Fibroblast growth factor 5-short (FGF5s) inhibits the activity of FGF5 in primary and secondary hair follicle dermal papilla cells of cashmere goats.

PubMed

He, Xiaolin; Chao, Yuan; Zhou, Guangxian; Chen, Yulin

2016-01-10

To determine the relationship between fibroblast growth factor 5 (FGF5) and FGF5-short (FGF5s) in dermal papilla cells of cashmere goat primary and secondary hair follicles. We isolated dermal papilla cells from primary hair follicle (PHF) and secondary hair follicle (SHF) of cashmere goat, and found that the FGF5 receptor, fibroblast growth factor receptor 1 (FGFR1), was expressed in these two types of dermal papilla cells. Moreover, adenovirus-mediated overexpression of FGF5 could upregulate the mRNA expression of insulin-like growth factor-1 (IGF-1), versican and noggin that were important for follicle growth maintenance, whereas downregulate the expression of anagen chalone bone morphogenetic protein 4 (BMP4) in dermal papilla cells. However, these alterations were partly reversed by FGF5s overexpression. In conclusion, our results demonstrated that FGF5s acted as an inhibitor of FGF5 in the regulation of anagen-catagen transition of cashmere goat dermal papilla cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Squarticles as a lipid nanocarrier for delivering diphencyprone and minoxidil to hair follicles and human dermal papilla cells.

PubMed

Aljuffali, Ibrahim A; Sung, Calvin T; Shen, Feng-Ming; Huang, Chi-Ting; Fang, Jia-You

2014-01-01

Delivery of diphencyprone (DPCP) and minoxidil to hair follicles and related cells is important in the treatment of alopecia. Here we report the development of "squarticles," nanoparticles formed from sebum-derived lipids such as squalene and fatty esters, for use in achieving targeted drug delivery to the follicles. Two different nanosystems, nanostructured lipid carriers (NLC) and nanoemulsions (NE), were prepared. The physicochemical properties of squarticles, including size, zeta potential, drug encapsulation efficiency, and drug release, were examined. Squarticles were compared to a free control solution with respect to skin absorption, follicular accumulation, and dermal papilla cell targeting. The particle size of the NLC type was 177 nm; that of the NE type was 194 nm. Approximately 80% of DPCP and 60% of minoxidil were entrapped into squarticles. An improved drug deposition in the skin was observed in the in vitro absorption test. Compared to the free control, the squarticles reduced minoxidil penetration through the skin. This may indicate a minimized absorption into systemic circulation. Follicular uptake by squarticles was 2- and 7-fold higher for DPCP and minoxidil respectively compared to the free control. Fluorescence and confocal images of the skin confirmed a great accumulation of squarticles in the follicles and the deeper skin strata. Vascular endothelial growth factor expression in dermal papilla cells was significantly upregulated after the loading of minoxidil into the squarticles. In vitro papilla cell viability and in vivo skin irritancy tests in nude mice suggested a good tolerability of squarticles to skin. Squarticles provide a promising nanocarrier for topical delivery of DPCP and minoxidil.

Sprouty / FGF signaling regulates the proximal-distal feather morphology and the size of dermal papillae

PubMed Central

Yue, Zhicao; Jiang, Ting Xin; Wu, Ping; Widelitz, Randall B; Chuong, Cheng Ming

2013-01-01

In a feather, there are distinct morphologies along the proximal-distal axis. The proximal part is a cylindrical stalk (calamus), whereas the distal part has barb and barbule branches. Here we focus on what molecular signaling activity can modulate feather stem cells to generate these distinct morphologies. We demonstrate the drastic tissue remodeling during feather cycling which includes initiation, growth and resting phases. In the growth phase, epithelial components undergo progressive changes from the collar growth zone to the ramogenic zone, to maturing barb branches along the proximal- distal axis. Mesenchymal components also undergo progressive changes from the dermal papilla, to the collar mesenchyme, to the pulp along the proximal- distal axis. Over-expression of Spry4, a negative regulator of receptor tyrosine kinases, promotes barb branch formation at the expense of the epidermal collar. It even induces barb branches from the follicle sheath (equivalent to the outer root sheath in hair follicles). The results are feathers with expanded feather vane regions and small or missing proximal feather shafts (the calamus). Spry4 also expands the pulp region while reducing the size of dermal papillae, leading to a failure to regenerate. In contrast, over-expressing Fgf10 increases the size of the dermal papillae, expands collar epithelia and mesenchyme, but also prevents feather branch formation and feather keratin differentiation. These results suggest that coordinated Sprouty/FGF pathway activity at different stages is important to modulate feather epidermal stem cells to form distinct feather morphologies along the proximal-distal feather axis. PMID:23000358

11β-Hydroxysteroid Dehydrogenase Type 1 Inhibition Attenuates the Adverse Effects of Glucocorticoids on Dermal Papilla Cells.

PubMed

Lee, Sang Eun; Lee, Eun Young; Kang, Sang Jin; Lee, Seung Hun

2017-11-01

Glucocorticoids, stress-related hormones, inhibit hair growth. Intracellular glucocorticoid availability is regulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). 11β-HSD1 was recently detected in keratinocytes and fibroblasts. However, the expression of 11β-HSD1 in human hair follicles remains unknown. We aimed to examine 11β-HSD1 expression in human dermal papilla cells (DPCs) and to investigate whether modulation of 11β-HSD1 activity can regulate the negative effects of glucocorticoids on DPCs. 11β-HSD1 expression in normal human scalp skin was examined by immunohistochemistry. 11β-HSD1 protein was detected in Western blots of human DPCs. Cultured human DPCs were treated with cortisol with or without a selective 11β-HSD1 inhibitor and subsequently stained for Ki-67 antibody. Expression levels of 11β-HSD1, Wnt5a, alkaline phosphatase (ALP), and vascular endothelial growth factor (VEGF) were analyzed by Western blotting. 11β-HSD1 was detected in dermal papilla in human scalp skin by immunohistochemistry. Human DPCs expressed 11β-HSD1 protein in vitro. Furthermore, cortisol stimulated the expression of 11β-HSD1 in DPCs. Glucocorticoids decreased cellular proliferation and the expression of Wnt5a, ALP, and VEGF in DPCs. A specific 11β-HSD1 inhibitor significantly attenuated the anti-proliferative effects of cortisol and reversed the cortisol-induced suppression of Wnt5a, ALP, and VEGF expression in DPCs. Our data demonstrated the expression of 11β-HSD1 in human DPCs and revealed that inhibition of 11β-HSD1 activity can partially prevent the negative effect of glucocorticoids on DPCs, suggesting the possible application of 11β-HSD1 inhibitors for stress-related hair loss. © Copyright: Yonsei University College of Medicine 2017

Molecular biological and immunohistological characterization of canine dermal papilla cells and the evaluation of culture conditions.

PubMed

Kobayashi, Tetsuro; Fujisawa, Akiko; Amagai, Masayuki; Iwasaki, Toshiroh; Ohyama, Manabu

2011-10-01

The dermal papilla (DP) plays pivotal roles in hair follicle morphogenesis and cycling. However, our understanding of the biology of the canine DP is extremely limited. The aim of this study was to elucidate molecular biological and immunohistochemical characteristics of canine DP cells and determine appropriate conditions for in vitro expansion. Histological investigation revealed that the canine DP expressed biomarkers of human and rodent DP, including alkaline phosphatase (ALP) and versican. When microdissected, canine DP, but not fibroblasts, strongly expressed the DP-related genes for alkaline phosphatase, Wnt inhibitory factor 1 and lymphoid enhancer-binding factor 1, confirming successful isolation. The growth rate of isolated canine DP cells was moderate in conventional culture conditions for rodent and human DP; however, AmnioMAX-C100 complete medium allowed more efficient cultivation. Dermal papilla marker gene expression was maintained in early passage cultured DP cells, but gradually lost after the third passage. Approaches to mimic the in vivo DP environment in culture, such as supplementation of keratinocyte-conditioned medium or use of extracellular matrix-coated dishes, moderately ameliorated loss of DP gene expression in canine DP cells. It is possible that constituent factors in AmnioMAX may influence culture. These findings suggested that further refinements of culture conditions may enable DP cell expansion without impairing intrinsic properties and, importantly, demonstrated that AmnioMAX-cultured early passage canine DP cells partly maintained the biological characteristics of in vivo canine DP cells. This study provides crucial information necessary for further optimization of culture conditions of canine DP. © 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.

Minoxidil-induced hair growth is mediated by adenosine in cultured dermal papilla cells: possible involvement of sulfonylurea receptor 2B as a target of minoxidil.

PubMed

Li, M; Marubayashi, A; Nakaya, Y; Fukui, K; Arase, S

2001-12-01

The mechanism by which minoxidil, an adenosine-triphosphate-sensitive potassium channel opener, induces hypertrichosis remains to be elucidated. Minoxidil has been reported to stimulate the production of vascular endothelial growth factor, a possible promoter of hair growth, in cultured dermal papilla cells. The mechanism of production of vascular endothelial growth factor remains unclear, however. We hypothesize that adenosine serves as a mediator of vascular endothelial growth factor production. Minoxidil-induced increases in levels of intracellular Ca(2+) and vascular endothelial growth factor production in cultured dermal papilla cells were found to be inhibited by 8-sulfophenyl theophylline, a specific antagonist for adenosine receptors, suggesting that dermal papilla cells possess adenosine receptors and sulfonylurea receptors, the latter of which is a well-known target receptor for adenosine-triphosphate-sensitive potassium channel openers. The expression of sulfonylurea receptor 2B and of the adenosine A1, A2A, and A2B receptors was detected in dermal papilla cells by means of reverse transcription polymerase chain reaction analysis. In order to determine which of the adenosine receptor subtypes contribute to minoxidil-induced hair growth, the effects of subtype-specific antagonists for adenosine receptors were investigated. Significant inhibition in increase in intracellular calcium level by minoxidil or adenosine was observed as the result of pretreatment with 8-cyclopentyl-1,3-dipropylxanthine, an antagonist for adenosine A1 receptor, but not by 3,7-dimethyl-1-propargyl-xanthine, an antagonist for adenosine A2 receptor, whereas vascular endothelial growth factor production was blocked by both adenosine A1 and A2 receptor antagonists. These results indicate that the effect of minoxidil is mediated by adenosine, which triggers intracellular signal transduction via both adenosine A1 and A2 receptors, and that the expression of sulfonylurea receptor 2B in

Combination of herbal extracts and platelet-rich plasma induced dermal papilla cell proliferation: involvement of ERK and Akt pathways.

PubMed

Rastegar, Hosein; Ahmadi Ashtiani, Hamidreza; Aghaei, Mahmoud; Ehsani, Amirohushang; Barikbin, Behrooz

2013-06-01

Recently, platelet-rich plasma (PRP) has attracted attention in various medical fields, including plastic surgery, treatment for problematic wounds, and dermatology. Specifically, PRP has been tested during hair transplantation to reduce swelling and pain and to increase hair density. We examined the effects of PRP and herbal extracts combination in order to identify potential stimulants of hair growth. PRP was prepared using the double-spin method and applied to dermal papilla cells (DPCs). MTT viability test and BrdU cell proliferation assay were used to study the effect of herbal extracts and PRP on proliferation of DPCs. To understand the mechanisms of herbal extracts and PRP involved in the regulation of hair growth, we evaluated signaling pathways and measured the expressions of ERK and Akt, by Western blot. Combination of herbal extracts and PRP was found to induce significant proliferation of human DPCs at concentrations ranging from 1.5% to 4.5%. The present study shows that herbal extracts and PRP affect the expressions of extracellular signal-regulated kinase (ERK) and Akt in DPCs. In this study, we have shown that combination of herbal extracts and PRP plays an active role in promoting the proliferation of human dermal papilla (DP) cells via the regulation of ERK and Akt proteins, and this may be applicable to the future development of herbal extracts and PRP combination therapeutics to enhance hair growth. © 2013 Wiley Periodicals, Inc.

Gene Expression Profiling of the Intact Dermal Sheath Cup of Human Hair Follicles.

PubMed

Niiyama, Shiro; Ishimatsu-Tsuji, Yumiko; Nakazawa, Yosuke; Yoshida, Yuzo; Soma, Tsutomu; Ideta, Ritsuro; Mukai, Hideki; Kishimoto, Jiro

2018-04-24

Cells that constitute the dermal papillae of hair follicles might be derived from the dermal sheath, the peribulbar component of which is the dermal sheath cup. The dermal sheath cup is thought to include the progenitor cells of the dermal papillae and possesses hair inductive potential; however, it has not yet been well characterized. This study investigated the gene expression profile of the intact dermal sheath cup, and identified dermal sheath cup signature genes, including extracellular matrix components and BMP-binding molecules, as well as TGF-b1 as an upstream regulator. Among these, GREM2, a member of the BMP antagonists, was found by in situ hybridization to be highly specific to the dermal sheath cup, implying that GREM2 is a key molecule contributing to maintenance of the properties of the dermal sheath cup.

Surface Tension Guided Hanging-Drop: Producing Controllable 3D Spheroid of High-Passaged Human Dermal Papilla Cells and Forming Inductive Microtissues for Hair-Follicle Regeneration.

PubMed

Lin, Bojie; Miao, Yong; Wang, Jin; Fan, Zhexiang; Du, Lijuan; Su, Yongsheng; Liu, Bingcheng; Hu, Zhiqi; Xing, Malcolm

2016-03-09

Human dermal papilla (DP) cells have been studied extensively when grown in the conventional monolayer. However, because of great deviation from the real in vivo three-dimensional (3D) environment, these two-dimensional (2D) grown cells tend to lose the hair-inducible capability during passaging. Hence, these 2D caused concerns have motivated the development of novel 3D culture techniques to produce cellular microtissues with suitable mimics. The hanging-drop approach is based on surface tension-based technique and the interaction between surface tension and gravity field that makes a convergence of liquid drops. This study used this technique in a converged drop to form cellular spheroids of dermal papilla cells. It leads to a controllable 3Dspheroid model for scalable fabrication of inductive DP microtissues. The optimal conditions for culturing high-passaged (P8) DP spheroids were determined first. Then, the morphological, histological and functional studies were performed. In addition, expressions of hair-inductive markers including alkaline phosphatase, α-smooth muscle actin and neural cell adhesion molecule were also analyzed by quantitative RT-PCR, immunostaining and immunoblotting. Finally, P8-DP microtissues were coimplanted with newborn mouse epidermal cells (EPCs) into nude mice. Our results indicated that the formation of 3D microtissues not only endowed P8-DP microtissues many similarities to primary DP, but also confer these microtissues an enhanced ability to induce hair-follicle (HF) neogenesis in vivo. This model provides a potential to elucidate the native biology of human DP, and also shows the promising for the controllable and scalable production of inductive DP cells applied in future follicle regeneration.

Different patterns of 5{alpha}-reductase expression, cellular distribution, and testosterone metabolism in human follicular dermal papilla cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Shicheng; Yamauchi, Hitoshi

Androgens regulate hair growth, and 5{alpha}-reductase (5{alpha}R) plays a pivotal role in the action of androgens on target organs. To clarify the molecular mechanisms responsible for controlling hair growth, the present study presents evidence that the human follicular dermal papilla cells (DPCs) from either beard (bDPCs) or scalp hair (sDPCs) possess endogenous 5{alpha}R activity. Real-time RT-PCR revealed that the highest level of 5{alpha}R1 mRNA was found in bDPCs, followed by sDPCs, and a low but detectable level of 5{alpha}R1 mRNA was observed in fibroblasts. Minimally detectable levels of 5{alpha}R2 mRNA were found in all three cell types. A weak bandmore » at 26 kDa corresponding to the human 5{alpha}R1 protein was detected by Western blot in both DPCs, but not in fibroblasts. Immuonofluorescence analysis confirmed that 5{alpha}R1 was localized to the cytoplasm rather than in the nuclei in both DPCs Furthermore, a 5{alpha}R assay using [{sup 14}C]testosterone labeling in intact cells revealed that testosterone was transformed primarily into androstenedione, and in small amounts, into DHT. Our results demonstrate that the 5{alpha}R activities of either bDPCs or sDPCs are stronger than that of dermal fibroblasts, despite the fact that the major steroidogenic activity is attributed to 17{beta}-HSD rather than 5{alpha}R among the three cell types. The 5{alpha}R1 inhibitor MK386 exhibited a more potent inhibitory effect on 5{alpha}R activity than finasteride (5{alpha}R2 inhibitor) in bDPCs.« less

Dermal Papilla Cells Improve the Wound Healing Process and Generate Hair Bud-Like Structures in Grafted Skin Substitutes Using Hair Follicle Stem Cells

PubMed Central

Leirós, Gustavo José; Kusinsky, Ana Gabriela; Drago, Hugo; Bossi, Silvia; Sturla, Flavio; Castellanos, María Lía; Stella, Inés Yolanda

2014-01-01

Tissue-engineered skin represents a useful strategy for the treatment of deep skin injuries and might contribute to the understanding of skin regeneration. The use of dermal papilla cells (DPCs) as a dermal component in a permanent composite skin with human hair follicle stem cells (HFSCs) was evaluated by studying the tissue-engineered skin architecture, stem cell persistence, hair regeneration, and graft-take in nude mice. A porcine acellular dermal matrix was seeded with HFSCs alone and with HFSCs plus human DPCs or dermal fibroblasts (DFs). In vitro, the presence of DPCs induced a more regular and multilayered stratified epidermis with more basal p63-positive cells and invaginations. The DPC-containing constructs more accurately mimicked the skin architecture by properly stratifying the differentiating HFSCs and developing a well-ordered epithelia that contributed to more closely recapitulate an artificial human skin. This acellular dermal matrix previously repopulated in vitro with HFSCs and DFs or DPCs as the dermal component was grafted in nude mice. The presence of DPCs in the composite substitute not only favored early neovascularization, good assimilation and remodeling after grafting but also contributed to the neovascular network maturation, which might reduce the inflammation process, resulting in a better healing process, with less scarring and wound contraction. Interestingly, only DPC-containing constructs showed embryonic hair bud-like structures with cells of human origin, presence of precursor epithelial cells, and expression of a hair differentiation marker. Although preliminary, these findings have demonstrated the importance of the presence of DPCs for proper skin repair. PMID:25161315

Comparative morphology of changeable skin papillae in octopus and cuttlefish.

PubMed

Allen, Justine J; Bell, George R R; Kuzirian, Alan M; Velankar, Sachin S; Hanlon, Roger T

2014-04-01

A major component of cephalopod adaptive camouflage behavior has rarely been studied: their ability to change the three-dimensionality of their skin by morphing their malleable dermal papillae. Recent work has established that simple, conical papillae in cuttlefish (Sepia officinalis) function as muscular hydrostats; that is, the muscles that extend a papilla also provide its structural support. We used brightfield and scanning electron microscopy to investigate and compare the functional morphology of nine types of papillae of different shapes, sizes and complexity in six species: S. officinalis small dorsal papillae, Octopus vulgaris small dorsal and ventral eye papillae, Macrotritopus defilippi dorsal eye papillae, Abdopus aculeatus major mantle papillae, O. bimaculoides arm, minor mantle, and dorsal eye papillae, and S. apama face ridge papillae. Most papillae have two sets of muscles responsible for extension: circular dermal erector muscles arranged in a concentric pattern to lift the papilla away from the body surface and horizontal dermal erector muscles to pull the papilla's perimeter toward its core and determine shape. A third set of muscles, retractors, appears to be responsible for pulling a papilla's apex down toward the body surface while stretching out its base. Connective tissue infiltrated with mucopolysaccharides assists with structural support. S. apama face ridge papillae are different: the contraction of erector muscles perpendicular to the ridge causes overlying tissues to buckle. In this case, mucopolysaccharide-rich connective tissue provides structural support. These six species possess changeable papillae that are diverse in size and shape, yet with one exception they share somewhat similar functional morphologies. Future research on papilla morphology, biomechanics and neural control in the many unexamined species of octopus and cuttlefish may uncover new principles of actuation in soft, flexible tissue.

PDGF-AA-induced filamentous mitochondria benefit dermal papilla cells in cellular migration.

PubMed

Mifude, C; Kaseda, K

2015-06-01

Human dermal papilla cells (HDPCs) play essential roles in hair follicular morphogenesis and postnatal hair growth cycles. Previous reports demonstrated that platelet-derived growth factor-AA (PDGF-AA) enhanced the formation of dermal condensates in hair follicular development. Additionally, PDGF-AA induces/maintains the anagen phase of the hair cycle. It is likely that mitochondrial morphology and functions are tightly coupled with maintenance of these energy-demanding activities. However, little is known about the mitochondrial regulation in HDPCs. Thus, we investigated the PDGF-involved mitochondrial regulation in HDPCs. The mitochondrial morphologies of HDPCs were examined in the presence or absence of PDGF-AA under a fluorescent microscope. ATP production and cellular motility were investigated. The relationship between mitochondrial morphology and the cellular functions was discussed. We observed that primary HDPCs contained mitochondria with filamentous and/or rounded morphologies. Both types of mitochondria showed similar membrane potentials. Interestingly, in the presence of PDGF-AA, but not PDGF-BB, the balance between the two morphologies shifted towards the filamentous form. Concomitantly, both mitochondrial enzymatic activity and total cellular ATP level were augmented by PDGF-AA. These two parameters were closely correlated, suggesting the mitochondrial involvement in the PDGF-augmented ATP production. Moreover, PDGF-AA accelerated the migration of HDPCs in a gap-filling assay, but did not change the rate of cellular proliferation. Notably, filamentous mitochondria dominated migrating HDPCs. PDGF-AA benefits HDPCs in the process of migration, by increasing the number of filamentous mitochondria. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Induction of hair follicle dermal papilla cell properties in human induced pluripotent stem cell-derived multipotent LNGFR(+)THY-1(+) mesenchymal cells

PubMed Central

Veraitch, Ophelia; Mabuchi, Yo; Matsuzaki, Yumi; Sasaki, Takashi; Okuno, Hironobu; Tsukashima, Aki; Amagai, Masayuki; Okano, Hideyuki; Ohyama, Manabu

2017-01-01

The dermal papilla (DP) is a specialised mesenchymal component of the hair follicle (HF) that plays key roles in HF morphogenesis and regeneration. Current technical difficulties in preparing trichogenic human DP cells could be overcome by the use of highly proliferative and plastic human induced pluripotent stem cells (hiPSCs). In this study, hiPSCs were differentiated into induced mesenchymal cells (iMCs) with a bone marrow stromal cell phenotype. A highly proliferative and plastic LNGFR(+)THY-1(+) subset of iMCs was subsequently programmed using retinoic acid and DP cell activating culture medium to acquire DP properties. The resultant cells (induced DP-substituting cells [iDPSCs]) exhibited up-regulated DP markers, interacted with human keratinocytes to up-regulate HF related genes, and when co-grafted with human keratinocytes in vivo gave rise to fibre structures with a hair cuticle-like coat resembling the hair shaft, as confirmed by scanning electron microscope analysis. Furthermore, iDPSCs responded to the clinically used hair growth reagent, minoxidil sulfate, to up-regulate DP genes, further supporting that they were capable of, at least in part, reproducing DP properties. Thus, LNGFR(+)THY-1(+) iMCs may provide material for HF bioengineering and drug screening for hair diseases. PMID:28220862

The dermal arteries of the human thumb pad

PubMed Central

Geyer, S H; Nöhammer, M M; Tinhofer, I E; Weninger, W J

2013-01-01

The arteries of the skin have been postulated to form a profound plexus at the dermal/hypodermal junction and a superficial plexus in the papillary dermis. Our article aims to rebut this concept and to provide an alternative description of the arrangement of the dermal arteries. Employing a novel technique, we produced digital volume data (volume size: 2739 × 2054 × 3000 μm3; voxel size: 1.07 × 1.07 × 2 μm3) from biopsies of the skin of the thumb pads of 15 body donors. Utilizing these data, we analysed the arrangement of the dermal arteries with the aid of virtual re-sectioning tools, and, in three specimens, with high-quality three-dimensional (3D) surface models. In all specimens we observed a tree-like ramification of discrete dermal arteries. The terminal branches of the arterial trees gave rise to the ascending segments of the capillary loops of the dermal papillae. None of the specimens showed a superficial arterial plexus. This suggests that the skin of the human thumb pad can be split in discrete ‘arterial units’. Each unit represents the zone of the papillary dermis and epidermal/dermal junction, to which blood is supplied exclusively by the branches of a single dermal artery. The concept of dermal arterial units is in contrast to all existing descriptions of the architecture of the dermal arteries. However, whether it can be transferred to the skin of other body parts, remains to be tested. Likewise, the consequences of arterial units for understanding the mechanisms of wound healing and the appearance and genesis of skin diseases remain to be examined. PMID:24205910

iTRAQ-Based Quantitative Proteomic Comparison of Early- and Late-Passage Human Dermal Papilla Cell Secretome in Relation to Inducing Hair Follicle Regeneration.

PubMed

Zhang, Huan; Zhu, Ning-Xia; Huang, Keng; Cai, Bo-Zhi; Zeng, Yang; Xu, Yan-Ming; Liu, Yang; Yuan, Yan-Ping; Lin, Chang-Min

2016-01-01

Alopecia is an exceedingly prevalent problem that lacks effective therapy. Recently, research has focused on early-passage dermal papilla cells (DPCs), which have hair inducing activity both in vivo and in vitro. Our previous study indicated that factors secreted from early-passage DPCs contribute to hair follicle (HF) regeneration. To identify which factors are responsible for HF regeneration and why late-passage DPCs lose this potential, we collected 48-h-culture medium (CM) from both of passage 3 and 9 DPCs, and subcutaneously injected the DPC-CM into NU/NU mice. Passage 3 DPC-CM induced HF regeneration, based on the emergence of a white hair coat, but passage 9 DPC-CM did not. In order to identify the key factors responsible for hair induction, CM from passage 3 and 9 DPCs was analyzed by iTRAQ-based quantitative proteomic technology. We identified 1360 proteins, of which 213 proteins were differentially expressed between CM from early-passage vs. late-passage DPCs, including SDF1, MMP3, biglycan and LTBP1. Further analysis indicated that the differentially-expressed proteins regulated the Wnt, TGF-β and BMP signaling pathways, which directly and indirectly participate in HF morphogenesis and regeneration. Subsequently, we selected 19 proteins for further verification by multiple reaction monitoring (MRM) between the two types of CM. These results indicate DPC-secreted proteins play important roles in HF regeneration, with SDF1, MMP3, biglycan, and LTBP1 being potential key inductive factors secreted by dermal papilla cells in the regeneration of hair follicles.

Titrated extract of Centella asiatica increases hair inductive property through inhibition of STAT signaling pathway in three-dimensional spheroid cultured human dermal papilla cells.

PubMed

Choi, Yeong Min; An, Sungkwan; Lee, Junwoo; Lee, Jae Ho; Lee, Jae Nam; Kim, Young Sam; Ahn, Kyu Joong; An, In-Sook; Bae, Seunghee

2017-12-01

Dermal papilla (DP) is a pivotal part of hair follicle, and the smaller size of the DP is related with the hair loss. In this study, we investigated the effect of titrated extract of Centella asiatica (TECA) on hair growth inductive property on 3D spheroid cultured human DP cells (HDP cells). Significantly increased effect of TECA on cell viability was only shown in 3D sphered HPD cells, not in 2D cultured HDP cells. Also, TECA treatment increased the sphere size of HDP cells. The luciferase activity of STAT reporter genes and the expression of STAT-targeted genes, SOCS1 and SOCS3, were significantly decreased. Also, TECA treatment increased the expression of the hair growth-related signature genes in 3D sphered HDP cells. Furthermore, TECA led to downregulation of the level of phosphorylated STAT proteins in 3D sphered HDP cells. Overall, TECA activates the potential of hair inductive capacity in HDP cells.

Ascorbigen induces dermal papilla cell proliferation in vitro, but fails to modulate chemotherapy-induced alopecia in vivo.

PubMed

Wang, Chih-Hsiu; Huang, Hsu-Shan; Dai, Niann-Tzyy; Sheu, Ming-Jen; Chang, Deh-Ming

2013-12-01

Ascorbigen (ABG) is the predominant indole-derived compound from Brassica vegetables. In this study, we attempted to evaluate the effects of ABG on hair growth. To this end, we examined the proliferation of isolated human dermal papilla (DP) cells and keratinocytes after incubation in various concentrations (0-1.25 mM) of ABG. Furthermore, hair shaft regrowth was monitored in a mouse model of chemotherapy-induced alopecia (CIA), and hematoxylin and eosin staining was performed for histological analyses. We found that 1.25 mM ABG induced a 1.2-fold increase in the growth of DP cells, but not keratinocytes. However, ABG did not exert significant protective effects against CIA in the mouse model. These findings suggest that ABG may not be able to counteract CIA and that further investigation of the therapeutic potential of ABG in disease models is required. Copyright © 2013 John Wiley & Sons, Ltd.

Establishment of dermal sheath cell line from Cashmere goat and characterizing cytokeratin 13 as its novel biomarker.

PubMed

Zhu, Bing; Guo, Zhili; Jin, Muzi; Bai, Yujuan; Yang, Wenliang; Hui, Lihua

2018-05-01

To establish a dermal sheath cell line, a dermal papilla cell line and a outer root sheath cell line from Cashmere goat and clarify the similarities and differences among them. We established a dermal sheath cell line, a dermal papilla cell line and a outer root sheath cell line from the pelage skin hair follicles of Cashmere goat. The growth rate of dermal sheath cells was intermediate between that of dermal papilla cells and outer root sheath cells. Immunofluorescence experiments and reverse transcription-polymerase chain reaction analysis showed that at both the transcriptional and translational levels, the dermal sheath cells were alpha-smooth muscle actin (α-SMA) + /cytokeratin 13 + , while the dermal papilla cells were α-SMA + /cytokeratin 13 - and the outer root sheath cells were α-SMA - /cytokeratin 13 + . Patterns of cytokeratin 13 expression could distinguish the dermal sheath cells from the dermal papilla cells. These results suggest that cytokeratin 13 could serve as a novel biomarker for dermal sheath cells of Cashmere goat, and should prove useful for researchers investigating dermal stem cells or interaction of different types of cells during hair cycle.

Effect of sinapic acid on hair growth promoting in human hair follicle dermal papilla cells via Akt activation.

PubMed

Woo, Hyunju; Lee, Seungjun; Kim, Seungbeom; Park, Deokhoon; Jung, Eunsun

2017-07-01

Hair loss known as alopecia is caused by abnormal hair follicle cycling including shortening of the anagen (growth) phase and changing of hair follicle morphology with miniaturization. In accordance with the life extension, the quality of life is considered to be a most important thing. The yearning for healthy and beautiful hair and low self esteem due to hair loss had negative influence on the quality of life with psychosocial maladjustment. The objective of this research was to identify new compound that can be used as a drug to promote hair growth. We investigated whether the function of sinapic acid (SA) is able to promote hair growth in human hair follicle dermal papilla cells (hHFDPC). We showed that treatment of SA in hHFDPC could induce proliferation and the activation of Akt signaling in HFDPC. In addition, SA could stimulate the expressions of the several growth factors, insulin-like growth factor 1, and vascular endothelial growth factor for hair growth. We showed that SA led to an increased level of phospho-GSK-3β and β-catenin accumulation in HFDPC. Finally, the promoting effect of SA in hHFDPC cell growth occurred by the induction of cell cycle progression. These results suggest that SA could be one of the potential candidate compounds for the treatment of alopecia by inducing hair growth through triggering the expressions of growth factors via activation of Akt and subsequent inactivation of GSK-3β /β-catenin pathway.

Dkk2/Frzb in the dermal papillae regulates feather regeneration

PubMed Central

Chu, Qiqi; Cai, Linyan; Fu, Yu; Chen, Xi; Yan, Zhipeng; Lin, Xiang; Zhou, Guixuan; Han, Hao; Widelitz, Randall B.; Chuong, Cheng-ming; Wu, Wei; Yue, Zhicao

2015-01-01

Avian feathers have robust growth and regeneration capability. To evaluate the contribution of signaling molecules and pathways in these processes, we profiled gene expression in the feather follicle using an absolute quantification approach. We identified hundreds of genes that mark specific components of the feather follicle: the dermal papillae (DP) which controls feather regeneration and axis formation, the pulp mesenchyme (Pp) which is derived from DP cells and nourishes the feather follicle, and the ramogenic zone epithelium (Erz) where a feather starts to branch. The feather DP is enriched in BMP/TGF-β signaling molecules and inhibitors for Wnt signaling including Dkk2/Frzb. Wnt ligands are mainly expressed in the feather epithelium and pulp. We find that while Wnt signaling is required for the maintenance of DP marker gene expression and feather regeneration, excessive Wnt signaling delays regeneration and reduces pulp formation. Manipulating Dkk2/Frzb expression by lentiviral-mediated overexpression, shRNA-knockdown, or by antibody neutralization resulted in dual feather axes formation. Our results suggest that the Wnt signaling in the proximal feather follicle is fine-tuned to accommodate feather regeneration and axis formation. PMID:24463139

Ginsenoside Rg3 up-regulates the expression of vascular endothelial growth factor in human dermal papilla cells and mouse hair follicles.

PubMed

Shin, Dae Hyun; Cha, Youn Jeong; Yang, Kyeong Eun; Jang, Ik-Soon; Son, Chang-Gue; Kim, Bo Hyeon; Kim, Jung Min

2014-07-01

Crude Panax ginseng has been documented to possess hair growth activity and is widely used to treat alopecia, but the effects of ginsenoside Rg3 on hair growth have not to our knowledge been determined. The aim of the current study was to identify the molecules through which Rg3 stimulates hair growth. The thymidine incorporation for measuring cell proliferation was determined. We used DNA microarray analysis to measure gene expression levels in dermal papilla (DP) cells upon treatment with Rg3. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) in human DP cells were measured by real-time polymerase chain reaction and immunohistochemistry, respectively. We also used immunohistochemistry assays to detect in vivo changes in VEGF and 3-stemness marker expressions in mouse hair follicles. Reverse transcription polymerase chain reaction showed dose-dependent increases in VEGF mRNA levels on treatment with Rg3. Immunohistochemical analysis showed that expression of VEGF was significantly up-regulated by Rg3 in a dose-dependent manner in human DP cells and in mouse hair follicles. In addition, the CD8 and CD34 were also up-regulated by Rg3 in the mouse hair follicles. It may be concluded that Rg3 might increase hair growth through stimulation of hair follicle stem cells and it has the potential to be used in hair growth products. Copyright © 2013 John Wiley & Sons, Ltd.

Quantitative analysis of epithelial papillae in patients with oral lichen planus.

PubMed

López-Jornet, P; Camacho-Alonso, F; Molina-Miñano, F

2009-06-01

The oral mucosa is relatively vulnerable to pathological processes, and is often affected by autoimmune and malignant diseases. The oral epithelium is normally non-homogeneous, and joins to the connective tissue through interlocking of its downward projections in the form of papillae. This study aims to conduct a histomorphometric study of the epithelial papillae in patients with oral lichen planus (OLP). This study was based on 100 cheek mucosa biopsies from patients with OLP (66 white reticular and 34 atrophic-erosive) (13 males and 87 females, with a mean age of 54.95 +/- 13.64 years). A histological and morphometric evaluation was made, based on imaging analysis with MIP software 4.5 for studying the papillary structure in the patients with OLP. The mean epithelial thickness was 227.5 +/- 78.5 microm. The different papillary measures--BLS (distance from basal layer to epithelial surface), DPS (distance from dermal papilla top to epithelial surface), DPW (dermal papilla width), and DPD (interdermal papilla distance between two papillae)--yielded no statistically significant differences with respect to age, sex, smoking and clinical form. However, a significant correlation was observed in relation to papilla width and inflammatory infiltrate (P = 0.031). The application of this imaging system is useful for measuring variations in epithelial papillary architecture.

Activating β-catenin signaling in CD133-positive dermal papilla cells increases hair inductivity

PubMed Central

Zhou, Linli; Yang, Kun; Xu, Mingang; Andl, Thomas; Millar, Sarah; Boyce, Steven; Zhang, Yuhang

2016-01-01

Bioengineering hair follicles using cells isolated from human tissue remains as a difficult task. Dermal papilla (DP) cells are known to guide the growth and cycling activities of hair follicles by interacting with keratinocytes. However, DP cells quickly lose their inductivity during in vitro passaging. Rodent DP cell cultures need external addition of chemical factors, including WNT and BMP molecules, to maintain the hair inductive property. CD133 is expressed by a small subpopulation of DP cells that are capable of inducing hair follicle formation in vivo. We report here that expression of a stabilized form of β-catenin promoted clonal growth of CD133-positive (CD133+) DP cells in in vitro three-dimensional hydrogel culture while maintaining expression of DP markers, including alkaline phosphatase (AP), CD133, and Integrin α8. After a two-week in vitro culture, cultured CD133+ DP cells with up-regulated β-catenin activity led to an accelerated in vivo hair growth in reconstituted skin than control cells. Further analysis showed that matrix cell proliferation and differentiation were significantly promoted in hair follicles when β-catenin signaling was upregulated in CD133+ DP cells. Our data highlight an important role for β-catenin signaling in promoting the inductive capability of CD133+ DP cells for in vitro expansion and in vivo hair follicle regeneration, which could potentially be applied to cultured human DP cells. PMID:27312243

Establishment of an immortalized mouse dermal papilla cell strain with optimized culture strategy.

PubMed

Guo, Haiying; Xing, Yizhan; Zhang, Yiming; He, Long; Deng, Fang; Ma, Xiaogen; Li, Yuhong

2018-01-01

Dermal papilla (DP) plays important roles in hair follicle regeneration. Long-term culture of mouse DP cells can provide enough cells for research and application of DP cells. We optimized the culture strategy for DP cells from three dimensions: stepwise dissection, collagen I coating, and optimized culture medium. Based on the optimized culture strategy, we immortalized primary DP cells with SV40 large T antigen, and established several immortalized DP cell strains. By comparing molecular expression and morphologic characteristics with primary DP cells, we found one cell strain named iDP6 was similar with primary DP cells. Further identifications illustrate that iDP6 expresses FGF7 and α-SMA, and has activity of alkaline phosphatase. During the process of characterization of immortalized DP cell strains, we also found that cells in DP were heterogeneous. We successfully optimized culture strategy for DP cells, and established an immortalized DP cell strain suitable for research and application of DP cells.

Establishment of an immortalized mouse dermal papilla cell strain with optimized culture strategy

PubMed Central

Zhang, Yiming; He, Long; Deng, Fang; Ma, Xiaogen

2018-01-01

Dermal papilla (DP) plays important roles in hair follicle regeneration. Long-term culture of mouse DP cells can provide enough cells for research and application of DP cells. We optimized the culture strategy for DP cells from three dimensions: stepwise dissection, collagen I coating, and optimized culture medium. Based on the optimized culture strategy, we immortalized primary DP cells with SV40 large T antigen, and established several immortalized DP cell strains. By comparing molecular expression and morphologic characteristics with primary DP cells, we found one cell strain named iDP6 was similar with primary DP cells. Further identifications illustrate that iDP6 expresses FGF7 and α-SMA, and has activity of alkaline phosphatase. During the process of characterization of immortalized DP cell strains, we also found that cells in DP were heterogeneous. We successfully optimized culture strategy for DP cells, and established an immortalized DP cell strain suitable for research and application of DP cells. PMID:29383288

Identification of a new plant extract for androgenic alopecia treatment using a non-radioactive human hair dermal papilla cell-based assay.

PubMed

Jain, Ruchy; Monthakantirat, Orawan; Tengamnuay, Parkpoom; De-Eknamkul, Wanchai

2016-01-21

Androgenic alopecia (AGA) is a major type of human scalp hair loss, which is caused by two androgens: testosterone (T) and 5α-dihydrotestosterone (5α-DHT). Both androgens bind to the androgen receptor (AR) and induce androgen-sensitive genes within the human hair dermal papilla cells (HHDPCs), but 5α-DHT exhibits much higher binding affinity and potency than T does in inducing the involved androgen-sensitive genes. Changes in the induction of androgen-sensitive genes during AGA are caused by the over-production of 5α-DHT by the 5α-reductase (5α-R) enzyme; therefore, one possible method to treat AGA is to inhibit this enzymatic reaction. RT-PCR was used to identify the presence of the 5α-R and AR within HHDPCs. A newly developed AGA-relevant HHDPC-based assay combined with non-radioactive thin layer chromatography (TLC) detection was used for screening crude plant extracts for the identification of new 5α-R inhibitors. HHDPCs expressed both 5α-R type 1 isoform of the enzyme (5α-R1) and AR in all of the passages used in this study. Among the thirty tested extracts, Avicennia marina (AM) displayed the highest inhibitory activity at the final concentration of 10 μg/ml, as the production of 5α-DHT decreased by 52% (IC50 = 9.21 ± 0.38 μg/ml). Avicennia marina (AM) was identified as a potential candidate for the treatment of AGA based on its 5α-R1-inhibitory activity.

Anti-PDGF receptor β antibody-conjugated squarticles loaded with minoxidil for alopecia treatment by targeting hair follicles and dermal papilla cells.

PubMed

Aljuffali, Ibrahim A; Pan, Tai-Long; Sung, Calvin T; Chang, Shu-Hao; Fang, Jia-You

2015-08-01

This study developed lipid nanocarriers, called squarticles, conjugated with anti-platelet-derived growth factor (PDGF)-receptor β antibody to determine whether targeted Minoxidil (MXD) delivery to the follicles and dermal papilla cells (DPCs) could be achieved. Squalene and hexadecyl palmitate (HP) were used as the matrix of the squarticles. The PDGF-squarticles showed a mean diameter and zeta potential of 195 nm and -46 mV, respectively. Nanoparticle encapsulation enhanced MXD porcine skin deposition from 0.11 to 0.23 μg/mg. The antibody-conjugated nanoparticles ameliorated follicular uptake of MXD by 3-fold compared to that of the control solution in the in vivo mouse model. Both vertical and horizontal skin sections exhibited a wide distribution of nanoparticles in the follicles, epidermis, and deeper skin strata. The encapsulated MXD moderately elicited proliferation of DPCs and vascular endothelial growth factor (VEGF) expression. The active targeting of PDGF-squarticles may be advantageous to improving the limited success of alopecia therapy. Topical use of minoxidil is only one of the very few treatment options for alopecia. Nonetheless, the current delivery method is far from ideal. In this article, the authors developed lipid nanocarriers with anti-platelet-derived growth factor receptor ? antibody to target dermal papilla cells, and showed enhanced uptake of minoxidil. Copyright © 2015 Elsevier Inc. All rights reserved.

Minoxidil activates β-catenin pathway in human dermal papilla cells: a possible explanation for its anagen prolongation effect.

PubMed

Kwack, Mi Hee; Kang, Bo Mi; Kim, Moon Kyu; Kim, Jung Chul; Sung, Young Kwan

2011-06-01

It is believed that the length of the actively growing phase of the anagen hair cycle mainly contributes to hair length. Recent studies showed that maintenance of β-catenin activity in the dermal papilla cells (DPCs) enables hair follicles to keep actively growing. Topical minoxidil treatment promotes hair growth in men with androgenetic alopecia, suggesting that minoxidil may prolong the actively growing phase of the anagen hair cycle. To investigate whether minoxidil prolongs the anagen hair cycle in mice and, if so, to investigate whether minoxidil activates β-catenin pathway in human DPCs. Dorsal skins of C57BL/6 mice were depilated to synchronize the hair cycle. After 10 days, 3% minoxidil were topically applied daily for 10 days. Sections of back skins were stained with hematoxylin and eosin. Hair follicles were graded and hair cycle score (HCS) was calculated. Cultured human DPCs were transiently transfected with the β-catenin responsive TCF reporter plasmid (pTopflash) and corresponding negative control reporter (pFopflash) to assess the activity of β-catenin signaling by minoxidil. Immunofluorescence staining and immunoblot were performed to examine the expression and localization of β-catenin in the presence or absence of minoxidil. Phosphorylation of GSK3β, PKA and PKB were also examined by immunoblot after minoxidil treatment. RT-PCR analysis and immunoblot were employed to investigate the expression of β-catenin pathway targets in DPCs, such as Axin2, Lef-1, and EP2. Modest extension of anagen phase thereby delay of catagen progression was observed by application of minoxidil in mice. Minoxidil stimulated the transcriptional activity of pTopflash but not pFopflash. Nuclear accumulation of β-catenin was also observed after minoxidil treatment. Immunoblot further showed that minoxidil treatment increases the phosphorylation of GSK3β, PKA and PKB. Moreover, minoxidil induced Axin2, Lef-1, and EP2 expression. Our results strongly suggest that

Experimental study on repairing of nude mice skin defects with composite skin consisting of xenogeneic dermis and epidermal stem cells and hair follicle dermal papilla cells.

PubMed

Qi, Shao-Hai; Liu, Po; Xie, Ju-Lin; Shu, Bin; Xu, Ying-Bin; Ke, Chang-Neng; Liu, Xu-Sheng; Li, Tian-Zeng

2008-05-01

To investigate the influence of hair follicle dermal papilla cells (DPCs) on biological features of composite skin. In the test group, xenogeneic acellular dermal matrix was employed as the frame, DPCs were seeded on the subcutaneous side, and epithelial stem cells onto the dermal papilla side of the dermal frame so as to construct a composite skin. In the control group, there was no DPC in the frame. The two kinds of composite skin were employed to cover skin defects on the back of the nude mice. Wound healing was observed 4 weeks after grafting and area was analyzed and contraction rate was calculated. The tissue samples in the grafted area were harvested for HE staining and the state of the composite skin was observed. The stress-strain curve of the sampled skin was measured, so as to calculate the maximal breaking power of the sample. The data were collected and statistically analyzed. HE staining indicated that the epithelial depth was increased (more than 10 layers of cells) in test group, with only 6-7 layers in control group. The skin contraction rate in test group on the 4th week after skin grafting (3.94+/-0.013)% was much lower than that in control group (29.07+/-0.018)% (P<0.05). It was indicated by biomechanical test that the stress-strain curve of the composite skin in the test group was closer to that of normal nude mice skin in comparison to that in control group. The maximal breaking force of the composite skin in test group was (1.835+/-0.035)N (Newton), while that in control group was (1.075+/-0.065)N (P<0.01). Reconstruction of epidermis in composite skin was promoted by dermal DPCs seeded in the dermal matrix frame. As a result, there was less skin contraction in the composite skin with DPCs, so that the biological characteristics of the skin were improved.

Hydroxyl radical mediates cisplatin-induced apoptosis in human hair follicle dermal papilla cells and keratinocytes through Bcl-2-dependent mechanism.

PubMed

Luanpitpong, Sudjit; Nimmannit, Ubonthip; Chanvorachote, Pithi; Leonard, Stephen S; Pongrakhananon, Varisa; Wang, Liying; Rojanasakul, Yon

2011-08-01

Induction of massive apoptosis of hair follicle cells by chemotherapy has been implicated in the pathogenesis of chemotherapy-induced alopecia (CIA), but the underlying mechanisms of regulation are not well understood. The present study investigated the apoptotic effect of cisplatin in human hair follicle dermal papilla cells and HaCaT keratinocytes, and determined the identity and role of specific reactive oxygen species (ROS) involved in the process. Treatment of the cells with cisplatin induced ROS generation and a parallel increase in caspase activation and apoptotic cell death. Inhibition of ROS generation by antioxidants inhibited the apoptotic effect of cisplatin, indicating the role of ROS in the process. Studies using specific ROS scavengers further showed that hydroxyl radical, but not hydrogen peroxide or superoxide anion, is the primary oxidative species responsible for the apoptotic effect of cisplatin. Electron spin resonance studies confirmed the formation of hydroxyl radicals induced by cisplatin. The mechanism by which hydroxyl radical mediates the apoptotic effect of cisplatin was shown to involve down-regulation of the anti-apoptotic protein Bcl-2 through ubiquitin-proteasomal degradation. Bcl-2 was also shown to have a negative regulatory role on hydroxyl radical. Together, our results indicate an essential role of hydroxyl radical in cisplatin-induced cell death of hair follicle cells through Bcl-2 regulation. Since CIA is a major side effect of cisplatin and many other chemotherapeutic agents with no known effective treatments, the knowledge gained from this study could be useful in the design of preventive treatment strategies for CIA through localized therapy without compromising the chemotherapy efficacy.

Osteogenic differentiation of human dental papilla mesenchymal cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ikeda, Etsuko; Hirose, Motohiro; Kotobuki, Noriko

We isolated dental papilla from impacted human molar and proliferated adherent fibroblastic cells after collagenase treatment of the papilla. The cells were negative for hematopoietic markers but positive for CD29, CD44, CD90, CD105, and CD166. When the cells were further cultured in the presence of {beta}-glycerophosphate, ascorbic acid, and dexamethasone for 14 days, mineralized areas together with osteogenic differentiation evidenced by high alkaline phosphatase activity and osteocalcin contents were observed. The differentiation was confirmed at both protein and gene expression levels. The cells can also be cryopreserved and, after thawing, could show in vivo bone-forming capability. These results indicate thatmore » mesenchymal type cells localize in dental papilla and that the cells can be culture expanded/utilized for bone tissue engineering.« less

Effect of Cinnamomum osmophloeum Kanehira Leaf Aqueous Extract on Dermal Papilla Cell Proliferation and Hair Growth

PubMed Central

Wen, Tung-Chou; Li, Yuan-Sheng; Rajamani, Karthyayani; Harn, Horng-Jyh; Lin, Shinn-Zong; Chiou, Tzyy-Wen

2018-01-01

In this study, we explored the effect of the water extract of Cinnamomum osmophloeum Kanehira (COK) leaves on hair growth by in vitro and in vivo assays. Using an in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, it was found that the proliferation of rat vibrissae and human hair dermal papilla cells (hDPCs) was significantly enhanced by the COK leaf extract treatment. As determined by quantitative real-time polymerase chain reaction (RT-PCR), the messenger RNA (mRNA) levels of some hair growth–related factors including vascular endothelial growth factor, keratinocyte growth factor (KGF), and transforming growth factor-β2 were found to be higher in the cultured hDPCs exposed to COK leaf extract than those in the untreated control group. In the hair-depilated C57BL/6 mouse model, the stimulation of hair growth was demonstrated in the group of COK leaf extract treatment. Both photographical and histological observations revealed the promotion of the anagen phase in the hair growth cycle by the COK leaf extract in the C57BL/6 mice. Finally, the ultra performance liquid chromatography (UPLC) showed that the COK extract contained mostly cinnamic aldehyde and a small amount of cinnamic acid. The results suggest that the COK leaf extract may find use for the treatment of hair loss. PMID:29637818

1α,25-dihydroxyvitamin D3 modulates the hair-inductive capacity of dermal papilla cells: therapeutic potential for hair regeneration.

PubMed

Aoi, Noriyuki; Inoue, Keita; Chikanishi, Toshihiro; Fujiki, Ryoji; Yamamoto, Hanako; Kato, Harunosuke; Eto, Hitomi; Doi, Kentaro; Itami, Satoshi; Kato, Shigeaki; Yoshimura, Kotaro

2012-08-01

Dermal papilla cells (DPCs) have the potential to induce differentiation of epithelial stem cells into hair, and Wnt signaling is deeply involved in the initiation process. The functional limitation of expanded adult DPCs has been a difficult challenge for cell-based hair regrowth therapy. We previously reported that 1α,25-dihydroxyvitamin D(3) (VD(3)) upregulates expression of transforming growth factor (TGF)-β2 and alkaline phosphatase (ALP) activity, both features of hair-inducing human DPCs (hDPCs). In this study, we further examined the effects and signaling pathways associated with VD(3) actions on DPCs. VD(3) suppressed hDPC proliferation in a dose-dependent, noncytotoxic manner. Among the Wnt-related genes investigated, Wnt10b expression was significantly upregulated by VD(3) in hDPCs. Wnt10b upregulation, as well as upregulation of ALPL (ALP, liver/bone/kidney) and TGF-β2, by VD(3) was specific in hDPCs and not detected in human dermal fibroblasts. Screening of paracrine or endocrine factors in the skin indicated that all-trans retinoic acid (atRA) upregulated Wnt10b gene expression, although synergistic upregulation (combined atRA and VD(3)) was not seen. RNA interference with vitamin D receptor (VDR) revealed that VD(3) upregulation of Wnt10b, ALPL, and TGF-β2 was mediated through the genomic VDR pathway. In a rat model of de novo hair regeneration by murine DPC transplantation, pretreatment with VD(3) significantly enhanced hair folliculogenesis. Specifically, a greater number of outgrowing hair shafts and higher maturation of regenerated follicles were observed. Together, these data suggest that VD(3) may promote functional differentiation of DPCs and be useful in preserving the hair follicle-inductive capacity of cultured DPCs for hair regeneration therapies.

1α,25-Dihydroxyvitamin D3 Modulates the Hair-Inductive Capacity of Dermal Papilla Cells: Therapeutic Potential for Hair Regeneration

PubMed Central

Aoi, Noriyuki; Inoue, Keita; Chikanishi, Toshihiro; Fujiki, Ryoji; Yamamoto, Hanako; Kato, Harunosuke; Eto, Hitomi; Doi, Kentaro; Itami, Satoshi; Kato, Shigeaki

2012-01-01

Dermal papilla cells (DPCs) have the potential to induce differentiation of epithelial stem cells into hair, and Wnt signaling is deeply involved in the initiation process. The functional limitation of expanded adult DPCs has been a difficult challenge for cell-based hair regrowth therapy. We previously reported that 1α,25-dihydroxyvitamin D3 (VD3) upregulates expression of transforming growth factor (TGF)-β2 and alkaline phosphatase (ALP) activity, both features of hair-inducing human DPCs (hDPCs). In this study, we further examined the effects and signaling pathways associated with VD3 actions on DPCs. VD3 suppressed hDPC proliferation in a dose-dependent, noncytotoxic manner. Among the Wnt-related genes investigated, Wnt10b expression was significantly upregulated by VD3 in hDPCs. Wnt10b upregulation, as well as upregulation of ALPL (ALP, liver/bone/kidney) and TGF-β2, by VD3 was specific in hDPCs and not detected in human dermal fibroblasts. Screening of paracrine or endocrine factors in the skin indicated that all-trans retinoic acid (atRA) upregulated Wnt10b gene expression, although synergistic upregulation (combined atRA and VD3) was not seen. RNA interference with vitamin D receptor (VDR) revealed that VD3 upregulation of Wnt10b, ALPL, and TGF-β2 was mediated through the genomic VDR pathway. In a rat model of de novo hair regeneration by murine DPC transplantation, pretreatment with VD3 significantly enhanced hair folliculogenesis. Specifically, a greater number of outgrowing hair shafts and higher maturation of regenerated follicles were observed. Together, these data suggest that VD3 may promote functional differentiation of DPCs and be useful in preserving the hair follicle-inductive capacity of cultured DPCs for hair regeneration therapies. PMID:23197867

β-Catenin activity in the dermal papilla of the hair follicle regulates pigment-type switching

PubMed Central

Enshell-Seijffers, David; Lindon, Catherine; Wu, Eleanor; Taketo, Makoto M.; Morgan, Bruce A.

2010-01-01

The switch between black and yellow pigment is mediated by the interaction between Melanocortin receptor 1 (Mc1r) and its antagonist Agouti, but the genetic and developmental mechanisms that modify this interaction to obtain different coat color in distinct environments are poorly understood. Here, the role of Wnt/β-catenin signaling in the regulation of pigment-type switching was studied. Loss and gain of function of β-catenin in the dermal papilla (DP) of the hair follicle results in yellow and black animals, respectively. β-Catenin activity in the DP suppresses Agouti expression and activates Corin, a negative regulator of Agouti activity. In addition, β-catenin activity in the DP regulates melanocyte activity by a mechanism that is independent of both Agouti and Corin. The coordinate and inverse regulation of Agouti and Corin renders pelage pigmentation sensitive to changes in β-catenin activity in the DP that do not alter pelage structure. As a result, the signals that specify two biologically distinct quantitative traits are partially uncoupled despite their common regulation by the β-catenin pathway in the same cells. PMID:21098273

Dermal Blimp1 Acts Downstream of Epidermal TGFβ and Wnt/β-Catenin to Regulate Hair Follicle Formation and Growth.

PubMed

Telerman, Stephanie B; Rognoni, Emanuel; Sequeira, Inês; Pisco, Angela Oliveira; Lichtenberger, Beate M; Culley, Oliver J; Viswanathan, Priyalakshmi; Driskell, Ryan R; Watt, Fiona M

2017-11-01

B-lymphocyte-induced maturation protein 1 (Blimp1) is a transcriptional repressor that regulates cell growth and differentiation in multiple tissues, including skin. Although in the epidermis Blimp1 is important for keratinocyte and sebocyte differentiation, its role in dermal fibroblasts is unclear. Here we show that Blimp1 is dynamically regulated in dermal papilla cells during hair follicle (HF) morphogenesis and the postnatal hair cycle, preceding dermal Wnt/β-catenin activation. Blimp1 ablation in E12.5 mouse dermal fibroblasts delayed HF morphogenesis and growth and prevented new HF formation after wounding. By combining targeted quantitative PCR screens with bioinformatic analysis and experimental validation we demonstrated that Blimp1 is both a target and a mediator of key dermal papilla inductive signaling pathways including transforming growth factor-β and Wnt/β-catenin. Epidermal overexpression of stabilized β-catenin was able to override the HF defects in Blimp1 mutant mice, underlining the close reciprocal relationship between the dermal papilla and adjacent HF epithelial cells. Overall, our study reveals the functional role of Blimp1 in promoting the dermal papilla inductive signaling cascade that initiates HF growth. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Minimizing shrinkage of interdental papilla height when treating multiple Miller Class III gingival recession defects.

PubMed

Mahn, Douglas H

2015-04-01

Miller Class III and IV gingival recession defects have interdental bone and soft-tissue loss that limit root coverage. Given the importance of the interdental papilla, protecting the integrity of this structure would seem prudent. Tunnel techniques have been successfully used to protect the interdental papilla. This article discusses the results of two cases in which multiple Miller Class III gingival recession defects were treated using tunnel-grafting techniques and an acellular dermal matrix. In both cases, root coverage was achieved while protecting the interdental papilla height.

BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties

PubMed Central

Rendl, Michael; Polak, Lisa; Fuchs, Elaine

2008-01-01

Hair follicle (HF) formation is initiated when epithelial stem cells receive cues from specialized mesenchymal dermal papilla (DP) cells. In culture, DP cells lose their HF-inducing properties, but during hair growth in vivo, they reside within the HF bulb and instruct surrounding epithelial progenitors to orchestrate the complex hair differentiation program. To gain insights into the molecular program that maintains DP cell fate, we previously purified DP cells and four neighboring populations and defined their cell-type-specific molecular signatures. Here, we exploit this information to show that the bulb microenvironment is rich in bone morphogenetic proteins (BMPs) that act on DP cells to maintain key signature features in vitro and hair-inducing activity in vivo. By employing a novel in vitro/in vivo hybrid knockout assay, we ablate BMP receptor 1a in purified DP cells. When DPs cannot receive BMP signals, they lose signature characteristics in vitro and fail to generate HFs when engrafted with epithelial stem cells in vivo. These results reveal that BMP signaling, in addition to its key role in epithelial stem cell maintenance and progenitor cell differentiation, is essential for DP cell function, and suggest that it is a critical feature of the complex epithelial–mesenchymal cross-talk necessary to make hair. PMID:18281466

Preventable effect of L-threonate, an ascorbate metabolite, on androgen-driven balding via repression of dihydrotestosterone-induced dickkopf-1 expression in human hair dermal papilla cells.

PubMed

Kwack, Mi Hee; Ahn, Ji Sup; Kim, Moon Kyu; Kim, Jung Chul; Sung, Young Kwan

2010-10-01

In a previous study, we recently claimed that dihydrotestosterone (DHT)-inducible dickkopf-1 (DKK-1) expression is one of the key factors involved in androgen-potentiated balding. We also demonstrated that L-ascorbic acid 2-phosphate (Asc 2-P) represses DHT-induced DKK-1 expression in cultured dermal papilla cells (DPCs). Here, we investigated whether or not L-threonate could attenuate DHT-induced DKK-1 expression. We observed via RT-PCR analysis and enzyme-linked immunosorbent assay that DHT-induced DKK-1 expression was attenuated in the presence of L-threonate. We also found that DHT-induced activation of DKK-1 promoter activity was significantly repressed by L-threonate. Moreover, a co-culture system featuring outer root sheath (ORS) keratinocytes and DPCs showed that DHT inhibited the growth of ORS cells, which was then significantly reversed by L-threonate. Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding.

Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline

PubMed Central

Chi, Woo; Wu, Eleanor; Morgan, Bruce A.

2013-01-01

Although the hair shaft is derived from the progeny of keratinocyte stem cells in the follicular epithelium, the growth and differentiation of follicular keratinocytes is guided by a specialized mesenchymal population, the dermal papilla (DP), that is embedded in the hair bulb. Here we show that the number of DP cells in the follicle correlates with the size and shape of the hair produced in the mouse pelage. The same stem cell pool gives rise to hairs of different sizes or types in successive hair cycles, and this shift is accompanied by a corresponding change in DP cell number. Using a mouse model that allows selective ablation of DP cells in vivo, we show that DP cell number dictates the size and shape of the hair. Furthermore, we confirm the hypothesis that the DP plays a crucial role in activating stem cells to initiate the formation of a new hair shaft. When DP cell number falls below a critical threshold, hair follicles with a normal keratinocyte compartment fail to generate new hairs. However, neighbouring follicles with a few more DP cells can re-enter the growth phase, and those that do exploit an intrinsic mechanism to restore both DP cell number and normal hair growth. These results demonstrate that the mesenchymal niche directs stem and progenitor cell behaviour to initiate regeneration and specify hair morphology. Degeneration of the DP population in mice leads to the types of hair thinning and loss observed during human aging, and the results reported here suggest novel approaches to reversing hair loss. PMID:23487317

Wnt1a maintains characteristics of dermal papilla cells that induce mouse hair regeneration in a 3D preculture system.

PubMed

Dong, Liang; Hao, Haojie; Liu, Jiejie; Tong, Chuan; Ti, Dongdong; Chen, Deyun; Chen, Li; Li, Meirong; Liu, Huiling; Fu, Xiaobing; Han, Weidong

2017-05-01

Hair follicle morphogenesis and regeneration depend on intensive but well-orchestrated interactions between epithelial and mesenchymal components. Therefore, an alternative strategy to reproduce the process of epithelial-mesenchymal interaction in vitro could use a 3D system containing appropriate cell populations. The 3D air-liquid culture system for reproducibly generating hair follicles from dissociated epithelial and dermal papilla (DP) cells combined with a collagen-chitosan scaffold is described in this study. Wnt-CM was prepared from the supernatant of Wnt1a-expressing bone marrow mesenchymal stem cells (BM-MSCs) that maintain the hair-inducing gene expression of DP cells. The collagen-chitosan scaffold cells (CCS cells) were constructed using a two-step method by inoculating the Wnt-CM-treated DP cells and epidermal (EP) cells into the CCS. The cells in the air-liquid culture formed dermal condensates and a proliferative cell layer in vitro. The CCS cells were able to induce hair regeneration in nude mice. The results demonstrate that Wnt-CM can maintain the hair induction ability of DP cells in expansion cultures, and this approach can be used for large-scale preparation of CCS cells in vitro to treat hair loss. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth

PubMed Central

Zhou, Linli; Yang, Kun; Carpenter, April; Lang, Richard A.; Andl, Thomas; Zhang, Yuhang

2016-01-01

Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment. PMID:27462123

CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth.

PubMed

Zhou, Linli; Yang, Kun; Carpenter, April; Lang, Richard A; Andl, Thomas; Zhang, Yuhang

2016-10-01

Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Clonal Growth of Dermal Papilla Cells in Hydrogels Reveals Intrinsic Differences between Sox2-Positive and -Negative Cells In Vitro and In Vivo

PubMed Central

Driskell, Ryan R; Juneja, Vikram R; Connelly, John T; Kretzschmar, Kai; Tan, David W -M; Watt, Fiona M

2012-01-01

In neonatal mouse skin, two types of dermal papilla (DP) are distinguished by Sox2 expression: CD133+Sox2+ DP are associated with guard/awl/auchene hairs, whereas CD133+Sox2− DP are associated with zigzag (ZZ) hairs. We describe a three-dimensional hydrogel culture system that supports clonal growth of CD133+Sox2+, CD133+Sox2−, and CD133−Sox2− (non-DP) neonatal dermal cells. All three cell populations formed spheres that expressed the DP markers alkaline phosphatase, α8 integrin, and CD133. Nevertheless, spheres formed by CD133− cells did not efficiently support hair follicle formation in skin reconstitution assays. In the presence of freshly isolated P2 dermal cells, CD133+Sox2+ and CD133+Sox2− spheres contributed to the DP of both AA and ZZ hairs. Hair type did not correlate with sphere size. Sox2 expression was maintained in culture, but not induced significantly in Sox2− cells in vitro or in vivo, suggesting that Sox2+ cells are a distinct cellular lineage. Although Sox2+ cells were least efficient at forming spheres, they had the greatest ability to contribute to DP and non-DP dermis in reconstituted skin. As the culture system supports clonal growth of DP cells and maintenance of distinct DP cell types, it will be useful for further analysis of intrinsic and extrinsic signals controlling DP function. PMID:22189784

Sox2 in the dermal papilla niche controls hair growth by fine-tuning Bmp signaling in differentiating hair shaft progenitors

PubMed Central

Clavel, Carlos; Grisanti, Laura; Zemla, Roland; Rezza, Amelie; Barros, Rita; Sennett, Rachel; Mazloom, Amin; Chung, Chi-Yeh; Cai, Xiaoqiang; Cai, Chen-Leng; Pevny, Larysa; Nicolis, Silvia; Ma’ayan, Avi; Rendl, Michael

2012-01-01

SUMMARY How dermal papilla (DP) niche cells regulate hair follicle progenitors to control hair growth remains unclear. Using Tbx18Cre to target embryonic DP precursors, we ablate the transcription factor Sox2 early and efficiently, resulting in diminished hair shaft outgrowth. We find that DP niche expression of Sox2 controls the migration rate of differentiating hair shaft progenitors. Transcriptional profiling of Sox2 null DPs reveals increased Bmp6 and decreased Bmp inhibitor Sostdc1, a direct Sox2 transcriptional target. Subsequently, we identify upregulated Bmp signaling in knockout hair shaft progenitors and demonstrate that Bmps inhibit cell migration, an effect that can be attenuated by Sostdc1. A shorter and Sox2-negative hair type lacks Sostdc1 in the DP and shows reduced migration and increased Bmp activity of hair shaft progenitors. Collectively, our data identify Sox2 as a key regulator of hair growth that controls progenitor migration by fine-tuning Bmp-mediated mesenchymal-epithelial crosstalk. PMID:23153495

Follicular dermal papilla structures by organization of epithelial and mesenchymal cells in interfacial polyelectrolyte complex fibers.

PubMed

Lim, Tze Chiun; Leong, Meng Fatt; Lu, Hongfang; Du, Chan; Gao, Shujun; Wan, Andrew C A; Ying, Jackie Y

2013-09-01

The hair follicle is a regenerating organ that produces a new hair shaft during each growth cycle. Development and cycling of the hair follicle is governed by interactions between the epithelial and mesenchymal components. Therefore, development of an engineered 3D hair follicle would be useful for studying these interactions to identify strategies for treatment of hair loss. We have developed a technique suitable for assembly of different cell types in close proximity in fibrous hydrogel scaffolds with resolutions of ∼50 μm. By assembly of dermal papilla (DP) and keratinocytes, structures similar to the native hair bulb arrangement are formed. Gene expression of these constructs showed up-regulation of molecules involved in epithelial-mesenchymal interactions of the hair follicle. Implantation of the follicular structures in SCID mice led to the formation of hair follicle-like structures, thus demonstrating their hair inductive ability. The transparency of the fiber matrix and the small dimensions of the follicular structures allowed the direct quantitation of DP cell proliferation by confocal microscopy, clearly illustrating the promoting or inhibitory effects of hair growth regulating agents. Collectively, our results suggested a promising application of these 3D engineered follicular structures for in vitro screening and testing of drugs for hair growth therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neurochemical markers of human fungiform papillae and taste buds.

PubMed

Astbäck, J; Arvidson, K; Johansson, O

1995-11-10

The presence of distribution of several neurochemical markers in human fungiform papillae and taste buds were investigated by the immunohistochemical technique. The gustatory cells of the taste buds are in synaptic contact with sensory nerve endings, and considering the taste buds strictly as specialized sensory organs, the amounts and distribution of some of the neurochemical markers were different to what we expected. For example, few structures showed immunoreactivity to the tachykinins substance P (SP), calcitonin gene-related peptide (CGRP), and neurokinin A (NKA) also for the peptides vasoactive intestinal polypeptide (VIP), neuropeptide tyrosine (NPY) and galanin, low amounts of immunoreactivity occurred. On the other hand, using antibodies to protein gene product 9.5 (PGP 9.5), protein S-100, and glutamate, numerous nerve fibres and/or immunoreactive cells were found in the fungiform papillae, in the epithelium, in the connective tissue and around blood vessels, as well as in or near taste buds. Incubation with the antibodies against somatostatin, enkephalin, bombesin, peptide histidine isoleucine amide (PHI), cholecystokinin (CCK)/gastrin and dopamine-beta-hydroxylase (DBH) was negative for the fungiform papillae. In conclusion, the present study has shown several immunoreactive structures using antibodies against certain neurochemical markers. Further investigations will hopefully correlate these morphological findings with functional taste perception data. Future studies of patients with taste disorders or other pathological changes correlated with taste and tongue will also be of utmost importance.

Human dermal absorption of chlorinated organophosphate flame retardants; implications for human exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abou-Elwafa Abdallah, Mohamed, E-mail: mae_abdallah@yahoo.co.uk; Department of Analytical Chemistry, Faculty of Pharmacy, Assiut University, 71526 Assiut; Pawar, Gopal

Tris-2-chloroethyl phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP) and tris-1,3-dichloropropyl phosphate (TDCIPP) are organophosphate flame retardants (PFRs) widely applied in a plethora of consumer products despite their carcinogenic potential. Human dermal absorption of these PFRs is investigated for the first time using human ex vivo skin and EPISKIN™ models. Results of human ex vivo skin experiments revealed 28%, 25% and 13% absorption of the applied dose (500 ng/cm{sup 2}, finite dose) of TCEP, TCIPP and TDCIPP, respectively after 24 h exposure. The EPISKIN™ model showed enhanced permeability values (i.e. weaker barrier), that were respectively 16%, 11% and 9% for TCEP, TCIPPmore » and TDCIPP compared to human ex vivo skin. However, this difference was not significant (P > 0.05). Estimated permeability constants (K{sub p}, cm/h) showed a significant negative correlation with log K{sub ow} for the studied contaminants. The effect of hand-washing on dermal absorption of PFRs was investigated. Washing reduced overall dermal absorption, albeit to varying degrees depending on the physicochemical properties of the target PFRs. Moreover, slight variations of the absorbed dose were observed upon changing the dosing solution from acetone to 20% Tween 80 in water, indicating the potential influence of the dose vehicle on the dermal absorption of PFRs. Finally, estimated dermal uptake of the studied PFRs via contact with indoor dust was higher in UK toddlers (median ΣPFRs = 36 ng/kg bw day) than adults (median ΣPFRs = 4 ng/kg bw day). More research is required to fully elucidate the toxicological implications of such exposure. - Highlights: • Human dermal absorption of PFRs was studied using human ex vivo skin and EPISKIN™. • Absorbed fractions of TCEP, TCIPP and TDCIPP were 28%, 25% and 13% of applied dose. • Permeability constants showed significant negative correlation to log K{sub ow} of PFRs. • Skin washing reduced the overall dermal

STAT5 Activation in the Dermal Papilla Is Important for Hair Follicle Growth Phase Induction.

PubMed

Legrand, Julien M D; Roy, Edwige; Ellis, Jonathan J; Francois, Mathias; Brooks, Andrew J; Khosrotehrani, Kiarash

2016-09-01

Hair follicles are skin appendages that undergo periods of growth (anagen), regression (catagen), and rest (telogen) regulated by their mesenchymal component, the dermal papilla (DP). On the basis of the reports of its specific expression in the DP, we investigated signal transducer and activator of transcription (STAT5) activation during hair development and cycling. STAT5 activation in the DP began in late catagen, reaching a peak in early anagen before disappearing for the rest of the cycle. This was confirmed by the expression profile of suppressor of cytokine signaling 2, a STAT5 target in the DP. This pattern of expression starts after the first postnatal hair cycle. Quantification of hair cycling using the Flash canonical Wnt signaling in vivo bioluminescence reporter found that conditional knockout of STAT5A/B in the DP targeted through Cre-recombinase under the control of the Sox18 promoter resulted in delayed anagen entry compared with control. Microarray analysis of STAT5 deletion versus control revealed key changes in tumor necrosis factor-α, Wnt, and fibroblast growth factor ligands, known for their role in inducing anagen entry. We conclude that STAT5 activation acts as a mesenchymal switch to trigger natural anagen entry in postdevelopmental hair follicle cycling. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Valproic acid promotes human hair growth in in vitro culture model.

PubMed

Jo, Seong Jin; Choi, Soon-Jin; Yoon, Sun-Young; Lee, Ji Yeon; Park, Won-Seok; Park, Phil-June; Kim, Kyu Han; Eun, Hee Chul; Kwon, Ohsang

2013-10-01

β-Catenin, the transducer of Wnt signaling, is critical for the development and growth of hair follicles. In the absence of Wnt signals, cytoplasmic β-catenin is phosphorylated by glycogen synthase kinase (GSK)-3 and then degraded. Therefore, inhibition of GSK-3 may enhance hair growth via β-catenin stabilization. Valproic acid is an anticonvulsant and a mood-stabilizing drug that has been used for decades. Recently, valproic acid was reported to inhibit GSK-3β in neuronal cells, but its effect on human hair follicles remains unknown. To determine the effect of VPA on human hair growth. We investigated the effect of VPA on cultured human dermal papilla cells and outer root sheath cells and on an in vitro culture of human hair follicles, which were obtained from scalp skin samples of healthy volunteers. Anagen induction by valproic acid was evaluated using C57BL/6 mice model. Valproic acid not only enhanced the viability of human dermal papilla cells and outer root sheath cells but also promoted elongation of the hair shaft and reduced catagen transition of human hair follicles in organ culture model. Valproic acid treatment of human dermal papilla cells led to increased β-catenin levels and nuclear accumulation and inhibition of GSK-3β by phosphorylation. In addition, valproic acid treatment accelerated the induction of anagen hair in 7-week-old female C57BL/6 mice. Valproic acid enhanced human hair growth by increasing β-catenin and therefore may serve as an alternative therapeutic option for alopecia. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Validation of in vitro assays in three-dimensional human dermal constructs.

PubMed

Idrees, Ayesha; Chiono, Valeria; Ciardelli, Gianluca; Shah, Siegfried; Viebahn, Richard; Zhang, Xiang; Salber, Jochen

2018-05-01

Three-dimensional cell culture systems are urgently needed for cytocompatibility testing of biomaterials. This work aimed at the development of three-dimensional in vitro dermal skin models and their optimization for cytocompatibility evaluation. Initially "murine in vitro dermal construct" based on L929 cells was generated, leading to the development of "human in vitro dermal construct" consisting of normal human dermal fibroblasts in rat tail tendon collagen type I. To assess the viability of the cells, different assays CellTiter-Blue ® , RealTime-Glo ™ MT, and CellTiter-Glo ® (Promega) were evaluated to optimize the best-suited assay to the respective cell type and three-dimensional system. Z-stack imaging (Live/Dead and Phalloidin/DAPI-Promokine) was performed to visualize normal human dermal fibroblasts inside matrix revealing filopodia-like morphology and a uniform distribution of normal human dermal fibroblasts in matrix. CellTiter-Glo was found to be the optimal cell viability assay among those analyzed. CellTiter-Blue reagent affected the cell morphology of normal human dermal fibroblasts (unlike L929), suggesting an interference with cell biological activity, resulting in less reliable viability data. On the other hand, RealTime-Glo provided a linear signal only with a very low cell density, which made this assay unsuitable for this system. CellTiter-Glo adapted to three-dimensional dermal construct by optimizing the "shaking time" to enhance the reagent penetration and maximum adenosine triphosphate release, indicating 2.4 times higher viability value by shaking for 60 min than for 5 min. In addition, viability results showed that cells were viable inside the matrix. This model would be further advanced with more layers of skin to make a full thickness model.

WNT5A inhibits human dental papilla cell proliferation and migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, L.; State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, Sichuan; Ye, L.

WNT proteins are a large family of cysteine-rich secreted molecules that are linked to both canonical and non-canonical signal pathways, and have been implicated in oncogenesis and tissue development. Canonical WNT proteins have been proven to play critical roles in tooth development, while little is known about the role of non-canonical WNT proteins such as WNT5A. In this study, WNT5A was localized to human dental papilla tissue and human dental papilla cells (HDPCs) cultured in vitro, using immunochemistry and RT-PCR. Recombinant adenovirus encoding full-length Wnt5a cDNA was constructed to investigate the biological role of WNT5A on HDPCs. The BrdU incorporationmore » assay, the MTT assay and flow cytometric analysis showed that over-expression of Wnt5a strongly inhibited the proliferation of HDPCs in vitro. Wound healing and transwell migration assays indicated that over-expression of WNT5A reduced migration of HDPCs. In conclusion, our results showed that WNT5A negatively regulates both proliferation and migration of HDPCs, suggesting its important role in odontogenesis via controlling the HDPCs.« less

Hydrocortisone effect on hyaluronate synthesis in a self-assembled human dermal equivalent.

PubMed

Deshpande, Madhura; Papp, Suzanne; Schaffer, Lana; Pouyani, Tara

2016-10-01

Human dermal matrix is a 'self-assembled' dermal equivalent containing large amounts of the glycosaminoglycan hyaluronic acid (hyaluronate, hyaluronan, HA). We sought to investigate the actions of the hormone hydrocortisone on hyaluronate synthesis in the human dermal matrix. To this end, human dermal fibroblasts were cultured under serum-free conditions, and in the absence of a three-dimensional matrix, in the presence of varying amounts of hydrocortisone. The resultant human dermal matrices were characterized. We report that low concentrations of hydrocortisone enhance hyaluronate synthesis in the human dermal equivalent and higher concentrations cause inhibition of hyaluronate synthesis. Other glycosaminoglycan (chondroitin sulphate) synthesis is not affected by changing hydrocortisone concentrations up to 500× (200 µg/ml) of the base value. In order to gain preliminary insight into the molecular mechanism of hyaluronate inhibition, a differential gene array analysis was conducted of human dermal matrix grown in the presence of 200 µg/ml hydrocortisone and in a physiological concentration (0.4 µg/ml, normal conditions). The results of these experiments demonstrate the differential expression of 43 genes in the 500× (200 µg/ml) hydrocortisone construct as compared to the construct grown under normal conditions (0.4 µg/ml hydrocortisone). These preliminary experiments suggest that hydrocortisone at higher concentrations may exert its inhibitory effect on hyaluronate synthesis early in the glycolytic pathway, leading to HA biosynthesis by downregulation of phosphoglucomutase and glucose phosphate isomerase, possibly leading to depletion of the cellular pool of UDP-sugar precursors necessary for HA synthesis. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

Dental Apical Papilla as Therapy for Spinal Cord Injury.

PubMed

De Berdt, P; Vanacker, J; Ucakar, B; Elens, L; Diogenes, A; Leprince, J G; Deumens, R; des Rieux, A

2015-11-01

Stem cells of the apical papilla (SCAP) represent great promise regarding treatment of neural tissue damage, such as spinal cord injury (SCI). They derive from the neural crest, express numerous neurogenic markers, and mediate neurite outgrowth and axonal targeting. The goal of the present work was to investigate for the first time their potential to promote motor recovery after SCI in a rat hemisection model when delivered in their original stem cell niche-that is, by transplantation of the human apical papilla tissue itself into the lesion. Control groups consisted of animals subjected to laminectomy only (shams) and to lesion either untreated or injected with a fibrin hydrogel with or without human SCAP. Basso-Beattie-Bresnahan locomotor scores at 1 and 3 d postsurgery confirmed early functional decline in all SCI groups. This significant impairment was reversed, as seen in CatWalk analyses, after transplantation of apical papilla into the injured spinal cord wound, whereas the other groups demonstrated persistent functional impairment. Moreover, tactile allodynia did not develop as an unwanted side effect in any of the groups, even though the SCAP hydrogel group showed higher expression of the microglial marker Iba-1, which has been frequently associated with allodynia. Notably, the apical papilla transplant group presented with reduced Iba-1 expression level. Masson trichrome and human mitochondria staining showed the preservation of the apical papilla integrity and the presence of numerous human cells, while human cells could no longer be detected in the SCAP hydrogel group at the 6-wk postsurgery time point. Altogether, our data suggest that the transplantation of a human apical papilla at the lesion site improves gait in spinally injured rats and reduces glial reactivity. It also underlines the potential interest for the application of delivering SCAP in their original niche, as compared with use of a fibrin hydrogel. © International & American

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

EPA Science Inventory

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 flowthrough diffusi...

The relationship between dermal papillary structure and skin surface properties, color, and elasticity.

PubMed

Mizukoshi, K; Nakamura, T; Oba, A

2016-08-01

The skin contains an undulating structure called the dermal papillary structure between the border of the epidermis and dermis. The physiological importance of the dermal papillary structures has been discussed, however, the dermal papillary structures have never been evaluated for their contribution to skin appearance. In this study, we investigated the correlation between the dermal papillary structure and skin color and elasticity. In addition, the relationship was validated with skin model experiments. The dermal papillary structures in the skin of the female cheek were quantitatively measured by in vivo confocal laser scanning microscopy images. In addition, the skin color and elasticity were measured at the same site. A skin model with dermal papilla-like structures was created by referring to the optical and shape properties of the skin using agar gel and a scattering sheet. Correlations were found between the dermal papillary structures and skin color irregularity and skin elasticity. These relationships were verified by the experiments employing a skin model. The results of this study indicated that the dermal papillary structure is also an important factor for skin appearance such as color and elasticity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Complex torso reconstruction with human acellular dermal matrix: long-term clinical follow-up.

PubMed

Nemeth, Nicole L; Butler, Charles E

2009-01-01

Although reports have demonstrated good early outcomes with human acellular dermal matrix even when used for complex, contaminated defects, no long-term outcomes have been reported. The authors reviewed the long-term outcomes of 13 patients who had complex torso reconstructions that included human acellular dermal matrix. All patients were at increased risk for mesh-related complications. Eight patients died as a result of progression of their oncologic disease at a mean of 258 days postoperatively. The mean follow-up for the remaining five patients was 43.7 months. Six patients had early complications (none were human acellular dermal matrix-related) and were reported on previously. Two patients had developed complications since the initial report. One patient developed a flap donor-site seroma remote from the reconstruction site, and another developed a recurrent ventral hernia. No patients have required additional surgery for human acellular dermal matrix-related complications. This follow-up report indicates that human acellular dermal matrix repair of large, complex torso defects can result in good long-term outcomes even when patients are at high risk for mesh-related complications.

l-Ascorbic acid 2-phosphate promotes elongation of hair shafts via the secretion of insulin-like growth factor-1 from dermal papilla cells through phosphatidylinositol 3-kinase.

PubMed

Kwack, M H; Shin, S H; Kim, S R; Im, S U; Han, I S; Kim, M K; Kim, J C; Sung, Y K

2009-06-01

l-Ascorbic acid 2-phosphate (Asc 2-P), a derivative of l-ascorbic acid, promotes elongation of hair shafts in cultured human hair follicles and induces hair growth in mice. To investigate whether the promotion of hair growth by Asc 2-P is mediated by insulin-like growth factor-1 (IGF-1) and, if so, to investigate the mechanism of the Asc 2-P-induced IGF-1 expression. Dermal papilla (DP) cells were cultured and IGF-1 level was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay after Asc 2-P treatment in the absence or presence of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Also, hair shaft elongation in cultured human scalp hair follicles and proliferation of cocultured keratinocytes were examined after Asc 2-P treatment in the absence or presence of neutralizing antibody against IGF-1. In addition, keratinocyte proliferation in cultured hair follicles after Asc 2-P treatment in the absence or presence of LY294002 was examined by Ki-67 immunostaining. IGF-1 mRNA in DP cells was upregulated and IGF-1 protein in the conditioned medium of DP cells was significantly increased after treatment with Asc 2-P. Immunohistochemical staining showed that IGF-1 staining is increased in the DP of cultured human hair follicles by Asc 2-P. The neutralizing antibody against IGF-1 significantly suppressed the Asc 2-P-mediated elongation of hair shafts in hair follicle organ culture and significantly attenuated Asc 2-P-induced growth of cocultured keratinocytes. LY294002 significantly attenuated Asc 2-P-inducible IGF-1 expression and proliferation of follicular keratinocytes in cultured hair follicles. These data show that Asc 2-P-inducible IGF-1 from DP cells promotes proliferation of follicular keratinocytes and stimulates hair follicle growth in vitro via PI3K.

Communication network in the follicular papilla and connective tissue sheath through gap junctions in human hair follicles.

PubMed

Iguchi, Makiko; Hara, Masahiro; Manome, Hideaki; Kobayasi, Hiromi; Tagami, Hachiro; Aiba, Setsuya

2003-06-01

Epithelial-mesenchymal interactions play a crucial role in the induction of life-long cyclic transformations of hair follicles. Many studies have already demonstrated several candidates for the soluble factors secreted from the mesenchymal components of the hair follicle, i.e. the follicular papilla (FP) and connective tissue sheath (CTS), which may be responsible for hair cycling. In this paper, we focused on cell-cell contact between FP cells (FPCs), between CTS cells (CTSCs), and between FPCs and CTSCs that may allow these mesenchymal components to function as a syncytium during hair cycling. Electron microscopic examination of the FP and the CTS obtained from human scalp revealed a tri-lamellar structure of the plasma membranes, which is a characteristic of gap junctions at the cell-cell contacting area. The immunohistochemical study with anticonnexin 43 Ab using a confocal laser scanning microscope demonstrated numerous spotted positive signals scattered throughout the FP. In the CTS, spotted positive signals were arranged linearly along the basement membrane of the hair follicle. In particular, these positive spots were aggregated in the transitional region between the FP and the CTS. By Western blot analysis of total protein extracts from the cultured FPCs and neonatal human dermal fibroblasts using anticonnexin 43 antibody, a positive band corresponding to connexin 43 was detected at 43 kDa on both the FPC lane and fibroblast lane. These findings suggest that the FP and the CTS form a communicating network through gap junctions, which may play a role in controlling the dynamic structural changes of hair follicles during hair cycling.

Human acellular dermal wound matrix: evidence and experience.

PubMed

Kirsner, Robert S; Bohn, Greg; Driver, Vickie R; Mills, Joseph L; Nanney, Lillian B; Williams, Marie L; Wu, Stephanie C

2015-12-01

A chronic wound fails to complete an orderly and timely reparative process and places patients at increased risk for wound complications that negatively impact quality of life and require greater health care expenditure. The role of extracellular matrix (ECM) is critical in normal and chronic wound repair. Not only is ECM the largest component of the dermal skin layer, but also ECM proteins provide structure and cell signalling that are necessary for successful tissue repair. Chronic wounds are characterised by their inflammatory and proteolytic environment, which degrades the ECM. Human acellular dermal matrices, which provide an ECM scaffold, therefore, are being used to treat chronic wounds. The ideal human acellular dermal wound matrix (HADWM) would support regenerative healing, providing a structure that could be repopulated by the body's cells. Experienced wound care investigators and clinicians discussed the function of ECM, the evidence related to a specific HADWM (Graftjacket(®) regenerative tissue matrix, Wright Medical Technology, Inc., licensed by KCI USA, Inc., San Antonio, TX), and their clinical experience with this scaffold. This article distills these discussions into an evidence-based and practical overview for treating chronic lower extremity wounds with this HADWM. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

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

PubMed

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.

IN VITRO DERMAL ABSORPTION OF PYRETHROID PESTICIDES IN RAT AND HUMAN SKIN

EPA Science Inventory

Pyrethriods are a class of neurotoxic pesticides and their use may lead to dermal exposure. This study examined the in vitro dermal absorption of pyrethroids in rat and human skin. Dorsal skin removed from adult male LD rats (hair clipped 24 h previously) was dermatomed and mou...

Hydrocortisone and triiodothyronine regulate hyaluronate synthesis in a tissue-engineered human dermal equivalent through independent pathways.

PubMed

Deshpande, Madhura; Papp, Suzanne; Schaffer, Lana; Pouyani, Tara

2015-02-01

Hydrocortisone (HC) and triiodothyronine (T3) have both been shown to be capable of independently inhibiting hyaluronate (HA, hyaluronic acid) synthesis in a self-assembled human dermal equivalent (human dermal matrix). We sought to investigate the action of these two hormones in concert on extracellular matrix formation and HA inhibition in the tissue engineered human dermal matrix. To this end, neonatal human dermal fibroblasts were cultured in defined serum-free medium for 21 days in the presence of each hormone alone, or in combination, in varying concentrations. Through a process of self-assembly, a substantial dermal extracellular matrix formed that was characterized. The results of these studies demonstrate that combinations of the hormones T3 and hydrocortisone showed significantly higher levels of hyaluronate inhibition as compared to each hormone alone in the human dermal matrix. In order to gain preliminary insight into the genes regulating HA synthesis in this system, a differential gene array analysis was conducted in which the construct prepared in the presence of 200 μg/mL HC and 0.2 nM T3 was compared to the normal construct (0.4 μg/mL HC and 20 pM T3). Using a GLYCOv4 gene chip containing approximately 1260 human genes, we observed differential expression of 131 genes. These data suggest that when these two hormones are used in concert a different mechanism of inhibition prevails and a combination of degradation and inhibition of HA synthesis may be responsible for HA regulation in the human dermal matrix. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Dermal Stem Cells Can Differentiate Down an Endothelial Lineage

PubMed Central

Bell, Emma; Richardson, Gavin D.; Jahoda, Colin A.; Gledhill, Karl; Phillips, Helen M.; Henderson, Deborah; Owens, W. Andrew

2012-01-01

In this study, we have demonstrated that cells of neural crest origin located in the dermal papilla (DP) exhibit endothelial marker expression and a functional activity. When grown in endothelial growth media, DP primary cultures upregulate expression of vascular endothelial growth factor receptor 1 (FLT1) mRNA and downregulate expression of the dermal stem cell marker α-smooth muscle actin. DP cells have demonstrated functional characteristics of endothelial cells, including the ability to form capillary-like structures on Matrigel, increase uptake of low-density lipoprotein and upregulate ICAM1 (CD54) in response to tumour necrosis factor alpha (TNF-α) stimulation. We confirmed that these observations were not due to contaminating endothelial cells, by using DP clones. We have also used the WNT1cre/ROSA26R and WNT1cre/YFP lineage-tracing mouse models to identify a population of neural crest-derived cells in DP cultures that express the endothelial marker PECAM (CD31); these cells also form capillary-like structures on Matrigel. Importantly, cells of neural crest origin that express markers of endothelial and mesenchymal lineages exist within the dermal sheath of the vibrissae follicle. PMID:22571645

Mycoplasma detection and elimination are necessary for the application of stem cell from human dental apical papilla to tissue engineering and regenerative medicine.

PubMed

Kim, Byung-Chul; Kim, So Yeon; Kwon, Yong-Dae; Choe, Sung Chul; Han, Dong-Wook; Hwang, Yu-Shik

2015-01-01

Recently, postnatal stem cells from dental papilla with neural crest origin have been considered as one of potent stem cell sources in regenerative medicine regarding their multi-differentiation capacity and relatively easy access. However, almost human oral tissues have been reported to be infected by mycoplasma which gives rise to oral cavity in teeth, and mycoplasma contamination of ex-vivo cultured stem cells from such dental tissues and its effect on stem cell culture has received little attention. In this study, mycoplama contamination was evaluated with stem cells from apical papilla which were isolated from human third molar and premolars from various aged patients undergoing orthodontic therapy. The ex-vivo expanded stem cells from apical papilla were found to express stem cell markers such as Stro-1, CD44, nestin and CD133, but mycoplama contamination was detected in almost all cell cultures of the tested 20 samples, which was confirmed by mycoplasma-specific gene expression and fluorescence staining. Such contaminated mycoplasma could be successfully eliminated using elimination kit, and proliferation test showed decreased proliferation activity in mycoplasma-contaminated cells. After elimination of contaminated mycoplasma, stem cells from apical papilla showed osteogenic and neural lineage differentiation under certain culture conditions. Our study proposes that the evaluation of mycoplasma contamination and elimination process might be required in the use of stem cells from apical papilla for their potent applications to tissue engineering and regenerative medicine.

Recellularizing of human acellular dermal matrices imaged by high-definition optical coherence tomography.

PubMed

Boone, Marc A L M; Draye, Jean Pierre; Verween, Gunther; Aiti, Annalisa; Pirnay, Jean-Paul; Verbeken, Gilbert; De Vos, Daniel; Rose, Thomas; Jennes, Serge; Jemec, Gregor B E; Del Marmol, Veronique

2015-05-01

High-definition optical coherence tomography (HD-OCT) permits real-time 3D imaging of the impact of selected agents on human skin allografts. The real-time 3D HD-OCT assessment of (i) the impact on morphological and cellular characteristics of the processing of human acellular dermal matrices (HADMs) and (ii) repopulation of HADMs in vitro by human fibroblasts and remodelling of the extracellular matrix by these cells. Four different skin decellularization methods, Dispase II/Triton X-100, Dispase II/SDS (sodium dodecyl sulphate), NaCl/Triton X-100 and NaCl/SDS, were analysed by HD-OCT. HD-OCT features of epidermal removal, dermo-epidermal junction (DEJ) integrity, cellularity and dermal architecture were correlated with reflectance confocal microscopy (RCM), histopathology and immunohistochemistry. Human adult dermal fibroblasts were in vitro seeded on the NaCl/Triton X-100 processed HADMs, cultured up to 19 days and evaluated by HD-OCT in comparison with MTT proliferation test and histology. Epidermis was effectively removed by all treatments. DEJ was best preserved after NaCl/Triton X-100 treatment. Dispase II/SDS treatment seemed to remove all cellular debris in comparison with NaCl/Triton X-100 but disturbed the DEJ severely. The dermal micro-architectural structure and vascular spaces of (sub)papillary dermis were best preserved with the NaCl/Triton X-100. The impact on the 3D structure and vascular holes was detrimental with Dispase II/SDS. Elastic fibre fragmentation was only observed after Dispase II incubation. HD-OCT showed that NaCl/Triton X-100 processed matrices permitted in vitro repopulation by human dermal fibroblasts (confirmed by MTT test and histology) and underwent remodelling upon increasing incubation time. Care must be taken in choosing the appropriate processing steps to maintain selected properties of the extracellular matrix in HADMs. Processing HADMs with NaCl/Triton X-100 permits in vitro the proliferation and remodelling activity of

Tricho-odonto-onycho-dermal dysplasia and WNT10A mutations.

PubMed

Kantaputra, P; Kaewgahya, M; Jotikasthira, D; Kantaputra, W

2014-04-01

We report on three novel (IVS2+1G>A splice site, c.1066G>T, and c.1039G>T, and one previously reported (c.637G>A) WNT10A mutations in three patients affected with odonto-onycho-dermal dysplasia (OODD; OMIM 275980). OODD is a rare form of autosomal recessive ectodermal dysplasia involving hair, teeth, nails, and skin, characterized by hypodontia (tooth agenesis), smooth tongue with marked reduction of filiform and fungiform papillae, nail dysplasia, dry skin, palmoplantar keratoderma, and hyperhidrosis of palms and soles. The novel IVS+1G>A splice site mutation is predicted to cause significant protein alteration. The other novel mutations we found including c.1066G>T and c.1039G>T are predicted to cause p.Gly356Cys and p.Glu347X, respectively. Barrel-shaped mandibular incisors and severe hypodontia appear to be associated with homozygous or compound heterozygous mutations of WNT10A. The name "tricho-odonto-onycho-dermal dysplasia" is suggested to replace "odonto-onycho-dermal dysplasia" because hair anomalies including hypotrichosis and slow-growing hair have been reported in numerous reported patients with this syndrome. © 2014 Wiley Periodicals, Inc.

Quantitative study of taste buds in fungiform and circumvallate papillae of young and aged rats.

PubMed

Mistretta, C M; Baum, B J

1984-03-01

To ascertain whether an age-related decrease in number of taste buds occurs in the tongue of aged rats, taste buds were counted in fungiform and circumvallate papillae of Wistar-derived rats aged 5-7 months and 23-24 months. There was no difference in number or size of taste buds in papillae in anterior and posterior areas of the tongue from the two age groups. However, both fungiform and circumvallate papillae were larger in old rats. These results complement a recent study demonstrating no difference in numbers of taste buds in human fungiform papillae from birth to old age (Arvidson, 1979). Both anatomical investigations and human taste threshold studies indicate that age-related differences in the gustatory system are not as substantial as investigators have suggested in the past.

Morphology of Floral Papillae in Maxillaria Ruiz & Pav. (Orchidaceae)

PubMed Central

DAVIES, K. L.; TURNER, M. P.

2004-01-01

• Background and Aims The labellar papillae and trichomes of Maxillaria Ruiz & Pav. show great diversity. Although papillae also occur upon other parts of the flower (e.g. column and anther cap), these have not yet been studied. Labellar trichomes of Maxillaria are useful in taxonomy, but hitherto the taxonomic value of floral papillae has not been assessed. The aim of this paper is to describe the range of floral papillae found in Maxillaria and to determine whether papillae are useful as taxonomic characters. • Methods Light microscopy, histochemistry, low‐vacuum scanning and transmission electron microscopy. • Key Results A total of 75 taxa were studied. Conical papillae with rounded or pointed tips were the most common. The column and anther cap usually bear conical, obpyriform or villiform papillae, whereas those around the stigmatic surface and at the base of the anther are often larger and swollen. Labellar papillae show greater diversity, and may be conical, obpyriform, villiform, fusiform or clavate. Papillae may also occur on multiseriate trichomes that perhaps function as pseudostamens. Labellar papillae contain protein but most lack lipid. The occurrence of starch, however, is more variable. Many papillae contain pigment or act as osmophores, thereby attracting insects. Rewards such as nectar or a protein‐rich, wax‐like, lipoidal substance may be secreted by papillae onto the labellar surface. Some papillae may have a protective role in preventing desiccation. Species of diverse vegetative morphology may have identical floral papillae, whereas others of similar vegetative morphology may not. • Conclusions Generally, floral papillae in Maxillaria have little taxonomic value. Nevertheless, the absence of papillae from members of the M. cucullata alliance, the occurrence of clavate papillae with distended apices in the M. rufescens alliance and the presence of papillose trichomes in some species may yet prove to be useful. PMID:14630691

Morphology of floral papillae in Maxillaria Ruiz & Pav. (Orchidaceae).

PubMed

Davies, K L; Turner, M P

2004-01-01

The labellar papillae and trichomes of Maxillaria Ruiz & Pav. show great diversity. Although papillae also occur upon other parts of the flower (e.g. column and anther cap), these have not yet been studied. Labellar trichomes of Maxillaria are useful in taxonomy, but hitherto the taxonomic value of floral papillae has not been assessed. The aim of this paper is to describe the range of floral papillae found in Maxillaria and to determine whether papillae are useful as taxonomic characters. Light microscopy, histochemistry, low-vacuum scanning and transmission electron microscopy. A total of 75 taxa were studied. Conical papillae with rounded or pointed tips were the most common. The column and anther cap usually bear conical, obpyriform or villiform papillae, whereas those around the stigmatic surface and at the base of the anther are often larger and swollen. Labellar papillae show greater diversity, and may be conical, obpyriform, villiform, fusiform or clavate. Papillae may also occur on multiseriate trichomes that perhaps function as pseudostamens. Labellar papillae contain protein but most lack lipid. The occurrence of starch, however, is more variable. Many papillae contain pigment or act as osmophores, thereby attracting insects. Rewards such as nectar or a protein-rich, wax-like, lipoidal substance may be secreted by papillae onto the labellar surface. Some papillae may have a protective role in preventing desiccation. Species of diverse vegetative morphology may have identical floral papillae, whereas others of similar vegetative morphology may not. Generally, floral papillae in Maxillaria have little taxonomic value. Nevertheless, the absence of papillae from members of the M. cucullata alliance, the occurrence of clavate papillae with distended apices in the M. rufescens alliance and the presence of papillose trichomes in some species may yet prove to be useful.

Morphology of the lingual papillae in the fishing cat.

PubMed

Emura, Shoichi; Okumura, Toshihiko; Chen, Huayue

2014-01-01

We examined the dorsal lingual surface of an adult fishing cat (Prionailurus viverrinus) by scanning electron microscopy. The filiform papillae on the lingual apex had several pointed processes. The connective tissue core of the filiform papillae resembleda a well in shape. The filiform papillae on the anterior part of the lingual body were large and cylindrical in shape. The connective tissue core of the filiform papillae consisted of a large conical papilla. The filiform papillae on the central part of the lingual body were large and conical. The connective tissue core of the filiform papillae consisted of a large main process and some secondary processes. The connective tissue core of the fungiform papillae did not have processes. The vallate papillae were surrounded by a groove and a pad. The top of the connective tissue core of the vallate papillae had a rough surface with no spines.

Red light accelerates the formation of a human dermal equivalent.

PubMed

Oliveira, Anna Cb; Morais, Thayz Fl; Bernal, Claudia; Martins, Virginia Ca; Plepis, Ana Mg; Menezes, Priscila Fc; Perussi, Janice R

2018-04-01

Development of biomaterials' substitutes and/or equivalents to mimic normal tissue is a current challenge in tissue engineering. Thus, three-dimensional cell culture using type I collagen as a polymeric matrix cell support designed to promote cell proliferation and differentiation was employed to create a dermal equivalent in vitro, as well to evaluate the photobiomodulation using red light. Polymeric matrix cell support was prepared from porcine serous collagen (1.1%) hydrolyzed for 96 h. The biomaterial exhibited porosity of 95%, a median pore of 44 µm and channels with an average distance between the walls of 78 ± 14 µm. The absorption of culture medium was 95%, and the sponge showed no cytotoxicity to Vero cells, a non-tumor cell line. Additionally, it was observed that irradiation with light at 630 nm (fluency 30 J cm -2 ) leads to the cellular photobiomodulation in both monolayer and human dermal equivalent (three-dimensional cell culture system). It was also verified that the cells cultured in the presence of the polymeric matrix cell support, allows differentiation and extracellular matrix secretion. Therefore, the results showed that the collagen sponge used as polymeric matrix cell support and the photobiomodulation at 630 nm are efficient for the production of a reconstructed human dermal equivalent in vitro.

Wnt/β-catenin signaling in dermal condensates is required for hair follicle formation

PubMed Central

Tsai, Su-Yi; Sennett, Rachel; Rezza, Amélie; Clavel, Carlos; Grisanti, Laura; Zemla, Roland; Najam, Sara; Rendl, Michael

2014-01-01

Broad dermal Wnt signaling is required for patterned induction of hair follicle placodes and subsequent Wnt signaling in placode stem cells is essential for induction of dermal condensates, cell clusters of precursors for the hair follicle dermal papilla (DP). Progression of hair follicle formation then requires coordinated signal exchange between dermal condensates and placode stem cells. However, it remains unknown whether continued Wnt signaling in DP precursor cells plays a role in this process, largely due to the long-standing inability to specifically target dermal condensates for gene ablation. Here we use the Tbx18Cre knockin mouse line to ablate the Wnt-responsive transcription factor β-catenin specifically in these cells at E14.5 during the first wave of guard hair follicle formation. In the absence of β-catenin, canonical Wnt signaling is effectively abolished in these cells. Sox2+ dermal condensates initiate normally, however by E16.5 guard hair follicle numbers are strongly reduced and by E18.5 most whiskers and guard hair follicles are absent, suggesting that active Wnt signaling in dermal condensates is important for hair follicle formation to proceed after induction. To explore the molecular mechanisms by which Wnt signaling in dermal condensates regulates hair follicle formation, we analyze genome-wide the gene expression changes in embryonic β-catenin null DP precursor cells. We find altered expression of several signaling pathway genes, including Fgfs and Activin, both previously implicated in hair follicle formation. In summary, these data reveal a functional role of Wnt signaling in DP precursors for embryonic hair follicle formation and identify Fgf and Activin signaling as potential effectors of Wnt signaling-regulated events. PMID:24309208

Radiation-induced changes in mouse duodenal papilla.

PubMed

Indran, M; Carr, K E; Boyle, F C

1988-11-01

Radiation-induced changes in duodenal mucosal morphology as seen by scanning electron microscopy have been widely reported in the literature. However, no comment has previously been made on any post-irradiation alteration in the duodenal papilla. This paper describes the preliminary results of an investigation into the effects of X rays on the papilla. The duodenal papilla was difficult to find in untreated and sham irradiated mice. It was identified in only two of six mice examined and was located 5.37 and 4.43 mm from the gastroduodenal junction. Eighteen hours after irradiation with 15 Gy X rays, there was little change in position or prominence of the papilla. However, 3 days after treatment, the papilla was only 2.19-3.83 mm from the pylorus. It was also more prominent, being found in all three animals studied and having a widely dilated orifice in contrast to the closed structure seen in the unirradiated specimens. It is concluded that treatment with X rays alters the structure of the duodenal papilla. There may be implications for duodenal function in this marked change in the papilla, which controls the flow of pancreatic and biliary secretions.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hughes, Michael F., E-mail: hughes.michaelf@epa.go; Edwards, Brenda C.

2010-07-15

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 skinmore » 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

Metrics of cellular and vascular infiltration of human acellular dermal matrix in ventral hernia repairs.

PubMed

Campbell, Kristin Turza; Burns, Nadja K; Ensor, Joe; Butler, Charles E

2012-04-01

Human acellular dermal matrix is used for ventral hernia repair, as it resists infection and remodels by means of surrounding tissue. However, the tissue source and impact of basement membrane on cell and vessel infiltration have not been determined. The authors hypothesized that musculofascia would be the primary tissue source of cells and vessels infiltrating into human acellular dermal matrix and that the basement membrane would inhibit infiltration. Fifty-six guinea pigs underwent inlay human acellular dermal matrix ventral hernia repair with the basement membrane oriented toward or away from the peritoneum. At postoperative weeks 1, 2, or 4, repair sites were completely excised. Histologic and immunohistochemical analyses were performed to quantify cell and vessel density within repair-site zones, including interface (lateral, beneath musculofascia) and center (beneath subcutaneous fat) zones. Cell and vessel quantities were compared as functions of zone, basement membrane orientation, and time. Cellular and vascular infiltration increased over time universally. The interface demonstrated greater mean cell density than the center (weeks 1 and 2, p = 0.01 and p < 0.0001, respectively). Cell density was greater with the basement membrane oriented toward the peritoneum at week 4 (p = 0.02). The interface zone had greater mean vessel density than the center zone at week 4 (p < 0.0001). Orienting the basement membrane toward the peritoneum increased vessel density at week 4 (p = 0.0004). Cellular and vascular infiltration into human acellular dermal matrix for ventral hernia repairs was greater from musculofascia than from subcutaneous fat, and the basement membrane inhibited cellular and vascular infiltration. Human acellular dermal matrix should be placed adjacent to the best vascularizing tissue to improve fibrovascular incorporation.

Method for Dissecting the Auditory Epithelium (Basilar Papilla) in Developing Chick Embryos.

PubMed

Levic, Snezana; Yamoah, Ebenezer N

2016-01-01

Chickens are an invaluable model for exploring auditory physiology. Similar to humans, the chicken inner ear is morphologically and functionally close to maturity at the time of hatching. In contrast, chicks can regenerate hearing, an ability lost in all mammals, including humans. The extensive morphological, physiological, behavioral, and pharmacological data available, regarding normal development in the chicken auditory system, has driven the progress of the field. The basilar papilla is an attractive model system to study the developmental mechanisms of hearing. Here, we describe the dissection technique for isolating the basilar papilla in developing chick inner ear. We also provide detailed examples of physiological (patch clamping) experiments using this preparation.

Endothelial network formed with human dermal microvascular endothelial cells in autologous multicellular skin substitutes.

PubMed

Ponec, Maria; El Ghalbzouri, Abdoelwaheb; Dijkman, Remco; Kempenaar, Johanna; van der Pluijm, Gabri; Koolwijk, Pieter

2004-01-01

A human skin equivalent from a single skin biopsy harboring keratinocytes and melanocytes in the epidermal compartment, and fibroblasts and microvascular dermal endothelial cells in the dermal compartment was developed. The results of the study revealed that the nature of the extracellular matrix of the dermal compartments plays an important role in establishment of endothelial network in vitro. With rat-tail type I collagen matrices only lateral but not vertical expansion of endothelial networks was observed. In contrast, the presence of extracellular matrix of entirely human origin facilitated proper spatial organization of the endothelial network. Namely, when human dermal fibroblasts and microvascular endothelial cells were seeded on the bottom of an inert filter and subsequently epidermal cells were seeded on top of it, fibroblasts produced extracellular matrix throughout which numerous branched tubes were spreading three-dimensionally. Fibroblasts also facilitated the formation of basement membrane at the epidermal/matrix interface. Under all culture conditions, fully differentiated epidermis was formed with numerous melanocytes present in the basal epidermal cell layer. The results of the competitive RT-PCR revealed that both keratinocytes and fibroblasts expressed VEGF-A, -B, -C, aFGF and bFGF mRNA, whereas fibroblasts also expressed VEGF-D mRNA. At protein level, keratinocytes produced 10 times higher amounts of VEGF-A than fibroblasts did. The generation of multicellular skin equivalent from a single human skin biopsy will stimulate further developments for its application in the treatment of full-thickness skin defects. The potential development of biodegradable, biocompatible material suitable for these purposes is a great challenge for future research.

DISPOSITION OF BROMODICHLOROMETHANE IN HUMANS FOLLOWING ORAL AND DERMAL EXPOSURE

EPA Science Inventory

DISPOSITION OF BROMODICHLOROMETHANE IN HUMANS FOLLOWING ORAL AND DERMAL EXPOSURE. TL Leavens1, MW Case1, RA Pegram1, BC Blount2, DM DeMarini1, MC Madden1, and JL Valentine3. 1NHEERL, USEPA, RTP, NC, USA; 2CDC, Atlanta, GA, USA; 3RTI, RTP, NC, USA.
The disinfection byproduct ...

IFN-Dependent and -Independent Reduction in West Nile Virus Infectivity in Human Dermal Fibroblasts

PubMed Central

Hoover, Lisa I.; Fredericksen, Brenda L.

2014-01-01

Although dermal fibroblasts are one of the first cell types exposed to West Nile virus (WNV) during a blood meal by an infected mosquito, little is known about WNV replication within this cell type. Here, we demonstrate that neuroinvasive, WNV-New York (WNV-NY), and nonneuroinvasive, WNV-Australia (WNV-AUS60) strains are able to infect and replicate in primary human dermal fibroblasts (HDFs). However, WNV-AUS60 replication and spread within HDFs was reduced compared to that of WNV-NY due to an interferon (IFN)-independent reduction in viral infectivity early in infection. Additionally, replication of both strains was constrained late in infection by an IFN-β-dependent reduction in particle infectivity. Overall, our data indicates that human dermal fibroblasts are capable of supporting WNV replication; however, the low infectivity of particles produced from HDFs late in infection suggests that this cell type likely plays a limited role as a viral reservoir in vivo. PMID:24662674

Dermal morphological changes following salicylic acid peeling and microdermabrasion.

PubMed

Abdel-Motaleb, Amira A; Abu-Dief, Eman E; Hussein, Mahmoud Ra

2017-12-01

Microdermabrasion and chemical peeling are popular, inexpensive, and safe methods for treatment of some skin disorders and to rejuvenate skin. To study the alterations of the dermal connective tissue following salicylic acid peeling and microdermabrasion. Twenty patients were participated in our study. All participants underwent facial salicylic acid 30% peel or microdermabrasion (10 cases in each group) weekly for 6 weeks. Punch biopsies were obtained from the clinically normal skin of the right postauricular region 1 week before treatment (control group). Other punch skin biopsies were obtained 1 week after the end of the treatments from the left postauricular area. This region was treated in a similar way to the adjacent lesional skin (treated group). We used routine histological techniques (H&E stain), special stains (Masson trichrome and orcein stains), and image analyzer to study the alterations of the dermal connective tissues. Our study demonstrates variations in the morphological changes between the control and the treated groups, and between chemical peels and microdermabrasion. Both salicylic acid 30% and microdermabrasion were associated with thickened epidermal layer, shallow dermal papillae, dense collagen, and elastic fibers. There was a significant increase among those treated sites vs control regarding epidermal thickness and collagen thickness. Also, there was a highly statistically significant increase among those treated with salicylic acid vs microdermabrasion regarding the epidermal, collagen, and elastin thickness. Both methods stimulate the repair process. The mechanisms underlying these variations are open for further investigations. © 2017 Wiley Periodicals, Inc.

Identification of the duodenal papilla by colon capsule endoscope.

PubMed

Karagiannis, S; Dücker, C; Dautel, P; Strubenhoff, J; Faiss, S

2010-07-01

The sensitivity of small-bowel capsule endoscopy in visualizing a single finding present in everyone, the duodenal papilla, is limited. In this retrospective case series study we evaluated whether the duodenal papilla can be better visualized by a capsule endoscope equipped with cameras on both ends. The recordings of 45 colonic capsule endoscopies (PillCam Colon) performed in a single tertiary center were re-evaluated seeking for the duodenal papilla. The two-hour sleeping period of the colon capsule endoscopy system led to the imaging of duodenum in 10 / 45 patients. The duodenal papilla was identified in 6 / 10 (60 %) patients while the number of frames where the papilla was clearly visualized ranged from 2 - 9. Consequently, a small-bowel capsule endoscope containing two cameras could better identify the duodenal papilla and theoretically other obscure areas of the small bowel, expanding its diagnostic accuracy.

Human Dermal Mast Cells Contain and Release Tumor Necrosis Factor α, which Induces Endothelial Leukocyte Adhesion Molecule 1

NASA Astrophysics Data System (ADS)

Walsh, Laurence J.; Trinchieri, Giorgio; Waldorf, Heidi A.; Whitaker, Diana; Murphy, George F.

1991-05-01

Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine that mediates endothelial leukocyte interactions by inducing expression of adhesion molecules. In this report, we demonstrate that human dermal mast cells contain sizeable stores of immunoreactive and biologically active TNF-α within granules, which can be released rapidly into the extracellular space upon degranulation. Among normal human dermal cells, mast cells are the predominant cell type that expresses both TNF-α protein and TNF-α mRNA. Moreover, induction of endothelial leukocyte adhesion molecule 1 expression is a direct consequence of release of mast cell-derived TNF-α. These findings establish a role for human mast cells as "gatekeepers" of the dermal microvasculature and indicate that mast cell products other than vasoactive amines influence endothelium in a proinflammatory fashion.

Mutation in WNT10A Is Associated with an Autosomal Recessive Ectodermal Dysplasia: The Odonto-onycho-dermal Dysplasia

PubMed Central

Adaimy, Lynn ; Chouery, Eliane ; Mégarbané, Hala ; Mroueh, Salman ; Delague, Valérie ; Nicolas, Elsa ; Belguith, Hanen ; de Mazancourt, Philippe ; Mégarbané, André 

2007-01-01

Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. We studied three consanguineous Lebanese Muslim Shiite families that included six individuals affected with odonto-onycho-dermal dysplasia. Using a homozygosity-mapping strategy, we assigned the disease locus to an ∼9-cM region at chromosome 2q35-q36.2, located between markers rs16853834 and D2S353, with a maximum multipoint LOD score of 5.7. Screening of candidate genes in this region led us to identify the same c.697G→T (p.Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in all patients. At the protein level, the mutation is predicted to result in a premature truncated protein of 232 aa instead of 417 aa. This is the first report to our knowledge of a human phenotype resulting from a mutation in WNT10A, and it is the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, expanding the list of WNT-related diseases. PMID:17847007

Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia.

PubMed

Adaimy, Lynn; Chouery, Eliane; Megarbane, Hala; Mroueh, Salman; Delague, Valerie; Nicolas, Elsa; Belguith, Hanen; de Mazancourt, Philippe; Megarbane, Andre

2007-10-01

Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. We studied three consanguineous Lebanese Muslim Shiite families that included six individuals affected with odonto-onycho-dermal dysplasia. Using a homozygosity-mapping strategy, we assigned the disease locus to an ~9-cM region at chromosome 2q35-q36.2, located between markers rs16853834 and D2S353, with a maximum multipoint LOD score of 5.7. Screening of candidate genes in this region led us to identify the same c.697G-->T (p.Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in all patients. At the protein level, the mutation is predicted to result in a premature truncated protein of 232 aa instead of 417 aa. This is the first report to our knowledge of a human phenotype resulting from a mutation in WNT10A, and it is the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, expanding the list of WNT-related diseases.

Morphological study of the lingual papillae in the ferret (Mustela putorius furo).

PubMed

Takemura, Akimichi; Uemura, Mamoru; Toda, Isumi; Fang, Gang; Hikida, Masaya; Suwa, Fumihiko

2009-05-01

We used four ferrets (Mustela putorius furo) and observed these animals dorsal tongue surface morphology via scanning electron microscope and light microscope. In this investigation, we focused on the food habits and discussed the morphology of the lingual papillae from the viewpoint of comparative anatomy. The ferret has conically-shaped filiform papillae in the posterior, middle and anterior region of the tongue body, and circular-distributed filiform papillae in the lingual apex region. The ferret has fungiform papillae with hemispheric shaped summits in the posterior and middle region with square-shaped summits in the anterior and the lingual apex region. The ferret has V-shaped vallate papillae with eight papillae in two lines or 12 papillae in three lines on the tongue root. No foliate papillae were observed on the dorsal tongue surface of the ferret. The ferret belongs to the carnivore family but has a highly developed vallate papillae which are taste bud papillae and many taste glands. Thus we conclude that the ferrets need a large amount of saliva to swallow food because it demonstrates a large number of taste glands.

[Human stem cells from apical papilla can regenerate dentin-pulp complex].

PubMed

Xiong, Huacui; Chen, Ke; Huang, Yibin; Liu, Caiqi

2013-10-01

To regenerate dentin-pulp complex by tissue engineering with human stem cells from apical papilla cells (SCAP) as the seed cells. SCAP was separated from from normal human impacted third molars with immature roots by outgrowth culture. The cells were then cultured in the differentiation medium for 3 weeks or in normal medium for 60 days, and analyzed for mineralization potential by Alizarin red staining. The osteo/odontogenic markers including alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OC) and dentin sialoprotein (DSP) were investigated by immunofluorescence staining and reverse transcription-polymerase chain reaction. The co-cultured mixture of SCAP and HA/TCP, or HA/TCP alone was implanted subcutaneously on the back of nude mice for 8 weeks, and the implants were collected and examined by HE and immunohistochemical staining. Round alizarin red-positive nodules formed in the isolated cells after cell culture in the differentiation medium for 3 weeks or in normal medium for 60 days with positive staining for osteo/odontogenic markers. SCAP with HA/TCP could regenerate pulp-dentin complex-like tissue in nude mice. The cells near the dentin-like tissue were positive for DSP. No mineral tissue was found in mice receiving HA/TCP implantation. SCAP may serve as a promising seed cell for dentin-pulp complex tissue engineering.

Anti-inflammatory activity of clove (Eugenia caryophyllata) essential oil in human dermal fibroblasts.

PubMed

Han, Xuesheng; Parker, Tory L

2017-12-01

Clove (Eugenia caryophyllata Thunb. [Myrtaceae]) essential oil (CEO) has been shown to possess antimicrobial, antifungal, antiviral, antioxidant, anti-inflammatory and anticancer properties. However, few studies have focused on its topical use. We investigated the biological activity of a commercially available CEO in a human skin disease model. We evaluated the effect of CEO on 17 protein biomarkers that play critical roles in inflammation and tissue remodelling in a validated human dermal fibroblast system, which was designed to model chronic inflammation and fibrosis. Four concentrations of CEO (0.011, 0.0037, 0.0012, and 0.00041%, v/v) were studied. The effect of 0.011% CEO on genome-wide gene expression was also evaluated. CEO at a concentration of 0.011% showed robust antiproliferative effects on human dermal fibroblasts. It significantly inhibited the increased production of several proinflammatory biomarkers such as vascular cell adhesion molecule-1 (VCAM-1), interferon γ-induced protein 10 (IP-10), interferon-inducible T-cell α chemoattractant (I-TAC), and monokine induced by γ interferon (MIG). CEO also significantly inhibited tissue remodelling protein molecules, namely, collagen-I, collagen-III, macrophage colony-stimulating factor (M-CSF), and tissue inhibitor of metalloproteinase 2 (TIMP-2). Furthermore, it significantly modulated global gene expression and altered signalling pathways critical for inflammation, tissue remodelling, and cancer signalling processes. CEO significantly inhibited VCAM-1 and collagen III at both protein and gene expression levels. This study provides important evidence of CEO-induced anti-inflammatory and tissue remodelling activity in human dermal fibroblasts. This study also supports the anticancer properties of CEO and its major active component eugenol.

Reconstruction of the pelvic floor with human acellular dermal matrix and omental flap following anterior pelvic exenteration.

PubMed

Momoh, Adeyiza O; Kamat, Ashish M; Butler, Charles E

2010-12-01

Pelvic floor reconstruction after pelvic exenteration is challenging, particularly with bacterial contamination and/or pelvic irradiation. Traditional regional myocutaneous flap options are not always avaliable, especially in the multiply operated patient. Human acellular dermal matrix (HADM) confers several advantages and is associated with less morbidity when compared to synthetic mesh used in these compromised wound beds. We report a clinical case of an elderly patient with an anterior pelvic floor defect, who underwent successful reconstruction with a combination of human acellular dermal matrix and an omental flap. Copyright © 2010. Published by Elsevier Ltd.

Novel aspects of intrinsic and extrinsic aging of human skin: beneficial effects of soy extract.

PubMed

Südel, Kirstin M; Venzke, Kirsten; Mielke, Heiko; Breitenbach, Ute; Mundt, Claudia; Jaspers, Sören; Koop, Urte; Sauermann, Kirsten; Knussman-Hartig, Elke; Moll, Ingrid; Gercken, Günther; Young, Anthony R; Stäb, Franz; Wenck, Horst; Gallinat, Stefan

2005-01-01

Biochemical and structural changes of the dermal connective tissue substantially contribute to the phenotype of aging skin. To study connective tissue metabolism with respect to ultraviolet (UV) exposure, we performed an in vitro (human dermal fibroblasts) and an in vivo complementary DNA array study in combination with protein analysis in young and old volunteers. Several genes of the collagen metabolism such as Collagen I, III and VI as well as heat shock protein 47 and matrix metalloproteinase-1 are expressed differentially, indicating UV-mediated effects on collagen expression, processing and degradation. In particular, Collagen I is time and age dependently reduced after a single UV exposure in human skin in vivo. Moreover, older subjects display a lower baseline level and a shorter UV-mediated increase in hyaluronan (HA) levels. To counteract these age-dependent changes, cultured fibroblasts were treated with a specific soy extract. This treatment resulted in increased collagen and HA synthesis. In a placebo-controlled in vivo study, topical application of an isoflavone-containing emulsion significantly enhanced the number of dermal papillae per area after 2 weeks. Because the flattening of the dermal-epidermal junction is the most reproducible structural change in aged skin, this soy extract appears to rejuvenate the structure of mature skin.

Human hair follicles contain two forms of ATP-sensitive potassium channels, only one of which is sensitive to minoxidil.

PubMed

Shorter, Katie; Farjo, Nilofer P; Picksley, Steven M; Randall, Valerie A

2008-06-01

Hair disorders cause psychological distress but are generally poorly controlled; more effective treatments are required. Despite the long-standing use of minoxidil for balding, its mechanism is unclear; suggestions include action on vasculature or follicle cells. Similar drugs also stimulate hair, implicating ATP-sensitive potassium (K(ATP)) channels. To investigate whether K(ATP) channels are present in human follicles, we used organ culture, molecular biological, and immunohistological approaches. Minoxidil and tolbutamide, a K(ATP) channel blocker, opposed each other's effects on the growing phase (anagen) of scalp follicles cultured in media with and without insulin. Reverse transcriptase-polymerase chain reaction identified K(ATP) channel component gene expression including regulatory sulfonylurea receptors (SUR) SUR1 and SUR2B but not SUR2A and pore-forming subunits (Kir) Kir6.1 and Kir6.2. When hair bulb tissues were examined separately, epithelial matrix expressed SUR1 and Kir6.2, whereas both dermal papilla and sheath exhibited SUR2B and Kir6.1. Immunohistochemistry demonstrated similar protein distributions. Thus, human follicles respond biologically to K(ATP) channel regulators in culture and express genes and proteins for two K(ATP) channels, Kir6.2/SUR1 and Kir6.1/SUR2B; minoxidil only stimulates SUR2 channels. These findings indicate that human follicular dermal papillae contain K(ATP) channels that can respond to minoxidil and that tolbutamide may suppress hair growth clinically; novel drugs designed specifically for these channels could treat hair disorders.

Survival of the Apical Papilla and Its Resident Stem Cells in a Case of Advanced Pulpal Necrosis and Apical Periodontitis.

PubMed

Chrepa, Vanessa; Pitcher, Brandon; Henry, Michael A; Diogenes, Anibal

2017-04-01

Apical papilla represents a source of an enriched mesenchymal stem cell (MSC) population (stem cells of the apical papilla [SCAPs]) that modulates root development and may participate in regenerative endodontic procedures in immature teeth with pulp necrosis. The characteristics and phenotype of this tissue in the presence of inflammation are largely unknown. The purpose of this study was to characterize a human apical papilla sample that was isolated from an immature tooth with pulp necrosis and apical periodontitis. Inflamed periapical tissue that included part of the apical papilla (apical papilla clinical sample [CS]) was collected from an immature mandibular premolar previously diagnosed with pulp necrosis and apical periodontitis during an apexification procedure. Harvested cells from this tissue (SCAP CS) were compared with inflamed periapical progenitor cells (IPAPCs) and normal SCAP (SCAP-RP89) in flow cytometry and quantitative osteogenesis experiments. Part of the issue was further processed for immunohistochemistry and compared with apical papilla and coronal pulp sections from normal immature teeth as well as inflamed periapical tissues from mature teeth. Similar to SCAP-RP89, 96.6% of the SCAP CS coexpressed the MSC markers CD73, CD90, and CD105, whereas only 66.3% of IPAPCs coexpressed all markers. The SCAP CS showed a significantly greater mineralization potential than both SCAP-RP89 and IPAPCs. Finally, immunohistochemical analysis revealed moderate infiltration of cells expressing the inflammatory markers CD45/68 in the apical papilla CS and prominent CD24, CD105, and von Willebrand factor expression. Under inflammatory conditions, human apical papilla was found moderately inflamed with retained SCAP vitality and stemness and increased osteogenic and angiogenesis potential. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Laminin peptide YIGSR induces collagen synthesis in Hs27 human dermal fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Jong Hyuk; Kim, Jaeyoon; Lee, Hyeongjoo

Highlights: Black-Right-Pointing-Pointer We identify a function of the YIGSR peptide to enhance collagen synthesis in Hs27. Black-Right-Pointing-Pointer YIGSR peptide enhanced collagen type 1 synthesis both of gene and protein levels. Black-Right-Pointing-Pointer There were no changes in cell proliferation and MMP-1 level in YIGSR treatment. Black-Right-Pointing-Pointer The YIGSR effect on collagen synthesis mediated activation of FAK, pyk2 and ERK. Black-Right-Pointing-Pointer The YIGSR-induced FAK and ERK activation was modulated by FAK and MEK inhibitors. -- Abstract: The dermal ECM is synthesized from fibroblasts and is primarily compromised of fibrillar collagen and elastic fibers, which support the mechanical strength and resiliency of skin,more » respectively. Laminin, a major glycoprotein located in the basement membrane, promotes cell adhesion, cell growth, differentiation, and migration. The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide, corresponding to the 929-933 sequence of the {beta}1 chain, is known to be a functional motif with effects on the inhibition of tumor metastasis, the regulation of sensory axonal response and the inhibition of angiogenesis through high affinity to the 67 kDa laminin receptor. In this study, we identified a novel function of the YIGSR peptide to enhance collagen synthesis in human dermal fibroblasts. To elucidate this novel function regarding collagen synthesis, we treated human dermal fibroblasts with YIGSR peptide in both a time- and dose-dependent manner. According to subsequent experiments, we found that the YIGSR peptide strongly enhanced collagen type 1 synthesis without changing cell proliferation or cellular MMP-1 level. This YIGSR peptide-mediated collagen type 1 synthesis was modulated by FAK inhibitor and MEK inhibitor. This study clearly reveals that YIGSR peptide plays a novel function on the collagen type 1 synthesis of dermal fibroblasts and also suggests that YIGSR is a strong

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

NASA Astrophysics Data System (ADS)

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.

Dermal application of nitric oxide releasing acidified nitrite-containing liniments significantly reduces blood pressure in humans.

PubMed

Opländer, Christian; Volkmar, Christine M; Paunel-Görgülü, Adnana; Fritsch, Thomas; van Faassen, Ernst E; Mürtz, Manfred; Grieb, Gerrit; Bozkurt, Ahmet; Hemmrich, Karsten; Windolf, Joachim; Suschek, Christoph V

2012-02-15

Vascular ischemic diseases, hypertension, and other systemic hemodynamic and vascular disorders may be the result of impaired bioavailability of nitric oxide (NO). NO but also its active derivates like nitrite or nitroso compounds are important effector and signal molecules with vasodilating properties. Our previous findings point to a therapeutical potential of cutaneous administration of NO in the treatment of systemic hemodynamic disorders. Unfortunately, no reliable data are available on the mechanisms, kinetics and biological responses of dermal application of nitric oxide in humans in vivo. The aim of the study was to close this gap and to explore the therapeutical potential of dermal nitric oxide application. We characterized with human skin in vitro and in vivo the capacity of NO, applied in a NO-releasing acidified form of nitrite-containing liniments, to penetrate the epidermis and to influence local as well as systemic hemodynamic parameters. We found that dermal application of NO led to a very rapid and significant transepidermal translocation of NO into the underlying tissue. Depending on the size of treated skin area, this translocation manifests itself through a significant systemic increase of the NO derivates nitrite and nitroso compounds, respectively. In parallel, this translocation was accompanied by an increased systemic vasodilatation and blood flow as well as reduced blood pressure. We here give evidence that in humans dermal application of NO has a therapeutic potential for systemic hemodynamic disorders that might arise from local or systemic insufficient availability of NO or its bio-active NO derivates, respectively. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical Evaluation of Papilla Reconstruction Using Subepithelial Connective Tissue Graft

PubMed Central

Kaushik, Alka; PK, Pal; Chopra, Deepak; Chaurasia, Vishwajit Rampratap; Masamatti, Vinaykumar S; DK, Suresh; Babaji, Prashant

2014-01-01

Objective: The aesthetics of the patient can be improved by surgical reconstruction of interdental papilla by using an advanced papillary flap interposed with subepithelial connective tissue graft. Materials and Methods: A total of fifteen sites from ten patients having black triangles/papilla recession in the maxillary anterior region were selected and subjected to presurgical evaluation. The sites were treated with interposed subepithelial connective tissue graft placed under a coronally advance flap. The integrity of the papilla was maintained by moving the whole of gingivopapillary unit coronally. The various parameters were analysed at different intervals. Results: There was a mean decrease in the papilla presence index score and distance from contact point to gingival margin, but it was statistically not significant. Also, there is increase in the width of the keratinized gingiva which was statistically highly significant. Conclusion: Advanced papillary flap with interposed sub–epithelial connective tissue graft can offer predictable results for the reconstruction of interdental papilla. If papilla loss occurs solely due to soft-tissue damage, reconstructive techniques can completely restore it; but if due to periodontal disease involving bone loss, reconstruction is generally incomplete and multiple surgical procedures may be required. PMID:25386529

Quantitative study of fungiform papillae and taste buds on the cat's tongue.

PubMed

Robinson, P P; Winkles, P A

1990-01-01

The number of fungiform papillae has been counted on the tongues of six adult cats and of kittens both at birth and aged 2 and 4 months. Papillae were sampled from different regions of the tongue, and their size and the number of taste buds they contained were determined using histological sections taken parallel to the tongue surface. There were approximately 250 fungiform papillae on the tongues of the adult cats, the papillae were most numerous at the tip of the tongue, and there was no significant difference between the number of papillae on each side. The size of the papillae increased from a mean maximum diameter of 0.28 mm at the tip of the tongue to 0.48 mm at the back; the mean number of taste buds increased correspondingly from 6.9 to 16.6. The kitten tongues had a number and distribution of fungiform papillae similar to that found in the adults. In the neonate, papillae were smaller and contained fewer taste buds; these parameters increased with the corresponding increase in tongue size in the 2- and 4-month-old kittens.

Morphology of the dorsal lingual papillae in the newborn panther and Asian black bear.

PubMed

Emura, S; Hayakawa, D; Chen, H; Shoumura, S

2001-12-01

The dorsal lingual surfaces of a newborn panther (Panthera pardus) and two newborn asian black bears (Selenarctos thibetanus) were examined by scanning electron microscopy (SEM). The tongues of the panther and asian black bear were about 40 mm in length and about 20 mm in width. Filiform, fungiform and vallate papillae were found. The filiform papillae were distributed over the entire dorsal surface of the tongue. In the panther, the filiform papillae on margin of the lingual apex were divided into two shapes which were horny or club-shaped papillae. The filiform papillae on the midportion were larger than those on the lateral region in size. The fungiform papillae also were divided into two shapes which were hemispherical or club-shaped papillae. In the asian black bear, the filiform papillae on the margin of the lingual apex were larger than those on margin of the panther tongue. The vallate papillae in the animals of two species were located on both sides of the posterior end of the lingual body. Each papilla was surrounded by a groove and crescent pad.

Evaluation of electric arc furnace-processed steel slag for dermal corrosion, irritation, and sensitization from dermal contact.

PubMed

Suh, Mina; Troese, Matthew J; Hall, Debra A; Yasso, Blair; Yzenas, John J; Proctor, Debora M

2014-12-01

Electric arc furnace (EAF) steel slag is alkaline (pH of ~11-12) and contains metals, most notably chromium and nickel, and thus has potential to cause dermal irritation and sensitization at sufficient dose. Dermal contact with EAF slag occurs in many occupational and environmental settings because it is used widely in construction and other industrial sectors for various applications including asphaltic paving, road bases, construction fill, and as feed for cement kilns construction. However, no published study has characterized the potential for dermal effects associated with EAF slag. To assess dermal irritation, corrosion and sensitizing potential of EAF slag, in vitro and in vivo dermal toxicity assays were conducted based on the Organisation for Economic Co-operation and Development (OECD) guidelines. In vitro dermal corrosion and irritation testing (OECD 431 and 439) of EAF slag was conducted using the reconstructed human epidermal (RHE) tissue model. In vivo dermal toxicity and delayed contact sensitization testing (OECD 404 and 406) were conducted in rabbits and guinea pigs, respectively. EAF slag was not corrosive and not irritating in any tests. The results of the delayed contact dermal sensitization test indicate that EAF slag is not a dermal sensitizer. These findings are supported by the observation that metals in EAF slag occur as oxides of low solubility with leachates that are well below toxicity characteristic leaching procedure (TCLP) limits. Based on these results and in accordance to the OECD guidelines, EAF slag is not considered a dermal sensitizer, corrosive or irritant. Copyright © 2014 John Wiley & Sons, Ltd.

Association between central papilla recession and gingival and interdental smile line.

PubMed

Kolte, Abhay P; Kolte, Rajashri A; Agrawal, Anshuka A; Shrirao, Tushar; Mankar, Kamal

2017-11-30

Interdental soft tissues play a critical role in pink esthetics. The presence and preservation of the interdental papillae in the esthetic zone is as crucial as the shape and contour of the anterior teeth in achieving an esthetically pleasing smile. The present study determines the association of central papilla recession with gingival and interdental smile line in periodontally healthy patients of different age groups. The present study included 200 patients equally divided into 21 to 40 years and 41 to 60 years age groups. The clinical and photographic evaluation of the central papilla, with midfacial gingiva, and its relationship with the vermilion border was performed. In total, 137 patients exhibited presence of central papilla, whilst 63 patients had central papilla recession with variable extent. The male patients predominantly had presence of central papilla in both the age groups, with 86% and 64%, compared with 74% and 50% in females, respectively. High gingival smile line was seen in the majority of the patients (62%), and this trend was similar to high interdental smile line (82% of the patients). Esthetics is affected in individuals having papilla recession along with high gingival smile line and interdental smile line as compared to individuals with low or cupid bow gingival smile line and interdental smile line.

Scanning electron microscopic study of the lingual papillae in the arctic fox (Alopex lagopus L., 1758).

PubMed

Jackowiak, H; Godynicki, S; Skieresz-Szewczyk, K; Trzcielińska-Lorych, J

2009-10-01

This study aims to show the distribution and the three-dimensional structure of the lingual papillae in the arctic fox. The macro- and microscopic structure of the tongue and its lingual papillae was studied in 11 adult arctic foxes. Two types of mechanical papillae were distinguished on the dorsal surface of the tongue--filiform papillae and conical papillae. The gustatory papillae in the arctic fox are represented by fungiform, vallate and foliate papillae. The keratinized filiform papillae on the anterior part of tongue are composed of one big posterior process accompanied by 10-12 secondary anterior processes. The number of anterior processes of filiform papillae undergo a complete reduction within the area between the posterior part of the body of the tongue and area of the vallate papillae. The conical papillae cover the whole dorsal surface of the root of the tongue, including the lateral parts surrounding the area of the vallate papillae and the posterior part of the root. The size of the conical papillae increases towards the root of the tongue but their density decreases. In the arctic fox, there are three pairs of vallate papillae distributed on the plan of a triangle. The diameter of vallate papillae in each successive pair is bigger. The wall surrounding the body of the vallate papilla and its gustatory trench is composed of six to eight conical papillae joined at various degree. The foliate papillae on both margins of the tongue consist of seven to nine laminae.

Chondrogenic potential of physically treated bovine cartilage matrix derived porous scaffolds on human dermal fibroblast cells.

PubMed

Moradi, Ali; Ataollahi, Forough; Sayar, Katayoun; Pramanik, Sumit; Chong, Pan-Pan; Khalil, Alizan Abdul; Kamarul, Tunku; Pingguan-Murphy, Belinda

2016-01-01

Extracellular matrices have drawn attention in tissue engineering as potential biomaterials for scaffold fabrication because of their bioactive components. Noninvasive techniques of scaffold fabrication and cross-linking treatments are believed to maintain the integrity of bioactive molecules while providing proper architectural and mechanical properties. Cartilage matrix derived scaffolds are designed to support the maintenance of chondrocytes and provide proper signals for differentiation of chondroinducible cells. Chondroinductive potential of bovine articular cartilage matrix derived porous scaffolds on human dermal fibroblasts and the effect of scaffold shrinkage on chondrogenesis were investigated. An increase in sulfated glycosaminoglycans production along with upregulation of chondrogenic genes confirmed that physically treated cartilage matrix derived scaffolds have chondrogenic potential on human dermal fibroblasts. © 2015 Wiley Periodicals, Inc.

Ballooning of the papilla during contrast injection: the semaphore of a choledochocele.

PubMed

Kim, M H; Myung, S J; Lee, S K; Yoo, B M; Seo, D W; Lee, M H; Jung, S A; Kim, Y S; Min, Y I

1998-09-01

Choledochocele is a rare abnormality involving the intramural segment of the common bile duct. ERCP is essential to demonstrate a choledochocele. The aim of this study was to investigate the duodenoscopic and cholangiographic findings during ERCP. Over a 4-year period, 17 symptomatic patients (8 men, 9 women; age range 45 to 83 years) were identified as having choledochoceles. The diagnosis of choledochocele was made by both duodenoscopic and cholangiographic findings. As a characteristic duodenoscopic finding, the enlarged bulging papilla was noted in 8 patients (47%), whereas a normal-appearing papilla was noted in 9 patients (53%) before the injection of contrast media. However, in all 17 patients progressive enlargement or ballooning of the papilla was noted during contrast injection. The maximum diameter of the choledochocele, determined by cholangiography, was significantly larger (19 +/-4 mm) in patients with initially bulging papilla than in those with normal-appearing papilla (9+/-3 mm) (p < 0.05). Ballooning of the papilla during contrast injection may be a specific duodenoscopic finding for choledochocele. To avoid missing the diagnosis of a choledochocele, especially when it is small, it is important to watch the papilla carefully during contrast injection.

[Three dimensional structure of the connective tissue papillae of the tongue in Suncus murinus].

PubMed

Kobayashi, K; Miyata, K; Iwasaki, S; Takahashi, K

1989-08-01

The surface structure of the connective tissue papillae (CP) of Suncus murinus tongue was observed by SEM after fixing with Karnovsky's fixative and removal of the epithelial cell layer with 3N or 8N HCl. On the surface of the slender conical tongue, there are densely distributed filiform papillae among which fungiform papillae are seen sporadically. A pair of vallate papillae are situated in the posterior region of the tongue. Filiform papillae appear somewhat different externally depending on the dorsal surface of the anterior tongue. At the tip of the tongue, filiform papillae are of a slender conical shape and have a slight depression in the anterior basal portion. The CP of these is seen as a spherical protrusion on which a shallow groove runs in the anteroposterior direction. In the middle region, somewhat large filiform papillae contain CP having one or two small round head-like structures on each spherical protrusion. These head-like structures are increased in number in the posterior region. In the most posterior region of the anterior tongue, there are distributed large filiform papillae having several slender protrusions that surround a basal anterior depression. These large branched filiform papillae have a glove finger like CP. Small conical filiform papillae are distributed in the posterior marginal region of the anterior tongue which have CP of a horse-shoe like protrusion that opens in the anterior direction. Spherical fungiform papillae have CP which are thick columnar in shape with many lateral thin folds running vertically and having a round depression on the top of each. CP of the vallate papillae appear as a beehive like structure.(ABSTRACT TRUNCATED AT 250 WORDS)

18ß-glycyrrhetinic acid derivative promotes proliferation, migration and aquaporin-3 expression in human dermal fibroblasts.

PubMed

Hung, Chi-Feng; Hsiao, Chien-Yu; Hsieh, Wen-Hao; Li, Hsin-Ju; Tsai, Yi-Ju; Lin, Chun-Nan; Chang, Hsun-Hsien; Wu, Nan-Lin

2017-01-01

Licorice (Glycyrrhiza) species have been widely used as a traditional medicine and a natural sweetener in foods. The 18β-glycyrrhetinic acid (18β-GA) is a bioactive compound in licorice that exhibits potential anti-cancer, anti-inflammatory, and anti-microbial activities. Many synthesized derivatives of 18β-GA have been reported to be cytotoxic and suggested for the treatment of malignant diseases. In this study, we explored the possible pharmacological roles of an 18β-GA derivative in skin biology using primary human dermal fibroblasts and HaCaT keratinocytes as cell models. We found that this 18β-GA derivative did not cause cell death, but significantly enhanced the proliferation of dermal fibroblasts and HaCaT keratinocytes. A scratch wound healing assay revealed that the 18β-GA derivative promoted the migration of fibroblasts. Due to the important role of aquaporin-3 in cell migration and proliferation, we also investigated the expression of aquaporin-3 and found this compound up-regulated the expression of aquaporin-3 in dermal fibroblasts and HaCaT keratinocytes. In dermal fibroblasts, the 18β-GA derivative induced the phosphorylation of Akt, ERK, and p38. The inhibitor of Akt predominantly suppressed the 18β-GA derivative-induced expression of aquaporin-3. Collectively, this compound had a positive effect on the proliferation, migration, and aquaporin-3 expression of skin cells, implying its potential role in the treatment of skin diseases characterized by impaired wound healing or dermal defects.

Scanning Electron Microscopic Structure of the Lingual Papillae of the Common Opossum (Didelphis marsupialis)

NASA Astrophysics Data System (ADS)

Okada, Shigenori; Schraufnagel, Dean E.

2005-08-01

The mammalian tongue has evolved for specialized functions in different species. The structure of its papillae tells about the animal's diet, habit, and taxonomy. The opossum has four kinds of lingual papillae (filiform, conical, fungiform, vallate). Scanning electron microscopy of the external features, connective tissue cores, and corrosion casts of the microvasculature show the filiform papillae have a spearhead-like main process and spiny accessory processes around the apical part of the main process. The shape and number of both processes depend on their position on the tongue. On the apex, the main processes have shovel-like capillary networks and the accessory processes have small conical networks. On the lingual radix, the processes have small capillary loops. In the patch region, conical papillae have capillaries arranged as a full sail curving posteriorly. The fungiform papillae are scattered among the filiform papillae and have capillary baskets beneath each taste bud. Giant fungiform papillae on the tongue tip are three to four times larger than the ones on the lingual body. Capillaries of giant papillae form a fan-shaped network. The opossum has three vallate papillae arranged in a triangle. Their tops have secondary capillary loops but not their lateral surfaces. Mucosal folds on the posterolateral border have irregular, fingerlike projections with cylindrical capillary networks. These findings and the structure of the rest of the masticatory apparatus suggest the lingual papillae of opossum have kept their ancestral carnivorous features but also developed the herbivore characteristics of other marsupials.

Scanning electron microscopic structure of the lingual papillae of the common opossum (Didelphis marsupialis).

PubMed

Okada, Shigenori; Schraufnagel, Dean E

2005-08-01

The mammalian tongue has evolved for specialized functions in different species. The structure of its papillae tells about the animal's diet, habit, and taxonomy. The opossum has four kinds of lingual papillae (filiform, conical, fungiform, vallate). Scanning electron microscopy of the external features, connective tissue cores, and corrosion casts of the microvasculature show the filiform papillae have a spearhead-like main process and spiny accessory processes around the apical part of the main process. The shape and number of both processes depend on their position on the tongue. On the apex, the main processes have shovel-like capillary networks and the accessory processes have small conical networks. On the lingual radix, the processes have small capillary loops. In the patch region, conical papillae have capillaries arranged as a full sail curving posteriorly. The fungiform papillae are scattered among the filiform papillae and have capillary baskets beneath each taste bud. Giant fungiform papillae on the tongue tip are three to four times larger than the ones on the lingual body. Capillaries of giant papillae form a fan-shaped network. The opossum has three vallate papillae arranged in a triangle. Their tops have secondary capillary loops but not their lateral surfaces. Mucosal folds on the posterolateral border have irregular, fingerlike projections with cylindrical capillary networks. These findings and the structure of the rest of the masticatory apparatus suggest the lingual papillae of opossum have kept their ancestral carnivorous features but also developed the herbivore characteristics of other marsupials.

Comparative transcriptome analysis of papilla and skin in the sea cucumber, Apostichopus japonicus.

PubMed

Zhou, Xiaoxu; Cui, Jun; Liu, Shikai; Kong, Derong; Sun, He; Gu, Chenlei; Wang, Hongdi; Qiu, Xuemei; Chang, Yaqing; Liu, Zhanjiang; Wang, Xiuli

2016-01-01

Papilla and skin are two important organs of the sea cucumber. Both tissues have ectodermic origin, but they are morphologically and functionally very different. In the present study, we performed comparative transcriptome analysis of the papilla and skin from the sea cucumber (Apostichopus japonicus) in order to identify and characterize gene expression profiles by using RNA-Seq technology. We generated 30.6 and 36.4 million clean reads from the papilla and skin and de novo assembled in 156,501 transcripts. The Gene Ontology (GO) analysis indicated that cell part, metabolic process and catalytic activity were the most abundant GO category in cell component, biological process and molecular funcation, respectively. Comparative transcriptome analysis between the papilla and skin allowed the identification of 1,059 differentially expressed genes, of which 739 genes were expressed at higher levels in papilla, while 320 were expressed at higher levels in skin. In addition, 236 differentially expressed unigenes were not annotated with any database, 160 of which were apparently expressed at higher levels in papilla, 76 were expressed at higher levels in skin. We identified a total of 288 papilla-specific genes, 171 skin-specific genes and 600 co-expressed genes. Also, 40 genes in papilla-specific were not annotated with any database, 2 in skin-specific. Development-related genes were also enriched, such as fibroblast growth factor, transforming growth factor-β, collagen-α2 and Integrin-α2, which may be related to the formation of the papilla and skin in sea cucumber. Further pathway analysis identified ten KEGG pathways that were differently enriched between the papilla and skin. The findings on expression profiles between two key organs of the sea cucumber should be valuable to reveal molecular mechanisms involved in the development of organs that are related but with morphological differences in the sea cucumber.

Dermal uptake of phthalates from clothing: Comparison of model to human participant results.

PubMed

Morrison, G C; Weschler, C J; Bekö, G

2017-05-01

In this research, we extend a model of transdermal uptake of phthalates to include a layer of clothing. When compared with experimental results, this model better estimates dermal uptake of diethylphthalate and di-n-butylphthalate (DnBP) than a previous model. The model predictions are consistent with the observation that previously exposed clothing can increase dermal uptake over that observed in bare-skin participants for the same exposure air concentrations. The model predicts that dermal uptake from clothing of DnBP is a substantial fraction of total uptake from all sources of exposure. For compounds that have high dermal permeability coefficients, dermal uptake is increased for (i) thinner clothing, (ii) a narrower gap between clothing and skin, and (iii) longer time intervals between laundering and wearing. Enhanced dermal uptake is most pronounced for compounds with clothing-air partition coefficients between 10 4 and 10 7 . In the absence of direct measurements of cotton cloth-air partition coefficients, dermal exposure may be predicted using equilibrium data for compounds in equilibrium with cellulose and water, in combination with computational methods of predicting partition coefficients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dermal reflectivity determined by optical coherence tomography is an indicator of epidermal hyperplasia and dermal edema within inflamed skin

NASA Astrophysics Data System (ADS)

Phillips, Kevin G.; Wang, Yun; Levitz, David; Choudhury, Niloy; Swanzey, Emily; Lagowski, James; Kulesz-Martin, Molly; Jacques, Steven L.

2011-04-01

Psoriasis is a common inflammatory skin disease resulting from genetic and environmental alterations of cutaneous immune responses. While numerous therapeutic targets involved in the immunopathogenesis of psoriasis have been identified, the in vivo dynamics of inflammation in psoriasis remain unclear. We undertook in vivo time course focus-tracked optical coherence tomography (OCT) imaging to noninvasively document cutaneous alterations in mouse skin treated topically with Imiquimod (IMQ), an established model of a psoriasis-like disease. Quantitative appraisal of dermal architectural changes was achieved through a two parameter fit of OCT axial scans in the dermis of the form A(x, y, z) = ρ(x, y)exp [ - μ(x, y)z]. Ensemble averaging over 2000 axial scans per mouse in each treatment arm revealed no significant changes in the average dermal attenuation rate, <μ>, however the average local dermal reflectivity <ρ>, decreased significantly following 1, 3, and 6 days of IMQ treatment (p < 0.001) in comparison to vehicle-treated control mice. In contrast, epidermal and dermal thickness changes were only significant when comparing controls and 6-day IMQ treated mice. This suggests that dermal alterations, attributed to collagen fiber bundle enlargement, occur prior to epidermal thickness changes due to hyperplasia and dermal thickness changes due to edema. Dermal reflectivity positively correlated with epidermal hyperplasia (repi2 = 0.78) and dermal edema (rderm2 = 0.86). Our results suggest that dermal reflectivity as measured by OCT can be utilized to quantify a psoriasis-like disease in mice, and thus has the potential to aid in the quantitative assessment of psoriasis in humans.

Sexual dimorphism of human vallate papillae: an in vivo study of normative morphology.

PubMed

Zdilla, M J; Gibson, L N; Hunt, A J

2015-01-01

The perimeters of vallate papillae (VP) house approximately half of the taste buds on the human tongue. However, little information exists regarding perimeter measurements of VP. Likewise, great diversity exists among reports of the number of VP and diameter of VP, in general. The research presents an analysis of the perimeters, counts, and diameters of VP in vivo. Endoscopic examination was performed on 79 individuals (40 females, 39 males) between 18 and 26 years of age. A total of 583 VP were counted, 565 of which were able to be measured. Data revealed a statistically significant difference between male and female VP count (t(75.6) = 4.5; p = 0.00003). Females had, on average, 2.22 more VP than males. Males were found to have larger mean VP diameter per person and mean VP perimeter per person than females (t(58.9) = -2.4; p = 0.021 and t(59.3) = -2.4; p = 0.019, respectively). The report demonstrates that VP are sexually dimorphic at the gross anatomical level.

18ß-glycyrrhetinic acid derivative promotes proliferation, migration and aquaporin-3 expression in human dermal fibroblasts

PubMed Central

Hung, Chi-Feng; Hsiao, Chien-Yu; Hsieh, Wen-Hao; Li, Hsin-Ju; Tsai, Yi-Ju; Lin, Chun-Nan; Chang, Hsun-Hsien; Wu, Nan-Lin

2017-01-01

Licorice (Glycyrrhiza) species have been widely used as a traditional medicine and a natural sweetener in foods. The 18β-glycyrrhetinic acid (18β-GA) is a bioactive compound in licorice that exhibits potential anti-cancer, anti-inflammatory, and anti-microbial activities. Many synthesized derivatives of 18β-GA have been reported to be cytotoxic and suggested for the treatment of malignant diseases. In this study, we explored the possible pharmacological roles of an 18β-GA derivative in skin biology using primary human dermal fibroblasts and HaCaT keratinocytes as cell models. We found that this 18β-GA derivative did not cause cell death, but significantly enhanced the proliferation of dermal fibroblasts and HaCaT keratinocytes. A scratch wound healing assay revealed that the 18β-GA derivative promoted the migration of fibroblasts. Due to the important role of aquaporin-3 in cell migration and proliferation, we also investigated the expression of aquaporin-3 and found this compound up-regulated the expression of aquaporin-3 in dermal fibroblasts and HaCaT keratinocytes. In dermal fibroblasts, the 18β-GA derivative induced the phosphorylation of Akt, ERK, and p38. The inhibitor of Akt predominantly suppressed the 18β-GA derivative-induced expression of aquaporin-3. Collectively, this compound had a positive effect on the proliferation, migration, and aquaporin-3 expression of skin cells, implying its potential role in the treatment of skin diseases characterized by impaired wound healing or dermal defects. PMID:28813533

Effect of microemulsions on cell viability of human dermal fibroblasts

NASA Astrophysics Data System (ADS)

Li, Juyi; Mironava, Tatsiana; Simon, Marcia; Rafailovich, Miriam; Garti, Nissim

Microemulsions are optically clear, thermostable and isotropic mixture consisting of water, oil and surfactants. Their advantages of ease preparation, spontaneous formation, long-term stability and enhanced solubility of bioactive materials make them great potentials as vehicles in food and pharmaceutical applications. In this study, comparative in vitro cytotoxicity tests were performed to select a best formulation of microemulsion with the least toxicity for human dermal fibroblasts. Three different kinds of oils and six different kinds of surfactants were used to form microemulsions by different ratios. The effect of oil type and surfactant type as well as their proportions on cell proliferation and viability were tested.

Dermal-epidermal membrane systems by using human keratinocytes and mesenchymal stem cells isolated from dermis.

PubMed

Salerno, Simona; Messina, Antonietta; Giordano, Francesca; Bader, Augustinus; Drioli, Enrico; De Bartolo, Loredana

2017-02-01

Dermal-epidermal membrane systems were developed by co-culturing human keratinocytes with Skin derived Stem Cells (SSCs), which are Mesenchymal Stem Cells (MSCs) isolated from dermis, on biodegradable membranes of chitosan (CHT), polycaprolactone (PCL) and a polymeric blend of CHT and PCL. The membranes display physico-chemical, morphological, mechanical and biodegradation properties that could satisfy and fulfil specific requirements in skin tissue engineering. CHT membrane exhibits an optimal biodegradation rate for acute wounds; CHT-PCL for the chronic ones. On the other hand, PCL membrane in spite of its very slow biodegradation rate exhibits mechanical properties similar to in vivo dermis, a lower hydrophilic character, and a surface roughness, all properties that make it able to sustain cell adhesion and proliferation for in vitro skin models. Both CHT-PCL and PCL membranes guided epidermal and dermal differentiation of SSCs as pointed out by the expression of cytokeratins and the deposition of the ECM protein fibronectin, respectively. In the dermal-epidermal membrane systems, a more suitable microenvironment for the SSCs differentiation was promoted by the interactions and the mutual interplay with keratinocytes. Being skin tissue-biased stem cells committed to their specific final dermal and/or epidermal cell differentiation, SSCs are more suitable for skin tissue engineering than other adult MSCs with different origin. For this reason, they represent a useful autologous cell source for engineering skin substitutes for both in vivo and in vitro applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Multiple Shh signaling centers participate in fungiform papilla and taste bud formation and maintenance

PubMed Central

Liu, H-X; Ermilov, A; Grachtchouk, M; Li, L; Gumucio, DL; Dlugosz, AA; Mistretta, CM

2014-01-01

The adult fungiform taste papilla is a complex of specialized cell types residing in the stratified squamous tongue epithelium. This unique sensory organ includes taste buds, papilla epithelium and lateral walls that extend into underlying connective tissue to surround a core of lamina propria cells. Fungiform papillae must contain long-lived, sustaining or stem cells and short-lived, maintaining or transit amplifying cells that support the papilla and specialized taste buds. Shh signaling has established roles in supporting fungiform induction, development and patterning. However, for a full understanding of how Shh transduced signals act in tongue, papilla and taste bud formation and maintenance, it is necessary to know where and when the Shh ligand and pathway components are positioned. We used immunostaining, in situ hybridization and mouse reporter strains for Shh, Ptch1, Gli1 and Gli2-expression and proliferation markers to identify cells that participate in hedgehog signaling. Whereas there is a progressive restriction in location of Shh ligand-expressing cells, from placode and apical papilla cells to taste bud cells only, a surrounding population of Ptch1 and Gli1 responding cells is maintained in signaling centers throughout papilla and taste bud development and differentiation. The Shh signaling targets are in regions of active cell proliferation. Using genetic-inducible lineage tracing for Gli1-expression, we found that Shh-responding cells contribute not only to maintenance of filiform and fungiform papillae, but also to taste buds. A requirement for normal Shh signaling in fungiform papilla, taste bud and filiform papilla maintenance was shown by Gli2 constitutive activation. We identified proliferation niches where Shh signaling is active and suggest that epithelial and mesenchymal compartments harbor potential stem and/or progenitor cell zones. In all, we report a set of hedgehog signaling centers that regulate development and maintenance of taste

Multiple Shh signaling centers participate in fungiform papilla and taste bud formation and maintenance.

PubMed

Liu, Hong Xiang; Ermilov, Alexandre; Grachtchouk, Marina; Li, Libo; Gumucio, Deborah L; Dlugosz, Andrzej A; Mistretta, Charalotte M

2013-10-01

The adult fungiform taste papilla is a complex of specialized cell types residing in the stratified squamous tongue epithelium. This unique sensory organ includes taste buds, papilla epithelium and lateral walls that extend into underlying connective tissue to surround a core of lamina propria cells. Fungiform papillae must contain long-lived, sustaining or stem cells and short-lived, maintaining or transit amplifying cells that support the papilla and specialized taste buds. Shh signaling has established roles in supporting fungiform induction, development and patterning. However, for a full understanding of how Shh transduced signals act in tongue, papilla and taste bud formation and maintenance, it is necessary to know where and when the Shh ligand and pathway components are positioned. We used immunostaining, in situ hybridization and mouse reporter strains for Shh, Ptch1, Gli1 and Gli2-expression and proliferation markers to identify cells that participate in hedgehog signaling. Whereas there is a progressive restriction in location of Shh ligand-expressing cells, from placode and apical papilla cells to taste bud cells only, a surrounding population of Ptch1 and Gli1 responding cells is maintained in signaling centers throughout papilla and taste bud development and differentiation. The Shh signaling targets are in regions of active cell proliferation. Using genetic-inducible lineage tracing for Gli1-expression, we found that Shh-responding cells contribute not only to maintenance of filiform and fungiform papillae, but also to taste buds. A requirement for normal Shh signaling in fungiform papilla, taste bud and filiform papilla maintenance was shown by Gli2 constitutive activation. We identified proliferation niches where Shh signaling is active and suggest that epithelial and mesenchymal compartments harbor potential stem and/or progenitor cell zones. In all, we report a set of hedgehog signaling centers that regulate development and maintenance of taste

Human dermal exposure to galaxolide from personal care products.

PubMed

Correia, P; Cruz, A; Santos, L; Alves, A

2013-06-01

Musks are synthetic fragrances applied on personal care and household products as fixatives, by retarding the release of other fragrances with higher volatility. Galaxolide is the most used polycyclic musk since the 90th decade, and it has been detected in several environmental and biological matrices, particularly in human tissues and fluids. For exposure assessment purposes, large-monitoring data need to be obtained and rapid but reliable analytical techniques are requested. The main objective of this study is to develop and validate a new and fast analytical methodology to quantify galaxolide in personal care products and to apply this method to real matrices like skin care products (creams and lotions), shower products (soap bar), hair care products (shampoo and hair conditioner) and oral care products (toothpaste), to evaluate the human dermal exposure risk. A dispersive solid-phase extraction is proposed, using QuEChERS methodology, followed by HPLC with fluorescence detection. Some extraction parameters were studied, like the ratio of sample/solvent amounts, the homogenization time, the salt addition effect and the used sorbents. The validation parameters of the developed method were the following: a linearity range of 0.005-1.002 mg kg⁻¹ sample, a limit of detection of 0.001 mg kg⁻¹ sample, repeatability between 0.7% and 11.3% (variation coefficient of six standard injections), an intermediate precision of 2.5% (variation coefficient of six independent analysis of the same sample), mean recoveries ranging from 65% (soap bar) to 95% (body cream) and 3% of global uncertainty in most of the working range. The time of analysis, including the extraction steps, is 60 min, allowing a throughput of 4 samples h⁻¹ . Galaxolide was detected in all of the seven analysed products in concentrations ranging from 0.04 ± 0.01 mg kg⁻¹ sample (toothpaste) to 280.78 ± 8.19 mg kg⁻¹ sample (perfumed body cream), which may correspond to a significant estimated

In vitro Dermal Absorption of Hydroquinone: Protocol Validation and Applicability on Illegal Skin-Whitening Cosmetics.

PubMed

Desmedt, Bart; Ates, Gamze; Courselle, Patricia; De Beer, Jacques O; Rogiers, Vera; Hendrickx, Benoit; Deconinck, Eric; De Paepe, Kristien

2016-01-01

In Europe, hydroquinone is a forbidden cosmetic ingredient. It is, however, still abundantly used because of its effective skin-whitening properties. The question arises as to whether the quantities of hydroquinone used become systemically available and may cause damage to human health. Dermal absorption studies can provide this information. In the EU, dermal absorption has to be assessed in vitro since the Cosmetic Regulation 1223/2009/EC forbids the use of animals. To obtain human-relevant data, a Franz diffusion cell protocol was validated using human skin. The results obtained were comparable to those from a multicentre validation study. The protocol was applied to hydroquinone and the dermal absorption ranged between 31 and 44%, which is within the range of published in vivo human values. This shows that a well-validated in vitro dermal absorption study using human skin provides relevant human data. The validated protocol was used to determine the dermal absorption of illegal skin-whitening cosmetics containing hydroquinone. All samples gave high dermal absorption values, rendering them all unsafe for human health. These results add to our knowledge of illegal cosmetics on the EU market, namely that they exhibit a negative toxicological profile and are likely to induce health problems. © 2017 S. Karger AG, Basel.

The chromene sargachromanol E inhibits ultraviolet A-induced ageing of skin in human dermal fibroblasts.

PubMed

Kim, J-A; Ahn, B-N; Kong, C-S; Kim, S-K

2013-05-01

Skin ageing is influenced by environmental factors such as ultraviolet (UV) radiation. The effects of UV radiation on skin functions should be investigated using human in vitro models to understand the mechanisms of skin ageing. Additionally, marine algae provide a valuable source for identifying and extracting biologically active substances. In this study, sargachromanol E was isolated from a marine brown alga, Sargassum horneri, and its inhibitory effect on skin ageing was investigated using UVA-irradiated dermal fibroblasts. Formation of intracellular reactive oxygen species (ROS), lipid peroxidation and protein oxidation induced by UVA irradiation were investigated in UVA-irradiated human dermal fibroblasts. The levels of matrix metalloproteinases (MMPs) were determined by reverse-transcriptase polymerase chain reaction and Western blot analysis. Sargachromanol E did not exhibit any significant cytotoxicity or phototoxicity in UVA-exposed dermal fibroblasts. Additionally, sargachromanol E suppressed intracellular formation of ROS, membrane protein oxidation, lipid peroxidation and expression of collagenases such as MMP-1, MMP-2 and MMP-9, all of which are caused by UVA exposure. It was further found that these inhibitions were related to an increase in the expression of the tissue inhibitor of metalloproteinase (TIMP) genes, TIMP1 and TIMP2. Moreover, we have shown that the transcriptional activation of activator protein 1 (AP-1) signalling caused by UVA irradiation was inhibited by treatment with sargachromanol E. This study suggests that UVA irradiation modulates MMP expression via the transcriptional activation of AP-1 signalling, whereas treatment with sargachromanol E protected cell damage caused by UVA irradiation. © 2013 The Authors. BJD © 2013 British Association of Dermatologists.

Evaluation of in vitro vs. in vivo methods for assessment of dermal absorption of organic flame retardants: a review.

PubMed

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

2015-01-01

There is a growing interest to study human dermal exposure to a large number of chemicals, whether in the indoor or outdoor environment. Such studies are essential to predict the systemic exposure to xenobiotic chemicals for risk assessment purposes and to comply with various regulatory guidelines. However, very little is currently known about human dermal exposure to persistent organic pollutants. While recent pharmacokinetic studies have highlighted the importance of dermal contact as a pathway of human exposure to brominated flame retardants, risk assessment studies had to apply assumed values for percutaneous penetration of various flame retardants (FRs) due to complete absence of specific experimental data on their human dermal bioavailability. Therefore, this article discusses the current state-of-knowledge on the significance of dermal contact as a pathway of human exposure to FRs. The available literature on in vivo and in vitro methods for assessment of dermal absorption of FRs in human and laboratory animals is critically reviewed. Finally, a novel approach for studying human dermal absorption of FRs using in vitro three-dimensional (3D) human skin equivalent models is presented and the challenges facing future dermal absorption studies on FRs are highlighted. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hydroquinone PBPK model refinement and application to dermal exposure.

PubMed

Poet, Torka S; Carlton, Betsy D; Deyo, James A; Hinderliter, Paul M

2010-11-01

A physiologically based pharmacokinetic (PBPK) model for hydroquinone (HQ) was refined to include an expanded description of HQ-glucuronide metabolites and a description of dermal exposures to support route-to-route and cross-species extrapolation. Total urinary excretion of metabolites from in vivo rat dermal exposures was used to estimate a percutaneous permeability coefficient (K(p); 3.6×10(-5) cm/h). The human in vivo K(p) was estimated to be 1.62×10(-4) cm/h, based on in vitro skin permeability data in rats and humans and rat in vivo values. The projected total multi-substituted glutathione (which was used as an internal dose surrogate for the toxic glutathione metabolites) was modeled following an exposure scenario based on submersion of both hands in a 5% aqueous solution of HQ (similar to black and white photographic developing solution) for 2 h, a worst-case exposure scenario. Total multi-substituted glutathione following this human dermal exposure scenario was several orders of magnitude lower than the internal total glutathione conjugates in rats following an oral exposure to the rat NOEL of 20 mg/kg. Thus, under more realistic human dermal exposure conditions, it is unlikely that toxic glutathione conjugates (primarily the di- and, to a lesser degree, the tri-glutathione conjugate) will reach significant levels in target tissues. Copyright © 2010. Published by Elsevier Ltd.

Effects of streptozotocin-induced diabetes on taste buds in rat vallate papillae.

PubMed

Pai, Man-Hui; Ko, Tsui-Ling; Chou, Hsiu-Chu

2007-01-01

Some studies have documented taste changes in patients with diabetes mellitus (DM). In order to understand the relationships between taste disorders caused by DM and the innervation and morphologic changes in the taste buds, we studied the vallate papillae and their taste buds in rats with DM. DM was induced in these rats with streptozotocin (STZ), which causes the death of beta cells of the pancreas. The rats were sacrificed and the vallate papillae were dissected for morphometric and quantitative immunohistochemical analyses. The innervations of the vallate papillae and taste buds in diabetic and control rats were detected using immunohistochemistry employing antibodies directed against protein gene product 9.5 (PGP 9.5) and calcitonin gene-related peptide (CGRP). The results showed that PGP 9.5- and CGRP-immunoreactive nerve fibers in the trench wall of diabetic vallate papillae, as well as taste cells in the taste buds, gradually decreased both intragemmally and intergemmally. The morphometry revealed no significant difference in papilla size between the control and diabetic groups, but there were fewer taste buds per papilla (per animal). The quantification of innervation in taste buds of the diabetic rats supported the visual assessment of immunohistochemical labeling, that the innervation of taste cells was significantly reduced in diabetic animals. These findings suggest that taste impairment in diabetic subjects may be caused by neuropathy defects and/or morphological changes in the taste buds.

bFGF Promotes the Migration of Human Dermal Fibroblasts under Diabetic Conditions through Reactive Oxygen Species Production via the PI3K/Akt-Rac1- JNK Pathways

PubMed Central

Shi, Hongxue; Cheng, Yi; Ye, Jingjing; Cai, Pingtao; Zhang, Jinjing; Li, Rui; Yang, Ying; Wang, Zhouguang; Zhang, Hongyu; Lin, Cai; Lu, Xianghong; Jiang, Liping; Hu, Aiping; Zhu, Xinbo; Zeng, Qiqiang; Fu, Xiaobing; Li, Xiaokun; Xiao, Jian

2015-01-01

Fibroblasts play a pivotal role in the process of cutaneous wound repair, whereas their migratory ability under diabetic conditions is markedly reduced. In this study, we investigated the effect of basic fibroblast growth factor (bFGF) on human dermal fibroblast migration in a high-glucose environment. bFGF significantly increased dermal fibroblast migration by increasing the percentage of fibroblasts with a high polarity index and reorganizing F-actin. A significant increase in intracellular reactive oxygen species (ROS) was observed in dermal fibroblasts under diabetic conditions following bFGF treatment. The blockage of bFGF-induced ROS production by either the ROS scavenger N-acetyl-L-cysteine (NAC) or the NADPH oxidase inhibitor diphenylene iodonium chloride (DPI) almost completely neutralized the increased migration rate of dermal fibroblasts promoted by bFGF. Akt, Rac1 and JNK were rapidly activated by bFGF in dermal fibroblasts, and bFGF-induced ROS production and promoted dermal fibroblast migration were significantly attenuated when suppressed respectively. In addition, bFGF-induced increase in ROS production was indispensable for the activation of focal adhesion kinase (FAK) and paxillin. Therefore, our data suggested that bFGF promotes the migration of human dermal fibroblasts under diabetic conditions through increased ROS production via the PI3K/Akt-Rac1-JNK pathways. PMID:26078726

Bryostatin and its synthetic analog, picolog rescue dermal fibroblasts from prolonged stress and contribute to survival and rejuvenation of human skin equivalents.

PubMed

Khan, Tapan K; Wender, Paul A; Alkon, Daniel L

2018-02-01

Skin health is associated with the day-to-day activity of fibroblasts. The primary function of fibroblasts is to synthesize structural proteins, such as collagen, extracellular matrix proteins, and other proteins that support the structural integrity of the skin and are associated with younger, firmer, and more elastic skin that is better able to resist and recover from injury. At sub-nanomolar concentrations (0.03-0.3 nM), bryostatin-1 and its synthetic analog, picolog (0.1-10 nM) sustained the survival and activation of human dermal fibroblasts cultured under the stressful condition of prolonged serum deprivation. Bryostatin-1 treatment stabilized human skin equivalents (HSEs), a bioengineered combination of primary human skin cells (keratinocytes and dermal fibroblasts) on an extracellular matrix composed of mainly collagen. Fibroblasts activated by bryostatin-1 protected the structural integrity of HSEs. Bryostatin-1 and picolog prolonged activation of Erk in fibroblasts to promote cell survival. Chronic stress promotes the progression of apoptosis. Dermal fibroblasts constitutively express all components of Fas associated apoptosis, including caspase-8, an initiator enzyme of apoptosis. Prolong bryostatin-1 treatment reduced apoptosis by decreasing caspase-8 and protected dermal fibroblasts. Our data suggest that bryostatin-1 and picolog could be useful in anti-aging skincare, and could have applications in tissue engineering and regenerative medicine. © 2017 Wiley Periodicals, Inc.

Characteristics of renal papillae in kidney stone formers.

PubMed

Marien, Tracy P; Miller, Nicole L

2016-12-01

The mechanism of kidney stone formation is not well understood. In order to better understand the pathophysiology for specific kidney stone compositions and systemic diseases associated with kidney stones, endoscopic papillary mapping studies with concurrent biopsies have been conducted. This review will summarize the findings of these studies and proposed mechanisms for thirteen disease processes associated with kidney stones. A review of the literature was performed identifying thirteen studies that endoscopically mapped and biopsied renal papillae of different stone formers. These studies characterized renal papillae based on amount of Randall's plaque, Bellini's duct pathology, papillary contour changes, presence of attached stones, pitting, and frequently papillary and cortical biopsies. The groups studied and reviewed here are kidney stone formers who have a history of idiopathic calcium oxalate stone formation, cystinuria, brushite stones, gastric bypass, ileostomy, small bowel resection, primary hyperparathyroidism, distal renal tubular acidosis (dRTA), primary hyperoxaluria, idiopathic calcium phosphate stone formation, medullary sponge kidney (MSK), uric acid stones, and struvite stones. A proposed standardized scoring system for papillary pathology was also reviewed. The series showed various degrees and types of changes to the renal papillae and corresponding histopathologic changes for each type of stone former reviewed. Those with predominantly alone Randall's plaque pathology had less tissue damage versus those with extensive Bellini's duct lesions who had more interstitial fibrosis and cortical pathology. Randall's plaques are associated with stone formers who have low urinary volume, high urinary calcium, and acidic urine and thus are frequently seen in those with brushite stones, primary hyperparathyroidism, small bowel resection, and idiopathic calcium phosphate stone formers. Bellini's duct plugging and pathology is theorized to occur via free

Aseptic Freeze-Dried versus Sterile Wet-Packaged Human Cadaveric Acellular Dermal Matrix in Immediate Tissue Expander Breast Reconstruction: A Propensity Score Analysis.

PubMed

Hanson, Summer E; Meaike, Jesse D; Selber, Jesse C; Liu, Jun; Li, Liang; Hassid, Victor J; Baumann, Donald P; Butler, Charles E; Garvey, Patrick B

2018-05-01

Although multiple acellular dermal matrix sources exist, it is unclear how its processing impacts complication rates. The authors compared complications between two preparations of human cadaveric acellular dermal matrix (freeze dried and ready-to-use) in immediate tissue expander breast reconstruction to analyze the effect of processing on complications. The authors retrospectively reviewed all alloplastic breast reconstructions with freeze-dried or ready-to-use human acellular dermal matrices between 2006 and 2016. The primary outcome measure was surgical-site occurrence defined as seroma, skin dehiscence, surgical-site infection, or reconstruction failure. The two groups were compared before and after propensity score matching. The authors included 988 reconstructions (freeze-dried, 53.8 percent; ready-to-use, 46.2 percent). Analysis of 384 propensity score-matched pairs demonstrated a slightly higher rate of surgical-site occurrence (21.4 percent versus 16.7 percent; p = 0.10) and surgical-site infection (9.6 percent versus 7.8 percent; p = 0.13) in the freeze-dried group than in the ready-to-use group, but the difference was not significant. However, failure was significantly higher for the freeze-dried versus ready-to-use group (7.8 percent versus 4.4 percent; p = 0.050). This is the largest study comparing the outcomes of alloplastic breast reconstruction using human acellular dermal matrix materials prepared by different methods. The authors demonstrated higher early complications with aseptic, freeze-dried matrix than with sterile ready-to-use matrix; reconstructive failure was the only outcome to achieve statistical significance. The authors conclude that acellular dermal matrix preparation has an independent impact on patient outcomes in their comparison of one company's product. Therapeutic, III.

On the function of the mammalian renal papilla and the peristalsis of the surrounding pelvis.

PubMed

Schmidt-Nielsen, Bodil; Schmidt-Nielsen, Bent

2011-07-01

This is an informal personal review of the development over time of my ideas about the concentrating mechanism of the mammalian renal papilla. It had been observed that animals with a need to produce a concentrated urine have a long renal papilla. I saw the function of the long papilla in desert rodents as an elongation of the counter-current concentrating mechanism of the inner medulla. This model led me to overlook contrary evidence. For example, in many experiments, the final urine has a higher osmolality than that of the tissue at the tip of the papilla. In addition, we had observations of the peristalsis of the renal pelvis surrounding the papilla. The urine concentration falls if the peristalsis is stopped. I was wrong; together, these lines of evidence show that the renal papilla is not just an elongation of the inner medulla. We are left without a full explanation of the concentrating mechanism of the mammalian renal papilla. It is hoped that other researchers will tackle this interesting problem. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

Comparison of dermal and inhalation routes of entry for organic chemicals

NASA Technical Reports Server (NTRS)

Jepson, Gary W.; Mcdougal, James N.; Clewell, Harvey J., III

1992-01-01

The quantitative comparison of the chemical concentration inside the body as the result of a dermal exposure versus an inhalation exposure is useful for assessing human health risks and deciding on an appropriate protective posture. In order to describe the relationship between dermal and inhalation routes of exposure, a variety of organic chemicals were evaluated. The types of chemicals chosen for the study were halogenated hydrocarbons, aromatic compounds, non-polar hydrocarbons and inhalation anesthetics. Both dermal and inhalation exposures were conducted in rats and the chemicals were in the form of vapors. Prior to the dermal exposure, rat fur was closely clipped and during the exposure rats were provided fresh breathing air through latex masks. Blood samples were taken during 4-hour exposures and analyzed for the chemical of interest. A physiologically based pharmacokinetic model was used to predict permeability constants (cm/hr) consistent with the observed blood concentrations of the chemical. The ratio of dermal exposure to inhalation exposure required to achieve the same internal dose of chemical was calculated for each test chemical. The calculated ratio in humans ranged from 18 for styrene to 1180 for isoflurane. This methodology can be used to estimate the dermal exposure required to reach the internal dose achieved by a specific inhalation exposure. Such extrapolation is important since allowable exposure standards are often set for inhalation exposures, but occupational exposures may be dermal.

Immunoglobulin-like transcript receptors on human dermal CD14+ dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming

PubMed Central

Banchereau, Jacques; Zurawski, Sandra; Thompson-Snipes, LuAnn; Blanck, Jean-Philippe; Clayton, Sandra; Munk, Adiel; Cao, Yanying; Wang, Zhiqing; Khandelwal, Sunaina; Hu, Jiancheng; McCoy, William H.; Palucka, Karolina A.; Reiter, Yoram; Fremont, Daved H.; Zurawski, Gerard; Colonna, Marco; Shaw, Andrey S.; Klechevsky, Eynav

2012-01-01

Human Langerhans cells (LCs) are highly efficient at priming cytolytic CD8+ T cells compared with dermal CD14+ dendritic cells (DCs). Here we show that dermal CD14+ DCs instead prime a fraction of naïve CD8+ T cells into cells sharing the properties of type 2 cytokine-secreting CD8+ T cells (TC2). Differential expression of the CD8-antagonist receptors on dermal CD14+ DCs, the Ig-like transcript (ILT) inhibitory receptors, explains the difference between the two types of DCs. Inhibition of CD8 function on LCs inhibited cytotoxic T lymphocytes (CTLs) and enhanced TC2 generation. In addition, blocking ILT2 or ILT4 on dermal CD14+ DCs enhanced the generation of CTLs and inhibited TC2 cytokine production. Lastly, addition of soluble ILT2 and ILT4 receptors inhibited CTL priming by LCs. Thus, ILT receptor expression explains the polarization of CD8+ T-cell responses by LCs vs. dermal CD14+ DCs. PMID:23112154

A case-control evaluation of fungiform papillae density in burning mouth syndrome.

PubMed

Naud, Jason M; Benca, Laura; Drangsholt, Mark T; LeResche, Linda; Coldwell, Susan E

2018-04-01

It has been hypothesized that high fungiform papillae density may be a risk factor for developing the taste and pain alterations characteristic of burning mouth syndrome. Evaluate whether fungiform papillae density, taste sensitivity, and mechanical pain sensitivity differ between burning mouth syndrome cases and controls. This case-control study compared cases diagnosed with primary burning mouth syndrome with pain-free controls. Participants (17 female cases and 23 female controls) rated the intensity of sucrose, sodium chloride, citric acid, and quinine applied separately to each side of the anterior tongue and sampled whole mouth. Mechanical pain sensitivity was assessed separately for each side of the tongue using weighted pins. Digital photographs of participants' tongues were used to count fungiform papillae. Burning mouth syndrome cases had increased whole mouth taste intensity. Cases also had increased sensitivity to quinine on the anterior tongue, as well as increased mechanical pain sensitivity on the anterior tongue. Fungiform papillae density did not differ significantly between cases and controls. Fungiform papillae density on the left and right sides of the tongue were correlated in controls; however, there was no left/right side correlation in cases. Cases had increased pain and taste perception on the anterior tongue. The lack of correlation between left and right fungiform papillae density in cases may be an indication of asymmetrical lingual innervation in these patients. 3b. Laryngoscope, 128:841-846, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Morphofunctional structure of the lingual papillae in three species of South American Camelids: Alpaca, guanaco, and llama.

PubMed

Erdoğan, Serkan; Villar Arias, Silvia; Pérez, William

2016-02-01

The aim of this study was to compare the anatomical and functional characteristics of the lingual papilla among the Camelidae. For this purpose, tongues of alpaca, guanaco, and llama were used. Numerous long and thin filiform papillae were located in the median groove and none were detected on the rest of the dorsal surface of the lingual apex in alpaca. Secondary papillae originated from the base of some filiform papillae on the ventral surface of alpaca tongue. The bases of some filiform papillae of the lateral surface of the lingual apex were inserted into conspicuous grooves in guanaco and tips of filiform papillae on the dorsal surface of the lingual body were ended by bifurcated apex. On the dorsal surface of the lingual apex of llama, there were no filiform papillae but there were numerous filiform papillae on both the lateral margins of the ventral surface of the lingual apex. Fungiform papillae were distributed randomly on dorsal lingual surface and ventral margins of the tongues of all camelid species. Lenticular papillae were located on the lingual torus and varied in size and topographical distribution for each species. Circumvallate papillae had irregular surfaces in llama and alpaca, and smooth surface in guanaco. In conclusion, llama and alpaca tongues were more similar to each other, and tongues of all camelid species displayed more similarities to those of Bactrian and dromedary camels in comparison with other herbivores and ruminants. © 2015 Wiley Periodicals, Inc.

SIRT-1 regulates TGF-β-induced dermal fibroblast migration via modulation of Cyr61 expression.

PubMed

Kwon, Eun-Jeong; Park, Eun-Jung; Yu, Hyeran; Huh, Jung-Sik; Kim, Jinseok; Cho, Moonjae

2018-05-01

SIRT1 is a NAD-dependent protein deacetylase that participates in cellular regulation. The increased migration of fibroblasts is an important phenotype in fibroblast activation. The role of SIRT1 in cell migration remains controversial as to whether SIRT1 acts as an activator or suppressor of cell migration. Therefore, we have established the role of SIRT1 in the migration of human dermal fibroblasts and explored targets of SIRT1 during dermal fibroblast migration. SIRT1 and Cyr61 were expressed in human dermal fibroblasts and the stimulation with TGF-β further induced their expression. Treatment with resveratrol (RSV), a SIRT1 agonist, or overexpression of SIRT1 also promoted the expression Cyr61 in human dermal fibroblasts, whereas the inhibition of SIRT1 activity by nicotinamide or knockdown of SIRT1 decreased the level of Cyr61, as well as TGF-β or RSV-induced Cyr61 expression. Blocking of ERK signaling by PD98509 reduced the expression of Cyr61 induced by TGF-β or RSV. TGF-β, RSV, or SIRT1 overexpression enhanced β-catenin as well as Cyr61 expression. This stimulation was reduced by the Wnt inhibitor XAV939. RSV increased migration and nicotinamide attenuated RSV-induced migration of human dermal fibroblasts. Furthermore, SIRT1 overexpression promoted cell migration, whereas blocking Cyr61 attenuated SIRT1-stimulated migration of human dermal fibroblasts. SIRT1 increased cell migration by stimulating Cyr61 expression and the ERK and Wnt/β-catenin signaling. SIRT1-induced Cyr61 activity is very important for human dermal fibroblasts migration.

Effects of Panax ginseng extract on human dermal fibroblast proliferation and collagen synthesis.

PubMed

Lee, Geum-Young; Park, Kang-Gyun; Namgoong, Sik; Han, Seung-Kyu; Jeong, Seong-Ho; Dhong, Eun-Sang; Kim, Woo-Kyung

2016-03-01

Current studies of Panax ginseng (or Korean ginseng) have demonstrated that it has various biological effects, including angiogenesis, immunostimulation, antimicrobial and anti-inflammatory effects. Therefore, we hypothesised that P. ginseng may also play an important role in wound healing. However, few studies have been conducted on the wound-healing effects of P. ginseng. Thus, the purpose of this in vitro pilot study was to determine the effects of P. ginseng on the activities of fibroblasts, which are key wound-healing cells. Cultured human dermal fibroblasts were treated with one of six concentrations of P. ginseng: 0, 1, 10 and 100 ng/ml and 1 and 10 µg/ml. Cell proliferation was determined 3 days post-treatment using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay, and collagen synthesis was evaluated by the collagen type I carboxy-terminal propeptide method. Cell proliferation levels and collagen synthesis were compared among the groups. The 10 ng/ml to 1 µg/ml P. ginseng treatments significantly increased cell proliferation, and the 1 ng/ml to 1 µg/ml concentrations significantly increased collagen synthesis. The maximum effects for both parameters were observed at 10 ng/ml. P. ginseng stimulated human dermal fibroblast proliferation and collagen synthesis at an optimal concentration of 10 ng/ml. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Biotransformation and toxicokinetics of the insect repellent IR3535® in male and female human subjects after dermal exposure.

PubMed

Broschard, Thomas H; Bohlmann, Anja M; Konietzny, Stefan; Schauer, Ute M D; Dekant, Wolfgang

2013-04-26

The absorption and excretion of the insect repellent IR3535(®) was studied in human subjects (five males and five females) after dermal application of approx. 3g of a formulation containing 20% IR3535(®), i.e. the amounts of IR3535(®) applied were between 1.94 and 3.4 mmol/person (418-731 mg/person). Blood and urinary concentrations of IR3535(®) and its only metabolite, IR3535(®)-free acid, were determined over time. In plasma, concentrations of the parent compound IR3535(®) were at or below the limit of quantification (0.037 μmol/L). IR3535(®)-free acid peaked in plasma samples 2-6h after dermal application. Cmax mean values were 5.7 μmol/L in males, 3.0 μmol/L in females and 4.2 μmol/L in all volunteers. Mean AUC values were 41.6, 24.5 and 33.9 μmolL(-1)h in males, females and all subjects, respectively. In urine samples from all human subjects, both IR3535(®) and IR3535(®)-free acid were detectable, however, only very small amounts of IR3535(®) were found. Concentrations of IR3535(®)-free acid were several thousand-fold higher than the parent compound and peaked at the first two sampling points (4h and 8h after dermal application). Overall, IR3535(®) and IR3535(®)-free acid excreted with urine over 48 h representing 13.3 ± 3.05% of the dose applied. Since IR3535(®) is rapidly and extensively metabolized, and IR3535(®)-free acid has a low molecular weight and high water solubility, it is expected that urinary excretion of IR3535(®)-free acid and IR3535(®) represents the total extent of absorption of IR3535(®) in humans. Based on the results of this study, the skin penetration rate of IR3535(®) is 13.3% in humans after dermal application. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Merkel Cell Polyomavirus Infection of Animal Dermal Fibroblasts.

PubMed

Liu, Wei; Krump, Nathan A; MacDonald, Margo; You, Jianxin

2018-02-15

Merkel cell polyomavirus (MCPyV) is the first polyomavirus to be associated with human cancer. Mechanistic studies attempting to fully elucidate MCPyV's oncogenic mechanisms have been hampered by the lack of animal models for MCPyV infection. In this study, we examined the ability of MCPyV-GFP pseudovirus (containing a green fluorescent protein [GFP] reporter construct), MCPyV recombinant virions, and several MCPyV chimeric viruses to infect dermal fibroblasts isolated from various model animals, including mouse ( Mus musculus ), rabbit ( Oryctolagus cuniculus ), rat ( Rattus norvegicus ), chimpanzee ( Pan troglodytes ), rhesus macaque ( Macaca mulatta ), patas monkey ( Erythrocebus patas ), common woolly monkey ( Lagothrix lagotricha ), red-chested mustached tamarin ( Saguinus labiatus ), and tree shrew ( Tupaia belangeri ). We found that MCPyV-GFP pseudovirus was able to enter the dermal fibroblasts of all species tested. Chimpanzee dermal fibroblasts were the only type that supported vigorous MCPyV gene expression and viral replication, and they did so to a level beyond that of human dermal fibroblasts. We further demonstrated that both human and chimpanzee dermal fibroblasts produce infectious MCPyV virions that can successfully infect new cells. In addition, rat dermal fibroblasts supported robust MCPyV large T antigen expression after infection with an MCPyV chimeric virus in which the entire enhancer region of the MCPyV early promoter has been replaced with the simian virus 40 (SV40) analog. Our results suggest that viral transcription and/or replication events represent the major hurdle for MCPyV cross-species transmission. The capacity of rat dermal fibroblasts to support MCPyV early gene expression suggests that the rat is a candidate model organism for studying viral oncogene function during Merkel cell carcinoma (MCC) oncogenic progression. IMPORTANCE MCPyV plays an important role in the development of a highly aggressive form of skin cancer, Merkel

The polypeptide in Chlamys farreri can protect human dermal fibroblasts from ultraviolet B damage

NASA Astrophysics Data System (ADS)

Zhang, Yujiang; Zhan, Songmei; Cao, Pengli; Liu, Ning; Chen, Xuehong; Wang, Yuejun; Wang, Chunbo

2005-09-01

To investigate the effect of polypeptide from Chlamys farreri (PCF) on NHDF in vitro, we modeled oxidative damage on normal human dermal fibroblasts (NHDF) exposed to ultraviolet B (UVB). In this study, 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) were tested to measure cell viability. Enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) and xanthine oxidase (XOD) were determined biochemically. Total antioxidative capacity (T-AOC) and anti-superoxide anion capacity (A-SAC) were also determined. Ultrastructure of fibroblasts was observed under transmission electron microscope. The results showed that: UVB (1.176×10-4 J/cm2) suppressed the growth of fibroblasts and the introduction of PCF (0.25% 1%) before UVB reduced the suppression in a concentration-dependent manner. PCF could enhance the activities of SOD, GSH-PX and T-AOC as well as A-SAC. Also PCF could inhibit XOD activity, while it did not affect CAT activity. Ultrastructure of fibroblasts were damaged after UVB irradiation, concentration-dependent PCF reduced the destructive effect of UVB on cells. These results indicated that PCF can protect human dermal fibroblasts from being harmed by UVB irradiation via its antioxidant proerty.

Usefulness of Cross-Linked Human Acellular Dermal Matrix as an Implant for Dorsal Augmentation in Rhinoplasty.

PubMed

Yang, Chae Eun; Kim, Soo Jung; Kim, Ji Hee; Lee, Ju Hee; Roh, Tai Suk; Lee, Won Jai

2018-02-01

Asian noses are relatively small and flat compared to Caucasians; therefore, rhinoplasty procedures often focus on dorsal augmentation and tip projection rather than reduction in the nasal framework. Various autologous and alloplastic implant materials have been used for dorsal augmentation. Recently, human acellular dermal matrices have been introduced as an implant material for dorsal augmentation, camouflaging autologous implants without an additional donor site. Here, we introduce a cross-linked human acellular dermal matrix as an implant material in augmentation rhinoplasty and share the clinical experiences. Eighteen patients who underwent augmentation rhinoplasty using acellular dermal matrix from April 2014 to November 2015 were reviewed retrospectively. Clinical outcomes and complications were assessed at the outpatient clinic during the follow-up period ranging from 8 to 38 months. Contour changes were assessed through comparison of preoperative and postoperative photographs by two independent plastic surgeons. Patient satisfaction was assessed at the outpatient clinic by six questions regarding aesthetic and functional aspects. Postoperative photographs demonstrated the height of the nasal dorsum did not decrease over time except two patients whose ADM was grafted into a subperiosteal pocket. Others who underwent supraperiosteal implantation showed acceptable maintenance of dorsal height. No major complication was reported. Overall, patient satisfaction scored 81.02 out of 100. Cross-linked human ADM has advantages of both autogenous and alloplastic materials. The surgical results remain stable without complications. Therefore, it is a suitable alternative implant material for dorsal augmentation in rhinoplasty. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Regulation of gene expression by tobacco product preparations in cultured human dermal fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malpass, Gloria E., E-mail: gloria.malpass@gmail.com; Arimilli, Subhashini, E-mail: sarimill@wakehealth.edu; Prasad, G.L., E-mail: prasadg@rjrt.com

Skin fibroblasts comprise the first barrier of defense against wounds, and tobacco products directly contact the oral cavity. Cultured human dermal fibroblasts were exposed to smokeless tobacco extract (STE), total particulate matter (TPM) from tobacco smoke, or nicotine at concentrations comparable to those found in these extracts for 1 h or 5 h. Differences were identified in pathway-specific genes between treatments and vehicle using qRT-PCR. At 1 h, IL1α was suppressed significantly by TPM and less significantly by STE. Neither FOS nor JUN was suppressed at 1 h by tobacco products. IL8, TNFα, VCAM1, and NFκB1 were suppressed after 5more » h with STE, whereas only TNFα and NFκB1 were suppressed by TPM. At 1 h with TPM, secreted levels of IL10 and TNFα were increased. Potentially confounding effects of nicotine were exemplified by genes such as ATF3 (5 h), which was increased by nicotine but suppressed by other components of STE. Within 2 h, TPM stimulated nitric oxide production, and both STE and TPM increased reactive oxygen species. The biological significance of these findings and utilization of the gene expression changes reported herein regarding effects of the tobacco product preparations on dermal fibroblasts will require additional research. - Highlights: • Tobacco product preparations (TPPs) alter gene expression in dermal fibroblasts. • Some immediate early genes critical to the inflammatory process are affected. • Different TPPs produce differential responses in certain pro-inflammatory genes.« less

Wound healing properties of ethyl acetate fraction of Moringa oleifera in normal human dermal fibroblasts.

PubMed

Gothai, Sivapragasam; Arulselvan, Palanisamy; Tan, Woan Sean; Fakurazi, Sharida

2016-01-01

Wounds are the outcome of injuries to the skin that interrupt the soft tissue. Healing of a wound is a complex and long-drawn-out process of tissue repair and remodeling in response to injury. A large number of plants are used by folklore traditions for the treatment of cuts, wounds and burns. Moringa oleifera (MO) is an herb used as a traditional folk medicine for the treatment of various skin wounds and associated diseases. The underlying mechanisms of wound healing activity of ethyl acetate fraction of MO leaves extract are completely unknown. In the current study, ethyl acetate fraction of MO leaves was investigated for its efficacy on cell viability, proliferation and migration (wound closure rate) in human normal dermal fibroblast cells. Results revealed that lower concentration (12.5 µg/ml, 25 µg/ml, and 50 µg/ml) of ethyl acetate fraction of MO leaves showed remarkable proliferative and migratory effect on normal human dermal fibroblasts. This study suggested that ethyl acetate fraction of MO leaves might be a potential therapeutic agent for skin wound healing by promoting fibroblast proliferation and migration through increasing the wound closure rate corroborating its traditional use.

TCDD induces dermal accumulation of keratinocyte-derived matrix metalloproteinase-10 in an organotypic model of human skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Abrew, K. Nadira; Thomas-Virnig, Christina L.; Rasmussen, Cathy A.

2014-05-01

The epidermis of skin is the first line of defense against the environment. A three dimensional model of human skin was used to investigate tissue-specific phenotypes induced by the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Continuous treatment of organotypic cultures of human keratinocytes with TCDD resulted in intracellular spaces between keratinocytes of the basal and immediately suprabasal layers as well as thinning of the basement membrane, in addition to the previously reported hyperkeratinization. These tissue remodeling events were preceded temporally by changes in expression of the extracellular matrix degrading enzyme, matrix metalloproteinase-10 (MMP-10). In organotypic cultures MMP-10 mRNA and protein were highlymore » induced following TCDD treatment. Q-PCR and immunoblot results from TCDD-treated monolayer cultures, as well as indirect immunofluorescence and immunoblot analysis of TCDD-treated organotypic cultures, showed that MMP-10 was specifically contributed by the epidermal keratinocytes but not the dermal fibroblasts. Keratinocyte-derived MMP-10 protein accumulated over time in the dermal compartment of organotypic cultures. TCDD-induced epidermal phenotypes in organotypic cultures were attenuated by the keratinocyte-specific expression of tissue inhibitor of metalloproteinase-1, a known inhibitor of MMP-10. These studies suggest that MMP-10 and possibly other MMP-10-activated MMPs are responsible for the phenotypes exhibited in the basement membrane, the basal keratinocyte layer, and the cornified layer of TCDD-treated organotypic cultures. Our studies reveal a novel mechanism by which the epithelial–stromal microenvironment is altered in a tissue-specific manner thereby inducing structural and functional pathology in the interfollicular epidermis of human skin. - Highlights: • TCDD causes hyperkeratosis and basement membrane changes in a model of human skin. • TCDD induces MMP-10 expression in organotypic

Papillae alterations around single-implant restorations in the anterior maxillae: thick versus thin mucosa

PubMed Central

Si, Mi-Si; Zhuang, Long-Fei; Huang, Xin; Gu, Ying-Xin; Chou, Chung-Hao; Lai, Hong-Chang

2012-01-01

To evaluate the papilla alterations around single-implant restorations in the anterior maxillae after crown attachment and to study the influence of soft tissue thickness on the papilla fill alteration. According to the inclusion criteria, 32 patients subjected to implant-supported single-tooth restorations in anterior maxillae were included. The patients were assigned to two groups according to the mucosal thickness: (i) group 1, 1.5 mm≤mucosal thickness≤3 mm; and (ii) group 2, 3 mmpapillae at the time of crown placement (baseline) and at 6-month postloading (follow-up) were made by two prosthodontists using papilla fill index (PFI). The mean mucosal thickness was (2.49±0.31) mm (group 1) and (3.81±0.31) mm (group 2) for the two groups respectively. A significant difference in PFI between the groups was detected at the baseline (P<0.001). PFI improvements over time occurred after 6-month follow-up irrespective of the groups. When compared to group 1, the likelihood to obtain papilla fill was significantly higher for group 2 with an odds ratio of 6.05 (P<0.001). The interproximal papilla level around single-implant restorations could improve significantly over time after 6-month restoration according to PFI assessment. The thicker mucosa before implant placement implied a more favorable esthetic outcome in papilla alteration. PMID:22627613

7-Phloroeckol promotes hair growth on human follicles in vitro.

PubMed

Bak, Soon-Sun; Sung, Young Kwan; Kim, Se-Kwon

2014-08-01

7-Phloroeckol, phloroglucinol derivative isolated from marine brown algae, has anti-oxidative, anti-inflammatory responses and MMP inhibitory activities. In this study, we evaluated the hair growth-promoting effects of 7-phloroeckol in human hair follicles. To investigate cell viability of human dermal papilla cells (DPCs) and outer root sheath (ORS) cells in the presence or absence of 7-phloroeckol treatment, MTT assay was employed. Moreover, gene expression and protein concentration of insulin-like growth factor (IGF)-1 was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. 7-Phloroeckol induced an increase in proliferation of DPCs and ORS cells. In addition, hair shaft growth was measured using the hair-follicle organ culture system. 7-Phloroeckol resulted in elongation of the hair shaft in cultured human hair follicles. 7-Phloroeckol induced an IGF-1 mRNA expression and protein concentration in DPCs and conditioned media, respectively. These results suggest that 7-phloroeckol promotes hair growth through stimulation of DPCs and ORS cells.

Post-mitotic human dermal fibroblasts efficiently support the growth of human follicular keratinocytes.

PubMed

Limat, A; Hunziker, T; Boillat, C; Bayreuther, K; Noser, F

1989-05-01

For growth at low seeding densities, keratinocytes isolated from human tissues like epidermis or hair follicles are dependent on mesenchyme-derived feeder cells such as the 3T3-cell employed so far. As an alternative method, the present study describes the use of post-mitotic human dermal fibroblasts sublethally irradiated or mitomycin C-treated. Special emphasis was put on efficient growth of primary keratinocyte cultures plated at very low seeding densities. Thus, outer root sheath cells isolated from two anagen human hair follicles and plated in a 35-mm culture dish (3 - 6 X 10(2) attached cells) grew to confluence within 3 weeks (6 - 8 X 10(5) cells). Similar results were obtained for interfollicular keratinocytes. A crucial point for the function of these fibroblast feeder cells is plating at appropriate densities, considering their tremendous increase in cell size at the post-mitotic state. Plating densities of 4 - 5 X 10(3/cm2 allow full spreading of the feeder cells and do not impede the settling and expansion of the keratinocytes. Major advantages of this system include easier handling and better reproducibility than using 3T3-cells. Moreover, homologous fibroblast feeders mimic more closely the physiologic situation and therefore might provide a valuable tool for studying interactions between human mesenchymal and epithelial cells. Finally, potential hazards of using transformed feeder cells from a different species in keratinocyte cultures raised for wound covering in humans could be thus avoided.

UVA radiation impairs phenotypic and functional maturation of human dermal dendritic cells.

PubMed

Furio, Laetitia; Berthier-Vergnes, Odile; Ducarre, Blandine; Schmitt, Daniel; Peguet-Navarro, Josette

2005-11-01

There is now strong evidence that the ultraviolet A (UVA) part of the solar spectrum contributes to the development of skin cancers. Its effect on the skin immune system, however, has not been fully investigated. Here, we analyzed the effects of UVA radiation on dermal dendritic cells (DDC), which, in addition, provided further characterization of these cells. Dermal sheets were obtained from normal human skin and irradiated, or not, with UVA at 2 or 12 J per cm2. After a 2 d incubation, the phenotype of emigrant cells was analyzed by double immunostaining and flow cytometry. Results showed that migratory DDC were best characterized by CD1c expression and that only few cells co-expressed the Langerhans cell marker Langerin. Whereas the DC extracted from the dermis displayed an immature phenotype, emigrant DDC showed increased expression of HLA-DR and acquired co-stimulation and maturation markers. We showed here that UVA significantly decreased the number of viable emigrant DDC, a process related to increased apoptosis. Furthermore, UVA irradiation impaired the phenotypic and functional maturation of migrating DDC into potent antigen-presenting cells, in a concentration-dependent manner. The results provide further evidence that UVA are immunosuppressive and suggest an additional mechanism by which solar radiation impairs immune response.

Ultrastructure studies on the papillae and the nonciliated sensory receptors of adult Spirometra erinacei (Cestoda, Pseudophyllidea).

PubMed

Okino, T; Hatsushika, R

1994-01-01

The small numerous papillae on the ventral surface of the gravid proglottid of adult Spirometra erinacei were studied by scanning electron microscopy. The arrangement of clumps of papillae was recognized on the surface of the central portion around the genital atrium, with lateral clumps being located above a pair of longitudinal nerve cords and marginal ones, on both sides of the proglottid. By transmission electron microscopy, two types of nonciliated sensory receptors were observed within the papillae. The type I, single receptor was embedded within a papilla. This dome-like sensory receptor contained two electron-dense collars and four rootlets surrounded by numerous thin filaments. The type II receptor was found arranged in groups in the area between the papillae, and the apical end was exposed to the external environment. This simple, club-like sensory receptor contained electron-lucent vesicles and microtubules. We believe that the papillae play an important role in cross-insemination.

Contaminated soils (II): in vitro dermal absorption of nickel (Ni-63) and mercury (Hg-203) in human skin.

PubMed

Moody, Richard P; Joncas, Julie; Richardson, Mark; Petrovic, Sanya; Chu, Ih

2009-01-01

Dermal absorption of heavy metal soil contaminants was tested in vitro with chloride salts of radioactive nickel (Ni-63) and mercury (Hg-203). Aqueous soil suspensions, spiked with either Ni-63 or Hg-203, were applied to fresh viable human breast skin tissue in Bronaugh diffusion cells perfused with Hanks HEPES buffered (pH 7.4) receptor containing 4% bovine serum albumin (BSA). Receptor fractions were collected every 6 h for 24 h when skin was soap washed. Tests were conducted concurrently in triplicate with and without soil for each skin specimen. Mean percent dermal absorption including the skin depot for Ni-63 was 1 and 22.8% with and without soil, respectively, while for Hg-203, values of 46.6 and 78.3% were obtained. Excluding the skin depot and considering only absorption in receptor, there was 0.5 and 1.8% absorption of Ni-63 with and without soil, respectively, and 1.5 and 1.4% for Hg-203. The potential bioavailability of the skin depot is discussed in relation to dermal exposure to these metals in contaminated soil.

Development and manufacture of an investigational human living dermal equivalent (ICX-SKN).

PubMed

Flasza, Marzena; Kemp, Paul; Shering, David; Qiao, Jizeng; Marshall, Damian; Bokta, Ausha; Johnson, Penny A

2007-11-01

To design and manufacture an investigational living skin graft replacement (ICX-SKN) that is able to incorporate into the host, providing healing by primary intent without the need for a second intervention. The ICX-SKN skin graft replacement has been designed as an allogeneic dermal substitute comprising an extracellular matrix composed largely of human collagen and human dermal fibroblast cells (HDFs). ICX-SKN is first formed by casting a provisional matrix of fibrin, into which HDFs are seeded. Through a process of maturation, HDFs are induced to lay down collagen and other extracellular matrix materials and, as the construct matures, the original fibrin is largely replaced by collagen, which provides tensile strength and flexibility to the construct. In order to design a product and manufacturing system that lends itself to large-scale production the process was developed as a discontinuous process consisting of four stages: 1. batch casting and maturation of the initial construct (pSKN), 2. freeze-drying of pSKN to produce a second intermediate (dSKN), 3. sterilization by gamma-irradiation of dSKN to produce a third intermediate (sSKN), and finally, 4. repopulation of sSKN by fresh HDFs to produce the final product, ICX-SKN skin graft replacement. Preliminary characterization of ICX-SKN and its application in a preclinical model are described. The 7-week maturation period resulted in a construct (pSKN) with robust handling properties, which was composed mainly of human collagen I. Following development of a process for freeze-drying and subsequent sterilization, the matrix was successfully repopulated with fresh HDFs. In addition, it was demonstrated that human keratinocytes attached and differentiated on the matrix. Application of human keratinocytes to the repopulated constructs (ICX-SKN) resulted in expression of markers of basement membranes that was largely dependent on the presence of living HDFs on the constructs. ICX-SKN graft replacements applied to

Relationship between gustatory function and average number of taste buds per fungiform papilla measured by confocal laser scanning microscopy in humans.

PubMed

Saito, Takehisa; Ito, Tetsufumi; Ito, Yumi; Manabe, Yasuhiro; Sano, Kazuo

2017-02-01

The aim of this study was to elucidate the relationship between the gustatory function and average number of taste buds per fungiform papilla (FP) in humans. Systemically healthy volunteers (n = 211), pre-operative patients with chronic otitis media (n = 79), and postoperative patients, with or without a chorda tympani nerve (CTN) severed during middle ear surgery (n = 63), were included. Confocal laser scanning microscopy was employed to observe fungiform taste buds because it allows many FP to be observed non-invasively in a short period of time. Taste buds in an average of 10 FP in the midlateral region of the tongue were counted. In total, 3,849 FP were observed in 353 subjects. The gustatory function was measured by electrogustometry (EGM). An inverse relationship was found between the gustatory function and average number of fungiform taste buds per papilla. The healthy volunteers showed a lower EGM threshold (better gustatory function) and had more taste buds than did the patients with otitis media, and the patients with otitis media showed a lower EGM threshold and had more taste buds than did postoperative patients, reflecting the severity of damage to the CTN. It was concluded that the confocal laser scanning microscope is a very useful tool for using to observe a large number of taste buds non-invasively. © 2017 Eur J Oral Sci.

The additive effects of minoxidil and retinol on human hair growth in vitro.

PubMed

Yoo, Hyeon Gyeong; Chang, In-Young; Pyo, Hyun Keol; Kang, Yong Jung; Lee, Seung Ho; Kwon, Oh Sang; Cho, Kwang Hyun; Eun, Hee Chul; Kim, Kyu Han

2007-01-01

Minoxidil enhances hair growth by prolonging the anagen phase and induces new hair growth in androgenetic alopecia (AGA), whereas retinol significantly improves scalp skin condition and promotes hair growth. We investigated the combined effects of minoxidil and retinol on human hair growth in vitro and on cultured human dermal papilla cells (DPCs) and epidermal keratinocytes (HaCaT). The combination of minoxidil and retinol additively promoted hair growth in hair follicle organ cultures. In addition, minoxidil plus retinol more effectively elevated phosphorylated Erk, phosphorylated Akt levels, and the Bcl-2/Bax ratio than minoxidil alone in DPCs and HaCaT. We found that the significant hair shaft elongation demonstrated after minoxidil plus retinol treatment would depend on the dual kinetics associated with the activations of Erk- and Akt-dependent pathways and the prevention of apoptosis by increasing the Bcl-2/Bax ratio.

Wound healing properties of ethyl acetate fraction of Moringa oleifera in normal human dermal fibroblasts

PubMed Central

Gothai, Sivapragasam; Arulselvan, Palanisamy; Tan, Woan Sean; Fakurazi, Sharida

2016-01-01

Background/Aim: Wounds are the outcome of injuries to the skin that interrupt the soft tissue. Healing of a wound is a complex and long-drawn-out process of tissue repair and remodeling in response to injury. A large number of plants are used by folklore traditions for the treatment of cuts, wounds and burns. Moringa oleifera (MO) is an herb used as a traditional folk medicine for the treatment of various skin wounds and associated diseases. The underlying mechanisms of wound healing activity of ethyl acetate fraction of MO leaves extract are completely unknown. Materials and Methods: In the current study, ethyl acetate fraction of MO leaves was investigated for its efficacy on cell viability, proliferation and migration (wound closure rate) in human normal dermal fibroblast cells. Results: Results revealed that lower concentration (12.5 µg/ml, 25 µg/ml, and 50 µg/ml) of ethyl acetate fraction of MO leaves showed remarkable proliferative and migratory effect on normal human dermal fibroblasts. Conclusion: This study suggested that ethyl acetate fraction of MO leaves might be a potential therapeutic agent for skin wound healing by promoting fibroblast proliferation and migration through increasing the wound closure rate corroborating its traditional use. PMID:27069722

A free gingival impression for achieving optimal interdental papilla height: a case report.

PubMed

Nozawa, Takeshi; Kitami, Norikazu; Tsurumaki, Shunzo; Enomoto, Hiroaki; Ito, Koichi

2011-02-01

Failure to tend to inadequate crown contours in the crown trial can cause long-term disharmony of the free gingival form. This case report describes a novel technique for free gingival impression from a final provisional restoration to a zirconia crown. Two die casts were manufactured from a silicone impression. The first die cast was for the zirconia crown; the second die cast was for the final provisional restoration and the provisionalized transfer coping. A free gingival impression was taken using a provisionalized transfer coping, and a soft gingival model was manufactured. The proximal contact position was managed using the predicted convex curve of the interdental papillae. One year after zirconia crown placement, no inflammation was observed around the pyramidal interdental papillae, and symmetric interdental papilla heights were evident. A free gingival impression using a two die-cast technique appears to be useful for achieving optimal interdental papilla height.

Viability and Burden of Leishmania in Extralesional Sites during Human Dermal Leishmaniasis

PubMed Central

Romero, Ibeth; Téllez, Jair; Suárez, Yazmín; Cardona, Maria; Figueroa, Roger; Zelazny, Adrian; Gore Saravia, Nancy

2010-01-01

Background The clinical and epidemiological significance of Leishmania DNA in extralesional sites is obscured by uncertainty of whether the DNA derives from viable parasites. To examine dissemination of Leishmania during active disease and the potential participation of human infection in transmission, Leishmania 7SLRNA was exploited to establish viability and estimate parasite burden in extralesional sites of dermal leishmaniasis patients. Methods The feasibility of discriminating parasite viability by PCR of Leishmania 7SLRNA was evaluated in relation with luciferase activity of luc transfected intracellular amastigotes in dose-response assays of Glucantime cytotoxicity. Monocytes, tonsil swabs, aspirates of normal skin and lesions of 28 cutaneous and 2 mucocutaneous leishmaniasis patients were screened by kDNA amplification/Southern blot. Positive samples were analyzed by quantitative PCR of Leishmania 7SLRNA genes and transcripts. Results 7SLRNA amplification coincided with luciferase activity, confirming discrimination of parasite viability. Of 22 patients presenting kDNA in extralesional samples, Leishmania 7SLRNA genes or transcripts were detected in one or more kDNA positive samples in 100% and 73% of patients, respectively. Gene and transcript copy number amplified from extralesional tissues were comparable to lesions. 7SLRNA transcripts were detected in 13/19 (68%) monocyte samples, 5/12 (42%) tonsil swabs, 4/11 (36%) normal skin aspirates, and 22/25 (88%) lesions; genes were quantifiable in 15/19 (79%) monocyte samples, 12/13 (92%) tonsil swabs, 8/11 (73%) normal skin aspirates. Conclusion Viable parasites are present in extralesional sites, including blood monocytes, tonsils and normal skin of dermal leishmaniasis patients. Leishmania 7SLRNA is an informative target for clinical and epidemiologic investigations of human leishmaniasis. PMID:20856851

Maxillary anterior papilla display during smiling: a clinical study of the interdental smile line.

PubMed

Hochman, Mark N; Chu, Stephen J; Tarnow, Dennis P

2012-08-01

The purpose of this research was to quantify the visual display (presence) or lack of display (absence) of interdental papillae during maximum smiling in a patient population aged 10 to 89 years. Four hundred twenty digital single-lens reflex photographs of patients were taken and examined for the visual display of interdental papillae between the maxillary anterior teeth during maximum smiling. Three digital photographs were taken per patient from the frontal, right frontal-lateral, and left frontal-lateral views. The data set of photographs was examined by two examiners for the presence or absence of the visual display of papillae. The visual display of interdental papillae during maximum smiling occurred in 380 of the 420 patients examined in this study, equivalent to a 91% occurrence rate. Eighty-seven percent of all patients categorized as having a low gingival smile line (n = 303) were found to display the interdental papillae upon smiling. Differences were noted for individual age groups according to the decade of life as well as a trend toward decreasing papillary display with increasing age. The importance of interdental papillae display during dynamic smiling should not be left undiagnosed since it is visible in over 91% of older patients and in 87% of patients with a low gingival smile line, representing a common and important esthetic element that needs to be assessed during smile analysis of the patient.

Circumvallate papilla of dog following suture of the hypoglossal and glossopharyngeal nerves.

PubMed

State, F A

1977-01-01

20 adult dogs were classified into five groups; in two animals of each group hypoglossa-glossopharyngeal suturing was done. In the other two animals glossopharyngeal nerve transection with concomitant central segment avulsion was done and these two animals were used as controls. The animals of the five groups were sacrified at 4-week intervals starting by the first group on the 4th post-operative week and ending by the fifth group on the 20th week; the circumvallate papillae were studied. On the 4th week following either operative procedure, few taste buds persisted on the circumvallate papillae. Invasion of the papillae by regenerating hypoglossal fibres from the 8th week onwards was not followed by any appreciable increase in the number of taste buds. The difference in number of taste buds between hypoglossal-glossopharyngeal suture and glossopharyngeal avulsion procedures was not statistically significant. from the 8th weeks following cross-innervation the reaction for acetylcholinesterase was more intense than in denervated papillae which showed a persistent weakly positive reaction up to the 20th post-operative week.

Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis

PubMed Central

Watanabe, Tomoya; Mlakar, Logan; Heywood, Jonathan; Malaab, Maya; Hoffman, Stanley

2017-01-01

The murine bleomycin (BLM)-induced fibrosis model is the most widely used in systemic sclerosis (SSc) studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness. Dermal thickness and the level of collagen in skin treated with high-dose BLM was significantly higher than in skin treated with low dose BLM or vehicle. A reduction in the thickness of the adipose layer was noted in both high and low dose groups at earlier time points suggesting that the loss of the fat layer precedes the onset of fibrosis. High-dose BLM also induced dermal fibrosis and increased expression of fibrosis-associated genes ex vivo in human skin, thus confirming and extending the in vivo findings, and demonstrating that a human organ culture model can be used to assess the effect of BLM on skin. In summary, our findings suggest that the BLM pump model is an attractive model to analyze the underlying mechanisms of fibrosis and test the efficacy of potential therapies. However, the choice of mouse strain, duration of BLM administration and dose must be carefully considered when using this model. PMID:28651005

Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis.

PubMed

Watanabe, Tomoya; Nishimoto, Tetsuya; Mlakar, Logan; Heywood, Jonathan; Malaab, Maya; Hoffman, Stanley; Feghali-Bostwick, Carol

2017-01-01

The murine bleomycin (BLM)-induced fibrosis model is the most widely used in systemic sclerosis (SSc) studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness. Dermal thickness and the level of collagen in skin treated with high-dose BLM was significantly higher than in skin treated with low dose BLM or vehicle. A reduction in the thickness of the adipose layer was noted in both high and low dose groups at earlier time points suggesting that the loss of the fat layer precedes the onset of fibrosis. High-dose BLM also induced dermal fibrosis and increased expression of fibrosis-associated genes ex vivo in human skin, thus confirming and extending the in vivo findings, and demonstrating that a human organ culture model can be used to assess the effect of BLM on skin. In summary, our findings suggest that the BLM pump model is an attractive model to analyze the underlying mechanisms of fibrosis and test the efficacy of potential therapies. However, the choice of mouse strain, duration of BLM administration and dose must be carefully considered when using this model.

Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tashiro, Kanae; Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka; Shishido, Mayumi

2014-01-03

Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Westernmore » blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.« less

A COMPARATIVE INVESTIGATION OF THE INFLUENCE OF DERMAL APPENDAGES (HAIR FOLLICLES) ON THE PERCUTANEOUS ABSORPTION OF ORGANOPHOSPHORUS (OP) INSECTICIDES USING QSAR AND PBPK/PD MODELS FOR HUMAN RISK ASSESSMENT

EPA Science Inventory

The successful use of the Exposure Related Dose Estimating Model (ERDEM) for assessment of dermal exposure of humans to OP pesticides requires the input of representative and comparable input parameters. In the specific case of dermal exposure, regional anatomical variation in...

Bythaelurus bachi n. sp., a new deep-water catshark (Carcharhiniformes, Scyliorhinidae) from the southwestern Indian Ocean, with a review of Bythaelurus species and a key to their identification.

PubMed

Weigmann, Simon; Ebert, David A; Clerkin, Paul J; Stehmann, Matthias F W; Naylor, Gavin J P

2016-12-19

A new deep-water catshark, Bythaelurus bachi, is described based on 44 specimens caught on the southern Madagascar Ridge in the southwestern Indian Ocean. The new species is the only stout-bodied Bythaelurus with oral papillae in the region and is distinguished from all congeners by the plain beige to light gray-brown coloration, high diversity in dermal denticle morphology, and presence of composite oral papillae. Despite resemblance in body shape, Bythaelurus bachi n. sp. is distinguished from its closest congener, B. naylori Ebert & Clerkin, 2015, by the presence of numerous large, partially composite papillae on the tongue and roof of the mouth (vs. papillae lacking), plain light coloration (vs. medium to dark brown ground color, light fin edges and a distinctly dark dusky-colored snout), only slightly enlarged dermal denticles on the anterior upper caudal-fin margin (vs. dermal denticles distinctly enlarged), a higher diversity in dermal denticle morphology in general, and smaller maximum size and size at maturity. The distinction of both species is also supported by molecular results. The new species differs from all other congeners in the western Indian Ocean in the stout body shape of large specimens, coloration, larger size, as well as several morphometrics, including larger claspers, longer eyes and dorsal fins, and shorter pelvic-anal and pelvic-caudal spaces. The genus is reviewed, a key to its species given.

Methylparaben-induced decrease in collagen production and viability of cultured human dermal fibroblasts.

PubMed

Majewska, Natalia; Zaręba, Ilona; Surażyński, Arkadiusz; Galicka, Anna

2017-09-01

Parabens owing to their many advantageous properties are widely applied in cosmetics, food products and pharmaceuticals. However, recent research results have shown that they possess the ability to accumulate in the human body and exert many adverse effects. In this study, the impact of methylparaben (MP) as the most frequently used preservative in cosmetics, on human dermal fibroblasts and collagen production was evaluated. In cells treated with 0.01, 0.03 and 0.05% MP a dose-dependent decrease in collagen biosynthesis was revealed, which was positively correlated with the activity of prolidase responsible for the recovery of proline. Consequently, the concentration of total collagen secreted into the medium was markedly diminished. A similar reduction in expression of the major skin collagen type I at both the protein and mRNA level as well as collagen type III and VI at the mRNA level was also detected. The decrease in the collagen level may result not only from the reduced synthesis but also increased degradation owing to MP-induced activation of pro-MMP-2 (72 kDa). The increase in activity of MMP-2 (66 kDa) was accompanied by a reduction in the inhibitory activity of TIMP-2. In addition, an inhibitory effect of MP on cell survival and proliferation was revealed in this study. The increased expression and nuclear translocation of caspase-3 as well as increased Bax and decreased Bcl-2 expression may suggest MP-induced cell apoptosis. In summary, we have provided new data on the adverse effects of methylparaben on human dermal fibroblasts and the main structural protein of the skin. Further studies on the mechanisms responsible for its action are in progress. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Methamphetamine residue dermal transfer efficiencies from household surfaces.

PubMed

Van Dyke, Mike; Martyny, John W; Serrano, Kate A

2014-01-01

Methamphetamine contamination from illegal production operations poses a potential health concern for emergency responders, child protective services, law enforcement, and children living in contaminated structures. The objective of this study was to evaluate dermal transfer efficiencies of methamphetamine from contaminated household surfaces. These transfer efficiencies are lacking for methamphetamine, and would be beneficial for use in exposure models. Surfaces were contaminated using a simulated smoking method in a stainless steel chamber. Household surfaces were carpet, painted drywall, and linoleum. Dermal transfer efficiencies were obtained using cotton gloves for two hand conditions, dry or saliva moistened (wet). In addition, three contact scenarios were evaluated for both hand conditions: one, two, or three contacts with contaminated surfaces. Dermal transfer efficiencies were calculated for both hand conditions and used as inputs in a Stochastic Human Exposure and Dose Simulation model (SHEDS-Multimedia, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, N.C.). Results of this study showed that average dermal transfer efficiencies of methamphetamine ranged from 11% for dry hands to 26% for wet hands. There was a significantly higher wet transfer as compared to dry transfer for all surfaces. For wet hands, dermal transfer depended on surface type with higher transfer from carpet and linoleum as compared to drywall. Based on our estimates of dermal transfer efficiency, a surface contamination clearance level of 1.5 μg/100 cm(2) may not ensure absorbed doses remain below the level associated with adverse health effects in all cases. Additional dermal transfer studies should be performed using skin surrogates that may better predict actual skin transfer.

Papillae formation on trichome cell walls requires the function of the mediator complex subunit Med25.

PubMed

Fornero, Christy; Suo, Bangxia; Zahde, Mais; Juveland, Katelyn; Kirik, Viktor

2017-11-01

Glassy Hair 1 (GLH1) gene that promotes papillae formation on trichome cell walls was identified as a subunit of the transcriptional mediator complex MED25. The MED25 gene is shown to be expressed in trichomes. The expression of the trichome development marker genes GLABRA2 (GL2) and Ethylene Receptor2 (ETR2) is not affected in the glh1 mutant. Presented data suggest that Arabidopsis MED25 mediator component is likely involved in the transcription of genes promoting papillae deposition in trichomes. The plant cell wall plays an important role in communication, defense, organization and support. The importance of each of these functions varies by cell type. Specialized cells, such as Arabidopsis trichomes, exhibit distinct cell wall characteristics including papillae. To better understand the molecular processes important for papillae deposition on the cell wall surface, we identified the GLASSY HAIR 1 (GLH1) gene, which is necessary for papillae formation. We found that a splice-site mutation in the component of the transcriptional mediator complex MED25 gene is responsible for the near papillae-less phenotype of the glh1 mutant. The MED25 gene is expressed in trichomes. Reporters for trichome developmental marker genes GLABRA2 (GL2) and Ethylene Receptor2 (ETR2) were not affected in the glh1 mutant. Collectively, the presented results show that MED25 is necessary for papillae formation on the cell wall surface of leaf trichomes and suggest that the Arabidopsis MED25 mediator component is likely involved in the transcription of a subset of genes that promote papillae deposition in trichomes.

Topical Application of Oleuropein Induces Anagen Hair Growth in Telogen Mouse Skin

PubMed Central

Tong, Tao; Kim, Nahyun; Park, Taesun

2015-01-01

We observed that oleuropein, the main constituent of the leaves and unprocessed olive drupes of Olea europaea, protected mice from high-fat diet-induced adiposity by up-regulation of genes involved in Wnt10b-mediated signaling in adipose tissue. The activation of Wnt/β-catenin pathway is also well established to positively regulate the anagen phase of hair growth cycle in mice skin. Methodology and Principal Findings Oleuropein promoted cultured human follicle dermal papilla cell proliferation and induced LEF1 and Cyc-D1 mRNA expression and β-catenin protein expression in dermal papilla cells. Nuclear accumulation of β-catenin in dermal papilla cells was observed after oleuropein treatment. Topical application of oleuropein (0.4 mg/mouse/day) to C57BL/6N mice accelerated the hair-growth induction and increased the size of hair follicles in telogenic mouse skin. The oleuropein-treated mouse skin showed substantial upregulation of Wnt10b, FZDR1, LRP5, LEF1, Cyc-D1, IGF-1, KGF, HGF, and VEGF mRNA expression and β-catenin protein expression. Conclusions and Significance These results demonstrate that topical oleuroepin administration induced anagenic hair growth in telogenic C57BL/6N mouse skin. The hair-growth promoting effect of oleuropein in mice appeared to be associated with the stimulation of the Wnt10b/β-catenin signaling pathway and the upregulation of IGF-1, KGF, HGF, and VEGF gene expression in mouse skin tissue. PMID:26060936

Light and scanning electron microscopic study on the lingual papillae and their connective tissue cores of the Cape hyrax Procavia capensis

PubMed Central

Yoshimura, Ken; Hama, Natsuki; Shindo, Junji; Kobayashi, Kan; Kageyama, Ikuo

2008-01-01

We examined the epithelial surface and connective tissue cores (CTCs) of each lingual papilla on the Paenungulata, Cape hyrax (Procavia capensis), by scanning electron microscopy and light microscopy. The tongue consisted of a lingual apex, lingual body and lingual root. Filiform, fungiform and foliate papillae were observed on the dorsal surface of the tongue; however, fungiform papillae were quite diminished on the lingual prominence. Moreover, no clearly distinguishable vallate papillae were found on the tongue. Instead of vallate papillae, numerous dome-like large fungiform papillae were arranged in a row just in front of the rather large foliate papillae. Foliate papillae were situated in the one-third postero-lateral margin of the lingual body. The epithelium of filiform papillae was covered by a keratinized layer with kerato-hyaline granules, whereas weak keratinization was observed on the interpapillary epithelium. The external surface of the filiform papillae was conical in shape. CTCs of the filiform papillae were seen as a hood-like core with a semicircular concavity in the anterior portion of each core. Large filiform papillae were distributed on the lingual prominence. The CTCs of large filiform papillae after exfoliation of their epithelium consisted of a concave primary core and were associated with several small protrusions. The surface of fungiform papillae was smooth and dome-like. After removal of the epithelium, CTCs appeared as a flower bud-like primary core and were associated with several protrusions that were arranged on the rim of the primary core. Several taste buds were found on the top of the dorsal part of the epithelium of both fungiform and large fungiform papillae. Well-developed foliate papillae were seen and numerous taste buds could be observed in the lateral wall of the epithelium in a slit-like groove. The morphological characteristics of the tongue of the Cape hyrax had similarities with other Paenungulata such as Sirenia

Human macrophage ATP7A is localized in the trans-Golgi apparatus, controls intracellular copper levels, and mediates macrophage responses to dermal wounds.

PubMed

Kim, Ha Won; Chan, Qilin; Afton, Scott E; Caruso, Joseph A; Lai, Barry; Weintraub, Neal L; Qin, Zhenyu

2012-02-01

The copper transporter ATP7A has attracted significant attention since the discovery of its gene mutation leading to human Menkes disease. We previously reported that ATP7A is highly expressed in the human vasculature and identified a novel vascular function of ATP7A in modulation of the expression and activity of extracellular superoxide dismutase. We recently identified that ATP7A expression in THP-1 cells (a monocyte/macrophage model cell line) plays a role in the oxidation of low density lipoproteins, indicating that it is necessary to further investigate its expression and function in monocytes/macrophages. In the current study, we demonstrated the protein and mRNA expression of ATP7A in human peripheral blood mononuclear cell (PBMC)-derived macrophages and alveolar macrophages. ATP7A was strongly co-localized with the trans-Golgi apparatus in PBMC-derived macrophages. Intracellular copper, detected by synchrotron X-ray fluorescence microscopy, was found to be distributed to the nucleus and cytoplasm in human THP-1 cells. To confirm the role of endogenous ATP7A in macrophage copper homeostasis, we performed inductively coupled plasma mass spectrometry in murine peritoneal macrophages, which showed markedly increased intracellular copper levels in macrophages isolated from ATP7A-deficient mice versus control mice. Moreover, the role of ATP7A in regulating macrophage responses to dermal wounds was studied by introduction of control and ATP7A-downregulated THP-1 cells into dermal wounds of nude mice. Infiltration of THP-1 cells into the wounded area (detected by expression of human macrophage markers MAC2 and CD68) was reduced in response to downregulation of ATP7A, hinting decreased macrophage accumulation subsequent to dermal wounds. In summary, alongside our previous studies, these findings indicate that human macrophage ATP7A is localized in the trans-Golgi apparatus, regulates intracellular copper levels, and mediates macrophage responses to a dermal wound.

Levels of bisphenol-A in different paper products in Guangzhou, China, and assessment of human exposure via dermal contact.

PubMed

Fan, Ruifang; Zeng, Biyan; Liu, Xiaosu; Chen, Chao; Zhuang, Qinwei; Wang, Yongjun; Hu, Mingli; Lv, Yanshan; Li, Junnan; Zhou, Yuanxiu; Lin, Zhi Yuan William

2015-03-01

Bisphenol A (BPA) is a chemical widely used both in plastics production as a food and beverage container and in thermal papers as a color developer. Dietary consumption is the main route of human exposure to BPA, but dermal absorption through handling different papers might be underestimated or ignored. In this study, BPA in different paper products, including different types of papers, receipts and Chinese currencies, were investigated. BPA was detected in receipts (n = 87) and Chinese currencies (n = 46) with concentrations of 0.17-2.675 × 10(4) μg per g paper and 0.09-288.55 μg per g paper, respectively. Except for parchment papers (n = 3), copy papers (n = 3) and food contact papers (n = 3), BPA was measured in all of the other paper products, with levels of 0.01-6.67 μg per g paper. BPA transferred from thermal papers to common papers increased with the increasing contact pressure. Compared with that in water, the migration speed of BPA was doubled in the synthetic sweat. Washing hands could reduce BPA dermal exposure, and washing hands with lotion was the most efficient way. However, about 19-47% of BPA was still found on hands after different washing methods. Dermal absorption via handling of receipts and papers was estimated to be 36.45 ng per day for the general population and 1.54 × 10(-3) to 248.73 μg per day for a cashier. These values are below the maximum doses recommended by the U.S. Environmental Protection Agency and the European Food Safety Authority. However, due to its uncertain adverse effects on human beings, long-term BPA exposure through dermal absorption should be paid more attention, particularly for some occupational populations.

23-Hydroxytormentic acid protects human dermal fibroblasts by attenuating UVA-induced oxidative stress.

PubMed

Youn, Hae Jeong; Kim, Ki Bbeum; Han, Hyo-Sun; An, In-Sook; Ahn, Kyu Joong

2017-03-01

Ultraviolet A (UVA), one of the major components of sunlight, can penetrate the dermal layer of the skin and generate reactive oxygen species (ROS). It causes alterations in the dermal connective tissue and gene expression, inflammation, photoaging, and DNA damage. Therefore, the harmful effects of UVA and strategies to reduce it have been consistently investigated. 23-Hydroxytormentic acid (23-HTA) has been demonstrated to improve drug-induced nephrotoxicity and exhibit several free radical scavenging effects with other molecules. Therefore, the aim of this study was to investigate the anti-inflammatory effects and extracellular matrix (ECM) reconstructive activity of 23-HTA in UVA-irradiated normal human dermal fibroblasts (NHDFs). The antioxidant capacity of 23-HTA was determined by examining its scavenging activities against hydrogen peroxide, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and diphenylpicrylhydrazyl in vitro. Its effect on cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium bromide, and 2,7-dichlorofluorescin diacetate was used to investigate intracellular ROS scavenging activity. The mRNA levels of antioxidant enzymes and pro-inflammatory cytokines were detected using quantitative real-time polymerase chain reaction. A senescence-associated β-galactosidase (SA-β-gal) staining kit was used to assess senescent cells. 23-HTA showed antioxidant capacity mediated by ROS scavenging and regulation of antioxidant-related gene expression. Further, the SA-β-gal analysis and mRNA expression of matrix metalloproteinases and type I procollagen suggested that 23-HTA regulates the gene expression of ECM proteins and cellular senescence under UVA-irradiated conditions. In conclusion, 23-HTA protects against and attenuates UVA-induced oxidative stress in NHDFs likely via the nuclear factor erythroid-derived 2-like 2 signaling pathway. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

DERMAL, ORAL, AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

EPA Science Inventory

Methyl tertiary butyl ether (MTBE), a gasoline additive, used to increase octane and reduce carbon monoxide emissions and ozone precursors has contaminated drinking water leading to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation ki...

Synthetic ligands of the elastin receptor induce elastogenesis in human dermal fibroblasts via activation of their IGF-1 receptors.

PubMed

Qa'aty, Nour; Vincent, Matthew; Wang, Yanting; Wang, Andrew; Mitts, Thomas F; Hinek, Aleksander

2015-12-01

We have previously reported that a mixture of peptides obtained after chemical or enzymatic degradation of bovine elastin, induced new elastogenesis in human skin. Now, we investigated the elastogenic potential of synthetic peptides mimicking the elastin-derived, VGVAPG sequence, IGVAPG sequence that we found in the rice bran, and a similar peptide, VGVTAG that we identified in the IGF-1-binding protein-1 (IGFBP-1). We now demonstrate that treatment with each of these xGVxxG peptides (recognizable by the anti-elastin antibody), up-regulated the levels of elastin-encoding mRNA, tropoelastin protein, and the deposition of new elastic fibers in cultures of human dermal fibroblasts and in cultured explants of human skin. Importantly, we found that such induction of new elastogenesis may involve two parallel signaling pathways triggered after activation of IGF-1 receptor. In the first one, the xGVxxG peptides interact with the cell surface elastin receptor, thereby causing the downstream activation of the c-Src kinase and a consequent cross-activation of the adjacent IGF-1R, even in the absence of its principal ligand. In the second pathway their hydrophobic association with the N-terminal domain (VGVTAG) of the serum-derived IGFBP-1 induces conformational changes of this IGF-1 chaperone allowing for the release of its cargo and a consequent ligand-specific phosphorylation of IGF-1R. We present a novel, clinically relevant mechanism in which products of partial degradation of dermal elastin may stimulate production of new elastic fibers by dermal fibroblasts. Our findings particularly encourage the use of biologically safe synthetic xGVxxG peptides for regeneration of the injured or aged human skin. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The microstructure of lingual papillae in the Egyptian fruit bat (Rousettus aegyptiacus) as observed by light microscopy and scanning electron microscopy.

PubMed

Jackowiak, Hanna; Trzcielińska-Lorych, Joanna; Godynicki, Szymon

2009-03-01

The microstructure of lingual papillae on the dorsal surface of the tongue of adult Egyptian fruit bats was examined by light microscopy (LM) and scanning electron microscopy (SEM). This elongated tongue with a rounded apex is approximately 3 cm long -- including the 1.7cm length of the anterior free part of the tongue -- which facilitates considerable freedom of movement. The surface of the tongue has four types of lingual papillae: two types of mechanical papillae -- filiform and conical papillae, and two types of gustatory papillae -- fungiform and vallate papillae. Most numerous are filiform papillae with well developed keratinized processes represented by four morphological subtypes -- small, giant, elongated, and bifid papillae. Our observations showed the small and giant filiform papillae to be present in the anterior part of the tongue and tilted to the back of the tongue. In the posterior part of the tongue, the filiform papillae with elongated processes were arranged on each side of the tongue and oriented perpendicularly to the median line of tongue. This arrangement of filiform papillae is considered to be useful for the efficient uptake of semiliquid food as it can be collected toward the median line of the tongue. Gustatory fungiform papillae were distributed among filiform papillae on the border of the apex and the anterior part of the body of the tongue and also on the posterior part of the tongue, while three vallate papillae surrounded by conical papillae were found on the root of the tongue. There were also taste buds along the ducts of the posterior lingual glands in the posterior-lateral part of the tongue. These morphological features are discussed in relation to adaptation to food uptake in the Egyptian fruit bat.

DERMAL, ORAL AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY-BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

EPA Science Inventory

Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhal...

A review of critical factors for assessing the dermal absorption of metal oxide nanoparticles from sunscreens applied to humans, and a research strategy to address current deficiencies.

PubMed

Gulson, Brian; McCall, Maxine J; Bowman, Diana M; Pinheiro, Teresa

2015-11-01

Metal oxide nanoparticles in sunscreens provide broad-spectrum ultraviolet protection to skin. All studies to assess dermal penetration of nanoparticles have unanimously concluded that the overwhelming majority of nanoparticles remain on the outer surface of the skin. However, possibly due to many different experimental protocols in use, conclusions over the potential penetration to viable skin are mixed. Here, we review several factors that may influence experimental results for dermal penetration including the species studied (human, or animal model), size and coating of the metal oxide nanoparticles, composition of the sunscreen formulation, site of sunscreen application, dose and number of applications, duration of the study, types of biological samples analysed, methods for analysing samples, exposure to UV and skin flexing. Based on this information, we suggest an appropriate research agenda involving international collaboration that maximises the potential for dermal absorption of nanoparticles, and their detection, under normal conditions of sunscreen use by humans. If results from this research agenda indicate no absorption is observed, then concerns over adverse health effects from the dermal absorption of nanoparticles in sunscreens may be allayed.

Aedes aegypti Rhesus glycoproteins contribute to ammonia excretion by larval anal papillae.

PubMed

Durant, Andrea C; Chasiotis, Helen; Misyura, Lidiya; Donini, Andrew

2017-02-15

In larval Aedes aegypti , transcripts of the Rhesus-like glycoproteins AeRh50-1 and AeRh50-2 have been detected in the anal papillae, sites of ammonia (NH 3 /NH 4 + ) excretion; however, these putative ammonia transporters have not been previously localized or functionally characterized. In this study, we show that the AeRh50s co-immunolocalize with apical V-type H + -ATPase as well as with basal Na + /K + -ATPase in the epithelium of anal papillae. The double-stranded RNA-mediated knockdown of AeRh50-1 and AeRh50-2 resulted in a significant reduction in AeRh50 protein abundance in the anal papillae, and this was coupled to decreased ammonia excretion. The knockdown of AeRh50-1 resulted in decreased hemolymph [NH 4 + ] and pH whereas knockdown of AeRh50-2 had no effect on these parameters. We conclude that the AeRh50s are important contributors to ammonia excretion at the anal papillae of larval A. aegypti , which may be the basis for their ability to inhabit areas with high ammonia levels. © 2017. Published by The Company of Biologists Ltd.

Morphological study of the lingual papillae of the giant panda (Ailuropoda melanoleuca) by scanning electron microscopy

PubMed Central

Pastor, J F; Barbosa, M; De Paz, F J

2008-01-01

Due to the scarcity of giant pandas, there are few descriptions of their morphology and even fewer of their microscopic anatomy and the ultrastructure of their organs. In this study of the complete tongue of an adult male giant panda, we describe the morphology of its lingual surface, the different types of papillae, their characteristics and topographic distribution. It was seen that there are four main types of lingual papillae: filiform, conical, fungiform and vallate. There was no sign of foliate papillae, tuberculum intermolare or sublingua. Papilla distribution was not limited to the dorsum of the tongue, but was also seen on the anterior and ventral surfaces of the tongue. In the anterior third of the midline there is a smooth area with no papillae at all. Morphology of the microgrooves and pores is similar to that observed in other mammals. The papillae share characteristics encountered in Carnivora and herbivorous species of mammals. A narrow bamboo-based diet and specialized manner of eating have together resulted in modification of the tongue of a carnivoran, giving it some characteristics typical of an herbivore. PMID:18254792

Regulation of gene expression by tobacco product preparations in cultured human dermal fibroblasts

PubMed Central

Malpass, Gloria E.; Arimilli, Subhashini; Prasad, G. L.; Howlett, Allyn C.

2015-01-01

Skin fibroblasts comprise the first barrier of defense against wounds, and tobacco products directly contact the oral cavity. Cultured human dermal fibroblasts were exposed to smokeless tobacco extract (STE), total particulate matter (TPM) from tobacco smoke, or nicotine at concentrations comparable to those found in these extracts for 1 h or 5 h. Differences were identified in pathway-specific genes between treatments and vehicle using qRT-PCR. At 1 h, IL1α was suppressed significantly by TPM and less significantly by STE. Neither FOS nor JUN was suppressed at 1 h by tobacco products. IL8, TNFα, VCAM1, and NFκB1 were suppressed after 5 h with STE, whereas only TNFα and NFκB1 were suppressed by TPM. At 1 h with TPM, secreted levels of IL10 and TNFα were increased. Potentially confounding effects of nicotine were exemplified by genes such as ATF3 (5 h), which was increased by nicotine but suppressed by other components of STE. Within 2 h, TPM stimulated nitric oxide production, and both STE and TPM increased reactive oxygen species. The biological significance of these findings and utilization of the gene expression changes reported herein regarding effects of the tobacco product preparations on dermal fibroblasts will require additional research. PMID:24927667

Assessment of the in vitro dermal irritation potential of cerium, silver, and titanium nanoparticles in a human skin equivalent model

EPA Science Inventory

AbstractDermal exposure to metals may res·ult in irritant contact dermatitis. This study examined the potential of metal nanoparticles to elicit irritant contact dermatitis in a human skin equivalent model (HSEM) derived from epidermal keratinocytes. These cultured cells form a m...

Homogeneous Inflammatory Gene Profiles Induced in Human Dermal Fibroblasts in Response to the Three Main Species of Borrelia burgdorferi sensu lato

PubMed Central

Meddeb, Mariam; Carpentier, Wassila; Cagnard, Nicolas; Nadaud, Sophie; Grillon, Antoine; Barthel, Cathy; De Martino, Sylvie Josiane; Jaulhac, Benoît; Boulanger, Nathalie

2016-01-01

In Lyme borreliosis, the skin is the key site for bacterial inoculation by the infected tick and for cutaneous manifestations. We previously showed that different strains of Borrelia burgdorferi sensu stricto isolated from tick and from different clinical stages of the Lyme borreliosis (erythema migrans, and acrodermatitis chronica atrophicans) elicited a very similar transcriptional response in normal human dermal fibroblasts. In this study, using whole transcriptome microarray chips, we aimed to compare the transcriptional response of normal human dermal fibroblasts stimulated by 3 Borrelia burgdorferi sensu lato strains belonging to 3 main pathogenic species (B. afzelii, B. garinii and B. burgdorferi sensu stricto) in order to determine whether “species-related” inflammatory pathways could be identified. The three Borrelia strains tested exhibited similar transcriptional profiles, and no species-specific fingerprint of transcriptional changes in fibroblasts was observed. Conversely, a common core of chemokines/cytokines (CCL2, CXCL1, CXCL2, CXCL6, CXCL10, IL-6, IL-8) and interferon-related genes was stimulated by all the 3 strains. Dermal fibroblasts appear to play a key role in the cutaneous infection with Borrelia, inducing a homogeneous inflammatory response, whichever Borrelia species was involved. PMID:27706261

UVB-Induced Senescence of Human Dermal Fibroblasts Involves Impairment of Proteasome and Enhanced Autophagic Activity.

PubMed

Cavinato, Maria; Koziel, Rafal; Romani, Nikolaus; Weinmüllner, Regina; Jenewein, Brigitte; Hermann, Martin; Dubrac, Sandrine; Ratzinger, Gudrun; Grillari, Johannes; Schmuth, Matthias; Jansen-Dürr, Pidder

2017-05-01

In the current study, we have extended previous findings aiming at a better understanding of molecular mechanisms underlying UVB-induced senescence of diploid human dermal fibroblasts (HDFs), an experimental model to study the process of photoaging in the skin. We provide evidence that the inhibition of proteasomal degradation of damaged proteins and the activation of autophagosome formation are early events in UVB-induced senescence of HDFs, dependent on UVB-induced accumulation of reactive oxygen species. Our data suggest that autophagy is required for the establishment of the senescent phenotype in UVB-treated HDFs and that inhibition of autophagy is sufficient to change the cell fate from senescence to cell death by apoptosis. Studies in reconstructed skin equivalents revealed that UVB irradiation triggers hallmarks of autophagy induction in the dermal layer. These findings have potential implications for fundamental as well as translational research into skin aging, in particular photoaging. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of plant sterols derived from Aloe vera gel on human dermal fibroblasts in vitro and on skin condition in Japanese women.

PubMed

Tanaka, Miyuki; Misawa, Eriko; Yamauchi, Koji; Abe, Fumiaki; Ishizaki, Chiaki

2015-01-01

Aloe is known for its topical use for treating wounds and burns. Many previous studies reported the healing effects of Aloe vera. However, there are few clinical studies on the effect of orally administered A. vera gel on the skin. Aloe sterols are a type of plant sterols that have the capability to regulate the metabolism of glucose and lipids. In a recent study, we confirmed that ingested Aloe sterols reached the peripheral tissues through the bloodstream. However, their influence on dermal fibroblasts has not been investigated. First, we investigated the capability of Aloe sterols (cycloartenol and lophenol) to stimulate human dermal fibroblasts in vitro. Then, we investigated the effect of intake of Aloe vera gel powder (AVGP) containing 40 μg Aloe sterols on the skin conditions in Japanese women with dry skin in a randomized, double-blind, placebo-controlled trial. After cocultivation with Aloe sterols, the production of collagen and hyaluronic acid increased by approximately two-fold and 1.5-fold, and gene expression levels of these enzymes responsible for their synthesis were also observed in human dermal fibroblasts. An increase in arm skin hydration was observed at 8 weeks in the AVGP group, whereas a slight decrease in arm skin hydration was noted in the placebo group. However, there was no statistical difference between AVGP and placebo groups in skin moisture. In subgroup analysis, the change in the mean wrinkle depth was significantly lower in the AVGP group than in the control group. In addition, percent body fat after 8 weeks was significantly lower in the AVGP group. No AVGP intake-dependent harmful phenomenon was observed during the intake period. The present study confirms that daily oral Aloe sterol-containing AVGP significantly reduced facial wrinkles in women aged ≥40 years, and Aloe sterols stimulate collagen and hyaluronic acid production by human dermal fibroblasts.

Simultaneous and multi-point measurement of ammonia emanating from human skin surface for the estimation of whole body dermal emission rate.

PubMed

Furukawa, Shota; Sekine, Yoshika; Kimura, Keita; Umezawa, Kazuo; Asai, Satomi; Miyachi, Hayato

2017-05-15

Ammonia is one of the members of odor gases and a possible source of odor in indoor environment. However, little has been known on the actual emission rate of ammonia from the human skin surface. Then, this study aimed to estimate the whole-body dermal emission rate of ammonia by simultaneous and multi-point measurement of emission fluxes of ammonia employing a passive flux sampler - ion chromatography system. Firstly, the emission fluxes of ammonia were non-invasively measured for ten volunteers at 13 sampling positions set in 13 anatomical regions classified by Kurazumi et al. The measured emission fluxes were then converted to partial emission rates using the surface body areas estimated by weights and heights of volunteers and partial rates of 13 body regions. Subsequent summation of the partial emission rates provided the whole body dermal emission rate of ammonia. The results ranged from 2.9 to 12mgh -1 with an average of 5.9±3.2mgh -1 per person for the ten healthy young volunteers. The values were much greater than those from human breath, and thus the dermal emission of ammonia was found more significant odor source than the breath exhalation in indoor environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Efferent innervation to the auditory basilar papilla of scincid lizards.

PubMed

Wibowo, Erik; Brockhausen, Jennifer; Köppl, Christine

2009-09-01

Hair cells of the inner ear of vertebrates are innervated by afferent neurons that transmit sensory information to the brain as well as efferent neurons that receive feedback from the brainstem. The function of the efferent feedback system is poorly understood and may have changed during evolution when different tetrapod groups acquired sensitivity to airborne sound and extended their hearing ranges to higher frequencies. Lizards show a unique subdivision of their basilar papilla (homologous to the mammalian organ of Corti) into a low-frequency (<1 kHz) and a high-frequency (approximately 1-5 kHz) region. The high-frequency region was reported to have lost its efferent innervation, suggesting it was insignificant or even functionally detrimental at higher frequencies. We re-examined the innervation to the basilar papilla of five species of Australian scincid lizards, by using immunohistochemistry. Anti-choline acetyltransferase (ChAT) was used as an efferent marker. Co-localization with anti-synaptic vesicle protein 2 confirmed the synaptic identity of label. Cholinergic terminals were observed along the whole length of the basilar papilla, including the regions that had previously been described as devoid of efferent innervation. However, there was a clear decrease in terminal density from apical, low-frequency to basal, high-frequency locations. Our findings suggest that efferent innervation is a general feature of the hair cells in the basilar papilla of lizards, irrespective of tonotopic location. This re-enforces the notion that efferent feedback control of hair cells is a fundamental and important property of all vertebrate hearing organs. (c) 2009 Wiley-Liss, Inc.

Dermal in vitro penetration of methiocarb, paclobutrazol, and pirimicarb: effect of nonylphenolethoxylate and protective gloves.

PubMed Central

Nielsen, J B; Andersen, H R

2001-01-01

Dermal exposure has become the major route of human occupational exposure to pesticides. Detergents are used as part of formulated pesticide products and are known to change the barrier properties of human skin in vitro. However, studies on the influence of detergents as well as protective glove materials on dermal penetration of pesticides are scarce. In an experiment using in vitro static diffusion cells mounted with human skin, we evaluated the effect of nonylphenol-ethoxylate on dermal penetration of three extensively used pesticides--methiocarb, paclobutrazol, and pirimicarb--and the protection against dermal penetration offered by protective gloves made of latex or nitrile. There was a general tendency, though not statistically significant for all pesticides, for nonylphenolethoxylate to decrease the percutaneous penetration of the three pesticides. The nitrile generally offered better protection against percutaneous penetration of pesticides than did latex, but the degree of protection decreased over time and depended on the pesticides used. PMID:11266321

Augmentation of Interdental Papilla with Platelet-rich Fibrin

PubMed Central

Ahila, E; Saravana Kumar, R; Reddy, Vineela Katam; Pratebha, B; Jananni, M; Priyadharshini, V

2018-01-01

Background: Dental esthetics has become a great concern for both dental practitioners and patients in addition to maintaining oral health. The presence of interproximal papillae between the maxillary anterior teeth is a key esthetic component. Recession of interdental papilla leads to various functional problems such as food impaction, phonetics and esthetic problems such as the formation of black triangle which poses a great challenge. Aim: This study aims to evaluate the augmentation of interdental papilla with platelet-rich fibrin. Materials and Methods: A total of 25 sites from systemically healthy individuals with papillary recession (Nordland and Tarnow class 1 and 2) were recruited in the study. Han and Takei procedure was planned and augmentation was done with platelet-rich fibrin. Various parameters such as distance from the tip of the contact point to the gingival margin, width of the keratinized gingiva, and Jemt score were measured at baseline, 3 and 6 months postoperatively. Healing index was measured at the 1st, 2nd, and 3rd week postoperatively. Results: Data collected were statistically analyzed. Mean value of distance from the contact point to the gingival margin was 4.38 mm at baseline and at 6-month postoperatively, it reduced to 0.36 mm. There was an increase in width of the keratinized gingiva which was clinically and statistically significant. Other parameters such as healing index, Jemt score, and visual analog scale (aesthetics) were also statistically significant postoperatively.

Characterization of vibrissa germinative cells: transition of cell types.

PubMed

Osada, A; Kobayashi, K

2001-12-01

Germinative cells, small cell masses attached to the stalks of dermal papillae that are able to differentiate into the hair shaft and inner root sheath, form follicular bulb-like structures when co-cultured with dermal papilla cells. We studied the growth characteristics of germinative cells to determine the cell types in the vibrissa germinative tissue. Germinative tissues, attaching to dermal papillae, were cultured on 3T3 feeder layers. The cultured keratinocytes were harvested and transferred, equally and for two passages, onto lined dermal papilla cells (LDPC) and/or 3T3 feeder layers. The resulting germinative cells were classified into three types in the present experimental condition. Type 1 cells grow very well on either feeder layer, whereas Type 3 cells scarcely grow on either feeder layer. Type 2 cells are very conspicuous and are reversible. They grow well on 3T3 but growth is suppressed on LDPC feeder layers. The Type 2 cells that grow well on 3T3 feeder layers, however, are suppressed when transferred onto LDPC and the Type 2 cells that are suppressed on LDPC begin to grow again on 3T3. The transition of one cell type to another in vitro and the cell types that these germinative cell types correspond to in vivo is discussed. It was concluded that stem cells or their close progenitors reside in the germinative tissues of the vibrissa bulb except at late anagen-early catagen.

Alterations of papilla dimensions after orthodontic closure of the maxillary midline diastema: a retrospective longitudinal study.

PubMed

Jeong, Jin-Seok; Lee, Seung-Youp; Chang, Moontaek

2016-06-01

The aim of this study was to evaluate alterations of papilla dimensions after orthodontic closure of the diastema between maxillary central incisors. Sixty patients who had a visible diastema between maxillary central incisors that had been closed by orthodontic approximation were selected for this study. Various papilla dimensions were assessed on clinical photographs and study models before the orthodontic treatment and at the follow-up examination after closure of the diastema. Influences of the variables assessed before orthodontic treatment on the alterations of papilla height (PH) and papilla base thickness (PBT) were evaluated by univariate regression analysis. To analyze potential influences of the 3-dimensional papilla dimensions before orthodontic treatment on the alterations of PH and PBT, a multiple regression model was formulated including the 3-dimensional papilla dimensions as predictor variables. On average, PH decreased by 0.80 mm and PBT increased after orthodontic closure of the diastema (P<0.01). Univariate regression analysis revealed that the PH (P=0.002) and PBT (P=0.047) before orthodontic treatment influenced the alteration of PH. With respect to the alteration of PBT, the diastema width (P=0.045) and PBT (P=0.000) were found to be influential factors. PBT before the orthodontic treatment significantly influenced the alteration of PBT in the multiple regression model. PH decreased but PBT increased after orthodontic closure of the diastema. The papilla dimensions before orthodontic treatment influenced the alterations of PH and PBT after closure of the diastema. The PBT increased more when the diastema width before the orthodontic treatment was larger.

Endoscopic minor papilla balloon dilation for the treatment of symptomatic pancreas divisum.

PubMed

Yamamoto, Natsuyo; Isayama, Hiroyuki; Sasahira, Naoki; Tsujino, Takeshi; Nakai, Yousuke; Miyabayashi, Koji; Mizuno, Suguru; Kogure, Hirofumi; Sasaki, Takashi; Hirano, Kenji; Tada, Minoru; Koike, Kazuhiko

2014-08-01

A subpopulation of patients with pancreas divisum experience symptomatic events such as recurrent acute pancreatitis and chronic pancreatitis. Minor papilla sphincterotomy has been reported as being an effective treatment. The aim of this study was to evaluate the safety and efficacy of endoscopic balloon dilation for the minor papilla. Between 2000 and 2012, 16 patients were retrospectively included in this study. After endoscopic balloon dilation for the minor papilla was received, a pancreatic stent or a nasal pancreatic drainage catheter was placed for 1 week. If a stricture or obstruction was evident, it was treated with balloon dilation followed by long-term stent placement (1 year). When an outflow of pancreatic juice was disturbed by a pancreatic stone, endoscopic stone extraction was performed. Balloon dilation and stent placement were achieved and were successful in all the cases (16/16; 100%). Clinical improvement was achieved in 7 (84.7%) of the 9 patients with recurrent acute pancreatitis and in 6 (85.7%) of the 7 patients with chronic pancreatitis. Early complications were observed in 1 (6.3%) patient. Pancreatitis or bleeding related to balloon dilation was not observed. Endoscopic balloon dilation for the minor papilla is feasible for the management of symptomatic pancreas divisum.

Lidocaine Impairs Proliferative and Biosynthetic Functions of Aged Human Dermal Fibroblasts.

PubMed

Bentov, Itay; Damodarasamy, Mamatha; Spiekerman, Charles; Reed, May J

2016-09-01

The aged are at increased risk of postoperative wound healing complications. Because local anesthetics are infiltrated commonly into the dermis of surgical wounds, we sought to determine whether local anesthetics adversely affect proliferative and biosynthetic functions of dermal fibroblasts. We also evaluated the effect of local anesthetics on insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1), growth factors that are important regulators of wound healing. Human dermal fibroblasts (HFB) from aged and young donors were exposed to local anesthetic agents at clinically relevant concentrations. We screened the effects of lidocaine, bupivacaine, mepivacaine, and ropivacaine on proliferation of HFB. Lidocaine was most detrimental to proliferation in HFB. We then evaluated the effect of lidocaine on expression and function of the growth factors, IGF-1 and TGF-β1. Lastly, concurrent exposure to lidocaine and IGF-1 or TGF-β1 was evaluated for their effects on proliferation and expression of dermal collagens, respectively. Lidocaine and mepivacaine inhibited proliferation in aged HFB (for lidocaine 88% of control, 95% confidence interval [CI], 80%-98%, P = .009 and for mepivacaine 90% of control, 95% CI, 81%-99%, P = .032) but not in young HFB. Ropivacaine and bupivacaine did not inhibit proliferation. Because of the clinical utility of lidocaine relative to mepivacaine, we focused on lidocaine. Lidocaine decreased proliferation in aged HFB, which was abrogated by IGF-1. Lidocaine inhibited transcripts for IGF-1 and insulin-like growth factor-1 receptor (IGF1R) in fibroblasts from aged donors (IGF-1, log2 fold-change -1.25 [42% of control, 95% CI, 19%-92%, P = .035] and IGF1R, log2 fold-change -1.00 [50% of control, 95% CI, 31%-81%, P = .014]). In contrast, lidocaine did not affect the expression of IGF-1 or IGF1R transcripts in the young HFB. Transcripts for collagen III were decreased after lidocaine exposure in aged and young HFB (log2

[In vitro tendon engineering using human dermal fibroblasts].

PubMed

Deng, Dan; Liu, Wei; Xu, Feng; Wu, Xiao-Li; Wei, Xian; Zhong, Bin; Cui, Lei; Cao, Yi-Lin

2008-04-01

To examine the feasibility of using human dermal fibroblasts (DFbs) and polyglycolic acids (PGA) to engineer tendon in vitro. Human dermal fibroblasts (DFbs) were isolated from the foreskin tissues of children obtained during operation with collagenase and cultured in vitro. Human tendon was obtained from a patient undergoing amputation during operation to isolate tenocytes. The DFbs of second passage were seeded on PGA fibers to form cell-scaffold constructs in shape of tendons. Those constructs were divided into 4 groups: experimental group (n = 15) with the DFbs inoculated on PGA scaffold under constant tension generated by a U-shaped spring, control group 1 (n = 15) with the DFbs inoculated on PGA scaffold without tension, control group 2 (n = 3), i. e., cell-free pure PGA scaffolds under tension, and control group 3 (n = 5), i. e., tenocyte-scaffold constructs under tension that was harvested only at the ninth week. Samples were harvested 2, 5, 9, 14, and 18 weeks later to undergo histological examination and biomechanical test. Two weeks later histological examination showed that the constructs were mainly composed of PGA fibers in both the experimental group and the group without tension. Transmission electron microscopy showed fine cell attachment and stretching on the scaffold. By the 5th week, a neo-tendon was formed in all groups except for the cell-free group, and histology revealed the formation of collagen fibers. At the 9th week, the PGA fibers of the cell-free group were broken and partially degraded, the neo-tendon's diameter of the experimental group was (1.18 +/- 0.25) mm, significantly thinner than that of the group without tension[ (2.43 +/- 0.49) mm, P = 0.017]. The gross morphology of tendons of the experimental group and tenocyte group were similar to each other except for more cells in the experimental group. In experimental group, immunohistochemistry revealed the production of fibers of collagen type I & III that were aligned

A new system for cultivation of human keratinocytes on acellular dermal matrix substitute with the use of human fibroblast feeder layer.

PubMed

Xiao, S; Zhu, S; Ma, B; Xia, Z-F; Yang, J; Wang, G

2008-01-01

To improve the proliferative potential of human keratinocytes (HK) cultured on acellular dermal matrix (ADM), HK and mitomycin C-treated human fibroblasts (MMC-HF) were seeded onto ADM to form four types of composite skin: type I, HK were seeded onto the epidermal side of ADM; type II, both HK and MMC-HF were seeded onto the epidermal side; type III, MMC-HF were preseeded onto the dermal side of ADM, and then HK were seeded onto the epidermal side, and type IV, where MMC-HF were preseeded onto both sides, and then HK were seeded onto the epidermal side. Compared with type I and III, the proliferative potential of HK of type II and IV was significantly higher on day 3, 5, 7 and 9 in vitro. In type I and III, HK grew into one layer on day 7-9, while in type II and IV keratinocytes grew into a confluent monolayer by day 4-6. The adherence to ADM of HK in types II and IV was stronger than that in type I and III. The take rate of type II and IV composite skin was also significantly higher. In conclusion, when MMC-HF and HK were cocultured on the epidermal side of ADM, MMC-HF could serve as excellent feeder cells. Copyright 2007 S. Karger AG, Basel.

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

PubMed

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

A comparison of human and porcine acellularized dermis: interactions with human fibroblasts in vitro.

PubMed

Armour, Alexis D; Fish, Joel S; Woodhouse, Kimberly A; Semple, John L

2006-03-01

Dermal substitutes derived from xenograft materials require elaborate processing at a considerable cost. Acellularized porcine dermis is a readily available material associated with minimal immunogenicity. The objective of this study was to evaluate acellularized pig dermis as a scaffold for human fibroblasts. In vitro methods were used to evaluate fibroblast adherence, proliferation, and migration on pig acellularized dermal matrix. Acellular human dermis was used as a control. Pig acellularized dermal matrix was found to be inferior to human acellularized dermal matrix as a scaffold for human fibroblasts. Significantly more samples of human acellularized dermal matrix (83 percent, n = 24; p < 0.05) demonstrated fibroblast infiltration below the cell-seeded surface than pig acellularized dermal matrix (31 percent, n = 49). Significantly more (p < 0.05) fibroblasts infiltrated below the surface of human acellularized dermal matrix (mean, 1072 +/- 80 cells per section; n = 16 samples) than pig acellularized dermal matrix (mean, 301 +/- 48 cells per section; n = 16 samples). Fibroblasts migrated significantly less (p < 0.05) distance from the cell-seeded pig acellularized dermal matrix surface than in the human acellularized dermal matrix (78.8 percent versus 38.3 percent cells within 150 mum from the surface, respectively; n = 5). Fibroblasts proliferated more rapidly (p < 0.05) on pig acellularized dermal matrix (n = 9) than on the human acellularized dermal matrix (7.4-fold increase in cell number versus 1.8-fold increase, respectively; n = 9 for human acellularized dermal matrix). There was no difference between the two materials with respect to fibroblast adherence (8120 versus 7436 average adherent cells per section, for pig and human acellularized dermal matrix, respectively; n = 20 in each group; p > 0.05). Preliminary findings suggest that substantial differences may exist between human fibroblast behavior in cell-matrix interactions of porcine and human

Estimation of intake and uptake of bisphenols and triclosan from personal care products by dermal contact.

PubMed

Lu, Shaoyou; Yu, Yuling; Ren, Lu; Zhang, Xiaolan; Liu, Guihua; Yu, Yingxin

2018-04-15

Increasing concern has been raised in respect of exposure to bisphenols and triclosan (TCS) due to their widespread use. However, little is known about their occurrence in personal care products (PCPs) or, particularly, their dermal uptake following daily application. It is therefore necessary to evaluate the human health risk of bisphenols and TCS via dermal absorption. In this study, 150 PCPs, covering 11 different categories, were collected in China. The concentrations of seven bisphenol analogues and TCS were measured, and the associated human health risks by dermal contact were estimated. High detection frequencies of TCS (46.7%) and bisphenol AF (38.7%) were found in the PCPs. The highest mean concentration of Σ 7 BPs (sum concentration of all seven bisphenols) was 77.8ngg -1 found in masks, and the highest mean concentration of TCS was 86.7ngg -1 in hand sanitizers. The bisphenol composition profiles varied among different categories. Bisphenol A and bisphenol F generally showed higher concentrations. Combining the concentrations of the target substances with the daily usage quantities of PCPs and other parameters, the total estimated dermal intakes and uptakes of Σ 7 BPs and TCS were calculated. The results showed that the former (12.1 and 1.06ng·kg -1 bw day -1 ) were markedly higher than the latter (1.21 and 9.58×10 -2 ng·kg -1 bw day -1 ), which included dermal absorption rates of the chemicals in the estimation. Although diet is the main source, and oral ingestion is the main route, for human BPA exposure, the results of the estimated dermal uptakes of BPA in the present study combined with those from a European study show that dermal contact is the main route with thermal paper being the main contributor when both unconjugated and conjugated BPA in the human body are considered. The present study also showed that exposure to BPA in PCPs following dermal contact should not be ignored. Copyright © 2017 Elsevier B.V. All rights reserved.

WDR1 Presence in the Songbird Basilar Papilla

PubMed Central

Adler, Henry J.; Sanovich, Elena; Brittan-Powell, Elizabeth F.; Yan, Kai; Dooling, Robert J.

2009-01-01

WD40 repeat 1 protein (WDR1) was first reported in the acoustically injured chicken inner ear, and bioinformatics revealed that WDR1 has numerous WD40 repeats, important for protein-protein interactions. It has significant homology to actin interacting protein 1 (Aip1) in several lower species such as yeast, roundworm, fruitfly and frog. Several studies have shown that Aip1 binds cofilin/actin depolymerizing factor, and that these interactions are pivotal for actin disassembly via actin filament severing and actin monomer capping. However, the role of WDR1 in auditory function has yet to be determined. WDR1 is typically restricted to hair cells of the normal avian basilar papilla, but is redistributed towards supporting cells after acoustic overstimulation, suggesting that WDR1 may be involved in inner ear response to noise stress. One aim of the present study was to resolve the question as to whether stress factors, other than intense sound, could induce changes in WDR1 presence in the affected avian inner ear. Several techniques were used to assess WDR1 presence in the inner ears of songbird strains, including Belgian Waterslager (BW) canary, an avian strain with degenerative hearing loss thought to have a genetic basis. Reverse transcription, followed by polymerase chain reactions with WDR1-specific primers, confirmed WDR1 presence in the basilar papillae of adult BW, non-BW canaries, and zebra finches. Confocal microscopy examinations, following immunocytochemistry with anti-WDR1 antibody, localized WDR1 to the hair cell cytoplasm along the avian sensory epithelium. In addition, little, if any, staining by anti-WDR1 antibody was observed among supporting cells in the chicken or songbird ear. The present observations confirm and extend the early findings of WDR1 localization in hair cells, but not in supporting cells, in the normal avian basilar papilla. However, unlike supporting cells in the acoustically damaged chicken basilar papilla, the inner ear of the BW

Alterations of papilla dimensions after orthodontic closure of the maxillary midline diastema: a retrospective longitudinal study

PubMed Central

2016-01-01

Purpose The aim of this study was to evaluate alterations of papilla dimensions after orthodontic closure of the diastema between maxillary central incisors. Methods Sixty patients who had a visible diastema between maxillary central incisors that had been closed by orthodontic approximation were selected for this study. Various papilla dimensions were assessed on clinical photographs and study models before the orthodontic treatment and at the follow-up examination after closure of the diastema. Influences of the variables assessed before orthodontic treatment on the alterations of papilla height (PH) and papilla base thickness (PBT) were evaluated by univariate regression analysis. To analyze potential influences of the 3-dimensional papilla dimensions before orthodontic treatment on the alterations of PH and PBT, a multiple regression model was formulated including the 3-dimensional papilla dimensions as predictor variables. Results On average, PH decreased by 0.80 mm and PBT increased after orthodontic closure of the diastema (P<0.01). Univariate regression analysis revealed that the PH (P=0.002) and PBT (P=0.047) before orthodontic treatment influenced the alteration of PH. With respect to the alteration of PBT, the diastema width (P=0.045) and PBT (P=0.000) were found to be influential factors. PBT before the orthodontic treatment significantly influenced the alteration of PBT in the multiple regression model. Conclusions PH decreased but PBT increased after orthodontic closure of the diastema. The papilla dimensions before orthodontic treatment influenced the alterations of PH and PBT after closure of the diastema. The PBT increased more when the diastema width before the orthodontic treatment was larger. PMID:27382507

Laser-induced transepidermal elimination of dermal content by fractional photothermolysis

NASA Astrophysics Data System (ADS)

Hantash, Basil M.; Bedi, Vikramaditya P.; Sudireddy, Vasanthi; Struck, Steven K.; Herron, G. Scott; Chan, Kin Foong

2006-07-01

The wound healing process in skin is studied in human subjects treated with fractional photothermolysis. In-vivo histological evaluation of vacuoles formed over microthermal zones (MTZs) and their content is undertaken. A 30-W, 1550-nm single-mode fiber laser system delivers an array of 60 µm or 140 µm 1/e2 incidence microbeam spot size at variable pulse energy and density. Treatments span from 6 to 20 mJ with skin excisions performed 1-day post-treatment. Staining with hematoxylin and eosin demonstrates an intact stratum corneum with vacuolar formation within the epidermis. The re-epithelialization process with repopulation of melanocytes and keratinocytes at the basal layer is apparent by 1-day post-treatment. The dermal-epidermal (DE) junction is weakened and separated just above zones of dermal coagulation. Complete loss of dermal cell viability is noted within the confines of the MTZs 1-day post-treatment, as assessed by lactate dehydrogenase. All cells falling outside the irradiation field remain viable. Content within the epidermal vacuoles stain positively with Gomori trichrome, suggesting a dermal origin. However, the positive staining could be due to loss of specificity after thermal alteration. Nevertheless, this dermal extrusion hypothesis is supported by very specific positive staining with an antihuman elastin antibody. Fractional photothermolysis creates microthermal lesions that allow transport and extrusion of dermal content through a compromised DE junction. Some dermal material is incorporated into the microepidermal necrotic debris and shuttled up the epidermis to eventually be exfoliated through the stratum corneum. This is the first report of a nonablative laser-induced transport mechanism by which dermal content can be predictably extruded biologically through the epidermis. Thus, treatment with the 1550-nm fiber laser may provide the first therapeutic option for clinical indications, including pigmentary disorders such as medically

Light and scanning electron microscopic study on the structure of the lingual papillae of the feathertail glider (Acrobates pygmeus, Burramyidae, Marsupialia).

PubMed

Jackowiak, Hanna; Godynicki, Szymon

2007-11-01

The structure of the tongue of the marsupial feathertail glider (Acrobates pygmeus) was observed under a light and scanning electron microscope. The elongated tongue with a sharpened apex is ca. 10 mm in length. Only the posterior half of the tongue is attached to the bottom of the oral cavity by the frenulum, which facilitates considerable mobility of the anterior free part of the tongue. On the dorsal surface of the tongue, three types of lingual papillae were distinguished, that is, mechanical filiform papillae and gustatory fungiform and vallate papillae. The arrangement, shape, and size of filiform papillae and the direction of their keratinized processes change depending on the part of the tongue, so that the surface of the apex and the body of the tongue resembles a brush adapted to effective holding of semiliquid food and collection of pollen. The fungiform papillae have a single taste bud and are uniformly scattered between filiform papillae only on the anterior half of the tongue. On the smooth root of the tongue, three oval vallate papillae are arranged in the form of a triangle, similarly as it is the case in other marsupials. The posterior biggest vallate papilla is oriented perpendicularly to the smaller anterior papillae. The results of the study on the feathertail glider show that the special arrangement of lingual papillae is strongly adapted to feeding behavior of this nectar-eating and frugivorous animal. Copyright 2007 Wiley-Liss, Inc.

Diversity of form in the amphibian papilla of Puerto Rican frogs

NASA Technical Reports Server (NTRS)

Lewis, E. R.; Hecht, E. I.; Narins, P. M.

1992-01-01

In modern frogs, the amphibian papilla exhibits a caudal extension whose shape, relative length, and proportion of hair cells vary markedly from species to species. Tuning in the caudal extension is organized tonotopically and evidently involves the tectorium. In terms of the proportion of amphibian-papillar hair cells in the caudal extension, we report more diversity among 8 species of a single genus (Eleutherodactylus) on a single island (Puerto Rico) than has been found so far among all of the (more than 50) other modern anurans examined for this feature from around the world. These 8 Puerto Rican species have overlapping habitat and conspicuous diversity in the male advertisement call. For 7 of the 8 species, we report that the call has transient spectral components in the frequency range of the amphibian papilla, and that the proportion of caudal extension hair cells and the frequency distribution of those components are correlated. Thus one might conclude that the selective pressures that led to diversity of calls among the 8 species also led to diversity in form of the amphibian papilla.

Hair-Loss Preventing Effect of Grateloupia elliptica

PubMed Central

Kang, Jung-Il; Kim, Sang-Cheol; Han, Sang-Chul; Hong, Hye-Jin; Jeon, You-Jin; Kim, Bora; Koh, Young-Sang; Yoo, Eun-Sook; Kang, Hee-Kyoung

2012-01-01

This study was conducted to evaluate the effect of Grateloupia elliptica, a seaweed native to Jeju Island, Korea, on the prevention of hair loss. When immortalized rat vibrissa dermal papilla cells were treated with extract of G. elliptica, the proliferation of dermal papilla cells significantly increased. In addition, the G. elliptica extract significantly inhibited the activity of 5α-reductase, which converts testosterone to dihydrotestosterone (DHT), a main cause of androgenetic alopecia. On the other hand, the G. elliptica extract promoted PGE2 production in HaCaT cells in a dose-dependent manner. The G. elliptica extract exhibited particularly high inhibitory effect on LPS-stimulated IL-12, IL-6, and TNF-α production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. The G. elliptica extract also showed inhibitory activity against Pityrosporum ovale, a main cause of dandruff. These results suggest that G. elliptica extract has the potential to treat alopecia via the proliferation of dermal papilla, 5α-reductase inhibition, increase of PGE2 production, decrease of LPS-stimulated pro-inflammatory cytokines and inhibitory activity against Pityrosporum ovale. PMID:24116284

Confocal laser-scanning microscopy of capillaries in normal and psoriatic skin

NASA Astrophysics Data System (ADS)

Archid, Rami; Patzelt, Alexa; Lange-Asschenfeldt, Bernhard; Ahmad, Sufian S.; Ulrich, Martina; Stockfleth, Eggert; Philipp, Sandra; Sterry, Wolfram; Lademann, Juergen

2012-10-01

An important and most likely active role in the pathogenesis of psoriasis has been attributed to changes in cutaneous blood vessels. The purpose of this study was to use confocal laser-scanning microscopy (CLSM) to investigate dermal capillaries in psoriatic and normal skin. The structures of the capillary loops in 5 healthy participants were compared with those in affected skin of 13 psoriasis patients. The diameters of the capillaries and papillae were measured for each group with CLSM. All investigated psoriasis patients showed elongated, widened, and tortuous microvessels in the papillary dermis, whereas all healthy controls showed a single capillary loop in each dermal papilla. The capillaries of the papillary loop and the dermal papilla were significantly enlarged in the psoriatic skin lesions (diameters 24.39±2.34 and 146.46±28.52 μm, respectively) in comparison to healthy skin (diameters 9.53±1.8 and 69.48±17.16 μm, respectively) (P<0.001). CLSM appears to represent a promising noninvasive technique for evaluating dermal capillaries in patients with psoriasis. The diameter of the vessels could be seen as a well-quantifiable indicator for the state of psoriatic skin. CLSM could be useful for therapeutic monitoring to delay possible recurrences.

Effects of plant sterols derived from Aloe vera gel on human dermal fibroblasts in vitro and on skin condition in Japanese women

PubMed Central

Tanaka, Miyuki; Misawa, Eriko; Yamauchi, Koji; Abe, Fumiaki; Ishizaki, Chiaki

2015-01-01

Background Aloe is known for its topical use for treating wounds and burns. Many previous studies reported the healing effects of Aloe vera. However, there are few clinical studies on the effect of orally administered A. vera gel on the skin. Aloe sterols are a type of plant sterols that have the capability to regulate the metabolism of glucose and lipids. In a recent study, we confirmed that ingested Aloe sterols reached the peripheral tissues through the bloodstream. However, their influence on dermal fibroblasts has not been investigated. Methods First, we investigated the capability of Aloe sterols (cycloartenol and lophenol) to stimulate human dermal fibroblasts in vitro. Then, we investigated the effect of intake of Aloe vera gel powder (AVGP) containing 40 μg Aloe sterols on the skin conditions in Japanese women with dry skin in a randomized, double-blind, placebo-controlled trial. Results After cocultivation with Aloe sterols, the production of collagen and hyaluronic acid increased by approximately two-fold and 1.5-fold, and gene expression levels of these enzymes responsible for their synthesis were also observed in human dermal fibroblasts. An increase in arm skin hydration was observed at 8 weeks in the AVGP group, whereas a slight decrease in arm skin hydration was noted in the placebo group. However, there was no statistical difference between AVGP and placebo groups in skin moisture. In subgroup analysis, the change in the mean wrinkle depth was significantly lower in the AVGP group than in the control group. In addition, percent body fat after 8 weeks was significantly lower in the AVGP group. No AVGP intake-dependent harmful phenomenon was observed during the intake period. Conclusion The present study confirms that daily oral Aloe sterol-containing AVGP significantly reduced facial wrinkles in women aged ≥40 years, and Aloe sterols stimulate collagen and hyaluronic acid production by human dermal fibroblasts. PMID:25759593

Lidocaine impairs proliferative and biosynthetic functions of aged human dermal fibroblasts

PubMed Central

Bentov, Itay; Damodarasamy, Mamatha; Spiekerman, Charles; Reed, May J

2016-01-01

Background The aged are at increased risk of postoperative wound healing complications. Since local anesthetics are commonly infiltrated into the dermis of surgical wounds, we sought to determine if local anesthetics adversely affect proliferative and biosynthetic functions of dermal fibroblasts. We also evaluated the effect of local anesthetics on IGF-1 and TGF-ß1, growth factors that are important regulators of wound healing. Methods Human dermal fibroblasts from aged and young donors (HFB) were exposed to local anesthetic agents at clinically relevant concentrations. We screened the effects of lidocaine, bupivacaine, mepivacaine and ropivacaine on proliferation of HFB. Lidocaine was the most detrimental to proliferation in HFB. We then evaluated the effect of lidocaine on expression and function of the growth factors, IGF-1 and TGF-ß1. Lastly, concurrent exposure to lidocaine and IGF-1 or TGF-ß1 were evaluated for their effects on proliferation and expression of dermal collagens, respectively. Results Lidocaine and mepivacaine inhibited proliferation in aged HFB (for lidocaine 88% of control, 95%CI 80%-98%, p=0.009 and for mepivacaine 90% of control, 95%CI 81%-99%, p=0.032), but not in young HFB. Ropivicaine and bupivicaine did not inhibit proliferation. Due to the clinical utility of lidocaine relative to mepivicaine, we focused on lidocaine. Lidocaine decreased proliferation in aged HFB, which was abrogated by IGF-1. Lidocaine inhibited transcripts for IGF-1 and IGF1R in fibroblasts from aged donors (IGF-1, log2 fold-change −1.25 {42% of control, 95%CI 19%-92%, p=0.035} and IGF1R, log2 fold-change of −1.00 {50% of control, 95%CI 31%-81%, p=0.014}). In contrast, lidocaine did not effect the expression of IGF-1 or IGF1R transcripts in the young HFB. Transcripts for collagen III were decreased after lidocaine exposure in aged and young HFB (log2 fold-change −1.28 {41% of control, 95%CI 20%-83%, p=0.022} in aged HFB and log2 fold-change −1.60 {33% of

Investigation of the effect of hydration on dermal collagen in ex vivo human skin tissue using second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Samatham, Ravikant; Wang, Nicholas K.; Jacques, Steven L.

2016-02-01

Effect of hydration on the dermal collagen structure in human skin was investigated using second harmonic generation microscopy. Dog ears from the Mohs micrographic surgery department were procured for the study. Skin samples with subject aged between 58-90 years old were used in the study. Three dimensional Multiphoton (Two-photon and backward SHG) control data was acquired from the skin samples. After the control measurement, the skin tissue was either soaked in deionized water for 2 hours (Hydration) or kept at room temperature for 2 hours (Desiccation), and SHG data was acquired. The data was normalized for changes in laser power and detector gain. The collagen signal per unit volume from the dermis was calculated. The desiccated skin tissue gave higher backward SHG compared to respective control tissue, while hydration sample gave a lower backward SHG. The collagen signal decreased with increase in hydration of the dermal collagen. Hydration affected the packing of the collagen fibrils causing a change in the backward SHG signal. In this study, the use of multiphoton microscopy to study the effect of hydration on dermal structure was demonstrated in ex vivo tissue.

Development of a high-throughput screening system for identification of novel reagents regulating DNA damage in human dermal fibroblasts.

PubMed

Bae, Seunghee; An, In-Sook; An, Sungkwan

2015-09-01

Ultraviolet (UV) radiation is a major inducer of skin aging and accumulated exposure to UV radiation increases DNA damage in skin cells, including dermal fibroblasts. In the present study, we developed a novel DNA repair regulating material discovery (DREAM) system for the high-throughput screening and identification of putative materials regulating DNA repair in skin cells. First, we established a modified lentivirus expressing the luciferase and hypoxanthine phosphoribosyl transferase (HPRT) genes. Then, human dermal fibroblast WS-1 cells were infected with the modified lentivirus and selected with puromycin to establish cells that stably expressed luciferase and HPRT (DREAM-F cells). The first step in the DREAM protocol was a 96-well-based screening procedure, involving the analysis of cell viability and luciferase activity after pretreatment of DREAM-F cells with reagents of interest and post-treatment with UVB radiation, and vice versa. In the second step, we validated certain effective reagents identified in the first step by analyzing the cell cycle, evaluating cell death, and performing HPRT-DNA sequencing in DREAM-F cells treated with these reagents and UVB. This DREAM system is scalable and forms a time-saving high-throughput screening system for identifying novel anti-photoaging reagents regulating DNA damage in dermal fibroblasts.

[Technologies for hair reconstruction and their applicability for pharmaceutical research].

PubMed

Matsuzaki, Takashi

2008-01-01

Hair follicles are the organs that produce hair shafts. They periodically regenerate throughout the life of the organisms, which is called the hair cycle. To develop new drugs to treat hair disorders and diseases, reproducible and high throughput assays or screening methods have been required to estimate the efficacy of various factors on hair follicle function. Although organ culture of hair follicles is one of the useful ways to carry out such research, it is not suitable for manipulating the genes or cells present in hair follicles. Patch assay is a method used to reconstruct hair follicles from enzymatically dissociated skin cells and has many advantages compared to the conventional Chamber method. Using the Patch method, transferring genes into follicular cells becomes easier than ever before. Chimeric follicles could be produced with dissociated cells by modifying the combination of cells or by simply merging cells of different origins. These applications certainly help the progress of hair research. However, we recently found that some functions of dermal papillae and follicular epithelia change during the growing phase (anagen) of the hair cycle. Dermal papillae produce different factors in early anagen and mid anagen. The signals from dermal papillae in early anagen could produce hair bulbs with clonogenic epithelial precursors but not with dormant epithelial precursors. On the other hand, the signals from dermal papillae in mid anagen strongly promote hair formation with dormant epithelial precursors. Therefore, more attention should be given to the hair cycle stages when using organ culture of hair follicles and conducting reconstruction experiments with follicularly derived cells.

A prototypic mathematical model of the human hair cycle.

PubMed

Al-Nuaimi, Yusur; Goodfellow, Marc; Paus, Ralf; Baier, Gerold

2012-10-07

The human hair cycle is a complex, dynamic organ-transformation process during which the hair follicle repetitively progresses from a growth phase (anagen) to a rapid apoptosis-driven involution (catagen) and finally a relative quiescent phase (telogen) before returning to anagen. At present no theory satisfactorily explains the origin of the hair cycle rhythm. Based on experimental evidence we propose a prototypic model that focuses on the dynamics of hair matrix keratinocytes. We argue that a plausible feedback-control structure between two key compartments (matrix keratinocytes and dermal papilla) leads to dynamic instabilities in the population dynamics resulting in rhythmic hair growth. The underlying oscillation consists of an autonomous switching between two quasi-steady states. Additional features of the model, namely bistability and excitability, lead to new hypotheses about the impact of interventions on hair growth. We show how in silico testing may facilitate testing of candidate hair growth modulatory agents in human HF organ culture or in clinical trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

Perilla frutescens leaves extract ameliorates ultraviolet radiation-induced extracellular matrix damage in human dermal fibroblasts and hairless mice skin.

PubMed

Bae, Jung-Soo; Han, Mira; Shin, Hee Soon; Kim, Min-Kyoung; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

2017-01-04

Perilla frutescens (L.) Britt. (Lamiaceae) is a traditional herb that is consumed in East Asian countries as a traditional medicine. This traditional herb has been documented for centuries to treat various diseases such as depression, allergies, inflammation and asthma. However, the effect of Perilla frutescens on skin has not been characterized well. The present study aimed to investigate the effect of Perilla frutescens leaves extract (PLE) on ultraviolet radiation-induced extracellular matrix damage in human dermal fibroblasts and hairless mice skin. Human dermal fibroblasts and Skh-1 hairless mice were irradiated with UV and treated with PLE. Protein and mRNA levels of various target molecules were analyzed by western blotting and quantitative RT-PCR, respectively. Histological changes of mouse skin were analyzed by H&E staining. To elucidate underlying mechanism of PLE, activator protein-1 (AP-1) DNA binding assay and the measurement of reactive oxygen species (ROS) were performed. PLE significantly inhibited basal and UV-induced MMP-1 and MMP-3 expression dose-dependently, and also decreased UV-induced phosphorylation of extracellular signal-regulated kinases and c-Jun N-terminal kinases. This inhibitory effects of PLE on MMP-1 and MMP-3 were mediated by reduction of ROS generation and AP-1 DNA binding activity induced by UV. Furthermore, PLE promoted type I procollagen production irrespective of UV irradiation. In the UV-irradiated animal model, PLE significantly reduced epidermal skin thickness and MMP-13 expression induced by UV. Our results demonstrate that PLE has the protective effect against UV-induced dermal matrix damage. Therefore, we suggest that PLE can be a potential agent for prevention of skin aging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison of interleukin 10 homologs on dermal wound healing using a novel human skin ex vivo organ culture model

PubMed Central

Balaji, Swathi; Moles, Chad M.; Bhattacharya, Sukanta S.; LeSaint, Maria; Dhamija, Yashu; Le, Louis D.; King, Alice; Kidd, Mykia; Bouso, Muhammad F.; Shaaban, Aimen; Crombleholme, Timothy M.; Bollyky, Paul; Keswani, Sundeep G.

2015-01-01

Background Anti-inflammatory cytokine interleukin (IL)-10 has been shown to induce regenerative healing in postnatal wounds. A viral homolog of IL-10 produced by human cytomegalovirus (CMV IL-10) similarly generates potent immunoregulatory effects, but its effects on wound healing have not been investigated. Currently, there are limited cost-effective methods of screening vulnerary therapeutics. Taken together, we aim to develop and validate a novel human ex vivo dermal wound model and hypothesize that CMV IL-10 will enhance dermal wound healing. Methods Full-thickness circular (6-mm) explants were taken from surgical skin samples and 3-mm full-thickness wounds were created. Explants were embedded in collagen I matrix and maintained in specially formulated media with the epidermis at air–liquid interface, and treated with human IL-10 or CMV IL-10 (200 ng/mL). The viability of cultured explants was validated by histology and lactate dehydrogenase (LDH) activity. Epithelial gap, epithelial height, basal keratinocyte migration, vascular endothelial growth factor levels, and neovascularization were measured at days 3 and 7 to determine IL-10 effects on wound healing. Results Culture explants at day 7 appeared similar to fresh skin in morphology, cell, and vessel density. By day 14, the epidermis separated from the dermis and the cell density diminished. Day 7 wounds appeared viable with advancing epithelial and basal keratinocyte migration with no evidence of necrosis. Cytotoxicity analysis via the quantification of LDH revealed no differences between controls and treated groups. There was a slight increase in the quantity of LDH in media at day 3; however, this decreased at day 5 and continued to decline up to day 21. CMV IL-10 treatment resulted in a significant decrease in the epithelial gap and an increase in epithelial height. There were no differences in the rates of basal keratinocyte migration at day 7 between treated and control groups. Interestingly, human

Leiomyomatous hamartoma of the incisive papilla.

PubMed

Corrêa, L; Lotufo, M; Martins, M T; Sugaya, N; de Sousa, S C

2001-01-01

A case of unusual hamartoma in a six-year-old otherwise healthy Brazilian girl is reported, with emphasis on histological and immunohistochemical features. A mass observed in the incisive papilla was detected whose appearance was similar to congenital epulis or fibroma. Histological findings showed interlacing fascicles of large spindle cells resembling smooth muscle cells. Immunohistochemical staining for desmin and for smooth-muscle actin was positive. The histological diagnosis was leiomyomatous hamartoma, based on clinical and microscopic observations.

Comparison between two different methods for evaluating rumen papillae measures related to different diets.

PubMed

Scocco, Paola; Brusaferro, Andrea; Catorci, Andrea

2012-07-01

Although the Geographical Information System (GIS), which integrates computerized drawing computer assisted design (CAD) and relational databases (data base management system (DBMS)), is best known for applications in geographical and planning cartography, it can also use many kinds of information concerning the territory. A multidisciplinary project was initiated since 5 years a multidisciplinary study was initiated to use GIS to integrate environmental and ecological data with findings on animal health, ethology, and anatomy. This study is chiefly aimed at comparing two different methods for measuring the absorptive surface of rumen papillae. To this scope, 21 female sheep (Ovis aries) on different alimentary regimes (e.g., milk and forage mixed diet, early herbaceous diet, dry hay diet, and fresh hay diet at the maximum of pasture flowering and at the maximum of pasture dryness) were used; after slaughtering, 20 papillae were randomly removed from each sample collected from four indicator regions of rumen wall, placed near a metric reference and digitally photographed. The images were developed with the ArcGIS™ software to calculate the area of rumen papillae by means of GIS and to measure their mid-level width and length to calculate the papillae area as previously performed with a different method. Spatial measurements were analyzed using univariate and multivariate methods. This work demonstrates that the GIS methodology can be efficiently used for measuring the absorptive surface of rumen papillae. In addition, GIS demonstrated to be a rapid, precise, and objective tool when compared with previously used method. Copyright © 2012 Wiley Periodicals, Inc.

Cannulation method for intra-diverticular papilla with long oral protrusion using biopsy forceps for axis alignment.

PubMed

Takenaka, Mamoru; Minaga, Kosuke; Kudo, Masatoshi

2018-06-22

Intra-diverticular papilla is considered as a difficult anatomical orientation for biliary cannulation. 1 2 3 To our knowledge, this is the first report to show the usefulness of biopsy forceps for cannulation not only to expose the ampulla in the case of an intra-diverticular papilla but also for axis alignment.An 85-year-old woman underwent endoscopic retrograde cholangiopancreatography for a common bile duct (CBD) stone. A duodenoscope (TJF TYPE 260V; Olympus Medical Systems, Tokyo, Japan) was inserted into Vater's papilla. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Fluorine-induced apoptosis and lipid peroxidation in human hair follicles in vitro.

PubMed

Wang, Zheng-hui; Li, Xiao-li; Yang, Zhuang-qun; Xu, Min

2010-12-01

Fluoride is an essential trace element for human body; however, exposure to high amounts of fluoride has been documented to be correlated with an increasing risk of hair loss. To date, little is known about the mechanism(s) of how fluoride affects hair follicles. Here, we demonstrated that middle (1.0 mmol/L) and high (10.0 mmol/L) concentrations of sodium fluoride (NaF) significantly inhibited hair follicle elongation in vitro, but low NaF (0.1 mmol/L) showed little influence. Moreover, treatment with high levels of NaF resulted in a marked increase in terminal dUTP nick end labeling-positive cells in the outer layer of the outer root sheath, the dermal sheath, and the lower bulb matrix surrounding dermal papilla. Furthermore, the enhanced apoptosis was coupled with an increased oxidative stress manifested as higher malondialdehyde content. Additionally, the presence of selenium considerably antagonized the effects of middle NaF on hair follicles, with regard to either the suppression of hair growth or the induction of oxidative stress and apoptosis. In conclusion, exposure to high levels of fluoride compromises hair follicle growth and accelerate cell apoptosis in vitro. The toxicity of fluoride can be reduced by selenium, at least partially via the suppression of intracellular oxidative stress.

Redox-active cerium oxide nanoparticles protect human dermal fibroblasts from PQ-induced damage.

PubMed

von Montfort, Claudia; Alili, Lirija; Teuber-Hanselmann, Sarah; Brenneisen, Peter

2015-01-01

Recently, it has been published that cerium (Ce) oxide nanoparticles (CNP; nanoceria) are able to downregulate tumor invasion in cancer cell lines. Redox-active CNP exhibit both selective pro-oxidative and antioxidative properties, the first being responsible for impairment of tumor growth and invasion. A non-toxic and even protective effect of CNP in human dermal fibroblasts (HDF) has already been observed. However, the effect on important parameters such as cell death, proliferation and redox state of the cells needs further clarification. Here, we present that nanoceria prevent HDF from reactive oxygen species (ROS)-induced cell death and stimulate proliferation due to the antioxidative property of these particles. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

[Penile augmentation using acellular dermal matrix].

PubMed

Zhang, Jin-ming; Cui, Yong-yan; Pan, Shu-juan; Liang, Wei-qiang; Chen, Xiao-xuan

2004-11-01

Penile enhancement was performed using acellular dermal matrix. Multiple layers of acellular dermal matrix were placed underneath the penile skin to enlarge its girth. Since March 2002, penile augmentation has been performed on 12 cases using acellular dermal matrix. Postoperatively all the patients had a 1.3-3.1 cm (2.6 cm in average) increase in penile girth in a flaccid state. The penis had normal appearance and feeling without contour deformities. All patients gained sexual ability 3 months after the operation. One had a delayed wound healing due to tight dressing, which was repaired with a scrotal skin flap. Penile enlargement by implantation of multiple layers of acellular dermal matrix was a safe and effective operation. This method can be performed in an outpatient ambulatory setting. The advantages of the acellular dermal matrix over the autogenous dermal fat grafts are elimination of donor site injury and scar and significant shortening of operation time.

Idiopathic hirsutism: local and peripheral expression of aromatase (CYP19A) and 5α-reductase genes (SRD5A1 and SRD5A2).

PubMed

Caglayan, A Okay; Dundar, Munis; Tanriverdi, Fatih; Baysal, Nuran A; Unluhizarci, Kursad; Ozkul, Yusuf; Borlu, Murat; Batukan, Cem; Kelestimur, Fahrettin

2011-08-01

To evaluate idiopathic hirsutism etiology via molecular studies testing peripheral and local aromatase and 5α-reductase expression. Assessment of the expression of messenger RNA (mRNA) for type 1 and 2,5α-reductase isoenzyme gene (SDR5A1, SDR5A2) and aromatase (CYP19A) in dermal papillae cells and peripheral blood mononuclear cells. University hospital. 28 untreated idiopathic hirsute patients and 20 healthy women (controls). Human skin biopsies and peripheral venous blood. SDR5A1, SDR5A2, CYP19A gene expression in skin biopsies and peripheral blood. A statistically significant reduction of SRD5A1, SRD5A2, and CYP19A gene expression was found in the dermal papillae cells and peripheral blood mononuclear cell between the study and control group. Further study, including protein expression and enzyme activity assays, are warranted to characterize the paradoxically low gene expression levels of local 5α-reductase and aromatase in women with idiopathic hirsutism. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Minipigs as an Animal Model for Dermal Vaccine Delivery

PubMed Central

Ploemen, Ivo HJ; Hirschberg, Hoang JHB; Kraan, Heleen; Zeltner, Adrian; van Kuijk, Sandra; Lankveld, Danielle PK; Royals, Michael; Kersten, Gideon FA; Amorij, Jean-Pierre

2014-01-01

Appropriate animal models for intradermal vaccine delivery are scarce. Given the high similarity of their skin anatomy to that of humans, minipigs may be a suitable model for dermal vaccine delivery. Here we describe the immunization of Göttingen minipigs by using intradermal and intramuscular delivery of hepatitis B surface antigen (HBsAg). Intradermal vaccine delivery by needle and syringe and by needle-free jet injection induced humoral antiHBsAg responses. Priming immunization by using the disposable syringe jet injector (DSJI) resulted in a higher antibody titer than did conventional intradermal immunization and a titer comparable to that after intramuscular vaccination with HBsAg and Al(OH)3 adjuvant. This study highlights the utility of the minipig model in vaccine studies assessing the efficacy of conventional and novel methods of dermal delivery. Moreover, we include suggestions regarding working with minipigs during dermal vaccine delivery studies, thereby fostering future work in this area of vaccinology. PMID:24512961

Function of the minor duodenal papilla in pancreas divisum as determined by duodenoscopy using indigo carmine dye and a pH sensor.

PubMed

Ohshima, Y; Tsukamoto, Y; Naitoh, Y; Hirooka, Y; Furukawa, T; Nakagawa, H; Hayakawa, T

1994-12-01

The objective of this study was to evaluate the function of the minor duodenal papilla and to investigate the relationship between the history of acute pancreatitis and individual dorsal pancreatogram findings and the minor papilla function in pancreas divisum. Eight of the 21 patients with PD diagnosed by endoscopic retrograde cholangiopancreatography had a history of acute pancreatitis (group A), and 13 patients did not (group B). The reaction of pancreatic juice excreted via the minor papilla was evaluated after intravenous administration of secretin, by observing the repulsion of indigo carmine dye scattered on the surface of the minor papilla. The function of the minor papilla was classified into two types. In 12 patients, all of the pigment on the minor papilla was repelled within 5 min of secretin administration (type I), and in the remaining nine patients it was not (type II). After secretin administration, the pH of the minor papilla surface in type I was significantly higher than that in type II. There was no significant difference between the type I and type II patients in exocrine pancreatic function, as evaluated by a BT-PABA test. In the group A patients, the rate of occurrence of dorsal duct dilation (including changes of the terminal shape) was significantly greater than in the group B patients. The function of the minor papilla in the group A patients was significantly worse than in the group B patients. Outflow obstruction of pancreatic group B patients. Outflow obstruction of pancreatic juice, i.e., "relative stenosis of the minor papilla," was considered to be present in the patients with type II papilla, and, therefore, the patients with type II papilla might suffer from acute pancreatitis resulting from poor drainage of pancreatic juice and excessive pressure in the dorsal duct. The finding that patients with PD have one of two types of minor papilla will be useful for understanding the condition and selecting the therapeutic plan for

NOTCH3 is expressed in human apical papilla and in subpopulations of stem cells isolated from the tissue.

PubMed

Jamal, Mohamed; Chogle, Sami M; Karam, Sherif M; Huang, George T-J

2015-09-01

NOTCH plays a role in regulating stem cell function and fate decision. It is involved in tooth development and injury repair. Information regarding NOTCH expression in human dental root apical papilla (AP) and its residing stem cells (SCAP) is limited. Here we investigated the expression of NOTCH3, its ligand JAG1, and mesenchymal stem cell markers CD146 and STRO-1 in the AP or in the primary cultures of SCAP isolated from AP. Our in situ immunostaining showed that in the AP NOTCH3 and CD146 were co-expressed and associated with blood vessels having NOTCH3 located more peripherally. In cultured SCAP, NOTCH3 and JAG1 were co-expressed. Flow cytometry analysis showed that 7%, 16% and 98% of the isolated SCAP were positive for NOTCH3, STRO-1 and CD146, respectively with a rare 1.5% subpopulation of SCAP co-expressing all three markers. The expression level of NOTCH3 reduced when SCAP underwent osteogenic differentiation. Our findings are the first step towards defining the regulatory role of NOTCH3 in SCAP fate decision.

The electrical properties of auditory hair cells in the frog amphibian papilla.

PubMed

Smotherman, M S; Narins, P M

1999-07-01

The amphibian papilla (AP) is the principal auditory organ of the frog. Anatomical and neurophysiological evidence suggests that this hearing organ utilizes both mechanical and electrical (hair cell-based) frequency tuning mechanisms, yet relatively little is known about the electrophysiology of AP hair cells. Using the whole-cell patch-clamp technique, we have investigated the electrical properties and ionic currents of isolated hair cells along the rostrocaudal axis of the AP. Electrical resonances were observed in the voltage response of hair cells harvested from the rostral and medial, but not caudal, regions of the AP. Two ionic currents, ICa and IK(Ca), were observed in every hair cell; however, their amplitudes varied substantially along the epithelium. Only rostral hair cells exhibited an inactivating potassium current (IA), whereas an inwardly rectifying potassium current (IK1) was identified only in caudal AP hair cells. Electrically tuned hair cells exhibited resonant frequencies from 50 to 375 Hz, which correlated well with hair cell position and the tonotopic organization of the papilla. Variations in the kinetics of the outward current contribute substantially to the determination of resonant frequency. ICa and IK(Ca) amplitudes increased with resonant frequency, reducing the membrane time constant with increasing resonant frequency. We conclude that a tonotopically organized hair cell substrate exists to support electrical tuning in the rostromedial region of the frog amphibian papilla and that the cellular mechanisms for frequency determination are very similar to those reported for another electrically tuned auditory organ, the turtle basilar papilla.

The effects of carbon nanotubes on lung and dermal cellular behaviors

PubMed Central

Luanpitpong, Sudjit; Wang, Liying; Rojanasakul, Yon

2016-01-01

Carbon nanotubes (CNTs) hold great promise to create new and better products, but their adverse health effect is a major concern. Human exposure to CNTs is primarily through inhalation and dermal contact, especially during the manufacturing and handling processes. Numerous animal studies have demonstrated the potential pulmonary and dermal hazards associated with CNT exposure, while in vitro studies have assessed the effects of CNT exposure on various cellular behaviors and have been used to perform mechanistic studies. In this review, we provide an overview of the pathological effects of CNTs and examine the acute and chronic effects of CNT exposure on lung and dermal cellular behaviors, beyond the generally discussed cytotoxicity. We then examine the linkage of cellular behaviors and disease pathogenesis, and discuss the pertinent mechanisms. PMID:24981653

Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds.

PubMed

Liu, Hong-Xiang; Komatsu, Yoshihiro; Mishina, Yuji; Mistretta, Charlotte M

2012-08-15

The epithelium of mammalian tongue hosts most of the taste buds that transduce gustatory stimuli into neural signals. In the field of taste biology, taste bud cells have been described as arising from "local epithelium", in distinction from many other receptor organs that are derived from neurogenic ectoderm including neural crest (NC). In fact, contribution of NC to both epithelium and mesenchyme in the developing tongue is not fully understood. In the present study we used two independent, well-characterized mouse lines, Wnt1-Cre and P0-Cre that express Cre recombinase in a NC-specific manner, in combination with two Cre reporter mouse lines, R26R and ZEG, and demonstrate a contribution of NC-derived cells to both tongue mesenchyme and epithelium including taste papillae and taste buds. In tongue mesenchyme, distribution of NC-derived cells is in close association with taste papillae. In tongue epithelium, labeled cells are observed in an initial scattered distribution and progress to a clustered pattern between papillae, and within papillae and early taste buds. This provides evidence for a contribution of NC to lingual epithelium. Together with previous reports for the origin of taste bud cells from local epithelium in postnatal mouse, we propose that NC cells migrate into and reside in the epithelium of the tongue primordium at an early embryonic stage, acquire epithelial cell phenotypes, and undergo cell proliferation and differentiation that is involved in the development of taste papillae and taste buds. Our findings lead to a new concept about derivation of taste bud cells that include a NC origin. Copyright © 2012 Elsevier Inc. All rights reserved.

Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds

PubMed Central

Liu, Hong-Xiang; Komatsu, Yoshihiro; Mishina, Yuji; Mistretta, Charlotte M.

2012-01-01

The epithelium of mammalian tongue hosts most of the taste buds that transduce gustatory stimuli into neural signals. In the field of taste biology, taste bud cells have been described as arising from “local epithelium”, in distinction from many other receptor organs that are derived from neurogenic ectoderm including neural crest (NC). In fact, contribution of NC to both epithelium and mesenchyme in the developing tongue is not fully understood. In the present study we used two independent, well-characterized mouse lines, Wnt1-Cre and P0-Cre that express Cre recombinase in a NC-specific manner, in combination with two Cre reporter mouse lines, R26R and ZEG, and demonstrate a contribution of NC-derived cells to both tongue mesenchyme and epithelium including taste papillae and taste buds. In tongue mesenchyme, distribution of NC-derived cells is in close association with taste papillae. In tongue epithelium, labeled cells are observed in an initial scattered distribution and progress to a clustered pattern between papillae, and within papillae and early taste buds. This provides evidence for a contribution of NC to lingual epithelium. Together with previous reports for the origin of taste bud cells from local epithelium in postnatal mouse, we propose that NC cells migrate into and reside in the epithelium of the tongue primordium at an early embryonic stage, acquire epithelial cell phenotypes, and undergo cell proliferation and differentiation that is involved in the development of taste papillae and taste buds. Our findings lead to a new concept about derivation of taste bud cells that include a NC origin. PMID:22659543

Mitochondrial tolerance to single and repeat exposure to simulated sunlight in human epidermal and dermal skin cells.

PubMed

Kelly, J; Murphy, J E J

2016-12-01

Sunlight represents the primary threat to mitochondrial integrity in skin given the unique nature of the mitochondrial genome and its proximity to the electron transport chain. The accumulation of mitochondrial DNA (mtDNA) mutations is a key factor in many human pathologies and this is linked to key roles of mitochondrial function in terms of energy production and cell regulation. The main objective of this study was to evaluate solar radiation induced changes in mitochondrial integrity, function and dynamics in human skin cells using a Q-Sun solar simulator to deliver a close match to the intensity of summer sunlight. Spontaneously immortalised human skin epidermal keratinocytes (HaCaT) and Human Dermal Fibroblasts (HDFn) were divided into two groups. Group A were irradiated once and Group B twice 7days apart and evaluated using cell survival, viability and mitochondrial membrane potential (MMP) and mass at 1, 4 and 7days post one exposure for Group A and 1, 4, 7 and 14days post second exposure for Group B. Viability and survival of HaCaT and HDFn cells decreased after repeat exposure to Simulated Sunlight Irradiation (SSI) with no recovery. HDFn cells showed no loss in MMP after one or two exposures to SSI compared to HaCaT cells which showed a periodic loss of MMP after one exposure with a repeat exposure causing a dramatic decrease from which cells did not recover. Mitochondrial Mass in exposed HDFn cells was consistent with control after one or two exposures to SSI; however mitochondrial mass was significantly decreased in HaCaT cells. Data presented here suggests that mitochondria in epidermal cells are more sensitive to sunlight damage compared to mitochondria in dermal cells, despite their origin, confirming a skin layer specific sensitivity to sunlight, but not as expected. Copyright © 2016 Elsevier B.V. All rights reserved.

Morphology and distribution of taste papillae and oral denticles in the developing oropharyngeal cavity of the bamboo shark, Chiloscyllium punctatum.

PubMed

Atkinson, Carla J L; Martin, Kyle J; Fraser, Gareth J; Collin, Shaun P

2016-12-15

Gustation in sharks is not well understood, especially within species that ingest food items using suction. This study examines the morphological and immunohistochemical characterisation of taste papillae and oral denticles in the oropharynx of the brown-banded bamboo shark Chiloscyllium punctatum and compares their distribution during development. Taste papillae of C. punctatum are located throughout the oropharyngeal region and are most concentrated on the oral valves (2125-3483 per cm 2 in embryos; 89-111 per cm 2 in mature adults) close to the tooth territories. Papillae appearance is comparable at all stages of development, with the exception of the embryos (unhatched specimens), where no microvilli are present. Oral valve papillae are comparable in structure to Type I taste buds of teleost fishes, whereas those of the rest of the oropharyngeal region are comparable to Type II. Both types of papillae show immunofluorescence for a number of markers of taste buds, including β-Catenin and Sox2. Taste papillae densities are highest in embryos with 420-941 per cm 2 compared to 8-29 per cm 2 in mature adults. The total number of papillae remains around 1900 for all stages of development. However, the papillae increase in diameter from 72±1 μm (mean±s.e.m.) in embryos to 310±7 μm in mature individuals. Microvilli protrude in multiple patches at the apical tip of the papilla covering ∼0.5% of the papillar surface area. We further document the relationship between taste papillae and the closely associated oral denticles within the shark orophayngeal cavity. Oral denticles first break through the epithelium in the antero-central region of the dorsal oral cavity, shortly after the emergence of teeth, around time of hatching. Denticles are located throughout the oropharyngeal epithelium of both immature and mature stages, with the highest concentrations in the antero-dorsal oral cavity and the central regions of the pharynx. These denticle-rich areas of the

CONTROLLED, SHORT-TERM DERMAL AND INHALATION EXPOSURE TO CHLOROFORM

EPA Science Inventory

Studies were conducted to determine the uptake by humans of chloroform as a result of controlled short-term dermal and inhalation exposures. The approach used continuous real-time breath analysis to determine exhaled-breath profiles and evaluate chloroform kinetics in the huma...

Ultrastructure of the filiform papillae on the tongue of the hamster.

PubMed Central

Fernandez, B; Suarez, I; Zapata, A

1978-01-01

The fine structure of the filiform papillae on the hamster tongue is described level by level from the basal layer to the surface. We did not observe two distinct types of cells with different morphology or components which could be held responsible for the production of two different types of keratin as have been described in other animals, but rather a uniformity of cell structures in each layer and only the so-called "smooth" type of keratin. However, keratin granules were more abundant in the anterior part of the papilla. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:689988

The levels and kinetics of oxygen tension detectable at the surface of human dermal fibroblast cultures.

PubMed

Tokuda, Y; Crane, S; Yamaguchi, Y; Zhou, L; Falanga, V

2000-03-01

Low oxygen tension has recently been shown to stimulate cell growth and clonal expansion, as well as synthesis and transcription of certain growth factors and extracellular matrix components. These results have been obtained by exposing cell cultures to a hypoxic environment. Using an oxygen probe, we have now studied how experimental conditions affect the oxygen tension detectable at the cell surface. Dissolved oxygen tension was directly related to the height of the medium above the cell surface (r = 0.8793, P = 0.021), but was constant when no cells were present in the flask (r = -0. 9732, P = 0.001). In both human dermal fibroblasts and NIH/3T3 cultures, oxygen tension decreased linearly as cell density increased (r = -0.835, P < 0.0001; r = -0.916, P < 0.0001, respectively). When human dermal fibroblasts were exposed to 2% O(2), maximum hypoxic levels (0 mmHg) were achieved within approximately 15 min, and the recovery time was within a similar time frame. The addition of rotenone, an inhibitor of cellular respiration, blocked this decrease in oxygen tension at the cell surface, suggesting that cellular consumption of oxygen is responsible for the decline. Finally, we examined the cell-surface oxygen tension in control and acutely wounded human skin equivalents (HSE), consisting of a keratinocyte layer over a type I collagen matrix containing fibroblasts. We found that oxygen tension dropped significantly (P < 0.0001) in acutely wounded areas of HSE as compared to unwounded areas of HSE and that this drop was prevented by the addition of mitomycin C. These results indicate that cell-surface oxygen tension is indirectly related to cell density, and that the amount of detectable oxygen at the cell surface is a function of cell density, the oxygen tension in the incubator, and increased cellular activity, as occurs after injury. Copyright 2000 Wiley-Liss, Inc.

Concentration gradient of oxalate from cortex to papilla in rat kidney.

PubMed

Nakatani, Tatsuya; Ishii, Keiichi; Sugimoto, Toshikado; Kamikawa, Sadanori; Yamamoto, Keisuke; Yoneda, Yukio; Kanazawa, Toshinao; Kishimoto, Taketoshi

2003-02-01

The kidney eliminates the major fraction of plasma oxalate. It is well known that oxalate is freely filtered by glomeruli and secreted by the proximal tubules. However, the renal handling of oxalate in distal nephrons, which is considered as playing an important role in stone formation, remains obscure. At 15-180 min after intravenous injection of 14C-oxalate to rats, the intrarenal localization of radioactivity was quantitatively measured by the radioluminographic method using a bioimaging analyzer. Tissue radioactivity was compared with plasma, and urinary radioactivities were measured by a liquid scintillation counter. The control study was conducted with 14C-inulin. The radioactivity of 14C-oxalate in the papilla was 10 times greater than in the cortex and eight times greater than in the medulla 180 min after injection when almost no radioactivity was present in the urine. In contrast, the radioactivity of 14C-inulin was nine times less in the papilla than in the cortex at the same time. Oxalate remains in the renal papilla for an extended period. This accumulation of oxalate may be attributed to calcium oxalate crystal fixation along the deep nephron which is considered to be the first step of stone formation.

Comparison of interleukin 10 homologs on dermal wound healing using a novel human skin ex vivo organ culture model.

PubMed

Balaji, Swathi; Moles, Chad M; Bhattacharya, Sukanta S; LeSaint, Maria; Dhamija, Yashu; Le, Louis D; King, Alice; Kidd, Mykia; Bouso, Muhammad F; Shaaban, Aimen; Crombleholme, Timothy M; Bollyky, Paul; Keswani, Sundeep G

2014-07-01

Anti-inflammatory cytokine interleukin (IL)-10 has been shown to induce regenerative healing in postnatal wounds. A viral homolog of IL-10 produced by human cytomegalovirus (CMV IL-10) similarly generates potent immunoregulatory effects, but its effects on wound healing have not been investigated. Currently, there are limited cost-effective methods of screening vulnerary therapeutics. Taken together, we aim to develop and validate a novel human ex vivo dermal wound model and hypothesize that CMV IL-10 will enhance dermal wound healing. Full-thickness circular (6-mm) explants were taken from surgical skin samples and 3-mm full-thickness wounds were created. Explants were embedded in collagen I matrix and maintained in specially formulated media with the epidermis at air-liquid interface, and treated with human IL-10 or CMV IL-10 (200 ng/mL). The viability of cultured explants was validated by histology and lactate dehydrogenase (LDH) activity. Epithelial gap, epithelial height, basal keratinocyte migration, vascular endothelial growth factor levels, and neovascularization were measured at days 3 and 7 to determine IL-10 effects on wound healing. Culture explants at day 7 appeared similar to fresh skin in morphology, cell, and vessel density. By day 14, the epidermis separated from the dermis and the cell density diminished. Day 7 wounds appeared viable with advancing epithelial and basal keratinocyte migration with no evidence of necrosis. Cytotoxicity analysis via the quantification of LDH revealed no differences between controls and treated groups. There was a slight increase in the quantity of LDH in media at day 3; however, this decreased at day 5 and continued to decline up to day 21. CMV IL-10 treatment resulted in a significant decrease in the epithelial gap and an increase in epithelial height. There were no differences in the rates of basal keratinocyte migration at day 7 between treated and control groups. Interestingly, human IL-10 increased vascular

Estimating dermal transfer from PCB-contaminated porous surfaces.

PubMed

Slayton, T M; Valberg, P A; Wait, A D

1998-06-01

Health risks posed by dermal contact with PCB-contaminated porous surfaces have not been directly demonstrated and are difficult to estimate indirectly. Surface contamination by organic compounds is commonly assessed by collecting wipe samples with hexane as the solvent. However, for porous surfaces, hexane wipe characterization is of limited direct use when estimating potential human exposure. Particularly for porous surfaces, the relationship between the amount of organic material collected by hexane and the amount actually picked up by, for example, a person's hand touch is unknown. To better mimic PCB pickup by casual hand contact with contaminated concrete surfaces, we used alternate solvents and wipe application methods that more closely mimic casual dermal contact. Our sampling results were compared to PCB pickup using hexane-wetted wipes and the standard rubbing protocol. Dry and oil-wetted samples, applied without rubbing, picked up less than 1% of the PCBs picked up by the standard hexane procedure; with rubbing, they picked up about 2%. Without rubbing, saline-wetted wipes picked up 2.5%; with rubbing, they picked up about 12%. While the nature of dermal contact with a contaminated surface cannot be perfectly reproduced with a wipe sample, our results with alternate wiping solvents and rubbing methods more closely mimic hand contact than the standard hexane wipe protocol. The relative pickup estimates presented in this paper can be used in conjunction with site-specific PCB hexane wipe results to estimate dermal pickup rates at sites with PCB-contaminated concrete.

Redescription and biology of Diopatra neapolitana (Annelida: Onuphidae), a protandric hermaphrodite with external spermaducal papillae

NASA Astrophysics Data System (ADS)

Arias, Andrés; Paxton, Hannelore; Budaeva, Nataliya

2016-06-01

A one-year study of the reproductive biology of a population of Diopatra neapolitana at Villaviciosa estuary, northern Spain, was undertaken. Field observations together with a histological study of monthly collected individuals revealed that the population was iteroparous, had a discontinuous reproductive season with a resting period during August and September and a spawning season from March to July. The study showed that D. neapolitana was not dioecious as previously suggested but consisted of protandric sequential hermaphrodites, pure males and pure females with a male biased sex ratio of 3:1. During the peak reproductive period from May to August we observed simultaneous hermaphrodites with two dorsal papillae per segment in the branchial region. Histological studies demonstrated that the papillae were acting as seminal vesicles, storing own sperm, and also as sperm ducts, providing an exit route; hence we termed them 'spermaducal papillae'. The papillae are not the only sperm repositories as the coelom of males and simultaneous hermaphrodites in smaller size classes is also filled with sperm. The worms are broadcast spawners with a brief pelagic larval stage as previously reported but the finer points of this unusual fertilisation system need still to be elaborated. Diopatra cryptornata was recently described as a new species, supposedly differing from D. neapolitana in chaetal detail and the possession of the papillae. We have shown conclusively with morphological and genetical studies that the former species is a junior synonym of the latter. In the absence of type material we are here designating a neotype from recently collected material from Naples.

Anti-photoaging effect of aaptamine in UVB-irradiated human dermal fibroblasts and epidermal keratinocytes.

PubMed

Kim, Min-Ji; Woo, Seon Wook; Kim, Myung-Suk; Park, Ji-Eun; Hwang, Jae-Kwan

2014-12-01

Chronic exposure to ultraviolet (UV) irradiation causes sunburn, inflammatory responses, skin cancer, and photoaging. Photoaging, in particular, generates reactive oxygen species (ROS) that stimulate mitogen-activated protein kinase (MAPK) signaling and transcription factors. UV irradiation also activates matrix metalloproteinases (MMPs) expression and inactivates collagen synthesis. Aaptamine, a marine alkaloid isolated from the marine sponge, has been reported to have antitumor, antimicrobial, antiviral, and antioxidant activities. However, the photo-protective effects of aaptamine have not been elucidated. In this study, our data demonstrated that aaptamine deactivated UVB-induced MAPK and activator protein-1 signaling by suppressing ROS, resulting in attenuating the expression of MMPs in UVB-irradiated human dermal fibroblasts. Aaptamine also decreased proinflammatory cytokines such as cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β, and nuclear factor-kappa B subunits in UVB-irradiated human keratinocytes. In conclusion, we suggest that aaptamine represents a novel and effective strategy for treatment and prevention of photoaging.

Interaction of New-Developed TiO2-Based Photocatalytic Nanoparticles with Pathogenic Microorganisms and Human Dermal and Pulmonary Fibroblasts

PubMed Central

Nica, Ionela Cristina; Stan, Miruna Silvia; Popa, Marcela; Chifiriuc, Mariana Carmen; Lazar, Veronica; Pircalabioru, Gratiela G.; Dumitrescu, Iuliana; Ignat, Madalina; Feder, Marcel; Tanase, Liviu Cristian; Mercioniu, Ionel; Diamandescu, Lucian; Dinischiotu, Anca

2017-01-01

TiO2-based photocatalysts were obtained during previous years in order to limit pollution and to ease human daily living conditions due to their special properties. However, obtaining biocompatible photocatalysts is still a key problem, and the mechanism of their toxicity recently received increased attention. Two types of TiO2 nanoparticles co-doped with 1% of iron and nitrogen (TiO2-1% Fe–N) atoms were synthesized in hydrothermal conditions at pH of 8.5 (HT1) and 5.5 (HT2), and their antimicrobial activity and cytotoxic effects exerted on human pulmonary and dermal fibroblasts were assessed. These particles exhibited significant microbicidal and anti-biofilm activity, suggesting their potential application for microbial decontamination of different environments. In addition, our results demonstrated the biocompatibility of TiO2-1% Fe–N nanoparticles at low doses on lung and dermal cells, which may initiate oxidative stress through dose accumulation. Although no significant changes were observed between the two tested photocatalysts, the biological response was cell type specific and time- and dose-dependent; the lung cells proved to be more sensitive to nanoparticle exposure. Taken together, these experimental data provide useful information for future photocatalytic applications in the industrial, food, pharmaceutical, and medical fields. PMID:28125053

The papilla of Vater just below the pylorus presenting as recurrent duodenal ulcer bleeding.

PubMed

Sung, Hye Young; Kim, Jin Il; Park, Yong Bum; Cheung, Dae Young; Cho, Se Hyun; Park, Soo-Heon; Han, Joon-Yeol; Kim, Jae Kwang

2007-01-01

The papilla of Vater emptying into the duodenal bulb site is extremely rare and considered an aberrant condition. We report here a case with recurrent duodenal ulcer bleeding associated with this anomaly. A 42-year-old man was admitted to St. Mary Hospital because of tarry stool for three days. Despite no documented etiology to explain recurrent ulceration, the patient had about ten episodes of ulcer bleeding since 1995. On duodenoscopy, 1.0 x 0.6 cm sized active stage duodenal ulcer with oozing was observed at the posterior wall side below the pylorus. The papilla of Vater was bulging just below the pylorus. Bile juice was excreted from its opening. Pancreatic duct and common bile duct, which drained into the bulb site, were observed on ERCP. In this report, we show that recurrent duodenal ulcer can be associated with the papilla of Vater just below the pylorus.

The long-term label retaining population of the renal papilla arises through divergent regional growth of the kidney.

PubMed

Adams, Derek C; Oxburgh, Leif

2009-09-01

Long-term pulse chase experiments previously identified a sizable population of BrdU-retaining cells within the renal papilla. The origin of these cells has been unclear, and in this work we test the hypothesis that they become quiescent early during the course of kidney development and organ growth. Indeed, we find that BrdU-retaining cells of the papilla can be labeled only by pulsing with BrdU from embryonic (E) day 11.25 to postnatal (P) day 7, the approximate period of kidney development in the mouse. BrdU signal in the cortex and outer medulla is rapidly diluted by cellular proliferation during embryonic development and juvenile growth, whereas cells within the papilla differentiate and exit the cell cycle during organogenesis. Indeed, by E17.5, little or no active proliferation can be seen in the distal papilla, indicating maturation of this structure in a distal-to-proximal manner during organogenesis. We conclude that BrdU-retaining cells of the papilla represent a population of cells that quiesce during embryonic development and localize within a region of the kidney that matures early. We therefore propose that selective papillary retention of BrdU arises through a combination of regionalized slowing of, and exit from, the cell cycle within the papilla during the period of ongoing kidney development, and extensive proliferative growth of the juvenile kidney resulting in dilution of BrdU below the detection level in extra-papillary regions.

A Ca2+-dependent remodelled actin network directs vesicle trafficking to build wall ingrowth papillae in transfer cells.

PubMed

Zhang, Hui-Ming; Colyvas, Kim; Patrick, John W; Offler, Christina E

2017-10-13

The transport function of transfer cells is conferred by an enlarged plasma membrane area, enriched in nutrient transporters, that is supported on a scaffold of wall ingrowth (WI) papillae. Polarized plumes of elevated cytosolic Ca2+ define loci at which WI papillae form in developing adaxial epidermal transfer cells of Vicia faba cotyledons that are induced to trans-differentiate when the cotyledons are placed on culture medium. We evaluated the hypothesis that vesicle trafficking along a Ca2+-regulated remodelled actin network is the mechanism that underpins this outcome. Polarized to the outer periclinal cytoplasm, a Ca2+-dependent remodelling of long actin bundles into short, thin bundles was found to be essential for assembling WI papillae but not the underlying uniform wall layer. The remodelled actin network directed polarized vesicle trafficking to sites of WI papillae construction, and a pharmacological study indicated that both exo- and endocytosis contributed to assembly of the papillae. Potential candidates responsible for the Ca2+-dependent actin remodelling, along with those underpinning polarized exo- and endocyotosis, were identified in a transcriptome RNAseq database generated from the trans-differentiating epidermal cells. Of most significance, endocytosis was controlled by up-regulated expression of a dynamin-like isoform. How a cycle of localized exo- and endocytosis, regulated by Ca2+-dependent actin remodelling, assembles WI papillae is discussed. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Angiogenic Potential and Secretome of Human Apical Papilla Mesenchymal Stem Cells in Various Stress Microenvironments.

PubMed

Bakopoulou, Athina; Kritis, Aristeidis; Andreadis, Dimitrios; Papachristou, Eleni; Leyhausen, Gabriele; Koidis, Petros; Geurtsen, Werner; Tsiftsoglou, Asterios

2015-11-01

Stem cells from the apical papilla (SCAP) of human adult teeth are considered an accessible source of cells with angiogenic properties. The aims of this study were to investigate the endothelial transdifferentiation of SCAP, the secretion of pro- and antiangiogenic factors from SCAP, and the paracrine effects of SCAP when exposed to environmental stress to stimulate tissue damage. SCAP were exposed to serum deprivation (SD), glucose deprivation (GD), and oxygen deprivation/hypoxia (OD) conditions, individually or in combination. Endothelial transdifferentiation was evaluated by in vitro capillary-like formation assays, real-time polymerase chain reaction, western blot, and flow cytometric analyses of angiogenesis-related markers; secretome by antibody arrays and enzyme-linked immunosorbent assays (ELISA); and paracrine impact on human umbilical vein endothelial cells (HUVECs) by in vitro transwell migration and capillary-like formation assays. The short-term exposure of SCAP to glucose/oxygen deprivation (GOD) in the presence, but mainly in deprivation, of serum (SGOD) elicited a proangiogenesis effect indicated by expression of angiogenesis-related genes involved in vascular endothelial growth factor (VEGF)/VEGFR and angiopoietins/Tie pathways. This effect was unachievable under SD in normoxia, suggesting that the critical microenvironmental condition inducing rapid endothelial shift of SCAP is the combination of SGOD. Interestingly, SCAP showed high adaptability to these adverse conditions, retaining cell viability and acquiring a capillary-forming phenotype. SCAP secreted higher numbers and amounts of pro- (angiogenin, IGFBP-3, VEGF) and lower amounts of antiangiogenic factors (serpin-E1, TIMP-1, TSP-1) under SGOD compared with SOD or SD alone. Finally, secretome obtained under SGOD was most effective in inducing migration and capillary-like formation by HUVECs. These data provide new evidence on the microenvironmental factors favoring endothelial

[Relationship between crown form of upper central incisors and papilla filling in Chinese Han-nationality youth].

PubMed

Yang, X; Le, D; Zhang, Y L; Liang, L Z; Yang, G; Hu, W J

2016-10-18

To explore a crown form classification method for upper central incisor which is more objective and scientific than traditional classification method based on the standardized photography technique. To analyze the relationship between crown form of upper central incisors and papilla filling in periodontally healthy Chinese Han-nationality youth. In the study, 180 periodontally healthy Chinese youth ( 75 males, and 105 females ) aged 20-30 (24.3±4.5) years were included. With the standardized upper central incisor photography technique, pictures of 360 upper central incisors were obtained. Each tooth was classified as triangular, ovoid or square by 13 experienced specialist majors in prothodontics independently and the final classification result was decided by most evaluators in order to ensure objectivity. The standardized digital photo was also used to evaluate the gingival papilla filling situation. The papilla filling result was recorded as present or absent according to naked eye observation. The papilla filling rates of different crown forms were analyzed. Statistical analyses were performed with SPSS 19.0. The proportions of triangle, ovoid and square forms of upper central incisor in Chinese Han-nationality youth were 31.4% (113/360), 37.2% (134/360) and 31.4% (113/360 ), respectively, and no statistical difference was found between the males and females. Average κ value between each two evaluators was 0.381. Average κ value was raised up to 0.563 when compared with the final classification result. In the study, 24 upper central incisors without contact were excluded, and the papilla filling rates of triangle, ovoid and square crown were 56.4% (62/110), 69.6% (87/125), 76.2% (77/101) separately. The papilla filling rate of square form was higher (P=0.007). The proportion of clinical crown form of upper central incisor in Chinese Han-nationality youth is obtained. Compared with triangle form, square form is found to favor a gingival papilla that fills the

FGF signaling refines Wnt gradients to regulate the patterning of taste papillae.

PubMed

Prochazkova, Michaela; Häkkinen, Teemu J; Prochazka, Jan; Spoutil, Frantisek; Jheon, Andrew H; Ahn, Youngwook; Krumlauf, Robb; Jernvall, Jukka; Klein, Ophir D

2017-06-15

The patterning of repeated structures is a major theme in developmental biology, and the inter-relationship between spacing and size of such structures is an unresolved issue. Fungiform papillae are repeated epithelial structures that house taste buds on the anterior tongue. Here, we report that FGF signaling is a crucial regulator of fungiform papillae development. We found that mesenchymal FGF10 controls the size of the papillary area, while overall patterning remains unchanged. Our results show that FGF signaling negatively affects the extent of canonical Wnt signaling, which is the main activation pathway during fungiform papillae development; however, this effect does not occur at the level of gene transcription. Rather, our experimental data, together with computational modeling, indicate that FGF10 modulates the range of Wnt effects, likely via induction of Sostdc1 expression. We suggest that modification of the reach of Wnt signaling could be due to local changes in morphogen diffusion, representing a novel mechanism in this tissue context, and we propose that this phenomenon might be involved in a broader array of mammalian developmental processes. © 2017. Published by The Company of Biologists Ltd.

The margin of internal exposure (MOIE) concept for dermal risk assessment based on oral toxicity data - A case study with caffeine.

PubMed

Bessems, Jos G M; Paini, Alicia; Gajewska, Monika; Worth, Andrew

2017-12-01

Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics. Caffeine was chosen to illustrate this approach. It is a substance that is often found in cosmetics and for which oral repeated dose toxicity data were available. A rat PBK model was constructed in order to convert the oral NOAEL to rat internal exposure dose metrics, i.e. the area under the curve (AUC) and the maximum concentration (C max ), both in plasma. A human oral PBK model was constructed and calibrated using human volunteer data and adapted to accommodate dermal absorption following human dermal exposure. Use of the MOIE approach based on internal dose metrics predictions provides excellent opportunities to investigate the consequences of variations in human dermal exposure scenarios. It can accommodate within-day variation in plasma concentrations and is scientifically more robust than assuming just an exposure in mg/kg bw/day. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Comparative transcriptome analysis of rumen papillae in suckling and weaned Japanese Black calves using RNA sequencing.

PubMed

Nishihara, Koki; Kato, Daichi; Suzuki, Yutaka; Kim, Dahye; Nakano, Misato; Yajima, Yu; Haga, Satoshi; Nakano, Miwa; Ishizaki, Hiroshi; Kawahara-Miki, Ryouka; Kono, Tomohiro; Katoh, Kazuo; Roh, Sang-Gun

2018-06-04

The length and density of rumen papillae starts to increase during weaning and growth of ruminants. This significant development increases the intraruminal surface area and the efficiency of VFA (acetate, propionate, butyrate, etc.) uptake. Thus, it is important to investigate the factors controlling the growth and development of rumen papillae during weaning. This study aimed to compare the transcriptomes of rumen papillae in suckling and weaned calves. Total RNA was extracted from the rumen papillae of 10 male Japanese Black calves (5 suckling calves, 5 wk old; 5 weaned calves, 15 wk old) and used in RNA-sequencing. Transcript abundance was estimated and differentially expressed genes were identified and these data were then used in Ingenuity Pathway Analysis (IPA) to predict the major canonical pathways and upstream regulators. Among the 871 differentially expressed genes screened by IPA, 466 genes were upregulated and 405 were downregulated in the weaned group. Canonical pathway analysis showed that "atherosclerosis" was the most significant pathway, and "tretinoin," a derivative of vitamin A, was predicted as the most active upstream regulator during weaning. Analyses also predicted IgG, lipopolysaccharides, and tumor-necrosis factor-α as regulators of the microbe-epithelium interaction that activates rumen-related immune responses. The functional category and the up-regulators found in this study provide a valuable resource for studying new candidate genes related to the proliferation and development of rumen papillae from suckling to weaning Japanese Black calves.

Development of a tissue-engineered human oral mucosa equivalent based on an acellular allogeneic dermal matrix: a preliminary report of clinical application to burn wounds.

PubMed

Iida, Takuya; Takami, Yoshihiro; Yamaguchi, Ryo; Shimazaki, Shuji; Harii, Kiyonori

2005-01-01

Tissue-engineered skin equivalents composed of epidermal and dermal components have been widely investigated for coverage of full-thickness skin defects. We developed a tissue-engineered oral mucosa equivalent based on an acellular allogeneic dermal matrix and investigated its characteristics. We also tried and assessed its preliminary clinical application. Human oral mucosal keratinocytes were separated from a piece of oral mucosa and cultured in a chemically-defined medium. The keratinocytes were seeded on to the acellular allogeneic dermal matrix and cultured. Histologically, the mucosa equivalent had a well-stratified epithelial layer. Immunohistochemical study showed that it was similar to normal oral mucosa. We applied this equivalent in one case with an extensive burn wound. The equivalent was transplanted three weeks after the harvest of the patient's oral mucosa and about 30% of the graft finally survived. We conclude that this new oral mucosa equivalent could become a therapeutic option for the treatment of extensive burns.

Dermal uptake and percutaneous penetration of ten flame retardants in a human skin ex vivo model.

PubMed

Frederiksen, Marie; Vorkamp, Katrin; Jensen, Niels Martin; Sørensen, Jens Ahm; Knudsen, Lisbeth E; Sørensen, Lars S; Webster, Thomas F; Nielsen, Jesper B

2016-11-01

The dermal uptake and percutaneous penetration of ten organic flame retardants was measured using an ex vivo human skin model. The studied compounds were DBDPE, BTBPE, TBP-DBPE, EH-TBB, BEH-TEBP, α, β and γ-HBCDD as well as syn- and anti-DDC-CO. Little or none of the applied flame retardants was recovered in either type of the receptor fluids used (physiological and worst-case). However, significant fractions were recovered in the skin depot, particularly in the upper skin layers. The primary effect of the worst-case receptor fluid was deeper penetration into the skin. The recovered mass was used to calculate lower- and upper-bound permeability coefficients kp. Despite large structural variation between the studied compounds, a clear, significant decreasing trend of kp was observed with increasing log Kow. The results indicate that the dermis may provide a significant barrier for these highly lipophilic compounds. However, based on our results, dermal uptake should be considered in exposure assessments, though it may proceed in a time-lagged manner compared to less hydrophobic compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vitro human epidermal permeation of nicotine from electronic cigarette refill liquids and implications for dermal exposure assessment.

PubMed

Frasch, H Frederick; Barbero, Ana M

2017-11-01

Nicotine plus flavorings in a propylene glycol (PG) vehicle are the components of electronic cigarette liquids (e-liquids), which are vaporized and inhaled by the user. Dermal exposure to nicotine and e-liquids may occur among workers in mixing and filling of e-cigarettes in the manufacturing process. Inadvertent skin contact among consumers is also a concern. In vitro nicotine permeation studies using heat-separated human epidermis were performed with surrogate and two commercial e-liquids, neat and aqueous nicotine donor formulations. Steady-state fluxes (J ss ), and lag times (t lag ) were measured for each formulation. In addition, transient (4 h) exposure and finite dose (1-10 μl/cm 2 ) experiments were undertaken using one commercial e-liquid. Average J ss (μg/cm 2 /h) from formulations were: nicotine in PG (24 mg/ml): 3.97; commercial e-liquid containing menthol (25 mg/ml nicotine): 10.2; commercial e-liquid containing limonene (25 mg/ml nicotine): 23.7; neat nicotine: 175. E-liquid lag times ranged from 5 to 10 h. Absorbed fraction of nicotine from finite doses was ≈0.3 at 48 h. The data were applied to transient exposure and finite dose dermal exposure assessment models and to a simple pharmacokinetic model. Three illustrative exposure scenarios demonstrate use of the data to predict systemic uptake and plasma concentrations from dermal exposure. The data demonstrate the potential for significant nicotine absorption through skin contact with e-cigarette refill solutions and the neat nicotine used to mix them.

440 Consecutive immediate, implant-based, single-surgeon breast reconstructions in 281 patients: a comparison of early outcomes and costs between SurgiMend fetal bovine and AlloDerm human cadaveric acellular dermal matrices.

PubMed

Butterfield, Jennifer L

2013-05-01

A 2010 nationwide survey of plastic and reconstructive surgeons indicated that approximately 83 percent performed predominantly implant-based breast reconstruction, with acellular dermal matrix used by approximately half of those practitioners. Although the medical literature documents well over 2000 cases of breast reconstruction with matrices, relatively few cases using other than human cadaveric acellular dermal matrices have been reported. The author compared complications and costs using SurgiMend fetal bovine and AlloDerm human cadaveric acellular dermal matrices. A retrospective review of a single surgeon's 5-year experience was performed for consecutive, nonrandomized immediate breast reconstructions with acellular dermal matrix from 2005 to 2010. Two hundred eighty-one patients had 440 implant-based reconstructions using SurgiMend [222 patients (79.0 percent)] or AlloDerm [59 patients (21.0 percent)]. No significant differences in complication rates were observed between SurgiMend and AlloDerm for hematoma, infection, major skin necrosis, or breast implant removal. Seroma was the most prevalent complication; the seroma rate for AlloDerm (15.7 percent) was significantly greater than that for SurgiMend (8.3 percent). Using recent product costs for equivalently sized AlloDerm and SurgiMend units, the cost of SurgiMend was $1024 less per breast than AlloDerm. SurgiMend fetal bovine and AlloDerm human cadaveric acellular dermal matrices demonstrate similar rates of major early complications in breast reconstruction in this study. This similarity in complication rates between SurgiMend and AlloDerm and the cost savings seen with the use of SurgiMend are factors for the surgeon to consider in choosing a matrix for breast reconstruction. : Therapeutic, III.

40 CFR 799.9325 - TSCA 90-day dermal toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Health Effects Test Guidelines § 799.9325 TSCA 90-day dermal toxicity. (a) Scope. This section is...-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure to a test... human exposure. (b) Source. The source material used in developing this TSCA test guideline is the...

40 CFR 799.9325 - TSCA 90-day dermal toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Health Effects Test Guidelines § 799.9325 TSCA 90-day dermal toxicity. (a) Scope. This section is...-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure to a test... human exposure. (b) Source. The source material used in developing this TSCA test guideline is the...

40 CFR 799.9325 - TSCA 90-day dermal toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Health Effects Test Guidelines § 799.9325 TSCA 90-day dermal toxicity. (a) Scope. This section is...-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure to a test... human exposure. (b) Source. The source material used in developing this TSCA test guideline is the...

40 CFR 799.9325 - TSCA 90-day dermal toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Health Effects Test Guidelines § 799.9325 TSCA 90-day dermal toxicity. (a) Scope. This section is...-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure to a test... human exposure. (b) Source. The source material used in developing this TSCA test guideline is the...

40 CFR 799.9325 - TSCA 90-day dermal toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Health Effects Test Guidelines § 799.9325 TSCA 90-day dermal toxicity. (a) Scope. This section is...-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure to a test... human exposure. (b) Source. The source material used in developing this TSCA test guideline is the...

In vivo study of dermal collagen of striae distensae by confocal Raman spectroscopy.

PubMed

Lung, Pam Wen; Tippavajhala, Vamshi Krishna; de Oliveira Mendes, Thiago; Téllez-Soto, Claudio A; Schuck, Desirée Cigaran; Brohem, Carla Abdo; Lorencini, Marcio; Martin, Airton Abrahão

2018-04-01

This research work mainly deals with studying qualitatively the changes in the dermal collagen of two forms of striae distensae (SD) namely striae rubrae (SR) and striae albae (SA) when compared to normal skin (NS) using confocal Raman spectroscopy. The methodology includes an in vivo human skin study for the comparison of confocal Raman spectra of dermis region of SR, SA, and NS by supervised multivariate analysis using partial least squares discriminant analysis (PLS-DA) to determine qualitatively the changes in dermal collagen. These groups are further analyzed for the extent of hydration of dermal collagen by studying the changes in the water content bound to it. PLS-DA score plot showed good separation of the confocal Raman spectra of dermis region into SR, SA, and NS data groups. Further analysis using loading plot and S-plot indicated the participation of various components of dermal collagen in the separation of these groups. Bound water content analysis showed that the extent of hydration of collagen is more in SD when compared to NS. Based on the results obtained, this study confirms the active involvement of dermal collagen in the formation of SD. It also emphasizes the need to study quantitatively the role of these various biochemical changes in the dermal collagen responsible for the variance between SR, SA, and NS.

Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells

PubMed Central

Zhang, Hui-ming; Talbot, Mark J.; McCurdy, David W.; Patrick, John W.; Offler, Christina E.

2015-01-01

Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca2+ levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane–microtubule inter-relationship is discussed. PMID:26136268

Protective role for miR-9-5p in the fibrogenic transformation of human dermal fibroblasts.

PubMed

Miguel, Verónica; Busnadiego, Oscar; Fierro-Fernández, Marta; Lamas, Santiago

2016-01-01

Excessive accumulation of extracellular matrix (ECM) proteins is the hallmark of fibrotic diseases, including skin fibrosis. This response relies on the activation of dermal fibroblasts that evolve into a pro-fibrogenic phenotype. One of the major players in this process is the cytokine transforming growth factor-β (TGF-β). MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression affecting a wide range of pathophysiological events including fibrogenesis. MicroRNA-9-5p (miR-9-5p) has been shown to exert a protective role in lung and peritoneal fibrosis. This study aimed to evaluate the role of miR-9-5p in skin fibrosis. miR-9-5p is up-regulated in TGF-β1-treated human dermal fibroblasts (HDFs). In silico identification of miR-9-5p targets spotted the type II TGF-β receptor (TGFBR2) as a potential TGF-β signaling-related effector for this miRNA. Consistently, over-expression of miR-9-5p in HDFs down-regulated TGFBR2 at both the mRNA and protein levels and reduced the phosphorylation of Smad2 and the translocation of Smad2/3 to the nucleus. In keeping, over-expression of miR-9-5p significantly delayed TGF-β1-dependent transformation of dermal fibroblasts, decreasing the expression of ECM protein collagen, type I, alpha 1 (Col1α1), and fibronectin (FN), the amount of secreted collagen proteins, and the expression of the archetypal myofibroblast marker alpha-smooth muscle actin (α-SMA). By contrast, specific inhibition of miR-9-5p resulted in enhanced presence of fibrosis markers. The expression of miR-9-5p was also detected in the skin and plasma in the mouse model of bleomycin-induced dermal fibrosis. Using lentiviral constructs, we demonstrated that miR-9-5p over-expression was also capable of deterring fibrogenesis in this same model. miR-9-5p significantly prevents fibrogenesis in skin fibrosis. This is mediated by an abrogation of TGF-β-mediated signaling through the down-regulation of TGFBR2 expression in HDFs

Percutaneous transhepatic biliary stenting in patients with intradiverticular papillae and biliary strictures caused by ampullary carcinoma: A case report

PubMed Central

NIU, HONG-TAO; HUANG, QIANG; ZHAI, REN-YOU

2014-01-01

Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy is a well-established procedure for the treatment of bile duct strictures. However, the procedure is difficult to perform in patients with intradiverticular papillae or tumor infiltration of the major papilla. Percutaneous transhepatic biliary stenting (PTBS) is commonly used in the management of malignant biliary stricture. The current study reports two cases of PTBS performed to treat malignant obstructive jaundice caused by ampullary carcinoma complicated with intradiverticular papillae. PTBS is potentially a safe technique for this relatively rare condition. PMID:24944703

Percutaneous transhepatic biliary stenting in patients with intradiverticular papillae and biliary strictures caused by ampullary carcinoma: A case report.

PubMed

Niu, Hong-Tao; Huang, Qiang; Zhai, Ren-You

2014-04-01

Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy is a well-established procedure for the treatment of bile duct strictures. However, the procedure is difficult to perform in patients with intradiverticular papillae or tumor infiltration of the major papilla. Percutaneous transhepatic biliary stenting (PTBS) is commonly used in the management of malignant biliary stricture. The current study reports two cases of PTBS performed to treat malignant obstructive jaundice caused by ampullary carcinoma complicated with intradiverticular papillae. PTBS is potentially a safe technique for this relatively rare condition.

[Hair growth effect of minoxidil].

PubMed

Otomo, Susumu

2002-03-01

The length and size of hair are depend on the anagen term in its hair cycle. It has been reported that the some cell growth factors, such as VEGF, FGF-5S, IGF-1 and KGF, induce the proliferation of cells in the matrix, dermal papilla and dermal papillary vascular system and increase the amount of extra cellular matrix in dermal papilla and then maintain follicles in the anagen phase. On the other hand, negative factors, like FGF-5, thrombospondin, or still unknown ones, terminate the anagen phase. If the negative factors become dominant against cell proliferation factors according to fulfilling some time set by the biological clock for hair follicles, TGF beta induced in the matrix tissues evokes apoptosis of matrix cells and shifts the follicles from anagen to catagen. Androgenetic alopecia is caused by miniaturizing of hair follicles located in the frontal or crown part of scalp and are hereditarily more sensitive to androgen. In their hair cycles, the androgen shortens the anagen phase of follicles and shifts them to the catagen phase earlier than usual. The mode of action of hair growth effect of minoxidil is not completely elucidated, but the most plausible explanation proposed here is that minoxidil works as a sulfonylurea receptor (SUR) activator and prolongs the anagen phase of hair follicles in the following manner: minoxidil (1) induces cell growth factors such as VEGF, HGF, IGF-1 and potentiates HGF and IGF-1 actions by the activation of uncoupled SUR on the plasma membrane of dermal papilla cells, (2) inhibits of TGF beta induced apoptosis of hair matrix cells by opening the Kir 6.0 channel pore coupled with SUR on the mitochondrial inner membrane, and (3) dilates hair follicle arteries and increases blood flow in dermal papilla by opening the Kir 6.0 channel pore coupled with SUR on the plasma membrane of vascular smooth muscle cells.

Cultivation of human dermal fibroblasts and epidermal keratinocytes on keratin-coated silica bead substrates.

PubMed

Tan, Bee Yi; Nguyen, Luong T H; Kim, Hyo-Sop; Kim, Jae-Ho; Ng, Kee Woei

2017-10-01

Human hair keratin is promising as a bioactive material platform for various biomedical applications. To explore its versatility further, human hair keratin was coated onto monolayers of silica beads to produce film-like substrates. This combination was hypothesized to provide a synergistic effect in improving the biochemical properties of the resultant composite. Atomic force microscopy analysis showed uniform coatings of keratin on the silica beads with a slight increase in the resulting surface roughness. Keratin-coated silica beads had higher surface energy and relatively lower negative charge than those of bare silica beads. To investigate cell response, human dermal fibroblasts (HDFs), and human epidermal keratinocytes (HEKs) were cultured on the substrates over 4 days. Results showed that keratin coatings significantly enhanced the metabolic activity of HDFs and encouraged cell spreading but did not exert any significant effects on HEKs. HDF expression of collagen I was significantly more intense on the keratin-coated compared to the bare silica substrates. Furthermore, HDF secretion of various cytokines suggested that keratin coatings triggered active cell responses related to wound healing. Collectively, our study demonstrated that human hair keratin-coated silica bead monolayers have the potential to modulate HDF behavior in culture and may be exploited further. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2789-2798, 2017. © 2017 Wiley Periodicals, Inc.

Paracoccidioides brasiliensis interacts with dermal dendritic cells and keratinocytes in human skin and oral mucosa lesions.

PubMed

Silva, Wellington Luiz Ferreira da; Pagliari, Carla; Duarte, Maria Irma Seixas; Sotto, Mirian N

2016-05-01

Paracoccidioidomycosis (PCM) is a systemic disease caused by the fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii. In PCM the skin and oral mucosa are often affected. Dendritic cells and keratinocytes of the integument play a role in innate and adaptive immune response against pathogens, due to their function as antigen presenting cells. Aiming to verify the interaction of P. brasiliensis with these cell populations, we studied 52 skin and 47 oral mucosa samples taken from patients with proven diagnosis of PCM. The biopsies were subjected to immunohistochemical and/or immunofluorescence staining with anti-factor XIIIa (marker of dermal dendrocytes), anti-CD207 (marker of mature Langerhans cells), anti-pan cytokeratins (AE1-AE3) and anti-P. brasiliensis antibodies. Analyses with confocal laser microscopy were also performed for better visualization of the interaction between keratinocytes and the fungi. In sum, 42% of oral mucosa samples displayed yeast forms in Factor XIIIa dermal dendrocytes cytoplasm. Langerhans cells in skin and oral mucosa samples did not show yeast cells in their cytoplasm. In sum, 54% of skin and 60% of mucosal samples displayed yeast cells in the cytoplasm of keratinocytes. The parasitism of keratinocytes may represent a possible mechanism of evasion of the fungus to local immune mechanisms. Factor XIIIa dendrocytes and keratinocytes may be acting as antigen-presenting cells to fulfill the probably impaired function of Langerhans cells in skin and oral mucosa of human PCM. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells.

PubMed

Zhang, Hui-ming; Talbot, Mark J; McCurdy, David W; Patrick, John W; Offler, Christina E

2015-09-01

Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca(2+) levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane-microtubule inter-relationship is discussed. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Prevalence of maxillary midline papillae recession and association with interdental smile line: a cross-sectional study.

PubMed

Kotsakis, Georgios A; Maragou, Theodora; Ioannou, Andreas L; Romanos, Georgios E; Hinrichs, James E

2014-01-01

The objectives of this study were to record the prevalence and degree of absence of the maxillary midline interdental papilla and the proportion of patients displaying the maxillary midline papilla during maximum smile among a Caucasian population. Papillary recession was found in 46.4% of study participants (n = 211), while the prevalence of visible recession among maxillary midline papilla during maximum smile was 38.4%, which was statistically significantly less than that of patients diagnosed intraorally with loss of papillary height (P < .001). Correlations between age and level of lip line as well as age and visible papillary recession were identified for individuals over 65 years of age. The high prevalence of midline papillary recession in the maxilla found in this population suggests that loss of papillary height constitutes a substantial clinical challenge.

Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells

PubMed Central

Milan, P. Brouki; Lotfibakhshaiesh, N.; Joghataie, M.T.; Ai, J.; Pazouki, A.; Kaplan, D.L.; kargozar, S.; Amini, N.; Hamblin, M.R.; Mozafari, M.; Samadikuchaksaraei, A.

2016-01-01

There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7 days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation. Statement of Significance The aim of the present study was to design a novel tissue-engineered system to promote angiogenesis, re-epithelization and granulation of skin tissue using human umbilical cord perivascular

Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells.

PubMed

Milan, P Brouki; Lotfibakhshaiesh, N; Joghataie, M T; Ai, J; Pazouki, A; Kaplan, D L; Kargozar, S; Amini, N; Hamblin, M R; Mozafari, M; Samadikuchaksaraei, A

2016-11-01

There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation. The aim of the present study was to design a novel tissue-engineered system to promote angiogenesis, re-epithelization and granulation of skin tissue using human umbilical cord perivascular stem cells and

Differences in the Density of Fungiform Papillae and Composition of Saliva in Patients With Taste Disorders Compared to Healthy Controls.

PubMed

Walliczek-Dworschak, Ute; Schöps, Franz; Feron, Gilles; Brignot, Helene; Hähner, Antje; Hummel, Thomas

2017-10-01

This study investigated the relation of the fungiform taste papillae density and saliva composition with the taste perception of patients suffering from diagnosed taste disorders. For this purpose, 81 patients and 40 healthy subjects were included. Taste was measured by means of regional and whole mouth chemosensory tests, and electrogustometry. Olfaction was assessed using the Sniffin Sticks. Fungiform papillae were quantified using the "Denver Papillae Protocol for Objective Analysis of Fungiform Papillae". In addition, salivary parameters [flow rate, total proteins, catalase, total anti-oxidative capacity (TAC), carbonic anhydrase VI (caVI), and pH] were determined and the Beck Depression Inventory was administered. Patients showed less taste papillae compared to healthy subjects. The number of papillae correlated with total taste strip score and salivary flow rate. Regarding salivary parameters, the flow rate, protein concentration, and TAC of patients were higher compared to controls. In addition, salivary flow rate, protease, caVI, and catalase values correlated with the summed taste strip score. Regarding various taste disorders, salty-dysgeusia patients showed the lowest taste test scores compared to those with bitter or metal-dysgeusia. Olfactory function of patients was significantly worse compared to healthy controls. This difference was most pronounced for ageusia patients. Compared to controls, patients also exhibited higher depressive symptoms. The density of fungiform papillae seemed to be positively associated with taste perception. Furthermore, patients exhibited changes in saliva composition (higher salivary flow rate, increased protein concentration, proteolysis, and TAC) compared to controls indicating that assessment of saliva may be critical for the diagnostic procedure in taste disorders. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Trivalent chromium activates Rac-1 and Src and induces switch in the cell death mode in human dermal fibroblasts.

PubMed

Rudolf, Emil; Cervinka, Miroslav

2009-08-10

In this study we examined interactions between human dermal fibroblasts and chromium acetate hydroxide originating from environmental waste sediments. We show that initially exposure of fibroblasts to Cr (III) induced membrane-dependent signaling including activation of Rac1 GTPase, Src and apoptosis signal-regulating kinase 1 (ASK-1) kinases leading to increased activities of p38 and particularly Jun N-terminal kinase (JNK) and subsequent activation of caspase-3. At later treatment intervals (48-96 h), caspase-3 activity became suppressed and markedly increased lactate dehydrogenase (LDH) release was observed. Further experiments demonstrated that LDH release occurred in the presence of increased oxidative stress, extensive DNA damage, overactivation of poly(ADP-ribose)polymerase-1 (PARP-1) and depletion of ATP. Using specific inhibitors it was demonstrated that oxidative stress along with PARP-1 activity are responsible for cell death mode switch and upon their inhibition caspase-3 activity could be restored. In conclusion, Cr (III) seems to induce a biphasic response in dermal fibroblasts, with initial apoptosis switched to necrosis via increased DNA damage and resulting PARP-1 activity.

On the relationship between gingival biotypes and supracrestal gingival height, crown form and papilla height.

PubMed

Fischer, Kai R; Grill, Eva; Jockel-Schneider, Yvonne; Bechtold, Markus; Schlagenhauf, Ulrich; Fickl, Stefan

2014-08-01

To determine the association between gingival biotypes and supracrestal gingival height (primary aim) and its relation to crown shape and papilla height (secondary aim). Eighty adult subjects were evaluated in this study. Based on the transparency of a periodontal probe through the buccal gingival margin, 38 subjects comprised the thin biotype group and 42 subjects comprised the thick biotype group, respectively. Three different parameters were clinically assessed: supracrestal gingival height (SGH) by bone sounding, crown width/crown length ratio and papilla height. No statistical difference (P > 0.05) was detected neither for the correlation between different biotypes (thick/thin) and SGH nor for the association of biotypes and crown width/crown length ratio. Papilla height was only significantly increased (P ≤ 0.05) in the area of teeth no. 21/22 for the thin periodontal biotype. Intra-examiner deviation was found to be very low for all clinical parameters (percentile agreement > 95%). Within the limits of this study, we found that in young Caucasians (i) soft tissue dimensions seem to be similar between biotypes (ii) and the traditional hypothesis that a thick gingiva merges with broad-short crown shape and flat papillae and a thin gingiva with a narrow-long crown shape and high scalloping, may be questionable. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery.

PubMed

Römgens, Anne M; Bader, Dan L; Bouwstra, Joke A; Baaijens, Frank P T; Oomens, Cees W J

2015-10-01

Delivering a drug into and through the skin is of interest as the skin can act as an alternative drug administration route for oral delivery. The development of new delivery methods, such as microneedles, makes it possible to not only deliver small molecules into the skin, which are able to pass the outer layer of the skin in therapeutic amounts, but also macromolecules. To provide insight into the administration of these molecules into the skin, the aim of this study was to assess the transport of macromolecules within and between its various layers. The diffusion coefficients in the epidermis and several locations in the papillary and reticular dermis were determined for fluorescein dextran of 40 and 500 kDa using a combination of fluorescent recovery after photobleaching experiments and finite element analysis. The diffusion coefficient was significantly higher for 40 kDa than 500 kDa dextran, with median values of 23 and 9 µm(2)/s in the dermis, respectively. The values only marginally varied within and between papillary and reticular dermis. For the 40 kDa dextran, the diffusion coefficient in the epidermis was twice as low as in the dermis layers. The adopted method may be used for other macromolecules, which are of interest for dermal and transdermal drug delivery. The knowledge about diffusion in the skin is useful to optimize (trans)dermal drug delivery systems to target specific layers or cells in the human skin. Copyright © 2015 Elsevier Ltd. All rights reserved.

Novel hyaluronic acid dermal filler: dermal gel extra physical properties and clinical outcomes.

PubMed

Monheit, Gary D; Baumann, Leslie S; Gold, Michael H; Goldberg, David J; Goldman, Mitchel P; Narins, Rhoda S; Bachtell, Nathan; Garcia, Emily; Kablik, Jeffrey; Gershkovich, Julia; Burkholder, David

2010-11-01

Dermal gel extra (DGE) is a new, tightly cross-linked hyaluronic acid (HA)-based dermal filler containing lidocaine engineered to resist gel deformation and degradation. To develop a firmer gel product (DGE) and compare the efficacy and safety of DGE with nonanimal stabilized HA (NASHA) for correction of nasolabial folds (NLFs). DGE physical properties were characterized, and 140 subjects with moderate to deep NLFs were treated with DGE and NASHA in a randomized, multicenter, split-face design study. Efficacy, pain, and satisfaction were measured using appropriate standard instruments. Adverse events were monitored throughout the study. DGE has a higher modulus and a higher gel:fluid ratio than other HA fillers. Similar optimal correction was observed with DGE and NASHA through 36 weeks (9 months). Study subjects required less volume (p<.001) and fewer touch-ups (p=.005) and reported less injection pain (p<.001) with DGE treatment. Most adverse events were mild to moderate skin reactions. DGE is a firm HA gel that required significantly less volume and fewer touch-ups to provide equivalent efficacy to NASHA for NLF correction; both dermal gels were well tolerated. DGE will provide a comfortable and cost-effective dermal filler option for clinicians and patients. © 2010 by the American Society for Dermatologic Surgery, Inc.

DNA Polymorphism Assay Distinguishes Isolates of Leishmania donovani That Cause Kala-Azar from Those That Cause Post-Kala-Azar Dermal Leishmaniasis in Humans

PubMed Central

Sreenivas, Gannavaram; Subba Raju, B. V.; Singh, Ruchi; Selvapandiyan, Angamuthu; Duncan, Robert; Sarkar, Dwijen; Nakhasi, Hira L.; Salotra, Poonam

2004-01-01

Leishmania donovani in India causes visceral infection (kala-azar) and dermal infection (post-kala-azar dermal leishmaniasis). We report here the identification of polymorphism in a well-defined genetic locus among the Leishmania parasites causing the visceral and dermal manifestations, in a comparison of 15 post-kala-azar dermal leishmaniasis and 12 kala-azar patient isolates. PMID:15071036

Dermal toxicity, eye and dermal irritation and skin sensitization evaluation of a new formulation of Bacillus thuringiensis var israelensis SH-14.

PubMed

Arteaga, M E; Mancebo, A; Molier, T; Gómez, D; González, C; Bada, A M; González, B; Rojas, N M; Rodríguez, G

2014-02-01

Bacillus thuringiensis (Bt) is the best known and most widely used of all pesticidal microbes. The aim of this study was to assess the toxicity of a new formulation of Bacillus thuringiensis var israelensis SH-14 in rats through acute dermal toxicity, dermal and eye irritation experiments. The acute dermal toxicity and dermal and eye irritation studies were performed using rabbits according to the United States Environmental Protection Agency guidelines 885.3100, 870.2500 and 870.2500, respectively. The skin sensitization study was carried out in accordance to the EPA OPPTS 870.2600 using guinea pigs. There was no mortality and no evidence of treatment-related toxicity in acute dermal toxicity test. No dermal responses, including erythema/eschar or edema, were found in rabbits treated with the new formulation of Bti SH-14. Minimum response was observed after eye application of test substance. No skin sensitization reactions were observed after the challenge with the new formulation of Bti SH-14 in the Bti SH-14-treated guinea pigs. In summary, the present study demonstrated that the new formulation of Bti SH-14 is not acutely toxic via dermal route, has low eye irritation and would not cause dermal irritation or hypersensitivity to tested animals. Copyright © 2013 Elsevier Inc. All rights reserved.

Immunohistochemical Analysis of Human Vallate Taste Buds

PubMed Central

Tizzano, Marco; Grigereit, Laura; Shultz, Nicole; Clary, Matthew S.

2015-01-01

The morphology of the vallate papillae from postmortem human samples was investigated with immunohistochemistry. Microscopically, taste buds were present along the inner wall of the papilla, and in some cases in the outer wall as well. The typical taste cell markers PLCβ2, GNAT3 (gustducin) and the T1R3 receptor stain elongated cells in human taste buds consistent with the Type II cells in rodents. In the human tissue, taste bud cells that stain with Type II cell markers, PLCβ2 and GNAT3, also stain with villin antibody. Two typical immunochemical markers for Type III taste cells in rodents, PGP9.5 and SNAP25, fail to stain any taste bud cells in the human postmortem tissue, although these antibodies do stain numerous nerve fibers throughout the specimen. Car4, another Type III cell marker, reacted with only a few taste cells in our samples. Finally, human vallate papillae have a general network of innervation similar to rodents and antibodies directed against SNAP25, PGP9.5, acetylated tubulin and P2X3 all stain free perigemmal nerve endings as well as intragemmal taste fibers. We conclude that with the exception of certain molecular features of Type III cells, human vallate papillae share the structural, morphological, and molecular features observed in rodents. PMID:26400924

Plasma Rich in Growth Factors Inhibits Ultraviolet B Induced Photoageing of the Skin in Human Dermal Fibroblast Culture.

PubMed

Anitua, Eduardo; Pino, Ander; Orive, Gorka

Ultraviolet irradiation is able to deeply penetrate into the dermis and alter fibroblast structure and function, leading to a degradation of the dermal extracellular matrix. The regenerative effect of plasma rich in growth factors (PRGF) on skin ageing was investigated using UVB photo-stressed human dermal fibroblasts as an in vitro culture model. PRGF was assessed over the main indicative features of ultraviolet B irradiation, including ROS formation, cell viability and death detection, apoptosis/ necrosis analysis and biosynthetic activity measurement. Four different UV irradiation protocols were tested in order to analyze the beneficial effects of PRGF. Ultraviolet irradiation exhibited a dose dependent cytotoxicity and dose of 400mJ/cm2 was selected for subsequent experiments. PRGF increased the cell viability and decreased the cell death comparing to the non-treated group. The apoptosis and necrosis were significantly lower in PRGF treated fibroblasts. ROS production after UV irradiation was significantly reduced in the presence of PRGF. Procollagen type I, hyaluronic acid and TIMP-1 levels were higher in the when treated with PRGF. This preliminary in vitro study suggests that PRGF is able to prevent UVB derived photooxidative stress and to diminish the cell damage caused by ultraviolet irradiation.

Assessment of dermal absorption of DEET-containing insect repellent and oxybenzone-containing sunscreen using human urinary metabolites.

PubMed

Yiin, Lih-Ming; Tian, Jia-Ni; Hung, Chien-Che

2015-05-01

Mutual enhancement of dermal absorption of N,N-diethyl-m-toluamide (DEET) and oxybenzone (OBZ) has been reported recently with DEET and OBZ being active ingredients of insect repellent and sunscreen, respectively. To assess the reported enhancing effect directly, we used human urinary metabolites as biomarkers; besides, we also sought to determine the best way for concurrent use of these two products without extra absorption of either. Four dermal application methods were used: DEET only (S1), OBZ only (S2), DEET on top of OBZ (S3), and OBZ on top of DEET (S4). Among the study methods, there was a significant difference (p = 0.013), which was attributed to the difference between S1 and S4, suggesting that applying OBZ over DEET on the skin lead to significantly higher absorption of DEET. Using both products in reverse order, (S3) did not result in extra DEET absorption significantly. As for OBZ permeation, no significant difference was observed among the methods. In summary, the enhancement of DEET absorption is confirmed for OBZ being applied over DEET on the skin; should concurrent use of both be necessary, applying sunscreen (OBZ) first and then insect repellent (DEET) with a 15-min interval is recommended.

Effect of Fish Collagen Hydrolysates on Type I Collagen mRNA Levels of Human Dermal Fibroblast Culture

PubMed Central

Sanchez, Ana; Blanco, Maria; Correa, Begoña

2018-01-01

Fish discards and subproducts may represent an important source of raw material, not only for the food industry, but for other different kind of industries, such as the nutraceutical and cosmetic industries. Collagen, which is mainly obtained from animal skins, is an important structural protein in the animal kingdom having many different applications. It is well known that fish skins constitute a significant subproduct in the fishery industry, especially in the case of some species, where fish skins may represent up to 20% of the total body weight of fish. Peptides from collagen hydrolysates have been described to be useful for preventing skin aging and osteoarthritis, however, the mechanism for these biological activities is not well known. Fibroblasts are the main cell types involved in the collagen synthesis, and in the present work, human dermal fibroblasts have been exposed to the treatment of collagen peptides of two different molecular weight ranges. Results show that higher molecular weight collagen peptides produce higher synthesis of collagen type I mRNA and, therefore, it may suggest that prior molecular weight selection may be an important step to maximize the effect of collagen hydrolysates on collagen type I synthesis by dermal fibroblasts. PMID:29701725

Genetics Home Reference: focal dermal hypoplasia

MedlinePlus

... in people with focal dermal hypoplasia is an omphalocele , which is an opening in the wall of ... Dermal Hypoplasia MedlinePlus Encyclopedia: Ectodermal dysplasia MedlinePlus Encyclopedia: Omphalocele General Information from MedlinePlus (5 links) Diagnostic Tests ...

The application of dermal papillary rings in dermatology by in vivo confocal laser scanning microscopy

NASA Astrophysics Data System (ADS)

Xiang, W. Z.; Xu, A. E.; Xu, J.; Bi, Z. G.; Shang, Y. B.; Ren, Q. S.

2010-08-01

Confocal laser scanning microscopy (CLSM) allows noninvasive visualization of human skin in vivo, without needing to fix or section the tissue. Melanocytes and pigmented keratinocytes at the level of the basal layer form bright dermal papillary rings which are readily amenable to identify in confocal images. Our purpose was to explore the role of dermal papillary rings in assessment of lesion location, the diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. Seventy-one patients were imaged with the VivaScope 1500 reflectance confocal microscope provided by Lucid, Inc. The results indicate that dermal papillary rings can assess the location of lesion; the application of dermal papillary rings can provide diagnostic support and differential diagnosis for vitiligo, nevus depigmentosus, tinea versicolor, halo nevus, common nevi, and assess the therapeutic efficacy of NBUVB phototherapy plus topical 0.1 percent tacrolimus ointment for vitiligo. In conclusion, our findings indicate that the dermal papillary rings play an important role in the assessment the location of lesion, diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. CLSM may be a promising tool for noninvasive examination in dermatology. However, larger studies are needed to expand the application of dermal papillary rings in dermatology.

Quantitative anatomical study of taste buds in fungiform papillae of young and old Fischer rats.

PubMed

Mistretta, C M; Oakley, I A

1986-05-01

To determine if differences in neural taste responses relate to taste bud loss in old age, taste buds were counted in fungiform papillae of Fischer 344 rats aged 4 to 6 months, 20 to 24 months, and 30 to 37 months. Papillae anterior to the intermolar eminence on one half of the tongue were examined in serial sections. Presence or absence of a taste bud was noted and taste bud diameter was measured. Average percentages of papillae that contained a taste bud in the three groups were 99.6, 99.3, and 94.7%. This is a significant age-related difference but actual number of taste buds lost in the oldest rats was small. Taste bud diameter did not differ with age and general anatomical characteristics of buds were similar in all groups. Thus, anatomical observations on taste bud maintenance in rats over a wide age range, coupled with neurophysiological data, demonstrate that the integrity of the peripheral gustatory system is not altered greatly in old age.

Dextran-shelled oxygen-loaded nanodroplets reestablish a normoxia-like pro-angiogenic phenotype and behavior in hypoxic human dermal microvascular endothelium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basilico, Nicoletta, E-mail: nicoletta.basilico@unimi.it; Magnetto, Chiara, E-mail: c.magnetto@inrim.it; D'Alessandro, Sarah, E-mail: sarah.dalessandro@unimi.it

In chronic wounds, hypoxia seriously undermines tissue repair processes by altering the balances between pro-angiogenic proteolytic enzymes (matrix metalloproteinases, MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) released from surrounding cells. Recently, we have shown that in human monocytes hypoxia reduces MMP-9 and increases TIMP-1 without affecting TIMP-2 secretion, whereas in human keratinocytes it reduces MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. Provided that the phenotype of the cellular environment is better understood, chronic wounds might be targeted by new oxygenating compounds such as chitosan- or dextran-shelled and 2H,3H-decafluoropentane-cored oxygen-loaded nanodroplets (OLNs). Here, we investigated the effects ofmore » hypoxia and dextran-shelled OLNs on the pro-angiogenic phenotype and behavior of human dermal microvascular endothelium (HMEC-1 cell line), another cell population playing key roles during wound healing. Normoxic HMEC-1 constitutively released MMP-2, TIMP-1 and TIMP-2 proteins, but not MMP-9. Hypoxia enhanced MMP-2 and reduced TIMP-1 secretion, without affecting TIMP-2 levels, and compromised cell ability to migrate and invade the extracellular matrix. When taken up by HMEC-1, nontoxic OLNs abrogated the effects of hypoxia, restoring normoxic MMP/TIMP levels and promoting cell migration, matrix invasion, and formation of microvessels. These effects were specifically dependent on time-sustained oxygen diffusion from OLN core, since they were not achieved by oxygen-free nanodroplets or oxygen-saturated solution. Collectively, these data provide new information on the effects of hypoxia on dermal endothelium and support the hypothesis that OLNs might be used as effective adjuvant tools to promote chronic wound healing processes. - Highlights: • Hypoxia enhances MMP-2 and reduces TIMP-1 secretion by dermal HMEC-1 cell line. • Hypoxia compromises migration and matrix invasion

Bio-artificial pleura using an autologous dermal fibroblast sheet

NASA Astrophysics Data System (ADS)

Kanzaki, Masato; Takagi, Ryo; Washio, Kaoru; Kokubo, Mami; Yamato, Masayuki

2017-10-01

Air leaks (ALs) are observed after pulmonary resections, and without proper treatment, can produce severe complications. AL prevention is a critical objective for managing patients after pulmonary resection. This study applied autologous dermal fibroblast sheets (DFS) to close ALs. For sealing ALs in a 44-year-old male human patient with multiple bullae, a 5 × 15-mm section of skin was surgically excised. From this skin specimen, primary dermal fibroblasts were isolated and cultured for 4 weeks to produce DFSs that were harvested after a 10-day culture. ALs were completely sealed using surgical placement of these autologous DFSs. DFS were found to be a durable long-term AL sealant, exhibiting requisite flexibility, elasticity, durability, biocompatibility, and usability, resulting reliable AL closure. DFS should prove to be an extremely useful tissue-engineered pleura substitute.

The influence of water mixtures on the dermal absorption of glycol ethers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Traynor, Matthew J.; Wilkinson, Simon C.; Williams, Faith M.

2007-01-15

Glycol ethers are solvents widely used alone and as mixtures in industrial and household products. Some glycol ethers have been shown to have a range of toxic effects in humans following absorption and metabolism to their aldehyde and acid metabolites. This study assessed the influence of water mixtures on the dermal absorption of butoxyethanol and ethoxyethanol in vitro through human skin. Butoxyethanol penetrated human skin up to sixfold more rapidly from aqueous solution (50%, 450 mg/ml) than from the neat solvent. Similarly penetration of ethoxyethanol was increased threefold in the presence of water (50%, 697 mg/ml). There was a correspondingmore » increase in apparent permeability coefficient as the glycol ether concentration in water decreased. The maximum penetration rate of water also increased in the presence of both glycol ethers. Absorption through a synthetic membrane obeyed Fick's Law and absorption through rat skin showed a similar profile to human skin but with a lesser effect. The mechanisms for this phenomenon involves disruption of the stratum corneum lipid bilayer by desiccation by neat glycol ether micelles, hydration with water mixtures and the physicochemical properties of the glycol ether-water mixtures. Full elucidation of the profile of absorption of glycol ethers from mixtures is required for risk assessment of dermal exposure. This work supports the view that risk assessments for dermal contact scenarios should ideally be based on absorption data obtained for the relevant formulation or mixture and exposure scenario and that absorption derived from permeability coefficients may be inappropriate for water-miscible solvents.« less

Electrical tuning and transduction in short hair cells of the chicken auditory papilla.

PubMed

Tan, Xiaodong; Beurg, Maryline; Hackney, Carole; Mahendrasingam, Shanthini; Fettiplace, Robert

2013-04-01

The avian auditory papilla contains two classes of sensory receptor, tall hair cells (THCs) and short hair cells (SHCs), the latter analogous to mammalian outer hair cells with large efferent but sparse afferent innervation. Little is known about the tuning, transduction, or electrical properties of SHCs. To address this problem, we made patch-clamp recordings from hair cells in an isolated chicken basilar papilla preparation at 33°C. We found that SHCs are electrically tuned by a Ca(2+)-activated K(+) current, their resonant frequency varying along the papilla in tandem with that of the THCs, which also exhibit electrical tuning. The tonotopic map for THCs was similar to maps previously described from auditory nerve fiber measurements. SHCs also possess an A-type K(+) current, but electrical tuning was observed only at resting potentials positive to -45 mV, where the A current is inactivated. We predict that the resting potential in vivo is approximately -40 mV, depolarized by a standing inward current through mechanotransducer (MT) channels having a resting open probability of ∼0.26. The resting open probability stems from a low endolymphatic Ca(2+) concentration (0.24 mM) and a high intracellular mobile Ca(2+) buffer concentration, estimated from perforated-patch recordings as equivalent to 0.5 mM BAPTA. The high buffer concentration was confirmed by quantifying parvalbumin-3 and calbindin D-28K with calibrated postembedding immunogold labeling, demonstrating >1 mM calcium-binding sites. Both proteins displayed an apex-to-base gradient matching that in the MT current amplitude, which increased exponentially along the papilla. Stereociliary bundles also labeled heavily with antibodies against the Ca(2+) pump isoform PMCA2a.

[Effect of KH2PO4 on the odonto- and osteogenic differentiation potential of human stem cells from apical papillae].

PubMed

Wang, Yan-ping; Wu, Jin-tao; Wang, Zi-lu; Zheng, Yang-yu; Zhang, Guang-dong; Yu, Jin-hua

2013-01-01

To determine the effects of KH2PO4 on the odonto- and osteogenic differentiation potential of human stem cells from apical papillae (SCAP) in vitro. SCAP were isolated and cultured respectively in alpha minimum essential medium (α-MEM) or α-MEM containing 1.8 mmol/L KH2PO4. Alkaline phosphatase (ALP) activity, alizarin red staining, real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to examine the odonto and osteogenic potential of SCAP in the two media. SCAP cultured in α-MEM containing 1.8 mmol/L KH2PO4 exhibited a higher ALP activity [(0.370 ± 0.013) Sigma unit×min(-1)×mg(-1)] at day 3 than control group [(0.285 ± 0.008) Sigma unit×min(-1)×mg(-1)] and KH2PO4-treated SCAP formed more calcified nodules at day 5 [(0.539 ± 0.007) µg/g] and day 7 [(1.617 ± 0.042) µg/g] than those in normal medium [(0.138 ± 0.037) µg/g, P < 0.01]. The expression of odonto- and osteogenic markers were significantly up-regulated after the stimulation of KH2PO4 at day 3 and 7 respectively, as compared with control group. 1.8 mmol/L KH2PO4 can promote the odonto and osteogenic differentiation potential of human SCAP.

ISSUES IN DERMAL EXPOSURE OF INFANTS

EPA Science Inventory

Infants' dermal exposures to environmental contaminants are expected to be different and, in many cases, much higher than adults. Because of the potential importance of the dermal exposure route, there is currently a significant amount of work being conducted to reduce the uncer...

Disseminated Autochthonous Dermal Leishmaniasis Caused by Leishmania siamensis (PCM2 Trang) in a Patient from Central Thailand Infected with Human Immunodeficiency Virus.

PubMed

Supsrisunjai, Chavalit; Kootiratrakarn, Tanawatt; Puangpet, Pailin; Bunnag, Thareena; Chaowalit, Prapaipit; Wessagowit, Vesarat

2017-05-01

AbstractSeveral case reports of autochthonous leishmaniasis in Thailand have been published since 1996. Most of the previous cases presented with visceral leishmaniasis (VL) and were mostly reported in southern part of Thailand. Recently, it has been evident that Leishmania martiniquensis is the main cause of Leishmania infection in Thailand. However, Leishmania siamensis (PCM2 Trang isolate) was found to be of a separate lineage with restricted distribution in southern Thailand and also a cause of disseminated dermal and visceral leishmaniasis in one published case. Here we report the first patient from central Thailand with human immunodeficiency virus infection presenting with disseminated dermal leishmaniasis. Polymerase chain reaction and DNA sequencing analysis (large subunit of RNA polymerase II and 18S ribosomal RNA internal transcribed spacer 1) from the tissue biopsy sample revealed the pathogen sequences to be highly homologous to PCM2 Trang strain previously reported from southern Thailand.

Disseminated Autochthonous Dermal Leishmaniasis Caused by Leishmania siamensis (PCM2 Trang) in a Patient from Central Thailand Infected with Human Immunodeficiency Virus

PubMed Central

Supsrisunjai, Chavalit; Kootiratrakarn, Tanawatt; Puangpet, Pailin; Bunnag, Thareena; Chaowalit, Prapaipit; Wessagowit, Vesarat

2017-01-01

Several case reports of autochthonous leishmaniasis in Thailand have been published since 1996. Most of the previous cases presented with visceral leishmaniasis (VL) and were mostly reported in southern part of Thailand. Recently, it has been evident that Leishmania martiniquensis is the main cause of Leishmania infection in Thailand. However, Leishmania siamensis (PCM2 Trang isolate) was found to be of a separate lineage with restricted distribution in southern Thailand and also a cause of disseminated dermal and visceral leishmaniasis in one published case. Here we report the first patient from central Thailand with human immunodeficiency virus infection presenting with disseminated dermal leishmaniasis. Polymerase chain reaction and DNA sequencing analysis (large subunit of RNA polymerase II and 18S ribosomal RNA internal transcribed spacer 1) from the tissue biopsy sample revealed the pathogen sequences to be highly homologous to PCM2 Trang strain previously reported from southern Thailand. PMID:28138050

Patterns of immunoreactivity specific for gustducin and for NCAM differ in developing rat circumvallate papillae and their taste buds.

PubMed

Iwasaki, Shin-Ichi; Aoyagi, Hidekazu; Asami, Tomoichiro; Wanichanon, Chaitip; Jackowiak, Hanna

2012-05-01

α-Gustducin and neural cell adhesion molecule (NCAM) are molecules previously found to be expressed in different cell types of mammalian taste buds. We examined the expression of α-gustducin and NCAM during the morphogenesis of circumvallate papillae and the formation of their taste buds by immunofluorescence staining and laser-scanning microscopy of semi-ultrathin sections of fetal and juvenile rat tongues. Images obtained by confocal laser scanning microscopy in transmission mode were also examined to provide outlines of histology and cell morphology. Morphogenesis of circumvallate papillae had already started on embryonic day 13 (E13) and was evident as the formation of placode. By contrast, taste buds in the circumvallate papillae started to appear between postnatal day 0 (P0) and P7. Although no cells with immunoreactivity specific for α-gustducin were detected in fetuses from E13 to E19, cells with NCAM-specific immunoreactivity were clearly apparent in the entire epithelium of the circumvallate papillary placode, the rudiment of each circumvallate papilla and the developing circumvallate papilla itself from E13 to E19. However, postnatally, both α-gustducin and NCAM became concentrated within taste cells as the formation of taste buds advanced. After P14, neither NCAM nor α-gustducin was detectable in the epithelium around the taste buds. In conclusion, α-gustducin appeared in the cytoplasm of taste cells during their formation after birth, while NCAM appeared in the epithelium of the circumvallate papilla-forming area. However, these two markers of taste cells were similarly distributed within mature taste cells. Copyright © 2011 Elsevier GmbH. All rights reserved.

Pattern of cytokine receptors expressed by human dendritic cells migrated from dermal explants.

PubMed Central

Larregina, A T; Morelli, A E; Kolkowski, E; Sanjuan, N; Barboza, M E; Fainboim, L

1997-01-01

Different reasons account for the lack of information about the expression of cytokine receptors on human dendritic cells (DC): (a) DC are a trace population; (b) the proteolytic treatment used to isolate DC may alter enzyme-sensitive epitopes; and (c) low numbers of receptors per cell. In the present work the expression of cytokine receptors was analysed by flow cytometry on the population of dermal DC (DDC) that spontaneously migrate from short-term culture dermal explants. DDC obtained after dermal culture were CD1alow, CD1b+, CD1c+, human leucocyte antigen (HLA)-DR+, CD11chigh, CD11b+ and CD32+. The DC lineage was confirmed by ultrastructural analysis. DDC expressed interleukin (IL)-1R type 1 (monoclonal antibody (mAb) hIL-1R1-M1; and 6B5); IL-1R type 2 (mAb hIL-1R2-M22); IL-2R alpha chain (mAb anti-Tac; and hIL-2R-M1) and IL-2R gamma chain (mAb 3B5; and AG14C). DDC did not stain for IL-2R beta chain using four mAbs recognizing two different epitopes of IL-2R beta (mAb 2R-B; Mik-beta 1; and CF1; Mik-beta 3, respectively). DDC were also positive for the cytokine binding chains (alpha chains) of IL-3R (mAb 9F5); IL-4R (mAb hIL-4R-M57; and S456C9); and IL-7R (mAb hIL-7R-M20; and R3434). DDC showed low levels of IL-6R alpha chain (mAb B-F19; B-R6; and B-E23) and its signal transducer gp130 (mAb A2; and B1). DDC strongly expressed interferon-gamma receptor (IFN-gamma R) (mAb GIR-208) and were negative for IL-8R (mAb B-G20; and B-F25). All DDC were highly positive for granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha chain (mAb hGM-CSFR-M1; SC06; SC04, and 8G6) and to a lesser extent for the common beta chain of GM-CSFR, IL-3R and IL-5R (mAb 3D7). On the other hand, reactivity was not found for granulocyte colony-stimulating factor receptor (G-CSFR) (mAb hGCSFR-M1) nor macrophage colony-stimulating factor receptor (M-CSFR) (mAb 7-7A3-17) confirming the DC lineage of DDC. As previously reported for lymphoid DC, DDC expressed tumour necrosis

Cell apoptosis of taste buds in circumvallate papillae in diabetic rats.

PubMed

Cheng, B; Pan, S; Liu, X; Zhang, S; Sun, X

2011-09-01

Diabetes mellitus may result in taste disturbance. The present study has revealed that cell apoptosis of taste buds in circumvallate papillae may contribute to the taste disturbance in a rat model of type2 diabetes. Type2 diabetes was induced in Wistar rats by feeding them with a high-fat diet (30% fat), and a single intraperitoneal injection of streptozotocin (30 mg/kg). The increased cell apoptosis of taste buds in circumvallate papilla sections was detected by TUNEL staining in diabetic rats, and the ultrastructure was further examined by transmission electronic microscopy. Immunohistochemical and Western blot analyses revealed the downregulation of Bcl-2, upregulation of Bax, and increased activation of caspase-9 and -3, in diabetic rats, indicating that the apoptosis of taste bud cells may be mediated via the intrinsic mitochondrial pathway in diabetics. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Dermal uptake of petroleum substances.

PubMed

Jakasa, Ivone; Kezic, Sanja; Boogaard, Peter J

2015-06-01

Petroleum products are complex substances comprising varying amounts of linear and branched alkanes, alkenes, cycloalkanes, and aromatics which may penetrate the skin at different rates. For proper interpretation of toxic hazard data, understanding their percutaneous absorption is of paramount importance. The extent and significance of dermal absorption of eight petroleum substances, representing different classes of hydrocarbons, was evaluated. Literature data on the steady-state flux and permeability coefficient of these substances were evaluated and compared to those predicted by mathematical models. Reported results spanned over 5-6 orders of magnitude and were largely dependent on experimental conditions in particular on the type of the vehicle used. In general, aromatic hydrocarbons showed higher dermal absorption than more lipophilic aliphatics with similar molecular weight. The results showed high variation and were largely influenced by experimental conditions emphasizing the need of performing the experiments under "in use" scenario. The predictive models overestimated experimental absorption. The overall conclusion is that, based on the observed percutaneous penetration data, dermal exposure to petroleum hydrocarbons, even of aromatics with highest dermal absorption is limited and highly unlikely to be associated with health risks under real use scenarios. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Reconstruction of the maxillary midline papilla following a combined orthodontic-periodontic treatment in adult periodontal patients.

PubMed

Cardaropoli, Daniele; Re, Stefania; Corrente, Giuseppe; Abundo, Roberto

2004-02-01

The aim of the present study was to evaluate the role of a combined orthodontic-periodontic treatment in determining the reconstruction of midline papilla lost following periodontitis. Twenty-eight patients, with infrabony defect and extrusion of one maxillary central incisor, were treated. At baseline, all patients presented opening of the interdental diastema and loss of the papilla. At 7-10 days after open-flap surgery, the intrusive movement started. For each patient, probing pocket depth (PPD), clinical attachment level (CAL) and papilla presence index (PI) were assessed at baseline, end of treatment and after 1 year. PI was also evaluated independently in patients with narrow or wide periodontal biotype (NPB-WPB). All parameters showed statistical improvement between the initial and final measurements, and showed no changes at follow-up time. The mean residual PPD was 2.50 mm, with a decrease of 4.29 mm, while the mean CAL gain was 5.93 mm. Twenty-three out of 28 patients improved the PI score at the end of therapy. No statistical difference was recorded in PI values between groups NPB and WPB. The presented clinical protocol resulted in the improvement of all parameters examined. At the end of orthodontic treatment, a predictable reconstruction of the interdental papilla was reported, both in patients with thin or wide gingiva. Copyright Blackwell Munksgaard, 2004.

Dermal extracellular lipid in birds.

PubMed

Stromberg, M W; Hinsman, E J; Hullinger, R L

1990-01-01

A light and electron microscopic study of the skin of domestic chickens, seagulls, and antarctic penguins revealed abundant extracellular dermal lipid and intracellular epidermal lipid. Dermal lipid appeared ultrastructurally as extracellular droplets varying from less than 1 micron to more than 25 microns in diameter. The droplets were often irregularly contoured, sometimes round, and of relatively low electron density. Processes of fibrocytes were often seen in contact with extracellular lipid droplets. Sometimes a portion of such a droplet was missing, and this missing part appeared to have been "digested away" by the cell process. In places where cells or cell processes are in contact with fact droplets, there are sometimes extracellular membranous whorls or fragments which have been associated with the presence of fatty acids. Occasionally (in the comb) free fat particles were seen in intimate contact with extravasated erythrocytes. Fat droplets were seen in the lumen of small dermal blood and lymph vessels. We suggest that the dermal extracellular lipid originates in the adipocyte layer and following hydrolysis the free fatty acids diffuse into the epidermis. Here they become the raw material for forming the abundant neutral lipid contained in many of the epidermal cells of both birds and dolphins. The heretofore unreported presence and apparently normal utilization of abundant extracellular lipid in birds, as well as the presence of relatively large droplets of neutral lipid in dermal vessels, pose questions which require a thorough reappraisal of present concepts of the ways in which fat is distributed and utilized in the body.

Immunohistochemical Analysis of Human Vallate Taste Buds.

PubMed

Tizzano, Marco; Grigereit, Laura; Shultz, Nicole; Clary, Matthew S; Finger, Thomas E

2015-11-01

The morphology of the vallate papillae from postmortem human samples was investigated with immunohistochemistry. Microscopically, taste buds were present along the inner wall of the papilla, and in some cases in the outer wall as well. The typical taste cell markers PLCβ2, GNAT3 (gustducin) and the T1R3 receptor stain elongated cells in human taste buds consistent with the Type II cells in rodents. In the human tissue, taste bud cells that stain with Type II cell markers, PLCβ2 and GNAT3, also stain with villin antibody. Two typical immunochemical markers for Type III taste cells in rodents, PGP9.5 and SNAP25, fail to stain any taste bud cells in the human postmortem tissue, although these antibodies do stain numerous nerve fibers throughout the specimen. Car4, another Type III cell marker, reacted with only a few taste cells in our samples. Finally, human vallate papillae have a general network of innervation similar to rodents and antibodies directed against SNAP25, PGP9.5, acetylated tubulin and P2X3 all stain free perigemmal nerve endings as well as intragemmal taste fibers. We conclude that with the exception of certain molecular features of Type III cells, human vallate papillae share the structural, morphological, and molecular features observed in rodents. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Ultraviolet-B Protective Effect of Flavonoids from Eugenia caryophylata on Human Dermal Fibroblast Cells.

PubMed

Patwardhan, Juilee; Bhatt, Purvi

2015-10-01

The exposure of skin to ultraviolet-B (UV-B) radiations leads to deoxyribonucleic acid (DNA) damage and can induce production of free radicals which imbalance the redox status of the cell and lead to increased oxidative stress. Clove has been traditionally used for its analgesic, anti-inflammatory, anti-microbial, anti-viral, and antiseptic effects. To evaluate the UV-B protective activity of flavonoids from Eugenia caryophylata (clove) buds on human dermal fibroblast cells. Protective ability of flavonoid-enriched (FE) fraction of clove was studied against UV-B induced cytotoxicity, anti-oxidant regulation, oxidative DNA damage, intracellular reactive oxygen species (ROS) generation, apoptotic morphological changes, and regulation of heme oxygenase-1 (HO-1) gene through nuclear factor E2-related factor 2 antioxidant response element (Nrf2 ARE) pathway. FE fraction showed a significant antioxidant potential. Pretreatment of cells with FE fraction (10-40 μg/ml) reversed the effects of UV-B induced cytotoxicity, depletion of endogenous enzymatic antioxidants, oxidative DNA damage, intracellular ROS production, apoptotic changes, and overexpression of Nrf2 and HO-1. The present study demonstrated for the first time that the FE fraction from clove could confer UV-B protection probably through the Nrf2-ARE pathway, which included the down-regulation of Nrf2 and HO-1. These findings suggested that the flavonoids from clove could potentially be considered as UV-B protectants and can be explored further for its topical application to the area of the skin requiring protection. Pretreatment of human dermal fibroblast with flavonoid-enriched fraction of Eugenia caryophylata attenuated effects of ultraviolet-B radiationsIt also conferred protection through nuclear factor E2-related factor 2-antioxidant response pathway and increased tolerance of cells against oxidative stressFlavonoid-enriched fraction can be explored further for topical application to the skin as a

THE DEVELOPMENT AND TESTING OF A DERMAL EXPOSURE SYSTEM FOR PHARMACOKINETIC STUDIES OF ADMINISTERED AND AMBIENT WATER CONTAMINANTS: METHODS AND RESULTS

EPA Science Inventory

INTRODUCTION: In order to investigate the pharmacokinetics of water-borne chemicals while eliminating exposures by other routes, a dermal exposure system was developed to expose the hand and forearm of human subjects. METHODS: The goal was, primarily, to study the dermal phar...

Mesenchymal stem cells induce dermal fibroblast responses to injury

PubMed Central

Smith, Andria N.; Willis, Elise; Chan, Vincent T.; Muffley, Lara A.; Isik, F. Frank; Gibran, Nicole S.; Hocking, Anne M.

2009-01-01

Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury. PMID:19666021

Mesenchymal stem cells induce dermal fibroblast responses to injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Andria N., E-mail: snosmith@u.washington.edu; Willis, Elise, E-mail: elise.willis@gmail.com; Chan, Vincent T.

2010-01-01

Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. Whenmore » co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.« less

Differential Response of Human Adipose Tissue-Derived Mesenchymal Stem Cells, Dermal Fibroblasts, and Keratinocytes to Burn Wound Exudates: Potential Role of Skin-Specific Chemokine CCL27

PubMed Central

van den Broek, Lenie J.; Kroeze, Kim L.; Waaijman, Taco; Breetveld, Melanie; Sampat-Sardjoepersad, Shakun C.; Niessen, Frank B.; Middelkoop, Esther; Scheper, Rik J.

2014-01-01

Many cell-based regenerative medicine strategies toward tissue-engineered constructs are currently being explored. Cell–cell interactions and interactions with different biomaterials are extensively investigated, whereas very few studies address how cultured cells will interact with soluble wound-healing mediators that are present within the wound bed after transplantation. The aim of this study was to determine how adipose tissue-derived mesenchymal stem cells (ASC), dermal fibroblasts, and keratinocytes will react when they come in contact with the deep cutaneous burn wound bed. Burn wound exudates isolated from deep burn wounds were found to contain many cytokines, including chemokines and growth factors related to inflammation and wound healing. Seventeen mediators were identified by ELISA (concentration range 0.0006–9 ng/mg total protein), including the skin-specific chemokine CCL27. Burn wound exudates activated both ASC and dermal fibroblasts, but not keratinocytes, to increase secretion of CXCL1, CXCL8, CCL2, and CCL20. Notably, ASC but not fibroblasts or keratinocytes showed significant increased secretion of vascular endothelial growth factor (5-fold) and interleukin-6 (253-fold), although when the cells were incorporated in bi-layered skin substitute (SS) these differences were less pronounced. A similar discrepancy between ASC and dermal fibroblast mono-cultures was observed when recombinant human-CCL27 was used instead of burn wound exudates. Although CCL27 did not stimulate the secretion of any of the wound-healing mediators by keratinocytes, these cells, in contrast to ASC or dermal fibroblasts, showed increased proliferation and migration. Taken together, these results indicate that on transplantation, keratinocytes are primarily activated to promote wound closure. In contrast, dermal fibroblasts and, in particular, ASC respond vigorously to factors present in the wound bed, leading to increased secretion of angiogenesis/granulation tissue

Platelet-Rich Fibrin Lysate Can Ameliorate Dysfunction of Chronically UVA-Irradiated Human Dermal Fibroblasts.

PubMed

Wirohadidjojo, Yohanes Widodo; Budiyanto, Arief; Soebono, Hardyanto

2016-09-01

To determine whether platelet-rich fibrin lysate (PRF-L) could restore the function of chronically ultraviolet-A (UVA)-irradiated human dermal fibroblasts (HDFs), we isolated and sub-cultured HDFs from six different human foreskins. HDFs were divided into two groups: those that received chronic UVA irradiation (total dosages of 10 J cm⁻²) and those that were not irradiated. We compared the proliferation rates, collagen deposition, and migration rates between the groups and between chronically UVA-irradiated HDFs in control and PRF-L-treated media. Our experiment showed that chronic UVA irradiation significantly decreased (p<0.05) the proliferation rates, migration rates, and collagen deposition of HDFs, compared to controls. Compared to control media, chronically UVA-irradiated HDFs in 50% PRF-L had significantly increased proliferation rates, migration rates, and collagen deposition (p<0.05), and the migration rates and collagen deposition of chronically UVA-irradiated HDFs in 50% PRF-L were equal to those of normal fibroblasts. Based on this experiment, we concluded that PRF-L is a good candidate material for treating UVA-induced photoaging of skin, although the best method for its clinical application remains to be determined.

Healing rates for challenging rotator cuff tears utilizing an acellular human dermal reinforcement graft

PubMed Central

Agrawal, Vivek

2012-01-01

Purpose: This study presents a retrospective case series of the clinical and structural outcomes (1.5 T MRI) of arthroscopic rotator cuff repair with acellular human dermal graft reinforcement performed by a single surgeon in patients with large, massive, and previously repaired rotator cuff tears. Materials and Methods: Fourteen patients with mean anterior to posterior tear size 3.87 ± 0.99 cm (median 4 cm, range 2.5–6 cm) were enrolled in the study and were evaluated for structural integrity using a high-field (1.5 T) MRI at an average of 16.8 months after surgery. The Constant-Murley scores, the Flexilevel Scale of Shoulder Function (Flex SF), scapular plane abduction, and strength were analyzed. Results: MRI results showed that the rotator cuff repair was intact in 85.7% (12/14) of the patients studied. Two patients had a Sugaya Type IV recurrent tear (2 of 14; 14.3%), which were both less than 1 cm. The Constant score increased from a preoperative mean of 49.72 (range 13–74) to a postoperative mean of 81.07 (range 45–92) (P value = 0.009). Flexilevel Scale of Shoulder Function (Flex SF) Score normalized to a 100-point scale improved from a preoperative mean of 53.69 to a postoperative mean of 79.71 (P value = 0.003). The Pain Score improved from a preoperative mean of 7.73 to a postoperative mean of 13.57 (P value = 0.008). Scapular plane abduction improved from a preoperative mean of 113.64° to a postoperative mean of 166.43° (P value = 0.010). The strength subset score improved from a preoperative mean of 1.73 kg to a postoperative mean of 7.52 kg (P value = 0.006). Conclusions: This study presents a safe and effective technique that may help improve the healing rates of large, massive, and revision rotator cuff tears with the use of an acellular human dermal allograft. This technique demonstrated favorable structural healing rates and statistically improved functional outcomes in the near term. Level of Evidence: 4. Retrospective case series. PMID

Human skin gene expression: Natural (trans) resveratrol versus five resveratrol analogs for dermal applications.

PubMed

Lephart, Edwin D; Andrus, Merritt B

2017-09-01

Resveratrol (RV) is a polyphenolic compound naturally produced by plants. Polyphenolic compounds incorporated into medicinal products are beneficial but, RV is rapidly metabolized with an associated decline in biological activity. This study tested RV as the standard and compared five structurally modified RV analogs: butyrate, isobutyrate, palmitoate, acetate, and diacetate (to improve functionality) at 1% concentration(s) for 24 h in epiderm full thickness cultures by gene array/qPCR mRNA analysis. When silent mating type information regulation 2 homolog 1, extracellular elements (collagen1A1, 3A1, 4A1; elastin, tissue inhibitor of matrix metalloproteinase 1, fibrillin 1 laminin beta1 and matrix metalloproteinase 9), anti-aging and aging genes, inflammatory biomarkers (interleukin-1A [IL1A], IL1R2, IL-6 and IL-8), nerve growth factor, and the antioxidants (proliferating cell nuclear antigen, catalase, superoxide dismutase and metallothionein 1H/2H) were evaluated, ranking each from highest-to-lowest for gene expression: butyrate > isobutyrate > diacetate > acetate > palmitoate. This study showed that the butyrate and isobutyrate analogs are more biologically active compared to resveratrol and have potential use in topical applications to improve dermal and other health applications. Impact statement Resveratrol has been reported to have a wide variety of health benefits but its rapid metabolism especially after oral ingestion results in very low bioavailability. Notably, the first human skin gene expression study of resveratrol was not published until 2014. The purpose of this study was to determine if increased stability and biological activity could be obtained by modifying the chemical structure of natural (trans) resveratrol and quantifying human gene expression by qPCR of skin biomarkers that enhance dermal health. Five resveratrol analogs were synthesized that increased their lipophilic index to enhance tissue penetration and augment

Enhanced Expansion and Sustained Inductive Function of Skin‐Derived Precursor Cells in Computer‐Controlled Stirred Suspension Bioreactors

PubMed Central

Agabalyan, Natacha A.; Borys, Breanna S.; Sparks, Holly D.; Boon, Kathryn; Raharjo, Eko W.; Abbasi, Sepideh; Kallos, Michael S.

2016-01-01

Abstract Endogenous dermal stem cells (DSCs) reside in the adult hair follicle mesenchyme and can be isolated and grown in vitro as self‐renewing colonies called skin‐derived precursors (SKPs). Following transplantation into skin, SKPs can generate new dermis and reconstitute the dermal papilla and connective tissue sheath, suggesting they could have important therapeutic value for the treatment of skin disease (alopecia) or injury. Controlled cell culture processes must be developed to efficiently and safely generate sufficient stem cell numbers for clinical use. Compared with static culture, stirred‐suspension bioreactors generated fivefold greater expansion of viable SKPs. SKPs from each condition were able to repopulate the dermal stem cell niche within established hair follicles. Both conditions were also capable of inducing de novo hair follicle formation and exhibited bipotency, reconstituting the dermal papilla and connective tissue sheath, although the efficiency was significantly reduced in bioreactor‐expanded SKPs compared with static conditions. We conclude that automated bioreactor processing could be used to efficiently generate large numbers of autologous DSCs while maintaining their inherent regenerative function. Stem Cells Translational Medicine 2017;6:434–443 PMID:28191777

Engineering three dimensional micro nerve tissue using postnatal stem cells from human dental apical papilla.

PubMed

Kim, Byung-Chul; Jun, Sung-Min; Kim, So Yeon; Kwon, Yong-Dae; Choe, Sung Chul; Kim, Eun-Chul; Lee, Jae-Hyung; Kim, Jinseok; Suh, Jun-Kyo Francis; Hwang, Yu-Shik

2017-04-01

The in vitro generation of cell-based three dimensional (3D) nerve tissue is an attractive subject to improve graft survival and integration into host tissue for neural tissue regeneration or to model biological events in stem cell differentiation. Although 3D organotypic culture strategies are well established for 3D nerve tissue formation of pluripotent stem cells to study underlying biology in nerve development, cell-based nerve tissues have not been developed using human postnatal stem cells with therapeutic potential. Here, we established a culture strategy for the generation of in vitro cell-based 3D nerve tissue from postnatal stem cells from apical papilla (SCAPs) of teeth, which originate from neural crest-derived ectomesenchyme cells. A stem cell population capable of differentiating into neural cell lineages was generated during the ex vivo expansion of SCAPs in the presence of EGF and bFGF, and SCAPs differentiated into neural cells, showing neural cell lineage-related molecular and gene expression profiles, morphological changes and electrophysical property under neural-inductive culture conditions. Moreover, we showed the first evidence that 3D cell-based nerve-like tissue with axons and myelin structures could be generated from SCAPs via 3D organotypic culture using an integrated bioprocess composed of polyethylene glycol (PEG) microwell-mediated cell spheroid formation and subsequent dynamic culture in a high aspect ratio vessel (HARV) bioreactor. In conclusion, the culture strategy in our study provides a novel approach to develop in vitro engineered nerve tissue using SCAPs and a foundation to study biological events in the neural differentiation of postnatal stem cells. Biotechnol. Bioeng. 2017;114: 903-914. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Change of the human taste bud volume over time.

PubMed

Srur, Ehab; Stachs, Oliver; Guthoff, Rudolf; Witt, Martin; Pau, Hans Wilhelm; Just, Tino

2010-08-01

The specific aim of this study is to measure the taste volume in healthy human subjects over a 2.5-month period and to demonstrate morphological changes of the peripheral taste organs. Eighteen human taste buds in four fungiform papillae (fPap) were examined over a 10-week period. The fungiform papillae investigated were selected based on the form of the papillae or the arrangement of surface taste pores. Measurements were performed over 10 consecutive weeks, with five scans in a day once a week. The following parameters were measured: height and diameter of the taste bud, diameter of the fungiform papilla and diameter of the taste pore. The findings of this exploratory study indicated that (1) taste bud volumes changed over a 10-week period, (2) the interval between two volume maxima within the 10-week period was 3-5 weeks, and (3) the diameter of the fPap did not correlate with the volume of a single taste bud or with the volume of all taste buds in the fPap within the 10-week period. This exploratory in vivo study revealed changes in taste bud volumes in healthy humans with age-related gustatory sensitivity. These findings need to be considered when studying the effect of denervation of fungiform papillae in vivo using confocal microscopy. Crown Copyright 2009. Published by Elsevier Ireland Ltd. All rights reserved.

Dermal, oral, and inhalation pharmacokinetics of methyl tertiary butyl ether (MTBE) in human volunteers.

PubMed

Prah, James; Ashley, David; Blount, Benjamin; Case, Martin; Leavens, Teresa; Pleil, Joachim; Cardinali, Frederick

2004-02-01

Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation kinetics, 14 volunteers were exposed to 51.3 microg/ml MTBE dermally in tap water for 1 h, drank 2.8 mg MTBE in 250 ml Gatorade(R), and inhaled 3.1 ppm. MTBE for 1 h. Blood and exhaled breath samples were then obtained. Blood MTBE peaked between 15 and 30 min following oral exposure, at the end of inhalation exposure, and ~5 min after dermal exposure. Elimination by each route was described well by a three-compartment model (Rsq >0.9). The Akaike Information Criterion for the three-compartment model was smaller than the two-compartment model, supporting it over the two-compartment model. One metabolite, tertiary butyl alcohol (TBA), measured in blood slowly increased and plateaued, but it did not return to the pre-exposure baseline at the 24-h follow-up. TBA is very water-soluble and has a blood:air partition ratio of 462, reducing elimination by exhalation. Oral exposure resulted in a significantly greater MTBE metabolism into TBA than by other routes based on a greater blood TBA:MTBE AUC ratio, implying significant first-pass metabolism. The slower TBA elimination may make it a better biomarker of MTBE exposure, though one must consider the exposure route when estimating MTBE exposure from TBA because of first-pass metabolism. Most subjects had a baseline blood TBA of 1-3 ppb. Because TBA is found in consumer products and can be used as a fuel additive, it is not a definitive marker of MTBE exposure. These data provide the risk assessment process of pharmacokinetic information relevant to the media through which most exposures occur-air and drinking water.

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

PubMed

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.

Evaluation of cultured human dermal- and dermo-epidermal substitutes focusing on extracellular matrix components: Comparison of protein and RNA analysis.

PubMed

Oostendorp, Corien; Meyer, Sarah; Sobrio, Monia; van Arendonk, Joyce; Reichmann, Ernst; Daamen, Willeke F; van Kuppevelt, Toin H

2017-05-01

Treatment of full-thickness skin defects with split-thickness skin grafts is generally associated with contraction and scar formation and cellular skin substitutes have been developed to improve skin regeneration. The evaluation of cultured skin substitutes is generally based on qualitative parameters focusing on histology. In this study we focused on quantitative evaluation to provide a template for comparison of human bio-engineered skin substitutes between clinical and/or research centers, and to supplement histological data. We focused on extracellular matrix proteins since these components play an important role in skin regeneration. As a model we analyzed the human dermal substitute denovoDerm and the dermo-epidermal skin substitute denovoSkin. The quantification of the extracellular matrix proteins type III collagen and laminin 5 in tissue homogenates using western blotting analysis and ELISA was not successful. The same was true for assaying lysyl oxidase, an enzyme involved in crosslinking of matrix molecules. As an alternative, gene expression levels were measured using qPCR. Various RNA isolation procedures were probed. The gene expression profile for specific dermal and epidermal genes could be measured reliably and reproducibly. Differences caused by changes in the cell culture conditions could easily be detected. The number of cells in the skin substitutes was measured using the PicoGreen dsDNA assay, which was found highly quantitative and reproducible. The (dis) advantages of assays used for quantitative evaluation of skin substitutes are discussed. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Lemongrass (Cymbopogon flexuosus) essential oil demonstrated anti-inflammatory effect in pre-inflamed human dermal fibroblasts.

PubMed

Han, Xuesheng; Parker, Tory L

2017-06-01

Lemongrass ( Cymbopogon flexuosus ) essential oil (LEO), which has citral as its main component, has exhibited anti-inflammatory effect in both animal and human cells. In this study, we evaluated the anti-inflammatory activity of a commercially available LEO in pre-inflamed human dermal fibroblasts. We first studied the impact of LEO on 17 protein biomarkers that are critically associated with inflammation and tissue remodeling. LEO significantly inhibited production of the inflammatory biomarkers vascular cell adhesion molecule 1 (VCAM-1), interferon gamma-induced protein 10 (IP-10), interferon-inducible T-cell alpha chemoattractant (I-TAC), and monokine induced by gamma interferon (MIG); decreased levels of the tissue remodeling biomarkers collagen-I and III, epidermal growth factor receptor (EGFR), and plasminogen activator inhibitor (PAI-1); and inhibited the immunomodulatory biomarker macrophage colony-stimulating factor (M-CSF). Furthermore, we studied the impact of LEO on genome-wide gene expression profiles. LEO significantly modulated global gene expression and robustly impacted signaling pathways, many of which are critical for inflammation and tissue remodeling processes. This study provides the first evidence of the anti-inflammatory activity of LEO in human skin cells and indicates that it is a good therapeutic candidate for treating inflammatory conditions of the skin.

Molecular mechanisms of UVB-induced senescence of dermal fibroblasts and its relevance for photoaging of the human skin.

PubMed

Cavinato, Maria; Jansen-Dürr, Pidder

2017-08-01

Due to its ability to cross the epidermis and reach the upper dermis where it causes cumulative DNA damage and increased oxidative stress, UVB is considered the most harmful component of sunlight to the skin. The consequences of chronic exposition to UVB are related to photoaging and photocarcinogenesis. There are limitations to the study of human skin aging and for this reason the use of models is required. Human dermal fibroblasts submitted to mild and repeated doses of UVB are considered a versatile model to study UVB effects in the process of skin photoaging, which depends on the accumulation of senescent cells, in particular in the dermis. Here we provide updated information about the current model of UVB-induced senescence with special emphasis on the process of protein quality control. Copyright © 2017 Elsevier Inc. All rights reserved.

Papilla regeneration by injectable stem cell therapy with regenerative medicine: long-term clinical prognosis.

PubMed

Yamada, Yoichi; Nakamura, Sayaka; Ueda, Minoru; Ito, Kenji

2015-03-01

Black triangle (BT), an open interproximal space between teeth, can cause aesthetic concerns, food impaction, phonetic difficulties and periodontitis. The aim of this study was to determine the possibility and long-term prognosis of novel papilla regeneration with regenerative medicine, i.e. tissue-engineered papilla (TEP), and to investigate the potential of a tissue-engineering method for soft-tissue augmentation, especially aesthetic improvement of BT, with mesenchymal stem cells (MSCs) as the isolated cells, platelet-rich plasma (PRP) as the growth factor and hyaluronic acid (HA) as the scaffold. The parameters were assessed from a clinical point of view by measuring the distance from the tip of the interproximal papilla to the base of the contact area in each study region. The mean volumes, operation times and follow-up periods of TEP were 1.32 ± 0.25 ml, 2.2 ± 1.62 times and 55.3 ± 17.7 months; the mean improved BT values were 2.55 ± 0.89 mm. An aesthetic improvement was achieved. TEP was able to provide aesthetic improvement of black triangle and predictable results, and could emerge as another novel option for periodontal regenerative therapy in periodontal diseases. Copyright © 2013 John Wiley & Sons, Ltd.

Antioxidant Nanoplatforms for Dermal Delivery: Melatonin.

PubMed

Milan, Aroha Sanchez; Campmany, Ana Cristina Calpena; Naveros, Beatriz Clares

2017-01-01

Melatonin is emerging as a promising therapeutic agent, mainly due to its role as antioxidant. Substantial evidences show that melatonin is potentially effective in a variety of diseases as cancer, inflammation and neurodegenerative diseases. The excellent antioxidant capacity with pharmacokinetics characteristics and the emerging search for new pharmaceutical nanotechnology based systems, make it particularly attractive to elaborate nanoplatforms based on melatonin for biomedical or cosmetic dermal applications. Different nanosystems for dermal delivery have been investigated. This review focuses on nanocarrier production strategies, dermal melatonin application and delivery advances in vivo and in vitro. Equally, future perspectives of this assisted melatonin delivery have also been discussed. In the current review, we have revised relevant articles of the available literature using the major scientific databases. One hundred and thirteen papers were included in the review, the majority of which represent latest researches in nanosized platforms for the dermal delivery of melatonin including liposomes, ethosomes, niosomes, polymeric nanoparticles, solid lipid nanoparticles and cyclodextrins. Furthermore, relevant papers reporting in vitro and in vivo application studies of these nano-based melatonin platforms were also discussed. The use of nanoplatforms for the dermal melatonin delivery as antioxidant agent could improve the efficacy of conventional melatonin administration due to the preservation of the drug from premature oxidation and the enhancement of drug permeation through the skin providing greater exposure times. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Chemical stabilization of polymers: Implications for dermal exposure to additives.

PubMed

Bartsch, N; Girard, M; Schneider, L; Weijgert, V Van De; Wilde, A; Kappenstein, O; Vieth, B; Hutzler, C; Luch, A

2018-04-16

Technical benefits of additives in polymers stand in marked contrast to their associated health risks. Here, a multi-analyte method based on gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) was developed to quantify polymer additives in complex matrices such as low-density polyethylene (LDPE) and isolated human skin layers after dermal exposure ex vivo. That way both technical aspects and dermal exposure were investigated. The effects of polymer additivation on the material were studied using the example of LDPE. To this end, a tailor-made polymer was applied in aging studies that had been furnished with two different mixtures of phenol- and diarylamine-based antioxidants, plasticizers and processing aids. Upon accelerated thermo-oxidative aging of the material, the formation of LDPE degradation products was monitored with attenuated total reflectance-Fourier transformed infrared (ATR-FTIR) spectroscopy. Compared to pure LDPE, a protective effect of added antioxidants could be observed on the integrity of the polymer. Further, thermo-oxidative degradation of the additives and its kinetics were investigated using LDPE or squalane as matrix. The half-lives of additives in both matrices revealed significant differences between the tested additives as well as between LDPE and squalane. For instance, 2-tert-butyl-6-[(3-tert-butyl-2-hydroxy-5-methylphenyl)methyl]-4-methylphenol (Antioxidant 2246) showed a half-life 12 times lower when incorporated in LDPE as compared to squalane. As a model for dermal exposure of consumers, human skin was brought into contact with the tailor-made LDPE containing additives ex vivo in static Franz diffusion cells. The skin was then analyzed for additives and decomposition products. This study proved 10 polymer additives of diverse pysicochemical properties and functionalities to migrate out of the polymer and eventually overcome the intact human skin barrier during contact. Moreover, their individual distribution within

GABA promotes elastin synthesis and elastin fiber formation in normal human dermal fibroblasts (HDFs).

PubMed

Uehara, Eriko; Hokazono, Hideki; Hida, Mariko; Sasaki, Takako; Yoshioka, Hidekatsu; Matsuo, Noritaka

2017-06-01

The multiple physiological effects of γ-aminobutyric acid (GABA) as a functional food component have been recently reported. We previously reported that GABA upregulated the expression of type I collagen in human dermal fibroblasts (HDFs), and that oral administration of GABA significantly increased skin elasticity. However, details of the regulatory mechanism still remain unknown. In this study, we further examined the effects of GABA on elastin synthesis and elastin fiber formation in HDFs. Real-time PCR indicated that GABA significantly increased the expression of tropoelastin transcript in a dose-dependent manner. Additionally, the expression of fibrillin-1, fibrillin-2, and fibulin-5/DANCE, but not lysyl oxidase and latent transforming factor-β-binding protein 4, were also significantly increased in HDFs. Finally, immunohistochemical analysis confirmed that treatment with GABA dramatically increased the formation of elastic fibers in HDFs. Taken together, our results showed that GABA improves skin elasticity in HDFs by upregulating elastin synthesis and elastin fiber formation.

Central Role for Dermal Fibroblasts in Skin Model Protection against Candida albicans.

PubMed

Kühbacher, Andreas; Henkel, Helena; Stevens, Philip; Grumaz, Christian; Finkelmeier, Doris; Burger-Kentischer, Anke; Sohn, Kai; Rupp, Steffen

2017-06-01

The fungal pathogen Candida albicans colonizes basically all human epithelial surfaces, including the skin. Under certain conditions, such as immunosuppression, invasion of the epithelia occurs. Not much is known about defense mechanisms against C. albicans in subepithelial layers such as the dermis. Using immune cell-supplemented 3D skin models we defined a new role for fibroblasts in the dermis and identified a minimal set of cell types for skin protection against C. albicans invasion. Dual RNA sequencing of individual host cell populations and C. albicans revealed that dermal invasion is directly impeded by dermal fibroblasts. They are able to integrate signals from the pathogen and CD4+ T cells and shift toward an antimicrobial phenotype with broad specificity that is dependent on Toll-like receptor 2 and interleukin 1β. These results highlight a central function of dermal fibroblasts for skin protection, opening new possibilities for treatment of infectious diseases. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes and dermal fibroblasts.

PubMed

Pomari, Elena; Dalla Valle, Luisa; Pertile, Paolo; Colombo, Lorenzo; Thornton, M Julie

2015-02-01

Peripheral intracrine sex steroid synthesis from adrenal precursors dehydroepiandrosterone (DHEA) and DHEA-sulfate has evolved in humans. We sought to establish if there are differences in intracrine, paracrine, and endocrine regulation of sex steroids by primary cultures of human skin epidermal keratinocytes and dermal fibroblasts. Microarray analysis identified multifunctional genes modulated by steroids, quantitative RT-PCR (qRT-PCR) mRNA expression, enzymatic assay aromatase activity, scratch assay cell migration, immunocytochemistry α-smooth muscle actin (α-SMA), and collagen gel fibroblast contraction. All steroidogenic components were present, although only keratinocytes expressed the organic anion organic anion transporter protein (OATP) 2B1 transporter. Both expressed the G-protein-coupled estrogen receptor (GPER1). Steroids modulated multifunctional genes, up-regulating genes important in repair and aging [angiopoietin-like 4 (ANGPTL4), chemokine (C-X-C motif) ligand 1 (CXCL1), lamin B1 (LMNB1), and thioredoxin interacting protein (TXNIP)]. DHEA-sulfate (DHEA-S), DHEA, and 17β-estradiol stimulated keratinocyte and fibroblast migration at early (4 h) and late (24-48 h) time points, suggesting involvement of genomic and nongenomic signaling. Migration was blocked by aromatase and steroid sulfatase (STS) inhibitors confirming intracrine synthesis to estrogen. Testosterone had little effect, implying it is not an intermediate. Steroids stimulated fibroblast contraction but not α-SMA expression. Mechanical wounding reduced fibroblast aromatase activity but increased keratinocyte activity, amplifying the bioavailability of intracellular estrogen. Cultured fibroblasts and keratinocytes provide a biologically relevant model system to investigate the complex pathways of sex steroid intracrinology in human skin. © FASEB.

Species Typing in Dermal Leishmaniasis

PubMed Central

Dujardin, Jean-Claude

2015-01-01

SUMMARY Leishmania is an infectious protozoan parasite related to African and American trypanosomes. All Leishmania species that are pathogenic to humans can cause dermal disease. When one is confronted with cutaneous leishmaniasis, identification of the causative species is relevant in both clinical and epidemiological studies, case management, and control. This review gives an overview of the currently existing and most used assays for species discrimination, with a critical appraisal of the limitations of each technique. The consensus taxonomy for the genus is outlined, including debatable species designations. Finally, a numerical literature analysis is presented that describes which methods are most used in various countries and regions in the world, and for which purposes. PMID:25672782

Human dermal and gingival fibroblasts in a three-dimensional culture: a comparative study on matrix remodeling.

PubMed

Chaussain Miller, C; Septier, D; Bonnefoix, M; Lecolle, S; Lebreton-Decoster, C; Coulomb, B; Pellat, B; Godeau, G

2002-03-01

Free-floating collagen lattice is considered a useful tool for assessing wound healing in vitro. This work compared extracellular matrix remodeling in collagen lattices populated by gingival or dermal fibroblasts. For 21 days we followed gel contraction and changes in cell number of collagen lattices seeded with l.5 x 10(5) fibroblasts of each tissue. We also used indirect immunodetection to study extracellular matrix components, metalloproteinases (MMPs), and their tissues inhibitors (TIMPs). In addition, the presence of MMPs and TIMPs in the culture media was analyzed by zymography and western blotting. No significant difference was found concerning gel contraction and changes in cell number. We observed the early expression of fibrillin I and collagen type III, apparently codistributed and at the end of the gel contraction their disappearance. Concomitantly we demonstrated the expression of MMPs and TIMPs, initially localized in cellular cytoplasm, then spreading in the extracellular compartment, and even found in the culture medium. This remodeling was more rapid and intense with gingival fibroblasts than dermal fibroblasts. In conclusion, gingival fibroblasts seem more efficient at remodeling the connective tissue than dermal fibroblasts and could lead to the better wound healing observed in vivo.

[Calcium and magnesium concentrations in "Healthy" and lithiasic human kidney (author's transl)].

PubMed

Terhorst, B; Stoeppler, M

1976-07-01

Calcium and magnesium levels in the cortex, medulla, and papilla of human kidney from 32 so-called healthy patients and from eleven patients with calcium-oxalate lithiasis were determined by atom-absorption spectralphotometry. A positive calcium gradient with the highest calcium concentration in the papilla was found in all kidneys. Compared to the control group, that calcium concentration in the lithiasic kidneys was reduced by 50% in the papilla, but in the cortex and medulla, the levels were the same. A relative depletion of calcium in the papilla in hypercalciuria goes against the theory that the papilla is the main center of development of calcium-containing stones. The magnesium concentration was practically the same in cortex, medulla, and papilla, and no significant difference was found between lithiasic and healthy kidneys. These findings underline the central role of calcium in the genesis of calcium-containing stones.

Quantitative analysis of the synthesis and secretion of type VII collagen in cultured human dermal fibroblasts with a sensitive sandwich enzyme-linked immunoassay.

PubMed

Amano, Satoshi; Ogura, Yuki; Akutsu, Nobuko; Nishiyama, Toshio

2007-02-01

Type VII collagen is the major component of anchoring fibrils in the epidermal basement membrane. Its expression has been analyzed by immunostaining or Northern blotting, but rarely at the protein level. In this study, we have quantitatively examined the effects of ascorbic acid and various cytokines/growth factors on the protein synthesis and secretion of type VII collagen by human dermal fibroblasts in culture, using a developed, highly sensitive sandwich enzyme-linked immunoassay with two kinds of specific monoclonal antibodies against the non-collagenous domain-1. Ascorbic acid and its derivative induced a twofold increase in type VII collagen synthesis, and markedly increased the secretion of type VII collagen into the medium when compared with the control culture. This effect was not influenced by the presence of transforming growth factor-beta1 (TGF-beta1). The synthesis of type VII collagen was elevated by TGF-beta1, platelet-derived growth factor, tumor necrosis factor-alpha, and interleukin-1beta, but not by TGF-alpha. Thus, our data indicate that the synthesis and secretion of type VII collagen in human dermal fibroblasts are regulated by ascorbate and the enhancement of type VII collagen gene expression by cytokines/growth factors is accompanied with elevated production of type VII collagen at the protein level.

An anthocyanin-rich strawberry extract protects against oxidative stress damage and improves mitochondrial functionality in human dermal fibroblasts exposed to an oxidizing agent.

PubMed

Giampieri, Francesca; Alvarez-Suarez, José M; Mazzoni, Luca; Forbes-Hernandez, Tamara Y; Gasparrini, Massimiliano; Gonzàlez-Paramàs, Ana M; Santos-Buelga, Celestino; Quiles, Josè L; Bompadre, Stefano; Mezzetti, Bruno; Battino, Maurizio

2014-08-01

This study investigates the protective effect of the Sveva strawberry polyphenol-rich extract on human dermal fibroblasts against AAPH-induced oxidative stress. The HPLC-DAD/ESI-MS analysis was used for evaluating the phenolic composition of the fruits. Sveva strawberry presented a high anthocyanin content (639.79 mg per kg fresh fruit), representing ∼86.08% of the total phenolic content, with Pg-3-glc as the most abundant representative (611.18 mg per kg fresh fruit). Only one ellagitannin (agrimoniin) was identified, while two quercetins, three kaempherol derivates, and three ellagic acid derivatives were detected and quantified. Strawberry pre-treatment (0.5 mg ml(-1)) markedly increased human dermal fibroblast viability, with a significant reduction of apoptotic and dead cells, and suppressed AAPH-induced ROS generation, after only 30 minutes of incubation with the oxidizing agent, and lipid peroxidation, against a range of AAPH concentrations tested. Notably, the strawberry extract also improved the mitochondrial functionality: the basal respiratory performance after treatment was ∼1.59-fold higher compared to control cells, while pre-treatment with strawberry extract before oxidative damage increased ∼2.70-fold compared to stressed cells. Our results confirm that the strawberry possesses antioxidant properties, and may be useful for the prevention of free radical-induced skin damage.

Protective effect of crocin on ultraviolet B‑induced dermal fibroblast photoaging.

PubMed

Deng, Mingwu; Li, Dong; Zhang, Yichen; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Wenjie

2018-06-11

Ultraviolet B (UVB) radiation induces the production of reactive oxygen species (ROS), resulting in the aging of dermal fibroblasts. Crocin, a bioactive constituent of Crocus sativus, possesses anti‑oxidation effects. The purpose of the present study was to evaluate the protective effect of crocin on UVB‑induced dermal fibroblast photoaging. Human dermal fibroblasts were isolated and cultured with different concentrations of crocin prior to and following exposure to UVB irradiation. The senescent phenotypes of cells were evaluated, including cell proliferation, cell cycle, senescence‑associated β‑galactosidase (SA‑β‑gal) expression, intracellular ROS, expression of antioxidant protein glutathione peroxidase 1 (GPX‑1) and extracellular matrix protein collagen type 1 (Col‑1). Crocin rescued the cell proliferation inhibited by UVB irradiation, prevented cell cycle arrest and markedly decreased the number of SA‑β‑gal‑positive cells. In addition, crocin reduced UVB‑induced ROS by increasing GPX‑1 expression and other direct neutralization effects. Furthermore, crocin promoted the expression of the extracellular matrix protein Col‑1. Crocin could effectively prevent UVB‑induced cell damage via the reduction of intracellular ROS; thus, it could potentially be used in the prevention of skin photoaging.

Repeated folding stress-induced morphological changes in the dermal equivalent.

PubMed

Arai, Koji Y; Sugimoto, Mami; Ito, Kanako; Ogura, Yuki; Akutsu, Nobuko; Amano, Satoshi; Adachi, Eijiro; Nishiyama, Toshio

2014-11-01

Repeated mechanical stresses applied to the same region of the skin are thought to induce morphological changes known as wrinkle. However, the underlying mechanisms are not fully understood. To study the mechanisms, we examined effects of repeated mechanical stress on the dermal equivalent. We developed a novel device to apply repeated folding stress to the dermal equivalent. After applying the mechanical stress, morphological changes of the dermal equivalent and expression of several genes related to extracellular matrix turn over and cell contraction were examined. The repeated folding stress induced a noticeable decrease in the width of the dermal equivalent. The mechanical stress altered orientations of collagen fibrils. Hydroxyproline contents, dry weights and cell viability of the dermal equivalents were not affected by the mechanical stress. On the other hand, Rho-associated coiled-coil-containing kinase (ROCK) specific inhibitor Y27632 completely suppressed the decrease in the width of the dermal equivalent. The present results revealed that either degradation of collagen or changes in the number of cells were not responsible for the decrease in the width of the dermal equivalent and indicate that the repeated mechanical stress induces unidirectional contraction in the dermal equivalent through the RhoA-ROCK signaling pathway. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Protective Effects of Triphala on Dermal Fibroblasts and Human Keratinocytes

PubMed Central

Varma, Sandeep R.; Sivaprakasam, Thiyagarajan O.; Mishra, Abheepsa; Kumar, L. M. Sharath; Prakash, N. S.; Prabhu, Sunil; Ramakrishnan, Shyam

2016-01-01

Human skin is body’s vital organ constantly exposed to abiotic oxidative stress. This can have deleterious effects on skin such as darkening, skin damage, and aging. Plant-derived products having skin-protective effects are well-known traditionally. Triphala, a formulation of three fruit products, is one of the most important rasayana drugs used in Ayurveda. Several skin care products based on Triphala are available that claim its protective effects on facial skin. However, the skin protective effects of Triphala extract (TE) and its mechanistic action on skin cells have not been elucidated in vitro. Gallic acid, ellagic acid, and chebulinic acid were deduced by LC-MS as the major constituents of TE. The identified key compounds were docked with skin-related proteins to predict their binding affinity. The IC50 values for TE on human dermal fibroblasts (HDF) and human keratinocytes (HaCaT) were 204.90 ± 7.6 and 239.13 ± 4.3 μg/mL respectively. The antioxidant capacity of TE was 481.33 ± 1.5 mM Trolox equivalents in HaCaT cells. Triphala extract inhibited hydrogen peroxide (H2O2) induced RBC haemolysis (IC50 64.95 μg/mL), nitric oxide production by 48.62 ± 2.2%, and showed high reducing power activity. TE also rescued HDF from H2O2-induced damage; inhibited H2O2 induced cellular senescence and protected HDF from DNA damage. TE increased collagen-I, involucrin and filaggrin synthesis by 70.72 ± 2.3%, 67.61 ± 2.1% and 51.91 ± 3.5% in HDF or HaCaT cells respectively. TE also exhibited anti-tyrosinase and melanin inhibition properties in a dose-dependent manner. TE increased the mRNA expression of collagen-I, elastin, superoxide dismutase (SOD-2), aquaporin-3 (AQP-3), filaggrin, involucrin, transglutaminase in HDF or HaCaT cells, and decreased the mRNA levels of tyrosinase in B16F10 cells. Thus, Triphala exhibits protective benefits on skin cells in vitro and can be used as a potential ingredient in skin care formulations. PMID:26731545

A new technique to assess dermal absorption of volatile chemicals in vitro by thermal gravimetric analysis.

PubMed

Rauma, Matias; Isaksson, Tina S; Johanson, Gunnar

2006-10-01

Potential health hazards of dermal exposure, variability in reported dermal absorption rates and potential losses from the skin by evaporation indicate a need for a simple, inexpensive and standardized procedure to measure dermal absorption and desorption of chemical substances. The aim of this study was to explore the possibility to measure dermal absorption and desorption of volatile chemicals using a new gravimetric technique, namely thermal gravimetric analysis (TGA), and trypsinated stratum corneum from pig. Changes in skin weight were readily detected before, during and after exposure to vapours of water, 2-propanol, methanol and toluene. The shape and height of the weight curves differed between the four chemicals, reflecting differences in diffusivity and partial pressure and skin:air partitioning, respectively. As the skin weight is highly sensitive to the partial pressure of volatile chemicals, including water, this technique requires carefully controlled conditions with respect to air flow, temperature, chemical vapour generation and humidity. This new technique may help in the assessment of dermal uptake of volatile chemicals. Only a small piece of skin is needed and skin integrity is not necessary, facilitating the use of human samples. The high resolution weight-time curves obtained may also help to elucidate the characteristics of absorption, desorption and diffusion of chemicals in skin.

Genotoxicity, acute oral and dermal toxicity, eye and dermal irritation and corrosion and skin sensitisation evaluation of silver nanoparticles.

PubMed

Kim, Jin Sik; Song, Kyung Seuk; Sung, Jae Hyuck; Ryu, Hyun Ryol; Choi, Byung Gil; Cho, Hyun Sun; Lee, Jin Kyu; Yu, Il Je

2013-08-01

To clarify the health risks related to silver nanoparticles (Ag-NPs), we evaluated the genotoxicity, acute oral and dermal toxicity, eye irritation, dermal irritation and corrosion and skin sensitisation of commercially manufactured Ag-NPs according to the OECD test guidelines and GLP. The Ag-NPs were not found to induce genotoxicity in a bacterial reverse mutation test and chromosomal aberration test, although some cytotoxicity was observed. In acute oral and dermal toxicity tests using rats, none of the rats showed any abnormal signs or mortality at a dose level of ∼ 2000 mg/kg. Similarly, acute eye and dermal irritation and corrosion tests using rabbits revealed no significant clinical signs or mortality and no acute irritation or corrosion reaction for the eyes and skin. In a skin sensitisation test using guinea pigs, one animal (1/20) showed discrete or patchy erythema, thus Ag-NPs can be classified as a weak skin sensitiser.

Dermal exposure assessment to benzene and toluene using charcoal cloth pads.

PubMed

van Wendel de Joode, Berna; Tielemans, Erik; Vermeulen, Roel; Wegh, Hillion; Kromhout, Hans

2005-01-01

Charcoal cloth pads have been used to assess volatile chemicals on the skin in a laboratory setting; however, they have not yet been applied to measure dermal exposure in occupational settings. This study aimed at evaluating whether charcoal pads can be used to assess dermal exposure to benzene and toluene in workers of a petrochemical plant. Inhalation and dermal exposure levels to benzene and toluene were assessed for workers of a petrochemical plant performing different jobs. Benzene uptake was assessed by determining S-phenylmercapturic acid in workers' urine samples. Dermal exposure levels on the charcoal pads were adjusted for ambient air levels of benzene and toluene by subtracting the amount of benzene or toluene measured in personal air from the amount of benzene or toluene measured on the charcoal pad. In general, measured external and internal exposure levels were low. The estimated contribution of the dermal route to internal benzene exposure levels was less than 0.06% for all jobs. Toluene personal air concentrations and benzene and toluene dermal exposure levels differed statistically significantly between job titles. For benzene, differences between jobs were larger for adjusted dermal exposures (maximum 17-fold, P = 0.02) than for inhalation exposures (maximum two-fold, P = 0.08). Also for toluene, although less clear, differences between jobs were larger for adjusted dermal exposures (maximum 23-fold, P = 0.01) as compared to inhalation exposures (maximum 10-fold, P = 0.01). Charcoal pads appeared to measure dermal exposures to benzene and toluene in addition to ambient air levels. Future studies applying charcoal cloth pads for the dermal exposure assessment at workplaces with higher dermal exposure to organic solvents may provide more insight into the biological relevance of dermal exposure levels measured by charcoal cloth pads. In addition, the design of the dermal sampler might be improved by configuring a dermal sampler, where part of the

10-Hydroxy-2-decenoic acid prevents ultraviolet A-induced damage and matrix metalloproteinases expression in human dermal fibroblasts.

PubMed

Zheng, Jinfen; Lai, Wei; Zhu, Guoxing; Wan, Miaojian; Chen, Jian; Tai, Yan; Lu, Chun

2013-10-01

10-Hydroxy-2-decenoic acid (10-HDA) is a major fatty acid component of royal jelly, which has been reported to have a variety of beneficial pharmacological characteristics. However, the effects of 10-HDA on skin photoageing and its potential mechanism of action are unclear. We investigated the protective effects of 10-HDA on ultraviolet (UV) A-induced damage in human dermal fibroblasts (HDFs). We then explored the inhibitory effects of 10-HDA on UVA-induced matrix metalloproteinases (MMPs) expression and elucidated the signalling pathways controlling MMPs inhibition. Primary human dermal fibroblasts were exposed to UVA. Cell proliferation, cellular senescent state and collagen content were analysed using CCK-8, senescence-associated β-galactosidase staining and Sircol collagen assay, respectively. Fluorometric assays were performed to detect the formation of reactive oxygen species (ROS) in the cells. The mRNA levels of MMP-1, MMP-3 and type I (α1) collagen were determined by quantitative real-time PCR. Western blot was applied to detect the expression of MMP-1, MMP-3, JNK and p38 MAPK. HDFs treated with 10-HDA were significantly protected from UVA-induced cytotoxicity, ROS, cellular senescence and stimulated collagen production. Moreover, 10-HDA suppressed the UVA-induced expression of MMP-1 and MMP-3 at both the transcriptional and protein levels. Treatment with 10-HDA also reduced the UVA-induced activation of the JNK and p38 MAPK pathways. The data obtained in this study provide evidence that 10-HDA could prevent UVA-induced damage and inhibit MMP-1 and MMP-3 expressions. Therefore, 10-HDA may be a potential agent for the prevention and treatment of skin photoageing. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Use of human and porcine dermal-derived bioprostheses in complex abdominal wall reconstructions: a literature review and case report.

PubMed

Baillie, Daniel R; Stawicki, S Peter; Eustance, Nicole; Warsaw, David; Desai, Darius

2007-05-01

The goal of abdominal wall reconstruction is to restore and maintain abdominal domain. A PubMed(R) review of the literature (including "old" MEDLINE through February 2007) suggests that bioprosthetic materials are increasingly used to facilitate complex abdominal wall reconstruction. Reported results (eight case reports/series involving 137 patients) are encouraging. The most commonly reported complications are wound seroma (18 patients, 13%), skin dehiscence with graft exposure without herniation (six, 4.4%), superficial and deep wound infections (five, 3.6%), hernia recurrence (four, 2.9%), graft failure with dehiscence (two), hematoma (two), enterocutaneous fistula (one), and flap necrosis (one). Two recent cases are reported herein. In one, a 46-year-old woman required open abdominal management after gastric remnant perforation following a Roux-en-Y gastric bypass procedure. Porcine dermal collagen combined with cutaneous flaps was used for definitive abdominal wall reconstruction. The patient's condition improved postoperatively and she was well 5 months after discharge from the hospital. In the second, a 54-year-old woman underwent repair of an abdominal wall defect following resection of a large leiomyosarcoma. Human acellular dermis combined with myocutaneous flaps was used to reconstruct the abdominal wall defect. The patient's recovery was uncomplicated and 20 weeks following surgery she was doing well with no evidence of recurrence or hernia. The results reported to date and the outcomes presented here suggest that bioprosthetic materials are safe and effective for repair of large abdominal wall defects. Prospective, randomized, controlled studies are needed to compare the safety and efficacy of other reconstructive techniques as well as human and porcine dermal-derived bioprostheses.

Protective effect of chromene isolated from Sargassum horneri against UV-A-induced damage in skin dermal fibroblasts.

PubMed

Kim, Jung-Ae; Ahn, Byul-Nim; Kong, Chang-Suk; Kim, Se-Kwon

2012-08-01

Skin homoeostasis is interrupted during UV-A irradiation. How the UV-A-altered skin components influences photoageing of skin should be investigated using human in vitro models that are important for understanding skin ageing. In this study, chromene compound, sargachromenol, was isolated from Sargassum horneri, and its potency on inhibition of photoageing was investigated in UV-A-irradiated dermal fibroblasts. Effects of sargachromenol on the prevention of photoageing were evaluated by measuring ROS production, membrane protein oxidation, lipid peroxidation and ageing-related gene expression in UV-A-irradiated human skin dermal fibroblasts. The results indicated that treatment with sargachromenol suppressed the collagenase matrix metalloproteinases (MMPs), MMP-1, MMP-2 and MMP-9 expression without any cytotoxicity and phototoxicity. It was further found that these inhibitions were because of increase in the expression of TIMP-1 and TIMP-2 genes. Furthermore, we confirmed that the UV-A-induced transcriptions of AP-1 signalling pathway were regulated by sargachromenol treatment in UV-A-irradiated dermal fibroblasts. © 2012 John Wiley & Sons A/S.

Steady state temperature distribution in dermal regions of an irregular tapered shaped human limb with variable eccentricity.

PubMed

Agrawal, M; Pardasani, K R; Adlakha, N

2014-08-01

The investigators in the past have developed some models of temperature distribution in the human limb assuming it as a regular circular or elliptical tapered cylinder. But in reality the limb is not of regular tapered cylindrical shape. The radius and eccentricity are not same throughout the limb. In view of above a model of temperature distribution in the irregular tapered elliptical shaped human limb is proposed for a three dimensional steady state case in this paper. The limb is assumed to be composed of multiple cylindrical substructures with variable radius and eccentricity. The mathematical model incorporates the effect of blood mass flow rate, metabolic activity and thermal conductivity. The outer surface is exposed to the environment and appropriate boundary conditions have been framed. The finite element method has been employed to obtain the solution. The temperature profiles have been computed in the dermal layers of a human limb and used to study the effect of shape, microstructure and biophysical parameters on temperature distribution in human limbs. The proposed model is one of the most realistic model as compared to conventional models as this can be effectively employed to every regular and nonregular structures of the body with variable radius and eccentricity to study the thermal behaviour. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brugia malayi infective larvae fail to activate Langerhans cells and dermal dendritic cells in human skin.

PubMed

Cotton, R N; McDonald-Fleming, R; Boyd, A; Spates, K; Nutman, T B; Tolouei Semnani, R

2015-02-01

Filarial infection in humans is initiated when a mosquito deposits third-stage parasite larvae (L3) in the skin. Langerhans cells (LCs) and dermal dendritic cells (DDCs) are the first cells that the parasite encounters, and L3s must evade these highly effective antigen-presenting cells to establish infection. To assess LC and DDC responses to L3 in human skin, we employed three models of increasing physiologic relevance: in vitro-generated LCs, epidermal blister explants and full-thickness human skin sections. In vitro-generated LCs expressed TLR1-10 and robustly produced IL-6 and TNF-α in response to PolyI:C, but pre-exposure to L3s did not alter inflammatory cytokine production or TLR expression. L3s did not modulate expression of LC markers CDH1, CD207, or CD1a, or the regulatory products TSLP or IDO in epidermal explants or in vitro-generated LC. LC, CD14+ DDC, CD1c+ DC and CD141+ DC from human skin sections were analysed by flow cytometry. While PolyI:C potently induced CCL22 production in LC, CD1c+ DC, and CD141+ DC, and IL-10 production in LC, L3s did not modulate the numbers of or cytokine production by any skin DC subset. L3s broadly failed to activate or modulate LCs or DDCs, suggesting filarial larvae expertly evade APC detection in human skin. © 2014 John Wiley & Sons Ltd.

Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis.

PubMed

Wu, Lian; Wang, Feng; Donly, Kevin J; Wan, Chunyan; Luo, Daoshu; Harris, Stephen E; MacDougall, Mary; Chen, Shuo

2015-11-01

Bmp2 is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta, showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain lot of primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. In this study, our goal was to generate an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2(ko/ko)dp) cell line by introducing Cre recombinase and green fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2(fx/fx)dp) cells. iBmp2(ko/ko)dp cells were confirmed by GFP and PCR. The deleted Bmp2 cells exhibited slow cell proliferation rate and cell growth was arrested in G2 phase. Expression of tooth-related marker genes and cell differentiation were decreased in the deleted cells. Importantly, extracellular matrix remodeling was impaired in the iBmp2(ko/ko)dp cells as reflected by the decreased Mmp-9 expression. In addition, with exogenous Bmp2 induction, these cell differentiation and mineralization were rescued as well as extracellular matrix remodeling was enhanced. Therefore, we for the first time described establishment of iBmp(ko/ko) cells that are useful for study of mechanisms in regulating dental papilla mesenchymal cell lineages. © 2015 Wiley Periodicals, Inc.

Dermal exposure to environmental contaminants in the Great Lakes.

PubMed Central

Moody, R P; Chu, I

1995-01-01

This paper reviews the literature to determine the importance of the dermal route of exposure for swimmers and bathers using Great Lakes waters and summarizes the chemical water contaminants of concern in the Great Lakes along with relevant dermal absorption data. We detail in vivo and in vitro methods of quantifying the degree of dermal absorption and discuss a preference for infinite dose data as opposed to finite dose data. The basic mechanisms of the dermal absorption process, routes of chemical entry, and the environmental and physiological factors affecting this process are also reviewed, and we discuss the concepts of surface slick exposure to lipophilic compounds and the adsorption of contaminants to water sediment. After presenting mathematical constructs for calculating the degree of exposure, we present in vitro data concerning skin absorption of polyaromatic hydrocarbons adsorbed to Great Lakes water sediment to show that in a worst-case scenario exposure via the dermal route can be equally important to the oral route. We have concluded that prolonged exposure of the skin, especially under conditions that may enhance dermal absorption (e.g., sunburn) may result in toxicologically significant amounts of certain water contaminants being absorbed. It is recommended that swimming should be confined to public beaches, people should refrain from swimming if they are sunburned, and skin should be washed with soap as soon as possible following exposure. Future studies should be conducted to investigate the importance of the dermal exposure route to swimmers and bathers. PMID:8635434

Immunohistochemical analysis of adhesive papillae of Clavelina lepadiformis (Müller, 1776) and Clavelina phlegraea (Salfi, 1929) (Tunicata, Ascidiacea).

PubMed

Pennati, Roberta; Groppelli, S; De Bernardi, F; Mastrototaro, F; Zega, G

2009-01-01

Almost all ascidian larvae bear three mucus secreting and sensory organs, the adhesive papillae, at the anterior end of the trunk, which play an important role during the settlement phase. The morphology and the cellular composition of these organs varies greatly in the different species. The larvae of the Clavelina genus bear simple bulbous papillae, which are considered to have only a secretory function. We analysed the adhesive papillae of two species belonging to this genus, C. lepadiformis and C. phlegraea, by histological sections and by immunolocalisation of b-tubulin and serotonin, in order to better clarify the cellular composition of these organs. We demonstrated that they contain at least two types of neurons: central neurons, bearing microvilli, and peripheral ciliated neurons. Peripheral neurons of C. lepadiformis contain serotonin. We suggest that these two neurons play different roles during settlement: the central ones may be chemo- or mechanoreceptors that sense the substratum, and the peripheral ones may be involved in the mechanism that triggers metamorphosis.

Dermal Discolorations and Burns at Neuromonitoring Electrodes in Pediatric Spine Surgery.

PubMed

Sanders, Austin; Andras, Lindsay; Lehman, Alison; Bridges, Nancy; Skaggs, David L

2017-01-01

Prospective review of consecutive patients. To evaluate the incidence and raise awareness of electrode discoloration that can occur in the operating room when using neuromonitoring. To our knowledge there are no articles that discuss dermal discolorations following spine surgery. Following recognition of dermal discolorations in some patients, a prospective evaluation of all patients undergoing spine surgery with somatosensory-evoked potential and motor-evoked potential neuromonitoring using subdermal needle electrodes was carried out over a 16-month period for quality assurance and improvement. A total of 201 consecutive patients with mean age of 14 years (4-25) were prospectively evaluated. Sixteen percent (33/201) had dermal discolorations associated with neuromonitoring. There were no significant differences in mean age (P = 0.624), height (P = 0.308), weight (P = 0.899), or body mass index (P = 0.571) between the patients with and without dermal discolorations. There was also no difference in prevalence of dermal discoloration by diagnosis (P = 0.490) or location of grounding pad and occurrence of dermal discoloration between groups (P = 0.268). The only difference noted was that patients without dermal discoloration had an average monopolar cautery setting of 46.8 W compared to 40.5 W for patients with dermal discolorations (P = 0.042). Of the 33 patients with a dermal discoloration, 27% (9/33) of these were on both the upper and lower extremities, 21% (7/33) on only the upper extremities, and 52% (17/33) on only the lower extremities. None of the dermal discolorations were painful or tender, and all resolved by 6-month follow-up. One patient did not have any dermal discoloration but did experience two full-thickness burns around the electrodes in one leg. The incidence of burns in this series was 0.5% (1/201). Dermal discolorations occurred in 16% of patients undergoing neuromonitoring for spine surgery. These common

Spectrum of PORCN mutations in Focal Dermal Hypoplasia

USDA-ARS?s Scientific Manuscript database

Focal Dermal Hypoplasia (FDH), also known as Goltz syndrome (OMIM 305600), is a genetic disorder that affects multiple organ systems early in development. Features of FDH include skin abnormalities, (hypoplasia, atrophy, linear pigmentation, and herniation of fat through dermal defects); papillomas...

Do gingival soft tissues benefit from the application of a papilla preservation flap technique in endodontic surgery?

PubMed

Taschieri, Silvio; Corbella, Stefano; Del Fabbro, Massimo

2014-10-01

A healthy gingival condition after endodontic surgery may depend on adequate soft tissue management. The aim of this study was to compare 2 incision techniques, papilla base incision (PBI) and intrasulcular flap (IS), which are currently used in endodontic surgery. In the present nonrandomized controlled clinical trial, patients requiring endodontic surgery on a single tooth were enrolled. PBI was used in 1 group and IS was used in the other group. The primary outcomes were changes in periodontal probing depth, gingival recession, and height of the interproximal mesial and distal papillae. Outcome variables were assessed preoperatively and 6 months after surgery. Between-group differences were evaluated through appropriate statistical analysis, with significance set at a P value equal to .05. Each group was composed of 12 patients and the 2 groups were comparable at baseline. Two weeks after surgery, papilla height decreased significantly in the IS group (2.05 and 1.80 mm at the mesial and distal aspects, respectively), whereas no significant decrease in papilla height was observed in the PBI group (0.10 and 0.20 mm). No statistically significant difference between groups was observed after 6 months. No significant difference between groups was found for gingival recession or probing depth at any follow-up time. Better soft tissue preservation in the early postoperative period was achieved using the PBI approach compared with the IS approach. The PBI can be recommended for endodontic surgical procedures involving esthetic regions. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Histologic evaluation of autogenous connective tissue and acellular dermal matrix grafts in humans.

PubMed

Cummings, Lewis C; Kaldahl, Wayne B; Allen, Edward P

2005-02-01

The clinical success of root coverage with autogenous connective tissue (CT) or acellular dermal matrix (ADM) has been well documented. However, limited histological results of CT grafts have been reported, and a case report of a human block section has been published documenting an ADM graft. The purpose of this study is to document the histological results of CT grafts, ADM grafts, and coronally advanced flaps to cover denuded roots in humans. This study included four patients previously treatment planned for extractions of three or more anterior teeth. Three teeth in each patient were selected and randomly designated to receive either a CT or ADM graft beneath a coronally advanced flap (tests) or coronally advanced flap alone (control). Six months postoperatively block section extractions were performed and the teeth processed for histologic evaluation with hematoxylin-eosin and Verhoeff's stains. Histologically, both the CT and ADM were well incorporated within the recipient tissues. New fibroblasts, vascular elements, and collagen were present throughout the ADM, while retention of the transplanted elastic fibers was apparent. No effect on the keratinization or connective tissue organization of the overlying alveolar mucosa was evident with either graft. For both materials, areas of cemental deposition were present within the root notches, the alveolar bone was essentially unaffected, and the attachments to the root surfaces were similar. Although CT and ADM have a slightly different histological appearance, both can successfully be used to cover denuded roots with similar attachments and no adverse healing.

Wound healing potential of Spirulina platensis extracts on human dermal fibroblast cells

PubMed Central

Syarina, Pauzi Nur Aimi; Karthivashan, Govindarajan; Abas, Faridah; Arulselvan, Palanisamy; Fakurazi, Sharida

2015-01-01

Blue-green alga (Spirulina platensis) is a well renowned nutri-supplement due to its high nutritional and medicinal properties. The aim of this study was to examine the wound healing efficiency of Spirulina platensis at various solvent extracts using in vitro scratch assay on human dermal fibroblast cells (HDF). Various gradient solvent extracts (50 μg/ml of methanolic, ethanolic and aqueous extracts) from Spirulina platensis were treated on HDF cells to acquire its wound healing properties through scratch assay and in this investigation we have used allantoin, as a positive control to compare efficacy among the phytoextracts. Interestingly, aqueous extract were found to stimulate proliferation and migration of HDF cells at given concentrations and enhanced closure rate of wound area within 24 hours after treatment. Methanolic and ethanolic extracts have shown proliferative effect, however these extracts did not aid in the migration and closure of wound area when compared to aqueous extract. Based on phytochemical profile of the plant extracts analyzed by LC-MS/MS, it was shown that compounds supposedly involved in accelerating wound healing are cinnamic acid, narigenin, kaempferol, temsirolimus, phosphatidylserine isomeric derivatives and sulphoquinovosyl diacylglycerol. Our findings concluded that blue-green algae may pose potential biomedical application to treat various chronic wounds especially in diabetes mellitus patients. PMID:27004048

Effects of extremely low-frequency magnetotherapy on proliferation of human dermal fibroblasts.

PubMed

Pasi, Francesca; Sanna, Samuele; Paolini, Alessandro; Alquati, Marco; Lascialfari, Alessandro; Corti, Maurizio Enrico; Liberto, Riccardo Di; Cialdai, Francesca; Monici, Monica; Nano, Rosanna

2016-01-01

Extremely low-frequency electromagnetic fields (ELF-EMFs) applied in magnetotherapy have frequency lower than 100 Hz and magnetic field intensity ranging from 0.1 to 20 mT. For many years, the use of magnetotherapy in clinics has been increasing because of its beneficial effects in many processes, e.g., skin diseases, inflammation and bone disorders. However, the understanding of the microscopic mechanisms governing such processes is still lacking and the results of the studies on the effects of ELF-EMFs are controversial because effects derive from different conditions and from intrinsic responsiveness of different cell types.In the present study, we studied the biological effects of 1.5 h exposure of human dermal fibroblasts to EMFs with frequencies of 5 and 50 Hz and intensity between 0.25 and 1.6 mT. Our data showed that the magnetic treatment did not produce changes in cell viability, but gave evidence of a sizeable decrease in proliferation at 24 h after treatment. In addition, immunofluorescence experiments displayed an increase in tubulin expression that could foreshadow changes in cell motility or morphology. The decrease in proliferation with unchanged viability and increase in tubulin expression could be consistent with the triggering of a transdifferentiation process after the exposure to ELF-EMFs.

Review of data on the dermal penetration of mineral oils and waxes used in cosmetic applications.

PubMed

Petry, T; Bury, D; Fautz, R; Hauser, M; Huber, B; Markowetz, A; Mishra, S; Rettinger, K; Schuh, W; Teichert, T

2017-10-05

Mineral oils and waxes used in cosmetic products, also referred to as "personal care products" outside the European Union, are mixtures of predominantly saturated hydrocarbons consisting of straight-chain, branched and ring structures with carbon chain lengths greater than C16. They are used in skin and lip care cosmetic products due to their excellent skin tolerance as well as their high protecting and cleansing performance and broad viscosity options. Recently, concerns have been raised regarding potential adverse health effects of mineral oils and waxes from dermal application of cosmetics. In order to be able to assess the risk for the consumer the dermal penetration potential of these ingredients has to be evaluated. The scope and objective of this review are to identify and summarize publicly available literature on the dermal penetration of mineral oils and waxes as used in cosmetic products. For this purpose, a comprehensive literature search was conducted. A total of 13 in vivo (human, animal) and in vitro studies investigating the dermal penetration of mineral oils and waxes has been identified and analysed. The majority of the substances were dermally adsorbed to the stratum corneum and only a minor fraction reached deeper skin layers. Overall, there is no evidence from the various studies that mineral oils and waxes are percutaneously absorbed and become systemically available. Thus, given the absence of dermal uptake, mineral oils and waxes as used in cosmetic products do not present a risk to the health of the consumer. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Polarized and persistent Ca²⁺ plumes define loci for formation of wall ingrowth papillae in transfer cells.

PubMed

Zhang, Hui-Ming; Imtiaz, Mohammad S; Laver, Derek R; McCurdy, David W; Offler, Christina E; van Helden, Dirk F; Patrick, John W

2015-03-01

Transfer cell morphology is characterized by a polarized ingrowth wall comprising a uniform wall upon which wall ingrowth papillae develop at right angles into the cytoplasm. The hypothesis that positional information directing construction of wall ingrowth papillae is mediated by Ca(2+) signals generated by spatiotemporal alterations in cytosolic Ca(2+) ([Ca(2+)]cyt) of cells trans-differentiating to a transfer cell morphology was tested. This hypothesis was examined using Vicia faba cotyledons. On transferring cotyledons to culture, their adaxial epidermal cells synchronously trans-differentiate to epidermal transfer cells. A polarized and persistent Ca(2+) signal, generated during epidermal cell trans-differentiation, was found to co-localize with the site of ingrowth wall formation. Dampening Ca(2+) signal intensity, by withdrawing extracellular Ca(2+) or blocking Ca(2+) channel activity, inhibited formation of wall ingrowth papillae. Maintenance of Ca(2+) signal polarity and persistence depended upon a rapid turnover (minutes) of cytosolic Ca(2+) by co-operative functioning of plasma membrane Ca(2+)-permeable channels and Ca(2+)-ATPases. Viewed paradermally, and proximal to the cytosol-plasma membrane interface, the Ca(2+) signal was organized into discrete patches that aligned spatially with clusters of Ca(2+)-permeable channels. Mathematical modelling demonstrated that these patches of cytosolic Ca(2+) were consistent with inward-directed plumes of elevated [Ca(2+)]cyt. Plume formation depended upon an alternating distribution of Ca(2+)-permeable channels and Ca(2+)-ATPase clusters. On further inward diffusion, the Ca(2+) plumes coalesced into a uniform Ca(2+) signal. Blocking or dispersing the Ca(2+) plumes inhibited deposition of wall ingrowth papillae, while uniform wall formation remained unaltered. A working model envisages that cytosolic Ca(2+) plumes define the loci at which wall ingrowth papillae are deposited. © The Author 2014. Published by Oxford

Anti-photoaging potential of propolis extract in UVB-irradiated human dermal fibroblasts through increasing the expression of FOXO3A and NGF genes.

PubMed

Ebadi, Parimah; Fazeli, Mehdi

2017-11-01

Propolis is a resinous compound that has been widely used in folk medicine. Different biological activities and therapeutic applications of propolis have been studied before. However, the effects of propolis on longevity-associated genes expression in the prevention of skin photoaging still remained unclear. Therefore in this study the protective effects of propolis on the expressions of two longevity-associated genes, FOXO3A and NGF genes, against UVB-induced photoaging in human dermal fibroblasts (HDF) were investigated. Propolis extract demonstrated a concentration-dependent free radical scavenging activity that was determined by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. Also, Folin-Ciocalteu method was used to measure the total phenolic content of the extract. The viability of HDF cells was decreased gradually with increasing UVB radiation doses and 248mJ/cm 2 was selected as the sub-cytotoxic dose. Pre-treatment with propolis extract increased the viability of UVB-irradiated human dermal fibroblasts and decreased the number of β-galactosidase positive cells as senescent cells among them. It also increased the expression of FOXO3A and NGF genes in irradiated and non-irradiated cells. Consequently, these findings suggest that propolis extract has anti-photoaging potential and this property, in addition to its strong antioxidant activity, may be due to its effects on upregulation of longevity-associated genes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Human amnion-derived mesenchymal stem cells protect against UVA irradiation-induced human dermal fibroblast senescence, in vitro

PubMed Central

Zhang, Chunli; Yuchi, Haishen; Sun, Lu; Zhou, Xiaoli; Lin, Jinde

2017-01-01

The aim of the present study was to determine if human amnion-derived mesenchymal stem cells (HAMSCs) exert a protective effect on ultraviolet A (UVA) irradiation-induced human dermal fibroblast (HDF) senescence. A senescence model was constructed as follows: HDFs (104–106 cells/well) were cultured in a six-well plate in vitro and then exposed to UVA irradiation at 9 J/cm2 for 30 min. Following the irradiation period, HDFs were co-cultured with HAMSCs, which were seeded on transwells. A total of 72 h following the co-culturing, senescence-associated β-galactosidase staining was performed and reactive oxygen species (ROS) content and mitochondrial membrane potential (Δψm) were detected in the HDFs via flow cytometric analysis. The results demonstrated that the percentage of HDFs, detected via staining with X-gal, were markedly decreased when co-cultured with human HAMSCs, compared with the group that were not co-cultured. The ROS content was decreased and the mitochondrial membrane potential (Δψm) recovered in cells treated with UVA and HAMSCs, compared with that of cells treated with UVA alone. Reverse transcription-quantitative polymerase chain reaction revealed the significant effects of HAMSCs on the HDF senescence marker genes p53 and matrix metalloproteinase-1 mRNA expression. In addition to this, western blot analysis verified the effects of HAMSCs on UVA induced senescence, providing a foundation for novel regenerative therapeutic methods. Furthermore, the results suggested that activation of the extracellular-signal regulated kinase 1/2 mitogen activated protein kinase signal transduction pathway, is essential for the HAMSC-mediated UVA protective effects. The decrease in ROS content additionally indicated that HAMSCs may exhibit the potential to treat oxidative stress-mediated UVA skin senescence in the future. PMID:28627622

Age-related morphological changes of the dermal matrix in human skin documented in vivo by multiphoton microscopy

NASA Astrophysics Data System (ADS)

Wang, Hequn; Shyr, Thomas; Fevola, Michael J.; Cula, Gabriela Oana; Stamatas, Georgios N.

2018-03-01

Two-photon fluorescence (TPF) and second harmonic generation (SHG) microscopy provide direct visualization of the skin dermal fibers in vivo. A typical method for analyzing TPF/SHG images involves averaging the image intensity and therefore disregarding the spatial distribution information. The goal of this study is to develop an algorithm to document age-related effects of the dermal matrix. TPF and SHG images were acquired from the upper inner arm, volar forearm, and cheek of female volunteers of two age groups: 20 to 30 and 60 to 80 years of age. The acquired images were analyzed for parameters relating to collagen and elastin fiber features, such as orientation and density. Both collagen and elastin fibers showed higher anisotropy in fiber orientation for the older group. The greatest difference in elastin fiber anisotropy between the two groups was found for the upper inner arm site. Elastin fiber density increased with age, whereas collagen fiber density decreased with age. The proposed analysis considers the spatial information inherent to the TPF and SHG images and provides additional insights into how the dermal fiber structure is affected by the aging process.

En bloc excision of a dermal sinus tract.

PubMed

Coumans, Jean-Valery; Walcott, Brian P; Redjal, Navid; Kahle, Kristopher T; Nahed, Brian V

2011-04-01

Dermal sinus tracts are a form of spinal dysraphism that arises from a failure of dysjunction early in embryogenesis. They are diagnosed in pediatric patients and who present with a dimple, infection, or neurologic deficit. The tract is surgically excised en bloc to avoid contamination from the tract, which harbors bacteria. However, dermal sinus tracts typically terminate intradurally, rendering their en bloc excision difficult. To avoid entering the tract, allowing for an en bloc excision, we modified the usual technique employed for accessing the spinal intradural space. An en bloc excision of the dermal sinus tract was successfully performed. The patient recovered from the procedure neurologically intact and her postoperative course was uncomplicated. We conclude that en bloc excision of a dermal sinus tract down to the intradural space is feasible with modifications to standard operative technique. Copyright © 2010 Elsevier Ltd. All rights reserved.

Strawberry extracts efficiently counteract inflammatory stress induced by the endotoxin lipopolysaccharide in Human Dermal Fibroblast.

PubMed

Gasparrini, Massimiliano; Giampieri, Francesca; Forbes-Hernandez, Tamara Y; Afrin, Sadia; Cianciosi, Danila; Reboredo-Rodriguez, Patricia; Varela-Lopez, Alfonso; Zhang, JiaoJiao; Quiles, Josè L; Mezzetti, Bruno; Bompadre, Stefano; Battino, Maurizio

2018-04-01

A protracted pro-inflammatory state is the common denominator in the development, progression and complication of the common chronic diseases. Dietary antioxidants represent an efficient tool to counteract this inflammatory state. The aim of the present work was to evaluate the effects of strawberry extracts on inflammation evoked by E. Coli lipopolysaccharide in Human Dermal Fibroblast, by measuring reactive oxygen species production, apoptosis rate, antioxidant enzymes activity, mitochondria functionality and also investigating the molecular pathway involved in inflammatory and antioxidant response. The results demonstrated that strawberry pre-treatment reduced intracellular reactive oxygen species levels, apoptotic rate, improved antioxidant defences and mitochondria functionality in lipopolysaccharide -treated cells. Strawberry exerted these protective activities through the inhibition of the NF-kB signalling pathway and the stimulation of the Nrf2 pathway, with a mechanism AMPK-dependent. These results confirm the health benefits of strawberry in the prevention of inflammation and oxidative stress condition in lipopolysaccharide-treated cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Restoring Effects of Natural Anti-Oxidant Quercetin on Cellular Senescent Human Dermal Fibroblasts.

PubMed

Sohn, Eun-Ju; Kim, Jung Min; Kang, Se-Hui; Kwon, Joseph; An, Hyun Joo; Sung, Jung-Suk; Cho, Kyung A; Jang, Ik-Soon; Choi, Jong-Soon

2018-05-08

The oxidative damage initiated by reactive oxygen species (ROS) is a major contributor to the functional decline and disability that characterizes aging. The anti-oxidant flavonoid, quercetin, is a plant polyphenol that may be beneficial for retarding the aging process. We examined the restoring properties of quercetin on human dermal fibroblasts (HDFs). Quercetin directly reduced either intracellular or extracellular ROS levels in aged HDFs. To find the aging-related target genes by quercetin, microarray analysis was performed and two up-regulated genes LPL and KCNE2 were identified. Silencing LPL increased the expression levels of senescence proteins such as p16 INK4A and p53 and silencing KCNE2 reversed gene expressions of EGR1 and p-ERK in quercetin-treated aged HDFs. Silencing of LPL and KCNE2 decreased the expression levels of antioxidant enzymes such as superoxide dismutase and catalase. Also, the mitochondrial dysfunction in aged HDFs was ameliorated by quercetin treatment. Taken together, these results suggest that quercetin has restoring effect on the cellular senescence by down-regulation of senescence activities and up-regulation of the gene expressions of anti-oxidant enzymes in aged HDFs.

Decursin inhibits UVB-induced MMP expression in human dermal fibroblasts via regulation of nuclear factor-κB.

PubMed

Hwang, Bo-Mi; Noh, Eun-Mi; Kim, Jong-Suk; Kim, Jeong-Mi; Hwang, Jin-Ki; Kim, Hye-Kyung; Kang, Jae-Seon; Kim, Do-Sung; Chae, Han-Jung; You, Yong-Ouk; Kwon, Kang-Beom; Lee, Young-Rae

2013-02-01

Decursin, a coumarin compound, was originally isolated from the roots of Angelica gigas almost four decades ago, and it was found to exhibit cytotoxicity against various types of human cancer cells and anti-amnesic activity in vivo through the inhibition of AChE activity. However, the anti-skin photoaging effects of decursin have not been reported to date. In the present study, we investigated the inhibitory effects of decursin on the expression of matrix metalloproteinase (MMP)-1 and MMP-3 in human dermal fibroblast (HDF) cells. Western blot analysis and real-time PCR revealed that decursin inhibited the ultraviolet (UV)B-induced expression of MMP-1 and MMP-3 in a dose-dependent manner. Decursin significantly blocked the UVB-induced activation of nuclear factor-κB (NF-κB). However, decursin showed no effect on MAPK or AP-1 activity. In this study, decursin prevented the UVB-induced expression of MMPs via the inhibition of NF-κB activation. In conclusion, decursin may be a potential agent for the prevention and treatment of skin photoaging.

Emergency endoscopic needle-knife precut papillotomy in acute severe cholangitis resulting from impacted common bile duct stones at duodenal papilla.

PubMed

Zheng, Mingwei; Liu, Xufeng; Li, Ning; Li, Wei-Zhi

2018-03-01

To evaluate the efficacy and safety of emergency endoscopic needle-knife precut papillotomy in acute severe cholangitis resulting from impacted common bile duct stones at duodenal papilla. Between January 2010 and January 2015, 118 cases of acute severe cholangitis with impacted common bile duct stones at the native papilla underwent emergency endoscopic retrograde cholangiopancreatography (ERCP) and early needle-knife precut papillotomy in a tertiary referral center. Precut techniques were performed according to the different locations of stones in the duodenal papilla. Clinical data about therapy and recovery of the 118 patients were recorded and analyzed. One hundred and eighteen patients underwent emergency ERCP within 24 h after hospitalization, with a total success rate of 100%. The mean operating time was 6.4 ± 4.1 min. Postoperative acute physiology and chronic health evaluation (APACHE) II scores, white blood cell count and liver function improved significantly. The complication rate was 4.2% (5/118); two with hemorrhage and three with acute pancreatitis. There was no procedure-related mortality. Emergency endoscopic needle-knife precut papillotomy is effective and safe for acute severe cholangitis resulting from impacted common bile duct stones at the duodenal papilla. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Melanogenesis in dermal melanocytes of Japanese Silky chicken embryos.

PubMed

Ortolani-Machado, C F; Freitas, P F; Faraco, C D

2009-08-01

The Japanese Silky chicken (SK) shows dermal and visceral hyperpigmentation. This study characterizes ultrastructurally the melanin granules developing in dermal melanocytes of the dorsal skin of SK, in an attempt to better understand the processes of melanogenesis in these permanently ectopic cells. The steps of melanogenesis are similar to those described for epidermal melanocytes, with melanosomes going from stage I to IV but, in SK, the maturation occurs in the cell body, as well as in the cytoplasmic processes. At stage III, the deposition of melanin is cumulative and can aggregate in rounded structures, which combine to turn into the mature granule. The final destiny of mature melanosomes is still unclear, although it was observed that dermal macrophages can accumulate melanin granules in their phagosomes. Even with the close proximity between melanocytes and other dermal cells, the transference of melanosomes was not observed. Our findings indicate that melanogenesis in dermal melanocytes in SK has the same morphological characteristics found in epidermal melanocytes, but the functional aspect still remains to be elucidated.

Optimizing RNA Extraction of Renal Papilla Biopsy Tissue in Kidney Stone Formers: A New Methodology for Genomic Study.

PubMed

Taguchi, Kazumi; Usawachintachit, Manint; Hamamoto, Shuzo; Unno, Rei; Tzou, David T; Sherer, Benjamin A; Wang, Yongmei; Okada, Atsushi; Stoller, Marshall L; Yasui, Takahiro; Chi, Thomas

2017-09-01

Endoscopic tools have provided versatile examination and treatment for kidney stone procedures. Despite endourologists researching urinary stone disease using endoscopes to collect tissue, this tissue collection method is limited. Endoscopically removed tissues are small in size, restricting the types of genome-based examination possible. We investigated a new method of renal papilla biopsy and RNA extraction to establish a genomic research methodology for kidney stone disease. We conducted a prospective multi-institutional study and collected renal papilla specimens from consecutive percutaneous nephrolithotomy and ureteroscopy (URS) cases performed for removal of upper urinary tract stones. Renal papilla tissue was extracted using ureteroscopic biopsy forceps after stone removal. RNA was extracted using two different extraction kits, and their quantity and quality were examined. Additionally, the impact of biopsy on surgical complications was compared between cases performed with and without biopsy by matched case-control analysis adjusted for age, gender, body mass index, bilaterality, and stone burden. A total of 90 biopsies from 49 patients were performed, and the median duration between specimen collection and RNA extraction was 61 days. Both univariate and multivariate analyses showed BIGopsy ® forceps usage significantly increased the total yield (p = 0.004) and quality (p = 0.001 for A260/280, p = 0.004 for A260/A230) of extracted RNA. Extraction using the RNeasy Micro Kit ® also improved A260/A230, whereas reduced RNA integrity number of extracted RNA by univariate and multivariate analyses (p = 0.002 and p < 0.001, respectively). Moreover, matched case-control study demonstrated that endoscopic renal papilla biopsy caused no significant surgical complications, including bleeding, decreased stone clearance and hematocrit, and renal dysfunction. Biopsies during URS imparted an average of 20 minutes of procedure time over nonbiopsy

Papilla and pontic area regeneration in patient with gingival smile: A clinical case

PubMed Central

Gómez-Meda, Ramón; Torres-Sanchez, Carlos; Mareque-Bueno, Santiago; Zufía-González, Juan; Gutierrez-Pérez, José-Luis

2018-01-01

Purpose Connective tissue grafts are widely documented as a predictable technique for treating Miller Class I and II recessions, as well as procedures in which soft tissue augmentation is required for aesthetic reasons. This article aims to explore the resolution of a clinical case with this type of problema. Clinical case This case describes a technique for reconstructing a pontic area and adjacent papilla by means of two consecutive connective tissue grafts. The first graft served to increase the amount of tissue in the horizontal direction, and the second promoted vertical reconstruction of the defect. Results and Conclusion In cases with aesthetic requirements, restorative intervention may be able to mask tissue loss, but it can hardly achieve optimal aesthetic results. Periodontal plastic surgery techniques can be used to achieve that ideal result. The clinician must diagnose conditions in order to select correct treatment regimen for each individual case. Key words:Papilla, gingival smile, pontic, restorative dentistry. PMID:29849978

Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid.

PubMed

Aihara, Eitaro; Mahe, Maxime M; Schumacher, Michael A; Matthis, Andrea L; Feng, Rui; Ren, Wenwen; Noah, Taeko K; Matsu-ura, Toru; Moore, Sean R; Hong, Christian I; Zavros, Yana; Herness, Scott; Shroyer, Noah F; Iwatsuki, Ken; Jiang, Peihua; Helmrath, Michael A; Montrose, Marshall H

2015-11-24

Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5(+)) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5(+) cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers. Furthermore, characterization of the cell cycle of the taste bud progenitor niche reveals striking dynamics of taste bud development and regeneration. Using this taste bud organoid culture system and FUCCI2 transgenic mice, we identify the stem/progenitor cells have at least 5 distinct cell cycle populations by tracking within 24-hour synchronized oscillations of proliferation. Additionally, we demonstrate that stem/progenitor cells have motility to form taste bud organoids. Taste bud organoids provides a system for elucidating mechanisms of taste signaling, disease modeling, and taste tissue regeneration.

Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid

PubMed Central

Aihara, Eitaro; Mahe, Maxime M.; Schumacher, Michael A.; Matthis, Andrea L.; Feng, Rui; Ren, Wenwen; Noah, Taeko K.; Matsu-ura, Toru; Moore, Sean R.; Hong, Christian I.; Zavros, Yana; Herness, Scott; Shroyer, Noah F.; Iwatsuki, Ken; Jiang, Peihua; Helmrath, Michael A.; Montrose, Marshall H.

2015-01-01

Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5+) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5+ cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers. Furthermore, characterization of the cell cycle of the taste bud progenitor niche reveals striking dynamics of taste bud development and regeneration. Using this taste bud organoid culture system and FUCCI2 transgenic mice, we identify the stem/progenitor cells have at least 5 distinct cell cycle populations by tracking within 24-hour synchronized oscillations of proliferation. Additionally, we demonstrate that stem/progenitor cells have motility to form taste bud organoids. Taste bud organoids provides a system for elucidating mechanisms of taste signaling, disease modeling, and taste tissue regeneration. PMID:26597788

Comparison of osteo/odontogenic differentiation of human adult dental pulp stem cells and stem cells from apical papilla in the presence of platelet lysate.

PubMed

Abuarqoub, Duaa; Awidi, Abdalla; Abuharfeil, Nizar

2015-10-01

Human dental pulp cells (DPSCs) and stem cells from apical papilla have been used for the repair of damaged tooth tissues. Human platelet lysate (PL) has been suggested as a substitute for fetal bovine serum (FBS) for large scale expansion of dental stem cells. However, biological effects and optimal concentrations of PL for proliferation and differentiation of human dental stem cells remain to be elucidated. DPSCs and SCAP cells were isolated from impacted third molars of young healthy donors, at the stage of root development and identified by markers using flow cytometry. For comparison the cells were cultured in media containing PL (1%, 5% and 10%) and FBS, with subsequent induction for osteogenic/odontogenic differentiation. The cultures were analyzed for; morphology, growth characteristics, mineralization potential (Alizarin Red method) and differentiation markers using ELISA and real time -polymerase chain reaction (qPCR). The proliferation rates of DPSCs and SCAP significantly increased when cells were treated with 5% PL (7X doubling time) as compared to FBS. 5% PL also enhanced mineralized differentiation of DPSCs and SCAP, as indicated by the measurement of alkaline phosphatase activity, osteocalcin and osteopontin, calcium deposition and q-PCR. Our findings suggest that using 5% platelet lysate, proliferation and osteo/odontogenesis of DPSCs and SCAP for a short period of time (15 days), was significantly improved. This may imply its use as an optimum concentration for expansion of dental stem cells in bone regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Postmitotic human dermal fibroblasts preserve intact feeder properties for epithelial cell growth after long-term cryopreservation.

PubMed

Limat, A; Hunziker, T; Boillat, C; Noser, F; Wiesmann, U

1990-07-01

In vitro, human dermal fibroblasts (HDF) differentiate through morphologically and biochemically identified compartments. In the course of this spontaneous differentiation through mitotic and postmitotic states, a tremendous increase in cellular and nuclear size occurs. Induction of postmitotic states can be accelerated by chemical (e.g., mitomycin C) or physical (e.g., x-ray) treatments. Such experimentally induced postmitotic HDF cells support very efficiently the growth of cutaneous epithelial cells, i.e. interfollicular keratinocytes and follicular outer root sheath cells, especially in primary cultures starting from very low cell seeding densities. The HDF feeder system provides more fundamental and also practical advantages, i.e. use of initially diploid human fibroblasts from known anatomic locations, easy handling and excellent reproducibility, and the possibility of long-term storage by incubation at 37 degrees C. Conditions for the cryogenic storage of postmitotic HDF cells in liquid nitrogen are presented and related to the feeder capacity for epithelial cell growth. Because postmitotic HDF cells preserve intact feeder properties after long-term storage, the immediate availability of feeder cells and the possibility to repeat experiments with identical materials further substantiate the usefulness of this feeder system.

IN VITRO DERMAL ABSORPTION OF FLAME RETARDANT CHEMICALS

EPA Science Inventory

ABSTRACT
The use of flame retardant chemicals in furniture fabric could pose a potential health risk to consumers from dermal absorption of these compounds. The objective of this study was to examine the in vitro dermal absorption of two flame retardant chemicals, [14C]-d...

Dermal and transdermal delivery of pharmaceutically relevant macromolecules.

PubMed

Münch, S; Wohlrab, J; Neubert, R H H

2017-10-01

The skin offers an attractive way for dermal and transdermal drug delivery that is why the drug still needs certain qualities to transcend the outermost layer of the skin, the stratum corneum. The requirements are: drugs with a maximum molecular weight of 1kDa, high lipophilicity and a certain polarity. This would restrict the use of a transdermal delivery of macromolecules, which would make the drug more effective in therapeutic administration. Various studies have shown that macromolecules without support do not penetrate the human skin. This effect can be achieved using physical and chemical methods, as well as biological peptides. The most popular physical method is the use of microneedles to create micropores in the skin and release the active agent in different sections. But also, other methods have been tested. Microjets, lasers, electroporation, sonophoresis and iontophoresis are also promising methods to successfully deliver dermal and transdermal macromolecules. Additionally, there are different penetration enhancer groups and biological peptides, which are also considered to be interesting approaches of enabling macromolecules to travel along the skin. All these methods will be described and evaluated in this review article. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment of an extended dataset of in vitro human dermal absorption studies on pesticides to determine default values, opportunities for read-across and influence of dilution on absorption.

PubMed

Aggarwal, M; Fisher, P; Hüser, A; Kluxen, F M; Parr-Dobrzanski, R; Soufi, M; Strupp, C; Wiemann, C; Billington, R

2015-06-01

Dermal absorption is a key parameter in non-dietary human safety assessments for agrochemicals. Conservative default values and other criteria in the EFSA guidance have substantially increased generation of product-specific in vitro data and in some cases, in vivo data. Therefore, data from 190 GLP- and OECD guideline-compliant human in vitro dermal absorption studies were published, suggesting EFSA defaults and criteria should be revised (Aggarwal et al., 2014). This follow-up article presents data from an additional 171 studies and also the combined dataset. Collectively, the data provide consistent and compelling evidence for revision of EFSA's guidance. This assessment covers 152 agrochemicals, 19 formulation types and representative ranges of spray concentrations. The analysis used EFSA's worst-case dermal absorption definition (i.e., an entire skin residue, except for surface layers of stratum corneum, is absorbed). It confirmed previously proposed default values of 6% for liquid and 2% for solid concentrates, irrespective of active substance loading, and 30% for all spray dilutions, irrespective of formulation type. For concentrates, absorption from solvent-based formulations provided reliable read-across for other formulation types, as did water-based products for solid concentrates. The combined dataset confirmed that absorption does not increase linearly beyond a 5-fold increase in dilution. Finally, despite using EFSA's worst-case definition for absorption, a rationale for routinely excluding the entire stratum corneum residue, and ideally the entire epidermal residue in in vitro studies, is presented. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Handling of thermal paper: Implications for dermal exposure to bisphenol A and its alternatives

PubMed Central

Bernier, Meghan R.

2017-01-01

Bisphenol A (BPA) is an endocrine disrupting chemical used in a wide range of consumer products including photoactive dyes used in thermal paper. Recent studies have shown that dermal absorption of BPA can occur when handling these papers. Yet, regulatory agencies have largely dismissed thermal paper as a major source of BPA exposure. Exposure estimates provided by agencies such as the European Food Safety Authority (EFSA) are based on assumptions about how humans interact with this material, stating that ‘typical’ exposures for adults involve only one handling per day for short periods of time (<1 minute), with limited exposure surfaces (three fingertips). The objective of this study was to determine how individuals handle thermal paper in one common setting: a cafeteria providing short-order meals. We observed thermal paper handling in a college-aged population (n = 698 subjects) at the University of Massachusetts’ dining facility. We find that in this setting, individuals handle receipts for an average of 11.5 min, that >30% of individuals hold thermal paper with more than three fingertips, and >60% allow the paper to touch their palm. Only 11% of the participants we observed were consistent with the EFSA model for time of contact and dermal surface area. Mathematical modeling based on handling times we measured and previously published transfer coefficients, concentrations of BPA in paper, and absorption factors indicate the most conservative estimated intake from handling thermal paper in this population is 51.1 ng/kg/day, similar to EFSA’s estimates of 59 ng/kg/day from dermal exposures. Less conservative estimates, using published data on concentrations in thermal paper and transfer rates to skin, indicate that exposures are likely significantly higher. Based on our observational data, we propose that the current models for estimating dermal BPA exposures are not consistent with normal human behavior and should be reevaluated. PMID:28570582

Handling of thermal paper: Implications for dermal exposure to bisphenol A and its alternatives.

PubMed

Bernier, Meghan R; Vandenberg, Laura N

2017-01-01

Bisphenol A (BPA) is an endocrine disrupting chemical used in a wide range of consumer products including photoactive dyes used in thermal paper. Recent studies have shown that dermal absorption of BPA can occur when handling these papers. Yet, regulatory agencies have largely dismissed thermal paper as a major source of BPA exposure. Exposure estimates provided by agencies such as the European Food Safety Authority (EFSA) are based on assumptions about how humans interact with this material, stating that 'typical' exposures for adults involve only one handling per day for short periods of time (<1 minute), with limited exposure surfaces (three fingertips). The objective of this study was to determine how individuals handle thermal paper in one common setting: a cafeteria providing short-order meals. We observed thermal paper handling in a college-aged population (n = 698 subjects) at the University of Massachusetts' dining facility. We find that in this setting, individuals handle receipts for an average of 11.5 min, that >30% of individuals hold thermal paper with more than three fingertips, and >60% allow the paper to touch their palm. Only 11% of the participants we observed were consistent with the EFSA model for time of contact and dermal surface area. Mathematical modeling based on handling times we measured and previously published transfer coefficients, concentrations of BPA in paper, and absorption factors indicate the most conservative estimated intake from handling thermal paper in this population is 51.1 ng/kg/day, similar to EFSA's estimates of 59 ng/kg/day from dermal exposures. Less conservative estimates, using published data on concentrations in thermal paper and transfer rates to skin, indicate that exposures are likely significantly higher. Based on our observational data, we propose that the current models for estimating dermal BPA exposures are not consistent with normal human behavior and should be reevaluated.

Pharyngeal arch deficiencies affect taste bud development in the circumvallate papilla with aberrant glossopharyngeal nerve formation.

PubMed

Okubo, Tadashi; Takada, Shinji

2015-07-01

The pharyngeal arches (PAs) generate cranial organs including the tongue. The taste placodes, formed in particular locations on the embryonic tongue surface, differentiate into taste buds harbored in distinct gustatory papillae. The developing tongue also has a complex supply of cranial nerves through each PA. However, the relationship between the PAs and taste bud development is not fully understood. Ripply3 homozygous mutant mice, which have impaired third/fourth PAs, display a hypoplastic circumvallate papilla and lack taste buds, although the taste placode is normally formed. Formation of the glossopharyngeal ganglia is defective and innervation toward the posterior tongue is completely missing in Ripply3 mutant embryos at E12.5. Moreover, the distribution of neuroblasts derived from the epibranchial placode is severely, but not completely, atenuated, and the neural crest cells are diminished in the third PA region of Ripply3 mutant embryos at E9.5-E10.5. In Tbx1 homozygous mutant embryos, which exhibit another type of deficiency in PA development, the hypoplastic circumvallate papilla is observed along with abnormal formation of the glossopharyngeal ganglia and severely impaired innervation. PA deficiencies affect multiple aspects of taste bud development, including formation of the cranial ganglia and innervation to the posterior tongue. © 2015 Wiley Periodicals, Inc.

Methods in hair research: how to objectively distinguish between anagen and catagen in human hair follicle organ culture.

PubMed

Kloepper, Jennifer Elisabeth; Sugawara, Koji; Al-Nuaimi, Yusur; Gáspár, Erzsébet; van Beek, Nina; Paus, Ralf

2010-03-01

The organ culture of human scalp hair follicles (HFs) is the best currently available assay for hair research in the human system. In order to determine the hair growth-modulatory effects of agents in this assay, one critical read-out parameter is the assessment of whether the test agent has prolonged anagen duration or induced catagen in vitro. However, objective criteria to distinguish between anagen VI HFs and early catagen in human HF organ culture, two hair cycle stages with a deceptively similar morphology, remain to be established. Here, we develop, document and test an objective classification system that allows to distinguish between anagen VI and early catagen in organ-cultured human HFs, using both qualitative and quantitative parameters that can be generated by light microscopy or immunofluorescence. Seven qualitative classification criteria are defined that are based on assessing the morphology of the hair matrix, the dermal papilla and the distribution of pigmentary markers (melanin, gp100). These are complemented by ten quantitative parameters. We have tested this classification system by employing the clinically used topical hair growth inhibitor, eflornithine, and show that eflornithine indeed produces the expected premature catagen induction, as identified by the novel classification criteria reported here. Therefore, this classification system offers a standardized, objective and reproducible new experimental method to reliably distinguish between human anagen VI and early catagen HFs in organ culture.

Dermal Exposure Assessment to Pesticides in Farming Systems in Developing Countries: Comparison of Models

PubMed Central

Lesmes Fabian, Camilo; Binder, Claudia R.

2015-01-01

In the field of occupational hygiene, researchers have been working on developing appropriate methods to estimate human exposure to pesticides in order to assess the risk and therefore to take the due decisions to improve the pesticide management process and reduce the health risks. This paper evaluates dermal exposure models to find the most appropriate. Eight models (i.e., COSHH, DERM, DREAM, EASE, PHED, RISKOFDERM, STOFFENMANAGER and PFAM) were evaluated according to a multi-criteria analysis and from these results five models (i.e., DERM, DREAM, PHED, RISKOFDERM and PFAM) were selected for the assessment of dermal exposure in the case study of the potato farming system in the Andean highlands of Vereda La Hoya, Colombia. The results show that the models provide different dermal exposure estimations which are not comparable. However, because of the simplicity of the algorithm and the specificity of the determinants, the DERM, DREAM and PFAM models were found to be the most appropriate although their estimations might be more accurate if specific determinants are included for the case studies in developing countries. PMID:25938911

Update on botulinum toxin and dermal fillers.

PubMed

Berbos, Zachary J; Lipham, William J

2010-09-01

The art and science of facial rejuvenation is an ever-evolving field of medicine, as evidenced by the continual development of new surgical and nonsurgical treatment modalities. Over the past 10 years, the use of botulinum toxin and dermal fillers for aesthetic purposes has risen sharply. Herein, we discuss properties of several commonly used injectable products and provide basic instruction for their use toward the goal of achieving facial rejuvenation. The demand for nonsurgical injection-based facial rejuvenation products has risen enormously in recent years. Used independently or concurrently, botulinum toxin and dermal filler agents offer an affordable, minimally invasive approach to facial rejuvenation. Botulinum toxin and dermal fillers can be used to diminish facial rhytides, restore facial volume, and sculpt facial contours, thereby achieving an aesthetically pleasing, youthful facial appearance.

Dermal Remodeling of Burn Scar by Fractional CO2 Laser.

PubMed

Lee, Sang-Jun; Suh, Dong-Hye; Lee, Ji Min; Song, Kye-Yong; Ryu, Hwa Jung

2016-10-01

Ablative CO2 fractional lasers have recently been introduced for burn scar treatment because of pronounced clinical outcomes with fewer treatment sessions than nonablative fractional laser. This study was conducted to observe clinical as well as histologic changes of burn scars after treatment with CO2 fractional laser. Eleven patients (one female and 10 males, aged 31-59 years) with skin phototypes III to V with burn scars received 10 sessions of fractional CO2 laser treatments (UltraPulse(®) Encore; Lumenis, Santa Clara, CA, USA) over an average 5-week interval. Two passes were performed using the following parameters: deep FX mode, 12.5-30 mJ, with a density setting of 5-10 %. Clinical evaluations by three blinded dermatologists were obtained at baseline and at 6 months after the final treatment via photographs using the Vancouver scar scale (VSS). Skin biopsies were done on four patients before and after treatment. All patients showed clinical improvement in their scars with significant decrease in VSS. Histologic findings showed the changes in the upper dermis with newly formed dermal papilla. This characteristic upper dermis change was presented as improvement in surface smoothness and skin tension clinically. Postinflammatory hyperpigmentation and itching sensation were the most common adverse effects. Burn scar treatment by fractional CO2 laser is effective by forming new collagen fibers mainly in the upper dermis. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Alteration of Skin Properties with Autologous Dermal Fibroblasts

PubMed Central

Thangapazham, Rajesh L.; Darling, Thomas N.; Meyerle, Jon

2014-01-01

Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA) while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices. PMID:24828202

Gadolinium-induced fibrosis is counter-regulated by CCN3 in human dermal fibroblasts: a model for potential treatment of nephrogenic systemic fibrosis.

PubMed

Riser, Bruce L; Bhagavathula, Narasimharao; Perone, Patricia; Garchow, Kendra; Xu, Yiru; Fisher, Gary J; Najmabadi, Feridoon; Attili, Durga; Varani, James

2012-06-01

We recently show that CCN3 is a counter-regulatory molecule for the pro-fibrotic protein CCN2, and a potentially novel fibrosis therapy. The goal of this study was to assess the role of CCN3 in fibroproliferative/fibrotic responses in human dermal fibroblasts exposed to Omniscan, one of the gadolinium-based contrast agents associated with development of nephrogenic systemic fibrosis (NSF) a rare but life-threatening disease thought to be complication of NMR diagnostics in renal impaired patients. Human dermal fibroblasts were exposed to Omniscan; or to platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) as controls. Proliferation was assessed along with matrix metalloproteinase-1, tissue inhibitor of metalloproteinases-1 and type 1 procollagen in the absence and presence of CCN3. In parallel, CCN3 production was assessed in control and Omniscan-treated cells. The results showed that PDGF stimulated fibroblast proliferation, production of Timp-1 and MMP-1 whereas exogenous CCN3 inhibited, in a dose response manner, cell proliferation (approx. 50 % max.) and production of MMP-1 (approx 35 % max.) but had little effect on TIMP-1. TGF-β stimulated type 1 procollagen production but not proliferation, Timp-1 or MMP-1 compared to non-TGF-ß treated control cells, and CCN3 treatment blocked (approx. 80 % max.) this up-regulation. Interestingly, untreated, control fibroblasts produced high constitutive levels of CCN3 and concentrations of Omniscan that induced fibroproliferative/fibrogenic changes in dermal fibroblasts correspondingly suppressed CCN3 production. The use of PDGF and TGF-β as positive controls, and the study of differential responses, including that to Omniscan itself, provide the first evidence for a role of fibroblast-derived CCN3 as an endogenous regulator of pro-fibrotic changes, elucidating possible mechanism(s). In conclusion, these data support our hypothesis of a role for fibroblast-derived CCN3 as an endogenous

Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Puente, Pilar de la, E-mail: pilardelapuentegarcia@gmail.com; Ludeña, Dolores; López, Marta

2013-02-01

Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12more » pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.« less

Dermal exposure and urinary 1-hydroxypyrene among asphalt roofing workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClean, M.D.; Rinehart, R.D.; Sapkota, A.

2007-07-01

The primary objective of this study was to identify significant determinants of dermal exposure to polycyclic aromatic compounds (PACs) among asphalt roofing workers and use urinary 1-hydroxyprene (1-OHP) measurements to evaluate the effect of dermal exposure on total absorbed dose. The study population included 26 asphalt roofing workers who performed three primary tasks: tearing off old roofs, putting down new roofs, and operating the kettle at ground level. During multiple consecutive work shifts, dermal patch samples were collected from the underside of each worker's wrists and were analyzed for PACs, pyrene, and benzo(a)pyrene (BAP). During the same work week, urinemore » samples were collected at pre-shift, post-shift, and bedtime each day and were analyzed for 1-OHP (205 urine samples). Linear mixed effects models were used to evaluate the dermal measurements for the purpose of identifying important determinants of exposure, and to evaluate urinary 1-OHP measurements for the purpose of identifying important determinants of total absorbed dose. Dermal exposures to PAC, pyrene, and BAP were found to vary significantly by roofing task and by the presence of an old coal tar pitch roof. For each of the three analytes, the adjusted mean dermal exposures associated with tear-off were approximately four times higher than exposures associated with operating the kettle. Exposure to coal tar pitch was associated with a 6-fold increase in PAC exposure, an 8-fold increase in pyrene exposure and a 35-fold increase in BAP exposure. The presence of coal tar pitch was the primary determinant of dermal exposure, particularly for exposure to BAP. However, the task-based differences that were observed while controlling for pitch suggest that exposure to asphalt also contributes to dermal exposures.« less

Estimating terrestrial amphibian pesticide body burden through dermal exposure

EPA Science Inventory

Dermal exposure presents a potentially significant but understudied route for pesticide uptake in terrestrial amphibians. Our study measured dermal uptake of pesticides of varying hydrophobicity (logKow) in frogs. Amphibians were indirectly exposed to one of five pesticide active...

Strawberry-Based Cosmetic Formulations Protect Human Dermal Fibroblasts against UVA-Induced Damage

PubMed Central

Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Y.; Afrin, Sadia; Reboredo-Rodriguez, Patricia; Cianciosi, Danila; Mezzetti, Bruno; Quiles, Josè L.; Bompadre, Stefano; Battino, Maurizio; Giampieri, Francesca

2017-01-01

Extreme exposure of skin to Ultraviolet A (UVA)-radiation may induce a dysregulated production of reactive oxygen species (ROS) which can interact with cellular biomolecules leading to oxidative stress, inflammation, DNA damage, and alteration of cellular molecular pathways, responsible for skin photoaging, hyperplasia, erythema, and cancer. For these reasons, the use of dietary natural bioactive compounds with remarkable antioxidant activity could be a strategic tool to counteract these UVA-radiation-caused deleterious effects. Thus, the purpose of the present work was to test the efficacy of strawberry (50 μg/mL)-based formulations supplemented with Coenzyme Q10 (100 μg/mL) and sun protection factor 10 in human dermal fibroblasts irradiated with UVA-radiation. The apoptosis rate, the amount of intracellular reactive oxygen species (ROS) production, the expression of proteins involved in antioxidant and inflammatory response, and mitochondrial functionality were evaluated. The results showed that the synergic topical use of strawberry and Coenzyme Q10 provided a significant (p < 0.05) photoprotective effect, reducing cell death and ROS, increasing antioxidant defense, lowering inflammatory markers, and improving mitochondrial functionality. The obtained results suggest the use of strawberry-based formulations as an innovative, natural, and useful tool for the prevention of UVA exposure-induced skin diseases in order to decrease or substitute the amount of synthetic sunscreen agents. PMID:28613256

What happens to an acellular dermal matrix after implantation in the human body? A histological and electron microscopic study.

PubMed

Boháč, Martin; Danišovič, Ľuboš; Koller, Ján; Dragúňová, Jana; Varga, Ivan

2018-01-22

Acellular matrices are used for various purposes and they have been studied extensively for their potential roles in regenerating tissues or organs. The acellular matrix generates physiological cues that mimic the native tissue microenvironment. Acellular dermal matrix (ADM) is a soft connective tissue graft generated by a decellularization process that preserves the intact extracellular skin matrix. Upon implantation, this structure serves as a scaffold for donor-side cells to facilitate subsequent incorporation and revascularization. In breast reconstruction, ADM is used mainly for lower pole coverage and the shaping of a new breast. It helps control the positioning of the implant in the inframammary fold, and prevent the formation of contractile pseudocapsule around the breast implant. In this study, we provide a comprehensive histological description of ADM used for human breast reconstruction over the course of several months following implementation. Using immunohistochemical methods (a panel of 12 antibodies) coupled with optical and transmission electron microscopy, we confirmed that the original acellular dermal matrix became recolonized by fibroblasts and myofibroblasts, and also by various other free cells of the connective tissue (lymphocytes, macrophages and multinucleated giant cells, granulocytes, mast cells) after implantation into the patient's body. Within the implanted ADM, there was a relatively rapid ingrowth of blood vessels. Lymphatic vessels were only detected in one case 9 months after the implantation of the ADM. These results suggest that lymphangiogenesis is a longer process than angiogenesis.

Osteopontin in Systemic Sclerosis and its Role in Dermal Fibrosis

PubMed Central

Wu, Minghua; Schneider, Daniel J.; Mayes, Maureen D; Assassi, Shervin; Arnett, Frank C.; Tan, Filemon K.; Blackburn, Michael R.; Agarwal, Sandeep K.

2012-01-01

Osteopontin (OPN) is a matricellular protein with proinflammatory and profibrotic properties. Previous reports demonstrate a role for OPN in wound healing and pulmonary fibrosis. Herein, we determined if OPN levels are increased in a large cohort of systemic sclerosis (SSc) patients and if OPN contributes dermal fibrosis. Plasma OPN levels were increased in SSc patients, including patients with limited and diffuse disease, compared to healthy controls. Immunohistology demonstrated OPN on fibroblast-like and inflammatory cells in SSc skin and lesional skin from mice in the bleomycin-induced dermal fibrosis model. OPN deficient (OPN−/−) mice developed less dermal fibrosis compared to wild-type mice in the bleomycin-induced dermal fibrosis model. Additional in vivo studies demonstrated that lesional skin from OPN−/− mice had fewer Mac-3+ cells, fewer myofibroblasts, decreased TGF-beta (TGFβ) and genes in the TGFβ pathway and decreased numbers of cells expressing phosphorylated SMAD2 (pSMAD) and ERK. In vitro, OPN−/− dermal fibroblasts had decreased migratory capacity but similar phosphorylation of SMAD2 by TGFβ. Finally, TGFβ production by OPN deficient macrophages was reduced compared to wild type. These data demonstrate an important role for OPN in the development of dermal fibrosis and suggest that OPN may be a novel therapeutic target in SSc. PMID:22402440

Matrix-directed differentiation of human adipose-derived mesenchymal stem cells to dermal-like fibroblasts that produce extracellular matrix.

PubMed

Sivan, Unnikrishnan; Jayakumar, K; Krishnan, Lissy K

2016-10-01

Commercially available skin substitutes lack essential non-immune cells for adequate tissue regeneration of non-healing wounds. A tissue-engineered, patient-specific, dermal substitute could be an attractive option for regenerating chronic wounds, for which adipose-derived mesenchymal stem cells (ADMSCs) could become an autologous source. However, ADMSCs are multipotent in nature and may differentiate into adipocytes, osteocytes and chondrocytes in vitro, and may develop into undesirable tissues upon transplantation. Therefore, ADMSCs committed to the fibroblast lineage could be a better option for in vitro or in vivo skin tissue engineering. The objective of this study was to standardize in vitro culture conditions for ADMSCs differentiation into dermal-like fibroblasts which can synthesize extracellular matrix (ECM) proteins. Biomimetic matrix composite, deposited on tissue culture polystyrene (TCPS), and differentiation medium (DM), supplemented with fibroblast-conditioned medium and growth factors, were used as a fibroblast-specific niche (FSN) for cell culture. For controls, ADMSCs were cultured on bare TCPS with either DM or basal medium (BM). Culture of ADMSCs on FSN upregulated the expression of differentiation markers such as fibroblast-specific protein-1 (FSP-1) and a panel of ECM molecules specific to the dermis, such as fibrillin-1, collagen I, collagen IV and elastin. Immunostaining showed the deposition of dermal-specific ECM, which was significantly higher in FSN compared to control. Fibroblasts derived from ADMSCs can synthesize elastin, which is an added advantage for successful skin tissue engineering as compared to fibroblasts from skin biopsy. To obtain rapid differentiation of ADMSCs to dermal-like fibroblasts for regenerative medicine, a matrix-directed differentiation strategy may be employed. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Papillary proliferation of the endometrium: a clinicopathologic study of 59 cases of simple and complex papillae without cytologic atypia.

PubMed

Ip, Philip P C; Irving, Julie A; McCluggage, W Glenn; Clement, Philip B; Young, Robert H

2013-02-01

Papillary proliferation of the endometrium (PPE) without cytologic atypia is uncommon and has only been studied in detail by Lehman and Hart in 2001. On histologic examination, PPE ranges from simple papillae with fibrovascular cores, often involving the surface of endometrial polyps, to complex intracystic proliferations; some consider the latter to be analogous to nonatypical complex hyperplasia. To further characterize PPE, with emphasis on the risk of and features associated with concurrent or subsequent neoplasia, the clinicopathologic features of 59 cases without cytologic atypia were studied. The cases were classified into 2 groups according to the degree of architectural complexity and extent of proliferation. Group 1 consisted of those with localized simple papillae. Simple papillae were defined as those with short, predominantly nonbranching stalks; those with occasional secondary branches and/or detached papillae were also included in this group. Localized proliferations were those with 1 or 2 foci involving the surface or the subjacent glands of polyps or nonpolypoid endometrium. Group 2 consisted of those with complex papillae and/or those with diffuse and crowded intracystic papillae. Complex papillae were those with either short or long stalks, with frequent secondary and complex branches. Diffuse proliferation was defined as presence of 3 or more foci within a specimen or involvement of >50% of the endometrial polyp by simple or complex PPE. Any coexistent or subsequent hyperplasia of conventional type (World Health Organization classification) or adenocarcinoma was recorded. The age of patients ranged from 23 to 82 years (median, 53 y); 36 (61%) were postmenopausal. The majority presented with abnormal vaginal bleeding. Sixteen patients (27%) were receiving hormonal preparations including 5 who were treated with a progestogen for preexisting endometrial hyperplasia or low-grade endometrioid adenocarcinoma. The histologic diagnosis of PPE was made

[Exploratory study on the micro-remodeling of dermal tissue].

PubMed

Jiang, Yu-zhi; Ding, Gui-fu; Lu, Shu-liang

2009-10-01

To explore the effect of three-dimensional structure of dermal matrix on biological behavior of fibroblasts (Fb) in the microcosmic perspective. The three-dimensional structure of dermal tissue was analyzed by plane geometric and trigonometric function. Microdots structure array with cell adhesion effect was designed by computer-assisted design software according to the adhesive and non-adhesive components of dermal tissue. Four sizes (8 microm x 3 microm, space 6 microm; 16 microm x 3 microm, space 6 microm; 16 microm x 5 microm, space 8 microm; 20 microm x 3 microm, space 2 microm) of micropier grid used for cell culture (MPGCC) with cell-adhesive microdots, built up with micro-pattern printing and molecule self-assembly method were used to culture dermal Fb. Fb cultured with cell culture matrix without micropier grid was set up as control. The expression of skeleton protein (alpha-SMA) of Fb, cell viability and cell secretion were detected with immunohistochemistry, fluorescent immunohistochemistry, MTT test and the hydroxyproline content assay. The three-dimensional structure of dermal tissue could be simulated by MPGCC as shown in arithmetic analysis. Compared with those of control group [(12 +/- 3)% and (0.53 +/- 0.03) microg/mg, (0.35 +/- 0.04)], the expression of alpha-SMA [(49 +/- 3)%, (61 +/- 3)%, (47 +/- 4)%, (51 +/- 3)%] and the content of hydroxyproline [(0.95 +/- 0.04), (0.87 +/- 0.03), (0.81 +/- 0.03), (0.77 +/- 0.03) microg/mg] were increased significantly (P < 0.05), the cell viability of Fb (0.12 +/- 0.03, 0.13 +/- 0.04, 0.14 +/- 0.03, 0.19 +/- 0.03) cultured in MPGCC was decreased significantly (P < 0.05). When the parameters of micropier grid were changed, the expression of alpha-SMA, the cell viability and the content of hydroxyproline of Fb cultured in four sizes of MPGCC were also significantly changed as compared with one another (P < 0.05). MPGCC may be the basic functional unit of dermal template, or unit of dermal template to call

Apigenin prevents ultraviolet-B radiation induced cyclobutane pyrimidine dimers formation in human dermal fibroblasts.

PubMed

Britto, S Mary; Shanthakumari, D; Agilan, B; Radhiga, T; Kanimozhi, G; Prasad, N Rajendra

2017-09-01

Exposure to solar ultraviolet-B (UVB) radiation leads to the formation of cyclobutane pyrimidine dimers (CPDs). We investigated the protective effect of apigenin against UVB-induced CPDs formation in human dermal fibroblasts cells (HDFa). For this purpose, HDFa cells were treated with apigenin (15μM) prior to UVB irradiation (20mJ/cm 2 ); DNA damage and subsequent molecular end points were observed. Exposure to UVB radiation increased significant CPDs formation in HDFa cells and the frequencies of CPDs were reduced by treatment with apigenin (15μM). UVB-induced CPDs downregulates the expression of nucleotide excision repair (NER) genes such as xeroderma pigmentosum complementation group C, B, G and F (XPC, XPB, XPG and XPF), transcription factor II human (TFIIH) and excision repair cross-complementation group 1 (ERCC1) in HDFa cells. Conversely, apigenin treatment restored UVB-induced loss of NER proteins in HDFa cells, which indicates its preventive effect against CPDs formation. Besides, single low dose UVB-exposure induced nuclear fragmentation, apoptotic frequency and apoptotic proteins expression (Bax and Caspase-3) have been prevented by the apigenin pretreatment. Furthermore, apigenin exhibits strong UV absorbance property and showed 10.08 SPF value. Thus, apigenin can protect skin cells against UVB-induced CPDs formation probably through its sunscreen effect. Hence, apigenin can be considered as an effective protective agent against UV induced skin damages. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of sensory input of the chorda tympani nerve and the number of fungiform papillae in burning mouth syndrome.

PubMed

Nasri-Heir, Cibele; Gomes, Julyana; Heir, Gary M; Ananthan, Sowmya; Benoliel, Rafael; Teich, Sorin; Eliav, Eli

2011-07-01

The aim of this study was to evaluate patients suffering from burning mouth syndrome (BMS) and control subjects by means of sensory testing and fungiform papillae count. The left and right anterior two-thirds of the tongue of of 25 BMS subjects and 20 healthy control subjects were evaluated for electric taste and electric detection threshold. The number of fungiform papillae/cm(2) was evaluated by using close-up digital photography. The electric taste/tingling detection threshold ratio was significantly higher in BMS compared with control subjects (P = .041). No difference was found between the number of fungiform papillae/cm(2) in the BMS compared with the control subjects (P = .277). Patients suffering from BMS for a prolonged period of time presented with a significantly elevated electric taste/tingling detection threshold ratio (P = .031). BMS may be a neurodegenerative process with chorda tympani nerve hypofunction potentially playing a role in the pathophysiology of this disorder. Copyright © 2011 Mosby, Inc. All rights reserved.

Dermal permeation data and models for the prioritization and screening-level exposure assessment of organic chemicals

EPA Science Inventory

High throughput screening (HTS) models are being developed and applied to prioritize chemicals for more comprehensive exposure and risk assessment. Dermal pathways are possible exposure routes to humans for thousands of chemicals found in personal care products and the indoor env...

Glycerolized Reticular Dermis as a New Human Acellular Dermal Matrix: An Exploratory Study

PubMed Central

Ferrando, Pietro Maria; Balmativola, Davide; Cambieri, Irene; Scalzo, Maria Stella; Bergallo, Massimiliano; Annaratone, Laura; Casarin, Stefania; Fumagalli, Mara; Stella, Maurizio; Sapino, Anna; Castagnoli, Carlotta

2016-01-01

Human Acellular Dermal Matrices (HADM) are employed in various reconstructive surgery procedures as scaffolds for autologous tissue regeneration. The aim of this project was to develop a new type of HADM for clinical use, composed of glycerolized reticular dermis decellularized through incubation and tilting in Dulbecco’s Modified Eagle’s Medium (DMEM). This manufacturing method was compared with a decellularization procedure already described in the literature, based on the use of sodium hydroxide (NaOH), on samples from 28 donors. Cell viability was assessed using an MTT assay and microbiological monitoring was performed on all samples processed after each step. Two surgeons evaluated the biomechanical characteristics of grafts of increasing thickness. The effects of the different decellularization protocols were assessed by means of histological examination and immunohistochemistry, and residual DNA after decellularization was quantified using a real-time TaqMan MGB probe. Finally, we compared the results of DMEM based decellularization protocol on reticular dermis derived samples with the results of the same protocol applied on papillary dermis derived grafts. Our experimental results indicated that the use of glycerolized reticular dermis after 5 weeks of treatment with DMEM results in an HADM with good handling and biocompatibility properties. PMID:26918526

The retrocuspid papilla. A clinical survey.

PubMed

Berman, F R; Fay, J T

1976-07-01

1. As mentioned previously in the literature, RCPs are commonly found in the young but become progressively less evident with advancing age. 2. The incidence of the RCP in Negroes is approximately the same as that in Caucasians. 3. Bilateral RCPs are more common than unilateral papillae. 4. The occurrence of RCPs is consistently more common in females than in males, in both Caucasians and Negroes. 5. Histologically, the RCPs are essentially normal, showing features indicative of those seen in frictional irritation during mastication and phonation. 6. The 72.5 per cent incidence of RCPs in children under 11 years of age confirms the trends of past studies and indicates that the RCP is a normal entity in pediatric dental patients and should be included in the literature as such. 7. The clinical significance of the RCP is that it be recognized as a normal anatomic structure that regresses with age and requires no treatment.

Comparison of International Guidelines of Dermal Absorption Tests Used in Pesticides Exposure Assessment for Operators

PubMed Central

So, Jaehwan; Ahn, Junyoung; Lee, Tae-Hee; Park, Kyung-Hun; Paik, Min-Kyoung; Jeong, Mihye; Cho, Myung-Haing

2014-01-01

The number of farmers who have suffered from non-fatal acute pesticide poisoning has been reported to vary from 5.7% to 86.7% in South Korea since 1975. Absorption through the skin is the main route of exposure to pesticides for farmers who operate with them. Several in vitro tests using the skins of humans or animal and in vivo tests using laboratory animals are introduced for the assessment of human dermal absorption level of pesticides. The objective of this study is to evaluate and compare international guidelines and strategies of dermal absorption assessments and to propose unique approaches for applications into pesticide registration process in our situation. Until present in our situation, pesticide exposure level to operator is determined just using default value of 10 as for skin absorption ratio because of data shortage. Dermal absorption tests are requested to get exposure level of pesticides and to ultimately know the safety of pesticides for operators through the comparison with the value of AOEL. When the exposure level is higher than AOEL, the pesticide cannot be approved. We reviewed the skin absorption test guidelines recommended by OECD, EFSA and EPA. The EPA recommends assessment of skin absorption of pesticides for humans through the TPA which includes all the results of in vitro human and animal and animal in vivo skin absorption studies. OECD and EFSA, employ a tiered approach, which the requirement of further study depends on the results of the former stage study. OECD guidelines accept the analysis of pesticide level absorbed through skin without radioisotope when the recovery using the non-labeled method is within 80~120%. Various factors are reviewed in this study, including the origin of skin (gender, animal species and sites of skin), thickness, temperature and, etc., which can influence the integrity of results. PMID:25584144

Vibration anesthesia for the reduction of pain with facial dermal filler injections.

PubMed

Mally, Pooja; Czyz, Craig N; Chan, Norman J; Wulc, Allan E

2014-04-01

Vibration anesthesia is an effective pain-reduction technique for facial cosmetic injections. The analgesic effect of this method was tested in this study during facial dermal filler injections. The study aimed to evaluate the safety and efficacy of vibration anesthesia for these facial injections. This prospective study analyzed 41 patients who received dermal filler injections to the nasolabial folds, tear troughs, cheeks, and other facial sites. The injections were administered in a randomly assigned split-face design. One side of the patient's face received vibration together with dermal filler injections, whereas the other side received dermal filler injections alone. The patients completed a posttreatment questionnaire pertaining to injection pain, adverse effects, and preference for vibration with future dermal filler injections. The patients experienced both clinically and statistically significant pain reduction when a vibration stimulus was co-administered with the dermal filler injections. No adverse events were reported. The majority of the patients (95 %) reported a preference for vibration anesthesia with subsequent dermal filler injections. Vibration is a safe and effective method of achieving anesthesia during facial dermal filler injections. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Acellular dermal matrix graft for gingival augmentation: a preliminary clinical, histologic, and ultrastructural evaluation.

PubMed

Scarano, Antonio; Barros, Raquel R M; Iezzi, Giovanna; Piattelli, Adriano; Novaes, Arthur B

2009-02-01

The aim of this study was to evaluate clinically, histologically, and ultrastructurally the integration process of the acellular dermal matrix used to increase the band of keratinized tissue while achieving gingival inflammation control. Ten patients exhibiting a mucogingival problem with bands of keratinized tissue dermal matrix. Clinical measurements were assessed at baseline and after 3 months. A specimen of the allograft and surrounding tissues was obtained immediately before the surgery and 4 minutes and 1, 2, 3, 4, 6, and 10 weeks after grafting. Clinically, a gain of keratinized tissue of 2.92 +/- 0.65 mm was observed after 3 months. Histologically and ultrastructurally, many macrophages were observed phagocytosing preexisting collagen fibers in the first weeks. From week 2 on, fibroblasts synthesizing new collagen, epithelial cells colonizing the graft surface, and revascularization were noticed. After 6 weeks it was difficult to find the acellular dermal matrix preexisting collagen fibers. This process of substitution was completed after 10 weeks, when the reepithelialization of the entire graft throughout a well-structured basement membrane was achieved. The acellular dermal matrix graft seemed to be an easily handled material for use in keratinized tissue augmentation that, in humans, was substituted and completely reepithelialized in 10 weeks according to histologic and ultrastructural results.

Human Keratinocyte Growth and Differentiation on Acellular Porcine Dermal Matrix in relation to Wound Healing Potential

PubMed Central

Zajicek, Robert; Mandys, Vaclav; Mestak, Ondrej; Sevcik, Jan; Königova, Radana; Matouskova, Eva

2012-01-01

A number of implantable biomaterials derived from animal tissues are now used in modern surgery. Xe-Derma is a dry, sterile, acellular porcine dermis. It has a remarkable healing effect on burns and other wounds. Our hypothesis was that the natural biological structure of Xe-Derma plays an important role in keratinocyte proliferation and formation of epidermal architecture in vitro as well as in vivo. The bioactivity of Xe-Derma was studied by a cell culture assay. We analyzed growth and differentiation of human keratinocytes cultured in vitro on Xe-Derma, and we compared the results with formation of neoepidermis in the deep dermal wounds treated with Xe-Derma. Keratinocytes cultured on Xe-Derma submerged in the culture medium achieved confluence in 7–10 days. After lifting the cultures to the air-liquid interface, the keratinocytes were stratified and differentiated within one week, forming an epidermis with basal, spinous, granular, and stratum corneum layers. Immunohistochemical detection of high-molecular weight cytokeratins (HMW CKs), CD29, p63, and involucrin confirmed the similarity of organization and differentiation of the cultured epidermal cells to the normal epidermis. The results suggest that the firm natural structure of Xe-Derma stimulates proliferation and differentiation of human primary keratinocytes and by this way improves wound healing. PMID:22629190

Human keratinocyte growth and differentiation on acellular porcine dermal matrix in relation to wound healing potential.

PubMed

Zajicek, Robert; Mandys, Vaclav; Mestak, Ondrej; Sevcik, Jan; Königova, Radana; Matouskova, Eva

2012-01-01

A number of implantable biomaterials derived from animal tissues are now used in modern surgery. Xe-Derma is a dry, sterile, acellular porcine dermis. It has a remarkable healing effect on burns and other wounds. Our hypothesis was that the natural biological structure of Xe-Derma plays an important role in keratinocyte proliferation and formation of epidermal architecture in vitro as well as in vivo. The bioactivity of Xe-Derma was studied by a cell culture assay. We analyzed growth and differentiation of human keratinocytes cultured in vitro on Xe-Derma, and we compared the results with formation of neoepidermis in the deep dermal wounds treated with Xe-Derma. Keratinocytes cultured on Xe-Derma submerged in the culture medium achieved confluence in 7-10 days. After lifting the cultures to the air-liquid interface, the keratinocytes were stratified and differentiated within one week, forming an epidermis with basal, spinous, granular, and stratum corneum layers. Immunohistochemical detection of high-molecular weight cytokeratins (HMW CKs), CD29, p63, and involucrin confirmed the similarity of organization and differentiation of the cultured epidermal cells to the normal epidermis. The results suggest that the firm natural structure of Xe-Derma stimulates proliferation and differentiation of human primary keratinocytes and by this way improves wound healing.

Validation and Comparison of Two Sampling Methods to Assess Dermal Exposure to Drilling Fluids and Crude Oil

PubMed Central

Galea, Karen S.; McGonagle, Carolyn; Sleeuwenhoek, Anne; Todd, David; Jiménez, Araceli Sánchez

2014-01-01

Dermal exposure to drilling fluids and crude oil is an exposure route of concern. However, there have been no published studies describing sampling methods or reporting dermal exposure measurements. We describe a study that aimed to evaluate a wipe sampling method to assess dermal exposure to an oil-based drilling fluid and crude oil, as well as to investigate the feasibility of using an interception cotton glove sampler for exposure on the hands/wrists. A direct comparison of the wipe and interception methods was also completed using pigs’ trotters as a surrogate for human skin and a direct surface contact exposure scenario. Overall, acceptable recovery and sampling efficiencies were reported for both methods, and both methods had satisfactory storage stability at 1 and 7 days, although there appeared to be some loss over 14 days. The methods’ comparison study revealed significantly higher removal of both fluids from the metal surface with the glove samples compared with the wipe samples (on average 2.5 times higher). Both evaluated sampling methods were found to be suitable for assessing dermal exposure to oil-based drilling fluids and crude oil; however, the comparison study clearly illustrates that glove samplers may overestimate the amount of fluid transferred to the skin. Further comparison of the two dermal sampling methods using additional exposure situations such as immersion or deposition, as well as a field evaluation, is warranted to confirm their appropriateness and suitability in the working environment. PMID:24598941

Red grape (Vitis vinifera L.) flavonoids down-regulate collagen type III expression after UV-A in primary human dermal blood endothelial cells.

PubMed

Di Francesco, Serena; Savio, Monica; Bloise, Nora; Borroni, Giovanni; Stivala, Lucia Anna; Borroni, Riccardo G

2018-05-09

Red grape (Vitis vinifera L.) flavonoids including flavan-3-ols (e.g., catechin and epicatechin), flavonols (e.g., quercetin) and anthocyanins (e.g., malvidin) exert anti-inflammatory and antioxidant activities. In the skin they also have a photoprotective action, and their effects have been extensively investigated in keratinocytes, melanocytes and fibroblasts. Despite their known effects also on blood vasculature, little is known on their activities on human dermal blood endothelial cells (HDBECs), which are critically involved in skin homeostasis as well as in the pathogenesis of neoplastic and inflammatory skin diseases. We sought to study the biological effects of selected red grape flavonoids in preventing the consequences of ultraviolet (UV)-A irradiation in vitro. Our results show that red grape flavonoids prevent UV-A-induced sICAM-1 release in HDBECs, suggesting that this cell type could represent an additional target of the anti-inflammatory activity of flavonoids. In addition, flavonoids effectively inhibited UV-A-induced synthesis of collagen type III at both RNA and protein level, indicating that dermal blood microvasculature could be actively involved in ECM remodelling as a consequence of skin photo-ageing, and that this can be prevented by red grape flavonoids. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Clinical Nonlinear Laser Imaging of Human Skin: A Review

PubMed Central

Pavone, Francesco Saverio

2014-01-01

Nonlinear optical microscopy has the potential of being used in vivo as a noninvasive imaging modality for both epidermal and dermal imaging. This paper reviews the capabilities of nonlinear microscopy as a noninvasive high-resolution tool for clinical skin inspection. In particular, we show that two-photon fluorescence microscopy can be used as a diagnostic tool for characterizing epidermal layers by means of a morphological examination. Additional functional information on the metabolic state of cells can be provided by measuring the fluorescence decay of NADH. This approach allows differentiating epidermal layers having different structural and cytological features and has the potential of diagnosing pathologies in a very early stage. Regarding therapy follow-up, we demonstrate that nonlinear microscopy could be successfully used for monitoring the effect of a treatment. In particular, combined two-photon fluorescence and second-harmonic generation microscopy were used in vivo for monitoring collagen remodeling after microablative fractional laser resurfacing and for quantitatively monitoring psoriasis on the basis of the morphology of epidermal cells and dermal papillae. We believe that the described microscopic modalities could find in the near future a stable place in a clinical dermatological setting for quantitative diagnostic purposes and as a monitoring method for various treatments. PMID:25250337

Dermal penetration and metabolism of p-aminophenol and p-phenylenediamine: application of the EpiDerm human reconstructed epidermis model.

PubMed

Hu, Ting; Bailey, Ruth E; Morrall, Stephen W; Aardema, Marilyn J; Stanley, Lesley A; Skare, Julie A

2009-07-24

To address the provision of the 7th Amendment to the EU Cosmetics Directive banning the use of in vivo genotoxicity assays for testing cosmetic ingredients in 2009, the 3D EpiDerm reconstructed human skin micronucleus assay has been developed. To further characterise the EpiDerm tissue for potential use in genotoxicity testing, we have evaluated the dermal penetration and metabolism of two hair dye ingredients, p-aminophenol (PAP) and p-phenylenediamine (PPD) in this reconstructed epidermis model. When EpiDerm tissue was topically exposed to PAP or PPD for 30 min (typical for a hair dye exposure), the majority (80->90%) of PAP or PPD was excluded from skin tissue and removed by rinsing. After a 23.5h recovery period, the PAP fraction that did penetrate was completely N-acetylated to acetaminophen (APAP). Similarly, 30 min topical application of PPD resulted in the formation of the N-mono- and N,N'-diacetylated metabolites of PPD. These results are consistent with published data on the dermal metabolism of these compounds from other in vitro systems as well as from in vivo studies. When tissue was exposed topically (PAP) or via the culture media (PPD) for 24h, there was good batch-to-batch and donor-to-donor reproducibility in the penetration and metabolism of PAP and PPD. Overall, the results demonstrate that these two aromatic amines are biotransformed in 3D EpiDerm tissue via N-acetylation. Characterising the metabolic capability of EpiDerm tissue is important for the evaluation of this model for use in genotoxicity testing.

A preliminary investigation into the morphology of oral papillae and denticles of blue sharks (Prionace glauca) with inferences about its functional significance across life stages.

PubMed

Rangel, Bianca de S; Wosnick, Natascha; Hammerschlag, Neil; Ciena, Adriano P; Kfoury Junior, José Roberto; Rici, Rose E G

2017-03-01

Sensory organs in elasmobranchs (sharks, skates, rays) detect and respond to a different set of biotic and/or abiotic stimuli, through sight, smell, taste, hearing, mechanoreception and electroreception. Although gustation is crucial for survival and essential for growth, mobility, and maintenance of neural activity and the proper functioning of the immune system, comparatively little is known about this sensory system in elasmobranchs. Here we present a preliminary investigation into the structural and dimensional characteristics of the oral papillae and denticles found in the oropharyngeal cavity of the blue shark (Prionace glauca) during embryonic development through adulthood. Samples were obtained from the dorsal and ventral surface of the oropharyngeal cavity collected from embryos at different development stages as well as from adults. Our results suggest that development of papillae occurs early in ontogeny, before the formation of the oral denticles. The diameter of oral papillae gradually increases during development, starting from 25 μm in stage I embryos, to 110 μm in stage IV embryos and 272-300 μm in adults. Embryos exhibit papillae at early developmental stages, suggesting that these structures may be important during early in life. The highest density of papillae was observed in the maxillary and mandibular valve regions, possibly related to the ability to identify, capture and process prey. The oral denticles were observed only in the final embryonic stage as well as in adults. Accordingly, we suggest that oral denticles likely aid in ram ventilation (through reducing the hydrodynamic drag), to protect papillae from injury during prey consumption and assist in the retention and consumption of prey (through adhesion), since these processes are only necessary after birth. © 2016 Anatomical Society.

Expression of Notch pathway genes in mammalian epidermis and modulation by beta-catenin.

PubMed

Ambler, Carrie A; Watt, Fiona M

2007-06-01

The Notch pathway is required for hair follicle maintenance and is activated through beta-catenin induced transcription of the Notch ligand Jagged1. We show that hair follicles in the resting phase express low levels of Jagged1 and Hes1, and other Notch target genes are undetectable. In growing (anagen) follicles, Jagged1 and Hes1 expression increases, Hes5 and HeyL are expressed in distinct cell layers, and Hey2 is expressed in the dermal papilla. When beta-catenin is activated by means of an inducible transgene, Jagged1, Hes1, Hes5, HeyL, and Hey2 are up-regulated, the sites of expression being the same in beta-catenin induced ectopic follicles as in anagen follicles. beta-Catenin also induces Hey1 in dermal papilla cells. beta-Catenin-induced up-regulation of Jagged1 precedes induction of other Notch target genes. The different sites of expression of Hes and Hey genes suggest input from additional signaling pathways. Copyright 2007 Wiley-Liss, Inc.

Promotive Effect of Minoxidil Combined with All-trans Retinoic Acid (tretinoin) on Human Hair Growth in Vitro

PubMed Central

Kwon, Oh Sang; Pyo, Hyun Keol; Oh, Youn Jin; Han, Ji Hyun; Lee, Se Rah; Chung, Jin Ho; Eun, Hee Chul

2007-01-01

Minoxidil induces hair growth in male pattern baldness and prolongs the anagen phase. All-trans retinoic acid (ATRA) has been reported to act synergistically with minoxidil in vivo: they can enhance more dense hair regrowth than either compound alone. We evaluated the effect of minoxidil combined with ATRA on hair growth in vitro. The effect of co-treatment of minoxidil and ATRA on hair growth was studied in hair follicle organ culture. In cultured human dermal papilla cells (DPCs) and normal human epidermal keratinocytes, the expressions of Erk, Akt, Bcl-2, Bax, P53 and P21 were evaluated by immunoblot analysis. Minoxidil plus ATRA additively promoted hair growth in vitro, compared with minoxidil alone. In addition, minoxidil plus ATRA elevated phosphorylated Erk, phosphorylated Akt and the ratio of Bcl-2/Bax, but decreased the expressions of P53 and P21 more effectively than by minoxidil alone. Our results suggest that minoxidil plus ATRA would additively enhance hair growth by mediating dual functions: 1) the prolongation of cell survival by activating the Erk and Akt signaling pathways, and 2) the prevention of apoptosis of DPCs and epithelial cells by increasing the ratio of Bcl-2/Bax and downregulating the expressions of P53 and P21. PMID:17449938

6-Gingerol inhibits hair shaft growth in cultured human hair follicles and modulates hair growth in mice.

PubMed

Miao, Yong; Sun, Yabin; Wang, Wenjun; Du, Benjun; Xiao, Shun-e; Hu, Yijue; Hu, Zhiqi

2013-01-01

Ginger (Zingiber officinale) has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal.

6-Gingerol Inhibits Hair Shaft Growth in Cultured Human Hair Follicles and Modulates Hair Growth in Mice

PubMed Central

Miao, Yong; Sun, Yabin; Wang, Wenjun; Du, Benjun; Xiao, Shun-e; Hu, Yijue; Hu, Zhiqi

2013-01-01

Ginger (Zingiber officinale) has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal. PMID:23437345

Genetic tracing of the gustatory neural pathway originating from Pkd1l3-expressing type III taste cells in circumvallate and foliate papillae

PubMed Central

Yamamoto, Kurumi; Ishimaru, Yoshiro; Ohmoto, Makoto; Matsumoto, Ichiro; Asakura, Tomiko; Abe, Keiko

2011-01-01

Polycystic kidney disease 1-like 3 (Pkd1l3) is expressed specifically in sour-sensing type III taste cells that have synaptic contacts with afferent nerve fibers in circumvallate and foliate papillae located in the posterior region of the tongue, though not in fungiform papillae or the palate. To visualize the gustatory neural pathways that originate from type III taste cells in circumvallate and foliate papillae, we established transgenic mouse lines that express the transneuronal tracer wheat germ agglutinin (WGA) under the control of the mouse Pkd1l3 gene promoter/enhancer. The WGA transgene was accurately expressed in Pkd1l3-expressing type III taste cells in circumvallate and foliate papillae. Punctate WGA protein signals appeared to be detected specifically in type III taste cells but not in other types of taste cells. WGA protein was transferred primarily to a subset of neurons located in close proximity to the glossopharyngeal nerve bundles in the nodose/petrosal ganglion. WGA signals were also observed in a small population of neurons in the geniculate ganglion. This result demonstrates the anatomical connection between taste receptor cells in the foliate papillae and the chorda tympani nerves. WGA protein was further conveyed to neurons in a rostro-central subdivision of the nucleus of the solitary tract. These findings demonstrate that the approximately 10 kb 5’-flanking region of the mouse Pkd1l3 gene functions as a type III taste cell-specific promoter/enhancer. In addition, experiments using the pkd1l3-WGA transgenic mice reveal a sour gustatory pathway that originates from taste receptor cells in the posterior region of the tongue. PMID:21883212

Treatment of photoaged skin with topical tretinoin increases epidermal-dermal anchoring fibrils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woodley, D.T.; Briggaman, R.A.; Zelickson, A.S.

Topical 0.1% tretinoin or vehicle control was applied daily to the forearm skin of six caucasian adults for 4 months. Two-millimeter punch biopsy specimens were obtained from treatment sites at the beginning and end of the study period for electron microscopy. Anchoring fibrils within the epidermal-dermal junction of skin treatment sites were quantitated by blinded, standardized, computer-assisted morphometry. After 4 months of continual daily treatment, skin sites that received topical tretinoin showed double the anchoring fibril density compared with vehicle control sites. The possible mechanism by which topical tretinoin increases anchoring fibrils in skin include the drug's property of inhibitingmore » collagenase, a dermal enzyme that degrades anchoring fibril collagen. The authors speculate that increased numbers of collagenous anchoring fibrils within the papillary dermis of human skin is one of the connective-tissue correlates of the clinical improvement observed in photoaged skin after treatment with topical tretinoin.« less

Biologic resurfacing arthroplasty with acellular human dermal allograft and platelet-rich plasma (PRP) in young patients with glenohumeral arthritis-average of 60 months of at mid-term follow-up.

PubMed

Lo, Eddie Y; Flanagin, Brody A; Burkhead, Wayne Z

2016-07-01

The treatment of young patients with glenohumeral arthritis has been challenging. Alternative treatment options include activity modification, arthroscopic débridement, and arthroplasty. Addressing the glenoid during arthroplasty in this population of patients continues to be a significant challenge. In this study, we evaluated the midterm outcomes of hemiarthroplasty with biologic resurfacing of the glenoid with human dermal matrix allograft. Between 2004 and 2011, 55 patients underwent hemiarthroplasty and biologic resurfacing of the glenoid with human dermal matrix allograft. The average age was 50 ± 9 years. Subjective evaluation was performed with the Western Ontario Osteoarthritis of the Shoulder Index, American Shoulder and Elbow Surgeons score, visual analog scale, and Single Assessment Numeric Evaluation. Patients returned to the clinic for clinical examination and radiographic evaluation. The average follow-up was 60 months. The average postoperative American Shoulder and Elbow Surgeons score was 76 ± 22, and the Western Ontario Osteoarthritis of the Shoulder Index score was 76% ± 22%. The visual analog scale score was 2.4 ± 2.6. The average preoperative Single Assessment Numeric Evaluation score was 33% ± 22%, which significantly improved to 72% ± 22% postoperatively. Eighty-one percent of the patients were satisfied (10/47) or highly satisfied (28/47) with their result. With radiographic evaluation, the average joint space was 1 ± 1 mm preoperatively and 2 ± 1 mm postoperatively. A total of 5 cases (9.1%) were revised to anatomic total shoulder arthroplasty with implantation of a glenoid component. Hemiarthroplasty with biologic resurfacing of the glenoid using human dermal matrix allograft can lead to successful midterm outcomes with satisfactory complication and revision rates. Both patient satisfaction and clinical outcome remain high regardless of radiographic outcome. Copyright © 2016 Journal of

U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--PESTICIDES IN DERMAL ANALYTICAL RESULTS

EPA Science Inventory

The Pesticides in Dermal Wipes data set contains analytical results for measurements of up to 8 pesticides in 86 dermal wipe samples over 86 households. Each sample was collected from the primary respondent within each household. The Dermal/Pesticide hand wipe was collected 7 d...

INFLUENCE OF MATRIX FORMULATION ON DERMAL PERCUTANEOUS ABSORPTION OF TRIAZOLE FUNGICIDES USING QSAR AND PBPK / PD MODELS

EPA Science Inventory

The objective of this work is to use the Exposure Related Dose Estimating Model (ERDEM) and quantitative structure-activity relationship (QSAR) models to develop an assessment tool for human exposure assessment to triazole fungicides. A dermal exposure route is used for the physi...

Validation and comparison of two sampling methods to assess dermal exposure to drilling fluids and crude oil.

PubMed

Galea, Karen S; McGonagle, Carolyn; Sleeuwenhoek, Anne; Todd, David; Jiménez, Araceli Sánchez

2014-06-01

Dermal exposure to drilling fluids and crude oil is an exposure route of concern. However, there have been no published studies describing sampling methods or reporting dermal exposure measurements. We describe a study that aimed to evaluate a wipe sampling method to assess dermal exposure to an oil-based drilling fluid and crude oil, as well as to investigate the feasibility of using an interception cotton glove sampler for exposure on the hands/wrists. A direct comparison of the wipe and interception methods was also completed using pigs' trotters as a surrogate for human skin and a direct surface contact exposure scenario. Overall, acceptable recovery and sampling efficiencies were reported for both methods, and both methods had satisfactory storage stability at 1 and 7 days, although there appeared to be some loss over 14 days. The methods' comparison study revealed significantly higher removal of both fluids from the metal surface with the glove samples compared with the wipe samples (on average 2.5 times higher). Both evaluated sampling methods were found to be suitable for assessing dermal exposure to oil-based drilling fluids and crude oil; however, the comparison study clearly illustrates that glove samplers may overestimate the amount of fluid transferred to the skin. Further comparison of the two dermal sampling methods using additional exposure situations such as immersion or deposition, as well as a field evaluation, is warranted to confirm their appropriateness and suitability in the working environment. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Photocytotoxicity in human dermal fibroblasts elicited by permanent makeup inks containing titanium dioxide.

PubMed

Wamer, Wayne G; Yin, Jun-Jie

2011-01-01

Titanium dioxide (TiO2) is a pigment widely used in decorative tattoo and permanent makeup inks. However, little is known about the risks associated with its presence in these products. We have developed an in vitro assay to identify inks containing TiO2 that are cytotoxic and/or photocytotoxic. The presence of TiO2 in ten permanent makeup inks was established by X-ray fluorescence. Using X-ray diffraction, we found that seven inks contained predominately TiO2 (anatase), the more photocatalytically active crystalline form of TiO2. The remaining inks contained predominately TiO2 (rutile). To identify cytotoxic and/or photocytotoxic inks, human dermal fibroblasts were incubated for 18 h in media containing inks or pigments isolated from inks. Fibroblasts were then irradiated with 10 J/cm2 UVA radiation combined with 45 J/cm2 visible light for determining photocytotoxicity, or kept in the dark for determining cytotoxicity. Toxicity was assessed as inhibition of colony formation. No inks were cytotoxic. However eight inks, and the pigments isolated from these inks, were photocytotoxic. Using ESR, we found that most pigments from photocytotoxic inks generated hydroxyl radicals when photoexcited with UV radiation. Therefore, the possibility of photocytotoxicity should be considered when evaluating the safety of permanent makeup inks containing TiO2.

LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development

PubMed Central

Lough, Kendall J.; Patel, Jeet H.; Descovich, Carlos Patiño; Curtis, T. Anthony

2016-01-01

Oral epithelia protect against constant challenges by bacteria, viruses, toxins and injury while also contributing to the formation of ectodermal appendages such as teeth, salivary glands and lingual papillae. Despite increasing evidence that differentiation pathway genes are frequently mutated in oral cancers, comparatively little is known about the mechanisms that regulate normal oral epithelial development. Here, we characterize oral epithelial stratification and describe multiple distinct functions for the mitotic spindle orientation gene LGN (Gpsm2) in promoting differentiation and tissue patterning in the mouse oral cavity. Similar to its function in epidermis, apically localized LGN directs perpendicular divisions that promote stratification of the palatal, buccogingival and ventral tongue epithelia. Surprisingly, however, in dorsal tongue LGN is predominantly localized basally, circumferentially or bilaterally and promotes planar divisions. Loss of LGN disrupts the organization and morphogenesis of filiform papillae but appears to be dispensable for embryonic hair follicle development. Thus, LGN has crucial tissue-specific functions in patterning surface ectoderm and its appendages by controlling division orientation. PMID:27317810

The Gustin (CA6) Gene Polymorphism, rs2274333 (A/G), as a Mechanistic Link between PROP Tasting and Fungiform Taste Papilla Density and Maintenance

PubMed Central

Melis, Melania; Atzori, Elena; Cabras, Stefano; Zonza, Andrea; Calò, Carla; Muroni, Patrizia; Nieddu, Mariella; Padiglia, Alessandra; Sogos, Valeria; Tepper, Beverly J.; Tomassini Barbarossa, Iole

2013-01-01

Taste sensitivity to PROP varies greatly among individuals and is associated with polymorphisms in the bitter receptor gene TAS2R38, and with differences in fungiform papilla density on the anterior tongue surface. Recently we showed that the PROP non-taster phenotype is strongly associated with the G variant of polymorphism rs2274333 (A/G) of the gene that controls the salivary trophic factor, gustin. The aims of this study were 1) to investigate the role of gustin gene polymorphism rs2274333 (A/G), in PROP sensitivity and fungiform papilla density and morphology, and 2) to investigate the effect of this gustin gene polymorphism on cell proliferation and metabolic activity. Sixty-four subjects were genotyped for both genes by PCR techniques, their PROP sensitivity was assessed by scaling and threshold methods, and their fungiform papilla density, diameter and morphology were determined. In vitro experiments examined cell proliferation and metabolic activity, following treatment with saliva of individuals with and without the gustin gene mutation, and with isolated protein, in the two iso-forms. Gustin and TAS2R38 genotypes were associated with PROP threshold (p=0.0001 and p=0.0042), but bitterness intensity was mostly determined by TAS2R38 genotypes (p<0.000001). Fungiform papillae densities were associated with both genotypes (p<0.014) (with a stronger effect for gustin; p=0.0006), but papilla morphology was a function of gustin alone (p<0.0012). Treatment of isolated cells with saliva from individuals with the AA form of gustin or direct application of the active iso-form of gustin protein increased cell proliferation and metabolic activity (p<0.0135). These novel findings suggest that the rs2274333 polymorphism of the gustin gene affects PROP sensitivity by acting on fungiform papilla development and maintenance, and could provide the first mechanistic explanation for why PROP super-tasters are more responsive to a broad range of oral stimuli. PMID:24040192

The gustin (CA6) gene polymorphism, rs2274333 (A/G), as a mechanistic link between PROP tasting and fungiform taste papilla density and maintenance.

PubMed

Melis, Melania; Atzori, Elena; Cabras, Stefano; Zonza, Andrea; Calò, Carla; Muroni, Patrizia; Nieddu, Mariella; Padiglia, Alessandra; Sogos, Valeria; Tepper, Beverly J; Tomassini Barbarossa, Iole

2013-01-01

Taste sensitivity to PROP varies greatly among individuals and is associated with polymorphisms in the bitter receptor gene TAS2R38, and with differences in fungiform papilla density on the anterior tongue surface. Recently we showed that the PROP non-taster phenotype is strongly associated with the G variant of polymorphism rs2274333 (A/G) of the gene that controls the salivary trophic factor, gustin. The aims of this study were 1) to investigate the role of gustin gene polymorphism rs2274333 (A/G), in PROP sensitivity and fungiform papilla density and morphology, and 2) to investigate the effect of this gustin gene polymorphism on cell proliferation and metabolic activity. Sixty-four subjects were genotyped for both genes by PCR techniques, their PROP sensitivity was assessed by scaling and threshold methods, and their fungiform papilla density, diameter and morphology were determined. In vitro experiments examined cell proliferation and metabolic activity, following treatment with saliva of individuals with and without the gustin gene mutation, and with isolated protein, in the two iso-forms. Gustin and TAS2R38 genotypes were associated with PROP threshold (p=0.0001 and p=0.0042), but bitterness intensity was mostly determined by TAS2R38 genotypes (p<0.000001). Fungiform papillae densities were associated with both genotypes (p<0.014) (with a stronger effect for gustin; p=0.0006), but papilla morphology was a function of gustin alone (p<0.0012). Treatment of isolated cells with saliva from individuals with the AA form of gustin or direct application of the active iso-form of gustin protein increased cell proliferation and metabolic activity (p<0.0135). These novel findings suggest that the rs2274333 polymorphism of the gustin gene affects PROP sensitivity by acting on fungiform papilla development and maintenance, and could provide the first mechanistic explanation for why PROP super-tasters are more responsive to a broad range of oral stimuli.

Expression of psoriasis-associated fatty acid-binding protein in senescent human dermal microvascular endothelial cells.

PubMed

Ha, Moon Kyung; Chung, Kee Yang; Lee, Ju Hee; Bang, Dongsik; Park, Yoon Kee; Lee, Kwang Hoon

2004-09-01

Aging is associated with the progressive pathophysiologic modification of endothelial cells. In vitro endothelial cell senescence is accompanied by proliferative activity failure and by perturbations in gene and protein expressions. Moreover, this cellular senescence in culture has been proposed to reflect processes that occur in aging organisms. In order to observe the changing patterns of protein expression in senescent human dermal microvascular endothelial cells (HDMECs), proteins obtained from both early- and late-passaged HDMECs were separated by two-dimensional electrophoresis, visualized by silver staining, and quantified by image processing. Proteins of interest were extracted by in-gel digestion with trypsin and quantified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), by searching the National Center for Biotechnology Information protein-sequence database. More than 2000 spots were detected by 2D electrophoresis within a linear pH range of 3-10. Twenty-two major differentially expressed spots were observed in serially passaged HDMECs and identified with high confidence by MALDI-TOF-MS. One of these spots was found to be a 14-15 kDa psoriasis-associated fatty acid-binding protein (PA-FABP) with high affinity for long-chain fatty acids. The expression of PA-FABP was confirmed to be elevated in senescent HDMECs (passage 20) by fluorescence-activated cell sorting (FACS), confocal laser microscopy, and by immunohistochemistry in aged human skin tissue. Our results suggest that the overexpression of FABP in cultured senescent HDMECs is closely related to skin aging.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Wei; Man, Xiao-Yong; Li, Chun-Ming

Vascular endothelial growth factor (VEGF) is one of the strongest regulators of physiological and pathological angiogenesis. VEGF receptor 2 (VEGFR-2), the primary receptor for VEGF, is thought to mediate major functional effects of VEGF. Previously, we have localized both VEGF and VEGFR-2 in human hair follicles. In this study, we further defined the expression and roles of VEGFR-2 on human hair follicle dermal papilla (DP) cells. The expression of VEGFR-2 on DP cells was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis separately, and localization of VEGFR-2 was defined by immunofluorescence. The effect of VEGF on DPmore » cells was analyzed by MTT assays and specific inhibitors. Finally, the role of VEGF involved in the signaling pathways was investigated by Western blot. RT-PCR and Western blot analysis demonstrated the expression of VEGFR-2 on DP cells. Immunostaining for VEGFR-2 showed strong signal on cultured human DP cells in vitro. Exogenous VEGF{sub 165} stimulated proliferation of DP cells in a dose-dependent manner. Furthermore, this stimulation was blocked by a VEGFR-2 neutralizing antibody (MAB3571) and an ERK inhibitor (PD98059). VEGF{sub 165}-induced phosphorylation of ERK1/2 was abolished by MAB3571 and PD98059, while the phosphorylation of p38, JNK and AKT were not changed by VEGF{sub 165}. Taken together, VEGFR-2 is expressed on primary human hair follicle DP cells and VEGF induces proliferation of DP cells through VEGFR-2/ERK pathway, but not p38, JNK or AKT signaling. -- Highlights: Black-Right-Pointing-Pointer We examine the expression of VEGFR-2 on cultured human dermal papilla (DP) cells. Black-Right-Pointing-Pointer VEGF{sub 165} stimulated proliferation of human DP cells in a dose-dependent manner. Black-Right-Pointing-Pointer This stimulation was through VEGFR-2-mediated activation of ERK.« less

Arabinogalactans from Mimosa tenuiflora (Willd.) Poiret bark as active principles for wound-healing properties: specific enhancement of dermal fibroblast activity and minor influence on HaCaT keratinocytes.

PubMed

Zippel, Janina; Deters, Alexandra; Hensel, Andreas

2009-07-30

Aqueous extracts from the bark of Mimosa tenuiflora (Willd.) Poirett (Mimosaceae), tradionally known as "tepescohuite", are widely used for wound-healing and burns in middle and South America. No pharmacological data are available on the influence of aqueous extracts and high molecular constituents on human skin cells. Tests were performed on human primary dermal fibroblasts and human HaCaT keratinocytes by quantification of mitochondrial activity (MTT, WST-1), proliferation (BrdU incorporation), necrosis (LDH) and gene expression profiling (RT-PCR). Water extract WE (10 and 100 microg/mL) expressed loss of cell viability and proliferation in dermal fibroblasts. Ethanol-precipitated compounds EPC (10 microg/mL), isolated from WE significantly stimulated mitochondrial activity and proliferation of dermal fibroblasts. Minor stimulation of human kerationocytes by EPC was found only at 100 microg/mL level. The differentiation behavior of keratinocytes was not influenced by EPC. EPC had no influence on the expression of specific proliferation and differentiation related genes so that the mode of action remains unclear. By bioactivity-guided fractionation two arabinogalactan-enriched fractions (F2, F3) were isolated from EPC and identified as the stimulating principles of EPC against fibroblasts. A significant in vitro stimulation of dermal fibroblast activity and proliferation by arabinogalactans from Mimosa tenuiflora provides a rational for the traditional use of the bark material for wound healing.

EVALUATING COMMERCIALLY AVAILABLE DERMAL ...

EPA Pesticide Factsheets

As the Human Exposure Program focuses on the exposure of children to pesticides, there are concerns about the effect, or perceived effect, of components of the sampling procedure on the health and well-being of the infant and the ability to collect pesticide residues. One concern involves the materials in wipes used to collect pesticide residues or other contact materials on the skin. In recent studies (e.g., National Human Exposure Assessment Survey; NHEXAS), isopropyl alcohol has been used as a solvent in conjunction with a cloth wipe to obtain samples from the hands of adults and children. Although isopropyl alcohol is generally considered innocuous, the use of commercially available products could eliminate concerns about exposure to alcohol. A few studies have evaluated the potential of commercially available baby wipes to collect personal exposure samples for metals research, but not for the area of pesticide research (Millson et al., 1994; Campbell et al., 1993; Lichtenwalner et al., 1993). Therefore, there is a need to evaluate the potential for using commercially available baby wipes for collecting pesticide samples from skin and other surfaces. Another concern involves establishing a convenient and safe method for assessing overall dermal exposure for children, especially for those in crawling stage. One route that the U .S. Environmental Protection Agency (EPA) would like to investigate is the use of cotton body suits (infant sleepers) as an indicator

Visible red light enhances physiological anagen entry in vivo and has direct and indirect stimulative effects in vitro.

PubMed

Sheen, Yi-Shuan; Fan, Sabrina Mai-Yi; Chan, Chih-Chieh; Wu, Yueh-Feng; Jee, Shiou-Hwa; Lin, Sung-Jan

2015-01-01

Hair follicles are located at the interface of the external and internal environments and their cycling has been shown to be regulated by intra- and extra-follicular factors. The aim of this study is to examine whether or how hair follicles respond to visible light. We examined the effect of 3 mW red (630 nm, 1 J/cm(2)), 2 mW green (522 nm, 1 J/cm(2)), and 2 mW blue light (463 nm, 1 J/cm(2)) on telogen in mice for 3 weeks. The photobiologic effects of red light on cell proliferation of outer root sheath keratinocytes and dermal papilla cells were studied in vitro. We found that red light accelerated anagen entry faster than green and blue light in mice. Red light irradiation stimulated the proliferation of both outer root sheath keratinocytes and dermal papilla cells in a dose-dependent manner by promoting cell cycle progression. This stimulative effect was mediated via extracellular signal-regulated kinase phosphorylation in both cells. In a co-culture condition, dermal papilla cells irradiated by red light further enhanced keratinocyte proliferation, suggesting enhanced epithelial-mesenchymal interaction. In search for factors that mediated this paracrine effect, we found fibroblast growth factor 7 was upregulated in both mRNA and protein levels. The stimulative paracrine effect on keratinocytes was significantly inhibited by neutralizing antibody against fibroblast growth factor 7. These results suggest that hair follicles respond to visible light in vivo. Red light may promote physiological telogen to anagen transition by directly stimulating outer root sheath keratinocytes and indirectly by enhancing epithelial-mesenchymal interaction in vitro. © 2014 Wiley Periodicals, Inc.

The protective effects of fucosterol against skin damage in UVB-irradiated human dermal fibroblasts.

PubMed

Hwang, Eunson; Park, Sang-Yong; Sun, Zheng-wang; Shin, Heon-Sub; Lee, Don-Gil; Yi, Tae Hoo

2014-06-01

Exposure to ultraviolet (UV) light causes matrix metalloproteinase (MMP) overexpression and extracellular matrix depletion, leading to skin photoaging. The activation of MMP is related to increased interlukin-6 (IL-6) and type I procollagen production, which is regulated by transforming growth factor-β1 (TGF-β1). Activator protein-1 (AP-1) activation induces MMP-1 production and reduces type I procollagen secretion. Fucosterol, which is extracted and purified from the brown algae Hizikia fusiformis, is a phytosterol. We assessed the effects of fucosterol on photodamage and investigated its molecular mechanism of action in UVB-irradiated normal human dermal fibroblasts by using enzyme-linked immunosorbent assay, Western blot analysis, and reverse transcription-polymerase chain reaction. Our results showed that fucosterol significantly decreased the UVB-induced expression of MMP-1, IL-6, p-c-Jun, and p-c-Fos. Additionally, fucosterol markedly increased the UVB-induced production of type I procollagen and TGF-β1. Our results indicate that fucosterol regulates MMP-1 and type I procollagen expression by modulating AP-1 and TGF-β1 signaling and that MMP-1 activation is correlated with IL-6. These data suggest that fucosterol is a promising botanical agent to protect against skin photodamage.

Organochlorine pesticides across the tributaries of River Ravi, Pakistan: Human health risk assessment through dermal exposure, ecological risks, source fingerprints and spatio-temporal distribution.

PubMed

Baqar, Mujtaba; Sadef, Yumna; Ahmad, Sajid Rashid; Mahmood, Adeel; Li, Jun; Zhang, Gan

2018-03-15

This study monitored the human health risks through dermal exposure, hazardous risks to ecological integrity, contamination levels, spatio-temporal distribution, and congener specific analysis of organochlorine pesticides (OCPs) across River Ravi and its three northern tributaries (Nullah Bein, Nullah Basanter and Nullah Deg). The residual levels of OCPs isomers were screened for water (n=54) and surface sediment (n=54) samples from twenty seven sampling sites in two alternate seasons (pre-monsoon and post-monsoon). The ∑OCPs concentrations ranged from 13.61 to 1992.18ng/g dry weight and 12.89 to 128.16ng/L with predominance of β-endosulfan and p,p'-DDT in sediment and water matrixes, respectively. Distribution pattern revealed significantly higher concentrations in upstream and midstream, suggesting considerable transboundary OCPs pollution. Calculated ratios of α-HCH/γ-HCH, o,p'-DDT/p,p'-DDT, (DDE+DDD)/∑DDTs and cis/trans-chlordane for water and sediments identified the fresh addition of lindane, technical DDTs and chlordane in the study area. Risk quotient (RQ) based ecological risk was found to be >1 at all studied streams during both seasons and elucidates higher risks for endosulfan (α-endosulfan) and endrin. Human health risk assessment indicated absence of hazardous (non-carcinogenic) risk through bathing in studied streams; as the hazard index values ranged from 1.09E-05 to 2.48E-02 (acceptable limit; <1). However, the calculated carcinogenic risk possessed by OCPs through dermal exposure ranged from 1.39E-10 to 1.98E-05 that highlighted the considerable carcinogenic risk associated to aldrin, dieldrin, p,p'-DDT and β-endosulfan at certain studied sites. Therefore, the high levels of ecological risk and carcinogenic human health risk had emphasized an immediate elimination of ongoing OCPs addition in the studied area. Copyright © 2017 Elsevier B.V. All rights reserved.

The cost effectiveness of acellular dermal matrix in expander-implant immediate breast reconstruction.

PubMed

Krishnan, Naveen M; Chatterjee, Abhishek; Rosenkranz, Kari M; Powell, Stephen G; Nigriny, John F; Vidal, Dale C

2014-04-01

Expander-implant breast reconstruction is often supplemented with acellular dermal matrix (ADM). The use of acellular dermal matrix has allowed for faster, less painful expansions and improved aesthetics, but with increased cost. Our goal was to provide the first cost utility analysis of using acellular dermal matrix in two-stage, expander-implant immediate breast reconstruction following mastectomy. A comprehensive literature review was conducted to identify complication rates for two-stage, expander-implant immediate breast reconstruction with and without acellular dermal matrix. The probabilities of the most common complications were combined with Medicare Current Procedural Terminology reimbursement codes and expert utility estimates to fit into a decision model. The decision model evaluated the cost effectiveness of acellular dermal matrix relative to reconstructions without it. Retail costs for ADM were derived from the LifeCell 2012 company catalogue for Alloderm. The overall complication rates were 30% and 34.5% with and without ADM. The decision model revealed a baseline cost increase of $361.96 when acellular dermal matrix is used. The increase in Quality-Adjusted Life Years (QALYs) is 1.37 in the population with acellular dermal matrix. This yields a cost effective incremental cost-utility ratio (ICUR) of $264.20/QALY. Univariate sensitivity analysis confirmed that using acellular dermal matrix is cost effective even when using retail costs for unilateral and bilateral reconstructions. Our study shows that, despite an increased cost, acellular dermal matrix is a cost effective technology for patients undergoing two-stage, expander-implant immediate breast reconstruction due to its increased utility in successful procedures. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Differential response of human dermal fibroblast subpopulations to visible and near-infrared light: Potential of photobiomodulation for addressing cutaneous conditions.

PubMed

Mignon, Charles; Uzunbajakava, Natallia E; Castellano-Pellicena, Irene; Botchkareva, Natalia V; Tobin, Desmond J

2018-04-17

The past decade has witnessed a rapid expansion of photobiomodulation (PBM), demonstrating encouraging results for the treatment of cutaneous disorders. Confidence in this approach, however, is impaired not only by a lack of understanding of the light-triggered molecular cascades but also by the significant inconsistency in published experimental outcomes, design of the studies and applied optical parameters. This study aimed at characterizing the response of human dermal fibroblast subpopulations to visible and near-infrared (NIR) light in an attempt to identify the optical treatment parameters with high potential to address deficits in aging skin and non-healing chronic wounds. Primary human reticular and papillary dermal fibroblasts (DF) were isolated from the surplus of post-surgery human facial skin. An in-house developed LED-based device was used to irradiate cell cultures using six discrete wavelengths (450, 490, 550, 590, 650, and 850 nm). Light dose-response at a standard oxygen concentration (20%) at all six wavelengths was evaluated in terms of cell metabolic activity. This was followed by an analysis of the transcriptome and procollagen I production at a protein level, where cells were cultured in conditions closer to in vivo at 2% environmental oxygen and 2% serum. Furthermore, the production of reactive oxygen species (ROS) was accessed using real-time fluorescence confocal microscopy imaging. Here, production of ROS in the presence or absence of antioxidants, as well as the cellular localization of ROS, was evaluated. In terms of metabolic activity, consecutive irradiation with short-wavelength light (⇐530 nm) exerted an inhibitory effect on DF, while longer wavelengths (>=590 nm) had essentially a neutral effect. Cell behavior following treatment with 450 nm was biphasic with two distinct states: inhibitory at low- to mid- dose levels (<=30 J/cm 2 ), and cytotoxic at higher dose levels (>30 J/cm 2 ). Cell response to blue light was

Photobiomodulation of distinct lineages of human dermal fibroblasts: a rational approach towards the selection of effective light parameters for skin rejuvenation and wound healing

NASA Astrophysics Data System (ADS)

Mignon, Charles; Uzunbajakava, Natallia E.; Raafs, Bianca; Moolenaar, Mitchel; Botchkareva, Natalia V.; Tobin, Desmond J.

2016-03-01

Distinct lineages of human dermal fibroblasts play complementary roles in skin rejuvenation and wound healing, which makes them a target of phototherapy. However, knowledge about differential responses of specific cell lineages to different light parameters and moreover the actual molecular targets remain to be unravelled. The goal of this study was to investigate the impact of a range of parameters of light on the metabolic activity, collagen production, and cell migration of distinct lineages of human dermal fibroblasts. A rational approach was used to identify parameters with high therapeutic potential. Fibroblasts exhibited both inhibitory and cytotoxic change when exposed to a high dose of blue and cyan light in tissue culture medium containing photo-reactive species, but were stimulated by high dose red and near infrared light. Cytotoxic effects were eliminated by refreshing the medium after light exposure by removing potential ROS formed by extracellular photo-reactive species. Importantly, distinct lineages of fibroblasts demonstrated opposite responses to low dose blue light treatment when refreshing the medium after exposure. Low dose blue light treatment also significantly increased collagen production by papillary fibroblasts; high dose significantly retarded closure of the scratch wound without signs of cytotoxicity, and this is likely to have involved effects on both cell migration and proliferation. We recommend careful selection of fibroblast subpopulations and their culture conditions, a systematic approach in choosing and translating treatment parameters, and pursuit of fundamental research on identification of photoreceptors and triggered molecular pathways, while seeking effective parameters to address different stages of skin rejuvenation and wound healing.

In vitro determination of transdermal permeation of synthetic musks and estimated dermal uptake through usage of personal care products.

PubMed

Zhang, Xiaolan; Yu, Yuling; Gu, Yue; Li, Xiaojing; Zhang, Xinyu; Yu, Yingxin

2017-04-01

Synthetic musks, chemical constituents of personal care products, enter the human body through dermal contact. Elucidation of the mechanisms underlying transdermal permeation of synthetic musks should enhance our understanding of their uptake and distribution in human skin and allow accurate evaluation of associated human exposure. Here, the transdermal permeation dynamics and distribution of galaxolide (HHCB) and tonalide (AHTN) were investigated using an in vitro skin diffusion model. The transdermal permeation amounts of HHCB and AHTN increased rapidly during the first 6 h. The applied HHCB and AHTN amounts did not affect percutaneous absorption rates. HHCB and AHTN remained primarily in the stratum corneum, accounting for 70.0% and 70.3% of the totals during the 24-h period, respectively. The percutaneous absorption rate of both chemicals was ∼11%. HHCB, AHTN, musk ketone, musk xylene, and Musk-T were detected in 29 personal care products. The average total concentrations of the musks were 3990, 54.0, 17.7, and 9.8 μg g -1 in perfume, shampoo, lotion, and shower gel, respectively. Among the four product categories, HHCB was dominant (57.4%-99.6%), followed by AHTN. The data clearly indicate that polycyclic and nitro musks are most commonly used in personal care products. The total estimated dermal intake (51.6 μg kg -1 bw  day -1 ) was markedly higher than total dermal uptake (5.9 μg kg -1 bw  day -1 ) when percutaneous absorption rates of the chemicals were added into the calculation. Uptake of HHCB and AHTN via dermal contact of personal care products was significantly higher than that from dust inhalation calculated according to earlier literature data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aging Alters Functionally Human Dermal Papillary Fibroblasts but Not Reticular Fibroblasts: A New View of Skin Morphogenesis and Aging

PubMed Central

Mine, Solène; Fortunel, Nicolas O.; Pageon, Hervé; Asselineau, Daniel

2008-01-01

Understanding the contribution of the dermis in skin aging is a key question, since this tissue is particularly important for skin integrity, and because its properties can affect the epidermis. Characteristics of matched pairs of dermal papillary and reticular fibroblasts (Fp and Fr) were investigated throughout aging, comparing morphology, secretion of cytokines, MMPs/TIMPs, growth potential, and interaction with epidermal keratinocytes. We observed that Fp populations were characterized by a higher proportion of small cells with low granularity and a higher growth potential than Fr populations. However, these differences became less marked with increasing age of donors. Aging was also associated with changes in the secretion activity of both Fp and Fr. Using a reconstructed skin model, we evidenced that Fp and Fr cells do not possess equivalent capacities to sustain keratinopoiesis. Comparing Fp and Fr from young donors, we noticed that dermal equivalents containing Fp were more potent to promote epidermal morphogenesis than those containing Fr. These data emphasize the complexity of dermal fibroblast biology and document the specific functional properties of Fp and Fr. Our results suggest a new model of skin aging in which marked alterations of Fp may affect the histological characteristics of skin. PMID:19115004

Protective Effect of Tetracycline against Dermal Toxicity Induced by Jellyfish Venom

PubMed Central

Kang, Changkeun; Jin, Yeung Bae; Kwak, Jeongsoo; Jung, Hongseok; Yoon, Won Duk; Yoon, Tae-Jin; Kim, Jong-Shu; Kim, Euikyung

2013-01-01

Background Previously, we have reported that most, if not all, of the Scyphozoan jellyfish venoms contain multiple components of metalloproteinases, which apparently linked to the venom toxicity. Further, it is also well known that there is a positive correlation between the inflammatory reaction of dermal tissues and their tissue metalloproteinase activity. Based on these, the use of metalloproteinase inhibitors appears to be a promising therapeutic alternative for the treatment of jellyfish envenomation. Methodology and Principal Findings Tetracycline (a metalloproteinase inhibitor) has been examined for its activity to reduce or prevent the dermal toxicity induced by Nemopilema nomurai (Scyphozoa: Rhizostomeae) jellyfish venom (NnV) using in vitro and in vivo models. HaCaT (human keratinocyte) and NIH3T3 (mouse fibroblast) incubated with NnV showed decreases in cell viability, which is associated with the inductions of metalloproteinase-2 and -9. This result suggests that the use of metalloproteinase inhibitors, such as tetracycline, may prevent the jellyfish venom-mediated local tissue damage. In vivo experiments showed that comparing with NnV-alone treatment, tetracycline pre-mixed NnV demonstrated a significantly reduced progression of dermal toxicity upon the inoculation onto rabbit skin. Conclusions/Significance It is believed that there has been no previous report on the therapeutic agent of synthetic chemical origin for the treatment of jellyfish venom-induced dermonecrosis based on understanding its mechanism of action except the use of antivenom treatment. Furthermore, the current study, for the first time, has proposed a novel mechanism-based therapeutic intervention for skin damages caused by jellyfish stings. PMID:23536767