Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

International Nuclear Information System (INIS)

Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2015-01-01

Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R 2 = 0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q 2 ext = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. - Highlights: • It was compiled the largest publicly-available skin permeability dataset. • Predictive QSAR models were developed for skin permeability. • No concordance between skin sensitization and

In vitro psoriasis models with focus on reconstructed skin models as promising tools in psoriasis research.

Science.gov (United States)

Desmet, Eline; Ramadhas, Anesh; Lambert, Jo; Van Gele, Mireille

2017-06-01

Psoriasis is a complex chronic immune-mediated inflammatory cutaneous disease associated with the development of inflammatory plaques on the skin. Studies proved that the disease results from a deregulated interplay between skin keratinocytes, immune cells and the environment leading to a persisting inflammatory process modulated by pro-inflammatory cytokines and activation of T cells. However, a major hindrance to study the pathogenesis of psoriasis more in depth and subsequent development of novel therapies is the lack of suitable pre-clinical models mimicking the complex phenotype of this skin disorder. Recent advances in and optimization of three-dimensional skin equivalent models have made them attractive and promising alternatives to the simplistic monolayer cultures, immunological different in vivo models and scarce ex vivo skin explants. Moreover, human skin equivalents are increasing in complexity level to match human biology as closely as possible. Here, we critically review the different types of three-dimensional skin models of psoriasis with relevance to their application potential and advantages over other models. This will guide researchers in choosing the most suitable psoriasis skin model for therapeutic drug testing (including gene therapy via siRNA molecules), or to examine biological features contributing to the pathology of psoriasis. However, the addition of T cells (as recently applied to a de-epidermized dermis-based psoriatic skin model) or other immune cells would make them even more attractive models and broaden their application potential. Eventually, the ultimate goal would be to substitute animal models by three-dimensional psoriatic skin models in the pre-clinical phases of anti-psoriasis candidate drugs. Impact statement The continuous development of novel in vitro models mimicking the psoriasis phenotype is important in the field of psoriasis research, as currently no model exists that completely matches the in vivo psoriasis

Alternatively activated macrophages (M2 macrophages) in the skin of patient with localized scleroderma.

Science.gov (United States)

Higashi-Kuwata, Nobuyo; Makino, Takamitsu; Inoue, Yuji; Takeya, Motohiro; Ihn, Hironobu

2009-08-01

Localized scleroderma is a connective tissue disorder that is limited to the skin and subcutaneous tissue. Macrophages have been reported to be particularly activated in patients with skin disease including systemic sclerosis and are potentially important sources for fibrosis-inducing cytokines, such as transforming growth factor beta. To clarify the features of immunohistochemical characterization of the immune cell infiltrates in localized scleroderma focusing on macrophages, skin biopsy specimens were analysed by immunohistochemistry. The number of cells stained with monoclonal antibodies, CD68, CD163 and CD204, was calculated. An evident macrophage infiltrate and increased number of alternatively activated macrophages (M2 macrophages) in their fibrotic areas were observed along with their severity of inflammation. This study revealed that alternatively activated macrophages (M2 macrophages) may be a potential source of fibrosis-inducing cytokines in localized scleroderma, and may play a crucial role in the pathogenesis of localized scleroderma.

Simulation-based cutaneous surgical-skill training on a chicken-skin bench model in a medical undergraduate program.

Science.gov (United States)

Denadai, Rafael; Saad-Hossne, Rogério; Martinhão Souto, Luís Ricardo

2013-05-01

Because of ethical and medico-legal aspects involved in the training of cutaneous surgical skills on living patients, human cadavers and living animals, it is necessary the search for alternative and effective forms of training simulation. To propose and describe an alternative methodology for teaching and learning the principles of cutaneous surgery in a medical undergraduate program by using a chicken-skin bench model. One instructor for every four students, teaching materials on cutaneous surgical skills, chicken trunks, wings, or thighs, a rigid platform support, needled threads, needle holders, surgical blades with scalpel handles, rat-tooth tweezers, scissors, and marking pens were necessary for training simulation. A proposal for simulation-based training on incision, suture, biopsy, and on reconstruction techniques using a chicken-skin bench model distributed in several sessions and with increasing levels of difficultywas structured. Both feedback and objective evaluations always directed to individual students were also outlined. The teaching of a methodology for the principles of cutaneous surgery using a chicken-skin bench model versatile, portable, easy to assemble, and inexpensive is an alternative and complementary option to the armamentarium of methods based on other bench models described.

Novel Inhibitory Effect of N-(2-Hydroxycyclohexylvaliolamine on Melanin Production in a Human Skin Model

Directory of Open Access Journals (Sweden)

Bum-Ho Bin

2014-07-01

Full Text Available Hyper-pigmentation causes skin darkness and medical disorders, such as post-inflammatory melanoderma and melasma. Therefore, the development of anti-melanogenic agents is important for treating these conditions and for cosmetic production. In our previous paper, we demonstrated that the anti-diabetic drug voglibose, a valiolamine derivative, is a potent anti-melanogenic agent. In addition, we proposed an alternative screening strategy to identify valiolamine derivatives with high skin permeability that act as anti-melanogenic agents when applied topically. In this study, we synthesized several valiolamine derivatives with enhanced lipophilicity and examined their inhibitory effects in a human skin model. N-(2-hydroxycyclohexylvaliolamine (HV possesses a stronger inhibitory effect on melanin production than voglibose in a human skin model, suggesting that HV is a more potent anti-melanogenic agent for the skin.

Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

Science.gov (United States)

Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2015-01-01

Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R2=0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q2ext = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. PMID:25560673

Multivariate Models for Prediction of Human Skin Sensitization Hazard.

Science.gov (United States)

One of the lnteragency Coordinating Committee on the Validation of Alternative Method's (ICCVAM) top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary to produce skin sensiti...

The use of henna as an alternative skin marker in breast disease

International Nuclear Information System (INIS)

Griffiths, Anna; Murphy, Fred

2012-01-01

The aim of this study was to identify an alternative temporary skin marker that could be used to mark the skin of the breast prior to surgery, providing the surgeon with longer lasting accurate guidance to the location of the patient's breast lesion. Materials and methods: The upper quadrant of the breast was marked on all participants (n = 20) with a code in both henna and the conventional skin marker and photographic images were taken every 3 days for 2 weeks to assess the degree of fade. In addition a questionnaire (n = 136) surveyed current clinical practice amongst other breast services in the region. Results: This study found that henna lasted on average 6 days longer on study participants than the original skin marker used. The skin marker lasted on average 3 days whereas henna lasted on average 9 days, in addition participants who showered and used body wash/soap found that the henna skin marker lasted longer on the skin than participants' who bathed and used exfoliate. The survey revealed comments on current products such as sterility, ease of use and quick to apply but interestingly only 9% considered their current marker to be clearly visible. Conclusion: Henna is an effective temporary skin marker that could be used to mark the breast of patients with breast disease pre-operatively. It is cost effective when purchased in bulk, is more easily applied over ultrasound gel and has the potential to reduce infection prior to surgery.

Simulation-based cutaneous surgical-skill training on a chicken-skin bench model in a medical undergraduate program

Directory of Open Access Journals (Sweden)

Rafael Denadai

2013-01-01

Full Text Available Background: Because of ethical and medico-legal aspects involved in the training of cutaneous surgical skills on living patients, human cadavers and living animals, it is necessary the search for alternative and effective forms of training simulation. Aims: To propose and describe an alternative methodology for teaching and learning the principles of cutaneous surgery in a medical undergraduate program by using a chicken-skin bench model. Materials and Methods: One instructor for every four students, teaching materials on cutaneous surgical skills, chicken trunks, wings, or thighs, a rigid platform support, needled threads, needle holders, surgical blades with scalpel handles, rat-tooth tweezers, scissors, and marking pens were necessary for training simulation. Results: A proposal for simulation-based training on incision, suture, biopsy, and on reconstruction techniques using a chicken-skin bench model distributed in several sessions and with increasing levels of difficultywas structured. Both feedback and objective evaluations always directed to individual students were also outlined. Conclusion: The teaching of a methodology for the principles of cutaneous surgery using a chicken-skin bench model versatile, portable, easy to assemble, and inexpensive is an alternative and complementary option to the armamentarium of methods based on other bench models described.

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

Science.gov (United States)

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

2016-01-01

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

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

Science.gov (United States)

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

2015-01-01

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

Multivariate Models for Prediction of Skin Sensitization Hazard in Humans

Science.gov (United States)

One of ICCVAM’s highest priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary for a substance to elicit a skin sensitization reaction suggests that no single alternative me...

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

Science.gov (United States)

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

2017-01-01

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

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

OpenAIRE

Schreiber, Sylvia

2010-01-01

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

Regression-based model of skin diffuse reflectance for skin color analysis

Science.gov (United States)

Tsumura, Norimichi; Kawazoe, Daisuke; Nakaguchi, Toshiya; Ojima, Nobutoshi; Miyake, Yoichi

2008-11-01

A simple regression-based model of skin diffuse reflectance is developed based on reflectance samples calculated by Monte Carlo simulation of light transport in a two-layered skin model. This reflectance model includes the values of spectral reflectance in the visible spectra for Japanese women. The modified Lambert Beer law holds in the proposed model with a modified mean free path length in non-linear density space. The averaged RMS and maximum errors of the proposed model were 1.1 and 3.1%, respectively, in the above range.

Development and Characterisation of a Human Chronic Skin Wound Cell Line-Towards an Alternative for Animal Experimentation.

Science.gov (United States)

Caley, Matthew; Wall, Ivan B; Peake, Matthew; Kipling, David; Giles, Peter; Thomas, David W; Stephens, Phil

2018-03-27

Background : Chronic skin wounds are a growing financial burden for healthcare providers, causing discomfort/immobility to patients. Whilst animal chronic wound models have been developed to allow for mechanistic studies and to develop/test potential therapies, such systems are not good representations of the human chronic wound state. As an alternative, human chronic wound fibroblasts (CWFs) have permitted an insight into the dysfunctional cellular mechanisms that are associated with these wounds. However, such cells strains have a limited replicative lifespan and therefore a limited reproducibility/usefulness. Objectives : To develop/characterise immortalised cell lines of CWF and patient-matched normal fibroblasts (NFs). Methods and Results : Immortalisation with human telomerase resulted in both CWF and NF proliferating well beyond their replicative senescence end-point (respective cell strains senesced as normal). Gene expression analysis demonstrated that, whilst proliferation-associated genes were up-regulated in the cell lines (as would be expected), the immortalisation process did not significantly affect the disease-specific genotype. Immortalised CWF (as compared to NF) also retained a distinct impairment in their wound repopulation potential (in line with CWF cell strains). Conclusions : These novel CWF cell lines are a credible animal alternative and could be a valuable research tool for understanding both the aetiology of chronic skin wounds and for therapeutic pre-screening.

Development and Characterisation of a Human Chronic Skin Wound Cell Line—Towards an Alternative for Animal Experimentation

Science.gov (United States)

Wall, Ivan B.; Peake, Matthew; Kipling, David; Giles, Peter; Thomas, David W.

2018-01-01

Background: Chronic skin wounds are a growing financial burden for healthcare providers, causing discomfort/immobility to patients. Whilst animal chronic wound models have been developed to allow for mechanistic studies and to develop/test potential therapies, such systems are not good representations of the human chronic wound state. As an alternative, human chronic wound fibroblasts (CWFs) have permitted an insight into the dysfunctional cellular mechanisms that are associated with these wounds. However, such cells strains have a limited replicative lifespan and therefore a limited reproducibility/usefulness. Objectives: To develop/characterise immortalised cell lines of CWF and patient-matched normal fibroblasts (NFs). Methods and Results: Immortalisation with human telomerase resulted in both CWF and NF proliferating well beyond their replicative senescence end-point (respective cell strains senesced as normal). Gene expression analysis demonstrated that, whilst proliferation-associated genes were up-regulated in the cell lines (as would be expected), the immortalisation process did not significantly affect the disease-specific genotype. Immortalised CWF (as compared to NF) also retained a distinct impairment in their wound repopulation potential (in line with CWF cell strains). Conclusions: These novel CWF cell lines are a credible animal alternative and could be a valuable research tool for understanding both the aetiology of chronic skin wounds and for therapeutic pre-screening. PMID:29584680

Elucidation of xenobiotic metabolism pathways in human skin and human skin models by proteomic profiling.

Directory of Open Access Journals (Sweden)

Sven van Eijl

Full Text Available BACKGROUND: Human skin has the capacity to metabolise foreign chemicals (xenobiotics, but knowledge of the various enzymes involved is incomplete. A broad-based unbiased proteomics approach was used to describe the profile of xenobiotic metabolising enzymes present in human skin and hence indicate principal routes of metabolism of xenobiotic compounds. Several in vitro models of human skin have been developed for the purpose of safety assessment of chemicals. The suitability of these epidermal models for studies involving biotransformation was assessed by comparing their profiles of xenobiotic metabolising enzymes with those of human skin. METHODOLOGY/PRINCIPAL FINDINGS: Label-free proteomic analysis of whole human skin (10 donors was applied and analysed using custom-built PROTSIFT software. The results showed the presence of enzymes with a capacity for the metabolism of alcohols through dehydrogenation, aldehydes through dehydrogenation and oxidation, amines through oxidation, carbonyls through reduction, epoxides and carboxylesters through hydrolysis and, of many compounds, by conjugation to glutathione. Whereas protein levels of these enzymes in skin were mostly just 4-10 fold lower than those in liver and sufficient to support metabolism, the levels of cytochrome P450 enzymes were at least 300-fold lower indicating they play no significant role. Four epidermal models of human skin had profiles very similar to one another and these overlapped substantially with that of whole skin. CONCLUSIONS/SIGNIFICANCE: The proteomics profiling approach was successful in producing a comprehensive analysis of the biotransformation characteristics of whole human skin and various in vitro skin models. The results show that skin contains a range of defined enzymes capable of metabolising different classes of chemicals. The degree of similarity of the profiles of the in vitro models indicates their suitability for epidermal toxicity testing. Overall, these

In vitro assessment of skin irritation potential of surfactant-based formulations by using a 3-D skin reconstructed tissue model and cytokine response.

Science.gov (United States)

Walters, Russel M; Gandolfi, Lisa; Mack, M Catherine; Fevola, Michael; Martin, Katharine; Hamilton, Mathew T; Hilberer, Allison; Barnes, Nicole; Wilt, Nathan; Nash, Jennifer R; Raabe, Hans A; Costin, Gertrude-Emilia

2016-12-01

The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing. 2016 FRAME.

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

Science.gov (United States)

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

2014-12-01

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

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

Science.gov (United States)

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

2015-09-01

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

Penetration of radionuclides across skin barriers of animal skin models in vitro

International Nuclear Information System (INIS)

Koprda, V.; Harangozo, M.; Bohacik, L.; Kassai, Z.

1998-01-01

In this paper: (i) the time dependence of permeation of 137 Cs + , 60 Co 2+ , and 147 Pm 3+ from aqueous solution through animal skin model has been studied, (ii) the biologic structure mostly responsible for the barrier effect was selected and proved, (iii) the relative importance of the main diffusion pathways for 137 Cs + , 60 Co 2+ and 147 Pm 3+ (the diffusion across the intact skin and the diffusion through the hair channels) was assessed. All experiments were done using radioactive tracers. Experimental arrangement consisted of Franz-type vertical permeation cells used with fresh skin from abdominal region of 5 day old rats (5DR) of Wistar strain (Breeding Farm Dobra Voda, SK) and 9 day old rats (9DR), respectively. 5DR are still hairless, and 9DR are just short haired. The 5DR skin was used in full form (intact), and then with decreasing thickness of horny layer after the skin had been stripped with Scotch type (3M) 5-20 times respectively, or the skin was splitted under 60 degC hot water so that the whole epidermis was removed. The penetrated amounts of ions were found to be proportional to the time at least in the first 7 hours. The permeation resistance of the skin is proportional to the thickness of the horny layer, the principal barrier mostly restricting the flux of ions. The more the skin is stripped, the more enhanced is the penetration of ions. This corroborates the fact that stratum corneum represents the most important barrier function of the whole skin (of rats). The additional diffusion through channels along hairs (follicules) can be of important value also in case of human skin where hair density is many times lower than in the case of the animal models used

Pred-Skin: A Fast and Reliable Web Application to Assess Skin Sensitization Effect of Chemicals.

Science.gov (United States)

Braga, Rodolpho C; Alves, Vinicius M; Muratov, Eugene N; Strickland, Judy; Kleinstreuer, Nicole; Trospsha, Alexander; Andrade, Carolina Horta

2017-05-22

Chemically induced skin sensitization is a complex immunological disease with a profound impact on quality of life and working ability. Despite some progress in developing alternative methods for assessing the skin sensitization potential of chemical substances, there is no in vitro test that correlates well with human data. Computational QSAR models provide a rapid screening approach and contribute valuable information for the assessment of chemical toxicity. We describe the development of a freely accessible web-based and mobile application for the identification of potential skin sensitizers. The application is based on previously developed binary QSAR models of skin sensitization potential from human (109 compounds) and murine local lymph node assay (LLNA, 515 compounds) data with good external correct classification rate (0.70-0.81 and 0.72-0.84, respectively). We also included a multiclass skin sensitization potency model based on LLNA data (accuracy ranging between 0.73 and 0.76). When a user evaluates a compound in the web app, the outputs are (i) binary predictions of human and murine skin sensitization potential; (ii) multiclass prediction of murine skin sensitization; and (iii) probability maps illustrating the predicted contribution of chemical fragments. The app is the first tool available that incorporates quantitative structure-activity relationship (QSAR) models based on human data as well as multiclass models for LLNA. The Pred-Skin web app version 1.0 is freely available for the web, iOS, and Android (in development) at the LabMol web portal ( http://labmol.com.br/predskin/ ), in the Apple Store, and on Google Play, respectively. We will continuously update the app as new skin sensitization data and respective models become available.

Vibroacoustic Skin Diagnostics Modeling

Directory of Open Access Journals (Sweden)

Svetlana М. Yatsun

2013-01-01

Full Text Available The article deals with the mathematical modeling of biological diagnosis of complex heterogeneous structure (skin, using non-destructive control method. The mathematical model, describing interaction of the material with electrodynamic vibration generator and sensor system, controlling the propagation of small disturbances was developed. The influence of material model parameters on the spectrum in the course of the propagation of the surface disturbance

Clinical application of a tissue-cultured skin autograft: an alternative for the treatment of non-healing or slowly healing wounds?

Science.gov (United States)

Zöller, Nadja; Valesky, Eva; Butting, Manuel; Hofmann, Matthias; Kippenberger, Stefan; Bereiter-Hahn, Jürgen; Bernd, August; Kaufmann, Roland

2014-01-01

The treatment regime of non-healing or slowly healing wounds is constantly improving. One aspect is surgical defect coverage whereby mesh grafts and keratinocyte suspension are applied. Tissue-cultured skin autografts may be an alternative for the treatment of full-thickness wounds and wounds that cover large areas of the body surface. Autologous epidermal and dermal cells were isolated, expanded in vitro and seeded on collagen-elastin scaffolds. The developed autograft was immunohistochemically characterized and subsequently transplanted onto a facial chronic ulceration of a 71-year-old patient with vulnerable atrophic skin. Characterization of the skin equivalent revealed comparability to healthy human skin due to the epidermal strata, differentiation and proliferation markers. Within 138 days, the skin structure at the transplantation site closely correlated with the adjacent undisturbed skin. The present study demonstrates the comparability of the developed organotypic skin equivalent to healthy human skin and the versatility for clinical applications.

Skin Diseases Modeling using Combined Tissue Engineering and Microfluidic Technologies.

Science.gov (United States)

Mohammadi, Mohammad Hossein; Heidary Araghi, Behnaz; Beydaghi, Vahid; Geraili, Armin; Moradi, Farshid; Jafari, Parya; Janmaleki, Mohsen; Valente, Karolina Papera; Akbari, Mohsen; Sanati-Nezhad, Amir

2016-10-01

In recent years, both tissue engineering and microfluidics have significantly contributed in engineering of in vitro skin substitutes to test the penetration of chemicals or to replace damaged skins. Organ-on-chip platforms have been recently inspired by the integration of microfluidics and biomaterials in order to develop physiologically relevant disease models. However, the application of organ-on-chip on the development of skin disease models is still limited and needs to be further developed. The impact of tissue engineering, biomaterials and microfluidic platforms on the development of skin grafts and biomimetic in vitro skin models is reviewed. The integration of tissue engineering and microfluidics for the development of biomimetic skin-on-chip platforms is further discussed, not only to improve the performance of present skin models, but also for the development of novel skin disease platforms for drug screening processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A molecular systems approach to modelling human skin pigmentation: identifying underlying pathways and critical components.

Science.gov (United States)

Raghunath, Arathi; Sambarey, Awanti; Sharma, Neha; Mahadevan, Usha; Chandra, Nagasuma

2015-04-29

Ultraviolet radiations (UV) serve as an environmental stress for human skin, and result in melanogenesis, with the pigment melanin having protective effects against UV induced damage. This involves a dynamic and complex regulation of various biological processes that results in the expression of melanin in the outer most layers of the epidermis, where it can exert its protective effect. A comprehensive understanding of the underlying cross talk among different signalling molecules and cell types is only possible through a systems perspective. Increasing incidences of both melanoma and non-melanoma skin cancers necessitate the need to better comprehend UV mediated effects on skin pigmentation at a systems level, so as to ultimately evolve knowledge-based strategies for efficient protection and prevention of skin diseases. A network model for UV-mediated skin pigmentation in the epidermis was constructed and subjected to shortest path analysis. Virtual knock-outs were carried out to identify essential signalling components. We describe a network model for UV-mediated skin pigmentation in the epidermis. The model consists of 265 components (nodes) and 429 directed interactions among them, capturing the manner in which one component influences the other and channels information. Through shortest path analysis, we identify novel signalling pathways relevant to pigmentation. Virtual knock-outs or perturbations of specific nodes in the network have led to the identification of alternate modes of signalling as well as enabled determining essential nodes in the process. The model presented provides a comprehensive picture of UV mediated signalling manifesting in human skin pigmentation. A systems perspective helps provide a holistic purview of interconnections and complexity in the processes leading to pigmentation. The model described here is extensive yet amenable to expansion as new data is gathered. Through this study, we provide a list of important proteins essential

Modelling the effect of hydration on skin conductivity.

Science.gov (United States)

Davies, L; Chappell, P; Melvin, T

2017-08-01

Electrical signals are recorded from and sent into the body via the skin in a number of applications. In practice, skin is often hydrated with liquids having different conductivities so a model was produced in order to determine the relationship between skin impedance and conductivity. A model representing the skin was subjected to a variety of electrical signals. The parts of the model representing the stratum corneum were given different conductivities to represent different levels of hydration. The overall impedance and conductivity of the cells did not vary at frequencies below 40 kHz. Above 40 kHz, levels of increased conductivity caused the overall impedance to decrease. The variation in impedance with conductivity between 5 and 50 mSm -1 can be modelled quadratically while variation in impedance with conductivity between 5 and 5000 mSm -1 can be modelled with a double exponential decay. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Structural characterization and viscoelastic constitutive modeling of skin.

Science.gov (United States)

Sherman, Vincent R; Tang, Yizhe; Zhao, Shiteng; Yang, Wen; Meyers, Marc A

2017-04-15

A fascinating material, skin has a tensile response which exhibits an extended toe region of minimal stress up to nominal strains that, in some species, exceed 1, followed by significant stiffening until a roughly linear region. The large toe region has been attributed to its unique structure, consisting of a network of curved collagen fibers. Investigation of the structure of rabbit skin reveals that it consists of layers of wavy fibers, each one with a characteristic orientation. Additionally, the existence of two preferred layer orientations is suggested based on the results of small angle X-ray scattering. These observations are used to construct a viscoelastic model consisting of collagen in two orientations, which leads to an in-plane anisotropic response. The structure-based model presented incorporates the elastic straightening and stretching of fibrils, their rotation towards the tensile axis, and the viscous effects which occur in the matrix of the skin due to interfibrillar and interlamellar sliding. The model is shown to effectively capture key features which dictate the mechanical response of skin. Examination by transmission and scanning electron microscopy of rabbit dermis enabled the identification of the key elements in its structure. The organization of collagen fibrils into flat fibers was identified and incorporated into a constitutive model that reproduces the mechanical response of skin. This enhanced quantitative predictive capability can be used in the design of synthetic skin and skin-like structures. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Model Predictions and Measured Skin Damage Thresholds for 1.54 Micrometers Laser Pulses in Porcine Skin

National Research Council Canada - National Science Library

Roach, William P; Cain, Clarence; Schuster, Kurt; Stockton, Kevin; Stolarski, David S; Galloway, Robert; Rockwell, Benjamin

2004-01-01

A new source-term thermal model was used to determine the skin temperature rise using porcine skin parameters for various wavelengths, pulse durations, and laser spot sizes and is compared to the Takata thermal model...

Modeling skin blood flow: a neuro-physiological approach

NARCIS (Netherlands)

Kingma, B.R.M.; Saris, W.H.M.; Frijns, A.J.H.; Steenhoven, van A.A.; Marken Lichtenbelt, van W.D.

2010-01-01

In humans skin blood flow (SBF) plays a major role in body heat loss. Therefore the accuracy of models ofhuman thermoregulation depends for a great deal on their ability to predict skin blood flow. Most SBFmodelsuse body temperatures directly for calculation of skin perfusion. However, humans do not

CADRE-SS, an in Silico Tool for Predicting Skin Sensitization Potential Based on Modeling of Molecular Interactions.

Science.gov (United States)

Kostal, Jakub; Voutchkova-Kostal, Adelina

2016-01-19

Using computer models to accurately predict toxicity outcomes is considered to be a major challenge. However, state-of-the-art computational chemistry techniques can now be incorporated in predictive models, supported by advances in mechanistic toxicology and the exponential growth of computing resources witnessed over the past decade. The CADRE (Computer-Aided Discovery and REdesign) platform relies on quantum-mechanical modeling of molecular interactions that represent key biochemical triggers in toxicity pathways. Here, we present an external validation exercise for CADRE-SS, a variant developed to predict the skin sensitization potential of commercial chemicals. CADRE-SS is a hybrid model that evaluates skin permeability using Monte Carlo simulations, assigns reactive centers in a molecule and possible biotransformations via expert rules, and determines reactivity with skin proteins via quantum-mechanical modeling. The results were promising with an overall very good concordance of 93% between experimental and predicted values. Comparison to performance metrics yielded by other tools available for this endpoint suggests that CADRE-SS offers distinct advantages for first-round screenings of chemicals and could be used as an in silico alternative to animal tests where permissible by legislative programs.

Growing skin: A computational model for skin expansion in reconstructive surgery

Science.gov (United States)

Buganza Tepole, Adrián; Joseph Ploch, Christopher; Wong, Jonathan; Gosain, Arun K.; Kuhl, Ellen

2011-10-01

The goal of this manuscript is to establish a novel computational model for stretch-induced skin growth during tissue expansion. Tissue expansion is a common surgical procedure to grow extra skin for reconstructing birth defects, burn injuries, or cancerous breasts. To model skin growth within the framework of nonlinear continuum mechanics, we adopt the multiplicative decomposition of the deformation gradient into an elastic and a growth part. Within this concept, we characterize growth as an irreversible, stretch-driven, transversely isotropic process parameterized in terms of a single scalar-valued growth multiplier, the in-plane area growth. To discretize its evolution in time, we apply an unconditionally stable, implicit Euler backward scheme. To discretize it in space, we utilize the finite element method. For maximum algorithmic efficiency and optimal convergence, we suggest an inner Newton iteration to locally update the growth multiplier at each integration point. This iteration is embedded within an outer Newton iteration to globally update the deformation at each finite element node. To demonstrate the characteristic features of skin growth, we simulate the process of gradual tissue expander inflation. To visualize growth-induced residual stresses, we simulate a subsequent tissue expander deflation. In particular, we compare the spatio-temporal evolution of area growth, elastic strains, and residual stresses for four commonly available tissue expander geometries. We believe that predictive computational modeling can open new avenues in reconstructive surgery to rationalize and standardize clinical process parameters such as expander geometry, expander size, expander placement, and inflation timing.

Dynamic skin deformation simulation using musculoskeletal model and soft tissue dynamics

Institute of Scientific and Technical Information of China (English)

Akihiko Murai; Q. Youn Hong; Katsu Yamane; Jessica K. Hodgins

2017-01-01

Deformation of skin and muscle is essential for bringing an animated character to life. This deformation is difficult to animate in a realistic fashion using traditional techniques because of the subtlety of the skin deformations that must move appropriately for the character design. In this paper, we present an algorithm that generates natural, dynamic, and detailed skin deformation (movement and jiggle) from joint angle data sequences. The algorithm has two steps: identification of parameters for a quasi-static muscle deformation model, and simulation of skin deformation. In the identification step, we identify the model parameters using a musculoskeletal model and a short sequence of skin deformation data captured via a dense marker set. The simulation step first uses the quasi-static muscle deformation model to obtain the quasi-static muscle shape at each frame of the given motion sequence (slow jump). Dynamic skin deformation is then computed by simulating the passive muscle and soft tissue dynamics modeled as a mass–spring–damper system. Having obtained the model parameters, we can simulate dynamic skin deformations for subjects with similar body types from new motion data. We demonstrate our method by creating skin deformations for muscle co-contraction and external impacts from four different behaviors captured as skeletal motion capture data. Experimental results show that the simulated skin deformations are quantitatively and qualitatively similar to measured actual skin deformations.

Dynamic skin deformation simulation using musculoskeletal model and soft tissue dynamics

Institute of Scientific and Technical Information of China (English)

Akihiko Murai; Q.Youn Hong; Katsu Yamane; Jessica K.Hodgins

2017-01-01

Deformation of skin and muscle is essential for bringing an animated character to life. This deformation is difficult to animate in a realistic fashion using traditional techniques because of the subtlety of the skin deformations that must move appropriately for the character design. In this paper, we present an algorithm that generates natural, dynamic, and detailed skin deformation(movement and jiggle) from joint angle data sequences. The algorithm has two steps: identification of parameters for a quasi-static muscle deformation model, and simulation of skin deformation. In the identification step, we identify the model parameters using a musculoskeletal model and a short sequence of skin deformation data captured via a dense marker set. The simulation step first uses the quasi-static muscle deformation model to obtain the quasi-static muscle shape at each frame of the given motion sequence(slow jump). Dynamic skin deformation is then computed by simulating the passive muscle and soft tissue dynamics modeled as a mass–spring–damper system. Having obtained the model parameters, we can simulate dynamic skin deformations for subjects with similar body types from new motion data. We demonstrate our method by creating skin deformations for muscle co-contraction and external impacts from four different behaviors captured as skeletal motion capture data. Experimental results show that the simulated skin deformations are quantitatively and qualitatively similar to measured actual skin deformations.

Mathematical Model to Predict Skin Concentration after Topical Application of Drugs

Directory of Open Access Journals (Sweden)

Hiroaki Todo

2013-12-01

Full Text Available Skin permeation experiments have been broadly done since 1970s to 1980s as an evaluation method for transdermal drug delivery systems. In topically applied drug and cosmetic formulations, skin concentration of chemical compounds is more important than their skin permeations, because primary target site of the chemical compounds is skin surface or skin tissues. Furthermore, the direct pharmacological reaction of a metabolically stable drug that binds with specific receptors of known expression levels in an organ can be determined by Hill’s equation. Nevertheless, little investigation was carried out on the test method of skin concentration after topically application of chemical compounds. Recently we investigated an estimating method of skin concentration of the chemical compounds from their skin permeation profiles. In the study, we took care of “3Rs” issues for animal experiments. We have proposed an equation which was capable to estimate animal skin concentration from permeation profile through the artificial membrane (silicone membrane and animal skin. This new approach may allow the skin concentration of a drug to be predicted using Fick’s second law of diffusion. The silicone membrane was found to be useful as an alternative membrane to animal skin for predicting skin concentration of chemical compounds, because an extremely excellent extrapolation to animal skin concentration was attained by calculation using the silicone membrane permeation data. In this chapter, we aimed to establish an accurate and convenient method for predicting the concentration profiles of drugs in the skin based on the skin permeation parameters of topically active drugs derived from steady-state skin permeation experiments.

Studies of biaxial mechanical properties and nonlinear finite element modeling of skin.

Science.gov (United States)

Shang, Xituan; Yen, Michael R T; Gaber, M Waleed

2010-06-01

The objective of this research is to conduct mechanical property studies of skin from two individual but potentially connected aspects. One is to determine the mechanical properties of the skin experimentally by biaxial tests, and the other is to use the finite element method to model the skin properties. Dynamic biaxial tests were performed on 16 pieces of abdominal skin specimen from rats. Typical biaxial stress-strain responses show that skin possesses anisotropy, nonlinearity and hysteresis. To describe the stress-strain relationship in forms of strain energy function, the material constants of each specimen were obtained and the results show a high correlation between theory and experiments. Based on the experimental results, a finite element model of skin was built to model the skin's special properties including anisotropy and nonlinearity. This model was based on Arruda and Boyce's eight-chain model and Bischoff et al.'s finite element model of skin. The simulation results show that the isotropic, nonlinear eight-chain model could predict the skin's anisotropic and nonlinear responses to biaxial loading by the presence of an anisotropic prestress state.

Skin sensitization: Modeling based on skin metabolism simulation and formation of protein conjugates

DEFF Research Database (Denmark)

Dimitrov, Sabcho; Low, Lawrence; Patlewicz, Grace

2005-01-01

alerting groups, three-dimensional (3D)-QSARs were developed to describe the multiplicity of physicochemical, steric, and electronic parameters. These 3D-QSARs, so-called pattern recognition-type models, were applied each time a latent alerting group was identified in a parent chemical or its generated...... in the model building. The TIssue MEtabolism Simulator (TIMES) software was used to integrate a skin metabolism simulator and 3D-QSARs to evaluate the reactivity of chemicals thus predicting their likely skin sensitization potency....

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

Science.gov (United States)

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

2017-01-01

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

Real-time Face Detection using Skin Color Model

Institute of Scientific and Technical Information of China (English)

LU Yao-xin; LIU Zhi-Qiang; ZHU Xiang-hua

2004-01-01

This paper presents a new face detection approach to real-time applications, which is based on the skin color model and the morphological filtering. First the non-skin color pixels of the input image are removed based on the skin color model in the YCrCb chrominance space, from which we extract candidate human face regions. Then a mathematical morphological filter is used to remove noisy regions and fill the holes in the candidate skin color regions. We adopt the similarity between the human face features and the candidate face regions to locate the face regions in the original image. We have implemented the algorithm in our smart media system. The experiment results show that this system is effective in real-time applications.

Skin mechanical properties and modeling: A review.

Science.gov (United States)

Joodaki, Hamed; Panzer, Matthew B

2018-04-01

The mechanical properties of the skin are important for various applications. Numerous tests have been conducted to characterize the mechanical behavior of this tissue, and this article presents a review on different experimental methods used. A discussion on the general mechanical behavior of the skin, including nonlinearity, viscoelasticity, anisotropy, loading history dependency, failure properties, and aging effects, is presented. Finally, commonly used constitutive models for simulating the mechanical response of skin are discussed in the context of representing the empirically observed behavior.

Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

Energy Technology Data Exchange (ETDEWEB)

Alves, Vinicius M. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Muratov, Eugene [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Laboratory of Theoretical Chemistry, A.V. Bogatsky Physical-Chemical Institute NAS of Ukraine, Odessa 65080 (Ukraine); Fourches, Denis [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Strickland, Judy; Kleinstreuer, Nicole [ILS/Contractor Supporting the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Andrade, Carolina H. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Tropsha, Alexander, E-mail: alex_tropsha@unc.edu [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States)

2015-04-15

Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. - Highlights: • It was compiled the largest publicly-available skin sensitization dataset. • Predictive QSAR models were developed for skin sensitization. • Developed models have higher prediction accuracy than OECD QSAR Toolbox. • Putative

Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

International Nuclear Information System (INIS)

Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2015-01-01

Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. - Highlights: • It was compiled the largest publicly-available skin sensitization dataset. • Predictive QSAR models were developed for skin sensitization. • Developed models have higher prediction accuracy than OECD QSAR Toolbox. • Putative

Cutaneous lasers and skin camouflage make-up: a useful alternative intervention for periorbital hairy congenital melanocytic naevus.

Science.gov (United States)

Townley, William A; Bragg, Thomas W H; Wright, Philip A; Cole, Richard P

2013-12-01

Periorbital congenital melanocytic naevi can be very disfiguring and difficult to treat effectively. Although surgical excision and reconstruction is the most widely accepted treatment strategy, we describe a case in which cutaneous lasers treatment followed by the application of cosmetic skin camouflage make-up provided an alternative solution delivering a good cosmetic improvement.

Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO2 nanoparticles

Science.gov (United States)

Park, Yoon-Hee; Jeong, Sang Hoon; Yi, Sang Min; Hyeok Choi, Byeong; Kim, Yu-Ri; Kim, In-Kyoung; Kim, Meyoung-Kon; Son, Sang Wook

2011-07-01

The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO2 nanoparticles using cultured keratinocytes, an HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO2 nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO2 nanoparticles

International Nuclear Information System (INIS)

Park, Yoon-Hee; Jeong, Sang Hoon; Yi, Sang Min; Choi, Byeong Hyeok; Son, Sang Wook; Kim, Yu-Ri; Kim, In-Kyoung; Kim, Meyoung-Kon

2011-01-01

The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO 2 nanoparticles using cultured keratinocytes, an HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO 2 nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

Reflectance spectrometry of normal and bruised human skins: experiments and modeling

International Nuclear Information System (INIS)

Kim, Oleg; Alber, Mark; McMurdy, John; Lines, Collin; Crawford, Gregory; Duffy, Susan

2012-01-01

A stochastic photon transport model in multilayer skin tissue combined with reflectance spectroscopy measurements is used to study normal and bruised skins. The model is shown to provide a very good approximation to both normal and bruised real skin tissues by comparing experimental and simulated reflectance spectra. The sensitivity analysis of the skin reflectance spectrum to variations of skin layer thicknesses, blood oxygenation parameter and concentrations of main chromophores is performed to optimize model parameters. The reflectance spectrum of a developed bruise in a healthy adult is simulated, and the concentrations of bilirubin, blood volume fraction and blood oxygenation parameter are determined for different times as the bruise progresses. It is shown that bilirubin and blood volume fraction reach their peak values at 80 and 55 h after contusion, respectively, and the oxygenation parameter is lower than its normal value during 80 h after contusion occurred. The obtained time correlations of chromophore concentrations in developing contusions are shown to be consistent with previous studies. The developed model uses a detailed seven-layer skin approximation for contusion and allows one to obtain more biologically relevant results than those obtained with previous models using one- to three-layer skin approximations. A combination of modeling with spectroscopy measurements provides a new tool for detailed biomedical studies of human skin tissue and for age determination of contusions. (paper)

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

Science.gov (United States)

Oesch, F; Fabian, E; Landsiedel, Robert

2018-06-18

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

Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO{sub 2} nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Park, Yoon-Hee; Jeong, Sang Hoon; Yi, Sang Min; Choi, Byeong Hyeok; Son, Sang Wook [Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology and Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul (Korea, Republic of); Kim, Yu-Ri; Kim, In-Kyoung; Kim, Meyoung-Kon [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

2011-07-06

The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO{sub 2} nanoparticles using cultured keratinocytes, an HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO{sub 2} nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

Immunological challenges associated with artificial skin grafts: available solutions and stem cells in future design of synthetic skin.

Science.gov (United States)

Dixit, Saurabh; Baganizi, Dieudonné R; Sahu, Rajnish; Dosunmu, Ejowke; Chaudhari, Atul; Vig, Komal; Pillai, Shreekumar R; Singh, Shree R; Dennis, Vida A

2017-01-01

The repair or replacement of damaged skins is still an important, challenging public health problem. Immune acceptance and long-term survival of skin grafts represent the major problem to overcome in grafting given that in most situations autografts cannot be used. The emergence of artificial skin substitutes provides alternative treatment with the capacity to reduce the dependency on the increasing demand of cadaver skin grafts. Over the years, considerable research efforts have focused on strategies for skin repair or permanent skin graft transplantations. Available skin substitutes include pre- or post-transplantation treatments of donor cells, stem cell-based therapies, and skin equivalents composed of bio-engineered acellular or cellular skin substitutes. However, skin substitutes are still prone to immunological rejection, and as such, there is currently no skin substitute available to overcome this phenomenon. This review focuses on the mechanisms of skin rejection and tolerance induction and outlines in detail current available strategies and alternatives that may allow achieving full-thickness skin replacement and repair.

How to improve skin notation

DEFF Research Database (Denmark)

Sartorelli, Pietro; Ahlers, Heinz W.; Alanko, Kristiina

2007-01-01

The ICOH Scientific Committee on Occupational and Environmental Dermatoses organized an International Workshop on "Dermal risk assessment at workplace" with the aim of focussing on the different ways of approaching the concept of skin notation (S) for chemicals. The Workshop participants presented...... their ideas on several aspects of S such as the problems related to the absorption through the compromised skin, the different approaches to S and models that can be used as alternatives to S. Participants agreed to produce a position paper with the goal of exploring the actions needed to improve the S system...

Comparative value of blood and skin samples for diagnosis of spotted fever group rickettsial infection in model animals.

Science.gov (United States)

Levin, Michael L; Snellgrove, Alyssa N; Zemtsova, Galina E

2016-07-01

The definitive diagnosis of spotted fever group (SFG) rickettsioses in humans is challenging due to the retrospective nature and cross reactivity of the serological methods and the absence of reliable and consistent samples for molecular diagnostics. Existing data indicate the transient character of bacteremia in experimentally infected animals. The ability of arthropod vectors to acquire rickettsial infection from the laboratory animals in the absence of systemic infection and known tropism of rickettsial agents to endothelial cells of peripheral blood vessels underline the importance of local infection and consequently the diagnostic potential of skin samples. In order to evaluate the diagnostic sensitivity of rickettsial DNA detection in blood and skin samples, we compared results of PCR testing in parallel samples collected from model laboratory animals infected with Rickettsia rickettsii, Rickettsia parkeri and Rickettsia slovaca-like agent at different time points after infection. Skin samples were collected from ears - away from the site of tick placement and without eschars. Overall, testing of skin samples resulted in a higher proportion of positive results than testing of blood samples. Presented data from model animals demonstrates that testing of skin samples from sites of rickettsial proliferation can provide definitive molecular diagnosis of up to 60-70% of tick-borne SFG rickettsial infections during the acute stage of illness. Detection of pathogen DNA in cutaneous samples is a valuable alternative to blood-PCR at least in model animals. Published by Elsevier GmbH.

Skin fluorescence model based on the Monte Carlo technique

Science.gov (United States)

Churmakov, Dmitry Y.; Meglinski, Igor V.; Piletsky, Sergey A.; Greenhalgh, Douglas A.

2003-10-01

The novel Monte Carlo technique of simulation of spatial fluorescence distribution within the human skin is presented. The computational model of skin takes into account spatial distribution of fluorophores following the collagen fibers packing, whereas in epidermis and stratum corneum the distribution of fluorophores assumed to be homogeneous. The results of simulation suggest that distribution of auto-fluorescence is significantly suppressed in the NIR spectral region, while fluorescence of sensor layer embedded in epidermis is localized at the adjusted depth. The model is also able to simulate the skin fluorescence spectra.

Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

Science.gov (United States)

Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2015-01-01

Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using random forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers were 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the ScoreCard database of possible skin or sense organ toxicants as primary candidates for experimental validation. PMID:25560674

A novel model of human skin pressure ulcers in mice.

Directory of Open Access Journals (Sweden)

Andrés A Maldonado

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

A retrospective analysis of in vivo eye irritation, skin irritation and skin sensitisation studies with agrochemical formulations: Setting the scene for development of alternative strategies.

Science.gov (United States)

Corvaro, M; Gehen, S; Andrews, K; Chatfield, R; Macleod, F; Mehta, J

2017-10-01

Analysis of the prevalence of health effects in large scale databases is key in defining testing strategies within the context of Integrated Approaches on Testing and Assessment (IATA), and is relevant to drive policy changes in existing regulatory toxicology frameworks towards non-animal approaches. A retrospective analysis of existing results from in vivo skin irritation, eye irritation, and skin sensitisation studies on a database of 223 agrochemical formulations is herein published. For skin or eye effects, high prevalence of mild to non-irritant formulations (i.e. per GHS, CLP or EPA classification) would generally suggest a bottom-up approach. Severity of erythema or corneal opacity, for skinor eye effects respectively, were the key drivers for classification, consistent with existing literature. The reciprocal predictivity of skin versus eye irritation and the good negative predictivity of the GHS additivity calculation approach (>85%) provided valuable non-testing evidence for irritation endpoints. For dermal sensitisation, concordance on data from three different methods confirmed the high false negative rate for the Buehler method in this product class. These results have been reviewed together with existing literature on the use of in vitro alternatives for agrochemical formulations, to propose improvements to current regulatory strategies and to identify further research needs. Copyright © 2017 Elsevier Inc. All rights reserved.

Surfactant-induced skin irritation and skin repair: evaluation of a cumulative human irritation model by noninvasive techniques.

Science.gov (United States)

Wilhelm, K P; Freitag, G; Wolff, H H

1994-12-01

Although surfactant-induced acute irritant dermatitis has been extensively studied, our understanding about the induction and repair of the clinically more relevant chronic form is limited. Our purpose was to investigate qualitative and quantitative differences in surfactant-induced irritant skin reactions from cumulative exposure to structurally unrelated surfactants and to compare the maximal irritant responses from this model with corresponding reactions noted in a previously reported acute irritation model. Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (7.5%) were applied for 20 minutes daily (for 8 consecutive days excluding the weekend) to the volar aspect of the forearm of 11 volunteers. Irritant reactions were repeatedly assessed until complete healing was indicated by visual assessment and by measurements of transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). Maximum irritant responses were compared with corresponding reactions from an acute irritation model. TEWL was increased by SLS and DTAB to the same extent, but erythema was significantly higher in DTAB-treated skin. Skin dryness, as demonstrated by decreased capacitance values and increased scores for scaling and fissuring, was significantly more pronounced than in an acute irritation model for SLS and DTAB, although no difference was detected between the two surfactants. Potassium soap led to a slight increase in TEWL, whereas the remaining features were not significantly changed. This chronic irritation model appears to represent the clinical situation of irritant contact dermatitis with pronounced skin dryness more closely than the acute irritation model. The present study confirms that an extended time is needed for complete healing of irritant skin reactions. We also demonstrated that the evaluation of the irritation potential of

4D-Fingerprint Categorical QSAR Models for Skin Sensitization Based on Classification Local Lymph Node Assay Measures

Science.gov (United States)

Li, Yi; Tseng, Yufeng J.; Pan, Dahua; Liu, Jianzhong; Kern, Petra S.; Gerberick, G. Frank; Hopfinger, Anton J.

2008-01-01

Currently, the only validated methods to identify skin sensitization effects are in vivo models, such as the Local Lymph Node Assay (LLNA) and guinea pig studies. There is a tremendous need, in particular due to novel legislation, to develop animal alternatives, eg. Quantitative Structure-Activity Relationship (QSAR) models. Here, QSAR models for skin sensitization using LLNA data have been constructed. The descriptors used to generate these models are derived from the 4D-molecular similarity paradigm and are referred to as universal 4D-fingerprints. A training set of 132 structurally diverse compounds and a test set of 15 structurally diverse compounds were used in this study. The statistical methodologies used to build the models are logistic regression (LR), and partial least square coupled logistic regression (PLS-LR), which prove to be effective tools for studying skin sensitization measures expressed in the two categorical terms of sensitizer and non-sensitizer. QSAR models with low values of the Hosmer-Lemeshow goodness-of-fit statistic, χHL2, are significant and predictive. For the training set, the cross-validated prediction accuracy of the logistic regression models ranges from 77.3% to 78.0%, while that of PLS-logistic regression models ranges from 87.1% to 89.4%. For the test set, the prediction accuracy of logistic regression models ranges from 80.0%-86.7%, while that of PLS-logistic regression models ranges from 73.3%-80.0%. The QSAR models are made up of 4D-fingerprints related to aromatic atoms, hydrogen bond acceptors and negatively partially charged atoms. PMID:17226934

Development of a Skin Burn Predictive Model adapted to Laser Irradiation

Science.gov (United States)

Sonneck-Museux, N.; Scheer, E.; Perez, L.; Agay, D.; Autrique, L.

2016-12-01

Laser technology is increasingly used, and it is crucial for both safety and medical reasons that the impact of laser irradiation on human skin can be accurately predicted. This study is mainly focused on laser-skin interactions and potential lesions (burns). A mathematical model dedicated to heat transfers in skin exposed to infrared laser radiations has been developed. The model is validated by studying heat transfers in human skin and simultaneously performing experimentations an animal model (pig). For all experimental tests, pig's skin surface temperature is recorded. Three laser wavelengths have been tested: 808 nm, 1940 nm and 10 600 nm. The first is a diode laser producing radiation absorbed deep within the skin. The second wavelength has a more superficial effect. For the third wavelength, skin is an opaque material. The validity of the developed models is verified by comparison with experimental results (in vivo tests) and the results of previous studies reported in the literature. The comparison shows that the models accurately predict the burn degree caused by laser radiation over a wide range of conditions. The results show that the important parameter for burn prediction is the extinction coefficient. For the 1940 nm wavelength especially, significant differences between modeling results and literature have been observed, mainly due to this coefficient's value. This new model can be used as a predictive tool in order to estimate the amount of injury induced by several types (couple power-time) of laser aggressions on the arm, the face and on the palm of the hand.

Modeling of skin cancer dermatoscopy images

Science.gov (United States)

Iralieva, Malica B.; Myakinin, Oleg O.; Bratchenko, Ivan A.; Zakharov, Valery P.

2018-04-01

An early identified cancer is more likely to effective respond to treatment and has a less expensive treatment as well. Dermatoscopy is one of general diagnostic techniques for skin cancer early detection that allows us in vivo evaluation of colors and microstructures on skin lesions. Digital phantoms with known properties are required during new instrument developing to compare sample's features with data from the instrument. An algorithm for image modeling of skin cancer is proposed in the paper. Steps of the algorithm include setting shape, texture generation, adding texture and normal skin background setting. The Gaussian represents the shape, and then the texture generation based on a fractal noise algorithm is responsible for spatial chromophores distributions, while the colormap applied to the values corresponds to spectral properties. Finally, a normal skin image simulated by mixed Monte Carlo method using a special online tool is added as a background. Varying of Asymmetry, Borders, Colors and Diameter settings is shown to be fully matched to the ABCD clinical recognition algorithm. The asymmetry is specified by setting different standard deviation values of Gaussian in different parts of image. The noise amplitude is increased to set the irregular borders score. Standard deviation is changed to determine size of the lesion. Colors are set by colormap changing. The algorithm for simulating different structural elements is required to match with others recognition algorithms.

Evaluation of Skin Surface as an Alternative Source of Reference DNA Samples: A Pilot Study.

Science.gov (United States)

Albujja, Mohammed H; Bin Dukhyil, Abdul Aziz; Chaudhary, Abdul Rauf; Kassab, Ahmed Ch; Refaat, Ahmed M; Babu, Saranya Ramesh; Okla, Mohammad K; Kumar, Sachil

2018-01-01

An acceptable area for collecting DNA reference sample is a part of the forensic DNA analysis development. The aim of this study was to evaluate skin surface cells (SSC) as an alternate source of reference DNA sample. From each volunteer (n = 10), six samples from skin surface areas (forearm and fingertips) and two traditional samples (blood and buccal cells) were collected. Genomic DNA was extracted and quantified then genotyped using standard techniques. The highest DNA concentration of SSC samples was collected using the tape/forearm method of collection (2.1 ng/μL). Cotton swabs moistened with ethanol yielded higher quantities of DNA than swabs moistened with salicylic acid, and it gave the highest percentage of full STR profiles (97%). This study supports the use of SSC as a noninvasive sampling technique and as a extremely useful source of DNA reference samples among certain cultures where the use of buccal swabs can be considered socially unacceptable. © 2017 American Academy of Forensic Sciences.

An evaluation of costs and effects of a nutrient-based skin care program as a component of prevention of skin tears in an extended convalescent center.

Science.gov (United States)

Groom, Marjorie; Shannon, Ronald J; Chakravarthy, Debashish; Fleck, Cynthia A

2010-01-01

A decision model was developed in a pilot study comparing a regimen using a skin care product line containing active ingredients and nutrients with a commercially available alternative skin care regimen in an elderly convalescent care hospital-based center. Using a decision-tree model, skin treatment with a nutrient-based skin care (NBSC) formulation was compared with products without nutrients. The number of skin-tear-free days was the primary outcome measure. A cost-effectiveness ratio was calculated for each skin treatment as the average cost for reaching a particular outcome. Incidence of skin tear data was collected from residents in a convalescent center from 2004 to 2005. An independent t test was used to compare differences in the number of skin tears between periods when NBSC and other formulations were used. All costs in the decision model were adjusted to 2007 dollars. Sensitivity analysis was used to test uncertain data. The NBSC provided more skin-tear-free days and was less costly than the use of non-NBSC products. The expected skin-tear-free days for a patient in the model treated with NBSC were 179.7 days compared with 154.6 days for non-NBSC products, yielding an incremental effect of 25.1 days. The expected cost of preventing skin tears and treatment via skin treatment per patient in the NBSC group was $281.00 versus $324.10 for periods when other products were used. The NBSC had a lower projected cost for prevention of skin tears and more skin-tear-free days when compared with non-NBSC products.

External wire-frame fixation of digital skin grafts: a non-invasive alternative to the K-wire insertion method.

Science.gov (United States)

Huang, Chenyu; Ogawa, Rei; Hyakusoku, Hiko

2014-08-01

The current skin graft fixation methods for digits, including the Kirschner wire insertion technique, can be limited by inadequate or excessive fixation and complications such as infection or secondary injuries. Therefore, the external wire-frame fixation method was invented and used for skin grafting of digits. This study aimed to investigate external wire-frame fixation of digital skin grafts as a non-invasive alternative to the K-wire insertion method. In 2005-2012, 15 patients with burn scar contractures on the hand digits received a skin graft that was then fixed with an external wire frame. The intra-operative time needed to make the wire frame, the postoperative time to frame and suture removal, the graft survival rate, the effect of contracture release and the complications were recorded. In all cases, the contracture release was 100%. The complete graft survival rate was 98.6%. Four patients had epithelial necrosis in wire-frame fixation is simple, minimally invasive and a custom-made technique for skin grafting of the fingers. It was designed for its potential benefits and the decreased risk it poses to patients with scar contractures on their fingers. It can be implemented in three phases of grafting, does not affect the epiphyseal line or subsequent finger growth and is suitable for children with multi-digit involvement. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

A skin abscess model for teaching incision and drainage procedures.

Science.gov (United States)

Fitch, Michael T; Manthey, David E; McGinnis, Henderson D; Nicks, Bret A; Pariyadath, Manoj

2008-07-03

Skin and soft tissue infections are increasingly prevalent clinical problems, and it is important for health care practitioners to be well trained in how to treat skin abscesses. A realistic model of abscess incision and drainage will allow trainees to learn and practice this basic physician procedure. We developed a realistic model of skin abscess formation to demonstrate the technique of incision and drainage for educational purposes. The creation of this model is described in detail in this report. This model has been successfully used to develop and disseminate a multimedia video production for teaching this medical procedure. Clinical faculty and resident physicians find this model to be a realistic method for demonstrating abscess incision and drainage. This manuscript provides a detailed description of our model of abscess incision and drainage for medical education. Clinical educators can incorporate this model into skills labs or demonstrations for teaching this basic procedure.

Validation of the 3D Skin Comet assay using full thickness skin models: Transferability and reproducibility.

Science.gov (United States)

Reisinger, Kerstin; Blatz, Veronika; Brinkmann, Joep; Downs, Thomas R; Fischer, Anja; Henkler, Frank; Hoffmann, Sebastian; Krul, Cyrille; Liebsch, Manfred; Luch, Andreas; Pirow, Ralph; Reus, Astrid A; Schulz, Markus; Pfuhler, Stefan

2018-03-01

Recently revised OECD Testing Guidelines highlight the importance of considering the first site-of-contact when investigating the genotoxic hazard. Thus far, only in vivo approaches are available to address the dermal route of exposure. The 3D Skin Comet and Reconstructed Skin Micronucleus (RSMN) assays intend to close this gap in the in vitro genotoxicity toolbox by investigating DNA damage after topical application. This represents the most relevant route of exposure for a variety of compounds found in household products, cosmetics, and industrial chemicals. The comet assay methodology is able to detect both chromosomal damage and DNA lesions that may give rise to gene mutations, thereby complementing the RSMN which detects only chromosomal damage. Here, the comet assay was adapted to two reconstructed full thickness human skin models: the EpiDerm™- and Phenion ® Full-Thickness Skin Models. First, tissue-specific protocols for the isolation of single cells and the general comet assay were transferred to European and US-American laboratories. After establishment of the assay, the protocol was then further optimized with appropriate cytotoxicity measurements and the use of aphidicolin, a DNA repair inhibitor, to improve the assay's sensitivity. In the first phase of an ongoing validation study eight chemicals were tested in three laboratories each using the Phenion ® Full-Thickness Skin Model, informing several validation modules. Ultimately, the 3D Skin Comet assay demonstrated a high predictive capacity and good intra- and inter-laboratory reproducibility with four laboratories reaching a 100% predictivity and the fifth yielding 70%. The data are intended to demonstrate the use of the 3D Skin Comet assay as a new in vitro tool for following up on positive findings from the standard in vitro genotoxicity test battery for dermally applied chemicals, ultimately helping to drive the regulatory acceptance of the assay. To expand the database, the validation will

Immune mechanisms in fish skin against monogeneans--a model.

Science.gov (United States)

Buchmann, K

1999-01-01

Host responses against skin inhabiting monogeneans are commonly observed but the responsible immune mechanisms in the fish skin are sufficiently described. Based on recent knowledge of fish immunity and skin response mechanisms in mammals a model for the skin immunity in fish to monogenean infections is proposed. Important cellular components of the model are the epithelial cells, the mucous cells and leucocytes. The release of cytokines, e.g., IL-1, following mechanical or chemical injury of the epithelial cells, initiates a series of events leading to decrease of the ectoparasite population. Cytokines (e.g., IL-1, TNF, INF) are suggested to affect secretions from mucous cell and attract neutrophils and macrophages. Leukotrienes are probably involved in the inflammatory reactions. The subsequent production of humoral substances (among others complement factors and peptides) could be responsible for the antiparasitic response in the later stages of infection. Although non-specific factors dominate the response, the involvement of specific antibodies and lymphocytes cannot be excluded.

Standardisation of defined approaches for skin sensitisation testing to support regulatory use and international adoption: position of the International Cooperation on Alternative Test Methods.

Science.gov (United States)

Casati, S; Aschberger, K; Barroso, J; Casey, W; Delgado, I; Kim, T S; Kleinstreuer, N; Kojima, H; Lee, J K; Lowit, A; Park, H K; Régimbald-Krnel, M J; Strickland, J; Whelan, M; Yang, Y; Zuang, Valérie

2018-02-01

Skin sensitisation is the regulatory endpoint that has been at the centre of concerted efforts to replace animal testing in recent years, as demonstrated by the Organisation for Economic Co-operation and Development (OECD) adoption of five non-animal methods addressing mechanisms under the first three key events of the skin sensitisation adverse outcome pathway. Nevertheless, the currently adopted methods, when used in isolation, are not sufficient to fulfil regulatory requirements on the skin sensitisation potential and potency of chemicals comparable to that provided by the regulatory animal tests. For this reason, a number of defined approaches integrating data from these methods with other relevant information have been proposed and documented by the OECD. With the aim to further enhance regulatory consideration and adoption of defined approaches, the European Union Reference Laboratory for Alternatives to Animal testing in collaboration with the International Cooperation on Alternative Test Methods hosted, on 4-5 October 2016, a workshop on the international regulatory applicability and acceptance of alternative non-animal approaches, i.e., defined approaches, to skin sensitisation assessment of chemicals used in a variety of sectors. The workshop convened representatives from more than 20 regulatory authorities from the European Union, United States, Canada, Japan, South Korea, Brazil and China. There was a general consensus among the workshop participants that to maximise global regulatory acceptance of data generated with defined approaches, international harmonisation and standardisation are needed. Potential assessment criteria were defined for a systematic evaluation of existing defined approaches that would facilitate their translation into international standards, e.g., into a performance-based Test Guideline. Informed by the discussions at the workshop, the ICATM members propose practical ways to further promote the regulatory use and facilitate

Dirt-binding particles consisting of hydrogenated castor oil beads constitute a nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination in a three-step programme of occupational skin protection.

Science.gov (United States)

Mahler, V; Erfurt-Berge, C; Schiemann, S; Michael, S; Egloffstein, A; Kuss, O

2010-04-01

In occupational fields with exposure to grease, oil, metal particles, coal, black lead or soot, cleansing formulations containing abrasive bodies (e.g. refined walnut shell, corn, wood, plastic or pumice) are used. These may constitute an irritant per se. As an alternative, hydrogenated castor oil (also known as castor wax) beads have been developed as dirt-binding particles. A polar surface contributes to their mechanical cleaning effects in removal of oily grime. Standardized examination of the in vivo effects upon the skin barrier of castor wax beads in comparison with abrasive bodies and pure detergent. Three cleansing preparations - (i) detergent, (ii) detergent containing castor wax beads, (iii) detergent containing walnut shell powder - were each repetitively applied in vivo (four times daily for 3 weeks), mimicking workplace conditions, in 30 healthy volunteers (15 with and 15 without an atopic skin diathesis) and compared vs. (iv) no treatment. The treatment effects upon the skin barrier were monitored by repeated measurements of functional parameters [transepidermal water loss (TEWL), redness] and surface topography. After a 3-week treatment, a significant global treatment effect (P dirt and use of skin protection and skin care measures under real workplace conditions, this component may now be used and examined further in different occupations.

A Game-Theoretic Model of Marketing Skin Whiteners.

Science.gov (United States)

Mendoza, Roger Lee

2015-01-01

Empirical studies consistently find that people in less developed countries tend to regard light or "white" skin, particularly among women, as more desirable or superior. This is a study about the marketing of skin whiteners in these countries, where over 80 percent of users are typically women. It proceeds from the following premises: a) Purely market or policy-oriented approaches toward the risks and harms of skin whitening are cost-inefficient; b) Psychosocial and informational factors breed uninformed and risky consumer choices that favor toxic skin whiteners; and c) Proliferation of toxic whiteners in a competitive buyer's market raises critical supplier accountability issues. Is intentional tort a rational outcome of uncooperative game equilibria? Can voluntary cooperation nonetheless evolve between buyers and sellers of skin whiteners? These twin questions are key to addressing the central paradox in this study: A robust and expanding buyer's market, where cheap whitening products abound at a high risk to personal and societal health and safety. Game-theoretic modeling of two-player and n-player strategic interactions is proposed in this study for both its explanatory and predictive value. Therein also lie its practical contributions to the economic literature on skin whitening.

Fish skin as a model membrane: structure and characteristics.

Science.gov (United States)

Konrádsdóttir, Fífa; Loftsson, Thorsteinn; Sigfússon, Sigurdur Dadi

2009-01-01

Synthetic and cell-based membranes are frequently used during drug formulation development for the assessment of drug availability. However, most of the currently used membranes do not mimic mucosal membranes well, especially the aqueous mucous layer of the membranes. In this study we evaluated catfish (Anarichas lupus L) skin as a model membrane. Permeation of hydrocortisone, lidocaine hydrochloride, benzocaine, diethylstilbestrol, naproxen, picric acid and sodium nitrate through skin from a freshly caught catfish was determined in Franz diffusion cells. Both lipophilic and hydrophilic molecules permeate through catfish skin via hydrated channels or aqueous pores. No correlation was observed between the octanol/water partition coefficient of the permeating molecules and their permeability coefficient through the skin. Permeation through catfish skin was found to be diffusion controlled. The results suggest that permeation through the fish skin proceeds via a diffusion-controlled process, a process that is similar to drug permeation through the aqueous mucous layer of a mucosal membrane. In addition, the fish skin, with its collagen matrix structure, appears to possess similar properties to the eye sclera.

Role of Stat in Skin Carcinogenesis: Insights Gained from Relevant Mouse Models

International Nuclear Information System (INIS)

Macias, E.; Rao, D.; DiGiovanni, J.; DiGiovanni, J.; DiGiovanni, J.

2013-01-01

Signal transducer and activator of transcription 3 (Stat) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat-deficient mice have revealed that Stat plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat-deficient mouse models has demonstrated that Stat is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat in skin tumor progression. Studies using similar Stat-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat is an attractive target for skin cancer prevention and treatment.

Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Xia, Xiaojun [The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Park, Eunmi [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Fischer, Susan M. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78967 (United States); Hu, Yinling, E-mail: huy2@mail.nih.gov [Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21701 (United States)

2013-02-15

Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside.

Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

International Nuclear Information System (INIS)

Xia, Xiaojun; Park, Eunmi; Fischer, Susan M.; Hu, Yinling

2013-01-01

Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside

Skin care products can aggravate epidermal function: studies in a murine model suggest a pathogenic role in sensitive skin.

Science.gov (United States)

Li, Zhengxiao; Hu, Lizhi; Elias, Peter M; Man, Mao-Qiang

2018-02-01

Sensitive skin is defined as a spectrum of unpleasant sensations in response to a variety of stimuli. However, only some skin care products provoke cutaneous symptoms in individuals with sensitive skin. Hence, it would be useful to identify products that could provoke cutaneous symptoms in individuals with sensitive skin. To assess whether vehicles, as well as certain branded skin care products, can alter epidermal function following topical applications to normal mouse skin. Following topical applications of individual vehicle or skin care product to C57BL/6J mice twice daily for 4 days, transepidermal water loss (TEWL) rates, stratum corneum (SC) hydration and skin surface pH were measured on treated versus untreated mouse skin with an MPA5 device and pH 900 pH meter. Our results show that all tested products induced abnormalities in epidermal functions of varying severity, including elevations in TEWL and skin surface pH, and reduced SC hydration. Our results suggest that mice can serve as a predictive model that could be used to evaluate the potential safety of skin care products in humans with sensitive skin. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Science.gov (United States)

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

2017-12-01

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

An alternative for the LF model

NARCIS (Netherlands)

Veldhuis, R.N.J.

1996-01-01

An alternative for the Liljencrants-Fant (LF) glottal-pulse model is presented. This alternative is derived from the Rosenberg model, so we have caned it the Rosenberg++ model. It is described by the same set of Tor R parameters as the LF model but has the advantage over the LF model that it is

Evaluation of Permacol as a cultured skin equivalent.

Science.gov (United States)

MacLeod, T M; Cambrey, A; Williams, G; Sanders, R; Green, C J

2008-12-01

Skin loss following severe burn requires prompt wound closure to avoid such complications as fluid and electrolyte imbalance, infection, immune suppression, and pain. In clinical situations in which insufficient donor skin is available, the development of cultured skin equivalents (dermal matrices seeded with keratinocytes and fibroblasts) may provide a useful alternative. The aim of this study was to assess the suitability of a porcine-derived dermal collagen matrix (Permacol) to function as a cultured skin equivalent in supporting the growth of keratinocytes in vitro and providing cover to full thickness wounds in the BALB C/nude mouse model. A histological comparison was against Glycerol treated-Ethylene Oxide Sterilised Porcine Dermis (Gly-EO Dermis) which has successfully been used as a cultured skin equivalent in previous studies. Both Gly-EO Dermis and to a lesser extent Permacol were able to support the growth of cultured keratinocytes following a 16-day period of cell culture, however, this study was only able to demonstrate the presence of an epidermal layer on Gly-EO dermis 2 weeks after grafting onto full-thickness wounds in the BALB C/nude mouse model.

An in vitro method for detecting chemical sensitization using human reconstructed skin models and its applicability to cosmetic, pharmaceutical, and medical device safety testing.

Science.gov (United States)

McKim, James M; Keller, Donald J; Gorski, Joel R

2012-12-01

Chemical sensitization is a serious condition caused by small reactive molecules and is characterized by a delayed type hypersensitivity known as allergic contact dermatitis (ACD). Contact with these molecules via dermal exposure represent a significant concern for chemical manufacturers. Recent legislation in the EU has created the need to develop non-animal alternative methods for many routine safety studies including sensitization. Although most of the alternative research has focused on pure chemicals that possess reasonable solubility properties, it is important for any successful in vitro method to have the ability to test compounds with low aqueous solubility. This is especially true for the medical device industry where device extracts must be prepared in both polar and non-polar vehicles in order to evaluate chemical sensitization. The aim of this research was to demonstrate the functionality and applicability of the human reconstituted skin models (MatTek Epiderm(®) and SkinEthic RHE) as a test system for the evaluation of chemical sensitization and its potential use for medical device testing. In addition, the development of the human 3D skin model should allow the in vitro sensitization assay to be used for finished product testing in the personal care, cosmetics, and pharmaceutical industries. This approach combines solubility, chemical reactivity, cytotoxicity, and activation of the Nrf2/ARE expression pathway to identify and categorize chemical sensitizers. Known chemical sensitizers representing extreme/strong-, moderate-, weak-, and non-sensitizing potency categories were first evaluated in the skin models at six exposure concentrations ranging from 0.1 to 2500 µM for 24 h. The expression of eight Nrf2/ARE, one AhR/XRE and two Nrf1/MRE controlled gene were measured by qRT-PCR. The fold-induction at each exposure concentration was combined with reactivity and cytotoxicity data to determine the sensitization potential. The results demonstrated that

Development and evaluation of a skin organ model for the analysis of radiation effects

International Nuclear Information System (INIS)

Meineke, V.; Mueller, K.; Ridi, R.; Cordes, N.; Beuningen, D. van; Koehn, F.M.; Ring, J.; Mayerhofer, A.

2004-01-01

Background and purpose: the reaction of tissues to ionizing radiation involves alterations in cell-cell and cell-matrix interactions mediated by cellular adhesion molecules. The aim of this study was to develop and evaluate an artificial skin organ model for the analysis of radiation effects. Material and methods: a human co-culture system consisting of the spontaneously immortalized keratinocyte cell line HaCaT and primary HDFa fibroblasts embedded into a collagen sponge was established. This skin organ model has been characterized and evaluated for its suitability for radiobiological investigations. For that purpose, expression of β 1 -integrin following irradiation was compared in the skin organ model and in HaCaT monolayer cells (FACScan and immunohistochemistry). Furthermore, the influence of ionizing radiation on DNA fragmentation was investigated in the skin organ model (TUNEL assay). Results: the novel skin organ model showed characteristics of human skin as demonstrated by cytokeratin and Ki-67 immunoreactivity and by electron microscopy. A single dose of 5 Gy X-irradiation induced an upregulation of β 1 -integrin expression both in the skin organ model and in HaCaT cells. Following irradiation, β 1 -integrin immunoreactivity was intensified in the upper layers of the epidermis equivalent whereas it was almost absent in the deeper layers. Additionally, irradiation of the skin organ model also caused a marked increase of DNA fragmentation. Conclusion: these results demonstrate that the novel skin organ model is suitable to investigate cellular radiation effects under three-dimensional conditions. This allows to investigate radiation effects which cannot be demonstrated in monolayer cell cultures. (orig.)

Air Quality Dispersion Modeling - Alternative Models

Science.gov (United States)

Models, not listed in Appendix W, that can be used in regulatory applications with case-by-case justification to the Reviewing Authority as noted in Section 3.2, Use of Alternative Models, in Appendix W.

The development of a non-melanoma skin cancer detection model

NARCIS (Netherlands)

Geer, van der S.; Kleingeld, P.A.M.; Snijders, C.C.P.; Rinkens, F.J.C.H.; Jansen, G.A.E.; Neumann, H.A.M.; Krekels, G.A.M.

2015-01-01

Background: The incidence and prevalence of skin cancer is rising. A detection model could support the (screening) process of diagnosing non-melanoma skin cancer. Methods: A questionnaire was developed containing potential actinic keratosis (AK) and basal cell carcinoma (BCC) characteristics. Three

Skin barrier disruption by acetone: observations in a hairless mouse skin model

NARCIS (Netherlands)

Rissmann, R.; Oudshoorn, M.H.M.; Hennink, W.E.; Ponec, M.; Bouwstra, J.A.

2009-01-01

To disrupt the barrier function of the skin, different in vivo methods have been established, e.g., by acetone wiping or tape-stripping. In this study, the acetone-induced barrier disruption of hairless mice was investigated in order to establish a reliable model to study beneficial, long-term

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

Science.gov (United States)

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

2012-01-01

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

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

Science.gov (United States)

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

2013-08-01

The frictional characteristics of skin-object interactions are important when handling objects, in the assessment of perception and comfort of products and materials and in the origins and prevention of skin injuries. In this study, based on statistical methods, a quantitative model is developed that describes the friction behaviour of human skin as a function of the subject characteristics, contact conditions, the properties of the counter material as well as environmental conditions. Although the frictional behaviour of human skin is a multivariable problem, in literature the variables that are associated with skin friction have been studied using univariable methods. In this work, multivariable models for the static and dynamic coefficients of friction as well as for the hydration of the skin are presented. A total of 634 skin-friction measurements were performed using a recently developed tribometer. Using a statistical analysis, previously defined potential influential variables were linked to the static and dynamic coefficient of friction and to the hydration of the skin, resulting in three predictive quantitative models that descibe the friction behaviour and the hydration of human skin respectively. Increased dynamic coefficients of friction were obtained from older subjects, on the index finger, with materials with a higher surface energy at higher room temperatures, whereas lower dynamic coefficients of friction were obtained at lower skin temperatures, on the temple with rougher contact materials. The static coefficient of friction increased with higher skin hydration, increasing age, on the index finger, with materials with a higher surface energy and at higher ambient temperatures. The hydration of the skin was associated with the skin temperature, anatomical location, presence of hair on the skin and the relative air humidity. Predictive models have been derived for the static and dynamic coefficient of friction using a multivariable approach. These

The human skin/chick chorioallantoic membrane model accurately predicts the potency of cosmetic allergens.

Science.gov (United States)

Slodownik, Dan; Grinberg, Igor; Spira, Ram M; Skornik, Yehuda; Goldstein, Ronald S

2009-04-01

The current standard method for predicting contact allergenicity is the murine local lymph node assay (LLNA). Public objection to the use of animals in testing of cosmetics makes the development of a system that does not use sentient animals highly desirable. The chorioallantoic membrane (CAM) of the chick egg has been extensively used for the growth of normal and transformed mammalian tissues. The CAM is not innervated, and embryos are sacrificed before the development of pain perception. The aim of this study was to determine whether the sensitization phase of contact dermatitis to known cosmetic allergens can be quantified using CAM-engrafted human skin and how these results compare with published EC3 data obtained with the LLNA. We studied six common molecules used in allergen testing and quantified migration of epidermal Langerhans cells (LC) as a measure of their allergic potency. All agents with known allergic potential induced statistically significant migration of LC. The data obtained correlated well with published data for these allergens generated using the LLNA test. The human-skin CAM model therefore has great potential as an inexpensive, non-radioactive, in vivo alternative to the LLNA, which does not require the use of sentient animals. In addition, this system has the advantage of testing the allergic response of human, rather than animal skin.

Skin image illumination modeling and chromophore identification for melanoma diagnosis

Science.gov (United States)

Liu, Zhao; Zerubia, Josiane

2015-05-01

The presence of illumination variation in dermatological images has a negative impact on the automatic detection and analysis of cutaneous lesions. This paper proposes a new illumination modeling and chromophore identification method to correct lighting variation in skin lesion images, as well as to extract melanin and hemoglobin concentrations of human skin, based on an adaptive bilateral decomposition and a weighted polynomial curve fitting, with the knowledge of a multi-layered skin model. Different from state-of-the-art approaches based on the Lambert law, the proposed method, considering both specular reflection and diffuse reflection of the skin, enables us to address highlight and strong shading effects usually existing in skin color images captured in an uncontrolled environment. The derived melanin and hemoglobin indices, directly relating to the pathological tissue conditions, tend to be less influenced by external imaging factors and are more efficient in describing pigmentation distributions. Experiments show that the proposed method gave better visual results and superior lesion segmentation, when compared to two other illumination correction algorithms, both designed specifically for dermatological images. For computer-aided diagnosis of melanoma, sensitivity achieves 85.52% when using our chromophore descriptors, which is 8~20% higher than those derived from other color descriptors. This demonstrates the benefit of the proposed method for automatic skin disease analysis.

Cylindrical SUV distribution model for detecting skin lesions in body trunk FDG-PET/CT images

International Nuclear Information System (INIS)

Nemoto, Mitsutaka; Nomura, Yukihiro; Masutani, Yoshitaka; Yoshikawa, Takeharu; Hayashi, Naoto; Yoshioka, Naoki; Ohtomo, Kuni; Hanaoka, Shouhei

2010-01-01

We have been developing a computerized detection method for skin lesions in body trunk fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT images. Spots on the skin with a high standard uptake value (SUV) are due not only to glucose metabolism in skin lesions but also to the physiological metabolism of organs near the skin. The distribution pattern of regional SUV on the skin is important information for the differential diagnosis of such high-SUV spots. In this study, we have developed a new skin lesion detection method based on a cylindrical SUV distribution model of the skin. The shape of the SUV distribution model is an approximation of the body trunk, and the SUV distribution model includes standard values for regional skin SUV. Classifier ensembles based on CT image features, SUV features, and subtraction features between the SUVs in FDG-PET images and the values in the SUV distribution model are used to extract and classify candidate regions for skin lesions. In a study of skin lesion detection using FDG-PET/CT images in 36 clinical cases, the true-positive rate was 61.7%, with 11.7 false-positive regions per case. The training results of the classifier ensemble for extracting and classifying candidate regions showed the effective features for detecting skin lesions in the study. (author)

From Cell to Tissue Properties-Modeling Skin Electroporation With Pore and Local Transport Region Formation.

Science.gov (United States)

Dermol-Cerne, Janja; Miklavcic, Damijan

2018-02-01

Current models of tissue electroporation either describe tissue with its bulk properties or include cell level properties, but model only a few cells of simple shapes in low-volume fractions or are in two dimensions. We constructed a three-dimensional model of realistically shaped cells in realistic volume fractions. By using a 'unit cell' model, the equivalent dielectric properties of whole tissue could be calculated. We calculated the dielectric properties of electroporated skin. We modeled electroporation of single cells by pore formation on keratinocytes and on the papillary dermis which gave dielectric properties of the electroporated epidermis and papillary dermis. During skin electroporation, local transport regions are formed in the stratum corneum. We modeled local transport regions and increase in their radii or density which affected the dielectric properties of the stratum corneum. The final model of skin electroporation accurately describes measured electric current and voltage drop on the skin during electroporation with long low-voltage pulses. The model also accurately describes voltage drop on the skin during electroporation with short high-voltage pulses. However, our results indicate that during application of short high-voltage pulses additional processes may occur which increase the electric current. Our model connects the processes occurring at the level of cell membranes (pore formation), at the level of a skin layer (formation of local transport region in the stratum corneum) with the tissue (skin layers) and even level of organs (skin). Using a similar approach, electroporation of any tissue can be modeled, if the morphology of the tissue is known.

Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex.

Directory of Open Access Journals (Sweden)

Yanan Guo

Full Text Available Tuberous Sclerosis Complex (TSC is an autosomal dominant tumor suppressor gene syndrome in which patients develop several types of tumors, including facial angiofibroma, subungual fibroma, Shagreen patch, angiomyolipomas, and lymphangioleiomyomatosis. It is due to inactivating mutations in TSC1 or TSC2. We sought to generate a mouse model of one or more of these tumor types by targeting deletion of the Tsc1 gene to fibroblasts using the Fsp-Cre allele. Mutant, Tsc1ccFsp-Cre+ mice survived a median of nearly a year, and developed tumors in multiple sites but did not develop angiomyolipoma or lymphangioleiomyomatosis. They did develop a prominent skin phenotype with marked thickening of the dermis with accumulation of mast cells, that was minimally responsive to systemic rapamycin therapy, and was quite different from the pathology seen in human TSC skin lesions. Recombination and loss of Tsc1 was demonstrated in skin fibroblasts in vivo and in cultured skin fibroblasts. Loss of Tsc1 in fibroblasts in mice does not lead to a model of angiomyolipoma or lymphangioleiomyomatosis.

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

Science.gov (United States)

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

2014-06-01

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

Electrode-Skin contact impedance: In vivo measurements on an ovine model

International Nuclear Information System (INIS)

Nguyen, D T; Kosobrodov, R; Jin, C; McEwan, A; Barry, M A; Chik, W; Thiagalingam, A; Oh, T I

2013-01-01

The problem of electrical impedance between the skin and the electrode is an on-going challenge in bio-electronics. This is particularly true in the case of Electrical Impedance Tomography (EIT), which uses a large number of skin-contact electrodes and is very sensitive to noise. In the present article, contact impedance is measured and compared for a range of electrodes placed on the thorax of an ovine model. The study has been approved by the Westmead Hospital Animal Ethics Committee. The electrode models that were employed in the research are Ag/AgCl electrodes (E1), commonly used for ECG and EIT measurements in both humans and animal models, stainless steel crocodile clips (E2), typically used on animal models, and novel multi-point dry electrodes in two modifications: bronze plated (E3) and nickel plated (E4). Further, since the contact impedance is mostly attributed to the acellular outer layer of the skin, in our experiment, we attempted to study the effect of this layer by comparing the results when the skin is intact and when electrodes are introduced underneath the skin through small cuts. This boundary effect was assessed by comparison of measurements obtained during E2 skin surface contact, and sub-cutaneous contact (E5). Twelve gauge intradermal needles were also tested as an electrode (E6). The full impedance spectrum, from 500 Hz to 300 kHz, was recorded, analysed and compared. As expected, the contact impedance in the more invasive cases, i.e the electrodes under the skin, is significantly lower than in the non-invasive cases. At the frequency of 50 kHz which is commonly used in lung EIT acquisition, electrodes E3, E4 and E6 demonstrated contact impedance of less than 200 Ω, compared to more than 400 Ω measured for electrodes E1, E2 and E5. In conclusion, the novel multipoint electrodes proved to be best suited for EIT purposes, because they are non-invasive and have lower contact impedance than Ag/AgCl and crocodile clips, in both invasive and

EPA Releases Draft Policy to Reduce Animal Testing for Skin Sensitization

Science.gov (United States)

The document, Draft Interim Science Policy: Use of Alternative Approaches for Skin Sensitization as a Replacement for Laboratory Animal Testing, describes the science behind the non-animal alternatives that can now be used to identify skin sensitization.

Dose-response models for the radiation-induction of skin tumours in mice

International Nuclear Information System (INIS)

Papworth, D.G.; Hulse, E.V.

1983-01-01

Extensive data on radiation-induced skin tumours in mice were examined using 8 models, all based on the concept that incidences of radiation-induced tumours depend on a combination of two radiation effects: a tumour induction process and the loss of reproductive integrity by the potential tumour cells. Models with and without a threshold were used, in spite of theoretical objections to threshold models. No model fitted well both the epidermal and the dermal tumour data and models which proved to be statistically satisfactory for some of the data were rejected for biological reasons. It is concluded that, for skin tumours, dose-response curves depending on a combination of cancer induction and loss of cellular reproductive integrity are distorted by some special, relatively radio-resistant, factor which we have previously postulated as being involved in radiation skin carcinogenesis. (author)

Modelling the effect of mixture components on permeation through skin.

Science.gov (United States)

Ghafourian, T; Samaras, E G; Brooks, J D; Riviere, J E

2010-10-15

A vehicle influences the concentration of penetrant within the membrane, affecting its diffusivity in the skin and rate of transport. Despite the huge amount of effort made for the understanding and modelling of the skin absorption of chemicals, a reliable estimation of the skin penetration potential from formulations remains a challenging objective. In this investigation, quantitative structure-activity relationship (QSAR) was employed to relate the skin permeation of compounds to the chemical properties of the mixture ingredients and the molecular structures of the penetrants. The skin permeability dataset consisted of permeability coefficients of 12 different penetrants each blended in 24 different solvent mixtures measured from finite-dose diffusion cell studies using porcine skin. Stepwise regression analysis resulted in a QSAR employing two penetrant descriptors and one solvent property. The penetrant descriptors were octanol/water partition coefficient, logP and the ninth order path molecular connectivity index, and the solvent property was the difference between boiling and melting points. The negative relationship between skin permeability coefficient and logP was attributed to the fact that most of the drugs in this particular dataset are extremely lipophilic in comparison with the compounds in the common skin permeability datasets used in QSAR. The findings show that compounds formulated in vehicles with small boiling and melting point gaps will be expected to have higher permeation through skin. The QSAR was validated internally, using a leave-many-out procedure, giving a mean absolute error of 0.396. The chemical space of the dataset was compared with that of the known skin permeability datasets and gaps were identified for future skin permeability measurements. Copyright 2010 Elsevier B.V. All rights reserved.

Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse. (I) Development of a model for screening studies in skin decontamination and protection.

Science.gov (United States)

Dorandeu, F; Taysse, L; Boudry, I; Foquin, A; Hérodin, F; Mathieu, J; Daulon, S; Cruz, C; Lallement, G

2011-06-01

Exposure to lethal chemical warfare agents (CWAs) is no longer only a military issue due to the terrorist threat. Among the CWAs of concern are the organophosphorus nerve agent O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX) and the vesicant sulfur mustard (SM). Although efficient means of decontamination are available, most of them lose their efficacy when decontamination is delayed after exposure of the bare skin. Alternatively, CWA skin penetration can be prevented by topical skin protectants. Active research in skin protection and decontamination is thus paramount. In vivo screening of decontaminants or skin protectants is usually time consuming and may be expensive depending on the animal species used. We were thus looking for a suitable, scientifically sound and cost-effective model, which is easy to handle. The euthymic hairless mouse Crl: SKH-1 (hr/hr) BR is widely used in some skin studies and has previously been described to be suitable for some experiments involving SM or SM analogs. To evaluate the response of this species, we studied the consequences of exposing male anaesthetized SKH-1 mice to either liquid VX or to SM, the latter being used in liquid form or as saturated vapours. Long-term effects of SM burn were also evaluated. The model was then used in the companion paper (Taysse et al.(1)).

An evaluation of selected in silico models for the assessment of skin sensitization potential – performance and practical utility considerations (QSAR conference)

Science.gov (United States)

Skin sensitization remains an important endpoint for consumers, manufacturers and regulators. Although the development of alternative approaches to assess skin sensitization potential has been extremely active over many years, the implication of regulations such as REACH and the ...

Modeling and analyzing stripe patterns in fish skin

Science.gov (United States)

Zheng, Yibo; Zhang, Lei; Wang, Yuan; Liang, Ping; Kang, Junjian

2009-11-01

The formation mechanism of stripe patterns in the skin of tropical fishes has been investigated by a coupled two variable reaction diffusion model. Two types of spatial inhomogeneities have been introduced into a homogenous system. Several Turing modes pumped by the Turing instability give rise to a simple stripe pattern. It is found that the Turing mechanism can only determine the wavelength of stripe pattern. The orientation of stripe pattern is determined by the spatial inhomogeneity. Our numerical results suggest that it may be the most possible mechanism for the forming process of fish skin patterns.

THP-1 monocytes but not macrophages as a potential alternative for CD34+ dendritic cells to identify chemical skin sensitizers

International Nuclear Information System (INIS)

Lambrechts, Nathalie; Verstraelen, Sandra; Lodewyckx, Hanne; Felicio, Ana; Hooyberghs, Jef; Witters, Hilda; Tendeloo, Viggo van; Cauwenberge, Paul van; Nelissen, Inge; Heuvel, Rosette van den; Schoeters, Greet

2009-01-01

Early detection of the sensitizing potential of chemicals is an emerging issue for chemical, pharmaceutical and cosmetic industries. In our institute, an in vitro classification model for prediction of chemical-induced skin sensitization based on gene expression signatures in human CD34 + progenitor-derived dendritic cells (DC) has been developed. This primary cell model is able to closely mimic the induction phase of sensitization by Langerhans cells in the skin, but it has drawbacks, such as the availability of cord blood. The aim of this study was to investigate whether human in vitro cultured THP-1 monocytes or macrophages display a similar expression profile for 13 predictive gene markers previously identified in DC and whether they also possess a discriminating capacity towards skin sensitizers and non-sensitizers based on these marker genes. To this end, the cell models were exposed to 5 skin sensitizers (ammonium hexachloroplatinate IV, 1-chloro-2,4-dinitrobenzene, eugenol, para-phenylenediamine, and tetramethylthiuram disulfide) and 5 non-sensitizers (L-glutamic acid, methyl salicylate, sodium dodecyl sulfate, tributyltin chloride, and zinc sulfate) for 6, 10, and 24 h, and mRNA expression of the 13 genes was analyzed using real-time RT-PCR. The transcriptional response of 7 out of 13 genes in THP-1 monocytes was significantly correlated with DC, whereas only 2 out of 13 genes in THP-1 macrophages. After a cross-validation of a discriminant analysis of the gene expression profiles in the THP-1 monocytes, this cell model demonstrated to also have a capacity to distinguish skin sensitizers from non-sensitizers. However, the DC model was superior to the monocyte model for discrimination of (non-)sensitizing chemicals.

A co-cultured skin model based on cell support membranes

International Nuclear Information System (INIS)

Dai, N.-T.; Yeh, M.-K.; Liu, Demeral David; Adams, E.F.; Chiang, C.-H.; Yen, C.-Y.; Shih, C.-M.; Sytwu, H.-K.; Chen, Tim-Mo; Wang, H.-J.; Williamson, M.R.; Coombes, A.G.A.

2005-01-01

Tissue engineering of skin based on collagen: PCL biocomposites using a designed co-culture system is reported. The collagen: PCL biocomposites having collagen: PCL (w/w) ratios of 1:4, 1:8, and 1:20 have been proven to be biocompatible materials to support both adult normal human epidermal Keratinocyte (NHEK) and mouse 3T3 fibroblast growth in cell culture, respectively, by Dai, Coombes, et al. in 2004. Films of collagen: PCL biocomposites were prepared using non-crosslinking method by impregnation of lyophilized collagen mats with PCL/dichloromethane solutions followed by solvent evaporation. To mimic the dermal/epidermal structure of skin, the 1:20 collagen: PCL biocomposites were selected for a feasibility study of a designed co-culture technique that would subsequently be used for preparing fibroblast/biocomposite/keratinocyte skin models. A 55.3% increase in cell number was measured in the designed co-culture system when fibroblasts were seeded on both sides of a biocomposite film compared with cell culture on one surface of the biocomposite in the feasibility study. The co-culture of human keratinocytes and 3T3 fibroblasts on each side of the membrane was therefore studied using the same co-culture system by growing keratinocytes on the top surface of membrane for 3 days and 3T3 fibroblasts underneath the membrane for 6 days. Scanning electron microscopy (SEM) and immunohistochemistry assay revealed good cell attachment and proliferation of both human keratinocytes and 3T3 fibroblasts with these two types of cells isolated well on each side of the membrane. Using a modified co-culture technique, a co-cultured skin model presenting a confluent epidermal sheet on one side of the biocomposite film and fibroblasts populated on the other side of the film was developed successfully in co-culture system for 28 days under investigations by SEM and immunohistochemistry assay. Thus, the design of a co-culture system based on 1:20 (w/w) collagen: PCL biocomposite

Primary skin fibroblasts as a model of Parkinson's disease

NARCIS (Netherlands)

Auburger, G.; Klinkenberg, M.; Droste, J.A.H.; Marcus, K.; Morales-Gordo, B.; Kunz, W.S.; Brandt, U.; Broccoli, V.; Reichmann, H.; Gispert, S.; Jendrach, M.

2012-01-01

Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts

Fabric-skin models to assess infection transfer for impetigo contagiosa in a kindergarten scenario.

Science.gov (United States)

Gerhardts, A; Henze, S V; Bockmühl, D; Höfer, D

2015-06-01

Children in community bodies like kindergartens are predisposed to suffer from impetigo. To consider important measures for infection prevention, direct and indirect transmission routes of pathogens must be revealed. Therefore, we studied the role of skin and fabrics in the spread of the impetigo pathogen Staphylococcus aureus and the strain Streptococcus equi (surrogate to Streptococcus pyogenes) in order to assess infection transfer in realistic scenarios. The transmission of test strains was studied with standardized fabric-skin models using a technical artificial skin and fabrics of different fiber types commonly occurring in German kindergartens. In synthetic pus, both test strains persisted on artificial skin and fabrics for at least 4 h. Friction enhanced transfer, depending on the fiber type or fabric construction. In a skin-to-skin setup, the total transfer was higher than via fabrics and no decrease in the transmission rates from donor to recipients could be observed after successive direct skin contacts. Children in kindergartens may be at risk of transmission for impetigo pathogens, especially via direct skin contact, but also by the joint use of fabrics, like towels or handicraft materials. Fabric-skin models used in this study enable further insight into the transmission factors for skin infections on the basis of a practical approach.

A tan in a test tube - in vitro models for investigating ultraviolet radiation-induced damage in skin.

Science.gov (United States)

Fernandez, Tara L; Dawson, Rebecca A; Van Lonkhuyzen, Derek R; Kimlin, Michael G; Upton, Zee

2012-06-01

Presently, global rates of skin cancers induced by ultraviolet radiation (UVR) exposure are on the rise. In view of this, current knowledge gaps in the biology of photocarcinogenesis and skin cancer progression urgently need to be addressed. One factor that has limited skin cancer research has been the need for a reproducible and physiologically-relevant model able to represent the complexity of human skin. This review outlines the main currently-used in vitro models of UVR-induced skin damage. This includes the use of conventional two-dimensional cell culture techniques and the major animal models that have been employed in photobiology and photocarcinogenesis research. Additionally, the progression towards the use of cultured skin explants and tissue-engineered skin constructs, and their utility as models of native skin's responses to UVR are described. The inherent advantages and disadvantages of these in vitro systems are also discussed. © 2012 John Wiley & Sons A/S.

Alternative dimensional models of personality disorder

DEFF Research Database (Denmark)

Widiger, Thomas A; Simonsen, Erik

2005-01-01

The recognition of the many limitations of the categorical model of personality disorder classification has led to the development of quite a number of alternative proposals for a dimensional classification. The purpose of this article is to suggest that future research work toward the integration...... of these alternative proposals within a common hierarchical structure. An illustration of a potential integration is provided using the constructs assessed within existing dimensional models. Suggestions for future research that will help lead toward a common, integrative dimensional model of personality disorder...

Gigapixel photography for skin cancer surveillance: a novel alternative to total-body photography.

Science.gov (United States)

Mikailov, Anar; Blechman, Adam

2013-11-01

There is substantial evidence supporting the use of cutaneous imaging in combination with standard total-body skin examinations for early detection and treatment of melanoma. In the last 2 decades, total-body photography (TBP) has been widely used in combination with standard total-body skin examinations for active skin cancer surveillance with proven clinical utility; however, the groundbreaking image detail provided by gigapixel photography (GP) could improve dermatologists' ability to monitor suspicious lesions and therefore could serve a critical role in supplementing traditional total-body skin examinations for skin cancer surveillance. Although it has been successfully implemented in other fields, future studies are required to determine the effectiveness of GP in dermatology.

Testing multi-alternative decision models with non-stationary evidence.

Science.gov (United States)

Tsetsos, Konstantinos; Usher, Marius; McClelland, James L

2011-01-01

Recent research has investigated the process of integrating perceptual evidence toward a decision, converging on a number of sequential sampling choice models, such as variants of race and diffusion models and the non-linear leaky competing accumulator (LCA) model. Here we study extensions of these models to multi-alternative choice, considering how well they can account for data from a psychophysical experiment in which the evidence supporting each of the alternatives changes dynamically during the trial, in a way that creates temporal correlations. We find that participants exhibit a tendency to choose an alternative whose evidence profile is temporally anti-correlated with (or dissimilar from) that of other alternatives. This advantage of the anti-correlated alternative is well accounted for in the LCA, and provides constraints that challenge several other models of multi-alternative choice.

Influential Factors of Mother-Infant Skin-to-Skin Contact Based on the Precede-Proceed Model from the Perspective of Midwives in Torbat Heydariyeh Hospitals

Directory of Open Access Journals (Sweden)

Mohadeseh Adeli

2016-07-01

Full Text Available Background & aim: Skin-to-skin contact immediately after birth plays a pivotal role in proper breastfeeding and mother-infant interaction. Despite numerous benefits of mother-infant skin-to-skin contact, this health behavior is not performed by many midwives. This study aimed to evaluate the influential factors for mother-infant skin-to-skin contact based on the Precede-Proceed model from the perspective of midwives in Torbat Heydariyeh hospitals. Methods:This cross-sectional study was conducted on 50 midwives working in hospitals of Torbat Heydariyeh, Iran in 2015. Demographic data of all participants were collected, and Mother-Newborn Skin-to-Skin Contact Questionnaire was also used based on the Precede-Proceed model. Data analysis was performed in SPSS V.16 using descriptive statistics, tables and graphs. Results: In this study, 88.1% of the midwives had positive attitudes towards skin-to-skin contact, and 90.5% had high perceived self-efficacy in performing the procedure. Major obstacles against establishing proper skin-to-skin contact were neonatal diseases and maternal fatigue (83.3% from the perspective of midwives. Moreover, 87.5% and 90.5% of the midwives emphasized the pivotal role of social support and motivation, respectively in implementing skin-to-skin contact. Also, more than 90% of the midwives considered training programs, service access and adequate facilities to be influential in the proper establishment of skin-to-skin contact. Conclusion: According to the results of this study, the majority of midwives believed that enabling and reinforcing factors had significant effects on the proper establishment of mother-infant skin-to-skin contact. Therefore, it is recommended thateducational interventions be planned for parents, their family members and health care personnel involved in processes of childbirth and infant care. Furthermore, organizational planning and executive procedures should be developed to study the

Retrieval of optical properties of skin from measurement and modeling the diffuse reflectance

Science.gov (United States)

Douven, Lucien F. A.; Lucassen, Gerald W.

2000-06-01

We present results on the retrieval of skin optical properties obtained by fitting of measurements of the diffuse reflectance of human skin. Reflectance spectra are simulated using an analytical model based on the diffusion approximation. This model is implemented in a simplex fit routine. The skin optical model used consists of five layers representing epidermis, capillary blood plexus, dermis, deep blood plexus and hypodermis. The optical properties of each layer are assumed homogeneously distributed. The main optical absorbers included are melanin in epidermis and blood. The experimental setup consists of a HP photospectrometer equipped with a remote fiber head. Total reflectance spectra were measured in the 400 - 820 nm wavelength range on the volar underarm of 19 volunteers under various conditions influencing the blood content and oxygenation degree. Changes in the reflectance spectra were observed. Using the fit routine changes in blood content in the capillary blood plexus and in the deep blood plexus could be quantified. These showed different influences on the total reflectance. The method can be helpful to quantitatively assess changes in skin color appearance such as occurs in the treatment of port wine stains, blanching, skin irritation and tanning.

Streamlined vessels for speedboats: Macro modifications of shark skin design applications

Science.gov (United States)

Ibrahim, M. D.; Amran, S. N. A.; Zulkharnain, A.; Sunami, Y.

2018-01-01

Functional properties of shark denticles have caught the attention of engineers and scientist today due to the hydrodynamic effects of its skin surface roughness. The skin of a fast swimming shark reveals riblet structures that help to reduce skin friction drag, shear stresses, making its movement to be more efficient and faster. Inspired by the structure of the shark skin denticles, our team has conducted a study on alternative on improving the hydrodynamic design of marine vessels by applying the simplified version of shark skin skin denticles on the surface hull of the vessels. Models used for this study are constructed and computational fluid dynamic (CFD) simulations are then carried out to predict the effectiveness of the hydrodynamic effects of the biomimetic shark skins on those models. Interestingly, the numerical calculated results obtained shows that the presence of biomimetic shark skin implemented on the vessels give improvements in the maximum speed as well as reducing the drag force experience by the vessels. The pattern of the wave generated post cruising area behind the vessels can also be observed to reduce the wakes and eddies. Theoretically, reduction of drag force provides a more efficient vessel with a better cruising speed. To further improve on this study, the authors are now actively arranging an experimental procedure in order to verify the numerical results obtained by CFD. The experimental test will be carried out using an 8 metre flow channel provided by University Malaysia Sarawak, Malaysia.

Assessment of dermal toxicity of nanosilica using cultured keratinocytes, a human skin equivalent model and an invivo model

International Nuclear Information System (INIS)

Park, Yoon-Hee; Kim, Ji Na; Jeong, Sang Hoon; Choi, Jae Eun; Lee, Seung-Ho; Choi, Byeong Hyeok; Lee, Jung Pyo; Sohn, Kyung Hee; Park, Kui Lea; Kim, Meyoung-Kon; Son, Sang Wook

2010-01-01

Assessments of skin irritation potentials are important aspects of the development of nanotechnology. Nanosilica is currently being widely used for commercial purposes, but little literature is available on its skin toxicity and irritation potential. This study was designed to determine whether nanosilica has the potential to cause acute cutaneous toxicity, using cultured HaCaT keratinocytes (CHK), a human skin equivalent model (HSEM), and invivo model. Nanosilica was characterized by scanning electron microscopy. We evaluated the cytotoxic effects of nanosilica on CHKs and the HSEM. In addition, we also investigated whether two commercially available nanosilicas with different sizes (7 and 10-20 nm) have different effects. To confirm invitro results, we evaluated the irritation potentials of nanosilicas on rabbit skin. Nanosilicas reduced the cell viabilities of CHKs in a dose-dependent manner. However, the HSEM revealed no irritation at 500 μg/ml of nanosilica. Furthermore, this result concurred with Draize skin irritation test findings. The present study data indicate that nanosilica does not cause acute cutaneous irritation. Furthermore, this study shows that the HSEM used provides more useful screening data than the conventional cell culture model on the relative toxicities of NPs.

Transport lattice models of heat transport in skin with spatially heterogeneous, temperature-dependent perfusion

Directory of Open Access Journals (Sweden)

Martin Gregory T

2004-11-01

Full Text Available Abstract Background Investigation of bioheat transfer problems requires the evaluation of temporal and spatial distributions of temperature. This class of problems has been traditionally addressed using the Pennes bioheat equation. Transport of heat by conduction, and by temperature-dependent, spatially heterogeneous blood perfusion is modeled here using a transport lattice approach. Methods We represent heat transport processes by using a lattice that represents the Pennes bioheat equation in perfused tissues, and diffusion in nonperfused regions. The three layer skin model has a nonperfused viable epidermis, and deeper regions of dermis and subcutaneous tissue with perfusion that is constant or temperature-dependent. Two cases are considered: (1 surface contact heating and (2 spatially distributed heating. The model is relevant to the prediction of the transient and steady state temperature rise for different methods of power deposition within the skin. Accumulated thermal damage is estimated by using an Arrhenius type rate equation at locations where viable tissue temperature exceeds 42°C. Prediction of spatial temperature distributions is also illustrated with a two-dimensional model of skin created from a histological image. Results The transport lattice approach was validated by comparison with an analytical solution for a slab with homogeneous thermal properties and spatially distributed uniform sink held at constant temperatures at the ends. For typical transcutaneous blood gas sensing conditions the estimated damage is small, even with prolonged skin contact to a 45°C surface. Spatial heterogeneity in skin thermal properties leads to a non-uniform temperature distribution during a 10 GHz electromagnetic field exposure. A realistic two-dimensional model of the skin shows that tissue heterogeneity does not lead to a significant local temperature increase when heated by a hot wire tip. Conclusions The heat transport system model of the

Recent developments in skin mimic systems to predict transdermal permeation.

Science.gov (United States)

Waters, Laura J

2015-01-01

In recent years there has been a drive to create experimental techniques that can facilitate the accurate and precise prediction of transdermal permeation without the use of in vivo studies. This review considers why permeation data is essential, provides a brief summary as to how skin acts as a natural barrier to permeation and discusses why in vivo studies are undesirable. This is followed by an in-depth discussion on the extensive range of alternative methods that have been developed in recent years. All of the major 'skin mimic systems' are considered including: in vitro models using synthetic membranes, mathematical models including quantitative structure-permeability relationships (QSPRs), human skin equivalents and chromatographic based methods. All of these model based systems are ideally trying to achieve the same end-point, namely a reliable in vitro-in vivo correlation, i.e. matching non-in vivo obtained data with that from human clinical trials. It is only by achieving this aim, that any new method of obtaining permeation data can be acknowledged as a potential replacement for animal studies, for the determination of transdermal permeation. In this review, the relevance and potential applicability of the various models systems will also be discussed.

Examination of the skin barrier repair/wound healing process using a living skin equivalent model and matrix-assisted laser desorption-ionization-mass spectrometry imaging.

Science.gov (United States)

Lewis, E E L; Barrett, M R T; Freeman-Parry, L; Bojar, R A; Clench, M R

2018-04-01

Examination of the skin barrier repair/wound healing process using a living skin equivalent (LSE) model and matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to identify lipids directly involved as potential biomarkers. These biomarkers may be used to determine whether an in vivo wound is going to heal for example if infected. An in vitro LSE model was wounded with a scalpel blade and assessed at day 4 post-wounding by histology and MALDI-MSI. Samples were sectioned at wound site and were either formalin-fixed paraffin-embedded (FFPE) for histology or snapped frozen (FF) for MSI analysis. The combination of using an in vitro wounded skin model with MSI allowed the identification of lipids involved in the skin barrier repair/wound healing process. The technique was able to highlight lipids directly in the wound site and distinguish differences in lipid distribution between the epidermis and wound site. This novel method of coupling an in vitro LSE with MSI allowed in-depth molecular analysis of the skin barrier repair/wound healing process. The technique allowed the identification of lipids directly involved in the skin barrier repair/wound healing process, indicating these biomarkers may be potentially be used within the clinic. These biomarkers will help to determine, which stage of the skin barrier repair/wound healing process the wound is in to provide the best treatment. © 2018 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Estimating the best laser parameters for skin cancer treatment using finite element models

International Nuclear Information System (INIS)

El-Berry, A.A.; El-Berry, A.A.; Solouma, N.H.; Hassan, F.; Ahmed, A.S.

2010-01-01

Skin cancer is an intimidating disease which necessitates the presence of a non-invasive treatment. Laser-induced thermo therapy is one of the recent noninvasive modalities of superficial lesion treatment. Although of its promising effect, this method still needs more effort to be quantized. Many studies are being conducted for this purpose. Modeling and simulating the process of skin lesion treatment by laser can lead to the best quantization of the treatment protocol. In this paper, we provide finite element models for the treatment of skin cancer using laser thermal effect. A comparison between the effects of using different laser parameters of diode laser (800nm) and Nd: Yag laser (1064 nm) revealed that Nd: Yag laser can be used effectively foe skin cancer treatment specially with high intensities of about 106 w/m 2 .

A New Kind of Biomaterials-Bullfrog Skin Collagen

Institute of Scientific and Technical Information of China (English)

He LI; Bai Ling LIU; Hua Lin CHEN; Li Zhen GAO

2003-01-01

Pepsin-soluble collagen was prepared from bullfrog skin and partially characterized. This study revealed interesting differences, such as molecular weight, amino acid composition, denaturation temperature (Td), in the frog skin collagen when compared to the known vertebrate collagens. This study gives hints that bullfrog skin can be a potential, safe alternative source of collagen from cattle for use in various fields.

New bioprinted skin, cosmetic in vitro model.

Science.gov (United States)

Cadau, Sebastien; Rival, Delphine; Andre-Frei, Valerie; Chavan M, Manasi; Fayol, Delphine; Salducci, Marine; Brisson, Bruno; Guillemot, Fabien

We developed a new evolution of three-dimensional skin equivalent due to the optimization of four-dimensional laser-assisted bioprinting and skin equivalent culture protocols. This allowed us to produce fully bioprinted skin equivalents that are closed to current skin equivalents and suitable to test cosmetic ingredients. Particularly, we performed preliminary evaluation of maturogens to improve the dermis maturation before the epidermal seeding and we designed a specific "micropattern" to reproduce the nonlinear aspect of the dermal-epidermal junction. Finally an active ingredient was applied during the production of the bioprinted skin equivalent.

Measurement of conformability and adhesion energy of polymeric ultrathin film to skin model

Science.gov (United States)

Sugano, Junki; Fujie, Toshinori; Iwata, Hiroyasu; Iwase, Eiji

2018-06-01

We measured the conformability and adhesion energy of a polymeric ultrathin film “nanosheet” with hundreds of nanometer thickness to a skin model with epidermal depressions. To compare the confirmability of the nanosheets with different thicknesses and/or under different attaching conditions, we proposed a measurement method using skin models with the same surface profile and defined the surface strain εS as the quantified value of the conformability. Then, we measured the adhesion energy of the nanosheet at each conformability through a vertical tensile test. Experimental results indicate that the adhesion energy does not depend on the liquid used in wetting the nanosheet before attaching to the skin model and increases monotonously as the surface strain εS increases.

An alternative method for facial resurfacing: supraclavicular skin prefabrication by perforator fascia flap.

Science.gov (United States)

Hocaoğlu, Emre

2014-01-01

Prefabrication of supraclavicular skin provides a useful source for flaps congruent with the face skin. Among various vascular sources that have been used for this purpose, anterolateral thigh fascia seems to represent a greater value because of having a long and strong vascular pedicle and negligible donor-site morbidity. In this regard, we present a technical report on using the lateral circumflex femoral artery perforator flap harvest technique in preparing an anterolateral thigh fascia flap for the prefabrication of the supraclavicular skin. The technique proved successful in resurfacing the facial skin of a young female patient with a giant congenital melanocytic hairy nevus on the left side of her face.

Numerical tension adjustment of x-ray membrane to represent goat skin kompang

Science.gov (United States)

Siswanto, Waluyo Adi; Abdullah, Muhammad Syiddiq Bin

2017-04-01

This paper presents a numerical membrane model of traditional musical instrument kompang that will be used to find the parameter of membrane tension of x-ray membrane representing the classical goat-skin membrane of kompang. In this study, the experiment towards the kompang is first conducted in an acoustical anechoic enclosure and in parallel a mathematical model of the kompang membrane is developed to simulate the vibration of the kompang membrane in polar coordinate by implementing Fourier-Bessel wave function. The wave equation in polar direction in mode 0,1 is applied to provide the corresponding natural frequencies of the circular membrane. The value of initial and boundary conditions in the function is determined from experiment to allow the correct development of numerical equation. The numerical mathematical model is coded in SMath for the accurate numerical analysis as well as the plotting tool. Two kompang membrane cases with different membrane materials, i.e. goat skin and x-ray film membranes with fixed radius of 0.1 m are used in the experiment. An alternative of kompang's membrane made of x-ray film with the appropriate tension setting can be used to represent the sound of traditional goat-skin kompang. The tension setting of the membrane to resemble the goat-skin is 24N. An effective numerical tool has been develop to help kompang maker to set the tension of x-ray membrane. In the future application, any tradional kompang with different size can be replaced by another membrane material if the tension is set to the correct tension value. The developed numerical tool is useful and handy to calculate the tension of the alternative membrane material.

Derivation and application of mathematical model for well test analysis with variable skin factor in hydrocarbon reservoirs

Directory of Open Access Journals (Sweden)

Pengcheng Liu

2016-06-01

Full Text Available Skin factor is often regarded as a constant in most of the mathematical model for well test analysis in oilfields, but this is only a kind of simplified treatment with the actual skin factor changeable. This paper defined the average permeability of a damaged area as a function of time by using the definition of skin factor. Therefore a relationship between a variable skin factor and time was established. The variable skin factor derived was introduced into existing traditional models rather than using a constant skin factor, then, this newly derived mathematical model for well test analysis considering variable skin factor was solved by Laplace transform. The dimensionless wellbore pressure and its derivative changed with dimensionless time were plotted with double logarithm and these plots can be used for type curve fitting. The effects of all the parameters in the expression of variable skin factor were analyzed based on the dimensionless wellbore pressure and its derivative. Finally, actual well testing data were used to fit the type curves developed which validates the applicability of the mathematical model from Sheng-2 Block, Shengli Oilfield, China.

Photoreactivity of tiaprofenic acid and suprofen using pig skin as an ex vivo model.

Science.gov (United States)

Sarabia, Z; Hernández, D; Castell, J V; van Henegouwen, G M

2000-10-01

The skin is repeatedly exposed to solar ultraviolet radiation. Photoreaction of drugs in the body may result in phototoxic or photoallergic side effects. Non-steroidal anti-inflammatory drugs, such as tiaprofenic acid (TPA) and the closely related isomer suprofen (SUP) are frequently associated with photosensitive disorders; they may mediate photosensitised damage to lipids, proteins and nucleic acids. Using ex vivo pig skin as a model, we investigated the photodegradation of TPA and SUP, and photobinding of these drugs to protein by means of HPLC analysis and drug-directed antibodies. Both with keratinocytes, which were first isolated from the pig skin and thereafter exposed to UVA and with keratinocytes which were isolated from pig skin after the skin was UVA exposed, time-dependent photodegradation of TPA and SUP was found, beside photoadduct formation to protein. The results of this work show that: (a) TPA and SUP were photodecomposed with similar efficiency; major photoproducts detected were decarboxytiaprofenic acid (DTPA) and decarboxysuprofen (DSUP), respectively. (b) Both drugs form photoadducts, as concluded from recognition by drug-specific antibodies. Pig skin appears to be a good model for studying the skin photosensitising potential of drugs.

Biochemical characteristics of four marine fish skins in Korea.

Science.gov (United States)

Cho, Jae-Kwon; Jin, Young-Guk; Rha, Sung-Ju; Kim, Seon-Jae; Hwang, Jae-Ho

2014-09-15

In this study, we investigated the biochemical characteristics of the fish skins of four industrial species: olive flounder (Paralichthys olivaceus), black rockfish (Sebastes schlegeli), sea bass (Lateolabrax maculatus) and red sea bream (Pagrus major). There is high domestic demand in Korea for farming of these fish for human consumption. Crude protein contents in the skin of these fish ranged from 73% to 94% by dry weight; this was in part due to a high content of the structural protein, collagen. Among the four species, olive flounder had the thickest dermal and epidermal layers in the dorsal skin. This species was also associated with the highest extraction ratio of acid-soluble collagen. We also examined whether fish skin could be a cost-effective alternative to current fish meal sources. Our analysis indicates that, when supplemented with additional fish oils and essential amino acids, fish skin is a viable alternative for fish meal formulations. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

OpenAIRE

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

2016-01-01

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

Examining Pedestrian Injury Severity Using Alternative Disaggregate Models

DEFF Research Database (Denmark)

Abay, Kibrom Araya

2013-01-01

This paper investigates the injury severity of pedestrians considering detailed road user characteristics and alternative model specification using a high-quality Danish road accident data. Such detailed and alternative modeling approach helps to assess the sensitivity of empirical inferences...... to the choice of these models. The empirical analysis reveals that detailed road user characteristics such as crime history of drivers and momentary activities of road users at the time of the accident provides an interesting insight in the injury severity analysis. Likewise, the alternative analytical...... specification of the models reveals that some of the conventionally employed fixed parameters injury severity models could underestimate the effect of some important behavioral attributes of the accidents. For instance, the standard ordered logit model underestimated the marginal effects of some...

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

Science.gov (United States)

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

2017-01-01

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

Characterization of dendritic cells subpopulations in skin and afferent lymph in the swine model.

Directory of Open Access Journals (Sweden)

Florian Marquet

Full Text Available Transcutaneous delivery of vaccines to specific skin dendritic cells (DC subsets is foreseen as a promising strategy to induce strong and specific types of immune responses such as tolerance, cytotoxicity or humoral immunity. Because of striking histological similarities between human and pig skin, pig is recognized as the most suitable model to study the cutaneous delivery of medicine. Therefore improving the knowledge on swine skin DC subsets would be highly valuable to the skin vaccine field. In this study, we showed that pig skin DC comprise the classical epidermal langerhans cells (LC and dermal DC (DDC that could be divided in 3 subsets according to their phenotypes: (1 the CD163(neg/CD172a(neg, (2 the CD163(highCD172a(pos and (3 the CD163(lowCD172a(pos DDC. These subtypes have the capacity to migrate from skin to lymph node since we detected them in pseudo-afferent lymph. Extensive phenotyping with a set of markers suggested that the CD163(high DDC resemble the antibody response-inducing human skin DC/macrophages whereas the CD163(negCD172(low DDC share properties with the CD8(+ T cell response-inducing murine skin CD103(pos DC. This work, by showing similarities between human, mouse and swine skin DC, establishes pig as a model of choice for the development of transcutaneous immunisation strategies targeting DC.

In vivo effect of carbon dioxide laser-skin resurfacing and mechanical abrasion on the skin's microbial flora in an animal model.

Science.gov (United States)

Manolis, Evangelos N; Tsakris, Athanassios; Kaklamanos, Ioannis; Markogiannakis, Antonios; Siomos, Konstadinos

2006-03-01

Although beam-scanning carbon dioxide (CO2) lasers have provided a highly efficient tool for esthetic skin rejuvenation there has been no comprehensive animal studies looking into microbial skin changes following CO2 laser skin resurfacing. To evaluate the in vivo effects of CO2 laser skin resurfacing in an experimental rat model in comparison with mechanical abrasion on the skin microbial flora. Four separate cutaneous sections of the right dorsal surface of 10 Wistar rats were treated with a CO2 laser, operating at 18 W and delivering a radiant energy of 5.76 J/cm2, while mechanical abrasions of the skin were created on four sections of the left dorsal surface using a scalpel. Samples for culture and biopsies were obtained from the skin surfaces of the rats on day 1 of application of the CO2 laser or mechanical abrasion, as well as 10, 30, and 90 days after the procedure. The presence of four microorganisms (staphylococci, streptococci, diphtheroids, and yeasts) was evaluated as a microbe index for the skin flora, and colony counts were obtained using standard microbiological methods. Skin biopsy specimens, following CO2 laser treatment, initially showed epidermal and papillary dermal necrosis and later a re-epithelization of the epidermis as well as the generation of new collagen on the upper papillary dermis. The reduction in microbial counts on day 1 of the CO2 laser-inflicted wound was statistically significant for staphylococci and diphtheroids compared with the baseline counts (p=.004 and pSkin resurfacing using CO2 lasers considerably reduces microbial counts of most microorganisms in comparison with either normal skin flora or a scalpel-inflicted wound. This might contribute to the positive clinical outcome of laser skin resurfacing.

Psychological interventions in the management of common skin conditions

Directory of Open Access Journals (Sweden)

Philip D Shenefelt

2010-03-01

Full Text Available Philip D ShenefeltDepartment of Dermatology and Cutaneous Surgery, College of Medicine, University of South Florida, Tampa, Florida, USAAbstract: The nervous system and the skin develop next to each other in the embryo and remain intimately interconnected and interactive throughout life. The nervous system can influence skin conditions through psychoneuroimmunoendocrine mechanisms and through behaviors. Understanding the pathophysiology aids in selection of treatment plans for correcting the negative effects of the psyche on specific skin conditions. Medication options include standard psychotropic medications and alternative herbs and supplements. Other options include biofeedback, cognitive-behavioral methods, hypnosis, meditation, progressive relaxation, the placebo effect, and suggestion. When simple measures fail, combining medications with other therapeutic options may produce better results. Skin conditions that have strong psychophysiologic aspects may respond well to techniques such as biofeedback, cognitive-behavioral methods, hypnosis, meditation, or progressive relaxation that help to counteract stress. Treatment of primary psychiatric disorders that negatively influence skin conditions often results in improvement of those skin conditions. Abnormal conditions of the skin, hair, and nails can also influence the psyche negatively. Treatment of secondary psychiatric disorders such as anxiety or depression that are triggered or exacerbated by the appearance of these skin conditions or the associated discomfort may also be required.Keywords: psychodermatology, psychosomatic, psychocutaneous, skin disorders, treatment, standard, alternative, non-drug

INTERACTION OF FEMTOSECOND LASER RADIATION WITH SKIN: MATHEMATICAL MODEL

Directory of Open Access Journals (Sweden)

Pavel Yu. Rogov

2017-03-01

Full Text Available The features of human skin response to the impact of femtosecond laser radiation were researched. The Monte–Carlo method was used for estimation of the radiation penetration depth into the skin cover. We used prevalent wavelength equal to 800 nm (for Ti: sapphire laser femtosecond systems. A mathematical model of heat transfer process was introduced based on the analytical solution of the system of equations describing the dynamics of the electron and phonon subsystems. An experiment was carried out to determine the threshold energy of biological tissue injury (chicken skin was used as a test object. The value of electronic subsystem relaxation time was determined from the experiment and is in keeping with literature data. The results of this work can be used to assess the maximum permissible exposure of laser radiation of different lengths that cause the damage of biological tissues, as well as for the formation of safe operation standards for femtosecond laser systems.

Modeling and Measurements of Alternating Magnetic Signatures of Ships

Directory of Open Access Journals (Sweden)

Zhiqiang Wu

2015-03-01

Full Text Available The alternating electric and magnetic fields are new contributors to the global electromagnetic silencing of ships. Thus, modeling and measurements of alternating magnetic signatures should be a research priority in maritime engineering. In this paper, an alternating horizontal electric dipole is adopted to model the electromagnetic fields related with corrosion. Formulas for alternating magnetic fields generated in shallow sea by horizontal electric dipole are derived based on an air-sea-seabed three-layered model and a numerical computer is also applied. In addition, the alternating magnetic fields of a ship are measured using a tri-axis fluxgate magnetometer fixed in a swaying platform. The characteristics of these fields are analyzed. Finally, the equivalent dipole moment of the trial ship is predicted by contrasting the model results and the observed data.

Modelling drug flux through microporated skin.

Science.gov (United States)

Rzhevskiy, Alexey S; Guy, Richard H; Anissimov, Yuri G

2016-11-10

A simple mathematical equation has been developed to predict drug flux through microporated skin. The theoretical model is based on an approach applied previously to water evaporation through leaf stomata. Pore density, pore radius and drug molecular weight are key model parameters. The predictions of the model were compared with results derived from a simple, intuitive method using porated area alone to estimate the flux enhancement. It is shown that the new approach predicts significantly higher fluxes than the intuitive analysis, with transport being proportional to the total pore perimeter rather than area as intuitively anticipated. Predicted fluxes were in good general agreement with experimental data on drug delivery from the literature, and were quantitatively closer to the measured values than those derived from the intuitive, area-based approach. Copyright © 2016 Elsevier B.V. All rights reserved.

Modeling and simulation of heat distribution in human skin caused by laser irradiation

NARCIS (Netherlands)

Luan, Y.; Dams, S.D.

2009-01-01

Study of light-based skin rejuvenation needs prospective insights of mechanism of laser tissue interaction. A well-built model plays a key role in predicting temperature distribution in human skin exposed to laser irradiation. Therefore, it not only provides guidance for in vitro experiment, but

An Animal Model of Trichloroethylene-Induced Skin Sensitization in BALB/c Mice.

Science.gov (United States)

Wang, Hui; Zhang, Jia-xiang; Li, Shu-long; Wang, Feng; Zha, Wan-sheng; Shen, Tong; Wu, Changhao; Zhu, Qi-xing

2015-01-01

Trichloroethylene (TCE) is a major occupational hazard and environmental contaminant that can cause multisystem disorders in the form of occupational medicamentosa-like dermatitis. Development of dermatitis involves several proinflammatory cytokines, but their role in TCE-mediated dermatitis has not been examined in a well-defined experimental model. In addition, few animal models of TCE sensitization are available, and the current guinea pig model has apparent limitations. This study aimed to establish a model of TCE-induced skin sensitization in BALB/c mice and to examine the role of several key inflammatory cytokines on TCE sensitization. The sensitization rate of dorsal painted group was 38.3%. Skin edema and erythema occurred in TCE-sensitized groups, as seen in 2,4-dinitrochlorobenzene (DNCB) positive control. Trichloroethylene sensitization-positive (dermatitis [+]) group exhibited increased thickness of epidermis, inflammatory cell infiltration, swelling, and necrosis in dermis and around hair follicle, but ear painted group did not show these histological changes. The concentrations of serum proinflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2 were significantly increased in 24, 48, and 72 hours dermatitis [+] groups treated with TCE and peaked at 72 hours. Deposition of TNF-α, IFN-γ, and IL-2 into the skin tissue was also revealed by immunohistochemistry. We have established a new animal model of skin sensitization induced by repeated TCE stimulations, and we provide the first evidence that key proinflammatory cytokines including TNF-α, IFN-γ, and IL-2 play an important role in the process of TCE sensitization. © The Author(s) 2015.

Sun Exposure, Tanning Beds, and Herbs That Cure: An Examination of Skin Cancer on Pinterest.

Science.gov (United States)

Tang, Lu; Park, Sung-Eun

2017-10-01

Skin cancer is the most common cancer affecting the U.S. Pinterest.com, a virtual bookmarking social media site, has the potential to disseminate skin cancer-related information among young women, the group with the fastest increase in skin cancer diagnosis. This article presents a quantitative content analysis of pins about skin cancer on Pinterest guided by agenda-setting theory and the health belief model. Overall, sun exposure and tanning beds were most frequently discussed as the causes of skin cancer, and alternative therapies such as herbal medicine were discussed more than traditional biomedical treatment or prevention. Highly repinned pins tend to include more information than regular pins. Different types of skin cancer (melanoma, squamous-cell carcinoma, and basal-cell carcinoma) received the same amount of coverage; however, pins about nonmelanoma skin cancer (such as squamous-cell carcinoma and basal-cell carcinoma) were often information-poor. They were less likely to include information on the causes, prevention, and the biomedical treatment of skin cancer and were less likely to include health belief constructs associated with the promotion of skin cancer prevention and treatment.

Full-thickness skin wound healing using autologous keratinocytes and dermal fibroblasts with fibrin: bilayered versus single-layered substitute.

Science.gov (United States)

Idrus, Ruszymah Bt Hj; Rameli, Mohd Adha bin P; Low, Kiat Cheong; Law, Jia Xian; Chua, Kien Hui; Latiff, Mazlyzam Bin Abdul; Saim, Aminuddin Bin

2014-04-01

Split-skin grafting (SSG) is the gold standard treatment for full-thickness skin defects. For certain patients, however, an extensive skin lesion resulted in inadequacies of the donor site. Tissue engineering offers an alternative approach by using a very small portion of an individual's skin to harvest cells for propagation and biomaterials to support the cells for implantation. The objective of this study was to determine the effectiveness of autologous bilayered tissue-engineered skin (BTES) and single-layer tissue-engineered skin composed of only keratinocytes (SLTES-K) or fibroblasts (SLTES-F) as alternatives for full-thickness wound healing in a sheep model. Full-thickness skin biopsies were harvested from adult sheep. Isolated fibroblasts were cultured using medium Ham's F12: Dulbecco modified Eagle medium supplemented with 10% fetal bovine serum, whereas the keratinocytes were cultured using Define Keratinocytes Serum Free Medium. The BTES, SLTES-K, and SLTES-F were constructed using autologous fibrin as a biomaterial. Eight full-thickness wounds were created on the dorsum of the body of the sheep. On 4 wounds, polyvinyl chloride rings were used as chambers to prevent cell migration at the edge. The wounds were observed at days 7, 14, and 21. After 3 weeks of implantation, the sheep were euthanized and the skins were harvested. The excised tissues were fixed in formalin for histological examination via hematoxylin-eosin, Masson trichrome, and elastin van Gieson staining. The results showed that BTES, SLTES-K, and SLTES-F promote wound healing in nonchambered and chambered wounds, and BTES demonstrated the best healing potential. In conclusion, BTES proved to be an effective tissue-engineered construct that can promote the healing of full-thickness skin lesions. With the support of further clinical trials, this procedure could be an alternative to SSG for patients with partial- and full-thickness burns.

An Alternative Treatment Strategy for Complicated Chronic Wounds: Negative Pressure Therapy over Mesh Skin Graft

Directory of Open Access Journals (Sweden)

Michele Maruccia

2017-01-01

Full Text Available Extensive skin defect represents a real problem and major challenge in plastic and reconstructive surgery. On one hand, skin grafts offer a practical method to deal with skin defects despite their unsuitability for several complicated wounds. On the other hand, negative pressure wound therapy (NPWT, applied before skin grafting, promotes granulation tissue growth. The aim of the study is to evaluate the improvement in wound healing given by the merger of these two different approaches. We treated 23 patients for large wounds of multiple factors. Of these, 15 were treated with the application of V.A.C.® Therapy (KCI Medical S.r.l., Milan, Italy, in combination with skin grafts after a prior unsuccessful treatment of 4 weeks with mesh skin grafts and dressings. Another 8 were treated with only mesh skin graft. Pain reduction and wound area reduction were found statistically significant (p<0.0009, p<0.0001. Infection was resolved in almost all patients. According to our study, the use of the negative pressure wound therapy over mesh skin grafts is significantly effective especially in wounds resistant to conventional therapies, thereby improving the rate of skin graft take.

The role of subcutaneous tissue stiffness on microneedle performance in a representative in vitro model of skin.

Science.gov (United States)

Moronkeji, K; Todd, S; Dawidowska, I; Barrett, S D; Akhtar, R

2017-11-10

There has been growing interest in the mechanical behaviour of skin due to the rapid development of microneedle devices for drug delivery applications into skin. However, most in vitro experimentation studies that are used to evaluate microneedle performance do not consider the biomechanical properties of skin or that of the subcutaneous layers. In this study, a representative experimental model of skin was developed which was comprised of subcutaneous and muscle mimics. Neonatal porcine skin from the abdominal and back regions was used, with gelatine gels of differing water content (67, 80, 88 and 96%) to represent the subcutaneous tissue, and a type of ballistic gelatine, Perma-Gel®, as a muscle mimic. Dynamic nanoindentation was used to characterize the mechanical properties of each of these layers. A custom-developed impact test rig was used to apply dense polymethylmethacrylate (PMMA) microneedles to the skin models in a controlled and repeatable way with quantification of the insertion force and velocity. Image analysis methods were used to measure penetration depth and area of the breach caused by microneedle penetration following staining and optical imaging. The nanoindentation tests demonstrated that the tissue mimics matched expected values for subcutaneous and muscle tissue, and that the compliance of the subcutaneous mimics increased linearly with water content. The abdominal skin was thinner and less stiff as compared to back skin. The maximum force decreased with gel water content in the abdominal skin but not in the back skin. Overall, larger and deeper perforations were found in the skin models with increasing water content. These data demonstrate the importance of subcutaneous tissue on microneedle performance and the need for representative skin models in microneedle technology development. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Modeling skin collimation using the electron pencil beam redefinition algorithm

International Nuclear Information System (INIS)

Chi, Pai-Chun M.; Hogstrom, Kenneth R.; Starkschall, George; Antolak, John A.; Boyd, Robert A.

2005-01-01

Skin collimation is an important tool for electron beam therapy that is used to minimize the penumbra when treating near critical structures, at extended treatment distances, with bolus, or using arc therapy. It is usually made of lead or lead alloy material that conforms to and is placed on patient surface. Presently, commercially available treatment-planning systems lack the ability to model skin collimation and to accurately calculate dose in its presence. The purpose of the present work was to evaluate the use of the pencil beam redefinition algorithm (PBRA) in calculating dose in the presence of skin collimation. Skin collimation was incorporated into the PBRA by terminating the transport of electrons once they enter the skin collimator. Both fixed- and arced-beam dose calculations for arced-beam geometries were evaluated by comparing them with measured dose distributions for 10- and 15-MeV beams. Fixed-beam dose distributions were measured in water at 88-cm source-to-surface distance with an air gap of 32 cm. The 6x20-cm 2 field (dimensions projected to isocenter) had a 10-mm thick lead collimator placed on the surface of the water with its edge 5 cm inside the field's edge located at +10 cm. Arced-beam dose distributions were measured in a 13.5-cm radius polystyrene circular phantom. The beam was arced 90 deg. (-45 deg. to +45 deg. ), and 10-mm thick lead collimation was placed at ±30 deg. . For the fixed beam at 10 MeV, the PBRA-calculated dose agreed with measured dose to within 2.0-mm distance to agreement (DTA) in the regions of high-dose gradient and 2.0% in regions of low dose gradient. At 15 MeV, the PBRA agreed to within a 2.0-mm DTA in the regions of high-dose gradient; however, the PBRA underestimated the dose by as much as 5.3% over small regions at depths less than 2 cm because it did not model electrons scattered from the edge of the skin collimation. For arced beams at 10 MeV, the agreement was 1-mm DTA in the high-dose gradient regions, and 2

Chronic ultraviolet exposure-induced p53 gene alterations in sencar mouse skin carcinogenesis model

International Nuclear Information System (INIS)

Tong, Ying; Smith, M.A.; Tucker, S.B.

1997-01-01

Alterations of the tumor suppressor gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12124 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → G, and one A → T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin. 40 refs., 5 figs., 1 tab

Methylquercetins stimulate melanin biosynthesis in a three-dimensional skin model.

Science.gov (United States)

Yamauchi, Kosei; Mitsunaga, Tohru

2018-03-01

In a previous study, we found that both synthetic 3-O-methylquercetin (3MQ) and 3,4',7-O-trimethylquercetin (34'7TMQ) increased extracellular melanin content. 34'7TMQ increased the activity of melanogenic enzymes by stimulating the p38 pathway and the expression of microphthalmia-associated transcription factor (MITF). In contrast, 3MQ increased the activity of melanogenic enzymes without the involvement of MITF, which suggests that 3MQ inhibits the degradation of melanogenic enzymes. In the present study, we investigated the effects of 3MQ and 34'7TMQ on melanogenesis in normal human melanocytes and using a commercial three-dimensional (3D) skin model system. Both 3MQ and 34'7TMQ elongated the dendrites of normal human melanocytes from a Caucasian donor, but did not stimulate melanogenesis in the melanocytes. In the 3D skin model, which included melanocytes from an Asian donor, 3MQ and 34'7TMQ increased and elongated the melanocytes and showed a tendency to stimulate melanogenesis. These results suggest that 3MQ and 34'7TMQ could be put to practical use in skin care products and agents aimed at preventing hair graying.

Evaluation of calcium alginate gel as electrode material for alternating current iontophoresis of lidocaine using excised rat skin.

Science.gov (United States)

Ebisawa, Tomoko; Nakajima, Atsushi; Haida, Haruka; Wakita, Ryo; Ando, Shizuka; Yoshioka, Tomohiko; Ikoma, Toshiyuki; Tanaka, Junzo; Fukayama, Haruhisa

2014-06-27

Iontophoresis (IOP) is a noninvasive method of delivering medication transcutaneously through the skin. The electrodes used in this method should tightly fit to rough and irregular surfaces and be biologically safe, easy to handle and prepare, and cost-effective. To satisfy these requirements, calcium alginate gel can be a candidate electrode for IOP. Using calcium alginate gel electrodes, we examined whether lidocaine can be effectively transported across an excised rat skin by squarewave alternating current (AC) application. A squarewave AC with either a 70% or 80% duty cycle was continuously applied to 0.5% calcium alginate gel electrodes containing 10% lidocaine at 10 V and 1 kHz for 60 min. Lidocaine concentration was measured using a spectrophotometer and the temperature of the gel was determined. The lidocaine concentrations for AC-IOP at the 70% and 80% duty cycles were significantly higher than that without AC-IOP. Furthermore, the group with the 80% duty cycle showed higher lidocaine concentrations than the group with the 70% duty cycle. The temperatures of all the groups were lower than 28 °C throughout the procedure. In conclusion, the calcium alginate gel can be used as a possible matrix for IOP electrodes.

Non-invasive method for quantitative evaluation of exogenous compound deposition on skin.

Science.gov (United States)

Stamatas, Georgios N; Wu, Jeff; Kollias, Nikiforos

2002-02-01

Topical application of active compounds on skin is common to both pharmaceutical and cosmetic industries. Quantification of the concentration of a compound deposited on the skin is important in determining the optimum formulation to deliver the pharmaceutical or cosmetic benefit. The most commonly used techniques to date are either invasive or not easily reproducible. In this study, we have developed a noninvasive alternative to these techniques based on spectrofluorimetry. A mathematical model based on diffusion approximation theory is utilized to correct fluorescence measurements for the attenuation caused by endogenous skin chromophore absorption. The limitation is that the compound of interest has to be either fluorescent itself or fluorescently labeled. We used the method to detect topically applied salicylic acid. Based on the mathematical model a calibration curve was constructed that is independent of endogenous chromophore concentration. We utilized the method to localize salicylic acid in epidermis and to follow its dynamics over a period of 3 d.

Effect of microneedle geometry and supporting substrate on microneedle array penetration into skin.

Science.gov (United States)

Kochhar, Jaspreet Singh; Quek, Ten Cheer; Soon, Wei Jun; Choi, Jaewoong; Zou, Shui; Kang, Lifeng

2013-11-01

Microneedles are being fast recognized as a useful alternative to injections in delivering drugs, vaccines, and cosmetics transdermally. Owing to skin's inherent elastic properties, microneedles require an optimal geometry for skin penetration. In vitro studies, using rat skin to characterize microneedle penetration in vivo, require substrates with suitable mechanical properties to mimic human skin's subcutaneous tissues. We tested the effect of these two parameters on microneedle penetration. Geometry in terms of center-to-center spacing of needles was investigated for its effect on skin penetration, when placed on substrates of different hardness. Both hard (clay) and soft (polydimethylsiloxane, PDMS) substrates underneath rat skin and full-thickness pig skin were used as animal models and human skins were used as references. It was observed that there was an increase in percentage penetration with an increase in needle spacing. Microneedle penetration with PDMS as a support under stretched rat skin correlated better with that on full-thickness human skin, while penetration observed was higher when clay was used as a substrate. We showed optimal geometries for efficient penetration together with recommendation for a substrate that could better mimic the mechanical properties of human subcutaneous tissues, when using microneedles fabricated from poly(ethylene glycol)-based materials. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Skin absorption through atopic dermatitis skin

DEFF Research Database (Denmark)

Halling-Overgaard, A-S; Kezic, S; Jakasa, I

2017-01-01

Patients with atopic dermatitis have skin barrier impairment in both lesional and non-lesional skin. They are typically exposed to emollients daily and topical anti-inflammatory medicaments intermittently, hereby increasing the risk of developing contact allergy and systemic exposed to chemicals...... ingredients found in these topical preparations. We systematically searched for studies that investigated skin absorption of various penetrants, including medicaments, in atopic dermatitis patients, but also animals with experimentally induced dermatitis. We identified 40 articles, i.e. 11 human studies...... examining model penetrants, 26 human studies examining atopic dermatitis drugs and 3 animal studies. We conclude that atopic dermatitis patients have nearly two-fold increased skin absorption when compared to healthy controls. There is a need for well-designed epidemiological and dermato...

Big bang nucleosynthesis - The standard model and alternatives

Science.gov (United States)

Schramm, David N.

1991-01-01

The standard homogeneous-isotropic calculation of the big bang cosmological model is reviewed, and alternate models are discussed. The standard model is shown to agree with the light element abundances for He-4, H-2, He-3, and Li-7 that are available. Improved observational data from recent LEP collider and SLC results are discussed. The data agree with the standard model in terms of the number of neutrinos, and provide improved information regarding neutron lifetimes. Alternate models are reviewed which describe different scenarios for decaying matter or quark-hadron induced inhomogeneities. The baryonic density relative to the critical density in the alternate models is similar to that of the standard model when they are made to fit the abundances. This reinforces the conclusion that the baryonic density relative to critical density is about 0.06, and also reinforces the need for both nonbaryonic dark matter and dark baryonic matter.

Frog skin function revisited

DEFF Research Database (Denmark)

Hviid Larsen, Erik; Ramløv, Hans

2013-01-01

of the epidermis. These mechanisms have evolved pari passu with life alternating between aquatic and terrestrial habitats associated with permeabilities of the skin controlled by external ion- and osmotic concentrations (loc. cit.). This allows for fast switching of the cutaneous uptake of chloride between active...

Surfactant-induced skin irritation and skin repair. Evaluation of the acute human irritation model by noninvasive techniques.

Science.gov (United States)

Wilhelm, K P; Freitag, G; Wolff, H H

1994-06-01

Although the induction of irritant dermatitis by surfactants has been extensively studied in recent years, our understanding of the repair phase of irritant dermatitis is limited. We investigated qualitative and quantitative differences in surfactant-induced irritant skin reactions from short-term exposure to three structurally different surfactants. Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (0.5%) were applied for 24 hours to the volar aspect of the forearm of 11 volunteers. Irritant reactions were assessed until complete healing was indicated by visual assessment and by various aspects of skin function, that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). SLS and DTAB induced similar degrees of erythema, whereas SLS induced significantly higher TEWL increase. Although both erythema and TEWL were highest 1 hour after exposure to surfactants, skin dryness was a symptom with delayed onset, justifying the long observation period in this study. Minimum hydration values were measured as late as 7 days after surfactant exposure. Dryness was significantly more pronounced in areas exposed to SLS than in areas exposed to DTAB. Complete repair of the irritant reaction induced by either SLS or DTAB was achieved 17 days after surfactant exposure. Stratum corneum hydration was the last feature to return to baseline values. Potassium soap did not significantly influence any skin function. We emphasize the importance of extended periods needed before a patient with irritant contact dermatitis can be reexposed to irritant substances. The evaluation of the irritation potential of diverse surfactants depended significantly on the feature (erythema vs hydration and TEWL) measured.

An Alternative Approach to the Extended Drude Model

Science.gov (United States)

Gantzler, N. J.; Dordevic, S. V.

2018-05-01

The original Drude model, proposed over a hundred years ago, is still used today for the analysis of optical properties of solids. Within this model, both the plasma frequency and quasiparticle scattering rate are constant, which makes the model rather inflexible. In order to circumvent this problem, the so-called extended Drude model was proposed, which allowed for the frequency dependence of both the quasiparticle scattering rate and the effective mass. In this work we will explore an alternative approach to the extended Drude model. Here, one also assumes that the quasiparticle scattering rate is frequency dependent; however, instead of the effective mass, the plasma frequency becomes frequency-dependent. This alternative model is applied to the high Tc superconductor Bi2Sr2CaCu2O8+δ (Bi2212) with Tc = 92 K, and the results are compared and contrasted with the ones obtained from the conventional extended Drude model. The results point to several advantages of this alternative approach to the extended Drude model.

Appraisal of alternative skin model for the study of epidermal restoration following exposure to various environmental stress agents: ionising radiation and UV B

International Nuclear Information System (INIS)

Isoir, M.

2006-06-01

Human skin is a major target tissue for ionising radiation (IR) and UV B. We developed a skin explant model and used 2 types of keratinocytes to study survival and oxidative stress induced by these radiations. We examined oxidative damages by measuring R.O.S. produced and cellular anti-oxidant defenses induced. We observed into skin exposed to IR a modulation of genes expression implied in the control of oxidative stress, confirmed by the decrease of catalase, glutathione peroxidase and superoxide dismutase enzymatic activities. The imbalance observed between anti- and pro-apoptotic genes expression shows that keratinocytes apoptosis may be partly dependent on radio-induced R.O.S. production. We showed the difference of radiosensitivity between N.H.E.K. and Ha Ca.T., which may be linked to their differential oxidative responses. In addition, during re-epithelialising, we demonstrated that activated N.H.E.K. after IR express keratin 6, release pro-inflammatory cytokines and proliferate, without modification of their differentiation. Treatment of N.H.E.K. with geranyl geranylacetone (G.G.A.) has a beneficial effect on their radio-induced activation by increasing IL-1 release, their migration in scrapped area and their survival. G.G.A. has an anti apoptotic ability (induction of Hsp70- caspase-3 pathway) and migratory properties (P38/RhoA activation) on N.H.E.K., but after IR, only caspase-3 pathway is induced. This work thus contributes to the understanding of cutaneous damages after IR and G.G.A. mechanism of action which accelerates re-epithelialising. (author)

Alternatives to quintessence model building

International Nuclear Information System (INIS)

Avelino, P.P.; Beca, L.M.G.; Pinto, P.; Carvalho, J.P.M. de; Martins, C.J.A.P.

2003-01-01

We discuss the issue of toy model building for the dark energy component of the universe. Specifically, we consider two generic toy models recently proposed as alternatives to quintessence models, respectively known as Cardassian expansion and the Chaplygin gas. We show that the former is entirely equivalent to a class of quintessence models. We determine the observational constraints on the latter, coming from recent supernovae results and from the shape of the matter power spectrum. As expected, these restrict the model to a behavior that closely matches that of a standard cosmological constant Λ

Sensitivity of light interaction computer model to the absorption properties of skin

Science.gov (United States)

Karsten, A. E.; Singh, A.

2011-06-01

Light based treatments offer major benefits to patients. Many of the light based treatments or diagnostic techniques need to penetrate the skin to reach the site of interest. Human skin is a highly scattering medium and the melanin in the epidermal layer of the skin is a major absorber of light in the visible and near infrared wavelength bands. The effect of increasing absorption in the epidermis is tested on skin simulating phantoms as well as on a computer model. Changing the absorption coefficient between 0.1 mm-1 and 1.0 mm-1 resulted in a decrease of light reaching 1 mm into the sample. Transmission through a 1 mm thick sample decreased from 48% to 13% and from 31% to 2% for the different scattering coefficients.

Effects of radiation on the skin

International Nuclear Information System (INIS)

Hopewell, J.W.

1985-01-01

The effects of X-irradiation on pig skin are described, comparing and contrasting the effects seen in human and rodent skin. It is concluded that, anatomically, pig skin is the best animal model for human skin. The applications of the 'pig skin model' to investigations of the problems of radiation therapy and radiological protection of human skin are discussed. (U.K.)

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

Science.gov (United States)

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

2017-09-01

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

Analytical model of diffuse reflectance spectrum of skin tissue

Energy Technology Data Exchange (ETDEWEB)

Lisenko, S A; Kugeiko, M M; Firago, V A [Belarusian State University, Minsk (Belarus); Sobchuk, A N [B.I. Stepanov Institute of Physics, National Academy of Sciences of Belarus, Minsk (Belarus)

2014-01-31

We have derived simple analytical expressions that enable highly accurate calculation of diffusely reflected light signals of skin in the spectral range from 450 to 800 nm at a distance from the region of delivery of exciting radiation. The expressions, taking into account the dependence of the detected signals on the refractive index, transport scattering coefficient, absorption coefficient and anisotropy factor of the medium, have been obtained in the approximation of a two-layer medium model (epidermis and dermis) for the same parameters of light scattering but different absorption coefficients of layers. Numerical experiments on the retrieval of the skin biophysical parameters from the diffuse reflectance spectra simulated by the Monte Carlo method show that commercially available fibre-optic spectrophotometers with a fixed distance between the radiation source and detector can reliably determine the concentration of bilirubin, oxy- and deoxyhaemoglobin in the dermis tissues and the tissue structure parameter characterising the size of its effective scatterers. We present the examples of quantitative analysis of the experimental data, confirming the correctness of estimates of biophysical parameters of skin using the obtained analytical expressions. (biophotonics)

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Universal in vivo Textural Model for Human Skin based on Optical Coherence Tomograms.

Science.gov (United States)

Adabi, Saba; Hosseinzadeh, Matin; Noei, Shahryar; Conforto, Silvia; Daveluy, Steven; Clayton, Anne; Mehregan, Darius; Nasiriavanaki, Mohammadreza

2017-12-20

Currently, diagnosis of skin diseases is based primarily on the visual pattern recognition skills and expertise of the physician observing the lesion. Even though dermatologists are trained to recognize patterns of morphology, it is still a subjective visual assessment. Tools for automated pattern recognition can provide objective information to support clinical decision-making. Noninvasive skin imaging techniques provide complementary information to the clinician. In recent years, optical coherence tomography (OCT) has become a powerful skin imaging technique. According to specific functional needs, skin architecture varies across different parts of the body, as do the textural characteristics in OCT images. There is, therefore, a critical need to systematically analyze OCT images from different body sites, to identify their significant qualitative and quantitative differences. Sixty-three optical and textural features extracted from OCT images of healthy and diseased skin are analyzed and, in conjunction with decision-theoretic approaches, used to create computational models of the diseases. We demonstrate that these models provide objective information to the clinician to assist in the diagnosis of abnormalities of cutaneous microstructure, and hence, aid in the determination of treatment. Specifically, we demonstrate the performance of this methodology on differentiating basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) from healthy tissue.

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

Science.gov (United States)

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

2017-01-01

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

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

NARCIS (Netherlands)

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

2013-01-01

Background The frictional characteristics of skin-object interactions are important when handling objects, in the assessment of perception and comfort of products and materials and in the origins and prevention of skin injuries. In this study, based on statistical methods, a quantitative model is

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

NARCIS (Netherlands)

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

2013-01-01

Background: The frictional characteristics of skin-object interactions are important when handling objects, in the assessment of perception and comfort of products and materials and in the origins and prevention of skin injuries. In this study, based on statistical methods, a quantitative model is

Stressed skin panels

Energy Technology Data Exchange (ETDEWEB)

Anon

2001-07-01

Advantages and disadvantages of stressed skin panels, also known as structural insulated panels (SIPs), are discussed as material and labour-saving alternatives to traditional stick framing. Stressed skin panels are manufactured 'sandwich' assemblies with a rigid insulating polystyrene foam core, whose interior and exterior surfaces are bonded into panels. The skins distribute and carry the structural loading while the bonded foam core provides insulation and keeps the two skins aligned. Since there are fewer framing members, there is little thermal bridging and the R-value remains high. SIPs are usually manufactured in four feet by eight feet panels, although some manufacturers can produce panels up to eight feet by forty feet. SIPs are resource efficient as they use less wood than conventional framing (about 25 per cent less); can structurally cover large spans, requiring less supplementary framing. Use of SIPs eliminate the need for headers over small openings; provide the ability to nail anywhere; create less scrap and waste; lessen vulnerability to unfavourable weather and other job-site hazards, can reduce delays, and often can produce significant savings in material and labour costs. Limitations include the more complex approaches to plumbing and electrical systems, although this can be minimized by designers by incorporating much of the plumbing and electrical work on interior (non-panel) walls. Most stressed skin panels require one-half inch interior gypsum drywall. If become wet, stressed skin panels take a long time to dry out and may harbour mold growth. Larger stressed-skin panels used in floors and roofs, may require cranes or other machinery for handling because of their weight. Although not without some environmental impact, overall, stressed skin panels are judged to be a resource-efficient building technology with significant energy-efficiency benefits and distinct advantages over stick framing. 3 photos.

Modelling response times in multi-alternative categorization with TVA

DEFF Research Database (Denmark)

Blurton, Steven Paul; Kyllingsbæk, Søren; Bundesen, Claus

, such as trial-to-trial variation in the Poisson processing rates and an extension of the random walk to n-alternatives. In an empirical test of the model we fitted the random walk model to data of a binary and a four-alternative orientation discrimination task. In both cases, the model predictions closely...

Dynamic impedance model of the skin-electrode interface for transcutaneous electrical stimulation.

Directory of Open Access Journals (Sweden)

José Luis Vargas Luna

Full Text Available Transcutaneous electrical stimulation can depolarize nerve or muscle cells applying impulses through electrodes attached on the skin. For these applications, the electrode-skin impedance is an important factor which influences effectiveness. Various models describe the interface using constant or current-depending resistive-capacitive equivalent circuit. Here, we develop a dynamic impedance model valid for a wide range stimulation intensities. The model considers electroporation and charge-dependent effects to describe the impedance variation, which allows to describe high-charge pulses. The parameters were adjusted based on rectangular, biphasic stimulation pulses generated by a stimulator, providing optionally current or voltage-controlled impulses, and applied through electrodes of different sizes. Both control methods deliver a different electrical field to the tissue, which is constant throughout the impulse duration for current-controlled mode or have a very current peak for voltage-controlled. The results show a predominant dependence in the current intensity in the case of both stimulation techniques that allows to keep a simple model. A verification simulation using the proposed dynamic model shows coefficient of determination of around 0.99 in both stimulation types. The presented method for fitting electrode-skin impedance can be simple extended to other stimulation waveforms and electrode configuration. Therefore, it can be embedded in optimization algorithms for designing electrical stimulation applications even for pulses with high charges and high current spikes.

In vitro modeling of skin dose and monitoring of DCA following therapeutic intervention

International Nuclear Information System (INIS)

Balajee, Adayabalam S.; Dainiak, Nicholas

2016-01-01

Human skin is the largest organ of the body accounting for approximately 16% of the total bodyweight. Skin is readily exposed to ionizing radiation during either accidental or intentional exposure such as radiotherapy or other medical procedures because it constitutes the interface between environment and internal organs. Estimation of accurate entrance skin dose and maximum absorbed dose (MAD) is crucial to prevent serious skin injuries. Cutaneous Radiation Syndrome (CRS) is defined by a number of pathological changes manifested in the skin and severity of these changes depend on Liner Energy Transfer (LET), dose, dose-rate, geometry of exposure and volume of body part exposed. In most of the radiological accident scenarios, reconstructive dosimetry in the skin has been performed using physical (thermoluminescence and optical stimulated luminescence), biological (cytogenetics) and computational methods/models to manage radiation exposed victims.Results of the cytogenetic testing performed at the CBL on a few patients will be discussed to illustrate the potential use of DCA and other cytogenetic techniques such as micronuclei and multicolor FISH in monitoring the health of radiotherapy patients

Penetration of radionuclides across the skin. Rat age dependent promethium permeation through skin in vitro

International Nuclear Information System (INIS)

Kassai, Z.; Kassai, A.; Bauerova, K.; Koprda, V.; Harangozo, M.; Bendova, P.; Bujnova, A.

2003-01-01

The composition and the permeation properties of the skin are dependent on age. In the animal models for permation studies, age affects the mechanical as well as the permeation properties significantly. The time dependence of permeation of 147 Pm 3+ from aqueous solution was established by the animal skin model and the age dependence of promethium permeation through the skin was examined. The aim was to find the optimum rat skin age model for radionuclide permeation studies and to assess the relative importance of the main permeation pathways: transepidermal and transfollicular permeation. The skin from 5-day-old rats (5DR) was found to represent the optimum animal model to study transepidermal permeation of ions. The skin from 9-day-old rats (9DR) was selected to study transfollicular permeation of ions. Comparison of the permeated amounts of promethium through the skin without hairs (3 DR to 6 DR) and with hairs (7DR to 12DR) showed that the additional permation mode via follicles significantly contributed to the permeation rate and extent. (author)

Interaction of 1.319 μm laser with skin: an optical-thermal-damage model and experimental validation

Science.gov (United States)

Jiao, Luguang; Yang, Zaifu; Wang, Jiarui

2014-09-01

With the widespread use of high-power laser systems operating within the wavelength region of approximately 1.3 to 1.4 μm, it becomes very necessary to refine the laser safety guidelines setting the exposure limits for the eye and skin. In this paper, an optical-thermal-damage model was developed to simulate laser propagation, energy deposition, heat transfer and thermal damage in the skin for 1.319 μm laser irradiation. Meanwhile, an experiment was also conducted in vitro to measure the tempreture history of a porcine skin specimen irradiated by a 1.319 μm laser. Predictions from the model included light distribution in the skin, temperature response and thermal damge level of the tissue. It was shown that the light distribution region was much larger than that of the incident laser at the wavelength of 1.319 μm, and the maximum value of the fluence rate located on the interior region of the skin, not on the surface. By comparing the calculated temperature curve with the experimentally recorded temperautre data, good agreement was shown betweeen them, which validated the numerical model. The model also indicated that the damage integral changed little when the temperature of skin tissue was lower than about 55 °C, after that, the integral increased rapidly and denatunation of the tissue would occur. Based on this model, we can further explore the damage mechanisms and trends for the skin and eye within the wavelength region of 1.3 μm to 1.4 μm, incorporating with in vivo experimental investigations.

Modeling skin cooling using optical windows and cryogens during laser induced hyperthermia in a multilayer vascularized tissue

International Nuclear Information System (INIS)

Singh, Rupesh; Das, Koushik; Okajima, Junnosuke; Maruyama, Shigenao; Mishra, Subhash C.

2015-01-01

This article deals with the spatial and the temporal evolution of tissue temperature during skin surface cooled laser induced hyperthermia. Three different skin surface cooling methodologies viz., optical window contact cooling, cryogenic spray cooling and cryogen cooled optical window contact cooling are considered. Sapphire, yttrium aluminum garnet, lithium tantalate, and magnesium oxide doped lithium niobate are the considered optical windows. The cryogens considered are liquid CO_2 and R1234yf. Heat transfer in the multilayer skin tissue embedded with thermally significant blood vessels pairs is modeled using the Pennes and Weinbaum–Jiji bioheat equations. Weinbaum–Jiji bioheat equation is used for the vascularized tissue. Laser transport in the tissue is modeled using the radiative transfer equation. Axial and radial (skin surface) temperature distributions for different combinations of optical windows and cryogens are analyzed. Liquid CO_2 cooled yttrium aluminum garnet is found to be the best surface cooling mechanism. - Highlights: • Skin surface cooled laser induced hyperthermia is studied. • A multi-layer 2-D cylindrical tissue geometry is considered. • Both Pennes and Weinbaum–Jiji bioheat models are considered. • Laser transport in the tissue is modeled using discrete ordinate method. • Results for 4 optical windows and 2 cryogens for skin cooling are presented.

Non-occlusive topical exposure of human skin in vitro as model for cytotoxicity testing of irritant compounds.

Science.gov (United States)

Lönnqvist, Susanna; Briheim, Kristina; Kratz, Gunnar

2016-02-01

Testing of irritant compounds has traditionally been performed on animals and human volunteers. Animal testing should always be restricted and for skin irritancy mice and rabbits hold poor predictive value for irritant potential in humans. Irritant testing on human volunteers is restricted by the duration subjects can be exposed, and by the subjectivity of interpreting the visual signs of skin irritation. We propose an irritant testing system using viable human full thickness skin with the loss of cell viability in the exposed skin area as end point measurement. Skin was exposed to sodium dodecyl sulfate (SDS) at 20% concentration by non-occluded topical exposure to establish a positive control response and subsequent test compounds were statistically compared with the 20% SDS response. Cell viability and metabolism were measured with 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The model presents correlation between increased concentration of SDS and decreased viability of cells in the exposed skin area (R(2) = 0.76). We propose the model to be used for cytotoxicity testing of irritant compounds. With fully intact barrier function, the model comprises all cells present in the skin with quantifiable end point measurement.

Modelling the healthcare costs of skin cancer in South Africa.

Science.gov (United States)

Gordon, Louisa G; Elliott, Thomas M; Wright, Caradee Y; Deghaye, Nicola; Visser, Willie

2016-04-02

Skin cancer is a growing public health problem in South Africa due to its high ambient ultraviolet radiation environment. The purpose of this study was to estimate the annual health system costs of cutaneous melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in South Africa, incorporating both the public and private sectors. A cost-of-illness study was used to measure the economic burden of skin cancer and a 'bottom-up' micro-costing approach. Clinicians provided data on the patterns of care and treatments while national costing reports and clinician fees provided cost estimates. The mean costs per melanoma and per SCC/BCC were extrapolated to estimate national costs using published incidence data and official population statistics. One-way and probabilistic sensitivity analyses were undertaken to address the uncertainty of the parameters used in the model. The estimated total annual cost of treating skin cancers in South Africa were ZAR 92.4 million (2015) (or US$15.7 million). Sensitivity analyses showed that the total costs could vary between ZAR 89.7 to 94.6 million (US$15.2 to $16.1 million) when melanoma-related variables were changed and between ZAR 78.4 to 113.5 million ($13.3 to $19.3 million) when non-melanoma-related variables were changed. The primary drivers of overall costs were the cost of excisions, follow-up care, radical lymph node dissection, cryotherapy and radiation therapy. The cost of managing skin cancer in South Africa is sizable. Since skin cancer is largely preventable through improvements to sun-protection awareness and skin cancer prevention programs, this study highlights these healthcare resources could be used for other pressing public health problems in South Africa.

Modeling the Mechanical Response of In Vivo Human Skin Under a Rich Set of Deformations

KAUST Repository

Flynn, Cormac; Taberner, Andrew; Nielsen, Poul

2011-01-01

Determining the mechanical properties of an individual's skin is important in the fields of pathology, biomedical device design, and plastic surgery. To address this need, we present a finite element model that simulates the skin of the anterior

Alternative models for academic family practices

Directory of Open Access Journals (Sweden)

Yarnall Kimberly SH

2006-03-01

Full Text Available Abstract Background The Future of Family Medicine Report calls for a fundamental redesign of the American family physician workplace. At the same time, academic family practices are under economic pressure. Most family medicine departments do not have self-supporting practices, but seek support from specialty colleagues or hospital practice plans. Alternative models for academic family practices that are economically viable and consistent with the principles of family medicine are needed. This article presents several "experiments" to address these challenges. Methods The basis of comparison is a traditional academic family medicine center. Apart of the faculty practice plan, our center consistently operated at a deficit despite high productivity. A number of different practice types and alternative models of service delivery were therefore developed and tested. They ranged from a multi-specialty office arrangement, to a community clinic operated as part of a federally-qualified health center, to a team of providers based in and providing care for residents of an elderly public housing project. Financial comparisons using consistent accounting across models are provided. Results Academic family practices can, at least in some settings, operate without subsidy while providing continuity of care to a broad segment of the community. The prerequisites are that the clinicians must see patients efficiently, and be able to bill appropriately for their payer mix. Conclusion Experimenting within academic practice structure and organization is worthwhile, and can result in economically viable alternatives to traditional models.

Alternative models of DSM-5 PTSD: Examining diagnostic implications.

Science.gov (United States)

Murphy, Siobhan; Hansen, Maj; Elklit, Ask; Yong Chen, Yoke; Raudzah Ghazali, Siti; Shevlin, Mark

2018-04-01

The factor structure of DSM-5 posttraumatic stress disorder (PTSD) has been extensively debated with evidence supporting the recently proposed seven-factor Hybrid model. However, despite myriad studies examining PTSD symptom structure few have assessed the diagnostic implications of these proposed models. This study aimed to generate PTSD prevalence estimates derived from the 7 alternative factor models and assess whether pre-established risk factors associated with PTSD (e.g., transportation accidents and sexual victimisation) produce consistent risk estimates. Seven alternative models were estimated within a confirmatory factor analytic framework using the PTSD Checklist for DSM-5 (PCL-5). Data were analysed from a Malaysian adolescent community sample (n = 481) of which 61.7% were female, with a mean age of 17.03 years. The results indicated that all models provided satisfactory model fit with statistical superiority for the Externalising Behaviours and seven-factor Hybrid models. The PTSD prevalence estimates varied substantially ranging from 21.8% for the DSM-5 model to 10.0% for the Hybrid model. Estimates of risk associated with PTSD were inconsistent across the alternative models, with substantial variation emerging for sexual victimisation. These findings have important implications for research and practice and highlight that more research attention is needed to examine the diagnostic implications emerging from the alternative models of PTSD. Copyright © 2017 Elsevier B.V. All rights reserved.

Fractional calculus model of electrical impedance applied to human skin.

Science.gov (United States)

Vosika, Zoran B; Lazovic, Goran M; Misevic, Gradimir N; Simic-Krstic, Jovana B

2013-01-01

Fractional calculus is a mathematical approach dealing with derivatives and integrals of arbitrary and complex orders. Therefore, it adds a new dimension to understand and describe basic nature and behavior of complex systems in an improved way. Here we use the fractional calculus for modeling electrical properties of biological systems. We derived a new class of generalized models for electrical impedance and applied them to human skin by experimental data fitting. The primary model introduces new generalizations of: 1) Weyl fractional derivative operator, 2) Cole equation, and 3) Constant Phase Element (CPE). These generalizations were described by the novel equation which presented parameter [Formula: see text] related to remnant memory and corrected four essential parameters [Formula: see text] We further generalized single generalized element by introducing specific partial sum of Maclaurin series determined by parameters [Formula: see text] We defined individual primary model elements and their serial combination models by the appropriate equations and electrical schemes. Cole equation is a special case of our generalized class of models for[Formula: see text] Previous bioimpedance data analyses of living systems using basic Cole and serial Cole models show significant imprecisions. Our new class of models considerably improves the quality of fitting, evaluated by mean square errors, for bioimpedance data obtained from human skin. Our models with new parameters presented in specific partial sum of Maclaurin series also extend representation, understanding and description of complex systems electrical properties in terms of remnant memory effects.

Fractional calculus model of electrical impedance applied to human skin.

Directory of Open Access Journals (Sweden)

Zoran B Vosika

Full Text Available Fractional calculus is a mathematical approach dealing with derivatives and integrals of arbitrary and complex orders. Therefore, it adds a new dimension to understand and describe basic nature and behavior of complex systems in an improved way. Here we use the fractional calculus for modeling electrical properties of biological systems. We derived a new class of generalized models for electrical impedance and applied them to human skin by experimental data fitting. The primary model introduces new generalizations of: 1 Weyl fractional derivative operator, 2 Cole equation, and 3 Constant Phase Element (CPE. These generalizations were described by the novel equation which presented parameter [Formula: see text] related to remnant memory and corrected four essential parameters [Formula: see text] We further generalized single generalized element by introducing specific partial sum of Maclaurin series determined by parameters [Formula: see text] We defined individual primary model elements and their serial combination models by the appropriate equations and electrical schemes. Cole equation is a special case of our generalized class of models for[Formula: see text] Previous bioimpedance data analyses of living systems using basic Cole and serial Cole models show significant imprecisions. Our new class of models considerably improves the quality of fitting, evaluated by mean square errors, for bioimpedance data obtained from human skin. Our models with new parameters presented in specific partial sum of Maclaurin series also extend representation, understanding and description of complex systems electrical properties in terms of remnant memory effects.

Radiation-induced skin injury in the animal model of scleroderma: implications for post-radiotherapy fibrosis

International Nuclear Information System (INIS)

Kumar, Sanath; Kolozsvary, Andrew; Kohl, Robert; Lu, Mei; Brown, Stephen; Kim, Jae Ho

2008-01-01

Radiation therapy is generally contraindicated for cancer patients with collagen vascular diseases (CVD) such as scleroderma due to an increased risk of fibrosis. The tight skin (TSK) mouse has skin which, in some respects, mimics that of patients with scleroderma. The skin radiation response of TSK mice has not been previously reported. If TSK mice are shown to have radiation sensitive skin, they may prove to be a useful model to examine the mechanisms underlying skin radiation injury, protection, mitigation and treatment. The hind limbs of TSK and parental control C57BL/6 mice received a radiation exposure sufficient to cause approximately the same level of acute injury. Endpoints included skin damage scored using a non-linear, semi-quantitative scale and tissue fibrosis assessed by measuring passive leg extension. In addition, TGF-β1 cytokine levels were measured monthly in skin tissue. Contrary to our expectations, TSK mice were more resistant (i.e. 20%) to radiation than parental control mice. Although acute skin reactions were similar in both mouse strains, radiation injury in TSK mice continued to decrease with time such that several months after radiation there was significantly less skin damage and leg contraction compared to C57BL/6 mice (p < 0.05). Consistent with the expected association of transforming growth factor beta-1 (TGF-β1) with late tissue injury, levels of the cytokine were significantly higher in the skin of the C57BL/6 mouse compared to TSK mouse at all time points (p < 0.05). TSK mice are not recommended as a model of scleroderma involving radiation injury. The genetic and molecular basis for reduced radiation injury observed in TSK mice warrants further investigation particularly to identify mechanisms capable of reducing tissue fibrosis after radiation injury

Baryon density in alternative BBN models

International Nuclear Information System (INIS)

Kirilova, D.

2002-10-01

We present recent determinations of the cosmological baryon density ρ b , extracted from different kinds of observational data. The baryon density range is not very wide and is usually interpreted as an indication for consistency. It is interesting to note that all other determinations give higher baryon density than the standard big bang nucleosynthesis (BBN) model. The differences of the ρ b values from the BBN predicted one (the most precise today) may be due to the statistical and systematic errors in observations. However, they may be an indication of new physics. Hence, it is interesting to study alternative BBN models, and the possibility to resolve the discrepancies. We discuss alternative cosmological scenarios: a BBN model with decaying particles (m ∼ MeV, τ ∼ sec) and BBN with electron-sterile neutrino oscillations, which permit to relax BBN constraints on the baryon content of the Universe. (author)

Contribution to the penetration of radionuclides across the skin. Age dependence of promethium through rat skin in vitro

International Nuclear Information System (INIS)

Kassai, Z.; Koprda, V.; Harangozo, M.; Bendova, P.; Bauerova, K.

2001-01-01

In this paper: - the time dependence of permeation of 147 Pm 3+ from aqueous solution through animal skin model was studied; - the age dependence of promethium through the skin was proved; - the optimum biological model of human skin was selected, and - the relative importance of the main diffusion pathways for 147 Pm 3+ the diffusion across the intact skin and the diffusion through the hair channels was assessed. Concluding it can be said, that: -it was proved, that the 5-day-old rats (5DR) represents the optimum animal model to the human skin; - in the case of 8DR to 11DR the dominant route of 147 Pm 3+ penetration is along the follicles; - the permeation resistance of the skin depends on the thickness and mechanical properties of the skin. Comparing amounts of penetrated ions of promethium through the skin without hairs (3DR to 6DR) and through the skin with hairs, it was showed that the additional diffusion along hair's follicles pronounced with animal skin can be important also in case of human skin where hair density is many times lower than in used animal models. (authors)

Materials used to simulate physical properties of human skin.

Science.gov (United States)

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

2016-02-01

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

TAFV Alternative Fuels and Vehicles Choice Model Documentation; TOPICAL

International Nuclear Information System (INIS)

Greene, D.L.

2001-01-01

A model for predicting choice of alternative fuel and among alternative vehicle technologies for light-duty motor vehicles is derived. The nested multinomial logit (NML) mathematical framework is used. Calibration of the model is based on information in the existing literature and deduction based on assuming a small number of key parameters, such as the value of time and discount rates. A spreadsheet model has been developed for calibration and preliminary testing of the model

Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester.

Science.gov (United States)

Lim, Kyung-Min; Bae, SeungJin; Koo, Jung Eun; Kim, Eun-Sun; Bae, Ok-Nam; Lee, Joo Young

2015-04-01

Skin inflammation plays a central role in the pathophysiology and symptoms of diverse chronic skin diseases including atopic dermatitis (AD). In this study, we examined if caffeic acid phenethyl ester (CAPE), a skin-permeable bioactive compound from propolis, was protective against skin inflammation using in vitro cell system and in vivo animal disease models. CAPE suppressed TNF-α-induced NF-κB activation and expression of inflammatory cytokines in human keratinocytes (HaCaT). The potency and efficacy of CAPE were superior to those of a non-phenethyl derivative, caffeic acid. Consistently, topical treatment of CAPE (0.5 %) attenuated 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced skin inflammation on mouse ear as CAPE reduced ear swelling and histologic inflammation scores. CAPE suppressed increased expression of pro-inflammatory molecules such as TNF-α, cyclooxygenase-2 and inducible NO synthase in TPA-stimulated skin. TPA-induced phosphorylation of IκB and ERK was blocked by CAPE suggesting that protective effects of CAPE on skin inflammation is attributed to inhibition of NF-κB activation. Most importantly, in an oxazolone-induced chronic dermatitis model, topical application of CAPE (0.5 and 1 %) was effective in alleviating AD-like symptoms such as increases of trans-epidermal water loss, skin thickening and serum IgE as well as histologic inflammation assessment. Collectively, our results propose CAPE as a promising candidate for a novel topical drug for skin inflammatory diseases.

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

Directory of Open Access Journals (Sweden)

Vishnu Hosur

2017-08-01

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

Modeling laser speckle imaging of perfusion in the skin (Conference Presentation)

Science.gov (United States)

Regan, Caitlin; Hayakawa, Carole K.; Choi, Bernard

2016-02-01

Laser speckle imaging (LSI) enables visualization of relative blood flow and perfusion in the skin. It is frequently applied to monitor treatment of vascular malformations such as port wine stain birthmarks, and measure changes in perfusion due to peripheral vascular disease. We developed a computational Monte Carlo simulation of laser speckle contrast imaging to quantify how tissue optical properties, blood vessel depths and speeds, and tissue perfusion affect speckle contrast values originating from coherent excitation. The simulated tissue geometry consisted of multiple layers to simulate the skin, or incorporated an inclusion such as a vessel or tumor at different depths. Our simulation used a 30x30mm uniform flat light source to optically excite the region of interest in our sample to better mimic wide-field imaging. We used our model to simulate how dynamically scattered photons from a buried blood vessel affect speckle contrast at different lateral distances (0-1mm) away from the vessel, and how these speckle contrast changes vary with depth (0-1mm) and flow speed (0-10mm/s). We applied the model to simulate perfusion in the skin, and observed how different optical properties, such as epidermal melanin concentration (1%-50%) affected speckle contrast. We simulated perfusion during a systolic forearm occlusion and found that contrast decreased by 35% (exposure time = 10ms). Monte Carlo simulations of laser speckle contrast give us a tool to quantify what regions of the skin are probed with laser speckle imaging, and measure how the tissue optical properties and blood flow affect the resulting images.

A Hydrogel/Carbon-Nanotube Needle-Free Device for Electrostimulated Skin Drug Delivery.

Science.gov (United States)

Guillet, Jean-François; Flahaut, Emmanuel; Golzio, Muriel

2017-10-06

The permeability of skin allows passive diffusion across the epidermis to reach blood vessels but this is possible only for small molecules such as nicotine. In order to achieve transdermal delivery of large molecules such as insulin or plasmid DNA, permeability of the skin and mainly the permeability of the stratum corneum skin layer has to be increased. Moreover, alternative routes that avoid the use of needles will improve the quality of life of patients. A method known as electropermeabilisation has been shown to increase skin permeability. Herein, we report the fabrication of an innovative hydrogel made of a nanocomposite material. This nanocomposite device aims to permeabilise the skin and deliver drug molecules at the same time. It includes a biocompatible polymer matrix (hydrogel) and double-walled carbon nanotubes (DWCNTs) in order to bring electrical conductivity and improve mechanical properties. Carbon nanotubes and especially DWCNTs are ideal candidates, combining high electrical conductivity with a very high specific surface area together with a good biocompatibility when included into a material. The preparation and characterization of the nanocomposite hydrogel as well as first results of electrostimulated transdermal delivery using an ex vivo mouse skin model are presented. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A methodology for assessing the market benefits of alternative motor fuels: The Alternative Fuels Trade Model

Energy Technology Data Exchange (ETDEWEB)

Leiby, P.N.

1993-09-01

This report describes a modeling methodology for examining the prospective economic benefits of displacing motor gasoline use by alternative fuels. The approach is based on the Alternative Fuels Trade Model (AFTM). AFTM development was undertaken by the US Department of Energy (DOE) as part of a longer term study of alternative fuels issues. The AFTM is intended to assist with evaluating how alternative fuels may be promoted effectively, and what the consequences of substantial alternative fuels use might be. Such an evaluation of policies and consequences of an alternative fuels program is being undertaken by DOE as required by Section 502(b) of the Energy Policy Act of 1992. Interest in alternative fuels is based on the prospective economic, environmental and energy security benefits from the substitution of these fuels for conventional transportation fuels. The transportation sector is heavily dependent on oil. Increased oil use implies increased petroleum imports, with much of the increase coming from OPEC countries. Conversely, displacement of gasoline has the potential to reduce US petroleum imports, thereby reducing reliance on OPEC oil and possibly weakening OPEC`s ability to extract monopoly profits. The magnitude of US petroleum import reduction, the attendant fuel price changes, and the resulting US benefits, depend upon the nature of oil-gas substitution and the supply and demand behavior of other world regions. The methodology applies an integrated model of fuel market interactions to characterize these effects.

Assessment of the potential skin irritation of lysine-derivative anionic surfactants using mouse fibroblast and human keratinocytes as an alternative to animal testing

OpenAIRE

Sánchez Molina, Lourdes; Mitjans Arnal, Montserrat; Infante Martínez-Pardo, Ma. Rosa; Vinardell Martínez-Hidalgo, Ma. Pilar

2004-01-01

Purpose. The aim of this study was to identify new surfactants with low skin irritant properties for use in pharmaceutical and cosmetic formulations, employing cell culture as an alternative method to in vivo testing. In addition, we sought to establish whether potential cytotoxic properties were related to the size of the counterions bound to the surfactants. Methods. Cytotoxicity was assessed in the mouse fibroblast cell line 3T6, and the human keratinocyte cell line NCTC 2544, using the MT...

Measurement of model coefficients of skin sympathetic vasoconstriction

International Nuclear Information System (INIS)

Severens, Natascha M W; Van Marken Lichtenbelt, Wouter D; Frijns, Arjan J H; Kingma, Boris R M; De Mol, Bas A J M; Van Steenhoven, Anton A

2010-01-01

Many researchers have already attempted to model vasoconstriction responses, commonly using the mathematical representation proposed by Stolwijk (1971 NASA Contractor Report CR-1855 (Washington, DC: NASA)). Model makers based the parameter values in this formulation either on estimations or by attributing the difference between their passive models and measurement data fully to thermoregulation. These methods are very sensitive to errors. This study aims to present a reliable method for determining physiological values in the vasoconstriction formulation. An experimental protocol was developed that enabled us to derive the local proportional amplification coefficients of the toe, leg and arm and the transient vasoconstrictor tone. Ten subjects participated in a cooling experiment. During the experiment, core temperature, skin temperature, skin perfusion, forearm blood flow and heart rate variability were measured. The contributions to the normalized amplification coefficient for vasoconstriction of the toe, leg and arm were 84%, 11% and 5%, respectively. Comparison with relative values in the literature showed that the estimated values of Stolwijk and the values mentioned by Tanabe et al (2002 Energy Build. 34 637–46) were comparable with our measured values, but the values of Gordon (1974 The response of a human temperature regulatory system model in the cold PhD Thesis University of California, Santa Barbara) and Fiala et al (2001 Int. J. Biometeorol. 45 143159) differed significantly. With the help of regression analysis a relation was formulated between the error signal of the standardized core temperature and the vasoconstrictor tone. This relation was formulated in a general applicable way, which means that it can be used for situations where vasoconstriction thresholds are shifted, like under anesthesia or during motion sickness

Underprediction of human skin erythema at low doses per fraction by the linear quadratic model

International Nuclear Information System (INIS)

Hamilton, Christopher S.; Denham, James W.; O'Brien, Maree; Ostwald, Patricia; Kron, Tomas; Wright, Suzanne; Doerr, Wolfgang

1996-01-01

Background and purpose. The erythematous response of human skin to radiotherapy has proven useful for testing the predictions of the linear quadratic (LQ) model in terms of fractionation sensitivity and repair half time. No formal investigation of the response of human skin to doses less than 2 Gy per fraction has occurred. This study aims to test the validity of the LQ model for human skin at doses ranging from 0.4 to 5.2 Gy per fraction. Materials and methods. Complete erythema reaction profiles were obtained using reflectance spectrophotometry in two patient populations: 65 patients treated palliatively with 5, 10, 12 and 20 daily treatment fractions (varying thicknesses of bolus, various body sites) and 52 patients undergoing prostatic irradiation for localised carcinoma of the prostate (no bolus, 30-32 fractions). Results and conclusions. Gender, age, site and prior sun exposure influence pre- and post-treatment erythema values independently of dose administered. Out-of-field effects were also noted. The linear quadratic model significantly underpredicted peak erythema values at doses less than 1.5 Gy per fraction. This suggests that either the conventional linear quadratic model does not apply for low doses per fraction in human skin or that erythema is not exclusively initiated by radiation damage to the basal layer. The data are potentially explained by an induced repair model

Effect of skin graft thickness on scar development in a porcine burn model.

Science.gov (United States)

DeBruler, Danielle M; Blackstone, Britani N; McFarland, Kevin L; Baumann, Molly E; Supp, Dorothy M; Bailey, J Kevin; Powell, Heather M

2018-06-01

Animal models provide a way to investigate scar therapies in a controlled environment. It is necessary to produce uniform, reproducible scars with high anatomic and biologic similarity to human scars to better evaluate the efficacy of treatment strategies and to develop new treatments. In this study, scar development and maturation were assessed in a porcine full-thickness burn model with immediate excision and split-thickness autograft coverage. Red Duroc pigs were treated with split-thickness autografts of varying thickness: 0.026in. ("thin") or 0.058in. ("thick"). Additionally, the thin skin grafts were meshed and expanded at 1:1.5 or 1:4 to evaluate the role of skin expansion in scar formation. Overall, the burn-excise-autograft model resulted in thick, raised scars. Treatment with thick split-thickness skin grafts resulted in less contraction and reduced scarring as well as improved biomechanics. Thin skin autograft expansion at a 1:4 ratio tended to result in scars that contracted more with increased scar height compared to the 1:1.5 expansion ratio. All treatment groups showed Matrix Metalloproteinase 2 (MMP2) and Transforming Growth Factor β1 (TGF-β1) expression that increased over time and peaked 4 weeks after grafting. Burns treated with thick split-thickness grafts showed decreased expression of pro-inflammatory genes 1 week after grafting, including insulin-like growth factor 1 (IGF-1) and TGF-β1, compared to wounds treated with thin split-thickness grafts. Overall, the burn-excise-autograft model using split-thickness autograft meshed and expanded to 1:1.5 or 1:4, resulted in thick, raised scars similar in appearance and structure to human hypertrophic scars. This model can be used in future studies to study burn treatment outcomes and new therapies. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

A new method for skin color enhancement

Science.gov (United States)

Zeng, Huanzhao; Luo, Ronnier

2012-01-01

Skin tone is the most important color category in memory colors. Reproducing it pleasingly is an important factor in photographic color reproduction. Moving skin colors toward their preferred skin color center improves the skin color preference on photographic color reproduction. Two key factors to successfully enhance skin colors are: a method to detect original skin colors effectively even if they are shifted far away from the regular skin color region, and a method to morph skin colors toward a preferred skin color region properly without introducing artifacts. A method for skin color enhancement presented by the authors in the same conference last year applies a static skin color model for skin color detection, which may miss to detect skin colors that are far away from regular skin tones. In this paper, a new method using the combination of face detection and statistical skin color modeling is proposed to effectively detect skin pixels and to enhance skin colors more effectively.

Interactions of donor sources and media influence the histo-morphological quality of full-thickness skin models.

Science.gov (United States)

Lange, Julia; Weil, Frederik; Riegler, Christoph; Groeber, Florian; Rebhan, Silke; Kurdyn, Szymon; Alb, Miriam; Kneitz, Hermann; Gelbrich, Götz; Walles, Heike; Mielke, Stephan

2016-10-01

Human artificial skin models are increasingly employed as non-animal test platforms for research and medical purposes. However, the overall histopathological quality of such models may vary significantly. Therefore, the effects of manufacturing protocols and donor sources on the quality of skin models built-up from fibroblasts and keratinocytes derived from juvenile foreskins is studied. Histo-morphological parameters such as epidermal thickness, number of epidermal cell layers, dermal thickness, dermo-epidermal adhesion and absence of cellular nuclei in the corneal layer are obtained and scored accordingly. In total, 144 full-thickness skin models derived from 16 different donors, built-up in triplicates using three different culture conditions were successfully generated. In univariate analysis both media and donor age affected the quality of skin models significantly. Both parameters remained statistically significant in multivariate analyses. Performing general linear model analyses we could show that individual medium-donor-interactions influence the quality. These observations suggest that the optimal choice of media may differ from donor to donor and coincides with findings where significant inter-individual variations of growth rates in keratinocytes and fibroblasts have been described. Thus, the consideration of individual medium-donor-interactions may improve the overall quality of human organ models thereby forming a reproducible test platform for sophisticated clinical research. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

Science.gov (United States)

Choi, Hyunjung; Shin, Ji Hyun; Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung

2016-01-01

The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

Directory of Open Access Journals (Sweden)

Hyunjung Choi

Full Text Available The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH-smoothened (Smo signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

Alternatives to animal testing in basic and preclinical research of atopic dermatitis.

Science.gov (United States)

Löwa, Anna; Jevtić, Marijana; Gorreja, Frida; Hedtrich, Sarah

2018-01-22

Atopic dermatitis (AD) is a chronic inflammatory skin disease of increasing prevalence, especially in industrialized countries. Roughly 25% of the children and 1%-3% of adults are affected. Although significant progress has been made in the understanding of the pathogenesis of AD, many aspects remain poorly understood. Moreover, there is a pressing need for improved therapeutic options. Studies to elucidate the pathophysiological pathways of AD and to identify novel therapeutic targets over the last few decades have been conducted almost exclusively in animal models. However, in vitro approaches such as 3D skin disease models have recently emerged due to an increasing awareness of distinct interspecies-related differences that hamper the effective translation of results from animal models to humans. In addition, there is growing political and social pressure to develop alternatives to animal models according to the 3Rs principle (reduction, refinement and replacement of animal models). © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Skin hydration analysis by experiment and computer simulations and its implications for diapered skin.

Science.gov (United States)

Saadatmand, M; Stone, K J; Vega, V N; Felter, S; Ventura, S; Kasting, G; Jaworska, J

2017-11-01

Experimental work on skin hydration is technologically challenging, and mostly limited to observations where environmental conditions are constant. In some cases, like diapered baby skin, such work is practically unfeasible, yet it is important to understand potential effects of diapering on skin condition. To overcome this challenge, in part, we developed a computer simulation model of reversible transient skin hydration effects. Skin hydration model by Li et al. (Chem Eng Sci, 138, 2015, 164) was further developed to simulate transient exposure conditions where relative humidity (RH), wind velocity, air, and skin temperature can be any function of time. Computer simulations of evaporative water loss (EWL) decay after different occlusion times were compared with experimental data to calibrate the model. Next, we used the model to investigate EWL and SC thickness in different diapering scenarios. Key results from the experimental work were: (1) For occlusions by RH=100% and free water longer than 30 minutes the absorbed amount of water is almost the same; (2) Longer occlusion times result in higher water absorption by the SC. The EWL decay and skin water content predictions were in agreement with experimental data. Simulations also revealed that skin under occlusion hydrates mainly because the outflux is blocked, not because it absorbs water from the environment. Further, simulations demonstrated that hydration level is sensitive to time, RH and/or free water on skin. In simulated diapering scenarios, skin maintained hydration content very close to the baseline conditions without a diaper for the entire duration of a 24 hours period. Different diapers/diaper technologies are known to have different profiles in terms of their ability to provide wetness protection, which can result in consumer-noticeable differences in wetness. Simulation results based on published literature using data from a number of different diapers suggest that diapered skin hydrates within

Mechanical modeling of skin

NARCIS (Netherlands)

Oomens, C.W.J.; Peters, G.W.M.; Kassab, G.S.; Sacks, M.S.

2016-01-01

The chapter describes the work that was performed in the soft tissue biomechanics laboratory at Eindhoven University of Technology on the biomechanics of skin. A rationale is given for the changes from standard testing methods to inverse methods, from in vitro to in vivo and back to in vitro testing

In vitro activation of the neuro-transduction mechanism in sensitive organotypic human skin model.

Science.gov (United States)

Martorina, Francesca; Casale, Costantino; Urciuolo, Francesco; Netti, Paolo A; Imparato, Giorgia

2017-01-01

Recent advances in tissue engineering have encouraged researchers to endeavor the production of fully functional three-dimensional (3D) thick human tissues in vitro. Here, we report the fabrication of a fully innervated human skin tissue in vitro that recapitulates and replicates skin sensory function. Previous attempts to innervate in vitro 3D skin models did not demonstrate an effective functionality of the nerve network. In our approach, we initially engineer functional human skin tissue based on fibroblast-generated dermis and differentiated epidermis; then, we promote rat dorsal root ganglion (DRG) neurons axon ingrowth in the de-novo developed tissue. Neurofilaments network infiltrates the entire native dermis extracellular matrix (ECM), as demonstrated by immunofluorescence and second harmonic generation (SHG) imaging. To prove sensing functionality of the tissue, we use topical applications of capsaicin, an agonist of transient receptor protein-vanilloid 1 (TRPV1) channel, and quantify calcium currents resulting from variations of Ca ++ concentration in DRG neurons innervating our model. Calcium currents generation demonstrates functional cross-talking between dermis and epidermis compartments. Moreover, through a computational fluid dynamic (CFD) analysis, we set fluid dynamic conditions for a non-planar skin equivalent growth, as proof of potential application in creating skin grafts tailored on-demand for in vivo wound shape. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation and comparison of alternative fleet-level selective maintenance models

International Nuclear Information System (INIS)

Schneider, Kellie; Richard Cassady, C.

2015-01-01

Fleet-level selective maintenance refers to the process of identifying the subset of maintenance actions to perform on a fleet of repairable systems when the maintenance resources allocated to the fleet are insufficient for performing all desirable maintenance actions. The original fleet-level selective maintenance model is designed to maximize the probability that all missions in a future set are completed successfully. We extend this model in several ways. First, we consider a cost-based optimization model and show that a special case of this model maximizes the expected value of the number of successful missions in the future set. We also consider the situation in which one or more of the future missions may be canceled. These models and the original fleet-level selective maintenance optimization models are nonlinear. Therefore, we also consider an alternative model in which the objective function can be linearized. We show that the alternative model is a good approximation to the other models. - Highlights: • Investigate nonlinear fleet-level selective maintenance optimization models. • A cost based model is used to maximize the expected number of successful missions. • Another model is allowed to cancel missions if reliability is sufficiently low. • An alternative model has an objective function that can be linearized. • We show that the alternative model is a good approximation to the other models

Central Role for Dermal Fibroblasts in Skin Model Protection against Candida albicans.

Science.gov (United States)

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.

Monitoring UV-induced signalling pathways in an ex vivo skin organ culture model using phospho-antibody array.

Science.gov (United States)

Lenain, Christelle; Gamboa, Bastien; Perrin, Agnes; Séraïdaris, Alexia; Bertino, Béatrice; Rival, Yves; Bernardi, Mathieu; Piwnica, David; Méhul, Bruno

2018-05-01

We investigated UV-induced signalling in an ex vivo skin organ culture model using phospho-antibody array. Phosphorylation modulations were analysed in time-course experiments following exposure to solar-simulated UV and validated by Western blot analyses. We found that UV induced P-p38 and its substrates, P-ERK1/2 and P-AKT, which were previously shown to be upregulated by UV in cultured keratinocytes and in vivo human skin. This indicates that phospho-antibody array applied to ex vivo skin organ culture is a relevant experimental system to investigate signalling events following perturbations. As the identified proteins are components of pathways implicated in skin tumorigenesis, UV-exposed skin organ culture model could be used to investigate the effect on these pathways of NMSC cancer drug candidates. In addition, we found that phospho-HCK is induced upon UV exposure, producing a new candidate for future studies investigating its role in the skin response to UV and UV-induced carcinogenesis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ex vivo study of the home-use TriPollar RF device using an experimental human skin model.

Science.gov (United States)

Boisnic, Sylvie; Branchet, Marie Christine

2010-09-01

A wide variety of professional radio frequency (RF) aesthetic treatments for anti-aging are available aiming at skin tightening. A new home-use RF device for facial treatments has recently been developed based on TriPollar technology. To evaluate the mechanism of the new home-use device, in the process of collagen remodeling, using an ex vivo skin model. Human skin samples were collected in order to evaluate the anti-aging effect of a home-use device for facial treatments on an ex vivo human skin model. Skin tightening was evaluated by dermal histology, quantitative analysis of collagen fibers and dosage of collagen synthesis. Significant collagen remodeling following RF treatment with the device was found in the superficial and mid-deep dermis. Biochemical measurement of newly synthesized collagen showed an increase of 41% in the treated samples as compared to UV-aged control samples. The new home-use device has been demonstrated to affect significant collagen remodeling, in terms of the structural and biochemical improvement of dermal collagen on treated skin samples.

Response-surface models for deterministic effects of localized irradiation of the skin by discrete {beta}/{gamma} -emitting sources

Energy Technology Data Exchange (ETDEWEB)

Scott, B.R.

1995-12-01

Individuals who work at nuclear reactor facilities can be at risk for deterministic effects in the skin from exposure to discrete {Beta}- and {gamma}-emitting ({Beta}{gamma}E) sources (e.g., {Beta}{gamma}E hot particles) on the skin or clothing. Deterministic effects are non-cancer effects that have a threshold and increase in severity as dose increases (e.g., ulcer in skin). Hot {Beta}{gamma}E particles are {sup 60}Co- or nuclear fuel-derived particles with diameters > 10 {mu}m and < 3 mm and contain at least 3.7 kBq (0.1 {mu}Ci) of radioactivity. For such {Beta}{gamma}E sources on the skin, it is the beta component of the dose that is most important. To develop exposure limitation systems that adequately control exposure of workers to discrete {Beta}{gamma}E sources, models are needed for systems that adequately control exposure of workers to discrete {Beta}{gamma}E sources, models are needed for evaluating the risk of deterministic effects of localized {Beta} irradiation of the skin. The purpose of this study was to develop dose-rate and irradiated-area dependent, response-surface models for evaluating risks of significant deterministic effects of localized irradiation of the skin by discrete {Beta}{gamma}E sources and to use modeling results to recommend approaches to limiting occupational exposure to such sources. The significance of the research results as follows: (1) response-surface models are now available for evaluating the risk of specific deterministic effects of localized irradiation of the skin; (2) modeling results have been used to recommend approaches to limiting occupational exposure of workers to {Beta} radiation from {Beta}{gamma}E sources on the skin or on clothing; and (3) the generic irradiated-volume, weighting-factor approach to limiting exposure can be applied to other organs including the eye, the ear, and organs of the respiratory or gastrointestinal tract and can be used for both deterministic and stochastic effects.

Response-surface models for deterministic effects of localized irradiation of the skin by discrete β/γ -emitting sources

International Nuclear Information System (INIS)

Scott, B.R.

1995-01-01

Individuals who work at nuclear reactor facilities can be at risk for deterministic effects in the skin from exposure to discrete Β- and γ-emitting (ΒγE) sources (e.g., ΒγE hot particles) on the skin or clothing. Deterministic effects are non-cancer effects that have a threshold and increase in severity as dose increases (e.g., ulcer in skin). Hot ΒγE particles are 60 Co- or nuclear fuel-derived particles with diameters > 10 μm and < 3 mm and contain at least 3.7 kBq (0.1 μCi) of radioactivity. For such ΒγE sources on the skin, it is the beta component of the dose that is most important. To develop exposure limitation systems that adequately control exposure of workers to discrete ΒγE sources, models are needed for systems that adequately control exposure of workers to discrete ΒγE sources, models are needed for evaluating the risk of deterministic effects of localized Β irradiation of the skin. The purpose of this study was to develop dose-rate and irradiated-area dependent, response-surface models for evaluating risks of significant deterministic effects of localized irradiation of the skin by discrete ΒγE sources and to use modeling results to recommend approaches to limiting occupational exposure to such sources. The significance of the research results as follows: (1) response-surface models are now available for evaluating the risk of specific deterministic effects of localized irradiation of the skin; (2) modeling results have been used to recommend approaches to limiting occupational exposure of workers to Β radiation from ΒγE sources on the skin or on clothing; and (3) the generic irradiated-volume, weighting-factor approach to limiting exposure can be applied to other organs including the eye, the ear, and organs of the respiratory or gastrointestinal tract and can be used for both deterministic and stochastic effects

Establishment and application of rat model of acute β-irradiated skin injury

International Nuclear Information System (INIS)

Shen Guoliang; Lu Xing'an; Tang Jun; Wang Xiuzhen; Wu Shiliang; Tian Ye

2006-01-01

Objective: To establish an experimental rat model of acute β-irradiated skin injury and to study the effects of superoxide dismutase (SOD) on wound healing. Methods: Areas of buttock skin (20 mm x 40 mm) of 40 male SD rats were irradiated with 45 Gy/β-rays generated by linear accelerator, and then the forty rats were divided into two groups randomly: treatment group administrated with SOD (n=20) and control group administrated with normal saline (NS) (n=20). The wound healing time and rate were observed. The pathological changes were observed by light microscopy. The expressions of VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) were determined by SP immunohistochemical method. Results: The deep second-degree burns was observed following 45 Gy irradiation. The wound healing time in treatment group was shorter than that of the control group (P<0.05). Strongly positive (+ + +) expression of VEGF, bFGF in treatment group and positive (+ +) expression of VEGF, bFGF in the control group were observed 6 weeks, 7 weeks and 8 weeks after the irradiation, while only weakly positive (+) expressions of VEGF and bFGF in both groups 4 weeks, 5 weeks and 9 weeks after the irradiation. Conclusions: The wound model of acute β-irradiated skin injury in rat was established and used in study of the effect of medicine on wound healing. SOD can promote the wound healing of acute β-irradiated skin injury. (authors)

Evaluation of skin absorption of drugs from topical and transdermal formulations

Directory of Open Access Journals (Sweden)

André Luís Morais Ruela

Full Text Available ABSTRACT The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed.

Digital dermoscopy to determine skin melanin index as an objective indicator of skin pigmentation

Directory of Open Access Journals (Sweden)

Sara Majewski

2016-04-01

Full Text Available Clinical assessment of skin photosensitivity is subjectively determined by erythema and tanning responses to sunlight recalled by the subject, alternatively known as Fitzpatrick Skin Phototype (SPT. Responses may be unreliable due to recall bias, subjective bias by clinicians and subjects, and lack of cultural sensitivity of the questions. Analysis of red-green-blue (RGB color spacing of digital images may provide an objective determination of SPT. This paper presents the studies to assess the melanin index (MI, as determined by RGB images obtained by both standard digital camera as well as by videodermoscope, and to correlate the MI with SPT based upon subjects’ verbal responses to standardized questions administered by a dermatologist.A sample of subjects representing all SPTs I–VI was selected. Both the digital camera and videodermoscope were calibrated at standard illumination, light source and white balance. Images of constitutive skin of the upper ventral arm were taken of each subject using both instruments.The studies showed that 58 subjects (20 M, 38 F were enrolled in the study (mean age: 47 years; range: 20–89, stratified to skin phototype I–VI. MI obtained by using both digital camera and videodermoscope increased significantly as the SPT increased p = 0.004 and p < 0.0001, respectively and positively correlated with dermatologist-assessed SPT (Spearman correlation, r = 0.48 and r = 0.84, respectively.Digital imaging can quantify melanin content in order to quantitatively approximate skin pigmentation in all skin phototypes including Type VI skin. This methodology holds promise as a simple, non-invasive, rapid and objective approach to reliably determine skin phototype and, with further investigation, may prove to be both practical and useful in the prediction of skin cancer risk.

3D cell printing of in vitro stabilized skin model and in vivo pre-vascularized skin patch using tissue-specific extracellular matrix bioink: A step towards advanced skin tissue engineering.

Science.gov (United States)

Kim, Byoung Soo; Kwon, Yang Woo; Kong, Jeong-Sik; Park, Gyu Tae; Gao, Ge; Han, Wonil; Kim, Moon-Bum; Lee, Hyungseok; Kim, Jae Ho; Cho, Dong-Woo

2018-06-01

3D cell-printing technique has been under spotlight as an appealing biofabrication platform due to its ability to precisely pattern living cells in pre-defined spatial locations. In skin tissue engineering, a major remaining challenge is to seek for a suitable source of bioink capable of supporting and stimulating printed cells for tissue development. However, current bioinks for skin printing rely on homogeneous biomaterials, which has several shortcomings such as insufficient mechanical properties and recapitulation of microenvironment. In this study, we investigated the capability of skin-derived extracellular matrix (S-dECM) bioink for 3D cell printing-based skin tissue engineering. S-dECM was for the first time formulated as a printable material and retained the major ECM compositions of skin as well as favorable growth factors and cytokines. This bioink was used to print a full thickness 3D human skin model. The matured 3D cell-printed skin tissue using S-dECM bioink was stabilized with minimal shrinkage, whereas the collagen-based skin tissue was significantly contracted during in vitro tissue culture. This physical stabilization and the tissue-specific microenvironment from our bioink improved epidermal organization, dermal ECM secretion, and barrier function. We further used this bioink to print 3D pre-vascularized skin patch able to promote in vivo wound healing. In vivo results revealed that endothelial progenitor cells (EPCs)-laden 3D-printed skin patch together with adipose-derived stem cells (ASCs) accelerates wound closure, re-epithelization, and neovascularization as well as blood flow. We envision that the results of this paper can provide an insightful step towards the next generation source for bioink manufacturing. Copyright © 2018 Elsevier Ltd. All rights reserved.

Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease.

Science.gov (United States)

Oji, Vinzenz; Eckl, Katja-Martina; Aufenvenne, Karin; Nätebus, Marc; Tarinski, Tatjana; Ackermann, Katharina; Seller, Natalia; Metze, Dieter; Nürnberg, Gudrun; Fölster-Holst, Regina; Schäfer-Korting, Monika; Hausser, Ingrid; Traupe, Heiko; Hennies, Hans Christian

2010-08-13

Generalized peeling skin disease is an autosomal-recessive ichthyosiform erythroderma characterized by lifelong patchy peeling of the skin. After genome-wide linkage analysis, we have identified a homozygous nonsense mutation in CDSN in a large consanguineous family with generalized peeling skin, pruritus, and food allergies, which leads to a complete loss of corneodesmosin. In contrast to hypotrichosis simplex, which can be associated with specific dominant CDSN mutations, peeling skin disease is characterized by a complete loss of CDSN expression. The skin phenotype is consistent with a recent murine Cdsn knockout model. Using three-dimensional human skin models, we demonstrate that lack of corneodesmosin causes an epidermal barrier defect supposed to account for the predisposition to atopic diseases, and we confirm the role of corneodesmosin as a decisive epidermal adhesion molecule. Therefore, peeling skin disease will represent a new model disorder for atopic diseases, similarly to Netherton syndrome and ichthyosis vulgaris in the recent past.

Modeling Skin Injury from Hot Rice Porridge Spills

Directory of Open Access Journals (Sweden)

Torgrim Log

2018-04-01

Full Text Available The present work analyzes skin burns from spills of hot rice and milk products. The traditional Norwegian rice porridge serves as an example. By testing spills on objects emulating an arm, it was concluded that spills were seldom thinner than 3 mm, and stayed in place due to the viscosity of the porridge for more than one minute. The Pennes bioheat equation was solved numerically for such spills, including heat conduction to the skin and convective heat losses from the porridge surface. Temperatures were analyzed in the porridge and skin layers, and the resulting skin injury was calculated based on the basal layer temperature. Parameters influencing burn severity, such as porridge layer thickness, porridge temperature, removal of the porridge and thermal effects of post scald tempered (15 °C water cooling were analyzed. The spilled porridge resulted in a prolonged heat supply to the skin, and the skin injury developed significantly with time. The porridge temperature turned out to be the most important injury parameter. A 70 °C porridge temperature could develop superficial partial-thickness burns. Porridge temperatures at processing temperatures nearly instantly developed severe burns. It was demonstrated that prompt removal of the hot porridge significantly reduced the injury development. The general advice is to avoid serving porridge and similar products at temperatures above 65 °C and, if spilled on the skin, to remove it quickly. After such scald incidents, it is advised to cool the injured area by tempered water for a prolonged period to stimulate healing.

Skin Diseases: Skin Health and Skin Diseases

Science.gov (United States)

Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin Health and Skin Diseases Past Issues / Fall 2008 Table of Contents ... acne to wrinkles Did you know that your skin is the largest organ of your body? It ...

A model for predicting skin dose received by patients from an x-ray ...

African Journals Online (AJOL)

We have done this by modifying a model for predicting skin dose derived by Edmonds for a triple-phase generator. Results for 100 patients based on the triple-phase generator output show a reasonable average agreement (»1%) between our present model and the Edmonds's model. Although our earlier estimated ...

Skin Segmentation Based on Graph Cuts

Institute of Scientific and Technical Information of China (English)

HU Zhilan; WANG Guijin; LIN Xinggang; YAN Hong

2009-01-01

Skin segmentation is widely used in many computer vision tasks to improve automated visualiza-tion. This paper presents a graph cuts algorithm to segment arbitrary skin regions from images. The detected face is used to determine the foreground skin seeds and the background non-skin seeds with the color probability distributions for the foreground represented by a single Gaussian model and for the background by a Gaussian mixture model. The probability distribution of the image is used for noise suppression to alle-viate the influence of the background regions having skin-like colors. Finally, the skin is segmented by graph cuts, with the regional parameter y optimally selected to adapt to different images. Tests of the algorithm on many real wodd photographs show that the scheme accurately segments skin regions and is robust against illumination variations, individual skin variations, and cluttered backgrounds.

Experimental testing and constitutive modeling of the mechanical properties of the swine skin tissue.

Science.gov (United States)

Łagan, Sylwia D; Liber-Kneć, Aneta

2017-01-01

The aim of the study was an estimation of the possibility of using hyperelastic material models to fit experimental data obtained in the tensile test for the swine skin tissue. The uniaxial tensile tests of samples taken from the abdomen and back of a pig was carried out. The mechanical properties of the skin such as the mean Young's modulus, the mean maximum stress and the mean maximum elongation were calculated. The experimental data have been used to identify the parameters in specific strain-energy functions given in seven constitutive models of hyperelastic materials: neo-Hookean, Mooney-Rivlin, Ogden, Yeoh, Martins, Humphrey and Veronda-Westmann. An analysis of errors in fitting of theoretical and experimental data was done. Comparison of load -displacement curves for the back and abdomen regions of skin taken showed a different scope of both the mean maximum loading forces and the mean maximum elongation. Samples which have been prepared from the abdominal area had lower values of the mean maximum load compared to samples from the spine area. The reverse trend was observed during the analysis of the values of elongation. An analysis of the accuracy of model fitting to the experimental data showed that, the least accurate were the model of neo- -Hookean, model of Mooney-Rivlin for the abdominal region and model of Veronda-Westmann for the spine region. An analysis of seven hyperelastic material models showed good correlations between the experimental and the theoretical data for five models.

Low Cost Skin Segmentation Scheme in Videos Using Two Alternative Methods for Dynamic Hand Gesture Detection Method

Directory of Open Access Journals (Sweden)

Eman Thabet

2017-01-01

Full Text Available Recent years have witnessed renewed interest in developing skin segmentation approaches. Skin feature segmentation has been widely employed in different aspects of computer vision applications including face detection and hand gestures recognition systems. This is mostly due to the attractive characteristics of skin colour and its effectiveness to object segmentation. On the contrary, there are certain challenges in using human skin colour as a feature to segment dynamic hand gesture, due to various illumination conditions, complicated environment, and computation time or real-time method. These challenges have led to the insufficiency of many of the skin color segmentation approaches. Therefore, to produce simple, effective, and cost efficient skin segmentation, this paper has proposed a skin segmentation scheme. This scheme includes two procedures for calculating generic threshold ranges in Cb-Cr colour space. The first procedure uses threshold values trained online from nose pixels of the face region. Meanwhile, the second procedure known as the offline training procedure uses thresholds trained out of skin samples and weighted equation. The experimental results showed that the proposed scheme achieved good performance in terms of efficiency and computation time.

Investigating the protective properties of milk phospholipids against ultraviolet light exposure in a skin equivalent model

Science.gov (United States)

Russell, Ashley; Laubscher, Andrea; Jimenez-Flores, Rafael; Laiho, Lily H.

2010-02-01

Current research on bioactive molecules in milk has documented health advantages of bovine milk and its components. Milk Phospholipids, selected for this study, represent molecules with great potential benefit in human health and nutrition. In this study we used confocal reflectance and multiphoton microscopy to monitor changes in skin morphology upon skin exposure to ultraviolet light and evaluate the potential of milk phospholipids in preventing photodamage to skin equivalent models. The results suggest that milk phospholipids act upon skin cells in a protective manner against the effect of ultraviolet (UV) radiation. Similar results were obtained from MTT tissue viability assay and histology.

Dynamic in vivo mapping of model moisturiser ingress into human skin by GARfield MRI.

Science.gov (United States)

Ciampi, Elisabetta; van Ginkel, Michael; McDonald, Peter J; Pitts, Simon; Bonnist, Eleanor Y M; Singleton, Scott; Williamson, Ann-Marie

2011-02-01

We describe the development of in vivo one-dimensional MRI (profiling) using a GARField (Gradient At Right angles to Field) magnet for the characterisation of side-of-hand human skin. For the first time and in vivo, we report measurements of the NMR longitudinal and transverse relaxation parameters and self-diffusivity of the upper layers of human skin with a nominal spatial resolution better than 10 µm. The results are correlated with in vivo confocal Raman spectroscopy measurements of water concentration and natural moisturiser factors, and discussed in terms of known skin biology and microstructure of the stratum corneum and viable epidermis. The application of model moisturiser solutions to the skin is followed and their dynamics of ingress are characterised using the MRI methodology developed. Selected hydrophilic and lipophilic formulations are studied. The results are corroborated by standard in vivo measurements of transepidermal water loss and hydration status. A further insight into moisturisation mechanisms is gained. The effect of two different penetration enhancers on a commonly used skin care oil is also discussed, and different timescales of oil penetration into the skin are reported depending on the type of enhancer. Copyright © 2010 John Wiley & Sons, Ltd.

Use of mouse thigh as a radiobiological model of radiation-induced skin reactions

International Nuclear Information System (INIS)

Smith, A.J.; Hagkyriakou, H.; Martin, R.F.

2000-01-01

Full text: The effects of radiation exposure on skin have been widely studied. One of the most useful and relatively easy methods for evaluating radiation-induced skin reactions is the mouse thigh model. This model is non-invasive and has the advantage of not requiring the use of anaesthetic. In the current adaptation of the mouse thigh model, female C3H/HeJ ARC mice (from the Animal Resource Centre, W.A.) were used. The mice were restrained in specially designed jigs where the right leg was held in place by a metal hook. Lead shielding ensured that only the right ventral thigh was exposed to the radiation beam. A 6MeV electron beam from a Varian 2100 Linac (20Gy / minute) was used, thus minimising the time for which the mice were restrained. Eight to twelve days after exposure to the radiation, the first skin reactions can be seen. These are scored according to a scale ranging from 0 (no visible reaction) to 3.5 (breakdown of the entire area with severe exudation). The skin reactions (erythema and moist desquamation) peak approximately 18-22 days after radiation exposure and may remain at peak for only 1-3 days. Therefore, the reactions need to be scored daily and this continues, generally until day 35, or until all moist desquamation has healed. The maximum score in a score versus time profile for each mouse in a group of 5-6 animals are averaged. Radiation-dose response data will be presented. Using the mouse thigh model, hair loss can also be measured (usually on about day 30-35) using a scale from 0-4, where 0 depicts no evident hair loss and 4 represents complete epilation. Leg contraction can also be measured as a late effect by comparison with the length of the unirradiated leg

Elementary of animal model for percutaneous and ocular penetration

Directory of Open Access Journals (Sweden)

Kalpesh Chhotalal Ashara

2016-12-01

Full Text Available Models of animal are the most appropriate method for assessments of human in-vivo percutaneous and ocular penetrations. Monkey and rodents are used for the same. There are several nuts and bolts of each one, so it is necessary to study each one separately. Monkey, porcine and guinea pig penetration are correlated with that of human skin. The skin of rodents, lupus, pigs, etc. has more penetration properties than human skin. Rabbit, goat and sheep eye are mostly used for ocular penetration. The researcher also used hen’s egg chorioallantoic membrane test for ocular irritation study. The other animals’ cornea, cul-de-sac, eyeballs and prepared corneal epithelial models are very less in practice. Web-based alternative non-animal models are also available instead of animal models too. This article describes characteristics of monkeys, pigs, rats, rabbits, guinea pigs and hairless rodents, HuSki model, Cellophane® membrane, egg membrane, gelatin membrane, animal models for ophthalmic delivery, hen’s egg chorioallantoic membrane test, prepared corneal epithelial models and web-based alternative non-animal database.

Skin care products can aggravate epidermal function: studies in a murine model suggest a pathogenic role in sensitive skin

OpenAIRE

Li, Z; Hu, L; Elias, PM; Man, M-Q

2018-01-01

Sensitive skin is defined as a spectrum of unpleasant sensations in response to a variety of stimuli. However, only some skin care products provoke cutaneous symptoms in individuals with sensitive skin. Hence, it would be useful to identify products that could provoke cutaneous symptoms in individuals with sensitive skin.To assess whether vehicles, as well as certain branded skin care products, can alter epidermal function following topical applications to normal mouse skin.Following topical ...

Adapting Evaluations of Alternative Payment Models to a Changing Environment.

Science.gov (United States)

Grannemann, Thomas W; Brown, Randall S

2018-04-01

To identify the most robust methods for evaluating alternative payment models (APMs) in the emerging health care delivery system environment. We assess the impact of widespread testing of alternative payment models on the ability to find credible comparison groups. We consider the applicability of factorial research designs for assessing the effects of these models. The widespread adoption of alternative payment models could effectively eliminate the possibility of comparing APM results with a "pure" control or comparison group unaffected by other interventions. In this new environment, factorial experiments have distinct advantages over the single-model experimental or quasi-experimental designs that have been the mainstay of recent tests of Medicare payment and delivery models. The best prospects for producing definitive evidence of the effects of payment incentives for APMs include fractional factorial experiments that systematically vary requirements and payment provisions within a payment model. © Health Research and Educational Trust.

Determination of the axial and circumferential mechanical properties of the skin tissue using experimental testing and constitutive modeling.

Science.gov (United States)

Karimi, Alireza; Navidbakhsh, Mahdi; Haghighatnama, Maedeh; Haghi, Afsaneh Motevalli

2015-01-01

The skin, being a multi-layered material, is responsible for protecting the human body from the mechanical, bacterial, and viral insults. The skin tissue may display different mechanical properties according to the anatomical locations of a body. However, these mechanical properties in different anatomical regions and at different loading directions (axial and circumferential) of the mice body to date have not been determined. In this study, the axial and circumferential loads were imposed on the mice skin samples. The elastic modulus and maximum stress of the skin tissues were measured before the failure occurred. The nonlinear mechanical behavior of the skin tissues was also computationally investigated through a suitable constitutive equation. Hyperelastic material model was calibrated using the experimental data. Regardless of the anatomic locations of the mice body, the results revealed significantly different mechanical properties in the axial and circumferential directions and, consequently, the mice skin tissue behaves like a pure anisotropic material. The highest elastic modulus was observed in the back skin under the circumferential direction (6.67 MPa), while the lowest one was seen in the abdomen skin under circumferential loading (0.80 MPa). The Ogden material model was narrowly captured the nonlinear mechanical response of the skin at different loading directions. The results help to understand the isotropic/anisotropic mechanical behavior of the skin tissue at different anatomical locations. They also have implications for a diversity of disciplines, i.e., dermatology, cosmetics industry, clinical decision making, and clinical intervention.

The Vitamin D–Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas

Directory of Open Access Journals (Sweden)

Patrice Jones

2018-04-01

Full Text Available Vitamin D is unique in being generated in our skin following ultraviolet radiation (UVR exposure. Ongoing research into vitamin D must therefore always consider the influence of UVR on vitamin D processes. The close relationship between vitamin D and UVR forms the basis of the “vitamin D–folate hypothesis”, a popular theory for why human skin colour has evolved as an apparent adaption to UVR environments. Vitamin D and folate have disparate sensitivities to UVR; whilst vitamin D may be synthesised following UVR exposure, folate may be degraded. The vitamin D–folate hypothesis proposes that skin pigmentation has evolved as a balancing mechanism, maintaining levels of these vitamins. There are several alternative theories that counter the vitamin D–folate hypothesis. However, there is significant overlap between these theories and the now known actions of vitamin D and folate in the skin. The focus of this review is to present an update on the vitamin D–folate hypothesis by integrating these current theories and discussing new evidence that supports associations between vitamin D and folate genetics, UVR, and skin pigmentation. In light of recent human migrations and seasonality in disease, the need for ongoing research into potential UVR-responsive processes within the body is also discussed.

Expression and significance of Bax protein in model of radiation injury in mouse skin

International Nuclear Information System (INIS)

Feng Yizhong; Mo Yahong

2002-01-01

Objective: The study is to find some valuable criteria for diagnosis and treatment of radiation injury in skin. Methods: The expression of Bax protein was studied by SP immunohistochemistry in 40 cases of model of radiation injury in mouse skin. Their relationship relating to radiation dose was also investigated. Results: The expression rates of Bax were 30%, 30%, 70%, 70% in 5 Gy group, 15 Gy group, 30 Gy group, 45 Gy group respectively. There was no significant correlation between the expression of Bax and radiation groups. Conclusions: The experiment shows that radiation can increase the expression of Bax protein which might be related to poor healing in radiation skin injury

Raman microspectroscopy as a diagnostic tool for the non-invasive analysis of fibrillin-1 deficiency in the skin and in the in vitro skin models.

Science.gov (United States)

Brauchle, Eva; Bauer, Hannah; Fernes, Patrick; Zuk, Alexandra; Schenke-Layland, Katja; Sengle, Gerhard

2017-04-01

Fibrillin microfibrils and elastic fibers are critical determinants of elastic tissues where they define as tissue-specific architectures vital mechanical properties such as pliability and elastic recoil. Fibrillin microfibrils also facilitate elastic fiber formation and support the association of epithelial cells with the interstitial matrix. Mutations in fibrillin-1 (FBN1) are causative for the Marfan syndrome, a congenital multisystem disorder characterized by progressive deterioration of the fibrillin microfibril/ elastic fiber architecture in the cardiovascular, musculoskeletal, ocular, and dermal system. In this study, we utilized Raman microspectroscopy in combination with principal component analysis (PCA) to analyze the molecular consequences of fibrillin-1 deficiency in skin of a mouse model (GT8) of Marfan syndrome. In addition, full-thickness skin models incorporating murine wild-type and Fbn1 GT8/GT8 fibroblasts as well as human HaCaT keratinocytes were generated and analyzed. Skin models containing GT8 fibroblasts showed an altered epidermal morphology when compared to wild-type models indicating a new role for fibrillin-1 in dermal-epidermal crosstalk. Obtained Raman spectra together with PCA allowed to discriminate between healthy and deficient microfibrillar networks in murine dermis and skin models. Interestingly, results obtained from GT8 dermis and skin models showed similar alterations in molecular signatures triggered by fibrillin-1 deficiency such as amide III vibrations and decreased levels of glycan vibrations. Overall, this study indicates that Raman microspectroscopy has the potential to analyze subtle changes in fibrillin-1 microfibrils and elastic fiber networks. Therefore Raman microspectroscopy may be utilized as a non-invasive and sensitive diagnostic tool to identify connective tissue disorders and monitor their disease progression. Mutations in building blocks of the fibrillin microfibril/ elastic fiber network manifest in disease

WE-AB-303-04: A Tissue Model of Cherenkov Emission From the Skin Surface During Megavoltage X-Ray Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Wiles, A. N.; Loyalka, S. K. [University of Missouri, Columbia, MO (United States); Izaguirre, E. W. [University of Missouri, Columbia, MO (United States); Baylor Scott & White Health, Temple, TX (United States)

2015-06-15

Purpose: To develop a tissue model of Cherenkov radiation emitted from the skin surface during external beam radiotherapy. Imaging Cherenkov radiation emitted from human skin allows visualization of the beam position and potentially surface dose estimates, and our goal is to characterize the optical properties of these emissions. Methods: We developed a Monte Carlo model of Cherenkov radiation generated in a semi-infinite tissue slab by megavoltage x-ray beams with optical transmission properties determined by a two-layered skin model. We separate the skin into a dermal and an epidermal layer in our model, where distinct molecular absorbers modify the Cherenkov intensity spectrum in each layer while we approximate the scattering properties with Mie and Rayleigh scattering from the highly structured molecular organization found in human skin. Results: We report on the estimated distributions of the Cherenkov wavelength spectrum, emission angles, and surface distribution for the modeled irradiated skin surface. The expected intensity distribution of Cherenkov radiation emitted from skin shows a distinct intensity peak around 475 nm, the blue region of the visible spectrum, between a pair of optical absorption bands in hemoglobin and a broad plateau beginning near 600 nm and extending to at least 700 nm where melanin and hemoglobin absorption are both low. We also find that the Cherenkov intensity decreases with increasing angle from the surface normal, the majority being emitted within 20 degrees of the surface normal. Conclusion: Our estimate of the spectral distribution of Cherenkov radiation emitted from skin indicates an advantage to using imaging devices with long wavelength spectral responsivity. We also expect the most efficient imaging to be near the surface normal where the intensity is greatest; although for contoured surfaces, the relative intensity across the surface may appear to vary due to decreasing Cherenkov intensity with increased angle from the

Topical Curcumin-Based Cream Is Equivalent to Dietary Curcumin in a Skin Cancer Model

International Nuclear Information System (INIS)

Sonavane, K.; Phillips, J.; Lakshmaiah, R. R.; Ekshyyan, O.; Moore-Medlin, T.; Rong, X.; Nathan, C. O.; Ekshyyan, O.; Moore-Medlin, T.; Rong, X.; Nathan, C.O.; Gill, J. R.; Clifford, J. L.; Abreo, F.; Boudreaux, D.; Nathan, C. O.

2012-01-01

Skin squamous cell carcinoma (SCC), the most common cancer in the USA, is a growing problem with the use of tanning booths causing sun-damaged skin. Antiproliferative effects of curcumin were demonstrated in an aggressive skin cancer cell line SRB12-p9 (ρ< 0.05 compared to control). Topical formulation was as effective as oral curcumin at suppressing tumor growth in a mouse skin cancer model. Curcumin at 15 mg administered by oral, topical, or combined formulation significantly reduced tumor growth compared to control (ρ=0.004). Inhibition of pAKT, pS6, p-4EBP1, pSTAT3, and pERK 1/2 was noted in SRB12-p9 cells post-curcumin treatment compared to control (ρ<0.05). Inhibition of pSTAT3 and pERK 1/2 was also noted in curcumin-treated groups in vivo. IHC analysis revealed human tumor specimens that expressed significantly more activated pERK ( ρ=0.006) and pS6 (ρ< 0.0001) than normal skin samples. This is the first study to compare topical curcumin to oral curcumin. Our data supports the use of curcumin as a chemo preventive for skin SCC where condemned skin is a significant problem. Prevention strategies offer the best hope of future health care costs in a disease that is increasing in incidence due to increased sun exposure.

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

Science.gov (United States)

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

2015-08-01

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

Cloud-based Monte Carlo modelling of BSSRDF for the rendering of human skin appearance (Conference Presentation)

Science.gov (United States)

Doronin, Alexander; Rushmeier, Holly E.; Meglinski, Igor; Bykov, Alexander V.

2016-03-01

We present a new Monte Carlo based approach for the modelling of Bidirectional Scattering-Surface Reflectance Distribution Function (BSSRDF) for accurate rendering of human skin appearance. The variations of both skin tissues structure and the major chromophores are taken into account correspondingly to the different ethnic and age groups. The computational solution utilizes HTML5, accelerated by the graphics processing units (GPUs), and therefore is convenient for the practical use at the most of modern computer-based devices and operating systems. The results of imitation of human skin reflectance spectra, corresponding skin colours and examples of 3D faces rendering are presented and compared with the results of phantom studies.

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

Directory of Open Access Journals (Sweden)

Zou Y

2017-10-01

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

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

NARCIS (Netherlands)

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

2002-01-01

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

Skin carcinogenesis in man and in experimental models

International Nuclear Information System (INIS)

Hecker, E.; Jung, E.G.; Marks, F.; Tilgen, W.

1993-01-01

This book presents an updated overview of the current state of the art in scientific, experimental and clinical investigations on the generation and the prevention of cancer of the skin. From the achievements presented, marked refinements in the assessment of the risk of cancer, by environmental and endogenous factors, including tumor virus, will be stimulated. They include the problem of the stratospheric 'ozone holes' above both poles of the earth causing much public concern as expressed by current headlines in the media and by the United Nations Environmental Program. Moreover, new ideas will merge for developing specific approaches to explore the mechanistic, i.e. ultimately the molecular-biological, causes of skin cancer and others. In addition, the experimental utilization of oncogens and of other techniques of molecular biology at all levels of the biology of tissues and cells, may open up entirely new facets in the research on skin cancer. Detailed knowledge of the mechanistic aspects of skin carcinogenesis may give important hints with respect to 'tailor-make' and utilize new anti-tumor agents in the therapy of skin cancer for the benefit of the cancer patient. (orig.). 67 figs., 44 tabs

Modelling of spray evaporation and penetration for alternative fuels

OpenAIRE

Azami, M. H.; Savill, Mark A.

2016-01-01

The focus of this work is on the modelling of evaporation and spray penetration for alternative fuels. The extension model approach is presented and validated for alternative fuels, namely, Kerosene (KE), Ethanol (ETH), Methanol (MTH), Microalgae biofuel (MA), Jatropha biofuel (JA), and Camelina biofuel (CA). The results for atomization and spray penetration are shown in a time variant condition. Comparisons have been made to visualize the transient behaviour of these fuels. The vapour pressu...

Skin color parameters and Fitzpatrick phototypes in estimating the risk of skin cancer: A case-control study in the Polish population.

Science.gov (United States)

Sitek, Aneta; Rosset, Iwona; Żądzińska, Elżbieta; Kasielska-Trojan, Anna; Neskoromna-Jędrzejczak, Aneta; Antoszewski, Bogusław

2016-04-01

Light skin pigmentation is a known risk factor for skin cancer. Skin color parameters and Fitzpatrick phototypes were evaluated in terms of their usefulness in predicting the risk of skin cancer. A case-control study involved 133 individuals with skin cancer (100 with basal cell carcinoma, 21 with squamous cell carcinoma, 12 with melanoma) and 156 healthy individuals. All of them had skin phototype determined and spectrophotometric skin color measurements were done on the inner surfaces of their arms and on the buttock. Using those data, prediction models were built and subjected to 17-fold stratified cross-validation. A model, based on skin phototypes, was characterized by area under the receiver operating characteristic curve = 0.576 and exhibited a lower predictive power than the models, which were mostly based on spectrophotometric variables describing pigmentation levels. The best predictors of skin cancer were R coordinate of RGB color space (area under the receiver operating characteristic curve 0.687) and melanin index (area under the receiver operating characteristic curve 0.683) for skin on the buttock. A small number of patients were studied. Models were not externally validated. Skin color parameters are more accurate predictors of skin cancer occurrence than skin phototypes. Spectrophotometry is a quick, easy, and affordable method offering relatively good predictive power. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Construction of a Three-Dimensional in vitro skin model on polycaprolactone fibers.

Science.gov (United States)

Liu, Qi; Zhang, Ru-Zhi; Xu, Bin

2017-05-16

To observe the morphological characteristics and the biological properties of human epidermal cells when cultured at an air-liquid interface in polycaprolactone (PCL) fibers as a three-dimensional scaffold for tissue engineering. In this study, the melanocytes and keratinocytes were obtained from human scalp skin, seeded onto a PCL film, and cocultured for 2 weeks to construct a three-dimensional (3D) skin model. The cells were then characterized by hematoxylin and eosin (H&E) staining, by immunohistochemical staining with antibodies to cytokeratin 15 (CK15), Ki-67, CD34, CD200 and HMB45 and by transmission electron microscopy. Keratinocytes and melanocytes grew well in the co-culture system. Hematoxylin and eosin staining revealed that the cells adhered to the PCLfiber scaffold well, the keratinocyte layer became a multilayered concentric structure and the surface became distinctly keratinized at the air-liquid interface. Immunohistochemical analyses exhibited a scattered distribution of cells expressing CK15, CD34, CD200, Ki-67 and/or HMB45. Transmission electron microscopy revealed that the keratinocytes contained a number of keratin fibrils and membrane-coated granules. The PCL scaffold has excellent adhesiveness and biocompatibility with human epidermal cells, and is suitable for constructing 3D skin models for tissue engineering in the future.

On the importance of body posture and skin modelling with respect to in situ electric field strengths in magnetic field exposure scenarios

Science.gov (United States)

Schmid, Gernot; Hirtl, Rene

2016-06-01

The reference levels and maximum permissible exposure values for magnetic fields that are currently used have been derived from basic restrictions under the assumption of upright standing body models in a standard posture, i.e. with arms laterally down and without contact with metallic objects. Moreover, if anatomical modelling of the body was used at all, the skin was represented as a single homogeneous tissue layer. In the present paper we addressed the possible impacts of posture and skin modelling in scenarios of exposure to a 50 Hz uniform magnetic field on the in situ electric field strength in peripheral tissues, which must be limited in order to avoid peripheral nerve stimulation. We considered different body postures including situations where body parts form large induction loops (e.g. clasped hands) with skin-to-skin and skin-to-metal contact spots and compared the results obtained with a homogeneous single-layer skin model to results obtained with a more realistic two-layer skin representation consisting of a low-conductivity stratum corneum layer on top of a combined layer for the cellular epidermis and dermis. Our results clearly indicated that postures with loops formed of body parts may lead to substantially higher maximum values of induced in situ electric field strengths than in the case of standard postures due to a highly concentrated current density and in situ electric field strength in the skin-to-skin and skin-to-metal contact regions. With a homogeneous single-layer skin, as is used for even the most recent anatomical body models in exposure assessment, the in situ electric field strength may exceed the basic restrictions in such situations, even when the reference levels and maximum permissible exposure values are not exceeded. However, when using the more realistic two-layer skin model the obtained in situ electric field strengths were substantially lower and no violations of the basic restrictions occurred, which can be explained by the

Radionuclide therapy of skin cancers and Bowen's disease using specially designed skin patch: A pilot study in an animal model and clinical trial

International Nuclear Information System (INIS)

Lee, J. D.; Park, K. K.; Lee, M. G.; Lee, J. T.; Yoo, H. S.; Kim, E. H.; Rhim, K. J.; Kim, Y. M.; Park, K. B.; Kim, J. R.

1997-01-01

Skin cancer is the most common malignant tumors in human. Therapeutic modalities of the skin cancers are local destruction, radiotherapy and surgery. External radiation therapy leads to good results, however, overall 5-6 weeks of treatment period is needed to deliver optimal radiation dose to tumors. In this study, β-emitting radionuclide, Ho-166, impregnated in a specially designed patch was utilized to superficial skin cancers and Bowen's disease for local irradiation. Methods; Animal study was employed in 10 mice with chemically induced skin tumors. Five- mm size patches containing 22.2 -72.15 MBq(0.6 - 1.95 mCi) of Ho-166 were applied to the tumor surface for 1 -2 hr. In clinical trial, patients with squamous carcinoma(n=3), basal cell carcinoma(n=1), and Bowen's disease(n=1) were treated with patches containing 273.8 - 999 MBq (7.4 - 27 mCi) of Ho-166 for 30 minutes to 1 hour. Pathologic examination was performed 4 - 7 weeks after the treatment in animal model. Skin biopsy was performed 8 weeks post-treatment in four patients. Results; Tumor destruction was seen 1 week post the treatment, however, radiation dermatitis or ulceration developed at the site of radionuclide application. Those reactions healed gradually with fibrosis or epithelialization, which was confirmed pathologically. No significant adverse reaction to radiation except subcutaneous fibrosis was found. Conclusion; Superficial skin tumors could be successfully treated by topical application of β-emitting radionuclides. (author)

Radiation sterilization of skin allograft

International Nuclear Information System (INIS)

Kairiyama, E.; Horak, C.; Spinosa, M.; Pachado, J.; Schwint, O.

2009-01-01

In the treatment of burns or accidental loss of skin, cadaveric skin allografts provide an alternative to temporarily cover a wounded area. The skin bank facility is indispensable for burn care. The first human skin bank was established in Argentina in 1989; later, 3 more banks were established. A careful donor selection is carried out according to the national regulation in order to prevent transmissible diseases. As cadaveric human skin is naturally highly contaminated, a final sterilization is necessary to reach a sterility assurance level (SAL) of 10 -6 . The sterilization dose for 106 batches of processed human skin was determined on the basis of the Code of Practice for the Radiation Sterilization of Tissue Allografts: Requirements for Validation and Routine Control (2004) and ISO 11137-2 (2006). They ranged from 17.6 to 33.4 kGy for bioburdens of >10-162.700 CFU/100 cm 2 . The presence of Gram negative bacteria was checked for each produced batch. From the analysis of the experimental results, it was observed that the bioburden range was very wide and consequently the estimated sterilization doses too. If this is the case, the determination of a tissue-specific dose per production batch is necessary to achieve a specified requirement of SAL. Otherwise if the dose of 25 kGy is preselected, a standardized method for substantiation of this dose should be done to confirm the radiation sterilization process.

Radiation sterilization of skin allograft

Science.gov (United States)

Kairiyama, E.; Horak, C.; Spinosa, M.; Pachado, J.; Schwint, O.

2009-07-01

In the treatment of burns or accidental loss of skin, cadaveric skin allografts provide an alternative to temporarily cover a wounded area. The skin bank facility is indispensable for burn care. The first human skin bank was established in Argentina in 1989; later, 3 more banks were established. A careful donor selection is carried out according to the national regulation in order to prevent transmissible diseases. As cadaveric human skin is naturally highly contaminated, a final sterilization is necessary to reach a sterility assurance level (SAL) of 10 -6. The sterilization dose for 106 batches of processed human skin was determined on the basis of the Code of Practice for the Radiation Sterilization of Tissue Allografts: Requirements for Validation and Routine Control (2004) and ISO 11137-2 (2006). They ranged from 17.6 to 33.4 kGy for bioburdens of >10-162.700 CFU/100 cm 2. The presence of Gram negative bacteria was checked for each produced batch. From the analysis of the experimental results, it was observed that the bioburden range was very wide and consequently the estimated sterilization doses too. If this is the case, the determination of a tissue-specific dose per production batch is necessary to achieve a specified requirement of SAL. Otherwise if the dose of 25 kGy is preselected, a standardized method for substantiation of this dose should be done to confirm the radiation sterilization process.

Modelling glucose and water dynamics in human skin

NARCIS (Netherlands)

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

2008-01-01

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

Neutron-skin thickness of finite nuclei in relativistic mean-field models with chiral limits

International Nuclear Information System (INIS)

Jiang Weizhou; Li Baoan; Chen Liewen

2007-01-01

We study several structure properties of finite nuclei using relativistic mean-field Lagrangians constructed according to the Brown-Rho scaling due to the chiral symmetry restoration at high densities. The models are consistent with current experimental constraints for the equations of state of symmetric matter at both normal and supranormal densities and of asymmetric matter at subsaturation densities. It is shown that these models can successfully describe the binding energies and charge radii of finite nuclei. Compared to calculations with usual relativistic mean-field models, these models give a reduced thickness of neutron skin in 208 Pb between 0.17 fm and 0.21 fm. The reduction of the predicted neutron skin thickness is found to be due to not only the softening of the symmetry energy but also the scaling property of ρ meson required by the partial restoration of chiral symmetry

Humanized Mouse Model of Skin Inflammation Is Characterized by Disturbed Keratinocyte Differentiation and Influx of IL-17A Producing T Cells

Science.gov (United States)

de Oliveira, Vivian L.; Keijsers, Romy R. M. C.; van de Kerkhof, Peter C. M.; Seyger, Marieke M. B.; Fasse, Esther; Svensson, Lars; Latta, Markus; Norsgaard, Hanne; Labuda, Tord; Hupkens, Pieter; van Erp, Piet E. J.; Joosten, Irma; Koenen, Hans J. P. M.

2012-01-01

Humanized mouse models offer a challenging possibility to study human cell function in vivo. In the huPBL-SCID-huSkin allograft model human skin is transplanted onto immunodeficient mice and allowed to heal. Thereafter allogeneic human peripheral blood mononuclear cells are infused intra peritoneally to induce T cell mediated inflammation and microvessel destruction of the human skin. This model has great potential for in vivo study of human immune cells in (skin) inflammatory processes and for preclinical screening of systemically administered immunomodulating agents. Here we studied the inflammatory skin response of human keratinocytes and human T cells and the concomitant systemic human T cell response. As new findings in the inflamed human skin of the huPBL-SCID-huSkin model we here identified: 1. Parameters of dermal pathology that enable precise quantification of the local skin inflammatory response exemplified by acanthosis, increased expression of human β-defensin-2, Elafin, K16, Ki67 and reduced expression of K10 by microscopy and immunohistochemistry. 2. Induction of human cytokines and chemokines using quantitative real-time PCR. 3. Influx of inflammation associated IL-17A-producing human CD4+ and CD8+ T cells as well as immunoregulatory CD4+Foxp3+ cells using immunohistochemistry and -fluorescence, suggesting that active immune regulation is taking place locally in the inflamed skin. 4. Systemic responses that revealed activated and proliferating human CD4+ and CD8+ T cells that acquired homing marker expression of CD62L and CLA. Finally, we demonstrated the value of the newly identified parameters by showing significant changes upon systemic treatment with the T cell inhibitory agents cyclosporine-A and rapamycin. In summary, here we equipped the huPBL-SCID-huSkin humanized mouse model with relevant tools not only to quantify the inflammatory dermal response, but also to monitor the peripheral immune status. This combined approach will gain our

Volumetric Visualization of Human Skin

Science.gov (United States)

Kawai, Toshiyuki; Kurioka, Yoshihiro

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

A Randomized Controlled Trial of an Appearance-focused Intervention to Prevent Skin Cancer

Science.gov (United States)

Hillhouse, Joel; Turrisi, Rob; Stapleton, Jerod; Robinson, June

2014-01-01

BACKGROUND Skin cancer represents a significant health threat with over 1.3 million diagnoses, 8000 melanoma deaths, and more than $1 billion spent annually for skin cancer healthcare in the US. Despite findings from laboratory, case-control, and prospective studies that indicate a link between youthful indoor tanning (IT) and skin cancer, IT is increasing among US youth. Appearance-focused interventions represent a promising method to counteract these trends. METHODS A total of 430 female indoor tanners were randomized into intervention or no intervention control conditions. Intervention participants received an appearance-focused booklet based on decision-theoretical models of health behavior. Outcome variables included self-reports of IT behavior and intentions, as well as measures of cognitive mediating variables. RESULTS Normative increases in springtime IT rates were significantly lower (ie, over 35%) at 6-month follow-up in intervention versus control participants with similar reductions in future intentions. Mediation analyses revealed 6 cognitive variables (IT attitudes, fashion attitudes, perceived susceptibility to skin cancer and skin damage, subjective norms, and image norms) that significantly mediated change in IT behavior. CONCLUSIONS The appearance-focused intervention demonstrated strong effects on IT behavior and intentions in young indoor tanners. Appearance-focused approaches to skin cancer prevention need to present alternative behaviors as well as alter IT attitudes. Mediational results provide guides for strengthening future appearance-focused interventions directed at behaviors that increase risk of skin cancer. PMID:18937268

Non-animal methods to predict skin sensitization (II): an assessment of defined approaches *.

Science.gov (United States)

Kleinstreuer, Nicole C; Hoffmann, Sebastian; Alépée, Nathalie; Allen, David; Ashikaga, Takao; Casey, Warren; Clouet, Elodie; Cluzel, Magalie; Desprez, Bertrand; Gellatly, Nichola; Göbel, Carsten; Kern, Petra S; Klaric, Martina; Kühnl, Jochen; Martinozzi-Teissier, Silvia; Mewes, Karsten; Miyazawa, Masaaki; Strickland, Judy; van Vliet, Erwin; Zang, Qingda; Petersohn, Dirk

2018-05-01

Skin sensitization is a toxicity endpoint of widespread concern, for which the mechanistic understanding and concurrent necessity for non-animal testing approaches have evolved to a critical juncture, with many available options for predicting sensitization without using animals. Cosmetics Europe and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods collaborated to analyze the performance of multiple non-animal data integration approaches for the skin sensitization safety assessment of cosmetics ingredients. The Cosmetics Europe Skin Tolerance Task Force (STTF) collected and generated data on 128 substances in multiple in vitro and in chemico skin sensitization assays selected based on a systematic assessment by the STTF. These assays, together with certain in silico predictions, are key components of various non-animal testing strategies that have been submitted to the Organization for Economic Cooperation and Development as case studies for skin sensitization. Curated murine local lymph node assay (LLNA) and human skin sensitization data were used to evaluate the performance of six defined approaches, comprising eight non-animal testing strategies, for both hazard and potency characterization. Defined approaches examined included consensus methods, artificial neural networks, support vector machine models, Bayesian networks, and decision trees, most of which were reproduced using open source software tools. Multiple non-animal testing strategies incorporating in vitro, in chemico, and in silico inputs demonstrated equivalent or superior performance to the LLNA when compared to both animal and human data for skin sensitization.

A randomized controlled trial of an appearance-focused intervention to prevent skin cancer.

Science.gov (United States)

Hillhouse, Joel; Turrisi, Rob; Stapleton, Jerod; Robinson, June

2008-12-01

Skin cancer represents a significant health threat with over 1.3 million diagnoses, 8000 melanoma deaths, and more than $1 billion spent annually for skin cancer healthcare in the US. Despite findings from laboratory, case-control, and prospective studies that indicate a link between youthful indoor tanning (IT) and skin cancer, IT is increasing among US youth. Appearance-focused interventions represent a promising method to counteract these trends. A total of 430 female indoor tanners were randomized into intervention or no intervention control conditions. Intervention participants received an appearance-focused booklet based on decision-theoretical models of health behavior. Outcome variables included self-reports of IT behavior and intentions, as well as measures of cognitive mediating variables. Normative increases in springtime IT rates were significantly lower (ie, over 35%) at 6-month follow-up in intervention versus control participants with similar reductions in future intentions. Mediation analyses revealed 6 cognitive variables (IT attitudes, fashion attitudes, perceived susceptibility to skin cancer and skin damage, subjective norms, and image norms) that significantly mediated change in IT behavior. The appearance-focused intervention demonstrated strong effects on IT behavior and intentions in young indoor tanners. Appearance-focused approaches to skin cancer prevention need to present alternative behaviors as well as alter IT attitudes. Mediational results provide guides for strengthening future appearance-focused interventions directed at behaviors that increase risk of skin cancer. (c) 2008 American Cancer Society

Alternative Public Service Delivery Models in Health, Water and ...

International Development Research Centre (IDRC) Digital Library (Canada)

The literature on public service delivery alternatives has to date been highly localized, sector specific and lacking in methodological consistency. This project seeks to analyze health, water and electricity delivery models in Africa, Asia and Latin America in order to identify and document successful alternatives to ...

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

NARCIS (Netherlands)

Römgens, A.M.; Bader, D.L.; Bouwstra, J.A.; Baaijens, F.P.T.; Oomens, C.W.J.

2015-01-01

Delivering a drug into and through the skin is of interest as the skin can act as an alternative drug administration route for oral delivery. The development of new delivery methods, such as microneedles, makes it possible to not only deliver small molecules into the skin, which are able to pass the

Modeling slug tests in unconfined aquifers with both oscillatory and overdamped responses, and with low-K and high-K skin effects

Science.gov (United States)

Thoma, M. J.; Malama, B.; Barrash, W.; Bohling, G.; Butler, J. J.

2009-12-01

We extend the models for slug tests developed by Hyder et al. (1994) and Butler and Zhan (2004) to obtain a single general model for slug tests in unconfined aquifers in partially penetrating wells with a near-well disturbed zone (skin). The full range of responses, oscillatory to overdamped, is considered since both types of responses are common in wells in unconsolidated coarse fluvial aquifers, and others. The general semi-analytical solution allows for skin and formation storage as well as anisotropy in skin and formation hydraulic conductivity (K). The water table is treated as a fixed head boundary so the solution is applicable for wells screened below the water table. The model is validated by comparison with other models and by matching field data from unconfined fluvial aquifers at sites in Nebraska (MSEA) and Idaho (BHRS). We examine the effects of varying skin K and skin thickness to simulate the impact of a near-well disturbed zone that is lower (damage) or higher (filter pack) K than the formation. Results indicate that, for a given set of measured behavior at an example test zone, minor progressive decreases in estimated formation K occur with increases in assumed skin K, and moderate increases in estimated formation K occur with decreases in assumed skin K. Major increases (orders of magnitude) in estimated formation K occur with increased thickness of low-K skin. The importance of incorporating a finite-thickness representation of the skin, rather than the conventional infinitely thin representation, is also addressed.

3D bioprinting of skin: a state-of-the-art review on modelling, materials, and processes.

Science.gov (United States)

Vijayavenkataraman, S; Lu, W F; Fuh, J Y H

2016-09-08

The skin is the largest organ of the body, having a complex multi-layered structure and guards the underlying muscles, bones, ligaments, and internal organs. It serves as the first line of defence to any external stimuli, hence it is the most vulnerable to injury and warrants the need for rapid and reliable regeneration methods. Tissue engineered skin substitutes help overcome the limitations of traditional skin treatment methods, in terms of technology, time, and cost. While there is commendable progress in the treating of superficial wounds and injuries with skin substitutes, treatment of full-thickness injuries, especially with third or fourth degree burns, still looks murkier. Engineering multi-layer skin architecture, conforming to the native skin structure is a tougher goal to achieve with the current tissue engineering methods, if not impossible, restoring all the functions of the native skin. The testing of drugs and cosmetics is another area, where engineered skins are very much needed, with bans being imposed on product testing on animals. Given this greater need, 3D bioprinting is a promising technology that can achieve rapid and reliable production of biomimetic cellular skin substitutes, satisfying both clinical and industrial needs. This paper reviews all aspects related to the 3D bioprinting of skin, right from imaging the injury site, 3D model creation, biomaterials that are used and their suitability, types of cells and their functions, actual bioprinting technologies, along with the challenges and future prospects.

Implementation, availability and regulatory status of an OECD accepted Reconstructed Human Epidermis model in Brazil

Directory of Open Access Journals (Sweden)

Rodrigo De Vecchi

2018-02-01

Full Text Available Introduction: In 2014, Brazil has joined the growing list of countries to ban cosmetic products from being tested on animal models. The new legislation comes into force in 2019. As a result, the interest for validated alternative testing methods for safety assessment has been increasing in academia, industry and associations. However, the lack of specific legislation on the use of biological material of human origin for toxicological tests makes the access to alternative in vitro models difficult. Furthermore, importation to Brazil is not possible on timely manner. Method: In this article, we report the implementation process of a Reconstructed Human Epidermis (SkinEthic™ RHE, an alternative model internationally accepted by OECD, through a technology transfer from EPISKIN® Lyon to Brazil. Regulatory evolution has been motivating the implementation and wide use of alternative methods to animal testing in several industry segments including cosmetic and pharmaceutical. Results: Protocol has been shown to be robust and highly reproducible. Quality control parameters (histological analysis, barrier function test and tissue viability were performed on 24 batches assembled in Brazil. SkinEthic™ RHE model use allows the full replacement of animal test methods for skin hazards identification. It has regulatory acceptance for several toxicological endpoints, such as the Draize test for skin irritation and corrosion. It allows the reduction and refining of pre-clinical protocols through tiered strategies. Implementation of SkinEthic™ RHE protocol is just a first and important step towards a new approach of toxicological safety testing in Brazil. Conclusion: The implementation was successfully done and reported here. However, in order to follow completely the new legislation up to 2019, the availability of validated models is essential. Quality control tests done on RHE batches produced in Brazil demonstrate that the model met OECD acceptance

Enhanced diagnostic of skin conditions by polarized laser speckles: phantom studies and computer modeling

Science.gov (United States)

Tchvialeva, Lioudmila; Lee, Tim K.; Markhvida, Igor; Zeng, Haishan; Doronin, Alexander; Meglinski, Igor

2014-03-01

The incidence of the skin melanoma, the most commonly fatal form of skin cancer, is increasing faster than any other potentially preventable cancer. Clinical practice is currently hampered by the lack of the ability to rapidly screen the functional and morphological properties of tissues. In our previous study we show that the quantification of scattered laser light polarization provides a useful metrics for diagnostics of the malignant melanoma. In this study we exploit whether the image speckle could improve skin cancer diagnostic in comparison with the previously used free-space speckle. The study includes skin phantom measurements and computer modeling. To characterize the depolarization of light we measure the spatial distribution of speckle patterns and analyse their depolarization ratio taken into account radial symmetry. We examine the dependences of depolarization ratio vs. roughness for phantoms which optical properties are of the order of skin lesions. We demonstrate that the variation in bulk optical properties initiates the assessable changes in the depolarization ratio. We show that image speckle differentiates phantoms significantly better than free-space speckle. The results of experimental measurements are compared with the results of Monte Carlo simulation.

Integrated Computational Solution for Predicting Skin Sensitization Potential of Molecules.

Directory of Open Access Journals (Sweden)

Konda Leela Sarath Kumar

Full Text Available Skin sensitization forms a major toxicological endpoint for dermatology and cosmetic products. Recent ban on animal testing for cosmetics demands for alternative methods. We developed an integrated computational solution (SkinSense that offers a robust solution and addresses the limitations of existing computational tools i.e. high false positive rate and/or limited coverage.The key components of our solution include: QSAR models selected from a combinatorial set, similarity information and literature-derived sub-structure patterns of known skin protein reactive groups. Its prediction performance on a challenge set of molecules showed accuracy = 75.32%, CCR = 74.36%, sensitivity = 70.00% and specificity = 78.72%, which is better than several existing tools including VEGA (accuracy = 45.00% and CCR = 54.17% with 'High' reliability scoring, DEREK (accuracy = 72.73% and CCR = 71.44% and TOPKAT (accuracy = 60.00% and CCR = 61.67%. Although, TIMES-SS showed higher predictive power (accuracy = 90.00% and CCR = 92.86%, the coverage was very low (only 10 out of 77 molecules were predicted reliably.Owing to improved prediction performance and coverage, our solution can serve as a useful expert system towards Integrated Approaches to Testing and Assessment for skin sensitization. It would be invaluable to cosmetic/ dermatology industry for pre-screening their molecules, and reducing time, cost and animal testing.

Stem cells in skin regeneration: biomaterials and computational models

Directory of Open Access Journals (Sweden)

Daniele eTartarini

2016-01-01

Full Text Available The increased incidence of diabetes and tumors, associated with global demographic issues (aging and life styles, has pointed out the importance to develop new strategies for the effective management of skin wounds. Individuals affected by these diseases are in fact highly exposed to the risk of delayed healing of the injured tissue that typically leads to a pathological inflammatory state and consequently to chronic wounds. Therapies based on stem cells have been proposed for the treatment of these wounds, thanks to the ability of stem cells to self-renew and specifically differentiate in response to the target bimolecular environment. Here we discuss how advanced biomedical devices can be developed by combining stem cells with properly engineered biomaterials and computational models. Examples include composite skin substitutes and bioactive dressings with controlled porosity and surface topography for controlling the infiltration and differentiation of the cells. In this scenario, mathematical frameworks for the simulation of cell population growth can provide support for the design of bio-constructs, reducing the need of expensive, time-consuming and ethically controversial animal experimentation.

Skin too thin? The developing utility of zebrafish skin (neuro)pharmacology for CNS drug discovery research.

Science.gov (United States)

Nguyen, Michael; Poudel, Manoj K; Stewart, Adam Michael; Kalueff, Allan V

2013-09-01

Skin coloration can be affected by many genetic, environmental and pharmacological factors. Zebrafish (Danio rerio) are a useful and versatile model organism in biomedical research due to their genetic tractability, physiological homology to mammals, low cost, reproducibility and high throughput. Zebrafish coloration is mediated by chromatophores - the skin color pigment cells largely controlled by endocrine and neural mechanisms. The characteristic darkening of zebrafish skin is caused by the dispersion (and paling - by aggregation) of melanosomes (pigment-containing organelles), which show high homology to mammalian structures. Various pharmacological agents potently affect zebrafish coloration - the phenotype that often accompanies behavioral effects of the drugs, and may be used for drug discovery. Although zebrafish behavior and skin responses are usually not directly related, they share common regulatory (neural, endocrine) mechanisms, and therefore may be assessed in parallel during psychotropic drug screening. For example, some psychoactive drugs can potently affect zebrafish skin coloration. Can we use this knowledge to refine phenotype-driven psychotropic drug discovery? Here, we present current models using zebrafish skin coloration assays, and discuss how these models may be applied to enhance in vivo CNS drug discovery. Copyright © 2013 Elsevier Inc. All rights reserved.

Preliminary experiments on quantification of skin condition

Science.gov (United States)

Kitajima, Kenzo; Iyatomi, Hitoshi

2014-03-01

In this study, we investigated a preliminary assessment method for skin conditions such as a moisturizing property and its fineness of the skin with an image analysis only. We captured a facial images from volunteer subjects aged between 30s and 60s by Pocket Micro (R) device (Scalar Co., Japan). This device has two image capturing modes; the normal mode and the non-reflection mode with the aid of the equipped polarization filter. We captured skin images from a total of 68 spots from subjects' face using both modes (i.e. total of 136 skin images). The moisture-retaining property of the skin and subjective evaluation score of the skin fineness in 5-point scale for each case were also obtained in advance as a gold standard (their mean and SD were 35.15 +/- 3.22 (μS) and 3.45 +/- 1.17, respectively). We extracted a total of 107 image features from each image and built linear regression models for estimating abovementioned criteria with a stepwise feature selection. The developed model for estimating the skin moisture achieved the MSE of 1.92 (μS) with 6 selected parameters, while the model for skin fineness achieved that of 0.51 scales with 7 parameters under the leave-one-out cross validation. We confirmed the developed models predicted the moisture-retaining property and fineness of the skin appropriately with only captured image.

The dynamic development of the muzzle imprint by contact gunshot: high-speed documentation utilizing the "skin-skull-brain model".

Science.gov (United States)

Thali, M J; Kneubuehl, B P; Dirnhofer, R; Zollinger, U

2002-07-17

Many contact gunshots produce a muzzle imprint in the skin of the victim. Different mechanisms have been discussed in literature as being responsible for the creation of the muzzle imprint. Experimenting upon the synthetic non biological skin-skull-brain model, our goal was to document and study the creation of the muzzle imprint with the aid of high-speed photography. In our experiments, we could document with our high-speed photography (at exposure rates in the range of nanoseconds) the bulging, the pressing against the muzzle, and the splitting of the artificial skin. Furthermore, it was possible to photographically record the back pattern of synthetic tissue particles. And, the soot and gunpowder cavity could be reproduced experimentally. In conclusion the experiments completed with the skin-skull-brain model, using high-speed photography for documentation, show the promising possibilities of experimental ballistics with body models.

Interaction of dermatologically relevant nanoparticles with skin cells and skin

Directory of Open Access Journals (Sweden)

Annika Vogt

2014-12-01

Full Text Available The investigation of nanoparticle interactions with tissues is complex. High levels of standardization, ideally testing of different material types in the same biological model, and combinations of sensitive imaging and detection methods are required. Here, we present our studies on nanoparticle interactions with skin, skin cells, and biological media. Silica, titanium dioxide and silver particles were chosen as representative examples for different types of skin exposure to nanomaterials, e.g., unintended environmental exposure (silica versus intended exposure through application of sunscreen (titanium dioxide or antiseptics (silver. Because each particle type exhibits specific physicochemical properties, we were able to apply different combinations of methods to examine skin penetration and cellular uptake, including optical microscopy, electron microscopy, X-ray microscopy on cells and tissue sections, flow cytometry of isolated skin cells as well as Raman microscopy on whole tissue blocks. In order to assess the biological relevance of such findings, cell viability and free radical production were monitored on cells and in whole tissue samples. The combination of technologies and the joint discussion of results enabled us to look at nanoparticle–skin interactions and the biological relevance of our findings from different angles.

Improvement of the equivalent sphere model for better estimates of skin or eye dose in space radiation environments

International Nuclear Information System (INIS)

Lin, Z.W.

2011-01-01

It is often useful to get a quick estimate of the dose or dose equivalent of an organ, such as blood-forming organs, the eye or the skin, in a radiation field. Sometimes an equivalent sphere is used to represent the organ for this purpose. For space radiation environments, recently it has been shown that the equivalent sphere model does not work for the eye or the skin in solar particle event environments. In this study, we improve the representation of the eye and the skin using a two-component equivalent sphere model. Motivated by the two-peak structure of the body organ shielding distribution for the eye and the skin, we use an equivalent sphere with two radius parameters, for example a partial spherical shell of a smaller thickness over a proper fraction of the full solid angle combined with a concentric partial spherical shell of a larger thickness over the rest of the full solid angle, to represent the eye or the skin. We find that using an equivalent sphere with two radius parameters instead of one drastically improves the accuracy of the estimates of dose and dose equivalent in space radiation environments. For example, in solar particle event environments the average error in the estimate of the skin dose equivalent using an equivalent sphere with two radius parameters is about 8%, while the average error of the conventional equivalent sphere model using one radius parameter is around 100%.

The use of ex vivo human skin tissue for genotoxicity testing

Energy Technology Data Exchange (ETDEWEB)

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

2012-06-01

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

The use of ex vivo human skin tissue for genotoxicity testing

International Nuclear Information System (INIS)

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

2012-01-01

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

The effect of low dose ionizing radiation on homeostasis and functional integrity in an organotypic human skin model

Energy Technology Data Exchange (ETDEWEB)

Neubeck, Claere von [German Cancer Consortium DKTK partner site Dresden, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden (Germany); German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Geniza, Matthew J. [Molecular and Cellular Biology Program, Oregon State University, Corvallis OR 97331 (United States); Kauer, Paula M.; Robinson, R. Joe; Chrisler, William B. [Health Impacts and Exposure Science, Pacific Northwest National Laboratory, Richland WA 99352 (United States); Sowa, Marianne B., E-mail: marianne.sowa@pnnl.gov [Health Impacts and Exposure Science, Pacific Northwest National Laboratory, Richland WA 99352 (United States)

2015-05-15

Highlights: • Low doses of high LET radiation influence skin homeostasis. • Effects on proliferation and differentiation profiles are LET dependent. • Skin barrier function is not compromised following low dose exposure. - Abstract: Outside the protection of Earth's atmosphere, astronauts are exposed to low doses of high linear energy transfer (LET) radiation. Future NASA plans for deep space missions or a permanent settlement on the moon are limited by the health risks associated with space radiation exposures. There is a paucity of direct epidemiological data for low dose exposures to space radiation-relevant high LET ions. Health risk models are used to estimate the risk for such exposures, though these models are based on high dose experiments. There is increasing evidence, however, that low and high dose exposures result in different signaling events at the molecular level, and may involve different response mechanisms. Further, despite their low abundance, high LET particles have been identified as the major contributor to health risk during manned space flight. The human skin is exposed in every external radiation scenario, making it an ideal epithelial tissue model in which to study radiation induced effects. Here, we exposed an in vitro three dimensional (3-D) human organotypic skin tissue model to low doses of high LET oxygen (O), silicon (Si) and iron (Fe) ions. We measured proliferation and differentiation profiles in the skin tissue and examined the integrity of the skin's barrier function. We discuss the role of secondary particles in changing the proportion of cells receiving a radiation dose, emphasizing the possible impact on radiation-induced health issues in astronauts.

Alternatives to animal testing: research, trends, validation, regulatory acceptance.

Science.gov (United States)

Huggins, Jane

2003-01-01

Current trends and issues in the development of alternatives to the use of animals in biomedical experimentation are discussed in this position paper. Eight topics are considered and include refinement of acute toxicity assays; eye corrosion/irritation alternatives; skin corrosion/irritation alternatives; contact sensitization alternatives; developmental/reproductive testing alternatives; genetic engineering (transgenic) assays; toxicogenomics; and validation of alternative methods. The discussion of refinement of acute toxicity assays is focused primarily on developments with regard to reduction of the number of animals used in the LD(50) assay. However, the substitution of humane endpoints such as clinical signs of toxicity for lethality in these assays is also evaluated. Alternative assays for eye corrosion/irritation as well as those for skin corrosion/irritation are described with particular attention paid to the outcomes, both successful and unsuccessful, of several validation efforts. Alternative assays for contact sensitization and developmental/reproductive toxicity are presented as examples of methods designed for the examination of interactions between toxins and somewhat more complex physiological systems. Moreover, genetic engineering and toxicogenomics are discussed with an eye toward the future of biological experimentation in general. The implications of gene manipulation for research animals, specifically, are also examined. Finally, validation methods are investigated as to their effectiveness, or lack thereof, and suggestions for their standardization and improvement, as well as implementation are reviewed.

Metabolism of skin-absorbed resveratrol into its glucuronized form in mouse skin.

Directory of Open Access Journals (Sweden)

Itsuo Murakami

Full Text Available Resveratrol (RESV is a plant polyphenol, which is thought to have beneficial metabolic effects in laboratory animals as well as in humans. Following oral administration, RESV is immediately catabolized, resulting in low bioavailability. This study compared RESV metabolites and their tissue distribution after oral uptake and skin absorption. Metabolomic analysis of various mouse tissues revealed that RESV can be absorbed and metabolized through skin. We detected sulfated and glucuronidated RESV metabolites, as well as dihydroresveratrol. These metabolites are thought to have lower pharmacological activity than RESV. Similar quantities of most RESV metabolites were observed 4 h after oral or skin administration, except that glucuronidated RESV metabolites were more abundant in skin after topical RESV application than after oral administration. This result is consistent with our finding of glucuronidated RESV metabolites in cultured skin cells. RESV applied to mouse ears significantly suppressed inflammation in the TPA inflammation model. The skin absorption route could be a complementary, potent way to achieve therapeutic effects with RESV.

The physico-chemical properties of pangas catfish (Pangasius pangasius) skin gelatin

Science.gov (United States)

Pradarameswari, K. A.; Zaelani, K.; Waluyo, E.; Nurdiani, R.

2018-04-01

Gelatin can be used as emulsifier and stabilizer in food products. Until now, the most widely used raw materials for the production of gelatin industry are cow bone, cow skin and pig skin. Fish gelatin has been highlighted as a better alternative to replace mammals gelatin based on ethical and religious perspective. Fish gelatin was extracted from Pangas catfish skin to determine its physico-chemical properties. Different temperatures (45 °C, 50 °C, 55 °C) were employed during gelatin extraction. Higher temperature increased the yield and fat contents of Pangas catfish skin gelatin. In contrary, higher water, protein, ash contents were observed during lower temperature. Temperature significantly (p fish skin gelatin. Based on the FTIR spectrum catfish skin gelatin functional groups can be identified as N-H, O-H, C = H, C-O and C-H.

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

Directory of Open Access Journals (Sweden)

Petkar K.C.

2007-05-01

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

Caspase-3 activation and DNA damage in pig skin organ culture after solar irradiation.

Science.gov (United States)

Bacqueville, Daniel; Mavon, Alain

2008-01-01

In the present study, a convenient and easy-to-handle skin organ culture was developed from domestic pig ears using polycarbonate Transwell culture inserts in 12-well plate. This alternative model was then tested for its suitability in analyzing the short-term effects of a single solar radiation dose (from 55 to 275 kJ.m(-2)). Differentiation of the pig skin was maintained for up to 48 h in culture, and its morphology was similar to that of fresh human skin. Solar irradiation induced a significant release of the cytosolic enzymes lactate dehydrogenase and extracellular signal-related kinase 2 protein in the culture medium 24 h after exposure. These photocytotoxic effects were associated with the formation of sunburn cells, thymine dimers and DNA strand breaks in both the epidermis and dermis. Interestingly, cell death was dose dependent and associated with p53 protein upregulation and strong caspase-3 activation in the basal epidermis. None of these cellular responses was observed in non-irradiated skin. Finally, topical application of a broad-spectrum UVB + A sunfilter formulation afforded efficient photoprotection in irradiated explants. Thus, the ex vivo pig ear skin culture may be a useful tool in the assessment of solar radiation-induced DNA damage and apoptosis, and for evaluating the efficacy of sunscreen formulations.

Effects of ultrasound and sodium lauryl sulfate on the transdermal delivery of hydrophilic permeants: Comparative in vitro studies with full-thickness and split-thickness pig and human skin.

Science.gov (United States)

Seto, Jennifer E; Polat, Baris E; Lopez, Renata F V; Blankschtein, Daniel; Langer, Robert

2010-07-01

The simultaneous application of ultrasound and the surfactant sodium lauryl sulfate (referred to as US/SLS) to skin enhances transdermal drug delivery (TDD) in a synergistic mechanical and chemical manner. Since full-thickness skin (FTS) and split-thickness skin (STS) differ in mechanical strength, US/SLS treatment may have different effects on their transdermal transport pathways. Therefore, we evaluated STS as an alternative to the well-established US/SLS-treated FTS model for TDD studies of hydrophilic permeants. We utilized the aqueous porous pathway model to compare the effects of US/SLS treatment on the skin permeability and the pore radius of pig and human FTS and STS over a range of skin electrical resistivity values. Our findings indicate that the US/SLS-treated pig skin models exhibit similar permeabilities and pore radii, but the human skin models do not. Furthermore, the US/SLS-enhanced delivery of gold nanoparticles and quantum dots (two model hydrophilic macromolecules) is greater through pig STS than through pig FTS, due to the presence of less dermis that acts as an artificial barrier to macromolecules. In spite of greater variability in correlations between STS permeability and resistivity, our findings strongly suggest the use of 700microm-thick pig STS to investigate the in vitro US/SLS-enhanced delivery of hydrophilic macromolecules. 2010 Elsevier B.V. All rights reserved.

Segmented phantoms reconstruction for skin dosimetry

International Nuclear Information System (INIS)

Antunes, Paula C.G.; Siqueira, Paulo T.D.; Yoriyaz, Helio; Fonseca, Gabriel P.; Furnari, Laura; Reis, Gabriela S.

2009-01-01

There are several radio-sensitive skin diseases. Skin dosimetry is a difficult task to be properly performed, not only due to skin extension and small thickness, but also because it is usually submitted to high dose gradients. High-resolution medical images along with methods that simulate the interaction of radiation with matter, as the Monte Carlo radiation transport codes, have been widely used in medical physics procedures. These images provide the construction of realistic computational anatomical models, which after being coupled to these codes, retrieve reliable dosimetric assessments. However, present day regular images are unsuitable to correctly perform skin dose distribution evaluations. This inability is due to improper skin discrimination in most of current medical images, once its thickness stands below image resolution, i.e. pixel characteristic sizes are larger than skin thickness. This paper proposes a methodology of voxelized phantom reconstruction and segmentation, by subdividing their basic elements - voxels. It is done in order to better discriminate the skin by assigning more adequate value for skin thickness and its actual localization. Aiming at a more realistic skin modeling one is expected to get more accurate skin dose evaluations. This task is an important issue in many radiotherapy procedures. A particular interest lays in Total Skin Electron Therapy (TSET), which highlights the treatment of the whole body irradiation, a radiotherapy procedure under implementation in the Hospital das Clinicas da Universidade de Sao Paulo (HC-USP). (author)

Development, standardization and testing of a bacterial wound infection model based on ex vivo human skin.

Directory of Open Access Journals (Sweden)

Christoph Schaudinn

Full Text Available Current research on wound infections is primarily conducted on animal models, which limits direct transferability of these studies to humans. Some of these limitations can be overcome by using-otherwise discarded-skin from cosmetic surgeries. Superficial wounds are induced in fresh ex vivo skin, followed by intradermal injection of Pseudomonas aeruginosa under the wound. Subsequently, the infected skin is incubated for 20 hours at 37°C and the CFU/wound are determined. Within 20 hours, the bacteria count increased from 107 to 109 bacteria per wound, while microscopy revealed a dense bacterial community in the collagen network of the upper wound layers as well as numerous bacteria scattered in the dermis. At the same time, IL-1alpha and IL-1beta amounts increased in all infected wounds, while-due to bacteria-induced cell lysis-the IL-6 and IL-8 concentrations rose only in the uninfected samples. High-dosage ciprofloxacin treatment resulted in a decisive decrease in bacteria, but consistently failed to eradicate all bacteria. The main benefits of the ex vivo wound model are the use of healthy human skin, a quantifiable bacterial infection, a measureable donor-dependent immune response and a good repeatability of the results. These properties turn the ex vivo wound model into a valuable tool to examine the mechanisms of host-pathogen interactions and to test antimicrobial agents.

Concepts of skin protection: Considerations for the evaluation and terminology of the performance of skin protective equipment

NARCIS (Netherlands)

Brouwer, D.H.; Aitken, R.J.; Oppl, R.; Cherrie, J.W.

2005-01-01

This article proposes a common language for better understanding processes involved in dermal exposure and skin protection. A conceptual model has been developed that systematically describes the transport of agent mass from sources, eventually resulting in "loading" of the skin surface or the skin

Teacher Preferences for Alternative School Site Administrative Models

Science.gov (United States)

Hewitt, Paul M.; Denny, George S.; Pijanowski, John C.

2012-01-01

Public school teachers with high leadership potential who stated that they had no interest in being school principals were surveyed on their attitudes about six alternative school site administrative organizational models. Of the 391 teachers surveyed, 53% identified the Co-Principal model as the preferred school site administrative structure. In…

Estimating physiological skin parameters from hyperspectral signatures

Science.gov (United States)

Vyas, Saurabh; Banerjee, Amit; Burlina, Philippe

2013-05-01

We describe an approach for estimating human skin parameters, such as melanosome concentration, collagen concentration, oxygen saturation, and blood volume, using hyperspectral radiometric measurements (signatures) obtained from in vivo skin. We use a computational model based on Kubelka-Munk theory and the Fresnel equations. This model forward maps the skin parameters to a corresponding multiband reflectance spectra. Machine-learning-based regression is used to generate the inverse map, and hence estimate skin parameters from hyperspectral signatures. We test our methods using synthetic and in vivo skin signatures obtained in the visible through the short wave infrared domains from 24 patients of both genders and Caucasian, Asian, and African American ethnicities. Performance validation shows promising results: good agreement with the ground truth and well-established physiological precepts. These methods have potential use in the characterization of skin abnormalities and in minimally-invasive prescreening of malignant skin cancers.

Teledermatologist expert skin advice: A unique model of care for managing skin disorders and adverse drug reactions in hepatitis C patients.

Science.gov (United States)

Charlston, Samuel; Siller, Gregory

2018-03-23

To conduct an audit of teledermatologist expert skin advice, a store and forward tele-dermatological service, to determine its effectiveness and user satisfaction in managing cutaneous adverse drug reactions in patients with hepatitis C, and to demonstrate a unique collaborative model of care for patients receiving specialised drug therapy. A retrospective analysis of data on teledermatologist expert skin advice referrals from January 2014 to December 2015 was performed. The primary outcomes assessed included number of referrals, referral locations, diagnoses, response times, quality of clinical information provided and user satisfaction ratings. Altogether 43 consultations from 29 referring sites were received from Australian metropolitan and rural settings. Of the patients, 43 were diagnosed with an adverse drug reaction related to the use of either telaprevir or simeprevir. The average time taken for the dermatologist to reply electronically with a final diagnosis and management plan was 1 h 57 min. As many as 26% of referrals required additional photos to establish a diagnosis due to poor-quality images or insufficient detail. Altogether 18 clinicians completed the customer satisfaction survey, all of whom rated teledermatologist expert skin advice nine or above on a scale of one to 10. Teledermatologist expert skin advice was regarded by clinicians as a valuable patient care service. The platform is a novel modality that supports patients undergoing specialised treatments at risk of cutaneous adverse drug reaction. © 2018 The Australasian College of Dermatologists.

Multimodality pH imaging in a mouse dorsal skin fold window chamber model

Science.gov (United States)

Leung, Hui Min; Schafer, Rachel; Pagel, Mark M.; Robey, Ian F.; Gmitro, Arthur F.

2013-03-01

Upregulate levels of expression and activity of membrane H+ ion pumps in cancer cells drives the extracellular pH (pHe,) to values lower than normal. Furthermore, disregulated pH is indicative of the changes in glycolytic metabolism in tumor cells and has been shown to facilitate extracellular tissue remodeling during metastasis Therefore, measurement of pHe could be a useful cancer biomarker for diagnostic and therapy monitoring evaluation. Multimodality in-vivo imaging of pHe in tumorous tissue in a mouse dorsal skin fold window chamber (DSFWC) model is described. A custom-made plastic window chamber structure was developed that is compatible with both imaging optical and MR imaging modalities and provides a model system for continuous study of the same tissue microenvironment on multiple imaging platforms over a 3-week period. For optical imaging of pHe, SNARF-1 carboxylic acid is injected intravenously into a SCID mouse with an implanted tumor. A ratiometric measurement of the fluorescence signal captured on a confocal microscope reveals the pHe of the tissue visible within the window chamber. This imaging method was used in a preliminary study to evaluate sodium bicarbonate as a potential drug treatment to reverse tissue acidosis. For MR imaging of pHe the chemical exchange saturation transfer (CEST) was used as an alternative way of measuring pHe in a DSFWC model. ULTRAVIST®, a FDA approved x-ray/CT contrast agent has been shown to have a CEST effect that is pH dependent. A ratiometric analysis of water saturation at 5.6 and 4.2 ppm chemical shift provides a means to estimate the local pHe.

SR 97. Alternative models project. Stochastic continuum modelling of Aberg

International Nuclear Information System (INIS)

Widen, H.; Walker, D.

1999-08-01

As part of studies into the siting of a deep repository for nuclear waste, Swedish Nuclear Fuel and Waste Management Company (SKB) has commissioned the Alternative Models Project (AMP). The AMP is a comparison of three alternative modelling approaches to bedrock performance assessment for a single hypothetical repository, arbitrarily named Aberg. The Aberg repository will adopt input parameters from the Aespoe Hard Rock Laboratory in southern Sweden. The models are restricted to an explicit domain, boundary conditions and canister location to facilitate the comparison. The boundary conditions are based on the regional groundwater model provided in digital format. This study is the application of HYDRASTAR, a stochastic continuum groundwater flow and transport-modelling program. The study uses 34 realisations of 945 canister locations in the hypothetical repository to evaluate the uncertainty of the advective travel time, canister flux (Darcy velocity at a canister) and F-ratio. Several comparisons of variability are constructed between individual canister locations and individual realisations. For the ensemble of all realisations with all canister locations, the study found a median travel time of 27 years, a median canister flux of 7.1 x 10 -4 m/yr and a median F-ratio of 3.3 x 10 5 yr/m. The overall pattern of regional flow is preserved in the site-scale model, as is reflected in flow paths and exit locations. The site-scale model slightly over-predicts the boundary fluxes from the single realisation of the regional model. The explicitly prescribed domain was seen to be slightly restrictive, with 6% of the stream tubes failing to exit the upper surface of the model. Sensitivity analysis and calibration are suggested as possible extensions of the modelling study

Acne: a new model of immune-mediated chronic inflammatory skin disease.

Science.gov (United States)

Antiga, E; Verdelli, A; Bonciani, D; Bonciolini, V; Caproni, M; Fabbri, P

2015-04-01

Acne is a chronic inflammatory disease of the sebaceous-pilosebaceous unit. Interestingly, inflammation can be detected by histopathological examination and immuohistochemical analysis even in the apparently non-inflammatory acneic lesions, such as comedones. In the last years, it has been clearly demonstrated that acne development is linked to the combination of predisposing genetic factors and environmental triggers, among which a prominent role is played by the follicular colonization by Propionibacterium acnes (P. acnes). P. acnes displays several activities able to promote the development of acne skin lesions, including the promotion of follicular hyperkeratinisation, the induction of sebogenesis, and the stimulation of an inflammatory response by the secretion of proinflammatory molecules and by the activation of innate immunity, that is followed by a P. acnes-specific adaptive immune response. In addition, P. acnes-independent inflammation mediated by androgens or by a neurogenic activation, followed by the secretion in the skin of pro-inflammatory neuropeptides, can occur in acne lesions. In conclusion, acne can be considered as a model of immune-mediated chronic inflammatory skin disease, characterized by an innate immune response that is not able to control P. acnes followed by a Th1-mediated adaptive immune response, that becomes self-maintaining independently from P. acnes itself.

Genetics perspective of UV rays and new alternatives for sun protection

International Nuclear Information System (INIS)

Vallejo, E.O.; Vargas, N.; Martínez, L.M.; Agudelo, C.A.; Ortiz, I.C.

2013-01-01

Ultraviolet (UV), has three different wavelengths: UVA (315-400 nm), UVB (280-315 nm) and UVC (100-280 nm), which impact in different ways on the skin of human beings, and may be responsible of skin aging, burns and cancers. Currently we have multiple sunscreen alternatives, ranging from conventional physical methods to complex molecular mechanisms and inducers of cell repair as Polypodium leucotomos. The purpose of this review is to show the implications of ultraviolet rays on human beings exposed to sunlight and the protection alternatives that are available and show what is to come in photo protection towards the future. (authors) [es

Development of an in vivo animal model for skin penetration in hairless rats assessed by mass balance

DEFF Research Database (Denmark)

Simonsen, Lene; Petersen, Mads B; Benfeldt, Eva

2002-01-01

acid and (14)C-butyl salicylate were topically applied. Rapid and differentiated percutaneous absorption of both compounds were shown by urinary excretion data. For (14)C-salicylic acid the amount on the skin surface, in the stratum corneum and in the viable skin was determined. Total mass balance...... rat and free mobility throughout the test period. By consecutive tape stripping, monitored by measurements of transepidermal water loss and confirmed by histological examination of skin biopsies, 10 tape strippings were found to remove the stratum corneum completely. For assessment of the model, (14)C-salicylic...

The imperative for emergency medicine to create its own alternative payment model.

Science.gov (United States)

Medford-Davis, Laura N

2017-06-01

Seven years after the Affordable Care Act legislated Alternative Payment Models, it is time for Emergency Medicine to find its place within this value-based trend by developing its own Alternative Payment Model. Copyright © 2017 Elsevier Inc. All rights reserved.

FEM modeling and histological analyses on thermal damage induced in facial skin resurfacing procedure with different CO2 laser pulse duration

Science.gov (United States)

Rossi, Francesca; Zingoni, Tiziano; Di Cicco, Emiliano; Manetti, Leonardo; Pini, Roberto; Fortuna, Damiano

2011-07-01

Laser light is nowadays routinely used in the aesthetic treatments of facial skin, such as in laser rejuvenation, scar removal etc. The induced thermal damage may be varied by setting different laser parameters, in order to obtain a particular aesthetic result. In this work, it is proposed a theoretical study on the induced thermal damage in the deep tissue, by considering different laser pulse duration. The study is based on the Finite Element Method (FEM): a bidimensional model of the facial skin is depicted in axial symmetry, considering the different skin structures and their different optical and thermal parameters; the conversion of laser light into thermal energy is modeled by the bio-heat equation. The light source is a CO2 laser, with different pulse durations. The model enabled to study the thermal damage induced into the skin, by calculating the Arrhenius integral. The post-processing results enabled to study in space and time the temperature dynamics induced in the facial skin, to study the eventual cumulative effects of subsequent laser pulses and to optimize the procedure for applications in dermatological surgery. The calculated data where then validated in an experimental measurement session, performed in a sheep animal model. Histological analyses were performed on the treated tissues, evidencing the spatial distribution and the entity of the thermal damage in the collageneous tissue. Modeling and experimental results were in good agreement, and they were used to design a new optimized laser based skin resurfacing procedure.

An alternative to the standard model

International Nuclear Information System (INIS)

Baek, Seungwon; Ko, Pyungwon; Park, Wan-Il

2014-01-01

We present an extension of the standard model to dark sector with an unbroken local dark U(1) X symmetry. Including various singlet portal interactions provided by the standard model Higgs, right-handed neutrinos and kinetic mixing, we show that the model can address most of phenomenological issues (inflation, neutrino mass and mixing, baryon number asymmetry, dark matter, direct/indirect dark matter searches, some scale scale puzzles of the standard collisionless cold dark matter, vacuum stability of the standard model Higgs potential, dark radiation) and be regarded as an alternative to the standard model. The Higgs signal strength is equal to one as in the standard model for unbroken U(1) X case with a scalar dark matter, but it could be less than one independent of decay channels if the dark matter is a dark sector fermion or if U(1) X is spontaneously broken, because of a mixing with a new neutral scalar boson in the models

Feasibility Study on a Microwave-Based Sensor for Measuring Hydration Level Using Human Skin Models.

Science.gov (United States)

Brendtke, Rico; Wiehl, Michael; Groeber, Florian; Schwarz, Thomas; Walles, Heike; Hansmann, Jan

2016-01-01

Tissue dehydration results in three major types of exsiccosis--hyper-, hypo-, or isonatraemia. All three types entail alterations of salt concentrations leading to impaired biochemical processes, and can finally cause severe morbidity. The aim of our study was to demonstrate the feasibility of a microwave-based sensor technology for the non-invasive measurement of the hydration status. Electromagnetic waves at high frequencies interact with molecules, especially water. Hence, if a sample contains free water molecules, this can be detected in a reflected microwave signal. To develop the sensor system, human three-dimensional skin equivalents were instituted as a standardized test platform mimicking reproducible exsiccosis scenarios. Therefore, skin equivalents with a specific hydration and density of matrix components were generated and microwave measurements were performed. Hydration-specific spectra allowed deriving the hydration state of the skin models. A further advantage of the skin equivalents was the characterization of the impact of distinct skin components on the measured signals to investigate mechanisms of signal generation. The results demonstrate the feasibility of a non-invasive microwave-based hydration sensor technology. The sensor bears potential to be integrated in a wearable medical device for personal health monitoring.

Feasibility Study on a Microwave-Based Sensor for Measuring Hydration Level Using Human Skin Models.

Directory of Open Access Journals (Sweden)

Rico Brendtke

Full Text Available Tissue dehydration results in three major types of exsiccosis--hyper-, hypo-, or isonatraemia. All three types entail alterations of salt concentrations leading to impaired biochemical processes, and can finally cause severe morbidity. The aim of our study was to demonstrate the feasibility of a microwave-based sensor technology for the non-invasive measurement of the hydration status. Electromagnetic waves at high frequencies interact with molecules, especially water. Hence, if a sample contains free water molecules, this can be detected in a reflected microwave signal. To develop the sensor system, human three-dimensional skin equivalents were instituted as a standardized test platform mimicking reproducible exsiccosis scenarios. Therefore, skin equivalents with a specific hydration and density of matrix components were generated and microwave measurements were performed. Hydration-specific spectra allowed deriving the hydration state of the skin models. A further advantage of the skin equivalents was the characterization of the impact of distinct skin components on the measured signals to investigate mechanisms of signal generation. The results demonstrate the feasibility of a non-invasive microwave-based hydration sensor technology. The sensor bears potential to be integrated in a wearable medical device for personal health monitoring.

Development and validation of a tokamak skin effect transformer model

International Nuclear Information System (INIS)

Romero, J.A.; Moret, J.-M.; Coda, S.; Felici, F.; Garrido, I.

2012-01-01

A lumped parameter, state space model for a tokamak transformer including the slow flux penetration in the plasma (skin effect transformer model) is presented. The model does not require detailed or explicit information about plasma profiles or geometry. Instead, this information is lumped in system variables, parameters and inputs. The model has an exact mathematical structure built from energy and flux conservation theorems, predicting the evolution and non-linear interaction of plasma current and internal inductance as functions of the primary coil currents, plasma resistance, non-inductive current drive and the loop voltage at a specific location inside the plasma (equilibrium loop voltage). Loop voltage profile in the plasma is substituted by a three-point discretization, and ordinary differential equations are used to predict the equilibrium loop voltage as a function of the boundary and resistive loop voltages. This provides a model for equilibrium loop voltage evolution, which is reminiscent of the skin effect. The order and parameters of this differential equation are determined empirically using system identification techniques. Fast plasma current modulation experiments with random binary signals have been conducted in the TCV tokamak to generate the required data for the analysis. Plasma current was modulated under ohmic conditions between 200 and 300 kA with 30 ms rise time, several times faster than its time constant L/R ≈ 200 ms. A second-order linear differential equation for equilibrium loop voltage is sufficient to describe the plasma current and internal inductance modulation with 70% and 38% fit parameters, respectively. The model explains the most salient features of the plasma current transients, such as the inverse correlation between plasma current ramp rates and internal inductance changes, without requiring detailed or explicit information about resistivity profiles. This proves that a lumped parameter modelling approach can be used to

Comparison of atmospheric microplasma and plasma jet irradiation for increasing of skin permeability

International Nuclear Information System (INIS)

Shimizu, K; Tran, N A; Hayashida, K; Blajan, M

2016-01-01

Atmospheric plasma is attracting interest for medical applications such as sterilization, treatment of cancer cells and blood coagulation. Application of atmospheric plasma in dermatology has potential as a novel tool for wound healing, skin rejuvenation and treatment of wrinkles. In this study, we investigated the enhancement of percutaneous absorption of dye as alternative agents of transdermal drugs. Hypodermic needles are often the only way to deliver large-molecule drugs into the dermis, although a safe transdermal drug delivery method that does not require needles would be desirable. We therefore explored the feasibility of using atmospheric microplasma irradiation to enhance percutaneous absorption of drugs, as an alternative delivery method to conventional hypodermic needles. Pig skin was used as a biological sample, exposed to atmospheric microplasma, and analyzed by attenuated total reflection-Fourier transform infrared spectroscopy. A tape stripping test, a representative method for evaluating skin barrier performance, was also conducted for comparison. Transepidermal water loss (TEWL) was measured and compared with and without atmospheric microplasma irradiation, to quantify water evaporation from the inner body through the skin barrier. The results show that the stratum corneum, the outermost skin layer, could be chemically and physically modified by atmospheric microplasma irradiation. Physical damage to the skin by microplasma irradiation and an atmospheric plasma jet was also assessed by observing the skin surface. The results suggest that atmospheric microplasma has the potential to enhance percutaneous absorption. (paper)

Amnion s and radio-sterilized porcine skin use as potential matrices for the development of human skin substitutes

International Nuclear Information System (INIS)

Martinez P, M. E.; Reyes F, M. L.; Reboyo B, D.; Velasquillo M, M. C.; Sanchez S, R.; Brena M, A. M.; Ibarra P, J. C.

2014-10-01

The injuries by burns constitute a primordial problem of public health; they cause a high mortality index, severe physical and psychological disability, etc. The autologous skin transplant is the replacement therapy recommended for its treatment, but in patients that present a high percentage of burnt skin; this is not possible to carry out. Another strategy is the transplant of donated skin; however, due to the little donation that exists in our country is not very feasible to apply this treatment. A challenge of the tissues engineering is to develop biological skin substitutes, based on cells and amnion s, favoring the cutaneous regeneration and quick repair of injuries, diminishing this way the hospitalization expenses. At present skin substitutes that can equal to the same skin do not exist. On the other hand, the mesenchymal stromal cells (Msc) represent an alternative to achieve this objective; since has been demonstrated that the Msc participate in the tissue repair by means of inhibition of pro-inflammatory cytokines and differentiation to dermal fibroblasts and keratinocytes. To apply the Msc in cutaneous injuries a support material is required that to allow transplanting these cells to a lesion or burn. The radio-sterilized human amnion and the radio-sterilized porcine skin, processed by the Radio-Sterilized Tissues Bank of the Instituto Nacional de Investigaciones Nucleares (ININ), are biomaterials that are used as temporary cutaneous coverings. We suppose that these two matrices will be appropriate for the growth and maintenance in cultivation of the Msc, to generate two biological skin substitutes, in collaboration with the Biotechnology Laboratory of the Instituto Nacional de Rehabilitacion. (Author)

Modeling the Influence of Early Skin-to-Skin Contact on Exclusive Breastfeeding in a Sample of Hispanic Immigrant Women.

Science.gov (United States)

Linares, Ana M; Wambach, Karen; Rayens, Mary K; Wiggins, Amanda; Coleman, Elizabeth; Dignan, Mark B

2017-10-01

Using data from a longitudinal study of breastfeeding in Hispanics, this study evaluated the influence of early skin-to-skin contact (SSC) on initiation and sustained exclusive breastfeeding (EBF) at 1 month postpartum. Two-thirds of the women in the sample participated in early SSC. At discharge, over half of the women were EBF; this proportion decreased to one-third at 1 month postpartum. Controlling for demographic and clinical variables in the model, participation in early SSC was associated with a greater than sevenfold increase in the odds of EBF at discharge (p = .005) but was not predictive of EBF at 1 month post-discharge (p = .7). Younger maternal age and increased prenatal infant feeding intention were associated with an increased likelihood of EBF across both timepoints. Promoting early SSC may help with initiation of EBF, while further breastfeeding support may be needed to maintain EBF following discharge for this vulnerable population.

Modeling, Design and Analysis of a Electrodynamic Levitation System by Considering the Skin Effect

Directory of Open Access Journals (Sweden)

Mohammad Rajabi Sabadani

2016-01-01

Full Text Available In this paper, lift and drag forces of permanent-magnet electrodynamic suspension (PMEDS System have been studied by considering the skin effect. Electrodynamic suspension is based on repulsive force between two magnetic fields with the same polarity. In this research the electrodynamic suspension system consists of a moving permanent magnet block levitated over a flat conducting plate with 2 mm thickness. At first, the analytical model of the PMEDS is proposed. For this propose, permanent magnet poles are modeled by the current sheets. Then the eddy current is calculated on aluminum sheet by considering the skin effect. Finally, the lift and drag forces are calculated in difference speed. The 2D finite element method is utilized to investigate the effect of speed variations on the performance of PMEDS at two different airgap. Two-dimensional finite element model, the accuracy of proposed analytical model is validated. The results of the finite element method are compared with results obtained by analytical model. It shows the accuracy of the analytical model in the estimation of the lift and drag forces of an electrodynamic suspension system.

Skin dose mapping for fluoroscopically guided interventions.

Science.gov (United States)

Johnson, Perry B; Borrego, David; Balter, Stephen; Johnson, Kevin; Siragusa, Daniel; Bolch, Wesley E

2011-10-01

To introduce a new skin dose mapping software system for interventional fluoroscopy dose assessment and to analyze the benefits and limitations of patient-phantom matching. In this study, a new software system was developed for visualizing patient skin dose during interventional fluoroscopy procedures. The system works by translating the reference point air kerma to the location of the patient's skin, which is represented by a computational model. In order to orient the model with the x-ray source, geometric parameters found within the radiation dose structured report (RDSR) are used along with a limited number of in-clinic measurements. The output of the system is a visual indication of skin dose mapped onto an anthropomorphic model at a resolution of 5 mm. In order to determine if patient-dependent and patient-sculpted models increase accuracy, peak skin dose was calculated for each of 26 patient-specific models and compared with doses calculated using an elliptical stylized model, a reference hybrid model, a matched patient-dependent model and one patient-sculpted model. Results were analyzed in terms of a percent difference using the doses calculated using the patient-specific model as the true standard. Anthropometric matching, including the use of both patient-dependent and patient-sculpted phantoms, was shown most beneficial for left lateral and anterior-posterior projections. In these cases, the percent difference using a reference model was between 8 and 20%, using a patient-dependent model between 7 and 15%, and using a patient-sculpted model between 3 and 7%. Under the table tube configurations produced errors less than 5% in most situations due to the flattening affects of the table and pad, and the fact that table height is the main determination of source-to-skin distance for these configurations. In addition to these results, several skin dose maps were produced and a prototype display system was placed on the in-clinic monitor of an interventional

The usual suspects-influence of physicochemical properties on lag time, skin deposition, and percutaneous penetration of nine model compounds

DEFF Research Database (Denmark)

Bo Nielsen, Jesper; Sørensen, Jens Ahm; Nielsen, Flemming

2009-01-01

The influence of physicochemical properties of nine model compounds on lag time, skin deposition, and percutaneous penetration was evaluated. Static diffusion cells mounted with human skin were used as the experimental model, and experiments were carried out in accordance with Organization for Ec...... agencies using experimental data for assessing systemic toxicity following dermal exposures as for development of structure activity relationships for dermal absorption of chemicals....

Estimation of Thermal Sensation Based on Wrist Skin Temperatures

Science.gov (United States)

Sim, Soo Young; Koh, Myung Jun; Joo, Kwang Min; Noh, Seungwoo; Park, Sangyun; Kim, Youn Ho; Park, Kwang Suk

2016-01-01

Thermal comfort is an essential environmental factor related to quality of life and work effectiveness. We assessed the feasibility of wrist skin temperature monitoring for estimating subjective thermal sensation. We invented a wrist band that simultaneously monitors skin temperatures from the wrist (i.e., the radial artery and ulnar artery regions, and upper wrist) and the fingertip. Skin temperatures from eight healthy subjects were acquired while thermal sensation varied. To develop a thermal sensation estimation model, the mean skin temperature, temperature gradient, time differential of the temperatures, and average power of frequency band were calculated. A thermal sensation estimation model using temperatures of the fingertip and wrist showed the highest accuracy (mean root mean square error [RMSE]: 1.26 ± 0.31). An estimation model based on the three wrist skin temperatures showed a slightly better result to the model that used a single fingertip skin temperature (mean RMSE: 1.39 ± 0.18). When a personalized thermal sensation estimation model based on three wrist skin temperatures was used, the mean RMSE was 1.06 ± 0.29, and the correlation coefficient was 0.89. Thermal sensation estimation technology based on wrist skin temperatures, and combined with wearable devices may facilitate intelligent control of one’s thermal environment. PMID:27023538

[Experimental model of severe local radiation injuries of the skin after X-rays].

Science.gov (United States)

Kotenko, K V; Moroz, B B; Nasonova, T A; Dobrynina, O A; LIpengolz, A A; Gimadova, T I; Deshevoy, Yu B; Lebedev, V G; Lyrschikova, A V; Eremin, I I

2013-01-01

The experimental model of severe local radiation injuries skin under the influence of a relatively soft X-rays on a modified device RAP 100-10 produced by "Diagnostica-M" (Russia) was proposed. The model can be used as pre-clinical studies in small experimental animals in order to improve the treatment of local radiation injuries, especially in the conditions of application of cellular therapy.

Comparison of acetate tape impression with squeezing versus skin scraping for the diagnosis of canine demodicosis.

Science.gov (United States)

Pereira, A V; Pereira, S A; Gremião, I D F; Campos, M P; Ferreira, A M R

2012-11-01

This study compared the sensitivity of acetate tape impression and skin squeezing with that of deep skin scraping for the diagnosis of demodicosis in dogs. Demodex canis was detected in 100% of acetate tape impressions obtained after skin squeezing and in 90% of deep skin scrapings. There was a significant difference (P < 0.001) between the techniques in the total number of mites detected. Acetate tape impression with skin squeezing was found to be more sensitive than deep skin scraping and is an alternative diagnostic method for canine demodicosis. © 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.

Friction and durability of virgin and damaged skin with and without skin cream treatment using atomic force microscopy

Directory of Open Access Journals (Sweden)

Bharat Bhushan

2012-11-01

Full Text Available Skin can be damaged by the environment easily. Skin cream is an effective and rapid way to moisten the skin by changing the skin surface properties. Rat skin and pig skin are common animal models for studies and were used as skin samples in this study. The nano- and macroscale friction and durability of damaged skin were measured and compared with those of virgin (intact/undamaged skin. The effect of skin cream on friction and durability of damaged and virgin skin samples is discussed. The effects of velocity, normal load, relative humidity and number of cycles were studied. The nanoscale studies were performed by using atomic force microscope (AFM, and macroscale studies were performed by using a pin-on-disk (POD reciprocating tribometer. It was found that damaged skin has different mechanical properties, surface roughness, contact angle, friction and durability compared to that of virgin skin. But similar changes occur after skin cream treatment. Rat and pig skin show similar trends in friction and durability.

Microneedle-Mediated Delivery of Copper Peptide Through Skin.

Science.gov (United States)

Li, Hairui; Low, Yong Sheng Jason; Chong, Hui Ping; Zin, Melvin T; Lee, Chi-Ying; Li, Bo; Leolukman, Melvina; Kang, Lifeng

2015-08-01

Copper peptide (GHK-Cu) plays an important role in skin regeneration and wound healing. However, its skin absorption remains challenging due to its hydrophilicity. Here we use polymeric microneedle array to pre-treat skin to enhance GHK-Cu skin penetration. Two in vitro skin models were used to assess the capability of microneedles in facilitating skin delivery of GHK-Cu. Histological assay and confocal laser scanning microscopy were performed to characterize and quantify the microconduits created by the microneedles inside skin. Cellular and porcine models were used to evaluate the safety of microneedle-assisted copper peptide delivery. The depth and percentage of microneedle penetration were correlated with application forces, which in turn influenced the extent of enhancement in the skin permeability of GHK-Cu. In 9 h, 134 ± 12 nanomoles of peptide and 705 ± 84 nanomoles of copper permeated though the microneedle treated human skin, while almost no peptide or copper permeated through intact human skin. No obvious signs of skin irritation were observed with the use of GHK-Cu after microneedle pretreatment. It is effective and safe to enhance the skin permeation of GHK-Cu by using microneedles. This approach may be useful to deliver similar peptides or minerals through skin.

Vibro-Perception of Optical Bio-Inspired Fiber-Skin.

Science.gov (United States)

Li, Tao; Zhang, Sheng; Lu, Guo-Wei; Sunami, Yuta

2018-05-12

In this research, based on the principle of optical interferometry, the Mach-Zehnder and Optical Phase-locked Loop (OPLL) vibro-perception systems of bio-inspired fiber-skin are designed to mimic the tactile perception of human skin. The fiber-skin is made of the optical fiber embedded in the silicone elastomer. The optical fiber is an instinctive and alternative sensor for tactile perception with high sensitivity and reliability, also low cost and susceptibility to the magnetic interference. The silicone elastomer serves as a substrate with high flexibility and biocompatibility, and the optical fiber core serves as the vibro-perception sensor to detect physical motions like tapping and sliding. According to the experimental results, the designed optical fiber-skin demonstrates the ability to detect the physical motions like tapping and sliding in both the Mach-Zehnder and OPLL vibro-perception systems. For direct contact condition, the OPLL vibro-perception system shows better performance compared with the Mach-Zehnder vibro-perception system. However, the Mach-Zehnder vibro-perception system is preferable to the OPLL system in the indirect contact experiment. In summary, the fiber-skin is validated to have light touch character and excellent repeatability, which is highly-suitable for skin-mimic sensing.

Quantitative detection of caffeine in human skin by confocal Raman spectroscopy--A systematic in vitro validation study.

Science.gov (United States)

Franzen, Lutz; Anderski, Juliane; Windbergs, Maike

2015-09-01

For rational development and evaluation of dermal drug delivery, the knowledge of rate and extent of substance penetration into the human skin is essential. However, current analytical procedures are destructive, labor intense and lack a defined spatial resolution. In this context, confocal Raman microscopy bares the potential to overcome current limitations in drug depth profiling. Confocal Raman microscopy already proved its suitability for the acquisition of qualitative penetration profiles, but a comprehensive investigation regarding its suitability for quantitative measurements inside the human skin is still missing. In this work, we present a systematic validation study to deploy confocal Raman microscopy for quantitative drug depth profiling in human skin. After we validated our Raman microscopic setup, we successfully established an experimental procedure that allows correlating the Raman signal of a model drug with its controlled concentration in human skin. To overcome current drawbacks in drug depth profiling, we evaluated different modes of peak correlation for quantitative Raman measurements and offer a suitable operating procedure for quantitative drug depth profiling in human skin. In conclusion, we successfully demonstrate the potential of confocal Raman microscopy for quantitative drug depth profiling in human skin as valuable alternative to destructive state-of-the-art techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

Palytoxin: exploiting a novel skin tumor promoter to explore signal transduction and carcinogenesis.

Science.gov (United States)

Wattenberg, Elizabeth V

2007-01-01

Palytoxin is a novel skin tumor promoter, which has been used to help probe the role of different types of signaling mechanisms in carcinogenesis. The multistage mouse skin model indicates that tumor promotion is an early, prolonged, and reversible phase of carcinogenesis. Understanding the molecular mechanisms underlying tumor promotion is therefore important for developing strategies to prevent and treat cancer. Naturally occurring tumor promoters that bind to specific cellular receptors have proven to be useful tools for investigating important biochemical events in multistage carcinogenesis. For example, the identification of protein kinase C as the receptor for the prototypical skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) (also called phorbol 12-myristate 13-acetate, PMA) provided key evidence that tumor promotion involves the aberrant modulation of signaling cascades that govern cell fate and function. The subsequent discovery that palytoxin, a marine toxin isolated from zoanthids (genus Palythoa), is a potent skin tumor promoter yet does not activate protein kinase C indicated that investigating palytoxin action could help reveal new aspects of tumor promotion. Interestingly, the putative receptor for palytoxin is the Na(+),K(+)-ATPase. This review focuses on palytoxin-stimulated signaling and how palytoxin has been used to investigate alternate biochemical mechanisms by which important targets in carcinogenesis can be modulated.

Modeling skin temperature to assess the effect of air velocity to mitigate heat stress among growing pigs

DEFF Research Database (Denmark)

Bjerg, Bjarne; Pedersen, Poul; Morsing, Svend

2017-01-01

It is generally accepted that increased air velocity can help to mitigate heat stress in livestock housing, however, it is not fully clear how much it helps and significant uncertainties exists when the air temperature approaches the animal body temperature. This study aims to develop a skin...... temperature model to generated data for determining the potential effect of air velocity to mitigate heat stress among growing pigs housed in warm environment. The model calculates the skin temperature as function of body temperature, air temperature and the resistances for heat transfer from the body...

Antibody-mediated delivery of interleukin 4 to the neo-vasculature reduces chronic skin inflammation.

Science.gov (United States)

Hemmerle, Teresa; Zgraggen, Silvana; Matasci, Mattia; Halin, Cornelia; Detmar, Michael; Neri, Dario

2014-11-01

The antibody-mediated delivery of cytokines ("immunocytokines") to sites of pathological angiogenesis represents an attractive strategy for the development of innovative biopharmaceuticals, capable of modulating the activity of the immune system in cancer and in chronic inflammatory conditions. Recombinant IL4 has previously been shown to be therapeutically active in patients with psoriasis. The antibody-mediated delivery of this cytokine to sites of chronic skin inflammatory conditions should lead to an improved potency and selectivity, compared to non-targeted IL4. The therapeutic activity of F8-IL4, a fusion protein of the F8 antibody (specific to the alternatively-spliced EDA domain of fibronectin) with murine IL4, was investigated in three immunocompetent mouse models of skin inflammation: two induced by the TLR7/8 ligand imiquimod (in Balb/c and C57BL/6) and one mediated by the over-expression of VEGF-A. The EDA domain of fibronectin, a marker for angiogenesis, is expressed in the inflamed skin in all three models and F8-IL4 selectively localized to inflamed skin lesions following intravenous administration. The F8-IL4 fusion protein mediated a therapeutic benefit, which was superior to the one of a non-targeted version of IL4 and led to increased levels of key regulatory cytokines (including IL5, IL10, IL13, and IL27) in the inflamed skin, while IL2 levels were not affected in all treatment groups. A murine version of etanercept and a murine anti-IL17 antibody were used as positive control in the therapy experiments. Skin inflammatory lesions can be selectively targeted using anti-EDA antibody-cytokine fusion proteins and the pharmacodelivery of IL4 confers a therapeutic benefit by shifting the cytokine balance. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Prediction of skin sensitizers using alternative methods to animal experimentation.

Science.gov (United States)

Johansson, Henrik; Lindstedt, Malin

2014-07-01

Regulatory frameworks within the European Union demand that chemical substances are investigated for their ability to induce sensitization, an adverse health effect caused by the human immune system in response to chemical exposure. A recent ban on the use of animal tests within the cosmetics industry has led to an urgent need for alternative animal-free test methods that can be used for assessment of chemical sensitizers. To date, no such alternative assay has yet completed formal validation. However, a number of assays are in development and the understanding of the biological mechanisms of chemical sensitization has greatly increased during the last decade. In this MiniReview, we aim to summarize and give our view on the recent progress of method development for alternative assessment of chemical sensitizers. We propose that integrated testing strategies should comprise complementary assays, providing measurements of a wide range of mechanistic events, to perform well-educated risk assessments based on weight of evidence. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

MODEL OF INTEGRATED VALUE OF PROJECTS IN THE FIELD OF ALTERNATIVE ENERGY

Directory of Open Access Journals (Sweden)

Наталія Ігорівна БОРИСОВА

2015-05-01

Full Text Available Development of alternative energy sources requires the implementation of complex problems, the solution of which is necessary to apply the project approach. The uniqueness of alternative energy projects (AEP necessitates individual approach to evaluating the effectiveness of each. The paper contains the results of the project management features's analysis in the field of alternative energy, determining the values and developing of the value management integrated conceptual model of AEP. In assessing the effectiveness of AEP considered the socio-economic and commercial aspects. Value management integrated conceptual model of AEP was obtained by combining the classical model of the project management goals with the project values model "Five "E" and two "A". The classical model of the project management goals have been complemented with risk parameters.

Long-term repetitive sodium lauryl sulfate-induced irritation of the skin: an in vivo study.

Science.gov (United States)

Branco, Nara; Lee, Ivy; Zhai, Hongbo; Maibach, Howard I

2005-11-01

Skin may adapt to topical irritants through accommodation. This study focuses on long-term exposure to irritants and attempts to demonstrate accommodation. Sodium lauryl sulfate (SLS) induced irritant contact dermatitis at 3 concentrations (0.025% to 0.075%). Distilled water, acetone and an empty chamber served as controls. Experimental compounds were applied to forearms of 7 healthy volunteers for 24 hr before replacing by a fresh chamber for 6 non-consecutive weeks over 103 days. Possible accommodation was quantified by visual scoring (erythema and dryness) and by bioengineering parameters: transepidermal water loss (TEWL), capacitance, chromametry and laser Doppler flowmetry (LDF). Significant erythema, dryness, elevated TEWL, skin colour reflectance and LDF values occurred during the exposure periods. Upon repeat exposure, an immediate and augmented response in erythema, TEWL, skin colour reflectance and LDF developed. However, irritant skin changes were not sustained. Irritation parameters return to baseline after cessation of exposure. There was no evidence of sustained irritation or accommodation after the last exposure. Study findings do not document sustained accommodation or adaptive hyposensitivity after long-term repetitive irritant exposure under these test conditions. Alternative models should be developed to prove or disprove the accommodation hypothesis.

Assessment of Skin Pathological Responses in the Yellowfin Seabream (Acanthopagrus latus under the Aeromonas hydrophila Exposure

Directory of Open Access Journals (Sweden)

Fatemeh Azadbakht

2018-01-01

Full Text Available Background: Bacterial diseases in cultured fish are considered the main problem to aquaculture system. Skin is the structure that covers the body in fish. Skin histopatological alterations were used to assess the effects of Aeromonas hydrophila exposure on the yellowfin seabream Acanthopagrus latus(. Methods: In this regard, 90 A. latus were exposed to sublethal concentrations of A. hydrophila (103,106 CFU/ml for 3 weeks. Results: Some more severe alternations found in the skin of fish exposed. The most frequent histopathological changes detected in the skin including hyperplasia of epidermis, hypertrophy and hyperplasia of the mucosal cells and dermis edema. Some more severe alternations found in the skin of fish exposed to higher level of A. hydrophila (106 CFU/ml included telangiectasia of dermis layer. In addition, according to the results of histometrical studies in treated fish compared to control group showed that thickness of epidermis and dermis layers were increased significantly (P<0.05. Conclusion: A. hydrophila can cause major histophatological changes in the skin of A. latus. In addition, histopathological changes of the skin provide helpful information about the environmental conditions and as particular biomarkers may provide imminent into evaluating the general health and stress status of fish.

Skin and scales of teleost fish: Simple structure but high performance and multiple functions

Science.gov (United States)

Vernerey, Franck J.; Barthelat, Francois

2014-08-01

Natural and man-made structural materials perform similar functions such as structural support or protection. Therefore they rely on the same types of properties: strength, robustness, lightweight. Nature can therefore provide a significant source of inspiration for new and alternative engineering designs. We report here some results regarding a very common, yet largely unknown, type of biological material: fish skin. Within a thin, flexible and lightweight layer, fish skins display a variety of strain stiffening and stabilizing mechanisms which promote multiple functions such as protection, robustness and swimming efficiency. We particularly discuss four important features pertaining to scaled skins: (a) a strongly elastic tensile behavior that is independent from the presence of rigid scales, (b) a compressive response that prevents buckling and wrinkling instabilities, which are usually predominant for thin membranes, (c) a bending response that displays nonlinear stiffening mechanisms arising from geometric constraints between neighboring scales and (d) a robust structure that preserves the above characteristics upon the loss or damage of structural elements. These important properties make fish skin an attractive model for the development of very thin and flexible armors and protective layers, especially when combined with the high penetration resistance of individual scales. Scaled structures inspired by fish skin could find applications in ultra-light and flexible armor systems, flexible electronics or the design of smart and adaptive morphing structures for aerospace vehicles.

Cost-Effectiveness Analysis of a Skin Awareness Intervention for Early Detection of Skin Cancer Targeting Men Older Than 50 Years.

Science.gov (United States)

Gordon, Louisa G; Brynes, Joshua; Baade, Peter D; Neale, Rachel E; Whiteman, David C; Youl, Philippa H; Aitken, Joanne F; Janda, Monika

2017-04-01

To assess the cost-effectiveness of an educational intervention encouraging self-skin examinations for early detection of skin cancers among men older than 50 years. A lifetime Markov model was constructed to combine data from the Skin Awareness Trial and other published sources. The model incorporated a health system perspective and the cost and health outcomes for melanoma, squamous and basal cell carcinomas, and benign skin lesions. Key model outcomes included Australian costs (2015), quality-adjusted life-years (QALYs), life-years, and counts of skin cancers. Univariate and probabilistic sensitivity analyses were undertaken to address parameter uncertainty. The mean cost of the intervention was A$5,298 compared with A$4,684 for usual care, whereas mean QALYs were 7.58 for the intervention group and 7.77 for the usual care group. The intervention was thus inferior to usual care. When only survival gain is considered, the model predicted the intervention would cost A$1,059 per life-year saved. The likelihood that the intervention was cost-effective up to A$50,000 per QALY gained was 43.9%. The model was stable to most data estimates; nevertheless, it relies on the specificity of clinical diagnosis of skin cancers and is subject to limited health utility data for people with skin lesions. Although the intervention improved skin checking behaviors and encouraged men to seek medical advice about suspicious lesions, the overall costs and effects from also detecting more squamous and basal cell carcinomas and benign lesions outweighed the positive health gains from detecting more thin melanomas. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Potential skin involvement in ALS: revisiting Charcot's observation - a review of skin abnormalities in ALS.

Science.gov (United States)

Paré, Bastien; Gros-Louis, François

2017-07-26

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons of the brain and spinal cord, leading to progressive paralysis and death. Interestingly, many skin changes have been reported in ALS patients, but never as yet fully explained. These observations could be due to the common embryonic origin of the skin and neural tissue known as the ectodermal germ layer. Following the first observation in ALS patients' skin by Dr Charcot in the 19th century, in the absence of bedsores unlike other bedridden patients, other morphological and molecular changes have been observed. Thus, the skin could be of interest in the study of ALS and other neurodegenerative diseases. This review summarizes skin changes reported in the literature over the years and discusses about a novel in vitro ALS tissue-engineered skin model, derived from patients, for the study of ALS.

Compensation of the skin effect in low-frequency potential drop measurements

OpenAIRE

Corcoran, J; Nagy, PB

2016-01-01

Potential drop measurements are routinely used in the non-destructive evaluation of component integrity. Potential drop measurements use either direct current (DC) or alternating current (AC), the latter will have superior noise performance due to the ability to perform phase sensitive detection and the reduction of flicker noise. AC measurements are however subject to the skin effect where the current is electromagnetically constricted to the surface of the component. Unfortunately, the skin...

Skin bioprinting: a novel approach for creating artificial skin from synthetic and natural building blocks.

Science.gov (United States)

Augustine, Robin

2018-05-12

Significant progress has been made over the past few decades in the development of in vitro-engineered substitutes that mimic human skin, either as grafts for the replacement of lost skin, or for the establishment of in vitro human skin models. Tissue engineering has been developing as a novel strategy by employing the recent advances in various fields such as polymer engineering, bioengineering, stem cell research and nanomedicine. Recently, an advancement of 3D printing technology referred as bioprinting was exploited to make cell loaded scaffolds to produce constructs which are more matching with the native tissue. Bioprinting facilitates the simultaneous and highly specific deposition of multiple types of skin cells and biomaterials, a process that is lacking in conventional skin tissue-engineering approaches. Bioprinted skin substitutes or equivalents containing dermal and epidermal components offer a promising approach in skin bioengineering. Various materials including synthetic and natural biopolymers and cells with or without signalling molecules like growth factors are being utilized to produce functional skin constructs. This technology emerging as a novel strategy to overcome the current bottle-necks in skin tissue engineering such as poor vascularization, absence of hair follicles and sweat glands in the construct.

Skin stem cell hypotheses and long term clone survival--explored using agent-based modelling.

Science.gov (United States)

Li, X; Upadhyay, A K; Bullock, A J; Dicolandrea, T; Xu, J; Binder, R L; Robinson, M K; Finlay, D R; Mills, K J; Bascom, C C; Kelling, C K; Isfort, R J; Haycock, J W; MacNeil, S; Smallwood, R H

2013-01-01

Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (progenitor cell with stochastic fate); and 3) populational asymmetry with stem cells. In this study, we investigated lineage dynamics using these hypotheses with a 3D agent-based model of the epidermis. The model simulated the growth and maintenance of the epidermis over three years. The offspring of each proliferative cell was traced. While all lineages were preserved in asymmetric division, the vast majority were lost when assuming populational asymmetry. The third hypothesis provided the most reliable mechanism for self-renewal by preserving genetic heterogeneity in quiescent stem cells, and also inherent mechanisms for skin ageing and the accumulation of genetic mutation.

In vitro assessment of eye irritancy using the Reconstructed Human Corneal Epithelial SkinEthic HCE model: application to 435 substances from consumer products industry.

Science.gov (United States)

Cotovio, José; Grandidier, Marie-Hélène; Lelièvre, Damien; Bremond, Christelle; Amsellem, Carolle; Maloug, Saber; Ovigne, Jean-Marc; Loisel-Joubert, Sophie; Lee, Aline Van Der; Minondo, Anne-Marie; Capallere, Christophe; Bertino, Béatrice; Alépée, Nathalie; Tinois-Tessonneaud, Estelle; de Fraissinette, Anne De Brugerolle; Meunier, Jean-Roch; Leclaire, Jacques

2010-03-01

The 7th amendment of the EU Cosmetics Directive led to the ban of eye irritation testing for cosmetic ingredients in animals, effective from March 11th 2009. Over the last 20years, many efforts have been made to find reliable and relevant alternative methods. The SkinEthic HCE model was used to evaluate the in vitro eye irritancy potential of substances from a cosmetic industry portfolio. An optimized protocol based on a specific 1-h treatment and a 16-h post-treatment incubation period was first assessed on a set of 102 substances. The prediction model (PM) based on a 50% viability cut-off, allowed to draw up two classes (Irritants and Non-Irritants), with good associated sensitivity (86.2%) and specificity (83.5%). To check the robustness of the method, the evaluated set was expanded up to 435 substances. Final performances maintained a high level and were characterized by an overall accuracy value > 82% when using EU or GHS classification rules. Results showed that the SkinEthic HCE test method is a promising in vitro tool for the prediction of eye irritancy. Optimization datasets were shared with the COLIPA Eye Irritation Project Team and ECVAM experts, and reviewed as part of an ongoing progression to enter an ECVAM prospective validation study for eye irritation. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Penicillin skin testing in the evaluation and management of penicillin allergy.

Science.gov (United States)

Fox, Stephanie; Park, Miguel A

2011-01-01

to review the role of penicillin skin testing in the evaluation and management of penicillin allergy mediated by IgE. PubMed and OVID search of English-language articles regarding penicillin allergy, penicillin allergy testing, and management of penicillin allergy. articles pertinent to the subject matter were selected and reviewed. the major determinant (benzylpenicillin polylysine) detects the greatest number of penicillin allergic patients during skin testing, and the minor determinants of penicillin increase the sensitivity of penicillin skin testing. Penicillin skin testing to the major and minor determinants was found to have a negative predictive value of 97% to 99%. The incidence of systemic adverse reaction to penicillin skin testing is less than 1%. a detailed history of the prior reaction to penicillin is an integral part of the evaluation, but it is not accurate in predicting a positive penicillin skin test result. A patient with a negative penicillin skin test result to the major and minor determinants is at a low risk of an immediate-type hypersensitivity reaction to penicillin. Patients with a positive skin test result should undergo desensitization to penicillin or an alternative antibiotic should be considered.

Artificial skin in perspective: concepts and applications.

Science.gov (United States)

Brohem, Carla A; Cardeal, Laura B da Silva; Tiago, Manoela; Soengas, María S; Barros, Silvia B de Moraes; Maria-Engler, Silvya S

2011-02-01

Skin, the largest organ of the human body, is organized into an elaborate layered structure consisting mainly of the outermost epidermis and the underlying dermis. A subcutaneous adipose-storing hypodermis layer and various appendages such as hair follicles, sweat glands, sebaceous glands, nerves, lymphatics, and blood vessels are also present in the skin. These multiple components of the skin ensure survival by carrying out critical functions such as protection, thermoregulation, excretion, absorption, metabolic functions, sensation, evaporation management, and aesthetics. The study of how these biological functions are performed is critical to our understanding of basic skin biology such as regulation of pigmentation and wound repair. Impairment of any of these functions may lead to pathogenic alterations, including skin cancers. Therefore, the development of genetically controlled and well characterized skin models can have important implications, not only for scientists and physicians, but also for manufacturers, consumers, governing regulatory boards and animal welfare organizations. As cells making up human skin tissue grow within an organized three-dimensional (3D) matrix surrounded by neighboring cells, standard monolayer (2D) cell cultures do not recapitulate the physiological architecture of the skin. Several types of human skin recombinants, also called artificial skin, that provide this critical 3D structure have now been reconstructed in vitro. This review contemplates the use of these organotypic skin models in different applications, including substitutes to animal testing. © 2010 John Wiley & Sons A/S.

Analysis of the 48Ca neutron skin using a nonlocal dispersive-optical-model self-energy

Science.gov (United States)

Atkinson, Mack; Mahzoon, Hossein; Dickhoff, Willem; Charity, Robert

2017-09-01

A nonlocal dispersive-optical-model (DOM) analysis of the 40Ca and 48Ca nuclei has been implemented. The real and imaginary potentials are constrained by fitting to elastic-scattering data, total and reaction cross sections, energy level information, particle number, and the charge densities of 40Ca and 48Ca, respectively. The nonlocality of these potentials permits a proper dispersive self-energy which accurately describes both positive and negative energy observables. 48Ca is of particular interest because it is doubly magic and has a neutron skin due to the excess of neutrons. The DOM neutron skin radius is found to be rskin = 0.245 , which is larger than most previous calculations. The neutron skin is closely related to the symmetry energy which is a crucial part of the nuclear equation of state. The combined analysis of 40Ca and 48Ca energy densities provides a description of the density dependence of the symmetry energy which is compared with the 48Ca neutron skin. Results for 208Pb will also become available in the near future. NSF.

Publishing and Alternative Licensing Model of Africa (PALM Africa ...

International Development Research Centre (IDRC) Digital Library (Canada)

Africa depends on learning materials published elsewhere, and has serious difficulty acquiring, producing and distributing them. In order to facilitate citizen access to these materials, the publishing sector in Africa needs to explore new business models and technologies. Publishing and Alternative Licensing Model of Africa ...

ANALYTICAL MODEL OF DAMAGED AIRCRAFT SKIN BONDED REPAIRS ASSUMING THE MATERIAL PROPERTIES DEGRADATION

Directory of Open Access Journals (Sweden)

2016-01-01

Full Text Available The search of optimal variants for composite repair patches allows to increase the service life of a damaged air- plane structure. To sensibly choose the way of repair, it is necessary to have a computational complex to predict the stress- strain condition of "structure-adhesive-patch" system and to take into account the damage growth considering the material properties change. The variant of the computational complex based on inclusion method is proposed.For calculation purposes the repair bonded joint is divided into two areas: a metal plate with patch-shaped hole and a "patch-adhesive layer-skin" composite plate (inclusion.Calculation stages:Evaluation of the patch influence to the skin stress-strain condition, stress distribution between skin and patch in the case of no damage. Calculation of the stress-strain condition is performed separately for the skin with hole and for the inclusion; solutions are coupled based on strain compatibility.Definition of the damage growth parameters at new stress-strain condition due to bonded patch existence. Skincrack stress intensity factors are found to identify the crack growth velocity. Patch is modelled as a set of "springs" bridging the crack.Degradation analysis of elasticity properties for the patch material.Repair effectiveness is evaluated with respect to crack growth velocity reduction in the initial material in compari- son with the case of the patch absence.Calculation example for the crack repair effectiveness depending on number of loading cycles for the 7075-T6 aluminum skin is given. Repair patches are carbon-epoxy, glass-epoxy and boron-epoxy material systems with quasi- isotropic layup and GLARE hybrid metal-polymeric material.The analysis shows the high effectiveness of the carbon-epoxy patch. Due to low stiffness, the glass-epoxy patchdemonstrates the least effectiveness. GLARE patch containing the fiberglass plies oriented across the crack has the same effectiveness as the carbon and

Neutron Skins and Neutron Stars

OpenAIRE

Piekarewicz, J.

2013-01-01

The neutron-skin thickness of heavy nuclei provides a fundamental link to the equation of state of neutron-rich matter, and hence to the properties of neutron stars. The Lead Radius Experiment ("PREX") at Jefferson Laboratory has recently provided the first model-independence evidence on the existence of a neutron-rich skin in 208Pb. In this contribution we examine how the increased accuracy in the determination of neutron skins expected from the commissioning of intense polarized electron be...

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

Science.gov (United States)

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

2017-11-01

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

A histopathologic evaluation of the Plasma Skin Regeneration System (PSR) versus a standard carbon dioxide resurfacing laser in an animal model.

Science.gov (United States)

Fitzpatrick, R; Bernstein, E; Iyer, S; Brown, D; Andrews, P; Penny, K

2008-02-01

A variety of high energy, pulsed, and scanned carbon dioxide lasers are available to perform cutaneous resurfacing. Rhytec has developed a device for skin regeneration that utilizes energy delivered via a burst of nitrogen plasma. This study was undertaken to benchmark the energy outputs of the plasma skin regeneration device as compared to an ultra-short pulsed carbon dioxide laser (the control device). The two systems were compared for time to complete healing, and the healing response post-treatment. Three Yucatan mini-pigs were utilized for this study. Following anesthesia, five experimental sites were marked along the skin atop the psoas muscle on each side of the spine. Treatment was applied using either the plasma skin regeneration system or the carbon dioxide laser, with one site remaining untreated as a control. Biopsies were taken from all treatment sites 0, 2, 7, 14, 30, and 60 days following treatment and processed to hematoxylin-eosin staining. Histopathologic examination was performed by observers blinded as to the treatment conditions. Skin treated with the plasma skin regeneration device showed a wider range of tissue effects across the energy settings used as compared to the laser treatment. All treatment sites had clinically regenerated epidermis by 7 days after treatment, with active cellular response below the D/E junction noted at the day 30 time-point at energies ranging from 2 to 4 J. The Rhytec PSR system provides an attractive alternative to standard CO2 laser with good remodeling of tissue architecture. Epidermis regenerated after PSR treatment shows a smoother surface profile than adjacent untreated tissue.

Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling, characterization, and ex vivo skin permeation.

Science.gov (United States)

Abdel Messih, Hanaa A; Ishak, Rania A H; Geneidi, Ahmed S; Mansour, Samar

2017-06-01

The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience. TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3 × 2 2 -level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (Y 1 ), vesicle size (Y 2 ), polydispersity index (Y 3 ), and zeta potential (Y 4 ) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug-excipient interactions, and vesicle stability were also investigated. The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (p transdermal TRO delivery.

Assessing alternative conceptual models of fracture flow

International Nuclear Information System (INIS)

Ho, C.K.

1995-01-01

The numerical code TOUGH2 was used to assess alternative conceptual models of fracture flow. The models that were considered included the equivalent continuum model (ECM) and the dual permeability (DK) model. A one-dimensional, layered, unsaturated domain was studied with a saturated bottom boundary and a constant infiltration at the top boundary. Two different infiltration rates were used in the studies. In addition, the connection areas between the fracture and matrix elements in the dual permeability model were varied. Results showed that the two conceptual models of fracture flow produced different saturation and velocity profiles-even under steady-state conditions. The magnitudes of the discrepancies were sensitive to two parameters that affected the flux between the fractures and matrix in the dual permeability model: (1) the fracture-matrix connection areas and (2) the capillary pressure gradients between the fracture and matrix elements

Biomimetic shark skin: design, fabrication and hydrodynamic function.

Science.gov (United States)

Wen, Li; Weaver, James C; Lauder, George V

2014-05-15

Although the functional properties of shark skin have been of considerable interest to both biologists and engineers because of the complex hydrodynamic effects of surface roughness, no study to date has successfully fabricated a flexible biomimetic shark skin that allows detailed study of hydrodynamic function. We present the first study of the design, fabrication and hydrodynamic testing of a synthetic, flexible, shark skin membrane. A three-dimensional (3D) model of shark skin denticles was constructed using micro-CT imaging of the skin of the shortfin mako (Isurus oxyrinchus). Using 3D printing, thousands of rigid synthetic shark denticles were placed on flexible membranes in a controlled, linear-arrayed pattern. This flexible 3D printed shark skin model was then tested in water using a robotic flapping device that allowed us to either hold the models in a stationary position or move them dynamically at their self-propelled swimming speed. Compared with a smooth control model without denticles, the 3D printed shark skin showed increased swimming speed with reduced energy consumption under certain motion programs. For example, at a heave frequency of 1.5 Hz and an amplitude of ± 1 cm, swimming speed increased by 6.6% and the energy cost-of-transport was reduced by 5.9%. In addition, a leading-edge vortex with greater vorticity than the smooth control was generated by the 3D printed shark skin, which may explain the increased swimming speeds. The ability to fabricate synthetic biomimetic shark skin opens up a wide array of possible manipulations of surface roughness parameters, and the ability to examine the hydrodynamic consequences of diverse skin denticle shapes present in different shark species. © 2014. Published by The Company of Biologists Ltd.

Rash with DERMABOND PRINEO Skin Closure System Use in Bilateral Reduction Mammoplasty: A Case Series

OpenAIRE

R. W. Knackstedt; J. A. Dixon; P. J. O’Neill; F. A. Herrera

2015-01-01

Background. Bilateral reduction mammoplasty is a common plastic surgery procedure that can be complicated by unfavorable scar formation along incision sites. Surgical adhesives can be utilized as an alternative or as an adjunct to conventional suture closures to help achieve good wound tension and provide an adequate barrier with excellent cosmesis. The recently introduced DERMABOND PRINEO Skin Closure System Skin Closure System combines the skin adhesive 2-octyl cyanoacrylate with a self-ad...

Skin Graft Fixation Using Hydrofiber (Aquacel® Extra).

Science.gov (United States)

Yen, Ya-Hui; Lin, Chih-Ming; Hsu, Honda; Chen, Ying-Chen; Chen, Yi-Wen; Li, Wan-Yu; Hsieh, Chia-Nan; Huang, Chieh-Chi

2018-06-01

The traditional method of skin graft fixation is with tie-over bollus dressing. The use of splints in the extremities for skin graft fixation is a common practice. However, these splints are heavy and uncomfortable and contribute considerably to our overall medical waste. Hydrofiber (Aquacel Extra) has a strong fluid absorption property and fixates well to the underlying wound once applied. In this study, we used hydrofiber for fixation, avoiding the use of splints after skin grafting. A total of 56 patients reconstructed with split-thickness skin graft that was fixated only with hydrofiber between March 2015 and March 2016 were included in this retrospective study. There were 44 men and 12 women with a mean age of 61 ± 18 years. The defect size ranged from 1 × 1 cm for fingertips to 30 × 12 cm for lower limb defects. The average defect size was 61 ± 78 cm. The mean skin graft take was 96% ± 6%. Because splints were not required, we saved around 48 kg of medical waste over the space of 1 year. The use of hydrofiber for skin graft fixation was effective and technically very simple. Splints were not required with this method, decreasing the medical waste created and increasing patient comfort. We suggest that this is an excellent alternative for skin graft fixation while at the same time decreasing our carbon footprint as surgeons.

IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation.

Science.gov (United States)

Ma, Hak-Ling; Liang, Spencer; Li, Jing; Napierata, Lee; Brown, Tom; Benoit, Stephen; Senices, Mayra; Gill, Davinder; Dunussi-Joannopoulos, Kyriaki; Collins, Mary; Nickerson-Nutter, Cheryl; Fouser, Lynette A; Young, Deborah A

2008-02-01

Psoriasis is a chronic skin disease resulting from the dysregulated interplay between keratinocytes and infiltrating immune cells. We report on a psoriasis-like disease model, which is induced by the transfer of CD4(+)CD45RB(hi)CD25(-) cells to pathogen-free scid/scid mice. Psoriasis-like lesions had elevated levels of antimicrobial peptide and proinflammatory cytokine mRNA. Also, similar to psoriasis, disease progression in this model was dependent on the p40 common to IL-12 and IL-23. To investigate the role of IL-22, a Th17 cytokine, in disease progression, mice were treated with IL-22-neutralizing antibodies. Neutralization of IL-22 prevented the development of disease, reducing acanthosis (thickening of the skin), inflammatory infiltrates, and expression of Th17 cytokines. Direct administration of IL-22 into the skin of normal mice induced both antimicrobial peptide and proinflammatory cytokine gene expression. Our data suggest that IL-22, which acts on keratinocytes and other nonhematopoietic cells, is required for development of the autoreactive Th17 cell-dependent disease in this model of skin inflammation. We propose that IL-22 antagonism might be a promising therapy for the treatment of human psoriasis.

Liposomogenic UV Absorbers are Water-Resistant on Pig Skin-A Model Study With Relevance for Sunscreens.

Science.gov (United States)

Herzog, Bernd; Hüglin, Dietmar; Luther, Helmut

2017-02-01

An important property of sunscreens is their water resistance after the application on human skin. In this work, the hypothesis that UV absorber molecules which are able to form liposomes, so-called liposomogenic UV absorbers, show better water resistance on a pig skin model than UV-absorbing molecules lacking this ability was tested. The assumption behind is that molecules which can form liposomes are able to integrate into the stratum corneum lipids of the skin. Three different liposomogenic UV absorbers were synthesized and their behavior investigated, leading to the confirmation of the hypothesis. With one of the liposomogenic UV absorbers, it was possible to show the integration of the UV absorber molecules into the bilayers of another liposome consisting of phosphatidylcholine, supporting the assumption that liposomogenic UV absorbers exhibit improved water resistance because they integrate into the skin lipids. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Phototoxicity: Its Mechanism and Animal Alternative Test Methods

Science.gov (United States)

Park, Hyeonji; Lim, Kyung-Min

2015-01-01

The skin exposure to solar irradiation and photoreactive xenobiotics may produce abnormal skin reaction, phototoxicity. Phototoxicity is an acute light-induced response, which occurs when photoreacive chemicals are activated by solar lights and transformed into products cytotoxic against the skin cells. Multifarious symptoms of phototoxicity are identified, skin irritation, erythema, pruritis, and edema that are similar to those of the exaggerated sunburn. Diverse organic chemicals, especially drugs, are known to induce phototoxicity, which is probably from the common possession of UV-absorbing benzene or heterocyclic rings in their molecular structures. Both UVB (290~320 nm) and UVA (320~400 nm) are responsible for the manifestation of phototoxicity. Absorption of photons and absorbed energy (hv) by photoactive chemicals results in molecular changes or generates reactive oxygen species and depending on the way how endogenous molecules are affected by phototoxicants, mechanisms of phototoxcity is categorized into two modes of action: Direct when unstable species from excited state directly react with the endogenous molecules, and indirect when endogeneous molecules react with secondary photoproducts. In order to identify phototoxic potential of a chemical, various test methods have been introduced. Focus is given to animal alternative test methods, i.e., in vitro, and in chemico assays as well as in vivo. 3T3 neutral red uptake assay, erythrocyte photohemolysis test, and phototoxicity test using human 3-dimensional (3D) epidermis model are examples of in vitro assays. In chemico methods evaluate the generation of reactive oxygen species or DNA strand break activity employing plasmid for chemicals, or drugs with phototoxic potential. PMID:26191378

Tanning Shade Gradations of Models in Mainstream Fitness and Muscle Enthusiast Magazines: Implications for Skin Cancer Prevention in Men.

Science.gov (United States)

Basch, Corey H; Hillyer, Grace Clarke; Ethan, Danna; Berdnik, Alyssa; Basch, Charles E

2015-07-01

Tanned skin has been associated with perceptions of fitness and social desirability. Portrayal of models in magazines may reflect and perpetuate these perceptions. Limited research has investigated tanning shade gradations of models in men's versus women's fitness and muscle enthusiast magazines. Such findings are relevant in light of increased incidence and prevalence of melanoma in the United States. This study evaluated and compared tanning shade gradations of adult Caucasian male and female model images in mainstream fitness and muscle enthusiast magazines. Sixty-nine U.S. magazine issues (spring and summer, 2013) were utilized. Two independent reviewers rated tanning shade gradations of adult Caucasian male and female model images on magazines' covers, advertisements, and feature articles. Shade gradations were assessed using stock photographs of Caucasian models with varying levels of tanned skin on an 8-shade scale. A total of 4,683 images were evaluated. Darkest tanning shades were found among males in muscle enthusiast magazines and lightest among females in women's mainstream fitness magazines. By gender, male model images were 54% more likely to portray a darker tanning shade. In this study, images in men's (vs. women's) fitness and muscle enthusiast magazines portrayed Caucasian models with darker skin shades. Despite these magazines' fitness-related messages, pro-tanning images may promote attitudes and behaviors associated with higher skin cancer risk. To date, this is the first study to explore tanning shades in men's magazines of these genres. Further research is necessary to identify effects of exposure to these images among male readers. © The Author(s) 2014.

Clinical system model for monitoring the physiological status of jaundice by extracting bilirubin components from skin diffuse reflectance spectra

Science.gov (United States)

Kumar, Alla S.; Clark, Joseph; Beyette, Fred R., Jr.

2009-02-01

Neonatal jaundice is a medical condition which occurs in newborns as a result of an imbalance between the production and elimination of bilirubin. The excess bilirubin in the blood stream diffuses into the surrounding tissue leading to a yellowing of the skin. As the bilirubin levels rise in the blood stream, there is a continuous exchange between the extra vascular bilirubin and bilirubin in the blood stream. Exposure to phototherapy alters the concentration of bilirubin in the vascular and extra vascular regions by causing bilirubin in the skin layers to be broken down. Thus, the relative concentration of extra vascular bilirubin is reduced leading to a diffusion of bilirubin out of the vascular region. Diffuse reflectance spectra from human skin contains physiological and structural information of the skin and nearby tissue. A diffuse reflectance spectrum must be captured before and after blanching in order to isolate the intravascular and extra vascular bilirubin. A new mathematical model is proposed with extra vascular bilirubin concentration taken into consideration along with other optical parameters in defining the diffuse reflectance spectrum from human skin. A nonlinear optimization algorithm has been adopted to extract the optical properties (including bilirubin concentration) from the skin reflectance spectrum. The new system model and nonlinear algorithm have been combined to enable extraction of Bilirubin concentrations within an average error of 10%.

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

Science.gov (United States)

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

2018-05-01

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

Can a one-layer optical skin model including melanin and inhomogeneously distributed blood explain spatially resolved diffuse reflectance spectra?

Science.gov (United States)

Karlsson, Hanna; Pettersson, Anders; Larsson, Marcus; Strömberg, Tomas

2011-02-01

Model based analysis of calibrated diffuse reflectance spectroscopy can be used for determining oxygenation and concentration of skin chromophores. This study aimed at assessing the effect of including melanin in addition to hemoglobin (Hb) as chromophores and compensating for inhomogeneously distributed blood (vessel packaging), in a single-layer skin model. Spectra from four humans were collected during different provocations using a twochannel fiber optic probe with source-detector separations 0.4 and 1.2 mm. Absolute calibrated spectra using data from either a single distance or both distances were analyzed using inverse Monte Carlo for light transport and Levenberg-Marquardt for non-linear fitting. The model fitting was excellent using a single distance. However, the estimated model failed to explain spectra from the other distance. The two-distance model did not fit the data well at either distance. Model fitting was significantly improved including melanin and vessel packaging. The most prominent effect when fitting data from the larger separation compared to the smaller separation was a different light scattering decay with wavelength, while the tissue fraction of Hb and saturation were similar. For modeling spectra at both distances, we propose using either a multi-layer skin model or a more advanced model for the scattering phase function.

Mechanistic applicability domain classification of a local lymph node assay dataset for skin sensitization.

Science.gov (United States)

Roberts, David W; Patlewicz, Grace; Kern, Petra S; Gerberick, Frank; Kimber, Ian; Dearman, Rebecca J; Ryan, Cindy A; Basketter, David A; Aptula, Aynur O

2007-07-01

The goal of eliminating animal testing in the predictive identification of chemicals with the intrinsic ability to cause skin sensitization is an important target, the attainment of which has recently been brought into even sharper relief by the EU Cosmetics Directive and the requirements of the REACH legislation. Development of alternative methods requires that the chemicals used to evaluate and validate novel approaches comprise not only confirmed skin sensitizers and non-sensitizers but also substances that span the full chemical mechanistic spectrum associated with skin sensitization. To this end, a recently published database of more than 200 chemicals tested in the mouse local lymph node assay (LLNA) has been examined in relation to various chemical reaction mechanistic domains known to be associated with sensitization. It is demonstrated here that the dataset does cover the main reaction mechanistic domains. In addition, it is shown that assignment to a reaction mechanistic domain is a critical first step in a strategic approach to understanding, ultimately on a quantitative basis, how chemical properties influence the potency of skin sensitizing chemicals. This understanding is necessary if reliable non-animal approaches, including (quantitative) structure-activity relationships (Q)SARs, read-across, and experimental chemistry based models, are to be developed.

Force sensor in simulated skin and neural model mimic tactile SAI afferent spiking response to ramp and hold stimuli.

Science.gov (United States)

Kim, Elmer K; Wellnitz, Scott A; Bourdon, Sarah M; Lumpkin, Ellen A; Gerling, Gregory J

2012-07-23

The next generation of prosthetic limbs will restore sensory feedback to the nervous system by mimicking how skin mechanoreceptors, innervated by afferents, produce trains of action potentials in response to compressive stimuli. Prior work has addressed building sensors within skin substitutes for robotics, modeling skin mechanics and neural dynamics of mechanotransduction, and predicting response timing of action potentials for vibration. The effort here is unique because it accounts for skin elasticity by measuring force within simulated skin, utilizes few free model parameters for parsimony, and separates parameter fitting and model validation. Additionally, the ramp-and-hold, sustained stimuli used in this work capture the essential features of the everyday task of contacting and holding an object. This systems integration effort computationally replicates the neural firing behavior for a slowly adapting type I (SAI) afferent in its temporally varying response to both intensity and rate of indentation force by combining a physical force sensor, housed in a skin-like substrate, with a mathematical model of neuronal spiking, the leaky integrate-and-fire. Comparison experiments were then conducted using ramp-and-hold stimuli on both the spiking-sensor model and mouse SAI afferents. The model parameters were iteratively fit against recorded SAI interspike intervals (ISI) before validating the model to assess its performance. Model-predicted spike firing compares favorably with that observed for single SAI afferents. As indentation magnitude increases (1.2, 1.3, to 1.4 mm), mean ISI decreases from 98.81 ± 24.73, 54.52 ± 6.94, to 41.11 ± 6.11 ms. Moreover, as rate of ramp-up increases, ISI during ramp-up decreases from 21.85 ± 5.33, 19.98 ± 3.10, to 15.42 ± 2.41 ms. Considering first spikes, the predicted latencies exhibited a decreasing trend as stimulus rate increased, as is observed in afferent recordings. Finally, the SAI afferent's characteristic response

Hyperspectral signature analysis of skin parameters

Science.gov (United States)

Vyas, Saurabh; Banerjee, Amit; Garza, Luis; Kang, Sewon; Burlina, Philippe

2013-02-01

The temporal analysis of changes in biological skin parameters, including melanosome concentration, collagen concentration and blood oxygenation, may serve as a valuable tool in diagnosing the progression of malignant skin cancers and in understanding the pathophysiology of cancerous tumors. Quantitative knowledge of these parameters can also be useful in applications such as wound assessment, and point-of-care diagnostics, amongst others. We propose an approach to estimate in vivo skin parameters using a forward computational model based on Kubelka-Munk theory and the Fresnel Equations. We use this model to map the skin parameters to their corresponding hyperspectral signature. We then use machine learning based regression to develop an inverse map from hyperspectral signatures to skin parameters. In particular, we employ support vector machine based regression to estimate the in vivo skin parameters given their corresponding hyperspectral signature. We build on our work from SPIE 2012, and validate our methodology on an in vivo dataset. This dataset consists of 241 signatures collected from in vivo hyperspectral imaging of patients of both genders and Caucasian, Asian and African American ethnicities. In addition, we also extend our methodology past the visible region and through the short-wave infrared region of the electromagnetic spectrum. We find promising results when comparing the estimated skin parameters to the ground truth, demonstrating good agreement with well-established physiological precepts. This methodology can have potential use in non-invasive skin anomaly detection and for developing minimally invasive pre-screening tools.

Skin friction under pressure. The role of micromechanics

Science.gov (United States)

Leyva-Mendivil, Maria F.; Lengiewicz, Jakub; Limbert, Georges

2018-03-01

The role of contact pressure on skin friction has been documented in multiple experimental studies. Skin friction significantly raises in the low-pressure regime as load increases while, after a critical pressure value is reached, the coefficient of friction of skin against an external surface becomes mostly insensitive to contact pressure. However, up to now, no study has elucidated the qualitative and quantitative nature of the interplay between contact pressure, the material and microstructural properties of the skin, the size of an indenting slider and the resulting measured macroscopic coefficient of friction. A mechanistic understanding of these aspects is essential for guiding the rational design of products intended to interact with the skin through optimally-tuned surface and/or microstructural properties. Here, an anatomically-realistic 2D multi-layer finite element model of the skin was embedded within a computational contact homogenisation procedure. The main objective was to investigate the sensitivity of macroscopic skin friction to the parameters discussed above, in addition to the local (i.e. microscopic) coefficient of friction defined at skin asperity level. This was accomplished via the design of a large-scale computational experiment featuring 312 analyses. Results confirmed the potentially major role of finite deformations of skin asperities on the resulting macroscopic friction. This effect was shown to be modulated by the level of contact pressure and relative size of skin surface asperities compared to those of a rigid slider. The numerical study also corroborated experimental observations concerning the existence of two contact pressure regimes where macroscopic friction steeply and non-linearly increases up to a critical value, and then remains approximately constant as pressure increases further. The proposed computational modelling platform offers attractive features which are beyond the reach of current analytical models of skin

UNDER GRADUATE RESEARCH An alternative model of doing ...

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. UNDER GRADUATE RESEARCH An alternative model of doing science. The main work force is undergraduate students. Using research as a tool in education. Advantages : High risk tolerance. Infinite energy. Uninhibited lateral thinking. Problems: Japanese ...

Neutron Skin Thickness of 48Ca from a Nonlocal Dispersive Optical-Model Analysis

Science.gov (United States)

Mahzoon, M. H.; Atkinson, M. C.; Charity, R. J.; Dickhoff, W. H.

2017-12-01

A nonlocal dispersive optical-model analysis has been carried out for neutrons and protons in 48Ca. Elastic-scattering angular distributions, total and reaction cross sections, single-particle energies, the neutron and proton numbers, and the charge distribution have been fitted to extract the neutron and proton self-energies both above and below the Fermi energy. From the single-particle propagator resulting from these self-energies, we have determined the charge and neutron matter distributions in 48Ca. A best fit neutron skin of 0.249 ±0.023 fm is deduced, but values up to 0.33 fm are still consistent. The energy dependence of the total neutron cross sections is shown to have a strong sensitivity to the skin thickness.

Measuring the effects of topically applied skin optical clearing agents and modeling the effects and consequences for laser therapies

Science.gov (United States)

Verkruysse, Wim; Khan, Misbah; Choi, Bernard; Svaasand, Lars O.; Nelson, J. Stuart

2005-04-01

Human skin prepared with an optical clearing agent manifests reduced scattering as a result of de-hydration and refractive index matching. This has potentially large effects for laser therapies of several skin lesions such as port wine stain, hair removal and tattoo removal. With most topically applied clearing agents the clearing effect is limited because they penetrate poorly through the intact superficial skin layer (stratum corneum). Agent application modi other than topical are impractical and have limited the success of optical clearing in laser dermatology. In recent reports, however, a mixture of lipofylic and hydrofylic agents was shown to successfully penetrate through the intact stratum corneum layer which has raised new interest in this field. Immediately after application, the optical clearing effect is superficial and, as the agent diffuses through the skin, reduced scattering is manifested in deeper skin layers. For practical purposes as well as to maximize therapeutic success, it is important to quantify the reduced scattering as well as the trans-cutaneous transport dynamics of the agent. We determined the time and tissue depth resolved effects of optically cleared skin by inserting a microscopic reflector array in the skin. Depth dependent light intensity was measured by quantifying the signal of the reflector array with optical coherence tomography. A 1-dimensional mass diffusion model was used to estimate a trans-cutaneous transport diffusion constant for the clearing agent mixture. The results are used in Monte Carlo modeling to determine the optimal time of laser treatment after topical application of the optical clearing agent.

Skin dose assessment in routine personnel beta/gamma dosimetry

International Nuclear Information System (INIS)

Christensen, P.

1980-01-01

Three alternative methods are outlined by which substantial improvements of the capabilities of existing routine monitoring systems for skin dose assessment can be obtained. The introduction of a supplementary skin dosemeter may be an attractive method for systems with badges that have a capability for an additional dosemeter already built-in. The two-side reading method has limited possibilities because of reduced accuracy for mixed radiation and technical difficulties in using it for TLD systems with planchet heating. The use of a boron diffused LiF layer for skin dose assessment seems to be most attractive method since the only modification needed here is replacement of a dosemeter. However the study of this method is so far only in a preliminary stage and further investigations are needed. (U.K.)

An Integrated Modelling and Toolpathing Approach for a Frameless Stressed Skin Structure, Fabricated Using Robotic Incremental Sheet Forming

DEFF Research Database (Denmark)

Nicholas, Paul; Stasiuk, David; Nørgaard, Esben Clausen

2016-01-01

with performance implications at material, element and structural scales. This paper briefly presents ISF as a method of fabrication, and introduces the context of structures where the skin plays an integral role. It describes the development of an integrated approach for the modelling and fabrication of Stressed...... Skins, an incrementally formed sheet metal structure. The paper then focus upon the use of prototypes and empirical testing as means to inform digital models about fabrication and material parameters including: material forming limits and thinning; the parameterisation of macro and meso simulations...

Elective penicillin skin testing in a pediatric outpatient setting.

Science.gov (United States)

Jost, Barbara Capes; Wedner, H James; Bloomberg, Gordon R

2006-12-01

Adverse reactions associated with penicillin-type antibiotics are common in pediatric practice, leading to the subsequent unnecessary use of alternative antibiotics. IgE-mediated penicillin allergy represents only a fraction of these adverse reactions. To examine (1) the trend of penicillin skin test reactivity during a recent 10-year interval, (2) the relative distribution of specific reagents related to a positive skin test result, and (3) skin test reactivity as a function of reaction history. Penicillin testing using 3 reagents--benzylpenicilloyl polylysine, penicillin G, and sodium penicilloate (penicillin A)--was conducted in a prospective study of 359 consecutive patients referred to an outpatient pediatric allergy clinic between January 1, 1993, and May 31, 2003. We also retrospectively reviewed penicillin skin test results for 562 children previously tested between January 1, 1979, and December 31, 1992. Between 1993 and 2003, the prevalence of penicillin skin test sensitivity markedly declined. Of all the positive skin test results between 1979 and 2002, either penicillin G or sodium penicilloate or both identified 34%, with sodium penicilloate alone responsible for 8.5%. The rate of positive skin test reactions was not significantly different between patients with vs without a history of suggestive IgE-mediated reactions. A marked decline in penicillin skin test sensitivity in the pediatric age group is identified. The minor determinant reagents penicillin G and sodium penicilloate are both necessary for determining potential penicillin allergy. Relating history alone to potential penicillin sensitivity is unreliable in predicting the presence or absence of a positive skin test result.

Dendritic cells and skin sensitization: Biological roles and uses in hazard identification

International Nuclear Information System (INIS)

Ryan, Cindy A.; Kimber, Ian; Basketter, David A.; Pallardy, Marc; Gildea, Lucy A.; Gerberick, G. Frank

2007-01-01

Recent advances have been made in our understanding of the roles played by cutaneous dendritic cells (DCs) in the induction of contact allergy. A number of associated changes in epidermal Langerhans cell phenotype and function required for effective skin sensitization are providing the foundations for the development of cellular assays (using DC and DC-like cells) for skin sensitization hazard identification. These alternative approaches to the identification and characterization of skin sensitizing chemicals were the focus of a Workshop entitled 'Dendritic Cells and Skin Sensitization: Biological Roles and Uses in Hazard Identification' that was given at the annual Society of Toxicology meeting held March 6-9, 2006 in San Diego, California. This paper reports information that was presented during the Workshop

Comparison between two race/skin color classifications in relation to health-related outcomes in Brazil

Directory of Open Access Journals (Sweden)

Szwarcwald Celia L

2011-08-01

Full Text Available Abstract Background This paper aims to compare the classification of race/skin color based on the discrete categories used by the Demographic Census of the Brazilian Institute of Geography and Statistics (IBGE and a skin color scale with values ranging from 1 (lighter skin to 10 (darker skin, examining whether choosing one alternative or the other can influence measures of self-evaluation of health status, health care service utilization and discrimination in the health services. Methods This is a cross-sectional study based on data from the World Health Survey carried out in Brazil in 2003 with a sample of 5000 individuals older than 18 years. Similarities between the two classifications were evaluated by means of correspondence analysis. The effect of the two classifications on health outcomes was tested through logistic regression models for each sex, using age, educational level and ownership of consumer goods as covariables. Results Both measures of race/skin color represent the same race/skin color construct. The results show a tendency among Brazilians to classify their skin color in shades closer to the center of the color gradient. Women tend to classify their race/skin color as a little lighter than men in the skin color scale, an effect not observed when IBGE categories are used. With regard to health and health care utilization, race/skin color was not relevant in explaining any of them, regardless of the race/skin color classification. Lack of money and social class were the most prevalent reasons for discrimination in healthcare reported in the survey, suggesting that in Brazil the discussion about discrimination in the health care must not be restricted to racial discrimination and should also consider class-based discrimination. The study shows that the differences of the two classifications of race/skin color are small. However, the interval scale measure appeared to increase the freedom of choice of the respondent.

In vitro permeation of platinum and rhodium through Caucasian skin.

Science.gov (United States)

Franken, A; Eloff, F C; Du Plessis, J; Badenhorst, C J; Jordaan, A; Du Plessis, J L

2014-12-01

During platinum group metals (PGMs) refining the possibility exists for dermal exposure to PGM salts. The dermal route has been questioned as an alternative route of exposure that could contribute to employee sensitisation, even though literature has been focused on respiratory exposure. This study aimed to investigate the in vitro permeation of platinum and rhodium through intact Caucasian skin. A donor solution of 0.3mg/ml of metal, K2PtCl4 and RhCl3 respectively, was applied to the vertical Franz diffusion cells with full thickness abdominal skin. The receptor solution was removed at various intervals during the 24h experiment, and analysed with high resolution ICP-MS. Skin was digested and analysed by ICP-OES. Results indicated cumulative permeation with prolonged exposure, with a significantly higher mass of platinum permeating after 24h when compared to rhodium. The mass of platinum retained inside the skin and the flux of platinum across the skin was significantly higher than that of rhodium. Permeated and skin retained platinum and rhodium may therefore contribute to sensitisation and indicates a health risk associated with dermal exposure in the workplace. Copyright © 2014 Elsevier Ltd. All rights reserved.

Alternative host models for Testing Anti-Protozoal or Antifungal Compounds and fungal infection.

Science.gov (United States)

Torrecilhas, Ana Claudia; Xander, Patricia; Ferreira, Karen Spadari; Batista, Wagner Luiz

2018-04-12

The neglected tropical diseases (NTDs) are caused by several parasites, fungi, bacteria and viruses and affect more than one billion people in the world. The control and prevention against NTDs need implementation of alternative methods for testing new compounds against these diseases. For the implementation of alternative methods, it is necessary to apply the principles of replacement, reduction and refinement (the 3Rs) for the use of laboratory animals. Accordingly, the present review addressed a variety of alternative models to study the infections caused by protozoa and fungi. Overall, vertebrate and invertebrate models of fungal infection have been used to elucidate hostpathogen interactions. However, until now the insect model has not been used in protozoal studies as an alternative method, but there is interest in the scientific community to try new tools to screen alternative drugs to control and prevent protozoal infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Science.gov (United States)

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

2000-09-01

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

Alternative (non-animal) methods for cosmetics testing: current status and future prospects-2010.

Science.gov (United States)

Adler, Sarah; Basketter, David; Creton, Stuart; Pelkonen, Olavi; van Benthem, Jan; Zuang, Valérie; Andersen, Klaus Ejner; Angers-Loustau, Alexandre; Aptula, Aynur; Bal-Price, Anna; Benfenati, Emilio; Bernauer, Ulrike; Bessems, Jos; Bois, Frederic Y; Boobis, Alan; Brandon, Esther; Bremer, Susanne; Broschard, Thomas; Casati, Silvia; Coecke, Sandra; Corvi, Raffaella; Cronin, Mark; Daston, George; Dekant, Wolfgang; Felter, Susan; Grignard, Elise; Gundert-Remy, Ursula; Heinonen, Tuula; Kimber, Ian; Kleinjans, Jos; Komulainen, Hannu; Kreiling, Reinhard; Kreysa, Joachim; Leite, Sofia Batista; Loizou, George; Maxwell, Gavin; Mazzatorta, Paolo; Munn, Sharon; Pfuhler, Stefan; Phrakonkham, Pascal; Piersma, Aldert; Poth, Albrecht; Prieto, Pilar; Repetto, Guillermo; Rogiers, Vera; Schoeters, Greet; Schwarz, Michael; Serafimova, Rositsa; Tähti, Hanna; Testai, Emanuela; van Delft, Joost; van Loveren, Henk; Vinken, Mathieu; Worth, Andrew; Zaldivar, José-Manuel

2011-05-01

The 7th amendment to the EU Cosmetics Directive prohibits to put animal-tested cosmetics on the market in Europe after 2013. In that context, the European Commission invited stakeholder bodies (industry, non-governmental organisations, EU Member States, and the Commission's Scientific Committee on Consumer Safety) to identify scientific experts in five toxicological areas, i.e. toxicokinetics, repeated dose toxicity, carcinogenicity, skin sensitisation, and reproductive toxicity for which the Directive foresees that the 2013 deadline could be further extended in case alternative and validated methods would not be available in time. The selected experts were asked to analyse the status and prospects of alternative methods and to provide a scientifically sound estimate of the time necessary to achieve full replacement of animal testing. In summary, the experts confirmed that it will take at least another 7-9 years for the replacement of the current in vivo animal tests used for the safety assessment of cosmetic ingredients for skin sensitisation. However, the experts were also of the opinion that alternative methods may be able to give hazard information, i.e. to differentiate between sensitisers and non-sensitisers, ahead of 2017. This would, however, not provide the complete picture of what is a safe exposure because the relative potency of a sensitiser would not be known. For toxicokinetics, the timeframe was 5-7 years to develop the models still lacking to predict lung absorption and renal/biliary excretion, and even longer to integrate the methods to fully replace the animal toxicokinetic models. For the systemic toxicological endpoints of repeated dose toxicity, carcinogenicity and reproductive toxicity, the time horizon for full replacement could not be estimated.

Calculating the dermal flux of chemicals with OELs based on their molecular structure: An attempt to assign the skin notation.

Science.gov (United States)

Kupczewska-Dobecka, Małgorzata; Jakubowski, Marek; Czerczak, Sławomir

2010-09-01

models; from among 112 chemicals 94 (84%) should have the skin notation in the OEL list based on the LFER calculations. The skin notation had been estimated by other published models for almost 94% of the chemicals. Twenty-nine (25.8%) chemicals were identified to have significant absorption and 65 (58%) the potential for dermal toxicity. We found major differences between alternative published analytical models and their ability to determine whether particular chemicals were potentially dermotoxic. Copyright © 2010 Elsevier B.V. All rights reserved.

Soap-scented oil skin patch in the treatment of fibromyalgia: A case series

Directory of Open Access Journals (Sweden)

Yon Doo Ough

2008-09-01

Full Text Available Yon Doo OughDepartment of Anesthesiology, Beloit Memorial Hospital, Beloit, WI, USAAbstract: Treatment for fibromyalgia is largely empiric and supportive, and favors a multidisciplinary approach. Despite treatment, symptomatic relief is often inadequate and temporary. Over 90% of fibromyalgia patients seek alternative medical care. There is much anecdotal evidence that applying a bar of soap to the skin can relieve leg cramps. Expanding on this idea, I created a skin patch from soap-scented oil, which was used to treat muscular pain and spasms. After receiving positive feedback from several patients, I hypothesized that the scent of the oil itself, applied directly to the skin, is responsible for the pain-relieving and muscle-relaxant properties of the skin patch. Furthermore, I hypothesize that this soap-scented oil skin patch is an effective treatment for the pain associated with fibromyalgia.Keywords: fibromyalgia, headache, soap-scented oil skin patch

Skin graft

Science.gov (United States)

Skin transplant; Skin autografting; FTSG; STSG; Split thickness skin graft; Full thickness skin graft ... donor site. Most people who are having a skin graft have a split-thickness skin graft. This takes ...

Keratinocytes propagated in serum-free, feeder-free culture conditions fail to form stratified epidermis in a reconstituted skin model.

Directory of Open Access Journals (Sweden)

Rebecca Lamb

Full Text Available Primary human epidermal stem cells isolated from skin tissues and subsequently expanded in tissue culture are used for human therapeutic use to reconstitute skin on patients and to generate artificial skin in culture for academic and commercial research. Classically, epidermal cells, known as keratinocytes, required fibroblast feeder support and serum-containing media for serial propagation. In alignment with global efforts to remove potential animal contaminants, many serum-free, feeder-free culture methods have been developed that support derivation and growth of these cells in 2-dimensional culture. Here we show that keratinocytes grown continually in serum-free and feeder-free conditions were unable to form into a stratified, mature epidermis in a skin equivalent model. This is not due to loss of cell potential as keratinocytes propagated in serum-free, feeder-free conditions retain their ability to form stratified epidermis when re-introduced to classic serum-containing media. Extracellular calcium supplementation failed to improve epidermis development. In contrast, the addition of serum to commercial, growth media developed for serum-free expansion of keratinocytes facilitated 3-dimensional stratification in our skin equivalent model. Moreover, the addition of heat-inactivated serum improved the epidermis structure and thickness, suggesting that serum contains factors that both aid and inhibit stratification.