blood. However, technological progress is outpacing the ability of the healthcare providers and patients to incorporate these new tests into existing clinical care, and further complicates many of the economic and ethical dilemmas in prenatal diagnosis. This review summarizes recent work in this field and discusses the integration of these new technologies into the clinic and society. Copyright © 2012 Elsevier Ltd. All rights reserved.

Relating friction on the human skin to the hydration and temperature of the skin

NARCIS (Netherlands)

Veijgen, N.K.; Masen, Marc Arthur; van der Heide, Emile

2013-01-01

The human skin is constantly in interaction with materials and products. Therefore, skin friction is relevant to all people. In the literature, the frictional properties of the skin have been linked to a large variety of variables, like age, gender and hydration. The present study compares the data

Biology and Function of Fetal and Pediatric Skin

OpenAIRE

Leung, Alice; Balaji, Swathi; Keswani, Sundeep G

2013-01-01

The development of the integumentary system is a series of events, which start in utero and continue throughout life. Although at birth, skin in full-term infants is anatomically mature, functional maturity develops during the first year of life. Pediatric skin transitions again with the onset of puberty. At each stage, there are changes in transepidermal water loss, skin hydration, and skin acidity that define the specific period of development.

Elevation of telomerase activity in chronic radiation ulcer of human skin

International Nuclear Information System (INIS)

Li Xiaoying; Zhao Po; Wang Dewen; Yang Zhixiang

1997-01-01

Objective: To investigate the levels of telomerase activity in chronic radiation ulcers of human skin and the possible relationship between the enzyme and cancer transformation. Method: Using nonisotopic telomere repeat amplification protocol (TRAP), detections were performed in 20 cases of chronic radiation ulcers of human skin, 5 cases of normal skin tissues and 5 cases of carcinoma. Results: The positive rates for telomerase activity were 30.0%(6/20), 0(0/5) and 100%(5/5) in chronic radiation ulcers of human skin, normal skin and carcinoma, respectively. The telomerase activity in radiation ulcer was weaker than in carcinoma. Conclusion: The telomerase activity assay might be used as a marker for predicting the prognosis and the effect of treatment in chronic radiation ulcer of human skin

3H-cyclosporine internalization and secretion by human fetal pancreatic islets

International Nuclear Information System (INIS)

Formby, B.; Walker, L.; Peterson, C.M.

1988-01-01

Human fetal pancreatic islets were isolated from 16- to 20-week-old fetuses by a collagenase technique and cultured 48 hr in RPMI 1640 containing 10% human adult serum and unlabeled 0 to 5 micrograms cyclosporine A (CsA)/ml. Insulin secretory capacity of human fetal islets was expressed as a fractional stimulatory ratio FSR = F2/F1 of the fractional secretion rates during two successive 1 hr static incubations first with 2 mM glucose (F1) to stabilize secretion followed by maximal stimulus, i.e., 25 mM glucose plus 10 mM L-leucine and 10 mM L-arginine (F2). Unlabeled CsA at the above concentrations had no significant effects on the insulin secretory capacity expressed by FSR-values. Studies of net uptake of 3H-CsA by islets cultured for varying periods up to 40 hr and expressed as picomole 3H-CsA per picomole islet insulin content demonstrated that uptake rate was slow and did not reach isotopic equilibrium over the 40 hr of culture. When isolated fetal islets were cultured for 48 hr in the presence of 3H-CsA and varying concentrations of unlabeled CsA it was found during two successive 1 hr static incubations that fetal islets secrete insulin concomitantly with 3H-CsA following maximal stimulus for secretion. An optimal secretory molar ratio of 3H-CsA to insulin of 4.0 +/- 1.3 (n = 7) was found after islets were cultured 48 hr in the presence of a saturating 2.128 micrograms 3H-CsA per milliliter culture medium. In three successive 30-min static incubations of 3H-CsA loaded islets, first with low glucose, followed by high glucose plus L-arginine and L-leucine, and finally with high glucose plus L-arginine and L-leucine and 10 mM theophylline, the proportional fractional secretion rates of insulin and 3H-CsA were of the same magnitude

Lens artifacts in human fetal eyes - the challenge of interpreting the histomorphology of human fetal lenses.

Science.gov (United States)

Herwig, Martina C; Müller, Annette M; Klarmann-Schulz, Ute; Holz, Frank G; Loeffler, Karin U

2014-01-01

Evaluation of the lens, including cataractous changes, is often of paramount importance in the classification of fetal syndromes or forensic questions. On histology, the crystalline lens is - especially in fetal and infant eyes - an organ susceptible to numerous artifacts. Thus, the aim of our study was to study various factors (including fixatives) that might have an impact on lens histomorphology. Twenty eyes from ten fetuses (formalin fixation: n = 10, glutaraldehyde fixation: n = 10), matched for gestational age and abortion (spontaneous vs. induced), were investigated macroscopically and by light microscopy. Sections were stained with routine hematoxylin & eosin (H&E), and periodic acid schiff (PAS). The age of the fetal eyes ranged from 15 to 36 weeks of gestation. Lens artifacts were analyzed and compared to fetal and adult lenses with definitive cataractous changes. In addition, 34 eyes from 27 fetuses with trisomy 21 were investigated for lens changes. All lenses showed artifacts of varying extent, in particular globules, vacuoles, clefts, anterior/posterior capsular separation, subcapsular proteinaceous material, fragmentation of the lens capsule/epithelium, and a posterior umbilication. Glutaraldehyde-fixed lenses displayed less artifacts compared to those fixed in formalin. Slight differences in the appearance of artifacts were found dependent on the fixative (formaldehyde vs glutaraldehyde) and the kind of abortion (iatrogenous vs spontaneous). The gestational age did not have a significant influence on the type and extent of lens artifacts. The lenses from fetuses with trisomy 21 displayed similar lens artifacts with no specific findings. Alterations in fetal lens morphology are extremely frequent and variable. These artifacts have to be carefully taken into account when interpreting post-mortem findings. Thus, the postmortem diagnosis of a fetal cataract should be made with great caution, and should include, in adherence to our proposed

Long chain poly-unsaturated fatty acids attenuate the IL-1?-induced pro-inflammatory response in human fetal intestinal epithelial cells

OpenAIRE

Wijendran, Vasuki; Brenna, JT; Wang, Dong Hao; Zhu, Weishu; Meng, Di; Ganguli, Kriston; Kothapalli, Kumar SD; Requena, Pilar; Innis, Sheila; Walker, WA

2015-01-01

Background Evidence suggests that excessive inflammation of the immature intestine may predispose premature infants to necrotizing enterocolitis (NEC). We investigated the anti-inflammatory effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (ARA) in human fetal and adult intestinal epithelial cells (IEC) in primary culture. Methods Human fetal IEC in culture were derived from a healthy fetal small intestine (H4) or resected small intestine of a neonate wit...

An in vitro human skin test for assessing sensitization potential.

Science.gov (United States)

Ahmed, S S; Wang, X N; Fielding, M; Kerry, A; Dickinson, I; Munuswamy, R; Kimber, I; Dickinson, A M

2016-05-01

Sensitization to chemicals resulting in an allergy is an important health issue. The current gold-standard method for identification and characterization of skin-sensitizing chemicals was the mouse local lymph node assay (LLNA). However, for a number of reasons there has been an increasing imperative to develop alternative approaches to hazard identification that do not require the use of animals. Here we describe a human in-vitro skin explant test for identification of sensitization hazards and the assessment of relative skin sensitizing potency. This method measures histological damage in human skin as a readout of the immune response induced by the test material. Using this approach we have measured responses to 44 chemicals including skin sensitizers, pre/pro-haptens, respiratory sensitizers, non-sensitizing chemicals (including skin-irritants) and previously misclassified compounds. Based on comparisons with the LLNA, the skin explant test gave 95% specificity, 95% sensitivity, 95% concordance with a correlation coefficient of 0.9. The same specificity and sensitivity were achieved for comparison of results with published human sensitization data with a correlation coefficient of 0.91. The test also successfully identified nickel sulphate as a human skin sensitizer, which was misclassified as negative in the LLNA. In addition, sensitizers and non-sensitizers identified as positive or negative by the skin explant test have induced high/low T cell proliferation and IFNγ production, respectively. Collectively, the data suggests the human in-vitro skin explant test could provide the basis for a novel approach for characterization of the sensitizing activity as a first step in the risk assessment process. Copyright © 2015 John Wiley & Sons, Ltd.

Fetal Microchimerism in Cancer Protection and Promotion: Current Understanding in Dogs and the Implications for Human Health.

Science.gov (United States)

Bryan, Jeffrey N

2015-05-01

Fetal microchimerism is the co-existence of small numbers of cells from genetically distinct individuals living within a mother's body following pregnancy. During pregnancy, bi-directional exchange of cells occurs resulting in maternal microchimerism and even sibling microchimerism in offspring. The presence of fetal microchimerism has been identified with lower frequency in patients with cancers such as breast and lymphoma and with higher frequency in patients with colon cancer and autoimmune diseases. Microchimeric cells have been identified in healing and healed tissues as well as normal and tumor tissues. This has led to the hypothesis that fetal microchimerism may play a protective role in some cancers and may provoke other cancers or autoimmune disease. The long periods of risk for these diseases make it a challenge to prospectively study this phenomenon in human populations. Dogs get similar cancers as humans, share our homes and environmental exposures, and live compressed life-spans, allowing easier prospective study of disease development. This review describes the current state of understanding of fetal microchimerism in humans and dogs and highlights the similarities of the common cancers mammary carcinoma, lymphoma, and colon cancer between the two species. Study of fetal microchimerism in dogs might hold the key to characterization of the type and function of microchimeric cells and their role in health and disease. Such an understanding could then be applied to preventing and treating disease in humans.

Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulates rejuvenation of human skin.

Science.gov (United States)

Kim, Yoon-Jin; Yoo, Sae Mi; Park, Hwan Hee; Lim, Hye Jin; Kim, Yu-Lee; Lee, Seunghee; Seo, Kwang-Won; Kang, Kyung-Sun

2017-11-18

Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) play an important role in cutaneous wound healing, and recent studies suggested that MSC-derived exosomes activate several signaling pathways, which are conducive in wound healing and cell growth. In this study, we investigated the roles of exosomes that are derived from USC-CM (USC-CM Exos) in cutaneous collagen synthesis and permeation. We found that USC-CM has various growth factors associated with skin rejuvenation. Our in vitro results showed that USC-CM Exos integrate in Human Dermal Fibroblasts (HDFs) and consequently promote cell migration and collagen synthesis of HDFs. Moreover, we evaluated skin permeation of USC-CM Exos by using human skin tissues. Results showed that Exo-Green labeled USC-CM Exos approached the outermost layer of the epidermis after 3 h and gradually approached the epidermis after 18 h. Moreover, increased expressions of Collagen I and Elastin were found after 3 days of treatment on human skin. The results showed that USC-CM Exos is absorbed into human skin, it promotes Collagen I and Elastin synthesis in the skin, which are essential to skin rejuvenation and shows the potential of USC-CM integration with the cosmetics or therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

Water vapour loss measurements on human skin.

NARCIS (Netherlands)

Valk, Petrus Gerardus Maria van der

1984-01-01

In this thesis, the results of a series of investigations into the barrier function of human skin are presented. In these investigations, the barrier function was assessed by water vapour loss measurements of the skin using a method based on gradient estimation.... Zie: Summary and conclusions

Chemical ecology of interactions between human skin microbiota and mosquitoes

NARCIS (Netherlands)

Verhulst, N.O.; Takken, W.; Dicke, M.; Schraa, G.; Smallegange, R.C.

2010-01-01

Microbiota on the human skin plays a major role in body odour production. The human microbial and chemical signature displays a qualitative and quantitative correlation. Genes may influence the chemical signature by shaping the composition of the microbiota. Recent studies on human skin microbiota,

Next generation human skin constructs as advanced tools for drug development.

Science.gov (United States)

Abaci, H E; Guo, Zongyou; Doucet, Yanne; Jacków, Joanna; Christiano, Angela

2017-11-01

Many diseases, as well as side effects of drugs, manifest themselves through skin symptoms. Skin is a complex tissue that hosts various specialized cell types and performs many roles including physical barrier, immune and sensory functions. Therefore, modeling skin in vitro presents technical challenges for tissue engineering. Since the first attempts at engineering human epidermis in 1970s, there has been a growing interest in generating full-thickness skin constructs mimicking physiological functions by incorporating various skin components, such as vasculature and melanocytes for pigmentation. Development of biomimetic in vitro human skin models with these physiological functions provides a new tool for drug discovery, disease modeling, regenerative medicine and basic research for skin biology. This goal, however, has long been delayed by the limited availability of different cell types, the challenges in establishing co-culture conditions, and the ability to recapitulate the 3D anatomy of the skin. Recent breakthroughs in induced pluripotent stem cell (iPSC) technology and microfabrication techniques such as 3D-printing have allowed for building more reliable and complex in vitro skin models for pharmaceutical screening. In this review, we focus on the current developments and prevailing challenges in generating skin constructs with vasculature, skin appendages such as hair follicles, pigmentation, immune response, innervation, and hypodermis. Furthermore, we discuss the promising advances that iPSC technology offers in order to generate in vitro models of genetic skin diseases, such as epidermolysis bullosa and psoriasis. We also discuss how future integration of the next generation human skin constructs onto microfluidic platforms along with other tissues could revolutionize the early stages of drug development by creating reliable evaluation of patient-specific effects of pharmaceutical agents. Impact statement Skin is a complex tissue that hosts various

KeyGenes, a Tool to Probe Tissue Differentiation Using a Human Fetal Transcriptional Atlas

NARCIS (Netherlands)

Roost, Matthias S; van Iperen, Liesbeth; Ariyurek, Yavuz; Buermans, Henk P; Arindrarto, Wibowo; Devalla, Harsha D; Passier, Robert; Mummery, Christine L; Carlotti, Françoise; de Koning, Eelco J P; van Zwet, Erik W; Goeman, Jelle J; Chuva de Sousa Lopes, Susana M

2015-01-01

Differentiated derivatives of human pluripotent stem cells in culture are generally phenotypically immature compared to their adult counterparts. Their identity is often difficult to determine with certainty because little is known about their human fetal equivalents in vivo. Cellular identity and

QSAR models of human data can enrich or replace LLNA testing for human skin sensitization

OpenAIRE

Alves, Vinicius M.; Capuzzi, Stephen J.; Muratov, Eugene; Braga, Rodolpho C.; Thornton, Thomas; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2016-01-01

Skin sensitization is a major environmental and occupational health hazard. Although many chemicals have been evaluated in humans, there have been no efforts to model these data to date. We have compiled, curated, analyzed, and compared the available human and LLNA data. Using these data, we have developed reliable computational models and applied them for virtual screening of chemical libraries to identify putative skin sensitizers. The overall concordance between murine LLNA and human skin ...

Human Wharton's Jelly Mesenchymal Stem Cells plasticity augments scar-free skin wound healing with hair growth.

Directory of Open Access Journals (Sweden)

Vikram Sabapathy

Full Text Available Human mesenchymal stem cells (MSCs are a promising candidate for cell-based transplantation and regenerative medicine therapies. Thus in the present study Wharton's Jelly Mesenchymal Stem Cells (WJ-MSCs have been derived from extra embryonic umbilical cord matrix following removal of both arteries and vein. Also, to overcome the clinical limitations posed by fetal bovine serum (FBS supplementation because of xenogeneic origin of FBS, usual FBS cell culture supplement has been replaced with human platelet lysate (HPL. Apart from general characteristic features of bone marrow-derived MSCs, wharton jelly-derived MSCs have the ability to maintain phenotypic attributes, cell growth kinetics, cell cycle pattern, in vitro multilineage differentiation plasticity, apoptotic pattern, normal karyotype-like intrinsic mesenchymal stem cell properties in long-term in vitro cultures. Moreover, the WJ-MSCs exhibited the in vitro multilineage differentiation capacity by giving rise to differentiated cells of not only mesodermal lineage but also to the cells of ectodermal and endodermal lineage. Also, WJ-MSC did not present any aberrant cell state upon in vivo transplantation in SCID mice and in vitro soft agar assays. The immunomodulatory potential assessed by gene expression levels of immunomodulatory factors upon exposure to inflammatory cytokines in the fetal WJ-MSCs was relatively higher compared to adult bone marrow-derived MSCs. WJ-MSCs seeded on decellularized amniotic membrane scaffold transplantation on the skin injury of SCID mice model demonstrates that combination of WJ-MSCs and decellularized amniotic membrane scaffold exhibited significantly better wound-healing capabilities, having reduced scar formation with hair growth and improved biomechanical properties of regenerated skin compared to WJ-MSCs alone. Further, our experimental data indicate that indocyanin green (ICG at optimal concentration can be resourcefully used for labeling of stem cells

Effect of placental factors on growth and function of the human fetal adrenal in vitro.

Science.gov (United States)

Riopel, L; Branchaud, C L; Goodyer, C G; Zweig, M; Lipowski, L; Adkar, V; Lefebvre, Y

1989-11-01

Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: 1) maximal response to PM was 2-5 times greater; 2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; 3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

Effect of placental factors on growth and function of the human fetal adrenal in vitro

Energy Technology Data Exchange (ETDEWEB)

Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y. (McGill Univ.-Montreal Children' s Hospital Research Institute, Quebec (Canada))

1989-11-01

Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

Effect of placental factors on growth and function of the human fetal adrenal in vitro

International Nuclear Information System (INIS)

Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y.

1989-01-01

Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland

A Case of Alloimmune Thrombocytopenia, Hemorrhagic Anemia-Induced Fetal Hydrops, Maternal Mirror Syndrome, and Human Chorionic Gonadotropin–Induced Thyrotoxicosis

Directory of Open Access Journals (Sweden)

Venu Jain

2013-05-01

Full Text Available Fetal/neonatal alloimmune thrombocytopenia (FNAIT can be a cause of severe fetal thrombocytopenia, with the common presentation being intracranial hemorrhage in the fetus, usually in the third trimester. A very unusual case of fetal anemia progressed to hydrops. This was further complicated by maternal Mirror syndrome and human chorionic gonadotropin–induced thyrotoxicosis. Without knowledge of etiology, and possibly due to associated cardiac dysfunction, fetal transfusion resulted in fetal demise. Subsequent testing revealed FNAIT as the cause of severe hemorrhagic anemia. In cases with fetal anemia without presence of red blood cell antibodies, FNAIT must be ruled out as a cause prior to performing fetal transfusion. Fetal heart may adapt differently to acute hemorrhagic anemia compared with a more subacute hemolytic anemia.

EPR detection of free radicals in UV-irradiated skin: mouse versus human

International Nuclear Information System (INIS)

Jurkiewicz, B.A.; Buettner, G.R.

1996-01-01

Ultraviolet radiation produces free radicals in Skh-1 mouse skin, contributing to photoaging and carcinogenesis. If a mouse model is a general indicator of free radical processes in human skin photobiology, then radical production observed in mouse and human skin should be directly comparative. In this work we show that UV radiation (λ > 300 nm, 14 μW/cm 2 UVB; 3.5 mW/cm 2 UVA) increases the ascorbate free radical (Asc) electron paramagnetic resonance (EPR) signal in both Skh-1 mouse skin (45%) and human facial skin biopsies (340%). Visible light (λ > 400 nm; 0.23 mW/cm 2 UVA) also increased the Ascsignal in human skin samples (45%) but did not increase baseline mouse Asc, indicating that human skin is more susceptible to free radical formation and that a chromophore for visible light may be present. Using EPR spin-trapping techniques, UV radiation produced spin adducts consistent with trapping lipid alkyl radicals in mouse skin (α-[4-pyridyl 1-oxide]-N-tert-butyl nitrone/alkyl radical adduct; a N = 15.56 G and a H 2.70 G) and lipid alkoxyl radicals in human skin (5,5-dimethylpyrroline -1-oxide/alkoxyl radical adduct; a N = 14.54 G and a H = 16.0 G). Topical application of the iron chelator Desferal to human skin significantly decreases these radicals (∼50%), indicating a role for iron in lipid peroxidation. (Author)

Induced pluripotent stem (iPS) cells from human fetal stem cells.

Science.gov (United States)

Guillot, Pascale V

2016-02-01

Pluripotency defines the ability of stem cells to differentiate into all the lineages of the three germ layers and self-renew indefinitely. Somatic cells can regain the developmental potential of embryonic stem cells following ectopic expression of a set of transcription factors or, in certain circumstances, via modulation of culture conditions and supplementation with small molecule, that is, induced pluripotent stem (iPS) cells. Here, we discuss the use of fetal tissues for reprogramming, focusing in particular on stem cells derived from human amniotic fluid, and the development of chemical reprogramming. We next address the advantages and disadvantages of deriving pluripotent cells from fetal tissues and the potential clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Nrf2-inducers tanshinone I and dihydrotanshinone protect human skin cells and reconstructed human skin against solar simulated UV☆

Science.gov (United States)

Tao, Shasha; Justiniano, Rebecca; Zhang, Donna D.; Wondrak, Georg T.

2013-01-01

Exposure to solar ultraviolet (UV) radiation is a causative factor in skin photocarcinogenesis and photoaging, and an urgent need exists for improved strategies for skin photoprotection. The redox-sensitive transcription factor Nrf2 (nuclear factor-E2-related factor 2), a master regulator of the cellular antioxidant defense against environmental electrophilic insult, has recently emerged as an important determinant of cutaneous damage from solar UV, and the concept of pharmacological activation of Nrf2 has attracted considerable attention as a novel approach to skin photoprotection. In this study, we examined feasibility of using tanshinones, a novel class of phenanthrenequinone-based cytoprotective Nrf2 inducers derived from the medicinal plant Salvia miltiorrhiza, for protection of cultured human skin cells and reconstructed human skin against solar simulated UV. Using a dual luciferase reporter assay in human Hs27 dermal fibroblasts pronounced transcriptional activation of Nrf2 by four major tanshinones [tanshinone I (T-I), dihydrotanshinone (DHT), tanshinone IIA (T-II-A) and cryptotanshinone (CT)] was detected. In fibroblasts, the more potent tanshinones T-I and DHT caused a significant increase in Nrf2 protein half-life via blockage of ubiquitination, ultimately resulting in upregulated expression of cytoprotective Nrf2 target genes (GCLC, NQO1) with the elevation of cellular glutathione levels. Similar tanshinone-induced changes were also observed in HaCaT keratinocytes. T-I and DHT pretreatment caused significant suppression of skin cell death induced by solar simulated UV and riboflavin-sensitized UVA. Moreover, feasibility of tanshinone-based cutaneous photoprotection was tested employing a human skin reconstruct exposed to solar simulated UV (80 mJ/cm2 UVB; 1.53 J/cm2 UVA). The occurrence of markers of epidermal solar insult (cleaved procaspase 3, pycnotic nuclei, eosinophilic cytoplasm, acellular cavities) was significantly attenuated in DHT

The Nrf2-inducers tanshinone I and dihydrotanshinone protect human skin cells and reconstructed human skin against solar simulated UV.

Science.gov (United States)

Tao, Shasha; Justiniano, Rebecca; Zhang, Donna D; Wondrak, Georg T

2013-01-01

Exposure to solar ultraviolet (UV) radiation is a causative factor in skin photocarcinogenesis and photoaging, and an urgent need exists for improved strategies for skin photoprotection. The redox-sensitive transcription factor Nrf2 (nuclear factor-E2-related factor 2), a master regulator of the cellular antioxidant defense against environmental electrophilic insult, has recently emerged as an important determinant of cutaneous damage from solar UV, and the concept of pharmacological activation of Nrf2 has attracted considerable attention as a novel approach to skin photoprotection. In this study, we examined feasibility of using tanshinones, a novel class of phenanthrenequinone-based cytoprotective Nrf2 inducers derived from the medicinal plant Salvia miltiorrhiza, for protection of cultured human skin cells and reconstructed human skin against solar simulated UV. Using a dual luciferase reporter assay in human Hs27 dermal fibroblasts pronounced transcriptional activation of Nrf2 by four major tanshinones [tanshinone I (T-I), dihydrotanshinone (DHT), tanshinone IIA (T-II-A) and cryptotanshinone (CT)] was detected. In fibroblasts, the more potent tanshinones T-I and DHT caused a significant increase in Nrf2 protein half-life via blockage of ubiquitination, ultimately resulting in upregulated expression of cytoprotective Nrf2 target genes (GCLC, NQO1) with the elevation of cellular glutathione levels. Similar tanshinone-induced changes were also observed in HaCaT keratinocytes. T-I and DHT pretreatment caused significant suppression of skin cell death induced by solar simulated UV and riboflavin-sensitized UVA. Moreover, feasibility of tanshinone-based cutaneous photoprotection was tested employing a human skin reconstruct exposed to solar simulated UV (80 mJ/cm(2) UVB; 1.53 J/cm(2) UVA). The occurrence of markers of epidermal solar insult (cleaved procaspase 3, pycnotic nuclei, eosinophilic cytoplasm, acellular cavities) was significantly attenuated in DHT

The Nrf2-inducers tanshinone I and dihydrotanshinone protect human skin cells and reconstructed human skin against solar simulated UV

Directory of Open Access Journals (Sweden)

Shasha Tao

2013-01-01

Full Text Available Exposure to solar ultraviolet (UV radiation is a causative factor in skin photocarcinogenesis and photoaging, and an urgent need exists for improved strategies for skin photoprotection. The redox-sensitive transcription factor Nrf2 (nuclear factor-E2-related factor 2, a master regulator of the cellular antioxidant defense against environmental electrophilic insult, has recently emerged as an important determinant of cutaneous damage from solar UV, and the concept of pharmacological activation of Nrf2 has attracted considerable attention as a novel approach to skin photoprotection. In this study, we examined feasibility of using tanshinones, a novel class of phenanthrenequinone-based cytoprotective Nrf2 inducers derived from the medicinal plant Salvia miltiorrhiza, for protection of cultured human skin cells and reconstructed human skin against solar simulated UV. Using a dual luciferase reporter assay in human Hs27 dermal fibroblasts pronounced transcriptional activation of Nrf2 by four major tanshinones [tanshinone I (T-I, dihydrotanshinone (DHT, tanshinone IIA (T-II-A and cryptotanshinone (CT] was detected. In fibroblasts, the more potent tanshinones T-I and DHT caused a significant increase in Nrf2 protein half-life via blockage of ubiquitination, ultimately resulting in upregulated expression of cytoprotective Nrf2 target genes (GCLC, NQO1 with the elevation of cellular glutathione levels. Similar tanshinone-induced changes were also observed in HaCaT keratinocytes. T-I and DHT pretreatment caused significant suppression of skin cell death induced by solar simulated UV and riboflavin-sensitized UVA. Moreover, feasibility of tanshinone-based cutaneous photoprotection was tested employing a human skin reconstruct exposed to solar simulated UV (80 mJ/cm2 UVB; 1.53 J/cm2 UVA. The occurrence of markers of epidermal solar insult (cleaved procaspase 3, pycnotic nuclei, eosinophilic cytoplasm, acellular cavities was significantly attenuated in DHT

QSAR models of human data can enrich or replace LLNA testing for human skin sensitization

Science.gov (United States)

Alves, Vinicius M.; Capuzzi, Stephen J.; Muratov, Eugene; Braga, Rodolpho C.; Thornton, Thomas; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2016-01-01

Skin sensitization is a major environmental and occupational health hazard. Although many chemicals have been evaluated in humans, there have been no efforts to model these data to date. We have compiled, curated, analyzed, and compared the available human and LLNA data. Using these data, we have developed reliable computational models and applied them for virtual screening of chemical libraries to identify putative skin sensitizers. The overall concordance between murine LLNA and human skin sensitization responses for a set of 135 unique chemicals was low (R = 28-43%), although several chemical classes had high concordance. We have succeeded to develop predictive QSAR models of all available human data with the external correct classification rate of 71%. A consensus model integrating concordant QSAR predictions and LLNA results afforded a higher CCR of 82% but at the expense of the reduced external dataset coverage (52%). We used the developed QSAR models for virtual screening of CosIng database and identified 1061 putative skin sensitizers; for seventeen of these compounds, we found published evidence of their skin sensitization effects. Models reported herein provide more accurate alternative to LLNA testing for human skin sensitization assessment across diverse chemical data. In addition, they can also be used to guide the structural optimization of toxic compounds to reduce their skin sensitization potential. PMID:28630595

Spectral Detection of Human Skin in VIS-SWIR Hyperspectral Imagery without Radiometric Calibration

Science.gov (United States)

2012-03-01

6 Spectral reflectance of human skin at VIS-SWIR wavelengths. Skin with less melanin appears brighter because it has higher reflectance...6 illustrates the spectral reflectance of human skin with different melanin levels. One paper proposes a Normalized Difference Skin Index (NDSI), a...1.4% Melanin 12.6% Melanin 23.2% Melanin 34.3% Melanin 45% Melanin Figure 6. Spectral reflectance of human skin at VIS-SWIR wavelengths. Skin with less

[Physiological features of skin ageing in human].

Science.gov (United States)

Tikhonova, I V; Tankanag, A V; Chemeris, N K

2013-01-01

The issue deals with the actual problem of gerontology, notably physiological features of human skin ageing. In the present review the authors have considered the kinds of ageing, central factors, affected on the ageing process (ultraviolet radiation and oxidation stress), as well as the research guidelines of the ageing changes in the skin structure and fuctions: study of mechanical properties, microcirculation, pH and skin thickness. The special attention has been payed to the methods of assessment of skin blood flow, and to results of investigations of age features of peripheral microhemodynamics. The laser Doppler flowmetry technique - one of the modern, noninvasive and extensively used methods for the assessmant of skin blood flow microcirculation system has been expanded in the review. The main results of the study of the ageing changes of skin blood perfusion using this method has been also presented.

Chronic effects of UV on human skin

International Nuclear Information System (INIS)

Cesarini, J.P.

1996-01-01

Chronic exposures and acute accidents of the skin to UV has been recognized as an important risk for skin cancers in human. Attempts have been made with mathematical models to correlate the ambient UV dose and occupational irradiations with the risk of skin cancers. Development of accurate global measurements of solar irradiance and personal dosimetry is expected in the future in order to reduce the exposure of the general population, to precise the measures to be taken for indoor and outdoor workers. (author)

Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis.

Science.gov (United States)

Li, Jingting; Sen, George L

2015-12-14

Organotypic cultures allow the reconstitution of a 3D environment critical for cell-cell contact and cell-matrix interactions which mimics the function and physiology of their in vivo tissue counterparts. This is exemplified by organotypic skin cultures which faithfully recapitulates the epidermal differentiation and stratification program. Primary human epidermal keratinocytes are genetically manipulable through retroviruses where genes can be easily overexpressed or knocked down. These genetically modified keratinocytes can then be used to regenerate human epidermis in organotypic skin cultures providing a powerful model to study genetic pathways impacting epidermal growth, differentiation, and disease progression. The protocols presented here describe methods to prepare devitalized human dermis as well as to genetically manipulate primary human keratinocytes in order to generate organotypic skin cultures. Regenerated human skin can be used in downstream applications such as gene expression profiling, immunostaining, and chromatin immunoprecipitations followed by high throughput sequencing. Thus, generation of these genetically modified organotypic skin cultures will allow the determination of genes that are critical for maintaining skin homeostasis.

Prediction of Human Pharmacokinetic Profile After Transdermal Drug Application Using Excised Human Skin.

Science.gov (United States)

Yamamoto, Syunsuke; Karashima, Masatoshi; Arai, Yuta; Tohyama, Kimio; Amano, Nobuyuki

2017-09-01

Although several mathematical models have been reported for the estimation of human plasma concentration profiles of drug substances after dermal application, the successful cases that can predict human pharmacokinetic profiles are limited. Therefore, the aim of this study is to investigate the prediction of human plasma concentrations after dermal application using in vitro permeation parameters obtained from excised human skin. The in vitro skin permeability of 7 marketed drug products was evaluated. The plasma concentration-time profiles of the drug substances in humans after their dermal application were simulated using compartment models and the clinical pharmacokinetic parameters. The transdermal process was simulated using the in vitro skin permeation rate and lag time assuming a zero-order absorption. These simulated plasma concentration profiles were compared with the clinical data. The result revealed that the steady-state plasma concentration of diclofenac and the maximum concentrations of nicotine, bisoprolol, rivastigmine, and lidocaine after topical application were within 2-fold of the clinical data. Furthermore, the simulated concentration profiles of bisoprolol, nicotine, and rivastigmine reproduced the decrease in absorption due to drug depletion from the formulation. In conclusion, this simple compartment model using in vitro human skin permeation parameters as zero-order absorption predicted the human plasma concentrations accurately. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Permeability of human placenta and fetal membranes to thyrotropin-stimulating hormone in vitro.

Science.gov (United States)

Bajoria, R; Fisk, N M

1998-05-01

We determined the placental transfer of TSH in an in vitro model of dually perfused isolated lobule in 28 human term placentas by adding varying concentrations (5-60 microIU mL(-1)) of TSH as a single bolus dose to the closed maternal circulation. Transmembrane transfer of TSH was also studied by adding 45 microIU mL(-1) to the maternal or fetal compartment of a dual chamber of fetal membranes in culture. Passage of freely diffusible markers creatinine and antipyrine were also studied in this model. TSH concentration was measured by third generation chemiluminescence assay with a sensitivity of 10 mIU mL(-1). In the perfusion experiments, at physiologic concentrations the slow decline of TSH in the maternal circulation was associated with a small linear increase in fetal levels to 0.11 +/- 0.04% of initial dose at 2 h. The placental transfer rate was 0.08 microIU min(-1). Increasing maternal concentrations of TSH were associated with proportional increases in transfer rate (y = 0.002x; R2 = 0.99) and placental uptake (y = 0.01x; R2 = 0.97). The placental permeability of TSH was 2.4 x 10(-4) mL min(-1) g(-1) and was proportional to its coefficients of diffusion in water and molecular size. The transmembrane transfer and permeability of TSH was comparable to those of the placenta. We conclude that TSH crosses the human term placenta and fetal membranes sparingly.

Cellular and molecular effect of MEHP Involving LXRα in human fetal testis and ovary.

Science.gov (United States)

Muczynski, Vincent; Lecureuil, Charlotte; Messiaen, Sébastien; Guerquin, Marie-Justine; N'tumba-Byn, Thierry; Moison, Delphine; Hodroj, Wassim; Benjelloun, Hinde; Baijer, Jan; Livera, Gabriel; Frydman, René; Benachi, Alexandra; Habert, René; Rouiller-Fabre, Virginie

2012-01-01

Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro. Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10(-4)M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array) and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro. We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells.

Cellular and molecular effect of MEHP Involving LXRα in human fetal testis and ovary.

Directory of Open Access Journals (Sweden)

Vincent Muczynski

Full Text Available Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro.Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10(-4M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro.We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells.

Skin Sensitive Difference of Human Body Sections under Clothing--Multiple Analysis of Skin Surface Temperature Changes

Institute of Scientific and Technical Information of China (English)

李俊; 吴海燕; 张渭源

2003-01-01

A new researching method on clothing comfort perception is developed.By it the skin surface temperature changes and subjective psychological perception of human body sections stimulated by the same cold stimulation are studied.With the multiple comparison analysis method the changing laws of skin temperature of main human body sections is obtained.

Epicardial excitation pattern as observed in the isolated revived and perfused fetal human heart

NARCIS (Netherlands)

Durrer, D.; Büller, J.; Graaff, P.; Lo, G.I.; Meijler, F.L.

1961-01-01

The resuscitated fetal human heart can be used as an experimental tooI for the investigation of the excitatory process in the human heart. During perfusion the configuration of the epicardial electrocardiograms does not change appreciably. For accurate recording permitting a detailed analysis, the

Radio-sterilization and processing of frozen human skin

International Nuclear Information System (INIS)

Zarate S, Herman; Aguirre H, Paulina; Silva R, Samy; Hitschfeld G, Mario

2006-01-01

The Laboratory of Radio-sterilized Biological Tissues Processing (LPTR) belonging to the Chilean Commission of Nuclear Energy and the International Atomic Energy Agency have played a paramount role in our country, concerning the biological tissue processing, which can be radio-sterilized as human skin, pig skin, amniotic membrane, human bone and bovine bone. The frozen radio.-sterilized human skin processing began in 2001, by means of putting into practice the knowledge acquired in training courses through the IAEA and the experience transferred by experts who visited our laboratory. The human skin processing of dead donor can be divided into 6 stages: a) Profuse washing with physiological sterilized serum in to remove the microorganisms, chemical and pharmacological compounds; b) immersion in glycerol solution at 10% to better keep the stored tissues; c) packing, to avoid post manipulation of the sterilized tissue; d) microbiological controls which allow and guarantee a sterility assurance level of 10 6 ; e) radio-sterilization, technique that consists of exposing the grafts to electromagnetic gamma waves which eliminate the microorganisms of the tissue, f) and finally, dispatching and liberation of the frozen sterilized human skin for its clinical use in different centers that take care of burned people. The LPTR receives feedback from surgeons who have used these tissues in order to improve the processing stages based in an integral quality system ISO 9001.2000. The State Health System in our country counts on limited and scarce resources to implement synthetic substitutes that is why It is considered necessary to spread the use of these noble tissues which have sterility assurance and they are processed at low price

The origin of fetal sterols in second-trimester amniotic fluid : endogenous synthesis or maternal-fetal transport?

NARCIS (Netherlands)

Baardman, Maria E.; Erwich, Jan Jaap H. M.; Berger, Rolf M. F.; Hofstra, Robert M. W.; Kerstjens-Frederikse, Wilhelmina S.; Luetjohann, Dieter; Plosch, Torsten; Lutjohann, D.

OBJECTIVE: Cholesterol is crucial for fetal development. To gain more insight into the origin of the fetal cholesterol pool in early human pregnancy, we determined cholesterol and its precursors in the amniotic fluid of uncomplicated, singleton human pregnancies. STUDY DESIGN: Total sterols were

Proof-of-concept: 3D bioprinting of pigmented human skin constructs.

Science.gov (United States)

Ng, Wei Long; Qi, Jovina Tan Zhi; Yeong, Wai Yee; Naing, May Win

2018-01-23

Three-dimensional (3D) pigmented human skin constructs have been fabricated using a 3D bioprinting approach. The 3D pigmented human skin constructs are obtained from using three different types of skin cells (keratinocytes, melanocytes and fibroblasts from three different skin donors) and they exhibit similar constitutive pigmentation (pale pigmentation) as the skin donors. A two-step drop-on-demand bioprinting strategy facilitates the deposition of cell droplets to emulate the epidermal melanin units (pre-defined patterning of keratinocytes and melanocytes at the desired positions) and manipulation of the microenvironment to fabricate 3D biomimetic hierarchical porous structures found in native skin tissue. The 3D bioprinted pigmented skin constructs are compared to the pigmented skin constructs fabricated by conventional a manual-casting approach; in-depth characterization of both the 3D pigmented skin constructs has indicated that the 3D bioprinted skin constructs have a higher degree of resemblance to native skin tissue in term of the presence of well-developed stratified epidermal layers and the presence of a continuous layer of basement membrane proteins as compared to the manually-cast samples. The 3D bioprinting approach facilitates the development of 3D in vitro pigmented human skin constructs for potential toxicology testing and fundamental cell biology research.

3D bioprinting of functional human skin: production and in vivo analysis.

Science.gov (United States)

Cubo, Nieves; Garcia, Marta; Del Cañizo, Juan F; Velasco, Diego; Jorcano, Jose L

2016-12-05

Significant progress has been made over the past 25 years in the development of in vitro-engineered substitutes that mimic human skin, either to be used as grafts for the replacement of lost skin, or for the establishment of in vitro human skin models. In this sense, laboratory-grown skin substitutes containing dermal and epidermal components offer a promising approach to skin engineering. In particular, a human plasma-based bilayered skin generated by our group, has been applied successfully to treat burns as well as traumatic and surgical wounds in a large number of patients in Spain. There are some aspects requiring improvements in the production process of this skin; for example, the relatively long time (three weeks) needed to produce the surface required to cover an extensive burn or a large wound, and the necessity to automatize and standardize a process currently performed manually. 3D bioprinting has emerged as a flexible tool in regenerative medicine and it provides a platform to address these challenges. In the present study, we have used this technique to print a human bilayered skin using bioinks containing human plasma as well as primary human fibroblasts and keratinocytes that were obtained from skin biopsies. We were able to generate 100 cm 2 , a standard P100 tissue culture plate, of printed skin in less than 35 min (including the 30 min required for fibrin gelation). We have analysed the structure and function of the printed skin using histological and immunohistochemical methods, both in 3D in vitro cultures and after long-term transplantation to immunodeficient mice. In both cases, the generated skin was very similar to human skin and, furthermore, it was indistinguishable from bilayered dermo-epidermal equivalents, handmade in our laboratories. These results demonstrate that 3D bioprinting is a suitable technology to generate bioengineered skin for therapeutical and industrial applications in an automatized manner.

The protective effect of ursodeoxycholic acid in an in vitro model of the human fetal heart occurs via targeting cardiac fibroblasts.

Science.gov (United States)

Schultz, Francisca; Hasan, Alveera; Alvarez-Laviada, Anita; Miragoli, Michele; Bhogal, Navneet; Wells, Sarah; Poulet, Claire; Chambers, Jenny; Williamson, Catherine; Gorelik, Julia

2016-01-01

Bile acids are elevated in the blood of women with intrahepatic cholestasis of pregnancy (ICP) and this may lead to fetal arrhythmia, fetal hypoxia and potentially fetal death in utero. The bile acid taurocholic acid (TC) causes abnormal calcium dynamics and contraction in neonatal rat cardiomyocytes. Ursodeoxycholic acid (UDCA), a drug clinically used to treat ICP, prevents adverse effects of TC. During development, the fetus is in a state of relative hypoxia. Although this is essential for the development of the heart and vasculature, resident fibroblasts can transiently differentiate into myofibroblasts and form gap junctions with cardiomyocytes in vitro, resulting in cardiomyocyte depolarization. We expanded on previously published work using an in vitro hypoxia model to investigate the differentiation of human fetal fibroblasts into myofibroblasts. Recent evidence shows that potassium channels are involved in maintaining the membrane potential of ventricular fibroblasts and that ATP-dependent potassium (KATP) channel subunits are expressed in cultured fibroblasts. KATP channels are a valuable target as they are thought to have a cardioprotective role during ischaemic and hypoxic conditions. We investigated whether UDCA could modulate fibroblast membrane potential. We established the isolation and culture of human fetal cardiomyocytes and fibroblasts to investigate the effect of hypoxia, TC and UDCA on human fetal cardiac cells. UDCA hyperpolarized myofibroblasts and prevented TC-induced depolarisation, possibly through the activation of KATP channels that are expressed in cultured fibroblasts. Also, similar to the rat model, UDCA can counteract TC-induced calcium abnormalities in human fetal cultures of cardiomyocytes and myofibroblasts. Under normoxic conditions, we found a higher number of myofibroblasts in cultures derived from human fetal hearts compared to cells isolated from neonatal rat hearts, indicating a possible increased number of myofibroblasts

Analysis of human skin tissue by millimeter-wave reflectometry

NARCIS (Netherlands)

Smulders, P.F.M.

2013-01-01

Background/pupose: Millimeter-wave reflectometry is a potentially interesting technique to analyze the human skin in vivo in order to determine the water content locally in the skin. Purpose of this work is to investigate the possibility of skin-tissue differentiation. In addition, it addresses the

Method of protecting human skin from actinic radiation

International Nuclear Information System (INIS)

Fusaro, R.M.

1975-01-01

Enhanced protection from sunlight is achieved by applying to human skin beforehand separate, time-spaced applications of (1) a carbonyl compound which is reactive with amino groups in human skin, for example dihydroxyacetone, and (2) a benzo- or naptho-quinone such as lawsone. Preferably several sequential applications of each active component in a separate carrier are made the evening before the first exposure, and protection is thereafter maintained by applying each component separately each evening

Tribology of skin : review and analysis of experimental results for the friction coefficient of human skin

NARCIS (Netherlands)

Derler, S.; Gerhardt, L.C.

2012-01-01

In this review, we discuss the current knowledge on the tribology of human skin and present an analysis of the available experimental results for skin-friction coefficients. Starting with an overview on the factors influencing the friction behaviour of skin, we discuss the up-to-date existing

Characterisation of mechanical behaviour of human skin in vivo

NARCIS (Netherlands)

Douven, L.F.A.; Meijer, R.; Oomens, C.W.J.

2000-01-01

Characterization of the biomechanical properties of human skin in vivo is studied both experimentally and by numerical modeling. These properties can be important in the evaluation of skin condition (e.g. aging) as well as skin disorders. In this study the authors focus on the static behavior of the

Skin age testing criteria: characterization of human skin structures by 500 MHz MRI multiple contrast and image processing

Energy Technology Data Exchange (ETDEWEB)

Sharma, Rakesh, E-mail: rs05h@fsu.ed [Departments of Chemical Engineering and Biomedical Engineering, FAMU-FSU College of Engineering, Tallahassee, FL 32310 (United States)

2010-07-21

Ex vivo magnetic resonance microimaging (MRM) image characteristics are reported in human skin samples in different age groups. Human excised skin samples were imaged using a custom coil placed inside a 500 MHz NMR imager for high-resolution microimaging. Skin MRI images were processed for characterization of different skin structures. Contiguous cross-sectional T1-weighted 3D spin echo MRI, T2-weighted 3D spin echo MRI and proton density images were compared with skin histopathology and NMR peaks. In all skin specimens, epidermis and dermis thickening and hair follicle size were measured using MRM. Optimized parameters TE and TR and multicontrast enhancement generated better MRI visibility of different skin components. Within high MR signal regions near to the custom coil, MRI images with short echo time were comparable with digitized histological sections for skin structures of the epidermis, dermis and hair follicles in 6 (67%) of the nine specimens. Skin % tissue composition, measurement of the epidermis, dermis, sebaceous gland and hair follicle size, and skin NMR peaks were signatures of skin type. The image processing determined the dimensionality of skin tissue components and skin typing. The ex vivo MRI images and histopathology of the skin may be used to measure the skin structure and skin NMR peaks with image processing may be a tool for determining skin typing and skin composition.

Skin age testing criteria: characterization of human skin structures by 500 MHz MRI multiple contrast and image processing

International Nuclear Information System (INIS)

Sharma, Rakesh

2010-01-01

Ex vivo magnetic resonance microimaging (MRM) image characteristics are reported in human skin samples in different age groups. Human excised skin samples were imaged using a custom coil placed inside a 500 MHz NMR imager for high-resolution microimaging. Skin MRI images were processed for characterization of different skin structures. Contiguous cross-sectional T1-weighted 3D spin echo MRI, T2-weighted 3D spin echo MRI and proton density images were compared with skin histopathology and NMR peaks. In all skin specimens, epidermis and dermis thickening and hair follicle size were measured using MRM. Optimized parameters TE and TR and multicontrast enhancement generated better MRI visibility of different skin components. Within high MR signal regions near to the custom coil, MRI images with short echo time were comparable with digitized histological sections for skin structures of the epidermis, dermis and hair follicles in 6 (67%) of the nine specimens. Skin % tissue composition, measurement of the epidermis, dermis, sebaceous gland and hair follicle size, and skin NMR peaks were signatures of skin type. The image processing determined the dimensionality of skin tissue components and skin typing. The ex vivo MRI images and histopathology of the skin may be used to measure the skin structure and skin NMR peaks with image processing may be a tool for determining skin typing and skin composition.

Studies on the isolation, structural analysis and tissue localization of fetal antigen 1 and its relation to a human adrenal-specific cDNA, pG2

DEFF Research Database (Denmark)

Jensen, Charlotte Harken; Teisner, Børge; Højrup, Peter

1993-01-01

Fetal antigen 1 was purified from second trimester human amniotic fluid by immunospecific affinity chromatography followed by reversed-phase chromatography. Fetal antigen 1 is a single chain glycoprotein with a M(r) of 32-38 kDa. The amino acid composition revealed a high content of cysteines......, prolines and amino acids (aa) with acidic side-chains indicating that fetal antigen 1 is a compactly folded, strongly hydrophilic molecule. The N-terminal amino acid sequence (37 aa) revealed no homology to other known protein sequences, implying that fetal antigen 1 is a 'novel' human protein. When the aa...... sequence was back-translated into the appropriate degenerate sequence of nucleic acids, fetal antigen 1 could be partially aligned to a 'human adrenal-specific mRNA, pG2'. The indirect immunoperoxidase technique demonstrated fetal antigen 1 in fetal hepatocytes, glandular cells of fetal pancreas...

Induction of Skin-Derived Precursor Cells from Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Sugiyama-Nakagiri, Yoriko; Fujimura, Tsutomu; Moriwaki, Shigeru

2016-01-01

The generation of full thickness human skin from dissociated cells is an attractive approach not only for treating skin diseases, but also for treating many systemic disorders. However, it is currently not possible to obtain an unlimited number of skin dermal cells. The goal of this study was to develop a procedure to produce skin dermal stem cells from induced pluripotent stem cells (iPSCs). Skin-derived precursor cells (SKPs) were isolated as adult dermal precursors that could differentiate into both neural and mesodermal progenies and could reconstitute the dermis. Thus, we attempted to generate SKPs from iPSCs that could reconstitute the skin dermis. Human iPSCs were initially cultured with recombinant noggin and SB431542, an inhibitor of activin/nodal and TGFβ signaling, to induce neural crest progenitor cells. Those cells were then treated with SKP medium that included CHIR99021, a WNT signal activator. The induction efficacy from neural crest progenitor cells to SKPs was more than 97%. No other modifiers tested were able to induce those cells. Those human iPSC-derived SKPs (hiPSC-SKPs) showed a similar gene expression signature to SKPs isolated from human skin dermis. Human iPSC-SKPs differentiated into neural and mesodermal progenies, including adipocytes, skeletogenic cell types and Schwann cells. Moreover, they could be induced to follicular type keratinization when co-cultured with human epidermal keratinocytes. We here provide a new efficient protocol to create human skin dermal stem cells from hiPSCs that could contribute to the treatment of various skin disorders.

First donation of human skin obtained from corpse

International Nuclear Information System (INIS)

Reyes F, M.L.; Luna Z, D.

2007-01-01

The first donation of human skin coming from a cadaverous donor was obtained in the State of Mexico. The skin was obtained of a 34 year-old multi organic donor, the extraction of the same was carried out in an operating theatre by medical personnel, supported by personal of the Radio sterilized Tissue Bank (BTR) of the ININ. The skin was transported to the BTR for it processing. (Author)

Design and fabrication of human skin by three-dimensional bioprinting.

Science.gov (United States)

Lee, Vivian; Singh, Gurtej; Trasatti, John P; Bjornsson, Chris; Xu, Xiawei; Tran, Thanh Nga; Yoo, Seung-Schik; Dai, Guohao; Karande, Pankaj

2014-06-01

Three-dimensional (3D) bioprinting, a flexible automated on-demand platform for the free-form fabrication of complex living architectures, is a novel approach for the design and engineering of human organs and tissues. Here, we demonstrate the potential of 3D bioprinting for tissue engineering using human skin as a prototypical example. Keratinocytes and fibroblasts were used as constituent cells to represent the epidermis and dermis, and collagen was used to represent the dermal matrix of the skin. Preliminary studies were conducted to optimize printing parameters for maximum cell viability as well as for the optimization of cell densities in the epidermis and dermis to mimic physiologically relevant attributes of human skin. Printed 3D constructs were cultured in submerged media conditions followed by exposure of the epidermal layer to the air-liquid interface to promote maturation and stratification. Histology and immunofluorescence characterization demonstrated that 3D printed skin tissue was morphologically and biologically representative of in vivo human skin tissue. In comparison with traditional methods for skin engineering, 3D bioprinting offers several advantages in terms of shape- and form retention, flexibility, reproducibility, and high culture throughput. It has a broad range of applications in transdermal and topical formulation discovery, dermal toxicity studies, and in designing autologous grafts for wound healing. The proof-of-concept studies presented here can be further extended for enhancing the complexity of the skin model via the incorporation of secondary and adnexal structures or the inclusion of diseased cells to serve as a model for studying the pathophysiology of skin diseases.

A novel model of human skin pressure ulcers in mice.

Directory of Open Access Journals (Sweden)

Andrés A Maldonado

Full Text Available INTRODUCTION: Pressure ulcers are a prevalent health problem in today's society. The shortage of suitable animal models limits our understanding and our ability to develop new therapies. This study aims to report on the development of a novel and reproducible human skin pressure ulcer model in mice. MATERIAL AND METHODS: Male non-obese, diabetic, severe combined immunodeficiency mice (n = 22 were engrafted with human skin. A full-thickness skin graft was placed onto 4×3 cm wounds created on the dorsal skin of the mice. Two groups with permanent grafts were studied after 60 days. The control group (n = 6 was focused on the process of engraftment. Evaluations were conducted with photographic assessment, histological analysis and fluorescence in situ hybridization (FISH techniques. The pressure ulcer group (n = 12 was created using a compression device. A pressure of 150 mmHg for 8 h, with a total of three cycles of compression-release was exerted. Evaluations were conducted with photographic assessment and histological analysis. RESULTS: Skin grafts in the control group took successfully, as shown by visual assessment, FISH techniques and histological analysis. Pressure ulcers in the second group showed full-thickness skin loss with damage and necrosis of all the epidermal and dermal layers (ulcer stage III in all cases. Complete repair occurred after 40 days. CONCLUSIONS: An inexpensive, reproducible human skin pressure ulcer model has been developed. This novel model will facilitate the development of new clinically relevant therapeutic strategies that can be tested directly on human skin.

Assessing human skin with diffuse reflectance spectroscopy and colorimetry

Science.gov (United States)

Seo, InSeok; Liu, Yang; Bargo, Paulo R.; Kollias, Nikiforos

2012-02-01

Colorimetry has been used as an objective measure of perceived skin color by human eye to document and score physiological responses of the skin from external insults. CIE color space values (L*, a* and b*) are the most commonly used parameters to correlate visually perceived color attributes such as L* for pigment, a* for erythema, and b* for sallowness of the skin. In this study, we investigated the relation of Lab color scale to the amount of major skin chromophores (oxy-, deoxyhemoglobin and melanin) calculated from diffuse reflectance spectroscopy. Thirty two healthy human subjects with ages from 20 to 70 years old, skin types I-VI, were recruited for the study. DRS and colorimetry measurements were taken from the left and right cheeks, and on the right upper inner arm. The melanin content calculated from 630-700 nm range of DRS measurements was shown to correlate with the lightness of skin (L*) for most skin types. For subjects with medium-to-light complexion, melanin measured at the blue part spectrum and hemoglobin interfered on the relation of lightness of the skin color to the melanin content. The sallowness of the skin that is quantified by the melanin contribution at the blue part spectrum of DRS was found to be related to b* scale. This study demonstrates the importance of documenting skin color by assessing individual skin chromophores with diffuse reflectance spectroscopy, in comparison to colorimetry assessment.

Amniotic oxytocin and vasopressin in relation to human fetal development and labour

NARCIS (Netherlands)

Oosterbaan, H. P.; Swaab, D. F.

1989-01-01

Previous experiments in rats revealed increased amniotic oxytocin (OXT) levels in the course of normal development and increased vasopressin (AVP) levels in retarded fetal growth. In order to see whether similar changes would also occur in human, OXT and AVP levels were determined in amniotic fluid,

Langerhans cell precursors acquire RANK/CD265 in prenatal human skin.

Science.gov (United States)

Schöppl, Alice; Botta, Albert; Prior, Marion; Akgün, Johnnie; Schuster, Christopher; Elbe-Bürger, Adelheid

2015-01-01

The skin is the first barrier against foreign pathogens and the prenatal formation of a strong network of various innate and adaptive cells is required to protect the newborn from perinatal infections. While many studies about the immune system in healthy and diseased adult human skin exist, our knowledge about the cutaneous prenatal/developing immune system and especially about the phenotype and function of antigen-presenting cells such as epidermal Langerhans cells (LCs) in human skin is still scarce. It has been shown previously that LCs in healthy adult human skin express receptor activator of NF-κB (RANK), an important molecule prolonging their survival. In this study, we investigated at which developmental stage LCs acquire this important molecule. Immunofluorescence double-labeling of cryostat sections revealed that LC precursors in prenatal human skin either do not yet [10-11 weeks of estimated gestational age (EGA)] or only faintly (13-15 weeks EGA) express RANK. LCs express RANK at levels comparable to adult LCs by the end of the second trimester. Comparable with adult skin, dermal antigen-presenting cells at no gestational age express this marker. These findings indicate that epidermal leukocytes gradually acquire RANK during gestation - a phenomenon previously observed also for other markers on LCs in prenatal human skin. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

A developmental stage-specific switch from DAZL to BOLL occurs during fetal oogenesis in humans, but not mice.

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Jing He

Full Text Available The Deleted in Azoospermia gene family encodes three germ cell-specific RNA-binding proteins (DAZ, DAZL and BOLL that are essential for gametogenesis in diverse species. Targeted disruption of Boll in mice causes male-specific spermiogenic defects, but females are apparently fertile. Overexpression of human BOLL promotes the derivation of germ cell-like cells from genetically female (XX, but not male (XY human ES cells however, suggesting a functional role for BOLL in regulating female gametogenesis in humans. Whether BOLL is expressed during oogenesis in mammals also remains unclear. We have therefore investigated the expression of BOLL during fetal oogenesis in humans and mice. We demonstrate that BOLL protein is expressed in the germ cells of the human fetal ovary, at a later developmental stage than, and almost mutually-exclusive to, the expression of DAZL. Strikingly, BOLL is downregulated, and DAZL re-expressed, as primordial follicles form, revealing BOLL expression to be restricted to a narrow window during fetal oogenesis. By quantifying the extent of co-expression of DAZL and BOLL with markers of meiosis, we show that this window likely corresponds to the later stages of meiotic prophase I. Finally, we demonstrate that Boll is also transiently expressed during oogenesis in the fetal mouse ovary, but is simultaneously co-expressed within the same germ cells as Dazl. These data reveal significant similarities and differences between the expression of BOLL homologues during oogenesis in humans and mice, and raise questions as to the validity of the Boll(-/- mouse as a model for understanding BOLL function during human oogenesis.

3D imaging of cleared human skin biopsies using light-sheet microscopy: A new way to visualize in-depth skin structure.

Science.gov (United States)

Abadie, S; Jardet, C; Colombelli, J; Chaput, B; David, A; Grolleau, J-L; Bedos, P; Lobjois, V; Descargues, P; Rouquette, J

2018-05-01

Human skin is composed of the superimposition of tissue layers of various thicknesses and components. Histological staining of skin sections is the benchmark approach to analyse the organization and integrity of human skin biopsies; however, this approach does not allow 3D tissue visualization. Alternatively, confocal or two-photon microscopy is an effective approach to perform fluorescent-based 3D imaging. However, owing to light scattering, these methods display limited light penetration in depth. The objectives of this study were therefore to combine optical clearing and light-sheet fluorescence microscopy (LSFM) to perform in-depth optical sectioning of 5 mm-thick human skin biopsies and generate 3D images of entire human skin biopsies. A benzyl alcohol and benzyl benzoate solution was used to successfully optically clear entire formalin fixed human skin biopsies, making them transparent. In-depth optical sectioning was performed with LSFM on the basis of tissue-autofluorescence observations. 3D image analysis of optical sections generated with LSFM was performed by using the Amira ® software. This new approach allowed us to observe in situ the different layers and compartments of human skin, such as the stratum corneum, the dermis and epidermal appendages. With this approach, we easily performed 3D reconstruction to visualise an entire human skin biopsy. Finally, we demonstrated that this method is useful to visualise and quantify histological anomalies, such as epidermal hyperplasia. The combination of optical clearing and LSFM has new applications in dermatology and dermatological research by allowing 3D visualization and analysis of whole human skin biopsies. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In vivo transformation of human skin with human papillomavirus type 11 from condylomatot acuminata

International Nuclear Information System (INIS)

Kreider, J.W.; Howett, M.K.; Lill, N.L.; Bartlett, G.L.; Zaino, R.J.; Sedlacek, T.V.; Mortel, R.

1986-01-01

Human papillomaviruses (HPVs) have been implicated in the development of a number of human malignancies, but direct tests of their involvement have not been possible. The authors describe a system in which human skin from various skin from various sites was infected with HPV type 11 (HPV-11) extracted from vulvar condylomata and was grafted beneath the renal capsule of athymic mice. Most of the skin grafts so treated underwent morphological transformation, resulting in the development of condylomata identical to those which occur spontaneously in patients. Foreskins responded with the most vigorous proliferative response to HPV-11. The lesions produced the characteristic intranuclear group-specific antigen of papillomaviruses. Both dot blot and Southern blot analysis of DNA from the lesions revealed the presence of HPV-11 DNA in the transformed grafts. These results demonstrate the first laboratory system for the study of the interaction of human skin with an HPV. The method may be useful in understanding the mechanisms of HPV transformation and replication and is free of the ethical restraints which have impeded study. This system will allow the direct study of factors which permit neoplastic progression of HPV-induced cutaneous lesions in human tissues

Composition of human skin microbiota affects attractiveness to malaria mosquitoes.

Directory of Open Access Journals (Sweden)

Niels O Verhulst

Full Text Available The African malaria mosquito Anopheles gambiae sensu stricto continues to play an important role in malaria transmission, which is aggravated by its high degree of anthropophily, making it among the foremost vectors of this disease. In the current study we set out to unravel the strong association between this mosquito species and human beings, as it is determined by odorant cues derived from the human skin. Microbial communities on the skin play key roles in the production of human body odour. We demonstrate that the composition of the skin microbiota affects the degree of attractiveness of human beings to this mosquito species. Bacterial plate counts and 16S rRNA sequencing revealed that individuals that are highly attractive to An. gambiae s.s. have a significantly higher abundance, but lower diversity of bacteria on their skin than individuals that are poorly attractive. Bacterial genera that are correlated with the relative degree of attractiveness to mosquitoes were identified. The discovery of the connection between skin microbial populations and attractiveness to mosquitoes may lead to the development of new mosquito attractants and personalized methods for protection against vectors of malaria and other infectious diseases.

Molecular cartography of the human skin surface in 3D

Science.gov (United States)

Bouslimani, Amina; Porto, Carla; Rath, Christopher M.; Wang, Mingxun; Guo, Yurong; Gonzalez, Antonio; Berg-Lyon, Donna; Ackermann, Gail; Moeller Christensen, Gitte Julie; Nakatsuji, Teruaki; Zhang, Lingjuan; Borkowski, Andrew W.; Meehan, Michael J.; Dorrestein, Kathleen; Gallo, Richard L.; Bandeira, Nuno; Knight, Rob; Alexandrov, Theodore; Dorrestein, Pieter C.

2015-01-01

The human skin is an organ with a surface area of 1.5–2 m2 that provides our interface with the environment. The molecular composition of this organ is derived from host cells, microbiota, and external molecules. The chemical makeup of the skin surface is largely undefined. Here we advance the technologies needed to explore the topographical distribution of skin molecules, using 3D mapping of mass spectrometry data and microbial 16S rRNA amplicon sequences. Our 3D maps reveal that the molecular composition of skin has diverse distributions and that the composition is defined not only by skin cells and microbes but also by our daily routines, including the application of hygiene products. The technological development of these maps lays a foundation for studying the spatial relationships of human skin with hygiene, the microbiota, and environment, with potential for developing predictive models of skin phenotypes tailored to individual health. PMID:25825778

Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies.

Science.gov (United States)

Pérez-Sánchez, Almudena; Barrajón-Catalán, Enrique; Herranz-López, María; Micol, Vicente

2018-03-24

The skin is the body's largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV) radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin.

Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies

Directory of Open Access Journals (Sweden)

Almudena Pérez-Sánchez

2018-03-01

Full Text Available The skin is the body’s largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin.

Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies

Science.gov (United States)

Pérez-Sánchez, Almudena; Micol, Vicente

2018-01-01

The skin is the body’s largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV) radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin. PMID:29587342

Ex vivo culture of human fetal gonads: manipulation of meiosis signalling by retinoic acid treatment disrupts testis development.

Science.gov (United States)

Jørgensen, A; Nielsen, J E; Perlman, S; Lundvall, L; Mitchell, R T; Juul, A; Rajpert-De Meyts, E

2015-10-01

What are the effects of experimentally manipulating meiosis signalling by addition of retinoic acid (RA) in cultured human fetal gonads? RA-treatment accelerated meiotic entry in cultured fetal ovary samples, while addition of RA resulted in a dysgenetic gonadal phenotype in fetal testis cultures. One of the first manifestations of sex differentiation is the initiation of meiosis in fetal ovaries. In contrast, meiotic entry is actively prevented in the fetal testis at this developmental time-point. It has previously been shown that RA-treatment mediates initiation of meiosis in human fetal ovary ex vivo. This was a controlled ex vivo study of human fetal gonads treated with RA in 'hanging-drop' tissue cultures. The applied experimental set-up preserves germ cell-somatic niche interactions and the investigated outcomes included tissue integrity and morphology, cell proliferation and survival and the expression of markers of meiosis and sex differentiation. Tissue from 24 first trimester human fetuses was included in this study, all from elective terminations at gestational week (GW) 7-12. Gonads were cultured for 2 weeks with and without addition of 1 µM RA. Samples were subsequently formalin-fixed and investigated by immunohistochemistry and cell counting. Proteins investigated and quantified included; octamer-binding transcription factor 4 (OCT4), transcription factor AP-2 gamma (AP2γ) (embryonic germ cell markers), SRY (sex determining region Y)-box 9 (SOX9), anti-Müllerian hormone (AMH) (immature Sertoli cell markers), COUP transcription factor 2 (COUP-TFII) (marker of interstitial cells), forkhead box L2 (FOXL2) (granulosa cell marker), H2A histone family, member X (γH2AX) (meiosis marker), doublesex and mab-3 related transcription factor 1 (DMRT1) (meiosis regulator), cleaved poly ADP ribose polymerase (PARP), cleaved Caspase 3 (apoptosis markers) and Ki-67 antigen (Ki-67) (proliferation marker). Also, proliferation was determined using a 5'-bromo-2

A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin

Directory of Open Access Journals (Sweden)

Nisma Mujahid

2017-06-01

Full Text Available The presence of dark melanin (eumelanin within human epidermis represents one of the strongest predictors of low skin cancer risk. Topical rescue of eumelanin synthesis, previously achieved in “redhaired” Mc1r-deficient mice, demonstrated significant protection against UV damage. However, application of a topical strategy for human skin pigmentation has not been achieved, largely due to the greater barrier function of human epidermis. Salt-inducible kinase (SIK has been demonstrated to regulate MITF, the master regulator of pigment gene expression, through its effects on CRTC and CREB activity. Here, we describe the development of small-molecule SIK inhibitors that were optimized for human skin penetration, resulting in MITF upregulation and induction of melanogenesis. When topically applied, pigment production was induced in Mc1r-deficient mice and normal human skin. These findings demonstrate a realistic pathway toward UV-independent topical modulation of human skin pigmentation, potentially impacting UV protection and skin cancer risk.

A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin.

Science.gov (United States)

Mujahid, Nisma; Liang, Yanke; Murakami, Ryo; Choi, Hwan Geun; Dobry, Allison S; Wang, Jinhua; Suita, Yusuke; Weng, Qing Yu; Allouche, Jennifer; Kemeny, Lajos V; Hermann, Andrea L; Roider, Elisabeth M; Gray, Nathanael S; Fisher, David E

2017-06-13

The presence of dark melanin (eumelanin) within human epidermis represents one of the strongest predictors of low skin cancer risk. Topical rescue of eumelanin synthesis, previously achieved in "redhaired" Mc1r-deficient mice, demonstrated significant protection against UV damage. However, application of a topical strategy for human skin pigmentation has not been achieved, largely due to the greater barrier function of human epidermis. Salt-inducible kinase (SIK) has been demonstrated to regulate MITF, the master regulator of pigment gene expression, through its effects on CRTC and CREB activity. Here, we describe the development of small-molecule SIK inhibitors that were optimized for human skin penetration, resulting in MITF upregulation and induction of melanogenesis. When topically applied, pigment production was induced in Mc1r-deficient mice and normal human skin. These findings demonstrate a realistic pathway toward UV-independent topical modulation of human skin pigmentation, potentially impacting UV protection and skin cancer risk. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

An in vitro model for detecting skin irritants: methyl green-pyronine staining of human skin explant cultures

NARCIS (Netherlands)

Jacobs, J. J. L.; Lehé, C.; Cammans, K. D. A.; Das, P. K.; Elliott, G. R.

2002-01-01

We evaluated the potential of human organotypic skin explant cultures (hOSECs) for screening skin irritants. Test chemicals were applied to the epidermis of the skin explants which were incubated for 4, 24 or 48 h in tissue culture medium. A decrease in epidermal RNA staining, visualised in frozen

Typing of human fetal organs for the histocompatibility antigens A, B and DR.

Science.gov (United States)

Tuch, B E; Doran, T J; Messel, N; Turtle, J R

1985-01-01

In the transplantation of human fetal pancreatic explants into diabetic man, the importance of matching the histocompatibility antigens of donor and recipient to decrease the chances of rejection is unknown. Before this question can be answered human fetuses must be tissue typed. We have shown that lymphocytes harvested from fetal liver, thymus, bone marrow and spleen can be successfully HLA DR typed in 64% and A and B typed in 57% of 58 fetuses aged 15 wk or more. Typing should ideally be carried out on unseparated T and B cells. Best results were achieved if all four of the above organs were available and more than one million viable cells were able to be harvested for typing. Whilst the DR antigens could be typed from all tissues, the A and B antigens could be typed, with few exceptions only from thymus, spleen and bone marrow. The efficacy of matching the histocompatibility antigens of recipient and donor fetuses, especially the DR antigens can now be tested in the human diabetic being transplanted with pancreatic explants.

Pig and guinea pig skin as surrogates for human in vitro penetration studies: a quantitative review.

Science.gov (United States)

Barbero, Ana M; Frasch, H Frederick

2009-02-01

Both human and animal skin in vitro models are used to predict percutaneous penetration in humans. The objective of this review is a quantitative comparison of permeability and lag time measurements between human and animal skin, including an evaluation of the intra and inter species variability. We limit our focus to domestic pig and rodent guinea pig skin as surrogates for human skin, and consider only studies in which both animal and human penetration of a given chemical were measured jointly in the same lab. When the in vitro permeability of pig and human skin were compared, the Pearson product moment correlation coefficient (r) was 0.88 (Ppig and 35% for human, and an inter species average coefficient of variation of 37% for the set of studied compounds (n=41). The lag times of pig skin and human skin did not correlate (r=0.35, P=0.26). When the in vitro permeability of guinea pig and human skin were compared, r=0.96 (Pguinea pig and 24% for human, and an inter species coefficient of variation of permeability of 41% for the set of studied compounds (n=15). Lag times of guinea pig and human skin correlated (r=0.90, Ppig skin (n=50) and guinea pig skin (n=25). For pig skin, 80% of measurements fell within the range 0.3guinea pig skin, 65% fell within that range. Both pig and guinea pig are good models for human skin permeability and have less variability than the human skin model. The skin model of choice will depend on the final purpose of the study and the compound under investigation.

Platelet-rich plasma can replace fetal bovine serum in human meniscus cell cultures

NARCIS (Netherlands)

Gonzales, V.K.; Mulder, E.L.W. de; Boer, T. den; Hannink, G.; Tienen, T.G. van; Heerde, W.L. van; Buma, P.

2013-01-01

Concerns over fetal bovine serum (FBS) limit the clinical application of cultured tissue-engineered constructs. Therefore, we investigated if platelet-rich plasma (PRP) can fully replace FBS for meniscus tissue engineering purposes. Human PRP and platelet-poor plasma (PPP) were isolated from three

Comparison of skin decontamination efficacy of commercial decontamination products following exposure to VX on human skin.

Science.gov (United States)

Thors, L; Koch, M; Wigenstam, E; Koch, B; Hägglund, L; Bucht, A

2017-08-01

The decontamination efficacy of four commercially available skin decontamination products following exposure to the nerve agent VX was evaluated in vitro utilizing a diffusion cell and dermatomed human skin. The products included were Reactive Skin Decontamination Lotion (RSDL), the Swedish decontamination powder 104 (PS104), the absorbent Fuller's Earth and the aqueous solution alldecontMED. In addition, various decontamination procedures were assessed to further investigate important mechanisms involved in the specific products, e.g. decontamination removal from skin, physical removal by sponge swabbing and activation of degradation mechanisms. The efficacy of each decontamination product was evaluated 5 or 30 min after dermal application of VX (neat or diluted to 20% in water). The RSDL-lotion was superior in reducing the penetration of VX through human skin, both when exposed as neat agent and when diluted to 20% in water. Swabbing with the RSDL-sponge during 2 min revealed decreased efficacy compared to applying the RSDL-lotion directly on the skin for 30 min. Decontamination with Fuller's Earth and alldecontMED significantly reduced the penetration of neat concentration of VX through human skin. PS104-powder was insufficient for decontamination of VX at both time-points, independently of the skin contact time of PS104. The PS104-slurry (a mixture of PS104-powder and water), slightly improved the decontamination efficacy. Comparing the time-points for initiated decontamination revealed less penetrated VX for RSDL and Fuller's Earth when decontamination was initiated after 5 min compared to 30 min post-exposure, while alldecontMED displayed similar efficacy at both time-points. Decontamination by washing with water only resulted in a significant reduction of penetrated VX when washing was performed 5 min after exposure, but not when decontamination was delayed to 30 min post-exposure of neat VX. In conclusion, early initiated decontamination with the

Tribological behaviour of skin equivalents and ex-vivo human skin against the material components of artificial turf in sliding

NARCIS (Netherlands)

Morales Hurtado, Marina; Peppelman, P.; Zeng, Xiangqiong; van Erp, P.E.J.; van der Heide, Emile

2016-01-01

This research aims to analyse the interaction of three artificial skin equivalents and human skin against the main material components of artificial turf. The tribological performance of Lorica, Silicone Skin L7350 and a recently developed Epidermal Skin Equivalent (ESE) were studied and compared to

The use of ex vivo human skin tissue for genotoxicity testing

Energy Technology Data Exchange (ETDEWEB)

Reus, Astrid A.; Usta, Mustafa [TNO Triskelion BV, Utrechtseweg 48, 3704 HE, Zeist (Netherlands); Krul, Cyrille A.M., E-mail: cyrille.krul@tno.nl [TNO, Utrechtseweg 48, 3704 HE Zeist (Netherlands)

2012-06-01

As a result of the chemical legislation concerning the registration, evaluation, authorization and restriction of chemicals (REACH), and the Seventh Amendment to the Cosmetics Directive, which prohibits animal testing in Europe for cosmetics, alternative methods for safety evaluation of chemicals are urgently needed. Current in vitro genotoxicity assays are not sufficiently predictive for the in vivo situation, resulting in an unacceptably high number of misleading positives. For many chemicals and ingredients of personal care products the skin is the first site of contact, but there are no in vitro genotoxicity assays available in the skin for additional evaluation of positive or equivocal responses observed in regulatory in vitro genotoxicity assays. In the present study ex vivo human skin tissue obtained from surgery was used for genotoxicity evaluation of chemicals by using the comet assay. Fresh ex vivo human skin tissue was cultured in an air–liquid interface and topically exposed to 20 chemicals, including true positive, misleading positive and true negative genotoxins. Based on the results obtained in the present study, the sensitivity, specificity and accuracy of the ex vivo skin comet assay to predict in vivo genotoxicity were 89%, 90% and 89%, respectively. Donor and experimental variability were mainly reflected in the magnitude of the response and not the difference between the presence and absence of a genotoxic response. The present study indicates that human skin obtained from surgery is a promising and robust model for safety evaluation of chemicals that are in direct contact with the skin. -- Highlights: ► We use human skin obtained from surgery for genotoxicity evaluation of chemicals. ► We use the comet assay as parameter for genotoxicity in ex vivo human skin. ► Sensitivity, specificity and accuracy to predict in vivo genotoxins are determined. ► Sensitivity, specificity and accuracy are 89%, 90% and 90%, respectively. ► The method

The use of ex vivo human skin tissue for genotoxicity testing

International Nuclear Information System (INIS)

Reus, Astrid A.; Usta, Mustafa; Krul, Cyrille A.M.

2012-01-01

As a result of the chemical legislation concerning the registration, evaluation, authorization and restriction of chemicals (REACH), and the Seventh Amendment to the Cosmetics Directive, which prohibits animal testing in Europe for cosmetics, alternative methods for safety evaluation of chemicals are urgently needed. Current in vitro genotoxicity assays are not sufficiently predictive for the in vivo situation, resulting in an unacceptably high number of misleading positives. For many chemicals and ingredients of personal care products the skin is the first site of contact, but there are no in vitro genotoxicity assays available in the skin for additional evaluation of positive or equivocal responses observed in regulatory in vitro genotoxicity assays. In the present study ex vivo human skin tissue obtained from surgery was used for genotoxicity evaluation of chemicals by using the comet assay. Fresh ex vivo human skin tissue was cultured in an air–liquid interface and topically exposed to 20 chemicals, including true positive, misleading positive and true negative genotoxins. Based on the results obtained in the present study, the sensitivity, specificity and accuracy of the ex vivo skin comet assay to predict in vivo genotoxicity were 89%, 90% and 89%, respectively. Donor and experimental variability were mainly reflected in the magnitude of the response and not the difference between the presence and absence of a genotoxic response. The present study indicates that human skin obtained from surgery is a promising and robust model for safety evaluation of chemicals that are in direct contact with the skin. -- Highlights: ► We use human skin obtained from surgery for genotoxicity evaluation of chemicals. ► We use the comet assay as parameter for genotoxicity in ex vivo human skin. ► Sensitivity, specificity and accuracy to predict in vivo genotoxins are determined. ► Sensitivity, specificity and accuracy are 89%, 90% and 90%, respectively. ► The method

Appreciating the image of God in all humanity: Towards a pastoral response to skin lightening as image enhancement to exit dark skin

Directory of Open Access Journals (Sweden)

Noah K. Tenai

2016-05-01

Full Text Available The practice of skin lightening is prevalent amongst dark-skinned people globally. Various current studies that map this practice and that seek motivations behind the practice are examined. It is observed that through shrewd marketing, dark-skinned people are offered a promise of a better quality of life, obtained by a lighter skin, through the use of skin lighteners. In spite of the severe health risks involved, the promise is ostensibly irresistible to some dark-skinned persons. A pastoral response is offered that affirms the full personhood and complete humanity of dark-skinned people as fully human and whole in their dark skins. Keywords: Skin lightening, Dark skin, Image of God

Fetal cardiology

International Nuclear Information System (INIS)

Meijboom, E.J.; Rijsterborgh, N.; Bom, N.

1986-01-01

Doppler echocardiography makes it possible to diagnose congenital heart disease in early pregnancy. It allows us to study the anatomical configuration of the fetal heart, and additionally, to evaluate the physiological conditions of the fetus. Evaluation of the direction, velocity, wave form pattern, and quantification of blood flow at the various sites in the fetal heart helps us to assess the characteristics of the fetal circulation and condition of the fetal heart. In order to use this technique in pathological situations, an initial study of the developing normal human fetal circulation was necessary. The authors studied 34 uncomplicated pregnancies by serial Doppler echocardiography. The studies were performed every 4 weeks from 16-weeks gestation to term. The pulsed Doppler sector scanner provided cardiac cross-sectional images, mitral and tricuspid blood velocities were obtained from apical four-chamber views. Angle corrected maximal and mean temporal velocities were calculated by digitizing the Doppler frequency shift recording on a graphic tablet computed with a minicomputer. The angle between the Doppler interrogation beam and the direction of blood flow was kept as small as possible in order to minimize the error

Transport and Biodistribution of Dendrimers Across Human Fetal Membranes: Implications for Intravaginal Administration of Dendrimers

Science.gov (United States)

Menjoge, Anupa R.; Navath, Raghavendra S.; Asad, Abbas; Kannan, Sujatha; Kim, Chong Jai; Romero, Roberto; Kannan, Rangaramanujam M.

2010-01-01

Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly(amidoamine)) dendrimers, across human fetal membrane (using a side-by-side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size~ 400 Da) and fluorophore-tagged G4-PAMAM dendrimers (~ 16 kDa). The fluorophore-tagged G4-PAMAM dendrimers were synthesized and characterized using 1H NMR, MALDI TOF-MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a five hour period, the dendrimer transport across all the three membranes was less than transport of FITC was relatively fast with as much as 49% transport across the amnion. The permeability of FITC (7.9 × 10-7 cm2/s) through the chorioamnion was 7-fold higher than that of the dendrimer (5.8 × 10-8 cm2/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5 to 4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be

STEREOLOGICAL STUDIES ON FETAL VASCULAR DEVELOPMENT IN HUMAN PLACENTAL VILLI

Directory of Open Access Journals (Sweden)

Terry M Mayhew

2011-05-01

Full Text Available In human pregnancy, fetal well-being depends on the development of placental villi and the creation and maintenance of fetal microvessels within them. The aim of this study was to define stereological measures of the growth, capillarization and maturation of villi and of fetoplacental angiogenesis and capillary remodelling. Placentas were collected at 12-41 weeks of gestation and assigned to six age groups spanning equal age ranges. Tissue samples were randomised for position and orientation. Overall growth of peripheral (intermediate and terminal villi and their capillaries was evaluated using total volumes, surface areas and lengths. Measures of villous capillarization comprised capillary volume, surface and length densities and capillary:villus surface and length ratios. Size and shape remodelling of villi and capillaries was assessed using mean cross-sectional areas, perimeters and shape coefficients (perimeter2/area. Group comparisons were drawn by analysis of variance. Villous and capillary volumes, surfaces and lengths increased significantly throughout gestation. Villous maturation involved phasic (capillary:villus surface and length ratios or progressive (volume, surface and length densities increases in indices of villous capillarization. It also involved isomorphic thinning (cross-sectional areas and perimeters declined but shape coefficients did not alter. In contrast, growth of capillaries did not involve changes in luminal areas or perimeters. The results show that villous growth and fetal angiogenesis involve increases in overall length rather than calibre and that villous differentiation involves increased capillarization. Although they do not distinguish between increases in the lengths versus numbers of capillary segments, other studies have shown that capillaries switch from branching to non-branching angiogenesis during gestation. Combined with maintenance of capillary calibres, these processes will contribute to the reduced

Essential role of RAB27A in determining constitutive human skin color.

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Yasuko Yoshida-Amano

Full Text Available Human skin color is predominantly determined by melanin produced in melanosomes within melanocytes and subsequently distributed to keratinocytes. There are many studies that have proposed mechanisms underlying ethnic skin color variations, whereas the processes involved from melanin synthesis in melanocytes to the transfer of melanosomes to keratinocytes are common among humans. Apart from the activities in the melanogenic rate-limiting enzyme, tyrosinase, in melanocytes and the amounts and distribution patterns of melanosomes in keratinocytes, the abilities of the actin-associated factors in charge of melanosome transport within melanocytes also regulate pigmentation. Mutations in genes encoding melanosome transport-related molecules, such as MYO5A, RAB27A and SLAC-2A, have been reported to cause a human pigmentary disease known as Griscelli syndrome, which is associated with diluted skin and hair color. Thus we hypothesized that process might play a role in modulating skin color variations. To address that hypothesis, the correlations of expression of RAB27A and its specific effector, SLAC2-A, to melanogenic ability were evaluated in comparison with tyrosinase, using human melanocytes derived from 19 individuals of varying skin types. Following the finding of the highest correlation in RAB27A expression to the melanogenic ability, darkly-pigmented melanocytes with significantly higher RAB27A expression were found to transfer significantly more melanosomes to keratinocytes than lightly-pigmented melanocytes in co-culture and in human skin substitutes (HSSs in vivo, resulting in darker skin color in concert with the difference observed in African-descent and Caucasian skins. Additionally, RAB27A knockdown by a lentivirus-derived shRNA in melanocytes concomitantly demonstrated a significantly reduced number of transferred melanosomes to keratinocytes in co-culture and a significantly diminished epidermal melanin content skin color intensity (�

Targeted sequencing of clade-specific markers from skin microbiomes for forensic human identification.

Science.gov (United States)

Schmedes, Sarah E; Woerner, August E; Novroski, Nicole M M; Wendt, Frank R; King, Jonathan L; Stephens, Kathryn M; Budowle, Bruce

2018-01-01

The human skin microbiome is comprised of diverse communities of bacterial, eukaryotic, and viral taxa and contributes millions of additional genes to the repertoire of human genes, affecting human metabolism and immune response. Numerous genetic and environmental factors influence the microbiome composition and as such contribute to individual-specific microbial signatures which may be exploited for forensic applications. Previous studies have demonstrated the potential to associate skin microbial profiles collected from touched items to their individual owner, mainly using unsupervised methods from samples collected over short time intervals. Those studies utilize either targeted 16S rRNA or shotgun metagenomic sequencing to characterize skin microbiomes; however, these approaches have limited species and strain resolution and susceptibility to stochastic effects, respectively. Clade-specific markers from the skin microbiome, using supervised learning, can predict individual identity using skin microbiomes from their respective donors with high accuracy. In this study the hidSkinPlex is presented, a novel targeted sequencing method using skin microbiome markers developed for human identification. The hidSkinPlex (comprised of 286 bacterial (and phage) family-, genus-, species-, and subspecies-level markers), initially was evaluated on three bacterial control samples represented in the panel (i.e., Propionibacterium acnes, Propionibacterium granulosum, and Rothia dentocariosa) to assess the performance of the multiplex. The hidSkinPlex was further evaluated for prediction purposes. The hidSkinPlex markers were used to attribute skin microbiomes collected from eight individuals from three body sites (i.e., foot (Fb), hand (Hp) and manubrium (Mb)) to their host donor. Supervised learning, specifically regularized multinomial logistic regression and 1-nearest-neighbor classification were used to classify skin microbiomes to their hosts with up to 92% (Fb), 96% (Mb

Chemokine Involvement in Fetal and Adult Wound Healing

Science.gov (United States)

Balaji, Swathi; Watson, Carey L.; Ranjan, Rajeev; King, Alice; Bollyky, Paul L.; Keswani, Sundeep G.

2015-01-01

Significance: Fetal wounds heal with a regenerative phenotype that is indistinguishable from surrounding skin with restored skin integrity. Compared to this benchmark, all postnatal wound healing is impaired and characterized by scar formation. The biologic basis of the fetal regenerative phenotype can serve as a roadmap to recapitulating regenerative repair in adult wounds. Reduced leukocyte infiltration, likely mediated, in part, through changes in the chemokine milieu, is a fundamental feature of fetal wound healing. Recent Advances: The contributions of chemokines to wound healing are a topic of active investigation. Recent discoveries have opened the possibility of targeting chemokines therapeutically to treat disease processes and improve healing capability, including the possibility of achieving a scarless phenotype in postnatal wounds. Critical Issues: Successful wound healing is a complex process, in which there is a significant interplay between multiple cell types, signaling molecules, growth factors, and extracellular matrix. Chemokines play a crucial role in this interplay and have been shown to have different effects in various stages of the healing process. Understanding how these chemokines are locally produced and regulated during wound healing and how the chemokine milieu differs in fetal versus postnatal wounds may help us identify ways in which we can target chemokine pathways. Future Directions: Further studies on the role of chemokines and their role in the healing process will greatly advance the potential for using these molecules as therapeutic targets. PMID:26543680

Central vagal sensory and motor connections: human embryonic and fetal development.

Science.gov (United States)

Cheng, Gang; Zhou, Xiangtian; Qu, Jia; Ashwell, Ken W S; Paxinos, G

2004-07-30

The embryonic and fetal development of the nuclear components and pathways of vagal sensorimotor circuits in the human has been studied using Nissl staining and carbocyanine dye tracing techniques. Eight fetal brains ranging from 8 to 28 weeks of development had DiI (1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate) inserted into either the thoracic vagus nerve at the level of the sternal angle (two specimens of 8 and 9 weeks of gestation) or into vagal rootlets at the surface of the medulla (at all other ages), while a further five were used for study of cytoarchitectural development. The first central labeling resulting from peripheral application of DiI to the thoracic vagus nerve was seen at 8 weeks. By 9 weeks, labeled bipolar cells at the ventricular surface around the sulcus limitans (sl) were seen after DiI application to the thoracic vagus nerve. Subnuclear organization as revealed by both Nissl staining and carbocyanine dye tracing was found to be advanced at a relatively early fetal age, with afferent segregation in the medial Sol apparent at 13 weeks and subnuclear organization of efferent magnocellular divisions of dorsal motor nucleus of vagus nerve noticeable at the same stage. The results of the present study also confirm that vagal afferents are distributed to the dorsomedial subnuclei of the human nucleus of the solitary tract, with particular concentrations of afferent axons in the gelatinosus subnucleus. These vagal afferents appeared to have a restricted zone of termination from quite early in development (13 weeks) suggesting that there is no initial exuberance in the termination field of vagal afferents in the developing human nucleus of the solitary tract. On the other hand, the first suggestion of afferents invading 10N from the medial Sol was not seen until 20 weeks and was not well developed until 24 weeks, suggesting that direct monosynaptic connections between the sensory and effector components of the vagal

Confocal laser scanning microscopy to estimate nanoparticles' human skin penetration in vitro.

Science.gov (United States)

Zou, Ying; Celli, Anna; Zhu, Hanjiang; Elmahdy, Akram; Cao, Yachao; Hui, Xiaoying; Maibach, Howard

2017-01-01

With rapid development of nanotechnology, there is increasing interest in nanoparticle (NP) application and its safety and efficacy on human skin. In this study, we utilized confocal laser scanning microscopy to estimate NP skin penetration. Three different-sized polystyrene NPs marked with red fluorescence were applied to human skin, and Calcium Green 5N was used as a counterstain. Dimethyl sulfoxide (DMSO) and ethanol were used as alternative vehicles for NPs. Tape stripping was utilized as a barrier-damaged skin model. Skin biopsies dosed with NPs were incubated at 4°C or 37°C for 24 hours and imaged using confocal laser scanning microscopy. NPs were localized in the stratum corneum (SC) and hair follicles without penetrating the epidermis/dermis. Barrier alteration with tape stripping and change in incubation temperature did not induce deeper penetration. DMSO enhanced NP SC penetration but ethanol did not. Except with DMSO vehicle, these hydrolyzed polystyrene NPs did not penetrate intact or barrier-damaged human "viable" epidermis. For further clinical relevance, in vivo human skin studies and more sensitive analytic chemical methodology are suggested.

RNA isolation for transcriptomics of human and mouse small skin biopsies

Directory of Open Access Journals (Sweden)

Breit Timo M

2011-10-01

Full Text Available Abstract Background Isolation of RNA from skin biopsies presents a challenge, due to the tough nature of skin tissue and a high presence of RNases. As we lacked the dedicated equipment, i.e. homogenizer or bead-beater, needed for the available RNA from skin isolation methods, we adapted and tested our zebrafish single-embryo RNA-isolation protocol for RNA isolation from skin punch biopsies. Findings We tested our new RNA-isolation protocol in two experiments: a large-scale study with 97 human skin samples, and a small study with 16 mouse skin samples. Human skin was sampled with 4.0 mm biopsy punches and for the mouse skin different punch diameter sizes were tested; 1.0, 1.5, 2.0, and 2.5 mm. The average RNA yield in human samples was 1.5 μg with an average RNA quality RIN value of 8.1. For the mouse biopsies, the average RNA yield was 2.4 μg with an average RIN value of 7.5. For 96% of the human biopsies and 100% of the mouse biopsies we obtained enough high-quality RNA. The RNA samples were successfully tested in a transcriptomics analysis using the Affymetrix and Roche NimbleGen platforms. Conclusions Using our new RNA-isolation protocol, we were able to consistently isolate high-quality RNA, which is apt for further transcriptomics analysis. Furthermore, this method is already useable on biopsy material obtained with a punch diameter as small as 1.5 mm.

Antimicrobial activity of a new intact skin antisepsis formulation.

Science.gov (United States)

Russo, Antonello; Viotti, Pier Luigi; Vitali, Matteo; Clementi, Massimo

2003-04-01

Different antiseptic formulations have shown limitations when applied to disinfecting intact skin, notably short-term tolerability and/or efficacy. The purpose of this study was optimizing a new antiseptic formulation specifically targeted at intact skin disinfection and evaluating its in vitro microbicidal activity and in vivo efficacy. The biocidal properties of the antiseptic solution containing 0.5% chloramine-T diluted in 50% isopropyl alcohol (Cloral; Eurospital SpA Trieste, Italy) were measured in vitro versus gram-positive-, gram-negative-, and acid-alcohol-resistant germs and fungi with standard suspension tests in the presence of fetal bovine serum. Virus-inhibiting activity was evaluated in vitro against human cytomegalovirus, herpes simplex virus, poliovirus, hepatitis B virus, and hepatitis C virus. Tests used different methods for the different biologic and in vitro replication capacity of these human viruses. Lastly, Cloral tolerability and skin colonization retardation efficacy after disinfection were studied in vivo. The antiseptic under review showed fast and sustained antimicrobial activity. The efficacy of Cloral against clinically important bacterial and viral pathogens and fungi was highlighted under the experimental conditions described in this article. Finally, microbial regrowth lag and no side effects were documented in vivo after disinfection of 11 volunteers. A stable chloramine-T solution in isopropyl alcohol may be suggested for intact skin antisepsis.

Comparison of rat epidermal keratinocyte organotypic culture (ROC) with intact human skin

DEFF Research Database (Denmark)

Pappinen, Sari; Hermansson, Martin; Kuntsche, Judith

2008-01-01

study was to compare the stratum corneum lipid content of ROC with the corresponding material from human skin. The lipid composition was determined by thin-layer chromatography (TLC) and mass-spectrometry, and the thermal phase transitions of stratum corneum were studied by differential scanning...... calorimetry (DSC). All major lipid classes of the stratum corneum were present in ROC in a similar ratio as found in human stratum corneum. Compared to human skin, the level of non-hydroxyacid-sphingosine ceramide (NS) was increased in ROC, while alpha-hydroxyacid-phytosphingosine ceramide (AP) and non...... compared to human skin, in agreement with the results from DSC. ROC underwent a lipid lamellar order to disorder transition (T2) at a slightly lower temperature (68 degrees C) than human skin (74 degrees C). These differences in stratum corneum lipid composition and the thermal phase transitions may...

Resveratrol inhibits steroidogenesis in human fetal adrenocortical cells at the end of first trimester

DEFF Research Database (Denmark)

Savchuk, Iuliia; Morvan, Marie-Line; Søeborg, Tue

2017-01-01

SCOPE: Resveratrol has a diverse array of healthful effects on metabolic parameters in different experimental paradigms but has also potential to inhibit steroidogenesis in rodent adrenals. The aim of the present study was to characterize the effects of resveratrol on human fetal adrenal...... steroidogenesis at gestational weeks (GW) 9-12. METHODS AND RESULTS: Adrenals from aborted fetuses (GW10-12) were used to prepare primary cultures of human fetal adrenocortical cells (HFAC). HFAC were treated in the presence or absence of ACTH (10 ng/ml) with or without resveratrol (10 μM) for 24 hours....... The production of steroids by HFAC was analyzed by gas and liquid chromatography coupled to tandem/mass spectrometry. The expression of steroidogenic enzymes at GW 9-12 was quantified by automated Western blotting. We observed that resveratrol significantly suppressed synthesis of dehydroepiandrosterone (DHEA...

A Brief Account of the Discovery of the Fetal/Placental Unit for Estrogen Production in Equine and Human Pregnancies: Relation to Human Medicine.

Science.gov (United States)

Raeside, James I

2017-09-01

The role of steroids in human medicine is well recognized, but the major contributions made by the large domestic animals as a source of material in the discovery, isolation, and determination of the structure of the steroid hormones is less well appreciated. After a brief reminder of the early efforts to obtain a reliable source of steroids for clinical use, the narrative here is to outline one example where success was ultimately achieved for estrogen replacement therapy. Whereas knowledge of the high concentrations of estrogens in urine of pregnant women and mares dates from the late 1920s, it was not until the 1940s that the latter was shown to be a practical source. Initially, the placenta was held to be responsible, but the involvement of the fetus in each case was eventually established. The remarkable enlargement of the human fetal adrenal glands and the fetal gonads in the horse, with characteristic features of steroid secreting tissues, suggested their participation. Ultimately, it was 16-hydroxylation by the fetal liver that resulted in estriol being the major estrogen type, by far, in late human pregnancy. In the mare, the pattern of estrogen production reflected that of the growth and later regression of the fetal gonads. The characteristic production ring-B, unsaturated estrogens in the mare is derived from an alternative pathway involving retention of the additional double bond in the biosynthesis of equilin.

Multiphoton spectroscopy of human skin in vivo

Science.gov (United States)

Breunig, Hans G.; Weinigel, Martin; König, Karsten

2012-03-01

In vivo multiphoton-intensity images and emission spectra of human skin are reported. Optical sections from different depths of the epidermis and dermis have been measured with near-infrared laser-pulse excitation. While the intensity images reveal information on the morphology, the spectra show emission characteristics of main endogenous skin fluorophores like keratin, NAD(P)H, melanin, elastin and collagen as well as of second harmonic generation induced by the excitation-light interaction with the dermal collagen network.

Low power cw-laser signatures on human skin

International Nuclear Information System (INIS)

Lihachev, A; Lesinsh, J; Jakovels, D; Spigulis, J

2011-01-01

Impact of cw laser radiation on autofluorescence features of human skin is studied. Two methods of autofluorescence detection are applied: the spectral method with the use of a fibreoptic probe and spectrometer for determining the autofluorescence recovery kinetics at a fixed skin area of ∼12 mm 2 , and the multispectral visualisation method with the use of a multispectral imaging camera for visualising long-term autofluorescence changes in a skin area of ∼4 cm 2 . The autofluorescence recovery kinetics after preliminary laser irradiation is determined. Skin autofluorescence images with visible long-term changes - 'signatures' of low power laser treatment are acquired. (application of lasers and laser-optical methods in life sciences)

Human Skin Is the Largest Epithelial Surface for Interaction with Microbes.

Science.gov (United States)

Gallo, Richard L

2017-06-01

Human skin contains an abundant and diverse population of microbial organisms. Many of these microbes inhabit follicular structures of the skin. Furthermore, numerous studies have shown that the interaction of some members of the skin microbiome with host cells will result in changes in cell function. However, estimates of the potential for the microbiome to influence human health through skin have ignored the inner follicular surface, and therefore vastly underestimated the potential of the skin microbiome to have a systemic effect on the human body. By calculating the surface area of follicular and the interfollicular epithelial surface it is shown that skin provides a vast interface for interactions with the microbiome. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Going skin deep: A direct comparison of penetration potential of lipid-based nanovesicles on the isolated perfused human skin flap model.

Science.gov (United States)

Ternullo, Selenia; de Weerd, Louis; Holsæter, Ann Mari; Flaten, Gøril Eide; Škalko-Basnet, Nataša

2017-12-01

Phospholipid-based nanocarriers are attractive drug carriers for improved local skin therapy. In the present study, the recently developed isolated perfused human skin flap (IPHSF) model was used to directly compare the skin penetration enhancing potential of the three commonly used nanocarriers, namely conventional liposomes (CLs), deformable liposomes (DLs) and solid lipid nanoparticles (SLNs). Two fluorescent markers, calcein (hydrophilic) or rhodamine (lipophilic), were incorporated individually in the three nanosystems. The nanocarrier size ranged between 200 and 300nm; the surface charge and entrapment efficiency for both markers were dependent on the lipid composition and the employed surfactant. Both carrier-associated markers could not penetrate the full thickness human skin, confirming their suitability for dermal drug delivery. CLs exhibited higher retention of both markers on the skin surface compared to DLs and SLNs, indicating a depo formation. DLs and SLNs enabled the deeper penetration of the two markers into the skin layers. In vitro and ex vivo skin penetration studies performed on the cellophane membrane and full thickness pig/human skin, respectively, confirmed the findings. In conclusion, efficient dermal drug delivery can be achieved by optimization of a lipid nanocarrier on the suitable skin-mimicking model to assure system's accumulation in the targeted skin layer. Copyright © 2017 Elsevier B.V. All rights reserved.

Human Wharton's jelly mesenchymal stem cells promote skin wound healing through paracrine signaling.

Science.gov (United States)

Arno, Anna I; Amini-Nik, Saeid; Blit, Patrick H; Al-Shehab, Mohammed; Belo, Cassandra; Herer, Elaine; Tien, Col Homer; Jeschke, Marc G

2014-02-24

The prevalence of nonhealing wounds is predicted to increase due to the growing aging population. Despite the use of novel skin substitutes and wound dressings, poorly vascularized wound niches impair wound repair. Mesenchymal stem cells (MSCs) have been reported to provide paracrine signals to promote wound healing, but the effect of human Wharton's jelly-derived MSCs (WJ-MSCs) has not yet been described in human normal skin. Human WJ-MSCs and normal skin fibroblasts were isolated from donated umbilical cords and normal adult human skin. Fibroblasts were treated with WJ-MSC-conditioned medium (WJ-MSC-CM) or nonconditioned medium. Expression of genes involved in re-epithelialization (transforming growth factor-β2), neovascularization (hypoxia-inducible factor-1α) and fibroproliferation (plasminogen activator inhibitor-1) was upregulated in WJ-MSC-CM-treated fibroblasts (P≤0.05). WJ-MSC-CM enhanced normal skin fibroblast proliferation (P≤0.001) and migration (P≤0.05), and promoted wound healing in an excisional full-thickness skin murine model. Under our experimental conditions, WJ-MSCs enhanced skin wound healing in an in vivo mouse model.

Deposition of contaminant aerosol on human skin

DEFF Research Database (Denmark)

Andersson, Kasper Grann; Roed, Jørn; Byrne, M.A.

2006-01-01

Over recent years, it has been established that deposition of various types of pollutant aerosols (e.g., radioactive) on human skin can have serious deleterious effects on health. However. only few investigations in the past have been devoted to measurement of deposition velocities on skin...... of particles of the potentially problematic sizes. An experimental programme has shown the deposition velocities on skin of particles in the ca. 0.5-5 mu m AMAD range to be high and generally associated with great variations. A series of investigations have been made to identify some of the factors that lead...... to this variation. Part of the variation was found to be caused by differences between individuals, whereas another part was found to be related to environmental factors, The identification of major influences on skin contaminant deposition is important in estimating health effects as well as in identifying means...

In an in-vitro model using human fetal membranes, 17-α hydroxyprogesterone caproate is not an optimal progestogen for inhibition of fetal membrane weakening.

Science.gov (United States)

Kumar, Deepak; Moore, Robert M; Mercer, Brian M; Mansour, Joseph M; Mesiano, Sam; Schatz, Frederick; Lockwood, Charles J; Moore, John J

2017-12-01

The progestogen 17-α hydroxyprogesterone caproate (17-OHPC) is 1 of only 2 agents recommended for clinical use in the prevention of spontaneous preterm delivery, and studies of its efficacy have been conflicting. We have developed an in-vitro model to study the fetal membrane weakening process that leads to rupture in preterm premature rupture of the fetal membranes (pPROM). Inflammation/infection associated with tumor necrosis factor-α (TNF-α) induction and decidual bleeding/abruption associated thrombin release are leading causes of preterm premature rupture of the fetal membranes. Both agents (TNF-α and thrombin) cause fetal membrane weakening in the model system. Furthermore, granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical intermediate for both TNF-α and thrombin-induced fetal membrane weakening. In a previous report, we demonstrated that 3 progestogens, progesterone, 17-alpha hydroxyprogesterone (17-OHP), and medroxyprogesterone acetate (MPA), each inhibit both TNF-α- and thrombin-induced fetal membrane weakening at 2 distinct points of the fetal membrane weakening pathway. Each block both the production of and the downstream action of the critical intermediate granulocyte-macrophage colony-stimulating factor. The objective of the study was to characterize the inhibitory effects of 17-OHPC on TNF-α- and thrombin-induced fetal membrane weakening in vitro. Full-thickness human fetal membrane fragments from uncomplicated term repeat cesarean deliveries were mounted in 2.5 cm Transwell inserts and cultured with/without 17-alpha hydroxyprogesterone caproate (10 -9 to 10 -7 M). After 24 hours, medium (supernatant) was removed and replaced with/without the addition of tumor necrosis factor-alpha (20 ng/mL) or thrombin (10 U/mL) or granulocyte-macrophage colony-stimulating factor (200 ng/mL). After 48 hours of culture, medium from the maternal side compartment of the model was assayed for granulocyte-macrophage colony

Confocal laser scanning microscopy to estimate nanoparticles’ human skin penetration in vitro

Science.gov (United States)

Elmahdy, Akram; Cao, Yachao; Hui, Xiaoying; Maibach, Howard

2017-01-01

Objective With rapid development of nanotechnology, there is increasing interest in nanoparticle (NP) application and its safety and efficacy on human skin. In this study, we utilized confocal laser scanning microscopy to estimate NP skin penetration. Methods Three different-sized polystyrene NPs marked with red fluorescence were applied to human skin, and Calcium Green 5N was used as a counterstain. Dimethyl sulfoxide (DMSO) and ethanol were used as alternative vehicles for NPs. Tape stripping was utilized as a barrier-damaged skin model. Skin biopsies dosed with NPs were incubated at 4°C or 37°C for 24 hours and imaged using confocal laser scanning microscopy. Results NPs were localized in the stratum corneum (SC) and hair follicles without penetrating the epidermis/dermis. Barrier alteration with tape stripping and change in incubation temperature did not induce deeper penetration. DMSO enhanced NP SC penetration but ethanol did not. Conclusion Except with DMSO vehicle, these hydrolyzed polystyrene NPs did not penetrate intact or barrier-damaged human “viable” epidermis. For further clinical relevance, in vivo human skin studies and more sensitive analytic chemical methodology are suggested. PMID:29184403

Transport and biodistribution of dendrimers across human fetal membranes: implications for intravaginal administration of dendrimer-drug conjugates.

Science.gov (United States)

Menjoge, Anupa R; Navath, Raghavendra S; Asad, Abbas; Kannan, Sujatha; Kim, Chong J; Romero, Roberto; Kannan, Rangaramanujam M

2010-06-01

Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly (amidoamine)) dendrimers, across human fetal membrane (using a side by side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size approximately 400 Da) and fluorophore-tagged G(4)-PAMAM dendrimers (approximately 16 kDa). The fluorophore-tagged G(4)-PAMAM dendrimers were synthesized and characterized using (1)H NMR, MALDI TOF MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a 5 h period, the dendrimer transport across all the three membranes was less than dendrimer (5.8 x 10(-8) cm(2)/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5-4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be restricted across the human fetal membranes when administered topically by intravaginal route, suggesting new ways of selectively delivering therapeutics to the mother

Repetitive reduction of uterine blood flow and its influence on fetal transcutaneous PO2 and cardiovascular variables.

Science.gov (United States)

Jensen, A; Künzel, W; Kastendieck, E

1985-04-01

The influence of repeated asphyxia on fetal transcutaneous PO2, relative local skin perfusion, heart rate, blood gases and pH was investigated in 15 experiments on 8 acutely instrumented sheep fetuses in utero between 125 and 145 days gestation (term is 147 days). Uterine blood flow was intermittently arrested (11 times within 33 min) by intra-vascular maternal aortic occlusion, exposing the fetuses to repeated episodes of asphyxia of 30 (n = 3), 60 (n = 9) and 90 (n = 3) s duration. The fetal transcutaneous PO2 fell as the duration of asphyxia (2 alpha less than 0.01), heart rate deceleration area (2 alpha less than 0.01) and acidaemia (2 alpha less than 0.01) increased. With decreasing skin perfusion, which was dependent on the duration of asphyxia (2 alpha less than 0.001) and acidaemia (2 alpha less than 0.001), a discrepancy developed between transcutaneous and arterial PO2. The increase (delta) in transcutaneous-arterial PO2 difference was related linearly to the duration of asphyxia (2 alpha less than 0.01), the mean haemoglobin oxygen saturation (2 alpha less than 0.001), acidaemia (2 alpha less than 0.001) and relative local skin flow (2 alpha less than 0.05). It was highest after severe episodes of asphyxia (90 s), when O2 saturation, skin blood flow and arterial blood pH values were low. Fetal heart rate deceleration area was only correlated with the cutaneous-arterial PO2 difference when the mean fetal haemoglobin oxygen saturation was below 35%. Thus, a discrimination of heart rate decelerations that are significant for the fetus seems to be possible, when associated with low transcutaneous PO2 values. We conclude that in the sheep fetus transcutaneous PO2 measurements during repeated asphyxial episodes yield information on fetal oxygenation and on the skin vasomotor response.

Characterization of ionizing radiation effects on human skin allografts

International Nuclear Information System (INIS)

Bourroul, Selma Cecilia

2004-01-01

The skin has a fundamental role in the viability of the human body. In the cases of extensive wounds, allograft skin provides an alternative to cover temporarily the damaged areas. After donor screening and preservation in glycerol (above 85%), the skin can be stored in the Skin Banks. The glycerol at this concentration has a bacteriostatic effect after certain time of preservation. On the other hand, skin sterilization by ionizing radiation may reduces the quarantine period for transplantation in patients and its safety is considered excellent. The objectives of this work were to establish procedures using two sources of ionizing radiation for sterilization of human skin allograft, and to evaluate the skin after gamma and electron beam irradiation. The analysis of stress-strain intended to verify possible effects of the radiation on the structure of preserved grafts. Skin samples were submitted to doses of 25 kGy and 50 kGy in an irradiator of 60 Co and in an electron beam accelerator. Morphology and ultra-structure studies were also accomplished. The samples irradiated with a dose of 25 kGy seemed to maintain the bio mechanic characteristics. The gamma irradiated samples with a dose of 50 kGy and submitted to an electron beam at doses of 25 kGy and 50 kGy presented significant differences in the values of the elasticity modulus, in relation to the control. The analysis of the ultramicrographies revealed modifications in the structure and alterations in the pattern of collagen fibrils periodicity of the irradiated samples. (author)

Births and deaths including fetal deaths

Data.gov (United States)

U.S. Department of Health & Human Services — Access to a variety of United States birth and death files including fetal deaths: Birth Files, 1968-2009; 1995-2005; Fetal death file, 1982-2005; Mortality files,...

Fermentation of Propionibacterium acnes, a commensal bacterium in the human skin microbiome, as skin probiotics against methicillin-resistant Staphylococcus aureus.

Directory of Open Access Journals (Sweden)

Muya Shu

Full Text Available Bacterial interference creates an ecological competition between commensal and pathogenic bacteria. Through fermentation of milk with gut-friendly bacteria, yogurt is an excellent aid to balance the bacteriological ecosystem in the human intestine. Here, we demonstrate that fermentation of glycerol with Propionibacterium acnes (P. acnes, a skin commensal bacterium, can function as a skin probiotic for in vitro and in vivo growth suppression of USA300, the most prevalent community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA. We also promote the notion that inappropriate use of antibiotics may eliminate the skin commensals, making it more difficult to fight pathogen infection. This study warrants further investigation to better understand the role of fermentation of skin commensals in infectious disease and the importance of the human skin microbiome in skin health.

Cutaneous in vivo metabolism of topical lidocaine formulation in human skin

DEFF Research Database (Denmark)

Rolsted, K; Benfeldt, E; Kissmeyer, A-M

2009-01-01

Little is known about the metabolising capacity of the human skin in relation to topically applied drugs and formulations. We chose lidocaine as a model compound since the metabolic pathways are well known from studies concerning hepatic metabolism following systemic drug administration. However......, the enzymes involved are also expressed in the skin. Hence, the aim of the current study was to investigate the extent of the cutaneous in vivo metabolism of topically applied lidocaine in human volunteers. A dose of 5 mg/cm(2) of Xylocaine(R) (5% lidocaine) ointment was applied onto the buttock skin...... of the volunteers. After 2 h, residual formulation was removed, and two 4-mm punch biopsies were taken from each volunteer. The quantity of lidocaine extracted from the skin samples (epidermis + dermis) was 109 +/- 43 ng/mm(2) skin. One metabolite (monoethylglycine xylidide, MEGX) was detected in skin from 7...

Distribution of 131I-labeled recombinant human erythropoietin in maternal and fetal organs following intravenous administration in pregnant rats

International Nuclear Information System (INIS)

Yilmaz, O.; Lambrecht, F.Y.; Durkan, K.; Gokmen, N.; Erbayraktar, S.

2007-01-01

The aim of the present study was to demonstrate the possible transplacental transmission of 131 I labeled recombinant human erythropoietin ( 131 I-rh-EPO) in pregnant rats and its distribution through maternal and fetal organs. Six Wistar Albino Rats in their pregnancy of 18 days were used 131 I labeled recombinant human erythropoietin (specific activity = 2.4 μCi/IU) was injected into the tail vein of rats. After 30 minutes labeled erythropoietin infusion maternal stomach, kidney, lung, liver, brain and heart as well as fetus were removed. Then, the same organs were removed from each fetus. Measuring weight of maternal and fetal organs as well as placenta were followed by radioactivity count via Cd(Te) detector. 131 I labeled recombinant human erythropoietin was found to be able to pass rat placenta and its distribution order in fetal organs was similar to those of maternal organs. Besides, as measurements were performed closer to cornu uteri, uptakes were decreasing in every fetus and its corresponding placenta. (author)

Reproducible pattern of microRNA in normal human skin

DEFF Research Database (Denmark)

Holst, Line; Kaczkowski, Bogumil; Gniadecki, Robert

2010-01-01

RNA expression pattern in normal human skin. Here we investigated miRNA expression profiles from skin biopsies of 8 healthy volunteers taken from sun protected and mildly photo damaged skin using the modified protocol for miRNA extraction. We were able to show a constant pattern of miRNA expression between......MicroRNAs (miRNAs) regulate cell growth, differentiation and apoptosis via specific targeting of messenger RNA (mRNA). Aberrant mRNA expression contributes to pathological processes such as carcinogenesis. To take advantage of miRNA profiling in skin disease it is essential to investigate mi...... different individuals. We did not find any significant differences in miRNA expression between sun protected and mildly photodamaged skin. These results may be valuable for future design of studies on miRNA expression in skin disease....

Reproducible pattern of microRNA in normal human skin

DEFF Research Database (Denmark)

Holst, Line; Kaczkowski, Bogumil; Gniadecki, Robert

2010-01-01

RNA expression pattern in normal human skin. Here we investigated miRNA expression profiles from skin biopsies of 8 healthy volunteers taken from sun protected and mildly photo damaged skin using the modified protocol for miRNA extraction. We were able to show a constant pattern of miRNA expression between...... different individuals. We did not find any significant differences in miRNA expression between sun protected and mildly photodamaged skin. These results may be valuable for future design of studies on miRNA expression in skin disease.......MicroRNAs (miRNAs) regulate cell growth, differentiation and apoptosis via specific targeting of messenger RNA (mRNA). Aberrant mRNA expression contributes to pathological processes such as carcinogenesis. To take advantage of miRNA profiling in skin disease it is essential to investigate mi...

Radiation absorbed dose to the human fetal thyroid

International Nuclear Information System (INIS)

Watson, E.E.

1992-01-01

The embryo/fetus is recognized to be particularly susceptible to damage from exposure to radiation. Many advisory groups have studied available information concerning radiation doses and radiation effects with the goal of reducing the risk to the embryo/fetus. Of particular interest are radioactive isotopes of iodine. Radioiodine taken into the body of a pregnant woman presents a possible hazard for the embryo/fetus. The fetal thyroid begins to concentrate iodine at about 13 weeks after conception and continues to do so throughout gestation. At term, the organic iodine concentration in the fetal blood is about 75% of that in the mother's blood. This paper presents a review the models that have been proposed for the calculation of the dose to the fetal thyroid from radioisotopes of iodine taken into the body of the pregnant woman as sodium iodide. A somewhat different model has been proposed, and estimates of the radiation dose to the fetal thyroid calculated from this model are given for each month of pregnancy from 123 I , 124 I , 125 I , and 131 I

Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells

Directory of Open Access Journals (Sweden)

Agneta Månsson-Broberg

2016-04-01

Full Text Available The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs has not been fully characterized. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts. Cells cultured on cardiac muscle laminin (LN-based substrata in combination with stimulation of the canonical Wnt/β-catenin pathway showed increased gene expression of ISL1, OCT4, KDR, and NKX2.5. The majority of cells stained positive for PDGFR-α, ISL1, and NKX2.5, and subpopulations also expressed the progenitor markers TBX18, KDR, c-KIT, and SSEA-1. Upon culture of the cardiac MSCs in differentiation media and on relevant LNs, portions of the cells differentiated into spontaneously beating cardiomyocytes, and endothelial and smooth muscle-like cells. Our protocol for large-scale culture of human fetal cardiac MSCs enables future exploration of the regenerative functions of these cells in the context of myocardial injury in vitro and in vivo.

Maternal methadone dosing schedule and fetal neurobehavior

Science.gov (United States)

Jansson, Lauren M.; DiPietro, Janet A.; Velez, Martha; Elko, Andrea; Knauer, Heather; Kivlighan, Katie T.

2008-01-01

Objective Daily methadone maintenance is the standard of care for opiate dependency during pregnancy. Previous research has indicated that single-dose maternal methadone administration significantly suppresses fetal neurobehaviors. The purpose of this study was to determine if split-dosing would have less impact on fetal neurobehavior than single-dose administration. Methods Forty methadone-maintained women were evaluated at peak and trough maternal methadone levels on single- and split-dosing schedules. Monitoring sessions occurred at 36 and 37 weeks gestation in a counterbalanced study design. Fetal measures included heart rate, variability, accelerations, motor activity and fetal movement-heart rate coupling (FM-FHR). Maternal measures included heart period, variability, skin conductance, respiration and vagal tone. Repeated measure analysis of variance was used to evaluate within-subject changes between split- and single-dosing regimens. Results All fetal neurobehavioral parameters were suppressed by maternal methadone administration, regardless of dosing regimen. Fetal parameters at peak were significantly lower during single vs. split methadone administration. FM-FHR coupling was less suppressed from trough to peak during split-dosing vs. single-dosing. Maternal physiologic parameters were generally unaffected by dosing condition. Conclusion Split- dosed fetuses displayed less neurobehavioral suppression from trough to peak maternal methadone levels as compared to single-dosed fetuses. Split-dosing may be beneficial for methadone-maintained pregnant women. PMID:19085624

Direct 3D cell-printing of human skin with functional transwell system.

Science.gov (United States)

Kim, Byoung Soo; Lee, Jung-Seob; Gao, Ge; Cho, Dong-Woo

2017-06-06

Three-dimensional (3D) cell-printing has been emerging as a promising technology with which to build up human skin models by enabling rapid and versatile design. Despite the technological advances, challenges remain in the development of fully functional models that recapitulate complexities in the native tissue. Moreover, although several approaches have been explored for the development of biomimetic human skin models, the present skin models based on multistep fabrication methods using polydimethylsiloxane chips and commercial transwell inserts could be tackled by leveraging 3D cell-printing technology. In this paper, we present a new 3D cell-printing strategy for engineering a 3D human skin model with a functional transwell system in a single-step process. A hybrid 3D cell-printing system was developed, allowing for the use of extrusion and inkjet modules at the same time. We began by revealing the significance of each module in engineering human skin models; by using the extrusion-dispensing module, we engineered a collagen-based construct with polycaprolactone (PCL) mesh that prevented the contraction of collagen during tissue maturation; the inkjet-based dispensing module was used to uniformly distribute keratinocytes. Taking these features together, we engineered a human skin model with a functional transwell system; the transwell system and fibroblast-populated dermis were consecutively fabricated by using the extrusion modules. Following this process, keratinocytes were uniformly distributed onto the engineered dermis by the inkjet module. Our transwell system indicates a supportive 3D construct composed of PCL, enabling the maturation of a skin model without the aid of commercial transwell inserts. This skin model revealed favorable biological characteristics that included a stabilized fibroblast-stretched dermis and stratified epidermis layers after 14 days. It was also observed that a 50 times reduction in cost was achieved and 10 times less medium was

Oxidative stress and CCN1 protein in human skin connective tissue aging

Directory of Open Access Journals (Sweden)

Zhaoping Qin

2016-06-01

Full Text Available Reactive oxygen species (ROS is an important pathogenic factor involved in human aging. Human skin is a primary target of oxidative stress from ROS generated from both extrinsic and intrinsic sources, like ultraviolet irradiation (UV and endogenous oxidative metabolism. Oxidative stress causes the alterations of collagen-rich extracellular matrix (ECM, the hallmark of skin connective tissue aging. Age-related alteration of dermal collagenous ECM impairs skin structural integrity and creates a tissue microenvironment that promotes age-related skin diseases, such as poor wound healing and skin cancer. Here, we review recent advances in our understanding of oxidative stress and CCN1 protein (first member of CCN family proteins, a critical mediator of oxidative stress-induced skin connective tissue aging.

Human fetal growth is constrained below optimal for perinatal survival

NARCIS (Netherlands)

Vasak, B.; Koenen, S. V.; Koster, M. P. H.; Hukkelhoven, C. W. P. M.; Franx, A.; Hanson, M. A.; Visser, GHA

ObjectiveThe use of fetal growth charts assumes that the optimal size at birth is at the 50(th) birth-weight centile, but interaction between maternal constraints on fetal growth and the risks associated with small and large fetal size at birth may indicate that this assumption is not valid for

The moisturizing effects of glycolipid biosurfactants, mannosylerythritol lipids, on human skin.

Science.gov (United States)

Yamamoto, Shuhei; Morita, Tomotake; Fukuoka, Tokuma; Imura, Tomohiro; Yanagidani, Shusaku; Sogabe, Atsushi; Kitamoto, Dai; Kitagawa, Masaru

2012-01-01

Glycolipid biosurfactants, such as mannosylerythritol lipids (MELs), are produced by different yeasts belonging to the genus Pseudozyma and have been attracting much attention as new cosmetic ingredients owing to their unique liquid-crystal-forming and moisturizing properties. In this study, the effects of different MEL derivatives on the skin were evaluated in detail using a three-dimensional cultured human skin model and an in vivo human study. The skin cells were cultured and treated with sodium dodecyl sulfate (SDS), and the effects of different lipids on the SDS-damaged cells were evaluated on the basis of cell viability. Most MEL derivatives efficiently recovered the viability of the cells and showed high recovery rates (over 80%) comparable with that of natural ceramide. It is interesting that the recovery rate with MEL-A prepared from olive oil was significantly higher than that of MEL-A prepared from soybean oil. The water retention properties of MEL-B were further investigated on human forearm skin in a preliminary study. Compared with the control, the aqueous solution of MEL-B (5 wt%) was estimated to considerably increase the stratum corneum water content in the skin. Moreover, perspiration on the skin surface was clearly suppressed by treatment with the MEL-B solution. These results suggest that MELs are likely to exhibit a high moisturizing action, by assisting the barrier function of the skin. Accordingly, the yeast glycolipids have a strong potential as a new ingredient for skin care products.

Fetal Mesenchymal Stromal Cells Differentiating towards Chondrocytes Acquire a Gene Expression Profile Resembling Human Growth Plate Cartilage

NARCIS (Netherlands)

van Gool, S.A.; Emons, J.A.M.; Leijten, Jeroen Christianus Hermanus; Decker, E.; Sticht, C.; van Houwelingen, J.C.; Goeman, J.J.; Kleijburg, C.; Scherjon, S.; Gretz, N.; Wit, J.M.; Rappold, G.; Post, Janine Nicole; Karperien, Hermanus Bernardus Johannes

2012-01-01

Abstract We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs) differentiating towards chondrocytes as an alternative model for the human growth plate (GP). Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether

125I-human epidermal growth factor specific binding to placentas and fetal membranes from varoius pregnancy states

International Nuclear Information System (INIS)

Hofmann, G.E.; Siddiqi, T.A.; Rao, Ch. V.; Carman, F.R.

1988-01-01

Specific binding of 125 I-human epidermal growth factor (hEGF) to homogenates of term human placentas and fetal membranes from normal and appropriate for gestational age (N = 20), intrauterine growth retarded (N = 9), twin (N = 11), White class A/B diabetic (N = 12), and large for gestational age (N = 13) pregnancies was measured. In all pregnancy states, placentas bound approximately four times more 125 I-hEGF than did fetal membranes (P 125 I-hEGF binding to fetal membranes from the various pregnancy states (P 125 I-hEGF specific binding to placentas from intrauterine growth retarded or twin pregnancies was significantly greater compared with placentas from normal and appropriate for gestational age pregnancies (P 125 I-hEGF specific binding did not differ between placentas from intrauterine growth retarded or twin pregnancies (P 125 I-hEGF binding did not vary with fetal sex, maternal race, placental weight, or gestational age between 37 to 42 weeks (P 125 I-hEGF binding increased with increasing infant weight when appropriate for gestational age and large for gestational age infants were included (P<0.05, r = 0.38, N = 32) but not for intrauterine growth retarded, appropriate for gestational age, or large for gestational age infants alone. (author)

Comparison of protocols for measuring cosmetic ingredient distribution in human and pig skin.

Science.gov (United States)

Gerstel, D; Jacques-Jamin, C; Schepky, A; Cubberley, R; Eilstein, J; Grégoire, S; Hewitt, N; Klaric, M; Rothe, H; Duplan, H

2016-08-01

The Cosmetics Europe Skin Bioavailability and Metabolism Task Force aims to improve the measurement and prediction of the bioavailability of topically-exposed compounds for risk assessment. Key parameters of the experimental design of the skin penetration studies were compared. Penetration studies with frozen human and pig skin were conducted in two laboratories, according to the SCCS and OECD 428 guidelines. The disposition in skin was measured 24h after finite topical doses of caffeine, resorcinol and 7-ethoxycoumarin. The bioavailability distribution in skin layers of cold and radiolabelled chemicals were comparable. Furthermore, the distribution of each chemical was comparable in human and pig skin. The protocol was reproducible across the two laboratories. There were small differences in the amount of chemical detected in the skin layers, which were attributed to differences in washing procedures and anatomical sites of the skin used. In conclusion, these studies support the use of pig skin as an alternative source of skin should the availability of human skin become a limiting factor. If radiolabelled chemicals are not available, cold chemicals can be used, provided that the influence of chemical stability, reactivity or metabolism on the experimental design and the relevance of the data obtained is considered. Copyright © 2016. Published by Elsevier Ltd.

Skin graft influence in human tissue radiated in nude mice regeneration

International Nuclear Information System (INIS)

Miranda, Jurandir Tomaz de

2016-01-01

Over the last few years it has increased the interest in the human skin grafts radio sterilized for application mainly in extensive and deep burns. Because these grafts quickly grip and present antigenic lower potential, compared with other treatments used. The purpose of this study was to evaluate the histoarchitecture of human skin grafts irradiated with doses 25 kGy, 50 kGy and non-irradiated during the repair tissue process in nude mice submitted by skin grafting in the dorsal region. Three groups of animals received irradiated human skin grafts (25 kGy and 50 kGy) and non-irradiated and were euthanized on the 3 rd , 7 th and 21 th day after the surgery. Indeed, routine histologic procedures, tissue samples were stained with hematoxylin and eosin (HE) for quantification of keratinocytes, fibroblasts, immune cells and blood vessels and immunofluorescence (IF) was performed to determine the expression human collagen type I and collagen type I and III mouse. Therefore, quantification of both the cells and the collagen types was performed by image analysis using Image-Pro Plus 6.0 software. Histologic results demonstrated at a dose of 25 kGy that human skin irradiation when grafted influences the increase in the number of cells in wound site over time and it provides better dispersion of these cells. In addition, on the 21 st day, three groups of animals with human skin graft were embedded part of the graft in the healing process. On the other hand, the group not irradiated showed greater incorporation of the graft (43 %), but less production of collagen type III mouse (22 %). Since the groups irradiated skin graft showed lower graft incorporation (6 and 15%), but with greater production of collagen type III mice (35 % and 28 % to 25 kGy and 50 kGy, respectively). In conclusion, this study presented that the group irradiated to 25 kGy and it has a higher cell proliferation and vessel formation, and better remodeling of the healing area. (author)

Experimental metagenomics and ribosomal profiling of the human skin microbiome.

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Ferretti, Pamela; Farina, Stefania; Cristofolini, Mario; Girolomoni, Giampiero; Tett, Adrian; Segata, Nicola

2017-03-01

The skin is the largest organ in the human body, and it is populated by a large diversity of microbes, most of which are co-evolved with the host and live in symbiotic harmony. There is increasing evidence that the skin microbiome plays a crucial role in the defense against pathogens, immune system training and homoeostasis, and microbiome perturbations have been associated with pathological skin conditions. Studying the skin resident microbial community is thus essential to better understand the microbiome-host crosstalk and to associate its specific configurations with cutaneous diseases. Several community profiling approaches have proved successful in unravelling the composition of the skin microbiome and overcome the limitations of cultivation-based assays, but these tools remain largely inaccessible to the clinical and medical dermatology communities. The study of the skin microbiome is also characterized by specific technical challenges, such as the low amount of microbial biomass and the extensive human DNA contamination. Here, we review the available community profiling approaches to study the skin microbiome, specifically focusing on the practical experimental and analytical tools necessary to generate and analyse skin microbiome data. We describe all the steps from the initial samples collection to the final data interpretation, with the goal of enabling clinicians and researchers who are not familiar with the microbiome field to perform skin profiling experiments. © 2016 The Authors. Experimental Dermatology Published by John Wiley & Sons Ltd.

Friction of Human Skin against Different Fabrics for Medical Use

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Luís Vilhena

2016-03-01

Full Text Available Knowledge of the tribology of human skin is essential to improve and optimize surfaces and materials in contact with the skin. Besides that, friction between the human skin and textiles is a critical factor in the formation of skin injuries, which are caused if the loads and shear forces are high enough and/or over long periods of time. This factor is of particular importance in bedridden patients, since they are not moving about or are confined to wheelchairs. Decubitus ulcers are one of the most frequently-reported iatrogenic injuries in developed countries. The risk of developing decubitus ulcers can be predicted by using the “Braden Scale for Predicting Pressure Ulcer Risk” that was developed in 1987 and contains six areas of risk (cognitive-perceptual, immobility, inactivity, moisture, nutrition, friction/shear, although there are limitations to the use of such tools. The coefficient of friction of textiles against skin is mainly influenced by: the nature of the textile, skin moisture content and ambient humidity. This study will investigate how skin friction (different anatomical regions varies, rubbing against different types of contacting materials (i.e., fabrics for medical use under different contact conditions and their relationship in the formation and prevention of decubitus ulcers.

Effects of Wnt3a on proliferation and differentiation of human epidermal stem cells

International Nuclear Information System (INIS)

Jia Liwei; Zhou Jiaxi; Peng Sha; Li Juxue; Cao Yujing; Duan Enkui

2008-01-01

Epidermal stem cells maintain development and homeostasis of mammalian epidermis throughout life. However, the molecular mechanisms involved in the proliferation and differentiation of epidermal stem cells are far from clear. In this study, we investigated the effects of Wnt3a and Wnt/β-catenin signaling on proliferation and differentiation of human fetal epidermal stem cells. We found both Wnt3a and active β-catenin, two key members of the Wnt/β-catenin signaling, were expressed in human fetal epidermis and epidermal stem cells. In addition, Wnt3a protein can promote proliferation and inhibit differentiation of epidermal stem cells in vitro culture. Our results suggest that Wnt/β-catenin signaling plays important roles in human fetal skin development and homeostasis, which also provide new insights on the molecular mechanisms of oncogenesis in human epidermis

Effect of Different Skin Penetration Promoters in Halobetasol Propionate Permeation and Retention in Human Skin

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Paulina Carvajal-Vidal

2017-11-01

Full Text Available Halobetasol propionate (HB is a potent synthetic corticosteroid used against inflammatory skin diseases, such as dermatitis, eczema, and psoriasis, among others. The aim of this study is to define how the presence of different skin penetration enhancers (nonane, menthone, limonene, azone, carene, decanol, linoleic acid and cetiol affects the penetration and retention in skin of HB. To determine drug penetration through skin, 5% of each promoter was used in an ex vivo system with human skin on Franz cells. The results showed that the highest permeation occurs in the presence of menthone, followed by nonane. Permeation parameters were determined. The in vivo test was assessed, and the formulation containing HB-menthone presented better anti-inflammatory efficacy. These results are useful to generate a specific treatment according to each patient’s needs, and the inflammatory characteristics of the disease.

In vivo study of the human skin by the method of laser-induced fluorescence spectroscopy

International Nuclear Information System (INIS)

Borisova, E.; Avramov, L.

2000-01-01

The goals of this study are to perform a preliminary evaluation of the diagnostic potential of noninvasive laser-induced auto-fluorescence spectroscopy (LIAFS) for human skin and optimize of detection and diagnosis of hollow organs and skin. In recent years, there has been growing interest in the use of laser-induced fluorescence to discriminate disease from normal surrounding tissue. The most fluorescence studies have used exogenous fluorophores of this discrimination. The laser-induced auto-fluorescence which is used for diagnosis of tissues in the human body avoids administration of any drugs. In this study a technique for optical biopsy of in vivo human skin is presented. The auto-fluorescence characterization of tissue relies on different spectral properties of tissues. It was demonstrated a differentiation between normal skin and skin with vitiligo. Two main endogenous fluorophores in the human skin account for most of the cellular auto-fluorescence for excitation wavelength 337 nm reduced from of nicotinamide adenine dinucleotide and collagen. The auto-fluorescence spectrum of human skin depend on main internal absorbers which are blood and melanin. In this study was described the effect caused by blood and melanin content on the shape of the auto-fluorescence spectrum of human skin. Human skin fluorescence spectrum might provide dermatologists with important information and such investigations are successfully used now in skin disease diagnostics, in investigation of the environmental factor impact or for evaluation of treatment efficiency. (authors)

Permeation of chromium salts through human skin in vitro

DEFF Research Database (Denmark)

Gammelgaard, Bente; Fullerton, A; Avnstorp, C

1992-01-01

Chromium permeation studies were performed on full thickness human skin in diffusion cells. All samples were analysed for the total chromium content by graphite furnace Zeeman-corrected atomic absorption spectrometry. Some samples were analysed by an ion chromatographic method permitting...... the simultaneous determination of Cr(VI) and Cr(III) as well. The amounts of chromium found in all skin layers were significantly higher when potassium dichromate was applied to the skin compared with chromium chloride or chromium nitrate. Chromium could only be detected in the recipient phase after application...... of the dichromate solution. Chromium skin levels increased with increasing concentrations of applied chromium salts up to 0.034 M Cr. The amount of chromium in recipient phase and skin layers increased with increasing pH when the applied solution contained potassium dichromate. This was ascribed to a decreased skin...

Fetal and perinatal outcomes in type 1 diabetes pregnancy: a randomized study comparing insulin aspart with human insulin in 322 subjects

DEFF Research Database (Denmark)

Hod, Moshe; Damm, Peter; Kaaja, Risto

2008-01-01

The objective of the study was a comparison of insulin aspart (IAsp) with human insulin (HI) in basal-bolus therapy with neutral protamine Hagedorn for fetal and perinatal outcomes of type 1 diabetes in pregnancy.......The objective of the study was a comparison of insulin aspart (IAsp) with human insulin (HI) in basal-bolus therapy with neutral protamine Hagedorn for fetal and perinatal outcomes of type 1 diabetes in pregnancy....

The human protooncogene product p33pim is expressed during fetal hematopoiesis and in diverse leukemias

International Nuclear Information System (INIS)

Amson, R.; Przedborski, S.; Telerman, A.; Sigaux, F.; Flandrin, G.; Givol, D.

1989-01-01

The authors measured the human pim-1 protooncogene (PIM) expression during fetal development and in hematopoietic malignancies. The data indicate that during human fetal hematopoiesis the 33-kDa pim product, p33pim, is highly expressed in the liver and the spleen. In contrast, a the adult stage it is only slightly expressed in circulating granulocytes. Out of 70 hematopoietic malignancies analyzed, 51 patients and 19 cell lines, p33pim was overexpressed in ∼ 30% of the samples, particularly in myeloid and lymphoid acute leukemias. This overexpression was unrelated to any stage of cellular differentiation and was not due to gene rearrangement or amplification. These results imply a physiological role of the pim-1 protooncogene during hematopoietic development and a deregulation in various leukemias

Human Epidermal Langerhans Cells Maintain Immune Homeostasis in Skin by Activating Skin Resident Regulatory T Cells

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Seneschal, Julien; Clark, Rachael A.; Gehad, Ahmed; Baecher-Allan, Clare M.; Kupper, Thomas S.

2013-01-01

Recent discoveries indicate that the skin of a normal individual contains 10-20 billion resident memory T cells ( which include various T helper, T cytotoxic, and T regulatory subsets, that are poised to respond to environmental antigens. Using only autologous human tissues, we report that both in vitro and in vivo, resting epidermal Langerhan cells (LC) selectively and specifically induced the activation and proliferation of skin resident regulatory T cells (Treg), a minor subset of skin resident memory T cells. In the presence of foreign pathogen, however, the same LC activated and induced proliferation of effector memory T (Tem) cells and limited Treg cells activation. These underappreciated properties of LC: namely maintenance of tolerance in normal skin, and activation of protective skin resident memory T cells upon infectious challenge, help clarify the role of LC in skin. PMID:22560445

Micro-patterned graphene-based sensing skins for human physiological monitoring

Science.gov (United States)

Wang, Long; Loh, Kenneth J.; Chiang, Wei-Hung; Manna, Kausik

2018-03-01

Ultrathin, flexible, conformal, and skin-like electronic transducers are emerging as promising candidates for noninvasive and nonintrusive human health monitoring. In this work, a wearable sensing membrane is developed by patterning a graphene-based solution onto ultrathin medical tape, which can then be attached to the skin for monitoring human physiological parameters and physical activity. Here, the sensor is validated for monitoring finger bending/movements and for recognizing hand motion patterns, thereby demonstrating its future potential for evaluating athletic performance, physical therapy, and designing next-generation human-machine interfaces. Furthermore, this study also quantifies the sensor’s ability to monitor eye blinking and radial pulse in real-time, which can find broader applications for the healthcare sector. Overall, the printed graphene-based sensing skin is highly conformable, flexible, lightweight, nonintrusive, mechanically robust, and is characterized by high strain sensitivity.

Confocal laser scanning microscopy to estimate nanoparticles’ human skin penetration in vitro

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Zou Y

2017-10-01

Full Text Available Ying Zou,1,2,* Anna Celli,2,3,* Hanjiang Zhu,2,* Akram Elmahdy,2 Yachao Cao,2 Xiaoying Hui,2 Howard Maibach2 1Skin & Cosmetic Research Department, Shanghai Skin Disease Hospital, Shanghai, People’s Republic of China; 2Department of Dermatology, School of Medicine, University of California San Francisco, San Francisco, CA, USA; 3San Francisco Veterans Medical Center, San Francisco, CA, USA *These authors contributed equally to this work Objective: With rapid development of nanotechnology, there is increasing interest in nanoparticle (NP application and its safety and efficacy on human skin. In this study, we utilized confocal laser scanning microscopy to estimate NP skin penetration.Methods: Three different-sized polystyrene NPs marked with red fluorescence were applied to human skin, and Calcium Green 5N was used as a counterstain. Dimethyl sulfoxide (DMSO and ethanol were used as alternative vehicles for NPs. Tape stripping was utilized as a barrier-damaged skin model. Skin biopsies dosed with NPs were incubated at 4°C or 37°C for 24 hours and imaged using confocal laser scanning microscopy.Results: NPs were localized in the stratum corneum (SC and hair follicles without penetrating the epidermis/dermis. Barrier alteration with tape stripping and change in incubation temperature did not induce deeper penetration. DMSO enhanced NP SC penetration but ethanol did not.Conclusion: Except with DMSO vehicle, these hydrolyzed polystyrene NPs did not penetrate intact or barrier-damaged human “viable” epidermis. For further clinical relevance, in vivo human skin studies and more sensitive analytic chemical methodology are suggested. Keywords: nanoparticles, skin penetration, stratum corneum, confocal laser scanning microscopy, tape stripping

Measurement of interstitial cetirizine concentrations in human skin

DEFF Research Database (Denmark)

Petersen, Lars Jelstrup; Church, M K; Rihoux, J P

1999-01-01

BACKGROUND: The purpose of the present study was to measure the concentrations of cetirizine in the extracellular water compartment in intact human skin and assess simultaneously inhibition of histamine-induced wheal and flare reactions. METHODS: Skin cetirizine levels were collected...... by the microdialysis technique and analyzed by high-pressure liquid chromatography with mass spectrometry detection. Skin levels in 20 subjects were compared to plasma levels for 4 h after a single oral dose of 10 or 20 mg of cetirizine. Skin prick tests were performed with histamine 100 mg/ml. RESULTS: Plasma...... cetirizine levels increased within 30 min to reach peak values of 315+/-10 and 786+/-45 ng/ml 90-120 min after administration of 10 and 20 mg of cetirizine. This was followed by a slow decline. In the skin, dialysate cetirizine levels (non-protein-bound fraction only) peaked at 1.6+/-0.1 and 2.4+/-0.3 ng...

Effect of fluocinolone acetonide cream on human skin blood flow

International Nuclear Information System (INIS)

Chimoskey, J.E.; Holloway, A. Jr.; Flanagan, W.J.

1975-01-01

Blood flow rate was measured in the forearm skin of human subjects exposed to ultraviolet irradiation. Blood flow was determined by the 133 Xe disappearance technique 18 hr after ultraviolet (UV) irradiation with a Westinghouse RS sunlamp held 10 inches from the skin for 10 min. Ultraviolet irradiation caused skin blood flow to increase. Application of fluocinolone acetonide cream, 0.025 percent, 4 times in the 16 hr following UV irradiation had no effect on either control skin blood flow or the UV-induced hyperemia

Insertion Testing of Polyethylene Glycol Microneedle Array into Cultured Human Skin with Biaxial Tension

Science.gov (United States)

Takano, Naoki; Tachikawa, Hiroto; Miyano, Takaya; Nishiyabu, Kazuaki

Aiming at the practical use of polyethylene glycol (PEG) microneedles for transdermal drug delivery system (DDS), a testing apparatus for their insertion into cultured human skin has been developed. To simulate the variety of conditions of human skin, biaxial tension can be applied to the cultured human skin. An adopted testing scheme to apply and control the biaxial tension is similar to the deep-draw forming technique. An attention was also paid to the short-time setup of small, thin and wet cultured skin. One dimensional array with four needles was inserted and influence of tension was discussed. It was found that tension, deflection of skin during insertion and original curvature of skin are the important parameters for microneedles array design.

Thyrotropin-releasing hormone (TRH promotes wound re-epithelialisation in frog and human skin.

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Natalia T Meier

Full Text Available There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression. Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters.

Thyrotropin-Releasing Hormone (TRH) Promotes Wound Re-Epithelialisation in Frog and Human Skin

Science.gov (United States)

Zhang, Guo-You; Emelianov, Vladimir; Paredes, Roberto; Debus, Sebastian; Augustin, Matthias; Funk, Wolfgang; Amaya, Enrique; Kloepper, Jennifer E.; Hardman, Matthew J.; Paus, Ralf

2013-01-01

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters. PMID:24023889

Ultrastructural age-related changes in the sensory corpuscles of the human genital skin.

Science.gov (United States)

Tammaro, A; Parisella, F R; Cavallotti, C; Persechino, S; Cavallotti, C

2013-01-01

In human genital skin the majority of superficial sensory corpuscles is represented by glomerular corpuscles. These corpuscles show an own morphology. Our aim is to compare the ultra-structure of superficial sensory corpuscles in the penis skin of younger and older subjects. In this report the ultra-structure of the sensitive corpuscle in the penis skin of the younger and older subjects was compared, showing that the genital skin of the older humans contains more simple complexes than the younger ones. Our findings support the view that the age-related changes that can be observed in human glomerular genital corpuscles are consistent with an increase of the simple complexes and a strong decrease of the poly-lamellar one in the older people. These findings demonstrate that human genital corpuscles underwent age-related changes. Moreover our morphological findings can be correlated in relation to the clinical evolution of the sensitivity in the genital skin.

Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth.

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Stacy Zamudio

2010-01-01

Full Text Available The most well known reproductive consequence of residence at high altitude (HA >2700 m is reduction in fetal growth. Reduced fetoplacental oxygenation is an underlying cause of pregnancy pathologies, including intrauterine growth restriction and preeclampsia, which are more common at HA. Therefore, altitude is a natural experimental model to study the etiology of pregnancy pathophysiologies. We have shown that the proximate cause of decreased fetal growth is not reduced oxygen availability, delivery, or consumption. We therefore asked whether glucose, the primary substrate for fetal growth, might be decreased and/or whether altered fetoplacental glucose metabolism might account for reduced fetal growth at HA.Doppler and ultrasound were used to measure maternal uterine and fetal umbilical blood flows in 69 and 58 residents of 400 vs 3600 m. Arterial and venous blood samples from mother and fetus were collected at elective cesarean delivery and analyzed for glucose, lactate and insulin. Maternal delivery and fetal uptakes for oxygen and glucose were calculated.The maternal arterial - venous glucose concentration difference was greater at HA. However, umbilical venous and arterial glucose concentrations were markedly decreased, resulting in lower glucose delivery at 3600 m. Fetal glucose consumption was reduced by >28%, but strongly correlated with glucose delivery, highlighting the relevance of glucose concentration to fetal uptake. At altitude, fetal lactate levels were increased, insulin concentrations decreased, and the expression of GLUT1 glucose transporter protein in the placental basal membrane was reduced.Our results support that preferential anaerobic consumption of glucose by the placenta at high altitude spares oxygen for fetal use, but limits glucose availability for fetal growth. Thus reduced fetal growth at high altitude is associated with fetal hypoglycemia, hypoinsulinemia and a trend towards lactacidemia. Our data support that

/sup 125/I-human epidermal growth factor specific binding to placentas and fetal membranes from varoius pregnancy states

Energy Technology Data Exchange (ETDEWEB)

Hofmann, G.E.; Siddiqi, T.A.; Rao, Ch. V.; Carman, F.R.

1988-01-01

Specific binding of /sup 125/I-human epidermal growth factor (hEGF) to homogenates of term human placentas and fetal membranes from normal and appropriate for gestational age (N = 20), intrauterine growth retarded (N = 9), twin (N = 11), White class AB diabetic (N = 12), and large for gestational age (N = 13) pregnancies was measured. In all pregnancy states, placentas bound approximately four times more /sup 125/I-hEGF than did fetal membranes (P<0.0001). There was no significant differnce in /sup 125/I-hEGF binding to fetal membranes from the various pregnancy states (P<0.05). /sup 125/I-hEGF specific binding to placentas from intrauterine growth retarded or twin pregnancies was significantly greater compared with placentas from normal and appropriate for gestational age pregnancies (P<0.05). The binding to placentas from pregnancies complicated by White class AB diabetes or large for gestational age infants, on the other hand, was not significantly different from that to placentas from normal and appropriate for gestational age pregnancies. /sup 125/I-hEGF specific binding did not differ between placentas from intrauterine growth retarded or twin pregnancies (P<0.05). Placental and fetal membrane /sup 125/I-hEGF binding did not vary with fetal sex, maternal race, placental weight, or gestational age between 37 to 42 weeks (P<0.05). Placental but not fetal membrane /sup 125/I-hEGF binding increased with increasing infant weight when appropriate for gestational age and large for gestational age infants were included (P<0.05, r = 0.38, N = 32) but not for intrauterine growth retarded, appropriate for gestational age, or large for gestational age infants alone.

Solar ultraviolet irradiation induces decorin degradation in human skin likely via neutrophil elastase.

Science.gov (United States)

Li, Yong; Xia, Wei; Liu, Ying; Remmer, Henriette A; Voorhees, John; Fisher, Gary J

2013-01-01

Exposure of human skin to solar ultraviolet (UV) irradiation induces matrix metalloproteinase-1 (MMP-1) activity, which degrades type I collagen fibrils. Type I collagen is the most abundant protein in skin and constitutes the majority of skin connective tissue (dermis). Degradation of collagen fibrils impairs the structure and function of skin that characterize skin aging. Decorin is the predominant proteoglycan in human dermis. In model systems, decorin binds to and protects type I collagen fibrils from proteolytic degradation by enzymes such as MMP-1. Little is known regarding alterations of decorin in response to UV irradiation. We found that solar-simulated UV irradiation of human skin in vivo stimulated substantial decorin degradation, with kinetics similar to infiltration of polymorphonuclear (PMN) cells. Proteases that were released from isolated PMN cells degraded decorin in vitro. A highly selective inhibitor of neutrophil elastase blocked decorin breakdown by proteases released from PMN cells. Furthermore, purified neutrophil elastase cleaved decorin in vitro and generated fragments with similar molecular weights as those resulting from protease activity released from PMN cells, and as observed in UV-irradiated human skin. Cleavage of decorin by neutrophil elastase significantly augmented fragmentation of type I collagen fibrils by MMP-1. Taken together, these data indicate that PMN cell proteases, especially neutrophil elastase, degrade decorin, and this degradation renders collagen fibrils more susceptible to MMP-1 cleavage. These data identify decorin degradation and neutrophil elastase as potential therapeutic targets for mitigating sun exposure-induced collagen fibril degradation in human skin.

Human Skin 3D Bioprinting Using Scaffold-Free Approach.

Science.gov (United States)

Pourchet, Léa J; Thepot, Amélie; Albouy, Marion; Courtial, Edwin J; Boher, Aurélie; Blum, Loïc J; Marquette, Christophe A

2017-02-01

Organ in vitro synthesis is one of the last bottlenecks between tissue engineering and transplantation of synthetic organs. Bioprinting has proven its capacity to produce 3D objects composed of living cells but highly organized tissues such as full thickness skin (dermis + epidermis) are rarely attained. The focus of the present study is to demonstrate the capability of a newly developed ink formulation and the use of an open source printer, for the production of a really complete skin model. Proofs are given through immunostaining and electronic microscopy that the bioprinted skin presents all characteristics of human skin, both at the molecular and macromolecular level. Finally, the printability of large skin objects is demonstrated with the printing of an adult-size ear. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Epidermal changes following application of 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol-13-acetate to human skin transplanted to nude mice studied with histological species markers

International Nuclear Information System (INIS)

Graem, N.

1986-01-01

Effects of the tumor initiator 7,12-dimethylbenz(a)anthracene (DMBA) and of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on epidermis of human fetal and adult skin were studied in the nude mouse/human skin model. Human skin grafts on NC nude mice were exposed to two topical applications of 1 mg of DMBA in 50 microliter of acetone with an interval of 3 days and/or to applications of 10 micrograms of TPA in 50 microliter of acetone twice weekly. In some animals, it was attempted to augment the susceptibility of the grafts to the tumor-initiating effect of DMBA by pretreatment with TPA or ultraviolet light. The mice were sacrificed 8-32 wk after the initial treatment. Tumors did not appear in the central portions of any of the grafts, but epidermal tumors were seen at the graft border in 34.9% of the DMBA-treated animals. To identify human epidermis on the grafts and to determine the species origin of the induced tumors, two independently working histological marker methods were applied. (a) The first is detection of a human Blood Group B-like antigen present in mouse epidermis and in chemically induced murine epidermal tumors. This antigen cannot be demonstrated in human epidermis and in epidermal tumors of human patients. (b) The second is histological staining with the DNA-specific fluorochrome, bisbenzimide, displaying a characteristic pattern of 5-10 intranuclear fluorescent bodies in murine nonneoplastic epidermal cells and in murine epidermal tumor cells. Such a pattern is not seen in human epidermis and in epidermal tumors of human patients. The studies showed that TPA treatment resulted in epidermal hyperplasia in both the human epidermis and the adjacent mouse epidermis and that the induced tumors were derived from murine tissue

Quantitative relationship between the local lymph node assay and human skin sensitization assays.

Science.gov (United States)

Schneider, K; Akkan, Z

2004-06-01

The local lymph node assay (LLNA) is a new test method which allows for the quantitative assessment of sensitizing potency in the mouse. Here, we investigate the quantitative correlation between results from the LLNA and two human sensitization tests--specifically, human repeat insult patch tests (HRIPTs) and human maximization tests (HMTs). Data for 57 substances were evaluated, of which 46 showed skin sensitizing properties in human tests, whereas 11 yielded negative results in humans. For better comparability data from mouse and human tests were transformed to applied doses per skin area, which ranged over four orders of magnitude for the substances considered. Regression analysis for the 46 human sensitizing substances revealed a significant positive correlation between the LLNA and human tests. The correlation was better between LLNA and HRIPT data (n=23; r=0.77) than between LLNA and HMT data (n=38; r=0.65). The observed scattering of data points is related to various uncertainties, in part associated with insufficiencies of data from older HMT studies. Predominantly negative results in the LLNA for another 11 substances which showed no skin sensitizing activity in human maximization tests further corroborate the correspondence between LLNA and human tests. Based on this analysis, the LLNA can be considered a reliable basis for relative potency assessments for skin sensitizers. Proposals are made for the regulatory exploitation of the LLNA: four potency groups can be established, and assignment of substances to these groups according to the outcome of the LLNA can be used to characterize skin sensitizing potency in substance-specific assessments. Moreover, based on these potency groups, a more adequate consideration of sensitizing substances in preparations becomes possible. It is proposed to replace the current single concentration limit for skin sensitizers in preparations, which leads to an all or nothing classification of a preparation as sensitizing to

Colony size distributions according to in vitro aging in human skin fibroblasts

International Nuclear Information System (INIS)

Kim, Jun Sang; Kim, Jae Sung; Cho, Moon June; Park, Jeong Kyu; Paik, Tae Hyun

1999-01-01

To investigate the percentage of colonies with 16 or more cells distribution of human skin fibroblast according to in vitro aging, and to evaluate the relationship between percentage of colonies with 16 or more cells and in vivo donor age in human skin fibroblast culture. C1, C2, C3a, and C3b human skin fibroblast samples from three breast cancer patients were used as subjects. The C1, C2, and C3a donor were 44, 54, and 55 years old, respectively. C3a and C3b cells were isolated from the same person. Single cell suspension of skin fibroblasts was prepared with primary explant technique. One hundred cells are plated into 100ml tissue culture flask and cultured for two weeks. The colony size was defined as colonies with 16 or more cells. The cultured cell was stained with crystal violet, and number of cells in each colony was determined with stereo microscope at x 10 magnification. Passage number of C1, C2, C3a and C3b skin fibroblast were 12th, 17th, and 14th, respectively. Percentage of colonies with 16 or more cells of skin fibroblast samples decreased with increasing in vitro passage number. In contrast, cumulative population doublings of skin fibroblast sample increased with increasing in vitro passage number. Percentage of colonies with 16 or more cells also decreased with increasing population doublings in human skin fibroblast culture. There was strong correlation with percentage of colonised with 16 or more cells and population doublings in C3a skin fibroblast sample. At the same point of population doublings, the percentage of colonies with 16 or more cells of the young C1 donor was higher level than the old C3a donor. The population doublings increased with increasing in vitro passage number but percentage of colonies with 16 or more cells decreased. The results of this study imply that percentage of colonies with 16 or more cells is useful as a indicator of in vitro human skin fibroblast aging and may estimate the in vivo donor age

In-Vivo Human Skin to Textiles Friction Measurements

Science.gov (United States)

Pfarr, Lukas; Zagar, Bernhard

2017-10-01

We report on a measurement system to determine highly reliable and accurate friction properties of textiles as needed for example as input to garment simulation software. Our investigations led to a set-up that allows to characterize not just textile to textile but also textile to in-vivo human skin tribological properties and thus to fundamental knowledge about genuine wearer interaction in garments. The method of test conveyed in this paper is measuring concurrently and in a highly time resolved manner the normal force as well as the resulting shear force caused by a friction subject intending to slide out of the static friction regime and into the dynamic regime on a test bench. Deeper analysis of various influences is enabled by extending the simple model following Coulomb's law for rigid body friction to include further essential parameters such as contact force, predominance in the yarn's orientation and also skin hydration. This easy-to-use system enables to measure reliably and reproducibly both static and dynamic friction for a variety of friction partners including human skin with all its variability there might be.

Percutaneous penetration of 2-phenoxyethanol through rat and human skin.

Science.gov (United States)

Roper, C S; Howes, D; Blain, P G; Williams, F M

1997-01-01

2-Phenoxyethanol applied in methanol was absorbed (64 +/- 4.4% at 24 hr) through unoccluded rat skin in vitro in the static diffusion cell with ethanol/water as receptor fluid. By comparison (43 +/- 3.7% in 24 hr) was absorbed in the flow-through diffusion system with tissue culture medium as receptor fluid. 2-Phenoxyethanol applied in methanol was absorbed (59.3 +/- 7.0% at 6 hr) through unoccluded human skin in vitro in the flow-through diffusion cell with tissue culture medium. With both unoccluded cells, 2-phenoxyethanol was lost by evaporation but occlusion of the static cell reduced evaporation and increased total absorption to 98.8 +/- 7.0%. Skin, post mitochondrial fraction, metabolized phenoxyethanol to phenoxyacetic acid at 5% of the rate for liver. Metabolism was inhibited by 1 mM pyrazole, suggesting involvement of alcohol dehydrogenase. However, first-pass metabolism of phenoxyethanol to phenoxyacetic acid was not detected during percutaneous penetration through viable rat skin in the flow-through system. First-pass metabolism in the skin does not therefore have an influence on systemic availability of dermally absorbed phenoxyethanol. These measures of phenoxyethanol absorption through rat and human skin in vitro agree well with those obtained previously in vivo.

The Protective Role of Melanin Against UV Damage in Human Skin

OpenAIRE

Brenner, Michaela; Hearing, Vincent J.

2008-01-01

Human skin is repeatedly exposed to ultraviolet radiation (UVR) that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, since melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin...

Tribology of human skin and mechanical skin equivalents in contact with textiles

NARCIS (Netherlands)

Derler, S.; Schrade, G.U.; Gerhardt, L.C.

2007-01-01

The friction of untreated human skin (finger) against a reference textile was investigated with 12 subjects using a force plate. In touch experiments, in which the subjects assessed the surface roughness of the textile at normal loads of 1.5 ± 0.7 N, the average friction coefficients ranged from

Influence of epidermal hydration on the friction of human skin against textiles

OpenAIRE

Gerhardt, L.-C; Strässle, V; Lenz, A; Spencer, N.D; Derler, S

2008-01-01

Friction and shear forces, as well as moisture between the human skin and textiles are critical factors in the formation of skin injuries such as blisters, abrasions and decubitus. This study investigated how epidermal hydration affects the friction between skin and textiles.

GLI3 Links Environmental Arsenic Exposure and Human Fetal Growth

Directory of Open Access Journals (Sweden)

Emily F. Winterbottom

2015-06-01

Full Text Available Although considerable evidence suggests that in utero arsenic exposure affects children's health, these data are mainly from areas of the world where groundwater arsenic levels far exceed the World Health Organization limit of 10 μg/L. We, and others, have found that more common levels of in utero arsenic exposure may also impact children's health. However, the underlying molecular mechanisms are poorly understood. To address this issue, we analyzed the expression of key developmental genes in fetal placenta in a birth cohort of women using unregulated water supplies in a US region with elevated groundwater arsenic. We identified several genes whose expression associated with maternal arsenic exposure in a fetal sex-specific manner. In particular, expression of the HEDGEHOG pathway component, GLI3, in female placentae was both negatively associated with arsenic exposure and positively associated with infant birth weight. This suggests that modulation of GLI3 in the fetal placenta, and perhaps in other fetal tissues, contributes to arsenic's detrimental effects on fetal growth. We showed previously that arsenic-exposed NIH3T3 cells have reduced GLI3 repressor protein. Together, these studies identify GLI3 as a key signaling node that is affected by arsenic, mediating a subset of its effects on developmental signaling and fetal health.

A methodology for extracting the electrical properties of human skin

International Nuclear Information System (INIS)

Birgersson, Ulrik; Nicander, Ingrid; Ollmar, Stig; Birgersson, Erik

2013-01-01

A methodology to determine dielectrical properties of human skin is presented and analyzed. In short, it is based on a mathematical model that considers the local transport of charge in the various layers of the skin, which is coupled with impedance measurements of both stripped and intact skin, an automated code generator, and an optimization algorithm. New resistivity and permittivity values for the stratum corneum soaked with physiological saline solution for 1 min and the viable skin beneath are obtained and expressed as easily accessible functions. The methodology can be extended to account for different electrode designs as well as more physical phenomena that are relevant to electrical impedance measurements of skin and their interpretation. (paper)

Hydrolysis of a series of parabens by skin microsomes and cytosol from human and minipigs and in whole skin in short-term culture

International Nuclear Information System (INIS)

Jewell, Christopher; Prusakiewicz, Jeffery J.; Ackermann, Chrisita; Payne, N. Ann; Fate, Gwendolyn; Voorman, Richard; Williams, Faith M.

2007-01-01

Parabens are esters of 4-hydroxybenzoic acid and used as anti-microbial agents in a wide variety of toiletries, cosmetics and pharmaceuticals. It is of interest to understand the dermal absorption and hydrolysis of parabens, and to evaluate their disposition after dermal exposure and their potential to illicit localised toxicity. The use of minipig as a surrogate model for human dermal metabolism and toxicity studies, justifies the comparison of paraben metabolism in human and minipig skin. Parabens are hydrolysed by carboxylesterases to 4-hydroxybenzoic acid. The effects of the carboxylesterase inhibitors paraoxon and bis-nitrophenylphosphate provided evidence of the involvement of dermal carboxylesterases in paraben hydrolysis. Loperamide, a specific inhibitor of human carboxylesterase-2 inhibited butyl- and benzylparaben hydrolysis in human skin but not methylparaben or ethylparaben. These results show that butyl- and benzylparaben are more selective substrates for human carboxylesterase-2 in skin than the other parabens examined. Parabens applied to the surface of human or minipig skin were absorbed to a similar amount and metabolised to 4-hydroxybenzoic acid during dermal absorption. These results demonstrate that the minipig is a suitable model for man for assessing dermal absorption and hydrolysis of parabens, although the carboxylesterase profile in skin differs between human and minipig

Variables influencing the frictional behaviour of in vivo human skin

NARCIS (Netherlands)

Veijgen, N.K.; Masen, Marc Arthur; van der Heide, Emile

2013-01-01

In the past decades, skin friction research has focused on determining which variables are important to affect the frictional behaviour of in vivo human skin. Until now, there is still limited knowledge on these variables. This study has used a large dataset to identify the effect of variables on

Influence of epidermal hydration on the friction of human skin against textile

NARCIS (Netherlands)

Gerhardt, L.C.; Strässle, V.; Lenz, A.; Spencer, N.D.; Derler, S.

2008-01-01

Friction and shear forces, as well as moisture between the human skin and textiles are critical factors in the formation of skin injuries such as blisters, abrasions and decubitus. This study investigated how epidermal hydration affects the friction between skin and textiles. The friction between

Comparison of the effect of fatty alcohols on the permeation of melatonin between porcine and human skin.

Science.gov (United States)

Andega, S; Kanikkannan, N; Singh, M

2001-11-09

Melatonin (MT) is a hormone secreted by the pineal gland that plays an important role in the regulation of the circadian sleep-wake cycle. It would be advantageous to administer MT using a transdermal delivery system for the treatment of sleep disorders such as delayed sleep syndrome, jet lag in travelers, cosmonauts and shift workers. The porcine skin has been found to have similar morphological and functional characteristics as human skin. The elastic fibres in the dermis, enzyme pattern of the epidermis, epidermal tissue turnover time, keratinous proteins and thickness of epidermis of porcine skin are similar to human skin. However, the fat deposition and vascularisation of the cutaneous glands of porcine skin are different from human skin. In addition, porcine skin has been found to have a close permeability character to human skin. However, the comparative effect of chemical penetration enhancers on the permeation of drugs between porcine and human skin has not been reported. The purpose of this study was to compare the effect of fatty alcohols on the permeability of porcine and human skin using MT as a model compound. The effect of saturated fatty alcohols (octanol, nonanol, decanol, undecanol, lauryl alcohol, tridecanol, myristyl alcohol) and unsaturated fatty alcohols (oleyl alcohol, linoleyl alcohol, linolenyl alcohol) at 5% concentration was tested across dermatomed porcine and human skin. Our studies showed a parabolic relationship between the carbon chain length of saturated fatty alcohols and permeation enhancement of MT with both porcine and human skin. Maximum permeation of MT was observed when fatty alcohol carbon chain length was 10. In general, as the level of unsaturation increased from one to two double bonds, there was an increase in the permeation of MT both in porcine and human skin. However, a decrease in the permeation was observed with three double bonds. Regression analysis using the steady state flux data showed a significant positive

Increased oxidative stress in human fetal membranes overlying the cervix from term non-labouring and post labour deliveries.

Science.gov (United States)

Chai, M; Barker, G; Menon, R; Lappas, M

2012-08-01

Enzymatic breakdown of the collagen-rich extracellular matrix (ECM) that connects the amnion and chorion layers of the fetal membranes is one of the key events leading to rupture of membranes. Oxidant stress caused by increased formation of reactive oxygen species and/or reduced antioxidant capacity may predispose to membrane rupture, a major cause of preterm birth. The aim of this study was to determine the effect of human labour and supracervical (SC) apposition on antioxidant enzymes and 8-isoprostane (a marker of lipid peroxidation). To determine the effect of human labour on oxidative stress status, fetal membranes from the SC site (SCS) were collected from women at term Caesarean section (no labour), and from the site of membrane rupture (SOR) after spontaneous labour onset and delivery (post labour). To determine the effect of SC apposition on oxidative stress status, amnion was collected from the SCS and a distal site (DS) in women at term Caesarean section in the absence of labour. The release of 8-isoprostane was significantly higher in amnion from the SCS compared to DS, and in fetal membranes from the SOR compared to the SCS. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were lower in amnion from the SC compared to DS. SOD gene expression and enzyme activity were lower in fetal membranes after labour. There was no difference in expression or activity in catalase, GPx and glutathione reductase (GSR) between no labour and post labour fetal membranes. In primary amnion cells, SOD supplementation significantly augmented IL-1β induced MMP-9 expression and activity. In summary, non-labouring SC fetal membranes are characterised by reduced antioxidant enzyme activity when compared to distal membranes, and, as such, may be more susceptible to oxidative damage and thus membrane rupture. Copyright © 2012 Elsevier Ltd. All rights reserved.

Degradation and protection of DNAzymes on human skin.

Science.gov (United States)

Marquardt, Kay; Eicher, Anna-Carola; Dobler, Dorota; Höfer, Frank; Schmidts, Thomas; Schäfer, Jens; Renz, Harald; Runkel, Frank

2016-10-01

DNAzymes are catalytic nucleic acid based molecules that have become a new class of active pharmaceutical ingredients (API). Until now, five DNAzymes have entered clinical trials. Two of them were tested for topical application, whereby dermally applied DNAzymes had been prone to enzymatic degradation. To protect the DNAzymes the enzymatic activity of human skin has to be examined. Therefore, the enzymatic activity of human skin was qualitatively and quantitatively analyzed. Activity similar to that of DNase II could be identified and the specific activity was determined to be 0.59Units/mg. These results were used to develop an in vitro degradation assay to screen different kinds of protective systems on human skin. The chosen protective systems consisted of biodegradable chitosans or polyethylenimine, which forms polyplexes when combined with DNAzymes. The polyplexes were characterized in terms of particle size, zeta potential, stability and degree of complexation. The screening revealed that the protective efficiency of the polyplexes depended on the polycation and the charge ratio (ξ). At a critical ξ ratio between 1.0 and 4.1 and at a maximal zeta potential, sufficient protection of the DNAzyme was achieved. The results of this study will be helpful for the development of a protective dermal drug delivery systems using polyplexes. Copyright © 2016 Elsevier B.V. All rights reserved.

Variables influencing the frictional behaviour of in vivo human skin

NARCIS (Netherlands)

Veijgen, N.K.; Masen, M.A.; Heide, E. van der

2013-01-01

In the past decades, skin friction research has focused on determining which variables are important to affect the frictional behaviour of in vivo human skin. Until now, there is still limited knowledge on these variables.This study has used a large dataset to identify the effect of variables on the

Protection against UVB-induced oxidative stress in human skin cells and skin models by methionine sulfoxide reductase A.

Science.gov (United States)

Pelle, Edward; Maes, Daniel; Huang, Xi; Frenkel, Krystyna; Pernodet, Nadine; Yarosh, Daniel B; Zhang, Qi

2012-01-01

Environmental trauma to human skin can lead to oxidative damage of proteins and affect their activity and structure. When methionine becomes oxidized to its sulfoxide form, methionine sulfoxide reductase A (MSRA) reduces it back to methionine. We report here the increase in MSRA in normal human epidermal keratinocytes (NHEK) after ultraviolet B (UVB) radiation, as well as the reduction in hydrogen peroxide levels in NHEK pre-treated with MSRA after exposure. Further, when NHEK were pre-treated with a non-cytotoxic pentapeptide containing methionine sulfoxide (metSO), MSRA expression increased by 18.2%. Additionally, when the media of skin models were supplemented with the metSO pentapeptide and then exposed to UVB, a 31.1% reduction in sunburn cells was evident. We conclude that the presence of MSRA or an externally applied peptide reduces oxidative damage in NHEK and skin models and that MSRA contributes to the protection of proteins against UVB-induced damage in skin.

Epigenetic regulation and fetal programming.

Science.gov (United States)

Gicquel, Christine; El-Osta, Assam; Le Bouc, Yves

2008-02-01

Fetal programming encompasses the role of developmental plasticity in response to environmental and nutritional signals during early life and its potential adverse consequences (risk of cardiovascular, metabolic and behavioural diseases) in later life. The first studies in this field highlighted an association between poor fetal growth and chronic adult diseases. However, environmental signals during early life may lead to adverse long-term effects independently of obvious effects on fetal growth. Adverse long-term effects reflect a mismatch between early (fetal and neonatal) environmental conditions and the conditions that the individual will confront later in life. The mechanisms underlying this risk remain unclear. However, experimental data in rodents and recent observations in humans suggest that epigenetic changes in regulatory genes and growth-related genes play a significant role in fetal programming. Improvements in our understanding of the biochemical and molecular mechanisms at play in fetal programming would make it possible to identify biomarkers for detecting infants at high risk of adult-onset diseases. Such improvements should also lead to the development of preventive and therapeutic strategies.

Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone.

Science.gov (United States)

Pearson, Helen; Britt, Rodney D; Pabelick, Christine M; Prakash, Y S; Amrani, Yassine; Pandya, Hitesh C

2015-12-01

Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Cultured fetal human ASM cells stimulated with TNF-α (0-20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases.

Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves.

Science.gov (United States)

Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

2014-01-01

Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW’s are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin.

Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves

Science.gov (United States)

Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J.; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

2014-07-01

Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW's are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin.

Isolation and characterization of neural stem cells from human fetal striatum

International Nuclear Information System (INIS)

Li Xiaoxia; Xu Jinchong; Bai Yun; Wang Xuan; Dai Xin; Liu Yinan; Zhang Jun; Zou Junhua; Shen Li; Li Lingsong

2005-01-01

This paper described that neural stem cells (hsNSCs) were isolated and expanded rapidly from human fetal striatum in adherent culture. The population was serum- and growth factor-dependent and expressed neural stem cell markers. They were capable of multi-differentiation into neurons, astrocytes, and oligodendrocytes. When plated in the dopaminergic neuron inducing medium, human striatum neural stem cells could differentiate into tyrosine hydroxylase positive neurons. hsNSCs were morphologically homogeneous and possessed high proliferation ability. The population doubled every 44.28 h and until now it has divided for more than 82 generations in vitro. Normal human diploid karyotype was unchanged throughout the in vitro culture period. Together, this study has exploited a method for continuous and rapid expansion of human neural stem cells as pure population, which maintained the capacity to generate almost fifty percent neurons. The availability of such cells may hold great interest for basic and applied neuroscience

Permeability of commercial solvents through living human skin

DEFF Research Database (Denmark)

Ursin, C; Hansen, C M; Van Dyk, J W

1995-01-01

A procedure has been developed for measuring the steady state rate of permeation of commercial solvents through living human skin. To get the most consistent results, it was necessary with some solvents to normalize the solvent permeation rate of a given skin sample with its [3H]water permeation...... rate. For other solvents this was not necessary, so the un-normalized data were used. High [3H]water permeation rate also was used as a criterion for "defective" skin samples that gave erroneous permeability rates, especially for solvents having slow permeability. The linearity of the steady state data...... of DMSO and octyl acetate were measured. No octyl acetate was detected and the permeability of DMSO was proportional to its mole fraction in the mixture. The effect of two hours of solvent exposure on the viability of skin (based on DNA synthesis) was measured and found to be very dependent on the solvent....

Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin

NARCIS (Netherlands)

Middelkamp-Hup, Maritza A.; Pathak, Madhu A.; Parrado, Concepcion; Goukassian, David; Rius-Díaz, Francisca; Mihm, Martín C.; Fitzpatrick, Thomas B.; González, Salvador

2004-01-01

BACKGROUND: UV radiation induces damage to human skin. Protection of skin by an oral photoprotective agent would have substantial benefits. Objective We investigated the photoprotective effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos (PL). METHODS: A

Validation of radiosterilization dose of human skin dressings for burnt treatment: preliminary study

International Nuclear Information System (INIS)

Castro, E.

2008-01-01

Full text: Due to the need for better materials to treat burnt patients, the Peruvian Institute of Nuclear Energy (IPEN) and the Rosa Guerzoni Chambergo Tissue Bank are collaborating for developing human skin dressings. Skin was procured from living donors, who surgically were performed a dermolipectomy. Exclusion criteria, stated by the Peruvian Organization for Transplant and Donation were observed. Glycerolized human skin dressings were processed at the tissue bank and sent to IPEN, where the gamma irradiation sterilizing dose was determined. The purpose of this work is to validate the radiation sterilization dose delivered to human skin dressings using the IAEA Code of Practice for the Radiation Sterilization of Tissue Allografts: Requirements for Validation and Routine Control. A batch of human skin dressings was tested. Average values of bioburden present in ten samples was 30 UFC/item, obtaining a sub-sterilization dose of 4 kGy. Irradiations were performed in the GammacellExcel 220. Sterility tests performed fulfilled the requirements established by the Code, achieving a validated dose value of 19.7 kGy. This preliminary study, that should be repeated in two other batches of processed human skin, allows to diminish 25 kGy the sterilizing dose to the stated above dose value, in a frame of a quality assurance system that also comprises the processes held at tissue banks previous irradiation. It also permit the availability of these materials in Peruvian hospitals. (Author)

Automation Diagnosis of Skin Disease in Humans using Dempster-Shafer Method

Science.gov (United States)

Khairina, Dyna Marisa; Hatta, Heliza Rahmania; Rustam; Maharani, Septya

2018-02-01

Skin disease is an infectious disease that is common in people of all ages. Disorders of the skin often occur because there are factors, among others, are climate, environment, shelter, unhealthy living habits, allergies and others. Skin diseases in Indonesia are mostly caused by bacterial, fungal, parasitic, and allergies. The objective of the research is to diagnose skin diseases in humans by using the method of making decision tree then performing the search by forward chaining and calculating the probability value of Dempster-Shafer method. The results of research in the form of an automated system that can resemble an expert in diagnosing skin disease accurately and can help in overcoming the problem of skin diseases.

Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development.

Directory of Open Access Journals (Sweden)

Keith M Godfrey

Full Text Available Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001 and at age 4 years (r = 0.16, P = 0.02. In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02. This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04. We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fat.

A novel approach to measuring the frictional behaviour of human skin in vivo

NARCIS (Netherlands)

Veijgen, N.K.; Masen, Marc Arthur; van der Heide, Emile

2012-01-01

Friction involving human skin plays a key role in human life. The availability of a portable tribometer improves the accessibility to large number of both subjects and anatomical sites. This is the first mobile device suitable to measure skin friction with a controlled and variable normal load

Nicotinic acid receptor abnormalities in human skin cancer: implications for a role in epidermal differentiation.

Directory of Open Access Journals (Sweden)

Yira Bermudez

Full Text Available Chronic UV skin exposure leads to epidermal differentiation defects in humans that can be largely restored by pharmacological doses of nicotinic acid. Nicotinic acid has been identified as a ligand for the human G-protein-coupled receptors GPR109A and GPR109B that signal through G(i-mediated inhibition of adenylyl cyclase. We have examined the expression, cellular distribution, and functionality of GPR109A/B in human skin and skin derived epidermal cells.Nicotinic acid increases epidermal differentiation in photodamaged human skin as judged by the terminal differentiation markers caspase 14 and filaggrin. Both GPR109A and GPR109B genes are transcribed in human skin and in epidermal keratinocytes, but expression in dermal fibroblasts is below limits of detection. Receptor transcripts are greatly over-expressed in squamous cell cancers. Receptor protein in normal skin is prominent from the basal through granular layers of the epidermis, with cellular localization more dispersive in the basal layer but predominantly localized at the plasma membrane in more differentiated epidermal layers. In normal human primary and immortalized keratinocytes, nicotinic acid receptors show plasma membrane localization and functional G(i-mediated signaling. In contrast, in a squamous cell carcinoma derived cell line, receptor protein shows a more diffuse cellular localization and the receptors are nearly non-functional.The results of these studies justify future genetic and pharmacological intervention studies to define possible specific role(s of nicotinic acid receptors in human skin homeostasis.

Microneedle Enhanced Delivery of Cosmeceutically Relevant Peptides in Human Skin

Science.gov (United States)

Mohammed, Yousuf H.; Yamada, Miko; Lin, Lynlee L.; Grice, Jeffrey E.; Roberts, Michael S.; Raphael, Anthony P.; Benson, Heather A. E.; Prow, Tarl W.

2014-01-01

Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length) on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides. PMID:25033398

Microneedle enhanced delivery of cosmeceutically relevant peptides in human skin.

Directory of Open Access Journals (Sweden)

Yousuf H Mohammed

Full Text Available Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides.

Analogs of human genetic skin disease in domesticated animals

Directory of Open Access Journals (Sweden)

Justin Finch, MD

2017-09-01

The genetic skin diseases we will review are pigmentary mosaicism, piebaldism, albinism, Griscelli syndrome, ectodermal dysplasias, Waardenburg syndrome, and mucinosis in both humans and domesticated animals.

The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Integration of Animal and Human Evidence for PFOA Effects on Fetal Growth

Science.gov (United States)

Koustas, Erica; Sutton, Patrice; Johnson, Paula I.; Atchley, Dylan S.; Sen, Saunak; Robinson, Karen A.; Axelrad, Daniel A.; Woodruff, Tracey J.

2014-01-01

Background: The Navigation Guide is a novel systematic review method to synthesize scientific evidence and reach strength of evidence conclusions for environmental health decision making. Objective: Our aim was to integrate scientific findings from human and nonhuman studies to determine the overall strength of evidence for the question “Does developmental exposure to perfluorooctanoic acid (PFOA) affect fetal growth in humans?” Methods: We developed and applied prespecified criteria to systematically and transparently a) rate the quality of the scientific evidence as “high,” “moderate,” or “low”; b) rate the strength of the human and nonhuman evidence separately as “sufficient,” “limited,” “moderate,” or “evidence of lack of toxicity”; and c) integrate the strength of the human and nonhuman evidence ratings into a strength of the evidence conclusion. Results: We identified 18 epidemiology studies and 21 animal toxicology studies relevant to our study question. We rated both the human and nonhuman mammalian evidence as “moderate” quality and “sufficient” strength. Integration of these evidence ratings produced a final strength of evidence rating in which review authors concluded that PFOA is “known to be toxic” to human reproduction and development based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. Conclusion: We concluded that developmental exposure to PFOA adversely affects human health based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. The results of this case study demonstrate the application of a systematic and transparent methodology, via the Navigation Guide, for reaching strength of evidence conclusions in environmental health. Citation: Lam J, Koustas E, Sutton P, Johnson PI, Atchley DS, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. 2014. The Navigation Guide—evidence-based medicine meets environmental health

Bioactive reagents used in mesotherapy for skin rejuvenation in vivo induce diverse physiological processes in human skin fibroblasts in vitro- a pilot study.

Science.gov (United States)

Jäger, Claudia; Brenner, Christiane; Habicht, Jüri; Wallich, Reinhard

2012-01-01

The promise of mesotherapy is maintenance and/or recovery of a youthful skin with a firm, bright and moisturized texture. Currently applied medications employ microinjections of hyaluronic acid, vitamins, minerals and amino acids into the superficial layer of the skin. However, the molecular and cellular processes underlying mesotherapy are still elusive. Here we analysed the effect of five distinct medication formulas on pivotal parameters involved in skin ageing, that is collagen expression, cell proliferation and morphological changes using normal human skin fibroblast cultures in vitro. Whereas in the presence of hyaluronic acid, NCTF135(®) and NCTF135HA(®) , cell proliferation was comparable to control cultures; however, with higher expression of collagen type-1, matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, addition of Soluvit(®) N and Meso-BK led to apoptosis and/or necrosis of human fibroblasts. The data indicate that bioactive reagents currently applied for skin rejuvenation elicit strikingly divergent physiological processes in human skin fibroblast in vitro. © 2011 John Wiley & Sons A/S.

Comparison of structure and organization of cutaneous lipids in a reconstructed skin model and human skin: spectroscopic imaging and chromatographic profiling.

Science.gov (United States)

Tfayli, Ali; Bonnier, Franck; Farhane, Zeineb; Libong, Danielle; Byrne, Hugh J; Baillet-Guffroy, Arlette

2014-06-01

The use of animals for scientific research is increasingly restricted by legislation, increasing the demand for human skin models. These constructs present comparable bulk lipid content to human skin. However, their permeability is significantly higher, limiting their applicability as models of barrier function, although the molecular origins of this reduced barrier function remain unclear. This study analyses the stratum corneum (SC) of one such commercially available reconstructed skin model (RSM) compared with human SC by spectroscopic imaging and chromatographic profiling. Total lipid composition was compared by chromatographic analysis (HPLC). Raman spectroscopy was used to evaluate the conformational order, lateral packing and distribution of lipids in the surface and skin/RSM sections. Although HPLC indicates that all SC lipid classes are present, significant differences are observed in ceramide profiles. Raman imaging demonstrated that the RSM lipids are distributed in a non-continuous matrix, providing a better understanding of the limited barrier function. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Activation of AMPK in human fetal membranes alleviates infection-induced expression of pro-inflammatory and pro-labour mediators.

Science.gov (United States)

Lim, R; Barker, G; Lappas, M

2015-04-01

In non-gestational tissues, the activation of adenosine monophosphate (AMP)-activated kinase (AMPK) is associated with potent anti-inflammatory actions. Infection and/or inflammation, by stimulating pro-inflammatory cytokines and matrix metalloproteinase (MMP)-9, play a central role in the rupture of fetal membranes. However, no studies have examined the role of AMPK in human labour. Fetal membranes, from term and preterm, were obtained from non-labouring and labouring women, and after preterm pre-labour rupture of membranes (PPROM). AMPK activity was assessed by Western blotting of phosphorylated AMPK expression. To determine the effect of AMPK activators on pro-inflammatory cytokines, fetal membranes were pre-treated with AMPK activators then stimulated with bacterial products LPS and flagellin or viral dsDNA analogue poly(I:C). Primary amnion cells were used to determine the effect of AMPK activators on IL-1β-stimulated MMP-9 expression. AMPK activity was decreased with term labour. There was no effect of preterm labour. AMPK activity was also decreased in preterm fetal membranes, in the absence of labour, with PROM compared to intact membranes. AMPK activators AICAR, phenformin and A769662 significantly decreased IL-6 and IL-8 stimulated by LPS, flagellin and poly(I:C). Primary amnion cells treated with AMPK activators significantly decreased IL-1β-induced MMP-9 expression. The decrease in AMPK activity in fetal membranes after spontaneous term labour and PPROM indicates an anti-inflammatory role for AMPK in human labour and delivery. The use of AMPK activators as possible therapeutics for threatened preterm labour would be an exciting future avenue of research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reduced cell number in the neocortical part of the human fetal brain in Down syndrome

DEFF Research Database (Denmark)

Larsen, K.B.; Laursen, H.; Graem, N.

2008-01-01

Mental retardation is seen in all individuals with Down syndrome (DS) and different brain abnormalities are reported. The aim of this study was to investigate if mental retardation at least in part is a result of a lower cell number in the neocortical part of the human fetal forebrain. We therefore...

Palladium nanoparticles exposure: Evaluation of permeation through damaged and intact human skin.

Science.gov (United States)

Larese Filon, Francesca; Crosera, Matteo; Mauro, Marcella; Baracchini, Elena; Bovenzi, Massimo; Montini, Tiziano; Fornasiero, Paolo; Adami, Gianpiero

2016-07-01

The intensified use of palladium nanoparticles (PdNPs) in many chemical reactions, jewellery, electronic devices, in car catalytic converters and in biomedical applications lead to a significant increase in palladium exposure. Pd can cause allergic contact dermatitis when in contact with the skin. However, there is still a lack of toxicological data related to nano-structured palladium and information on human cutaneous absorption. In fact, PdNPs, can be absorbed through the skin in higher amounts than bulk Pd because NPs can release more ions. In our study, we evaluated the absorption of PdNPs, with a size of 10.7 ± 2.8 nm, using intact and damaged human skin in Franz cells. 0.60 mg cm(-2) of PdNPs were applied on skin surface for 24 h. Pd concentrations in the receiving solutions at the end of experiments were 0.098 ± 0.067 μg cm(-2) and 1.06 ± 0.44 μg cm(-2) in intact skin and damaged skin, respectively. Pd flux permeation after 24 h was 0.005 ± 0.003 μg cm(-2) h(-1) and 0.057 ± 0.030 μg cm(-2) h(-1) and lag time 4.8 ± 1.7 and 4.2 ± 3.6 h, for intact and damaged skin respectively. This study indicates that Pd can penetrate human skin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization of the early local immune response to Ixodes ricinus tick bites in human skin.

Science.gov (United States)

Glatz, Martin; Means, Terry; Haas, Josef; Steere, Allen C; Müllegger, Robert R

2017-03-01

Little is known about the immunomodulation by tick saliva during a natural tick bite in human skin, the site of the tick-host interaction. We examined the expression of chemokines, cytokines and leucocyte markers on the mRNA levels and histopathologic changes in human skin biopsies of tick bites (n=37) compared to unaffected skin (n=9). Early tick-bite skin lesions (skin. With longer tick attachment (>24 hours), the numbers of innate immune cells and mediators (not significantly) declined, whereas the numbers of lymphocytes (not significantly) increased. Natural tick bites by Ixodes ricinus ticks initially elicit a strong local innate immune response in human skin. Beyond 24 hours of tick attachment, this response usually becomes less, perhaps because of immunomodulation by tick saliva. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Skin Blood Perfusion and Oxygenation Colour Affect Perceived Human Health

Science.gov (United States)

Stephen, Ian D.; Coetzee, Vinet; Law Smith, Miriam; Perrett, David I.

2009-01-01

Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice. PMID:19337378

The safety of donor skin preserved with glycerol - Evaluating the Euro Skin Bank preservation procedures of human donor skin against the prEN 12442 standard

NARCIS (Netherlands)

Geertsma RE; Wassenaar C; LGM

2000-01-01

The procedures for preservation of human donor skin with glycerol, as applied by the Euro Skin Bank (ESB), were evaluated against the prEN 12442 standard: animal tissues and their derivatives used in the manufacture of medical devices. The focus chosen for this review is on risks related to the

Studies in Fetal Behavior: Revisited, Renewed, and Reimagined

Science.gov (United States)

DiPietro, Janet A.; Costigan, Kathleen A.; Voegtline, Kristin M.

2016-01-01

Among the earliest volumes of this Monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodermal activity and fetal heart rate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include: within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physiological processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship. We pose a number of open questions for future research. Although the human fetus remains just out of reach, new

Dermal absorption behavior of fluorescent molecules in nanoparticles on human and porcine skin models.

Science.gov (United States)

Debotton, Nir; Badihi, Amit; Robinpour, Mano; Enk, Claes D; Benita, Simon

2017-05-30

The percutaneous passage of poorly skin absorbed molecules can be improved using nanocarriers, particularly biodegradable polymeric nanospheres (NSs) or nanocapsules (NCs). However, penetration of the encapsulated molecules may be affected by other factors than the nanocarrier properties. To gain insight information on the skin absorption of two fluorescent cargos, DiIC 18 (5) and coumarin-6 were incorporated in NSs or NCs and topically applied on various human and porcine skin samples. 3D imaging techniques suggest that NSs and NCs enhanced deep dermal penetration of both probes similarly, when applied on excised human skin irrespective of the nature of the cargo. However, when ex vivo pig skin was utilized, the cutaneous absorption of DiIC 18 (5) was more pronounced by means of PLGA NCs than NSs. In contrast, PLGA NSs noticeably improved the porcine skin penetration of coumarin-6, as compared to the NCs. Furthermore, the porcine skin results were reproducible when triplicated whereas from various human skin samples, as expected, the results were not sufficiently reproducible and large deviations were observed. The overall findings from this comprehensive comparison emphasize the potential of PLGA NCs or NSs to promote cutaneous bioavailability of encapsulated drugs, exhibiting different physicochemical properties but depending on the nature of the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

A Role for Human Skin Mast Cells in Dengue Virus Infection and Systemic Spread.

Science.gov (United States)

Troupin, Andrea; Shirley, Devon; Londono-Renteria, Berlin; Watson, Alan M; McHale, Cody; Hall, Alex; Hartstone-Rose, Adam; Klimstra, William B; Gomez, Gregorio; Colpitts, Tonya M

2016-12-01

Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious global human disease and mortality. Skin immune cells are an important component of initial DENV infection and systemic spread. Here, we show that mast cells are a target of DENV in human skin and that DENV infection of skin mast cells induces degranulation and alters cytokine and growth factor expression profiles. Importantly, to our knowledge, we also demonstrate for the first time that DENV localizes within secretory granules in infected skin mast cells. In addition, DENV within extracellular granules was infectious in vitro and in vivo, trafficking through lymph to draining lymph nodes in mice. We demonstrate an important role for human skin mast cells in DENV infection and identify a novel mechanism for systemic spread of DENV infection from the initial peripheral mosquito injection site. Copyright © 2016 by The American Association of Immunologists, Inc.

Genetic deletion of amphiregulin restores the normal skin phenotype in a mouse model of the human skin disease tylosis

Directory of Open Access Journals (Sweden)

Vishnu Hosur

2017-08-01

Full Text Available In humans, gain-of-function (GOF mutations in RHBDF2 cause the skin disease tylosis. We generated a mouse model of human tylosis and show that GOF mutations in RHBDF2 cause tylosis by enhancing the amount of amphiregulin (AREG secretion. Furthermore, we show that genetic disruption of AREG ameliorates skin pathology in mice carrying the human tylosis disease mutation. Collectively, our data suggest that RHBDF2 plays a critical role in regulating EGFR signaling and its downstream events, including development of tylosis, by facilitating enhanced secretion of AREG. Thus, targeting AREG could have therapeutic benefit in the treatment of tylosis.

Human fetal liver stromal cells that overexpress bFGF support growth and maintenance of human embryonic stem cells.

Directory of Open Access Journals (Sweden)

Jiafei Xi

Full Text Available In guiding hES cell technology toward the clinic, one key issue to be addressed is to culture and maintain hES cells much more safely and economically in large scale. In order to avoid using mouse embryonic fibroblasts (MEFs we isolated human fetal liver stromal cells (hFLSCs from 14 weeks human fetal liver as new human feeder cells. hFLSCs feeders could maintain hES cells for 15 passages (about 100 days. Basic fibroblast growth factor (bFGF is known to play an important role in promoting self-renewal of human embryonic stem (hES cells. So, we established transgenic hFLSCs that stably express bFGF by lentiviral vectors. These transgenic human feeder cells--bFGF-hFLSCs maintained the properties of H9 hES cells without supplementing with any exogenous growth factors. H9 hES cells culturing under these conditions maintained all hES cell features after prolonged culture, including the developmental potential to differentiate into representative tissues of all three embryonic germ layers, unlimited and undifferentiated proliferative ability, and maintenance of normal karyotype. Our results demonstrated that bFGF-hFLSCs feeder cells were central to establishing the signaling network among bFGF, insulin-like growth factor 2 (IGF-2, and transforming growth factor β (TGF-β, thereby providing the framework in which hES cells were instructed to self-renew or to differentiate. We also found that the conditioned medium of bFGF-hFLSCs could maintain the H9 hES cells under feeder-free conditions without supplementing with bFGF. Taken together, bFGF-hFLSCs had great potential as feeders for maintaining pluripotent hES cell lines more safely and economically.

Recognizing different tissues in human fetal femur cartilage by label-free Raman microspectroscopy

Science.gov (United States)

Kunstar, Aliz; Leijten, Jeroen; van Leuveren, Stefan; Hilderink, Janneke; Otto, Cees; van Blitterswijk, Clemens A.; Karperien, Marcel; van Apeldoorn, Aart A.

2012-11-01

Traditionally, the composition of bone and cartilage is determined by standard histological methods. We used Raman microscopy, which provides a molecular "fingerprint" of the investigated sample, to detect differences between the zones in human fetal femur cartilage without the need for additional staining or labeling. Raman area scans were made from the (pre)articular cartilage, resting, proliferative, and hypertrophic zones of growth plate and endochondral bone within human fetal femora. Multivariate data analysis was performed on Raman spectral datasets to construct cluster images with corresponding cluster averages. Cluster analysis resulted in detection of individual chondrocyte spectra that could be separated from cartilage extracellular matrix (ECM) spectra and was verified by comparing cluster images with intensity-based Raman images for the deoxyribonucleic acid/ribonucleic acid (DNA/RNA) band. Specific dendrograms were created using Ward's clustering method, and principal component analysis (PCA) was performed with the separated and averaged Raman spectra of cells and ECM of all measured zones. Overall (dis)similarities between measured zones were effectively visualized on the dendrograms and main spectral differences were revealed by PCA allowing for label-free detection of individual cartilaginous zones and for label-free evaluation of proper cartilaginous matrix formation for future tissue engineering and clinical purposes.

Mechanical response of human female breast skin under uniaxial stretching.

Science.gov (United States)

Kumaraswamy, N; Khatam, Hamed; Reece, Gregory P; Fingeret, Michelle C; Markey, Mia K; Ravi-Chandar, Krishnaswamy

2017-10-01

Skin is a complex material covering the entire surface of the human body. Studying the mechanical properties of skin to calibrate a constitutive model is of great importance to many applications such as plastic or cosmetic surgery and treatment of skin-based diseases like decubitus ulcers. The main objective of the present study was to identify and calibrate an appropriate material constitutive model for skin and establish certain universal properties that are independent of patient-specific variability. We performed uniaxial tests performed on breast skin specimens freshly harvested during mastectomy. Two different constitutive models - one phenomenological and another microstructurally inspired - were used to interpret the mechanical responses observed in the experiments. Remarkably, we found that the model parameters that characterize dependence on previous maximum stretch (or preconditioning) exhibited specimen-independent universal behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low vascularization of the nephrogenic zone of the fetal kidney suggests a major role for hypoxia in human nephrogenesis.

Science.gov (United States)

Gerosa, C; Fanni, D; Faa, A; Van Eyken, P; Ravarino, A; Fanos, V; Faa, G

2017-09-01

CD31 reactivity is generally utilized as a marker of endothelial cells. CD31 immunoreactivity in the developing human kidney revealed that fetal glomerular capillary endothelial cells change their immunohistochemical phenotype during maturation. The aim of this study was to analyze CD31 reactivity in the fetal human kidney in the different stages of intrauterine development: We observed different distribution of CD31-reactive vascular progenitors in the different areas of the developing kidney. In particular, the nephrogenic zone and the renal capsule were characterized by a scarcity of CD31-reactive cells at all gestational ages. These data suggest the hypothesis that nephrogenesis does not need high oxygen levels and confirms a major role of hypoxia in nephrogenesis.

Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells.

Science.gov (United States)

Gledhill, Karl; Guo, Zongyou; Umegaki-Arao, Noriko; Higgins, Claire A; Itoh, Munenari; Christiano, Angela M

2015-01-01

The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs) present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes.

Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells.

Directory of Open Access Journals (Sweden)

Karl Gledhill

Full Text Available The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes.

Climate change, ozone depletion and the impact on ultraviolet exposure of human skin

International Nuclear Information System (INIS)

Diffey, Brian

2004-01-01

For 30 years there has been concern that anthropogenic damage to the Earth's stratospheric ozone layer will lead to an increase of solar ultraviolet (UV) radiation reaching the Earth's surface, with a consequent adverse impact on human health, especially to the skin. More recently, there has been an increased awareness of the interactions between ozone depletion and climate change (global warming), which could also impact on human exposure to terrestrial UV. The most serious effect of changing UV exposure of human skin is the potential rise in incidence of skin cancers. Risk estimates of this disease associated with ozone depletion suggest that an additional peak incidence of 5000 cases of skin cancer per year in the UK would occur around the mid-part of this century. Climate change, which is predicted to lead to an increased frequency of extreme temperature events and high summer temperatures, will become more frequent in the UK. This could impact on human UV exposure by encouraging people to spend more time in the sun. Whilst future social trends remain uncertain, it is likely that over this century behaviour associated with climate change, rather than ozone depletion, will be the largest determinant of sun exposure, and consequent impact on skin cancer, of the UK population. (topical review)

Studies of the in vivo radiosensitivity of human skin fibroblasts

International Nuclear Information System (INIS)

Hill, Richard P.; Kaspler, Pavel; Griffin, Anthony M.; O'Sullivan, Brian; Catton, Charles; Alasti, Hamideh; Abbas, Ahmar; Heydarian, Moustafa; Ferguson, Peter; Wunder, Jay S.; Bell, Robert S.

2007-01-01

Background and purpose: To examine the radiosensitivity of skin cells obtained directly from the irradiated skin of patients undergoing fractionated radiation treatment prior to surgery for treatment of soft tissue sarcoma (STS) and to determine if there was a relationship with the development of wound healing complications associated with the surgery post-radiotherapy. Methods: Micronucleus (MN) formation was measured in cells (primarily dermal fibroblasts) obtained from human skin at their first division after being removed from STS patients during post-radiotherapy surgery (2-9 weeks after the end of the radiotherapy). At the time of radiotherapy (planned tumor dose - 50 Gy in 25 daily fractions) measurements were made of surface skin dose at predetermined marked sites. Skin from these sites was obtained at surgery and cell suspensions were prepared directly for the cytokinesis-blocked MN assay. Cultured strains of the fibroblasts were also established from skin nominally outside the edge of the radiation beam and DNA damage (MN formation) was examined following irradiation in vitro for comparison with the results from the in situ irradiations. Results: Extensive DNA damage (MN) was detectable in fibroblasts from human skin at extended periods after irradiation (2-9 weeks after the end of the 5-week fractionated radiotherapy). Analysis of skin receiving a range of doses demonstrated that the level of damage observed was dose dependent. There was no clear correlation between the level of damage observed after irradiation in situ and irradiation of cell strains in culture. Similarly, there was no correlation between the extent of MN formation following in situ irradiation and the propensity for the patient to develop wound healing complications post-surgery. Conclusions: Despite the presence of DNA damage in dermal fibroblasts weeks after the end of the radiation treatment, there was no relationship between this damage and wound healing complications following

Flexible Nanosomes (SECosomes) Enable Efficient siRNA Delivery in Cultured Primary Skin Cells and in the Viable Epidermis of Ex Vivo Human Skin

NARCIS (Netherlands)

Geusens, Barbara; Van Gele, Mireille; Braat, Sien; De Smedt, Stefaan C.; Stuart, Marc C. A.; Prow, Tarl W.; Sanchez, Washington; Roberts, Michael S.; Sanders, Niek N.; Lambert, Jo

2010-01-01

The extent to which nanoscale-engineered systems cross intact human skin and can exert pharmacological effects in viable epidermis is controversial. This research seeks to develop a new lipid-based nanosome that enables the effective delivery of siRNA into human skin. The major finding is that an

21 CFR 864.7455 - Fetal hemoglobin assay.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7455 Fetal hemoglobin...

Photoprotection by pistachio bioactives in a 3-dimensional human skin equivalent tissue model.

Science.gov (United States)

Chen, C-Y Oliver; Smith, Avi; Liu, Yuntao; Du, Peng; Blumberg, Jeffrey B; Garlick, Jonathan

2017-09-01

Reactive oxygen species (ROS) generated during ultraviolet (UV) light exposure can induce skin damage and aging. Antioxidants can provide protection against oxidative injury to skin via "quenching" ROS. Using a validated 3-dimensional (3D) human skin equivalent (HSE) tissue model that closely mimics human skin, we examined whether pistachio antioxidants could protect HSE against UVA-induced damage. Lutein and γ-tocopherol are the predominant lipophilic antioxidants in pistachios; treatment with these compounds prior to UVA exposure protected against morphological changes to the epithelial and connective tissue compartments of HSE. Pistachio antioxidants preserved overall skin thickness and organization, as well as fibroblast morphology, in HSE exposed to UVA irradiation. However, this protection was not substantiated by the analysis of the proliferation of keratinocytes and apoptosis of fibroblasts. Additional studies are warranted to elucidate the basis of these discordant results and extend research into the potential role of pistachio bioactives promoting skin health.

Anatomical relationships between testis and epididymis during the fetal period in humans (10-36 weeks postconception)

NARCIS (Netherlands)

Favorito, LA; Sampaio, FJB

1998-01-01

Objective: To determine the anatomy of the epididymis and its relationship with the testis during the fetal period in normal individuals. Methods: We studied bilaterally 146 testes and epididymides taken from 73 normal fresh human fetuses ranging in age from 10 to 36 weeks postconception. The

Ultrasonic evaluation of local human skin anisotropy

Czech Academy of Sciences Publication Activity Database

Tokar, Daniel; Převorovský, Zdeněk; Hradilová, Jana

2014-01-01

Roč. 19, č. 12 (2014) ISSN 1435-4934. [European Conference on Non-Destructive Testing (ECNDT 2014) /11./. Praha, 06.10.2014-10.10.2014] Institutional support: RVO:61388998 Keywords : anisotropy * ultrasonic testing * human skin in-vivo * fabric-fiber composite * signal processing Subject RIV: BI - Acoustics http://www.ndt.net/events/ECNDT2014/app/content/Paper/324_Tokar.pdf

A role for human mitochondrial complex II in the production of reactive oxygen species in human skin

Directory of Open Access Journals (Sweden)

Alasdair Anderson

2014-01-01

Full Text Available The mitochondrial respiratory chain is a major generator of cellular oxidative stress, thought to be an underlying cause of the carcinogenic and ageing process in many tissues including skin. Previous studies of the relative contributions of the respiratory chain (RC complexes I, II and III towards production of reactive oxygen species (ROS have focussed on rat tissues and certainly not on human skin which is surprising as this tissue is regularly exposed to UVA in sunlight, a potent generator of cellular oxidative stress. In a novel approach we have used an array of established specific metabolic inhibitors and DHR123 fluorescence to study the relative roles of the mitochondrial RC complexes in cellular ROS production in 2 types of human skin cells. These include additional enhancement of ROS production by exposure to physiological levels of UVA. The effects within epidermal and dermal derived skin cells are compared to other tissue cell types as well as those harbouring a compromised mitochondrial status (Rho-zero A549. The results show that the complex II inhibitor, TTFA, was the only RC inhibitor to significantly increase UVA-induced ROS production in both skin cell types (P<0.05 suggesting that the role of human skin complex II in terms of influencing ROS production is more important than previously thought particularly in comparison to liver cells. Interestingly, two-fold greater maximal activity of complex II enzyme was observed in both skin cell types compared to liver (P<0.001. The activities of RC enzymes appear to decrease with increasing age and telomere length is correlated with ageing. Our study showed that the level of maximal complex II activity was higher in the MRC5/hTERT (human lung fibroblasts transfected with telomerase cells than the corresponding wild type cells (P=0.0012 which can be considered (in terms of telomerase activity as models of younger and older cells respectively.

Characterisation of human skin models - stability, metabolic capacity and comparative investigations in percutaneous absorption

OpenAIRE

Schreiber, Sylvia

2010-01-01

In recent years, the demand for alternative test methods in safety assessment of cosmetics, risk assessment of chemicals, and testing of pharmaceuticals was increasingly included in the EU directives. Thereby, alternative test methods for the determination of percutaneous absorption should achieve a more reliable in vivo prediction of the response of human skin than animal skin. Even though freshly excised human skin is considered as a preferred test matrix its routine use is often difficult ...

Effects of environmental Bisphenol A exposures on germ cell development and Leydig cell function in the human fetal testis.

Directory of Open Access Journals (Sweden)

Soria Eladak

Full Text Available Using an organotypic culture system termed human Fetal Testis Assay (hFeTA we previously showed that 0.01 μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models.Using the hFeTA system, first trimester testes were cultured for 3 days with 0.01 to 10 μM BPA. For xenografts, adult castrate male nude mice were injected with hCG and grafted with first trimester testes. Host mice received 10 μM BPA (~ 500 μg/kg/day in their drinking water for 5 weeks. Plasma levels of total and unconjugated BPA were 0.10 μM and 0.038 μM respectively. Mice grafted with second trimester testes received 0.5 and 50 μg/kg/day BPA by oral gavage for 5 weeks.With first trimester human testes, using the hFeTA model, 10 μM BPA increased germ cell apoptosis. In xenografts, germ cell density was also reduced by BPA exposure. Importantly, BPA exposure significantly decreased the percentage of germ cells expressing the pluripotency marker AP-2γ, whilst the percentage of those expressing the pre-spermatogonial marker MAGE-A4 significantly increased. BPA exposure did not affect hCG-stimulated androgen production in first and second trimester xenografts as evaluated by both plasma testosterone level and seminal vesicle weight in host mice.Exposure to BPA at environmentally relevant concentrations impairs germ cell development in first trimester human fetal testis, whilst gonadotrophin-stimulated testosterone production was unaffected in both first and second trimester testis. Studies using first trimester human fetal testis demonstrate the complementarity of the FeTA and xenograft models for determining the respective short-term and long term effects of environmental exposures.

Technical note: comparing von Luschan skin color tiles and modern spectrophotometry for measuring human skin pigmentation.

Science.gov (United States)

Swiatoniowski, Anna K; Quillen, Ellen E; Shriver, Mark D; Jablonski, Nina G

2013-06-01

Prior to the introduction of reflectance spectrophotometry into anthropological field research during the 1950s, human skin color was most commonly classified by visual skin color matching using the von Luschan tiles, a set of 36 standardized, opaque glass tiles arranged in a chromatic scale. Our goal was to establish a conversion formula between the tile-based color matching method and modern reflectance spectrophotometry to make historical and contemporary data comparable. Skin pigmentation measurements were taken on the forehead, inner upper arms, and backs of the hands using both the tiles and a spectrophotometer on 246 participants showing a broad range of skin pigmentation. From these data, a second-order polynomial conversion formula was derived by jackknife analysis to estimate melanin index (M-index) based on tile values. This conversion formula provides a means for comparing modern data to von Luschan tile measurements recorded in historical reports. This is particularly important for populations now extinct, extirpated, or admixed for which tile-based measures of skin pigmentation are the only data available. Copyright © 2013 Wiley Periodicals, Inc.

Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation?

Science.gov (United States)

Burnouf, Thierry; Strunk, Dirk; Koh, Mickey B C; Schallmoser, Katharina

2016-01-01

The essential physiological role of platelets in wound healing and tissue repair builds the rationale for the use of human platelet derivatives in regenerative medicine. Abundant growth factors and cytokines stored in platelet granules can be naturally released by thrombin activation and clotting or artificially by freeze/thaw-mediated platelet lysis, sonication or chemical treatment. Human platelet lysate prepared by the various release strategies has been established as a suitable alternative to fetal bovine serum as culture medium supplement, enabling efficient propagation of human cells under animal serum-free conditions for a multiplicity of applications in advanced somatic cell therapy and tissue engineering. The rapidly increasing number of studies using platelet derived products for inducing human cell proliferation and differentiation has also uncovered a considerable variability of human platelet lysate preparations which limits comparability of results. The main variations discussed herein encompass aspects of donor selection, preparation of the starting material, the possibility for pooling in plasma or additive solution, the implementation of pathogen inactivation and consideration of ABO blood groups, all of which can influence applicability. This review outlines the current knowledge about human platelet lysate as a powerful additive for human cell propagation and highlights its role as a prevailing supplement for human cell culture capable to replace animal serum in a growing spectrum of applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Navigation Guide - evidence-based medicine meets environmental health: integration of animal and human evidence for PFOA effects on fetal growth.

Science.gov (United States)

Lam, Juleen; Koustas, Erica; Sutton, Patrice; Johnson, Paula I; Atchley, Dylan S; Sen, Saunak; Robinson, Karen A; Axelrad, Daniel A; Woodruff, Tracey J

2014-10-01

The Navigation Guide is a novel systematic review method to synthesize scientific evidence and reach strength of evidence conclusions for environmental health decision making. Our aim was to integrate scientific findings from human and nonhuman studies to determine the overall strength of evidence for the question "Does developmental exposure to perfluorooctanoic acid (PFOA) affect fetal growth in humans?" We developed and applied prespecified criteria to systematically and transparently a) rate the quality of the scientific evidence as "high," "moderate," or "low"; b) rate the strength of the human and nonhuman evidence separately as "sufficient," "limited," "moderate," or "evidence of lack of toxicity"; and c) integrate the strength of the human and nonhuman evidence ratings into a strength of the evidence conclusion. We identified 18 epidemiology studies and 21 animal toxicology studies relevant to our study question. We rated both the human and nonhuman mammalian evidence as "moderate" quality and "sufficient" strength. Integration of these evidence ratings produced a final strength of evidence rating in which review authors concluded that PFOA is "known to be toxic" to human reproduction and development based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. We concluded that developmental exposure to PFOA adversely affects human health based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. The results of this case study demonstrate the application of a systematic and transparent methodology, via the Navigation Guide, for reaching strength of evidence conclusions in environmental health.

Percutaneous absorption and skin decontamination of PCBs: In vitro studies with human skin and in vivo studies in the rhesus monkey

International Nuclear Information System (INIS)

Wester, R.C.; Maibach, H.I.; Bucks, D.A.; McMaster, J.; Mobayen, M.; Sarason, R.; Moore, A.

1990-01-01

Knowledge of the entry of polychlorinated biphenyls through the skin into the body and subsequent disposition aids estimation of potential for human health hazard. [14C]Aroclor 1242 and [14C]Aroclor 1254 were separately administered intravenously and topically to rhesus monkeys. Following iv administration, 30-d excretion was 39.4 +/- 5.9% urine and 16.1 +/- 0.8% feces (total 55.5 +/- 5.1%) for Aroclor 1242, and 7.0 +/- 2.2% urine and 19.7 +/- 5.8% feces (total 26.7 +/- 7.5%) for Aroclor 1254. Mineral oil and trichlorobenzene are common PCB cosolvents in transformers. Skin absorption of Aroclor 1242 was 20.4 +/- 8.5% formulated in mineral oil and 18.0 +/- 3.8% in trichlorobenzene (p greater than .05). Absorption of Aroclor 1254 was 20.8 +/- 8.3% in mineral oil and 14.6 +/- 3.6% in trichlorobenzene (p greater than .05). PCBs are thus absorbed through skin, and excretion from the body is slow. Vehicle (trichlorobenzene or mineral oil) did not affect percutaneous absorption. In vitro skin absorption in human cadaver skin did not correlate with in vivo findings. This was due to lack of PCB partition from skin into the water receptor fluid, even with addition of 6% Oleth 20 (Volpo 20) solubilizer. Skin decontamination of PCBs showed soap and water to be as effective as or better than the solvent ethanol, mineral oil, and trichlorobenzene in removing PCBs from skin. There is a dynamic time lapse for PCBs between initial skin contact and skin absorption (irreversible removal). Thus initially most PCBs could be removed from skin, but this ability decreased with time to the point where at 24 h only about 25% of the initial PCB skin dose could be recovered with skin washing

UV decreases the synthesis of free fatty acids and triglycerides in the epidermis of human skin in vivo, contributing to development of skin photoaging.

Science.gov (United States)

Kim, Eun Ju; Jin, Xing-Ji; Kim, Yeon Kyung; Oh, In Kyung; Kim, Ji Eun; Park, Chi-Hyun; Chung, Jin Ho

2010-01-01

Although fatty acids are known to be important in various skin functions, their roles on photoaging in human skin are poorly understood. We investigated the alteration of lipid metabolism in the epidermis by photoaging and acute UV irradiation in human skin. UV irradiated young volunteers (21-33 years, n=6) and elderly volunteers (70-75 years, n=7) skin samples were obtained by punch biopsy. Then the epidermis was separated from dermis and lipid metabolism was investigated. We observed that the amounts of free fatty acids (FFA) and triglycerides (TG) in the epidermis of photoaged or acutely UV irradiated human skin were significantly decreased. The expressions of genes related to lipid synthesis, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD), sterol regulatory element binding proteins (SREBPs), and peroxisome proliferator-activated receptors (PPARgamma) were also markedly decreased. To elucidate the significance of these changes of epidermal lipids in human skin, we investigated the effects of TG or various inhibitors for the enzymes involved in TG synthesis on the expression of matrix metalloproteinase-1 (MMP-1) in cultured human epidermal keratinocytes. We demonstrated that triolein (TG) reduced basal and UV-induced MMP-1 mRNA expression. In addition, each inhibitor for various lipid synthesis enzymes, such as TOFA (ACC inhibitor), cerulenin (FAS inhibitor) and trans-10, cis-12-CLA (SCD inhibitor), increased the MMP-1 expression significantly in a dose-dependent manner. We also demonstrated that triolein could inhibit cerulenin-induced MMP-1 expression. Furthermore, topical application of triolein (10%) significantly prevented UV-induced MMP-13, COX-2, and IL-1beta expression in hairless mice. Our results suggest that TG and FFA may play important roles in photoaging of human skin. Copyright 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Lipidomic analysis of epidermal lipids: a tool to predict progression of inflammatory skin disease in humans.

Science.gov (United States)

Li, Shan; Ganguli-Indra, Gitali; Indra, Arup K

2016-05-01

Lipidomics is the large-scale profiling and characterization of lipid species in a biological system using mass spectrometry. The skin barrier is mainly comprised of corneocytes and a lipid-enriched extracellular matrix. The major skin lipids are ceramides, cholesterol and free fatty acids (FFA). Lipid compositions are altered in inflammatory skin disorders with disrupted skin barrier such as atopic dermatitis (AD). Here we discuss some of the recent applications of lipidomics in human skin biology and in inflammatory skin diseases such as AD, psoriasis and Netherton syndrome. We also review applications of lipidomics in human skin equivalent and in pre-clinical animal models of skin diseases to gain insight into the pathogenesis of the skin disease. Expert commentary: Skin lipidomics analysis could be a fast, reliable and noninvasive tool to characterize the skin lipid profile and to monitor the progression of inflammatory skin diseases such as AD.

In situ depletion of CD4(+) T cells in human skin by Zanolimumab

DEFF Research Database (Denmark)

Villadsen, L.S.; Skov, L.; Dam, T.N.

2007-01-01

CD4(+) T cells, in activated or malignant form, are involved in a number of diseases including inflammatory skin diseases such as psoriasis, and T cell lymphomas such as the majority of cutaneous T cell lymphomas (CTCL). Targeting CD4 with an antibody that inhibits and/or eliminates disease......-driving T cells in situ may therefore be a useful approach in the treatment of inflammatory and malignant skin diseases. Depletion of CD4(+) T cells in intact inflamed human skin tissue by Zanolimumab, a fully human therapeutic monoclonal antibody (IgG1, kappa) against CD4, was studied in a human psoriasis......(+), but not CD8(+) CD3(+) T cells. The capacity of Zanolimumab to deplete the CD4(+) T cells in the skin may be of importance in diseases where CD4(+) T cells play a central role. Indeed, in a phase II clinical trial Zanolimumab has shown a dose-dependent clinical response in patients with CTCL and the antibody...

Screening Test for Shed Skin Cells by Measuring the Ratio of Human DNA to Staphylococcus epidermidis DNA.

Science.gov (United States)

Nakanishi, Hiroaki; Ohmori, Takeshi; Hara, Masaaki; Takahashi, Shirushi; Kurosu, Akira; Takada, Aya; Saito, Kazuyuki

2016-05-01

A novel screening method for shed skin cells by detecting Staphylococcus epidermidis (S. epidermidis), which is a resident bacterium on skin, was developed. Staphylococcus epidermidis was detected using real-time PCR. Staphylococcus epidermidis was detected in all 20 human skin surface samples. Although not present in blood and urine samples, S. epidermidis was detected in 6 of 20 saliva samples, and 5 of 18 semen samples. The ratio of human DNA to S. epidermidisDNA was significantly smaller in human skin surface samples than in saliva and semen samples in which S. epidermidis was detected. Therefore, although skin cells could not be identified by detecting only S. epidermidis, they could be distinguished by measuring the S. epidermidis to human DNA ratio. This method could be applied to casework touch samples, which suggests that it is useful for screening whether skin cells and human DNA are present on potential evidentiary touch samples. © 2016 American Academy of Forensic Sciences.

Human skin in vitro permeation of bentazon and isoproturon formulations with or without protective clothing suit.

Science.gov (United States)

Berthet, Aurélie; Hopf, Nancy B; Miles, Alexandra; Spring, Philipp; Charrière, Nicole; Garrigou, Alain; Baldi, Isabelle; Vernez, David

2014-01-01

Skin exposures to chemicals may lead, through percutaneous permeation, to a significant increase in systemic circulation. Skin is the primary route of entry during some occupational activities, especially in agriculture. To reduce skin exposures, the use of personal protective equipment (PPE) is recommended. PPE efficiency is characterized as the time until products permeate through material (lag time, Tlag). Both skin and PPE permeations are assessed using similar in vitro methods; the diffusion cell system. Flow-through diffusion cells were used in this study to assess the permeation of two herbicides, bentazon and isoproturon, as well as four related commercial formulations (Basagran(®), Basamais(®), Arelon(®) and Matara(®)). Permeation was measured through fresh excised human skin, protective clothing suits (suits) (Microchem(®) 3000, AgriSafe Pro(®), Proshield(®) and Microgard(®) 2000 Plus Green), and a combination of skin and suits. Both herbicides, tested by itself or as an active ingredient in formulations, permeated readily through human skin and tested suits (Tlag < 2 h). High permeation coefficients were obtained regardless of formulations or tested membranes, except for Microchem(®) 3000. Short Tlag, were observed even when skin was covered with suits, except for Microchem(®) 3000. Kp values tended to decrease when suits covered the skin (except when Arelon(®) was applied to skin covered with AgriSafe Pro and Microgard(®) 2000), suggesting that Tlag alone is insufficient in characterizing suits. To better estimate human skin permeations, in vitro experiments should not only use human skin but also consider the intended use of the suit, i.e., the active ingredient concentrations and type of formulations, which significantly affect skin permeation.

Towards a new era in fetal medicine in the Nordic countries

DEFF Research Database (Denmark)

Sitras, Vasilis; Brodszki, Jana; Carlsson, Ylva

2016-01-01

Fetal medicine is a subspecialty of obstetrics investigating the development, growth and disease of the human fetus. The advances in fetal imaging (ultrasonography, MRI) and molecular diagnostic techniques, together with the possibility of intervention in utero, make fetal medicine an important, ...

Development of steroid signaling pathways during primordial follicle formation in the human fetal ovary.

Science.gov (United States)

Fowler, Paul A; Anderson, Richard A; Saunders, Philippa T; Kinnell, Hazel; Mason, J Ian; Evans, Dean B; Bhattacharya, Siladitya; Flannigan, Samantha; Franks, Stephen; Monteiro, Ana; O'Shaughnessy, Peter J

2011-06-01

Ovarian primordial follicle formation is critical for subsequent human female fertility. It is likely that steroid, and especially estrogen, signaling is required for this process, but details of the pathways involved are currently lacking. The aim was to identify and characterize key members of the steroid-signaling pathway expressed in the second trimester human fetal ovary. We conducted an observational study of the female fetus, quantifying and localizing steroid-signaling pathway members. The study was conducted at the Universities of Aberdeen, Edinburgh, and Glasgow. Ovaries were collected from 43 morphologically normal human female fetuses from women undergoing elective termination of second trimester pregnancies. We measured mRNA transcript levels and immunolocalized key steroidogenic enzymes and steroid receptors, including those encoded by ESR2, AR, and CYP19A1. Levels of mRNA encoding the steroidogenic apparatus and steroid receptors increased across the second trimester. CYP19A1 transcript increased 4.7-fold during this period with intense immunostaining for CYP19A detected in pregranulosa cells around primordial follicles and somatic cells around oocyte nests. ESR2 was localized primarily to germ cells, but androgen receptor was exclusively expressed in somatic cells. CYP17A1 and HSD3B2 were also localized to oocytes, whereas CYP11A1 was detected in oocytes and some pregranulosa cells. The human fetal ovary expresses the machinery to produce and detect multiple steroid signaling pathways, including estrogenic signaling, with the oocyte acting as a key component. This study provides a step-change in our understanding of local dynamics of steroid hormone signaling during the key period of human primordial follicle formation.

Approach to quantify human dermal skin aging using multiphoton laser scanning microscopy

Science.gov (United States)

Puschmann, Stefan; Rahn, Christian-Dennis; Wenck, Horst; Gallinat, Stefan; Fischer, Frank

2012-03-01

Extracellular skin structures in human skin are impaired during intrinsic and extrinsic aging. Assessment of these dermal changes is conducted by subjective clinical evaluation and histological and molecular analysis. We aimed to develop a new parameter for the noninvasive quantitative determination of dermal skin alterations utilizing the high-resolution three-dimensional multiphoton laser scanning microscopy (MPLSM) technique. To quantify structural differences between chronically sun-exposed and sun-protected human skin, the respective collagen-specific second harmonic generation and the elastin-specific autofluorescence signals were recorded in young and elderly volunteers using the MPLSM technique. After image processing, the elastin-to-collagen ratio (ELCOR) was calculated. Results show that the ELCOR parameter of volar forearm skin significantly increases with age. For elderly volunteers, the ELCOR value calculated for the chronically sun-exposed temple area is significantly augmented compared to the sun-protected upper arm area. Based on the MPLSM technology, we introduce the ELCOR parameter as a new means to quantify accurately age-associated alterations in the extracellular matrix.

Permeability of commercial solvents through living human skin

DEFF Research Database (Denmark)

Ursin, C; Hansen, C M; Van Dyk, J W

1995-01-01

A procedure has been developed for measuring the steady state rate of permeation of commercial solvents through living human skin. To get the most consistent results, it was necessary with some solvents to normalize the solvent permeation rate of a given skin sample with its [3H]water permeation...... rate. For other solvents this was not necessary, so the un-normalized data were used. High [3H]water permeation rate also was used as a criterion for "defective" skin samples that gave erroneous permeability rates, especially for solvents having slow permeability. The linearity of the steady state data...... was characterized by calculation of the "percent error of the slope." The following permeability rates (g/m2h) of single solvents were measured: dimethyl sulfoxide (DMSO), 176; N-methyl-2-pyrrolidone, 171; dimethyl acetamide, 107; methyl ethyl ketone, 53; methylene chloride, 24; [3H]water, 14.8; ethanol, 11...

Expression of telomerase reverse transcriptase in radiation-induced chronic human skin ulcer

International Nuclear Information System (INIS)

Zhao Po; Li Zhijun; Lu Yali; Zhong Mei; Gu Qingyang; Wang Dewen

2001-01-01

Objective: To investigate the expression of the catalytic subunit of telomerase, telomerase reverse transcriptase (TRT) and the possible relationship between the TRT and cancer transformation or poor healing in radiation-induced chronic ulcer of human skin. Methods: Rabbit antibody against human TRT and SP immunohistochemical method were used to detect TRT expression in 24 cases of formalin-fixed, paraffin-embed human skin chronic ulcer tissues induced by radiation, 5 cases of normal skin, 2 of burned skin, and 8 of carcinoma. Results: The positive rate for TRT was 58.3%(14/24) in chronic radiation ulcers, of which the strongly positive rate was 41.7%(10/24) and the weakly positive 16.7%(4/24), 0% in normal (0/5) and burned skin (0/2), and 100% in carcinoma (8/8). The strongly positive expression of TRT was observed almost always in the cytoplasm and nucleus of squamous epithelial cells of proliferative epidermis but the negative and partly weakly positive expression in the smooth muscles, endothelia of small blood vessels and capillaries, and fibroblasts. Chronic inflammtory cells, plasmacytes and lymphocytes also showed weakly positive for TRT. Conclusion: TRT expression could be involved in the malignant transformation of chronic radiation ulcer into squamous carcinoma, and in the poor healing caused by sclerosis of small blood vessels and lack of granulation tissue consisting of capillaries and fibroblasts

Signatures of human skin in the millimetre wave band (80-100) GHz

Science.gov (United States)

Owda, Amani Y.; Rezgui, Nacer-Ddine; Salmon, Neil A.

2017-10-01

With the performance of millimeter wave security screening imagers improving (reduced speckle, greater sensitivity, and better spatial resolution) attention is turning to identification of anomalies which appear on the human body. Key to this identification is the understanding of how the emissive and reflective properties vary over the human body and between different categories of people, defined by age and gender for example. As the interaction of millimetre waves with the human body is only a fraction of a millimetre into the skin, precise measurement of the emission and reflection of this radiation will allow comparisons with the norm for that region of the body and person category. On an automated basis at security screening portals, this will increase detection probabilities and reduce false alarm rates, ensuring high throughputs at entrances to future airport departure lounges and transport networks. A technique to measure the human skin emissivity in vivo over the frequency band 80 GHz to 100 GHz is described. The emissivities of the skin of a sample of 60 healthy participants (36 males and 24 females) measured using a 90 GHz calibrated radiometer was found to range from 0.17+/-0.002 to 0.68+/-0.002. The radiometric measurements were made at four locations on the arm, namely: palm of hand, back of hand, dorsal surface of the forearm, and volar side of the forearm, where the water content and the skin thickness are known to be different. These measurements show significant variation in emissivity from person to person and, more importantly, significant variation at different locations on the arms of individuals. Males were found to have an emissivity 0.03 higher than those of females. The emissivity of the back of the hand, where the skin is thinner and the blood vessels are closer to the skin surface, was found to be lower by 0.0681 than the emissivity of the palm of the hand, where the skin is thicker. The measurements also show that the emissivity of the

Studies on the absorption of epoxy resin 14C-epidian 5 through the skin of guinea pigs

International Nuclear Information System (INIS)

Woyton, A.; Wozniak, M.; Dobryszycka, W.

1976-01-01

The absorption and spread of epoxy resin labelled with 14 C-epidian 5, was evaluated by measurements of radioactivity of the skin and individual organs in guinea pigs and of the ovum in pregnant guinea pigs. It has been demonstrated that the radioactive resin is slowly absorbed through the skin and reaches, by blood vessels, inner organs and the skin distant from the smeared site. The liver participates actively in the metabolism of epidian 5. The radioactivity of the nervous tissue and urine of the guinea pig bladder increased successively with the length of time, which indicates this way of excretion of the resin. In fetal membranes the level of radioactivity was considerably higher than in the placental tissue and fetal fluids. Worthy of note is also that livers of guinea pig fetuses showed an isotope mark and that radioactivity increased in the fetal pulmonary tissue. (author)

Fetal hyperglycemia changes human preadipocyte function in adult life

DEFF Research Database (Denmark)

Hansen, Ninna Schiøler; Strasko, Klaudia Stanislawa; Hjort, Line

2017-01-01

Context: Offspring of women with gestational diabetes (O-GDM) or type 1 diabetes mellitus (O-T1DM) have been exposed to hyperglycemia in utero and have an increased risk of developing metabolic disease in adulthood. Design: In total, we recruited 206 adult offspring comprising the two fetal...... acid supply. Conclusions: Taken together, these findings show that intrinsic epigenetic and functional changes exist in preadipocyte cultures from individuals exposed to fetal hyperglycemia who are at increased risk of developing metabolic disease....

A library based fitting method for visual reflectance spectroscopy of human skin

International Nuclear Information System (INIS)

Verkruysse, Wim; Zhang Rong; Choi, Bernard; Lucassen, Gerald; Svaasand, Lars O; Nelson, J Stuart

2005-01-01

The diffuse reflectance spectrum of human skin in the visible region (400-800 nm) contains information on the concentrations of chromophores such as melanin and haemoglobin. This information may be extracted by fitting the reflectance spectrum with an optical diffusion based analytical expression applied to a layered skin model. With the use of the analytical expression, it is assumed that light transport is dominated by scattering. For port wine stain (PWS) and highly pigmented human skin, however, this assumption may not be valid resulting in a potentially large error in visual reflectance spectroscopy (VRS). Monte Carlo based techniques can overcome this problem but are currently too computationally intensive to be combined with previously used fitting procedures. The fitting procedure presented herein is based on a library search which enables the use of accurate reflectance spectra based on forward Monte Carlo simulations or diffusion theory. This allows for accurate VRS to characterize chromophore concentrations in PWS and highly pigmented human skin. The method is demonstrated using both simulated and measured reflectance spectra. An additional advantage of the method is that the fitting procedure is very fast

A library based fitting method for visual reflectance spectroscopy of human skin

Energy Technology Data Exchange (ETDEWEB)

Verkruysse, Wim [Beckman Laser Institute, University of California, Irvine, CA 92612 (United States); Zhang Rong [Beckman Laser Institute, University of California, Irvine, CA 92612 (United States); Choi, Bernard [Beckman Laser Institute, University of California, Irvine, CA 92612 (United States); Lucassen, Gerald [Personal Care Institute, Philips Research, Prof Holstlaan 4, Eindhoven (Netherlands); Svaasand, Lars O [Department of Physical Electronics Norwegian University of Science and Technology, N-7491 Trondheim (Norway); Nelson, J Stuart [Beckman Laser Institute, University of California, Irvine, CA 92612 (United States)

2005-01-07

The diffuse reflectance spectrum of human skin in the visible region (400-800 nm) contains information on the concentrations of chromophores such as melanin and haemoglobin. This information may be extracted by fitting the reflectance spectrum with an optical diffusion based analytical expression applied to a layered skin model. With the use of the analytical expression, it is assumed that light transport is dominated by scattering. For port wine stain (PWS) and highly pigmented human skin, however, this assumption may not be valid resulting in a potentially large error in visual reflectance spectroscopy (VRS). Monte Carlo based techniques can overcome this problem but are currently too computationally intensive to be combined with previously used fitting procedures. The fitting procedure presented herein is based on a library search which enables the use of accurate reflectance spectra based on forward Monte Carlo simulations or diffusion theory. This allows for accurate VRS to characterize chromophore concentrations in PWS and highly pigmented human skin. The method is demonstrated using both simulated and measured reflectance spectra. An additional advantage of the method is that the fitting procedure is very fast.

A library based fitting method for visual reflectance spectroscopy of human skin

Science.gov (United States)

Verkruysse, Wim; Zhang, Rong; Choi, Bernard; Lucassen, Gerald; Svaasand, Lars O.; Nelson, J. Stuart

2005-01-01

The diffuse reflectance spectrum of human skin in the visible region (400-800 nm) contains information on the concentrations of chromophores such as melanin and haemoglobin. This information may be extracted by fitting the reflectance spectrum with an optical diffusion based analytical expression applied to a layered skin model. With the use of the analytical expression, it is assumed that light transport is dominated by scattering. For port wine stain (PWS) and highly pigmented human skin, however, this assumption may not be valid resulting in a potentially large error in visual reflectance spectroscopy (VRS). Monte Carlo based techniques can overcome this problem but are currently too computationally intensive to be combined with previously used fitting procedures. The fitting procedure presented herein is based on a library search which enables the use of accurate reflectance spectra based on forward Monte Carlo simulations or diffusion theory. This allows for accurate VRS to characterize chromophore concentrations in PWS and highly pigmented human skin. The method is demonstrated using both simulated and measured reflectance spectra. An additional advantage of the method is that the fitting procedure is very fast.

MSCs can be differentially isolated from maternal, middle and fetal segments of the human umbilical cord.

Science.gov (United States)

Lim, Jezamine; Razi, Zainul Rashid Mohamad; Law, Jiaxian; Nawi, Azmawati Mohammed; Idrus, Ruszymah Binti Haji; Ng, Min Hwei

2016-12-01

Human Wharton's jelly-derived mesenchymal stromal cells (hWJMSCs) are possibly the most suitable allogeneic cell source for stromal cell therapy and tissue engineering applications because of their hypo-immunogenic and non-tumorigenic properties, easy availability and minimal ethical concerns. Furthermore, hWJMSCs possess unique properties of both adult mesenchymal stromal cells and embryonic stromal cells. The human umbilical cord (UC) is approximately 50-60 cm long and the existing studies in the literature have not provided information on which segment of the UC was studied. In this study, hWJMSCs derived from three anatomical segments of the UC are compared. Three segments of the whole UC, each 3 cm in length, were identified anatomically as the maternal, middle and fetal segments. The hWJMSCs from the different segments were analyzed via trypan blue exclusion assay to determine the growth kinetics and cell viability, flow cytometry for immunophenotyping and immunofluorescence and reverse transcriptase polymerase chain reaction (RT-PCR) for expression of stromal cell transcriptional factors. Furthermore, the trilineage differentiation potential (osteogenic, adipogenic and chondrogenic) of these cells was also assessed. hWJMSCs isolated from the maternal and fetal segments displayed greater viability and possessed a significantly higher proliferation rate compared with cells from the middle segment. Immunophenotyping revealed that hWJMSCs derived from all three segments expressed the MSC markers CD105, CD73, CD90, CD44, CD13 and CD29, as well as HLA-ABC and HLA-DR, but were negative for hematopoietic markers CD14, CD34 and CD45. Analysis of the embryonic markers showed that all three segments expressed Nanog and Oct 3/4, but only the maternal and fetal segments expressed SSEA 4 and TRA-160. Cells from all three segments were able to differentiate into chondrogenic, osteogenic and adipogenic lineages with the middle segments showing much lower differentiation

Illuminant color estimation based on pigmentation separation from human skin color

Science.gov (United States)

Tanaka, Satomi; Kakinuma, Akihiro; Kamijo, Naohiro; Takahashi, Hiroshi; Tsumura, Norimichi

2015-03-01

Human has the visual system called "color constancy" that maintains the perceptive colors of same object across various light sources. The effective method of color constancy algorithm was proposed to use the human facial color in a digital color image, however, this method has wrong estimation results by the difference of individual facial colors. In this paper, we present the novel color constancy algorithm based on skin color analysis. The skin color analysis is the method to separate the skin color into the components of melanin, hemoglobin and shading. We use the stationary property of Japanese facial color, and this property is calculated from the components of melanin and hemoglobin. As a result, we achieve to propose the method to use subject's facial color in image and not depend on the individual difference among Japanese facial color.

Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts.

Directory of Open Access Journals (Sweden)

Linn S Strandberg

Full Text Available Congenital heart block (CHB is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB.We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation. Using human fetal hearts (20-22 wks gestation, our immunoprecipitation (IP, Western blot analysis and immunofluorescence (IF staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I. Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN cells.Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.

Nanotribological characterization of human hair and skin using atomic force microscopy

International Nuclear Information System (INIS)

LaTorre, Carmen; Bhushan, Bharat

2005-01-01

Healthy hair and skin is highly desired. Characterization of their morphological, frictional, and adhesive properties (tribological properties) is essential to enhance understanding of hair and skin and to advance the science. Literature on the tribological characterization of hair and skin is scarce to date. The paper presents nanotribological data and analysis on hair (Caucasian, Asian, and African hair at virgin, chemo-mechanically damaged, and treated conditions) and synthetic hair and skin, as well as roughness data of human skin replica. Roughness statistics are presented to characterize the vertical and spatial surface parameters. Average coefficient of friction values were determined for each ethnicity and hair type, and are discussed. The directionality dependence of friction is also discussed. Magnitude and spatial distribution of adhesive force are used to estimate thickness and distribution of the conditioner film

Robust Lentiviral Gene Delivery But Limited Transduction Capacity of Commonly Used Adeno-Associated Viral Serotypes in Xenotransplanted Human Skin.

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Jakobsen, Maria; Askou, Anne Louise; Stenderup, Karin; Rosada, Cecilia; Dagnæs-Hansen, Frederik; Jensen, Thomas G; Corydon, Thomas J; Mikkelsen, Jacob Giehm; Aagaard, Lars

2015-08-01

Skin is an easily accessible organ, and therapeutic gene transfer to skin remains an attractive alternative for the treatment of skin diseases. Although we have previously documented potent lentiviral gene delivery to human skin, vectors based on adeno-associated virus (AAV) rank among the most promising gene delivery tools for in vivo purposes. Thus, we compared the potential usefulness of various serotypes of recombinant AAV vectors and lentiviral vectors for gene transfer to human skin in a xenotransplanted mouse model. Vector constructs encoding firefly luciferase were packaged in AAV capsids of serotype 1, 2, 5, 6, 8, and 9 and separately administered by intradermal injection in human skin transplants. For all serotypes, live bioimaging demonstrated low levels of transgene expression in the human skin graft, and firefly luciferase expression was observed primarily in neighboring tissue outside of the graft. In contrast, gene delivery by intradermally injected lentiviral vectors was efficient and led to extensive and persistent firefly luciferase expression within the human skin graft only. The study demonstrates the limited capacity of single-stranded AAV vectors of six commonly used serotypes for gene delivery to human skin in vivo.

Rab11 family expression in the human placenta: Localization at the maternal-fetal interface

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Artemiuk, Patrycja A.; Hanscom, Sara R.; Lindsay, Andrew J.; Wuebbolt, Danielle; Breathnach, Fionnuala M.; Tully, Elizabeth C.; Khan, Amir R.; McCaffrey, Mary W.

2017-01-01

Rab proteins are a family of small GTPases involved in a variety of cellular processes. The Rab11 subfamily in particular directs key steps of intracellular functions involving vesicle trafficking of the endosomal recycling pathway. This Rab subfamily works through a series of effector proteins including the Rab11-FIPs (Rab11 Family-Interacting Proteins). While the Rab11 subfamily has been well characterized at the cellular level, its function within human organ systems is still being explored. In an effort to further study these proteins, we conducted a preliminary investigation of a subgroup of endosomal Rab proteins in a range of human cell lines by Western blotting. The results from this analysis indicated that Rab11a, Rab11c(Rab25) and Rab14 were expressed in a wide range of cell lines, including the human placental trophoblastic BeWo cell line. These findings encouraged us to further analyse the localization of these Rabs and their common effector protein, the Rab Coupling Protein (RCP), by immunofluorescence microscopy and to extend this work to normal human placental tissue. The placenta is a highly active exchange interface, facilitating transfer between mother and fetus during pregnancy. As Rab11 proteins are closely involved in transcytosis we hypothesized that the placenta would be an interesting human tissue model system for Rab investigation. By immunofluorescence microscopy, Rab11a, Rab11c(Rab25), Rab14 as well as their common FIP effector RCP showed prominent expression in the placental cell lines. We also identified the expression of these proteins in human placental lysates by Western blot analysis. Further, via fluorescent immunohistochemistry, we noted abundant localization of these proteins within key functional areas of primary human placental tissues, namely the outer syncytial layer of placental villous tissue and the endothelia of fetal blood vessels. Overall these findings highlight the expression of the Rab11 family within the human

Evaluation of 3D-human skin equivalents for assessment of human dermal absorption of some brominated flame retardants.

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Abdallah, Mohamed Abou-Elwafa; Pawar, Gopal; Harrad, Stuart

2015-11-01

Ethical and technical difficulties inherent to studies in human tissues are impeding assessment of the dermal bioavailability of brominated flame retardants (BFRs). This is further complicated by increasing restrictions on the use of animals in toxicity testing, and the uncertainties associated with extrapolating data from animal studies to humans due to inter-species variations. To overcome these difficulties, we evaluate 3D-human skin equivalents (3D-HSE) as a novel in vitro alternative to human and animal testing for assessment of dermal absorption of BFRs. The percutaneous penetration of hexabromocyclododecanes (HBCD) and tetrabromobisphenol-A (TBBP-A) through two commercially available 3D-HSE models was studied and compared to data obtained for human ex vivo skin according to a standard protocol. No statistically significant differences were observed between the results obtained using 3D-HSE and human ex vivo skin at two exposure levels. The absorbed dose was low (less than 7%) and was significantly correlated with log Kow of the tested BFR. Permeability coefficient values showed increasing dermal resistance to the penetration of γ-HBCD>β-HBCD>α-HBCD>TBBPA. The estimated long lag times (>30 min) suggests that frequent hand washing may reduce human exposure to HBCDs and TBBPA via dermal contact. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fetal injury induced by Ca-DTPA in dogs

International Nuclear Information System (INIS)

Taylor, G.N.; Mays, C.W.

1978-01-01

The chelating agent Ca-DTPA, used to remove plutonium from the body, has produced fetal deaths and deformities in mice and rats. Damage is caused by depletion of essential trace elements, particularly zinc and manganese. It is suggested that a relationship may exist between the daily amount of Ca-DTPA,per kg body weight needed,to produce fetal toxicity and the daily intake of dietary zinc per kg body weight, and that this relationship could be used to predict fetal toxicity thresholds in various species. Results of a study on beagles are presented. Ca-DTPA treatment at the dose levels used in human therapy did not produce any symptoms in the pregnant dams but the fetuses showed depressed birth weight, abnormal hair colour due to pigmentary deficiency, brain damage and neutropenia. Extrapolation from dogs to humans predicts a toxic fetal dose less that one sixth of the daily dosage presently used for an adult woman, and emphasizes the hazards of Ca-DTPA therapy during pregnancy. (author)

Association of common genetic variants with human skin color variation in Indian populations.

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Sarkar, Anujit; Nandineni, Madhusudan R

2018-01-01

Human skin color is one of the most conspicuously variable physical traits that has attracted the attention of physical anthropologists, social scientists and human geneticists. Although several studies have established the underlying genes and their variants affecting human skin color, they were mostly confined to Europeans and Africans and similar studies in Indian populations have been scanty. Studying the association between candidate genetic variants and skin color will help to validate previous findings and to better understand the molecular mechanism of skin color variation. In this study, 22 candidate SNPs from 12 genes were tested for association with skin color in 299 unrelated samples sourced from nine geographical locations in India. Our study establishes the association of 9 SNPs with the phenotype in Indian populations and could explain ∼31% of the variance in skin color. Haplotype analysis of chromosome 15 revealed a significant association of alleles G, A and C of SNPs rs1426654, rs11070627, and rs12913316, respectively, to the phenotype, and accounted for 17% of the variance. Latitude of the sampling location was also a significant factor, contributing to ∼19% of the variation observed in the samples. These observations support the findings that rs1426654 and rs4775730 located in SLC24A5, and rs11070627 and rs12913316 located in MYEF2 and CTXN2 genes respectively, are major contributors toward skin pigmentation and would aid in further unraveling the genotype-phenotype association in Indian populations. These findings can be utilized in forensic DNA applications for criminal investigations. © 2017 Wiley Periodicals, Inc.

Analysis of Reparative Activity of Platelet Lysate: Effect on Cell Monolayer Recovery In Vitro and Skin Wound Healing In Vivo.

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Sergeeva, N S; Shanskii, Ya D; Sviridova, I K; Karalkin, P A; Kirsanova, V A; Akhmedova, S A; Kaprin, A D

2016-11-01

Platelet lysate prepared from donor platelet concentrate and pooled according to a developed technique stimulates migration of multipotent mesenchymal stromal cells of the human adipose tissue and promotes healing of the monolayer defect in cultures of human fibroblasts and multipotent mesenchymal stromal cells in vitro in concentrations close those of fetal calf serum (5-10%). Lysate of platelets from platelet-rich rat blood plasma stimulated healing of the skin defect by promoting epithelialization and granulation tissue formation. The regenerative properties of platelet lysate in vivo increased with increasing its concentration.

Vehicle effects on human stratum corneum absorption and skin penetration.

Science.gov (United States)

Zhang, Alissa; Jung, Eui-Chang; Zhu, Hanjiang; Zou, Ying; Hui, Xiaoying; Maibach, Howard

2017-05-01

This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and diffusion of the [ 14 C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.

Formation of a protection film on the human skin by microparticles

International Nuclear Information System (INIS)

Lademann, J; Schanzer, S; Richter, H; Knorr, F; Sterry, W; Patzelt, A; Antoniou, C

2008-01-01

Laser scanning microscopy and tape stripping, in combination with optical methods, were used to analyze the distribution and penetration of a barrier cream into the horny layer (stratum corneum) of the human skin under in vivo conditions. The barrier cream contained microparticles of 10 – 100 μm loaded with antioxidant substances. The cream was designed for protection of the skin surface against the destructive action of free radicals, produced by systemically applied chemotherapeutic agents reaching the skin surface via the sweat. Both methods were able to demonstrate that the barrier cream was distributed homogeneously on the skin surface forming a protection film. A penetration into deeper parts of the stratum corneum (SC) was not observed

Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.

Directory of Open Access Journals (Sweden)

Kei Takahashi

Full Text Available Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transplantation into the chorionic villi under ultrasound guidance in the murine model.Pregnant C57BL/6 (B6 mice on day 10 of gestation were anesthetized and imaged by high resolution ultrasound. Murine embryos and their placenta were positioned to get a clear view in B-mode with power mode of the labyrinth, which is the equivalent of chorionic villi in the human. Bone marrow cells (BMCs from B6-Green Fluorescence Protein (B6GFP transgenic mice were injected into the fetal side of the placenta which includes the labyrinth with glass microcapillary pipettes. Each fetal mouse received 2 x 105 viable GFP-BMCs. After birth, we evaluated the humoral and cell-mediated immune response against GFP.Bone marrow transfer into fetal side of placenta efficiently distributed donor cells to the fetal mice. The survival rate of this procedure was 13.5%(5 out of 37. Successful engraftment of the B6-GFP donor skin grafts was observed in all recipient (5 out of 5 mice 6 weeks after birth. Induction of anti-GFP antibodies was completely inhibited. Cytotoxic immune reactivity of thymic cells against cells harboring GFP was suppressed by ELISPOT assay.In this study, we utilized early gestational placental injection targeting the murine fetus, to transfer donor cells carrying a foreign protein into the fetal circulation. This approach is sufficient to induce both humoral and cell-mediated immune tolerance against the foreign protein.

Migration of human antigen-presenting cells in a human skin graft onto nude mice model after contact sensitization

NARCIS (Netherlands)

Hoefakker, S.; Balk, H.P.; Boersma, W.J.A.; Joost, T. van; Notten, W.R.F.; Claassen, E.

1995-01-01

Fluorescent contact chemical allergens provoke sensitization after application on both syngeneic and allogeneic skin grafts in mice. We attempted to determine whether the functional activity in a contact sensitization response of human skin graft was affected at the level of antigen uptake and

Porphyrin metabolisms in human skin commensal Propionibacterium acnes bacteria: potential application to monitor human radiation risk.

Science.gov (United States)

Shu, M; Kuo, S; Wang, Y; Jiang, Y; Liu, Y-T; Gallo, R L; Huang, C-M

2013-01-01

Propionibacterium acnes (P. acnes), a Gram-positive anaerobic bacterium, is a commensal organism in human skin. Like human cells, the bacteria produce porphyrins, which exhibit fluorescence properties and make bacteria visible with a Wood's lamp. In this review, we compare the porphyrin biosynthesis in humans and P. acnes. Also, since P. acnes living on the surface of skin receive the same radiation exposure as humans, we envision that the changes in porphyrin profiles (the absorption spectra and/or metabolism) of P. acnes by radiation may mirror the response of human cells to radiation. The porphyrin profiles of P. acnes may be a more accurate reflection of radiation risk to the patient than other biodosimeters/biomarkers such as gene up-/down-regulation, which may be non-specific due to patient related factors such as autoimmune diseases. Lastly, we discuss the challenges and possible solutions for using the P. acnes response to predict the radiation risk.

In vivo study of human skin using pulsed terahertz radiation

Energy Technology Data Exchange (ETDEWEB)

Pickwell, E [Semiconductor Physics Group, Cavendish Laboratory, Cambridge University, Madingley Road, Cambridge CB3 0HE (United Kingdom); Cole, B E [TeraView Ltd, Unit 302/4 Cambridge Science Park, Cambridge CB4 0WG (United Kingdom); Fitzgerald, A J [TeraView Ltd, Unit 302/4 Cambridge Science Park, Cambridge CB4 0WG (United Kingdom); Pepper, M [Semiconductor Physics Group, Cavendish Laboratory, Cambridge University, Madingley Road, Cambridge CB3 0HE (United Kingdom); Wallace, V P [TeraView Ltd, Unit 302/4 Cambridge Science Park, Cambridge CB4 0WG (United Kingdom)

2004-05-07

Studies in terahertz (THz) imaging have revealed a significant difference between skin cancer (basal cell carcinoma) and healthy tissue. Since water has strong absorptions at THz frequencies and tumours tend to have different water content from normal tissue, a likely contrast mechanism is variation in water content. Thus, we have previously devised a finite difference time-domain (FDTD) model which is able to closely simulate the interaction of THz radiation with water. In this work we investigate the interaction of THz radiation with normal human skin on the forearm and palm of the hand in vivo. We conduct the first ever systematic in vivo study of the response of THz radiation to normal skin. We take in vivo reflection measurements of normal skin on the forearm and palm of the hand of 20 volunteers. We compare individual examples of THz responses with the mean response for the areas of skin under investigation. Using the in vivo data, we demonstrate that the FDTD model can be applied to biological tissue. In particular, we successfully simulate the interaction of THz radiation with the volar forearm. Understanding the interaction of THz radiation with normal skin will form a step towards developing improved imaging algorithms for diagnostic detection of skin cancer and other tissue disorders using THz radiation.

In vivo study of human skin using pulsed terahertz radiation

International Nuclear Information System (INIS)

Pickwell, E; Cole, B E; Fitzgerald, A J; Pepper, M; Wallace, V P

2004-01-01

Studies in terahertz (THz) imaging have revealed a significant difference between skin cancer (basal cell carcinoma) and healthy tissue. Since water has strong absorptions at THz frequencies and tumours tend to have different water content from normal tissue, a likely contrast mechanism is variation in water content. Thus, we have previously devised a finite difference time-domain (FDTD) model which is able to closely simulate the interaction of THz radiation with water. In this work we investigate the interaction of THz radiation with normal human skin on the forearm and palm of the hand in vivo. We conduct the first ever systematic in vivo study of the response of THz radiation to normal skin. We take in vivo reflection measurements of normal skin on the forearm and palm of the hand of 20 volunteers. We compare individual examples of THz responses with the mean response for the areas of skin under investigation. Using the in vivo data, we demonstrate that the FDTD model can be applied to biological tissue. In particular, we successfully simulate the interaction of THz radiation with the volar forearm. Understanding the interaction of THz radiation with normal skin will form a step towards developing improved imaging algorithms for diagnostic detection of skin cancer and other tissue disorders using THz radiation

Studies on the absorption of epoxy resin /sup 14/C-epidian 5 through the skin of guinea pigs

Energy Technology Data Exchange (ETDEWEB)

Woyton, A; Wozniak, M; Dobryszycka, W [Akademia Medyczna, Wroclaw (Poland)

1976-01-01

The absorption and spread of epoxy resin labelled with /sup 14/C-epidian 5 was evaluated by measurements of radioactivity of the skin and individual organs in guinea pigs and of the ovum in pregnant guinea pigs. It has been demonstrated that the radioactive resin is slowly absorbed through the skin and reaches, by blood vessels, inner organs and the skin distant from the smeared site. The liver participates actively in the metabolism of epidian 5. The radioactivity of the nervous tissue and urine of the guinea pig bladder increased successively with the length of time, which indicates this way of excretion of the resin. In fetal membranes the level of radioactivity was considerably higher than in the placental tissue and fetal fluids. Worthy of note is also that livers of guinea pig fetuses showed an isotope mark and that radioactivity increased in the fetal pulmonary tissue.

Structural and biophysical characteristics of human skin in maintaining proper epidermal barrier function

Directory of Open Access Journals (Sweden)

Magdalena Boer

2016-02-01

Full Text Available The complex structure of human skin and its physicochemical properties turn it into an efficient outermost defence line against exogenous factors, and help maintain homeostasis of the human body. This role is played by the epidermal barrier with its major part – stratum corneum. The condition of the epidermal barrier depends on individual and environmental factors. The most important biophysical parameters characterizing the status of this barrier are the skin pH, epidermal hydration, transepidermal water loss and sebum excretion. The knowledge of biophysical skin processes may be useful for the implementation of prophylactic actions whose aim is to restore the barrier function.

New methods for field collection of human skin volatiles and perspectives for their application in the chemical ecology of human-pathogen-vector interactions.

Science.gov (United States)

Dormont, Laurent; Bessière, Jean-Marie; McKey, Doyle; Cohuet, Anna

2013-08-01

Odours emitted by human skin are of great interest to biologists in many fields, with practical applications in forensics, health diagnostic tools and the ecology of blood-sucking insect vectors of human disease. Convenient methods are required for sampling human skin volatiles under field conditions. We experimentally compared four modern methods for sampling skin odours: solvent extraction, headspace solid-phase micro-extraction (SPME), and two new techniques not previously used for the study of mammal volatiles, contact SPME and dynamic headspace with a chromatoprobe design. These methods were tested and compared both on European subjects under laboratory conditions and on young African subjects under field conditions. All four methods permitted effective trapping of skin odours, including the major known human skin volatile compounds. In both laboratory and field experiments, contact SPME, in which the time of collection was restricted to 3 min, provided results very similar to those obtained with classical headspace SPME, a method that requires 45 min of collection. Chromatoprobe sampling also proved to be very sensitive, rapid and convenient for the collection of human-produced volatiles in natural settings. Both contact SPME and chromatoprobe design may considerably facilitate the study of human skin volatiles under field conditions, opening new possibilities for examining the olfactory cues mediating the host-seeking behaviour of mosquito vectors implicated in the transmission of major diseases.

UV irradiation-induced methionine oxidation in human skin keratins: Mass spectrometry-based non-invasive proteomic analysis.

Science.gov (United States)

Lee, Seon Hwa; Matsushima, Keita; Miyamoto, Kohei; Oe, Tomoyuki

2016-02-05

Ultraviolet (UV) radiation is the major environmental factor that causes oxidative skin damage. Keratins are the main constituents of human skin and have been identified as oxidative target proteins. We have recently developed a mass spectrometry (MS)-based non-invasive proteomic methodology to screen oxidative modifications in human skin keratins. Using this methodology, UV effects on methionine (Met) oxidation in human skin keratins were investigated. The initial screening revealed that Met(259), Met(262), and Met(296) in K1 keratin were the most susceptible oxidation sites upon UVA (or UVB) irradiation of human tape-stripped skin. Subsequent liquid chromatography/electrospray ionization-MS and tandem MS analyses confirmed amino acid sequences and oxidation sites of tryptic peptides D(290)VDGAYMTK(298) (P1) and N(258)MQDMVEDYR(267) (P2). The relative oxidation levels of P1 and P2 increased in a time-dependent manner upon UVA irradiation. Butylated hydroxytoluene was the most effective antioxidant for artifactual oxidation of Met residues. The relative oxidation levels of P1 and P2 after UVA irradiation for 48 h corresponded to treatment with 100mM hydrogen peroxide for 15 min. In addition, Met(259) was oxidized by only UVA irradiation. The Met sites identified in conjunction with the current proteomic methodology can be used to evaluate skin damage under various conditions of oxidative stress. We demonstrated that the relative Met oxidation levels in keratins directly reflected UV-induced damages to human tape-stripped skin. Human skin proteins isolated by tape stripping were analyzed by MS-based non-invasive proteomic methodology. Met(259), Met(262), and Met(296) in K1 keratin were the most susceptible oxidation sites upon UV irradiation. Met(259) was oxidized by only UVA irradiation. Quantitative LC/ESI-SRM/MS analyses confirmed a time-dependent increase in the relative oxidation of target peptides (P1 and P2) containing these Met residues, upon UVA irradiation

The use of small interfering RNAs to inhibit adipocyte differentiation in human preadipocytes and fetal-femur-derived mesenchymal cells

International Nuclear Information System (INIS)

Xu, Y.; Mirmalek-Sani, S.-H.; Yang, X.; Zhang, J.; Oreffo, R.O.C.

2006-01-01

RNA interference (RNAi) has been used in functional genomics and offers innovative approaches in the development of novel therapeutics. Human mesenchymal stem cells offer a unique cell source for tissue engineering/regeneration strategies. The current study examined the potential of small interfering RNAs (siRNA) against human peroxisome proliferator activated receptor gamma (PPARγ) to suppress adipocyte differentiation (adipogenesis) in human preadipocytes and fetal-femur-derived mesenchymal cells. Adipogenesis was investigated using cellular and biochemical analysis. Transient transfection with PPARγ-siRNA using a liposomal-based strategy resulted in a significant inhibition of adipogenesis in human preadipocytes and fetal-femur-derived mesenchymal cells, compared to controls (cell, liposomal and negative siRNA). The inhibitory effect of PPARγ-siRNA was supported by testing human PPARγ mRNA and adipogenic associated genes using reverse transcription polymerase chain reaction (RT-PCR) to adiponectin receptor 1 and 2 as well as examination of fatty acid binding protein 3 (FABP 3 ) expression, an adipocyte-specific marker. The current studies indicate that PPARγ-siRNA is a useful tool to study adipogenesis in human cells, with potential applications both therapeutic and in the elucidation of mesenchymal cell differentiation in the modulation of cell differentiation in human mesenchymal cells

Transfection of Primary Human Skin Fibroblasts for Peroxisomal Studies

NARCIS (Netherlands)

Koster, Janet; Waterham, Hans R.

2017-01-01

Functional studies with primary human skin fibroblasts from patients with a peroxisomal disorder often require efficient transfection with plasmids to correct the genetic defect or to express heterologous reporter proteins. Here, we describe a protocol we commonly use for efficient nonviral

Malnutrition during fetal life, fetal programming and implications for farm aninals productivity

DEFF Research Database (Denmark)

Nielsen, Mette Olaf; Khanal, Prabhat; Johnsen, Lærke

Some 20 years ago, observations from human epidemiological research revolutionized the scientific view of the importance of fetal life development for body functions in postnatal life. Until then, it was believed that the genome received from the parents at conception in mammals would define the ...

Airborne polycyclic aromatic hydrocarbons trigger human skin cells aging through aryl hydrocarbon receptor.

Science.gov (United States)

Qiao, Yuan; Li, Qiang; Du, Hong-Yang; Wang, Qiao-Wei; Huang, Ye; Liu, Wei

2017-07-01

Accumulating evidence suggests that polycyclic aromatic hydrocarbons (PAH) which adsorbed on the surface of ambient air particulate matters (PM), are the major toxic compound to cause cardiovascular and respiratory diseases, even cancer. However, its detrimental effects on human skin cell remain unclear. Here, we demonstrated that SRM1649b, a reference urban dust material of PAH, triggers human skin cells aging through cell cycle arrest, cell growth inhibition and apoptosis. Principally, SRM1649b facilitated Aryl hydrocarbon receptor (AhR) translocated into nucleus, subsequently activated ERK/MAPK signaling pathway, and upregulated aging-related genes expression. Most important, we found that AhR antagonist efficiently revert the aging of skin cells. Thus our novel findings firstly revealed the mechanism of skin aging under PAH contamination and provided potential strategy for clinical application. Copyright © 2017. Published by Elsevier Inc.

Inhibition of ultraviolet irradiation response of human skin by topical phlogostatic compounds

International Nuclear Information System (INIS)

Weirich, E.G.; Lutz, U.C.

1977-01-01

By adaption of the model of UV dermatitis in human skin a test procedure has been developed which facilitates realistic assessment of topical contra-inflammatory activity of steroidal as well as non-steroidal compounds. Sixt typical skin drug agents were tested according to their reaction inhibition effect. (orig./MG) [de

Optimization of PIXE-sensitivity for detection of Ti in thin human skin sections

International Nuclear Information System (INIS)

Pallon, Jan; Garmer, Mats; Auzelyte, Vaida; Elfman, Mikael; Kristiansson, Per; Malmqvist, Klas; Nilsson, Christer; Shariff, Asad; Wegden, Marie

2005-01-01

Modern sunscreens contain particles like TiO 2 having sizes of 25-70 nm and acting as a reflecting substance. For cosmetic reasons the particle size is minimized. Questions have been raised to what degree these nano particles penetrate the skin barrier, and how they do affect the human. The EU funded project 'Quality of skin as a barrier to ultra-fine particles' - NANODERM has started with the purpose to evaluate the possible risks of TiO 2 penetration into vital skin layers. The purpose of the work presented here was to find the optimal conditions for micro-PIXE analysis of Ti in thin skin sections. In the skin region where Ti is expected to be found, the naturally occurring major elements phosphorus, chlorine, sulphur and potassium have steep gradients and thus influence the X-ray background in a non-predictable manner. Based on experimental studies of Ti-exposed human skin sections using proton energies ranging from 1.8-2.55 MeV, the corresponding PIXE detection limits for Ti were calculated. The energy that was found to be the most favourable, 1.9 MeV, was then selected for future studies

Development of the penis during the human fetal period (13 to 36 weeks after conception).

Science.gov (United States)

Gallo, Carla B M; Costa, Waldemar S; Furriel, Angelica; Bastos, Ana L; Sampaio, Francisco J B

2013-11-01

We analyzed the development of the area of the penis and erectile structures (corpora cavernosa and corpus spongiosum) and the thickness of the tunica albuginea during the fetal period (13 to 36 weeks after conception) in humans to establish normative patterns of growth. We studied 56 male human fetuses at 13 to 36 weeks after conception. We used histochemical and morphometric techniques to analyze the parameters of total penile area, area of corpora cavernosa, area of corpus spongiosum, and thickness of tunica albuginea in the dorsal and ventral regions using ImageJ software (National Institutes of Health, Bethesda, Maryland). Between 13 and 36 weeks after conception the area of the penis varies from 0.95 to 24.25 mm2. The area of the corpora cavernosa varies from 0.28 to 9.12 mm2, and the area of the corpus spongiosum varies from 0.14 to 3.99 mm2. The thickness of the tunica albuginea varies from 0.029 to 0.296 mm in the dorsal region and from 0.014 to 0.113 mm in the ventral region of the corpora cavernosa. We found a strong correlation between the total penile area, corpora cavernosa and corpus spongiosum with fetal age (weeks following conception). The growth rate was more intense during the second trimester (13 to 24 weeks of gestation) compared to the third trimester (25 to 36 weeks). Tunica albuginea thickness also was strongly correlated with fetal age and this structure was thicker in the dorsal vs ventral region. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A multivariable model for predicting the frictional behaviour and hydration of the human skin.