Platelet factor XIIIa release during platelet aggregation and plasma clot strength measured by thrombelastography in patients with coronary artery disease treated with clopidogrel.

PubMed

Kreutz, Rolf P; Owens, Janelle; Lu, Deshun; Nystrom, Perry; Jin, Yan; Kreutz, Yvonne; Desta, Zeruesenay; Flockhart, David A

2015-01-01

It has been estimated that up to half of circulating factor XIIIa (FXIIIa) is stored in platelets. The release of FXIIIa from platelets upon stimulation with adenosine diphosphate (ADP) in patients with coronary artery disease treated with dual antiplatelet therapy has not been previously examined. Samples from 96 patients with established coronary artery disease treated with aspirin and clopidogrel were examined. Platelet aggregation was performed by light transmittance aggregometry in platelet-rich plasma (PRP), with platelet-poor plasma (PPP) as reference, and ADP 5 µM as agonist. Kaolin-activated thrombelastography (TEG) was performed in citrate PPP. PRP after aggregation was centrifuged and plasma supernatant (PSN) collected. FXIIIa was measured in PPP and PSN. Platelet aggregation after stimulation with ADP 5 µM resulted in 24% additional FXIIIa release in PSN as compared to PPP (99.3 ± 27 vs. 80.3 ± 24%, p < 0.0001). FXIIIa concentration in PSN correlated with maximal plasma clot strength (TEG-G) (r = 0.48, p < 0.0001), but not in PPP (r = 0.15, p = 0.14). Increasing quartiles of platelet-derived FXIIIa were associated with incrementally higher TEG-G (p = 0.012). FXIIIa release was similar between clopidogrel responders and non-responders (p = 0.18). In summary, platelets treated with aspirin and clopidogrel release a significant amount of FXIIIa upon aggregation by ADP. Platelet-derived FXIIIa may contribute to differences in plasma TEG-G, and thus, in part, provide a mechanistic explanation for high clot strength observed as a consequence of platelet activation. Variability in clopidogrel response does not significantly influence FXIIIa release from platelets.

CD34-reactive fibrous papule of the nose.

PubMed

Shea, C R; Salob, S; Reed, J A; Lugo, J; McNutt, N S

1996-08-01

In human skin, the CD34 antigen is expressed on endothelium, periadnexal cells, and a population of reticular dermal interstitial cells. CD34 expression is characteristic of dermatofibrosarcoma protuberans and several other neoplasms, but not of typical fibrous papules of the nose. We describe a 16-year-old white girl with a slowly growing papule on the nose. Histopathology showed a dermal tumor with a superficial component of branched, thin-walled blood vessels and a deeper component of benign-appearing, spindle-shaped cells. These cells uniformly and strongly expressed CD34, but not factor XIIIa or markers of melanocytic, neural, muscular, vascular, or histiocytic differentiation. We consider this lesion a CD34-reactive fibrous papule. This benign tumor must be clearly distinguished from dermatofibrosarcoma protuberans, which also is composed of bundles of CD34-reactive spindle-shaped cells in most cases but has locally aggressive behavior.

Generation of hyaline cartilaginous tissue from mouse adult dermal fibroblast culture by defined factors

PubMed Central

Hiramatsu, Kunihiko; Sasagawa, Satoru; Outani, Hidetatsu; Nakagawa, Kanako; Yoshikawa, Hideki; Tsumaki, Noriyuki

2011-01-01

Repair of cartilage injury with hyaline cartilage continues to be a challenging clinical problem. Because of the limited number of chondrocytes in vivo, coupled with in vitro de-differentiation of chondrocytes into fibrochondrocytes, which secrete type I collagen and have an altered matrix architecture and mechanical function, there is a need for a novel cell source that produces hyaline cartilage. The generation of induced pluripotent stem (iPS) cells has provided a tool for reprogramming dermal fibroblasts to an undifferentiated state by ectopic expression of reprogramming factors. Here, we show that retroviral expression of two reprogramming factors (c-Myc and Klf4) and one chondrogenic factor (SOX9) induces polygonal chondrogenic cells directly from adult dermal fibroblast cultures. Induced cells expressed marker genes for chondrocytes but not fibroblasts, i.e., the promoters of type I collagen genes were extensively methylated. Although some induced cell lines formed tumors when subcutaneously injected into nude mice, other induced cell lines generated stable homogenous hyaline cartilage–like tissue. Further, the doxycycline-inducible induction system demonstrated that induced cells are able to respond to chondrogenic medium by expressing endogenous Sox9 and maintain chondrogenic potential after substantial reduction of transgene expression. Thus, this approach could lead to the preparation of hyaline cartilage directly from skin, without generating iPS cells. PMID:21293062

Multinucleate cell angiohistiocytoma: a fibrohistiocytic proliferation with increased mast cell numbers and vascular hyperplasia.

PubMed

Puig, Lluís; Fernández-Figueras, María-Teresa; Bielsa, Isabel; Lloveras, Betlem; Alomar, Agustín

2002-04-01

Multinucleate cell angiohistiocytoma (MCAH) is an uncommon lesion clinically characterized by multiple papules usually located on the face and acral regions of elderly women. Histopathologically, MCAH is characterized by dermal vascular hyperplasia associated with increased number of factor XIIIa-positive fibrohistiocytic cells and multinucleate cells with scalloped borders. We report the clinical, histopathological and immunohistochemical features of three cases of MCAH, with ulstrastructural study in one of them. The patients were a woman and two men of 56, 40 and 70 years of age, respectively. They all had multiple dull-red papules, which had appeared over several years and were located on the face, the trunk and the dorsa of the hands, respectively. The reticular dermis presented a fibrohistiocytic proliferation of factor XIIIa-positive cells, with abundant bizarre multinucleate cells and vascular hyperplasia. Increased mast cell numbers were seen in all cases, often in apposition to multinucleate cells. Histopathological differential diagnosis of MCAH includes mainly angiofibromas and dermatofibromas, even though vascular hyperplasia can be prominent and has led to many authors to classify MCAH among vascular tumors. Bizarre multinucleate cells can be found in reactive, neoplastic and inflammatory lesions in many sites of the body, and mast cells can play a role in their morphogenesis.

Dermal bioavailability of benzo[a]pyrene on lampblack: implications for risk assessment.

PubMed

Stroo, Hans F; Roy, Timothy A; Liban, Cris B; Kreitinger, Joseph P

2005-06-01

Lampblack is the principal source of contamination in soils at manufactured gas plant (MGP) sites where oil was used as the feedstock. Risks and cleanup criteria at these sites are determined primarily by the total carcinogenic polynuclear aromatic hydrocarbon (PAH) content, particularly the concentration of benzo[a]pyrene (BaP). Dermal contact with soils at oil-gas MGP sites is a significant component of the overall risks. Seven samples were collected from oil-gas MGP sites and the steady-state dermal fluxes were measured over 96 h in vitro. The standard dermal bioassay technique (in which 3H-BaP is added to the soil matrix) was modified to allow direct measurement of the dermal absorption of the native BaP in the samples. The experimentally derived dermal absorption factors for BaP were 14 to 107 times lower than the default assumption of 15% over 24 h (55-fold lower on average). The dermal fluxes were correlated positively to the total BaP and total carbon concentrations. The measured dermal absorption factors were compared to the default risk-assessment calculations for all seven samples. The calculated excess cancer risk was reduced as a result of using the measured absorption factors by 97% on average (with reductions ranging from 93 to 99%). This work indicates the risks at oil-gas MGP sites currently are overestimated by one to two orders of magnitude, and provides a protocol for the testing and data analysis needed to generate site-specific cleanup levels.

Benefits of plasma rich in growth factors (PRGF) in skin photodamage: clinical response and histological assessment.

PubMed

Díaz-Ley, B; Cuevast, J; Alonso-Castro, L; Calvo, M I; Ríos-Buceta, L; Orive, G; Anitua, E; Jaén, P

2015-01-01

Skin ageing is characterized by small and fine wrinkles, roughness, laxity, and pigmentation as a result of epidermal thinning, collagen degradation, dermal atrophy, and fewer fibroblasts. Plasma rich in growth factors (PRGF) is an autologous plasma preparation enriched in proteins obtained from patient's own blood aimed at accelerating tissue repair and regeneration. To evaluate the benefits of PRGF in skin photodamage, 10 healthy volunteers were treated with three consecutive intradermal injections of PRGF in the facial area. Clinical outcomes and histological analysis were performed. A statistically significant increase in the epidermis and papillary dermis thickness was seen after PRGF treatment (p < 0.001). Skin thickening was observed in all patients studied, being more intense in the group of patients with photodamage (p < 0.001). After PRGF treatment, a reduction of the average area fraction of solar elastosis was observed in patients with clinical and histological signs of skin photodamage (p < 0.05).No changeswere observed in the number of CD31, XIIIa factor, cKit, CD10, nor p53-positive cells. The improvement score after PRGF use was 0.75 (9/12) for the group of patients with signs of skin photodamage. Intradermal PRGF infiltration appears to be an effective treatment for the photodamaged skin. © 2015 Wiley Periodicals, Inc.

Racial and genetic determinants of plasma factor XIII activity.

PubMed

Saha, N; Aston, C E; Low, P S; Kamboh, M I

2000-12-01

Factor XIII (F XIII), a plasma transglutaminase, is essential for normal hemostasis and fibrinolysis. Plasma F XIII consists of two catalytic A (F XIIIA) and two non-catalytic B (F XIIIB) subunits. Activated F XIII is involved in the formation of fibrin gel by covalently crosslinking fibrin monomers. As the characteristics of the fibrin gel structure have been shown to be associated with the risk of coronary heart disease (CHD), F XIII activity may play a seminal role in its etiology. In this investigation, we determined plasma F XIII activity in two racial groups, including Asian Indians (n = 258) and Chinese (n = 385). Adjusted plasma F XIII activity was significantly higher in Indian men (142 vs. 110%; P<0.0001) and women (158 vs. 111%; P<0.0001) than their Chinese counterparts. As compared to Indians where the distribution of F XIII activity was almost normal, in Chinese it was skewed towards low activity. In both racial groups, bivariate and multivariate analyses showed strong correlation of F XIII activity with plasma fibrinogen and plasminogen levels. Race explained about 25% of the variation in F XIII activity even after the adjustment of significant correlates. We also determined the contribution of common genetic polymorphisms in the F XIIIA and F XIIIB genes in affecting plasma F XIII activity. Both loci showed significant and independent effects on plasma F XIII activity in Indians (F XIIIA, P< 0.01; F XIIIB, P<0.05) and Chinese (F XIIIA, P<0.0001; F XIIIB, P<0.13) in a gene dosage fashion. This study shows that both racial and genetic components play a significant role in determining plasma F XIII activity, and consequently it may affect the quantitative risk of CHD. Copyright 2000 Wiley-Liss, Inc.

Estradiol Protects Dermal Hyaluronan/Versican Matrix during Photoaging by Release of Epidermal Growth Factor from Keratinocytes*

PubMed Central

Röck, Katharina; Meusch, Michael; Fuchs, Nikola; Tigges, Julia; Zipper, Petra; Fritsche, Ellen; Krutmann, Jean; Homey, Bernhard; Reifenberger, Julia; Fischer, Jens W.

2012-01-01

Hyaluronan (HA) and versican are key components of the dermis and are responsive to ultraviolet (UV)B-induced remodeling. The aim of this study was to explore the molecular mechanisms mediating the effects of estrogen (E2) on HA-rich extracellular matrix during photoaging. Hairless skh-1 mice were irradiated with UVB (three times, 1 minimal erythema dose (80 mJ/cm2), weekly) for 10 weeks, and endogenous sex hormone production was abrogated by ovariectomy. Subcutaneous substitution of E2 by means of controlled-release pellets caused a strong increase in the dermal HA content in both irradiated and nonirradiated skin. The increase in dermal HA correlated with induction of HA synthase HAS3 by E2. Expression of splice variant 2 of the HA-binding proteoglycan versican was also increased by E2. In search of candidate mediators of these effects, it was found that E2 strongly induced the expression of epidermal growth factor (EGF) in UVB-irradiated epidermis in vivo and in keratinocytes in vitro. EGF in turn up-regulated the expression of HAS3 and versican V2 in dermal fibroblasts. HAS3 knockdown by shRNA caused inhibition of fibroblast proliferation. Furthermore, HAS3 and versican V2 induction by E2 correlated positively with proliferation in vivo. In addition, the accumulation of inflammatory macrophages, expression of inducible cyclooxygenase 2, as well as proinflammatory monocyte chemotactic protein 1 were decreased in response to E2 in the dermis. Collectively, these data suggest that E2 treatment increases the amount of dermal HA and versican V2 via paracrine release of EGF, which may be implicated in the pro-proliferative and anti-inflammatory effects of E2 during photoaging. PMID:22493503

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

Crosslinked hyaluronic acid dermal fillers: a comparison of rheological properties.

PubMed

Falcone, Samuel J; Berg, Richard A

2008-10-01

Temporary dermal fillers composed of crosslinked hyaluronic acid (XLHA) are space filling gels that are readily available in the United States and Europe. Several families of dermal fillers based on XLHA are now available and here we compare the physical and rheological properties of these fillers to the clinical effectiveness. The XLHA fillers are prepared with different crosslinkers, using HA isolated from different sources, have different particle sizes, and differ substantially in rheological properties. For these fillers, the magnitude of the complex viscosity, |eta*|, varies by a factor of 20, the magnitude of the complex rigidity modulus, |G*|, and the magnitude of the complex compliance, |J*| vary by a factor of 10, the percent elasticity varies from 58% to 89.9%, and the tan delta varies from 0.11 to 0.70. The available clinical data cannot be correlated with either the oscillatory dynamic or steady flow rotational rheological properties of the various fillers. However, the clinical data appear to correlate strongly with the total concentration of XLHA in the products and to a lesser extent with percent elasticity. Hence, our data suggest the following correlation: dermal filler persistence = [polymer] x [% elasticity] and the clinical persistence of a dermal filler composed of XLHA is dominated by the mass and elasticity of the material implanted. This work predicts that the development of future XLHA dermal filler formulations should focus on increasing the polymer concentration and elasticity to improve the clinical persistence.

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.

Critical Evaluation of Risk Factors and Early Complications in 564 Consecutive Two-Stage Implant-Based Breast Reconstructions Using Acellular Dermal Matrix at a Single Center.

PubMed

Selber, Jesse C; Wren, James H; Garvey, Patrick B; Zhang, Hong; Erickson, Cameron; Clemens, Mark W; Butler, Charles E

2015-07-01

Acellular dermal matrix for implant-based breast reconstruction appears to cause higher early complication rates, but long-term outcomes are perceived to be superior. This dichotomy is the subject of considerable debate. The authors hypothesized that patient characteristics and operative variables would have a greater impact on complications than the type of acellular dermal matrix used. A retrospective cohort study was performed of consecutive patients who underwent two-stage, implant-based breast reconstruction with human cadaveric or bovine acellular dermal matrix from 2006 to 2012 at a single institution. Patient characteristics and operative variables were analyzed using logistic regression analyses to identify risk factors for complications. The authors included 564 reconstructions in the study. Radiation therapy and obesity increased the odds of all complications. Every 100-ml increase in preoperative breast volume increased the odds of any complication by 1 percent, the odds of infection by 27 percent, and the risk of explantation by 16 percent. The odds of seroma increased linearly with increasing surface area of acellular dermal matrix. Odds of infection were higher with an intraoperative expander fill volume greater than 50 percent of the total volume. Risk of explantation was twice as high when intraoperative expander fill volume was greater than 300 ml. Radiation therapy, obesity, larger breasts, higher intraoperative fill volumes, and larger acellular dermal matrices are all independent risk factors for early complications. Maximizing the initial mastectomy skin envelope fill must be balanced with the understanding that higher complication rates may result from a larger intraoperative breast mound. Risk, III.

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.

Estimating terrestrial amphibian pesticide body burden through dermal exposure.

PubMed

Van Meter, Robin J; Glinski, Donna A; Hong, Tao; Cyterski, Mike; Henderson, W Matthew; Purucker, S Thomas

2014-10-01

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 ingredients through contact with contaminated soil: imidacloprid (logKow = 0.57), atrazine (logKow = 2.5), triadimefon (logKow = 3.0), fipronil (logKow = 4.11) or pendimethalin (logKow = 5.18). All amphibians had measurable body burdens at the end of the exposure in concentrations ranging from 0.019 to 14.562 μg/g across the pesticides tested. Atrazine produced the greatest body burdens and bioconcentration factors, but fipronil was more permeable to amphibian skin when application rate was considered. Soil partition coefficient and water solubility were much better predictors of pesticide body burden, bioconcentration factor, and skin permeability than logKow. Dermal uptake data can be used to improve risk estimates of pesticide exposure among amphibians as non-target organisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Respiratory and dermal symptoms in Thai nurses using latex products.

PubMed

Supapvanich, C; Povey, A C; de Vocht, F

2013-09-01

Despite known health risks related to the use of powdered latex gloves (PLGs), they are still widely used in hospitals in developing countries due to the high cost of alternatives. To determine the prevalence of dermal and respiratory symptoms associated with latex glove use in nurses in Thailand and evaluate the influence of previously reported occupational risk factors in this population. A cross-sectional study in female nurses working in three Thai hospitals. Participants completed a questionnaire on demographics, occupational and personal history, use of latex products at work and dermal and respiratory symptoms attributed to occupational use of latex gloves. Of 899 nurses, 18% reported health effects attributed to the use of latex products. After adjustment for confounding, occupational risk factors associated with increased reporting of dermal symptoms included wearing more than 15 pairs of PLG per day (odds ratio (OR): 2.10, 95% confidence interval (CI): [1.32-3.34]), using chlorhexidine (OR: 2.07, 95% CI: [1.22-3.52]) and being an operating theatre nurse (OR: 2.46, 95% CI: [1.47-4.12]). Being a labour ward nurse (OR: 3.52, 95% CI: [1.26-9.85]) was the only factor associated with increased reporting of respiratory symptoms. Continuing use of PLGs in Thai nurses is associated with increased prevalence of dermal symptoms compared with data from developed countries. Measures to reduce such health effects are well established and should be considered. Additionally, replacement of chlorhexidine with an alternative detergent seems advisable.

[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.

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

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.

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.

Interleukin-1β Attenuates Myofibroblast Formation and Extracellular Matrix Production in Dermal and Lung Fibroblasts Exposed to Transforming Growth Factor-β1

PubMed Central

Mia, Masum M.; Boersema, Miriam; Bank, Ruud A.

2014-01-01

One of the most potent pro-fibrotic cytokines is transforming growth factor (TGFβ). TGFβ is involved in the activation of fibroblasts into myofibroblasts, resulting in the hallmark of fibrosis: the pathological accumulation of collagen. Interleukin-1β (IL1β) can influence the severity of fibrosis, however much less is known about the direct effects on fibroblasts. Using lung and dermal fibroblasts, we have investigated the effects of IL1β, TGFβ1, and IL1β in combination with TGFβ1 on myofibroblast formation, collagen synthesis and collagen modification (including prolyl hydroxylase, lysyl hydroxylase and lysyl oxidase), and matrix metalloproteinases (MMPs). We found that IL1β alone has no obvious pro-fibrotic effect on fibroblasts. However, IL1β is able to inhibit the TGFβ1-induced myofibroblast formation as well as collagen synthesis. Glioma-associated oncogene homolog 1 (GLI1), the Hedgehog transcription factor that is involved in the transformation of fibroblasts into myofibroblasts is upregulated by TGFβ1. The addition of IL1β reduced the expression of GLI1 and thereby also indirectly inhibits myofibroblast formation. Other potentially anti-fibrotic effects of IL1β that were observed are the increased levels of MMP1, −2, −9 and −14 produced by fibroblasts exposed to TGFβ1/IL1β in comparison with fibroblasts exposed to TGFβ1 alone. In addition, IL1β decreased the TGFβ1-induced upregulation of lysyl oxidase, an enzyme involved in collagen cross-linking. Furthermore, we found that lung and dermal fibroblasts do not always behave identically towards IL1β. Suppression of COL1A1 by IL1β in the presence of TGFβ1 is more pronounced in lung fibroblasts compared to dermal fibroblasts, whereas a higher upregulation of MMP1 is seen in dermal fibroblasts. The role of IL1β in fibrosis should be reconsidered, and the differences in phenotypical properties of fibroblasts derived from different organs should be taken into account in future anti

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.

Clotting of mammalian fibrinogens by papain: a re-examination.

PubMed

Doolittle, Russell F

2014-10-28

Papain has long been known to cause the gelation of mammalian fibrinogens. It has also been reported that papain-fibrin is insoluble in dispersing solvents like strong urea or sodium bromide solutions, similar to what is observed with thrombin-generated clots in the presence of factor XIIIa and calcium. In those old studies, both the gelation and subsequent clot stabilization were attributed to papain, although the possibility that the second step might be due to contaminating factor XIII in fibrinogen preparations was considered. I have revisited this problem in light of knowledge acquired over the past half-century about thiol proteases like papain, which mostly cleave peptide bonds, and transglutaminases like factor XIIIa that catalyze the formation of ε-lysyl-γ-glutamyl cross-links. Recombinant fibrinogen, inherently free of factor XIII and other plasma proteins, formed a stable gel when treated with papain alone. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the intermolecular cross-linking in papain-fibrin leads to γ-chain dimers, trimers, and tetramers, just as is the case with thrombin-factor XIIIa-stabilized fibrin. Mass spectrometry of bands excised from gels showed that the cross-linked material is quite different from what occurs with factor XIIIa, however. With papain, the cross-linking occurs between γ chains in neighboring protofibrils becoming covalently linked in a "head-to-tail" fashion by a transpeptidation reaction involving the α-amino group of γ-Tyr1 and a papain cleavage site at γ-Gly403 near the carboxy terminus, rather than by the (reciprocal) "tail-to-tail" manner that occurs with factor XIIIa and that depends on cross-links between γ-Lys406 and γ-Gln398.

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

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.

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 ...

Agminated Clear Cell Tumor: An Impostor of PEComa and Distinctive Dermal Clear Cell Mesenchymal Neoplasm.

PubMed

Teixeira, Ana Isabel; Soares-Almeida, Luís; Kutzner, Heinz

2017-03-01

Cutaneous clear cell tumors are a heterogeneous group of cutaneous neoplasms, which may show a wide range of histogenesis. We report the clinicopathological features of an agminated clear cell tumor, arising in a 67-year-old man, otherwise asymptomatic, with distinct histopathological and immunohistochemical features, which did not fit into any existing diagnostic categories. The patient presented with several skin-colored papules at the lateral and posterior aspects of the neck, which on histopathological examination showed circumscribed lobular aggregates of clear cells within the dermis. The immunohistochemical marker panel performed showed diffuse expression of vimentin, NKI-C3, and CD64 while revealing marked negativity for factor XIIIa, CD10, CD13, CD14, CD34, CD68, CD163, lysozyme, HMB45, Renal Cell Carcinoma antigen, calponin, h-caldesmon, Anti-alpha smooth muscle actin antibody [1 A4], S100, and pancytokeratin, leading the authors to postulate a monocytic origin.

Cadherin 11 Involved in Basement Membrane Damage and Dermal Changes in Melasma.

PubMed

Kim, Nan-Hyung; Choi, Soo-Hyun; Lee, Tae Ryong; Lee, Chang-Hoon; Lee, Ai-Young

2016-06-15

Basement membrane (BM) disruption and dermal changes (elastosis, collagenolysis, vascular ectasia) have been reported in melasma. Although ultraviolet (UV) irradiation can induce these changes, UV is not always necessary for melasma development. Cadherin 11 (CDH11), which is upregulated in some melasma patients, has previously been shown to stimulate melanogenesis. Because CDH11 action requires cell-cell adhesion between fibroblasts and melanocytes, BM disruption in vivo should facilitate this. The aim of this study was to examine whether CDH11 overexpression leads to BM disruption and dermal changes, independent of UV irradiation. Immunohistochemistry/immunofluorescence, real-time PCR, Western blotting, and zymography suggested that BM disruption/dermal changes and related factors were present in the hyperpigmented skin of CDH11-upregulated melasma patients and in CDH11-overexpressing fibroblasts/keratinocytes. The opposite was seen in CDH11-knockdown cells. UV irradiation of the cultured cells did not increase CDH11 expression. Collectively, these data demonstrate that CDH11 overexpression could induce BM disruption and dermal changes in melasma, regardless of UV exposure.

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

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...

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.

Glycyrrhizic acid attenuates stem cell-like phenotypes of human dermal papilla cells.

PubMed

Kiratipaiboon, Chayanin; Tengamnuay, Parkpoom; Chanvorachote, Pithi

2015-12-15

Although the growth of unwanted hair or hirsutism is a harmless condition, many people find it bothersome and embarrassing. Maintaining stem cell features of dermal papilla cells is a critical biological process that keeps the high rate of hair growth. Glycyrrhizic acid has been reported to impair hair growth in some studies; however, its underlying mechanism has not yet been investigated. This study aimed to explore the effect and underlying mechanism of glycyrrhizic acid on stemness of human dermal papilla cells. The stem cell molecular markers, epithelial to mesenchymal markers and Wnt/β-catenin-associated proteins of human dermal papilla cell line and primary human dermal papilla cells were analysed by western blot analysis and immunocytochemistry. The present study demonstrated that glycyrrhizic acid significantly depressed the stemness of dermal papilla cells in dose- and time-dependent manners. Clonogenicity and stem cell markers in the glycyrrhizic acid-treated cells were found to gradually decrease in the culture in a time-dependent manner. Our results demonstrated that glycyrrhizic acid exerted the stem cell suppressing effects through the interruption of ATP-dependent tyrosine kinase/glycogen synthase kinase3β-dependent mechanism which in turn down-regulated the β-catenin signalling pathway, coupled with decreased its down-stream epithelial-mesenchymal transition and self-renewal transcription factors, namely, Oct-4, Nanog, Sox2, ZEB1 and Snail. The effect of glycyrrhizic acid on the reduction of stem cell features was also observed in the primary dermal papilla cells directly obtained from human hair follicles. These results revealed a novel molecular mechanism of glycyrrhizic acid in regulation of dermal papilla cells and provided the evidence supporting the use of this compound in suppressing the growth of unwanted hair. Copyright © 2015 Elsevier GmbH. All rights reserved.

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.

Primary cell culture and morphological characterization of canine dermal papilla cells and dermal fibroblasts.

PubMed

Bratka-Robia, Christine B; Mitteregger, Gerda; Aichinger, Amanda; Egerbacher, Monika; Helmreich, Magdalena; Bamberg, Elmar

2002-02-01

Skin biopsies were taken from female dogs, the primary hair follicles isolated and the dermal papilla dissected. After incubation in supplemented Amniomax complete C100 medium in 24-well culture plates, the dermal papilla cells (DPC) grew to confluence within 3 weeks. Thereafter, they were subcultivated every 7 days. Dermal fibroblast (DFB) cultures were established by explant culture of interfollicular dermis in serum-free medium, where they reached confluence in 10 days. They were subcultivated every 5 days. For immunohistochemistry, cells were grown on cover slips for 24 h, fixed and stained with antibodies against collagen IV and laminin. DPC showed an aggregative growth pattern and formation of pseudopapillae. Intensive staining for collagen IV and laminin could be observed until the sixth passage. DFB grew as branching, parallel lines and showed only weak staining for collagen IV and laminin.

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.

Accessory cells in physiological lymphoid tissue from the intestine: an immunohistochemical study.

PubMed

Sarsfield, P; Rinne, A; Jones, D B; Johnson, P; Wright, D H

1996-03-01

We report a study of the organization of accessory cell populations, in normal mucosal lymphoid tissue from small intestine (8 cases), large intestine (6) and appendix (9) using a panel of monoclonal antibodies and polyclonal antisera in paraffin-embedded tissue. Two populations were identified in dome areas, one positive for acid cysteine proteinase inhibitor and HLA class II (WR18) only and the second positive for S-100 protein, CD68, and WR18 and negative for acid cysteine proteinase inhibitor and factor XIIIa. Superficial colonic mucosal and small intestinal villous tip macrophages stained positively with CD68 and WR18 only, while deeper cryptal and submucosal populations exhibited additional positivity for factor XIIIa, but both populations were negative for acid cysteine proteinase inhibitor and S-100 protein. Germinal centre macrophages were positive for CD68, WR18 and acid cysteine proteinase inhibitor and negative for factor XIIIa, and S-100 protein. T zone dendritic cells included a population which stained positively for S-100 protien, WR18 and were negative for factor XIIIa, CD68 and acid cysteine proteinase inhibitor, an immunophenotype typical of interdigitating dendritic reticulum cells. This distribution of phenotypically identifiable accessory cell subpopulations was apparent at all three sites examined. We suggest that the specialized subpopulations of dendritic cells staining for S-100 protein and for acid cysteine proteinase inhibitor which are restricted to the dome areas, may have a potential role in the transfer of antigen across the epithelium to the germinal centres, while factor XIIIa appears to identify a tissue macrophage population with a potential role in stromal modulation distant from direct antigen challenge.

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

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.

A quantitative method for estimating dermal benzene absorption from benzene-containing hydrocarbon liquids.

PubMed

Petty, Stephen E; Nicas, Mark; Boiarski, Anthony A

2011-01-01

This study examines a method for estimating the dermal absorption of benzene contained in hydrocarbon liquids that contact the skin. This method applies to crude oil, gasoline, organic solvents, penetrants, and oils. The flux of benzene through occluded skin as a function of the percent vol/vol benzene in the liquid is derived by fitting a curve to experimental data; the function is supralinear at benzene concentrations < or = 5% vol/vol. When a liquid other than pure benzene is on nonoccluded skin, benzene may preferentially evaporate from the liquid, which thereby decreases the benzene flux. We present a time-averaging method here for estimating the reduced dermal flux during evaporation. Example calculations are presented for benzene at 2% vol/vol in gasoline, and for benzene at 0.1% vol/vol in a less volatile liquid. We also discuss other factors affecting dermal absorption.

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.

Assessment of relevant factors and relationships concerning human dermal exposure to pesticides in greenhouse applications.

PubMed

Martínez Vidal, Jose L; Egea González, Francisco J; Garrido Frenich, Antonia; Martínez Galera, María; Aguilera, Pedro A; López Carrique, Enrique

2002-08-01

Principal component analysis (PCA) was applied to the gas chromatographic data obtained from 23 different greenhouse trials. This was used to establish which factors, including application technique (very small, small, medium and large drop-size), crop characteristics (short/tall, thin/dense) and pattern application of the operator (walking towards or away from the treated area) are relevant to the dermal exposure levels of greenhouse applicators. The results showed that the highest exposure by pesticides during field applications in greenhouses, in the climatic conditions and in the crop conditions typical of a southern European country, occurs on the lower legs and front thighs of the applicators. Similar results were obtained by hierarchical cluster analysis (HCA). Drop-size seems to be very important in determining total exposure, while height and density of crops have little influence on total exposure under the conditions of the present study. No pesticide type is a major factor in total exposure. The application of multiple regression analysis (MRA) allowed assessment of the relationships between the pesticide exposure of the less affected parts of the body with the most affected parts.

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

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.

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

A short-term and long-term comparison of root coverage with an acellular dermal matrix and a subepithelial graft.

PubMed

Harris, Randall J

2004-05-01

Obtaining predictable and esthetic root coverage has become important. Unfortunately, there is only a limited amount of information available on the long-term results of root coverage procedures. The goal of this study was to evaluate the short-term and long-term root coverage results obtained with an acellular dermal matrix and a subepithelial graft. An a priori power analysis was done to determine that 25 was an adequate sample size for each group in this study. Twenty-five patients treated with either an acellular dermal matrix or a subepithelial graft for root coverage were included in this study. The short-term (mean 12.3 to 13.2 weeks) and long-term (mean 48.1 to 49.2 months) results were compared. Additionally, various factors were evaluated to determine whether they could affect the results. This study was a retrospective study of patients in a fee-for-service private periodontal practice. The patients were not randomly assigned to treatment groups. The mean root coverages for the short-term acellular dermal matrix (93.4%), short-term subepithelial graft (96.6%), and long-term subepithelial graft (97.0%) were statistically similar. All three were statistically greater than the long-term acellular dermal matrix mean root coverage (65.8%). Similar results were noted in the change in recession. There were smaller probing reductions and less of an increase in keratinized tissue with the acellular dermal matrix than the subepithelial graft. None of the factors evaluated resulted in the acellular dermal graft having a statistically significant better result than the subepithelial graft. However, in long-term cases where multiple defects were treated with an acellular dermal matrix, the mean root coverage (70.8%) was greater than the mean root coverage in long-term cases where a single defect was treated with an acellular dermal matrix (50.0%). The mean results with the subepithelial graft held up with time better than the mean results with an acellular dermal

Role of clothing in both accelerating and impeding dermal absorption of airborne SVOCs.

PubMed

Morrison, Glenn C; Weschler, Charles J; Bekö, Gabriel; Koch, Holger M; Salthammer, Tunga; Schripp, Tobias; Toftum, Jørn; Clausen, Geo

2016-01-01

To assess the influence of clothing on dermal uptake of semi-volatile organic compounds (SVOCs), we measured uptake of selected airborne phthalates for an individual wearing clean clothes or air-exposed clothes and compared these results with dermal uptake for bare-skinned individuals under otherwise identical experimental conditions. Using a breathing hood to isolate dermal from inhalation uptake, we measured urinary metabolites of diethylphthalate (DEP) and di-n-butylphthalate (DnBP) from an individual exposed to known concentrations of these compounds for 6 h in an experimental chamber. The individual wore either clean (fresh) cotton clothes or cotton clothes that had been exposed to the same chamber air concentrations for 9 days. For a 6-h exposure, the net amounts of DEP and DnBP absorbed when wearing fresh clothes were, respectively, 0.017 and 0.007 μg/kg/(μg/m(3)); for exposed clothes the results were 0.178 and 0.261 μg/kg/(μg/m(3)), respectively (values normalized by air concentration and body mass). When compared against the average results for bare-skinned participants, clean clothes were protective, whereas exposed clothes increased dermal uptake for DEP and DnBP by factors of 3.3 and 6.5, respectively. Even for non-occupational environments, wearing clothing that has adsorbed/absorbed indoor air pollutants can increase dermal uptake of SVOCs by substantial amounts relative to bare skin.

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.

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

Identification of Cadherin 11 as a Mediator of Dermal Fibrosis and Possible Role in Systemic Sclerosis

PubMed Central

Wu, Minghua; Pedroza, Mesias; Lafyatis, Robert; George, Anuh-Teresa; Mayes, Maureen D.; Assassi, Shervin; Tan, Filemon K.; Brenner, Michael B.; Agarwal, Sandeep K.

2014-01-01

Objective Systemic sclerosis (SSc) is a chronic autoimmune disease clinically manifesting as progressive fibrosis of the skin and internal organs. Recent microarray studies demonstrated that cadherin 11 (Cad-11) expression is increased in the affected skin of patients with SSc. The purpose of this study was to examine our hypothesis that Cad-11 is a mediator of dermal fibrosis. Methods Biopsy samples of skin from SSc patients and healthy control subjects were used for real-time quantitative polymerase chain reaction analysis to assess Cad-11 expression and for immunohistochemistry to determine the expression pattern of Cad-11. To determine whether Cad-11 is a mediator of dermal fibrosis, Cad-11–deficient mice and anti–Cad-11 monoclonal antibodies (mAb) were used in the bleomycin-induced dermal fibrosis model. In vitro studies with dermal fibroblasts and bone marrow–derived macrophages were used to determine the mechanisms by which Cad-11 contributes to the development of tissue fibrosis. Results Levels of messenger RNA for Cad-11 were increased in skin biopsy samples from patients with SSc and correlated with the modified Rodnan skin thickness scores. Cad-11 expression was localized to dermal fibroblasts and macrophages in SSc skin. Cad-11–knockout mice injected with bleomycin had markedly attenuated dermal fibrosis, as quantified by measurements of skin thickness, collagen levels, myofibroblast accumulation, and profibrotic gene expression, in lesional skin as compared to the skin of wild-type mice. In addition, anti–Cad-11 mAb decreased fibrosis at various time points in the bleomycin-induced dermal fibrosis model. In vitro studies demonstrated that Cad-11 regulated the production of transforming growth factor β (TGFβ) by macrophages and the migration of fibroblasts. Conclusion These data demonstrate that Cad-11 is a mediator of dermal fibrosis and TGFβ production and suggest that Cad-11 may be a therapeutic target in SSc. PMID:24757152

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...

Integrin-linked kinase is required for TGF-β1 induction of dermal myofibroblast differentiation.

PubMed

Vi, Linda; de Lasa, Cristina; DiGuglielmo, Gianni M; Dagnino, Lina

2011-03-01

Cutaneous repair after injury requires activation of resident dermal fibroblasts and their transition to myofibroblasts. The key stimuli for myofibroblast formation are activation of transforming growth factor-β (TGF-β) receptors and mechanotransduction mediated by integrins and associated proteins. We investigated the role of integrin-linked kinase (ILK) in TGF-β1 induction of dermal fibroblast transition to myofibroblasts. ILK-deficient fibroblasts treated with TGF-β1 exhibited attenuation of Smad 2 and 3 phosphorylation, accompanied by impaired transcriptional activation of Smad targets, such as α-smooth muscle actin. These alterations were not limited to Smad-associated TGF-β1 responses, as stimulation of noncanonical mitogen-activated protein kinase pathways by this growth factor was also diminished in the absence of ILK. ILK-deficient fibroblasts exhibited abnormalities in the actin cytoskeleton, and did not form supermature focal adhesions or contractile F-actin stress fibers, indicating a severe impairment in their capacity to differentiate into myofibroblasts. These defects extended to the inability of cells to contract extracellular matrices when embedded in collagen lattices. We conclude that ILK is necessary to transduce signals implicated in the transition of dermal fibroblasts to myofibroblasts originating from matrix substrates and TGF-β1.

Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function

PubMed Central

Ivaskevicius, Vytautas; Biswas, Arijit; Bevans, Carville; Schroeder, Verena; Kohler, Hans Peter; Rott, Hannelore; Halimeh, Susan; Petrides, Petro E.; Lenk, Harald; Krause, Manuele; Miterski, Bruno; Harbrecht, Ursula; Oldenburg, Johannes

2010-01-01

Background Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer. Design and Methods We analyzed ten index patients and three relatives for factor XIII activity using a photometric assay and sequenced their F13A and F13B genes. Additionally, structural analysis of the wild-type protein structure from a previously reported X-ray crystallographic model identified potential structural and functional effects of the missense mutations. Results All individuals except one were heterozygous for factor XIIIA mutations (average factor XIII activity 51%), while the remaining homozygous individual was found to have severe factor XIII deficiency (<5% of normal factor XIII activity). Eight of the 12 heterozygous patients exhibited a bleeding tendency upon provocation. Conclusions The identified missense (Pro289Arg, Arg611His, Asp668Gly) and nonsense (Gly390X, Trp664X) mutations are causative for factor XIII deficiency. A Gly592Ser variant identified in three unrelated index patients, as well as in 200 healthy controls (minor allele frequency 0.005), and two further Tyr167Cys and Arg540Gln variants, represent possible candidates for rare F13A gene polymorphisms since they apparently do not have a significant influence on the structure of the factor XIIIA protein. Future in vitro expression studies of the factor XIII mutations are required to confirm their pathological mechanisms. PMID:20179087

Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function.

PubMed

Ivaskevicius, Vytautas; Biswas, Arijit; Bevans, Carville; Schroeder, Verena; Kohler, Hans Peter; Rott, Hannelore; Halimeh, Susan; Petrides, Petro E; Lenk, Harald; Krause, Manuele; Miterski, Bruno; Harbrecht, Ursula; Oldenburg, Johannes

2010-06-01

Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer. We analyzed ten index patients and three relatives for factor XIII activity using a photometric assay and sequenced their F13A and F13B genes. Additionally, structural analysis of the wild-type protein structure from a previously reported X-ray crystallographic model identified potential structural and functional effects of the missense mutations. All individuals except one were heterozygous for factor XIIIA mutations (average factor XIII activity 51%), while the remaining homozygous individual was found to have severe factor XIII deficiency (<5% of normal factor XIII activity). Eight of the 12 heterozygous patients exhibited a bleeding tendency upon provocation. The identified missense (Pro289Arg, Arg611His, Asp668Gly) and nonsense (Gly390X, Trp664X) mutations are causative for factor XIII deficiency. A Gly592Ser variant identified in three unrelated index patients, as well as in 200 healthy controls (minor allele frequency 0.005), and two further Tyr167Cys and Arg540Gln variants, represent possible candidates for rare F13A gene polymorphisms since they apparently do not have a significant influence on the structure of the factor XIIIA protein. Future in vitro expression studies of the factor XIII mutations are required to confirm their pathological mechanisms.

Effects of mitomycin-C on normal dermal fibroblasts.

PubMed

Chen, Theodore; Kunnavatana, Shaun S; Koch, R James

2006-04-01

To evaluate the effects of mitomycin-C on the growth and autocrine growth factor production of human dermal fibroblasts from the face. In vitro study using normal adult dermal fibroblast cell lines in a serum-free model. Cell cultures were exposed to 4 mg/mL, 0.4 mg/mL, 0.04 mg/mL, 0.004 mg/mL, and 0.0004 mg/mL concentrations of mitomycin-C solution. Cell counts were performed, and the cell-free supernatants were collected at 0, 1, 3, and 5 days after the initial exposure. Population doubling times were calculated and supernatants were quantitatively assayed for basic fibroblast growth factor (bFGF) and transforming growth factor (TGF)-beta1. Continuous exposure to mitomycin-C caused fibroblast cell death by day 7 at all tested concentrations. A 4 minute exposure to mitomycin-C at 4 mg/mL caused rapid fibroblast cell death. A 4-minute exposure to mitomycin-C at either 0.4 mg/mL or 0.04 mg/mL resulted in decreased fibroblast proliferation. A 4 minute exposure to mitomycin-C at 0.4 mg/mL resulted in a marked increase in the production of both bFGF and TGF-beta1. A clinically ideal concentration of mitomycin-C would slow fibroblast proliferation yet not cause cell death to allow for a wound healing response. Mitomycin-C 0.4 mg/mL for 4 minutes satisfies the above criteria in vitro.

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.

Chronic exposure of interleukin-13 suppress the induction of matrix metalloproteinase-1 by tumour necrosis factor α in normal and scleroderma dermal fibroblasts through protein kinase B/Akt.

PubMed

Brown Lobbins, M L; Shivakumar, B R; Postlethwaite, A E; Hasty, K A

2018-01-01

Peripheral blood mononuclear cells taken from patients with scleroderma express increased levels of interleukin (IL)-13. Moreover, the expression of matrix metalloproteinase-1 (MMP-1) from involved scleroderma skin fibroblasts is refractory to stimulation by tumour necrosis factor (TNF)-α. To elucidate the mechanism(s) involved, we examined the effect of IL-13 on TNF-α-induced MMP-1 expression in normal and scleroderma human dermal fibroblast lines and studied the involvement of serine/threonine kinase B/protein kinase B (Akt) in this response. Dermal fibroblast lines were stimulated with TNF-α in the presence of varying concentrations of IL-13. Total Akt and pAkt were quantitated using Western blot analyses. Fibroblasts were treated with or without Akt inhibitor VIII in the presence of IL-13 followed by TNF-α stimulation. MMP-1 expression was analysed by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using analysis of variance (anova) or Student's t-test. Upon TNF-α stimulation, normal dermal fibroblasts secrete more MMP-1 than systemic sclerosis (SSc) fibroblasts. This increase in MMP-1 is lost when fibroblasts are co-incubated with IL-13 and TNF-α. IL-13 induced a significant increase in levels of pAkt in dermal fibroblasts, while Akt inhibitor VIII reversed the suppressive effects of IL-13 on the response of cultured fibroblasts to TNF-α, increasing their expression of MMP-1. We show that IL-13 suppresses MMP-1 in TNF-α-stimulated normal and scleroderma dermal fibroblast. Akt inhibitor VIII is able to reverse the suppressive effect of IL-13 on MMP-1 expression and protein synthesis. Our data suggest that IL-13 regulates MMP-1 expression in response to TNF-α through an Akt-mediated pathway and may play a role in fibrotic diseases such as scleroderma. © 2017 British Society for Immunology.

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.

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...

Plasma rich in growth factors promotes dermal fibroblast proliferation, migration and biosynthetic activity.

PubMed

Anitua, E; Pino, A; Orive, G

2016-11-02

The use of plasma rich in growth factors (PRGF) has gained importance in many medical fields due to its regenerative potential. The aim of this study is to evaluate the effects of PRGF on primary skin fibroblasts assessing cell proliferation, migration and secretion of growth factors. The age of the patients from who PRGF was prepared was also studied to determine whether it influenced the outcomes. Human dermal fibroblasts were isolated from three healthy volunteers. Using PRGF-Endoret technology, PRGF was prepared from two groups of different ages (18-35 years and 50+ years). The effects of increasing concentration of PRGF (5%, 10% and 20%) on cell proliferation and migration was evaluated. Biosynthetic behaviour of cells was also analysed measuring vascular endothelial growth factor (VEGF), transforming growth factor b1 (TGFb1) and pro-collagen type I secreted levels with or without PRGF treatment. Mean platelet enrichment reached 2.4X and 2X in 18-35 and 50+ groups respectively. A dose-dependent response was observed in proliferation assays achieving the highest levels with 20% PRGF. Migration was also promoted in cells but not in a dose-dependent manner. Cell proliferation and migration outcomes obtained with PRGF (from both groups) were significantly higher compared to non-stimulated groups (p<0.05), with no statistical significances were observed between the different age groups. Production of VEGF, TGFb and procollagen type I was significantly increased by cells treated with PRGF, however, with the exception of VEGF, no statistical significances were observed between the different age groups. Results from this study concluded that PRGF is safe and effective in stimulating skin regeneration by enhancing proliferation, migration and expression of pivotal bioactive molecules involved in wound healing and haemostasis.

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.

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

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

Promoting Wound Healing Using Low Molecular Weight Fucoidan in a Full-Thickness Dermal Excision Rat Model

PubMed Central

Park, Jun-Hyeong; Choi, Seong-Hun; Park, Soo-Jin; Lee, Young Joon; Park, Jong Hyun; Song, Phil Hyun; Cho, Chang-Mo; Ku, Sae-Kwang; Song, Chang-Hyun

2017-01-01

Low molecular weight fucoidan (LMF) has been reported to possess anti-inflammatory and antioxidant activities. Thus, we examined the effects of LMF extracted from Undaria pinnatifida on dermal wounds. Five round dermal wounds were created on the dorsal back of rats, and they were then treated topically with distilled water (DW), Madecasol Care™ (MC) or LMF at 200, 100 and 50 mg/mL, twice a day for a week. There were dose-dependent increases in wound contraction in the groups receiving LMF but not in the MC group, compared with the DW. Histopathological examination revealed that LMF treatment accelerated wound healing, which was supported by increases in granular tissue formation on day four post-treatment but a decrease on day seven, accompanied by an evident reduction in inflammatory cells. In the LMF-treated wounds, collagen distribution and angiogenesis were increased in the granular tissue on days four and seven post-treatment. Immunoreactive cells for transforming growth factor-β1, vascular endothelial growth factor receptor-2 or matrix metalloproteinases 9 were also increased, probably due to tissue remodeling. Furthermore, LMF treatment reduced lipid peroxidation and increased antioxidant activities. These suggested that LMF promotes dermal wound healing via complex and coordinated antioxidant, anti-inflammatory and growth factor-dependent activities. PMID:28387729

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

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

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...

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.

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

Potential Health Effects Associated with Dermal Exposure to Occupational Chemicals

PubMed Central

Anderson, Stacey E; Meade, B Jean

2014-01-01

There are a large number of workers in the United States, spanning a variety of occupational industries and sectors, who are potentially exposed to chemicals that can be absorbed through the skin. Occupational skin exposures can result in numerous diseases that can adversely affect an individual’s health and capacity to perform at work. In general, there are three types of chemical–skin interactions of concern: direct skin effects, immune-mediated skin effects, and systemic effects. While hundreds of chemicals (metals, epoxy and acrylic resins, rubber additives, and chemical intermediates) present in virtually every industry have been identified to cause direct and immune-mediated effects such as contact dermatitis or urticaria, less is known about the number and types of chemicals contributing to systemic effects. In an attempt to raise awareness, skin notation assignments communicate the potential for dermal absorption; however, there is a need for standardization among agencies to communicate an accurate description of occupational hazards. Studies have suggested that exposure to complex mixtures, excessive hand washing, use of hand sanitizers, high frequency of wet work, and environmental or other factors may enhance penetration and stimulate other biological responses altering the outcomes of dermal chemical exposure. Understanding the hazards of dermal exposure is essential for the proper implementation of protective measures to ensure worker safety and health. PMID:25574139

Potential health effects associated with dermal exposure to occupational chemicals.

PubMed

Anderson, Stacey E; Meade, B Jean

2014-01-01

There are a large number of workers in the United States, spanning a variety of occupational industries and sectors, who are potentially exposed to chemicals that can be absorbed through the skin. Occupational skin exposures can result in numerous diseases that can adversely affect an individual's health and capacity to perform at work. In general, there are three types of chemical-skin interactions of concern: direct skin effects, immune-mediated skin effects, and systemic effects. While hundreds of chemicals (metals, epoxy and acrylic resins, rubber additives, and chemical intermediates) present in virtually every industry have been identified to cause direct and immune-mediated effects such as contact dermatitis or urticaria, less is known about the number and types of chemicals contributing to systemic effects. In an attempt to raise awareness, skin notation assignments communicate the potential for dermal absorption; however, there is a need for standardization among agencies to communicate an accurate description of occupational hazards. Studies have suggested that exposure to complex mixtures, excessive hand washing, use of hand sanitizers, high frequency of wet work, and environmental or other factors may enhance penetration and stimulate other biological responses altering the outcomes of dermal chemical exposure. Understanding the hazards of dermal exposure is essential for the proper implementation of protective measures to ensure worker safety and health.

[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

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.

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 .

Improvement of dermal parameters in aged skin after oral use of a nutrient supplement

PubMed Central

Addor, Flávia Alvim Sant’Anna; Cotta Vieira, Juliana; Abreu Melo, Camila Sirieiro

2018-01-01

Purpose Skin aging is a progressive and degenerative process caused by a decrease in the physiological functions of the skin tissue. In addition, environmental factors as well as concomitant diseases and lifestyle (nutrition, sedentary lifestyle, smoking, etc) negatively impact the aging process. An association between oral administration of collagen peptides combined with vitamin C and extracts of Hibiscus sabdariffa and Aristotelia chilensis (Delphynol®) (Eximia Firmalize Age complex®) on dermal thickness was studied and the improvement in aging signs was evaluated. Patients and methods Female adult patients received an oral nutritional supplement containing collagen peptides, vitamin C, H. sabdariffa, and A. chilensis (Delphynol) in a sachet and were instructed to consume 1 sachet diluted in 200 mL of water once daily for 12 weeks. They were evaluated clinically, by high frequency ultrasound and cutometry. Results There was a significant improvement of firmness and elasticity and an increase in dermal thickness by ultrasound after 3 months of use. Conclusion The association of collagen peptides, vitamin C, H. sabdariffa and A. chilensis (Delphynol) could improve the signs of dermal skin aging. PMID:29750046

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.

Soil organic matter content effects on dermal pesticide bioconcentration in American toads (Bufo americanus).

EPA Science Inventory

Pesticides have been implicated as a major factor in global amphibian declines and may pose great risk to terrestrial phase amphibians moving to and from breeding ponds on agricultural landscapes. Dermal uptake from soil is known to occur in amphibians, but predicting pesticide a...

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...

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.

Effects of chronic alcohol consumption on dermal penetration of pesticides in rats.

PubMed

Brand, R M; Charron, A R; Dutton, L; Gavlik, T L; Mueller, C; Hamel, F G; Chakkalakal, D; Donohue, T M

2004-01-23

Topically applied ethanol is a well-known dermal penetration enhancer. The purpose of this work was to determine if ethanol consumption might also increase transdermal penetration. Male rats were fed either an ethanol containing or control diet for 6-8 wk. After the feeding regime was completed, skin was removed and placed in an in vitro diffusion system. The transdermal absorption of four very commonly used herbicides was determined. Penetration through skin from ethanol-fed rats was enhanced when compared to control by a factor of 5.3 for paraquat, 2.4 for atrazine, and 2.2 for 2,4-dichlorophenoxyacetic acid (2,4-D), and reduced by a factor 0.6 for trifluralin. Comparison of physical factors of the herbicides to the penetration enhancement revealed an inverse linear correlation with lipophilicity, as defined by log octanol/water partition coefficient (log Kow) with r2 =.98. These changes were at least partially reversible after 1 wk of abstinence from ethanol. These experiments demonstrate that regular ethanol consumption can alter the properties of the dermal barrier, leading to increased absorption of some chemicals through rat skin. If ethanol consumption has the same effect on human skin it could potentially have adverse health effects on people regularly exposed to agricultural, environmental, and industrial chemicals.

Clinical outcome in 94 cases of dermal haemangiosarcoma in dogs treated with surgical excision: 1993-2007*.

PubMed

Szivek, A; Burns, R E; Gericota, B; Affolter, V K; Kent, M S; Rodriguez, C O; Skorupski, K A

2012-03-01

Canine dermal haemangiosarcoma (HSA) is believed to have a better prognosis compared to HSA in other organs, but outcome has only been reported in a small number of dogs. The purpose of this study was to assess outcome and prognostic factors in a larger cohort of dogs with dermal HSA. Clinical data was collected retrospectively for 94 dogs and histopathology was reviewed in 53 dogs. Median overall survival time was 987 days. Dogs of predisposed breed with ventral location and histologic solar changes had longer survivals. Loco-regional recurrence occurred in 72/94 (77%) dogs. Predisposed breeds with ventral location and multiple masses were more likely to develop recurrence. Non-predisposed breeds with invasive tumours were more likely to develop metastasis. Results suggest that dogs with solar-induced dermal HSA may have high recurrence rates, but prolonged survivals. Dogs with non-solar tumours may be at increased risk for metastasis and shorter survival. © 2011 Blackwell Publishing Ltd.

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

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.

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.

Aneurysmal and haemangiopericytoma-like fibrous histiocytoma.

PubMed Central

Zelger, B W; Zelger, B G; Steiner, H; Ofner, D

1996-01-01

AIM: To describe the clinicopathological features of 33 aneurysmal fibrous histiocytomas (AFH), including five cases with a haemangiopericytoma-like pattern. METHODS: Thirty three cases of AFH were studied by using routine histology and immunohistochemistry for factor XIIIa, the "cell activity marker" E9 (anti-metallothionein), NK1C3 (CD57), smooth muscle actin (SMA), factor VIII, ulex europaeus agglutinin, JC70A (CD31), and QBEND10 (CD34). The time dependent variation in histopathological features was evaluated by statistical methods (Pearson chi 2, likelihood ratio chi 2). RESULTS: Of the AFHs, 29 of 33 occurred on the extremities of adults (age range 30 to 50 years), six of which were associated with rapid growth, probably caused by trauma, and pain. Twenty one lesions were thought to be vascular and/or melanocytic lesions, including two melanomas, because of a bluish-black and/or cystic appearance. Histologically, large areas of haemorrhage, up to 50% of the tumour bulk, lacking an endothelial lining were seen in otherwise typical fibrous histiocytomas. Five cases resembled nodular stages of Kaposi's sarcoma. Variable haemosiderin deposition in histiocytes (18/33) and giant cells (11/33) was suggestive of haemosiderotic histiocytoma. A haemangiopericytoma-like pattern was seen in five otherwise indistinguishable cases. On immunohistochemistry, variable reactivity was seen for factor XIIIa (18/30), with E9 (18/30), NK1C3 (19/30), and for SMA (14/30), but labelling for vascular markers was not detected. Early lesions without iron deposition were factor XIIIa positive; late lesions with iron deposition were factor XIIIa negative. Labelling for SMA correlated with prominent sclerosis. CONCLUSION: AFHs, including a haemangiopericytoma-like variant, have a characteristic time dependent histological and immunophenotypic profile, clearly different from nodular type Kaposi's sarcoma. Images PMID:8655708

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

LINKING DERMAL MODELING AND LOADING DATA TO PREDICT LONG-TERM DOSES FROM INTERMITTENT DERMAL CONTACT

EPA Science Inventory

In this paper we assess dermal exposure and dose resulting from intermittent contact with residue-contaminated surfaces. These estimates require an understanding of (1) the quantitative relationship between exposure and absorbed dose; (2) the impact of intermittent exposure on ...

Human dermal papilla cells and outer root sheath cells: no follicular differentiation in nude mice and chicken embryos.

PubMed

Chiu, H C; Chang, C H; Jee, S H; Chang, C C; Wu, Y C

1994-09-01

Human scalp specimens were incubated in 5 U/ml dispase solution at 4 degrees C overnight before the isolation of dermal papillae and follicle epithelium. This pretreatment not only facilitated the attachment and cell outgrowth of dermal papillae but also made it easier to pluck out hairs with intact follicle epithelium. The outer root sheath cells were released from the follicle epithelium and grown on a feeder layer of mitomycin C-treated human dermal fibroblasts. The subcultured outer root sheath cells were grown in a serum-free medium. When the mixtures of early-passage dermal papilla cells and outer root sheath cells were injected into the subcutis of nude mice, an epidermal cyst surrounded by layers of fibrous tissue was found in three weeks. No hair follicles were found when the mixtures were implanted onto the chorioallantoic membrane of nine-day-old chicken embryos. A keratinized mass lying on the chorionic epithelium with or without smaller similar masses in the chorioallantoic membrane was found in eight days. No hair follicle-like structure could be found. Possible factors contributing to the failure to undergo follicular differentiation in this study are discussed.

Influence of dermal exposure to ultraviolet radiation and coal tar (polycyclic aromatic hydrocarbons) on the skin aging process.

PubMed

Borska, Lenka; Andrys, Ctirad; Krejsek, Jan; Palicka, Vladimir; Vorisek, Viktor; Hamakova, Kvetoslava; Kremlacek, Jan; Borsky, Pavel; Fiala, Zdenek

2016-03-01

Ultraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D). To determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs). The study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT. Intensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05). Dermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dermal Filler Injection: A Novel Approach for Limiting Infarct Expansion

PubMed Central

Ryan, Liam P.; Matsuzaki, Kanji; Noma, Mio; Jackson, Benjamin M.; Eperjesi, Thomas J.; Plappert, Theodore J.; St. John-Sutton, Martin G.; Gorman, Joseph H.; Gorman, Robert C.

2011-01-01

Background Early infarct expansion after coronary occlusion compromises contractile function in perfused myocardial regions and promotes adverse long-term left ventricular (LV) remodeling. We hypothesized that injection of a tissue-expanding dermal filler material into a myocardial infarction (MI) would attenuate infarct expansion and limit LV remodeling. Methods Fifteen sheep were subjected to an anteroapical MI involving approximately 20% of the LV followed by the injection of 1.3 mL of a calcium hydroxyapatite–based dermal filler into the infarct. Real-time three-dimensional echocardiography was performed at baseline, 30 minutes after MI, and 15 minutes after injection to assess infarct expansion. Sixteen additional sheep were subjected to the same infarction and followed echocardiographically and hemodynamically for 4 weeks after MI to assess chronic remodeling. Eight animals had injection with dermal filler as described above immediately after MI, and 8 animals were injected with an equal amount of saline solution. Results All animals exhibited infarct expansion soon after coronary occlusion. The regional ejection fraction of the apex became negative after infarction, consistent with systolic dyskinesia. Injection of the dermal filler converted the apical wall motion from dyskinetic to akinetic and resulted immediately in significant decreases in global, regional, and segmental LV volumes. Chronically, relative to saline control, dermal filler injection significantly reduced LV end-systolic volume (62.2 ± 3.6 mL versus 44.5 ± 3.9 mL; p < 0.05) and improved global ejection fraction (0.295 ± 0.016 versus 0.373 ± 0.017; p < 0.05) at 4 weeks after infarction. Conclusions Injection of an acellular dermal filler into an MI immediately after coronary occlusion reduces early infarct expansion and limits chronic LV remodeling. PMID:19101288

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.

NHEXAS PHASE I ARIZONA STUDY--PESTICIDES IN DERMAL WIPES ANALYTICAL RESULTS

EPA Science Inventory

The Pesticides in Dermal Wipes data set contains analytical results for measurements of up to 3 pesticides in 177 dermal wipe samples over 177 households. Each sample was collected from the primary respondent within each household during Stage III of the NHEXAS study. The Derma...

NHEXAS PHASE I MARYLAND STUDY--PESTICIDES IN DERMAL WIPES ANALYTICAL RESULTS

EPA Science Inventory

The Pesticides in Dermal Wipe Samples data set contains analytical results for measurements of up to 8 pesticides in 40 dermal wipe samples over 40 households. Each sample was collected from the primary respondent within each household. The sampling period occurred on the last ...

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

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.

Survey of dermal protection in Washington State collision repair industry.

PubMed

Ceballos, Diana M; Fent, Kenneth W; Whittaker, Stephen G; Gaines, Linda G T; Thomasen, Jennifer M; Flack, Sheila L; Nylander-French, Leena A; Yost, Michael G; Reeb-Whitaker, Carolyn K

2011-09-01

Substantial exposure to isocyanates may occur during spray painting in autobody shops, yet information is lacking on the efficacy of the protective clothing used during spray painting. We investigated the personal and workplace factors associated with painters' dermal protection use during a large-scale exposure assessment study. Survey data indicated that 69% of painters always used gloves, with latex gloves (47%) and nitrile gloves (34%) used most frequently. Among latex glove users, 53% used thin latex (0.05-0.13 mm), 6% used medium latex (0.15-0.20 mm), and 12% used thick latex (> 0.20 mm). Among nitrile glove users, 27% used thin nitrile and 45% used medium nitrile. Sixty-three percent of painters always used coveralls, 44% preferring one particular brand. Although overspray presents an opportunity for dermal exposure to the neck and face, only 19% of painters protected these areas with personal protective equipment. Painters who always used coveralls were more likely to use gloves (odds ratio = 7.9, p = 0.061). Painters who reported ever having smoked cigarettes used gloves (p = 0.05) and coveralls (p = 0.04) more frequently. Painters who sprayed more than 34 clear coat jobs per month used coveralls most frequently (p = 0.038). Exact logistic regressions along with random sample calculations indicated that the survey results were independent of the shops. Because of the small sample size in this study, future research is warranted to corroborate these results. Studying the effectiveness of gloves and coveralls against polyurethane paints and understanding the underlying motivators and preferences for painters and business owners is needed for the development of best practices for the selection and use of dermal protection.

Evaluation of dermal wound healing activity of synthetic peptide SVVYGLR.

PubMed

Uchinaka, Ayako; Kawaguchi, Naomasa; Ban, Tsuyoshi; Hamada, Yoshinosuke; Mori, Seiji; Maeno, Yoshitaka; Sawa, Yoshiki; Nagata, Kohzo; Yamamoto, Hirofumi

2017-09-23

SVVYGLR peptide (SV peptide) is a 7-amino-acid sequence with angiogenic properties that is derived from osteopontin in the extracellular matrix and promotes differentiation of fibroblasts to myofibroblast-like cells and the production of collagen type Ⅲ by cardiac fibroblasts. However, the effects of SV peptide on dermal cells and tissue are unknown. In this study, we evaluated the effects of this peptide in a rat model of dermal wound healing. The synthetic SV peptide was added to dermal fibroblasts or keratinocytes, and their cellular motility was evaluated. In an in vivo wound healing exeriment, male rats aged 8 weeks were randomly assigned to the SV peptide treatment, non-treated control, or phosphate-buffered saline (PBS) groups. Wound healing was assessed by its repair rate and histological features. Scratch assay and cell migration assays using the Chemotaxicell method showed that SV peptide significantly promoted the cell migration in both fibroblasts and keratinocytes. In contrast the proliferation potency of these cells was not affected by SV peptide. In the rat model, wound healing progressed faster in the SV peptide-treated group than in the control and PBS groups. The histopathological analyses showed that the SV peptide treatment stimulated the migration of fibroblasts to the wound area and increased the number of myofibroblasts. Immunohistochemical staining showed a marked increase of von Willebland factor-positive neomicrovessels in the SV peptide-treated group. In conclusion, SV peptide has a beneficial function to promote wound healing by stimulating granulation via stimulating angiogenesis, cell migration, and the myofibroblastic differentiation of fibroblasts. Copyright © 2017 Elsevier Inc. All rights reserved.

Safety Evaluation of Silk Protein Film (A Novel Wound Healing Agent) in Terms of Acute Dermal Toxicity, Acute Dermal Irritation and Skin Sensitization

PubMed Central

Padol, Amol R.; Jayakumar, K.; Shridhar, N. B.; Narayana Swamy, H. D.; Narayana Swamy, M.; Mohan, K.

2011-01-01

Acute dermal toxicity study was conducted in rats. The parameters studied were body weight, serum biochemistry and gross pathology. The animals were also observed for clinical signs and mortality after the application of test film. The dermal irritation potential of silk protein film was examined using Draize test. In the initial test, three test patches were applied sequentially for 3 min, 1 and 4 hours, respectively, and skin reaction was graded. The irritant or negative response was confirmed using two additional animals, each with one patch, for an exposure period of 4 hours. The responses were scored at 1, 24, 48 and 72 hours after the patch removal. Skin sensitization study was conducted according to Buehler test in guinea pigs, in which on day 0, 7 and 14, the animals were exposed to test material for 6 hours (Induction phase) and on day 28, the animals were exposed for a period of 24 hours (Challenge phase). The skin was observed and recorded at 24 and 48 hours after the patch removal. In acute dermal toxicity study, the rats dermally treated with silk film did not show any abnormal clinical signs and the body weight, biochemical parameters and gross pathological observations were not significantly different from the control group. In acute dermal irritation study, the treated rabbits showed no signs of erythema, edema and eschar, and the scoring was given as “0” for all time points of observations according to Draize scoring system. In skin sensitization study, there were no skin reactions 24 and 48 hours after the removal of challenge patch, which was scored “0” based on Magnusson/Kligman grading scale. PMID:21430915

Treatment of Linear Scleroderma (en Coup de Sabre) With Dermal Fat Grafting.

PubMed

Barin, Ensar Zafer; Cinal, Hakan; Cakmak, Mehmet Akif; Tan, Onder

2016-05-01

Linear scleroderma, also known as "en coup de sabre," is a subtype of localized scleroderma that warrants aesthetic correction because it appears on the forehead region in children. To report dermal fat grafting as a novel and effective surgical treatment option in linear scleroderma. Under local anesthesia, a dermal fat graft was successfully placed into a subcutaneous pocket that was prepared underneath the depressed scar. The donor site was closed primarily. No early or late complications developed postoperatively. After 1-year follow-up, the dermal fat graft was viable, the depressed scar was adequately augmented, and a good aesthetic result and patient satisfaction were obtained. We believe that dermal fat grafting is a cost-effective option and provides a long-lasting aesthetic outcome in the management of linear scleroderma. © The Author(s) 2015.

NHEXAS PHASE I ARIZONA STUDY--METALS IN DERMAL WIPES ANALYTICAL RESULTS

EPA Science Inventory

The Metals in Dermal Wipes data set contains analytical results for measurements of up to 11 metals in 179 dermal wipe samples over 179 households. Each sample was collected from the primary respondent within each household during Stage III of the NHEXAS study. The sampling per...

NHEXAS PHASE I MARYLAND STUDY--METALS IN DERMAL WIPES ANALYTICAL RESULTS

EPA Science Inventory

The Metals in Dermal Wipe Samples data set contains analytical results for measurements of up to 4 metals in 343 dermal wipe samples over 80 households. Each sample was collected from the primary respondent within each household. The sampling period occurred on the first day of...

Porcine dermal lesions produced by 1540-nm laser radiation pulses

NASA Astrophysics Data System (ADS)

Roach, William P.; Johnson, Thomas E.

2001-07-01

Completion of recent studies within our group indicates a breed-based difference in dermal response to 1540 nm 0.8 millisecond laser pulses. Laser exposure to Yucatan Mini- Pigs (highly pigmented skin) and Yorkshire pigs (lightly pigmented skin) demonstrate statistical differences between the ED50's of the two breeds. Laser delivery is accomplished using an Er:Glass system producing 1540 nm of light at millisecond exposure times and in the range of 5 to 95 J/cm2. Dermal lesion development was evaluated for acute, 1 hour, and 24-hour post exposure presentation. Our data contradicts the theory that water absorption is the sole mechanism of dermal tissue damage observed from 1540 nm laser exposures, as skin chromophores appear to play a role in lesion development.

Pesticide risk assessment: A study on inhalation and dermal exposure to 2,4-D and paraquat among Malaysian paddy farmers.

PubMed

Baharuddin, Mohd Rafee B; Sahid, Ismail B; Noor, Mohamad Azhar B Mohd; Sulaiman, Norela; Othman, Fadzil

2011-01-01

A cross-section analytical study was conducted to evaluate the risk of pesticide exposure to those applying the Class II pesticides 2,4-D and paraquat in the paddy-growing areas of Kerian, Perak, Malaysia. It investigated the influence of weather on exposure as well as documented health problems commonly related to pesticide exposure. Potential inhalation and dermal exposure for 140 paddy farmers (handlers of pesticides) were assessed. Results showed that while temperature and humidity affected exposure, windspeed had the strongest impact on pesticide exposure via inhalation. However, the degree of exposure to both herbicides via inhalation was below the permissible exposure limits set by United States National Institute of Occupational Safety and Health (NIOSH). Dermal Exposure Assessment Method (DREAM) readings showed that dermal exposure with manual spraying ranged from moderate to high. With motorized sprayers, however, the level of dermal exposure ranged from low to moderate. Dermal exposure was significantly negatively correlated with the usage of protective clothing. Various types of deleterious health effects were detected among users of manual knapsack sprayers. Long-term spraying activities were positively correlated with increasing levels of the gamma-glutamyl transpeptidase (GGT) liver enzyme. The type of spraying equipment, usage of proper protective clothing and adherence to correct spraying practices were found to be the most important factors influencing the degree of pesticide exposure among those applying pesticides.

Dermal insecticide residues from birds inhabiting an orchard

USGS Publications Warehouse

Vyas, N.B.; Spann, J.W.; Hulse, C.S.; Gentry, S.; Borges, S.L.

2007-01-01

The US Environmental Protection Agency conducts risk assessments of insecticide applications to wild birds using a model that is limited to the dietary route of exposure. However, free-flying birds are also exposed to insecticides via the inhalation and dermal routes. We measured azinphos-methyl residues on the skin plus feathers and the feet of brown-headed cowbirds (Molothrus ater) in order to quantify dermal exposure to songbirds that entered and inhabited an apple (Malus x domestica) orchard following an insecticide application. Exposure to azinphos-methyl was measured by sampling birds from an aviary that was built around an apple tree. Birds sampled at 36 h and 7-day post-application were placed in the aviary within 1 h after the application whereas birds exposed for 3 days were released into the aviary 4-day post-application. Residues on vegetation and soil were also measured. Azinphos-methyl residues were detected from the skin plus feathers and the feet from all exposure periods. Our results underscore the importance of incorporating dermal exposure into avian pesticide risk assessments.

Optical coherence tomography for image-guided dermal filler injection and biomechanical evaluation

NASA Astrophysics Data System (ADS)

Singh, Manmohan; Wang, Shang; Yee, Richard W.; Han, Zhaolong; Aglyamov, Salavat R.; Larin, Kirill V.

2017-02-01

Dermal fillers are a very popular anti-ag ing treatment with estimated sales in the billions of dollars and millions of procedures performed. As the aging population continues to grow, these figures are only e xpected to increase. Dermal fillers have various compositions depending on their intended applicati on. Reactions to dermal fillers can be severe, such as ischemic events and filler migration to the eyes. Howe ver, these adverse reactions are rare. Nevertheless, the capability to perform imag e-guided filler injections would minimize th e risk of such reacti ons. In addition, the biomechanical properties of various fillers have been evalua ted, but there has been no investigation on the effects of filler on the biomechanical properties of skin. In this work, we utilize optical cohe rence tomography (OCT) for visualizing dermal filler injections with micrometer-scale sp atial resolution. In addition, we utilize noncontact optical coherence elastography (OCE) to quantify the changes in the biomechan ical properties of pig skin after the dermal filler injections. OCT was successfully able to visualize the dermal filler injecti on process, and OCE showed that the viscoelasticity of the pig skin was increased locally at the filler injection sites. OCT may be able to provide real-time image guidance in 3D, and when combined with functional OCT techniques such as optical microangiography, could be used to avoid blood vessels during the injection.

[Penile augmentation and elongation using autologous dermal-fat strip grafting].

PubMed

Yang, Zhe; Li, Yang-qun; Tang, Yong; Chen, Wen; Li, Qiang; Zhou, Chuan-de; Zhao, Mu-xin; Hu, Chun-mei

2012-05-01

To investigate the effect of autologous dermal-fat strip grafting in penile augmentation and elongation. From May 2004 to December 2010, 24 patients underwent penile enhancement with free dermal-fat strip grafting. Through suprapubic incision, the superior suspensory ligament and part deep suspensory ligament are cutted off to lengthen the penis. The resulted dead space is filled with the autologous dermal-fat strip (6.0-9.5 cm in length, 1.2-1.5 cm in width and 0.6-0.8 cm in depth) to enhance the penis. Primary healing was achieved in 23 cases. Incisional fat liquefaction happened in one case which healed after dressing change. The penile appearance was satisfactory both at rest or erection. The penile length and circumference increased by 2.5-4.8 cm (average, 3.2 cm) and 1.8-3.0 cm (average, 2.4 cm), respectively. 18 patients were followed up for 3 months to 5 years. All the patients were satisfactory on the cosmetic and functional results. No complication happened. It is safe and effective for penile augmention and elongation with autologous dermal-fat strip grafting and disconnection of penile suspensory ligament.

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

Posterior repair with perforated porcine dermal graft.

PubMed

Taylor, G Bernard; Moore, Robert D; Miklos, John R; Mattox, T Fleming

2008-01-01

To compare postoperative vaginal incision separation and healing in patients undergoing posterior repair with perforated porcine dermal grafts with those that received grafts without perforations. Secondarily, the tensile properties of the perforated and non-perforated grafts were measured and compared. This was a non-randomized retrospective cohort analysis of women with stage II or greater rectoceles who underwent posterior repair with perforated and non-perforated porcine dermal grafts (Pelvicol(TM) CR Bard Covington, GA USA). The incidence of postoperative vaginal incision separation (dehiscence) was compared. A secondary analysis to assess graft tensile strength, suture pull out strength, and flexibility after perforation was performed using standard test method TM 0133 and ASTM bending and resistance protocols. Seventeen percent of patients (21/127) who received grafts without perforations developed vaginal incision dehiscence compared to 7% (5/71) of patients who received perforated grafts (p = 0.078). Four patients with vaginal incision dehiscence with non-perforated grafts required surgical revision to facilitate healing. Neither tensile strength or suture pull out strength were significantly different between perforated and non-perforated grafts (p = 0.81, p = 0.29, respectively). There was no difference in the flexibility of the two grafts (p = 0.20). Perforated porcine dermal grafts retain their tensile properties and are associated with fewer vaginal incision dehiscences.

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.

Dermal Sensitization Potential of Triethyleneglycol Dinitrate (TEGDN) in Guinea Pigs

DTIC Science & Technology

1989-01-01

mutagenicity assay, acute oral toxicity tests in rats and mice, acute dermal toxicity in rabbits, dermal and ocular irritation studies in rabbits, and...conditions: 85E0102 had diffuse tracheitis, mild endocarditis , mild hepatitis, and diffuse pigment granules in the small intestine; 85E0103 had mild...severe ulceration progressing to necrosis. Sensitization is manifested as indirect inflammation mediated by components of the immune system in

Assessment of platelet-derived growth factor using A splinted full thickness dermal wound model in bearded dragons (Pogona vitticeps).

PubMed

Keller, Krista A; Paul-Murphy, Joanne; Weber, E P Scott; Kass, Philip H; Guzman, Sanchez-Migallon David; Park, Shin Ae; Raghunathan, Vijay Krishna; Gustavsen, Kate A; Murphy, Christopher J

2014-12-01

Wounds in reptiles are a common reason for presentation to a veterinarian. At this time there is limited information on effective topical medications to aid in wound closure. The objectives of this study were to translate the splinted, full-thickness dermal wound model, validated in mice, to the bearded dragon (Pogona vitticeps) and to determine the effect of topical becaplermin (BP), a platelet-derived growth factor (0.01%), on the rate of wound closure. Ten bearded dragons were anesthetized and two full-thickness cutaneous wounds were made on the dorsum of each lizard. Encircling splints were applied surrounding each wound and subsequently covered by a semi-occlusive dressing. Five lizards had one wound treated with BP and the adjacent wound treated with a vehicle control. Five additional lizards had one wound treated with saline and the second wound treated with a vehicle control. Wounds were imaged daily, and the wound area was measured using digital image analysis. The change in percentage wound closure over 17 days and the time to 50% wound closure was compared among the four treatment groups. There was no significant difference in wound closure rates between BP-treated and saline-treated wounds or in the time to 50% wound closure between any treatments. Vehicle-treated wounds adjacent to saline-treated wounds closed significantly slower than did BP (P < 0.010), saline (P < 0.001), and vehicle-treated wounds adjacent to BP-treated wounds (P < 0.013). Our preliminary study indicates that the splinted wound model, with modifications, may be used to determine wound closure rates in bearded dragons. When compared with saline, BP did not have a significant effect on wound closure rates, while the vehicle alone delayed wound closure. Histologic analysis of experimentally created wounds throughout the wound healing process is needed to further evaluate the effects of these treatments on reptile dermal wound healing.

Liposomal gene transfer of keratinocyte growth factor improves wound healing by altering growth factor and collagen expression.

PubMed

Pereira, Clifford T; Herndon, David N; Rocker, Roland; Jeschke, Marc G

2007-05-15

Growth factors affect the complex cascade of wound healing; however, interaction between different growth factors during dermal and epidermal regeneration are still not entirely defined. In the present study, we thought to determine the interaction between keratinocyte growth factor (KGF) administered as liposomal cDNA with other dermal and epidermal growth factors and collagen synthesis in an acute wound. Rats received an acute wound and were divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.22 microg, vehicle), or liposomes plus the KGF cDNA (2.2 microg) and Lac-Z gene (0.22 microg). Histological and immunohistochemical techniques were used to determine growth factor, collagen expression, and dermal and epidermal structure. KGF cDNA increased insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), and fibroblast growth factor (FGF), decreased transforming growth factor-beta (TGF-beta), while it had no effect on platelet-derived growth factor (PDGF) levels in the wound. KGF cDNA significantly increased collagen Type IV at both the wound edge as well as the wound bed, while it had no effect on collagen Type I and III. KGF cDNA increased re-epithelialization, improved dermal regeneration, and increased neovascularization. Exogenous administered KGF cDNA causes increases in IGF-I, IGF-BP3, FGF, and collagen IV and decreases TGF-beta concentration. KGF gene transfer accelerates wound healing without causing an increase in collagen I or III.

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.

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

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

Characterization of dermal plates from armored catfish Pterygoplichthys pardalis reveals sandwich-like nanocomposite structure.

PubMed

Ebenstein, Donna; Calderon, Carlos; Troncoso, Omar P; Torres, Fernando G

2015-05-01

Dermal plates from armored catfish are bony structures that cover their body. In this paper we characterized structural, chemical, and nanomechanical properties of the dermal plates from the Amazonian fish Pterygoplichthys pardalis. Analysis of the morphology of the plates using scanning electron microscopy (SEM) revealed that the dermal plates have a sandwich-like structure composed of an inner porous matrix surrounded by two external dense layers. This is different from the plywood-like laminated structure of elasmoid fish scales but similar to the structure of osteoderms found in the dermal armour of some reptiles and mammals. Chemical analysis performed using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results revealed similarities between the composition of P. pardalis plates and the elasmoid fish scales of Arapaima gigas. Reduced moduli of P. pardalis plates measured using nanoindentation were also consistent with reported values for A. gigas scales, but further revealed that the dermal plate is an anisotropic and heterogeneous material, similar to many other fish scales and osteoderms. It is postulated that the sandwich-like structure of the dermal plates provides a lightweight and tough protective layer. Copyright © 2015 Elsevier Ltd. All rights reserved.

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...

Non-cross-linked porcine acellular dermal matrices for abdominal wall reconstruction.

PubMed

Burns, Nadja K; Jaffari, Mona V; Rios, Carmen N; Mathur, Anshu B; Butler, Charles E

2010-01-01

Non-cross-linked porcine acellular dermal matrices have been used clinically for abdominal wall repair; however, their biologic and mechanical properties and propensity to form visceral adhesions have not been studied. The authors hypothesized that their use would result in fewer, weaker visceral adhesions than polypropylene mesh when used to repair ventral hernias and form a strong interface with the surrounding musculofascia. Thirty-four guinea pigs underwent inlay repair of surgically created ventral hernias using polypropylene mesh, porcine acellular dermal matrix, or a composite of the two. The animals were killed at 4 weeks, and the adhesion tenacity grade and surface area of the repair site involved by adhesions were measured. Sections of the repair sites, including the implant-musculofascia interface, underwent histologic analysis and uniaxial mechanical testing. The incidence of bowel adhesions to the repair site was significantly lower with the dermal matrix (8 percent, p < 0.01) and the matrix/mesh combination (0 percent, p < 0.001) than with polypropylene mesh alone (70 percent). The repairs made with the matrix or the matrix/mesh combination, compared with the polypropylene mesh repairs, had significantly lower mean adhesion surface areas [12.8 percent (p < 0.001), 9.2 percent (p < 0.001), and 79.9 percent] and grades [0.6 (p < 0.001), 0.6 (p < 0.001), and 2.9]. The dermal matrix underwent robust cellular and vascular infiltration. The ultimate tensile strength at the implant-musculofascia interface was similar in all groups. Porcine acellular dermal matrix becomes incorporated into the host tissue and causes fewer adhesions to repair sites than does polypropylene mesh, with similar implant-musculofascia interface strength. It also inhibits adhesions to adjacent dermal matrix in the combination repairs. It has distinct advantages over polypropylene mesh for complex abdominal wall repairs, particularly when material placement directly over bowel is

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.

Chitosan solutions as injectable systems for dermal filler applications: Rheological characterization and biological evidence.

PubMed

Halimi, C; Montembault, A; Guerry, A; Delair, T; Viguier, E; Fulchiron, R; David, L

2015-01-01

A new generation of dermal filler for wrinkle filler based on chitosan was compared to current hyaluronic acid-based dermal fillers by using a new rheological performance criterion based on viscosity during injection related to Newtonian viscosity. In addition an in vivo evaluation was performed for preclinical evidence of chitosan use as dermal filler. In this way, biocompatibility and dermis reconstruction was evaluated on a pig model.

Characterization and evolution of dermal filaments from patients with Morgellons disease

PubMed Central

Middelveen, Marianne J; Mayne, Peter J; Kahn, Douglas G; Stricker, Raphael B

2013-01-01

Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either self-implanted by patients or accidentally adhering to lesions, and conclude that patients with this disease have delusions of infestation. We present histological observations and electron microscopic imaging from representative Morgellons disease samples revealing that dermal filaments in these cases are keratin and collagen in composition and result from proliferation and activation of keratinocytes and fibroblasts in the epidermis. Spirochetes were detected in the dermatological specimens from our study patients, providing evidence that Morgellons disease is associated with an infectious process. PMID:23326202

Characterization and evolution of dermal filaments from patients with Morgellons disease.

PubMed

Middelveen, Marianne J; Mayne, Peter J; Kahn, Douglas G; Stricker, Raphael B

2013-01-01

Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either self-implanted by patients or accidentally adhering to lesions, and conclude that patients with this disease have delusions of infestation. We present histological observations and electron microscopic imaging from representative Morgellons disease samples revealing that dermal filaments in these cases are keratin and collagen in composition and result from proliferation and activation of keratinocytes and fibroblasts in the epidermis. Spirochetes were detected in the dermatological specimens from our study patients, providing evidence that Morgellons disease is associated with an infectious process.

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.

Linking existing in vitro dermal absorption data to physicochemical properties: Contribution to the design of a weight-of-evidence approach for the safety evaluation of cosmetic ingredients with low dermal bioavailability.

PubMed

Ates, Gamze; Steinmetz, Fabian P; Doktorova, Tatyana Yordanova; Madden, Judith C; Rogiers, Vera

2016-04-01

To characterize the risk of cosmetic ingredients when threshold toxicity is assumed, often the "margin of safety" (MoS) is calculated. This uncertainty factor is based on the systemic no observable (adverse) effect level (NO(A)EL) which can be derived from in vivo repeated dose toxicity studies. As in vivo studies for the purpose of the cosmetic legislation are no longer allowed in Europe and a validated in vitro alternative is not yet available, it is no longer possible to derive a NO(A)EL value for a new cosmetic ingredient. Alternatively, cosmetic ingredients with a low dermal bioavailability might not need repeated dose data, as internal exposure will be minimal and systemic toxicity might not be an issue. This study shows the possibility of identifying compounds suspected to have a low dermal bioavailability based on their physicochemical properties (molecular weight, melting point, topological polar surface area and log P) and their in vitro dermal absorption data. Although performed on a limited number of compounds, the study suggests a strategic opportunity to support the safety assessor's reasoning to omit a MoS calculation and to focus more on local toxicity and mutagenicity/genotoxicity for ingredients for which limited systemic exposure is to be expected. Copyright © 2016 Elsevier Inc. All rights reserved.

Predictors of dermal exposures to polycyclic aromatic compounds among hot-mix asphalt paving workers.

PubMed

Cavallari, Jennifer M; Osborn, Linda V; Snawder, John E; Kriech, Anthony J; Olsen, Larry D; Herrick, Robert F; McClean, Michael D

2012-03-01

The primary objective of this study was to identify the source and work practices that affect dermal exposure to polycyclic aromatic compounds (PACs) among hot-mix asphalt (HMA) paving workers. Four workers were recruited from each of three asphalt paving crews (12 workers) and were monitored for three consecutive days over 4 weeks for a total of 12 sampling days per worker (144 worker days). Two sampling weeks were conducted under standard conditions for dermal exposures. The third week included the substitution of biodiesel for diesel oil used to clean tools and equipment and the fourth week included dermal protection through the use of gloves, hat and neck cloth, clean pants, and long-sleeved shirts. Dermal exposure to PACs was quantified using two methods: a passive organic dermal (POD) sampler specifically developed for this study and a sunflower oil hand wash technique. Linear mixed-effects models were used to evaluate predictors of PAC exposures. Dermal exposures measured under all conditions via POD and hand wash were low with most samples for each analyte being below the limit of the detection with the exception of phenanthrene and pyrene. The geometric mean (GM) concentrations of phenanthrene were 0.69 ng cm(-2) on the polypropylene layer of the POD sampler and 1.37 ng cm(-2) in the hand wash sample. The GM concentrations of pyrene were 0.30 ng cm(-2) on the polypropylene layer of the POD sampler and 0.29 ng cm(-2) in the hand wash sample. Both the biodiesel substitution and dermal protection scenarios were effective in reducing dermal exposures. Based on the results of multivariate linear mixed-effects models, increasing frequency of glove use was associated with significant (P < 0.0001) reductions for hand wash and POD phenanthrene and pyrene concentrations; percent reductions ranged from 40 to 90%. Similar reductions in hand wash concentrations of phenanthrene (P = 0.01) and pyrene (P = 0.003) were observed when biodiesel was substituted for diesel oil

Cell plasticity in wound healing: paracrine factors of M1/ M2 polarized macrophages influence the phenotypical state of dermal fibroblasts

PubMed Central

2013-01-01

Background Macrophages and fibroblasts are two major players in tissue repair and fibrosis. Despite the relevance of macrophages and fibroblasts in tissue homeostasis, remarkably little is known whether macrophages are able to influence the properties of fibroblasts. Here we investigated the role of paracrine factors secreted by classically activated (M1) and alternatively activated (M2) human macrophages on human dermal fibroblasts (HDFs). Results HDFs stimulated with paracrine factors from M1 macrophages showed a 10 to > 100-fold increase in the expression of the inflammatory cytokines IL6, CCL2 and CCL7 and the matrix metalloproteinases MMP1 and MMP3. This indicates that factors produced by M1 macrophages induce a fibroblast phenotype with pro-inflammatory and extracellular matrix (ECM) degrading properties. HDFs stimulated with paracrine factors secreted by M2 macrophages displayed an increased proliferation rate. Interestingly, the M1-activated pro-inflammatory fibroblasts downregulated, after exposure to paracrine factors produced by M2 macrophages or non-conditioned media, the inflammatory markers as well as MMPs and upregulated their collagen production. Conclusions Paracrine factors of M1 or M2 polarized macrophages induced different phenotypes of HDFs and the HDF phenotypes can in turn be reversed, pointing to a high dynamic plasticity of fibroblasts in the different phases of tissue repair. PMID:23601247

Penile Reconstruction with Skin Grafts and Dermal Matrices: Indications and Management

PubMed Central

Triana Junco, Paloma; Dore, Mariela; Nuñez Cerezo, Vanesa; Jimenez Gomez, Javier; Miguel Ferrero, Miriam; Díaz González, Mercedes; Lopez-Pereira, Pedro; Lopez-Gutierrez, Juan Carlos

2017-01-01

Introduction  The penis eventually needs specific cutaneous coverage in the context of reconstructive procedures following trauma or congenital anomalies. Local flaps are the first choice but are not always available after multiple previous procedures. In these cases, skin graft and dermal matrices should be considered. Materials and Methods  This study was a retrospective review of the past 4 years of four patients with severe loss of penile shaft skin who underwent skin reconstruction. Dermal matrices and skin grafts were utilized. Dermal matrices were placed for a median of 4.5 weeks (3.0–6.0 weeks). The skin graft was harvested from the inner thigh region for split-thickness skin graft (STSG) and the inguinal region for full-thickness skin graft (FTSG). Results  The four patients presented with complete loss of skin in the penile shaft. One patient had a vesical exstrophy, one had a buried penis with only one corpus cavernosum, one had a wide congenital lymphedema of the genitalia, and one had a lack of skin following circumcision at home. They underwent reconstruction with three patients undergoing split-thickness skin graft; two dermal matrices; and one full-thickness graft, respectively, thereby achieving a good cosmetic and functional result. There were no complications, and all the patients successfully accepted the graft. Conclusion  Dermal matrices and skin grafts may serve as effective tools in the management of severe penile skin defects unable to be covered with local flaps. PMID:28868232

Dynamic interactions between dermal macrophages and Staphylococcus aureus.

PubMed

Feuerstein, Reinhild; Kolter, Julia; Henneke, Philipp

2017-01-01

The dermis, a major reservoir of immune cells in immediate vicinity to the colonizing skin microflora, serves as an important site of host-pathogen interactions. Macrophages (Mϕ) are the most frequent resident immune cell type in the dermis. They protect the host from invasive infections by highly adapted bacteria, such as staphylococci via pattern recognition of bacterial effectors, phagocytosis, and recruitment of other myeloid cells from the blood. Already under homeostatic conditions, the dermal Mϕ population receives a dynamic input of monocytes invading from the bloodstream. This quantitative renewal is promoted further at the beginning of life, when prenatally seeded cells are rapidly replaced and in healing phases after injuries or infections. Here, we discuss the potential implications of the dynamic dermal Mϕ biology on the establishment and maintenance of immunity against Staphylococcus aureus, which can either be a harmless colonizer or an invasive pathogen. The understanding of the heterogeneity of the "mature" dermal Mϕ compartment driven both by the influx of differentiating monocytes and by a bone marrow-independent Mϕ persistence and expansion may help to explain failing immunity and immunopathology originating from the skin, the important interface between host and environment. © Society for Leukocyte Biology.

Inhalational and dermal exposures during spray application of biocides.

PubMed

Berger-Preiss, Edith; Boehncke, Andrea; Könnecker, Gustav; Mangelsdorf, Inge; Holthenrich, Dagmar; Koch, Wolfgang

2005-01-01

Data on inhalational and potential dermal exposures during spray application of liquid biocidal products were generated. On the one hand, model experiments with different spraying devices using fluorescent tracers were carried out to investigate the influence of parameters relevant to the exposure (e.g. spraying equipment, nozzle size, direction of application). On the other hand, measurements were performed at selected workplaces (during disinfection operations in food and feed areas; pest control operations for private, public and veterinary hygiene; wood protection and antifouling applications) after application of biocidal products such as Empire 20, Responsar SC, Omexan-forte, Actellic, Perma-forte; Fendona SC, Pyrethrum mist; CBM 8, Aldekol Des 03, TAD CID, Basileum, Basilit. The measurements taken in the model rooms demonstrated dependence of the inhalation exposure on the type of spraying device used, in the following order: "spraying with low pressure" < "airless spraying" < "fogging" indicating that the particle diameter of the released spray droplets is the most important parameter. In addition inhalation exposure was lowest when the spraying direction was downward. Also for the potential dermal exposure, the spraying direction was of particular importance: overhead spraying caused the highest contamination of body surfaces. The data of inhalational and potential dermal exposures gained through workplace measurements showed considerable variation. During spraying procedures with low-pressure equipments, dose rates of active substances inhaled by the operators ranged from 7 to 230 microg active substance (a.s.)/h. An increase in inhaled dose rates (6-33 mg a.s./h) was observed after use of high application volumes/time unit during wood protection applications indoors. Spraying in the veterinary sector using medium-pressure sprayers led to inhaled dose rates between 2 and 24mga.s./h. The highest inhaled dose rates were measured during fogging (114 mg a

Prosurvival Factors Improve Functional Engraftment of Myogenically Converted Dermal Cells into Dystrophic Skeletal Muscle

PubMed Central

Muir, Lindsey A.; Murry, Charles E.

2016-01-01

In Duchenne muscular dystrophy (DMD) and other muscle wasting disorders, cell therapies are a promising route for promoting muscle regeneration by supplying a functional copy of the missing dystrophin gene and contributing new muscle fibers. The clinical application of cell-based therapies is resource intensive, and it will therefore be necessary to address key limitations that reduce cell engraftment into muscle tissue. A pressing issue is poor donor cell survival following transplantation, which in preclinical studies limits the ability to effectively test the impact of cell-based therapy on whole muscle function. We, therefore, sought to improve engraftment and the functional impact of in vivo myogenically converted dermal fibroblasts (dFbs) using a prosurvival cocktail (PSC) that includes heat shock followed by treatment with insulin-like growth factor-1, a caspase inhibitor, a Bcl-XL peptide, a KATP channel opener, basic fibroblast growth factor, Matrigel, and cyclosporine A. Advantages of dFbs include compatibility with the autologous setting, ease of isolation, and greater proliferative potential than DMD satellite cells. dFbs expressed tamoxifen-inducible MyoD and carried a mini-dystrophin gene driven by a muscle-specific promoter. After transplantation into muscles of mdx mice, a 70% reduction in donor cells was observed by day 5, and a 94% reduction by day 28. However, treatment with PSC gave a nearly three-fold increase in donor cells in early engraftment, and greatly increased the number of donor-contributed muscle fibers and total engrafted area in transplanted muscles. Furthermore, dystrophic muscles that received dFbs with PSC displayed reduced injury with eccentric contractions and an increase in maximum isometric force. Thus, enhancing survival of myogenic cells increases engraftment and improves structure and function of dystrophic muscle. PMID:27503462

Prosurvival Factors Improve Functional Engraftment of Myogenically Converted Dermal Cells into Dystrophic Skeletal Muscle.

PubMed

Muir, Lindsey A; Murry, Charles E; Chamberlain, Jeffrey S

2016-09-07

In Duchenne muscular dystrophy (DMD) and other muscle wasting disorders, cell therapies are a promising route for promoting muscle regeneration by supplying a functional copy of the missing dystrophin gene and contributing new muscle fibers. The clinical application of cell-based therapies is resource intensive, and it will therefore be necessary to address key limitations that reduce cell engraftment into muscle tissue. A pressing issue is poor donor cell survival following transplantation, which in preclinical studies limits the ability to effectively test the impact of cell-based therapy on whole muscle function. We, therefore, sought to improve engraftment and the functional impact of in vivo myogenically converted dermal fibroblasts (dFbs) using a prosurvival cocktail (PSC) that includes heat shock followed by treatment with insulin-like growth factor-1, a caspase inhibitor, a Bcl-XL peptide, a K ATP channel opener, basic fibroblast growth factor, Matrigel, and cyclosporine A. Advantages of dFbs include compatibility with the autologous setting, ease of isolation, and greater proliferative potential than DMD satellite cells. dFbs expressed tamoxifen-inducible MyoD and carried a mini-dystrophin gene driven by a muscle-specific promoter. After transplantation into muscles of mdx mice, a 70% reduction in donor cells was observed by day 5, and a 94% reduction by day 28. However, treatment with PSC gave a nearly three-fold increase in donor cells in early engraftment, and greatly increased the number of donor-contributed muscle fibers and total engrafted area in transplanted muscles. Furthermore, dystrophic muscles that received dFbs with PSC displayed reduced injury with eccentric contractions and an increase in maximum isometric force. Thus, enhancing survival of myogenic cells increases engraftment and improves structure and function of dystrophic muscle.

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...

Sinonasal hemangiopericytomas: a clinicopathologic and immunohistochemical study of seven cases.

PubMed

Catalano, P J; Brandwein, M; Shah, D K; Urken, M L; Lawson, W; Biller, H F

1996-01-01

Sinonasal hemangiopericytoma (SNHPC) is a rare lesion usually of low-grade malignant potential. Aggressive and metastatic cases are uncommon, and experience using adjuvant therapy on these cases has been limited. Tumor-induced osteomalacia has a very rare association with SNHPC. Further, the diagnosis of SNHPC remains one of histologic-pattern recognition. Traditionally, immunohistochemistry has aided in excluding other diagnoses; only vimentin has been consistently expressed by the tumor spindle cells of HPC. Recent studies have shown that Factor XIIIa is also expressed by HPC, (as well as tumors of fibrohistiocytic differentiation) and hence may be yet another helpful positive marker in establishing an immunohistochemical profile. We identified 7 patients at this institution with SNHPC from 1990 to 1994. Immunohistochemistry was performed on seven formalin-fixed paraffin-embedded tumors utilizing antibodies to factor XIIIa as well as antibodies to vimentin, factor VIII, muscle-specific antigen, cytokeratin, and S-100. All 7 patients were initially seen with nasal obstruction or epistaxis and underwent surgical resection. The period of follow-up was from 3 months to 14 years (mean 54 months) for 7 patients. Three patients had recurrent disease after 3, 5, and 10 years. The first 2 were known to have been originally treated by polypectomy. One patient required adjuvant radiotherapy for metastatic disease and local extension. One patient was initially seen with tumor-induced osteomalacia which dramatically improved following resection of the lesion. The immunohistochemical profile revealed strong expression of vimentin in 7/7 cases, and of factor XIIIa in 4/7 cases; tumor cells did not express the other markers studied. Adequate surgical resection with negative margins appears to be the appropriate therapy for SNHPC. Our 1 case associated with tumor-induced osteomalacia was reversible after surgical excision of the tumor. The immunohistochemical results suggest that

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.

DERMAL DRUG LEVELS OF ANTIBIOTIC (CEPHALEXIN) DETERMINED BY ELECTROPORATION AND TRANSCUTANEOUS SAMPLING (ETS) TECHNIQUE

PubMed Central

Sammeta, SM; Vaka, SRK; Murthy, S. Narasimha

2009-01-01

The purpose of this project was to assess the validity of a novel “Electroporation and transcutaneous sampling (ETS)” technique for sampling cephalexin from the dermal extracellular fluid (ECF). This work also investigated the plausibility of using cephalexin levels in the dermal ECF as a surrogate for the drug level in the synovial fluid. In vitro and in vivo studies were carried out using hair less rats to assess the workability of ETS. Cephalexin (20mg/kg) was administered i.v. through tail vein and the time course of drug concentration in the plasma was determined. In the same rats, cephalexin concentration in the dermal ECF was determined by ETS and microdialysis techniques. In a separate set of rats, only intraarticular microdialysis was carried out determine the time course of cephalexin concentration in synovial fluid. The drug concentration in the dermal ECF determined by ETS and microdialysis did not differ significantly from each other and so as were the pharmacokinetic parameters. The results provide validity to the ETS technique. Further, there was a good correlation (~0.9) between synovial fluid and dermal ECF levels of cephalexin indicating that dermal ECF levels could be used as a potential surrogate for cephalexin concentration in the synovial fluid. PMID:19067398

Functional factor XIII-A is exposed on the stimulated platelet surface

PubMed Central

Mitchell, Joanne L.; Lionikiene, Ausra S.; Fraser, Steven R.; Whyte, Claire S.; Booth, Nuala A.

2014-01-01

Factor XIII (FXIII) stabilizes thrombi against fibrinolysis by cross-linking α2-antiplasmin (α2AP) to fibrin. Cellular FXIII (FXIII-A) is abundant in platelets, but the extracellular functions of this pool are unclear because it is not released by classical secretion mechanisms. We examined the function of platelet FXIII-A using Chandler model thrombi formed from FXIII-depleted plasma. Platelets stabilized FXIII-depleted thrombi in a transglutaminase-dependent manner. FXIII-A activity on activated platelets was unstable and was rapidly lost over 1 hour. Inhibiting platelet activation abrogated the ability of platelets to stabilize thrombi. Incorporating a neutralizing antibody to α2AP into FXIII-depleted thrombi revealed that the stabilizing effect of platelet FXIII-A on lysis was α2AP dependent. Platelet FXIII-A activity and antigen were associated with the cytoplasm and membrane fraction of unstimulated platelets, and these fractions were functional in stabilizing FXIII-depleted thrombi against lysis. Fluorescence confocal microscopy and flow cytometry revealed exposure of FXIII-A on activated membranes, with maximal signal detected with thrombin and collagen stimulation. FXIII-A was evident in protruding caps on the surface of phosphatidylserine-positive platelets. Our data show a functional role for platelet FXIII-A through exposure on the activated platelet membrane where it exerts antifibrinolytic function by cross-linking α2AP to fibrin. PMID:25331118

Differential Apoptosis in Mucosal and Dermal Wound Healing

PubMed Central

Johnson, Ariel; Francis, Marybeth; DiPietro, Luisa Ann

2014-01-01

Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase–polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; p<0.05), Casp7 (at D5; p<0.05), Trp53 (at 24 h and D5; p<0.05), Tnfrsf1b (at 24 h; p<0.05), FasR (at 24 h, D5, and D7; p<0.05), and Casp8 (at 24 h; p<0.05) and significantly lower gene expression of Tradd (at 24 h; p<0.05). Innovation: Our observations indicate differential execution of apoptosis in oral wound healing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing. PMID:25493209

Polypoid dermal hemangiopericytoma: a case report.

PubMed

Pollock, A M; Sweeney, E C

1998-10-01

A polypoid dermal lesion with histologic, immunohistochemical, and ultrastructural features of hemangiopericytoma is described. Such tumors, arising in the dermis, are exceptionally rare, and whereas the tumor bears some resemblance to meningioma-like tumors of the skin and the well-recognized animal counterpart, canine hemangiopericytoma, it is histologically distinct.

40 CFR 798.4100 - Dermal sensitization.

Code of Federal Regulations, 2014 CFR

2014-07-01

... system selected is recommended; (ii) Animals may act as their own controls or groups of induced animals... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4100 Dermal... hypersensitive state is developed. (3) Induction exposure is an experimental exposure of a subject to a test...

40 CFR 798.4100 - Dermal sensitization.

Code of Federal Regulations, 2012 CFR

2012-07-01

... system selected is recommended; (ii) Animals may act as their own controls or groups of induced animals... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4100 Dermal... hypersensitive state is developed. (3) Induction exposure is an experimental exposure of a subject to a test...

40 CFR 798.4100 - Dermal sensitization.

Code of Federal Regulations, 2013 CFR

2013-07-01

... system selected is recommended; (ii) Animals may act as their own controls or groups of induced animals... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4100 Dermal... hypersensitive state is developed. (3) Induction exposure is an experimental exposure of a subject to a test...

40 CFR 798.4100 - Dermal sensitization.

Code of Federal Regulations, 2011 CFR

2011-07-01

... system selected is recommended; (ii) Animals may act as their own controls or groups of induced animals... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4100 Dermal... hypersensitive state is developed. (3) Induction exposure is an experimental exposure of a subject to a test...

A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration

PubMed Central

Zhang, Peipei; Kling, Russell E; Ravuri, Sudheer K; Kokai, Lauren E; Rubin, J Peter; Chai, Jia-ke

2014-01-01

Alopecia is an exceedingly prevalent problem effecting men and women of all ages. The standard of care for alopecia involves either transplanting existing hair follicles to bald areas or attempting to stimulate existing follicles with topical and/or oral medication. Yet, these treatment options are fraught with problems of cost, side effects, and, most importantly, inadequate long-term hair coverage. Innovative cell-based therapies have focused on the dermal papilla cell as a way to grow new hair in previously bald areas. However, despite this attention, many obstacles exist, including retention of dermal papilla inducing ability and maintenance of dermal papilla productivity after several passages of culture. The use of adipocyte lineage cells, including adipose-derived stem cells, has shown promise as a cell-based solution to regulate hair regeneration and may help in maintaining or increasing dermal papilla cells inducing hair ability. In this review, we highlight recent advances in the understanding of the cellular contribution and regulation of dermal papilla cells and summarize adipocyte lineage cells in hair regeneration. PMID:25383178

Cleft Palate Fistula Closure Utilizing Acellular Dermal Matrix.

PubMed

Emodi, Omri; Ginini, Jiriys George; van Aalst, John A; Shilo, Dekel; Naddaf, Raja; Aizenbud, Dror; Rachmiel, Adi

2018-03-01

Fistulas represent failure of cleft palate repair. Secondary and tertiary fistula repair is challenging, with high recurrence rates. In the present retrospective study, we review the efficacy of using acellular dermal matrix as an interposition layer for cleft palate fistula closure in 20 consecutive patients between 2013 and 2016. Complete fistula closure was obtained in 16 patients; 1 patient had asymptomatic recurrent fistula; 2 patients had partial closure with reduction of fistula size and minimal nasal regurgitation; 1 patient developed a recurrent fistula without changes in symptoms (success rate of 85%). We conclude that utilizing acellular dermal matrix for cleft palate fistula repair is safe and simple with a high success rate.

Cleft Palate Fistula Closure Utilizing Acellular Dermal Matrix

PubMed Central

Emodi, Omri; van Aalst, John A.; Shilo, Dekel; Naddaf, Raja; Aizenbud, Dror; Rachmiel, Adi

2018-01-01

Summary: Fistulas represent failure of cleft palate repair. Secondary and tertiary fistula repair is challenging, with high recurrence rates. In the present retrospective study, we review the efficacy of using acellular dermal matrix as an interposition layer for cleft palate fistula closure in 20 consecutive patients between 2013 and 2016. Complete fistula closure was obtained in 16 patients; 1 patient had asymptomatic recurrent fistula; 2 patients had partial closure with reduction of fistula size and minimal nasal regurgitation; 1 patient developed a recurrent fistula without changes in symptoms (success rate of 85%). We conclude that utilizing acellular dermal matrix for cleft palate fistula repair is safe and simple with a high success rate. PMID:29707449

The Use of Meshed Dermal Autograft in Breast Reconstruction.

PubMed

Zingaretti, Nicola; Guarneri, Gianni Franco; De Biasio, Fabrizio; Shoeib, Mohamed A; Parodi, Pier Camillo

2018-02-01

The advantages and disadvantages of acellular dermal matrix (ADM) in breast reconstruction have been well documented. ADM is commonly used in breast reconstruction, but it adds cost to the procedure and has been associated with an increased risk of seroma, flap necrosis and infectious complications. A dermal autograft may be a useful alternative to matrices, and it has a lot of advantages: more biocompatible and more likely to be retained as a free graft, low cost, well tolerated, readily available and integrated. This report discusses a new surgical technique that uses an autologous dermis, which was harvested from the controlateral breast in patients having simultaneous breast reduction/mastopexy. Before the insertion, the autologous dermal matrix was meshed at a ratio of 3:1 to increase the graft surface area, to provide additional draining and to improve the engraftment of the autologous dermal matrix. Consequently, the resulting meshed graft allows for the cover of the inferior pole of a larger breast size implant and decreases the complication rate. In our clinic, this method was used on five women; there was one limited necrosis of the mastectomy flaps. The described technique is straightforward and reliable, it adds minimally to the operative time, and it eliminates costs and covers a bigger part of the prosthesis and promises good results. No Level Assigned 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 .

Dermis, acellular dermal matrix, and fibroblasts from different layers of pig skin exhibit different profibrotic characteristics: evidence from in vivo study

PubMed Central

Zuo, Yanhai; Lu, Shuliang

2017-01-01

To explore the profibrotic characteristics of the autografted dermis, acellular dermal matrix, and dermal fibroblasts from superficial/deep layers of pig skin, 93 wounds were established on the dorsa of 7 pigs. 72 wounds autografted with the superficial/deep dermis and acellular dermal matrix served as the superficial/deep dermis and acellular dermal matrix group, respectively, and were sampled at 2, 4, and 8 weeks post-wounding. 21 wounds autografted with/without superficial/deep dermal fibroblasts served as the superficial/deep dermal fibroblast group and the control group, respectively, and were sampled at 2 weeks post-wounding. The hematoxylin and eosin staining showed that the wounded skin thicknesses in the deep dermis group (superficial acellular dermal matrix group) were significantly greater than those in the superficial dermis group (deep acellular dermal matrix group) at each time point, the thickness of the cutting plane in the deep dermal fibroblast group was significantly greater than that in the superficial dermal fibroblast group and the control group. The western blots showed that the α-smooth muscle actin expression in the deep dermis group (superficial acellular dermal matrix group) was significantly greater than that in the superficial dermis group (deep acellular dermal matrix group) at each time point. In summary, the deep dermis and dermal fibroblasts exhibited more profibrotic characteristics than the superficial ones, on the contrary, the deep acellular dermal matrix exhibited less profibrotic characteristics than the superficial one. PMID:28423561

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

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.

Dermal fibroblasts from acute inflamed atopic dermatitis lesions display increased eotaxin/CCL11 responsiveness to interleukin-4 stimulation.

PubMed

Gahr, N; Fölster-Holst, R; Weichenthal, M; Christophers, E; Schröder, J-M; Bartels, J

2011-03-01

The presence of eosinophils and/or eosinophil-derived products in the dermis is characteristic for involved skin of patients with atopic dermatitis and contributes to the observed tissue injury. CCL11 is a potent chemoattractant and activator of human eosinophils and interleukin (IL)-4 is a potent inducer of CCL11 expression in dermal fibroblasts. As increased fibroblast CCL11 expression may explain eosinophilic infiltration of involved skin areas in atopic dermatitis, we asked whether dermal fibroblasts from atopic patients differ from fibroblasts of healthy individuals in their ability to express CCL11. We compared IL-4-induced CCL11 mRNA expression using reverse transcription-polymerase chain reaction from cultured dermal fibroblasts derived from biopsies of chronic lesional and acute lesional atopic skin as well as from skin biopsies derived from normal skin of healthy donors. Considerable variability in IL-4-induced relative CCL11 mRNA expression was detected in fibroblasts derived from biopsies of different individuals. The lowest median IL-4 concentration inducing half maximal CCL11 mRNA expression (EC(50)) was found in fibroblasts derived from acute inflamed atopic lesions. Inducibility of CCL11 in dermal fibroblasts upon stimulation with Th2 cytokines explains the tissue eosinophilia observed in the presence of Th2 cytokines and the localization of eosinophils to the dermis. Decreased EC(50) values of IL-4-induced CCL11 expression in fibroblasts from acute inflamed atopic skin lesions indicates increased IL-4 responsiveness in these lesions and further substantiates the special role for IL-4-induced dermal fibroblast CCL11 expression in acute lesions. Variable CCL11 expression in fibroblasts from different patients with atopic dermatitis indicates heterogeneity of factors determining atopic phenotype in atopic dermatitis. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Immunopotentiator from Pantoea agglomerans 1 (IP-PA1) Promotes Murine Hair Growth and Human Dermal Papilla Cell Gene Expression.

PubMed

Wakame, Koji; Okawa, Hiroshi; Komatsu, Ken-Ich; Nakata, Akifumi; Sato, Keisuke; Ingawa, Hiroyuki; Kohchi, Chie; Nishizawa, Takashi; Soma, Gen-Ichiro

2016-07-01

The lipopolysaccharide (LPS)-like compound derived from Pantoea agglomerans (immunopotentiator from Pantoea agglomerans 1 (IP-PA1)) has been used not only as dietary supplement or cosmetic for humans, but also by Japanese veterinarians as an anti-tumor, anti-allergy, "keep a fine coat of fur" and hair growth-promoting functional food for dogs and cats. In the present study, we focused on the hair growth-promoting effects of IP-PA1 on a hair-shaved animal model and its mechanism of action. We also investigated its potential on gene expression after stimulating human dermal papilla cells with IP-PA1. The hair on the back of a C3H/HeN mouse was shaved and IP-PA1 was orally administered or applied to the skin. The status of hair growth was observed and recorded for 14 days. Skin was collected and histological tissue examination was performed with respect to hair growth status using hematoxylin and eosin staining. After IP-PA1 administration (2 and 10 μg/ml) to human dermal papilla cell culture system for 24 h, fibroblast growth factor-7 (FGF-7) and vascular endothelial growth factor (VEGF) mRNA expression were measured using real-time polymerase chain reaction (PCR) analysis. IP-PA1, when given orally, showed a tendency to promote hair growth in mice. In addition, skin application also significantly promoted hair growth, while histopathological examinations further demonstrated hair elongation from dermal papilla cells. In the human dermal papilla cell culture system, significant FGF-7 and VEGF mRNA expressions were observed (p<0.05). An underlying mechanism of gene expression by which IP-PA1 promotes hair growth was suggested to be different from that of medicine and traditional hair tonics, such as minoxidil and adenosine. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Liposome-containing Hibiscus sabdariffa calyx extract formulations with increased antioxidant activity, improved dermal penetration and reduced dermal toxicity.

PubMed

Pinsuwan, Sirirat; Amnuaikit, Thanaporn; Ungphaiboon, Suwipa; Itharat, Arunporn

2010-12-01

Hibiscus sabdariffa Linn, or Roselle, is a medicinal plant used extensively in traditional Thai medicine since ancient times. The extracts of Roselle calyces possess antioxidant activity and have potential for development as active ingredients in cosmetic products. However the limitations of using Roselle extracts in cosmetics are its low skin permeation and dermal irritation. Liposome technology is an obvious approach that might overcome these problems. Liposome formulations of standardized Roselle extracts were developed with various lipid components. The formulation showing the highest entrapment efficiency was selected for stability, skin permeation and dermal irritability studies. The liposome formulation with the highest entrapment efficiency (83%) and smalôlest particle size (332 mm) was formulated with phosphatidylcholine from soybean (SPC): Tween 80: deoxycholic acid (DA); 84:16:2.5 weight ratio, total lipid of 200 g/mL and 10% w/v Roselle extract in final liposomal preparation. This liposome formulation was found to be stable after storage at 4 degrees C, protected from light, for 2 months. The in vitro skin permeation studies, using freshly excised pig skin and modified Franz-diffusion cells, showed that the liposome formulation was able to considerably increased the rate of permeation of active compounds in Roselle extracts compared to the Roselle extract solution. The in vivo dermal irritability testing on rabbit skin showed that the liposome formulation dramatically decreased skin irritability compared to the unformulated extract. These results showed that the liposomes containing Roselle extracts had good stability, high entrapment efficacy, increased skin permeation and low skin irritation.

U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--METALS IN DERMAL ANALYTICAL RESULTS

EPA Science Inventory

The Metals in Dermal Wipes data set contains analytical results for measurements of up to 11 metals in 86 dermal wipe samples over 86 households. Each sample was collected from the primary respondent within each household. The sampling period occurred on the first day of the fi...

Acute dermal toxicity and sensitization studies of novel nano-enhanced UV absorbers.

PubMed

Piasecka-Zelga, Joanna; Zelga, Piotr; Górnicz, Magdalena; Strzelczyk, Paweł; Sójka-Ledakowicz, Jadwiga

2015-01-01

Many employees working outside are exposed to the harmful effects of UV radiation. A growing problem is also sensitization to textile materials and allergic reactions to active compounds. Groups of inorganic UV blockers with nanoparticles may provide superior properties over organic UV absorbers with relatively less potential of provoking dermatitis. To assess acute dermal irritation and sensitization of nano UV absorbers. Five UV absorbers with nano-sized particles (Z11, TiO2 - SiO2 [TDPK], TK44, TK11, A8G) and 2 vehicles (paste-based on 10% PEG, and dispersion with 1% HEC) were tested. Acute dermal irritation was tested using group of 3 rabbits for each absorber. The sensitization study was carried out on groups of 15 guinea pigs for each tested textile with a UV absorber showing an Ultraviolet Protection Factor (UPF)>40. This research was designed according to OECD Test Guideline No. 404 and 406, and 21 rabbits and 60 guinea pigs were used in the study. In acute dermal irritation, Z11 and A8G modifiers and the analyzed paste gave results of 0.047 to 0.33 which classifies them as barely perceptible irritants, whereas the other analyzed modifiers and dispersion gave results of 0.00 and were classified as nonirritating. Only the textile with TK 11 did not have UPF>40. The analyzed barrier materials were classified as nonsenitizers (TDPK, A8G) or mild sensitizers (TK44, Z11). None of the analyzed materials or modifiers induced major skin reactions in animals. Therefore, they present low risk of provoking skin reactions in humans.

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 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.

Triolein reduces MMP-1 upregulation in dermal fibroblasts generated by ROS production in UVB-irradiated keratinocytes.

PubMed

Leirós, Gustavo J; Kusinsky, Ana Gabriela; Balañá, María Eugenia; Hagelin, Karin

2017-02-01

Cytokine production and oxidative stress generated by ultraviolet radiation B (UVB) skin exposure are main factors of skin photoaging. Interleukin-6 (IL-6) produced by irradiated keratinocytes is proposed to have a role in metalloproteinases (MMPs) expression activation in dermal fibroblasts. We examined the effect of triolein treatment of UVB-irradiated keratinocytes on MMP1 (interstitial collagenase) expression response of dermal fibroblasts. We assayed UVB-irradiated keratinocytes soluble signals, mainly IL-6 and reactive oxygen species (ROS). IL-6 expression and ROS generation were assayed in UVB-irradiated keratinocytes. MMP1 mRNA expression response was assayed in fibroblasts grown in keratinocytes conditioned medium. We evaluated the effect of treating keratinocytes with triolein on IL-6 expression and ROS generation in keratinocytes, and MMP1 expression in fibroblasts. The irradiation of epidermal cells with sublethal UVB doses increased IL-6 expression and ROS generation. Conditioned culture medium collected from keratinocytes was used to culture dermal fibroblasts. MMP1 mRNA expression increase was observed in fibroblasts cultured in medium collected from UVB-irradiated keratinocytes. Triolein treatment reduced the IL-6 expression and ROS generation in keratinocytes and this effect was reflected in downregulation of MMP1 expression in fibroblasts. Triolein reduces both the expression of IL-6 and ROS generation in irradiated keratinocytes. It seems to exert an anti-inflammatory and anti-oxidative stress effect on irradiated keratinocytes that in turn reduces MMP1 expression in dermal fibroblasts. Collectively, these results indicate that triolein could act as a photoprotective agent. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Three-dimensional organization of dermal fibroblasts by macromass culture.

PubMed

Deshpande, Manisha

2008-01-01

The three-dimensional organization of cells by high-cell-seeding-density culture, termed 'macromass culture', is described. By macromass culture, dermal fibroblasts can be made to organize themselves into a unified three-dimensional form without the aid of a scaffold, and macroscopic constructs, named macromasses, can be made wholly from cells. The sole factor causing three-dimensional organization is culture of cells at high cell seeding density per unit area. No scaffold or extraneous matrix is used for the generation of macromasses; they are of completely cellular origin. No other agents or external influences such as tissue-inducing chemicals, tissue-inducing growth factors, substratum with special properties, rotational culture, centrifugation etc. are employed for macromass formation, and all seeded cells become part of the cohesive construct. These three-dimensional constructs have the potential for use as in vitro tissue analogues, and a possible application for in vitro cytotoxicity testing is demonstrated.

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.

Successful treatment of complex traumatic and surgical wounds with a foetal bovine dermal matrix.

PubMed

Hayn, Ernesto

2014-12-01

A foetal bovine dermal repair scaffold (PriMatrix, TEI Biosciences) was used to treat complex surgical or traumatic wounds where the clinical need was to avoid skin flaps and to build new tissue in the wound that could be reepithelialised from the wound margins or closed with a subsequent application of a split-thickness skin graft (STSG). Forty-three consecutive cases were reviewed having an average size of 79·3 cm(2) , 50% of which had exposed tendon and/or bone. In a subset of wounds (44·7%), the implantation of the foetal dermal collagen scaffold was also augmented with negative pressure wound therapy (NPWT). Complete wound healing was documented in over 80% of the wounds treated, whether the wound was treated with the foetal bovine dermal scaffold alone (95·2%) or when supplemented with NPWT (82·4%). The scaffold successfully incorporated into wounds with exposed tendon and/or bone to build vascularised, dermal-like tissue. The new tissue in the wound supported STSGs however, in the majority of the cases (88·3%); wound closure was achieved through reepithelialisation of the incorporated dermal scaffold by endogenous wound keratinocytes. The foetal bovine dermal repair scaffold was found to offer an effective alternative treatment strategy for definitive closure of challenging traumatic or surgical wounds on patients who were not suitable candidates for tissue flaps. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Hair Follicle Generation by Injections of Adult Human Follicular Epithelial and Dermal Papilla Cells into Nude Mice

PubMed Central

Nilforoushzadeh, Mohammadali; Rahimi Jameh, Elham; Jaffary, Fariba; Abolhasani, Ehsan; Keshtmand, Gelavizh; Zarkob, Hajar; Mohammadi, Parvaneh; Aghdami, Nasser

2017-01-01

Objective Dermal papilla and hair epithelial stem cells regulate hair formation and the growth cycle. Damage to or loss of these cells can cause hair loss. Although several studies claim to reconstitute hairs using rodent cells in an animal model, additional research is needed to develop a stable human hair follicle reconstitution protocol. In this study, we have evaluated hair induction by injecting adult cultured human dermal papilla cells and a mixture of hair epithelial and dermal papilla cells in a mouse model. Materials and Methods In this experimental study, discarded human scalp skins were used to obtain dermal papilla and hair epithelial cells. After separation, cells were cultured and assessed for their characteristics. We randomly allocated 15 C57BL/6 nude mice into three groups that received injections in their dorsal skin. The first group received cultured dermal papilla cells, the second group received a mixture of cultured epithelial and dermal papilla cells, and the third group (control) received a placebo [phosphate-buffered saline (PBS-)]. Results Histopathologic examination of the injection sites showed evidence of hair growth in samples that received cells compared with the control group. However, the group that received epithelial and dermal papilla cells had visible evidence of hair growth. PKH tracing confirmed the presence of transplanted cells in the new hair. Conclusion Our data showed that injection of a combination of adult human cultured dermal papilla and epithelial cells could induce hair growth in nude mice. This study emphasized that the combination of human adult cultured dermal papilla and epithelial cells could induce new hair in nude mice. PMID:28670518

Rheological properties of cross-linked hyaluronic acid dermal fillers.

PubMed

Santoro, Stefano; Russo, Luisa; Argenzio, Vincenzo; Borzacchiello, Assunta

2011-01-01

Ha based dermal fillers in recent years aroused big interest in the area of cosmetic surgery for the rejuvenation of the dermis. There is not a ideal dermal filler (DF) for all applications and in commerce there are many types of DF that differ for their chemical-physical properties. So the aim of this paper is to correlate the rheological and physical properties of different DF to their clinical effectiveness. In this frame the samples have been subjected to oscillation dynamic rheological and steady shear measurements. Our results demonstrate that the viscoelastic properties of different DF varie strongly also considering fillers of the same family. Furthermore it was found that the materials physical properties influence significantly the performance of dermal filler. In particular the clinical data appear to correlate with the concentration of the polymer and with the product between the concentration and the percent elasticity, so these should be crucial parameters for the clinical performance of DF. So rheological data can be a tool to have an indication on the efficacy and longevity of DF but it has to be considered that production technology, in-vivo-conditions, injector skills and experience influence them also significantly.

PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis.

PubMed

Cho, John S; Fang, Terry C; Reynolds, Taylor L; Sofia, Daniel J; Hamann, Stefan; Burkly, Linda C

2016-01-01

Systemic sclerosis (SSc) is a chronic autoimmune disorder that can result in extensive tissue damage in the skin and, in advanced cases, internal organs. Vasculopathy, aberrant immune activation, and tissue fibrosis are three hallmarks of the disease that have been identified, with vasculopathy and aberrant immunity being amongst the earliest events. However, a mechanistic link between these processes has not been established. Here, we have identified a novel role of platelet derived growth factor-BB (PDGF-BB)/PDGFRβ activation in combination with dermal injury induced by bleomycin as a driver of early, aberrant expression of interferon stimulatory genes (ISGs) and inflammatory monocyte infiltration. Activation of PDGFRβ in combination with bleomycin-induced dermal injury resulted in increased dermal thickness, vascular density, monocyte/macrophage infiltration, and exacerbation of tissue injury. Many of these features were dependent on IFNAR-signaling, and an increase in the number of interferon-beta (IFN-β) producing monocytes cells was found in the skin lesions. Taken together, these results identify a novel link between PDGFRβ activation, and Type I IFN-driven vascular maintenance and monocyte/macrophage cell recruitment, and provide a potential explanation linking key features of SSc that were previously thought to be unrelated.

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...

The Dermal Apron Technique for Immediate Implant Socket Management: A Novel Technique.

PubMed

Levin, Barry P

2016-01-01

With immediate implant placement and provisionalization (IIP) in the esthetic zone, measures to counter hard and soft tissue loss are frequently necessary. To reduce the morbidity associated with bone and connective tissue procurement, various exogenous materials are utilized. The "Dermal Apron Technique" presented in this article demonstrates the use of a composite bone particulate (allograft/xenograft) plus a dermal allograft, adapted around screw-retained temporary crowns and secured within a subperiosteal pouch. The purpose is to augment the thickness of peri-implant mucosa for the purpose of preserving ridge dimensions and preventing mucosal recession. Controlled studies are required to further support its use. Clinical significance: Soft tissue health and harmony are critical for successful implant therapy in the esthetic regions of the dentition. Often, autogenous soft tissue grafts are used to augment peri-implant soft tissues. The Dermal Apron Technique is a method, that in specific situations, obviates the need for autogenous grafting. This reduces treatment time and morbidity associated with procurement of these grafts. The Dermal Apron Technique is used simultaneous with immediate placement and provisionalization and can improve long-term esthetic outcomes for patients. © 2016 Wiley Periodicals, Inc.

Race Does Not Predict Melanocyte Heterogeneous Responses to Dermal Fibroblast-Derived Mediators

PubMed Central

Sirimahachaiyakul, Pornthep; Sood, Ravi F.; Muffley, Lara A.; Seaton, Max; Lin, Cheng-Ta; Qiao, Liang; Armaly, Jeffrey S.; Hocking, Anne M.; Gibran, Nicole S.

2015-01-01

Introduction Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery. Wound depth and patient characteristics influence scar pigmentation. However, we know little about the pathophysiology leading to hyperpigmentation in healed shallow wounds and hypopigmentation in deep dermal wound scars. We sought to determine whether dermal fibroblast signaling influences melanocyte responses. Methods and Materials Epidermal melanocytes from three Caucasians and three African-Americans were genotyped for single nucleotide polymorphisms (SNPs) across the entire genome. Melanocyte genetic profiles were determined using principal component analysis. We assessed melanocyte phenotype and gene expression in response to dermal fibroblast-conditioned medium and determined potential mesenchymal mediators by proteome profiling the fibroblast-conditioned medium. Results Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium. Genetic profiling for SNPs in receptors for 13 identified soluble fibroblast-secreted mediators demonstrated considerable heterogeneity, potentially explaining the variable melanocyte responses to fibroblast-conditioned medium. Discussion Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring. PMID:26418010

Dermal exposure to monoterpenes during wood work.

PubMed

Eriksson, Kare; Wiklund, Leif

2004-06-01

The dermal exposure to the suspected allergenic monoterpenes [small alpha]-pinene, [small beta]-pinene and [capital Delta](3)-carene was assessed with a patch sampling technique. The patch used was made of activated charcoal sandwiched between two layers of cotton cloth. Patches were fastened at 12 different spots on a sampling overall and at the front of a cap to estimate the potential exposure of the body. Fastening two patches on a cotton glove, one patch representing the dorsal side and one patch representing the palm of the hand respectively, assessed the exposure on the hands. Sampling was carried out during collecting of pine and spruce boards in sawmills and during sawing of pine wood pieces in joinery shops respectively. The potential dermal exposure of the total body was 29.0-1 890 mg h(-1) with a geometric mean (GM) of 238 mg h(-1) during sawing. During collecting the GM was estimated to 100 mg h(-1) with a range of 12.2-959 mg h(-1). The hands had a mean exposure of 9.24 mg h(-1) during sawing and 3.25 mg h(-1) during collecting respectively. The good correlation between the mass of contamination on the individual body parts and the potential body exposure indicates that sampling can be performed on one body part to give a good estimation of the potential body exposure. Monoterpenes were detected at patches fastened underneath the protective clothing indicating a contamination of the skin of the worker. The patch used may overestimate the dermal exposure.

Insights into reptile dermal contaminant exposure: Reptile skin permeability to pesticides.

PubMed

Weir, Scott M; Talent, Larry G; Anderson, Todd A; Salice, Christopher J

2016-07-01

There is growing interest in improving ecological risk assessment exposure estimation, specifically by incorporating dermal exposure. At the same time, there is a growing interest in amphibians and reptiles as receptors in ecological risk assessment, despite generally receiving less research than more traditional receptors. Previous research has suggested that dermal exposure may be more important than previously considered for reptiles. We measured reptile skin permeability to four pesticides (thiamethoxam, malathion, tebuthiuron, trifluralin) using ventral skin samples. All four pesticides penetrated the skin but generally had low permeability. There was no apparent relationship between physicochemical properties and permeability coefficients. Malathion had a significantly greater permeability rate at all time points compared to the other pesticides. Tebuthiuron had a greater permeability than thiamethoxam. Reptiles and mammals appear to have similar skin permeability suggesting that dermal exposure estimates for mammals may be representative of reptiles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Management of gingival recession with acellular dermal matrix graft: A clinical study

PubMed Central

Balaji, V. R.; Ramakrishnan, T.; Manikandan, D.; Lambodharan, R.; Karthikeyan, B.; Niazi, Thanvir Mohammed; Ulaganathan, G.

2016-01-01

Aims and Objectives: Obtaining root coverage has become an important part of periodontal therapy. The aims of this studyare to evaluate the clinical efficacy of acellular dermal matrix graft in the coverage of denuded roots and also to examine the change in the width of keratinized gingiva. Materials and Methods: A total of 20 sites with more than or equal to 2 mm of recession depth were taken into the study, for treatment with acellular dermal matrix graft. The clinical parameters such as recession depth, recession width, width of keratinized gingiva, probing pocket depth (PD), and clinical attachment level (CAL) were measured at the baseline, 8th week, and at the end of the study (16th week). The defects were treated with a coronally positioned pedicle graft combined with acellular dermal matrix graft. Results: Out of 20 sites treated with acellular dermal matrix graft, seven sites showed complete root coverage (100%), and the mean root coverage obtained was 73.39%. There was a statistically significant reduction in recession depth, recession width, and probing PD. There was also a statistically significant increase in width of keratinized gingiva and also gain in CAL. The postoperative results were both clinically and statistically significant (P < 0.0001). Conclusion: The results of this study were esthetically acceptable to the patients and clinically acceptable in all cases. From this study, it may be concluded that acellular dermal matrix graft is an excellent substitute for autogenous graft in coverage of denuded roots. PMID:27829749

A systematic review of dermal fillers for age-related lines and wrinkles.

PubMed

Sturm, Lana P; Cooter, Rodney D; Mutimer, Keith L; Graham, John C; Maddern, Guy J

2011-01-01

Dermal fillers are gaining popularity for rapid aesthetic improvement. Long-term efficacy and safety have not been well documented. The aim of this systematic review was to assess the safety and efficacy of injectable dermal fillers compared with other facial augmentation techniques for the management of age-related lines and wrinkles. Studies including patients receiving injectable semi-permanent or permanent dermal fillers for age-related lines and wrinkles were included in this review. Efficacy outcomes (including changes in skin thickness and patient satisfaction) and safety outcomes (including mortality, lumps and infections) were examined. Three randomized control trials and six case series were included. Permanent and semi-permanent dermal fillers improved subjective ratings of appearance and resulted in higher patient satisfaction than temporary fillers. Long-term efficacy appeared good in the few studies that reported it. Short-term safety appeared favourable. Lumps were reported in all but one study but received little follow-up. Long-term safety data were limited. The treatment of age-related lines and wrinkles with permanent and semi-permanent dermal fillers is more efficacious compared with temporary fillers in those studies that compared them. Case series evidence suggests that these fillers achieve their objective, which is to decrease the visible effects of age-related changes. These fillers appear at least as safe as temporary fillers in the short term in those studies that compared them. Long-term safety could not be determined. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

Absorption, distribution, metabolism and excretion of loxoprofen after dermal application of loxoprofen gel to rats.

PubMed

Sawamura, Ryoko; Kazui, Miho; Kurihara, Atsushi; Izumi, Takashi

2014-11-01

1. Loxoprofen (LX), is a prodrug of the pharmacologically active form, trans-alcohol metabolite (trans-OH form), which shows very potent analgesic effect. In this study, the pharmacokinetics and metabolism of [(14)C]LX-derived radioactivity after dermal application of [(14)C]LX gel (LX-G) to rats were evaluated. 2. The area under concentration-time curve (AUC0-∞) of radioactivity in the plasma after the dermal application was 13.6% of that of the oral administration (p < 0.05). 3. After the dermal application, the radioactivity remained in the skin and skeletal muscle at the treated site for 168 h, whereas the AUC0-168 h of the radioactivity concentration in every tissue examined except the treated site was statistically lower than that after the oral administration (p < 0.05). 4. The trans-OH form was observed at high levels in the treated skin site at 0.5 h. Metabolite profiles in plasma, non-treated skin site and urine after the dermal application were comparable with those after the oral administration. 5. Renal excretion was the main route of elimination after the dermal application. 6. In conclusion, compared to the oral administration, the dermal application of [(14)C]LX-G showed lower systemic and tissue exposure with higher exposure in the therapeutic target site. The radioactivity revealed similar metabolite profiles in both administration routes.

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...

Transdermal Delivery of Iron Using Soluble Microneedles: Dermal Kinetics and Safety.

PubMed

Modepalli, Naresh; Shivakumar, H Nanjappa; McCrudden, Maeliosa T C; Donnelly, Ryan F; Banga, Ajay; Murthy, S Narasimha

2016-03-01

Currently, the iron compounds are administered via oral and parenteral routes in patients of all ages, to treat iron deficiency. Despite continued efforts to supplement iron via these conventional routes, iron deficiency still remains the most prevalent nutritional disorder all over the world. Transdermal replenishment of iron is a novel, potential approach of iron replenishment. Ferric pyrophosphate (FPP) was found to be a suitable source of iron for transdermal replenishment. The safety of FPP was assessed in this project by challenging the dermal fibroblast cells with high concentration of FPP. The cell viability assay and reactive oxygen species assay were performed. The soluble microneedle array was developed, incorporated with FPP and the kinetics of free iron in the skin; extracellular fluid following dermal administration of microneedle array was investigated in hairless rats. From the cell based assays, FPP was selected as one of the potential iron sources for transdermal delivery. The microneedles were found to dissolve in the skin fluid within 3 hours of administration. The FPP concentration in the dermal extracellular fluid declined after complete dissolution of the microneedle array. Overall, the studies demonstrated the safety of FPP for dermal delivery and the feasibility of soluble microneedle approach for transdermal iron replenishment therapy. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Dominant-negative Sox18 function inhibits dermal papilla maturation and differentiation in all murine hair types.

PubMed

Villani, Rehan; Hodgson, Samantha; Legrand, Julien; Greaney, Jessica; Wong, Ho Yi; Pichol-Thievend, Cathy; Adolphe, Christelle; Wainwight, Brandon; Francois, Mathias; Khosrotehrani, Kiarash

2017-05-15

SOX family proteins SOX2 and SOX18 have been reported as being essential in determining hair follicle type; however, the role they play during development remains unclear. Here, we demonstrate that Sox18 regulates the normal differentiation of the dermal papilla of all hair types. In guard (primary) hair dermal condensate (DC) cells, we identified transient Sox18 in addition to SOX2 expression at E14.5, which allowed fate tracing of primary DC cells until birth. Similarly, expression of Sox18 was detected in the DC cells of secondary hairs at E16.5 and in tertiary hair at E18.5. Dominant-negative Sox18 mutation (opposum) did not prevent DC formation in any hair type. However, it affected dermal papilla differentiation, restricting hair formation especially in secondary and tertiary hairs. This Sox18 mutation also prevented neonatal dermal cells or dermal papilla spheres from inducing hair in regeneration assays. Microarray expression studies identified WNT5A and TNC as potential downstream effectors of SOX18 that are important for epidermal WNT signalling. In conclusion, SOX18 acts as a mesenchymal molecular switch necessary for the formation and function of the dermal papilla in all hair types. © 2017. Published by The Company of Biologists Ltd.

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.

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.

Dermal bioaccessibility of flame retardants from indoor dust and the influence of topically applied cosmetics.

PubMed

Pawar, Gopal; Abdallah, Mohamed Abou-Elwafa; de Sáa, Eugenia Villaverde; Harrad, Stuart

2017-01-01

Despite extensive literature on their potential adverse health effects, there is a lack of information on human dermal exposure to organic flame retardant chemicals (FRs). This study applies an in vitro physiologically based extraction test to provide new insights into the dermal bioaccessibility of various FRs from indoor dust to synthetic sweat/sebum mixture (SSSM). The bioaccessible fractions of α-, β- and γ-hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) to 1:1 (sweat/sebum) mixture were 41%, 47%, 50% and 40%, respectively. For Tris-2-chloroethyl phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP) and tris-1,3-dichloropropyl phosphate (TDCIPP), bioaccessible fractions were 10%, 17% and 19%. Composition of the SSSM and compound-specific physicochemical properties were the major factors influencing the bioaccessibility of target FRs. Except for TBBPA, the presence of cosmetics (moisturising cream, sunscreen lotion, body spray and shower gel) had a significant effect (P<0.05) on the bioaccessibility of the studied FRs. The presence of cosmetics decreased the bioaccessibility of HBCDs from indoor dust, whereas shower gel and sunscreen lotion enhanced the bioaccessibility of target PFRs. Our bioaccessibility data were applied to estimate the internal exposure of UK adults and toddlers to the target FRs via dermal contact with dust. Our worst-case scenario exposure estimates fell far below available health-based limit values for TCEP, TCIPP and TDCIPP. However, future research may erode the margin of safety for these chemicals.

Pharmacokinetics of loxoprofen and its active metabolite after dermal application of loxoprofen gel to rats.

PubMed

Sawamura, R; Kazui, M; Kurihara, A; Izumi, T

2015-02-01

This study was conducted to evaluate the pharmacokinetics of loxoprofen (LX) and its active metabolite (trans-OH form) after a single dermal application of LX gel (LX-G) to rats. In the skin at the treated site, generation of the trans-OH form was detected and both LX and the trans-OH form remained at high concentrations for 24 h after dermal application. Furthermore, both LX and the trans-OH form also remained in the skeletal muscle over 24 h after the single dermal application, while they eliminated rapidly after the single oral administration. The area under the curve up to the last measurable point (AUC(0-t)) for plasma concentrations of LX or the trans-OH form after dermal application of LX-G was less than 11% of that after oral administration of LX. In addition, C(max) and AUC(0-t) increased in a saturable manner while increasing the dose. Overall, these results demonstrated that the trans-OH form was generated at the treated site with the process of dermal absorption of LX and it remained at the target site for a long period with low systemic exposure compared to oral administration.

Use of porcine acellular dermal matrix following early dermabrasion reduces length of stay in extensive deep dermal burns.

PubMed

Guo, Zhi-Qian; Qiu, Le; Gao, You; Li, Jin-Hu; Zhang, Xin-He; Yang, Xin-Lei; Peszel, April; Chen, Xu-Lin

2016-05-01

Extensive deep partial-thickness burns still seriously challenge the surgeon's abilities. This study aimed to assess the impact of early dermabrasion combined with porcine acellular dermal matrix (ADM) in extensive deep dermal burns. From September 2009 to September 2013, a total of 60 adult patients sustained greater than 50% total body surface area (TBSA) burn by hot water or gas explosion were divided into three groups based on dermabrasion: group A (early dermabrasion and porcine ADM), group B (early dermabrasion and nano-silver dressings), and group C (conservative group). The wound healing time and length of hospital stay were analyzed. Scar assessment was performed at 3 and 12 months after the injury with a modified Vancouver Scar Scale linked with TBSA (mVSS-TBSA). No significant difference was found in mean burn size, burn depth, age, male-to-female ratio, or incidence of inhalation injury between the patients in the three groups (p>0.05). Compared with groups B and C, the patients that received early dermabrasion combined with porcine ADM had a shorter wound healing time (p<0.01). The burn patients treated with early dermabrasion and porcine ADM coverage had a mean length of hospital stay of 28.3 days (±7.2), which was significantly shorter than that of groups B and C (p<0.05-0.01). The mVSS-TBSA of patients in group A was significantly improved in comparison with groups B and C at 3 and 12 months after the injury. There was no significant difference in the mortality rate between the three groups (p>0.05). Early dermabrasion combined with porcine ADM coverage facilitates wound healing, reduces the length of hospital stay, and improves esthetic and functional results in extensive deep dermal burns with burn size over 50% TBSA. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

The relationship between inadvertent ingestion and dermal exposure pathways: a new integrated conceptual model and a database of dermal and oral transfer efficiencies.

PubMed

Gorman Ng, Melanie; Semple, Sean; Cherrie, John W; Christopher, Yvette; Northage, Christine; Tielemans, Erik; Veroughstraete, Violaine; Van Tongeren, Martie

2012-11-01

Occupational inadvertent ingestion exposure is ingestion exposure due to contact between the mouth and contaminated hands or objects. Although individuals are typically oblivious to their exposure by this route, it is a potentially significant source of occupational exposure for some substances. Due to the continual flux of saliva through the oral cavity and the non-specificity of biological monitoring to routes of exposure, direct measurement of exposure by the inadvertent ingestion route is challenging; predictive models may be required to assess exposure. The work described in this manuscript has been carried out as part of a project to develop a predictive model for estimating inadvertent ingestion exposure in the workplace. As inadvertent ingestion exposure mainly arises from hand-to-mouth contact, it is closely linked to dermal exposure. We present a new integrated conceptual model for dermal and inadvertent ingestion exposure that should help to increase our understanding of ingestion exposure and our ability to simultaneously estimate exposure by the dermal and ingestion routes. The conceptual model consists of eight compartments (source, air, surface contaminant layer, outer clothing contaminant layer, inner clothing contaminant layer, hands and arms layer, perioral layer, and oral cavity) and nine mass transport processes (emission, deposition, resuspension or evaporation, transfer, removal, redistribution, decontamination, penetration and/or permeation, and swallowing) that describe event-based movement of substances between compartments (e.g. emission, deposition, etc.). This conceptual model is intended to guide the development of predictive exposure models that estimate exposure from both the dermal and the inadvertent ingestion pathways. For exposure by these pathways the efficiency of transfer of materials between compartments (for example from surfaces to hands, or from hands to the mouth) are important determinants of exposure. A database of

Dermal changes in superficial basal cell carcinoma, melanoma in situ and actinic keratosis and their implications

PubMed Central

Kazlouskaya, Viktoryia; Malhotra, Saurabh; Navarro, Raquel; Wu, Karen Nguyen; Shvartsbeyn, Marianna; Shengli, Chen; Gui, Jiang; Elston, Dirk M.

2018-01-01

Background Basal cell carcinoma (BCC) has a characteristic stroma, but less is known about the dermal characteristics associated with melanoma in situ (MIS) and actinic keratosis (AK). Materials and methods Dermal changes were studied in 301 specimens of AK, BCC and MIS. Subsequently, blinded images of dermal changes from 90 randomly selected cases of those entities were used to assess the predictive value of the dermal changes. Agreement with the final diagnosis was calculated using kappa coefficient (κ). Results Fibromyxoid stroma was present in 82% of BCC cases; fibrous stroma was seen in 25% of BCC, 58% of MIS and 35.6% of AK specimens (p <0.05). A lichenoid inflammatory infiltrate was frequently associated with AK and a perifollicular infiltrate with periadnexal fibrosis with MIS. Blinded evaluation of images of the dermal changes associated with the tumors yielded the correct diagnosis in (54.4, 41.1 and 27.8%; average 41.2%) by the three appraisers. Coefficient of agreement in blinded imaged evaluation with the actual diagnosis was higher in the BCC and MIS compared with AK (κ = 0.37, p = 0.0001; κ = 0.2, p = 0.0005 and κ = −0.06, p = 0.84, respectively). Conclusion Dermal features may be helpful in predicting the correct diagnosis when tumor is not visible. PMID:24117926

PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATES

EPA Science Inventory

PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATES

M.J.K. Selgrade, E.H. Boykin, N.H. Coates, D.L. Doerfler, S.H. Gavett
Experimental Toxicology Div., National Health and Environmental Research Laboratory, Office of Research and Developmen...

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.

Dermal absorption and urinary elimination of N-methyl-2-pyrrolidone.

PubMed

Bader, Michael; Keener, Stephen A; Wrbitzky, Renate

2005-09-01

The dermal absorption of the solvent N-methyl-2-pyrrolidone (NMP) and its elimination in urine was investigated in an experimental study. Seven volunteers were exposed to 1045 mg of liquid NMP under occlusive conditions for 2 h. Urine was collected before, during and up to 72 h after the exposure and analysed for NMP by GC/MS after liquid-liquid extraction. Additionally, the remaining NMP in the pads was determined to estimate the total dermal uptake. The concentration of NMP in urine increased rapidly after beginning of the exposure up to 1 h after the exposure was completed. A peak concentration of 1,836+/-863 microg/l was observed, the half-life in urine was 3.2 h. About 0.5% of the absorbed dose was excreted metabolically unchanged. An average dermal absorption of 5.5 mg cm(-2) h(-1) was calculated. The results of this study show that the percutaneous absorption of NMP may contribute significantly to the overall uptake of the solvent, e.g. in the workplace. Therefore, a biological monitoring of NMP exposed workers is essential for occupational-medical surveillance.

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.

Functional trade-off between strength and thermal capacity of dermal armor: Insights from girdled lizards.

PubMed

Broeckhoven, Chris; du Plessis, Anton; Hui, Cang

2017-10-01

The presence of dermal armor is often unambiguously considered the result of an evolutionary predator-prey arms-race. Recent studies focusing predominantly on osteoderms - mineralized elements embedded in the dermis layer of various extant and extinct vertebrates - have instead proposed that dermal armor might exhibit additional functionalities besides protection. Multiple divergent functionalities could impose conflicting demands on a phenotype, yet, functional trade-offs in dermal armor have rarely been investigated. Here, we use high-resolution micro-computed tomography and voxel-based simulations to test for a trade-off between the strength and thermal capacity of osteoderms using two armored cordylid lizards as model organisms. We demonstrate that high vascularization, associated with improved thermal capacity might limit the strength of osteoderms. These results call for a holistic, cautionary future approach to studies investigating dermal armor, especially those aiming to inspire artificial protective materials. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Coagulation Factor XIIIA (F13A1): Novel Perspectives in Treatment and Pharmacogenetics.

PubMed

Gemmati, Donato; Vigliano, Marco; Burini, Francesco; Mari, Rosella; El Mohsein, Hodeib Hossam Abd; Parmeggiani, Francesco; Serino, Maria L

2016-01-01

Factor XIII (FXIII) is a key molecule in the field of blood coagulation and in the last decades it has weakened attention within the field of angiogenesis and tissue repair. FXIII positively influences wound healing in several tissues by exerting multiple plasma and cellular functions. In the field of haemostasis, FXIII cross-links the neo formed fibrin fibers and supports platelet adhesion to the damaged sub-endothelium warranting a solid architecture. In addition, the pro-angiogenic functions of FXIII are directed by the interaction of vascular endothelial growth factor receptor 2 (VEGFR2) and the integrin αVβ3, on the cell membrane, favouring an important step in the formation of granulation tissue at the wound site for optimal tissue healing. Conversely, the same mechanisms could lead to undesired increased neovascularisation, for example in inflammatory bowel disease or in the retinal degenerative pathologies. The classical symptoms of FXIII deficiency span from intracranial haemorrhage to delay bleeding or the staying of chronic wounds in the skin including impaired mucosal healing. In this view, FXIII bridges primary haemostasis, coagulation and definite tissue healing. Another important recently discovered function ascribed to FXIII is its ability to limit bacterial spreading from the lesion by incorporating specific macromolecules addressed to cellular infiltration, favouring in turn cell migration and survival, as observed also in fibrin-heart cultures for stem cell recruitment. In the field of the novel prognostic biomarkers, the monitoring of the residual circulating FXIII level during acute myocardial infarction has been considered predictive of the post-myocardial infarction healing. Accordingly, adequate FXIII levels can drive and predict the prognosis of complex diseases and the outcome of the associated therapies or interventions. In addition, peculiar pharmacogenetics aspects of the FXIII gene are of extraordinary interest. The present review

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.

Quantitative dermal measurements following treatment with AirGent.

PubMed

Kobus, Kazimierz F; Dydymski, Tomasz

2010-09-01

As an alternative to other minimally-invasive approaches to facial rejuvenation, enhancement and treatment of the dermis with a compressed air molecule of hyaluronic acid (HA) is a promising method in that it lacks some of the drawbacks of other procedures. The novelty of these systems, one of which is tested in this study, is based on the supposition that jet lateral dispersion of HA produces both instant dermal augmentation and specific wound-healing processes, leading to its long-term dermal thickening. The authors report on the efficacy and safety of the AirGent system (PerfAction, Rehovot, Israel), which is a renewal system designed to initiate a wound-healing process in the dermal layer. It is a computer-guided system that delivers treatment through compressed air molecules of HA to the dermal layer of the skin. The authors treated 20 patients (a total of 105 treatment sessions) with the AirGent system between May 2008 and November 2008. Each patient received three treatments at three- to four-week intervals. Each patient's skin thickness was measured with ultrasonography pretreatment, immediately after each session, and at six months posttreatment. Seven days after the last procedure, an increase in skin thickness was observed in all patients. The most significant differences were noted in the upper lip area, where the thickness had increased by an average of 1.3 mm. Six months after the last session, an increase in skin thickness was still noted in most patients, at which time the biggest difference was noted around the eyes, where the skin remained thicker by an average of 0.77 mm over baseline. According to the results of the Global Improvement Assessment questionnaire, at the six-month follow-up to evaluate their satisfaction with the long-term results, at least 59.9% of patients still noted at least a slight improvement in their appearance. Although a small group of patients and a relatively short period of observation limit the scope of our conclusions

Compaction of fibrin clots reveals the antifibrinolytic effect of factor XIII.

PubMed

Rijken, D C; Abdul, S; Malfliet, J J M C; Leebeek, F W G; Uitte de Willige, S

2016-07-01

Essentials Factor XIIIa inhibits fibrinolysis by forming fibrin-fibrin and fibrin-inhibitor cross-links. Conflicting studies about magnitude and mechanisms of inhibition have been reported. Factor XIIIa most strongly inhibits lysis of mechanically compacted or retracted plasma clots. Cross-links of α2-antiplasmin to fibrin prevent the inhibitor from being expelled from the clot. Background Although insights into the underlying mechanisms of the effect of factor XIII on fibrinolysis have improved considerably in the last few decades, in particular with the discovery that activated FXIII (FXIIIa) cross-links α2 -antiplasmin to fibrin, the topic remains a matter of debate. Objective To elucidate the mechanisms of the antifibrinolytic effect of FXIII. Methods and Results Platelet-poor plasma clot lysis, induced by the addition of tissue-type plasminogen activator, was measured in the presence or absence of a specific FXIIIa inhibitor. Both in a turbidity assay and in a fluorescence assay, the FXIIIa inhibitor had only a small inhibitory effect: 1.6-fold less tissue-type plasminogen activator was required for 50% clot lysis in the presence of the FXIIIa inhibitor. However, when the plasma clot was compacted by centrifugation, the FXIIIa inhibitor had a strong inhibitory effect, with 7.7-fold less tissue-type plasminogen activator being required for 50% clot lysis in the presence of the FXIIIa inhibitor. In both experiments, the effects of the FXIIIa inhibitor were entirely dependent on the cross-linking of α2 -antiplasmin to fibrin. The FXIIIa inhibitor reduced the amount of α2 -antiplasmin present in the compacted clots from approximately 30% to < 4%. The results were confirmed with experiments in which compaction was achieved by platelet-mediated clot retraction. Conclusions Compaction or retraction of fibrin clots reveals the strong antifibrinolytic effect of FXIII. This is explained by the cross-linking of α2 -antiplasmin to fibrin by FXIIIa, which prevents the

Nitrotyrosine localization to dermal nerves in borderline leprosy.

PubMed

Schön, T; Hernández-Pando, R; Baquera-Heredia, J; Negesse, Y; Becerril-Villanueva, L E; Eon-Contreras, J C L; Sundqvist, T; Britton, S

2004-03-01

Nerve damage is a common and disabling feature of leprosy, with unclear aetiology. It has been reported that the peroxidizing agents of myelin lipids-nitric oxide (NO) and peroxynitrite-are produced in leprosy skin lesions. To investigate the localization of nitrotyrosine (NT)-a local end-product of peroxynitrite-in leprosy lesions where dermal nerves are affected by a granulomatous reaction. We investigated by immunohistochemistry and immunoelectron microscopy the localization of the inducible NO synthase (iNOS) and NT in biopsies exhibiting dermal nerves from patients with untreated leprosy. There were abundant NT-positive and iNOS-positive macrophages in the borderline leprosy granulomas infiltrating peripheral nerves identified by light microscopy, S-100 and neurofilament immunostaining. Immunoelectron microscopy showed NT reactivity in neurofilament aggregates and in the cell wall of Mycobacterium leprae. Our results suggest that NO and peroxynitrite could be involved in the nerve damage following borderline leprosy.

Hair growth-promoting effect of Geranium sibiricum extract in human dermal papilla cells and C57BL/6 mice.

PubMed

Boisvert, William A; Yu, Miri; Choi, Youngbin; Jeong, Gi Hee; Zhang, Yi-Lin; Cho, Sunghun; Choi, Changsun; Lee, Sanghyun; Lee, Bog-Hieu

2017-02-13

Geranium sibiricum L. has been used as a medicinal plant to treat diarrhea, bacterial infection, and cancer in Bulgaria, Peru, and Korea. However, its hair growth-promoting effect was not investigated so far. This study examined the effects of Geranium sibiricum L. extract (GSE) on hair growth, using in vitro and in vivo models. Antioxidant, proliferation and migration assay of GSE was performed with human dermal papilla cells (hDPCs). Hair-growth promoting effect was measured in animal model. Relative expression of interleukin-1, vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor beta 1 was determined by real time RT-PCR. Expression of Ki-67 and stem cell factor were analyzed by immunohistochemistry. GSE treatment proliferated and migrated human dermal papilla cells (hDPCs) more than treatment of 10 μM minoxidil. GSE significantly stimulated the expression of Ki-67 protein and the mRNA levels of hepatocyte growth factor and vascular endothelial growth factor in hDPCs. Topical application of 1,000 ppm GSE for 3 weeks promoted more significant hair growth on shaved C57BL/6 mice than did 5% minoxidil. The histological morphology of hair follicles demonstrated an active anagen phase with the induction of stem cell factor. GSE treatment significantly reduced the number of mast cells and the expression of transforming growth factor beta 1 in mouse skin tissues. These results demonstrated that GSE promotes hair growth in vitro and in vivo by regulating growth factors and the cellular response.

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

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.

Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth

PubMed Central

Higgins, Claire A.; Chen, James C.; Cerise, Jane E.; Jahoda, Colin A. B.; Christiano, Angela M.

2013-01-01

De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin. PMID:24145441

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.

Dermal exposure of applicators to chlorpyrifos on rice farms in Ghana.

PubMed

Atabila, Albert; Phung, Dung Tri; Hogarh, Jonathan N; Osei-Fosu, Paul; Sadler, Ross; Connell, Des; Chu, Cordia

2017-07-01

Studies evaluating dermal exposure to pesticides among applicators in tropical countries have largely been conducted using the patch dosimetry and hand wiping/washing techniques. This study used the more accurate whole-body dosimetry technique to evaluate dermal exposure to chlorpyrifos among applicators on rice farms in Ghana. The exposure levels were plotted as Cumulative Probability Distribution (CPD). Total Dermal Exposure (TDE) of chlorpyrifos among the median exposed and the 5% highly exposed groups during a spray event were 24 mg and 48 mg, respectively. When these were converted as a percentage of the quantity of active ingredient applied (Unit Exposure, UE), UE values of 0.03% and 0.06% were found among the median exposed and the 5% highly exposed groups, respectively. Overall, the hands were the most contaminated anatomical regions of the applicators, both in terms of proportion of TDE (39%) and skin loading (13 μg/cm 2 ). Also, the lower anatomical region was more contaminated (82% of TDE) compared to the upper anatomical region (18% of TDE). The levels of chlorpyrifos TDE among the applicators were found to be influenced by the quantity of insecticide applied and the height of the crops sprayed (p < 0.05). The pesticide UE data of the present study can be used to estimate the levels of dermal exposure under similar pesticide use scenarios among applicators. The findings of the present study suggest that protecting the hands and the lower anatomical regions with appropriate PPE may significantly reduce exposure among applicators. Copyright © 2017 Elsevier Ltd. All rights reserved.

DERMAL EXPOSURE ASSESSMENT: A SUMMARY OF EPA APPROACHES

EPA Science Inventory

This final report presents a concise description and evaluation of the approaches used in the Agency for dermal exposure assessment including a discussion about harmonization and research needs in this area. The report is intended to be used by EPA program offices in their effort...

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

Interposition Ankle Arthroplasty Using Acellular Dermal Matrix: A Small Series.

PubMed

Carpenter, Brian; Duncan, Kyle; Ernst, Jordan; Ryba, Dalton; Suzuki, Sumihiro

Although ankle arthrodesis is the reference standard for end-stage ankle arthritis, loss of mobility and adjacent joint arthritis are consequences that alternatives to arthrodesis attempt to avoid. The purpose of the present study was to report the clinical results of interpositional arthroplasty using acellular dermal matrix in 4 patients (age 32 to 42 years) for the treatment of advanced ankle osteoarthritis. The primary findings included relief of pain, with improvement in tibiotalar joint range of motion from a mean of 16.5° (range 0° to 24°) preoperatively to a mean of 31° (range 25° to 40°) postoperatively. All 4 patients underwent open arthrotomy of the anterior and posterior tibiotalar capsule with plafond exostectomy and debridement of all deleterious tissue within the ankle capsule. The articular surface of the talar dome was denuded down to smooth subchondral bone, and microfracture was performed. Autologous calcaneal bone marrow aspirate was applied, and talar resurfacing was achieved using an acellular dermal matrix. Knotless anchors placed medially and laterally within the anterior and posterior dome were used to affix the dermal matrix. The follow-up period ranged from 12 to 18 (mean 14) months. The mean pre- and 12-month postoperative Association of Orthopaedic Foot and Ankle Society hindfoot-ankle scale scores were 35 and 88.5, respectively. These outcomes suggest that interpositional tibiotalar arthroplasty using an acellular dermal matrix is successful in improving function and range of motion and decreasing pain. As an alternative to tibiotalar arthrodesis, interpositional tibiotalar arthroplasty might be the procedure of choice for young patients with end-stage ankle arthritis. Longer follow-up periods, histologic testing, and arthroscopic evaluations would be advantageous to further assess the durability of this procedure. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

An interspecies correlation model to predict acute dermal toxicity of plant protection products to terrestrial life stages of amphibians using fish acute toxicity and bioconcentration data.

PubMed

Weltje, Lennart; Janz, Philipp; Sowig, Peter

2017-12-01

This paper presents a model to predict acute dermal toxicity of plant protection products (PPPs) to terrestrial amphibian life stages from (regulatory) fish data. By combining existing concepts, including interspecies correlation estimation (ICE), allometric relations, lethal body burden (LBB) and bioconcentration modelling, an equation was derived that predicts the amphibian median lethal dermal dose (LD 50 ) from standard acute toxicity values (96-h LC 50 ) for fish and bioconcentration factors (BCF) in fish. Where possible, fish BCF values were corrected to 5% lipid, and to parent compound. Then, BCF values were adjusted to an exposure duration of 96 h, in case steady state took longer to be achieved. The derived correlation equation is based on 32 LD 50 values from acute dermal toxicity experiments with 15 different species of anuran amphibians, comprising 15 different PPPs. The developed ICE model can be used in a screening approach to estimate the acute risk to amphibian terrestrial life stages from dermal exposures to PPPs with organic active substances. This has the potential to reduce unnecessary testing of vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

[Differences between plaque-like variants of dermatofibrosarcoma protuberans and plaque-like dermal fibromatosis (dermatomyofibroma)].

PubMed

Hügel, H; Kutzner, H; Rütten, A; Biess, B

1994-05-01

On the basis of two cases the differences between the plaque-like variant of dermatofibrosarcoma protuberans (PDFSP) and the plaque-like dermal fibromatosis (synonym: dermatomyofibroma; PDF) are presented. PDFSP and PDF are two clinically very similar dermal fibrous proliferations, but differentiation is important because of their different therapy and prognosis. Histologically and immunohistochemically PDFSP and PDF can be recognized as separate entities.

Solar-simulated radiation and heat treatment induced metalloproteinase-1 expression in cultured dermal fibroblasts via distinct pathways: implications on reduction of sun-associated aging.

PubMed

Lan, Cheng-Che E; Wu, Ching-Shang; Yu, Hsin-Su

2013-12-01

Sun exposure is an important environmental factor affecting human beings. Most knowledge regarding solar aging focused on light radiation (photoaging), and little emphasis has been placed on heat, a factor that is also closely associated with sun exposure. This study was launched to evaluate the effects of simulated solar radiation (SSR) and environmental heat on skin fibroblasts in terms of dermal aging. Cultured human dermal fibroblasts were treated with moderate amount of SSR (200J/cm(2)) and heat (+2°C). The metalloproteinase-1 (MMP-1) expression was used as a surrogate marker for dermal aging and the involved regulatory mechanisms were explored. Both treatment conditions did not affect viability but significantly increased the expressions of MMP-1. In parallel, both treatments increased the intracellular levels of reactive oxygen species (ROS), but the increase induced by SSR is much greater than heat. In contrast, transient receptor potential vanilloid 1 (TRPV-1), the sensor of environmental heat, was upregulated by heat but not SSR treatment. Pretreating fibroblasts with antioxidant abrogated the SSR-induced MMP-1 but has limited effect on heat-induced MMP-1. On the other hand, TRPV-1 antagonist pretreatment reduced heat-induced MMP-1 in fibroblasts but not their SSR-treated counterparts. Both SSR and heat induced MMP-1 expression in dermal fibroblasts but through different pathways. As current strategies for reducing sun-related aging focused on filtering of light and use of antioxidants, future strategies design to reduce solar aging should also incorporate heat-induced aging into consideration. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

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.

Distinct requirements for cranial ectoderm and mesenchyme-derived wnts in specification and differentiation of osteoblast and dermal progenitors.

PubMed

Goodnough, L Henry; Dinuoscio, Gregg J; Ferguson, James W; Williams, Trevor; Lang, Richard A; Atit, Radhika P

2014-02-01

The cranial bones and dermis differentiate from mesenchyme beneath the surface ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal and osteoblast fate selection. Using conditional genetics, we eliminate secretion of all Wnt ligands from cranial surface ectoderm or undifferentiated mesenchyme, to uncover distinct roles for ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt ligands induce osteoblast and dermal fibroblast progenitor specification while initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are subsequently essential during differentiation of dermal and osteoblast progenitors. Finally, ectoderm-derived Wnt ligands provide an inductive cue to the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast lineages. Thus two sources of Wnt ligands perform distinct functions during osteoblast and dermal fibroblast formation.

Creeping attachment after 10 years of treatment of a gingival recession with acellular dermal matrix: a case report.

PubMed

Santos, Antonio; Goumenos, George; Pascual, Andrés; Nart, Jose

2011-02-01

Acellular dermal matrix grafts have become a good alternative to autogenous soft tissue grafts in root coverage. Until now, the literature has reported short- or medium-term data regarding the stability of the gingival margin after the use of acellular dermal matrix on root coverage. The aim of this article is to describe a case report with 10 years of evolution with creeping attachment that developed bucally on a moderate recession of a maxillary canine with an old composite restoration subsequent to an acellular dermal matrix. Long-term creeping attachment and complete root coverage on a restored tooth treated with acellular dermal matrix has not been previously reported in the dental literature.

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.

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.

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

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.

Assessment of dermal exposure and histopathologic changes of different sized nano-silver in healthy adult rabbits

NASA Astrophysics Data System (ADS)

kazem Koohi, Mohammad; Hejazy, Marzie; Asadi, Farzad; Asadian, Peyman

2011-07-01

The purpose of this study is to evaluate the dermal toxicity (Irritation/Corrosion) of three sizes of nanosilver particles (10, 20 and 30 nm) during 3 min, 1 and 4 hours according to the OECD/OCDE guideline Histopathological effects in secondary organs from liver, kidney, heart, spleen and brain 14 day post dermal administration are also reported. 10 and 20 nm Ag nanoparticles treated group showed well defined dermal erythema and oedema. Histopathological findings of 10 and 20 nm (4 hours exposure) on 14-day post dermal administration showed hyperkeratosis, acanthosis, hair-filled follicles and papillomatosis in an irregular epidermis, fibrosis, hyperemia, erythema, intracellular oedema and hyalinisation of collagen in dermis of skin. Liver revealed midzonal and periacinar necrosis, portal mononuclear infiltration, liver fatty change, liver congestion and hyperemic central vein. Splenic red pulp congestion and white pulp hyperreactivity, splenic trabeculae and sinusoidal congestion and hyaline change were found in spleen. Fatty degeneration in some cardiovascular cells and subendocardial hemorrhage without inflammation was perceived. Picnotic appearance of pyramidal neurons in the brain cortex, gliosis and mild perineuronal oedema ischemic cell change and hyperemic meninges was observed in brain. Our research concluded that dermal exposure to lesser sizes of silver nanoparticles is more disastrous than greater ones.

Design of an elastin-layered dermal regeneration template.

PubMed

Mithieux, Suzanne M; Weiss, Anthony S

2017-04-01

We demonstrate a novel approach for the production of tunable quantities of elastic fibers. We also show that exogenous tropoelastin is rate-limiting for elastin synthesis regardless of the age of the dermal fibroblast donor. Additionally, we provide a strategy to further enhance synthesis by older cells through the application of conditioned media. We show that this approach delivers an elastin layer on one side of the leading dermal repair template for contact with the deep dermis in order to deliver prefabricated elastic fibers to a physiologically appropriate site during subsequent surgery. This system is attractive because it provides for the first time a viable path for sufficient, histologically detectable levels of patient elastin into full-thickness wound sites that have until now lacked this elastic underlayer. The scars of full thickness wounds typically lack elasticity. Elastin is essential for skin elasticity and is enriched in the deep dermis. This paper is significant because it shows that: (1) we can generate elastic fibers in tunable quantities, (2) tropoelastin is the rate-limiting component in elastin synthesis in vitro, (3) we can generate elastin fibers regardless of donor age, (4) we describe a novel approach to further increase the numbers and thickness of elastic fibers for older donors, (5) we improve on Integra Dermal Regeneration Template and generate a new hybrid biomaterial intended to subsequently surgically deliver these elastic fibers, (6) the elastic fiber layer is presented on the side of Integra that is intended for delivery into its physiologically appropriate site i.e. the deep dermis. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bovine versus porcine acellular dermal matrix for complex abdominal wall reconstruction.

PubMed

Clemens, Mark W; Selber, Jesse C; Liu, Jun; Adelman, David M; Baumann, Donald P; Garvey, Patrick B; Butler, Charles E

2013-01-01

Abdominal wall reconstruction with bioprosthetic mesh is associated with lower rates of mesh infection, fistula formation, and mesh explantation than reconstruction with synthetic mesh. The authors directly compared commonly used bioprosthetic meshes in terms of clinical outcomes and complications. A database of consecutive patients who underwent abdominal wall reconstruction with porcine or bovine acellular dermal matrix and midline musculofascial closure at their institution between January of 2008 and March of 2011 was reviewed. Surgical outcomes were compared. One hundred twenty patients were identified who underwent a nonbridged, inlay abdominal wall reconstruction with porcine [69 patients (57.5 percent)] or bovine acellular dermal matrix (51 patients (42.5 percent)]. The mean follow-up time was 21.0 ± 9.9 months. The overall complication rate was 36.6 percent; the porcine matrix group had a significantly higher complication rate (44.9 percent) than the bovine matrix group (25.5 percent; p = 0.04) and statistically equivalent surgical complications (29.2 percent versus 21.6 percent; p = 0.34). There were no significant differences in rates of recurrent hernia (2.9 percent versus 3.9 percent; p = 0.99) or bulge (7.2 percent versus 0 percent; p = 0.07). However, the rate of intraoperative adverse events in the porcine matrix group [seven events (10.1 percent)] was significantly higher than that in the bovine matrix group (0 percent; p = 0.02). In patients who undergo complex abdominal wall reconstruction, both bovine and porcine acellular dermal matrix are associated with similar rates of postoperative surgical complications and appear to result in similar outcomes. Porcine acellular dermal matrix may be prone to intraoperative device failure. Therapeutic, III.

PAF involvement in dermal extravasation in the reverse passive Arthus reaction

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

Deacon, R.W.; Melden, M.K.; Saunders, R.N.

The reverse passive erthus reaction (RPAR) is characterized by PMN infiltration, increased vascular permeability leading to plasma extravasation and vessel damage. In the skin RPAR is an inflammatory response initiated by deposition of immune complexes and attributed to complement activation. As PAF can elicit similar dermal reactions, they examined the PAF antagonist SRI 63-072 in the RPAR. Guinea pigs were given an i.v. injection of /sup 125/I-BSA (Ag-20 mg/kg with 20 mg/kg Evan's blue as a permeability tracer), followed by intradermal (i.d.) injections (0.1 ml/site) of anti-BSA antibodies (Ab). After 30 min, dermal sites (2 cm diam.) were removed, countedmore » and the ..mu..l plasma/site (over background counts) calculated from plasma radioactivity measurements. The plasma leakage (..mu..l plasma/site) was dose-dependent upon Ab dose (6-200 ..mu..g/site). At the ultrastructural level, the presence of neutrophils and eosinophils were observed in the extravascular spaces. The luminal endothelium exhibited cytotoxic characteristics and loss of junctional integrity. SRI 63-072 exhibited 50% maximal inhibition when given i.d. with the Ab (0.1 ..mu..g/site) but only 5-10% when given at 3.0 mg/kg i.v. with Ag. No further inhibition of dermal extravasation was observed using SRI 63-441, a competitive receptor antagonist with 3-30 fold the in vivo potency of SRI 63-072. As dermal extravasation in RPAR is only partially inhibited by a PAF antagonist, it appears that other vasoactive mediators, possibly histamine, may be influencing vessel permeability as well.« less

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.

Thymosin β4 has a major role in dermal burn wound healing that involves actin cytoskeletal remodelling via heat-shock protein 70.

PubMed

Kim, Sokho; Kwon, Jungkee

2017-04-01

Rapid vascular remodelling of damaged dermal tissue is required to heal burn wounds. Thymosin β4 (Tβ4) is a growth factor that has been shown to promote angiogenesis and dermal wound repair. However, the underlying mechanisms based on Tβ4 function have not yet been fully investigated. In the present study, we investigated how Tβ4 improves dermal burn wound healing via actin cytoskeletal remodelling and the action of heat-shock proteins (HSPs), which are a vital set of chaperone proteins that respond to heat shock. Our in vitro results achieved with the use of human umbilical vein endothelial cells (HUVECs) revealed a possible signal between Tβ4 and HSP70. Moreover, we confirmed that remodelling of filamentous actin (F-actin) was regulated by Tβ4-induced HSP70 in HUVECs. Based on these in vitro results, we confirmed the healing effects of Tβ4 in an adapted dermal burn wound in vivo model. Tβ4 improved wound-healing markers, such as wound closure and vascularization. Moreover, Tβ4 maintained the long-term expression of HSP70, which is associated with F-actin regulation during the wound-healing period. These results suggest that an association between Tβ4 and HSP70 is responsible for the healing of burn wounds, and that this association may regulate F-actin remodelling. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Impact of Clothing on Dermal Exposure to Phthalates: Observations and Insights from Sampling Both Skin and Clothing.

PubMed

Gong, Mengyan; Weschler, Charles J; Zhang, Yinping

2016-04-19

Clothing can either retard or accelerate dermal exposure to phthalates. To investigate the impact of clothing on dermal exposure to six phthalates (DMP/DEP/DiBP/DnBP/BBzP/DEHP) in real environments, two sets of experiments have been conducted: (1) Skin wipes were collected from 11 adults to examine the phthalate levels on both bare-skin (hand/forehead) and clothing-covered body locations (arm/back/calf); (2) Five adults were asked to wear just-washed jeans for 1 day (1(st) experiment), 5 days (2(nd) experiment), and 10 days (3(rd) experiment). Phthalate levels on their legs were measured on selected days during the wearing period, and phthalate levels in the jeans were measured at the end of each experiment and again after washing. Measured phthalate levels on body locations covered by clothing were lower than those on uncovered locations, but still substantial. Dermal uptake would be underestimated by a factor of 2 to 5 if absorption through body locations covered by clothing were neglected. Phthalate levels in the jeans and on the legs increased with the wearing time. However, the levels in the jeans and on the legs were not strongly correlated, indicating that other pathways, e.g, contact with bedding or bedclothes, likely contribute to the levels on the legs. The efficiency with which laundering washing removed phthalates from the jeans increased with decreasing Kow; median values ranged from very low (<5%) for DEHP to very high (∼75%) for DMP.

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

The Use of Fetal Bovine Dermal Scaffold (PriMatrix) in the Management of Full-Thickness Hand Burns.

PubMed

Parcells, Alexis Lanteri; Karcich, Jenika; Granick, Mark S; Marano, Michael A

2014-01-01

Management of full-thickness burn wounds represents a challenge when reconstructive options are not applicable. Fetal bovine dermal matrix is a bioactive collagen scaffold that assimilates into wounds and stimulates vascularization and dermal regeneration. We present the use of fetal bovine dermal scaffold PriMatrix in the treatment of a patient who sustained scald-immersion full-thickness burns of her bilateral hands that failed conventional wound therapy. A 71-year-old woman with advanced Parkinson's disease sustained self-induced 5% mixed second- and third-degree scald-immersion burns of her bilateral hands and fingers. The patient underwent extensive debridement that resulted in partially avascular wounds measuring 66 cm(2) and 72 cm(2) with exposed extensor tendons and no evidence of bleeding. Meshed homograft was applied, but her hands remained partly avascular. PriMatrix fetal bovine dermal scaffold was applied to provide tissue remodeling over the bones, which allowed successful skin grafting and complete wound healing. Our experience shows fetal bovine dermal scaffold to be an effective method in management of complicated burn wounds in selected cases. Further studies need to be implemented to confer this conclusion.

The Use of Fetal Bovine Dermal Scaffold (PriMatrix) in the Management of Full-Thickness Hand Burns

PubMed Central

Karcich, Jenika; Granick, Mark S.; Marano, Michael A.

2014-01-01

Objective: Management of full-thickness burn wounds represents a challenge when reconstructive options are not applicable. Fetal bovine dermal matrix is a bioactive collagen scaffold that assimilates into wounds and stimulates vascularization and dermal regeneration. Methods: We present the use of fetal bovine dermal scaffold PriMatrix in the treatment of a patient who sustained scald-immersion full-thickness burns of her bilateral hands that failed conventional wound therapy. Results: A 71-year-old woman with advanced Parkinson's disease sustained self-induced 5% mixed second- and third-degree scald-immersion burns of her bilateral hands and fingers. The patient underwent extensive debridement that resulted in partially avascular wounds measuring 66 cm2 and 72 cm2 with exposed extensor tendons and no evidence of bleeding. Meshed homograft was applied, but her hands remained partly avascular. PriMatrix fetal bovine dermal scaffold was applied to provide tissue remodeling over the bones, which allowed successful skin grafting and complete wound healing. Conclusions: Our experience shows fetal bovine dermal scaffold to be an effective method in management of complicated burn wounds in selected cases. Further studies need to be implemented to confer this conclusion. PMID:25328569

Augmentation Phalloplasty With Autologous Dermal Fat Graft in the Treatment of "Small Penis".

PubMed

Xu, Lisi; Zhao, Muxin; Chen, Wen; Li, Yangqun; Yang, Zhe; Ma, Ning; Wang, Weixin; Feng, Jun; Liu, Qiyu; Ma, Tong

2016-02-01

Our objective is to report on the efficacy and safety of dermal fat graft in augmentation phalloplasty performed on patients who presented complaining of "small penis," and evaluate the cosmetic and psychological outcomes of it. From April 2010 and January 2015, 23 Chinese adult patients aged 18 to 33 years (average, 23 years) with subjective perception of small penis were included; all who requested an increase in the penile dimension underwent penile elongation (suprapubic skin advancement-ligamentolysis) and girth enhancement by dermal fat graft. Besides objective measurement, Male Genital Image Scale was used to facilitate selection of patients and evaluate the outcome, respectively. The change and shrinkage of the dermal fat strips was evaluated by ultrasound examination and computed tomography. No major complications or erection deficiencies occurred during the postoperative follow-up period. After 6 months, the mean flaccid length was increased by 2.27 ± 0.54 cm, whereas the mean flaccid circumference gain was 1.67 ± 0.46 cm. Significant improvement of genital satisfaction was reported during the follow-up. The shrinkage of dermal fat strips was inconspicuous, and no curvature was observed due to fibrosis. With strict patient selection, this procedure is proved to be a plausible and reasonable option for patients with penile dysmorphophobia. Also, it provides a potential alternative procedure to current dominant methods and promotes the aesthetic results with penile lengthening.

ISSUES IN UNDERSTANDING DERMAL EXPOSURES RESULTING FROM CONTACT WITH CONTAMINATED SURFACES, MEASURING SURFACE CONTAMINATION, AND CHARACTERIZING TRANSFERS

EPA Science Inventory

Although monitoring for surface contamination in work with radioactive materials and dermal monitoring of pesticide exposure to agricultural workers have been standard practice for 50 years, regular surface sampling and dermal monitoring methods have only been applied to indust...

The treatment of deep dermal hand burns: How do we achieve better results? Should we use allogeneic keratinocytes or skin grafts?

PubMed

Haslik, W; Kamolz, L-P; Lumenta, D B; Hladik, M; Beck, H; Frey, M

2010-05-01

The treatment of deep dermal burns has a broad spectrum and has been subject to discussion over the past years. The treatment of hand burns is challenging due to the high requirements to aesthetic and functional outcome. 27 patients, 7 women and 20 men with deep dermal hand burns with a mean age of 41.3+/-16.5 and a mean TBSA of 15%+/-19.6% were treated either with allogeneic cryopreserved keratinocytes or with split skin grafts. Long-term follow-up revealed no statistical significant differences between the two groups concerning Vancouver Scar Scale as well as hand function judged by the DASH score; however there was a tendency to higher VSS scores and impaired aesthetic results in the keratinocyte group. Allogeneic keratinocytes are a suitable armentarium for the treatment of deep dermal hand burns; and, if used correctly, they can produce a timely healing comparable to split-thickness skin grafts. Limited availability, high costs as well as the need for special skills are key factors, which render application of this technique outside specialist burn centres virtually impossible. In our opinion, the cultivation and use of keratinocytes should be reserved to these centres in order to facilitate a sensible application for a full range of indications. We recommend usage of allogeneic keratinocytes for deep dermal hand burns only in severely burned patients with a lack of donor sites. Patients with unrestricted availability of donor sites seem to profit from the application of split-thickness skin grafts according to our results. Copyright 2009 Elsevier Ltd and ISBI. All rights reserved.

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.

Dual-dermal-barrier fashion flaps for the treatment of sacral pressure sores.

PubMed

Hsiao, Yen-Chang; Chuang, Shiow-Shuh

2015-02-01

The sacral region is one of the most vulnerable sites for the development of pressure sores. Even when surgical reconstruction is performed, there is a high chance of recurrence. Therefore, the concept of dual-dermal-barrier fashion flaps for sacral pressure sore reconstruction was proposed. From September 2007 to June 2010, nine patients with grade IV sacral pressures were enrolled. Four patients received bilateral myocutaneous V-Y flaps, four patients received bilateral fasciocutaneous V-Y flaps, and one patient received bilateral rotation-advanced flaps for sacral pressure reconstruction. The flaps were designed based on the perforators of the superior gluteal artery in one patient's reconstructive procedure. All flaps' designs were based on dual-dermal-barrier fashion. The mean follow-up time was 16 months (range = 12-25). No recurrence was noted. Only one patient had a complication of mild dehiscence at the middle suture line, occurring 2 weeks after the reconstructive surgery. The dual-dermal fashion flaps are easily duplicated and versatile. The study has shown minimal morbidity and a reasonable outcome.

Coverage of Deep Cutaneous Wounds Using Dermal Template in Combination with Negative-pressure Therapy and Subsequent Skin Graft

PubMed Central

Chang, Alexandre A.; Lobato, Rodolfo C.; Nakamoto, Hugo A.; Tuma, Paulo; Ferreira, Marcus C.

2014-01-01

Background: We consider the use of dermal matrix associated with a skin graft to cover deep wounds in the extremities when tendon and bone are exposed. The objective of this article was to evaluate the efficacy of covering acute deep wounds through the use of a dermal regeneration template (Integra) associated with vacuum therapy and subsequent skin grafting. Methods: Twenty patients were evaluated prospectively. All of them had acute (up to 3 weeks) deep wounds in the limbs. We consider a deep wound to be that with exposure of bone, tendon, or joint. Results: The average area of integration of the dermal regeneration template was 86.5%. There was complete integration of the skin graft over the dermal matrix in 14 patients (70%), partial integration in 5 patients (25%), and total loss in 1 case (5%). The wound has completely closed in 95% of patients. Conclusions: The use of Integra dermal template associated with negative-pressure therapy and skin grafting showed an adequate rate of resolution of deep wounds with low morbidity. PMID:25289363

Genetic Predisposition for Dermal Problems in Hexavalent Chromium Exposed Population

PubMed Central

Sharma, Priti; Bihari, Vipin; Agarwal, Sudhir K.; Goel, Sudhir K.

2012-01-01

We studied the effect of genetic susceptibility on hexavalent chromium induced dermal adversities. The health status of population was examined from the areas of Kanpur (India) having the elevated hexavalent chromium levels in groundwater. Blood samples were collected for DNA isolation to conduct polymorphic determination of genes, namely: NQO1 (C609T), hOGG1 (C1245G), GSTT1, and GSTM1 (deletion). Symptomatic exposed subjects (n = 38) were compared with asymptomatic exposed subjects (n = 108) along with asymptomatic controls (n = 148) from a non contaminated reference community. Exposed symptomatic group consisted of 36.8% subjects who were GSTM1 null genotyped as compared to asymptomatic where only 19.4% subjects were null. The exposed subjects with GSTM1 null genotype were more susceptible to dermal adversities in comparison with wild genotyped subjects (OR = 2.42; 95% CI = 1.071–5.451). Age, smoking, gender or duration of residence were not found to have any confounding effect towards this association. Association with other genes was not statistically significant, nonetheless, possible contribution by these genes cannot be ruled out. In conclusion, variation in the polymorphic status of GSTM1 gene may influence dermal outcomes among residents from Cr(VI) contaminated areas. Further studies are therefore, needed to examine these observations among different population groups. PMID:22919465

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...

Acute dermal toxicity of guanidine hydrochloride in rabbits. Report for 18 May-1 August 1984

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

Hiatt, G.F.; Sanso, S.K.; Korte, D.W.

1989-12-01

The acute dermal toxicity of guanidine hydrochloride was evaluated in five male and five female New Zealand White rabbits. Guanidine hydrochloride (2 g/kg) was applied topically to the clipped dorsal skin surface for 24 hours. No compound-related deaths or clinical signs were observed; however, guanidine hydrochloride did produce dermal irritation, necrosis, and eschar formation under conditions of the study.

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.

Ornamentation of dermal bones of Placodermi from the Lower Devonian of Morocco as a measure of biodiversity

NASA Astrophysics Data System (ADS)

Antczak, Mateusz; Berkowski, Błażej

2017-06-01

Dermal bones are formed early during growth and thus constitute an important tool in studies of ontogenetic and evolutionary changes amongst early vertebrates. Ornamentation of dermal bones of terrestrial vertebrates is often used as a taxonomic tool, for instance in Aetosauria, extant lungfishes (Dipnoi) and ray-finned fishes (Actinopterygii), for which it have been proved to be of use in differentiating specimens to species level. However, it has not been utilised to the same extent in placoderms. Several features of the ornamentation of Early Devonian placoderms from Hamar Laghdad (Morocco) were examined using both optical and scanning electron microscopy to determine whether it is possible to distinguish armoured Palaeozoic fishes. Four distinct morphotypes, based on ornamentation of dermal bones, are differentiated. These distinct types of ornamentation may be the result of either different location of dermal plates on the body or of ontogenetic (intraspecific) and/or interspecific variation.

Steroidal glycosides from the bulbs of Easter lily (Lilium longiflorum Thunb.) promote dermal fibroblast migration in vitro.

PubMed

Esposito, Debora; Munafo, John P; Lucibello, Teresa; Baldeon, Manuel; Komarnytsky, Slavko; Gianfagna, Thomas J

2013-07-09

Preparations derived from bulbs of various Lilium species have been used to promote the healing of skin abrasions, sores and burns and to aid in healing wounds in Traditional Chinese and Greco-Roman Medicine. To evaluate fractionated Easter lily bulb extracts and their steroidal glycosides (1-5) for the promotion of dermal fibroblast migration in vitro, a model for the early events in wound healing. An activity-guided screening approach was used by coupling sequential solvent extraction, gel permeation chromatography (GPC), and semi-preparative reverse-phase high performance liquid chromatography (RP-HPLC) with an in vitro dermal fibroblast migration assay. Cytotoxicity was evaluated with methyl thiazole tetrazolium (MTT). To gain insight into the mode of action of the steroidal glycosides, nitric oxide (NO) production, and expression of genes for transforming growth factor beta-1 (TGF-β) and its receptors were evaluated. Fractionated bulb extracts and the two isolated steroidal glycoalkaloids (1) and (2) induced NO production and TGF-β receptor I mRNA expression in fibroblast cell culture. In a cytotoxicity assay, steroidal glycosides (1) and (3) had IC50 values of 8.2 and 8.7 µM, but the natural acetylation of the C-6″' hydroxy of the terminal glucose unit in (2) resulted in a 3-fold decrease in cell cytotoxicity when compared with (1). Results from the dermal fibroblast migration assay revealed that the steroidal glycoalkaloids (1) and (2), and the furostanol saponin (3) promoted fibroblast migration from the range of 23.7±5.7 to 37.7±5.1%, as compared with the control. Collectively, our data demonstrate that the steroidal glycosides present in Easter lily bulbs induce, at least in part, the observed dermal fibroblast migration activity of the bulb extracts. This is the first evidence that steroidal glycosides from Lilium longiflorum may potentially play a role in the wound healing process and may provide a scientific basis for the historical use of lily

Comparing Urinary Biomarkers of Airborne and Dermal Exposure to Polycyclic Aromatic Compounds in Asphalt-Exposed Workers

PubMed Central

Sobus, Jon R.; McClean, Michael D.; Herrick, Robert F.; Waidyanatha, Suramya; Nylander-French, Leena A.; Kupper, Lawrence L.; Rappaport, Stephen M.

2009-01-01

When working with hot mix asphalt, road pavers are exposed to polycyclic aromatic hydrocarbons (PAHs) through the inhalation of vapors and particulate matter (PM) and through dermal contact with PM and contaminated surfaces. Several PAHs with four to six rings are potent carcinogens which reside in these particulate emissions. Since urinary biomarkers of large PAHs are rarely detectable in asphalt workers, attention has focused upon urinary levels of the more volatile and abundant two-ring and three-ring PAHs as potential biomarkers of PAH exposure. Here, we compare levels of particulate polycyclic aromatic compounds (P-PACs, a group of aromatic hydrocarbons containing PAHs and heterocyclic compounds with four or more rings) in air and dermal patch samples from 20 road pavers to the corresponding urinary levels of naphthalene (U-Nap) (two rings), phenanthrene (U-Phe) (three rings), monohydroxylated metabolites of naphthalene (OH-Nap) and phenanthrene (OH-Phe), and 1-hydroxypyrene (OH-Pyr) (four rings), the most widely used biomarker of PAH exposure. For each worker, daily breathing-zone air (n = 55) and dermal patch samples (n = 56) were collected on three consecutive workdays along with postshift, bedtime, and morning urine samples (n = 149). Measured levels of P-PACs and the urinary analytes were used to statistically model exposure–biomarker relationships while controlling for urinary creatinine, smoking status, age, body mass index, and the timing of urine sampling. Levels of OH-Phe in urine collected postshift, at bedtime, and the following morning were all significantly associated with levels of P-PACs in air and dermal patch samples. For U-Nap, U-Phe, and OH-Pyr, both air and dermal patch measurements of P-PACs were significant predictors of postshift urine levels, and dermal patch measurements were significant predictors of bedtime urine levels (all three analytes) and morning urine levels (U-Nap and OH-Pyr only). Significant effects of

Wound healing effects of collagen-laminin dermal matrix impregnated with resveratrol loaded hyaluronic acid-DPPC microparticles in diabetic rats.

PubMed

Gokce, Evren H; Tuncay Tanrıverdi, Sakine; Eroglu, Ipek; Tsapis, Nicolas; Gokce, Goksel; Tekmen, Isıl; Fattal, Elias; Ozer, Ozgen

2017-10-01

An alternative formulation for the treatment of diabetic foot wounds that heal slowly is a requirement in pharmaceutical field. The aim of this study was to develop a dermal matrix consisting of skin proteins and lipids with an antioxidant that will enhance healing and balance the oxidative stress in the diabetic wound area due to the high levels of glucose. Thus a novel three dimensional collagen-laminin porous dermal matrix was developed by lyophilization. Resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine microparticles were combined with this dermal matrix. Characterization, in vitro release, microbiological and in vivo studies were performed. Spherical microparticles were obtained with a high RSV encapsulation efficacy. The microparticles were well dispersed in the dermal matrix from the surface to deeper layers. Collagenase degraded dermal matrix, however the addition of RSV loaded microparticles delayed the degradation time. The release of RSV was sustained and reached 70% after 6h. Histological changes and antioxidant parameters in different treatment groups were investigated in full-thickness excision diabetic rat model. Collagen fibers were intense and improved by the presence of formulation without any signs of inflammation. The highest healing score was obtained with the dermal matrix impregnated with RSV-microparticles with an increased antioxidant activity. Collagen-laminin dermal matrix with RSV microparticles was synergistically effective due to presence of skin components in the formulation and controlled release achieved. This combination is a safe and promising option for the treatment of diabetic wounds requiring long recovery. Copyright © 2017 Elsevier B.V. All rights reserved.

Acellular dermal matrix scaffolds coated with connective tissue growth factor accelerate diabetic wound healing by increasing fibronectin through PKC signalling pathway.

PubMed

Yan, Wenxia; Liu, Hanping; Deng, Xiaoyuan; Jin, Ying; Wang, Ning; Chu, Jing

2018-03-01

The regional injection of connective tissue growth factor (CTGF) for diabetic wound healing requires multiple components and results in a substantial loss of its biological activity. Acellular dermal matrix (ADM) scaffolds are optimal candidates for delivering these factors to local ischaemic environments. In this study, we explored whether CTGF loaded on ADM scaffolds can enhance fibronectin (FN) expression to accelerate diabetic wound healing via the protein kinase C (PKC) signalling pathway. The performance of CTGF and CTGF + PKC inhibitor, which were loaded on ADM scaffolds to treat dorsal skin wounds in streptozotocin-induced diabetic mice, was evaluated with naked ADM as a control. Wound closure showed that ADM scaffolds loaded with CTGF induced greater diabetic wound healing in the early stage of the wound in diabetic mice. Moreover, ADM scaffolds loaded with CTGF obviously increased the expression of FN both at the mRNA and protein levels, whereas the expression of FN was significantly reduced in the inhibitor group. Furthermore, the ADM + CTGF group, which produce FN, obviously promoted alpha-smooth muscle actin and transforming growth factor-beta expression and enhanced neovasculature and collagen synthesis at the wound sites. ADM scaffolds loaded with CTGF + PKC inhibitor delayed diabetic wound healing, indicating that FN expression was mediated by the PKC signalling pathway. Our findings offer new perspectives for the treatment of diabetic wound healing and suggest a rationale for the clinical evaluation of CTGF use in diabetic wound healing. Copyright © 2017 John Wiley & Sons, Ltd.

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 carotenoid measurement is inversely related to anxiety in patients with breast cancer

PubMed Central

Li, David G; LeCompte, Gabrielle; Golod, Lev; Cecchi, Gary; Irwin, David; Harken, Alden; Matecki, Amy

2017-01-01

Breast cancer is the most prevalent malignancy among women worldwide. Increased oxidative stress and poor subjective health outcomes have been associated with increased risk of cancer recurrence and metastasis, but few studies until now have explored the relationship between oxidative stress and chronic stress/anxiety. This study aims to examine the association between anxiety and a potential dermal correlate of oxidative stress in patients with breast cancer. 102 breast cancer patients were enrolled in a cross-sectional study at Highland Hospital, a county hospital in Oakland, California. Each participant’s skin carotenoid score (SCS), a potential dermal correlate of oxidative stress, was recorded via Raman spectroscopy. Patient demographics, breast cancer stage, and subjective health measures (anxiety and self-rated health) were ascertained. Multivariate linear regression analysis was performed to quantify any associations between SCS and the above health correlates. Higher levels of skin carotenoids were associated with decreased severity of anxiety, lower BMI, increased servings of vegetables/fruits in daily diet, Hispanic race, lower educational status, and nonsmoking status. Severity of anxiety as graded by the GAD-7 was inversely associated with dermal carotenoid measurements via SCS. Conclusions. Increased levels of oxidative stress as quantified by SCS is associated with greater severity of anxiety. Because chronic stress has been associated with tumor progression, increased recurrence rates, and increased metastatic risk in breast cancer, non-invasive dermal carotenoid measurements could be used as a novel objective correlate of subjective health during cancer treatment. PMID:28923881

Failure of Ibuprofen to prevent progressive dermal ischemia after burning in guinea pigs.

PubMed

Tan, Qian; Lin, Zihao; Ma, Wenxi; Chen, Huairen; Wang, Lei; Ning, Guansen; Zhou, Xu

2002-08-01

It is controversial whether the use of prostaglandin inhibitors could prevent progressive dermal ischemia in the postburn stasis zone. This study evaluated the effect of Ibuprofen on preventing postburn dermal ischemia using an animal model of India ink perfusion and skin transparent preparation techniques. The closely clipped backs of the guinea pigs were bathed in 75 degrees C water for 10s. Ibuprofen-treated groups were fed intragastrically with Ibuprofen (12.5mg/kg) every 6h. All animals were perfused with 70% India ink via a cervical artery cannula at 16 kPa constant pressure at 0, 8, 16, 24h postburn. Skin transparent preparations were made, and 6-keto-PGF(1 alpha) and T x B(2) levels in skin tissue were assessed. India ink filling rates in skin capillary plexuses decreased gradually with postburn time elapsing (P<0.01). 6-keto-PGF(1 alpha) and T x B(2) levels in two groups increased. The increase of T x B(2) was dominant, which was related to postburn dermal ischemia (r=0.742, P<0.01). Though levels of 6-keto-PGF(1 alpha) and T x B(2) decreased in Ibuprofen-treated groups, India ink filling rates showed no significant difference between controls and experimental groups (P>0.05). The results were also confirmed by observation of skin transparent preparations. This study suggests that Ibuprofen has no preventive effect on progressive dermal ischemia after burning.

Safety assessment and toxicological profiling of a novel combinational sunprotective dermal formulation containing melatonin and pumpkin seed oil.

PubMed

Bora, Nilutpal Sharma; Pathak, Manash Pratim; Mandal, Santa; Mazumder, Bhaskar; Policegoudra, Rudragoud; Raju, Pakalapati Srinivas; Chattopadhyay, Pronobesh

2017-10-01

Ultraviolet (UV) radiation exposure has been known to cause irreparable damages to human skin. The daunting risk of UV radiation exposure faced by military personnel led to the development of a sunscreen formulation which has superior sun protection factor combined with the ability to counteract reactive oxygen species. The present work deals with the preclinical safety evaluation of the sunscreen formulation comprising of four US FDA approved UV filters; namely avobenzone, octinoxate, oxybenzone, titanium dioxide along with melatonin and pumpkin seed oil, via OECD protocols of assessing acute oral and dermal toxicity; skin sensitizing; skin irritating; ocular irritating and genotoxic potential. Both oral and dermal LD 50 values were found to be ˃2000 mg/kg body weight in adult Wistar albino rats using acute dermal and oral toxicity tests. The sunscreen formulation was found to be non-sensitizing to the skin of guinea pigs and non-irritating to both skin and eyes of rabbits. The sunscreen formulation was also found to be non-mutagenic which was affirmed by a battery of genotoxicity and muagenicity assays. The results obtained from this preclinical study indicated that the sunscreen formulation is non toxic and safe in animal models. This study along with additional preclinical evaluations may serve as a basis for considering the formulation as a potential candidate for further trials to establish its efficacy, tolerability and applicability. Copyright © 2017 Elsevier Inc. All rights reserved.

TGF-beta is specifically expressed in human dermal papilla cells and modulates hair folliculogenesis.

PubMed

Inoue, Keita; Aoi, Noriyuki; Yamauchi, Yuji; Sato, Takahiro; Suga, Hirotaka; Eto, Hitomi; Kato, Harunosuke; Tabata, Yasuhiko; Yoshimura, Kotaro

2009-01-01

Dermal papilla cells (DPCs) in the mammalian hair follicle have been shown to develop hair follicles through epithelial-mesenchymal interactions. A cell therapy to regenerate human hair is theoretically possible by expanding autologous human DPCs (hDPCs) and transplanting them into bald skin, though much remains to be overcome before clinical success. In this study, we compared gene signatures of hDPCs at different passages and human dermal fibroblasts, and found transforming growth factor (TGF)-beta(2) to be highly expressed in cultured hDPCs. Keratinocyte conditioned medium, which is known to help preserve the hair-inducing capacity of hDPCs, up-regulated TGF-beta(2) expression of hDPCs and also enhanced their alkaline phosphatase (ALP) activity, a known index for hair-inductive capacity. Through screening of components secreted from keratinocytes, the vitamin D(3) analogue was found to promote TGF-beta(2) expression and ALP activity of hDPCs. In animal hair folliculogenesis models using rat epidermis and expanded hDPCs, inhibition of TGF-beta(2) signalling at the ligand or receptor level significantly impaired hair folliculogenesis and maturation. These results suggest an important role for TGF-beta(2) in hair follicle morphogenesis and provide insights into the establishment of future cell therapies for hair regrowth by transplanting expanded DPCs.

Histology of the heterostracan dermal skeleton: Insight into the origin of the vertebrate mineralised skeleton.

PubMed

Keating, Joseph N; Marquart, Chloe L; Donoghue, Philip C J

2015-06-01

Living vertebrates are divided into those that possess a fully formed and fully mineralised skeleton (gnathostomes) versus those that possess only unmineralised cartilaginous rudiments (cyclostomes). As such, extinct phylogenetic intermediates of these living lineages afford unique insights into the evolutionary assembly of the vertebrate mineralised skeleton and its canonical tissue types. Extinct jawless and jawed fishes assigned to the gnathostome stem evidence the piecemeal assembly of skeletal systems, revealing that the dermal skeleton is the earliest manifestation of a homologous mineralised skeleton. Yet the nature of the primitive dermal skeleton, itself, is poorly understood. This is principally because previous histological studies of early vertebrates lacked a phylogenetic framework required to derive evolutionary hypotheses. Nowhere is this more apparent than within Heterostraci, a diverse clade of primitive jawless vertebrates. To this end, we surveyed the dermal skeletal histology of heterostracans, inferred the plesiomorphic heterostracan skeleton and, through histological comparison to other skeletonising vertebrate clades, deduced the ancestral nature of the vertebrate dermal skeleton. Heterostracans primitively possess a four-layered skeleton, comprising a superficial layer of odontodes composed of dentine and enameloid; a compact layer of acellular parallel-fibred bone containing a network of vascular canals that supply the pulp canals (L1); a trabecular layer consisting of intersecting radial walls composed of acellular parallel-fibred bone, showing osteon-like development (L2); and a basal layer of isopedin (L3). A three layered skeleton, equivalent to the superficial layer L2 and L3 and composed of enameloid, dentine and acellular bone, is possessed by the ancestor of heterostracans + jawed vertebrates. We conclude that an osteogenic component is plesiomorphic with respect to the vertebrate dermal skeleton. Consequently, we interpret the

[Health protection for rural workers: the need to standardize techniques for quantifying dermal exposure to pesticides].

PubMed

Selmi, Giuliana da Fontoura Rodrigues; Trapé, Angelo Zanaga

2014-05-01

Quantification of dermal exposure to pesticides in rural workers, used in risk assessment, can be performed with different techniques such as patches or whole body evaluation. However, the wide variety of methods can jeopardize the process by producing disparate results, depending on the principles in sample collection. A critical review was thus performed on the main techniques for quantifying dermal exposure, calling attention to this issue and the need to establish a single methodology for quantification of dermal exposure in rural workers. Such harmonization of different techniques should help achieve safer and healthier working conditions. Techniques that can provide reliable exposure data are an essential first step towards avoiding harm to workers' health.

Cyclosporin A reduces matrix metalloproteinases and collagen expression in dermal fibroblasts from regenerative FOXN1 deficient (nude) mice

PubMed Central

2013-01-01

Background Cyclosporin A (CsA), an immunosuppressive agent modifies the wound healing process through an influence on extracellular matrix metabolism. We have compared the effects of CsA on dermal fibroblasts from nude (FOXN1 deficient) mice, a genetic model of skin scarless healing, and from control (C57BL/6 J (B6) mice to evaluate metabolic pathways that appear to have important roles in the process of scarless healing/regeneration. Results High levels of matrix metalloproteinases (MMPs) and collagen III expression in dermal fibroblasts from nude (regenerative) mice were down-regulated by CsA treatment to the levels observed in dermal fibroblasts from B6 (non-regenerative) mice. In contrast, dermal fibroblasts from control mice respond to CsA treatment with a minor reduction of Mmps mRNA and 2.5-fold increase expression of collagen I mRNA. An in vitro migratory assay revealed that CsA treatment profoundly delayed the migratory behavior of dermal fibroblasts from both nude and control mice. Conclusion The data suggest that by alternation of the accumulation of extracellular matrix components CsA treatment stimulates the transition from a scarless to a scar healing. PMID:23547542

Efficient dermal delivery of retinyl palmitate: Progressive polarimetry and Raman spectroscopy to evaluate the structure and efficacy.

PubMed

Lee, Jun Bae; Lee, Dong Ryeol; Choi, Nak Cho; Jang, Jihui; Park, Chun Ho; Yoon, Moung Seok; Lee, Miyoung; Won, Kyoungae; Hwang, Jae Sung; Kim, B Moon

2015-10-12

Over the past decades, there has been a growing interest in dermal drug delivery. Although various novel delivery devices and methods have been developed, dermal delivery is still challenging because of problems such as poor drug permeation, instability of vesicles and drug leakage from vesicles induced by fusion of vesicles. To solve the vesicle instability problems in current dermal delivery systems, we developed materials comprised of liquid crystals as a new delivery vehicle of retinyl palmitate and report the characterization of the liquid crystals using a Mueller matrix polarimetry. The stability of the liquid-crystal materials was evaluated using the polarimeter as a novel evaluation tool along with other conventional methods. The dermal delivery of retinyl palmitate was investigated through the use of confocal Raman spectroscopy. The results indicate that the permeation of retinyl palmitate was enhanced by up to 106% compared to that using an ordinary emulsion with retinyl palmitate. Copyright © 2015 Elsevier B.V. All rights reserved.

Dermal Exposure to Jet Fuel JP-8 Significantly Contributes to the Production of Urinary Naphthols in Fuel-Cell Maintenance Workers

PubMed Central

Chao, Yi-Chun E.; Kupper, Lawrence L.; Serdar, Berrin; Egeghy, Peter P.; Rappaport, Stephen M.; Nylander-French, Leena A.

2006-01-01

Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure. PMID:16451852

Dermal exposure to jet fuel JP-8 significantly contributes to the production of urinary naphthols in fuel-cell maintenance workers.

PubMed

Chao, Yi-Chun E; Kupper, Lawrence L; Serdar, Berrin; Egeghy, Peter P; Rappaport, Stephen M; Nylander-French, Leena A

2006-02-01

Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure.

Acellular dermal matrix as an adjunct in treatment of neuropathic pain at the wrist.

PubMed

Peterson, Steven L; Adham, Mehdi N

2006-08-01

Traumatic or surgical injury to superficial sensory nerves at the wrist can lead to significant morbidity. Multiple treatment modalities have been proposed, including the use of flap coverage to provide soft-tissue padding and decrease tactile irritation. In this report, acellular dermal matrix (AlloDerm) was used as an alternative to flap coverage, thereby avoiding the need for a donor site. Five patients with postsurgical and five patients with posttraumatic neuropathic pain at the wrist underwent neuroma excision and/or neurolysis followed by interposition of acellular dermal matrix allograft between skin and nerve. Patients were followed from 12 to 25 months and demonstrated substantial improvement in pain. Eight previously employed patients returned to their prior occupations. Dermal matrix allograft may provide cushioning and/or a gliding surface for the nerve and represents a simple alternative to flap coverage in the treatment of neuropathic pain at the wrist.

NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation

PubMed Central

Jiao, Delong; Wong, Chun-Kwok; Qiu, Huai-Na; Dong, Jie; Cai, Zhe; Chu, Man; Hon, Kam-Lun; Tsang, Miranda Sin-Man; Lam, Christopher Wai-Kei

2016-01-01

The skin of patients with atopic dermatitis (AD) has a unique predisposition for colonization by Staphylococcus aureus (S. aureus), which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and toll-like receptor 2 (TLR2) ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions. Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil–fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway by which S. aureus contributes to the pathophysiology of AD. PMID:26388234

Dermal Matrices and Bioengineered Skin Substitutes: A Critical Review of Current Options

PubMed Central

Hamdi, Moustapha; Abberton, Keren; Morrison, Wayne

2015-01-01

Background: Over recent decades, scientists and surgeons have collaborated to develop various bioengineered and synthetic products as an alternative to skin grafts. Despite the numerous articles and reviews written about dermal skin substitutes, there is no general consensus. Methods: This article reviews dermal skin scaffolds used in clinical applications and experimental settings. For scaffold evaluation, we focused on clinical and/or histological results, and conclusions are listed. Explanations for general trends were sought based on existing knowledge about tissue engineering principles and wound healing mechanisms. Results: Decellularized dermis seems to remain the best option with no other acellular scaffold being clinically proven to gain better results yet. In general, chemically cross-linked products were seen to be less effective in skin tissue engineering. Biocompatibility could be enhanced by preseeding substitutes with fibroblasts to allow some natural scaffold remodeling before product application. Conclusions: Skin substitutes are a useful tool in plastic and reconstructive surgery practices as an alternative to skin grafts. In the choice of substitute, the general plastic surgery principle of replacing like tissue with like tissue seems to be still standing, and products most resembling the natural dermal extracellular matrix should be preferred. PMID:25674365

Myeloid Wnt ligands are required for normal development of dermal lymphatic vasculature.

PubMed

Muley, Ajit; Odaka, Yoshi; Lewkowich, Ian P; Vemaraju, Shruti; Yamaguchi, Terry P; Shawber, Carrie; Dickie, Belinda H; Lang, Richard A

2017-01-01

Resident tissue myeloid cells play a role in many aspects of physiology including development of the vascular systems. In the blood vasculature, myeloid cells use VEGFC to promote angiogenesis and can use Wnt ligands to control vascular branching and to promote vascular regression. Here we show that myeloid cells also regulate development of the dermal lymphatic vasculature using Wnt ligands. Using myeloid-specific deletion of the WNT transporter Wntless we show that myeloid Wnt ligands are active at two distinct stages of development of the dermal lymphatics. As lymphatic progenitors are emigrating from the cardinal vein and intersomitic vessels, myeloid Wnt ligands regulate both their numbers and migration distance. Later in lymphatic development, myeloid Wnt ligands regulate proliferation of lymphatic endothelial cells (LEC) and thus control lymphatic vessel caliber. Myeloid-specific deletion of WNT co-receptor Lrp5 or Wnt5a gain-of-function also produce elevated caliber in dermal lymphatic capillaries. These data thus suggest that myeloid cells produce Wnt ligands to regulate lymphatic development and use Wnt pathway co-receptors to regulate the balance of Wnt ligand activity during the macrophage-LEC interaction.

Outcomes After Dermal Allograft Reconstruction of Chronic or Subacute Pectoralis Major Tendon Ruptures.

PubMed

Neumann, Julie A; Klein, Christopher M; van Eck, Carola F; Rahmi, Hithem; Itamura, John M

2018-01-01

Avoiding delay in the surgical management of pectoralis major (PM) ruptures optimizes outcomes. However, this is not always possible, and when a tear becomes chronic or when a subacute tear has poor tissue quality, a graft can facilitate reconstruction. The primary aim was to evaluate the clinical outcomes of PM reconstruction with dermal allograft augmentation for chronic tears or for subacute tears with poor tissue quality. A second aim was to determine patient and surgical factors affecting outcome. Case series; Level of evidence, 4. Nineteen consecutive patients (19 PM ruptures) with a mean ± SD age of 39.1 ± 8.4 years were retrospectively reviewed at 26.4 ± 16.0 months following PM tendon reconstruction with dermal allograft. Surgery was performed at 19.2 ± 41.2 months after injury (median, 7.6 months; range, 1.1-185.4 months). Several outcome scores were recorded pre- and postoperatively, including Disabilities of the Arm, Shoulder, and Hand (DASH), as well as visual analog scale (VAS) (range, 0-10; 0 = no pain) and Single Assessment Numeric Evaluation (SANE). Range of motion, Constant score, American Shoulder and Elbow Surgeons (ASES) score, Simple Shoulder Test score, and complications/reoperations were recorded postoperatively. Scores improved significantly for the DASH (preoperative, 34.9; postoperative, 8.0; P < .001) and VAS (preoperative, 5.0; postoperative, 1.5; P = .011). There was a trend toward improved SANE scores (preoperative, 15.0; postoperative, 80.0; P = .097), but the difference was not statistically significant, likely because of the small number of patients having preoperative SANE scores for review. Increased age was associated with higher VAS scores ( r = 0.628, P = .016) and less forward flexion ( r = -0.502, P = .048) and external rotation ( r = -0.654, P = .006). Patients with workers' compensation had lower scores for 3 measures: SANE (75.8 vs 88.4, P = .040), Constant (86.7 vs 93.4, P = .019), and ASES (81.9 vs 97.4, P = .016

A Bayesian statistical analysis of mouse dermal tumor promotion assay data for evaluating cigarette smoke condensate.

PubMed

Kathman, Steven J; Potts, Ryan J; Ayres, Paul H; Harp, Paul R; Wilson, Cody L; Garner, Charles D

2010-10-01

The mouse dermal assay has long been used to assess the dermal tumorigenicity of cigarette smoke condensate (CSC). This mouse skin model has been developed for use in carcinogenicity testing utilizing the SENCAR mouse as the standard strain. Though the model has limitations, it remains as the most relevant method available to study the dermal tumor promoting potential of mainstream cigarette smoke. In the typical SENCAR mouse CSC bioassay, CSC is applied for 29 weeks following the application of a tumor initiator such as 7,12-dimethylbenz[a]anthracene (DMBA). Several endpoints are considered for analysis including: the percentage of animals with at least one mass, latency, and number of masses per animal. In this paper, a relatively straightforward analytic model and procedure is presented for analyzing the time course of the incidence of masses. The procedure considered here takes advantage of Bayesian statistical techniques, which provide powerful methods for model fitting and simulation. Two datasets are analyzed to illustrate how the model fits the data, how well the model may perform in predicting data from such trials, and how the model may be used as a decision tool when comparing the dermal tumorigenicity of cigarette smoke condensate from multiple cigarette types. The analysis presented here was developed as a statistical decision tool for differentiating between two or more prototype products based on the dermal tumorigenicity. Copyright (c) 2010 Elsevier Inc. All rights reserved.

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.

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

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...

Laboratory Validation and Field Assessment of Petroleum Laboratory Technicians' Dermal Exposure to Crude Oil Using a Wipe Sampling Method.

PubMed

Galea, Karen S; Mueller, Will; Arfaj, Ayman M; Llamas, Jose L; Buick, Jennifer; Todd, David; McGonagle, Carolyn

2018-05-21

Crude oil may cause adverse dermal effects therefore dermal exposure is an exposure route of concern. Galea et al. (2014b) reported on a study comparing recovery (wipe) and interception (cotton glove) dermal sampling methods. The authors concluded that both methods were suitable for assessing dermal exposure to oil-based drilling fluids and crude oil but that glove samplers may overestimate the amount of fluid transferred to the skin. We describe a study which aimed to further evaluate the wipe sampling method to assess dermal exposure to crude oil, with this assessment including extended sample storage periods and sampling efficiency tests being undertaken at environmental conditions to mimic those typical of outdoor conditions in Saudi Arabia. The wipe sampling method was then used to assess the laboratory technicians' actual exposure to crude oil during typical petroleum laboratory tasks. Overall, acceptable storage efficiencies up to 54 days were reported with results suggesting storage stability over time. Sampling efficiencies were also reported to be satisfactory at both ambient and elevated temperature and relative humidity environmental conditions for surrogate skin spiked with known masses of crude oil and left up to 4 h prior to wiping, though there was an indication of reduced sampling efficiency over time. Nineteen petroleum laboratory technicians provided a total of 35 pre- and 35 post-activity paired hand wipe samples. Ninety-three percent of the pre-exposure paired hand wipes were less than the analytical limit of detection (LOD), whereas 46% of the post-activity paired hand wipes were less than the LOD. The geometric mean paired post-activity wipe sample measurement was 3.09 µg cm-2 (range 1.76-35.4 µg cm-2). It was considered that dermal exposure most frequently occurred through direct contact with the crude oil (emission) or via deposition. The findings of this study suggest that the wipe sampling method is satisfactory in quantifying

Isolation of intact sub-dermal secretory cavities from Eucalyptus

PubMed Central

2010-01-01

Background The biosynthesis of plant natural products in sub-dermal secretory cavities is poorly understood at the molecular level, largely due to the difficulty of physically isolating these structures for study. Our aim was to develop a protocol for isolating live and intact sub-dermal secretory cavities, and to do this, we used leaves from three species of Eucalyptus with cavities that are relatively large and rich in essential oils. Results Leaves were digested using a variety of commercially available enzymes. A pectinase from Aspergillus niger was found to allow isolation of intact cavities after a relatively short incubation (12 h), with no visible artifacts from digestion and no loss of cellular integrity or cavity contents. Several measurements indicated the potential of the isolated cavities for further functional studies. First, the cavities were found to consume oxygen at a rate that is comparable to that estimated from leaf respiratory rates. Second, mRNA was extracted from cavities, and it was used to amplify a cDNA fragment with high similarity to that of a monoterpene synthase. Third, the contents of the cavity lumen were extracted, showing an unexpectedly low abundance of volatile essential oils and a sizeable amount of non-volatile material, which is contrary to the widely accepted role of secretory cavities as predominantly essential oil repositories. Conclusions The protocol described herein is likely to be adaptable to a range of Eucalyptus species with sub-dermal secretory cavities, and should find wide application in studies of the developmental and functional biology of these structures, and the biosynthesis of the plant natural products they contain. PMID:20807444

A novel dermal matrix generated from burned skin as a promising substitute for deep-degree burns therapy

PubMed Central

YU, GUANYING; YE, LAN; TAN, WEI; ZHU, XUGUO; LI, YAONAN; JIANG, DUYIN

2016-01-01

The extensive skin defects induced by severe burns are dangerous and can be fatal. Currently, the most common therapy is tangential excision to remove the necrotic or denatured areas of skin, followed by skin grafting. Xenogeneic dermal substitutes, such as porcine acellular dermal matrix (ADM), are typically used to cover the burn wounds, and may accelerate wound healing. It is assumed that burned skin that still maintains partial biological activity may be recycled to construct an autologous acellular dermal matrix, termed 'deep-degree burned dermal matrix (DDBDM)'. In theory, DDBDM may avoid the histoincompatibility issues associated with foreign or xenogeneic dermal matrices, and reduce therapy costs by making full use of discarded skin. In the present study, the collagens within prepared DDBDM were thickened, disorganized and partially fractured, however, they still maintained their reticular structure and tensile strength (P<0.01). Through microarray analysis of the cytokines present in ADM and DDBDM, it was determined that the DDBDM did not produce excessive levels of harmful burn toxins. Following 4 weeks of subcutaneous implantation, ADM and DDBDM were incompletely degraded and maintained good integrity. No significant inflammatory reaction or rejection were observed, which indicated that ADM and DDBDM have good histocompatibility. Therefore, DDBDM may be a useful material for the treatment of deep-degree burns. PMID:26846279

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.

Comparison of Calcium and Barium Microcapsules as Scaffolds in the Development of Artificial Dermal Papillae.

PubMed

Liu, Yang; Lin, Changmin; Zeng, Yang; Li, Haihong; Cai, Bozhi; Huang, Keng; Yuan, Yanping; Li, Yu

2016-01-01

This study aimed to develop and evaluate barium and calcium microcapsules as candidates for scaffolding in artificial dermal papilla. Dermal papilla cells (DPCs) were isolated and cultured by one-step collagenase treatment. The DPC-Ba and DPC-Ca microcapsules were prepared by using a specially designed, high-voltage, electric-field droplet generator. Selected microcapsules were assessed for long-term inductive properties with xenotransplantation into Sprague-Dawley rat ears. Both barium and calcium microcapsules maintained xenogenic dermal papilla cells in an immunoisolated environment and induced the formation of hair follicle structures. Calcium microcapsules showed better biocompatibility, permeability, and cell viability in comparison with barium microcapsules. Before 18 weeks, calcium microcapsules gathered together, with no substantial immune response. After 32 weeks, some microcapsules were near inflammatory cells and wrapped with fiber. A few large hair follicles were found. Control samples showed no marked changes at the implantation site. Barium microcapsules were superior to calcium microcapsules in structural and mechanical stability. The cells encapsulated in hydrogel barium microcapsules exhibited higher short-term viability. This study established a model to culture DPCs in 3D culture conditions. Barium microcapsules may be useful in short-term transplantation study. Calcium microcapsules may provide an effective scaffold for the development of artificial dermal papilla.

Effect of gel re-organization and tensional forces on alpha2beta1 integrin levels in dermal fibroblasts.

PubMed

Jenkins, G; Redwood, K L; Meadows, L; Green, M R

1999-07-01

Mechanical forces are known to play an important role in regulating cell function in a wide range of biological systems. This is of particular relevance to dermal fibroblast function, given that the skin is known to be held under an intrinsic natural tension. To understand more about the generation of force by dermal fibroblasts and their ability to respond to changes in it, we have studied the role of the beta1 integrin receptors expressed by dermal fibroblasts in their ability to generate tensional forces within a collagen type I matrix and the effect of altered tensional force on integrin expression by dermal fibroblasts. Using a purpose-built culture force monitor, function-blocking antibodies directed towards the beta1 receptors dramatically reduced the tensional forces generated by dermal fibroblasts in a 3D collagen I matrix. However, the specific involvement of alpha1 or alpha2 subunits could not be demonstrated. Analysis of cellular response demonstrated that cells isolated from contracting collagen gels expressed fourfold higher levels of alpha2 mRNA than cells isolated from fully restrained gels. The levels of beta1 messenger RNA were relatively unaffected by reductions in force. Cells exposed to single reductions in force, however, did not exhibit alterations in either alpha1 or beta1 mRNA levels. We propose, therefore that alpha2beta1 integrin receptor levels in dermal fibroblasts are not altered in response to single reductions of gel tension, but do change following a continual change in force and associated matrix re-organization

40 CFR 795.225 - Dermal pharmacokinetics of DGBE and DGBA.

Code of Federal Regulations, 2010 CFR

2010-07-01

... this section because they will facilitate the work and improve the reliability of quantitative... for this purpose. (ii) Biotransformation after dermal dosing. Appropriate qualitative and quantitative... tabular form. (2) Evaluation of results. All observed results, quantitative or incidental, shall be...

40 CFR 795.225 - Dermal pharmacokinetics of DGBE and DGBA.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Dermal pharmacokinetics of DGBE and DGBA. 795.225 Section 795.225 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional Health Effects...

40 CFR 795.225 - Dermal pharmacokinetics of DGBE and DGBA.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Dermal pharmacokinetics of DGBE and DGBA. 795.225 Section 795.225 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional Health Effects...

40 CFR 795.225 - Dermal pharmacokinetics of DGBE and DGBA.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Dermal pharmacokinetics of DGBE and DGBA. 795.225 Section 795.225 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional Health Effects...

40 CFR 795.225 - Dermal pharmacokinetics of DGBE and DGBA.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 33 2012-07-01 2012-07-01 false Dermal pharmacokinetics of DGBE and DGBA. 795.225 Section 795.225 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional Health Effects...

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

One-stage Reconstruction of Soft Tissue Defects with the Sandwich Technique: Collagen-elastin Dermal Template and Skin Grafts

PubMed Central

Wollina, Uwe

2011-01-01

Background: A full-thickness soft tissue defect closure often needs complex procedures. The use of dermal templates can be helpful in improving the outcome. Objective: The objective was to evaluate a sandwich technique combining the dermal collagen–elastin matrix with skin grafts in a one-stage procedure. Materials and Methods: Twenty-three patients with 27 wounds were enrolled in this prospective single-centre observational study. The mean age was 74.8 ± 17.2 years. Included were full-thickness defects with exposed bone, cartilage and/ or tendons. The dermal collagen–elastin matrix was applied onto the wound bed accomplished by skin transplants, i.e. ‘sandwich’ transplantation. In six wounds, the transplants were treated with intermittent negative pressure therapy. Results: The size of defects was ≤875 cm2. The use of the dermal template resulted in a complete and stable granulation in 100% of wounds. Seventeen defects showed a complete closure and 19 achieved a complete granulation with an incomplete closure. There was a marked pain relief. No adverse events were noted due to the dermal template usage. Conclusions: Sandwich transplantation with the collagen–elastin matrix is a useful tool when dealing with full-thickness soft tissue defects with exposed bone, cartilage or tendons. PMID:22279382

Securing the Airway in Pretracheal Dermal Metastases From Oropharyngeal Carcinoma: A Case Report.

PubMed

Truong, Angela T; Truong, Dam-Thuy; Gillenwater, Ann M; Soliz, Jose M; Rahlfs, Thomas F

2018-04-23

Dermal metastases reflect the ominous and aggressive spread of oropharyngeal squamous cell carcinomas. The rampant proliferation of these metastatic tumors to the neck results in respiratory distress and impending airway obstruction. We report a case of a patient with massive neck dermal metastases requiring urgent airway control for intermittent stridor. Awake tracheostomy is generally regarded as the gold standard to manage the compromised airway. However, in this unusual case, after discussion between surgeon and anesthesiologist, because of the anticipated formidable difficulties in performing awake tracheostomy, it was decided that awake fiberoptic intubation would provide the best chance of success.

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.

Occupational dermal exposure to nanoparticles and nano-enabled products: Part 2, exploration of exposure processes and methods of assessment.

PubMed

Brouwer, Derk H; Spaan, Suzanne; Roff, Martin; Sleeuwenhoek, Anne; Tuinman, Ilse; Goede, Henk; van Duuren-Stuurman, Birgit; Filon, Francesca Larese; Bello, Dhimiter; Cherrie, John W

2016-08-01

Over the past decade, the primary focus of nanotoxicology and nanoenvironmental health and safety efforts has been largely on inhalation exposure to engineered nanomaterials, at the production stage, and much less on considering risks along the life cycle of nano-enabled products. Dermal exposure to nanomaterials and its health impact has been studied to a much lesser extent, and mostly in the context of intentional exposure to nano-enabled products such as in nanomedicine, cosmetics and personal care products. How concerning is dermal exposure to such nanoparticles in the context of occupational exposures? When and how should we measure it? In the first of a series of two papers (Larese Filon et al., 2016), we focused our attention on identifying conditions or situations, i.e. a combination of nanoparticle physico-chemical properties, skin barrier integrity, and occupations with high prevalence of skin disease, which deserve further investigation. This second paper focuses on the broad question of dermal exposure assessment to nanoparticles and attempts to give an overview of the mechanisms of occupational dermal exposure to nanoparticles and nano-enabled products and explores feasibility and adequacy of various methods of quantifying dermal exposure to NOAA. We provide here a conceptual framework for screening, prioritization, and assessment of dermal exposure to NOAA in occupational settings, and integrate it into a proposed framework for risk assessment. Copyright © 2016 Elsevier GmbH. All rights reserved.

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.

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

Chronic UVB-irradiation actuates perpetuated dermal matrix remodeling in female mice: Protective role of estrogen

PubMed Central

Röck, Katharina; Joosse, Simon Andreas; Müller, Julia; Heinisch, Nina; Fuchs, Nicola; Meusch, Michael; Zipper, Petra; Reifenberger, Julia; Pantel, Klaus; Fischer, Jens Walter

2016-01-01

Chronic UVB-exposure and declined estradiol production after menopause represent important factors leading to extrinsic and intrinsic aging, respectively. Remodeling of the extracellular matrix (ECM) plays a crucial role in both responses. Whether the dermal ECM is able to recover after cessation of UVB-irradiation in dependence of estradiol is not known, however of relevance when regarding possible treatment options. Therefore, the endogenous sex hormone production was depleted by ovariectomy in female mice. Half of the mice received estradiol substitution. Mice were UVB-irradiated for 20 weeks and afterwards kept for 10 weeks without irradiation. The collagen-, hyaluronan- and proteoglycan- (versican, biglycan, lumican) matrix, collagen cleavage products and functional skin parameters were analyzed. The intrinsic aging process was characterized by increased collagen fragmentation and accumulation of biglycan. Chronic UVB-irradiation additionally augmented the lumican, versican and hyaluronan content of the dermis. In the absence of further UVB-irradiation the degradation of collagen and accumulation of biglycan in the extrinsically aged group was perpetuated in an excessive matter. Whereas estradiol increased the proteoglycan content, it reversed the effects of the perpetuated extrinsic response on collagen degradation. Suspension of the intrinsic pathway might therefore be sufficient to antagonize UVB-evoked long-term damage to the dermal ECM. PMID:27460287

Proof-of-Principle Dermal Decontamination Experiments: Swine Skin

DTIC Science & Technology

2007-04-01

approvals it was decided to first demonstrate the proof-of-principle of dermal decontamination for this model using swine skin samples ex vivo . When...appropriate individual protection equipment (IPE) and dosimetry . 3. All activities were monitored by the DRDC Ottawa RadSO. 4. The workstation...while working with the radionuclides, as well as the necessary dosimetry . All personnel wore standard Health Canada issued thermo- luminescent

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.

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

BREATH MEASUREMENT AND MODELS TO ASSESS VOC DERMAL ABSORPTION IN WATER

EPA Science Inventory

Dermal exposure to volatile organic compounds (VOCs) in water results from environmental contamination of surface, ground-, and drinking waters. This exposure occurs both in occupational and residential settings. Compartmental models incorporating body burden measurements have ...

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

A decision support framework for characterizing and managing dermal exposures to chemicals during Emergency Management and Operations.

PubMed

Dotson, G Scott; Hudson, Naomi L; Maier, Andrew

2015-01-01

Emergency Management and Operations (EMO) personnel are in need of resources and tools to assist in understanding the health risks associated with dermal exposures during chemical incidents. This article reviews available resources and presents a conceptual framework for a decision support system (DSS) that assists in characterizing and managing risk during chemical emergencies involving dermal exposures. The framework merges principles of three decision-making techniques: 1) scenario planning, 2) risk analysis, and 3) multicriteria decision analysis (MCDA). This DSS facilitates dynamic decision making during each of the distinct life cycle phases of an emergency incident (ie, preparedness, response, or recovery) and identifies EMO needs. A checklist tool provides key questions intended to guide users through the complexities of conducting a dermal risk assessment. The questions define the scope of the framework for resource identification and application to support decision-making needs. The framework consists of three primary modules: 1) resource compilation, 2) prioritization, and 3) decision. The modules systematically identify, organize, and rank relevant information resources relating to the hazards of dermal exposures to chemicals and risk management strategies. Each module is subdivided into critical elements designed to further delineate the resources based on relevant incident phase and type of information. The DSS framework provides a much needed structure based on contemporary decision analysis principles for 1) documenting key questions for EMO problem formulation and 2) a method for systematically organizing, screening, and prioritizing information resources on dermal hazards, exposures, risk characterization, and management.

A decision support framework for characterizing and managing dermal exposures to chemicals during Emergency Management and Operations

PubMed Central

Dotson, G. Scott; Hudson, Naomi L.; Maier, Andrew

2016-01-01

Emergency Management and Operations (EMO) personnel are in need of resources and tools to assist in understanding the health risks associated with dermal exposures during chemical incidents. This article reviews available resources and presents a conceptual framework for a decision support system (DSS) that assists in characterizing and managing risk during chemical emergencies involving dermal exposures. The framework merges principles of three decision-making techniques: 1) scenario planning, 2) risk analysis, and 3) multicriteria decision analysis (MCDA). This DSS facilitates dynamic decision making during each of the distinct life cycle phases of an emergency incident (ie, preparedness, response, or recovery) and identifies EMO needs. A checklist tool provides key questions intended to guide users through the complexities of conducting a dermal risk assessment. The questions define the scope of the framework for resource identification and application to support decision-making needs. The framework consists of three primary modules: 1) resource compilation, 2) prioritization, and 3) decision. The modules systematically identify, organize, and rank relevant information resources relating to the hazards of dermal exposures to chemicals and risk management strategies. Each module is subdivided into critical elements designed to further delineate the resources based on relevant incident phase and type of information. The DSS framework provides a much needed structure based on contemporary decision analysis principles for 1) documenting key questions for EMO problem formulation and 2) a method for systematically organizing, screening, and prioritizing information resources on dermal hazards, exposures, risk characterization, and management. PMID:26312660

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

IN VIVO DERMAL ABSORPTION OF PYRETHROID PESTICIDES IN THE RAT

EPA Science Inventory

The potential for exposure to pyrethroid pesticides has risen recently because of their increased agricultural and residential use. The objective of this study was to examine the in vivo dermal absorption of bifenthrin, deltamethrin and cis-permethrin in the rat. Hair on...

In vivo dermal absorption of pyrethroid pesticides in the rat.

EPA Science Inventory

The potential for exposure to pyrethroid pesticides has risen recently because of their increased use. The objective of this study was to examine the in vivo dermal absorption of bifenthrin, deltamethrin and permethrin in the rat. Hair on the dorsal side of anesthetized adult m...

Acellular dermal matrices in breast implant surgery: defining the problem and proof of concept.

PubMed

Baxter, Richard A

2012-04-01

The use of acellular dermal matrices (ADMs) has become a useful adjunct to implant-based breast reconstruction and revision of the augmented breast. In both instances, the goal is replacement or reinforcement of thinned or missing tissues for implant support and control of the implant pocket. This article reviews the factors that contribute to periprosthetic tissue thinning, and the advantages and limitations of the use of ADMs for revision breast surgery and breast reconstruction. Proof of concept for the use of ADMs in the periprosthetic space is detailed from early clinical experience and histologic analysis documenting vascular ingrowth and cellular repopulation. Copyright © 2012 Elsevier Inc. All rights reserved.

Distribution of kerosene components in rats following dermal exposure.

PubMed

Tsujino, Y; Hieda, Y; Kimura, K; Eto, H; Yakabe, T; Takayama, K; Dekio, S

2002-08-01

The systemic distribution of kerosene components in blood and tissues was analysed in rats following dermal exposure. Four types of trimethylbenzenes (TMBs) and aliphatic hydrocarbons (AHCs) with carbon numbers 9-16 (C(9)-C(16)) were analysed as major kerosene components by capillary gas chromatography/mass spectrometry (GC/MS). The kerosene components were detected in blood and all tissues after a small piece of cotton soaked with kerosene was applied to the abdominal skin. The amounts of TMBs detected were higher than those of AHCs. Greater increases in TMB levels were found in adipose tissue in an exposure duration-dependent manner. The amounts of TMBs detected were only at trace levels following post-mortem dermal exposure to kerosene. These findings suggest that kerosene components were absorbed percutaneously and distributed to various organs via the blood circulation. Post-mortem or ante-mortem exposure to kerosene could be distinguished when the exposure duration was relatively long. Adipose tissue would seem to be the most useful for estimating the degree of kerosene exposure.

Advective and diffusive dermal processes for estimating terrestrial amphibian pesticide exposure

EPA Science Inventory

Background/Question/Methods Dermal exposure presents a potentially significant but understudied route for pesticide uptake in terrestrial amphibians. Historically, evaluation of pesticide risk to both amphibians and reptiles has been achieved by comparing ingestion and inhalat...

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.

Dermal carotenoid measurement is inversely related to anxiety in patients with breast cancer.

PubMed

Li, David G; LeCompte, Gabrielle; Golod, Lev; Cecchi, Gary; Irwin, David; Harken, Alden; Matecki, Amy

2018-02-01

Breast cancer is the most prevalent malignancy among women worldwide. Increased oxidative stress and poor subjective health outcomes have been associated with increased risk of cancer recurrence and metastasis, but few studies until now have explored the relationship between oxidative stress and chronic stress/anxiety. This study aims to examine the association between anxiety and a potential dermal correlate of oxidative stress in patients with breast cancer. 102 breast cancer patients were enrolled in a cross-sectional study at Highland Hospital, a county hospital in Oakland, California. Each participant's skin carotenoid score (SCS), a potential dermal correlate of oxidative stress, was recorded via Raman spectroscopy. Patient demographics, breast cancer stage, and subjective health measures (anxiety and self-rated health) were ascertained. Multivariate linear regression analysis was performed to quantify any associations between SCS and the above health correlates. Higher levels of skin carotenoids were associated with decreased severity of anxiety, lower BMI, increased servings of vegetables/fruits in daily diet, Hispanic race, lower educational status, and nonsmoking status. Severity of anxiety as graded by the GAD-7 was inversely associated with dermal carotenoid measurements via SCS. Increased levels of oxidative stress as quantified by SCS is associated with greater severity of anxiety. Because chronic stress has been associated with tumor progression, increased recurrence rates, and increased metastatic risk in breast cancer,non-invasive dermal carotenoid measurements could be used as a novel objective correlate of subjective health during cancer treatment. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Preventing the Complications Associated with the Use of Dermal Fillers in Facial Aesthetic Procedures: An Expert Group Consensus Report.

PubMed

Urdiales-Gálvez, Fernando; Delgado, Nuria Escoda; Figueiredo, Vitor; Lajo-Plaza, José V; Mira, Mar; Ortíz-Martí, Francisco; Del Rio-Reyes, Rosa; Romero-Álvarez, Nazaret; Del Cueto, Sofía Ruiz; Segurado, María A; Rebenaque, Cristina Villanueva

2017-06-01

The use of dermal fillers in minimally invasive facial aesthetic procedures has become increasingly popular of late, yet as the indications and the number of procedures performed increase, the number of complications is also likely to increase. Paying special attention to specific patient characteristics and to the technique used can do much to avoid these complications. Indeed, a well-trained physician can also minimize the impact of such problems when they do occur. A multidisciplinary group of experts in aesthetic treatments reviewed the main factors associated with the complications that arise when using dermal fillers. A search of English, French and Spanish language articles in PubMed was performed using the terms "complications" OR "soft filler complications" OR "injectable complications" AND "dermal fillers". An initial document was drafted that reflected the complications identified and recommendations as to how they should be handled. This document was then reviewed and modified by the expert panel, until a final text was agreed upon and validated. The panel addressed consensus recommendations about the preparation, the procedure and the post-procedural care. The panel considered it crucial to obtain an accurate medical history to prevent potential complications. An additional clinical assessment, including standardized photography, is also crucial to evaluate the outcomes and prevent potential complications. Furthermore, the state of the operating theatre, the patient's health status and the preparation of the skin are critical to prevent superficial soft tissue infections. Finally, selecting the appropriate technique, based on the physician's experience, as well as the characteristics of the patient and filler, helps to ensure successful outcomes and limits the complications. This consensus document provides key elements to help clinicians who are starting to use dermal fillers to employ standard procedures and to understand how best to prevent

The effects of heat on skin barrier function and in vivo dermal absorption.

PubMed

Oliveira, Gabriela; Leverett, Jesse C; Emamzadeh, Mandana; Lane, Majella E

2014-04-10

Enhanced delivery of ingredients across the stratum corneum (SC) is of great interest for improving the efficacy of topically applied formulations. Various methods for improving dermal penetration have been reported including galvanic devices and micro-needles. From a safety perspective it is important that such approaches do not compromise SC barrier function. This study investigates the influence of topically applied heat in vivo on the dermal uptake and penetration of a model active, allantoin from gel and lotion formulations. A custom designed device was used to deliver 42°C for 30s daily to human subjects after application of two formulations containing allantoin. The results were compared with sites treated with formulations containing no active and no heat, and a control site. In addition to penetration of allantoin, the integrity of the SC was monitored using trans-epidermal water loss (TEWL) measurements. The results showed that just 30s of 42°C topically applied heat was enough to cause significantly more penetration of allantoin from the lotion formulation compared with no application of heat. TEWL data indicated that the integrity of the skin was not compromised by the treatment. However, the application of heat did not promote enhanced penetration of the active from the gel formulation. Vehicle composition is therefore an important factor when considering thermal enhancement strategies for targeting actives to the skin. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections.

PubMed

Draughn, G Logan; Allen, C Leigh; Routh, Patricia A; Stone, Maria R; Kirker, Kelly R; Boegli, Laura; Schuchman, Ryan M; Linder, Keith E; Baynes, Ronald E; James, Garth; Melander, Christian; Pollard, Angela; Cavanagh, John

2017-01-01

2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus , we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.

Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections

PubMed Central

Draughn, G Logan; Allen, C Leigh; Routh, Patricia A; Stone, Maria R; Kirker, Kelly R; Boegli, Laura; Schuchman, Ryan M; Linder, Keith E; Baynes, Ronald E; James, Garth; Melander, Christian; Pollard, Angela; Cavanagh, John

2017-01-01

2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound. PMID:28138218

Sustained release of stromal cell derived factor-1 from an antioxidant thermoresponsive hydrogel enhances dermal wound healing in diabetes.

PubMed

Zhu, Yunxiao; Hoshi, Ryan; Chen, Siyu; Yi, Ji; Duan, Chongwen; Galiano, Robert D; Zhang, Hao F; Ameer, Guillermo A

2016-09-28

Diabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus. Altered cell migration due to microcirculatory deficiencies as well as excessive and prolonged reactive oxygen species production are implicated in the delayed healing of DFUs. The goal of this research was to assess whether sustained release of SDF-1, a chemokine that promotes endothelial progenitor cell homing and angiogenesis, from a citrate-based antioxidant thermoresponsive polymer would significantly improve impaired dermal wound healing in diabetes. Poly (polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) was synthesized via sequential polycondensation and free radical polymerization reactions. SDF-1 was entrapped via gelation of the PPCN+SDF-1 solution above its lower critical solution temperature (LCST) and its release and bioactivity was measured. The effect of sustained release of SDF-1 from PPCN (PPCN+SDF-1) versus a bolus application of SDF-1 in phosphate buffered saline (PBS) on wound healing was evaluated in a diabetic murine splinted excisional dermal wound model using gross observation, histology, immunohistochemistry, and optical coherence tomography microangiography. Increasing PPCN concentration decreased SDF-1 release rate. The time to 50% wound closure was 11days, 16days, 14days, and 17days for wounds treated with PPCN+SDF-1, SDF-1 only, PPCN only, and PBS, respectively. Wounds treated with PPCN+SDF-1 had the shortest time for complete healing (24days) and exhibited accelerated granulation tissue production, epithelial maturation, and the highest density of perfused blood vessels. In conclusion, sustained release of SDF-1 from PPCN is a promising and easy to use therapeutic strategy to improve the treatment of chronic non-healing DFUs. Copyright © 2016 Elsevier B.V. All rights reserved.

Respiratory response to toluene diisocyanate depends on prior frequency and concentration of dermal sensitization in mice.

PubMed

Vanoirbeek, Jeroen A J; Tarkowski, Maciej; Ceuppens, Jan L; Verbeken, Erik K; Nemery, Benoit; Hoet, Peter H M

2004-08-01

Occupational asthma is the principal cause of work-related respiratory disease in the industrial world. In the absence of satisfactory models for predicting the potential of low molecular weight chemicals to cause asthma, we verified that dermal sensitization prior to intranasal challenge influences the respiratory response using toluene diisocyanate (TDI), a known respiratory sensitizer. BALB/c mice received TDI or vehicle (acetone/olive oil) on each ear on three consecutive days (days 1, 2, and 3; 0.3 or 3% TDI) or only once (day 1, 1% TDI). On day 7, the mice received similar dermal applications of vehicle or the same concentration of TDI as before ("boost"). On day 10, they received an intranasal dose of TDI (0.1%) or vehicle. Ventilatory function was monitored by whole body plethysmography for 40 min after intranasal application, and reactivity to inhaled methacholine was assessed 24 h later. Pulmonary inflammation was assessed by bronchoalveolar lavage and histology. Mice that received an intranasal dose of TDI without having received a prior dermal application of TDI did not exhibit any ventilatory response or inflammatory changes compared to vehicle controls. In contrast, mice that had received prior application(s) of TDI, even if only on day 7, exhibited the following: ventilatory responses, compatible with bronchoconstriction, immediately after intranasal application with TDI; enhanced methacholine responsiveness 24 h later; and pulmonary inflammation characterized by neutrophils. This was, however, not the case in mice that received the highest dermal amount of TDI (3% on days 1, 2, and 3). These findings suggest that respiratory response to TDI depends on prior frequency and concentration of dermal sensitization in mice.

Dermal necrosis following coumarin: is it immunologically induced?

PubMed

Hislop, I G; Zilko, P J; Petersen, M; Ahmed, N

1980-02-01

Two patients with dermal necrosis due to anticoagulation therapy with warfarin are reported. Both patients demonstrated some disturbance in immunological function. It appears possible that warfarin may act as a hapten in the induction of hypersensitivity to the drug. It is recommended that future cases should be studied to determine whether there is a defect in immunoregulation, and whether circulating immune complexes are responsible for the typical skin lesions.

Quantitative and qualitative evaluation of dermal elastin of draught horses with chronic progressive lymphoedema.

PubMed

De Cock, H E V; Van Brantegem, L; Affolter, V K; Oosterlinck, M; Ferraro, G L; Ducatelle, R

2009-01-01

Chronic progressive lymphoedema (CPL) in horses, a disease of certain draught breeds, is associated with altered elastin metabolism. The characteristic lesions are seen in the skin of the lower (distal) limbs. This study was based on horses of susceptible breeds, with and without CPL, and on horses of a non-susceptible breed. Skin samples were obtained for examination from the neck (considered a non-affected region) and from the distal limb. The skin lesions were characterized histologically and the dermal elastic fibres were evaluated morphologically and quantitatively. In all horses the mean elastin concentrations were highest in the superficial dermis, gradually decreasing in the mid-dermis and deep dermis. As compared with horses of a non-susceptible breed, affected horses had increased amounts of dermal elastin in both the distal limb and neck, while non-affected horses of a susceptible breed had decreased amounts. The findings support an earlier hypothesis that CPL of horses is a generalized disease. Reduced efficiency of the elastic network in supporting the dermal lymphatics may explain the development of CPL.

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

Bovine versus Porcine Acellular Dermal Matrix: A Comparison of Mechanical Properties.

PubMed

Adelman, David M; Selber, Jesse C; Butler, Charles E

2014-05-01

Porcine and bovine acellular dermal matrices (PADM and BADM, respectively) are the most commonly used biologic meshes for ventral hernia repair. A previous study suggests a higher rate of intraoperative device failures using PADM than BADM. We hypothesize that this difference is, in part, related to intrinsic mechanical properties of the matrix substrate and source material. The following study directly compares these 2 matrices to identify any potential differences in mechanical properties that may relate to clinical outcomes. Sections of PADM (Strattice; Lifecell, Branchburg, N.J.) and BADM (SurgiMend; TEI Biosciences, Boston, Mass.) were subjected to a series of biomechanical tests, including suture retention, tear strength, and uniaxial tensile strength. Results were collected and compared statistically. In all parameters, BADM exhibited a superior mechanical strength profile compared with PADM of similar thickness. Increased BADM thickness correlated with increased mechanical strength. In suture tear-through testing with steel wire, failure of the steel wire occurred in the 4-mm-thick BADM, whereas the matrix material failed in all other thicknesses of BADM and PADM. Before implantation, BADM is inherently stronger than PADM at equivalent thicknesses and considerably stronger at increased thicknesses. These results corroborate clinical data from a previous study in which PADM was associated with a higher intraoperative device failure rate. Although numerous properties of acellular dermal matrix contribute to clinical outcomes, surgeons should consider initial mechanical strength properties when choosing acellular dermal matrices for load-bearing applications such as hernia repair.

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.

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

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.

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.

Soil Organic Matter Content Effects on Dermal Pesticide ...

EPA Pesticide Factsheets

Agricultural landscapes serve as active amphibian breeding grounds despite their seemingly poor habitat value. Activity of adults and dispersal of metamorphs to and from agricultural ponds occurs in most species from spring through late summer or early fall, a time that coincides with pesticide applications on farm fields and crops. In terrestrial landscapes, dermal contact with contaminated soil and plant matter may lead to bioconcentration as well as lethal and sublethal effects in amphibians.Although the physiological structure of the amphibian dermis may facilitate pesticide uptake, soil properties may ultimately dictate bioavailability of pesticides in terrestrial habitats. The organic matter fraction of soil readily binds to pesticides, potentially decreasing the availability of pesticides adhering to biological matter. Soil partition coefficient dermal uptake of five pesticide active ingredients on either high or low organic matter soils. We predicted that amphibian body burdens would be a function of soil carbon content or Koc. with greater bioconcentration in individuals exposed to pesticides on sa

UVA Causes Dual Inactivation of Cathepsin B and L Underlying Lysosomal Dysfunction in Human Dermal Fibroblasts

PubMed Central

Lamore, Sarah D.; Wondrak, Georg T.

2013-01-01

Cutaneous exposure to chronic solar UVA-radiation is a causative factor in photocarcinogenesis and photoaging. Recently, we have identified the thiol-dependent cysteine-protease cathepsin B as a novel UVA-target undergoing photo-oxidative inactivation upstream of autophagic-lysosomal dysfunction in fibroblasts. In this study, we examined UVA effects on a wider range of cathepsins and explored the occurrence of UVA-induced cathepsin inactivation in other cultured skin cell types. In dermal fibroblasts, chronic exposure to non-cytotoxic doses of UVA caused pronounced inactivation of the lysosomal cysteine-proteases cathepsin B and L, effects not observed in primary keratinocytes and occurring only to a minor extent in primary melanocytes. In order to determine if UVA-induced lysosomal impairment requires single or dual inactivation of cathepsin B and/or L, we used a genetic approach (siRNA) to selectively downregulate enzymatic activity of these target cathepsins. Monitoring an established set of protein markers (including LAMP1, LC3-II, and p62) and cell ultrastructural changes detected by electron microscopy, we observed that only dual genetic antagonism (targeting both CTSB and CTSL expression) could mimic UVA-induced autophagic-lysosomal alterations, whereas single knockdown (targeting CTSB or CTSL only) did not display ‘UVA-mimetic’ effects failing to reproduce the UVA-induced phenotype. Taken together, our data demonstrate that chronic UVA inhibits both cathepsin B and L enzymatic activity and that dual inactivation of both enzymes is a causative factor underlying UVA-induced impairment of lysosomal function in dermal fibroblasts. PMID:23603447

DERMAL AND MOUTHING TRANSFERS OF SURFACE RESIDUES MEASURED USING FLUORESCENCE IMAGING

EPA Science Inventory

To reduce the uncertainty associated with current estimates of children's exposure to pesticides by dermal contact and non-dietary ingestion, residue transfer data are required. Prior to conducting exhaustive studies, a screening study to develop and test methods for measuring...

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

Dermatopharmacokinetic and pharmacodynamic evaluation of ethosomes of griseofulvin designed for dermal delivery

NASA Astrophysics Data System (ADS)

Aggarwal, Nidhi; Goindi, Shishu

2013-10-01

The present study is aimed at evaluation of the dermal delivery potential of griseofulvin-loaded ethosomes. Griseofulvin-loaded ethosomes were prepared using "Cold technique" (Indian Patent Application 208/DEL/2009). The optimized formulation was characterized for vesicular shape and size, drug entrapment efficiency, drug content, pH, stability, and spreadability. Ex vivo skin permeation, dermatopharmacokinetics, and skin sensitivity studies were carried out using male Laca mice. In vivo antifungal activity was assessed against Microsporum canis using guinea pig model for dermatophytosis. The optimized formulation E7 possessing 2 % phospholipid (PL) and 30 % ethanol exhibited the highest drug entrapment (72.94 ± 0.80 %) and optimum vesicle size (148.5 ± 0.48 nm). E7 illustrated remarkably higher drug permeation and skin retention when compared with liposomes. Pharmacodynamic studies in guinea pigs induced with M. canis revealed that the dermal fungal infection was completely cured in 8 days upon twice daily topical application of griseofulvin-loaded ethosomes whereas liposomes led to complete cure in 14 days. The formulation was observed to be non-sensitizing, histopathologically safe, and stable at 5 ± 3, 25 ± 2, and 40 ± 2 °C for a period of 1 year. Results indicated that dermal delivery of griseofulvin employing ethosomes could be a commendable alternative to reduce the bio-burden associated with conventional oral formulations.

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

Fossil Fishes from China Provide First Evidence of Dermal Pelvic Girdles in Osteichthyans

PubMed Central

Zhu, Min; Yu, Xiaobo; Choo, Brian; Qu, Qingming; Jia, Liantao; Zhao, Wenjin; Qiao, Tuo; Lu, Jing

2012-01-01

Background The pectoral and pelvic girdles support paired fins and limbs, and have transformed significantly in the diversification of gnathostomes or jawed vertebrates (including osteichthyans, chondrichthyans, acanthodians and placoderms). For instance, changes in the pectoral and pelvic girdles accompanied the transition of fins to limbs as some osteichthyans (a clade that contains the vast majority of vertebrates – bony fishes and tetrapods) ventured from aquatic to terrestrial environments. The fossil record shows that the pectoral girdles of early osteichthyans (e.g., Lophosteus, Andreolepis, Psarolepis and Guiyu) retained part of the primitive gnathostome pectoral girdle condition with spines and/or other dermal components. However, very little is known about the condition of the pelvic girdle in the earliest osteichthyans. Living osteichthyans, like chondrichthyans (cartilaginous fishes), have exclusively endoskeletal pelvic girdles, while dermal pelvic girdle components (plates and/or spines) have so far been found only in some extinct placoderms and acanthodians. Consequently, whether the pectoral and pelvic girdles are primitively similar in osteichthyans cannot be adequately evaluated, and phylogeny-based inferences regarding the primitive pelvic girdle condition in osteichthyans cannot be tested against available fossil evidence. Methodology/Principal Findings Here we report the first discovery of spine-bearing dermal pelvic girdles in early osteichthyans, based on a new articulated specimen of Guiyu oneiros from the Late Ludlow (Silurian) Kuanti Formation, Yunnan, as well as a re-examination of the previously described holotype. We also describe disarticulated pelvic girdles of Psarolepis romeri from the Lochkovian (Early Devonian) Xitun Formation, Yunnan, which resemble the previously reported pectoral girdles in having integrated dermal and endoskeletal components with polybasal fin articulation. Conclusions/Significance The new findings reveal

Increase in gap junctional intercellular communication by high molecular weight hyaluronic acid associated with fibroblast growth factor 2 and keratinocyte growth factor production in normal human dermal fibroblasts.

PubMed

Park, Jeong Ung; Tsuchiya, Toshie

2002-07-01

The effects of different molecular weights of hyaluronic acid (HA), a major component of extracellular matrix, on gap junctional intercellular communication (GJIC) in normal human dermal fibroblasts (NHDF cells) were investigated. NHDF cells were cultured for 4 days with different molecular weights of HA and then the extent of GJIC was assessed by the scrape-loading dye transfer method, using Lucifer yellow. The area of dye transfer was greater in the dishes coated with HA than in those to which HA was added. Thus, NHDF cells cultured on surfaces coated with high molecular weight (HMW) HA (MW, 800 kDa) showed greatly enhanced GJIC. Furthermore, another aim of this study was to evaluate the effects of different molecular weights of HA on the production of FGF-2 and KGF, because both are important cytokines produced by NHDF cells. When FGF-2 and KGF cultured levels of cell extracts and media were determined by ELISA, both levels were significantly enhanced when cells were grown on plates coated with HMW HA. This finding indicated that the function of gap junction channels in NHDF cells grown on plates coated with HMW HA may promote the biosynthesis of growth factors such as FGF-2 and KGF.

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.

Evaluation of Veriox as a Skin Decontamination Product after Dermal Exposure to the Nerve Agent VX

DTIC Science & Technology

2016-09-01

in hair -clipped, unanesthetized guinea pigs. Efficacy was established by generating VX dose-lethality curves for each DC product based on 24 survival...This study compared the effectiveness of Veriox® to RSDL when each was used as a DC product 2 min after dermal exposure to VX in hair -clipped...by the dermal LD90 of VX in untreated animals. A LD90 value of 188 μg/kg generated in hair -clipped, unanesthetized guinea pigs (Clarkson, personal

Dermal Uptake of Benzophenone-3 from Clothing.

PubMed

Morrison, Glenn C; Bekö, Gabriel; Weschler, Charles J; Schripp, Tobias; Salthammer, Tunga; Hill, Jonathan; Andersson, Anna-Maria; Toftum, Jørn; Clausen, Geo; Frederiksen, Hanne

2017-10-03

Benzophenone-3 (also known as BP-3 or oxybenzone) is added to sunscreens, plastics, and some coatings to filter UV radiation. The suspected endocrine disruptor BP-3 has been detected in the air and settled dust of homes and is expected to redistribute from its original sources to other indoor compartments, including clothing. Given its physical and chemical properties, we hypothesized that dermal uptake from clothing could contribute to the body burden of this compound. First, cotton shirts were exposed to air at an elevated concentration of BP-3 for 32 days; the final air concentration was 4.4 μg/m 3 . Next, three participants wore the exposed shirts for 3 h. After 3 h of exposure, participants wore their usual clothing during the collection of urine samples for the next 48 h. Urine was analyzed for BP-3, a metabolite (BP-1), and six other UV filters. The rate of urinary excretion of the sum of BP-1 and BP-3 increased for all participants during and following the 3 h of exposure. The summed mass of BP-1 and BP-3 excreted during the first 24 h attributable to wearing exposed t-shirts were 12, 9.9, and 82 μg for participants 1, 2, and 3, respectively. Analysis of these results, coupled with predictions of steady-state models, suggest that dermal uptake of BP-3 from clothing could meaningfully contribute to overall body burden.

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

Icariin promotes mouse hair follicle growth by increasing insulin-like growth factor 1 expression in dermal papillary cells.

PubMed

Su, Y-S; Fan, Z-X; Xiao, S-E; Lin, B-J; Miao, Y; Hu, Z-Q; Liu, H

2017-04-01

Icariin is a major flavonoid isolated from Epimedium spp. leaves (Epimedium Herba), and has multiple pharmacological functions, including anti-angiogenesis, anti-oxidant, anti-inflammatory and immunoprotective effects. To investigate whether icariin can stimulate growth of hair follicles in mice and the underlying mechanism. In vitro, the effect of icariin on hair growth was assessed by using a vibrissae hair follicle (VHF) organ-culture model. The proliferation of hair matrix keratinocytes and the expression of insulin-like growth factor (IGF)-1 in follicles were examined by double immunostaining for 5-bromo-2'-deoxyuridine and IGF-1, in the presence or absence of icariin. Dermal papilla cells (DPCs) were cultured and IGF-1 level was measured by reverse transcription-PCR and ELISA after icariin treatment. In vivo, the effect of icariin on hair growth was examined by gavage feeding of icariin to mice whose backs had been depilated, and the conversion of telogen to anagen hair was observed. Treatment with icariin promoted hair shaft elongation, prolonged the hair cycle growth phase (anagen) in cultured VHFs, and accelerated transition of hair cycle from telogen to anagen phase in the dorsal skin of mice. There was significant proliferation of matrix keratinocytes and an increased level of IGF-1 in cultured VHFs. Moreover, icariin treatment upregulated IGF-1 mRNA expression in DPCs and increased IGF-1 protein content in the conditioned medium of DPCs. These results suggest that icariin can promote mouse hair follicle growth via stimulation of IGF-1 expression in DPCs. © 2017 British Association of Dermatologists.

Reepithelialization from stem cells of hair follicles of dermal graft of the scalp in acute treatment of third-degree burns: first clinical and histologic study.

PubMed

Zakine, Gilbert; Mimoun, Maurice; Pham, Julien; Chaouat, Marc

2012-07-01

The scalp, an excellent donor site for thin skin grafts, presents a limited surface but is rich in keratinocyte stem cells. The purpose of this study was to double scalp harvesting in one procedure and to evaluate the capacity of the dermal layer to spontaneously reepithelialize from hair follicle stem cells. Two layers of 0.2-mm split-thickness skin graft, a dermoepidermal graft and a dermal graft, were harvested from scalp during the same procedure. Fifteen burn patients were included in this study. Healing of the scalp donor site and percentage of graft taken were evaluated. The Vancouver Scar Scale was used at 3 months and 1 year. Histologic studies were performed at day 0 and 3 months on grafts, and on the scalp at day 28. Nine patients were treated on the limbs with meshed dermal graft. Six were treated on the hands with unmeshed dermal graft. Graft take was good for both types of grafts. The mean time for scalp healing was 9.3 days. Histologic study confirmed that the second layer was a dermal graft with numerous annexes and that, at 3 months, the dermis had normal thickness but with rarer and smaller epidermal crests than dermal graft. The difference between the mean Vancouver Scar Scale score of dermal graft and dermoepidermal graft was not significant. The authors' study shows the efficacy of dermal graft from the scalp and good scalp healing. Therapeutic, II.

Preparation and evaluation of novel microemulsion-based hydrogels for dermal delivery of benzocaine.

PubMed

Üstündağ Okur, Neslihan; Çağlar, Emre Şefik; Arpa, Muhammet Davut; Karasulu, H Yeşim

2017-06-01

The purpose of the current research was to prepare and evaluate the potential use of microemulsion-based hydrogel (MBH) formulations for dermal delivery of benzocaine (BZN). The pseudoternary-phase diagrams were constructed for various microemulsions composed of isopropyl myristate (IPM) as oil phase, Span 20, Tween 20, Tween 80, cremophor EL and cremophor RH40 as surfactants, ethanol as cosurfactant and distilled water as aqueous phase. Finally, concentration of BZN in microemulsions was 2% (w/w). The physicochemical properties, such as conductivity, viscosity, pH, droplet size, polydispersity index and zeta potential of microemulsions, were measured. Carbopol 940 was used to convert BZN-loaded microemulsions into gel form without affecting their structure. Furthermore, excised rat abdominal skin was used to compare permeation and penetration properties of BZN loaded M3 and M3BHs with BZN solution. According to ex vivo study results, BZN-loaded M3BH1 showed highest flux values and high release rate values, and furthermore, this gel formulation had low surfactant content. Finally, in order to learn the localization of formulations within the dermal penetration, formulations and BZN solution were labeled with red oil O and subjected to fluorescence observation. In conclusion, BZN-loaded MBHs could be offered as a promising strategy for dermal drug delivery.

Primary dermal pleomorphic liposarcoma: utility of adipophilin and MDM2/CDK4 immunostainings.

PubMed

Ramírez-Bellver, Jose L; López, Joaquín; Macías, Elena; Alegría-Landa, Victoria; Gimeno, Ignacio; Pérez-Plaza, Alejandra; Kutzner, Heinz; Requena, Luis

2017-03-01

Liposarcoma, usually arises in deep soft tissues and pleomorphic liposarcoma (PL), is the rarest histopathologic variant. However, 15 cases of entirely dermal PL have been reported. We describe a case of a 79-year-old man who developed a rapidly growing nodule on his thorax. Excisional biopsy was performed and immunohistochemical studies were carried. The lesion was a well-circumscribed dermal nodule composed of multivacuolated pleomorphic lipoblasts and atypical mitotic figures. Neoplastic cells expressed CD10 and resulted negative S100 protein, Melan-A, MITF-1, AE1/AE3, CD4, CD68 (PGM1), retinoblastoma gene family protein, pericentrine and lysozyme. Adipophilin stain showed the lipid contents in the cytoplasm of the neoplastic cells. MDM2 and CDK4 resulted both negative. A diagnosis of primary dermal PL was made. This case shows the utility of adipophilin immunostaining to prove the lipid contents in neoplastic cells, which has the advantage of using formalin-fixed paraffin-embedded tissue and making needless frozen sections and ultrastructural studies to show these findings. Negative MDM2/CDK4 staining in our case argues against the possibility of dedifferentiated liposarcoma and further supports the diagnosis of true PL. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Transient Dermal Exposure II: Post-Exposure Absorption and Evaporation of Volatile Compounds

PubMed Central

FRASCH, H. FREDERICK; BUNGE, ANNETTE L.

2016-01-01

The transient dermal exposure is one where the skin is exposed to chemical for a finite duration, after which the chemical is removed and no residue remains on the skin’s surface. Chemical within the skin at the end of the exposure period can still enter the systemic circulation. If it has some volatility, a portion of it will evaporate from the surface before it has a chance to be absorbed by the body. The fate of this post-exposure “skin depot” is the focus of this theoretical study. Laplace domain solutions for concentration distribution, flux, and cumulative mass absorption and evaporation are presented, and time domain results are obtained through numerical inversion. The Final Value Theorem is applied to obtain the analytical solutions for the total fractional absorption by the body and evaporation from skin at infinite time following a transient exposure. The solutions depend on two dimensionless variables: χ, the ratio of evaporation rate to steady-state dermal permeation rate; and the ratio of exposure time to membrane lag time. Simple closed form algebraic equations are presented that closely approximate the complete analytical solutions. Applications of the theory to the dermal risk assessment of pharmaceutical, occupational, and environmental exposures are presented for four example chemicals. PMID:25611182

NHEXAS PHASE I ARIZONA STUDY--STANDARD OPERATING PROCEDURE FOR EXTRACTION OF PESTICIDES FROM DERMAL WIPE SAMPLES (BCO-L-12.1)

EPA Science Inventory

The purpose of this SOP is to describe procedures for extracting and preparing a dermal wipe sample for GC/MS analysis of pesticides. This procedure was followed to ensure consistent data retrieval during the Arizona NHEXAS project and the "Border" study. Keywords: dermal wipe;...

Enrichment of skin-derived neural precursor cells from dermal cell populations by altering culture conditions.

PubMed

Bayati, Vahid; Gazor, Rohoullah; Nejatbakhsh, Reza; Negad Dehbashi, Fereshteh

2016-01-01

As stem cells play a critical role in tissue repair, their manipulation for being applied in regenerative medicine is of great importance. Skin-derived precursors (SKPs) may be good candidates for use in cell-based therapy as the only neural stem cells which can be isolated from an accessible tissue, skin. Herein, we presented a simple protocol to enrich neural SKPs by monolayer adherent cultivation to prove the efficacy of this method. To enrich neural SKPs from dermal cell populations, we have found that a monolayer adherent cultivation helps to increase the numbers of neural precursor cells. Indeed, we have cultured dermal cells as monolayer under serum-supplemented (control) and serum-supplemented culture, followed by serum free cultivation (test) and compared. Finally, protein markers of SKPs were assessed and compared in both experimental groups and differentiation potential was evaluated in enriched culture. The cells of enriched culture concurrently expressed fibronectin, vimentin and nestin, an intermediate filament protein expressed in neural and skeletal muscle precursors as compared to control culture. In addition, they possessed a multipotential capacity to differentiate into neurogenic, glial, adipogenic, osteogenic and skeletal myogenic cell lineages. It was concluded that serum-free adherent culture reinforced by growth factors have been shown to be effective on proliferation of skin-derived neural precursor cells (skin-NPCs) and drive their selective and rapid expansion.

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 ...

Fetal Bovine Dermal Repair Scaffold Used for the Treatment of Difficult-to- Heal Complex Wounds.

PubMed

Strauss, Neil H; Brietstein, Richard J

2012-11-01

 Introduction. Treating difficult-to-heal wounds with complexities, including those with exposed tendon/bone or infection, is a challenge that regularly confronts practitioners in a variety of clinical environments. The purpose of this study was to review the effectiveness of an acellular fetal bovine dermal repair scaffold (PriMatrix Dermal Repair Scaffold, TEI Biosciences, Inc, Boston, MA) used to treat complex difficult-to-heal wounds presenting in the authors' practice. A retrospective chart review was conducted of a single practice with multiple practicing physicians between 2008 and 2010. Over this time period, 70 patients with 83 wounds were treated with the acellular fetal bovine dermis following surgical debridement of the wound. Forty-nine patients (58 wounds) met established inclusion/exclusioncriteria and were critically evaluated. Wounds treated with the acellular fetal bovine dermis included chronic diabetic wounds, venous wounds, and pressure ulcers, as well as wounds caused by trauma and surgery. Additionally, the patients treated had comorbidities commonly associated with recalcitrant wounds. Of the wounds evaluated in this study, 75.9% successfully healed; 63.8% reepithelialized, and 12.1% were closed with a skin graft subsequent to treatment. Notably, the majority (58.6%) of the wounds reepithelialized by 12 weeks following a single application of the dermal repair scaffold. In the subset of challenging wounds with exposed tendon/bone, 80.8% of the wounds were treated successfully (61.5% reepithelialized, and 19.3% were skin grafted), indicating the successful regeneration and reepithelialization of new vascularized tissue by fetal dermal collagen in relatively avascular wound defects. The acellular fetal bovine dermal repair scaffold can be used as part of an effective treatment regimen to heal complex wounds with exposed tendon/bone caused by varying etiologies. The product actively participates in the generation of a new

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

ESTIMATING CONTAMINANT DOSE FOR INTERMITTENT DERMAL CONTACT: MODEL DEVELOPMENT, TESTING, AND APPLICATION

EPA Science Inventory

Assessments of aggregate exposure to pesticides and other surface contamination in residential environments are often driven by assumptions about dermal contacts. Accurately predicting cumulative doses from realistic skin contact scenarios requires characterization of exposure sc...

Dermal microdialysis of inflammatory markers induced by aliphatic hydrocarbons in rats

PubMed Central

Patlolla, Ram R.; Mallampati, Ramya; Fulzele, Suniket V.; Babu, R. Jayachandra; Singh, Mandip

2010-01-01

In the present study we made an attempt to understand the skin irritation cascade of selected aliphatic hydrocarbons using microdialysis technique. Microdialysis probes were inserted into dermis in the dorsal skin of hairless rats. After 2 h of probes insertion, occlusive dermal exposure (2 h) was carried out with 230 μl of nonane, dodecane and tetradecane, using Hill top chambers®. Inflammatory biomarkers such as substance P (SP), α-melanocyte stimulating hormone (α-MSH) Interleukin 6 (IL-6) and prostaglandin E2 (PGE2) were analyzed in the dialysis samples by enzyme immunoassay (EIA). SP, α-MSH and IL6 were released in significant amounts following the dermal exposure of nonane and dodecane, whereas tetradecane did not induce any of these markers in significant amounts compared to control. Nonane increased the PGE2 levels in significant amounts within 2 h of chemical exposure compared to dodecane and tetradecane. IL-6 response was found to be slow and 2–3-fold increase in IL-6 levels was observed after 5 h following nonane and dodecane application. The magnitude of skin irritation exerted by all three chemicals was in the order of nonane ≥ dodecane ≥ tetradecane. The results demonstrate that microdialysis can be used to measure the inflammatory biomarkers in the skin irritation studies and irritation response of chemicals was quantifiable by this method. In conclusion, microdialysis was found to be an excellent tool to measure several inflammatory biomarkers as a function of time after dermal exposures with irritant chemicals. PMID:19152832

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

Dermal γδ T Cells Do Not Freely Re-Circulate Out of Skin and Produce IL-17 to Promote Neutrophil Infiltration during Primary Contact Hypersensitivity

PubMed Central

Jiang, Xiaodong; Park, Chang Ook; Geddes Sweeney, Jenna; Yoo, Min Jae; Gaide, Olivier; Kupper, Thomas Seth

2017-01-01

The role of mouse dermal γδ T cells in inflammatory skin disorders and host defense has been studied extensively. It is known that dendritic epidermal T cells (DETC) have a monomorphic γδ T cell receptor (TCR) and reside in murine epidermis from birth. We asked if dermal γδ cells freely re-circulated out of skin, or behaved more like dermal resident memory T cells (TRM) in mice. We found that, unlike epidermal γδ T cells (DETC), dermal γδ cells are not homogeneous with regard to TCR, express the tissue resident T cell markers CD69 and CD103, bear skin homing receptors, and produce IL-17 and IL-22. We created GFP+: GFP− parabiotic mice and found that dermal γδ T cells re-circulate very slowly—more rapidly than authentic αβ TCR TRM, but more slowly than the recently described dermal αβ TCR T migratory memory cells (TMM). Mice lacking the TCR δ gene (δ-/-) had a significant reduction of 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity (CHS). We created mice deficient in dermal γδ T cells but not DETC, and these mice also showed a markedly reduced CHS response after DNFB challenge. The infiltration of effector T cells during CHS was not reduced in dermal γδ T cell-deficient mice; however, infiltration of Gr-1+CD11b+ neutrophils, as well as ear swelling, was reduced significantly. We next depleted Gr-1+ neutrophils in vivo, and demonstrated that neutrophils are required for ear swelling, the accepted metric for a CHS response. Depletion of IL-17-producing dermal Vγ4+ cells and neutralization of IL-17 in vivo, respectively, also led to a significantly reduced CHS response and diminished neutrophil infiltration. Our findings here suggest that dermal γδ T cells have an intermediate phenotype of T cell residence, and play an important role in primary CHS through producing IL-17 to promote neutrophil infiltration. PMID:28081153

Acute Dermal Toxicity of Trimethylolethane Trinitrate (TMETN) in Rabbits

DTIC Science & Technology

1989-07-01

attributed to dermal exposure to TMETN at the 2 ml/kg dose level. Otitis media was confirmed in rabbit 84F608 and malocclusion of the teeth was observed in...84F608 36288 F Otitis Media , Purulent, Right Ear 84F609 36289 F Cecum - Pinworms 84F610 36290 F Cecum - -pinwormis 84F612 36291 M Cecum - Pinworms 84F613

Operator dermal exposure and protection provided by personal protective equipment and working coveralls during mixing/loading, application and sprayer cleaning in vineyards.

PubMed

Thouvenin, Isabelle; Bouneb, Françoise; Mercier, Thierry

2017-06-01

The efficiency of a working coverall combined with personal protective equipment to protect operators against dermal exposure to plant protection products under field conditions was studied. Operators wore a non-certified water-repellent finish polyester/cotton coverall plus a certified gown during the mixing/loading and the cleaning phases. Insecticide foliar application to a vineyard was selected as the exposure scenario. The overall dermal residue levels measured in this study were in the range of data recently collected in Europe. The water-repellent finish working coverall reduced body exposure by a factor of approximately 95%. Wearing a Category III Type 3 partial body gown during mixing/loading and cleaning of the application equipment led to a further protective effect of 98.7%. The combination of a water-repellent finish working coverall and partial body protection during specific tasks provided satisfactory levels of protection and can be considered as suitable protection for the conditions of use studied.

Nanoemulsion as pharmaceutical carrier for dermal and transdermal drug delivery: Formulation development, stability issues, basic considerations and applications.

PubMed

Rai, Vineet Kumar; Mishra, Nidhi; Yadav, Kuldeep Singh; Yadav, Narayan Prasad

2018-01-28

The use of nanoemulsion in augmenting dermal and transdermal effectiveness of drugs has now well established. The development of nanoemulsion based semisolid dosage forms is an active area of present research. However, thickening or liquid-to-semisolid conversion of the nanoemulsions provides opportunities to the formulation scientist to explore novel means of solving instability issues during transformation. Extending knowledge about the explicit role of nature/magnitude of zeta potential, types of emulsifiers and selection of appropriate semisolid bases could place these versatile carriers from laboratory to industrial scale. This article reviews the progressive advancement in the delivery of medicament via nanoemulsion with special reference to the dermal and transdermal administration. It is attempted to explore the most suitable semi solid dosage form for the particular type of nanoemulsion (o/w, w/o and others) and effect of particle size and zeta potential on the delivery of drugs through dermal or transdermal route. Finally, this review also highlights the basic principles and fundamental considerations of nanoemulsion manufacture, application of nanoemulsion based semisolid dosage forms in the dermal/transdermal administration and basic considerations during the nanoemulsion absorption into and through skin. Copyright © 2017 Elsevier B.V. All rights reserved.

Atypical fibroxanthoma and pleomorphic dermal sarcoma harbor frequent NOTCH1/2 and FAT1 mutations and similar DNA copy number alteration profiles.

PubMed

Griewank, Klaus G; Wiesner, Thomas; Murali, Rajmohan; Pischler, Carina; Müller, Hansgeorg; Koelsche, Christian; Möller, Inga; Franklin, Cindy; Cosgarea, Ioana; Sucker, Antje; Schadendorf, Dirk; Schaller, Jörg; Horn, Susanne; Brenn, Thomas; Mentzel, Thomas

2018-03-01

Atypical fibroxanthomas and pleomorphic dermal sarcomas are tumors arising in sun-damaged skin of elderly patients. They have differing prognoses and are currently distinguished using histological criteria, such as invasion of deeper tissue structures, necrosis and lymphovascular or perineural invasion. To investigate the as-yet poorly understood genetics of these tumors, 41 atypical fibroxanthomas and 40 pleomorphic dermal sarcomas were subjected to targeted next-generation sequencing approaches as well as DNA copy number analysis by comparative genomic hybridization. In an analysis of the entire coding region of 341 oncogenes and tumor suppressor genes in 13 atypical fibroxanthomas using an established hybridization-based next-generation sequencing approach, we found that these tumors harbor a large number of mutations. Gene alterations were identified in more than half of the analyzed samples in FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter. The presence of these alterations was verified in 26 atypical fibroxanthoma and 35 pleomorphic dermal sarcoma samples by targeted amplicon-based next-generation sequencing. Similar mutation profiles in FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter were identified in both atypical fibroxanthoma and pleomorphic dermal sarcoma. Activating RAS mutations (G12 and G13) identified in 3 pleomorphic dermal sarcoma were not found in atypical fibroxanthoma. Comprehensive DNA copy number analysis demonstrated a wide array of different copy number gains and losses, with similar profiles in atypical fibroxanthoma and pleomorphic dermal sarcoma. In summary, atypical fibroxanthoma and pleomorphic dermal sarcoma are highly mutated tumors with recurrent mutations in FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter, and a range of DNA copy number alterations. These findings suggest that atypical fibroxanthomas and pleomorphic dermal sarcomas are genetically related, potentially representing two ends of a common tumor spectrum

Biocompatible polymer microneedle for topical/dermal delivery of tranexamic acid.

PubMed

A Machekposhti, S; Soltani, M; Najafizadeh, P; Ebrahimi, S A; Chen, P

2017-09-10

Recently-introduced biocompatible polymeric microneedles offer an efficient method for drug delivery. Tranexamic acid is a novel drug for treating melasma that is administered both locally and orally and inhibits excessive melanin via melanocyte. The tranexamic acid biocompatible polymer microneedle used in this study was fabricated from PVP and methacrylic acid, using the lithography method. The required mechanical strength to pierce skin was attained by optimizing the ratio of PVP to methacrylic acid. Acute dermal toxicity was done, and drug diffusion in skin layers was simulated by calculating the diffusion coefficient of tranexamic acid in interstitial fluid (plasma). The biocompatible polymer microneedle was fabricated at 60°C. Needles could sustain 0.6N that is enough to pierce stratum corneum. 34% of the released drug was locally effective and the rest permeated through the skin. The pyramidal polymer microneedle in this study was fully released in skin in approx. 7h. This polymer microneedle has no dermal toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Staphylococcus aureus induces hypoxia and cellular damage in porcine dermal explants

USDA-ARS?s Scientific Manuscript database

Methicillin-resistant Staphylococcus aureus (MRSA) can infect wounds and produce difficult-to- treat biofilms. To determine the extent that MRSA biofilms can deplete oxygen, change pH and damage host tissue, we developed a porcine dermal explant model on which we cultured GFP-labeled MRSA biofilms. ...

Estimating Dermal Transfer of Copper Particles from the ...

EPA Pesticide Factsheets

Lumber pressure-treated with micronized copper was examined for the release of copper and copper micro/nanoparticles using a surface wipe method to simulate dermal transfer. In 2003, the wood industry began replacing CCA treated lumber products for residential use with copper based formulations. Micronized copper (nano to micron sized particles) has become the preferred treatment formulation. There is a lack of information on the release of copper, the fate of the particles during dermal contact, and the copper exposure level to children from hand-to-mouth transfer. For the current study, three treated lumber products, two micronized copper and one ionic copper, were purchased from commercial retailers. The boards were left to weather outdoors for approximately 1 year. Over the year time period, hand wipe samples were collected periodically to determine copper transfer from the wood surfaces. The two micronized formulations and the ionic formulation released similar levels of total copper. The amount of copper released was high initially, but decreased to a constant level (~1.5 mg m-2) after the first month of outdoor exposure. Copper particles were identified on the sampling cloths during the first two months of the experiment, after which the levels of copper were insufficient to collect interpretable data. After 1 month, the particles exhibited minimal changes in shape and size. At the end of 2-months, significant deterioration of the particles was

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...

Assessment of dermal exposure of greenhouse workers to the pesticide bupirimate.

PubMed

Jongen, M J; Engel, R; Leenheers, L H

1992-01-01

An HPLC method was developed for estimation of dermal exposure of greenhouse workers to the pesticide bupirimate. Chromatography was performed on a cyano-modified silica column with methanol-water (6:4 by volume) containing 5 g/L ammonium sulfate as eluent. UV detection at 310 nm was used for quantitation. Dermal exposure was assessed by letting the workers wear cotton gloves and by measuring foliar dislodgable residues in the greenhouses as potential exposure. The analytical procedure was validated for measurement of bupirimate on cotton gloves and in solutions used for the estimation of foliar dislodgable residues. Gloves were extracted with methanol. Recovery of bupirimate from fortified gloves was complete. Methanol extracts with one volume of water added and solutions containing dislodgable residues were injected directly onto the HPLC system. The limit of detection was 30 micrograms/L. Between-day coefficients of variation were 7 and 4% at concentrations of 0.6 and 28 mg/L, respectively.

Epidermal regulation of dermal fibroblast activity.

PubMed

Garner, W L

1998-07-01

Although the association between delayed burn wound healing and subsequent hypertrophic scar formation is well-established, the mechanism for this relationship is unknown. Unhealed burn wounds lack an epidermis, suggesting a possible regulatory role for the epidermis in controlling dermal fibroblast matrix synthesis. Therefore, we examined the effect of epidermal cells and media conditioned by epidermal cells on fibroblast collagen synthesis and replication. Purified fibroblast and keratinocyte cell strains were developed from discarded normal adult human skin. Conditioned media were created by incubation of cytokine-free and serum-free medium with either confluent fibroblast or keratinocyte cultures for 18 hours (n = 3). Nearly confluent fibroblast cultures were exposed for 48 hours to graded concentrations of either unconditioned medium (control), conditioned medium, or varying numbers of keratinocytes. Replication was quantified by the incorporation of 3H-thymidine. Collagen synthesis was measured by the incorporation of 3H-proline into collagenase-sensitive protein. Data were compared using analysis of variance (ANOVA) and linear regression. Keratinocyte conditioned medium induced a significant increase in replication (n = 3) (p = 0.004) and a decrease in collagen synthesis (n = 6) (p < 0.001). In contrast, neither fibroblast conditioned medium nor control medium had an effect on fibroblast replication or collagen synthesis. Co-culture of fibroblast with a graded number of keratinocytes similarly decreased collagen synthesis (n = 6) (p < 0.001). Dermal fibroblast collagen synthesis appears to be regulated by a soluble keratinocyte product. This result suggests a mechanism for the clinical observation that unhealed burn wounds, which lack the epidermis, demonstrate excess collagen production and scar. Clinical strategies to decrease hypertrophic scar should include an attempt at early wound closure with skin grafting or the application of cultured epithelial

Biomaterials as novel penetration enhancers for transdermal and dermal drug delivery systems.

PubMed

Chen, Yang; Wang, Manli; Fang, Liang

2013-01-01

The highly organized structure of the stratum corneum provides an effective barrier to the drug delivery into or across the skin. To overcome this barrier function, penetration enhancers are always used in the transdermal and dermal drug delivery systems. However, the conventional chemical enhancers are often limited by their inability to delivery large and hydrophilic molecules, and few to date have been routinely incorporated into the transdermal formulations due to their incompatibility and local irritation issues. Therefore, there has been a search for the compounds that exhibit broad enhancing activity for more drugs without producing much irritation. More recently, the use of biomaterials has emerged as a novel method to increase the skin permeability. In this paper, we present an overview of the investigations on the feasibility and application of biomaterials as penetration enhancers for transdermal or dermal drug delivery systems.

Effect of mitomycin on normal dermal fibroblast and HaCat cell: an in vitro study

PubMed Central

Wang, Yao-wen; Ren, Ji-hao; Xia, Kun; Wang, Shu-hui; Yin, Tuan-fang; Xie, Ding-hua; Li, Li-hua

2012-01-01

Objective: To evaluate the effects of mitomycin on the growth of human dermal fibroblast and immortalized human keratinocyte line (HaCat cell), particularly the effect of mitomycin on intracellular messenger RNA (mRNA) synthesis of collagen and growth factors of fibroblast. Methods: The normal dermal fibroblast and HaCat cell were cultured in vitro. Cell cultures were exposed to 0.4 and 0.04 mg/ml of mitomycin solution, and serum-free culture medium was used as control. The cellular morphology change, growth characteristics, cell proliferation, and apoptosis were observed at different intervals. For the fibroblasts, the mRNA expression changes of transforming growth factor (TGF)-β1, basic fibroblast growth factor (bFGF), procollagen I, and III were detected by reverse transcription polymerase chain reaction (RT-PCR). Results: The cultured normal human skin fibroblast and HaCat cell grew exponentially. A 5-min exposure to mitomycin at either 0.4 or 0.04 mg/ml caused marked dose-dependent cell proliferation inhibition on both fibroblasts and HaCat cells. Cell morphology changed, cell density decreased, and the growth curves were without an exponential phase. The fibroblast proliferated on the 5th day after the 5-min exposure of mitomycin at 0.04 mg/ml. Meanwhile, 5-min application of mitomycin at either 0.04 or 0.4 mg/ml induced fibroblast apoptosis but not necrosis. The apoptosis rate of the fibroblast increased with a higher concentration of mytomycin (p<0.05). A 5-min exposure to mitomycin at 0.4 mg/ml resulted in a marked decrease in the mRNA production of TGF-β1, procollagen I and III, and a marked increase in the mRNA production of bFGF. Conclusions: Mitomycin can inhibit fibroblast proliferation, induce fibroblast apoptosis, and regulate intracellular protein expression on mRNA levels. In additon, mitomycin can inhibit HaCat cell proliferation, so epithelial cell needs more protecting to avoid mitomycin’s side effect when it is applied clinically. PMID

The breast reconstruction evaluation of acellular dermal matrix as a sling trial (BREASTrial): design and methods of a prospective randomized trial.

PubMed

Agarwal, Jayant P; Mendenhall, Shaun D; Anderson, Layla A; Ying, Jian; Boucher, Kenneth M; Liu, Ting; Neumayer, Leigh A

2015-01-01

Recent literature has focused on the advantages and disadvantages of using acellular dermal matrix in breast reconstruction. Many of the reported data are from low level-of-evidence studies, leaving many questions incompletely answered. The present randomized trial provides high-level data on the incidence and severity of complications in acellular dermal matrix breast reconstruction between two commonly used types of acellular dermal matrix. A prospective randomized trial was conducted to compare outcomes of immediate staged tissue expander breast reconstruction using either AlloDerm or DermaMatrix. The impact of body mass index, smoking, diabetes, mastectomy type, radiation therapy, and chemotherapy on outcomes was analyzed. Acellular dermal matrix biointegration was analyzed clinically and histologically. Patient satisfaction was assessed by means of preoperative and postoperative surveys. Logistic regression models were used to identify predictors of complications. This article reports on the study design, surgical technique, patient characteristics, and preoperative survey results, with outcomes data in a separate report. After 2.5 years, we successfully enrolled and randomized 128 patients (199 breasts). The majority of patients were healthy nonsmokers, with 41 percent of patients receiving radiation therapy and 49 percent receiving chemotherapy. Half of the mastectomies were prophylactic, with nipple-sparing mastectomy common in both cancer and prophylactic cases. Preoperative survey results indicate that patients were satisfied with their premastectomy breast reconstruction education. Results from the Breast Reconstruction Evaluation Using Acellular Dermal Matrix as a Sling Trial will assist plastic surgeons in making evidence-based decisions regarding acellular dermal matrix-assisted tissue expander breast reconstruction. Therapeutic, II.

Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.

PubMed

Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Röhr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

2014-01-01

From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH.

Altered Dynamics in the Circadian Oscillation of Clock Genes in Dermal Fibroblasts of Patients Suffering from Idiopathic Hypersomnia

PubMed Central

Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Röhr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

2014-01-01

From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues – mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep – wake rhythms in IH. PMID:24454829

Improving reptile ecological risk assessment: oral and dermal toxicity of pesticides to a common lizard species (Sceloporus occidentalis).

PubMed

Weir, Scott M; Yu, Shuangying; Talent, Larry G; Maul, Jonathan D; Anderson, Todd A; Salice, Christopher J

2015-08-01

Reptiles have been understudied in ecotoxicology, which limits consideration in ecological risk assessments. The goals of the present study were 3-fold: to improve oral and dermal dosing methodologies for reptiles, to generate reptile toxicity data for pesticides, and to correlate reptile and avian toxicity. The authors first assessed the toxicity of different dosing vehicles: 100 μL of water, propylene glycol, and acetone were not toxic. The authors then assessed the oral and dermal toxicity of 4 pesticides following the up-and-down procedure. Neither brodifacoum nor chlorothalonil caused mortality at doses ≤ 1750 μg/g. Under the "neat pesticide" oral exposure, endosulfan (median lethal dose [LD50] = 9.8 μg/g) was more toxic than λ-cyhalothrin (LD50 = 916.5 μg/g). Neither chemical was toxic via dermal exposure. An acetone dosing vehicle increased λ-cyhalothrin toxicity (oral LD50 = 9.8 μg/g; dermal LD50 = 17.5 μg/g), but not endosulfan. Finally, changes in dosing method and husbandry significantly increased dermal λ-cyhalothrin LD50s, which highlights the importance of standardized methods. The authors combined data from the present study with other reptile LD50s to correlate with available avian data. When only definitive LD50s were used in the analysis, a strong correlation was found between avian and reptile toxicity. The results suggest it is possible to build predictive relationships between avian and reptile LD50s. More research is needed, however, to understand trends associated with chemical classes and modes of action. © 2015 SETAC.

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.

Dermal glands in freshwater mites Limnesia undulata (O.F. Müller, 1776) and Limnesia fulgida (C.L. Koch, 1836) (Acariformes, Limnesiidae).

PubMed

Shatrov, Andrew B; Soldatenko, Elena V

2016-07-01

Dermal glands in the water mites Limnesia undulata (O.F. Müller, 1776) and Limnesia fulgida (C.L. Koch, 1836) and their secretion were studied by means of light microscopical, transmission electron microscopical (TEM) and scanning electron microscopical (SEM) methods. These mites possess two types of dermal glands - the 'common' dermal glands in a number of 14 pairs and one pair of the so-called 'idiosomal' dermal glands. The common dermal glands are bi-lobed organs and consist of high prismatic secretory cells directed to the gland mouth and mostly replacing the intra-alveolar lumen. The cells contain numerous cisterns of rough endoplasmic reticulum (RER) and specifically organized Golgi bodies (GB) producing electron-dense elongated secretory granules. These granules are released from the cells via apocrine secretion and come to the gland mouth, where they are sometimes accompanied by secretory cell cytoplasm. The final secretion may show a fibrous character. The idiosomal glands are sac-like organs stretched along the ventral body wall in posterior direction from the gland orifice corresponding to the epimeroglandularia 4. The secretory epithelium leaves a large intra-alveolar lumen filled with an electron-dense secretory material. Golgi bodies are organized identically with those in the common glands, which indicates the general homology of these two types of dermal glands. The glands' orifices are organized similarly in all glands and possess an internal funnel-shaped sclerite with muscle armament, an internal valve, medial epicuticular flaps and an external circular cuticular ring. All glandularia, except for E4 and V1, are accompanied with a long and thin sensitive seta. During fixation, secretion of the common dermal glands is extruded to the exterior in the form of large amounts of convoluted tube-like structures. In the living organisms, being secreted in mass from the glands, this secretion acquires the form of long rigid mostly hollow un

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

Pharmacokinetic Modeling to Simulate the Concentration-Time Profiles After Dermal Application of Rivastigmine Patch.

PubMed

Nozaki, Sachiko; Yamaguchi, Masayuki; Lefèvre, Gilbert

2016-07-01

Rivastigmine is an inhibitor of acetylcholinesterases and butyrylcholinesterases for symptomatic treatment of Alzheimer disease and is available as oral and transdermal patch formulations. A dermal absorption pharmacokinetic (PK) model was developed to simulate the plasma concentration-time profile of rivastigmine to answer questions relative to the efficacy and safety risks after misuse of the patch (e.g., longer application than 24 h, multiple patches applied at the same time, and so forth). The model comprised 2 compartments which was a combination of mechanistic dermal absorption model and a basic 1-compartment model. The initial values for the model were determined based on the physicochemical characteristics of rivastigmine and PK parameters after intravenous administration. The model was fitted to the clinical PK profiles after single application of rivastigmine patch to obtain model parameters. The final model was validated by confirming that the simulated concentration-time curves and PK parameters (Cmax and area under the drug plasma concentration-time curve) conformed to the observed values and then was used to simulate the PK profiles of rivastigmine. This work demonstrated that the mechanistic dermal PK model fitted the clinical data well and was able to simulate the PK profile after patch misuse. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Intraepidermal but not dermal T lymphocytes are positive for a cell-cycle-associated antigen (Ki-67) in mycosis fungoides.

PubMed Central

Nickoloff, B. J.; Griffiths, C. E.

1990-01-01

The Ki-67 antibody, which reacts with nuclei of actively proliferating cells, was used in an immunohistochemical study to determine if there was any difference between T cells located in the epidermis rather than the dermis, in mycosis fungoides. In 12 of 14 cases of patch/plaque stage mycosis fungoides, the epidermal T cells were Ki-67 positive, while the dermal T cells were Ki-67 negative in all cases. Both epidermal and dermal T cells belonged primarily to the memory-versus-naive subset. The intraepidermal Ki-67-positive T cells were slightly larger than the dermal Ki-67-negative cells and could be easily distinguished from occasional basal keratinocytes that were also Ki-67 positive. We conclude that dermal T cells, despite expressing HLA-DR and a memory phenotype, are essentially in a resting (Go or noncycling state) in mycosis fungoides. Furthermore, it appears that the movement of T cells into the epidermal compartment is associated with activation and entry into the cell cycle. Such intraepidermal activation may lead to lymphokine release, and play an important pathophysiologic role in mycosis fungoides. Images Figure 1 Figure 5 PMID:1968314

A hyaluronic acid membrane delivery system for cultured keratinocytes: clinical "take" rates in the porcine kerato-dermal model.

PubMed

Myers, S R; Grady, J; Soranzo, C; Sanders, R; Green, C; Leigh, I M; Navsaria, H A

1997-01-01

The clinical take rates of cultured keratinocyte autografts are poor on a full-thickness wound unless a dermal bed is provided. Even under these circumstances two important problems are the time delay in growing autografts and the fragility of the grafts. A laser-perforated hyaluronic acid membrane delivery system allows grafting at early confluence without requiring dispase digestion to release grafts from their culture dishes. We designed this study to investigate the influence of this membrane on clinical take rates in an established porcine kerato-dermal grafting model. The study demonstrated a significant reduction in take as a result of halving the keratinocyte seeding density onto the membrane. The take rates, however, of grafts grown on the membrane at half or full conventional seeding density and transplanted to a dermal wound bed were comparable, if not better, than those of keratinocyte sheet grafts.

Full-mouth esthetic rehabilitation with acellular dermal matrix.

PubMed

Clozza, Emanuele; Suzuki, Takanori; Engebretson, Steven P

2014-01-01

Treatment of multiple recession defects with the adjunct use of a connective tissue graft (CTG) represents a challenge when diagnosed in several teeth of the mouth. The amount of CTG harvested from the palate may not be adequate to address this condition. In such scenarios, alternative sources such as acellular dermal matrix (ADM) are preferred due to the unlimited availability. A case report is presented, dealing with the treatment of multiple gingival recessions affecting the majority of dentition using ADM, with a 6-month follow-up.

Potential Dermal Exposure to Flonicamid and Risk Assessment of Applicators During Treatment in Apple Orchards.

PubMed

Zhao, Mei-Ai; Yu, Aili; Zhu, Yong-Zhe; Kim, Jeong-Han

2015-01-01

Exposure and risk assessments of flonicamid for applicators were performed in apple orchards in Korea. Fifteen experiments were done with two experienced applicators under typical field conditions using a speed sprayer. In this study, cotton gloves, socks, masks, and dermal patches were used to monitor potential dermal exposure to flonicamid, and personal air samplers with XAD-2 resin and glass fiber filter were used to monitor potential inhalation exposure. The analytical methods were validated for the limit of detection, limit of quantitation, reproducibility, linearity of the calibration curve, and recovery of flonicamid from various exposure matrices. The results were encouraging and acceptable for an exposure study. The applicability of XAD-2 resin was evaluated via a trapping efficiency and breakthrough test. During the mixing/loading, the average total dermal exposure was 22.6 μg of flonicamid, corresponding to 4.5×10(-5)% of the prepared amount. For the spraying, the potential dermal exposure was 9.32 mg, and the ratio to applied amount was 1.9 × 10(-2%). The primary exposed body parts were the thigh (2.90 mg), upper arm (1.75 mg), and lower leg (1.66 mg). By comparison, absorbable quantity of exposure was small, only 1.62 μg (3.2×10(-6)%). The margin of safety (MOS) were calculated for risk assessment, in all sets of trials, MOS > 1, indicating the exposure level of flonicamid was considered to be safe in apple orchards. Although this was a limited study, it provided a good estimate of flonicamid exposure for orchard applicators.

Effect of a chemical mixture on dermal penetration of arsenic and nickel in male pig in vitro.

PubMed

Turkall, Rita M; Skowronski, Gloria A; Suh, Duck H; Abdel-Rahman, Mohamed S

2003-04-11

The effect of a chemical mixture on the dermal penetration of arsenic or nickel was assessed by applying arsenic-73 or nickel-63 alone or with the chemical mixture to dermatomed male pig skin samples in flow-through diffusion cells. The chemical mixture consisted of chloroform, phenanthrene, and toluene for arsenic penetration studies and phenol, toluene, and trichloroethylene (TCE) for nickel studies. These are predominant chemicals found at hazardous waste sites. Arsenic and nickel bind to skin after dermal exposure. Total penetration of arsenic and nickel in the chemical mixture were significantly increased by 33% and 20% compared to arsenic and nickel alone, respectively. While more radioactivity penetrated skin with chemical treatment than metal alone, significantly less radioactivity was loosely adsorbed to skin and could be easily washed off from the skin surface with soap and water. The results of this study indicate that the potential health risk from dermal exposure to arsenic or nickel is enhanced if other chemicals are present.

Phacomatosis pigmento-pigmentaria: aberrant dermal melanocytosis and nevus spilus.

PubMed

Wolf, Ronni; Ruocco, Eleonora; Baroni, Adone

2011-08-15

We present a dermal melanocytosis with superimposed nevus spilus on the arm of a 5-year-old boy. We recently introduced a new type of phacomatosis, which we termed "phacomatosis pigmentopigmentalis," that is analogous to phacomatosis pigmentokeratotica or pigmentovascularis, for describing the association of two pigmented nevi. The present case is an example of this type of phacomatosis, which now we prefer to define phacomatosis pigmento-pigmentaria according to the correct Latin terminology.

Free factor XIII activation peptide (fAP-FXIII) is a regulator of factor XIII activity via factor XIII-B.

PubMed

Dodt, Johannes; Pasternack, Ralf; Seitz, Rainer; Volkers, Peter

2016-02-01

In a factor XIIIa (FXIIIa) generation assay with recombinant FXIII-A2 (rFXIII-A2 ) free FXIII activation peptide (fAP-FXII) prolonged the time to peak (TTP) but did not affect the area under the curve (AUC) or concentration at peak (CP). Addition of recombinant factorXIII-B2 (rFXIII-B2 ) restored the characteristics of the FXIIIa generation parameters (AUC, TTP and CP) to those observed for plasma FXIII (FXIII-A2 B2 ). FXIII-A2 B2 reconstituted from rFXIII-A2 and rFXIII-B2 showed a similar effect on AUC, TTP and CP in the presence of fAP-FXII as observed for plasma FXIII-A2 B2 , indicating a role for FXIII-B in this observation. An effect of fAP-FXIII on thrombin, the proteolytic activator of FXIII, was excluded by thrombin generation assays and clotting experiments. In a purified system, fAP-FXIII did not interfere with the FXIIIa activity development of thrombin-cleaved rFXIII-A2 (rFXIII-A2 ') also excluding direct inhibition of FXIIIa. However, FXIIIa activity development of FXIII-A2 'B2 was inhibited in a concentration-dependent manner by fAP-FXIII, indicating that an interaction between AP-FXIII and FXIII-B2 contributes to the overall stability of FXIII-A2 'B2 . In addition to its well-known role, FXIII-B also contributes to FXIII-A2 B2 stability or dissociation depending on fAP-FXIII and calcium concentrations. © 2015 John Wiley & Sons Ltd.

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

Malva verticillata seed extracts upregulate the Wnt pathway in human dermal papilla cells.

PubMed

Lee, E Y; Choi, E-J; Kim, J A; Hwang, Y L; Kim, C-D; Lee, M H; Roh, S S; Kim, Y H; Han, I; Kang, S

2016-04-01

Mesenchymal-epithelial interactions are important in controlling hair growth and the hair cycle. The β-catenin pathway of dermal papilla cells (DPCs) plays a pivotal role in morphogenesis and normal regeneration of hair follicles. Deletion of β-catenin in the dermal papilla reduces proliferation of the hair follicle progenitor cells that generate the hair shaft and induces an early onset of the catagen phase. In this study, a modulator of the Wnt/β-catenin activity was studied in oriental herb extracts on cultured human DPCs. The effect of Malva verticillata (M. verticillata) seeds on human DPCs was investigated by a Wnt/β-catenin reporter activity assay system (β-catenin-TCF/LEF reporter gene) and cell proliferation analysis. The synthesis of the factors related to hair growth and cycling was measured at both the mRNA and the protein level by semi-quantitative PCR and Western blot analysis, respectively. An extract from M. verticillata seeds increased Wnt reporter activity in a concentration-dependent manner and also led to increased β-catenin levels in cultured human DPCs. Myristoleic acid, identified as an effective compound of M. verticillata seeds, stimulated the proliferation of DPCs in a dose-dependent manner and increased transcription levels of the downstream targets: IGF-1, KGF, VEGF and HGF. Myristoleic acid also enhanced the phosphorylation of MAPKs (Akt and p38). Overall, the data suggest that this extract of M. verticillata seeds could be a good candidate for treating hair loss by modulating the Wnt/β-catenin pathway in DPCs. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

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.

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.

FEASIBILITY OF USING THE MACROACTIVITY APPROACH TO ASSESS CHILDREN'S DERMAL EXPOSURE TO PESTICIDES

EPA Science Inventory

Results derived from an initial assessment of critical exposure pathways for children indicate that dermal contact may result in high residential exposures to pesticides. However, data on children's exposures and activities are insufficient to support quantitative assessments ...

Measurements of dermal uptake of nicotine directly from air and clothing.

PubMed

Bekö, G; Morrison, G; Weschler, C J; Koch, H M; Pälmke, C; Salthammer, T; Schripp, T; Toftum, J; Clausen, G

2017-03-01

In this preliminary study, we have investigated whether dermal uptake of nicotine directly from air or indirectly from clothing can be a meaningful exposure pathway. Two participants wearing only shorts and a third participant wearing clean cotton clothes were exposed to environmental tobacco smoke (ETS), generated by mechanically "smoking" cigarettes, for three hours in a chamber while breathing clean air from head-enveloping hoods. The average nicotine concentration (420 μg/m 3 ) was comparable to the highest levels reported for smoking sections of pubs. Urine samples were collected immediately before exposure and 60 hour post-exposure for bare-skinned participants. For the clothed participant, post-exposure urine samples were collected for 24 hour. This participant then entered the chamber for another three-hour exposure wearing a hood and clothes, including a shirt that had been exposed for five days to elevated nicotine levels. The urine samples were analyzed for nicotine and two metabolites-cotinine and 3OH-cotinine. Peak urinary cotinine and 3OH-cotinine concentrations for the bare-skinned participants were comparable to levels measured among non-smokers in hospitality environments before smoking bans. The amount of dermally absorbed nicotine for each bare-skinned participant was conservatively estimated at 570 μg, but may have been larger. For the participant wearing clean clothes, uptake was ~20 μg, and while wearing a shirt previously exposed to nicotine, uptake was ~80 μg. This study demonstrates meaningful dermal uptake of nicotine directly from air or from nicotine-exposed clothes. The findings are especially relevant for children in homes with smoking or vaping. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

What are the necessary practice competencies for two providers: dermal fillers and botulinum toxin type A injections?

PubMed

Spear, Marcia

2010-01-01

There has been a steady increase in the number of individuals who undergo dermal fillers and botulinum toxin Type A injections. The majority of these procedures are performed by nurse providers. The purpose of this study was to collect national data on the current practice among nursing providers within the American Society of Plastic Surgical Nurses (ASPSN). The goal was to utilize the national data and develop a document of the necessary competencies to guide the practice of providers of dermal fillers and botulinum toxin Type A injections. A survey tool was developed and validated for content by expert nursing providers among the membership of the ASPSN and disseminated via e-mail to the membership of the ASPSN. In addition, data from investigator training, mentoring, and evidence from a review of the literature were also incorporated into the competency document utilizing the Competency Outcomes and Performance Assessment (COPA) model. Common core issues became apparent that included contraindications for the use of botulinum toxin Type A and dermal fillers, postprocedure complications as well as strategies in terms of managing complications. The data also revealed that there is no common method providers are taught to assess the aesthetic patient and a lack of a collaborative relationship in current practice. Overwhelmingly, the respondents supported the need for defined practice competencies. A competency document to guide the practice of providers of dermal fillers and botulinum toxin Type A has been developed for completion of this DNP project.

NHEXAS PHASE I ARIZONA STUDY--STANDARD OPERATING PROCEDURE FOR COLLECTION OF DERMAL WIPE SAMPLES FOR PESTICIDES OR METALS (UA-F-9.1)

EPA Science Inventory

The purpose of this SOP is to describe the procedures for collecting a dermal wipe sample from a participant's hands for the measurement of pesticide or metal residues on the skin. This procedure covers the preparation of the dermal wipe material and field activities. This prot...

A comparative study of root coverage using two different acellular dermal matrix products.

PubMed

Barker, Thomas S; Cueva, Marco A; Rivera-Hidalgo, Francisco; Beach, M Miles; Rossmann, Jeffrey A; Kerns, David G; Crump, T Bradley; Shulman, Jay D

2010-11-01

Gingival recession remains an important problem in dental esthetics. A new dermal matrix material has been introduced, but its effectiveness has not been studied and compared to current dermal matrix material. The aim of this study is to compare the healing associated with a coronally advanced flap for root coverage in areas of localized tissue recession when using Alloderm (ADM) and Puros Dermis (PDM). A split-mouth design was used for this study, with 52 contralateral sites in 14 patients with Miller Class I or III facial tissue recession. Twenty-six sites were treated with coronally advanced flap using PDM, and 26 sites were treated with coronally advanced flap using ADM, all followed for 6 months. Clinical measurements of vertical recession, keratinized tissue, probing depths, and attachment levels were made initially, at 3 months, and at 6 months. Both groups had significant improvement in the amount of recession coverage with means of 2.83 mm for the PDM and 3.13 mm for the ADM. The percentage of root coverage was 81.4% for the PDM and 83.4% for the ADM; differences between the materials were not statistically significant. Based on the results of this study, there was no statistical or clinical difference in the amount of root coverage, probing depth, or keratinized tissue in coronally advanced flaps for root coverage with either of the two acellular dermal matrix materials. Both materials were successful in achieving root coverage.

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.

Dermal exposure to chromium in the grinding of stainless and acid-proof steel.

PubMed

Mäkinen, Milja; Linnainmaa, Markku

2004-04-01

The aim of the study was to measure the dermal exposure levels of chromium dust during grinding of stainless and acid-proof steel parts. The potential dermal exposure of the body was measured with a patch sampling method and the actual exposure of hands with a hand-wash method. Simultaneously, personal air samples were also collected. The range of body and hand exposure to chromium dust was 4.04-3406 and 0.72-79.7 mg/h, respectively. Dust was distributed quite evenly to different body parts. Workers using hand-held grinding tools were more exposed than those using band grinders. It was judged that the sampling methods applied in this study gave a realistic estimation of exposure levels, because of the uniform distribution of contamination during grinding. Respiratory exposure was high compared to Finnish occupational exposure limit values.

Immunomodulatory effects of tick saliva on dermal cells exposed to Borrelia burgdorferi, the agent of Lyme disease.

PubMed

Scholl, Dorothy C; Embers, Monica E; Caskey, John R; Kaushal, Deepak; Mather, Thomas N; Buck, Wayne R; Morici, Lisa A; Philipp, Mario T

2016-07-08

The prolonged feeding process of ixodid ticks, in combination with bacterial transmission, should lead to a robust inflammatory response at the blood-feeding site. Yet, factors present in tick saliva may down-regulate such responses, which may be beneficial to spirochete transmission. The primary goal of this study was to test the hypothesis that tick saliva, in the context of Borrelia burgdorferi, can have widespread effects on the production of immune mediators in skin. A cross-section of tick feeding on skin was examined histologically. Human THP-1 cells stimulated with B. burgdorferi and grown in the presence or absence of tick saliva were examined by human DNA microarray, cytokine bead array, sandwich ELISA, and qRT-PCR. Similar experiments were also conducted using dermal fibroblasts. Tick feeding on skin showed dermal infiltration of histiocytes and granulocytes at the bite location. Changes in monocytic transcript levels during co-culture with B. burgdorferi and saliva indicated that tick saliva had a suppressive effect on the expression of certain pro-inflammatory mediators, such as IL-8 (CXCL8) and TLR2, but had a stimulatory effect on specific molecules such as the Interleukin 10 receptor, alpha subunit (IL-10RA), a known mediator of the immunosuppressive signal of IL-10. Stimulated cell culture supernatants were analyzed via antigen-capture ELISA and cytokine bead array for inflammatory mediator production. Treatment of monocytes with saliva significantly reduced the expression of several key mediators including IL-6, IL-8 and TNF-alpha. Tick saliva had an opposite effect on dermal fibroblasts. Rather than inhibiting, saliva enhanced production of pro-inflammatory mediators, including IL-8 and IL-6 from these sentinel skin cells. The effects of ixodid tick saliva on resident skin cells is cell type-dependent. The response to both tick and pathogen at the site of feeding favors pathogen transmission, but may not be wholly suppressed by tick saliva.

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

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.

Exploratory breath analyses for assessing toxic dermal exposures of firefighters during suppression of structural burns.

PubMed

Pleil, Joachim D; Stiegel, Matthew A; Fent, Kenneth W

2014-09-01

Firefighters wear fireproof clothing and self-contained breathing apparatus (SCBA) during rescue and fire suppression activities to protect against acute effects from heat and toxic chemicals. Fire services are also concerned about long-term health outcomes from chemical exposures over a working lifetime, in particular about low-level exposures that might serve as initiating events for adverse outcome pathways (AOP) leading to cancer. As part of a larger US National Institute for Occupational Safety and Health (NIOSH) study of dermal exposure protection from safety gear used by the City of Chicago firefighters, we collected pre- and post-fire fighting breath samples and analyzed for single-ring and polycyclic aromatic hydrocarbons as bioindicators of occupational exposure to gas-phase toxicants. Under the assumption that SCBA protects completely against inhalation exposures, any changes in the exhaled profile of combustion products were attributed to dermal exposures from gas and particle penetration through the protective clothing. Two separate rounds of firefighting activity were performed each with 15 firefighters per round. Exhaled breath samples were collected onto adsorbent tubes and analyzed with gas-chromatography-mass spectrometry (GC-MS) with a targeted approach using selective ion monitoring. We found that single ring aromatics and some PAHs were statistically elevated in post-firefighting samples of some individuals, suggesting that fire protective gear may allow for dermal exposures to airborne contaminants. However, in comparison to a previous occupational study of Air Force maintenance personnel where similar compounds were measured, these exposures are much lower suggesting that firefighters' gear is very effective. This study suggests that exhaled breath sampling and analysis for specific targeted compounds is a suitable method for assessing systemic dermal exposure in a simple and non-invasive manner.

Enriched Astaxanthin Extract from Haematococcus pluvialis Augments Growth Factor Secretions to Increase Cell Proliferation and Induces MMP1 Degradation to Enhance Collagen Production in Human Dermal Fibroblasts

PubMed Central

Chou, Hsin-Yu; Lee, Chelsea; Pan, Jian-Liang; Wen, Zhi-Hong; Huang, Shu-Hung; Lan, Chi-Wei John; Liu, Wang-Ta; Hour, Tzyh-Chyuan; Hseu, You-Cheng; Hwang, Byeong Hee; Cheng, Kuo-Chen; Wang, Hui-Min David

2016-01-01

Among many antioxidants that are used for the repairing of oxidative stress induced skin damages, we identified the enriched astaxanthin extract (EAE) from Haematococcus pluvialis as a viable ingredient. EAE was extracted from the red microalgae through supercritical fluid carbon dioxide extraction. To compare the effectiveness, EAE wastreated on human dermal fibroblasts with other components, phorbol 12-myristate 13-acetate (PMA), and doxycycline. With sirius red staining and quantitative real-time polymerase chain reaction (qRT-PCR), we found that PMA decreased the collagen concentration and production while overall the addition of doxycycline and EAE increased the collagen concentration in a trial experiments. EAE increased collagen contents through inhibited MMP1 and MMP3 mRNA expression and induced TIMP1, the antagonists of MMPs protein, gene expression. As for when tested for various proteins through western blotting, it was seen that the addition of EAE increased the expression of certain proteins that promote cell proliferation. Testing those previous solutions using growth factor assay, it was noticeable that EAE had a positive impact on cell proliferation and vascular endothelial growth factor (VEGF) than doxycycline, indicating that it was a better alternative treatment for collagen production. To sum up, the data confirmed the possible applications as medical cosmetology agentsand food supplements. PMID:27322248

Developing COSHH Essentials: dermal exposure, personal protective equipment and first aid.

PubMed

Garrod, A N I; Rajan-Sithamparanadarajah, R

2003-10-01

The 'control banding' approach in COSHH Essentials combines the potential for harm with the potential for exposure by inhalation to band measures to control exposure at source, as generic strategies. These are simply adapted to specific tasks and circumstances to produce specific control advice. Where it is not possible or practical to use this control advice, the control bands can suggest adequate respiratory protective equipment using 'protection factors'. Proposals in the paper enable the user to identify the right level of respiratory protective equipment (RPE), and to begin selecting suitable RPE. Selection is made through a formatted questionnaire, enabling the user to give the right facts to the supplier. COSHH Essentials applies mainly to exposure by inhalation. However, skin exposure is very common and uptake via the skin can be an important contributor to body dose. This paper examines the factors concerning skin exposure, and the options for banding the potential for harm to the skin or via the skin. Proposals have then been made for dermal exposure control. Planning for emergencies is an important facet of risk control. Proposals are outlined to band chemical hazards for emergency planning according to a minimum of information, i.e. the danger symbol on a product label.

Nanocrystals of medium soluble actives--novel concept for improved dermal delivery and production strategy.

PubMed

Zhai, Xuezhen; Lademann, Jürgen; Keck, Cornelia M; Müller, Rainer H

2014-08-15

After use in oral pharmaceutical products, nanocrystals are meanwhile applied to improve the dermal penetration of cosmetic actives (e.g. rutin, hesperidin) and of drugs. By now, nanocrystals are only dermally applied made from poorly soluble actives. The novel concept is to formulate nanocrystals also from medium soluble actives, and to apply a dermal formulation containing additionally nanocrystals. The nanocrystals should act as fast dissolving depot, increase saturation solubility and especially accumulate in the hair follicles, to further increase skin penetration. Caffeine was used as model compound with relevance to market products, and a particular process was developed for the production of caffeine nanocrystals to overcome the supersaturation related effect of crystal growth and fiber formation - typical with medium soluble compounds. It is based on low energy milling (pearl milling) in combination with low dielectric constant dispersion media (water-ethanol or ethanol-propylene glycol mixtures) and optimal stabilizers. Most successful was Carbopol(®) 981 (e.g. 20% caffeine in ethanol-propylene glycol 3:7 with 2% Carbopol, w/w). Nanocrystals with varied sizes can now be produced in a controlled process e.g. 660 nm (optimal for hair follicle accumulation) to 250 nm (optimal for fast dissolution). The short term test proved stability over 2 months of the present formulation being sufficient to perform in vivo testing of the novel concept. Copyright © 2014 Elsevier B.V. All rights reserved.

Repair of Postoperative Abdominal Hernia in a Child with Congenital Omphalocele Using Porcine Dermal Matrix

PubMed Central

Mylona, E.; Tsakalidis, C.; Spyridakis, I.; Mitsiakos, G.; Karagianni, P.

2016-01-01

Introduction. Incisional hernias are a common complication appearing after abdominal wall defects reconstruction, with omphalocele and gastroschisis being the most common etiologies in children. Abdominal closure of these defects represents a real challenge for pediatric surgeons with many surgical techniques and various prosthetic materials being used for this purpose. Case Report. We present a case of repair of a postoperative ventral hernia occurring after congenital omphalocele reconstruction in a three-and-a-half-year-old child using an acellular, sterile, porcine dermal mesh. Conclusion. Non-cross-linked acellular porcine dermal matrix is an appropriate mesh used for the reconstruction of abdominal wall defects and their postoperative complications like large ventral hernias with success and preventing their recurrence. PMID:27110247

Repair of Postoperative Abdominal Hernia in a Child with Congenital Omphalocele Using Porcine Dermal Matrix.

PubMed

Lambropoulos, V; Mylona, E; Mouravas, V; Tsakalidis, C; Spyridakis, I; Mitsiakos, G; Karagianni, P

2016-01-01

Introduction. Incisional hernias are a common complication appearing after abdominal wall defects reconstruction, with omphalocele and gastroschisis being the most common etiologies in children. Abdominal closure of these defects represents a real challenge for pediatric surgeons with many surgical techniques and various prosthetic materials being used for this purpose. Case Report. We present a case of repair of a postoperative ventral hernia occurring after congenital omphalocele reconstruction in a three-and-a-half-year-old child using an acellular, sterile, porcine dermal mesh. Conclusion. Non-cross-linked acellular porcine dermal matrix is an appropriate mesh used for the reconstruction of abdominal wall defects and their postoperative complications like large ventral hernias with success and preventing their recurrence.

Growth, nutritional, and gastrointestinal aspects of focal dermal hypoplasia (Goltz-Gorlin syndrome)

USDA-ARS?s Scientific Manuscript database

Focal dermal hypoplasia (FDH) is a rare genetic disorder caused by mutations in the PORCN gene located on the X-chromosome. In the present study, we characterized the pattern of growth, body composition, and the nutritional and gastrointestinal aspects of children and adults (n'='19) affected with t...

Phenotypic differences between oral and skin fibroblasts in wound contraction and growth factor expression.

PubMed

Shannon, Diane B; McKeown, Scott T W; Lundy, Fionnuala T; Irwin, Chris R

2006-01-01

Wounds of the oral mucosa heal in an accelerated fashion with reduced scarring compared with cutaneous wounds. The differences in healing outcome between oral mucosa and skin could be because of phenotypic differences between the respective fibroblast populations. This study compared paired mucosal and dermal fibroblasts in terms of collagen gel contraction, alpha-smooth muscle actin expression (alpha-SMA), and production of the epithelial growth factors: keratinocyte growth factor (KGF) and hepatocyte growth factor/scatter factor (HGF). The effects of transforming growth factor -beta1 and -beta3 on each parameter were also determined. Gel contraction in floating collagen lattices was determined over a 7-day period. alpha-SMA expression by fibroblasts was determined by Western blotting. KGF and HGF expression were determined by an enzyme-linked immunosorbent assay. Oral fibroblasts induced accelerated collagen gel contraction, yet surprisingly expressed lower levels of alpha-SMA. Oral cells also produced significantly greater levels of both KGF and HGF than their dermal counterparts. Transforming growth factor-beta1 and -beta3, over the concentration range of 0.1-10 ng/mL, had similar effects on cell function, stimulating both gel contraction and alpha-SMA production, but inhibiting KGF and HGF production by both cell types. These data indicate phenotypic differences between oral and dermal fibroblasts that may well contribute to the differences in healing outcome between these two tissues.

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

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.

Analyses of the correlation between dermal and blood carotenoids in female cattle by optical methods

NASA Astrophysics Data System (ADS)

Klein, Julia; Darvin, Maxim E.; Meinke, Martina C.; Schweigert, Florian J.; Müller, Kerstin E.; Lademann, Jürgen

2013-06-01

Herd health programs for the maintenance of welfare and productivity in cattle need efficient tools for monitoring the health of individual animals. Recent reports demonstrate that the oxidative status is related to various stress conditions in dairy cows. Biomarkers, among other carotenoids, could serve as indicators of stress originating from the environment (e.g., heat stress or sun radiation) or from the animal itself (e.g., disease). To date, only invasive in vitro tests are available to assess the oxidative status in cattle. The present study compares the results of optical noninvasive in vivo measurements of dermal carotenoids in cattle udder skin using an LED-based miniaturized spectroscopic system (MSS) with those obtained by photometric analysis of beta carotene in whole blood samples using a portable device. Correlations between the concentrations of dermal and blood carotenoids were calculated under consideration of the nutritional status of the animals. Significant correlation (R=0.86) was found for cattle with a moderate to obese body condition. Thus, the blood and skin concentrations of the marker substance beta carotene are comparable under stable stress conditions of the cattle. This demonstrates that the MSS is suitable for noninvasive assessment of dermal carotenoid concentrations in cattle.

A Complex Genomic Rearrangement Involving the Endothelin 3 Locus Causes Dermal Hyperpigmentation in the Chicken

PubMed Central

Dorshorst, Ben; Molin, Anna-Maja; Rubin, Carl-Johan; Johansson, Anna M.; Strömstedt, Lina; Pham, Manh-Hung; Chen, Chih-Feng; Hallböök, Finn; Ashwell, Chris; Andersson, Leif

2011-01-01

Dermal hyperpigmentation or Fibromelanosis (FM) is one of the few examples of skin pigmentation phenotypes in the chicken, where most other pigmentation variants influence feather color and patterning. The Silkie chicken is the most widespread and well-studied breed displaying this phenotype. The presence of the dominant FM allele results in extensive pigmentation of the dermal layer of skin and the majority of internal connective tissue. Here we identify the causal mutation of FM as an inverted duplication and junction of two genomic regions separated by more than 400 kb in wild-type individuals. One of these duplicated regions contains endothelin 3 (EDN3), a gene with a known role in promoting melanoblast proliferation. We show that EDN3 expression is increased in the developing Silkie embryo during the time in which melanoblasts are migrating, and elevated levels of expression are maintained in the adult skin tissue. We have examined four different chicken breeds from both Asia and Europe displaying dermal hyperpigmentation and conclude that the same structural variant underlies this phenotype in all chicken breeds. This complex genomic rearrangement causing a specific monogenic trait in the chicken illustrates how novel mutations with major phenotypic effects have been reused during breed formation in domestic animals. PMID:22216010

Dermal arteritis of the nasal philtrum in a Giant Schnauzer and three Saint Bernard dogs.

PubMed

Torres, Sheila M F; Brien, Timothy O; Scott, Danny W

2002-10-01

Arteritis of the nasal philtrum is described in four dogs. Two of the Saint Bernards were related. The lesions were solitary, well-circumscribed, linear ulcers that were neither pruritic nor painful. The age of the dogs at the time the owners first noticed the lesion ranged from 3 to 6 years. The ulcers had been present for 0.5-5 years before diagnosis was pursued. Three of the dogs experienced repeated, mild episodes of arterial bleeding from the ulcers. Two dogs also experienced a severe episode of bleeding that required surgical intervention. Histopathological findings included a V-shaped ulcer, neutrophilic dermal inflammation subjacent to the ulcer and lymphoplasmacytic dermatitis bordering the ulcer. The most remarkable pathological findings were present in the deep dermal arteries and arterioles subjacent to the ulcer. The changes were characterized by subendothelial spindle cell proliferation with marked extracellular matrix deposition that stained blue with Alcian Blue (mucin) and Masson's trichrome (collagen) and resulted in intimal thickening, and stenosis of dermal arteries and arterioles. Immunohistochemical studies suggested that the proliferating spindle cells were of either myofibroblast or smooth muscle origin (actin and vimentin positive). Anti-inflammatory therapy (glucocorticoids; tetracycline and niacinamide; fish oil) may be beneficial for long-term control of this condition, however, long-term maintenance treatment appears to be necessary.

Comparison of native porcine skin and a dermal substitute using tensiometry and digital image speckle correlation.

PubMed

Fritz, Jason R; Phillips, Brett T; Conkling, Nicole; Fourman, Mitchell; Melendez, Mark M; Bhatnagar, Divya; Simon, Marcia; Rafailovich, Miriam; Dagum, Alexander B

2012-10-01

Dermal substitutes are currently used in plastic surgery to cover various soft tissue defects caused by trauma, burns, or ablative cancer surgery. Little information is available on the biomechanical properties of these dermal substitutes after adequate incorporation as compared to normal skin. Determining parameters such as tensile strength in these skin substitutes will help us further understand their wound healing properties and potential in developing artificial tissue constructs. We hypothesize that a dermal substitute has a lower stress-strain curve and altered stress-induced deformation quantified with tensiometry and digital image speckle correlation (DISC) analysis. Two separate 5×10-cm full-thickness wounds were created on the dorsum of 3 female swine. Fibrin glue was applied before either a full-thickness skin graft (FTSG) or application of artificial dermal matrix. On day 42, cultured autologous keratinocytes were applied as a cell sheet to the wound covered with Integra. On day 56, the wounds were fully excised and fresh tissue specimens, including normal skin, were stored in a physiological solution and prepared for analysis. Rectangular samples were excised from the center of each specimen measuring 4×4×30 mm. Using a tensiometer and DISC analysis, we evaluated the tensile strength of 3 different groups of skin, namely, normal, FTSG, and Integra. There is a significant difference between the Integra specimen when compared to normal skin and FTSG. We found a minimal difference in the stress-strain curves of the latter two. Integra alone shows plastic deformation with continued stretching before ultimate midline fracture. There is significant change between the Young's moduli of the normal skin and the Integra, whereas there is little difference between the FTSG and the normal skin; DISC confirms this analysis. The normal skin and FTSG show a convergence of vectors to a linear plane, whereas Integra shows very little organization. Using 2 different

U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--STANDARD OPERATING PROCEDURE FOR EXTRACTION OF PESTICIDES FROM DERMAL WIPE SAMPLES (BCO-L-12.1)

EPA Science Inventory

The purpose of this SOP is to describe procedures for extracting and preparing a dermal wipe sample for GC/MS analysis of pesticides. This procedure was followed to ensure consistent data retrieval during the Arizona NHEXAS project and the Border study. Keywords: dermal wipe; p...

Scented traces--Dermal exposure of synthetic musk fragrances in personal care products and environmental input assessment.

PubMed

Homem, Vera; Silva, Eduardo; Alves, Arminda; Santos, Lúcia

2015-11-01

Synthetic musks are organic compounds used as fragrance and fixative additives in several personal care products. Until now, little is known about their occurrence and distribution in these household commodities. However, this information is essential to perform a human dermal exposure assessment. Therefore, this study gives an overview on the levels of 12 synthetic musks in 140 personal care products from 7 different categories (body and hair wash, toilet soaps, shaving products, dentifrice products, deodorants/antiperspirants, moisturizers and perfumes). They were analysed by QuEChERS extraction followed by gas chromatography-mass spectrometry. Detection limits were found between 0.01ngg(-1) (galaxolide) and 5.00ngg(-1) (musk xylene). Higher average concentrations of total synthetic musks were detected in perfumes (5245.05μgg(-1)) and shampoos (487.67μgg(-1)) for adults. Galaxolide, exaltolide and cashmeran were the most detected compounds. Combining these results with the daily usage amounts, an average daily dermal exposure of 75.69μgkgbw(-1)day(-1) for adults and 15.54μgkgbw(-1)day(-1) for babies/children was achieved. The main contributors for adult and babies/children dermal exposure were perfumes and lotions, respectively. About 40% of the adult daily dermal exposure is related to exaltolide, 30% galaxolide, and 15% tonalide, while for babies/children 96% occurs due to exaltolide. An estimate of the amount of musks discharged "down-the-drain" into the wastewater treatment systems through the use of toiletries was also performed. An average emission per capita of 6.7mgday(-1) was determined and galaxolide and exaltolide were the predominant musks in the effluents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Further delineation of the odonto-onycho-dermal dysplasia syndrome.

PubMed

Mégarbané, Hala; Haddad, May; Delague, Valérie; Renoux, Julien; Boehm, Nelly; Mégarbané, André

2004-08-30

We report on three boys, two brothers and their maternal cousin, presenting with dry hair, pilar keratosis, severe hypodontia, smooth tongue, onychodysplasia, and keratoderma and hyperhidrosis of palms and soles. Histology of the skin showed orthokeratotic, hyperkeratosis, hypergranulosis, and mild acanthosis in the epidermis. Scanning electron microscopic examination of the hair showed longitudinal depressions in some hair. These features are close to a rare entity: the odonto-onycho-dermal dysplasia but with some differing features. Copyright 2004 Wiley-Liss, Inc.

Management of gingival recession by the use of an acellular dermal graft material: a 12-case series.

PubMed

Santos, A; Goumenos, G; Pascual, A

2005-11-01

Different soft tissue defects can be treated by a variety of surgical procedures. Most of these techniques require the palatal area as a donor site. Recently, an acellular dermal graft has become available that can substitute for palatal donor tissue. This study describes the surgical technique for gingival augmentation and root coverage and the results of 12 clinical cases. A comparison between the three most popular mucogingival procedures for root coverage is also presented. The results of the 12 patients and the 26 denuded surfaces have shown that we can obtain a mean root coverage of 74% with the acellular dermal graft. Thirteen out of the 26 denuded surfaces had complete root coverage. The average increase in keratinized tissue was 1.19 mm. It seems that the long-term results of the cases are stable. The proposed technique of root coverage with an acellular dermal graft can be a good alternative to soft tissue grafts for root coverage, and it should be part of our periodontal plastic surgery armamentarium.

Biometrical evaluation of the performance of the revised OECD Test Guideline 402 for assessing acute dermal toxicity.

PubMed

Mielke, H; Strickland, J; Jacobs, M N; Mehta, J M

2017-10-01

A comprehensive biometrical assessment was conducted to compare the performance of multiple test designs for acute dermal systemic toxicity to support the animal welfare update to the original OECD Test Guideline (TG) 402 for acute dermal toxicity. The test designs evaluated included: (1) two, three, or five animals per dose group (2) evident toxicity or lethality endpoints and (3) absence or presence of a one-animal sighting study. The revision of TG 402 respected the 3R principles (replace, reduce, refine) of animal testing. The results demonstrate that the TG 402 test design can be optimised with reduced animal numbers per test group, such that a scenario of two animals per group following a sighting study at a starting dose of 200 mg/kg bw (unless further information is available to better define the starting dose) would provide a classification which in most cases is conservative, without compromising both the statistical ability of the study to assess dermal toxicity, or the relevant classification outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage

PubMed Central

Thomas, Susan N.; Rutkowski, Joseph M.; Pasquier, Miriella; Kuan, Emma L.; Alitalo, Kari; Randolph, Gwendalyn J.; Swartz, Melody A.

2012-01-01

Lymphatic vessels transport interstitial fluid, soluble antigen, and immune cells from peripheral tissues to lymph nodes (LNs), yet the contribution of peripheral lymphatic drainage to adaptive immunity remains poorly understood. We examined immune responses to dermal vaccination and contact hypersensitivity (CHS) challenge in K14-VEGFR-3-Ig mice, which lack dermal lymphatic capillaries and experience markedly depressed transport of solutes and dendritic cells from the skin to draining LNs. In response to dermal immunization, K14-VEGFR-3-Ig mice produced lower antibody titers. In contrast, although delayed, T cell responses were robust after 21 days, including high levels of antigen-specific CD8+ T cells and production of IFN-γ, IL-4 and IL-10 upon restimulation. T cell-mediated CHS responses were strong in K14-VEGFR-3-Ig mice, but importantly, their ability to induce CHS tolerance in the skin was impaired. Additionally, one-year-old mice displayed multiple signs of autoimmunity. These data suggest that lymphatic drainage plays more important roles in regulating humoral immunity and peripheral tolerance than in effector T cell immunity. PMID:22844119

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.

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.

Augmentation of Distal Biceps Repair With an Acellular Dermal Graft Restores Native Biomechanical Properties in a Tendon-Deficient Model.

PubMed

Conroy, Christine; Sethi, Paul; Macken, Craig; Wei, David; Kowalsky, Marc; Mirzayan, Raffy; Pauzenberger, Leo; Dyrna, Felix; Obopilwe, Elifho; Mazzocca, Augustus D

2017-07-01

The majority of distal biceps tendon injuries can be repaired in a single procedure. In contrast, complete chronic tears with severe tendon substance deficiency and retraction often require tendon graft augmentation. In cases with extensive partial tears of the distal biceps, a human dermal allograft may be used as an alternative to restore tendon thickness and biomechanical integrity. Dermal graft augmentation will improve load to failure compared with nonaugmented repair in a tendon-deficient model. Controlled laboratory study. Thirty-six matched specimens were organized into 1 of 4 groups: native tendon, native tendon with dermal graft augmentation, tendon with an attritional defect, and tendon with an attritional defect repaired with a graft. To mimic a chronic attritional biceps lesion, a defect was created by a complete tear, leaving 30% of the tendon's width intact. The repair technique in all groups consisted of cortical button and interference screw fixation. All specimens underwent cyclical loading for 3000 cycles and were then tested to failure; gap formation and peak load at failure were documented. The mean (±SD) load to failure (320.9 ± 49.1 N vs 348.8 ± 77.6 N, respectively; P = .38) and gap formation (displacement) (1.8 ± 1.4 mm vs 1.6 ± 1.1 mm, respectively; P = .38) did not differ between the native tendon groups with and without graft augmentation. In the tendon-deficient model, the mean load to failure was significantly improved with graft augmentation compared with no graft augmentation (282.1 ± 83.8 N vs 199.7 ± 45.5 N, respectively; P = .04), while the mean gap formation was significantly reduced (1.2 ± 1.0 mm vs 2.7 ± 1.4 mm, respectively; P = .04). The mean load to failure of the deficient tendon with graft augmentation (282.1 N) compared with the native tendon (348.8 N) was not significantly different ( P = .12). This indicates that the native tendon did not perform differently from the grafted deficient tendon. In a tendon

Adult epidermal Notch activity induces dermal accumulation of T cells and neural crest derivatives through upregulation of jagged 1

PubMed Central

Ambler, Carrie A.; Watt, Fiona M.

2010-01-01

Notch signalling regulates epidermal differentiation and tumour formation via non-cell autonomous mechanisms that are incompletely understood. This study shows that epidermal Notch activation via a 4-hydroxy-tamoxifen-inducible transgene caused epidermal thickening, focal detachment from the underlying dermis and hair clumping. In addition, there was dermal accumulation of T lymphocytes and stromal cells, some of which localised to the blisters at the epidermal-dermal boundary. The T cell infiltrate was responsible for hair clumping but not for other Notch phenotypes. Notch-induced stromal cells were heterogeneous, expressing markers of neural crest, melanocytes, smooth muscle and peripheral nerve. Although Slug1 expression was expanded in the epidermis, the stromal cells did not arise through epithelial-mesenchymal transition. Epidermal Notch activation resulted in upregulation of jagged 1 in both epidermis and dermis. When Notch was activated in the absence of epidermal jagged 1, jagged 1 was not upregulated in the dermis, and epidermal thickening, blister formation, accumulation of T cells and stromal cells were inhibited. Gene expression profiling revealed that epidermal Notch activation resulted in upregulation of several growth factors and cytokines, including TNFα, the expression of which was dependent on epidermal jagged 1. We conclude that jagged 1 is a key mediator of non-cell autonomous Notch signalling in skin. PMID:20940224

Adult epidermal Notch activity induces dermal accumulation of T cells and neural crest derivatives through upregulation of jagged 1.

PubMed

Ambler, Carrie A; Watt, Fiona M

2010-11-01

Notch signalling regulates epidermal differentiation and tumour formation via non-cell autonomous mechanisms that are incompletely understood. This study shows that epidermal Notch activation via a 4-hydroxy-tamoxifen-inducible transgene caused epidermal thickening, focal detachment from the underlying dermis and hair clumping. In addition, there was dermal accumulation of T lymphocytes and stromal cells, some of which localised to the blisters at the epidermal-dermal boundary. The T cell infiltrate was responsible for hair clumping but not for other Notch phenotypes. Notch-induced stromal cells were heterogeneous, expressing markers of neural crest, melanocytes, smooth muscle and peripheral nerve. Although Slug1 expression was expanded in the epidermis, the stromal cells did not arise through epithelial-mesenchymal transition. Epidermal Notch activation resulted in upregulation of jagged 1 in both epidermis and dermis. When Notch was activated in the absence of epidermal jagged 1, jagged 1 was not upregulated in the dermis, and epidermal thickening, blister formation, accumulation of T cells and stromal cells were inhibited. Gene expression profiling revealed that epidermal Notch activation resulted in upregulation of several growth factors and cytokines, including TNFα, the expression of which was dependent on epidermal jagged 1. We conclude that jagged 1 is a key mediator of non-cell autonomous Notch signalling in skin.

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.

Methylphenidate Transdermal System: A Multisite, Open-Label Study of Dermal Reactions in Pediatric Patients Diagnosed With ADHD

PubMed Central

Squires, Liza; Li, Yunfeng; Civil, Richard; Paller, Amy S.

2010-01-01

Objective: To characterize dermal reactions and examine methylphenidate (MPH) sensitization in subjects receiving methylphenidate transdermal system (MTS). Method: This multicenter, open-label, dose-optimization study utilized MTS doses of 10, 15, 20, and 30 mg in children aged 6 to 12 years, inclusive (N = 305), with a DSM-IV-TR primary diagnosis of attention-deficit/hyperactivity disorder. The study was conducted between January 8, 2007, and August 23, 2007. Subjects wore MTS on their hips for 9 hours per day, alternating sides daily for a total of 7 weeks. Assessments included the Experience of Discomfort scale, Transdermal System Adherence scale, and Dermal Response Scale (DRS; 0 = no irritation, 7 = strong reaction). On-study reevaluations were conducted to characterize DRS scores ≥ 4. Epicutaneous allergy patch testing was conducted for DRS scores ≥ 6, persistent DRS scores ≥ 4, DRS score increase following an assessment of ≥ 4, or DRS scores of 4 or 5 following elective discontinuation. Results: Approximately half of subjects experienced definite erythema at the patch site that generally dissipated within 24 hours. Four subjects experienced a DRS score of 4 (1%): erythema in 1 subject resolved on study treatment, 2 cases resolved poststudy and subjects tolerated oral MPH, and 1 subject discontinued treatment. The latter subject was referred for patch testing and was diagnosed with allergic contact sensitization to MPH. Conclusions: Few severe dermal effects were seen with MTS treatment. Dermal reactions were characterized as contact dermatitis and dissipated rapidly. On patch testing, 1 subject (0.3%) manifested sensitization to MPH. Trial Registration: clinicaltrials.gov Identifier: NCT00434213 PMID:21494336

Effect of Arctium lappa (burdock) extract on canine dermal fibroblasts.

PubMed

Pomari, Elena; Stefanon, Bruno; Colitti, Monica

2013-12-15

Although the biological activities of Arctium lappa (burdock) have been already investigated in human and other species, data evaluating the molecular mechanisms have not been reported in the dog. In this study we analyzed for the first time the effect of a root extract of burdock on molecular responses in canine dermal fibroblasts with H2O2 stimulation (H group), with burdock treatment (B group) and with H2O2 stimulation and burdock treatment (BH group), using RNAseq technology. Differentially expressed genes (P<0.05) of H, B and BH groups in comparison to the untreated sample (negative control, C group) were identified with MeV software and were functional annotated and monitored for signaling pathways and candidate biomarkers using the Ingenuity Pathways Analysis (IPA). The expression profile of canine dermal fibroblasts treated with burdock extract with or without H2O2 stimulation, showed an up-regulation of mitochondrial superoxide dismutase (SOD2), disheveled 3 (DVL3) and chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2). The data suggested that burdock has implications in cell adhesion and gene expression with the modulation of Wnt/β catenin signaling and Chondroitin Sulphate Biosynthesis that are particularly important for the wound healing process. © 2013 Elsevier B.V. All rights reserved.

Key Regulatory Role of Dermal Fibroblasts in Pigmentation as Demonstrated Using a Reconstructed Skin Model: Impact of Photo-Aging

PubMed Central

Duval, Christine; Cohen, Catherine; Chagnoleau, Corinne; Flouret, Virginie; Bourreau, Emilie; Bernerd, Françoise

2014-01-01

To study cutaneous pigmentation in a physiological context, we have previously developed a functional pigmented reconstructed skin model composed of a melanocyte-containing epidermis grown on a dermal equivalent comprising living fibroblasts. The present studies, using the same model, aimed to demonstrate that dermal fibroblasts influence skin pigmentation up to the macroscopic level. The proof of principle was performed with pigmented skins differing only in the fibroblast component. First, the in vitro system was reconstructed with or without fibroblasts in order to test the global influence of the presence of this cell type. We then assessed the impact of the origin of the fibroblast strain on the degree of pigmentation using fetal versus adult fibroblasts. In both experiments, impressive variation in skin pigmentation at the macroscopic level was observed and confirmed by quantitative parameters related to skin color, melanin content and melanocyte numbers. These data confirmed the responsiveness of the model and demonstrated that dermal fibroblasts do indeed impact the degree of skin pigmentation. We then hypothesized that a physiological state associated with pigmentary alterations such as photo-aging could be linked to dermal fibroblasts modifications that accumulate over time. Pigmentation of skin reconstructed using young unexposed fibroblasts (n = 3) was compared to that of tissues containing natural photo-aged fibroblasts (n = 3) which express a senescent phenotype. A stimulation of pigmentation in the presence of the natural photo-aged fibroblasts was revealed by a significant increase in the skin color (decrease in Luminance) and an increase in both epidermal melanin content and melanogenic gene expression, thus confirming our hypothesis. Altogether, these data demonstrate that the level of pigmentation of the skin model is influenced by dermal fibroblasts and that natural photo-aged fibroblasts can contribute to the hyperpigmentation that is

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

Dermal and inhalation acute toxic class methods: test procedures and biometric evaluations for the Globally Harmonized Classification System.

PubMed

Holzhütter, H G; Genschow, E; Diener, W; Schlede, E

2003-05-01

The acute toxic class (ATC) methods were developed for determining LD(50)/LC(50) estimates of chemical substances with significantly fewer animals than needed when applying conventional LD(50)/LC(50) tests. The ATC methods are sequential stepwise procedures with fixed starting doses/concentrations and a maximum of six animals used per dose/concentration. The numbers of dead/moribund animals determine whether further testing is necessary or whether the test is terminated. In recent years we have developed classification procedures for the oral, dermal and inhalation routes of administration by using biometric methods. The biometric approach assumes a probit model for the mortality probability of a single animal and assigns the chemical to that toxicity class for which the best concordance is achieved between the statistically expected and the observed numbers of dead/moribund animals at the various steps of the test procedure. In previous publications we have demonstrated the validity of the biometric ATC methods on the basis of data obtained for the oral ATC method in two-animal ring studies with 15 participants from six countries. Although the test procedures and biometric evaluations for the dermal and inhalation ATC methods have already been published, there was a need for an adaptation of the classification schemes to the starting doses/concentrations of the Globally Harmonized Classification System (GHS) recently adopted by the Organization for Economic Co-operation and Development (OECD). Here we present the biometric evaluation of the dermal and inhalation ATC methods for the starting doses/concentrations of the GHS and of some other international classification systems still in use. We have developed new test procedures and decision rules for the dermal and inhalation ATC methods, which require significantly fewer animals to provide predictions of toxicity classes, that are equally good or even better than those achieved by using the conventional LD(50)/LC

Unraveling the Relative Importance of Oral and Dermal Contaminant Exposure in Reptiles: Insights from Studies Using the Western Fence Lizard (Sceloporus occidentalis)

PubMed Central

Weir, Scott M.; Talent, Larry G.; Anderson, Todd A.; Salice, Christopher J.

2014-01-01

Despite widespread recognition of significant data deficiencies, reptiles remain a relatively understudied taxon in ecotoxicology. To conduct ecological risk assessments on reptiles frequently requires using surrogate taxa such as birds, but recent research suggests that reptiles have significantly different exposure profiles and toxicant sensitivity. We exposed western fence lizards, Sceloporus occidentalis, to the same quantities of three model chemicals via oral (gavage) and dermal (ventral skin application) exposure for either 24 or 48 hours. Three phthalate esters (di-methyl phthalate [DMP], di-iso-butyl phthalate [DIBP], and di-n-octyl phthalate [DNOP]) were chosen as model chemicals because they represent a gradient of lipophilicity but are otherwise structurally similar. Overall, the more lipophilic phthalates (DIBP and DNOP) were found to have higher concentrations in tissues than the less lipophilic DMP. Significant differences in tissue concentrations between DIBP and DNOP were tissue-dependent, suggesting that delivery to a site of action following exposure is not only a simple function of lipophilicity. In dermal treatments, DMP usually had fewer detections (except in ventral skin samples), suggesting that lipophilicity (log Kow>2) is a requirement for uptake across the skin. In general, tissue residues were greater in oral treatments than dermal treatments (significant in adipose and liver tissue), but differences were driven strongly by differences in DMP which did not appear to be absorbed well across skin. When differences in tissue residue concentrations between oral and dermal exposure did occur, the difference was not drastic. Taken together these results suggest that dermal exposure should be considered in risk assessments for reptilian receptors. Dermal exposure may be an especially important route for reptiles as their ectothermic physiology translates to lower energetic demands and dietary exposure compared to birds and mammals. PMID

Unraveling the relative importance of oral and dermal contaminant exposure in reptiles: insights from studies using the western fence lizard (Sceloporus occidentalis).

PubMed

Weir, Scott M; Talent, Larry G; Anderson, Todd A; Salice, Christopher J

2014-01-01

Despite widespread recognition of significant data deficiencies, reptiles remain a relatively understudied taxon in ecotoxicology. To conduct ecological risk assessments on reptiles frequently requires using surrogate taxa such as birds, but recent research suggests that reptiles have significantly different exposure profiles and toxicant sensitivity. We exposed western fence lizards, Sceloporus occidentalis, to the same quantities of three model chemicals via oral (gavage) and dermal (ventral skin application) exposure for either 24 or 48 hours. Three phthalate esters (di-methyl phthalate [DMP], di-iso-butyl phthalate [DIBP], and di-n-octyl phthalate [DNOP]) were chosen as model chemicals because they represent a gradient of lipophilicity but are otherwise structurally similar. Overall, the more lipophilic phthalates (DIBP and DNOP) were found to have higher concentrations in tissues than the less lipophilic DMP. Significant differences in tissue concentrations between DIBP and DNOP were tissue-dependent, suggesting that delivery to a site of action following exposure is not only a simple function of lipophilicity. In dermal treatments, DMP usually had fewer detections (except in ventral skin samples), suggesting that lipophilicity (log Kow>2) is a requirement for uptake across the skin. In general, tissue residues were greater in oral treatments than dermal treatments (significant in adipose and liver tissue), but differences were driven strongly by differences in DMP which did not appear to be absorbed well across skin. When differences in tissue residue concentrations between oral and dermal exposure did occur, the difference was not drastic. Taken together these results suggest that dermal exposure should be considered in risk assessments for reptilian receptors. Dermal exposure may be an especially important route for reptiles as their ectothermic physiology translates to lower energetic demands and dietary exposure compared to birds and mammals.

Attenuation fluctuations and local dermal reflectivity are indicators of immune cell infiltrate and epidermal hyperplasia in skin inflammation

NASA Astrophysics Data System (ADS)

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

2012-02-01

Psoriasis is a common inflammatory skin disease resulting from genetic and environmental alterations of cutaneous immune responses responsible for skin homeostasis. While numerous therapeutic targets involved in the immunopathogenesis of psoriasis have been identified, the in vivo dynamics of psoriasis remains under investigated. To elucidate the spatial-temporal morphological evolution of psoriasis we undertook in vivo time course focus-tracked optical coherence tomography (OCT) imaging to non-invasively document dermal alterations due to immune cell infiltration and epidermal hyperplasia in an Imiquimod (IMQ) induced model of psoriasis-like inflammation in DBA2/C57Bl6 hybrid mice. Quantitative appraisal of dermal architectural changes was achieved through a three parameter fit of OCT axial scans in the dermis of the form A(z) = ρ exp(-mu;z +ɛ(z)). Ensemble averaging of the fit parameters over 2000 axial scans per mouse in each treatment arm revealed that the local dermal reflectivity ρ, decreased significantly in response to 6 day IMQ treatment (p = 0.0001), as did the standard deviation of the attenuation fluctuation std(ɛ(z)), (p = 0.04), in comparison to cream controls and day 1 treatments. No significant changes were observed in the average dermal attenuation rate, μ. Our results suggest these label-free OCT-based metrics can be deployed to investigate new therapeutic targets in animal models as well as aid in clinical staging of psoriasis in conjunction with the psoriasis area and severity index.

STUDY TO TEST THE FEASIBILITY OF USING THE MACROACTIVITY APPROACH TO ASSESS DERMAL EXPOSURE

EPA Science Inventory

In the macroactivity approach, dermal exposure is estimated using empirically-derived transfer coefficients to aggregate the mass transfer associated with a series of contacts with a contaminated medium. The macroactivity approach affords the possibility of developing screenin...

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.

Community based study to compare the incidence and health services utilization pyramid for gastrointestinal, respiratory and dermal symptoms.

PubMed

Najnin, Nusrat; Sinclair, Martha; Forbes, Andrew; Leder, Karin

2012-07-23

Gastrointestinal (GI), respiratory and dermal symptoms are common and cause substantial morbidity, although the information on their exact incidence and comparative burden is limited. The aim of this study was to describe the epidemiology and rate these three major symptom complexes in order to improve our understanding of the health burden imposed by these symptoms. We used data from a community based randomised control trial conducted from June 2007 to August 2008 among 277 South Australian families consuming rainwater. Using weekly health diaries, we prospectively collected information on GI (diarrhoea or vomiting), respiratory (sore throat, runny nose or cough) and dermal (rash, generalised itch or dermal infection) symptoms, as well as on relevant GP visits, time off work and/or hospitalisation due to these symptoms. Data were analysed using generalized estimating equations approach taking into account the variable number of weeks of follow-up of each individual and within-family clustering of responses. Over one year, at least one episode of GI symptoms was reported by 54% of participants (95% CI 50%-58%), at least one respiratory episode by 91% (95% CI 88%-93%) and at least one episode of dermal symptoms by 27% (95% CI 24%-30%). The average number of weeks per year during which respiratory symptoms occurred was four times greater than for GI or dermal symptoms (4.9, 1.2 and 1.2 weeks, respectively, p<0.001), with an average number of GP visits per person per year being twice as frequent (0.48, 0.26, 0.19 respectively, p<0.001). However, on a per episode basis, a higher proportion of people saw a GP or were hospitalised for GI symptoms. This first comparative study of three different symptom complexes showed that although respiratory symptoms are most common, GI symptoms cause a greater per episode burden on healthcare resources. Measuring and comparing the community based burden of these symptom complexes will assist evidence-based allocation of resources.

Oral mucosa: an alternative epidermic cell source to develop autologous dermal-epidermal substitutes from diabetic subjects

PubMed Central

GUZMÁN-URIBE, Daniela; ALVARADO-ESTRADA, Keila Neri; PIERDANT-PÉREZ, Mauricio; TORRES-ÁLVAREZ, Bertha; SÁNCHEZ-AGUILAR, Jesus Martin; ROSALES-IBÁÑEZ, Raúl

2017-01-01

Abstract Oral mucosa has been highlighted as a suitable source of epidermal cells due to its intrinsic characteristics such as its higher proliferation rate and its obtainability. Diabetic ulcers have a worldwide prevalence that is variable (1%-11%), meanwhile treatment of this has been proven ineffective. Tissue-engineered skin plays an important role in wound care focusing on strategies such autologous dermal-epidermal substitutes. Objective The aim of this study was to obtain autologous dermal-epidermal skin substitutes from oral mucosa from diabetic subjects as a first step towards a possible clinical application for cases of diabetic foot. Material and Methods Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group). Epidermal cells were isolated and cultured using autologous fibrin to develop dermal-epidermal in vitro substitutes by the air-liquid technique with autologous human serum as a supplement media. Substitutes were immunocharacterized with collagen IV and cytokeratin 5-14 as specific markers. A Student´s t- test was performed to assess the differences between both groups. Results It was possible to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects and develop autologous dermal-epidermal skin substitutes using autologous serum as a supplement. Differences in the expression of specific markers were observed and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and the collagen IV expression was higher in the diabetic substitutes when compared with the healthy group, showing a significant difference. Conclusion Cells from oral mucosa could be an alternative and less invasive source for skin substitutes and wound healing. A difference in collagen production of diabetic cells suggests diabetic substitutes could improve diabetic wound healing. More research is needed to determine the crosstalk between components of these skin substitutes and damaged tissues. PMID:28403359

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.

A novel, simple method for achieving hemostasis of fingertip dermal avulsion injuries.

PubMed

Lin, Brian Wai

2015-06-01

Distal fingertip pad dermal avulsion injuries can be challenging for emergency physicians. A common occurrence with these injuries is difficult-to-control bleeding. The nature of these wounds is such that conventional primary closure to achieve hemostasis is not feasible. Often, direct pressure, even for prolonged periods, will not adequately control the bleeding. Currently recommended techniques are inadequate to control bleeding, and commercially available hemostatic products may be more costly and not widely available. To present a simple method to achieve permanent hemostasis of these injuries using a tourniquet and tissue adhesive glue. A tourniquet is placed around the proximal digit, and the digit is exsanguinated and elevated to achieve short-term hemostasis. Several layers of commercially available tissue adhesive glue are applied sequentially over the avulsed region of the digit and allowed to dry. The tourniquet is then removed. A clean, bloodless dressing is created over the avulsed fingertip. This technique provides a rapid, simple, and likely safe means to control bleeding from a fingertip dermal avulsion injury. Copyright © 2015 Elsevier Inc. All rights reserved.

Spinal Intramedullary Abscess Secondary to Dermal Sinus in Children.

PubMed

Prasad, G Lakshmi; Hegde, Ajay; Divya, S

2018-06-01

 Congenital dermal sinuses (CDS) are uncommon lesions. They are most often noted in lumbosacral region and may lead to meningitis or spinal abscess. Intramedullary spinal cord abscess (IMSCA) due to CDS is rare and often co-exists with an inclusion tumor such as dermoid/epidermoid cyst.  Literature review was done to analyze all cases of pediatric IMSCA secondary to CDS by searching online databases starting from the oldest case reported.  Only 50 cases have been reported and were analyzed. Mean age was 22.6 months (range 1 month-15 years). Fever, acute flaccid lower limb weakness, and urinary disturbances were the most common presenting features. Dermal sinus was commonest in lumbosacral region. Inclusion cysts were observed in 50% of cases. Staphylococcus aureus was the most the common organism. Mean follow-up duration was 18.2 months (range 1 week-156 months). Majority of the cases underwent multilevel laminectomy with myelotomy and drainage of abscess. Outcome was good-to-excellent in around 60% cases with four deaths. Presence of fever and limb weakness was significantly associated with poor outcomes.  Intramedullary abscess secondary to CDS is very rare. Complete sinus tract excision, myelotomy and drainage of abscess, and decompression of co-existent inclusion cysts with prolonged antibiotic therapy remain the standard treatment. Approximately 60% cases achieve good outcomes. Fever and limb weakness portend poorer outcomes than those without. Georg Thieme Verlag KG Stuttgart · New York.

Effect of molecular weight of hyaluronic acid (HA) on viscoelasticity and particle texturing feel of HA dermal biphasic fillers.

PubMed

Chun, Cheolbyong; Lee, Deuk Yong; Kim, Jin-Tae; Kwon, Mi-Kyung; Kim, Young-Zu; Kim, Seok-Soon

2016-01-01

Hyaluronic acid (HA) dermal biphasic fillers are synthesized for their efficacy in correcting aesthetic defects such as wrinkles, scars and facial contouring defects. The fillers consist of crosslinked HA microspheres suspended in a noncrosslinked HA. To extend the duration of HAs within the dermis and obtain the particle texturing feel, HAs are crosslinked to obtain the suitable mechanical properties. Hyaluronic acid (HA) dermal biphasic fillers are prepared by mixing the crosslinked HA microspheres and the noncrosslinked HAs. The elastic modulus of the fillers increased with raising the volume fraction of the microspheres. The mechanical properties and the particle texturing feel of the fillers made from crosslinked HA (1058 kDa) microspheres suspended in noncrosslinked HA (1368 kDa) are successfully achieved, which are adequate for the fillers. Dermal biphasic HA fillers made from 1058 kDa exhibit suitable elastic moduli (211 to 420 Pa) and particle texturing feel (scale 7 ~ 9).

Nestin is expressed in HMB-45 negative melanoma cells in dermal parts of nodular melanoma.

PubMed

Kanoh, Maho; Amoh, Yasuyuki; Tanabe, Kenichi; Maejima, Hideki; Takasu, Hiroshi; Katsuoka, Kensei

2010-06-01

Nestin, a marker of neural stem cells, is expressed in the stem cells of the mouse hair follicle. The nestin-expressing hair follicle stem cells can differentiate into neurons, glia, keratocytes, smooth muscle cells and melanocytes in vitro. These pluripotent nestin-expressing stem cells are keratin 15 (K15)-negative, suggesting that they are in a relatively undifferentiated state. Recent studies suggest that the epithelial stem cells are important in tumorigenesis, and nestin expression is thought to be important in tumorigenesis. In the present study, we examined the expression of the hair follicle and neural stem cell marker nestin, as well as S-100 and HMB-45, in melanoma. Nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in all five cases of amelanotic nodular melanomas. Moreover, nestin immunoreactivity was observed in the dermal parts in seven of 10 cases of melanotic nodular melanomas. Especially, nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in the dermal parts of all 10 cases of HMB-45-negative amelanotic and melanotic nodular melanomas. On the other hand, nestin expression was negative in 10 of 12 cases of superficial spreading melanoma. These results suggest that nestin is an important marker of HMB-45-negative melanoma cells in the dermal parts of patients with nodular melanoma.

Lecithin based lamellar liquid crystals as a physiologically acceptable dermal delivery system for ascorbyl palmitate.

PubMed

Gosenca, Mirjam; Bešter-Rogač, Marija; Gašperlin, Mirjana

2013-09-27

Liquid crystalline systems with a lamellar structure have been extensively studied as dermal delivery systems. Ascorbyl palmitate (AP) is one of the most studied and used ascorbic acid derivatives and is employed as an antioxidant to prevent skin aging. The aim of this study was to develop and characterize skin-compliant dermal delivery systems with a liquid crystalline structure for AP. First, a pseudoternary phase diagram was constructed using Tween 80/lecithin/isopropyl myristate/water at a Tween 80/lecithin mass ratio of 1/1, and the region of lamellar liquid crystals was identified. Second, selected unloaded and AP-loaded lamellar liquid crystal systems were physicochemically characterized with polarizing optical microscopy, small-angle X-ray scattering, differential scanning calorimetry, and rheology techniques. The interlayer spacing and rheological parameters differ regarding quantitative composition, whereas the microstructure of the lamellar phase was affected by the AP incorporation, resulting either in additional micellar structures (at 25 and 32 °C) or being completely destroyed at higher temperature (37°C). After this, the study was oriented towards in vitro cytotoxicity evaluation of lamellar liquid crystal systems on a keratinocyte cell line. The results suggest that the lamellar liquid crystals that were developed could be used as a physiologically acceptable dermal delivery system. Copyright © 2013 Elsevier B.V. All rights reserved.

Evaluation of Furfuryl Alcohol Sensitization Potential Following Dermal and Pulmonary Exposure: Enhancement of Airway Responsiveness

PubMed Central

Franko, Jennifer; Jackson, Laurel G.; Hubbs, Ann; Kashon, Michael; Meade, B. J.; Anderson, Stacey E.

2015-01-01

Furfuryl alcohol is considered by the U.S. Environmental Protection Agency to be a high volume production chemical, with over 1 million pounds produced annually. Due to its high production volume and its numerous industrial and consumer uses, there is considerable potential for work-related exposure, as well as exposure to the general population, through pulmonary, oral, and dermal routes of exposure. Human exposure data report a high incidence of asthma in foundry mold workers exposed to furan resins, suggesting potential immunologic effects. Although furfuryl alcohol was nominated and evaluated for its carcinogenic potential by the National Toxicology Program, studies evaluating its immunotoxicity are lacking. The studies presented here evaluated the immunotoxic potential of furfuryl alcohol following exposure by the dermal and pulmonary routes using a murine model. When tested in a combined irritancy local lymph node assay, furfuryl alcohol was identified to be an irritant and mild sensitizer (EC3 = 25.6%). Pulmonary exposure to 2% furfuryl alcohol resulted in enhanced airway hyperreactivity, eosinophilic infiltration into the lungs, and enhanced cytokine production (IL-4, IL-5, and interferon-γ) by ex vivo stimulated lung-associated draining lymphoid cells. Airway hyperreactivity and eosinophilic lung infiltration were augmented by prior dermal exposure to furfuryl alcohol. These results suggest that furfuryl alcohol may play a role in the development of allergic airway disease and encourage the need for additional investigation. PMID:22003193

Design of a Novel Two-Component Hybrid Dermal Scaffold for the Treatment of Pressure Sores.

PubMed

Sharma, Vaibhav; Kohli, Nupur; Moulding, Dale; Afolabi, Halimat; Hook, Lilian; Mason, Chris; García-Gareta, Elena

2017-11-01

The aim of this study is to design a novel two-component hybrid scaffold using the fibrin/alginate porous hydrogel Smart Matrix combined to a backing layer of plasma polymerized polydimethylsiloxane (Sil) membrane to make the fibrin-based dermal scaffold more robust for the treatment of the clinically challenging pressure sores. A design criteria are established, according to which the Sil membranes are punched to avoid collection of fluid underneath. Manual peel test shows that native silicone does not attach to the fibrin/alginate component while the plasma polymerized silicone membranes are firmly bound to fibrin/alginate. Structural characterization shows that the fibrin/alginate matrix is intact after the addition of the Sil membrane. By adding a Sil membrane to the original fibrin/alginate scaffold, the resulting two-component scaffolds have a significantly higher shear or storage modulus G'. In vitro cell studies show that dermal fibroblasts remain viable, proliferate, and infiltrate the two-component hybrid scaffolds during the culture period. These results show that the design of a novel two-component hybrid dermal scaffold is successful according to the proposed design criteria. To the best of the authors' knowledge, this is the first study that reports the combination of a fibrin-based scaffold with a plasma-polymerized silicone membrane. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acellular dermal matrix allograft used to gain attached gingiva in a case of epidermolysis bullosa.

PubMed

Buduneli, Eralp; Ilgenli, Tunç; Buduneli, Nurcan; Ozdemir, Fezal

2003-11-01

Epidermolysis bullosa (EB) is an acquired disease or inherited as either autosomal dominant or recessive with an incidence of 1/50,000. The prominent clinical characteristic of the disease is the development of bullae or vesicles in mucosa or skin in response to minor trauma. A female patient with a dystrophic type of EB had been put in a maintenance regimen after completion of the initial phase of periodontal therapy and followed for 7 years. The purpose of this report is to document acellular dermal matrix allograft application to increase the width of the attached gingiva in this patient experiencing difficulty in chewing and performing plaque control due to the dramatic loss of attached gingiva after 7 years of supportive periodontal therapy. Under local anaesthesia and antibiotic coverage, the acellular dermal matrix allograft was applied in the anterior region of the upper jaw in order to increase the width of attached gingiva, thereby improving patient comfort. The healing was uneventful and a significant gain in attached gingiva dimensions was observed 9 months after the periodontal surgery. The procedure avoided a second surgical site, provided satisfactory results from an aesthetic point of view, and improved patient comfort. Acellular dermal matrix allograft may be regarded as an alternative in the treatment of EB cases to increase the width of attached gingiva and facilitate maintenance of the dentition.

Nano-titanium dioxide modulates the dermal sensitization potency of DNCB

PubMed Central

2012-01-01

We determined the ability of a model nanoparticle (NP) (titanium dioxide, TiO2) to modulate sensitization induced by a known potent dermal sensitizer (dinitrochlorobenzene) using a variant of the local lymph node assay called lymph node proliferation assay. BALB/c mice received sub-cutaneous injections of vehicle (2.5 mM sodium citrate), TiO2 NPs (0.004, 0.04 or 0.4 mg/ml) or pigment particles (0.04 mg/ml) both stabilized in sodium citrate buffer at the base of each ear (2x50μl), before receiving dermal applications (on both ears) of 2,4-Dinitrochlorobenzene (DNCB) (2x25μl of 0.1%) or its vehicle (acetone olive oil – AOO (4:1)) on days 0, 1 and 2. On day 5, the stimulation index (SI) was calculated as a ratio of 3HTdR incorporation in lymphocytes from DNBC-treated mice and AOO-treated controls. In a second experiment the EC3-value for DNCB (0 to 0.1%) was assessed in the absence or presence of 0.04 mg/ml TiO2. In a third experiment, the lymphocyte subpopulations and the cytokine secretion profile were analyzed after TiO2 (0.04 mg/ml) and DNCB (0.1%) treatment. Injection of NPs in AOO-treated control mice did not have any effect on lymph node (LN) proliferation. DNCB sensitization resulted in LN proliferation, which was further increased by injection of TiO2 NPs before DNCB sensitization. The EC3 of DNCB, with prior injection of vehicle control was 0.041%, while injection with TiO2 decreased the EC3 of DNCB to 0.015%. TiO2 NPs pre-treatment did not alter the lymphocyte subpopulations, but significantly increased the level of IL-4 and decreased IL-10 production in DNCB treated animals. In conclusion, our study demonstrates that administration of nano-TiO2 increases the dermal sensitization potency of DNCB, by augmenting a Th2 response, showing the immunomodulatory abilities of NPs. PMID:22621278

Histological changes to the skin of Merino sheep following deep dermal and subcutaneous injections of sodium lauryl sulfate.

PubMed

Lee, E J; Rothwell, J T

2010-04-01

To characterise the changes caused to sheep skin by deep dermal and subcutaneous injections of sodium lauryl sulfate (SLS) and describe the subsequent healing process. On 6 sheep 20 small areas of skin were each given deep dermal and subcutaneous injections of 0.2 mL of 7% SLS. Biopsies were collected at intervals up to 28 days after treatment and the histological changes in each of the treated skin samples were assessed and graded. There was no evidence of alterations in behaviour, weight gain or appetite of the sheep following the injections. Initial swelling of the treated site subsided by day 14, leaving a firm, slightly raised crust. At day 21, the treated area was depressed and covered by a scab, which sloughed completely by day 28. There was necrosis of the subcutis and deep dermis 2 min after treatment, followed by inflammation, fibroplasia, angiogenesis and tissue remodelling. Injection of SLS caused almost immediate local necrosis followed by eschar formation, sloughing and scarring of treated skin. Deep dermal and subcutaneous SLS is potentially useful as a chemical alternative to mulesing.

Safety of Pochonia chlamydosporia var catenulata in acute oral and dermal toxicity/pathogenicity evaluations in rats and rabbits.

PubMed

García, Liseth; Bulnes, Carlos; Melchor, Gleiby; Vega, Ernesto; Ileana, Miranda; de Oca, Nivian Montes; Hidalgo, Leopoldo; Marrero, Eva

2004-10-01

The nematophagous fungus, Pochonia chlamydosporia var. catenulata (Kamyschlco ex Barron & Onions) Zare & W-Gams, was investigated as a potential biocontrol agent in integrated pest management strategy for Meloidogyne incognita (Kofoid and White) Chitwood in vegetable crops in Cuba. An acute oral and dermal toxicity/patogenicity study was performed to determine the safety of this fungus in non-target organisms. In the first study, a 1-dose level of 5 x 10(8) units of the microbial pest control agent/treated rat was used. Mortality or clinical signs were not evident and no adverse effects on body weight, hematology, microbiology and gross or microscopic pathology were observed. Food and water consumption was not significantly different between control and treated groups. In the acute dermal toxicity study, there was neither mortality nor clinical signs of toxicity, and no toxic effects in gross and microscopic pathology were detected. Thus, Pochonia chlamydosporia var. catenulate (Vcc-108, IMI SD 187), administered oral and dermally to rats and rabbits respectively, was safe in toxicity/pathogenicity studies.

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.

PBTK Modeling Demonstrates Contribution of Dermal and Inhalation Exposure Components to End-Exhaled Breath Concentrations of Naphthalene

PubMed Central

Kim, David; Andersen, Melvin E.; Chao, Yi-Chun E.; Egeghy, Peter P.; Rappaport, Stephen M.; Nylander-French, Leena A.

2007-01-01

Background Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Objective Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. Methods The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. Results The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 × 10−5 cm/hr, b) permeability coefficient for the viable epidermis 3.0 × 10−3 cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers’ exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). Conclusions PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures. PMID:17589597

PBTK modeling demonstrates contribution of dermal and inhalation exposure components to end-exhaled breath concentrations of naphthalene.

PubMed

Kim, David; Andersen, Melvin E; Chao, Yi-Chun E; Egeghy, Peter P; Rappaport, Stephen M; Nylander-French, Leena A

2007-06-01

Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 x 10(-5) cm/hr, b) permeability coefficient for the viable epidermis 3.0 x 10(-3) cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers' exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures.

[Autogenous platelet-rich plasma gel with acellular xenogeneic dermal matrix for treatment of deep II degree burns].

PubMed

Hao, Tianzhi; Zhu, Jingmin; Hu, Wenbo; Zhang, Hua; Gao, Zhenhui; Wen, Xuehui; Zhou, Zhi; Lu, Gang; Liu, Jingjie; Li, Wen

2010-06-01

To investigate the effectiveness of autogenous platelet-rich plasma (PRP) gel with acellular xenogeneic dermal matrix in the treatment of deep II degree burns. From January 2007 to December 2009, 30 cases of deep II degree burns were treated. There were 19 males and 11 females with an average age of 42.5 years (range, 32-57 years). The burn area was 10% to 48% of total body surface area. The time from burn to hospitalization was 30 minutes to 8 hours. All patients were treated with tangential excision surgery, one side of the wounds were covered with autogenous PRP gel and acellular xenogeneic dermal matrix (PRP group), the other side of the wounds were covered with acellular xenogeneic dermal matrix only (control group). The healing rate, healing time, infection condition, and scar formation were observed. At 7 days after operation, the infection rate in PRP group (6.7%, 2/30) was significantly lower than that in control group (16.7%, 5/30, P < 0.05). The healing times were (18 +/- 4) days and (22 +/- 4) days respectively in PRP group and control group, showing significant difference (P < 0.05). The healing rates at 14 days and 21 days were 75% +/- 7% and 88% +/- 5% in PRP group, were 62% +/- 15% and 73% +/- 7% in control group, showing significant difference (P < 0.05). RPR group was superior to control group in elasticity, color, appearance, softness, scar formation, and healing quality. Autogenous PRP gel with acellular xenogeneic dermal matrix can accelerate the wound healing of deep II degree burns as well as alleviate the scar proliferation.

Dermal Collagen and Lipid Deposition Correlate with Tissue Swelling and Hydraulic Conductivity in Murine Primary Lymphedema

PubMed Central

Rutkowski, Joseph M.; Markhus, Carl Erik; Gyenge, Christina C.; Alitalo, Kari; Wiig, Helge; Swartz, Melody A.

2010-01-01

Primary lymphedema is a congenital pathology of dysfunctional lymphatic drainage characterized by swelling of the limbs, thickening of the dermis, and fluid and lipid accumulation in the underlying tissue. Two mouse models of primary lymphedema, the Chy mouse and the K14-VEGFR-3-Ig mouse, both lack dermal lymphatic capillaries and exhibit a lymphedematous phenotype attributable to disrupted VEGFR-3 signaling. Here we show that the differences in edematous tissue composition between these two models correlated with drastic differences in hydraulic conductivity. The skin of Chy mice possessed significantly higher levels of collagen and fat, whereas K14-VEGFR-3-Ig mouse skin composition was relatively normal, as compared with their respective wild-type controls. Functionally, this resulted in a greatly increased dermal hydraulic conductivity in K14-VEGFR3-Ig, but not Chy, mice. Our data suggest that lymphedema associated with increased collagen and lipid accumulation counteracts an increased hydraulic conductivity associated with dermal swelling, which in turn further limits interstitial transport and swelling. Without lipid and collagen accumulation, hydraulic conductivity is increased and overall swelling is minimized. These opposing tissue responses to primary lymphedema imply that tissue remodeling—predominantly collagen and fat deposition—may dictate tissue swelling and govern interstitial transport in lymphedema. PMID:20110415

Dermal collagen and lipid deposition correlate with tissue swelling and hydraulic conductivity in murine primary lymphedema.

PubMed

Rutkowski, Joseph M; Markhus, Carl Erik; Gyenge, Christina C; Alitalo, Kari; Wiig, Helge; Swartz, Melody A

2010-03-01

Primary lymphedema is a congenital pathology of dysfunctional lymphatic drainage characterized by swelling of the limbs, thickening of the dermis, and fluid and lipid accumulation in the underlying tissue. Two mouse models of primary lymphedema, the Chy mouse and the K14-VEGFR-3-Ig mouse, both lack dermal lymphatic capillaries and exhibit a lymphedematous phenotype attributable to disrupted VEGFR-3 signaling. Here we show that the differences in edematous tissue composition between these two models correlated with drastic differences in hydraulic conductivity. The skin of Chy mice possessed significantly higher levels of collagen and fat, whereas K14-VEGFR-3-Ig mouse skin composition was relatively normal, as compared with their respective wild-type controls. Functionally, this resulted in a greatly increased dermal hydraulic conductivity in K14-VEGFR3-Ig, but not Chy, mice. Our data suggest that lymphedema associated with increased collagen and lipid accumulation counteracts an increased hydraulic conductivity associated with dermal swelling, which in turn further limits interstitial transport and swelling. Without lipid and collagen accumulation, hydraulic conductivity is increased and overall swelling is minimized. These opposing tissue responses to primary lymphedema imply that tissue remodeling--predominantly collagen and fat deposition--may dictate tissue swelling and govern interstitial transport in lymphedema.

Development of nanovesicular systems for dermal imiquimod delivery: physicochemical characterization and in vitro/in vivo evaluation.

PubMed

Ma, Man; Wang, Jinping; Guo, Fang; Lei, Mingzhu; Tan, Fengping; Li, Nan

2015-06-01

The aim of the current investigation was to develop and statistically evaluate nanovesicular systems for dermal imiquimod delivery. To this purpose, transethosomes were prepared with phospholipid, ethanol and different permeation enhancers. Conventional ethosomes, with soy phospholipid and ethanol, were used as control. The prepared vesicles were characterized for size, zeta potential, stability and entrapment efficiency. The optimal transethosomal formulation with mean particle size of 82.3 ± 9.5 nm showed the higher entrapment efficiency (68.69 ± 1.7%). In vitro studies, permeation results of accumulated drug and local accumulation efficiency were significantly higher for transethosomes (24.64 µg/cm(2) and 6.70, respectively) than control (14.45 µg/cm(2) and 3.93, respectively). Confocal laser scanning microscopy of rhodamine 6G-loaded transethosomes revealed an enhanced retention into the deeper skin layers as compared to conventional ethosomes. Besides, Fourier-transform infra-red spectroscopy studies were also performed to understand the mechanism of interaction between skin and carriers. What's more, results of in vivo studies indicated the transethosomes of imiquimod providing the most effectiveness for dermal delivery among all of the formulations. These results suggested that transethosomes would be a promising dermal carrier for imiquimod in actinic keratose treatment.

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.

Three types of dermal grafts in rats: the importance of mechanical property and structural design.

PubMed

You, Chuangang; Wang, Xingang; Zheng, Yurong; Han, Chunmao

2013-12-04

To determine how the mechanical property and micro structure affect tissue regeneration and angiogenesis, three types of scaffolds were studied. Acellular dermal matrices (ADM), produced from human skin by removing the epidermis and cells, has been widely used in wound healing because of its high mechanical strength. Collagen scaffolds (CS) incorporated with poly(glycolide-co-L-lactide) (PLGA) mesh forms a well-supported hybrid dermal equivalent poly(glycolide-co-L-lactide) mesh/collagen scaffolds (PMCS). We designed this scaffold to enhance the CS mechanical property. These three different dermal substitutes-ADM, CS and PMCSs are different in the tensile properties and microstructure. Several basic physical characteristics of dermal substitutes were investigated in vitro. To characterize the angiogenesis and tissue regeneration, the materials were embedded subcutaneously in Sprague-Dawley (SD) rats. At weeks 1, 2, 4 and 8 post-surgery, the tissue specimens were harvested for histology, immunohistochemistry and real-time quantitative PCR (RT-qPCR). In vitro studies demonstrated ADM had a higher Young's modulus (6.94 MPa) rather than CS (0.19 MPa) and PMCS (3.33 MPa) groups in the wet state. Compared with ADMs and CSs, PMCSs with three-dimensional porous structures resembling skin and moderate mechanical properties can promote tissue ingrowth more quickly after implantation. In addition, the vascularization of the PMCS group is more obvious than that of the other two groups. The incorporation of a PLGA knitted mesh in CSs can improve the mechanical properties with little influence on the three-dimensional porous microstructure. After implantation, PMCSs can resist the contraction and promote cell infiltration, neotissue formation and blood vessel ingrowth, especially from the mesh side. Although ADM has high mechanical strength, its vascularization is poor because the pore size is too small. In conclusion, the mechanical properties of scaffolds are important for

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

Standardized Scalp Massage Results in Increased Hair Thickness by Inducing Stretching Forces to Dermal Papilla Cells in the Subcutaneous Tissue

PubMed Central

Kobayashi, Kazuhiro; Hama, Takanori; Murakami, Kasumi; Ogawa, Rei

2016-01-01

Objective: In this study, we evaluated the effect of scalp massage on hair in Japanese males and the effect of stretching forces on human dermal papilla cells in vitro. Methods: Nine healthy men received 4 minutes of standardized scalp massage per day for 24 weeks using a scalp massage device. Total hair number, hair thickness, and hair growth rate were evaluated. The mechanical effect of scalp massage on subcutaneous tissue was analyzed using a finite element method. To evaluate the effect of mechanical forces, human dermal papilla cells were cultured using a 72-hour stretching cycle. Gene expression change was analyzed using DNA microarray analyses. In addition, expression of hair cycle-related genes including IL6, NOGGIN, BMP4, and SMAD4 were evaluated using real-time reverse transcription-polymerase chain reaction. Results: Standardized scalp massage resulted in increased hair thickness 24 weeks after initiation of massage (0.085 ± 0.003 mm vs 0.092 ± 0.001 mm). Finite element method showed that scalp massage caused z-direction displacement and von Mises stress on subcutaneous tissue. In vitro, DNA microarray showed gene expression change significantly compared with nonstretching human dermal papilla cells. A total of 2655 genes were upregulated and 2823 genes were downregulated. Real-time reverse transcription-polymerase chain reaction demonstrated increased expression of hair cycle–related genes such as NOGGIN, BMP4, SMAD4, and IL6ST and decrease in hair loss–related genes such as IL6. Conclusions: Stretching forces result in changes in gene expression in human dermal papilla cells. Standardized scalp massage is a way to transmit mechanical stress to human dermal papilla cells in subcutaneous tissue. Hair thickness was shown to increase with standardized scalp massage. PMID:26904154

Accelerated expansion of epidermal keratinocyte and improved dermal reconstruction achieved by engineered amniotic membrane.

PubMed

Huang, Guofeng; Ji, Shizhao; Luo, Pengfei; Liu, Houqi; Zhu, Shihui; Wang, Guangyi; Zhou, Panyu; Xiao, Shichu; Xia, Zhaofan

2013-01-01

In this study, we used human amniotic membrane (AM) to prepare a dermal scaffold with intact basement membrane (BM) and good biostability for quick expansion and transplantation of epidermal keratinocytes (EKs). Fresh AM was treated by repeated freeze-thaw cycles and DNase digestion. This new method was able to cleanse the cell components effectively and retain the BM structure with continuous distributions of laminin, collagen IV, VI, and VII. Subsequently, the acellular amniotic membrane (AAM) was cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) for 5 min, 30 min, and 6 h. With the time of cross-linking prolonging, the mechanical strength and biostability of AAM increased gradually, while its cytotoxicity to EKs also increased. The 5-min cross-linked AAM (5min-AAM) had no significant cytotoxicity with good histocompatibility. The relative cell viability of EKs seeded on the 5min-AAM surface was 367 ± 33% and 631 ± 43% at 7 and 14 days of culture, respectively, both higher than 294 ± 30% and 503 ± 41% of the conventional cell culture dish (CCD) group, and the proportion of P63-positive cells was significantly higher than that of the CCD group on day 7 (54.32 ± 4.27% vs. 33.32 ± 3.18%, p < 0.05). When the 5min-AAM loaded with EKs (EK-AAM) was grafted onto full-thickness skin defects in nude mice, the cells survived well and formed an epidermis similar to normal skin. The new epidermis was thicker, and reconstruction of the dermal structure was good with an intact BM. Four weeks after transplantation, the wound contraction rate in the EK-AAM group was 43.09 ± 7.05%, significantly lower than that in the EK sheet group (57.49 ± 5.93%) and control group (69.94 ± 9.47%) (p < 0.05). In conclusion, repeated freeze-thaw treatment with appropriate EDC cross-linking offers AAM an intact BM structure with good operability and biostability. It may prove to be an ideal dermal scaffold to promote expansion of EKs in vitro and be transplanted for

ESTIMATING CHILDREN'S DERMAL AND NON-DIETARY INGESTION EXPOSURE AND DOSE WITH EPA'S SHEDS MODEL

EPA Science Inventory

A physically-based stochastic model (SHEDS) has been developed to estimate pesticide exposure and dose to children via dermal residue contact and non-dietary ingestion. Time-location-activity data are sampled from national survey results to generate a population of simulated ch...

Computational prediction of dermal diffusivity for large number of chemicals – challenges and applications

EPA Science Inventory

The assessment of risk from dermal exposure for thousands of chemicals, such as consumer products, due to their potential to enter the environment as contaminants is a daunting task. A strategy has been developed to integrate high-throughput technologies with toxicity, known as ...

Gelatin/Carboxymethyl chitosan based scaffolds for dermal tissue engineering applications.

PubMed

Agarwal, Tarun; Narayan, Rajan; Maji, Somnath; Behera, Shubhanath; Kulanthaivel, Senthilguru; Maiti, Tapas Kumar; Banerjee, Indranil; Pal, Kunal; Giri, Supratim

2016-12-01

The present study delineates the preparation, characterization and application of gelatin-carboxymethyl chitosan scaffolds for dermal tissue engineering. The effect of carboxymethyl chitosan and gelatin ratio was evaluated for variations in their physico-chemical-biological characteristics and drug release kinetics. The scaffolds were prepared by freeze drying method and characterized by SEM and FTIR. The study revealed that the scaffolds were highly porous with pore size ranging between 90 and 170μm, had high water uptake (400-1100%) and water retention capacity (>300%). The collagenase mediated degradation of the scaffolds was dependent on the amount of gelatin present in the formulation. A slight yet significant variation in their biological characteristics was also observed. All the formulations supported adhesion, spreading, growth and proliferation of 3T3 mouse fibroblasts. The cells seeded on the scaffolds also demonstrated expression of collagen type I, HIF1α and VEGF, providing a clue regarding their growth and proliferation along with potential to support angiogenesis during wound healing. In addition, the scaffolds showed sustained ampicillin and bovine serum albumin release, confirming their suitability as a therapeutic delivery vehicle during wound healing. All together, the results suggest that gelatin-carboxymethyl chitosan based scaffolds could be a suitable matrix for dermal tissue engineering applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantitative risk assessment of the aggregate dermal exposure to the sensitizing fragrance geraniol in personal care products and household cleaning agents.

PubMed

Nijkamp, M M; Bokkers, B G H; Bakker, M I; Ezendam, J; Delmaar, J E

2015-10-01

A quantitative risk assessment was performed to establish if consumers are at risk for being dermally sensitized by the fragrance geraniol. Aggregate dermal exposure to geraniol was estimated using the Probabilistic Aggregate Consumer Exposure Model, containing data on the use of personal care products and household cleaning agents. Consumer exposure to geraniol via personal care products appeared to be higher than via household cleaning agents. The hands were the body parts receiving the highest exposure to geraniol. Dermal sensitization studies were assessed to derive the point of departure needed for the estimation of the Acceptable Exposure Level (AEL). Two concentrations were derived, one based on human studies and the other from dose-response analysis of the available murine local lymph node assay data. The aggregate dermal exposure assessment resulted in body part specific median exposures up to 0.041 μg/cm(2) (highest exposure 102 μg/cm(2)) for hands. Comparing the exposure to the lowest AEL (55 μg/cm(2)), shows that a range of 0.02-0.86% of the population may have an aggregated exposure which exceeds the AEL. Furthermore, it is demonstrated that personal care products contribute more to the consumer's geraniol exposure compared to household cleaning agents. Copyright © 2015 Elsevier Inc. All rights reserved.

Appraisal of the sensitising potential of orally and dermally administered mercaptobenzothiazole by a biphasic protocol of the local lymph node assay.

PubMed

Ahuja, Varun; Wanner, Reinhard; Platzek, Thomas; Stahlmann, Ralf

2009-10-01

Mercaptobenzothiazole (MBT) is used while manufacturing natural rubber products. Our study deals with assessing its allergenic potential following dermal and oral routes of exposure, using a biphasic local lymph node assay (LLNA). Female Balb/c mice were treated with MBT (dermally 3, 10, 30% concentrations in DMSO; orally 1, 10, 100 mg/kg doses in corn oil) on the back (dermal study) or through oral administration (oral study) on days 1-3 followed by auricular application of 3, 10 and 30% concentrations, respectively, on days 15-17. End points determined on day 19 included ear thickness, ear punch weight, lymph node weight, lymph node cell count, and lymphocyte subpopulations (CD4+, CD8+, CD45+). After dermal application of 3% or 10% solution, a significant increase in cell count and lymph node weight along with significant decrease in CD8+ cells was observed. After initial oral administration of 1 mg/kg, we noticed a significant amplification in cell count. Following oral administration of 10 mg/kg, we observed a similar increase in cell count and lymph node weight. The results of our study show that the modified biphasic LLNA protocol can be used to study the sensitising potential of a compound also following the oral route of exposure.

Spontaneous dermal abscesses and ulcers as a result of Serratia marcescens.

PubMed

Friedman, N Deborah; Peterson, Neeraja B; Sumner, William T; Alexander, Barbara D

2003-08-01

Serratia sp have only rarely been reported as isolates from leg ulcers. We describe the case of a middle-aged man with a medical history significant for alcohol-induced cirrhosis who presented with rapidly progressive skin ulcers initially starting as purple nodules. These skin ulcers and underlying dermal abscesses were found to be a result of S marcescens, with the presumed portal of entry being a toe-web infection.

Treatment Failure and Miltefosine Susceptibility in Dermal Leishmaniasis Caused by Leishmania Subgenus Viannia Species

PubMed Central

Obonaga, Ricardo; Fernández, Olga Lucía; Valderrama, Liliana; Rubiano, Luisa Consuelo; Castro, Maria del Mar; Barrera, Maria Claudia; Gomez, Maria Adelaida

2014-01-01

Treatment failure and parasite drug susceptibility in dermal leishmaniasis caused by Leishmania (Viannia) species are poorly understood. Prospective evaluation of drug susceptibility of strains isolated from individual patients before drug exposure and at clinical failure allows intrinsic and acquired differences in susceptibility to be discerned and analyzed. To determine whether intrinsic susceptibility or loss of susceptibility to miltefosine contributed to treatment failure, we evaluated the miltefosine susceptibility of intracellular amastigotes and promastigotes of six Leishmania (Viannia) braziliensis and six Leishmania (Viannia) panamensis strains isolated sequentially, at diagnosis and treatment failure, from two children and four adults ≥55 years old with concurrent conditions. Four patients presented only cutaneous lesions, one had mucosal disease, and one had disseminated mucocutaneous disease. Expression of the Leishmania drug transporter genes abca2, abca3, abcc2, abcc3, abcg4, abcg6, and LbMT was evaluated by quantitative reverse transcription-PCR (qRT-PCR). Intracellular amastigotes (median 50% effective concentration [EC50], 10.7 μmol/liter) were more susceptible to miltefosine than promastigotes (median EC50, 55.3 μmol/liter) (P < 0.0001). Loss of susceptibility at failure, demonstrated by a miltefosine EC50 of >32 μmol/liter (the upper limit of intracellular amastigote assay), occurred in L. panamensis infection in a child and in L. braziliensis infection in an adult and was accompanied by decreased expression of the miltefosine transporter LbMT (LbMT/β-tubulin, 0.42- to 0.26-fold [P = 0.039] and 0.70- to 0.57-fold [P = 0.009], respectively). LbMT gene polymorphisms were not associated with susceptibility phenotype. Leishmania ABCA3 transporter expression was inversely correlated with miltefosine susceptibility (r = −0.605; P = 0.037). Loss of susceptibility is one of multiple factors involved in failure of miltefosine treatment in dermal

Feasibility and effectiveness of electrochemical dermal conductance measurement for the screening of diabetic neuropathy in primary care. DECODING Study (Dermal Electrochemical Conductance in Diabetic Neuropathy). Rationale and design.

PubMed

Cabré, Juan J; Mur, Teresa; Costa, Bernardo; Barrio, Francisco; López-Moya, Charo; Sagarra, Ramon; García-Barco, Montserrat; Vizcaíno, Jesús; Bonaventura, Immaculada; Ortiz, Nicolau; Flores-Mateo, Gemma

2018-05-01

Diabetes mellitus is the leading cause of polyneuropathy in the Western world. Diabetic neuropathy is a frequent complication of diabetes and may have great clinical transcendence due to pain and possible ulceration of the lower extremities. It is also a relevant cause of morbidity and mortality in patients with diabetes. Although the cause of polyneuropathy in patients with diabetes is only partially known, it has been associated with chronic hyperglycemia suggesting the possible etiopathogenic implication of advanced glycosylation end products. The strategy of choice in the medical management of diabetic neuropathy is early detection since glycaemic control and the use of certain drugs may prevent or slow the development of this disease. Diabetic neuropathy most often presents with a dysfunction of unmyelinated C-fibers, manifested as an alteration of the sweat reflex of the eccrine glands. This dysfunction can now be demonstrated using a newly developed technology which measures dermal electrochemical conductivity. This noninvasive test is easy and cost-effective. The aim of the present study is to evaluate the feasibility and effectiveness of dermal electrochemical conductance measurement (quantitative expression of the sudomotor reflex) as a screening test for the diagnosis of diabetic neuropathy in patients in primary care.

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.

A COMPARISON OF CYTOKINE MESSAGE AND PROTEIN PROFILES OBTAINED FOLLOWING DERMAL EXPOSURE TO DIISOCYANATES.

EPA Science Inventory

Exposure to certain low molecular weight chemicals is associated with asthma. A simple method to identify this hazard is needed. Increased expression of Th2 cytokine mRNA in draining lymph nodes following dermal exposure and increased production of Th2 cytokines by cultured cell...

Tumors Alter Inflammation and Impair Dermal Wound Healing in Female Mice

PubMed Central

Pyter, Leah M.; Husain, Yasmin; Calero, Humberto; McKim, Daniel B.; Lin, Hsin-Yun; Godbout, Jonathan P.; Sheridan, John F.; Engeland, Christopher G.; Marucha, Phillip T.

2016-01-01

Tissue repair is an integral component of cancer treatment (e.g., due to surgery, chemotherapy, radiation). Previous work has emphasized the immunosuppressive effects of tumors on adaptive immunity and has shown that surgery incites cancer metastases. However, the extent to which and how tumors may alter the clinically-relevant innate immune process of wound healing remains an untapped potential area of improvement for treatment, quality of life, and ultimately, mortality of cancer patients. In this study, 3.5 mm full-thickness dermal excisional wounds were placed on the dorsum of immunocompetent female mice with and without non-malignant flank AT-84 murine oral squamous cell carcinomas. Wound closure rate, inflammatory cell number and inflammatory signaling in wounds, and circulating myeloid cell concentrations were compared between tumor-bearing and tumor-free mice. Tumors delayed wound closure, suppressed inflammatory signaling, and altered myeloid cell trafficking in wounds. An in vitro scratch “wounding” assay of adult dermal fibroblasts treated with tumor cell-conditioned media supported the in vivo findings. This study demonstrates that tumors are sufficient to disrupt fundamental and clinically-relevant innate immune functions. The understanding of these underlying mechanisms provides potential for therapeutic interventions capable of improving the treatment of cancer while reducing morbidities and mortality. PMID:27548621

PKCε Increases Extracellular Elastin and Fibulin-5/DANCE in Dermal Fibroblasts.

PubMed

Nishizaki, Tomoyuki

2018-01-01

In the earlier study, the selective PKCε activator DCP-LA increased elastic fibres in the dermis of HR-1 hairless mice. As a process of elastic fibre formation, tropoelastin, an elastin monomer, is secreted into the extracellular space. Secreted tropoelastin is delivered to the microfibrils by fibulin-5/developmental arteries and neural crest epidermal growth factor-like (DANCE) and undergoes self-association. Then, tropoelastin assembles around the microfibrils, growing into elastin and elastic fibres by lysyl oxidase (LOX)- or LOX-like (LOXL)-mediated cross-linking. The present study was conducted to understand the mechanism underlying DCP-LA-induced increase in elastin/elastic fibre. Western blotting, immunocytochemistory, and real-time reverse transcription-polymerase chain reaction (RT-PCR) were carried out in cultured human dermal fibroblasts. PKCε, mammalian target of rapamycin complex (mTOR), and p70 S6 kinase (S6K) were knocked-down by transfecting each siRNA. DCP-LA increased elastin and fibulin-5/DANCE in a treatment time (6-24 h)- and a bell-shaped concentration (1 nM-1 µM)-dependent manner in the culture medium of human dermal fibroblasts. DCP-LA markedly increased elastic fibres in the extracellular space of cultured fibroblasts. DCP-LA-induced increase in extracellular elastin and fibulin-5/DANCE was abolished by a PKC inhibitor or knocking-down PKCε. DCP-LA did not affect expression of mRNAs for tropoelastin and fiblin-5/DANCE in cultured fibroblasts. DCP-LA-induced increase in extracellular elastin and fibulin-5/DANCE was not inhibited by the protein synthesis inhibitor cycloheximide or by knocking-down mTOR and S6K. DCP-LA never increased extracellular elastin in the presence of elastase, that breaks down elastin. An inhibitor of matrix metalloproteinase 9, that degrades multiple extracellular matrix components including elastin, had no effect on the basal levels and the DCP-LA-induced increase levels of extracellular elastin. The results of

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

USE OF THE MACROACTIVITY APPROACH TO ASSESS CHILDREN'S DERMAL EXPOSURE TO PESTICIDES IN RESIDENTIAL ENVIRONMENTS

EPA Science Inventory

In the macroactivity approach, dermal exposure is estimated using empirically-derived transfer coefficients (TC) to aggregate the mass transfer associated with a series of contacts with a contaminated medium. The macroactivity approach affords the possibility of developing scr...

Nociceptive Sensory Fibers Drive Interleukin-23 Production from CD301b+ Dermal Dendritic Cells and Drive Protective Cutaneous Immunity.

PubMed

Kashem, Sakeen W; Riedl, Maureen S; Yao, Chen; Honda, Christopher N; Vulchanova, Lucy; Kaplan, Daniel H

2015-09-15

Innate resistance to Candida albicans in mucosal tissues requires the production of interleukin-17A (IL-17A) by tissue-resident cells early during infection, but the mechanism of cytokine production has not been precisely defined. In the skin, we found that dermal γδ T cells were the dominant source of IL-17A during C. albicans infection and were required for pathogen resistance. Induction of IL-17A from dermal γδ T cells and resistance to C. albicans required IL-23 production from CD301b(+) dermal dendritic cells (dDCs). In addition, we found that sensory neurons were directly activated by C. albicans. Ablation of sensory neurons increased susceptibility to C. albicans infection, which could be rescued by exogenous addition of the neuropeptide CGRP. These data define a model in which nociceptive pathways in the skin drive production of IL-23 by CD301b(+) dDCs resulting in IL-17A production from γδ T cells and resistance to cutaneous candidiasis. Copyright © 2015 Elsevier Inc. All rights reserved.

Oral mucosa: an alternative epidermic cell source to develop autologous dermal-epidermal substitutes from diabetic subjects.

PubMed

Guzmán-Uribe, Daniela; Alvarado-Estrada, Keila Neri; Pierdant-Pérez, Mauricio; Torres-Álvarez, Bertha; Sánchez-Aguilar, Jesus Martin; Rosales-Ibáñez, Raúl

2017-01-01

The aim of this study was to obtain autologous dermal-epidermal skin substitutes from oral mucosa from diabetic subjects as a first step towards a possible clinical application for cases of diabetic foot. Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group). Epidermal cells were isolated and cultured using autologous fibrin to develop dermal-epidermal in vitro substitutes by the air-liquid technique with autologous human serum as a supplement media. Substitutes were immunocharacterized with collagen IV and cytokeratin 5-14 as specific markers. A Student´s t- test was performed to assess the differences between both groups. It was possible to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects and develop autologous dermal-epidermal skin substitutes using autologous serum as a supplement. Differences in the expression of specific markers were observed and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and the collagen IV expression was higher in the diabetic substitutes when compared with the healthy group, showing a significant difference. Cells from oral mucosa could be an alternative and less invasive source for skin substitutes and wound healing. A difference in collagen production of diabetic cells suggests diabetic substitutes could improve diabetic wound healing. More research is needed to determine the crosstalk between components of these skin substitutes and damaged tissues.

Chronic dermal sinuses as a manifestation of histiocytosis X.

PubMed Central

Sacks, S H; Hall, I; Ragge, N; Pritchard, J

1986-01-01

Two young patients presented with generalised lymphadenopathy, otorrhoea, otitis, and rash. Over the next few years chronically discharging sinuses began to form over enlarged nodes and histological appearances were typical of histiocytosis X. In neither case were micro-organisms isolated from the lesions, and in both patients healing occurred with immunosuppressive agents. Chronic dermal sinus formation secondary to lymph node disease has never before been recorded as a manifestation of histiocytosis X. Histiocytosis X should therefore be considered in the differential diagnosis of "suppurative" lymphadenopathy so that appropriate treatment may be given without delay. Images Case 1 PMID:3084014

Dermal oncogenicity bioassays of monofunctional and multifunctional acrylates and acrylate-based oligomers.

PubMed

DePass, L R; Maronpot, R R; Weil, C S

1985-01-01

Several important components of photocurable coatings were studied for dermal tumorigenic activity by repeated application to the skin of mice. The substances tested were 2-ethylhexyl acrylate (EHA) and methylcarbamoyloxyethyl acrylate (MCEA) (monomers); neopentyl glycol diacrylate (NPGDA), esterdiol-204-diacrylate (EDDA), and pentaerythritol tri(tetra)acrylate (PETA) (cross-linkers); and three acrylated urethane oligomers. For each bioassay, 40 C3H/HeJ male mice were dosed 3 times weekly on the dorsal skin for their lifetime with the highest dose of the test agent that caused no local irritation or reduction in body weight gain. Two negative control groups received acetone (diluent) only. A positive control group received 0.2% methylcholanthrene (MC). NPGDA and EHA had significant tumorigenic activity with tumor yields of eight and six tumor-bearing mice (three and two malignancies), respectively. The MC group had 34 mice with carcinomas and 1 additional mouse with a papilloma. MCEA had no dermal tumorigenic activity but resulted in early mortality. No skin tumors in the treatment area were observed in the other groups. Additional studies will be necessary to elucidate possible relationships between structure and tumorigenic activity for the acrylates.

In Silico Estimation of Skin Concentration Following the Dermal Exposure to Chemicals.

PubMed

Hatanaka, Tomomi; Yoshida, Shun; Kadhum, Wesam R; Todo, Hiroaki; Sugibayashi, Kenji

2015-12-01

To develop an in silico method based on Fick's law of diffusion to estimate the skin concentration following dermal exposure to chemicals with a wide range of lipophilicity. Permeation experiments of various chemicals were performed through rat and porcine skin. Permeation parameters, namely, permeability coefficient and partition coefficient, were obtained by the fitting of data to two-layered and one-layered diffusion models for whole and stripped skin. The mean skin concentration of chemicals during steady-state permeation was calculated using the permeation parameters and compared with the observed values. All permeation profiles could be described by the diffusion models. The estimated skin concentrations of chemicals using permeation parameters were close to the observed levels and most data fell within the 95% confidence interval for complete prediction. The permeability coefficient and partition coefficient for stripped skin were almost constant, being independent of the permeant's lipophilicity. Skin concentration following dermal exposure to various chemicals can be accurately estimated based on Fick's law of diffusion. This method should become a useful tool to assess the efficacy of topically applied drugs and cosmetic ingredients, as well as the risk of chemicals likely to cause skin disorders and diseases.

Ingestion, inhalation, and dermal exposures to chloroform and trichloroethene from tap water.

PubMed Central

Weisel, C P; Jo, W K

1996-01-01

Individuals are exposed to volatile compounds present in tap water by ingestion, inhalation, and dermal absorption. Traditional risk assessments for water often only consider ingestion exposure to toxic chemicals, even though showering has been shown to increase the body burden of certain chemicals due to inhalation exposure and dermal absorption. We collected and analyzed time-series samples of expired alveolar breath to evaluate changes in concentrations of volatile organic compounds being expired, which reflects the rate of change in the bloodstream due to expiration, metabolism, and absorption into tissues. Analysis of chloroform and trichloethene in expired breath, compounds regulated in water, was also used to determine uptake from tap water by each route (inhalation, ingestion, or absorption). Each route of exposure contributed to the total exposure of these compounds from daily water use. Further, the ingestion dose was completely metabolized before entering the bloodstream, whereas the dose from the other routes was dispersed throughout the body. Thus, differences in potential biologically effective doses depend on route, target organ, and whether the contaminant or metabolite is the biologically active agent. Images Figure 1. A Figure 1. B Figure 1. C Figure 2. A Figure 2. B PMID:8834861

Acute dermal abscesses caused by Serratia marcescens.

PubMed

Soria, Xavier; Bielsa, Isabel; Ribera, Miquel; Herrero, María José; Domingo, Helena; Carrascosa, José Manuel; Ferrándiz, Carlos

2008-05-01

Primary acute cutaneous infections caused by Serratia marcescens are extremely unusual. Nevertheless, Serratia infections are especially frequent in chronic granulomatous disease, which is a primary immunodeficiency that affects phagocytic cells of the innate immune system. We report a young man without history of infections, who developed multiple dermal abscesses on a leg with chronic lymphoedema attributed to S marcescens. Laboratory investigations showed a delayed partial neutrophilic oxidative function. It is remarkable that the patient did not have any other infections during childhood, when most of the innate immune deficiencies are diagnosed, and he had no history of granulomatous lesions. We hypothesize that the delayed neutrophilic oxidative function could be explained by a partial neutrophilic oxidative function, which could be enough to maintain the patient asymptomatic until this infection.

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

A quantitative model for dermal infection and oedema in BALB/c mice pinna.

PubMed

Marino-Marmolejo, Erika Nahomy; Flores-Hernández, Flor Yohana; Flores-Valdez, Mario Alberto; García-Morales, Luis Felipe; González-Villegas, Ana Cecilia; Bravo-Madrigal, Jorge

2016-12-12

Pharmaceutical industry demands innovation for developing new molecules to improve effectiveness and safety of therapeutic medicines. Preclinical assays are the first tests performed to evaluate new therapeutic molecules using animal models. Currently, there are several models for evaluation of treatments, for dermal oedema or infection. However, the most common or usual way is to induce the inflammation with chemical substances instead of infectious agents. On the other hand, this kind of models require the implementation of histological techniques and the interpretation of pathologies to verify the effectiveness of the therapy under assessment. This work was focused on developing a quantitative model of infection and oedema in mouse pinna. The infection was achieved with a strain of Streptococcus pyogenes that was inoculated in an injury induced at the auricle of BALB/c mice, the induced oedema was recorded by measuring the ear thickness with a digital micrometer and histopathological analysis was performed to verify the damage. The presence of S. pyogenes at the infection site was determined every day by culture. Our results showed that S. pyogenes can infect the mouse pinna and that it can be recovered at least for up to 4 days from the infected site; we also found that S. pyogenes can induce a bigger oedema than the PBS-treated control for at least 7 days; our results were validated with an antibacterial and anti-inflammatory formulation made with ciprofloxacin and hydrocortisone. The model we developed led us to emulate a dermal infection and allowed us to objectively evaluate the increase or decrease of the oedema by measuring the thickness of the ear pinna, and to determine the presence of the pathogen in the infection site. We consider that the model could be useful for assessment of new anti-inflammatory or antibacterial therapies for dermal infections.

Atypical post kala azar dermal leishmaniasis with "muzzle area" swelling.

PubMed

Arora, Sandeep; Bal, Arvinder Singh; Baveja, Sukriti; Sood, Aradhana; Rathi, Khushi Ram; Patil, Pradeep

2015-01-01

A 50-year-old male presented with recurrent swelling of the muzzle area of the face with history of low-grade intermittent fever of 3 year duration managed variously with antibiotics, systemic steroids, and antituberculous therapy. Skin biopsy revealed a granulomatous infiltration negative for acid-fast bacilli and leishmania donovan bodies. Immunochromatography test for rK 39 antigen and polymerase chain reaction for leishmania was positive. He was diagnosed as a case of post kala azar dermal leishmaniasis, managed with injection sodium stibogluconate and followed-up thereafter.

Proteomic Characterization of Dermal Interstitial Fluid Extracted Using a Novel Microneedle-Assisted Technique.

PubMed

Tran, Bao Quoc; Miller, Philip R; Taylor, Robert M; Boyd, Gabrielle; Mach, Phillip M; Rosenzweig, C Nicole; Baca, Justin T; Polsky, Ronen; Glaros, Trevor

2018-01-05

As wearable fitness devices have gained commercial acceptance, interest in real-time monitoring of an individual's physiological status using noninvasive techniques has grown. Microneedles have been proposed as a minimally invasive technique for sampling the dermal interstitial fluid (ISF) for clinical monitoring and diagnosis, but little is known about its composition. In this study, a novel microneedle array was used to collect dermal ISF from three healthy human donors and compared with matching serum and plasma samples. Using a shotgun quantitative proteomic approach, 407 proteins were quantified with at least one unique peptide, and of those, 135 proteins were differently expressed at least 2-fold. Collectively, these proteins tended to originate from the cytoplasm, membrane bound vesicles, and extracellular vesicular exosomes. Proteomic analysis confirmed previously published work that indicates that ISF is highly similar to both plasma and serum. In this study, less than one percent of proteins were uniquely identified in ISF. Taken together, ISF could serve as a minimally invasive alternative for blood-derived fluids with potential for real-time monitoring applications.

The effects of topical oxygen therapy on equine distal limb dermal wound healing.

PubMed

Tracey, Alexandra K; Alcott, Cody J; Schleining, Jennifer A; Safayi, Sina; Zaback, Peter C; Hostetter, Jesse M; Reinertson, Eric L

2014-12-01

Topical oxygen therapy (TOT) has been used in human medicine to promote healing in chronic wounds. To test the efficacy and safety of TOT in horses, an experimental wound model was created by making 1 standardized dermal wound on each limb of 4 healthy horses (n = 16). Each wound was fitted with an oxygen delivery cannula and covered with a bandage. One limb of each front and hind pair was randomly assigned to the treatment group (fitted with an oxygen concentrator device), with the contralateral limb assigned to the control group (no device). Wound area, epithelial area, and contraction were measured every 3 to 4 d. Biopsy samples and culture swabs were taken on days 16 and 32 to evaluate angiogenesis, fibroplasia, epithelial hyperplasia, inflammation and bacterial growth. Mean healing time in treated wounds (45 d, range: 38 to 52 d) was not significantly different from that in the paired control wounds (50 d, range: 38 to 62 d). Topical oxygen therapy had little effect on dermal wound healing in this experimental wound model in healthy horses.

The use of acellular dermal matrix membrane for vertical soft tissue augmentation during submerged implant placement: a case series.

PubMed

Puisys, Algirdas; Vindasiute, Egle; Linkevciene, Laura; Linkevicius, Tomas

2015-04-01

To evaluate the efficiency of acellular dermal matrix membrane to augment vertical peri-implant soft tissue thickness during submerged implant placement. Forty acellular dermal matrix-derived allogenic membranes (AlloDerm, BioHorizons, Birmingham, AL, USA) and 42 laser-modified surface internal hex implants (BioHorizons Tapered Laser Lok, Birmingham, AL, USA) were placed in submerged approach in 40 patients (15 males and 25 females, mean age 42.5 ± 1.7) with a thin vertical soft tissue thickness of 2 mm or less. After 3 months, healing abutments were connected to implants, and the augmented soft tissue thickness was measured with periodontal probe. The gain in vertical soft tissue volume was calculated. Mann-Whitney U-test was applied and significance was set to 0.05. All 40 allografts healed successfully. Thin soft tissue before augmentation had an average thickness of 1.54 ± 0.51 mm SD (range, 0.5-2.0 mm, median 1.75 mm), and after soft tissue augmentation with acellular dermal matrix, thickness increased to 3.75 ± 0.54 mm SD (range, 3.0-5.0 mm, median 4.0 mm) at 3 months after placement. This difference between medians was found to be statistically significant (P < 0.001). Mean increase in soft tissue thickness was 2.21 ± 0.85 mm SD (range, 1.0-4.5 mm, median 2.0 mm). It can be concluded that acellular dermal matrix membrane can be successfully used for vertical soft tissue augmentation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Dermal carbonyl modification is related to the yellowish color change of photo-aged Japanese facial skin.

PubMed

Ogura, Yuki; Kuwahara, Tomohiro; Akiyama, Minoru; Tajima, Shingo; Hattori, Kazuhisa; Okamoto, Kouhei; Okawa, Shinpei; Yamada, Yukio; Tagami, Hachiro; Takahashi, Motoji; Hirao, Tetsuji

2011-10-01

The photo-aged facial skin is characterized by various unique features such as dark spots, wrinkles, and sagging. Elderly people, particularly Asians, tend to show a yellowish skin color change with photo-aging. However, there has been no analytical study conducted on this unique skin color change of the aged facial skin. The purpose of the present study is to examine whether the carbonyl modification in the dermal protein is involved in the yellowish color change that occurs in the photo-aged skin. Normal skin samples excised from the face, abdomen and buttock of variously aged Japanese were separated into the epidermal and the dermal portions. These skin samples were histologically examined for carbonyl modification. Moreover, an in vitro constructed dermis model composed of a contracted collagen gel was treated with acrolein or 4-hydroxynonenal. All these samples were also studied colorimetrically. The dermal samples obtained from the photo-aged facial skin exhibited an appearance of yellowish color, whereas neither the facial epidermis nor the dermis obtained from the abdomen or buttock showed such a yellowish discoloration. The upper layer of the dermis that revealed the yellowish color showed elastosis whose elastic fibers were found to colocalize with carbonyl protein as detected by a labeled hydrazide, as well as by an immunohistochemical examination using the antibody against acrolein adduct. Experimental induction of carbonyl modification in a dermis model in vitro by a long-term treatment with acrolein or 4-hydroxynonenal was found to show the appearance of the yellowish change which was also proven by an increase in b* value of colorimetry. It was more pronounced than that induced by glycation. Our present results strongly suggest that carbonyl modification of the dermal protein is involved in the production of the yellowish color change that is noted in the photo-aged facial skin. Copyright © 2011 Japanese Society for Investigative Dermatology

U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--STANDARD OPERATING PROCEDURE FOR COLLECTION OF DERMAL WIPE SAMPLES FOR PESTICIDES AND METALS ANALYSIS (UA-F-9.1)

EPA Science Inventory

The purpose of this SOP is to describe the procedures for collecting a dermal wipe sample from a participant's hands for the measurement of pesticide or metal residues on the skin. This procedure covers the preparation of the dermal wipe material and field activities. This prot...

Fingertip reconstruction with a palmar advancement flap and free dermal graft: a report of six cases.

PubMed

Arons, M S

1985-03-01

The palmar thumb advancement flap was first described by Moberg in 1964. It was further utilized for the thumb and defined by Posner and Smith in 1971. In 1980, Macht and Watson favorably reported their technique of palmar advancement that was applicable not only for the thumb, but also for all five digits with soft tissue tip losses. A further refinement of their technique is to augment the digital tip with an autogenous dermal graft. This dermal "padding" is placed directly over the bony tuft to act as a "shock absorber," add bulk and contour to the distal tip of the finger, increase soft tissue stability, eliminate direct percussive tenderness of the bone, and decrease disability for specific occupations such as those requiring typewriting. Six cases are reported.

Perlecan and vascular endothelial growth factor-encoding DNA-loaded chitosan scaffolds promote angiogenesis and wound healing.

PubMed

Lord, Megan S; Ellis, April L; Farrugia, Brooke L; Whitelock, John M; Grenett, Hernan; Li, Chuanyu; O'Grady, Robert L; DeCarlo, Arthur A

2017-03-28

The repair of dermal wounds, particularly in the diabetic population, poses a significant healthcare burden. The impaired wound healing of diabetic wounds is attributed to low levels of endogenous growth factors, including vascular endothelial growth factor (VEGF), that normally stimulate multiple phases of wound healing. In this study, chitosan scaffolds were prepared via freeze drying and loaded with plasmid DNA encoding perlecan domain I and VEGF189 and analyzed in vivo for their ability to promote dermal wound healing. The plasmid DNA encoding perlecan domain I and VEGF189 loaded scaffolds promoted dermal wound healing in normal and diabetic rats. This treatment resulted in an increase in the number of blood vessels and sub-epithelial connective tissue matrix components within the wound beds compared to wounds treated with chitosan scaffolds containing control DNA or wounded controls. These results suggest that chitosan scaffolds containing plasmid DNA encoding VEGF189 and perlecan domain I have the potential to induce angiogenesis and wound healing. Copyright © 2017 Elsevier B.V. All rights reserved.