An unexpected metastasis of breast cancer mimicking wheal rush

PubMed Central

DAMASKOS, C.; DIMITROULIS, D.; PERGIALIOTIS, V.; DOULA, C.; KOULERMOU, G.; ANTONIOU, E.A.; FRANGOULIS, M.; STERGIOS, K.; KONTZOGLOU, K.

2016-01-01

Breast cancer is the most common cancer among women and ranks second in cancer deaths worldwide. Breast cancer can metastasize to the skin but rarely, cutaneous metastases may be the first indication of the cancer. Skin metastases of breast cancer are usually found on the chest and close to the point of the mastectomy. We present the rare clinical entity of a breast cancer which was first diagnosed due to the skin metastasis away from the breast tumor. This is a rare case because the skin lesions usually appear simultaneously or secondary. Also, while the existing metastasis; the only symptom was the wheal rash. PMID:27734799

An in vitro human skin test for assessing sensitization potential.

PubMed

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

2016-05-01

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

International regulatory requirements for skin sensitization testing.

PubMed

Daniel, Amber B; Strickland, Judy; Allen, David; Casati, Silvia; Zuang, Valérie; Barroso, João; Whelan, Maurice; Régimbald-Krnel, M J; Kojima, Hajime; Nishikawa, Akiyoshi; Park, Hye-Kyung; Lee, Jong Kwon; Kim, Tae Sung; Delgado, Isabella; Rios, Ludmila; Yang, Ying; Wang, Gangli; Kleinstreuer, Nicole

2018-06-01

Skin sensitization test data are required or considered by chemical regulation authorities around the world. These data are used to develop product hazard labeling for the protection of consumers or workers and to assess risks from exposure to skin-sensitizing chemicals. To identify opportunities for regulatory uses of non-animal replacements for skin sensitization tests, the needs and uses for skin sensitization test data must first be clarified. Thus, we reviewed skin sensitization testing requirements for seven countries or regions that are represented in the International Cooperation on Alternative Test Methods (ICATM). We noted the type of skin sensitization data required for each chemical sector and whether these data were used in a hazard classification, potency classification, or risk assessment context; the preferred tests; and whether alternative non-animal tests were acceptable. An understanding of national and regional regulatory requirements for skin sensitization testing will inform the development of ICATM's international strategy for the acceptance and implementation of non-animal alternatives to assess the health hazards and risks associated with potential skin sensitizers. Copyright © 2018 Elsevier Inc. All rights reserved.

Meta-Profiles of Gene Expression during Aging: Limited Similarities between Mouse and Human and an Unexpectedly Decreased Inflammatory Signature

PubMed Central

Swindell, William R.; Johnston, Andrew; Sun, Liou; Xing, Xianying; Fisher, Gary J.; Bulyk, Martha L.; Elder, James T.; Gudjonsson, Johann E.

2012-01-01

Background Skin aging is associated with intrinsic processes that compromise the structure of the extracellular matrix while promoting loss of functional and regenerative capacity. These processes are accompanied by a large-scale shift in gene expression, but underlying mechanisms are not understood and conservation of these mechanisms between humans and mice is uncertain. Results We used genome-wide expression profiling to investigate the aging skin transcriptome. In humans, age-related shifts in gene expression were sex-specific. In females, aging increased expression of transcripts associated with T-cells, B-cells and dendritic cells, and decreased expression of genes in regions with elevated Zeb1, AP-2 and YY1 motif density. In males, however, these effects were contrasting or absent. When age-associated gene expression patterns in human skin were compared to those in tail skin from CB6F1 mice, overall human-mouse correspondence was weak. Moreover, inflammatory gene expression patterns were not induced with aging of mouse tail skin, and well-known aging biomarkers were in fact decreased (e.g., Clec7a, Lyz1 and Lyz2). These unexpected patterns and weak human-mouse correspondence may be due to decreased abundance of antigen presenting cells in mouse tail skin with age. Conclusions Aging is generally associated with a pro-inflammatory state, but we have identified an exception to this pattern with aging of CB6F1 mouse tail skin. Aging therefore does not uniformly heighten inflammatory status across all mouse tissues. Furthermore, we identified both intercellular and intracellular mechanisms of transcriptome aging, including those that are sex- and species-specific. PMID:22413003

Striatal and midbrain connectivity with the hippocampus selectively boosts memory for contextual novelty

PubMed Central

Kafkas, Alexandros; Montaldi, Daniela

2015-01-01

The role of contextual expectation in processing familiar and novel stimuli was investigated in a series of experiments combining eye tracking, functional magnetic resonance imaging, and behavioral methods. An experimental paradigm emphasizing either familiarity or novelty detection at retrieval was used. The detection of unexpected familiar and novel stimuli, which were characterized by lower probability, engaged activity in midbrain and striatal structures. Specifically, detecting unexpected novel stimuli, relative to expected novel stimuli, produced greater activity in the substantia nigra/ventral tegmental area (SN/VTA), whereas the detection of unexpected familiar, relative to expected, familiar stimuli, elicited activity in the striatum/globus pallidus (GP). An effective connectivity analysis showed greater functional coupling between these two seed areas (GP and SN/VTA) and the hippocampus, for unexpected than for expected stimuli. Within this network of midbrain/striatal–hippocampal interactions two pathways are apparent; the direct SN–hippocampal pathway sensitive to unexpected novelty and the perirhinal–GP–hippocampal pathway sensitive to unexpected familiarity. In addition, increased eye fixations and pupil dilations also accompanied the detection of unexpected relative to expected familiar and novel stimuli, reflecting autonomic activity triggered by the functioning of these two pathways. Finally, subsequent memory for unexpected, relative to expected, familiar, and novel stimuli was characterized by enhanced recollection, but not familiarity, accuracy. Taken together, these findings suggest that a hippocampal–midbrain network, characterized by two distinct pathways, mediates encoding facilitation and most critically, that this facilitation is driven by contextual novelty, rather than by the absolute novelty of a stimulus. This contextually sensitive neural mechanism appears to elicit increased exploratory behavior, leading subsequently to greater recollection of the unexpected stimulus. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:25708843

Unexpected complication associated with balneotherapy: Skin and soft tissue infection

NASA Astrophysics Data System (ADS)

Alım, Bülent; Bostancı, Fahrettin; Servi, M. Alperen; Ćetinel, Sinan; Bingöl, M. Ozan

2017-04-01

Balneotherapy cure is an ongoing process, but patients can benefit most when cure is complete. For these reason, patients should be closely monitored and necessary precautions should be taken in terms of the complications that may occur in order to prevent the interruption or discontinuation of balneotherapy. Here, we wanted to represent a case that developed left leg soft tissue infection during the application of balneotherapy and because of this reason we stopped the balneotherapy As a result, when balneotherapy is planned for patients with risk factors such as diabetes and obesity, frequent examination of the skin and the application of skin moisturizers will be beneficial to prevent itching and skin dryness.

Peri-implant bony overgrowth as a cause of revision surgery in auditory osseointegrated implantation.

PubMed

Tompkins, Jared J; Petersen, Dana K; Sharbel, Daniel D; McKinnon, Brian J; MacDonald, C Bruce

2016-07-01

Implantation of auditory osseointegrated implants, also known as bone-anchored hearing systems (BAHS), represents a surgical option for select pediatric patients aged 5 years or older with hearing loss. Functional indications in this patient population include conductive or mixed hearing loss. Common complications of implantation include skin infections, chronic skin irritation, hypertrophic skin overgrowth, and loose abutments. In a case series of 15 pediatric patients, we discovered an unexpectedly high skin-related complication rate requiring surgical revision of 53%. During revision surgery, we discovered 5 patients who exhibited significant bony overgrowth at the abutment site, a complication infrequently noted in past literature. Published by Elsevier Ireland Ltd.

Adjuvant effect of short chain triacylglycerol tributyrin on a mouse contact hypersensitivity model.

PubMed

Sekiguchi, Kota; Ogawa, Erina; Kurohane, Kohta; Konishi, Hideyuki; Mochizuki, Narumi; Manabe, Kei; Imai, Yasuyuki

2018-03-01

Little attention has been paid to chemicals that can enhance hypersensitivity caused by other chemicals. We have demonstrated that phthalate esters with short chain alcohols enhance fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) in a mouse model. Furthermore, phthalate esters with such an enhancing effect were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels, which are expressed on a part of sensory neurons, using a TRPA1-expressing cell line. In this study, we examined these activities of esters comprising glycerol and a short chain fatty acid, i.e. dibutyrin and tributyrin. We carried out chemical synthesis of dibutyrin isomers. Each dibutyrin isomer weakly activated TRPA1 and slightly enhanced skin sensitization to FITC. Unexpectedly, TRPA1 activation and enhancement of FITC-CHS were much more evident in the presence of tributyrin. Mechanistically, tributyrin induced increased dendritic cell trafficking from the skin to draining lymph nodes. Tributyrin enhanced interferon-γ (IFN-γ) production by draining lymph nodes, while its effect on interleukin-4 (IL-4) production was relatively less prominent. These results suggested that tributyrin concomitantly caused TRPA1 activation and an adjuvant effect on FITC-CHS. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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

Alves, Vinicius M.; Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599; Muratov, Eugene

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 putativemore » 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 chemical hazards in the Scorecard database were found using our models.« less

IL-10+ innate-like B cells are part of the skin immune system and require α4β1 integrin to migrate between the peritoneum and inflamed skin1

PubMed Central

Glabman, Raisa A.; Ruthel, Gordon; Hamann, Alf; Debes, Gudrun F.

2016-01-01

The skin is an important barrier organ and frequent target of autoimmunity and allergy. Here we found innate-like B cells that expressed the anti-inflammatory cytokine IL-10 in the skin of humans and mice. Unexpectedly, innate-like B1 and conventional B2 cells showed differential homing capacities with peritoneal B1 cells preferentially migrating into the inflamed skin of mice. Importantly, the skin-homing B1 cells included IL-10 secreting cells. B1 cell homing into the skin was independent of typical skin-homing trafficking receptors and instead required α4β1-integrin. Moreover, B1 cells constitutively expressed activated β1 integrin and relocated from the peritoneum to the inflamed skin and intestine upon innate stimulation, indicating an inherent propensity to extravasate into inflamed and barrier sites. We conclude that innate-like B cells migrate from central reservoirs into skin, adding an important cell type with regulatory and protective functions to the skin immune system. PMID:26851219

Self-reported skin colour and erythemal sensitivity vs. objectively measured constitutive skin colour in an African population with predominantly dark skin.

PubMed

Wright, Caradee Y; Wilkes, Marcus; du Plessis, Johan L; Reeder, Anthony I

2015-11-01

Skin colour is an important factor in skin-related diseases. Accurate determination of skin colour is important for disease prevention and supporting healthy sun behaviour, yet such data are lacking for dark skin types. Self-perceived, natural skin colour and sun-skin reaction were compared with objectively measured skin colour among an African population with predominantly dark skin. Unexposed skin of 556 adults (70.1% Black) was measured with a reflectance spectrophotometer to calculate an individual typology angle (°ITA). Participants reported self-perceived skin colour and erythemal sensitivity. There was a strong, positive monotonic correlation between self-reported and measured skin colour (Spearman ρ = 0.6438, P < 0.001), but only a weak correlation between self-reported erythemal sensitivity and measured skin colour (Spearman ρ = 0.2713, P < 0.001). Self-report biases in underestimation and overestimation of skin colour were evident. Many participants with 'dark brown' and 'black' skin had difficulty in classifying erythemal sensitivity. In Africa, self-reported skin colour could potentially be used in lieu of spectrophotometer measurements, but options for questions on sunburn and tanning require suitable adjustment. Our study provides evidence of range in °ITA values among residents in Africa and reinforces previous results that self-report may be reliable for determining skin colour, but not erythemal sensitivity, for dark skin individuals. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Efficacy of the combined use of a facial cleanser and moisturizers for the care of mild acne patients with sensitive skin.

PubMed

Isoda, Kenichi; Seki, Tsuyoshi; Inoue, Yosuke; Umeda, Koji; Nishizaka, Takahiro; Tanabe, Hisateru; Takagi, Yutaka; Ishida, Koichi; Mizutani, Hitoshi

2015-02-01

Acne is a common skin disease that involves the seborrheic area of the face and results from the obstruction of hair follicles followed by inflammation. Careful face washing helps to improve and prevent acne; however, intensive washing has a risk of inducing skin barrier impairment and dry skin, especially in sensitive skin. We hypothesized that skin care combining mild skin cleansing and intensive moisturizing ("combination skin care") may be effective in the care of acne in subjects with dry skin and/or sensitive skin. We developed a combination skin care with a weakly acidic foaming facial skin cleanser based on a mild detergent, an aqueous lotion with eucalyptus extract and a moisturizing gel containing pseudo-ceramide and eucalyptus extract. To optimize an ideal facial skin care system for mild acne on sensitive skin, we performed a 4-week clinical trial with 29 post-adolescent Japanese women with mild acne with dry and sensitive skin. The acne significantly decreased after this trial accompanied by the improvement of dry skin, a significantly increased endogenous ceramide level in the stratum corneum and an elongated alkyl chain length of the non-hydroxy acyl sphingosine type ceramide. No adverse events due to the test samples were observed. Based on diagnosis by a dermatologist, 97% of the subjects found the combination skin care to be "useful" or "slightly useful". Based on these findings, the combined use of a facial skin cleanser and moisturizers is safe and effective for the care of acne in post-adolescent Japanese women with sensitive skin. © 2014 Japanese Dermatological Association.

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

PubMed Central

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

Prevalence of potent skin sensitizers in oxidative hair dye products in Korea.

PubMed

Kim, Hyunji; Kim, Kisok

2016-09-01

The objective of the present study was to elucidate the prevalence of potent skin sensitizers in oxidative hair dye products manufactured by Korean domestic companies. A database on hair dye products made by domestic companies and selling in the Korean market in 2013 was used to obtain information on company name, brand name, quantity of production, and ingredients. The prevalence of substances categorized as potent skin sensitizers was calculated using the hair dye ingredient database, and the pattern of concomitant presence of hair dye ingredients was analyzed using network analysis software. A total of 19 potent skin sensitizers were identified from a database that included 99 hair dye products manufactured by Korean domestic companies. Among 19 potent skin sensitizers, the four most frequent were resorcinol, m-aminophenol, p-phenylenediamine (PPD), and p-aminophenol; these four skin-sensitizing ingredients were found in more than 50% of the products studied. Network analysis showed that resorcinol, m-aminophenol, and PPD existed together in many hair dye products. In 99 products examined, the average product contained 4.4 potent sensitizers, and 82% of the products contained four or more skin sensitizers. The present results demonstrate that oxidative hair dye products made by Korean domestic manufacturers contain various numbers and types of potent skin sensitizers. Furthermore, these results suggest that some hair dye products should be used with caution to prevent adverse effects on the skin, including allergic contact dermatitis.

[Sensitive skin: a complex syndrome].

PubMed

Escalas-Taberner, J; González-Guerra, E; Guerra-Tapia, A

2011-10-01

Epidemiologic studies indicate that ever larger numbers of people report having sensitive skin, for which a European prevalence of 50% is estimated. Sensitive skin is characterized by hyperreactivity, with manifestations varying in relation to many factors. The pathogenesis of this disorder is poorly understood, although studies point to a biophysical mechanism. Objective diagnosis of sensitive skin is difficult, as information comes mainly from the patient's report of symptoms in the absence of effective, strongly predictive tests because of great interindividual variability in skin sensitivity. Substances that trigger a reaction in hypersensitive skin also vary greatly. The impact of this syndrome on quality of life is considerable and patients often present psychiatric symptoms; therefore, dermatologists should explore this possibility when taking a patient's history. Patient cooperation and physician persistence are both essential for treating sensitive skin. Copyright © 2011 Elsevier España, S.L. y AEDV. All rights reserved.

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

PubMed

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.

Reflectance confocal microscopy for the evaluation of sensitive skin.

PubMed

Ma, Y-F; Yuan, C; Jiang, W-C; Wang, X-L; Humbert, P

2017-05-01

Nowadays, the diagnosis for sensitive skin relies on subjective assessment or on the combination of subjective and objective evaluation. No quantitative evaluation is available. It could be expected that confocal microscopy imaging could be of interest to better define the condition. Total 166 healthy female subjects were recruited in this study. Firstly, all subjects completed the sensitive questionnaire. Then, the cutaneous structures were measured by the reflectance confocal microscopy (RCM) on the face and fossa cubitalia. The lactic acid sting test was conducted finally. According to the results of self-perception sensitive skin questionnaire and lactic acid stinging test to evaluate facial skin sensitivity the both positive subjects were regarded as sensitive skin group and both negative group as healthy control group. The results of RCM indicating that the proportion of 'disarranged honeycomb pattern' and 'spongiform edema' in the sensitive group and healthy control group were statistically different (P < 0.05), respectively; The following report 'damaged dermal papilla rings' was not a distinctive pattern, with no significant statistical difference (P > 0.05). The epidermal thickness was 38.88 ± 6.81 μm, healthy control group was 40.31 ± 9.37 μm in, respectively, sensitive skin group and healthy control group, there was no significant statistical difference between the two groups (P > 0.05). The honeycomb structure depth of sensitive group was 20.57 ± 4.86 μm. It was for 23.27 ± 6.38 μm, healthy control group the difference being statistically different between the two groups (P < 0.05). Based on the RCM results, 'epidermal honeycomb structure' and 'spongiform edema' may be used as new skin signs of RCM evaluation of sensitive skin effectively. Indeed, sensitive skin honeycomb structure depth was thinner compared with healthy control group. Such a specific pattern has good clinical and monitoring value for the further exploration. RCM could provide new data and patterns for the evaluation of sensitive skin. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The sensitization potential of sunscreen after ablative fractional skin resurfacing using modified human repeated insult patch test.

PubMed

Boonchai, Waranya; Sathaworawong, Angkana; Wongpraparut, Chanisada; Wanitphakdeedecha, Rungsima

2015-10-01

Ablative fractional skin resurfacing has become popular and proven to be useful in treating scars, photoaging and wrinkles. Although post-inflammatory hyperpigmentation (PIH) is the most common complication especially in dark-skinned patients like Asian. Several modalities have been used to overcome the PIH. To determine the sensitization potential of sunscreen applied immediately after ablative fractional skin resurfacing. Sixty volunteers were recruited. Of these 30 subjects were from previous ablative fractional skin resurfacing study who applied broad-spectrum sunscreen containing anti-inflammatory agent starting on the first day after resurfacing and another 30 non-resurfacing subjects had applied the same sunscreen on the intact skin. All subjects were patch/photopatch tested for sensitization study by using modified human repeated insult patch test (HRIPT). There were significantly higher sensitization rate of UV-filter, octocrylene and the sunscreen in resurfacing group than in non-resurfacing group. Early application of sunscreen after ablative fractional skin resurfacing has increased the incidence of sensitization potential of sunscreen. The sunscreen is recommended to start using from D3 after fractional ablative skin resurfacing to ensure the complete recovery of skin barrier and minimize the risk of sensitization.

Severe facial dermatitis as a late complication of aesthetic rhinoplasty; a case report

PubMed Central

Rajabian, Mohammad Hossain; Sodaify, Manoochehr; Aghaei, Shahin

2004-01-01

Background Contact dermatitis, as a cutaneous complication after rhinoplasty, is of early onset, limited and transient. The cause of this dermatitis is irritant or allergic. Late onset skin complications are rare and non-inflammatory. Case presentation We are reporting an unexpected, severe allergic contact dermatitis of the face, in a young female, appearing one month following aesthetic rhinoplasty. She failed to respond to ordinary treatments for dermatitis. We did standard battery – including nitrofurazone, tincture of benzoin and hydrocortisone – patch test for the patient that showed sensitivity to benzoin and corticosteroid. Conclusions In summary we report a case of a severe allergic contact dermatitis of the face, in a 21-year-old girl who underwent corrective aesthetic rhinoplasty, appearing one month following surgical operation. We were unable to find a similar report in the medical literature. PMID:15056395

Development of a Perfusion Platform for Dynamic Cultivation of in vitro Skin Models.

PubMed

Strüver, Kay; Friess, Wolfgang; Hedtrich, Sarah

2017-01-01

Reconstructed skin models are suitable test systems for toxicity testing and for basic investigations on (patho-)physiological aspects of human skin. Reconstructed human skin, however, has clear limitations such as the lack of immune cells and a significantly weaker skin barrier function compared to native human skin. Potential reasons for the latter might be the lack of mechanical forces during skin model cultivation which is performed classically in static well-plate setups. Mechanical forces and shear stress have a major impact on tissue formation and, hence, tissue engineering. In the present work, a perfusion platform was developed allowing dynamic cultivation of in vitro skin models. The platform was designed to cultivate reconstructed skin at the air-liquid interface with a laminar and continuous medium flow below the dermis equivalent. Histological investigations confirmed the formation of a significantly thicker stratum corneum compared to the control cultivated under static conditions. Moreover, the skin differentiation markers involucrin and filaggrin as well as the tight junction proteins claudin 1 and occludin showed increased expression in the dynamically cultured skin models. Unexpectedly, despite improved differentiation, the skin barrier function of the dynamically cultivated skin models was not enhanced compared with the skin models cultivated under static conditions. © 2017 S. Karger AG, Basel.

Analysis of Publically Available Skin Sensitization Data from REACH Registrations 2008–2014

PubMed Central

Luechtefeld, Thomas; Maertens, Alexandra; Russo, Daniel P.; Rovida, Costanza; Zhu, Hao; Hartung, Thomas

2017-01-01

Summary The public data on skin sensitization from REACH registrations already included 19,111 studies on skin sensitization in December 2014, making it the largest repository of such data so far (1,470 substances with mouse LLNA, 2,787 with GPMT, 762 with both in vivo and in vitro and 139 with only in vitro data). 21% were classified as sensitizers. The extracted skin sensitization data was analyzed to identify relationships in skin sensitization guidelines, visualize structural relationships of sensitizers, and build models to predict sensitization. A chemical with molecular weight > 500 Da is generally considered non-sensitizing owing to low bioavailability, but 49 sensitizing chemicals with a molecular weight > 500 Da were found. A chemical similarity map was produced using PubChem’s 2D Tanimoto similarity metric and Gephi force layout visualization. Nine clusters of chemicals were identified by Blondel’s module recognition algorithm revealing wide module-dependent variation. Approximately 31% of mapped chemicals are Michael’s acceptors but alone this does not imply skin sensitization. A simple sensitization model using molecular weight and five ToxTree structural alerts showed a balanced accuracy of 65.8% (specificity 80.4%, sensitivity 51.4%), demonstrating that structural alerts have information value. A simple variant of k-nearest neighbors outperformed the ToxTree approach even at 75% similarity threshold (82% balanced accuracy at 0.95 threshold). At higher thresholds, the balanced accuracy increased. Lower similarity thresholds decrease sensitivity faster than specificity. This analysis scopes the landscape of chemical skin sensitization, demonstrating the value of large public datasets for health hazard prediction. PMID:26863411

Use of genotoxicity information in the development of integrated testing strategies (ITS) for skin sensitization.

PubMed

Mekenyan, Ovanes; Patlewicz, Grace; Dimitrova, Gergana; Kuseva, Chanita; Todorov, Milen; Stoeva, Stoyanka; Kotov, Stefan; Donner, E Maria

2010-10-18

Skin sensitization is an end point of concern for various legislation in the EU, including the seventh Amendment to the Cosmetics Directive and Registration Evaluation, Authorisation and Restriction of Chemicals (REACH). Since animal testing is a last resort for REACH or banned (from 2013 onward) for the Cosmetics Directive, the use of intelligent/integrated testing strategies (ITS) as an efficient means of gathering necessary information from alternative sources (e.g., in vitro, (Q)SARs, etc.) is gaining widespread interest. Previous studies have explored correlations between mutagenicity data and skin sensitization data as a means of exploiting information from surrogate end points. The work here compares the underlying chemical mechanisms for mutagenicity and skin sensitization in an effort to evaluate the role mutagenicity information can play as a predictor of skin sensitization potential. The Tissue Metabolism Simulator (TIMES) hybrid expert system was used to compare chemical mechanisms of both end points since it houses a comprehensive set of established structure-activity relationships for both skin sensitization and mutagenicity. The evaluation demonstrated that there is a great deal of overlap between skin sensitization and mutagenicity structural alerts and their underlying chemical mechanisms. The similarities and differences in chemical mechanisms are discussed in light of available experimental data. A number of new alerts for mutagenicity were also postulated for inclusion into TIMES. The results presented show that mutagenicity information can provide useful insights on skin sensitization potential as part of an ITS and should be considered prior to any in vivo skin sensitization testing being initiated.

Multivariate Models for Prediction of Human Skin Sensitization Hazard

PubMed Central

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

2016-01-01

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

Immunosuppressive Environment in Basal Cell Carcinoma: The Role of Regulatory T Cells.

PubMed

Omland, Silje H; Nielsen, Patricia S; Gjerdrum, Lise M R; Gniadecki, Robert

2016-11-02

Interaction between tumour survival tactics and anti-tumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed by immunohistochemistry followed by automated image analysis in facial BCC, peritumoural skin and normal, buttock skin. Quantitative real-time PCR (qRT-PCR) was performed for FOXP3 and cytokines involved in T-reg attraction and T-cell activation. T-regs comprised 45% of CD4-cells surrounding BCC. FOXP3 was highly expressed in BCC, but absent in buttock skin. Unexpectedly, expression of FOXP3 was increased in peritumoural skin, with the FOXP3/CD3 fractions exceeding those of BCC (p?=?0.0065). Transforming growth factor (TGF)-? and T-reg chemokine expression was increased in BCC and peritumoural skin, but not in buttock skin, with expression levels correlating with FOXP3. T-regs are abundantly present both in BCC and in peritumoural skin, mediating an immunosuppressed microenvironment permissive for skin cancer.

Integrated Decision Strategies for Skin Sensitization Hazard

EPA Science Inventory

One of the top priorities of the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) is the identification and evaluation of non-animal alternatives for skin sensitization testing. Although skin sensitization is a complex process, the key biologi...

Enhancement of Skin Penetration of Hydrophilic and Lipophilic Compounds by pH-sensitive Liposomes.

PubMed

Tokudome, Yoshihiro; Nakamura, Kaoru; Itaya, Yurina; Hashimoto, Fumie

2015-01-01

Enhance skin penetration of hydrophilic and lipophilic compounds using liposomes that are responsible to the pH of the skin surface. pH-sensitive liposomes were prepared by a thin layer and freeze-thaw method with dioleoyl phosphatidyl ethanolamine and cholesteryl hemisuccinate. Liposomal fusion with stratum corneum lipid liposomes was measured using fluorescence resonance energy transfer. Particle diameter and zeta potential of the liposomes after fusion were measured by dynamic light scattering and electrophoresis. Under neutral pH conditions, the diameter of the pH-sensitive liposomes was 130 nm and their zeta potential was -70 mV. In weakly acidic conditions, the diameter was larger than 3,000 nm and the zeta potential was -50 mV. In contrast, the particle diameter and the zeta potential of the non-pH-sensitive liposomes remained constant under various pH conditions. A skin penetration study was performed on hairless mice skin using vertical diffusion cells, showing that the fusion ability of pH-sensitive liposomes was higher than that of non-pH-sensitive liposomes. In the skin penetration study was carried out using hydrophilic (calcein) and lipophilic (N-(7-nitrobenz- 2-oxa-1,3-diazol-4yl)-PE) (NBD-PE) model compounds which were applied to the skin with pH-sensitive liposomes as carrier. The fluorescent compounds contained within the pH-sensitive liposomes permeated the skin more effectively than those within non-pH-sensitive liposomes, and this ability was further enhanced with the lipophilic compound. These studies suggest that pH-sensitive liposomes have potential as an important tool for delivery of compounds into the skin.

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

PubMed Central

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

Multivariate Models for Prediction of Human Skin Sensitization ...

EPA Pesticide Factsheets

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

Skin sensitization induced Langerhans' cell mobilization: variable requirements for tumour necrosis factor-α.

PubMed

Eaton, Laura H; Roberts, Ruth A; Kimber, Ian; Dearman, Rebecca J; Metryka, Aleksandra

2015-01-01

Upon antigen/allergen recognition, epidermal Langerhans' cells (LC) are mobilized and migrate to the local lymph node where they play a major role in initiating or regulating immune responses. It had been proposed that all chemical allergens induce LC migration via common cytokine signals delivered by TNF-α and IL-1β. Here the dependence of LC migration on TNF-α following treatment of mice with various chemical allergens has been investigated. It was found that under standard conditions the allergens oxazolone, paraphenylene diamine, and trimellitic anhydride, in addition to the skin irritant sodium lauryl sulfate, were unable to trigger LC mobilization in the absence of TNF-α signalling. In contrast, two members of the dinitrohalobenezene family (2,4-dinitrochlorobenzene [DNCB] and 2,4-dinitrofluorobenzene [DNFB]) promoted LC migration independently of TNF-R2 (the sole TNF-α receptor expressed by LC) and TNF-α although the presence of IL-1β was still required. However, increasing doses of oxazolone overcame the requirement of TNF-α for LC mobilization, whereas lower doses of DNCB were still able to induce LC migration in a TNF-α-independent manner. These novel findings demonstrate unexpected heterogeneity among chemical allergens and furthermore that LC can be induced to migrate from the epidermis via different mechanisms that are either dependent or independent of TNF-α. Although the exact mechanisms with regard to the signals that activate LC have yet to be elucidated, these differences may translate into functional speciation that will likely impact on the extent and quality of allergic sensitization. © 2014 John Wiley & Sons Ltd.

Skin sensitivity and skin microbiota: Is there a link?

PubMed

Seite, Sophie; Misery, Laurent

2018-05-21

Sensitive skin is defined by the occurrence of unpleasant sensations, accompanied or not by erythema, in response to stimuli which normally should not provoke such sensations and that cannot be linked to skin disease. Even if its pathophysiology is not completely known, hyper-reactivity of the cutaneous nervous system associated with an abnormal skin barrier has been hypothesized as a primary culprit including more recently a role of the cutaneous microbiota. The objective of this short review is to discuss the relationship between the skin microbiota, skin sensitivity and the skin barrier function. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

EPA Releases Draft Policy to Reduce Animal Testing for Skin Sensitization

EPA Pesticide Factsheets

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.

The Measurement of Stress in Nonvisual Travel.

ERIC Educational Resources Information Center

Ponchillia, Paul E.; And Others

1984-01-01

Measurement of stress in nonvisual travel was attempted with both an electromyograph and a galvonic skin response unit in four travel situations. Results revealed significantly greater stress response when unexpected contact with objects was made than with expected contacts and street crossings. Instructors' intervention also increased stress.…

Ionizing Radiation Selectively Reduces Skin Regulatory T Cells and Alters Immune Function

PubMed Central

Zhou, Yu; Ni, Houping; Balint, Klara; Sanzari, Jenine K.; Dentchev, Tzvete; Diffenderfer, Eric S.; Wilson, Jolaine M.; Cengel, Keith A.; Weissman, Drew

2014-01-01

The skin serves multiple functions that are critical for life. The protection from pathogens is achieved by a complicated interaction between aggressive effectors and controlling functions that limit damage. Inhomogeneous radiation with limited penetration is used in certain types of therapeutics and is experienced with exposure to solar particle events outside the protection of the Earth’s magnetic field. This study explores the effect of ionizing radiation on skin immune function. We demonstrate that radiation, both homogeneous and inhomogeneous, induces inflammation with resultant specific loss of regulatory T cells from the skin. This results in a hyper-responsive state with increased delayed type hypersensitivity in vivo and CD4+ T cell proliferation in vitro. The effects of inhomogeneous radiation to the skin of astronauts or as part of a therapeutic approach could result in an unexpected enhancement in skin immune function. The effects of this need to be considered in the design of radiation therapy protocols and in the development of countermeasures for extended space travel. PMID:24959865

Discrimination of skin sensitizers from non-sensitizers by interleukin-1α and interleukin-6 production on cultured human keratinocytes.

PubMed

Jung, Daun; Che, Jeong-Hwan; Lim, Kyung-Min; Chun, Young-Jin; Heo, Yong; Seok, Seung Hyeok

2016-09-01

In vitro testing methods for classifying sensitizers could be valuable alternatives to in vivo sensitization testing using animal models, such as the murine local lymph node assay (LLNA) and the guinea pig maximization test (GMT), but there remains a need for in vitro methods that are more accurate and simpler to distinguish skin sensitizers from non-sensitizers. Thus, the aim of our study was to establish an in vitro assay as a screening tool for detecting skin sensitizers using the human keratinocyte cell line, HaCaT. HaCaT cells were exposed to 16 relevant skin sensitizers and 6 skin non-sensitizers. The highest dose used was the dose causing 75% cell viability (CV75) that we determined by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The levels of extracellular production of interleukin-1α (IL-1α) and IL-6 were measured. The sensitivity of IL-1α was 63%, specificity was 83% and accuracy was 68%. In the case of IL-6, sensitivity: 69%, specificity: 83% and accuracy: 73%. Thus, this study suggests that measuring extracellular production of pro-inflammatory cytokines IL-1α and IL-6 by human HaCaT cells may potentially classify skin sensitizers from non-sensitizers. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Multivariate Models for Prediction of Skin Sensitization Hazard in Humans

EPA Science Inventory

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...

Multivariate models for skin sensitization hazard and potency

EPA Science Inventory

One of the top priorities being addressed by ICCVAM is the identification and validation of non-animal alternatives for skin sensitization testing. Although skin sensitization is a complex process, the key biological events have been well characterized in an adverse outcome pathw...

Multivariate Models for Prediction of Human Skin Sensitization Hazard

EPA Science Inventory

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

Surface contamination to UV-curable acrylates in the furniture and parquet industry.

PubMed

Surakka, J; Lindh, T; Rosén, G; Fischer, T

2001-03-01

Surface contamination to ultraviolet radiation curable coatings (UV coatings), used increasingly in the parquet and furniture industry, is a matter of concern as a source for skin contamination. UV coatings contain chemically and biologically reactive acrylates, well known as skin contact irritants and sensitizers. Surface contamination may spread secondarily to equipment and other unexpected areas even outside the workplace. Yet, studies concerning this type of contamination are lacking due to lack of suitable sampling methods. Surface contamination of the work environment with risk for skin exposure to UV coating was measured employing a quantitative adhesive tape sampling method developed for this purpose. A pilot study was first performed at three workplaces to evaluate the contamination. In the main study, we wanted to locate and identify in detail the surface contamination of areas where problems exist, and to determine the extent of the problem. Measurements were performed at seven workplaces on two separate workdays (round 1 and 2) within a six-month period. Samples were collected from the workplaces based on the video monitoring of skin contact frequency with the surfaces and categorized into three groups to analyze risk. The pilot study indicated that surface contamination to TPGDA containing UV coatings was common, found in 76 percent of the surfaces, and varied with a maximum of 909 microg TPGDA 10 cm(-2) sampling area. In the main study TPGDA was found in 153 out of 196 collected samples (78.1%); for round one 78.1 percent (82 out of 105 samples) and for round two 78.0 percent (71 out of 91 samples). The average TPGDA mass on positive surface samples was on the first round 2,247 +/- 7,462 microg, and on the second round 2,960 +/- 4,590 microg. We conclude that surface contamination to uncured UV coatings at UV-curing lines is common and this involves a risk for harmful, unintentional skin exposure to acrylates.

Skylab

NASA Image and Video Library

1973-05-01

The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the the station uninhabitable, threatening foods, medicines, films, and experiments. This image shows the sun-ravaged skin of the Orbital Workshop, bared by the missing heat shield, with blister scars and tarnish from temperatures that reached 300 degrees F. The rectangular opening at the upper center is the scientific airlock through which the parasol to protect the workshop from sun's rays was later deployed. This view was taken during a fly-around inspection by the Skylab-2 crew. The Marshall Space Flight Center had a major role in developing the procedures to repair the damaged Skylab.

The skin sensitization potential of four alkylalkanolamines.

PubMed

Leung, H W; Blaszcak, D L

1998-04-01

The skin sensitization potential of 4 alkylalkanolamines (N-methylethanolamine, N,N-dimethylethanolamine, N-methyldiethanolamine and N,N-diethylethanolamine), was evaluated in a guinea pig maximation procedure by the method of Magnusson and Kligman. While all 4 alkylalkanolamines tested were irritating to the guinea pig skin, only N-methylethanolamine showed potential to induce allergic contact dermatitis. None of the remaining 3 alkylalkanolamines exhibited clear skin responses suggestive of sensitization.

Experimental studies on the nature of sensitive skin.

PubMed

Kligman, A M; Sadiq, Iqbal; Zhen, Yaxian; Crosby, Marilyn

2006-11-01

In the USA, Europe and Japan 40 to 50% of women report that they have sensitive skin, defined as abnormal sub-clinical sensory responses to drugs, cosmetics and toiletries in the absence of visible signs of irritation. Itching, burning, stinging and tightness are the commonest complaints, which mainly afflict women. Manufacturers of skin care products have made available a large variety of products which are designed for persons with sensitive skin. Such products are not required by regulatory agencies to submit evidence of safety and efficacy, allowing marketers to make claims that are often exaggerated, irrational and even preposterous. The consumer with self-assessed sensitive skin has no way of judging which products are likely to be most beneficial and least harmful. The marketplace is awash with products for which there is no evidence that the rosy claims have been substantiated by appropriate testing procedures. There is no internationally accepted consensus regarding the criteria which define sensitive skin. Many papers have been published in the last 15 years, mainly originating from industry, which express widely differing views regarding what constitutes sensitive skin. For some, any adverse reaction to a product topically applied to sensitive skin, including breakouts, redness, scaling etc., a panoply of adverse reactions which is virtually meaningless. Others include environmental factors as causative, including cold, dry wind, heat and high humidity, solar radiation, etc., which add to the manifest complexities of the subject. This is the first paper in a series which provides a comprehensive review of the subject, emphasizing the all too many controversies and confusions arising from the lack of a consensus regarding the identification, classification, epidemiology, prevalence and pathogenesis of sensitive skin. Sensitive skin is a biologic reality and not a psychological, fashionable fantasy on the part of impressionable women. There is an urgent necessity to establish rigorous methodologies for estimating the quality and severity of sensitive skin, a heterogeneous condition involving multi-factorial factors. Subsequent papers in this series will describe in detail the experimental approach our group has used to bring some clarity and credibility to this querulous, but important subject.

Machine Learning Approaches for Predicting Human Skin Sensitization Hazard

EPA Science Inventory

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

Assessment of hypoallergenicity of ten skincare products.

PubMed

Brandt, Staci; Lio, Peter

2014-03-01

Sensitive skin is a common skin complaint frequently associated with skin diseases or adverse reactions to cosmetic products. Manufacturers have produced numerous products targeted for patients with sensitive skin and frequently label these products as being hypoallergenic. This term implies that the product may be less likely to cause an allergic reaction and be better suited for those with sensitive skin. However, there is no federal regulatory definition of this term and products may not have clinical support of their claim. Patch testing ingredients is frequently done to identify potential irritants; however, patch-testing product formulations may provide more realistic expectations about potential skin sensitivity and help support claims of hypoallergenicity. Ten skincare products were assessed for their sensitizing potential and hypoallergenicity in 14 repeat insult patch test clinical studies, involving over 2,000 subjects. In these studies, the products were deemed to be hypoallergenic if there was no evidence of sensitization or allergic reactions. The results from these trials demonstrated that all ten products were well tolerated, showed no sensitization or allergic reactions, and support claims of hypoallergenicity.

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

PubMed

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.

Tailoring force sensitivity and selectivity by microstructure engineering of multidirectional electronic skins

NASA Astrophysics Data System (ADS)

Park, Jonghwa; Kim, Jinyoung; Hong, Jaehyung; Lee, Hochan; Lee, Youngoh; Cho, Seungse; Kim, Sung-Woo; Kim, Jae Joon; Kim, Sung Youb; Ko, Hyunhyub

2018-04-01

Electronic skins (e-skins) with high sensitivity to multidirectional mechanical stimuli are crucial for healthcare monitoring devices, robotics, and wearable sensors. In this study, we present piezoresistive e-skins with tunable force sensitivity and selectivity to multidirectional forces through the engineered microstructure geometries (i.e., dome, pyramid, and pillar). Depending on the microstructure geometry, distinct variations in contact area and localized stress distribution are observed under different mechanical forces (i.e., normal, shear, stretching, and bending), which critically affect the force sensitivity, selectivity, response/relaxation time, and mechanical stability of e-skins. Microdome structures present the best force sensitivities for normal, tensile, and bending stresses. In particular, microdome structures exhibit extremely high pressure sensitivities over broad pressure ranges (47,062 kPa-1 in the range of <1 kPa, 90,657 kPa-1 in the range of 1-10 kPa, and 30,214 kPa-1 in the range of 10-26 kPa). On the other hand, for shear stress, micropillar structures exhibit the highest sensitivity. As proof-of-concept applications in healthcare monitoring devices, we show that our e-skins can precisely monitor acoustic waves, breathing, and human artery/carotid pulse pressures. Unveiling the relationship between the microstructure geometry of e-skins and their sensing capability would provide a platform for future development of high-performance microstructured e-skins.

Progress on Reconstructed Human Skin Models for Allergy Research and Identifying Contact Sensitizers.

PubMed

Rodrigues Neves, Charlotte; Gibbs, Susan

2018-06-23

Contact with the skin is inevitable or desirable for daily life products such as cosmetics, hair dyes, perfumes, drugs, household products, and industrial and agricultural products. Whereas the majority of these products are harmless, a number can become metabolized and/or activate the immunological defense via innate and adaptive mechanisms resulting in sensitization and allergic contact dermatitis upon following exposures to the same substance. Therefore, strict safety (hazard) assessment of actives and ingredients in products and drugs applied to the skin is essential to determine I) whether the chemical is a potential sensitizer and if so II) what is the safe concentration for human exposure to prevent sensitization from occurring. Ex vivo skin is a valuable model for skin penetration studies but due to logistical and viability limitations the development of in vitro alternatives is required. The aim of this review is to give a clear overview of the organotypic in vitro skin models (reconstructed human epidermis, reconstructed human skin, immune competent skin models incorporating Langerhans Cells and T-cells, skin-on-chip) that are currently commercially available or which are being used in a laboratory research setting for hazard assessment of potential sensitizers and for investigating the mechanisms (sensitization key events 1-4) related to allergic contact dermatitis. The limitations of the models, their current applications, and their future potential in replacing animals in allergy-related science are discussed.

A strong and stretchable self-healing film with self-activated pressure sensitivity for potential artificial skin applications

PubMed Central

Hou, Chengyi; Huang, Tao; Wang, Hongzhi; Yu, Hao; Zhang, Qinghong; Li, Yaogang

2013-01-01

Artificial skin, which mimics the functions of natural skin, will be very important in the future for robots used by humans in daily life. However, combining skin's pressure sensitivity and mechanical self-healing properties in a man-made material remains a challenging task. Here, we show that graphene and polymers can be integrated into a thin film which mimics both the mechanical self-healing and pressure sensitivity behavior of natural skin without any external power supply. Its ultimate strain and tensile strength are even two and ten times larger than the corresponding values of human skin, respectively. It also demonstrates highly stable sensitivity to a very light touch (0.02 kPa), even in bending or stretching states. PMID:24190511

Evaluating a Skin Sensitization Model and Examining Common Assumptions of Skin Sensitizers (QSAR conference)

EPA Science Inventory

Skin sensitization is an adverse outcome that has been well studied over many decades. Knowledge of the mechanism of action was recently summarized using the Adverse Outcome Pathway (AOP) framework as part of the OECD work programme (OECD, 2012). Currently there is a strong focus...

A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

USDA-ARS?s Scientific Manuscript database

Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization integrated approaches combining different chemical, biological and in silico methods are recommended to r...

Prediction of Skin Sensitization with a Particle Swarm Optimized Support Vector Machine

PubMed Central

Yuan, Hua; Huang, Jianping; Cao, Chenzhong

2009-01-01

Skin sensitization is the most commonly reported occupational illness, causing much suffering to a wide range of people. Identification and labeling of environmental allergens is urgently required to protect people from skin sensitization. The guinea pig maximization test (GPMT) and murine local lymph node assay (LLNA) are the two most important in vivo models for identification of skin sensitizers. In order to reduce the number of animal tests, quantitative structure-activity relationships (QSARs) are strongly encouraged in the assessment of skin sensitization of chemicals. This paper has investigated the skin sensitization potential of 162 compounds with LLNA results and 92 compounds with GPMT results using a support vector machine. A particle swarm optimization algorithm was implemented for feature selection from a large number of molecular descriptors calculated by Dragon. For the LLNA data set, the classification accuracies are 95.37% and 88.89% for the training and the test sets, respectively. For the GPMT data set, the classification accuracies are 91.80% and 90.32% for the training and the test sets, respectively. The classification performances were greatly improved compared to those reported in the literature, indicating that the support vector machine optimized by particle swarm in this paper is competent for the identification of skin sensitizers. PMID:19742136

STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS

PubMed Central

Landsteiner, K.; Chase, M. W.

1939-01-01

Experiments are described on the latency period in sensitization to poison ivy and on the time necessary for the agent to remain in contact with the skin. The chief matter of investigation concerned the manner in which the whole skin becomes sensitive following treatment at a particular site, and especially whether this is effected by way of the epidermis. Two methods were used to interrupt the continuity of the skin, one by cutting through both skin and the underlying thin muscular layer, the other by removing a strip of skin so as to spare the skin muscle. These procedures led to different results when poison ivy extract was applied to the areas thus isolated. In the first case, sensitization was mostly prevented, whereas with the second method generalized hypersensitiveness occurred almost uniformly. An explanation is to be found in the severance of the lymph vessels lying on the surface of the muscular layer, pointing to the necessity of a free lymph passage. On the other hand the experiments prove that general sensitization is not dependent upon maintaining the integrity of the skin around a treated area. An inhibition of sensitization by incisions extending through the panniculus carnosus was seen to some extent in anaphylactic sensitization with protein antigens, namely when sufficiently small amounts were employed. PMID:19870876

State of the art in non-animal approaches for skin sensitization testing: from individual test methods towards testing strategies.

PubMed

Ezendam, Janine; Braakhuis, Hedwig M; Vandebriel, Rob J

2016-12-01

The hazard assessment of skin sensitizers relies mainly on animal testing, but much progress is made in the development, validation and regulatory acceptance and implementation of non-animal predictive approaches. In this review, we provide an update on the available computational tools and animal-free test methods for the prediction of skin sensitization hazard. These individual test methods address mostly one mechanistic step of the process of skin sensitization induction. The adverse outcome pathway (AOP) for skin sensitization describes the key events (KEs) that lead to skin sensitization. In our review, we have clustered the available test methods according to the KE they inform: the molecular initiating event (MIE/KE1)-protein binding, KE2-keratinocyte activation, KE3-dendritic cell activation and KE4-T cell activation and proliferation. In recent years, most progress has been made in the development and validation of in vitro assays that address KE2 and KE3. No standardized in vitro assays for T cell activation are available; thus, KE4 cannot be measured in vitro. Three non-animal test methods, addressing either the MIE, KE2 or KE3, are accepted as OECD test guidelines, and this has accelerated the development of integrated or defined approaches for testing and assessment (e.g. testing strategies). The majority of these approaches are mechanism-based, since they combine results from multiple test methods and/or computational tools that address different KEs of the AOP to estimate skin sensitization potential and sometimes potency. Other approaches are based on statistical tools. Until now, eleven different testing strategies have been published, the majority using the same individual information sources. Our review shows that some of the defined approaches to testing and assessment are able to accurately predict skin sensitization hazard, sometimes even more accurate than the currently used animal test. A few defined approaches are developed to provide an estimate of the potency sub-category of a skin sensitizer as well, but these approaches need further independent evaluation with a new dataset of chemicals. To conclude, this update shows that the field of non-animal approaches for skin sensitization has evolved greatly in recent years and that it is possible to predict skin sensitization hazard without animal testing.

Self-estimation or phototest measurement of skin UV sensitivity and its association with people's attitudes towards sun exposure.

PubMed

Falk, Magnus

2014-02-01

Fitzpatrick's classification is the most common way of assessing skin UV sensitivity. The study aim was to investigate how self-estimated and actual UV sensitivity, as measured by phototest, are associated with attitudes towards sunbathing and the propensity to increase sun protection, as well as the correlation between self-estimated and actual UV sensitivity. A total of 166 primary healthcare patients filled-out a questionnaire investigating attitudes towards sunbathing and the propensity to increase sun protection. They reported their skin type according to Fitzpatrick, and a UV sensitivity phototest was performed. Self-rated low UV sensitivity (skin type III-VI) was associated with a more positive attitude towards sunbathing and a lower propensity to increase sun protection, compared to high UV sensitivity. The correlation between the two methods was weak. The findings might indicate that individuals with a perceived low but in reality high UV sensitivity do not seek adequate sun protection with regard to skin cancer risk. Furthermore, the poor correlation between self-reported and actual UV sensitivity, measured by phototest, makes the clinical use of Fitzpatrick's classification questionable.

Cutaneous exposure to clinically-relevant pigeon pea (Cajanus cajan) proteins promote TH2-dependent sensitization and IgE-mediated anaphylaxis in Balb/c mice.

PubMed

Kumar Gupta, Rinkesh; Kumar, Sandeep; Gupta, Kriti; Sharma, Akanksha; Roy, Ruchi; Kumar Verma, Alok; Chaudhari, Bhushan P; Das, Mukul; Ahmad Ansari, Irfan; Dwivedi, Premendra D

2016-11-01

Epicutaneous (EC) sensitization to food allergens may occur when the skin has been lightly damaged. The study here tested whether cutaneous exposure to pigeon pea protein(s) may cause allergic sensitization. BALB/c mice were either orally gavaged or epicutaneously sensitized by repeated application of pigeon pea crude protein extract (CPE) on undamaged areas of skin without any adjuvant; afterwards, both groups were orally challenged with the pigeon pea CPE. Anaphylactic symptoms along with measures of body temperature, MCPT-1, TSLP, pigeon pea-specific IgE and IgG 1 , myeloperoxidase (MPO) activity, T H 2 cytokines, T H 2 transcription factors (TFs) and filaggrin expression were determined. Mast cell staining, eosinophil levels and histopathological analysis of the skin and intestines were also performed. In the epicutaneously-sensitized mice, elevated levels of specific IgE and IgG 1 , as well as of MCPT-1, TSLP, T H 2 cytokines and TFs, higher anaphylactic scores and histological changes in the skin and intestine were indicative of sensitization ability via both routes in the pigeon pea CPE-treated hosts. Elevated levels of mast cells were observed in both the skin and intestine; increased levels of eosinophils and MPO activity were noted only in the skin. Decreased levels of filaggrin in skin may have played a key role in the skin barrier dysfunction, increasing the chances of sensitization. Therefore, the experimental data support the hypothesis that in addition to oral exposure, skin exposure to food allergens can promote T H 2-dependent sensitization, IgE-mediated anaphylaxis and intestinal changes after oral challenge. Based on this, an avoidance of cutaneous exposures to allergens might prevent development of food anaphylaxis.

Sensitive skin: review of an ascending concept*

PubMed Central

Duarte, Ida; Silveira, Jéssica Eleonora P. S.; Hafner, Mariana de Figueiredo Silva; Toyota, Raquel; Pedroso, Debora Midori M.

2017-01-01

Sensitive skin is a condition characterized by stinging, burning and itching sensations. The diagnosis, pathophysiology and treatment of sensitive skin are still under discussion. In the last years, studies on its epidemiology have been performed, showing a high prevalence and impact on quality of life. Brazilian population was also considered in these studies. Cosmetics, climate changes and skin barrier impairment are the main factors that contribute for skin hyperreactivity. New studies are trying to bring new knowledge about the theme. This review will describe data on epidemiology, triggering factors, pathophysiology, diagnosis and treatment. PMID:28954102

THE SEDIMENTATION PROPERTIES OF THE SKIN-SENSITIZING ANTIBODIES OF RAGWEED-SENSITIVE PATIENTS

PubMed Central

Andersen, Burton R.; Vannier, Wilton E.

1964-01-01

The sedimentation coefficients of the skin-sensitizing antibodies to ragweed were evaluated by the moving partition cell method and the sucrose density gradient method. The most reliable results were obtained by sucrose density gradient ultracentrifugation which showed that the major portion of skin-sensitizing antibodies to ragweed sediment with an average value of 7.7S (7.4 to 7.9S). This is about one S unit faster than γ-globulins (6.8S). The data from the moving partition cell method are in agreement with these results. Our studies failed to demonstrate heterogeneity of the skin-sensitizing antibodies with regard to sedimentation rate. PMID:14194391

Prediction error and somatosensory insula activation in women recovered from anorexia nervosa

PubMed Central

Frank, Guido K.W.; Collier, Shaleise; Shott, Megan E.; O’Reilly, Randall C.

2016-01-01

Background Previous research in patients with anorexia nervosa showed heightened brain response during a taste reward conditioning task and heightened sensitivity to rewarding and punishing stimuli. Here we tested the hypothesis that individuals recovered from anorexia nervosa would also experience greater brain activation during this task as well as higher sensitivity to salient stimuli than controls. Methods Women recovered from restricting-type anorexia nervosa and healthy control women underwent fMRI during application of a prediction error taste reward learning paradigm. Results Twenty-four women recovered from anorexia nervosa (mean age 30.3 ± 8.1 yr) and 24 control women (mean age 27.4 ± 6.3 yr) took part in this study. The recovered anorexia nervosa group showed greater left posterior insula activation for the prediction error model analysis than the control group (family-wise error– and small volume–corrected p < 0.05). A group × condition analysis found greater posterior insula response in women recovered from anorexia nervosa than controls for unexpected stimulus omission, but not for unexpected receipt. Sensitivity to punishment was elevated in women recovered from anorexia nervosa. Limitations This was a cross-sectional study, and the sample size was modest. Conclusion Anorexia nervosa after recovery is associated with heightened prediction error–related brain response in the posterior insula as well as greater response to unexpected reward stimulus omission. This finding, together with behaviourally increased sensitivity to punishment, could indicate that individuals recovered from anorexia nervosa are particularly responsive to punishment. The posterior insula processes somatosensory stimuli, including unexpected bodily states, and greater response could indicate altered perception or integration of unexpected or maybe unwanted bodily feelings. Whether those findings develop during the ill state or whether they are biological traits requires further study. PMID:26836623

Prediction error and somatosensory insula activation in women recovered from anorexia nervosa.

PubMed

Frank, Guido K W; Collier, Shaleise; Shott, Megan E; O'Reilly, Randall C

2016-08-01

Previous research in patients with anorexia nervosa showed heightened brain response during a taste reward conditioning task and heightened sensitivity to rewarding and punishing stimuli. Here we tested the hypothesis that individuals recovered from anorexia nervosa would also experience greater brain activation during this task as well as higher sensitivity to salient stimuli than controls. Women recovered from restricting-type anorexia nervosa and healthy control women underwent fMRI during application of a prediction error taste reward learning paradigm. Twenty-four women recovered from anorexia nervosa (mean age 30.3 ± 8.1 yr) and 24 control women (mean age 27.4 ± 6.3 yr) took part in this study. The recovered anorexia nervosa group showed greater left posterior insula activation for the prediction error model analysis than the control group (family-wise error- and small volume-corrected p < 0.05). A group × condition analysis found greater posterior insula response in women recovered from anorexia nervosa than controls for unexpected stimulus omission, but not for unexpected receipt. Sensitivity to punishment was elevated in women recovered from anorexia nervosa. This was a cross-sectional study, and the sample size was modest. Anorexia nervosa after recovery is associated with heightened prediction error-related brain response in the posterior insula as well as greater response to unexpected reward stimulus omission. This finding, together with behaviourally increased sensitivity to punishment, could indicate that individuals recovered from anorexia nervosa are particularly responsive to punishment. The posterior insula processes somatosensory stimuli, including unexpected bodily states, and greater response could indicate altered perception or integration of unexpected or maybe unwanted bodily feelings. Whether those findings develop during the ill state or whether they are biological traits requires further study.

Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

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

Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina

2012-11-01

Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here wemore » examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.« less

Community structure analysis of rejection sensitive personality profiles: A common neural response to social evaluative threat?

PubMed

Kortink, Elise D; Weeda, Wouter D; Crowley, Michael J; Gunther Moor, Bregtje; van der Molen, Melle J W

2018-06-01

Monitoring social threat is essential for maintaining healthy social relationships, and recent studies suggest a neural alarm system that governs our response to social rejection. Frontal-midline theta (4-8 Hz) oscillatory power might act as a neural correlate of this system by being sensitive to unexpected social rejection. Here, we examined whether frontal-midline theta is modulated by individual differences in personality constructs sensitive to social disconnection. In addition, we examined the sensitivity of feedback-related brain potentials (i.e., the feedback-related negativity and P3) to social feedback. Sixty-five undergraduate female participants (mean age = 19.69 years) participated in the Social Judgment Paradigm, a fictitious peer-evaluation task in which participants provided expectancies about being liked/disliked by peer strangers. Thereafter, they received feedback signaling social acceptance/rejection. A community structure analysis was employed to delineate personality profiles in our data. Results provided evidence of two subgroups: one group scored high on attachment-related anxiety and fear of negative evaluation, whereas the other group scored high on attachment-related avoidance and low on fear of negative evaluation. In both groups, unexpected rejection feedback yielded a significant increase in theta power. The feedback-related negativity was sensitive to unexpected feedback, regardless of valence, and was largest for unexpected rejection feedback. The feedback-related P3 was significantly enhanced in response to expected social acceptance feedback. Together, these findings confirm the sensitivity of frontal midline theta oscillations to the processing of social threat, and suggest that this alleged neural alarm system behaves similarly in individuals that differ in personality constructs relevant to social evaluation.

IATA for skin sensitization potential – 1 out of 2 or 2 out of 3? (ESCD meeting)

EPA Science Inventory

To meet EU regulatory requirements and to avoid or minimize animal testing, there is a need for non-animal methods to assess skin sensitization potential. Given the complexity of the skin sensitization endpoint, there is an expectation that integrated testing and assessment appro...

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

EPA Science Inventory

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 ...

IATA for skin sensitization potential – 1 out of 2 or 2 out of 3? (ASCCT meeting)

EPA Science Inventory

To meet EU regulatory requirements and to avoid or minimize animal testing, there is a need for non-animal methods to assess skin sensitization potential. Given the complexity of the skin sensitization endpoint, there is an expectation that integrated testing and assessment appro...

Evaluating a Skin Sensitization Model and Examining Common Assumptions of Skin Sensitizers (ASCCT meeting)

EPA Science Inventory

Skin sensitization is an adverse outcome that has been well studied over many decades. It was summarized using the adverse outcome pathway (AOP) framework as part of the OECD work programme (OECD, 2012). Currently there is a strong focus on how AOPs can be applied for different r...

Natural rubber latex skin testing reagents: safety and diagnostic accuracy of nonammoniated latex, ammoniated latex, and latex rubber glove extracts.

PubMed

Hamilton, R G; Adkinson, N F

1996-11-01

Nonammoniated latex, ammoniated latex, and rubber glove extracts are the only sources of natural rubber (Hevea brasiliensis) latex that have potential for use as skin testing reagents in the diagnosis of latex allergy. Their diagnostic sensitivity and specificity as skin test reagents are unknown. We conducted a phase 1/2 clinical study to examine the safety and diagnostic accuracy (sensitivity and specificity) of nonammoniated latex, ammoniated latex, and rubber glove extracts as skin test extracts to identify the most efficacious source material for future skin test reagent development. Twenty-four adults not allergic to latex, 19 adults with hand dermatitis or pruritus, and 59 adults with a latex allergy were identified by clinical history. All provided blood and then received puncture skin tests and intradermal skin tests with nonammoniated latex, ammoniated latex, and rubber glove extracts from Malaysian H. brasiliensis latex by use of sequential titration. A glove provocation test and IgE anti-latex RAST were used to clarify positive history-negative skin test response and negative history-positive skin test response mismatches. All three extracts were biologically safe and sterile. After normalization to 1 mg/ml of total protein, all three extracts produced equivalent diagnostic sensitivity and specificity in puncture skin tests and intradermal skin tests at various extract concentrations. Optimal diagnostic accuracy was safely achieved at 100 micrograms/ml for intradermal skin tests (e.g., nonammoniated latex: puncture skin test sensitivity 96%, specificity 100%; intradermal skin test sensitivity 93%, specificity 96%). The presence of IgE antibody in skin was highly correlated with IgE anti-latex in serum (nonammoniated latex: r = 0.98, p < 0.001; ammoniated latex: r = 0.94, p < 0.001; rubber glove extract: r = 0.96, p < 0.001). All five available subjects with a positive history, negative skin test response, and absence of IgE antibody in serum had a negative glove provocation test response, indicating no clinical evidence of latex allergy. No systemic or large local allergic reactions were observed with puncture skin tests or intradermal skin tests. Equivalent diagnostic sensitivity and specificity were observed with the nonammoniated latex, ammoniated latex, and rubber glove extract skin test reagents after normalization for total protein; nonammoniated latex may be considered the reagent of choice on the basis of practical quality control and reproducibility considerations.

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

PubMed

Schneider, K; Akkan, Z

2004-06-01

The local lymph node assay (LLNA) is a new test method which allows for the quantitative assessment of sensitizing potency in the mouse. Here, we investigate the quantitative correlation between results from the LLNA and two human sensitization tests--specifically, human repeat insult patch tests (HRIPTs) and human maximization tests (HMTs). Data for 57 substances were evaluated, of which 46 showed skin sensitizing properties in human tests, whereas 11 yielded negative results in humans. For better comparability data from mouse and human tests were transformed to applied doses per skin area, which ranged over four orders of magnitude for the substances considered. Regression analysis for the 46 human sensitizing substances revealed a significant positive correlation between the LLNA and human tests. The correlation was better between LLNA and HRIPT data (n=23; r=0.77) than between LLNA and HMT data (n=38; r=0.65). The observed scattering of data points is related to various uncertainties, in part associated with insufficiencies of data from older HMT studies. Predominantly negative results in the LLNA for another 11 substances which showed no skin sensitizing activity in human maximization tests further corroborate the correspondence between LLNA and human tests. Based on this analysis, the LLNA can be considered a reliable basis for relative potency assessments for skin sensitizers. Proposals are made for the regulatory exploitation of the LLNA: four potency groups can be established, and assignment of substances to these groups according to the outcome of the LLNA can be used to characterize skin sensitizing potency in substance-specific assessments. Moreover, based on these potency groups, a more adequate consideration of sensitizing substances in preparations becomes possible. It is proposed to replace the current single concentration limit for skin sensitizers in preparations, which leads to an all or nothing classification of a preparation as sensitizing to skin ("R43") in the European Union, by differentiated concentration limits derived from the limits for the four potency groups.

Multivariate models for prediction of human skin sensitization hazard.

PubMed

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

2017-03-01

One of the Interagency Coordinating Committee on the Validation of Alternative Method's (ICCVAM) top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary to produce skin sensitization suggests that no single alternative method will replace the currently accepted animal tests. ICCVAM is evaluating an integrated approach to testing and assessment based on the adverse outcome pathway for skin sensitization that uses machine learning approaches to predict human skin sensitization hazard. We combined data from three in chemico or in vitro assays - the direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT) and KeratinoSens™ assay - six physicochemical properties and an in silico read-across prediction of skin sensitization hazard into 12 variable groups. The variable groups were evaluated using two machine learning approaches, logistic regression and support vector machine, to predict human skin sensitization hazard. Models were trained on 72 substances and tested on an external set of 24 substances. The six models (three logistic regression and three support vector machine) with the highest accuracy (92%) used: (1) DPRA, h-CLAT and read-across; (2) DPRA, h-CLAT, read-across and KeratinoSens; or (3) DPRA, h-CLAT, read-across, KeratinoSens and log P. The models performed better at predicting human skin sensitization hazard than the murine local lymph node assay (accuracy 88%), any of the alternative methods alone (accuracy 63-79%) or test batteries combining data from the individual methods (accuracy 75%). These results suggest that computational methods are promising tools to identify effectively the potential human skin sensitizers without animal testing. Published 2016. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Published 2016. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Electrocutaneous sensitivity: effects of skin temperature.

PubMed

Larkin, W D; Reilly, J P

1986-01-01

The effect of human skin temperature on electrocutaneous sensitivity was examined using brief capacitive discharges. Stimuli were designed to ensure that sensory effects would be independent of skin resistance and would reflect underlying neural excitability as closely as possible. Skin temperature was manipulated by immersing the forearm in circulating hot or cold air. Detection thresholds on the arm and fingertip were raised by cooling, but were not altered by heating. Temperature-related sensitivity shifts were described by the same multiplicative factors for both threshold and suprathreshold levels. The temperature coefficient (Q10) for cutaneous sensitivity under these conditions was approximately 1.3.

An evaluation of selected in silico models for the assessment ...

EPA Pesticide Factsheets

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 Cosmetics Directive in EU has provided a much stronger impetus to actualize this research into practical tools for decision making. Thus there has been considerable focus on the development, evaluation, and integration of alternative approaches for skin sensitization hazard and risk assessment. This includes in silico approaches such as (Q)SARs and expert systems. This study aimed to evaluate the predictive performance of a selection of in silico models and then to explore whether combining those models led to an improvement in accuracy. A dataset of 473 substances that had been tested in the local lymph node assay (LLNA) was compiled. This comprised 295 sensitizers and 178 non-sensitizers. Four freely available models were identified - 2 statistical models VEGA and MultiCASE model A33 for skin sensitization (MCASE A33) from the Danish National Food Institute and two mechanistic models Toxtree’s Skin sensitization Reaction domains (Toxtree SS Rxn domains) and the OASIS v1.3 protein binding alerts for skin sensitization from the OECD Toolbox (OASIS). VEGA and MCASE A33 aim to predict sensitization as a binary score whereas the mechanistic models identified reaction domains or structura

Gentle cleansing and moisturizing for patients with atopic dermatitis and sensitive skin.

PubMed

Cheong, Wai Kwong

2009-01-01

Atopic dermatitis is a common condition characterized by pruritus, inflammation, and dryness of the skin. Inflammation disrupts the barrier function of the stratum corneum, predisposing the skin to be dry, and increases susceptibility to irritants and secondary bacterial infection. Sensitive skin is common, reported by 40-50% of women and 30% of men in the US, Europe, and Japan. Basic requirements in managing eczema and sensitive skin include effective cleansers that do not compromise skin barrier integrity, alleviation of skin dryness, and restoration of skin barrier function through the use of therapeutic moisturizers. The selection of a skin cleanser is therefore an important part of managing these conditions. Studies have reported clinical improvement with the use of soap-free cleansers in combination with topical treatments. While topical corticosteroids and immunosuppressive agents are mainstays of treatment for atopic dermatitis, therapeutic moisturizers are important adjuncts. Moisturizers improve skin hydration, reduce susceptibility to irritation, restore the integrity of the stratum corneum, and enhance the efficacy of topical corticosteroids.

Sensitive skin is highly frequent in extrinsic atopic dermatitis and correlates with disease severity markers but not necessarily with skin barrier impairment.

PubMed

Yatagai, Tsuyoshi; Shimauchi, Takatoshi; Yamaguchi, Hayato; Sakabe, Jun-Ichi; Aoshima, Masahiro; Ikeya, Shigeki; Tatsuno, Kazuki; Fujiyama, Toshiharu; Ito, Taisuke; Ojima, Toshiyuki; Tokura, Yoshiki

2018-01-01

Sensitive skin is a condition of cutaneous hypersensitivity to environmental factors. Lactic acid stinging test (LAST) is commonly used to assess sensitive skin and composed of four distinct sensations (pain, burning sensation, itch, and crawly feeling). A link between sensitive skin and barrier dysfunction has been proposed in atopic dermatitis (AD) patients. However, clinical and laboratory factors that are associated with sensitive skin remain unelucidated. To investigate relationship between sensitive skin and AD-associated markers. Forty-two Japanese AD patients and 10 healthy subjects (HS) were enrolled. AD patients were divided into extrinsic (EAD; high IgE levels) and intrinsic (IAD; normal IgE levels) types. We conducted 1% LAST by assessing the four distinct sensations and calculated the frequencies of sensitive skin in EAD, IAD, and HS. We also performed clinical AD-related tests, including transepidermal water loss (TEWL), visual analogue scale (VAS) of pruritus, and quality of life, and measured laboratory markers, including blood levels of IgE, CCL17/TARC, lactate dehydrogenase (LDH) and eosinophil counts, and concentration levels of serum Th1/Th2 cytokines. Filaggrin (FLG) mutations were examined in 21 patients. These values were subjected to correlation analyses with each of the four sensation elements. According to the standard criteria for LAST positivity, the frequencies of LAST-positive subjects were 54.8% and 10.0% in AD and HS, respectively (P=0.014). EAD patients showed a significantly (P=0.026) higher frequency of positive LAST (65.6%) than did IAD patients (20.0%). Among the four LAST sensation elements, the crawly feeling and pain scores positively correlated with VAS of pruritus, total serum IgE, mite-specific IgE, CCL17/TARC, and/or LDH. There was no association of the LAST scores with serum Th1/Th2 cytokine levels. Notably, neither TEWL nor FLG mutations correlated with LAST positivity or any sensation scores. The frequency of sensitive skin is higher in EAD than in IAD. Sensitive skin is associated with AD severity, but not necessarily with barrier condition. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

A rare subset of skin-tropic regulatory T cells expressing Il10/Gzmb inhibits the cutaneous immune response.

PubMed

Ikebuchi, Ryoyo; Teraguchi, Shunsuke; Vandenbon, Alexis; Honda, Tetsuya; Shand, Francis H W; Nakanishi, Yasutaka; Watanabe, Takeshi; Tomura, Michio

2016-10-19

Foxp3 + regulatory T cells (Tregs) migrating from the skin to the draining lymph node (dLN) have a strong immunosuppressive effect on the cutaneous immune response. However, the subpopulations responsible for their inhibitory function remain unclear. We investigated single-cell gene expression heterogeneity in Tregs from the dLN of inflamed skin in a contact hypersensitivity model. The immunosuppressive genes Ctla4 and Tgfb1 were expressed in the majority of Tregs. Although Il10-expressing Tregs were rare, unexpectedly, the majority of Il10-expressing Tregs co-expressed Gzmb and displayed Th1-skewing. Single-cell profiling revealed that CD43 + CCR5 + Tregs represented the main subset within the Il10/Gzmb-expressing cell population in the dLN. Moreover, CD43 + CCR5 + CXCR3 - Tregs expressed skin-tropic chemokine receptors, were preferentially retained in inflamed skin and downregulated the cutaneous immune response. The identification of a rare Treg subset co-expressing multiple immunosuppressive molecules and having tissue-remaining capacity offers a novel strategy for the control of skin inflammatory responses.

Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation.

PubMed

Zhong, Franklin L; Mamaï, Ons; Sborgi, Lorenzo; Boussofara, Lobna; Hopkins, Richard; Robinson, Kim; Szeverényi, Ildikó; Takeichi, Takuya; Balaji, Reshmaa; Lau, Aristotle; Tye, Hazel; Roy, Keya; Bonnard, Carine; Ahl, Patricia J; Jones, Leigh Ann; Baker, Paul J; Lacina, Lukas; Otsuka, Atsushi; Fournie, Pierre R; Malecaze, François; Lane, E Birgitte; Akiyama, Masashi; Kabashima, Kenji; Connolly, John E; Masters, Seth L; Soler, Vincent J; Omar, Salma Samir; McGrath, John A; Nedelcu, Roxana; Gribaa, Moez; Denguezli, Mohamed; Saad, Ali; Hiller, Sebastian; Reversade, Bruno

2016-09-22

Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of the Efficacy of Atopalm(®) Multi-Lamellar Emulsion Cream and Physiogel(®) Intensive Cream in Improving Epidermal Permeability Barrier in Sensitive Skin.

PubMed

Jeong, Sekyoo; Lee, Sin Hee; Park, Byeong Deog; Wu, Yan; Man, George; Man, Mao-Qiang

2016-03-01

The management of sensitive skin, which affects over 60% of the general population, has been a long-standing challenge for both patients and clinicians. Because defective epidermal permeability barrier is one of the clinical features of sensitive skin, barrier-enhancing products could be an optimal regimen for sensitive skin. In the present study, we evaluated the efficacy and safety of two barrier-enhancing products, i.e., Atopalm (®) Multi-Lamellar Emulsion (MLE) Cream and Physiogel (®) Intensive Cream for sensitive skin. 60 patients with sensitive skin, aged 22-40 years old, were randomly assigned to one group treated with Atopalm MLE Cream, and another group treated with Physiogel Intensive Cream twice daily for 4 weeks. Lactic acid stinging test scores (LASTS), stratum hydration (SC) and transepidermal water loss (TEWL) were assessed before, 2 and 4 weeks after the treatment. Atopalm MLE Cream significantly lowered TEWL after 2 and 4 weeks of treatment (p < 0.01). In contrast, Physiogel Intensive Cream significantly increased TEWL after 2 weeks of treatment (p < 0.05) while TEWL significantly decreased after 4-week treatments. Moreover, both Atopalm MLE Cream and Physiogel Intensive Cream significantly increased SC hydration, and improved LASTS after 4 weeks of treatment. Both barrier-enhancing products are effective and safe for improving epidermal functions, including permeability barrier, SC hydration and LASTS, in sensitive skin. These products could be a valuable alternative for management of sensitive skin. Veterans Affairs Medical Center, San Francisco, California, USA, and NeoPharm Co., Ltd., Daejeon, Korea.

Comparison of methods for assessing photoprotection against ultraviolet A in vivo

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

Kaidbey, K.; Gange, R.W.

Photoprotection against ultraviolet A (UVA) by three sunscreens was evaluated in humans, with erythema and pigmentation used as end points in normal skin and in skin sensitized with 8-methoxypsoralen and anthracene. The test sunscreens were Parsol 1789 (2%), Eusolex 8020 (2%), and oxybenzone (3%). UVA was obtained from two filtered xenon-arc sources. UVA protection factors were found to be significantly higher in sensitized skin compared with normal skin. Both Parsol and Eusolex provided better and comparable photoprotection (approximately 3.0) than oxybenzone (approximately 2.0) in sensitized skin, regardless of whether 8-methoxypsoralen or anthracene was used. In normal unsensitized skin, Parsol 1789more » and Eusolex 8020 were also comparable and provided slightly better photoprotection (approximately 1.8) than oxybenzone (approximately 1.4) when pigmentation was used as an end point. The three sunscreens, however, were similar in providing photoprotection against UVA-induced erythema. Protection factors obtained in artificially sensitized skin are probably not relevant to normal skin. It is concluded that pigmentation, either immediate or delayed, is a reproducible and useful end point for the routine assessment of photoprotection of normal skin against UVA.« less

Do Unexpected Panic Attacks Occur Spontaneously?

PubMed Central

Meuret, Alicia E.; Rosenfield, David; Wilhelm, Frank H.; Zhou, Enlu; Conrad, Ansgar; Ritz, Thomas; Roth, Walton T.

2012-01-01

Background Spontaneous or unexpected panic attacks, per definition, occur out-of-the blue, in absence of cues or triggers. Accordingly, physiological arousal or instability should occur at the onset of or during the attack, but not preceding it. To test this hypothesisweexaminedif points of significant autonomic changes preceded the onset of spontaneous panic attacks. Methods Forty-three panic disorder patients underwent repeated 24-hour ambulatory monitoring. Thirteen naturally panic attacks were recorded during 1,960 hours of monitoring. Minute-by-minute epochs beginning 60 minutes before, and continuing to 10 minutes after, the onset of individual attacks were examined for respiration, heart rate, and skin conductance level. Measures were controlled for physical activity and vocalization, and compared to time matched control periods within the same person. Results Significant patterns of instability across a numberof autonomic and respiratory variables were detected as early as 47 minutes before panic onset. The final minutes prior to onset were dominated by respiratory changes, with significant decreases in tidal volume followed by abrupt PCO2 increases. Panic attack onset was characterized by heart rate and tidal volume increases and a drop in PCO2. Symptom report was consistent with these changes. Skin conductance levels were generally elevated in the hour before and duringthe attacks. Changes in the matched control periods were largely absent. Conclusions Significant autonomic irregularities preceded the onset of attacks that were reported as abrupt and unexpected. The findings invite reconsideration of the current diagnostic distinction betweenuncuedand cued panic attacks. PMID:21783179

Selective skin sensitivity changes and sensory reweighting following short-duration space flight.

PubMed

Lowrey, Catherine R; Perry, Stephen D; Strzalkowski, Nicholas D J; Williams, David R; Wood, Scott J; Bent, Leah R

2014-03-15

Skin sensory input from the foot soles is coupled with vestibular input to facilitate body orientation in a gravitational environment. Anecdotal observations suggest that foot sole skin becomes hypersensitive following space flight. The veritable level of skin sensitivity and its impact on postural disequilibrium observed post space flight have not been documented. Skin sensitivity of astronauts (n = 11) was measured as vibration perception at the great toe, fifth metatarsal and heel. Frequencies targeted four classes of receptors: 3 and 25 Hz for slow-adapting (SA) receptors and 60 and 250 Hz for fast-adapting (FA) receptors. Data were collected pre- and post-space flight. We hypothesized that skin sensitivity would increase post-space flight and correlate to balance measures. Decreased skin sensitivity was found on landing day at 3 and 25 Hz on the great toe. Hypersensitivity was found for a subset of astronauts (n = 6) with significantly increased sensitivity to 250 Hz at the heel. This subset displayed a greater reduction in computerized dynamic posturography (CDP) equilibrium (EQ) scores (-54%) on landing vs. non-hypersensitive participants (-11%). Observed hyposensitivity of SA (pressure) receptors may indicate a strategy to reduce pressure input during periods of unloading. Hypersensitivity of FAs coupled with reduced EQ scores may reflect targeted sensory reweighting. Altered gravito-inertial environments reduce vestibular function in balance control which may trigger increased weighting of FAs (that signal foot contact, slips). Understanding modulations to skin sensitivity has translational implications for mitigating postural disequilibrium following space flight and for on-Earth preventative strategies for imbalance in older adults.

Fragment-based prediction of skin sensitization using recursive partitioning

NASA Astrophysics Data System (ADS)

Lu, Jing; Zheng, Mingyue; Wang, Yong; Shen, Qiancheng; Luo, Xiaomin; Jiang, Hualiang; Chen, Kaixian

2011-09-01

Skin sensitization is an important toxic endpoint in the risk assessment of chemicals. In this paper, structure-activity relationships analysis was performed on the skin sensitization potential of 357 compounds with local lymph node assay data. Structural fragments were extracted by GASTON (GrAph/Sequence/Tree extractiON) from the training set. Eight fragments with accuracy significantly higher than 0.73 ( p < 0.1) were retained to make up an indicator descriptor fragment. The fragment descriptor and eight other physicochemical descriptors closely related to the endpoint were calculated to construct the recursive partitioning tree (RP tree) for classification. The balanced accuracy of the training set, test set I, and test set II in the leave-one-out model were 0.846, 0.800, and 0.809, respectively. The results highlight that fragment-based RP tree is a preferable method for identifying skin sensitizers. Moreover, the selected fragments provide useful structural information for exploring sensitization mechanisms, and RP tree creates a graphic tree to identify the most important properties associated with skin sensitization. They can provide some guidance for designing of drugs with lower sensitization level.

Is skin penetration a determining factor in skin sensitization potential and potency? Refuting the notion of a LogKow threshold for Skin Sensitization

EPA Science Inventory

Summary:Background. It is widely accepted that substances that cannot penetrate through the skin will not be sensitisers. Thresholds based on relevant physicochemical parameters such as a LogKow > 1 and a MW < 500, are assumed and widely accepted as self-evident truths. Objective...

In vivo and in vitro analysis of low level light therapy: a useful therapeutic approach for sensitive skin.

PubMed

Choi, M; Kim, J E; Cho, K H; Lee, J H

2013-11-01

Sensitive skin is a relatively common dermatologic condition and no optimal treatments have been established so far. Low-level laser/light therapy (LLLT) has been used for its biostimulative effect in various clinical settings. The purpose of this study was to investigate whether low-level laser/light therapy can improve sensitive skin clinically and to evaluate the effects of LLLT on skin in vitro. Twenty-eight patients complaining of sensitive skin were treated with low-level polarized light, and clinical results were evaluated using subjective and objective method. To investigate possible working mechanism of LLLT on skin, cultured human keratinocytes pretreated with nontoxic concentration of sodium lauryl sulfate (SLS) were used. Cytokines released from irritated keratinocytes after LLLT were analyzed. All patients showed subjective and objective improvement after treatment. No adverse effects were reported. The average number of LLLT sessions required to achieve clinical improvement was 9.9, and cumulative dose of LLLT was 71.3 J/cm(2) on the average. Erythema index decreased significantly after LLLT treatment (p = 0.017). In vitro assay showed that LLLT significantly reduced the release of VEGF from SLS-pretreated keratinocytes (p = 0.021). Our results suggest that LLLT could be a useful and safe treatment modality for sensitive skin, and modification of inflammatory cytokines released from irritated keratinocytes may be considered as one of plausible mechanisms in sensitive skin treated with LLLT.

Carbon dioxide instantly sensitizes female yellow fever mosquitoes to human skin odours.

PubMed

Dekker, Teun; Geier, Martin; Cardé, Ring T

2005-08-01

Female mosquitoes are noted for their ability to use odours to locate a host for a blood meal. Two sensory organs contribute to their sense of smell: the maxillary palps, which measure the level of CO2, and the antennae, which detect other host-released odours. To establish the relative importance and interactions of CO2 and other body emissions in freely flying mosquitoes, we presented female yellow fever mosquitoes Aedes aegypti L. with broad plumes of human skin odour and CO2 at natural concentrations and dilutions thereof in a wind tunnel. 3-D video-recorded flight tracks were reconstructed. Activation, flight velocity, upwind turning and source finding waned quickly as skin odours were diluted, whereas in the presence of CO2 these parameters remained unchanged over more than a 100-fold dilution from exhaled concentrations. Although mosquitoes were behaviourally less sensitive to skin odours than to CO2, their sensitivity to skin odours increased transiently by at least fivefold immediately following a brief encounter with a filament of CO2. This sensitization was reflected in flight velocity, track angle, turning rate upon entering and exiting the broad odour plume and, ultimately, in the source-finding rate. In Ae. aegypti, CO2 thus functions as a ;releaser' for a higher sensitivity and responsiveness to skin odours. The initially low responsiveness of mosquitoes to skin odours, their high sensitivity to CO2, and the sensitization of the olfactory circuitry by CO2 are ecologically relevant, because rapidly fluctuating CO2 levels reliably signal a potential host. Possible mechanisms of the instantaneous sensitization are considered.

Skylab

NASA Image and Video Library

1973-05-01

The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Intrnal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image shows astronaut Kerwin cutting the metal strap to free and deploy the Orbital Workshop solar array. Kerwin used special cutting tools developed by engineers at the Marshall Space Flight Center (MSFC). The MSFC had a major role in developing the procedures to repair the damaged Skylab.

Skylab

NASA Image and Video Library

1973-05-01

The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows the station's remaining solar panel jammed against its side. The Marshall Space Flight Center had a major role in developing the procedures to repair the damaged Skylab.

Skin, ear and testis--unusual sites of tuberculosis.

PubMed

Ene, Cătălina Elena; Toma, Claudia; Belaconi, Ionela; Dumitrache-Rujinski, Stefan; Jipa, Daniela; Tudor, Adrian; Leonte, Diana; Bogdan, Miron Alexandru

2016-01-01

Pulmonary localization is the most common site of tuberculosis (TB)and the most contagious form. Extrapulmonary tuberculosis with the rarest and most unexpected localizations represents a significant proportion of all cases of tuberculosis and remains an important public health problem. We report three unusual TB locations: skin, ear and testis occurred in three immunocompetent patients. In the case of skin and testicular lesions, diagnosis was based on pathological confirmation of granulomas with caseous necrosis. In the third case the diagnosis was made possible by identification of positive Acid-Fast Bacilli smear and positive culture from othic drainage fluid. The outcome at all three patients was good with antituberculous treatment. These unusual localization of tuberculosis also highlight the possibility of extrapulmonary tuberculosis as a differential diagnosis in many common diseases.

Multivariate Models for Prediction of Human Skin Sensitization Hazard.

EPA Science Inventory

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...

Prediction of Chemical Respiratory Sensitizers Using GARD, a Novel In Vitro Assay Based on a Genomic Biomarker Signature

PubMed Central

Albrekt, Ann-Sofie; Borrebaeck, Carl A. K.; Lindstedt, Malin

2015-01-01

Background Repeated exposure to certain low molecular weight (LMW) chemical compounds may result in development of allergic reactions in the skin or in the respiratory tract. In most cases, a certain LMW compound selectively sensitize the skin, giving rise to allergic contact dermatitis (ACD), or the respiratory tract, giving rise to occupational asthma (OA). To limit occurrence of allergic diseases, efforts are currently being made to develop predictive assays that accurately identify chemicals capable of inducing such reactions. However, while a few promising methods for prediction of skin sensitization have been described, to date no validated method, in vitro or in vivo, exists that is able to accurately classify chemicals as respiratory sensitizers. Results Recently, we presented the in vitro based Genomic Allergen Rapid Detection (GARD) assay as a novel testing strategy for classification of skin sensitizing chemicals based on measurement of a genomic biomarker signature. We have expanded the applicability domain of the GARD assay to classify also respiratory sensitizers by identifying a separate biomarker signature containing 389 differentially regulated genes for respiratory sensitizers in comparison to non-respiratory sensitizers. By using an independent data set in combination with supervised machine learning, we validated the assay, showing that the identified genomic biomarker is able to accurately classify respiratory sensitizers. Conclusions We have identified a genomic biomarker signature for classification of respiratory sensitizers. Combining this newly identified biomarker signature with our previously identified biomarker signature for classification of skin sensitizers, we have developed a novel in vitro testing strategy with a potent ability to predict both skin and respiratory sensitization in the same sample. PMID:25760038

The N400 and the P300 are not all that independent.

PubMed

Arbel, Yael; Spencer, Kevin M; Donchin, Emanuel

2011-06-01

This study assessed whether two ERP components that are elicited by unexpected events interact. The conditions that are known to elicit the N400 and the P300 ERP components were applied separately and in combination to terminal-words in sentences. Each sentence ended with a terminal-word that was highly expected, semantically unexpected, physically deviant, or both semantically unexpected and physically deviant. In addition, we varied the level of semantic relatedness between the unexpected terminal-words and the expected exemplars. Physically deviant words elicited a P300, whereas semantically unexpected words elicited an N400, whose amplitude was sensitive to the level of semantic relatedness. Words that were both semantically unexpected and physically deviant elicited both an N400 with enhanced amplitude, and a P300 with reduced amplitude. These results suggest an interaction between the processes manifested by the two components. Copyright © 2010 Society for Psychophysiological Research.

Characterization of Mus musculus Papillomavirus 1 Infection In Situ Reveals an Unusual Pattern of Late Gene Expression and Capsid Protein Localization

PubMed Central

Handisurya, Alessandra; Day, Patricia M.; Thompson, Cynthia D.; Buck, Christopher B.; Pang, Yuk-Ying S.; Lowy, Douglas R.

2013-01-01

Full-length genomic DNA of the recently identified laboratory mouse papillomavirus 1 (MusPV1) was synthesized in vitro and was used to establish and characterize a mouse model of papillomavirus pathobiology. MusPV1 DNA, whether naked or encapsidated by MusPV1 or human papillomavirus 16 (HPV 16) capsids, efficiently induced the outgrowth of papillomas as early as 3 weeks after application to abraded skin on the muzzles and tails of athymic NCr nude mice. High concentrations of virions were extracted from homogenized papillomatous tissues and were serially passaged for >10 generations. Neutralization by L1 antisera confirmed that infectious transmission was capsid mediated. Unexpectedly, the skin of the murine back was much less susceptible to virion-induced papillomas than the muzzle or tail. Although reporter pseudovirions readily transduced the skin of the back, infection with native MusPV1 resulted in less viral genome amplification and gene expression on the back, including reduced expression of the L1 protein and very low expression of the L2 protein, results that imply skin region-specific control of postentry aspects of the viral life cycle. Unexpectedly, L1 protein on the back was predominantly cytoplasmic, while on the tail the abundant L1 was cytoplasmic in the lower epithelial layers and nuclear in the upper layers. Nuclear localization of L1 occurred only in cells that coexpressed the minor capsid protein, L2. The pattern of L1 protein staining in the infected epithelium suggests that L1 expression occurs earlier in the MusPV1 life cycle than in the life cycle of high-risk HPV and that virion assembly is regulated by a previously undescribed mechanism. PMID:24067981

Detection of Onchocerca volvulus in Skin Snips by Microscopy and Real-Time Polymerase Chain Reaction: Implications for Monitoring and Evaluation Activities.

PubMed

Thiele, Elizabeth A; Cama, Vitaliano A; Lakwo, Thomson; Mekasha, Sindeaw; Abanyie, Francisca; Sleshi, Markos; Kebede, Amha; Cantey, Paul T

2016-04-01

Microscopic evaluation of skin biopsies is the monitoring and evaluation (M and E) method currently used by multiple onchocerciasis elimination programs in Africa. However, as repeated mass drug administration suppresses microfilarial loads, the sensitivity and programmatic utility of skin snip microscopy is expected to decrease. Using a pan-filarial real-time polymerase chain reaction with melt curve analysis (qPCR-MCA), we evaluated 1) the use of a single-step molecular assay for detecting and identifying Onchocerca volvulus microfilariae in residual skin snips and 2) the sensitivity of skin snip microscopy relative to qPCR-MCA. Skin snips were collected and examined with routine microscopy in hyperendemic regions of Uganda and Ethiopia (N= 500 each) and "residual" skin snips (tissue remaining after induced microfilarial emergence) were tested with qPCR-MCA. qPCR-MCA detected Onchocerca DNA in 223 residual snips: 139 of 147 microscopy(+) and 84 among microscopy(-) snips, suggesting overall sensitivity of microscopy was 62.3% (139/223) relative to qPCR-MCA (75.6% in Uganda and 28.6% in Ethiopia). These findings demonstrate the insufficient sensitivity of skin snip microscopy for reliable programmatic monitoring. Molecular tools such as qPCR-MCA can augment sensitivity and provide diagnostic confirmation of skin biopsies and will be useful for evaluation or validation of new onchocerciasis M and E tools. © The American Society of Tropical Medicine and Hygiene.

Comparison of the skin sensitizing potential of unsaturated compounds as assessed by the murine local lymph node assay (LLNA) and the guinea pig maximization test (GPMT).

PubMed

Kreiling, R; Hollnagel, H M; Hareng, L; Eigler, D; Lee, M S; Griem, P; Dreessen, B; Kleber, M; Albrecht, A; Garcia, C; Wendel, A

2008-06-01

The skin sensitization potential of eight unsaturated and one saturated lipid (bio)chemicals was tested in both the LLNA and the GPMT to address the hypothesis that chemicals with unsaturated carbon-carbon double bonds may result in a higher number of unspecific (false positive) results in the LLNA compared to the GPMT. Seven substances (oleic acid, linoleic acid, linolenic acid, undecylenic acid, maleic acid, squalene and octinol) gave clear positive results in the LLNA (stimulation index (SI)> or = 3) and thus would require labelling as skin sensitizer. Fumaric acid and succinic acid gave clearly negative results. In the GPMT, besides some sporadic skin reactions, reproducible skin reactions indicating an allergic response were found in a few animals for four test substances. Based on the GPMT results, only undecylenic acid would have to be classified and labelled as a skin sensitizer according to the European Dangerous Substance Directive (67/548/EEC) (results for linoleic acid were inconclusive), while the other seven test substances would not require labelling. Possible mechanisms for unspecific skin cell stimulation and lymph node responses are discussed. In conclusion, the suitability of the LLNA for unsaturated compounds bearing structural similarity to the tested substances should be carefully considered and the GPMT should remain available as an accepted test method for skin sensitization hazard identification.

Sensitivity to Sunburn Is Associated with Susceptibility to Ultraviolet Radiation–Induced Suppression of Cutaneous Cell–Mediated Immunity

PubMed Central

Kelly, Deirdre A.; Young, Antony R.; McGregor, Jane M.; Seed, Paul T.; Potten, Christopher S.; Walker, Susan L.

2000-01-01

Skin cancer incidence is highest in white-skinned people. Within this group, skin types I/II (sun sensitive/tan poorly) are at greater risk than skin types III/IV (sun tolerant/tan well). Studies in mice demonstrate that ultraviolet radiation (UVR)-induced suppression of cell-mediated immune function plays an important role in the development of skin cancer and induces a susceptibility to infectious disease. A similar role is suspected in humans, but we lack quantitative human data to make risk assessments of ambient solar exposure on human health. This study demonstrates that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo (n = 93). There was a linear relationship between increase in erythema and suppression of CHS (P < 0.001), and a moderate sunburn (two minimal erythema doses [2 MED]) was sufficient to suppress CHS in all volunteers by 93%. However, a single suberythemal exposure of either 0.25 or 0.5 MED suppressed CHS responses by 50 and 80%, respectively, in skin types I/II, whereas 1 MED only suppressed CHS by 40% in skin types III/IV. The two- to threefold greater sensitivity of skin types I/II for a given level of sunburn may play a role in their greater sensitivity to skin cancer. PMID:10662801

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

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

Lambrechts, Nathalie; Verstraelen, Sandra; Lodewyckx, Hanne

2009-04-15

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{sup +} 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 expressionmore » 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.« less

Fabrication of High-Sensitivity Skin-Attachable Temperature Sensors with Bioinspired Microstructured Adhesive.

PubMed

Oh, Ju Hyun; Hong, Soo Yeong; Park, Heun; Jin, Sang Woo; Jeong, Yu Ra; Oh, Seung Yun; Yun, Junyeong; Lee, Hanchan; Kim, Jung Wook; Ha, Jeong Sook

2018-02-28

In this study, we demonstrate the fabrication of a highly sensitive flexible temperature sensor with a bioinspired octopus-mimicking adhesive. A resistor-type temperature sensor consisting of a composite of poly(N-isopropylacrylamide) (pNIPAM)-temperature sensitive hydrogel, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate, and carbon nanotubes exhibits a very high thermal sensitivity of 2.6%·°C -1 between 25 and 40 °C so that the change in skin temperature of 0.5 °C can be accurately detected. At the same time, the polydimethylsiloxane adhesive layer of octopus-mimicking rim structure coated with pNIPAM is fabricated through the formation of a single mold by utilizing undercut phenomenon in photolithography. The fabricated sensor shows stable and reproducible detection of skin temperature under repeated attachment/detachment cycles onto skin without any skin irritation for a long time. This work suggests a high potential application of our skin-attachable temperature sensor to wearable devices for medical and health-care monitoring.

Responding In-the-Moment: Learning to Prepare for the Unexpected

ERIC Educational Resources Information Center

Mason, John

2015-01-01

Becoming aware of something unexpected can be a form of awakening: sharpening attention, enriching noticing, opening up fresh possibilities of action, and educating awareness so as to enable a sensitive response to similar situations in the future. However it can also trigger tunnel vision (few if any actions available) or freezing (no actions…

The abdominal skin of female Sprague-Dawley rats is more sensitive than the back skin to drug-induced phototoxicity.

PubMed

Kuga, Kazuhiro; Yasuno, Hironobu; Sakai, Yumi; Harada, Yumiko; Shimizu, Fumi; Miyamoto, Yumiko; Takamatsu, Yuki; Miyamoto, Makoto; Sato, Keiichiro

2017-11-01

In vivo phototoxicity studies are important to predict drug-induced phototoxicity in humans; however, a standard methodology has not established. To determine differences in sensitivity to drug-induced phototoxicity among various skin sites, we evaluated phototoxic reactions in the back and abdominal skin of female Sprague-Dawley rats orally dosed with phototoxic drugs (pirfenidone, 8-methoxysoraren, doxycycline, and lomefloxacin) or a non-phototoxic drug (gatifloxacin) followed by solar-simulated light irradiation comprising 18J/cm 2 ultraviolet A. Tissue reactions were evaluated by macroscopic and microscopic examination and immunohistochemistry for γ-H2AX, and tissue concentrations of pirfenidone, doxycycline, and lomefloxacin were measured by tandem mass spectrometry. In addition, the thicknesses of the skin layers at both sites were measured in drug-naïve rats. The abdominal skin showed more severe reactions to all phototoxic drugs than the back skin, whereas the minimal erythema dose in drug-naïve rats and skin concentrations of each drug were comparable between the sites. Furthermore, histopathological lesions and γ-H2AX-positive cells in the abdominal skin were detected in deeper layers than in the back skin. The stratum corneum and dermis in the abdominal skin were significantly thinner than in the back skin, indicating a difference in the depth of light penetration and potentially contributing to the site differences observed in sensitivity to phototoxicity. Gatifloxacin did not induce any phototoxic reactions at either site. In conclusion, the abdominal skin is more sensitive to drug-induced phototoxicity than the back skin and may represent a preferable site for irradiation in this rat phototoxicity model. Copyright © 2017 Elsevier Inc. All rights reserved.

Tolerance of fragranced and fragrance-free facial cleansers in adults with clinically sensitive skin.

PubMed

Draelos, Zoe D; Fowler, Joseph; Larsen, Walter G; Hornby, Sidney; Walters, Russel M; Appa, Yohini

2015-10-01

Although mild, fragrance-free, nonfoaming cleansers generally are recommended for individuals with sensitive skin, many consumers choose fragranced foaming cleansers. The addition of hydrophobically modified polymers (HMPs) to mild facial cleansers has been shown to improve product tolerability in individuals with sensitive skin while facilitating foaming. The objective of the 2 studies reported here was to assess the tolerability of a mild, HMP-containing, foaming facial cleanser with a fragrance that was free of common allergens and irritating essential oils in patients with sensitive skin. In the first study, 8 participants with clinically diagnosed fragrance sensitivity used a gentle foaming HMP-containing facial cleanser with or without fragrance for 3 weeks. Both cleansers improved global disease severity, irritation, and erythema with similar cleansing effectiveness. The second study was a 3-week, prospective, double-blind, randomized, 2-center study of 153 participants with clinically diagnosed sensitive skin. In this study, the fragranced gentle foaming cleanser with HMP was as well tolerated as a benchmark gentle, fragrance-free, nonfoaming cleanser. Itching, irritation, and desquamation were most improved from baseline in both groups. The participant-rated effectiveness of the cleanser with HMP was similar or better than the benchmark cleanser after 3 weeks of use. In conclusion, the gentle facial cleanser with HMPs and a fragrance offers a new option for adults with sensitive skin who may prefer, and commonly use, a fragranced and foaming product.

Quantitative risk assessment for skin sensitization: Success or failure?

PubMed

Kimber, Ian; Gerberick, G Frank; Basketter, David A

2017-02-01

Skin sensitization is unique in the world of toxicology. There is a combination of reliable, validated predictive test methods for identification of skin sensitizing chemicals, a clearly documented and transparent approach to risk assessment, and effective feedback from dermatology clinics around the world delivering evidence of the success or failure of the hazard identification/risk assessment/management process. Recent epidemics of contact allergy, particularly to preservatives, have raised questions of whether the safety/risk assessment process is working in an optimal manner (or indeed is working at all!). This review has as its focus skin sensitization quantitative risk assessment (QRA). The core toxicological principles of QRA are reviewed, and evidence of use and misuse examined. What becomes clear is that skin sensitization QRA will only function adequately if two essential criteria are met. The first is that QRA is applied rigourously, and the second is that potential exposure to the sensitizing substance is assessed adequately. This conclusion will come as no surprise to any toxicologist who appreciates the basic premise that "risk = hazard x exposure". Accordingly, use of skin sensitization QRA is encouraged, not least because the essential feedback from dermatology clinics can be used as a tool to refine QRA in situations where this risk assessment tool has not been properly used. Copyright © 2016 Elsevier Inc. All rights reserved.

Thoroughness of skin examination by melanoma patients: Influence of age, sex and partner

PubMed Central

Boone, Susan L; Stapleton, Jerod; Turrisi, Rob; Ortiz, Sara; Robinson, June K; Mallett, Kimberly A

2010-01-01

The aim of this study was to determine the thoroughness of deliberate skin examination by people with a history of melanoma. Patients were randomized into one of two conditions: either to receive the brief educational and skills training intervention alone or as a couple with their spouse or cohabiting partner. Subjects recorded concerning lesions on body maps. At the 4-month visit, a total body skin examination was performed by a dermatologist blinded to the subjects’ condition and to their recorded responses. The skin surface was divided according to the region’s visibility during skin self-examination and sexual connotations: visible/not sexually sensitive, non-visible/not sexually sensitive and sexually sensitive. The primary point of comparison was missed lesions, defined as the difference between lesions recorded by the subjects and their partners and those recorded by the dermatologist. Among 130 participants, 56 subjects reported partner assistance while performing SSE. Participants missed more lesions in sexually sensitive areas than in the other regions. With the increasing age of the patient, the number of missed lesions in non-visible/not sexually sensitive and sexually sensitive areas decreased. Male patients assisted by female partners missed fewer lesions in all three regions than female patients assisted by male partners. In easily visible areas, male patients missed significantly fewer lesions than female patients (P = 0.01). Older couples performed more thorough partner-assisted skin examinations in non-visible and sexually sensitive areas than younger couples. Male patients who were assisted by female partners performed more thorough partner-assisted skin examinations than female patients assisted by male partners. PMID:19659978

Skin Sensitizing Potency of Halogenated Platinum Salts.

EPA Science Inventory

The relationship between occupational exposure to halogenated platinum (Pt) salts and Pt-specific allergic sensitization is well-established. Although human case reports and clinical studies demonstrate that Pt salts are potent skin sensitizers, no studies have been published tha...

Prediction of Skin Sensitization Potency Using Machine Learning Approaches

EPA Science Inventory

Replacing animal tests currently used for regulatory hazard classification of skin sensitizers is one of ICCVAM’s top priorities. Accordingly, U.S. federal agency scientists are developing and evaluating computational approaches to classify substances as sensitizers or nons...

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

PubMed

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.

Competition between skin-sensitizing chemicals in the mouse

PubMed Central

Wallington, T. B.; Jones, J. Verrier

1974-01-01

The skin contact sensitivity responses to picryl chloride in CBA mice can be reduced by prior sensitization with oxazolone. Initial experiments showed this reduction to be significant when the interval between skin paintings was 7 days. In further experiments to study the time course of this effect, the depression was found to be maximal when the interval between skin paintings was between 3 and 7 days. Prior painting with a non-immunogenic chemical irritant, oil of turpentine, did not depress responses to picryl chloride. The relation of this phenomenon to antigenic competition in antibody production is discussed. PMID:4851120

Highly Flexible and Sensitive Wearable E-Skin Based on Graphite Nanoplatelet and Polyurethane Nanocomposite Films in Mass Industry Production Available.

PubMed

Wu, Jianfeng; Wang, Huatao; Su, Zhiwei; Zhang, Minghao; Hu, Xiaodong; Wang, Yijie; Wang, Ziao; Zhong, Bo; Zhou, Weiwei; Liu, Junpeng; Xing, Scott Guozhong

2017-11-08

Graphene and nanomaterials based flexible pressure sensors R&D activities are becoming hot topics due to the huge marketing demand on wearable devices and electronic skin (E-Skin) to monitor the human body's actions for dedicated healthcare. Herein, we report a facile and efficient fabrication strategy to construct a new type of highly flexible and sensitive wearable E-Skin based on graphite nanoplates (GNP) and polyurethane (PU) nanocomposite films. The developed GNP/PU E-Skin sensors are highly flexible with good electrical conductivity due to their unique binary microstructures with synergistic interfacial characteristics, which are sensitive to both static and dynamic pressure variation, and can even accurately and quickly detect the pressure as low as 0.005 N/50 Pa and momentum as low as 1.9 mN·s with a gauge factor of 0.9 at the strain variation of up to 30%. Importantly, our GNP/PU E-Skin is also highly sensitive to finger bending and stretching with a linear correlation between the relative resistance change and the corresponding bending angles or elongation percentage. In addition, our E-Skin shows excellent sensitivity to voice vibration when exposed to a volunteer's voice vibration testing. Notably, the entire E-Skin fabrication process is scalable, low cost, and industrially available. Our complementary experiments with comprehensive results demonstrate that the developed GNP/PU E-Skin is impressively promising for practical healthcare applications in wearable devices, and enables us to monitor the real-world force signals in real-time and in-situ mode from pressing, hitting, bending, stretching, and voice vibration.

What makes a chemical an allergen?

PubMed

Kimber, Ian; Dearman, Rebecca J

2003-05-01

To consider the factors that confer on chemicals the ability to cause allergic sensitization, with particular emphasis on the induction of skin sensitization. Original and review articles available in the scientific literature. The expert opinion of the authors was used to select studies for inclusion in this review. A number of requirements must be met if a chemical is to induce skin sensitization. The most important requirements are access to the viable epidermis, the formation of stable conjugates with proteins, elicitation of cytokine production by skin cells, and the initiation of T-lymphocyte responses. In addition, qualitative aspects of induced immune responses influence the form of allergic sensitization. An increasingly sophisticated understanding of the factors required for the development of skin sensitization and other forms of chemical-induced allergy provides new opportunities for toxicological investigation and clinical management.

Bee venom processes human skin lipids for presentation by CD1a

PubMed Central

Bourgeois, Elvire A.; Subramaniam, Sumithra; Cheng, Tan-Yun; De Jong, Annemieke; Layre, Emilie; Ly, Dalam; Salimi, Maryam; Legaspi, Annaliza; Modlin, Robert L.; Salio, Mariolina; Cerundolo, Vincenzo

2015-01-01

Venoms frequently co-opt host immune responses, so study of their mode of action can provide insight into novel inflammatory pathways. Using bee and wasp venom responses as a model system, we investigated whether venoms contain CD1-presented antigens. Here, we show that venoms activate human T cells via CD1a proteins. Whereas CD1 proteins typically present lipids, chromatographic separation of venoms unexpectedly showed that stimulatory factors partition into protein-containing fractions. This finding was explained by demonstrating that bee venom–derived phospholipase A2 (PLA2) activates T cells through generation of small neoantigens, such as free fatty acids and lysophospholipids, from common phosphodiacylglycerides. Patient studies showed that injected PLA2 generates lysophospholipids within human skin in vivo, and polyclonal T cell responses are dependent on CD1a protein and PLA2. These findings support a previously unknown skin immune response based on T cell recognition of CD1a proteins and lipid neoantigen generated in vivo by phospholipases. The findings have implications for skin barrier sensing by T cells and mechanisms underlying phospholipase-dependent inflammatory skin disease. PMID:25584012

Method for detecting the reactivity of chemicals towards peptides as an alternative test method for assessing skin sensitization potential.

PubMed

Cho, Sun-A; Jeong, Yun Hyeok; Kim, Ji Hoon; Kim, Seoyoung; Cho, Jun-Cheol; Heo, Yong; Heo, Young; Suh, Kyung-Do; Shin, Kyeho; An, Susun

2014-02-10

Cosmetics are normally composed of various ingredients. Some cosmetic ingredients can act as chemical haptens reacting toward proteins or peptides of human skin and they can provoke an immunologic reaction, called as skin sensitization. This haptenation process is very important step of inducing skin sensitization and evaluating the sensitizing potentials of cosmetic ingredients is very important for consumer safety. Therefore, animal alternative methods focusing on monitoring haptenation potential are undergoing vigorous research. To examine the further usefulness of spectrophotometric methods to monitor reactivity of chemicals toward peptides for cosmetic ingredients. Forty chemicals (25 sensitizers and 15 non-sensitizers) were reacted with 2 synthetic peptides, e.g., the cysteine peptides (Ac-RFAACAA-COOH) with free thiol group and the lysine peptides (Ac-RFAAKAA-COOH) with free amine group. Unreacted peptides can be detected after incubating with 5,5'-dithiobis-2-nitrobenzoic acid or fluorescamine™ as detection reagents for free thiol and amine group, respectively. Chemicals were categorized as sensitizers when they induced more than 10% depletion of cysteine peptides or more than 30% depletion of lysine peptides. The sensitivity, specificity, and accuracy were 80.0%, 86.7% and 82.5%, respectively. These results demonstrate that spectrophotometric methods can be an easy, fast, and high-throughput screening tools predicting the skin sensitization potential of chemical including cosmetic ingredient. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Structure-activity relationships for skin sensitization: recent improvements to Derek for Windows.

PubMed

Langton, Kate; Patlewicz, Grace Y; Long, Anthony; Marchant, Carol A; Basketter, David A

2006-12-01

Derek for Windows (DfW) is a knowledge-based expert system that predicts the toxicity of a chemical from its structure. Its predictions are based in part on alerts that describe structural features or toxicophores associated with toxicity. Recently, improvements have been made to skin sensitization alerts within the DfW knowledge base in collaboration with Unilever. These include modifications to the alerts describing the skin sensitization potential of aldehydes, 1,2-diketones, and isothiazolinones and consist of enhancements to the toxicophore definition, the mechanistic classification, and the extent of supporting evidence provided. The outcomes from this collaboration demonstrate the importance of updating and refining computer models for the prediction of skin sensitization as new information from experimental and theoretical studies becomes available.

Squamous cell carcinoma-like and pox lesions occurring simultaneously in chorioallantoic membranes of chicken embryos inoculated with materials from squamous cell carcinoma and pox lesions in broiler chickens.

PubMed

Fallavena, L C; Rodrigues, N C; Moraes, H L; Salle, C T; da Silva, A B; Nascimento, V P; Rodrigues, O

1997-01-01

The finding of closely associated squamous cell carcinoma (SCC)-like lesions and pox lesions in chorioallantoic membranes (CAMs) inoculated with skin and palate samples taken from broilers is described. The samples were obtained from two broilers coming from different flocks that were not vaccinated against fowl pox. Both birds presented skin lesions, which were diagnosed in one bird as fowl pox, and in the other as SCC. After inoculation of CAMs with fresh tissues from both birds, histologic examination revealed, in all CAMs, lesions that were characteristic of fowl pox together with lesions consistent with those seen in the skin of broilers affected with SCC. This finding was unexpected and may shed some light on the etiology of SCC.

LLNA variability: An essential ingredient for a comprehensive assessment of non-animal skin sensitization test methods and strategies.

PubMed

Hoffmann, Sebastian

2015-01-01

The development of non-animal skin sensitization test methods and strategies is quickly progressing. Either individually or in combination, the predictive capacity is usually described in comparison to local lymph node assay (LLNA) results. In this process the important lesson from other endpoints, such as skin or eye irritation, to account for variability reference test results - here the LLNA - has not yet been fully acknowledged. In order to provide assessors as well as method and strategy developers with appropriate estimates, we investigated the variability of EC3 values from repeated substance testing using the publicly available NICEATM (NTP Interagency Center for the Evaluation of Alternative Toxicological Methods) LLNA database. Repeat experiments for more than 60 substances were analyzed - once taking the vehicle into account and once combining data over all vehicles. In general, variability was higher when different vehicles were used. In terms of skin sensitization potential, i.e., discriminating sensitizer from non-sensitizers, the false positive rate ranged from 14-20%, while the false negative rate was 4-5%. In terms of skin sensitization potency, the rate to assign a substance to the next higher or next lower potency class was approx.10-15%. In addition, general estimates for EC3 variability are provided that can be used for modelling purposes. With our analysis we stress the importance of considering the LLNA variability in the assessment of skin sensitization test methods and strategies and provide estimates thereof.

Highly sensitive, self-powered and wearable electronic skin based on pressure-sensitive nanofiber woven fabric sensor.

PubMed

Zhou, Yuman; He, Jianxin; Wang, Hongbo; Qi, Kun; Nan, Nan; You, Xiaolu; Shao, Weili; Wang, Lidan; Ding, Bin; Cui, Shizhong

2017-10-11

The wearable electronic skin with high sensitivity and self-power has shown increasing prospects for applications such as human health monitoring, robotic skin, and intelligent electronic products. In this work, we introduced and demonstrated a design of highly sensitive, self-powered, and wearable electronic skin based on a pressure-sensitive nanofiber woven fabric sensor fabricated by weaving PVDF electrospun yarns of nanofibers coated with PEDOT. Particularly, the nanofiber woven fabric sensor with multi-leveled hierarchical structure, which significantly induced the change in contact area under ultra-low load, showed combined superiority of high sensitivity (18.376 kPa -1 , at ~100 Pa), wide pressure range (0.002-10 kPa), fast response time (15 ms) and better durability (7500 cycles). More importantly, an open-circuit voltage signal of the PPNWF pressure sensor was obtained through applying periodic pressure of 10 kPa, and the output open-circuit voltage exhibited a distinct switching behavior to the applied pressure, indicating the wearable nanofiber woven fabric sensor could be self-powered under an applied pressure. Furthermore, we demonstrated the potential application of this wearable nanofiber woven fabric sensor in electronic skin for health monitoring, human motion detection, and muscle tremor detection.

Air-borne and tissue-borne sensitivities of bioacoustic sensors used on the skin surface.

PubMed

Zañartu, Matías; Ho, Julio C; Kraman, Steve S; Pasterkamp, Hans; Huber, Jessica E; Wodicka, George R

2009-02-01

Measurements of body sounds on the skin surface have been widely used in the medical field and continue to be a topic of current research, ranging from the diagnosis of respiratory and cardiovascular diseases to the monitoring of voice dosimetry. These measurements are typically made using light-weight accelerometers and/or air-coupled microphones attached to the skin. Although normally neglected, air-borne sounds generated by the subject or other sources of background noise can easily corrupt such recordings, which is particularly critical in the recording of voiced sounds on the skin surface. In this study, the sensitivity of commonly used bioacoustic sensors to air-borne sounds was evaluated and compared with their sensitivity to tissue-borne body sounds. To delineate the sensitivity to each pathway, the sensors were first tested in vitro and then on human subjects. The results indicated that, in general, the air-borne sensitivity is sufficiently high to significantly corrupt body sound signals. In addition, the air-borne and tissue-borne sensitivities can be used to discriminate between these components. Although the study is focused on the evaluation of voiced sounds on the skin surface, an extension of the proposed methods to other bioacoustic applications is discussed.

Comparative analysis of skin sensitization potency of acrylates (methyl acrylate, ethyl acrylate, butyl acrylate, and ethylhexyl acrylate) using the local lymph node assay.

PubMed

Dearman, Rebecca J; Betts, Catherine J; Farr, Craig; McLaughlin, James; Berdasco, Nancy; Wiench, Karin; Kimber, Ian

2007-10-01

There are currently available no systematic experimental data on the skin sensitizing properties of acrylates that are of relevance in occupational settings. Limited information from previous guinea-pig tests or from the local lymph node assay (LLNA) is available; however, these data are incomplete and somewhat contradictory. For those reasons, we have examined in the LLNA 4 acrylates: butyl acrylate (BA), ethyl acrylate (EA), methyl acrylate (MA), and ethylhexyl acrylate (EHA). The LLNA data indicated that all 4 compounds have some potential to cause skin sensitization. In addition, the relative potencies of these acrylates were measured by derivation from LLNA dose-response analyses of EC3 values (the effective concentration of chemical required to induce a threefold increase in proliferation of draining lymph node cells compared with control values). On the basis of 1 scheme for the categorization of skin sensitization potency, BA, EA, and MA were each classified as weak sensitizers. Using the same scheme, EHA was considered a moderate sensitizer. However, it must be emphasized that the EC3 value for this chemical of 9.7% is on the borderline between moderate (<10%) and weak (>10%) categories. Thus, the judicious view is that all 4 chemicals possess relatively weak skin sensitizing potential.

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

PubMed

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.

Advanced Development of Leishmania Topical Skin Test Antigen

DTIC Science & Technology

2012-09-28

can cause sensitization manifest by the conversion of a negative to positive delayed-type hypersensitivity (DTH) skin test. This was observed on the...third skin test with 30 ug and 50 ug doses of the crude lysate administered intradermally at monthly intervals. Fractionation of the lysate...identified dominant proteins at 8 kDa, 20 kDa, and 56-58 kDa. Skin tests in L. tropica sensitized guinea pigs with each of these fractions revealed

Biodegradable Polymers Induce CD54 on THP-1 Cells in Skin Sensitization Test.

PubMed

Jung, Yeon Suk; Kato, Reiko; Tsuchiya, Toshie

2011-01-01

Currently, nonanimal methods of skin sensitization testing for various chemicals, biodegradable polymers, and biomaterials are being developed in the hope of eliminating the use of animals. The human cell line activation test (h-CLAT) is a skin sensitization assessment that mimics the functions of dendritic cells (DCs). DCs are specialized antigen-presenting cells, and they interact with T cells and B cells to initiate immune responses. Phenotypic changes in DCs, such as the production of CD86 and CD54 and internalization of MHC class II molecules, have become focal points of the skin sensitization test. In this study, we used h-CLAT to assess the effects of biodegradable polymers. The results showed that several biodegradable polymers increased the expression of CD54, and the relative skin sensitizing abilities of biodegradable polymers were PLLG (75 : 25) < PLLC (40 : 60) < PLGA (50 : 50) < PCG (50 : 50). These results may contribute to the creation of new guidelines for the use of biodegradable polymers in scaffolds or allergenic hazards.

Evaluation of Cytology for Diagnosing Avian Pox in Wild Turkeys ( Meleagris gallopavo).

PubMed

Hydock, Kira; Brown, Holly; Nemeth, Nicole; Poulson, Rebecca; Casalena, Mary Jo; Johnson, Joshua B; Brown, Justin

2018-03-01

Avian pox virus is a common cause of proliferative skin disease in wild turkeys ( Meleagris gallopavo); however, other etiologies may produce grossly indistinguishable lesions. Common methods for diagnosing avian pox include histopathology, virus isolation, and PCR. While these methods are sufficient in most cases, each has their limitations. Cytology is a cost-effective and rapid approach that may be useful when traditional diagnostics are not feasible. The objective of this study was to evaluate the performance of cytology relative to histopathology and PCR for avian pox diagnosis in wild turkeys. Fifty wild turkeys were submitted for necropsy due to nodular skin lesions on unfeathered skin of the head. Of these, five had similar skin lesions on the unfeathered legs and 26 had plaques on the mucosa of the oropharynx or esophagus. Representative skin, oropharyngeal, and esophageal lesions from all birds were examined with cytology and histopathology. Skin lesions on the head of each bird were also tested for avian pox virus via PCR. Histopathology and PCR were equally sensitive in diagnosing avian pox from skin lesions on the head. There were no significant differences between cytologic and histopathologic diagnosis of avian pox from skin lesions on the head (sensitivity = 97.4%, specificity = 100.0%), legs (sensitivity = 75.0%, specificity = 100.0%), or from lesions in the oropharynx and esophagus (sensitivity of 62.5%). Similarly, there were no significant differences between PCR and cytology for diagnosis of pox viral skin lesions of the head. Relative to PCR detection of avian pox virus, cytology had a sensitivity of 90.0% and a specificity of 90.0%. These results suggest that cytology is a useful tool for diagnosis of avian pox in wild turkeys.

Mechanism for initiation of food allergy: Dependence on skin barrier mutations and environmental allergen costimulation.

PubMed

Walker, Matthew T; Green, Jeremy E; Ferrie, Ryan P; Queener, Ashley M; Kaplan, Mark H; Cook-Mills, Joan M

2018-05-01

Mechanisms for the development of food allergy in neonates are unknown but clearly linked in patient populations to a genetic predisposition to skin barrier defects. Whether skin barrier defects contribute functionally to development of food allergy is unknown. The purpose of the study was to determine whether skin barrier mutations, which are primarily heterozygous in patient populations, contribute to the development of food allergy. Mice heterozygous for the filaggrin (Flg) ft and Tmem79 ma mutations were skin sensitized with environmental and food allergens. After sensitization, mice received oral challenge with food allergen, and then inflammation, inflammatory mediators, and anaphylaxis were measured. We define development of inflammation, inflammatory mediators, and food allergen-induced anaphylaxis in neonatal mice with skin barrier mutations after brief concurrent cutaneous exposure to food and environmental allergens. Moreover, neonates of allergic mothers have increased responses to suboptimal sensitization with food allergens. Importantly, responses to food allergens by these neonatal mice were dependent on genetic defects in skin barrier function and on exposure to environmental allergens. ST2 blockade during skin sensitization inhibited the development of anaphylaxis, antigen-specific IgE, and inflammatory mediators. Neonatal anaphylactic responses and antigen-specific IgE were also inhibited by oral pre-exposure to food allergen, but interestingly, this was blunted by concurrent pre-exposure of the skin to environmental allergen. These studies uncover mechanisms for food allergy sensitization and anaphylaxis in neonatal mice that are consistent with features of human early-life exposures and genetics in patients with clinical food allergy and demonstrate that changes in barrier function drive development of anaphylaxis to food allergen. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Incorporating uncertainty into medical decision making: an approach to unexpected test results.

PubMed

Bianchi, Matt T; Alexander, Brian M; Cash, Sydney S

2009-01-01

The utility of diagnostic tests derives from the ability to translate the population concepts of sensitivity and specificity into information that will be useful for the individual patient: the predictive value of the result. As the array of available diagnostic testing broadens, there is a temptation to de-emphasize history and physical findings and defer to the objective rigor of technology. However, diagnostic test interpretation is not always straightforward. One significant barrier to routine use of probability-based test interpretation is the uncertainty inherent in pretest probability estimation, the critical first step of Bayesian reasoning. The context in which this uncertainty presents the greatest challenge is when test results oppose clinical judgment. It is this situation when decision support would be most helpful. The authors propose a simple graphical approach that incorporates uncertainty in pretest probability and has specific application to the interpretation of unexpected results. This method quantitatively demonstrates how uncertainty in disease probability may be amplified when test results are unexpected (opposing clinical judgment), even for tests with high sensitivity and specificity. The authors provide a simple nomogram for determining whether an unexpected test result suggests that one should "switch diagnostic sides.'' This graphical framework overcomes the limitation of pretest probability uncertainty in Bayesian analysis and guides decision making when it is most challenging: interpretation of unexpected test results.

Prevalence of pollen sensitization in younger children who have asthma.

PubMed

Ogershok, Paul R; Warner, Daniel J; Hogan, Mary Beth; Wilson, Nevin W

2007-01-01

It is commonly believed that young children are incapable of pollen sensitization; therefore, skin testing usually is not performed to these allergens. The purpose of this study was to identify the frequency of positive skin tests to outdoor allergens among younger children who have asthma. Patients who have asthma, aged 6 months to 10 years, were evaluated for pollen sensitization over a 10-year period. Skin-prick testing was performed to relevant individual aeroallergens including trees, grasses, and weeds. Testing for perennial indoor allergens such as dust mites, cats, dogs, cockroaches, and molds was performed also. A total of 687 children with asthma were evaluated. No child <12 months old was sensitized to pollens. Children between 12 and 24 months of age had a 29% incidence of pollen sensitization. Three-year-old children were as likely to be skin test positive to pollen as an indoor allergen. Notably, 49% of 3- and 4-year olds were sensitized to outdoor allergens. Primary sensitizing pollens in this age group were short ragweed, box elder, and June grass. In this population, pollen sensitization was not related to tobacco or wood smoke exposure. Although it is widely believed that young children with asthma are most commonly allergic to indoor allergens, almost 40% of our 1- to 3-year old children with asthma showed IgE-mediated sensitivity to outdoor allergens. Pediatric allergists should consider performing skin-prick testing to their local common aeroallergens in young children with asthma and seasonal symptoms.

Skin exposure promotes a Th2 - dependent sensitization to peanut allergens

USDA-ARS?s Scientific Manuscript database

Sensitization to foods often occurs in infancy without known prior oral exposure, which suggests that alternative routes of exposure contribute to food allergy. We hypothesized that peanut activates innate immune pathways in the skin that promote sensitization. We tested this hypothesis by topical...

The processing of unexpected positive response outcomes in the mediofrontal cortex.

PubMed

Ferdinand, Nicola K; Mecklinger, Axel; Kray, Jutta; Gehring, William J

2012-08-29

The human mediofrontal cortex, especially the anterior cingulate cortex, is commonly assumed to contribute to higher cognitive functions like performance monitoring. How exactly this is achieved is currently the subject of lively debate but there is evidence that an event's valence and its expectancy play important roles. One prominent theory, the reinforcement learning theory by Holroyd and colleagues (2002, 2008), assigns a special role to feedback valence, while the prediction of response-outcome (PRO) model by Alexander and Brown (2010, 2011) claims that the mediofrontal cortex is sensitive to unexpected events regardless of their valence. However, paradigms examining this issue have included confounds that fail to separate valence and expectancy. In the present study, we tested the two competing theories of performance monitoring by using an experimental task that separates valence and unexpectedness of performance feedback. The feedback-related negativity of the event-related potential, which is commonly assumed to be a reflection of mediofrontal cortex activity, was elicited not only by unexpected negative feedback, but also by unexpected positive feedback. This implies that the mediofrontal cortex is sensitive to the unexpectedness of events in general rather than their valence and by this supports the PRO model.

The pain of altruism.

PubMed

Finlay, Barbara L; Syal, Supriya

2014-12-01

Sociality and cooperation are benefits to human cultures but may carry unexpected costs. We suggest that both the human experience of pain and the expression of distress may result from many causes not experienced as painful in our close primate relatives, because human ancestors motivated to ask for help survived in greater numbers than either the thick-skinned or the stoic. Copyright © 2014 Elsevier Ltd. All rights reserved.

The pilosebaceous unit—a phthalate-induced pathway to skin sensitization

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

Simonsson, Carl, E-mail: carl.simonsson@chem.gu.se; Stenfeldt, Anna-Lena; Karlberg, Ann-Therese

2012-10-01

Allergic contact dermatitis (ACD) is caused by low-molecular weight compounds called haptens. It has been shown that the potency of haptens can depend on the formulation in which they are applied on the skin. Specifically the sensitization potency of isothiocyanates, a group of haptens which can be released from e.g. adhesive tapes and neoprene materials, increases with the presence of phthalates; however, the underlying mechanisms are not clear. A better understanding of the mechanisms governing the potency of haptens is important, e.g. to improve the risk assessment and the formulation of chemicals in consumer products. In this study we havemore » explored phthalate-induced effects on the sensitization potency, skin distribution, and reactivity of fluorescent model isothiocyanate haptens using non-invasive two-photon microscopy to provide new insights regarding vehicle effects in ACD. The data presented in this paper indicate that the sensitization potency of isothiocyanates increases when applied in combination with dibutylphthalate due to a specific uptake via the pilosebaceous units. The results highlight the importance of shunt pathways when evaluating the bioavailability of skin sensitizers. The findings also indicate that vehicle-dependent hapten reactivity towards stratum corneum proteins regulates the bioavailability, and thus the potency, of skin sensitizers. -- Highlights: ► Vehicle effects on sensitization potency were investigated in the LLNA. ► In vivo cutaneous absorption of contact sensitizers was visualized using TPM. ► Sensitizing potency of isothiocyanates depends on the presence of a phthalate. ► Phthalate induced cutaneous absorption via the pilosebaceous units. ► Vehicle-dependent reactivity regulates sensitization potency.« less

Prevalence of and risk factors for latex sensitization in patients with spina bifida.

PubMed

Bernardini, R; Novembre, E; Lombardi, E; Mezzetti, P; Cianferoni, A; Danti, A D; Mercurella, A; Vierucci, A

1998-11-01

We determined the prevalence of and risk factors for latex sensitization in patients with spina bifida. A total of 59 consecutive subjects 2 to 40 years old with spina bifida answered a questionnaire, and underwent a latex skin prick test and determination of serum IgE specific for latex by RAST CAP radioimmunoassay. We also noted the relationships of total serum IgE skin prick tests to common air and food allergens. In addition, skin prick plus prick tests were also done with fresh foods, including kiwi, pear, orange, almond, pineapple, apple, tomato and banana. Latex sensitization was present in 15 patients (25%) according to the presence of IgE specific to latex, as detected by a skin prick test in 9 and/or RAST CAP in 13. Five latex sensitized patients (33.3%) had clinical manifestations, such as urticaria, conjuctivitis, angioedema, rhinitis and bronchial asthma, while using a latex glove and inflating a latex balloon. Atopy was present in 21 patients (35.6%). In 14 patients (23%) 1 or more skin tests were positive for fresh foods using a prick plus prick technique. Tomato, kiwi, and pear were the most common skin test positive foods. Univariate analysis revealed that a history of 5 or more operations, atopy and positive prick plus prick tests results for pear and kiwi were significantly associated with latex sensitization. Multivariate analysis demonstrated that only atopy and a history of 5 or more operations were significantly and independently associated with latex sensitization. A fourth of the patients with spina bifida were sensitized to latex. Atopy and an elevated number of operations were significant and independent predictors of latex sensitization in these cases.

ISOLATION OF RABBIT IGA ANTIHAPTEN ANTIBODY AND DEMONSTRATION OF SKIN-SENSITIZING ACTIVITY IN HOMOLOGOUS SKIN

PubMed Central

Onoue, Kaoru; Yagi, Yasuo; Pressman, David

1966-01-01

Multiple antibody components of rabbit antisera against p-azobenzenearsonate (Rp) were studied with respect to their globulin nature and skin-sensitizing activity. IgA antibody was characterized by isolating two IgA-rich fractions from a specifically purified antibody preparation. Examination of these fractions showed that IgA antibodies existed in two molecular forms, one with a sedimentation constant of 7S and the other 9S. Skin-sensitizing activity was examined by a P-K type test and a PCA test with Rp-rabbit serum albumin in homologous (rabbit) species. Only the 7S but not 9S IgA antibody sensitized rabbit skin. IgM antibody showed no activity and IgG antibody showed very low activity. In contrast, only IgG antibody was active in the P-K type test to sensitize a heterologous species (guinea pig). None of the antibodies of other classes showed sensitizing activity in heterologous skin. The 7S IgA antibody lost its sensitizing activity upon reduction and alkylation, although no change in its molecular size could be observed. The loss of sensitizing activity was not due to the destruction of antigen-binding activity since the treated 7S IgA antibody retained this activity as shown by radioimmunoelectrophoresis and by binding to the specific immunoadsorbent. The 9S IgA antibody was more resistant to these treatments than the IgM antibody and showed no indication of dissociation. The treated 9S IgA also retained antigen-binding activity. Both the P-K type and PCA reactions were considerably stronger when the interval between injections of antibody and antigen was 24 hr rather than 4 to 5 hr. PMID:4159250

Local lymph node assay (LLNA) for detection of sensitization capacity of chemicals.

PubMed

Gerberick, G Frank; Ryan, Cindy A; Dearman, Rebecca J; Kimber, Ian

2007-01-01

The local lymph node assay (LLNA) is a murine model developed to evaluate the skin sensitization potential of chemicals. The LLNA is an alternative approach to traditional guinea pig methods and in comparison provides important animal welfare benefits. The assay relies on measurement of events induced during the induction phase of skin sensitization, specifically lymphocyte proliferation in the draining lymph nodes which is a hallmark of a skin sensitization response. Since its introduction the LLNA has been the subject of extensive evaluation on a national and international scale, and has been successfully validated and incorporated worldwide into regulatory guidelines. Experience gained in recent years has demonstrated that adherence to published procedures and guidelines for the LLNA (e.g., with respect to dose and vehicle selection) is critical for the successful conduct and eventual interpretation of the data. In addition to providing a robust method for skin sensitization hazard identification, the LLNA has proven very useful in assessing the skin sensitizing potency of test chemicals, and this has provided invaluable information to risk assessors. The primary method to make comparisons of the relative potency of chemical sensitizers is to use linear interpolation to estimate the concentration of chemical required to induce a stimulation index of three relative to concurrent vehicle-treated controls (EC3). In certain situations where there are available less than optimal dose response data a log-linear extrapolation method can be used to estimate an EC3 value which can reduce significantly the need for repeat testing of chemicals. The LLNA, when conducted according to published guidelines, provides a robust method for skin sensitization testing that not only provides reliable hazard identification information but also data necessary for effective risk assessment and risk management.

Unsaturated fatty acids show clear elicitation responses in a modified local lymph node assay with an elicitation phase, and test positive in the direct peptide reactivity assay.

PubMed

Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Miyazaki, Hiroshi; Itagaki, Hiroshi

2015-12-01

The Organisation for Economic Co-operation and Development (OECD) Test Guidelines (TG) adopted the murine local lymph node assay (LLNA) and guinea pig maximization test (GPMT) as stand-alone skin sensitization test methods. However, unsaturated carbon-carbon double-bond and/or lipid acids afforded false-positive results more frequently in the LLNA compared to those in the GPMT and/or in human subjects. In the current study, oleic, linoleic, linolenic, undecylenic, fumaric, maleic, and succinic acid and squalene were tested in a modified LLNA with an elicitation phase (LLNA:DAE), and in a direct peptide reactivity assay (DPRA) to evaluate their skin-sensitizing potential. Oleic, linoleic, linolenic, undecylenic and maleic acid were positive in the LLNA:DAE, of which three, linoleic, linolenic, and maleic acid were positive in the DPRA. Furthermore, the results of the cross-sensitizing tests using four LLNA:DAE-positive chemicals were negative, indicating a chemical-specific elicitation response. In a previous report, the estimated concentration needed to produce a stimulation index of 3 (EC3) of linolenic acid, squalene, and maleic acid in the LLNA was < 10%. Therefore, these chemicals were classified as moderate skin sensitizers in the LLNA. However, the skin-sensitizing potential of all LLNA:DAE-positive chemicals was estimated as weak. These results suggested that oleic, linoleic, linolenic, undecylenic, and maleic acid had skin-sensitizing potential, and that the LLNA overestimated the skin-sensitizing potential compared to that estimated by the LLNA:DAE.

Laser Doppler assessment of skin blood flow in arteriopathic limbs.

PubMed

Allen, P I; Goldman, M

1987-05-01

In severely ischaemic lower limbs, the skin response to changing posture from lying to standing is a diagnostic flush. We investigated this observation by measurements of the microcirculation using the non-invasive laser Doppler technique. Eleven patients with ankle: brachial pressure (A:B) ratios less than 0.7 were compared with 13 age-matched controls (A:B ratios greater than 1). In normal subjects, mean horizontal skin blood flow (SBF) was 30.2 +/- 14.9 (+/- SD), significantly greater than mean SBF in the ischaemic group: 12.4 +/- 9.2 (P less than 0.01, Student's t test). Mean SBF fell in the normal group on dependency to 27.5 +/- 16.4 but this change was not significant. Unexpectedly mean SBF rose in the ischaemic limbs to 20.7 +/- 13.8 (P less than 0.05). The pattern of SBF response to change in posture is different in normal and arteriopathic limbs.

The local lymph node assay and skin sensitization testing.

PubMed

Kimber, Ian; Dearman, Rebecca J

2010-01-01

The mouse local lymph node assay (LLNA) is a method for the identification and characterization of skin sensitization hazards. In this context the method can be used both to identify contact allergens, and also determine the relative skin sensitizing potency as a basis for derivation of effective risk assessments.The assay is based on measurement of proliferative responses by draining lymph node cells induced following topical exposure of mice to test chemicals. Such responses are known to be causally and quantitatively associated with the acquisition of skin sensitization and therefore provide a relevant marker for characterization of contact allergic potential.The LLNA has been the subject of exhaustive evaluation and validation exercises and has been assigned Organization for Economic Cooperation and Development (OECD) test guideline 429. Herein we describe the conduct and interpretation of the LLNA.

Effects of unexpected chords and of performer's expression on brain responses and electrodermal activity.

PubMed

Koelsch, Stefan; Kilches, Simone; Steinbeis, Nikolaus; Schelinski, Stefanie

2008-07-09

There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition. These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music.

Animal origin of 13th-century uterine vellum revealed using noninvasive peptide fingerprinting

PubMed Central

Fiddyment, Sarah; Holsinger, Bruce; Ruzzier, Chiara; Devine, Alexander; Binois, Annelise; Albarella, Umberto; Fischer, Roman; Nichols, Emma; Curtis, Antoinette; Cheese, Edward; Teasdale, Matthew D.; Checkley-Scott, Caroline; Milner, Stephen J.; Rudy, Kathryn M.; Johnson, Eric J.; Vnouček, Jiří; Garrison, Mary; McGrory, Simon; Bradley, Daniel G.; Collins, Matthew J.

2015-01-01

Tissue-thin parchment made it possible to produce the first pocket Bibles: Thousands were made in the 13th century. The source of this parchment, often called “uterine vellum,” has been a long-standing controversy in codicology. Use of the Latin term abortivum in many sources has led some scholars to suggest that the skin of fetal calves or sheep was used. Others have argued that it would not be possible to sustain herds if so many pocket Bibles were produced from fetal skins, arguing instead for unexpected alternatives, such as rabbit. Here, we report a simple and objective technique using standard conservation treatments to identify the animal origin of parchment. The noninvasive method is a variant on zooarchaeology by mass spectrometry (ZooMS) peptide mass fingerprinting but extracts protein from the parchment surface by using an electrostatic charge generated by gentle rubbing of a PVC eraser on the membrane surface. Using this method, we analyzed 72 pocket Bibles originating in France, England, and Italy and 293 additional parchment samples that bracket this period. We found no evidence for the use of unexpected animals; however, we did identify the use of more than one mammal species in a single manuscript, consistent with the local availability of hides. These results suggest that ultrafine vellum does not necessarily derive from the use of abortive or newborn animals with ultrathin hides, but could equally well reflect a production process that allowed the skins of maturing animals of several species to be rendered into vellum of equal quality and fineness. PMID:26598667

In vivo optical elastography: stress and strain imaging of human skin lesions

NASA Astrophysics Data System (ADS)

Es'haghian, Shaghayegh; Gong, Peijun; Kennedy, Kelsey M.; Wijesinghe, Philip; Sampson, David D.; McLaughlin, Robert A.; Kennedy, Brendan F.

2015-03-01

Probing the mechanical properties of skin at high resolution could aid in the assessment of skin pathologies by, for example, detecting the extent of cancerous skin lesions and assessing pathology in burn scars. Here, we present two elastography techniques based on optical coherence tomography (OCT) to probe the local mechanical properties of skin. The first technique, optical palpation, is a high-resolution tactile imaging technique, which uses a complaint silicone layer positioned on the tissue surface to measure spatially-resolved stress imparted by compressive loading. We assess the performance of optical palpation, using a handheld imaging probe on a skin-mimicking phantom, and demonstrate its use on human skin. The second technique is a strain imaging technique, phase-sensitive compression OCE that maps depth-resolved mechanical variations within skin. We show preliminary results of in vivo phase-sensitive compression OCE on a human skin lesion.

In vivo observation of age-related structural changes of dermal collagen in human facial skin using collagen-sensitive second harmonic generation microscope equipped with 1250-nm mode-locked Cr:Forsterite laser

NASA Astrophysics Data System (ADS)

Yasui, Takeshi; Yonetsu, Makoto; Tanaka, Ryosuke; Tanaka, Yuji; Fukushima, Shu-ichiro; Yamashita, Toyonobu; Ogura, Yuki; Hirao, Tetsuji; Murota, Hiroyuki; Araki, Tsutomu

2013-03-01

In vivo visualization of human skin aging is demonstrated using a Cr:Forsterite (Cr:F) laser-based, collagen-sensitive second harmonic generation (SHG) microscope. The deep penetration into human skin, as well as the specific sensitivity to collagen molecules, achieved by this microscope enables us to clearly visualize age-related structural changes of collagen fiber in the reticular dermis. Here we investigated intrinsic aging and/or photoaging in the male facial skin. Young subjects show dense distributions of thin collagen fibers, whereas elderly subjects show coarse distributions of thick collagen fibers. Furthermore, a comparison of SHG images between young and elderly subjects with and without a recent life history of excessive sun exposure show that a combination of photoaging with intrinsic aging significantly accelerates skin aging. We also perform image analysis based on two-dimensional Fourier transformation of the SHG images and extracted an aging parameter for human skin. The in vivo collagen-sensitive SHG microscope will be a powerful tool in fields such as cosmeceutical sciences and anti-aging dermatology.

Application of the KeratinoSens™ assay for assessing the skin sensitization potential of agrochemical active ingredients and formulations.

PubMed

Settivari, Raja S; Gehen, Sean C; Amado, Ricardo Acosta; Visconti, Nicolo R; Boverhof, Darrell R; Carney, Edward W

2015-07-01

Assessment of skin sensitization potential is an important component of the safety evaluation process for agrochemical products. Recently, non-animal approaches including the KeratinoSens™ assay have been developed for predicting skin sensitization potential. Assessing the utility of the KeratinoSens™ assay for use with multi-component mixtures such as agrochemical formulations has not been previously evaluated and is a significant need. This study was undertaken to evaluate the KeratinoSens™ assay prediction potential for agrochemical formulations. The assay was conducted for 8 agrochemical active ingredients (AIs) including 3 sensitizers (acetochlor, meptyldinocap, triclopyr), 5 non-sensitizers (aminopyralid, clopyralid, florasulam, methoxyfenozide, oxyfluorfen) and 10 formulations for which in vivo sensitization data were available. The KeratinoSens™ correctly predicted the sensitization potential of all the AIs. For agrochemical formulations it was necessary to modify the standard assay procedure whereby the formulation was assumed to have a common molecular weight. The resultant approach correctly predicted the sensitization potential for 3 of 4 sensitizing formulations and all 6 non-sensitizing formulations when compared to in vivo data. Only the meptyldinocap-containing formulation was misclassified, as a result of high cytotoxicity. These results demonstrate the promising utility of the KeratinoSens™ assay for evaluating the skin sensitization potential of agrochemical AIs and formulations. Copyright © 2015 Elsevier Inc. All rights reserved.

Thresholds of skin sensitivity are partially influenced by mechanical properties of the skin on the foot sole

PubMed Central

Strzalkowski, Nicholas D J; Triano, John J; Lam, Chris K; Templeton, Cale A; Bent, Leah R

2015-01-01

Across the foot sole, there are vibration and monofilament sensory differences despite an alleged even distribution of cutaneous afferents. Mechanical property differences across foot sole sites have been proposed to account for these differences. Vibration (VPT; 3 Hz, 40 Hz, 250 Hz), and monofilament (MF) perception threshold measurements were compared with skin hardness, epidermal thickness, and stretch response across five foot sole locations in young healthy adults (n = 22). Perceptual thresholds were expected to correlate with all mechanical property measurements to help address sensitivity differences between sites. Following this hypothesis, the MedArch was consistently found to be the thinnest and softest site and demonstrated the greatest sensitivity. Conversely, the Heel was found to be the thickest and hardest site, and was relatively insensitive across perceptual tests. Site differences were not observed for epidermal stretch response measures. Despite an apparent trend of elevated sensory threshold at harder and thicker sites, significant correlations between sensitivity measures and skin mechanical properties were not observed. Skin hardness and epidermal thickness appeared to have a negligible influence on VPT and minor influence on MF within this young healthy population. When normalized (% greater or smaller than subject mean) to the subject mean for each variable, significant positive correlations were observed between MF and skin hardness (R2 = 0.422, P < 0.0001) and epidermal thickness (R2 = 0.433, P < 0.0001) providing evidence that skin mechanics can influence MF threshold. In young healthy adults, differences in sensitivity are present across the foot sole, but cannot solely be accounted for by differences in the mechanical properties of the skin. PMID:26059035

Tolerability of Crisaborole Ointment for Application on Sensitive Skin Areas: A Randomized, Double-Blind, Vehicle-Controlled Study in Healthy Volunteers.

PubMed

Zane, Lee T; Hughes, Matilda H; Shakib, Sepehr

2016-10-01

Inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis often present in sensitive and thin-skinned areas that are at higher risk for topical treatment-related skin irritation (e.g., burning, stinging). Our objective was to address the need for topical treatments that can be safely applied to these areas. We assessed the local tolerability of crisaborole topical ointment when applied to sensitive and thin-skinned areas of healthy volunteers. In this phase I, randomized, double-blind, vehicle-controlled, single-center study, 32 subjects were randomized 3:1 to twice-daily application of crisaborole topical ointment, 2 %, (n = 24) or vehicle ointment (n = 8) for 21 days to 13 anatomic skin areas, including the face/hairline, genitals, extensor, and intertriginous areas. The primary endpoint was assessment of the frequency and severity of local tolerability symptoms (burning/stinging, erythema, and pruritus) using the Local Tolerability Scale. Overall, 98.8 % of all tolerability assessments had a grade of 0 (no signs/symptoms of irritation) and 0.1 % had a grade >1 (mild); no differences were observed in the frequency of local tolerability scores between treatment groups. The total frequency of local tolerability assessments graded >0 (none) was lower across all application sites with crisaborole ointment (0.0-2.2 %) than with vehicle ointment (2.4-7.1 %). Local tolerability did not change over time, and was comparable between sensitive and nonsensitive skin areas. Crisaborole ointment application to sensitive skin areas was well tolerated in healthy volunteers, supporting its potential role as a topical treatment alternative for patients with AD or psoriasis.

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

PubMed

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.

Laser-evoked potentials mediated by mechano-insensitive nociceptors in human skin.

PubMed

Dusch, M; van der Ham, J; Weinkauf, B; Benrath, J; Rukwied, R; Ringkamp, M; Schmelz, M; Treede, R-D; Baumgärtner, U

2016-05-01

Laser-evoked potentials (LEP) were assessed after peripheral nerve block of the lateral femoral cutaneous nerve (LFCN) in healthy volunteers from partially anesthetized skin areas to differentially stimulate mechano-insensitive nociceptors. An ultrasound-guided nerve block of the LFCN was performed in 12 healthy male subjects with Ropivacain 1%. After 30 min, the nerve block induced significantly larger anesthetic areas to mechanical stimuli than to electrical stimuli revealing an area of differential sensitivity. LEPs, reaction times and pain ratings were recorded in response to the laser stimuli of (1) completely anesthetic skin, (2) mechano-insensitive, but electrically excitable skin ('differential sensitivity'), (3) normal skin. LEP latencies in the area of differential sensitivity were increased compared to unaffected skin (228 ± 8.5 ms, vs. 181 ± 3.6 ms, p < 0.01) and LEP amplitudes were reduced (14.8 ± 1.2 μV vs. 24.6 ± 1.7 μV, p < 0.01). Correspondingly, psychophysically assessed response latencies in the differentially anesthetic skin were increased (649 ms vs. 427 ms, p < 0.01) and pain ratings reduced (1.5/10 vs. 5/10 NRS, p < 0.01). The increase in LEP latency suggests that mechano-insensitive heat-sensitive Aδ nociceptors (MIA, type II) have a slower conduction velocity or higher utilization time than mechano-sensitive type II Aδ nociceptors. Moreover, widely branched, slowly conducting and mechano-insensitive branches of Aδ nociceptors can explain our finding. LEPs in the differentially anesthetized skin provide specific information about a mechanically insensitive but heat-sensitive subpopulation of Aδ nociceptors. These findings support the concept that A-fibre nociceptors exhibit a similar degree of modality specificity as C-fibre nociceptors. © 2015 European Pain Federation - EFIC®

Gelatin prepared from tuna skin: a risk factor for fish allergy or sensitization?

PubMed

André, Françoise; Cavagna, Sylvie; André, Claude

2003-01-01

Although fish gelatin may represent a useful alternative to bovine or porcine gelatin, the clearly recognized high prevalence of fish allergy could increase the risk of anaphylaxis to gelatin. The rationale for investigating tuna gelatin rather than gelatin from more allergenic fishes is the availability of an industrial gelatin under development. The infrequent occurrence of tuna allergy should influence the safety of a derived product. The present study investigated IgE antibodies to tuna-skin-derived gelatin in adults and children with documented fish allergy or sensitization. Serum samples were taken from 100 consecutive patients with fish allergy or sensitization and tested for IgE antibodies against hydrolyzed or nonhydrolyzed gelatin extracted from tuna skin as compared to extracts from tuna flesh, tuna skin as well as bovine or porcine gelatin. Patients with tuna allergies or sensitization were sensitive to the same tuna species (yellowfin) as that from which the gelatin was obtained. IgE antibodies to these various extracts were analyzed using SDS-PAGE and immunoblotting. Only 3 of the 100 serum samples tested gave evidence of reactivity to gelatin extracted from tuna skin. Cross-reactivity between bovine/porcine and fish gelatin was not observed. The risk of adverse reactions to tuna skin gelatin seems to be significantly lower than the risk of fish allergy. Fish gelatin may represent a valuable alternative to bovine or porcine gelatin. Copyright 2003 S. Karger AG, Basel

Body Site Is a More Determinant Factor than Human Population Diversity in the Healthy Skin Microbiome

PubMed Central

Perez Perez, Guillermo I.; Gao, Zhan; Jourdain, Roland; Ramirez, Julia; Gany, Francesca; Clavaud, Cecile; Demaude, Julien

2016-01-01

We studied skin microbiota present in three skin sites (forearm, axilla, scalp) in men from six ethnic groups living in New York City. Methods. Samples were obtained at baseline and after four days following use of neutral soap and stopping regular hygiene products, including shampoos and deodorants. DNA was extracted using the MoBio Power Lyzer kit and 16S rRNA gene sequences determined on the IIlumina MiSeq platform, using QIIME for analysis. Results. Our analysis confirmed skin swabbing as a useful method for sampling different areas of the skin because DNA concentrations and number of sequences obtained across subject libraries were similar. We confirmed that skin location was the main factor determining the composition of bacterial communities. Alpha diversity, expressed as number of species observed, was greater in arm than on scalp or axilla in all studied groups. We observed an unexpected increase in α-diversity on arm, with similar tendency on scalp, in the South Asian group after subjects stopped using their regular shampoos and deodorants. Significant differences at phylum and genus levels were observed between subjects of the different ethnic origins at all skin sites. Conclusions. We conclude that ethnicity and particular soap and shampoo practices are secondary factors compared to the ecological zone of the human body in determining cutaneous microbiota composition. PMID:27088867

Electrically induced reorganization phenomena of liquid metal film printed on biological skin

NASA Astrophysics Data System (ADS)

Guo, Cangran; Yi, Liting; Yu, Yang; Liu, Jing

2016-12-01

Liquid metal has been demonstrated to be directly printable on biological skin as physiological measurement elements. However, many fundamental issues remained unclear so far. Here, we disclosed an intriguing phenomenon of electrically induced reorganization of liquid metal film. According to the experiments, when applying an external electric field to liquid metal films which were spray printed on biological skin, it would induce unexpected transformations of the liquid metals among different morphologies and configurations. These include shape shift from a large liquid metal film into a tiny sphere and contraction of liquid metal pool into spherical one. For comprehensively understanding the issues, the impacts of the size, voltage, orientations of the liquid metal electrodes, etc., were clarified. Further, effects of various substrates such as in vitro skin and in vivo skin affecting the liquid metal transformations were experimentally investigated. Compared to the intact tissues, the contraction magnitude of the liquid metal electrode appears weaker on in vivo skin of nude mice under the same electric field. The mechanisms lying behind such phenomena were interpreted through theoretical modeling. Lastly, typical applications of applying the current effect into practical elements such as electrical gating devices were also illustrated as an example. The present findings have both fundamental and practical values, which would help design future technical strategies in fabricating electronically controlled liquid metal electronics on skin.

Non-Darcian flow to a partially penetrating well in a confined aquifer with a finite-thickness skin

NASA Astrophysics Data System (ADS)

Feng, Qinggao; Wen, Zhang

2016-08-01

Non-Darcian flow to a partially penetrating well in a confined aquifer with a finite-thickness skin was investigated. The Izbash equation is used to describe the non-Darcian flow in the horizontal direction, and the vertical flow is described as Darcian. The solution for the newly developed non-Darcian flow model can be obtained by applying the linearization procedure in conjunction with the Laplace transform and the finite Fourier cosine transform. The flow model combines the effects of the non-Darcian flow, partial penetration of the well, and the finite thickness of the well skin. The results show that the depression cone spread is larger for the Darcian flow than for the non-Darcian flow. The drawdowns within the skin zone for a fully penetrating well are smaller than those for the partially penetrating well. The skin type and skin thickness have great impact on the drawdown in the skin zone, while they have little influence on drawdown in the formation zone. The sensitivity analysis indicates that the drawdown in the formation zone is sensitive to the power index ( n), the length of well screen ( w), the apparent radial hydraulic conductivity of the formation zone ( K r2), and the specific storage of the formation zone ( S s2) at early times, and it is very sensitive to the parameters n, w and K r2 at late times, especially to n, while it is not sensitive to the skin thickness ( r s).

An unexpected advantage of whiteness in horses: the most horsefly-proof horse has a depolarizing white coat.

PubMed

Horváth, Gábor; Blahó, Miklós; Kriska, György; Hegedüs, Ramón; Gerics, Balázs; Farkas, Róbert; Akesson, Susanne

2010-06-07

White horses frequently suffer from malign skin cancer and visual deficiencies owing to their high sensitivity to the ultraviolet solar radiation. Furthermore, in the wild, white horses suffer a larger predation risk than dark individuals because they can more easily be detected. In spite of their greater vulnerability, white horses have been highly appreciated for centuries owing to their natural rarity. Here, we show that blood-sucking tabanid flies, known to transmit disease agents to mammals, are less attracted to white than dark horses. We also demonstrate that tabanids use reflected polarized light from the coat as a signal to find a host. The attraction of tabanids to mainly black and brown fur coats is explained by positive polarotaxis. As the host's colour determines its attractiveness to tabanids, this parameter has a strong influence on the parasite load of the host. Although we have studied only the tabanid-horse interaction, our results can probably be extrapolated to other host animals of polarotactic tabanids, as the reflection-polarization characteristics of the host's body surface are physically the same, and thus not species-dependent.

The occurrence of herpes simplex viruses 1 and 2 in skin and mucosal lesions in patients with suspicion of genital herpes.

PubMed

Gorka, Emilia; Mlynarczyk-Bonikowska, Beata; Machura, Paulina; Majewska, Anna; Dzieciqtkowski, Tomasz; Mlynarzyk, Grazyna; Malejczyk, Magdalena; Majewski, Slawomir

Infection with herpes simplex viruses 1 and 2 (HSV 1 and 2 or Human herpesvirus HHV) are one of the most common infections in human. Real time PCR is a sensitive and specific method for diagnostics of HHV infections. The aim of the study was to investigate the occurrence of HHV 1 and HHV 2 DNA in patient with clinical symptoms suggesting HHV infection. We used real time PCR to investigate swabs from genital and perianal lesions from 74 patients of the Department of Dermatology and Venereology Medical University Warsaw and of gynecological outpatient clinics in Warsaw 40 women and 34 men. The results were positive for HHV 2 in 25 cases (34%), for HHV 1 in 19 cases (26%) and for both viruses in 20 cases (27%). 10 samples were negative for both viruses. The results confirm that the main cause of symptomatic genital herpes is HHV 2, however the percentage of HHV 1 and specially of mixed HHV 1/HHV 2 infections was unexpectedly high.

Assessment of the skin sensitization potency of eugenol and its dimers using a non-radioisotopic modification of the local lymph node assay.

PubMed

Takeyoshi, Masahiro; Noda, Shuji; Yamazaki, Shunsuke; Kakishima, Hiroshi; Yamasaki, Kanji; Kimber, Ian

2004-01-01

Allergic contact dermatitis is a serious health problem. There is a need to identify and characterize skin sensitization hazards, particularly with respect to relative potency, so that accurate risk assessments can be developed. For these purposes the murine local lymph node assay (LLNA) was developed. Here, we have investigated further a modi fi cation of this assay, non-radioisotopic LLNA, which in place of tritiated thymidine to measure lymph node cell proliferation employs incorporation of 5-bromo-2'-deoxyuridine. Using this method we have examined the skin sensitizing activity of eugenol, a known human contact allergen, and its dimers 2,2'-dihydroxyl-3,3'-dimethoxy-5,5'-diallyl-biphenyl (DHEA) and 4,5'-diallyl-2'-hydroxy-2,3'-dimethoxy phenyl ether (DHEB). Activity in the guinea pig maximization test (GPMT) also measured. On the basis of GPMT assays, eugenol was classified as a mild skin sensitizer, DHEA as a weak skin sensitizer and DHEB as an extreme skin sensitizer. In the non-radioisotopic LLNA all chemicals were found to give positive responses insofar as each was able to provoke a stimulation index (SI) of >or=3 at one or more test concentrations. The relative skin sensitizing potency of these chemicals was evaluated in the non-radioisotopic LLNA by derivation of an ec(3) value (the concentration of chemical required to provoke an SI of 3). The ec(3) values calculated were 25.1% for eugenol, >30% for DHEA and 2.3% for DHEB. Collectively these data suggest that assessments of relative potency deriving from non-radioisotopic LLNA responses correlate well with evaluations based on GPMT results. These investigations provide support for the proposal that the non-radioisotopic LLNA may serve as an effective alternative to the GPMT where there is a need to avoid the use of radioisotopes. Copyright 2004 John Wiley & Sons, Ltd.

[Profile of sensitization to allergens in children with atopic dermatitis assisting to Allergology Service of University Hospital, Nuevo Leon, Mexico].

PubMed

Yong-Rodríguez, Adrián; Macías-Weinmann, Alejandra; Palma-Gómez, Samuel; Arias-Cruz, Alfredo; Pérez-Vanzzini, Rafael; Gutiérrez-Mujica, José Julio; González-Díaz, Sandra Nora

2015-01-01

Sensitization to allergens in atopic dermatitis patients is a risk factor for developing asthma and allergic rhinitis in the future,as well as an aggravating factor in the course of the disease. Recent studies have attributed the activity of the proteases of some antigens to cause a grater defect in the epithelial barrier and a more severe disease. To know the sensitization to allergens pattern in children with atopic dermatitis attended at Allergology Service of University Hospital of UANL, Mexico, and to know if these children have higher sensitization to antigens with proteolytic activity. A retrospective study was done reviewing the skin prick test reports done in our service to children ranging from 5 months to 16 years old, diagnosed with atopic dermatitis during a period of 2 years, from January 2012 to January 2014. The frequency of sensitization to aeroallergens and food were analyzed as well as the weal size (≥6mm) on the skin in response to each particular allergen in the case of food skin prick test. Reports of skin tests of 66 children, 30 boys and 36 girls, were included; 37 of children were sensitized to more than one allergen,18/66 had asthma and/or allergic rhinitis, 40/66 60% skin prick tests were positive to high activity protease aeroallergens (Dermatophagoides pteronyssinus/Dermatophagoides farinae). Regarding food, sensitization was seen in 38 children; fruits and vegetables were the two most common foods. Only seven children had skin prick weal bigger than 6 mm, mainly to egg, fish and cow's milk. Children with atopic dermatitis are often sensitized to high protease activity aeroallergens, polysensitization is very common and the association with airway allergy is seen early in life. Sensitization to food is also common in these patients, but only a small percentage showed a response large enough to be associated with disease severity.

Skin prick test reactivity to lupin in comparison to peanut, pea, and soybean in atopic and non-atopic German subjects: A preliminary cross-sectional study

PubMed Central

Bähr, Melanie; Fechner, Anita; Kaatz, Martin; Jahreis, Gerhard

2014-01-01

The increasing use of lupin in food processing poses a problem of potential (cross-)allergic reactions. To evaluate the prevalence of sensitization to lupin in comparison to that of other legumes skin prick tests were performed with lupin, pea, peanut, and soybean in atopic (n = 81) and non-atopic (n = 102) German adults. Of these 183 subjects, 20 subjects had to be excluded due to invalid skin prick tests (reaction to histamine <3 mm or to sodium chloride >2 mm). Thus, skin prick tests of 163 subjects were included in final analyses. Of 163 subjects, 18 had a positive reaction to at least one legume tested. Overall skin prick test reactivity was different among non-atopic and atopic subjects (P = 0.005). Altogether, six subjects (4%) were sensitized to lupin, 12 (7%) to pea, 5 (3%) to peanut, and 8 (5%) to soybean. Two (2%) of the 92 non-atopic subjects and 4 (6%) of the 71 atopic subjects had a positive skin prick test to lupin. Of the 6 subjects sensitized to lupin, 3 (50%) were also sensitized to pea, 3 (50%) to peanut, and 5 (83%) to soybean. In conclusion, the prevalence rates of lupin sensitization were comparable to or even lower than those of pea, peanut, and soybean. To date, lupin allergy is suspected to be relatively uncommon in the overall German population since lupin sensitization occurred in only 2% of non-atopic subjects. However, there is a clear risk of a lupin allergy in predisposed subjects, since the frequency of lupin sensitization was 6% in atopic subjects. In particular, subjects with existing sensitization or allergy to other legumes are at higher risk for a sensitization or allergy to lupin due to cross-reactivity. PMID:25400931

Three-dimensional conformal graphene microstructure for flexible and highly sensitive electronic skin

NASA Astrophysics Data System (ADS)

Yang, Jun; Ran, Qincui; Wei, Dapeng; Sun, Tai; Yu, Leyong; Song, Xuefen; Pu, Lichun; Shi, Haofei; Du, Chunlei

2017-03-01

We demonstrate a highly stretchable electronic skin (E-skin) based on the facile combination of microstructured graphene nanowalls (GNWs) and a polydimethylsiloxane (PDMS) substrate. The microstructure of the GNWs was endowed by conformally growing them on the unpolished silicon wafer without the aid of nanofabrication technology. Then a stamping transfer method was used to replicate the micropattern of the unpolished silicon wafer. Due to the large contact interface between the 3D graphene network and the PDMS, this type of E-skin worked under a stretching ratio of nearly 100%, and showed excellent mechanical strength and high sensitivity, with a change in relative resistance of up to 6500% and a gauge factor of 65.9 at 99.64% strain. Furthermore, the E-skin exhibited an obvious highly sensitive response to joint movement, eye movement and sound vibration, demonstrating broad potential applications in healthcare, body monitoring and wearable devices.

Photoprotective substance occurs primarily in outer layers of fish skin

USGS Publications Warehouse

Fabacher, D.L.; Little, E.E.

1998-01-01

Methanol extracts of dorsal skin layers, eyes, gills, and livers from ultraviolet-B (UVB) radiation-sensitive and UVB-tolerant species of freshwater fish were examined for a substance that appears to be photoprotective. Significantly larger amounts of this substance were found in extracts of outer dorsal skin layers from both UVB-sensitive and UVB-tolerant fish when compared with extracts of inner dorsal skin layers. This substance occurred in minor amounts or was not detected in eye, gill, and liver extracts. The apparent primary function of this substance in fish is to protect the cells in outer dorsal skin layers from harmful levels of UVB radiation.

Photoprotective substance occurs primarily in outer layers of fish skin.

PubMed

Fabacher, D L; Little, E E

1998-01-01

Methanol extracts of dorsal skin layers, eyes, gills, and livers from ultraviolet-B (UVB) radiation-sensitive and UVB-tolerant species of freshwater fish were examined for a substance that appears to be photoprotective. Significantly larger amounts of this substance were found in extracts of outer dorsal skin layers from both UVB-sensitive and UVB-tolerant fish when compared with extracts of inner dorsal skin layers. This substance occurred in minor amounts or was not detected in eye, gill, and liver extracts. The apparent primary function of this substance in fish is to protect the cells in outer dorsal skin layers from harmful levels of UVB radiation.

The respiratory allergen glutaraldehyde in the local lymph node assay: sensitization by skin exposure, but not by inhalation.

PubMed

van Triel, Jos J; van Bree, Bianca W J; Roberts, David W; Muijser, Hans; Duistermaat, Evert; Woutersen, Ruud A; Kuper, C Frieke

2011-01-11

Previously, a selection of low molecular weight contact and respiratory allergens had tested positive in both a skin and a respiratory local lymph node assay (LLNA), but formaldehyde was negative for sensitization by inhalation. To investigate whether this was due to intrinsic properties of aldehyde sensitizers, the structurally related allergen glutaraldehyde (GA) was tested. BALB/c mice were exposed by inhalation to 6 or 18ppm GA (respiratory LLNA), both generated as a vapor and as an aerosol. Other groups received 0.25% or 2.5% GA on the skin of the ears (skin LLNA). Lymphocyte proliferation and cytokine production were measured in the draining lymph nodes. GA was positive in the skin LLNA and its cytokine profile (IL-4/IFN-γ) skewed towards a Th2-type immune response with increasing dose. Inhalation exposure did not result in increased lymphocyte proliferation or increased cytokine levels, despite comparable tissue damage (irritation) in the skin and respiratory tract. We hypothesize that the highly reactive and hydrophilic GA oligomerizes in the protein-rich mucous layer of the respiratory tract, which impedes sensitization but still facilitates local irritation. Within the context of risk assessment in respiratory allergy, our results stress the importance of prevention of skin--besides inhalation-- exposure to aldehydes like GA. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Further search for selectivity of positron annihilation in the skin and cancerous systems

NASA Astrophysics Data System (ADS)

Liu, Guang; Chen, Hongmin; Chakka, Lakshmi; Cheng, Mei-Ling; Gadzia, Joseph E.; Suzuki, R.; Ohdaira, T.; Oshima, N.; Jean, Y. C.

2008-10-01

Positronium annihilation lifetime (PAL) spectroscopy and Doppler broadening energy spectra (DBES) have been used to search for selectivity and sensitivity for cancerous skin samples with and without cancer. This study is to further explore the melanoma cancerous system and other different types of skin samples. We found that the S parameter in melanoma skin samples cut at 0.39 mm depth from the same patient's skin is smaller than near the skin surface. However in 10 melanoma samples from different patients, the S parameters vary significantly. Similarly, among 10 normal skin samples without cancer, the S parameters also vary largely among different patients. To understand the sensitivity of PAS as a tool to detect cancer formation at the early stage, we propose a controlled and systematic study of in vivo experiments using UV-induced cancer skin from living animals.

[Comparison of the antibiotic sensitivity of lipophilic Corynebacterium sp. isolated from patients on the day of admission and during hospitalization].

PubMed

Ciok-Pater, Emilia; Mikucka, Agnieszka; Gospodarek, Eugenia

2005-01-01

Lipophilic species of Corynebacterium are increasing problem in hospital infections. The aim of this study was to evaluate occurrence of these microorganisms in the materials taken from patients in the day of admission and during the hospitalization as well as comparison of their antibiotic sensitivity. The investigation included 65 strains isolated from hospitalized patients and 48 strains isolated from unchanged skin. Using Api Coryne test 5 species were identified. C. urealyticum dominated, the other were C. subsp. lipophilum and C. jeikeium. Among strains isolated from unchanged diseased skin the most C. jeikeium and C. accolens occurred. All strains were sensitive to glycopeptide, quinupristin/dalphopristin. The strains isolated from hospitalized patients were usually sensitive to fuside acid, doxycycline as well as tetracycline. Strains isolated from unchanged skin were sensitive to almost all tested antibiotics. In the group of 65 strains isolated from hospitalized patients 99.0% were multiresistant. In the group of strains isolated from unchanged skin only two strains were multiresistant. Differences in antibiotic sensitivity among analysed Corynebacterium sp. were confirmed. Majority of the "hospital strains" were characterized by multiresistance. Basing on these results it is possible to suppose, that multiresistance is main factor that favours lipophilic Corynebacterium species in the process of colonization of mucous membranes, skins as well as developing infections.

Unexpected source of latex sensitization in a neonatal intensive care unit.

PubMed

Wynn, R J; Boneberg, A; Lakshminrusimha, S

2007-09-01

We report a term infant with gastroschisis who presented with a systemic allergic reaction at a specific time of each day coinciding with infusion from a new preparation of total parenteral nutrition and intravenous lipid emulsion. The source of latex was traced to the rubber stopper of the lipid emulsion. We present this case to highlight the possibility of allergy from this unexpected source in a neonate.

High correlation of double Debye model parameters in skin cancer detection.

PubMed

Truong, Bao C Q; Tuan, H D; Fitzgerald, Anthony J; Wallace, Vincent P; Nguyen, H T

2014-01-01

The double Debye model can be used to capture the dielectric response of human skin in terahertz regime due to high water content in the tissue. The increased water proportion is widely considered as a biomarker of carcinogenesis, which gives rise of using this model in skin cancer detection. Therefore, the goal of this paper is to provide a specific analysis of the double Debye parameters in terms of non-melanoma skin cancer classification. Pearson correlation is applied to investigate the sensitivity of these parameters and their combinations to the variation in tumor percentage of skin samples. The most sensitive parameters are then assessed by using the receiver operating characteristic (ROC) plot to confirm their potential of classifying tumor from normal skin. Our positive outcomes support further steps to clinical application of terahertz imaging in skin cancer delineation.

Opiate-sensitivity: clinical characteristics and the role of skin prick testing.

PubMed

Nasser, S M; Ewan, P W

2001-07-01

The value of skin prick testing in opiate-sensitive individuals is uncertain as opiates cause non-specific weals by direct degranulation of mast cells. To define whether skin prick test (SPT) responses to opiates in opiate-sensitive individuals are different to those seen in the normal population and to describe the clinical characteristics of this group of subjects. The SPT responses of eight opiate-sensitive subjects to morphine 10 mg/mL, pethidine (meperidine) 50 mg/mL and papaveretum 15.4 mg/mL at four different concentrations (undiluted, 1/10, 1/50 and 1/100) were compared with the responses of 100 (32 atopic) non-opiate-sensitive control subjects. Four of the opiate-sensitive subjects had a clinical history of asthma, rhinitis or urticaria on occupational exposure to morphine. One subject developed urticaria with codeine, one developed urticaria and asthma with morphine and diamorphine and two subjects reacted to intravenous papaveretum with anaphylaxis or urticaria. Five out of the eight cases had opiate sensitivity confirmed by single-blind placebo-controlled oral challenge. Skin prick tests to all three opiates were not significantly different when the eight opiate-sensitive subjects were compared with either the entire normal control group or the subgroup of 47 definite opiate-tolerant controls that had previously received opiates for clinical indications. Furthermore, there were no significant differences in size of opiate SPT responses between atopic and non-atopic control subjects. In the control subjects, there was a positive correlation in SPT weal size between the three opiates. Skin prick testing is not useful in the diagnosis of opiate sensitivity and placebo-controlled challenge should be considered.

Skin acceptability of a cosmetic moisturizer formulation in female subjects with sensitive skin.

PubMed

Nisbet, Stephanie J

2018-01-01

This 3-week, open-label, noncomparative clinical study evaluated the skin acceptability of a cosmetic moisturizer in subjects with sensitive skin, by monitoring adverse events (AEs) and cutaneous discomfort related to normal usage. Female subjects aged between 18-60 years, with Fitzpatrick phototype classification I-IV and sensitive skin, verified by a positive reaction on the stinging test at screening, were included. Subjects applied the moisturizer to their face and body twice daily for 21±2 days at home and recorded study product usage and feelings of cutaneous discomfort (eg, dryness, prickling, stinging, and itching) in a diary; any AEs were reported to the clinic. At study end, skin acceptability of the moisturizer was investigator-assessed based on the nature of AEs and subjects' self-reported feelings of discomfort, and by clinical evaluation of skin reactions in the area of moisturizer application (appearance of erythema, formation of edema, and skin desquamation; scored according to an adapted Draize and Kligman scale). Only subjects with a treatment compliance of ≥80% were included in the final analysis. In total, 35 subjects initiated and completed the study; all were compliant to the minimum study product usage. Per investigator clinical dermatological assessment at study end, none of the 35 subjects had skin reactions in the area of moisturizer application and there were no reported AEs. One subject reported sensations of mild prickling and itching immediately after applying the moisturizer (not classified as AEs), which spontaneously remitted after complete absorption of the product and were noted only in exposed areas. These events were considered by the investigator as being possibly/probably related to the use of study product; however, no clinical signs of skin reaction were observed in the exposed areas. This cosmetic moisturizer appears generally well tolerated and suitable for topical use in subjects with sensitive skin.

Skin acceptability of a cosmetic moisturizer formulation in female subjects with sensitive skin

PubMed Central

Nisbet, Stephanie J

2018-01-01

Purpose This 3-week, open-label, noncomparative clinical study evaluated the skin acceptability of a cosmetic moisturizer in subjects with sensitive skin, by monitoring adverse events (AEs) and cutaneous discomfort related to normal usage. Materials and methods Female subjects aged between 18–60 years, with Fitzpatrick phototype classification I–IV and sensitive skin, verified by a positive reaction on the stinging test at screening, were included. Subjects applied the moisturizer to their face and body twice daily for 21±2 days at home and recorded study product usage and feelings of cutaneous discomfort (eg, dryness, prickling, stinging, and itching) in a diary; any AEs were reported to the clinic. At study end, skin acceptability of the moisturizer was investigator-assessed based on the nature of AEs and subjects’ self-reported feelings of discomfort, and by clinical evaluation of skin reactions in the area of moisturizer application (appearance of erythema, formation of edema, and skin desquamation; scored according to an adapted Draize and Kligman scale). Only subjects with a treatment compliance of ≥80% were included in the final analysis. Results In total, 35 subjects initiated and completed the study; all were compliant to the minimum study product usage. Per investigator clinical dermatological assessment at study end, none of the 35 subjects had skin reactions in the area of moisturizer application and there were no reported AEs. One subject reported sensations of mild prickling and itching immediately after applying the moisturizer (not classified as AEs), which spontaneously remitted after complete absorption of the product and were noted only in exposed areas. These events were considered by the investigator as being possibly/probably related to the use of study product; however, no clinical signs of skin reaction were observed in the exposed areas. Conclusion This cosmetic moisturizer appears generally well tolerated and suitable for topical use in subjects with sensitive skin. PMID:29750047

Comprehensive Monte-Carlo simulator for optimization of imaging parameters for high sensitivity detection of skin cancer at the THz

NASA Astrophysics Data System (ADS)

Ney, Michael; Abdulhalim, Ibrahim

2016-03-01

Skin cancer detection at its early stages has been the focus of a large number of experimental and theoretical studies during the past decades. Among these studies two prominent approaches presenting high potential are reflectometric sensing at the THz wavelengths region and polarimetric imaging techniques in the visible wavelengths. While THz radiation contrast agent and source of sensitivity to cancer related tissue alterations was considered to be mainly the elevated water content in the cancerous tissue, the polarimetric approach has been verified to enable cancerous tissue differentiation based on cancer induced structural alterations to the tissue. Combining THz with the polarimetric approach, which is considered in this study, is examined in order to enable higher detection sensitivity than previously pure reflectometric THz measurements. For this, a comprehensive MC simulation of radiative transfer in a complex skin tissue model fitted for the THz domain that considers the skin`s stratified structure, tissue material optical dispersion modeling, surface roughness, scatterers, and substructure organelles has been developed. Additionally, a narrow beam Mueller matrix differential analysis technique is suggested for assessing skin cancer induced changes in the polarimetric image, enabling the tissue model and MC simulation to be utilized for determining the imaging parameters resulting in maximal detection sensitivity.

Designing skin response meter for psycho galvanic reflex

NASA Astrophysics Data System (ADS)

Dhokalia, Dhruv M.; Atreya, Parul; Kumar, Arun

2011-12-01

Human skin offers some resistance to current and voltage. This resistance changes with the emotional state of the body. The circuit proposed here measures changes in our skin resistance following changes in our mental state. In the relaxed state, the resistance offered by the skin is as high as 2 mega-ohms or more, which reduces to 500 kilo-ohms or less when the emotional stress is too high. The reduction in skin resistance is related to increased blood flow and permeability followed by the physiological changes during high stress. This increases the electrical conductivity of the skin. This circuit is useful to monitor the skin's response to relaxation techniques. It is very sensitive and shows response during a sudden moment of stress. Even a deep sigh will give response in the circuit. The circuit uses a sensitive amplifier to sense variations in the skin resistance. IC CA3140 is designed as a resistance- to-voltage converter that outputs varying voltage based on the skin's conductivity.

A nanofiber based artificial electronic skin with high pressure sensitivity and 3D conformability

NASA Astrophysics Data System (ADS)

Zhong, Weibin; Liu, Qiongzhen; Wu, Yongzhi; Wang, Yuedan; Qing, Xing; Li, Mufang; Liu, Ke; Wang, Wenwen; Wang, Dong

2016-06-01

Pressure sensors with 3D conformability are highly desirable components for artificial electronic skin or e-textiles that can mimic natural skin, especially for application in real-time monitoring of human physiological signals. Here, a nanofiber based electronic skin with ultra-high pressure sensitivity and 3D conformability is designed and built by interlocking two elastic patterned nanofibrous membranes. The patterned membrane is facilely prepared by casting conductive nanofiber ink into a silicon mould to form an array of semi-spheroid-like protuberances. The protuberances composed of intertwined elastic POE nanofibers and PPy@PVA-co-PE nanofibers afford a tunable effective elastic modulus that is capable of capturing varied strains and stresses, thereby contributing to a high sensitivity for pressure sensing. This electronic skin-like sensor demonstrates an ultra-high sensitivity (1.24 kPa-1) below 150 Pa with a detection limit as low as about 1.3 Pa. The pixelated sensor array and a RGB-LED light are then assembled into a circuit and show a feasibility for visual detection of spatial pressure. Furthermore, a nanofiber based proof-of-concept wireless pressure sensor with a bluetooth module as a signal transmitter is proposed and has demonstrated great promise for wireless monitoring of human physiological signals, indicating a potential for large scale wearable electronic devices or e-skin.Pressure sensors with 3D conformability are highly desirable components for artificial electronic skin or e-textiles that can mimic natural skin, especially for application in real-time monitoring of human physiological signals. Here, a nanofiber based electronic skin with ultra-high pressure sensitivity and 3D conformability is designed and built by interlocking two elastic patterned nanofibrous membranes. The patterned membrane is facilely prepared by casting conductive nanofiber ink into a silicon mould to form an array of semi-spheroid-like protuberances. The protuberances composed of intertwined elastic POE nanofibers and PPy@PVA-co-PE nanofibers afford a tunable effective elastic modulus that is capable of capturing varied strains and stresses, thereby contributing to a high sensitivity for pressure sensing. This electronic skin-like sensor demonstrates an ultra-high sensitivity (1.24 kPa-1) below 150 Pa with a detection limit as low as about 1.3 Pa. The pixelated sensor array and a RGB-LED light are then assembled into a circuit and show a feasibility for visual detection of spatial pressure. Furthermore, a nanofiber based proof-of-concept wireless pressure sensor with a bluetooth module as a signal transmitter is proposed and has demonstrated great promise for wireless monitoring of human physiological signals, indicating a potential for large scale wearable electronic devices or e-skin. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02678h

On the modeling and characterization of an interlocked flexible electronic skin

NASA Astrophysics Data System (ADS)

Khalili, Nazanin; Shen, Xuechen; Naguib, Hani E.

2017-04-01

Development of an electronic skin with ultra-high pressure sensitivity is now of critical importance due its broad range of applications including prosthetic skins and biomimetic robotics. Microstructured conductive composite elastomers can acquire mechanical and electrical properties analogous to those of natural skin. One of the most prominent features of human skin is its tactile sensing property which can be mimicked in an electronic skin. Herein, an electrically conductive composite comprising polydimethylsiloxane and conductive fillers is used as a flexible and stretchable piezoresistive sensor. The electrical conductivity is induced within the elastomer matrix via carbon nanotubes whereas the piezoresistivity is obtained by means of microstructuring the surface of the substrate. An interlocked array of pyramids in micro-scale allows the change in the contact resistance between two thin layers of the composite upon application of an external load. Deformation of the interlocked arrays endows the sensor with an ultra-high sensitivity to the external pressures within the range of human skin perception. Moreover, using finite element analysis, the change in the contact are between the two layers was captured for different geometries. The structure of the sensor can be optimized through an optimization model in order to acquire maximum sensitivity.

Filling the concept with data: integrating data from different in vitro and in silico assays on skin sensitizers to explore the battery approach for animal-free skin sensitization testing.

PubMed

Natsch, Andreas; Emter, Roger; Ellis, Graham

2009-01-01

Tests for skin sensitization are required prior to the market launch of new cosmetic ingredients. Significant efforts are made to replace the current animal tests. It is widely recognized that this cannot be accomplished with a single in vitro test, but that rather the integration of results from different in vitro and in silico assays will be needed for the prediction of the skin sensitization potential of chemicals. This has been proposed as a theoretical scheme so far, but no attempts have been made to use experimental data to prove the validity of this concept. Here we thus try for the first time to fill this widely cited concept with data. To this aim, we integrate and report both novel and literature data on 116 chemicals of known skin sensitization potential on the following parameters: (1) peptide reactivity as a surrogate for protein binding, (2) induction of antioxidant/electrophile responsive element dependent luciferase activity as a cell-based assay; (3) Tissue Metabolism Simulator skin sensitization model in silico prediction; and (4) calculated octanol-water partition coefficient. The results of the in vitro assays were scaled into five classes from 0 to 4 to give an in vitro score and compared to the local lymph node assay (LLNA) data, which were also scaled from 0 to 4 (nonsensitizer/weak/moderate/strong/extreme). Different ways of evaluating these data have been assessed to rate the hazard of chemicals (Cooper statistics) and to also scale their potency. With the optimized model an overall accuracy for predicting sensitizers of 87.9% was obtained. There is a linear correlation between the LLNA score and the in vitro score. However, the correlation needs further improvement as there is still a relatively high variation in the in vitro score between chemicals belonging to the same sensitization potency class.

Facial and Periorbital Cellulitis due to Skin Peeling with Jet Stream by an Unauthorized Person.

PubMed

Kaptanoglu, Asli Feride; Mullaaziz, Didem; Suer, Kaya

2014-01-01

Technologies and devices for cosmetic procedures are developing with each passing day. However, increased and unauthorized use of such emerging technologies may also lead to increases in unexpected results and complications as well. Here, we report a case of facial cellulitis after a "beauty parlor" session of skin cleaning with jet stream peeling device in 19-year old female patient for the first time. Complications due to improper and unauthorized use of jet stream peeling devices may also cause doubts about the safety and impair the reputation of the technology as well. In order to avoid irreversible complications, local authorities should follow the technology and update the regulations where the dermatologists should take an active role.

Elective penicillin skin testing in a pediatric outpatient setting.

PubMed

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.

Effects of Unexpected Chords and of Performer's Expression on Brain Responses and Electrodermal Activity

PubMed Central

Koelsch, Stefan; Kilches, Simone; Steinbeis, Nikolaus; Schelinski, Stefanie

2008-01-01

Background There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. Methodology/Principal Findings This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition. Conclusions/Significance These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music. PMID:18612459

Adherence performances of pressure sensitive adhesives on a model viscoelastic synthetic film: a tool for the understanding of adhesion on the human skin.

PubMed

Renvoise, Julien; Burlot, Delphine; Marin, Gérard; Derail, Christophe

2009-02-23

This work deals with the rheological behavior and adherence properties of pressure sensitive adhesive formulations dedicated to medical applications. We have developed a specific viscoelastic substrate which mimics adhesion on human skin to measure the adherence properties of PSAs when they are stuck on the human skin. By comparing peeling results of PSAs, dedicated to medical applications, stuck on human skin and on this viscoelastic substrate we show that this substrate, based on a blend of natural proteins, presents a better representation of the interactions occurring at the skin/adhesive interface than conventional substrates used for peel test (i.e. glass and steel).

High sensitivity optical measurement of skin gloss

PubMed Central

Ezerskaia, Anna; Ras, Arno; Bloemen, Pascal; Pereira, Silvania F.; Urbach, H. Paul; Varghese, Babu

2017-01-01

We demonstrate a low-cost optical method for measuring the gloss properties with improved sensitivity in the low gloss regime, relevant for skin gloss properties. The gloss estimation method is based on, on the one hand, the slope of the intensity gradient in the transition regime between specular and diffuse reflection and on the other on the sum over the intensities of pixels above threshold, derived from a camera image obtained using unpolarized white light illumination. We demonstrate the improved sensitivity of the two proposed methods using Monte Carlo simulations and experiments performed on ISO gloss calibration standards with an optical prototype. The performance and linearity of the method was compared with different professional gloss measurement devices based on the ratio of specular to diffuse intensity. We demonstrate the feasibility for in-vivo skin gloss measurements by quantifying the temporal evolution of skin gloss after application of standard paraffin cream bases on skin. The presented method opens new possibilities in the fields of cosmetology and dermatopharmacology for measuring the skin gloss and resorption kinetics and the pharmacodynamics of various external agents. PMID:29026683

High sensitivity optical measurement of skin gloss.

PubMed

Ezerskaia, Anna; Ras, Arno; Bloemen, Pascal; Pereira, Silvania F; Urbach, H Paul; Varghese, Babu

2017-09-01

We demonstrate a low-cost optical method for measuring the gloss properties with improved sensitivity in the low gloss regime, relevant for skin gloss properties. The gloss estimation method is based on, on the one hand, the slope of the intensity gradient in the transition regime between specular and diffuse reflection and on the other on the sum over the intensities of pixels above threshold, derived from a camera image obtained using unpolarized white light illumination. We demonstrate the improved sensitivity of the two proposed methods using Monte Carlo simulations and experiments performed on ISO gloss calibration standards with an optical prototype. The performance and linearity of the method was compared with different professional gloss measurement devices based on the ratio of specular to diffuse intensity. We demonstrate the feasibility for in-vivo skin gloss measurements by quantifying the temporal evolution of skin gloss after application of standard paraffin cream bases on skin. The presented method opens new possibilities in the fields of cosmetology and dermatopharmacology for measuring the skin gloss and resorption kinetics and the pharmacodynamics of various external agents.

Investigating the effect of various extracting solvents on the potential use of red-apple skin (Malus domestica) as natural sensitizer for dye-sensitized solar cell

NASA Astrophysics Data System (ADS)

Saputro, Aldhi; Mizan, Adlan; Sofyan, Nofrijon; Yuwono, Akhmad Herman

2017-03-01

In the current investigation, the natural dye extracted from red-apple (Malus domestica) skin was used as natural sensitizer for dye sensitized solar cell (DSSC) application. The present study was specifically aimed at observing the effect of different solvents, i.e. deionized water, ethanol, and acidified ethanol, on the performance of the natural dye and thus the DSSC. For synthesis purposes, red-apple skin was peeled off, dried, crushed and furthermore extracted with ratio red-apple skin powder to solvent 1:20 w/v for 2 hours at 50°C under mechanical stirring. Subsequently, the resulting natural dyes with different solvents were examined by Fourier transform infrared (FTIR) to analyze their functional groups, UV-Vis spectroscopy to observe their absorption spectra for a wide range of wavelength, while TiO2 nanoparticle used as the semiconductor oxide layer in the device was characterized by field emission scanning electron microscope (FESEM). The FTIR results showed that the red-apple skin has anthocyanin group which functions as the sensitizer agent for photon energy absorption from the sunlight. The UV-Vis spectroscopy results showed that ethanol solvent has higher absorption of sunlight wavelength as compared to those of deionized water and acidified ethanol solvents. The performance test of the fabricated DSSC showed the prototype made of the red apple skin dye extracted by ethanol solvent can provide the highest open circuit voltage (Voc) up to 324 mV and efficiency around 0.046%. On the basis of investigation, it has been found that ethanol was the best solvent to extract anthocyanin from the red-apple skin.

Food allergy in South African children with atopic dermatitis.

PubMed

Gray, Claudia L; Levin, Michael E; Zar, Heather J; Potter, Paul C; Khumalo, Nonhlanhla P; Volkwyn, Lucia; Fenemore, Bartha; du Toit, George

2014-10-01

The prevalence of food allergy in South Africa is unknown, but previously thought to be rare in black South Africans. This study aimed to determine the prevalence of, and risk factors for, IgE-mediated food allergy in South African children with atopic dermatitis (AD). This was a prospective, observational study in a paediatric university hospital in Cape Town. Children with AD, aged 6 months to 10 yrs, were randomly recruited from the dermatology clinic. They were assessed for sensitization and allergy by questionnaire, skin prick tests, Immuno Solid Phase Allergen Chip (ISAC) test and incremental food challenges. 100 participants (59 black Africans and 41 of mixed race) were enrolled, median age 42 months. There were high overall rates of food sensitization (66%) and food allergy (40%). Egg (25%) and peanut (24%) were the most common allergies. Black participants had comparable sensitization (69% vs. 61%) but lower allergy rates (34% vs. 46%) than mixed race participants. This was especially evident for peanut allergy (15% Blacks vs. 37% mixed race allergic to peanut, p = 0.01). Early-onset AD (<6 months), severe eczema, and young age <2 yrs were significant risk factors for food allergy. The prevalence of food allergy is unexpectedly high in South African children with AD, and comparable with food allergy rates in patients with AD in developed countries. There are ethnic differences, with significantly lower peanut allergy rates in Blacks compared to mixed race patients. These results are not generalizable to an unselected South African population, which requires further study. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Photosensitivity enhancement with TiO2 in semitransparent light-sensitive skins of nanocrystal monolayers.

PubMed

Akhavan, Shahab; Yeltik, Aydan; Demir, Hilmi Volkan

2014-06-25

We propose and demonstrate light-sensitive nanocrystal skins that exhibit broadband sensitivity enhancement based on electron transfer to a thin TiO2 film grown by atomic layer deposition. In these photosensors, which operate with no external bias, photogenerated electrons remain trapped inside the nanocrystals. These electrons generally recombine with the photogenerated holes that accumulate at the top interfacing contact, which leads to lower photovoltage buildup. Because favorable conduction band offset aids in transferring photoelectrons from CdTe nanocrystals to the TiO2 layer, which decreases the exciton recombination probability, TiO2 has been utilized as the electron-accepting material in these light-sensitive nanocrystal skins. A controlled interface thickness between the TiO2 layer and the monolayer of CdTe nanocrystals enables a photovoltage buildup enhancement in the proposed nanostructure platform. With TiO2 serving as the electron acceptor, we observed broadband sensitivity improvement across 350-475 nm, with an approximately 22% enhancement. Furthermore, time-resolved fluorescence measurements verified the electron transfer from the CdTe nanocrystals to the TiO2 layer in light-sensitive skins. These results could pave the way for engineering nanocrystal-based light-sensing platforms, such as smart transparent windows, light-sensitive walls, and large-area optical detection systems.

40 CFR 156.70 - Precautionary statements for human hazards.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., dermal, inhalation toxicity) Irritation effects (skin and eye) Sensitizer (There are no categories of... or spray mist]. Do not get in eyes, on skin, or on clothing. [Front panel first aid statement required.] Corrosive, causes eye and skin damage [or skin irritation]. Do not get in eyes on skin, or on...

40 CFR 156.70 - Precautionary statements for human hazards.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., dermal, inhalation toxicity) Irritation effects (skin and eye) Sensitizer (There are no categories of... or spray mist]. Do not get in eyes, on skin, or on clothing. [Front panel first aid statement required.] Corrosive, causes eye and skin damage [or skin irritation]. Do not get in eyes on skin, or on...

Use of skin temperature to predict tolerance to thermal environments.

DOT National Transportation Integrated Search

1971-01-01

Skin temperature is a sensitive index of the effect of the thermal environment on the seminude man. Skin temperatures and tolerance times from several studies have been utilized in an attempt to establish a relationship between (1) final skin tempera...

Melanin directly converts light for vertebrate metabolic use: heuristic thoughts on birds, Icarus and dark human skin.

PubMed

Goodman, Geoffrey; Bercovich, Dani

2008-08-01

Pigments serve many visually obvious animal functions (e.g. hair, skin, eyes, feathers, scales). One is 'melanin', unusual in an absorption across the UV-visual spectrum which is controversial. Any polymer or macro-structure of melanin monomers is 'melanin'. Its roles derive from complex structural and physical-chemical properties e.g. semiconductor, stable radical, conductor, free radical scavenger, charge-transfer. Clinicians and researchers are well acquainted with melanin in skin and ocular pathologies and now increasingly are with internal, melanized, pathology-associated sites not obviously subject to light radiation (e.g. brain, cochlea). At both types of sites some findings puzzle: positive and negative neuromelanin effects in Parkinsons; unexpected melanocyte action in the cochlea, in deafness; melanin reduces DNA damage, but can promote melanoma; in melanotic cells, mitochondrial number was 83% less, respiration down 30%, but development similar to normal amelanotic cells. A little known, avian anatomical conundrum may help resolve melanin paradoxes. One of many unique adaptations to flight, the pecten, strange intra-ocular organ with unresolved function(s), is much enlarged and heavily melanized in birds fighting gravity, hypoxia, thirst and hunger during long-distance, frequently sub-zero, non-stop migration. The pecten may help cope with energy and nutrient needs under extreme conditions, by a marginal but critical, melanin-initiated conversion of light to metabolic energy, coupled to local metabolite recycling. Similarly in Central Africa, reduction in body hair and melanin increase may also have lead to 'photomelanometabolism' which, though small scale/ unit body area, in total may have enabled a sharply increased development of the energy-hungry cortex and enhanced human survival generally. Animal inability to utilize light energy directly has been traditionally assumed. Melanin and the pecten may have unexpected lessons also for human physiology and medicine.

Evaluation Methodology between Globalization and Localization Features Approaches for Skin Cancer Lesions Classification

NASA Astrophysics Data System (ADS)

Ahmed, H. M.; Al-azawi, R. J.; Abdulhameed, A. A.

2018-05-01

Huge efforts have been put in the developing of diagnostic methods to skin cancer disease. In this paper, two different approaches have been addressed for detection the skin cancer in dermoscopy images. The first approach uses a global method that uses global features for classifying skin lesions, whereas the second approach uses a local method that uses local features for classifying skin lesions. The aim of this paper is selecting the best approach for skin lesion classification. The dataset has been used in this paper consist of 200 dermoscopy images from Pedro Hispano Hospital (PH2). The achieved results are; sensitivity about 96%, specificity about 100%, precision about 100%, and accuracy about 97% for globalization approach while, sensitivity about 100%, specificity about 100%, precision about 100%, and accuracy about 100% for Localization Approach, these results showed that the localization approach achieved acceptable accuracy and better than globalization approach for skin cancer lesions classification.

Occupational dermal exposure to nanoparticles and nano-enabled products: Part I-Factors affecting skin absorption.

PubMed

Larese Filon, Francesca; Bello, Dhimiter; Cherrie, John W; Sleeuwenhoek, Anne; Spaan, Suzanne; Brouwer, Derk H

2016-08-01

The paper reviews and critically assesses the evidence on the relevance of various skin uptake pathways for engineered nanoparticles, nano-objects, their agglomerates and aggregates (NOAA). It focuses especially in occupational settings, in the context of nanotoxicology, risk assessment, occupational medicine, medical/epidemiological surveillance efforts, and the development of relevant exposure assessment strategies. Skin uptake of nanoparticles is presented in the context of local and systemic health effects, especially contact dermatitis, skin barrier integrity, physico-chemical properties of NOAA, and predisposing risk factors, such as stratum corneum disruption due to occupational co-exposure to chemicals, and the presence of occupational skin diseases. Attention should be given to: (1) Metal NOAA, since the potential release of ions may induce local skin effects (e.g. irritation and contact dermatitis) and absorption of toxic or sensitizing metals; (2) NOAA with metal catalytic residue, since potential release of ions may also induce local skin effects and absorption of toxic metals; (3) rigid NOAA smaller than 45nm that can penetrate and permeate the skin; (4) non rigid or flexible NOAA, where due to their flexibility liposomes and micelles can penetrate and permeate the intact skin; (5) impaired skin condition of exposed workers. Furthermore, we outline possible situations where health surveillance could be appropriate where there is NOAA occupational skin exposures, e.g. when working with nanoparticles made of sensitizer metals, NOAA containing sensitizer impurities, and/or in occupations with a high prevalence of disrupted skin barrier integrity. The paper furthermore recommends a stepwise approach to evaluate risk related to NOAA to be applied in occupational exposure and risk assessment, and discusses implications related to health surveillance, labelling, and risk communication. Copyright © 2016 Elsevier GmbH. All rights reserved.

A Prototype Lip Balm: Summary of Three Dermatological Studies Demonstrating Safety and Acceptability for Sensitive Skin.

PubMed

Nisbet, Stephanie

Data were generated from three studies to assess the tolerability and acceptability of a prototype cosmetic lip balm. Dermatological assessments of topical compatibility (primary and cumulative irritability and sensitization), photoirritant and topical photosensitizer potential, and acceptability for safe use of a prototype cosmetic lip balm on sensitive skin are summarized. In Study 1, the product was applied to the volunteers' backs under a semiocclusive patch followed by patch removal/reapplication over 6 weeks to assess the irritant and allergic potential of the product. Dermatological assessments were performed at the beginning and end of the study or when there was evidence of positivity or adverse event. Study 2 was conducted by applying the product to the volunteers' backs under a semiocclusive patch, followed by patch removal/reapplication and irradiation of the test area with ultraviolet A (UVA) radiation at various intervals over 5 weeks. Dermatological assessments were performed to assess the product's role in the induction of photoirritancy and photosensitization. Clinical and subjective assessments for acceptability were obtained during Study 3 in volunteers with a diagnosis of sensitive skin and those who used the product as per instructions for use during the study period. The data generated from the three studies demonstrated no evidence of primary or cumulative dermal irritation or of dermal sensitization. In addition, no photoirritation potential or photosensitization potential was observed. As assessed by dermatologic monitoring and subject diary entries, the prototype lip balm did not cause irritation or sensitization reactions when used for 28 days in volunteers with a diagnosis of sensitive skin. Based on these findings, the prototype lip balm can be considered suitable for use for people with sensitive skin.

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

PubMed

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 both the MatTek and SkinEthic models performed in a manner consistent with data previously reported with the human keratinocyte (HaCaT) cell line. The system was tested further by evaluating chemicals known to be associated with the manufacture of medical devices. In all cases, the human skin models performed as well or better than the HaCaT cell model previously evaluated. In addition, this study identifies a clear unifying trigger that controls both the Nrf2/ARE pathway and essential biochemical events required for the development of ACD. Finally, this study has demonstrated that by utilizing human reconstructed skin models, it is possible to evaluate non-polar extracts from medical devices and low solubility finished products.

Overview of the status of predictive computer models for skin sensitization (JRC Expert meeting on pre- and pro-haptens )

EPA Science Inventory

No abstract was prepared or requested. This is a short presentation aiming to present a status of what in silico models and approaches exists in the prediction of skin sensitization potential and/or potency.

Hair Follicular Expression and Function of Group X Secreted Phospholipase A2 in Mouse Skin*

PubMed Central

Yamamoto, Kei; Taketomi, Yoshitaka; Isogai, Yuki; Miki, Yoshimi; Sato, Hiroyasu; Masuda, Seiko; Nishito, Yasumasa; Morioka, Kiyokazu; Ishimoto, Yoshikazu; Suzuki, Noriko; Yokota, Yasunori; Hanasaki, Kohji; Ishikawa, Yukio; Ishii, Toshiharu; Kobayashi, Tetsuyuki; Fukami, Kiyoko; Ikeda, Kazutaka; Nakanishi, Hiroki; Taguchi, Ryo; Murakami, Makoto

2011-01-01

Although perturbed lipid metabolism can often lead to skin abnormality, the role of phospholipase A2 (PLA2) in skin homeostasis is poorly understood. In the present study we found that group X-secreted PLA2 (sPLA2-X) was expressed in the outermost epithelium of hair follicles in synchrony with the anagen phase of hair cycling. Transgenic mice overexpressing sPLA2-X (PLA2G10-Tg) displayed alopecia, which was accompanied by hair follicle distortion with reduced expression of genes related to hair development, during a postnatal hair cycle. Additionally, the epidermis and sebaceous glands of PLA2G10-Tg skin were hyperplasic. Proteolytic activation of sPLA2-X in PLA2G10-Tg skin was accompanied by preferential hydrolysis of phosphatidylethanolamine species with polyunsaturated fatty acids as well as elevated production of some if not all eicosanoids. Importantly, the skin of Pla2g10-deficient mice had abnormal hair follicles with noticeable reduction in a subset of hair genes, a hypoplasic outer root sheath, a reduced number of melanin granules, and unexpected up-regulation of prostanoid synthesis. Collectively, our study highlights the spatiotemporal expression of sPLA2-X in hair follicles, the presence of skin-specific machinery leading to sPLA2-X activation, a functional link of sPLA2-X with hair follicle homeostasis, and compartmentalization of the prostanoid pathway in hair follicles and epidermis. PMID:21266583

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

NASA Astrophysics Data System (ADS)

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.

A Clinical Aid for Detecting Skin Cancer: The Triage Amalgamated Dermoscopic Algorithm (TADA).

PubMed

Rogers, T; Marino, M L; Dusza, S W; Bajaj, S; Usatine, R P; Marchetti, M A; Marghoob, A A

Family physicians (FPs) frequently evaluate skin lesions but may not have the necessary training to accurately and confidently identify lesions that require skin biopsy or specialist referral. We evaluated the diagnostic performance of a new, simplified dermoscopy algorithm for skin cancer detection. In this cross-sectional, observation study, attendees of a dermoscopy course evaluated 50 polarized dermoscopy images of skin lesions (27 malignant and 23 benign) using the Triage Amalgamated Dermoscopic Algorithm (TADA). The dermoscopic criteria of TADA include architectural disorder (ie, disorganized or asymmetric distribution of colors and/or structures), starburst pattern, blue-black or gray color, white structures, negative network, ulcer, and vessels. The study occurred after 1 day of basic dermoscopy training. Clinical information related to palpation (ie, firm, dimpling) was provided when relevant. Of 200 course attendees, 120 (60%) participated in the study. Participants included 64 (53.3%) dermatologists and 41 (34.2%) primary care physicians, 19 (46.3%) of whom were FPs. Fifty-two (43%) individuals had no previous dermoscopy training. Overall, the sensitivity and specificity of TADA for malignant skin lesions was 94.8% and 72.3%, respectively. Previous dermoscopy training and years of dermoscopy experience were not associated with diagnostic sensitivity (P = .13 and P = .05, respectively) or specificity (P = .36 and P = .21, respectively). Specialty type was not associated with sensitivity (P = .37) but dermatologists had a higher specificity than nondermatologists (79% v. 72%, P = .008). After basic instruction, TADA may be a useful dermoscopy algorithm for FPs who examine skin lesions as it has a high sensitivity for detecting skin cancer. © Copyright 2016 by the American Board of Family Medicine.

Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis.

PubMed

Noti, Mario; Kim, Brian S; Siracusa, Mark C; Rak, Gregory D; Kubo, Masato; Moghaddam, Amin E; Sattentau, Quentin A; Comeau, Michael R; Spergel, Jonathan M; Artis, David

2014-05-01

Exposure to food allergens through a disrupted skin barrier has been recognized as a potential factor in the increasing prevalence of food allergy. We sought to test the immunologic mechanisms by which epicutaneous sensitization to food allergens predisposes to intestinal food allergy. Mice were epicutaneously sensitized with ovalbumin or peanut on an atopic dermatitis-like skin lesion, followed by intragastric antigen challenge. Antigen-specific serum IgE levels and T(H)2 cytokine responses were measured by ELISA. Expression of type 2 cytokines and mast cell proteases in the intestine were measured by using real-time PCR. Accumulation of basophils in the skin and mast cells in the intestine was examined by using flow cytometry. In vivo basophil depletion was achieved by using diphtheria toxin treatment of Baso-DTR mice. For cell-transfer studies, the basophil population was expanded in vivo by means of hydrodynamic tail vein injection of thymic stromal lymphopoietin (TSLP) cDNA plasmid. Sensitization to food allergens through an atopic dermatitis-like skin lesion is associated with an expansion of TSLP-elicited basophils in the skin that promote antigen-specific T(H)2 cytokine responses, increased antigen-specific serum IgE levels, and accumulation of mast cells in the intestine, promoting the development of intestinal food allergy. Critically, disruption of TSLP responses or depletion of basophils reduced the susceptibility to intestinal food allergy, whereas transfer of TSLP-elicited basophils into intact skin promoted disease. Epicutaneous sensitization on a disrupted skin barrier is associated with accumulation of TSLP-elicited basophils, which are necessary and sufficient to promote antigen-induced intestinal food allergy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Exposure to food allergens through inflamed skin promotes intestinal food allergy via the TSLP-basophil axis

PubMed Central

Noti, Mario; Kim, Brian S.; Siracusa, Mark C.; Rak, Gregory D.; Kubo, Masato; Moghaddam, Amin E.; Sattentau, Quentin A.; Comeau, Michael R.; Spergel, Jonathan M.; Artis, David

2014-01-01

Background Exposure to food allergens through a disrupted skin barrier has been recognized as a potential factor in the increasing prevalence of food allergy. Objective To test the immunological mechanisms by which epicutaneous sensitization to food allergens predisposes to intestinal food allergy. Methods Mice were epicutaneously sensitized with ovalbumin (OVA) or peanut on an atopic dermatitis-like skin lesion followed by intragastric antigen challenge. Antigen-specific serum IgE levels and Th2 cytokine responses were measured by ELISA. Expression of type-2 cytokines and mast cell proteases in the intestine were measured by real-time PCR. Accumulation of basophils in the skin and mast cells in the intestine was examined by flow cytometry. In vivo basophil depletion was achieved by diphtheria toxin treatment of Baso-DTR mice. For cell transfer studies, the basophil population was expanded in vivo by hydrodynamic tail vein injection of thymic stromal lymphopoietin cDNA plasmid. Results Sensitization to food allergens through an atopic dermatitis-like skin lesion is associated with an expansion of TSLP-elicited basophils in the skin that promote antigen-specific Th2 cytokine responses, elevated antigen-specific serum IgE levels and the accumulation of mast cells in the intestine promoting the development of intestinal food allergy. Critically, disruption of TSLP responses or depletion of basophils reduced the susceptibility to intestinal food allergy while transfer of TSLP-elicited basophils into intact skin promoted disease. Conclusion Epicutaneous sensitization on a disrupted skin barrier is associated with the accumulation of TSLP-elicited basophils that are necessary and sufficient to promote antigen-induced intestinal food allergy. PMID:24560412

The effects of topically applied glycolic acid and salicylic acid on ultraviolet radiation-induced erythema, DNA damage and sunburn cell formation in human skin.

PubMed

Kornhauser, Andrija; Wei, Rong-Rong; Yamaguchi, Yuji; Coelho, Sergio G; Kaidbey, Kays; Barton, Curtis; Takahashi, Kaoruko; Beer, Janusz Z; Miller, Sharon A; Hearing, Vincent J

2009-07-01

alpha-Hydroxy acids (alphaHAs) are reported to reduce signs of aging in the skin and are widely used cosmetic ingredients. Several studies suggest that alphaHA can increase the sensitivity of skin to ultraviolet radiation. More recently, beta-hydroxy acids (betaHAs), or combinations of alphaHA and betaHA have also been incorporated into antiaging skin care products. Concerns have also arisen about increased sensitivity to ultraviolet radiation following use of skin care products containing beta-HA. To determine whether topical treatment with glycolic acid, a representative alphaHA, or with salicylic acid, a betaHA, modifies the short-term effects of solar simulated radiation (SSR) in human skin. Fourteen subjects participated in this study. Three of the four test sites on the mid-back of each subject were treated daily Monday-Friday, for a total of 3.5 weeks, with glycolic acid (10%), salicylic acid (2%), or vehicle (control). The fourth site received no treatment. After the last treatment, each site was exposed to SSR, and shave biopsies from all four sites were obtained. The endpoints evaluated in this study were erythema (assessed visually and instrumentally), DNA damage and sunburn cell formation. Treatment with glycolic acid resulted in increased sensitivity of human skin to SSR, measured as an increase in erythema, DNA damage and sunburn cell formation. Salicylic acid did not produce significant changes in any of these biomarkers. Short-term topical application of glycolic acid in a cosmetic formulation increased the sensitivity of human skin to SSR, while a comparable treatment with salicylic acid did not.

The Effects of Topically Applied Glycolic Acid and Salicylic Acid on Ultraviolet Radiation-Induced Erythema, DNA Damage and Sunburn Cell Formation in Human Skin

PubMed Central

Kornhauser, Andrija; Wei, Rong-Rong; Yamaguchi, Yuji; Coelho, Sergio G.; Kaidbey, Kays; Barton, Curtis; Takahashi, Kaoruko; Beer, Janusz Z.; Miller, Sharon A.; Hearing, Vincent J.

2009-01-01

Background α-Hydroxy acids (αHA) are reported to reduce signs of aging in the skin and are widely used cosmetic ingredients. Several studies suggest that αHA can increase the sensitivity of skin to ultraviolet radiation. More recently, β-hydroxy acids (βHA), or combinations of αHA and βHA have also been incorporated into antiaging skin care products. Concerns have also arisen about increased sensitivity to ultraviolet radiation following use of skin care products containing β-HA. Objective To determine whether topical treatment with glycolic acid, a representative αHA, or with salicylic acid, a βHA, modifies the short-term effects of solar simulated radiation (SSR) in human skin. Methods Fourteen subjects participated in this study. Three of the four test sites on the mid-back of each subject were treated daily Monday - Friday, for a total of 3.5 weeks, with glycolic acid (10%), salicylic acid (2%), or vehicle (control). The fourth site received no treatment. After the last treatment, each site was exposed to SSR, and shave biopsies from all 4 sites were obtained. The endpoints evaluated in this study were erythema (assessed visually and instrumentally), DNA damage and sunburn cell formation. Results Treatment with glycolic acid resulted in increased sensitivity of human skin to SSR, measured as an increase in erythema, DNA damage and sunburn cell formation. Salicylic acid did not produce significant changes in any of these biomarkers. Conclusions Short-term topical application of glycolic acid in a cosmetic formulation increased the sensitivity of human skin to SSR, while a comparable treatment with salicylic acid did not. PMID:19411163

29 CFR 1910.1048 - Formaldehyde.

Code of Federal Regulations, 2011 CFR

2011-07-01

... evidence of irritation or sensitization of the skin and respiratory system, shortness of breath, or... make a decision within six months of the date the employee was removed as to whether the employee can... sensitization of the skin and respiratory system, eye and throat irritation, and acute toxicity. (2...

29 CFR 1910.1048 - Formaldehyde.

Code of Federal Regulations, 2010 CFR

2010-07-01

... evidence of irritation or sensitization of the skin and respiratory system, shortness of breath, or... make a decision within six months of the date the employee was removed as to whether the employee can... sensitization of the skin and respiratory system, eye and throat irritation, and acute toxicity. (2...

Evidence that two alkyl ester quaternary ammonium compounds lack substantial human skin-sensitizing potential.

PubMed

Jowsey, Ian R; Kligman, Albert M; White, Ian R; Goossens, An; Basketter, David A

2007-03-01

Alkyl ester quaternary ammonium compounds (ester quats) are used extensively in fabric rinse conditioners. It is important to document in the literature the outcome of historical studies that were performed to assess the risk of adverse skin effects associated with their use. (1) To document the outcomes of historical studies performed to evaluate the skin sensitizing potential of two ester quats (the di-[hardened tallow fatty acid] ester of 2,3-dihydroxypropyl-trimethyl ammonium chloride [HEQ] and the dialkyl ester of triethanol ammonium methyl sulfate [TEA-Quat]) and (2) to demonstrate that these ester quats lack marked skin-sensitizing potential in humans, such that they do not present a risk of contact allergy for consumers who use fabric rinse conditioners. Each material was assessed in the human maximization test in a panel of 25 volunteers. Diagnostic patch testing was also performed with each material in a population of 239 patients undergoing routine patch testing for suspected allergic contact dermatitis. These data are also considered in the context of an exposure-based quantitative risk assessment. Neither HEQ nor TEA-Quat was found to cause skin sensitization under the conditions of the human maximization test. No evidence of contact allergy to the materials was found among the relatively small population assessed by diagnostic patch testing. This study provides evidence that HEQ and TEA-Quat lack substantial skin-sensitizing potential in humans. Taken together with similar data for other ester quats, it suggests that compounds in this class are unlikely to be significant human contact allergens.

Prevention of oral food allergy sensitization via skin application of food allergen in a mouse model.

PubMed

Li, W; Zhang, Z; Saxon, A; Zhang, K

2012-05-01

Treatment options for food allergy remain limited. Development of novel approaches for the prevention and/or treatment of severe peanut allergy and other food allergies is urgently needed. The objective of this study was to test whether skin application of food allergen can be used as a prophylactic and/or therapeutic intervention for food allergy. Balb/C mice were given 5 weekly cutaneous application of complete peanut extract (CPE) or ovalbumin (OVA) ranging from 10 to 1000 μg on the shaved back skin, followed by 5 weekly treatments with oral CPE or OVA plus cholera toxin to induce allergic reactivity to the food. At various time points, the immunologic responses and allergic clinical manifestations to allergens were examined. Skin application of a 10-1000 μg dose of CPE or OVA to structurally intact skin did not lead to allergic sensitization to peanut or OVA. Rather, cutaneous allergen application blocked, in a dose-dependent fashion, the subsequent induction of the oral sensitization including inhibiting oral sensitization-induced CPE-specific IgE, IgG1, and IgG2a production, suppressing the peanut anaphylaxis, and modulating the oral sensitization-promoted cytokine production. The cutaneous OVA application also resulted in similar results as seen with CPE application. Cutaneous application of intact skin with peanut or OVA can block the development of orally induced corresponding food allergies, suggesting that allergic tolerance to peanuts and OVA might be achieved via allergen cutaneous application. © 2012 John Wiley & Sons A/S.

Integrated Decision Strategies for Skin Sensitization Hazard

PubMed Central

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

2016-01-01

One of the top priorities of ICCVAM is the identification and evaluation of non-animal alternatives for skin sensitization testing. Although skin sensitization is a complex process, the key biological events of the process have been well characterized in an adverse outcome pathway (AOP) proposed by OECD. Accordingly, ICCVAM is working to develop integrated decision strategies based on the AOP using in vitro, in chemico, and in silico information. Data were compiled for 120 substances tested in the murine local lymph node assay (LLNA), direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT), and KeratinoSens assay. Data for six physicochemical properties that may affect skin penetration were also collected, and skin sensitization read-across predictions were performed using OECD QSAR Toolbox. All data were combined into a variety of potential integrated decision strategies to predict LLNA outcomes using a training set of 94 substances and an external test set of 26 substances. Fifty-four models were built using multiple combinations of machine learning approaches and predictor variables. The seven models with the highest accuracy (89–96% for the test set and 96–99% for the training set) for predicting LLNA outcomes used a support vector machine (SVM) approach with different combinations of predictor variables. The performance statistics of the SVM models were higher than any of the non-animal tests alone and higher than simple test battery approaches using these methods. These data suggest that computational approaches are promising tools to effectively integrate data sources to identify potential skin sensitizers without animal testing. PMID:26851134

Sensitive skin at menopause; dew point and electrometric properties of the stratum corneum.

PubMed

Paquet, F; Piérard-Franchimont, C; Fumal, I; Goffin, V; Paye, M; Piérard, G E

1998-01-12

A number of menopausal women experience skin sensitive to various environmental threats. Two panels of 15 menopausal women on or without HRT were compared. We studied the response of their stratum corneum to variations in environmental humidity, either in air or in response to an emollient. Environment dew point and electrometric measurements on the skin were recorded to search for correlations. Data show that the baseline stratum corneum hydration is influenced by the dew point. HRT improves the barrier function of the skin. The use of emollient further extends the improvement in the functional properties of skin in menopausal women. Both HRT and an emollient can counteract in part some of the deleterious effects of cold and dry weather.

Hypersensitivity of skin fibroblasts from basal cell nevus syndrome patients to killing by ultraviolet B but not by ultraviolet C radiation

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

Applegate, L.A.; Goldberg, L.H.; Ley, R.D.

Basal cell nevus syndrome (BCNS) is an autosomal dominant genetic disorder in which the afflicted individuals are extremely susceptible to sunlight-induced skin cancers, particularly basal cell carcinomas. However, the cellular and molecular basis for BCNS is unknown. To ascertain whether there is any relationship between genetic predisposition to skin cancer and increased sensitivity of somatic cells from BCNS patients to killing by UV radiation, we exposed skin fibroblasts established from unexposed skin biopsies of several BCNS and age- and sex-matched normal individuals to either UV-B (280-320 nm) or UV-C (254 nm) radiation and determined their survival. The results indicated thatmore » skin fibroblasts from BCNS patients were hypersensitive to killing by UV-B but not UV-C radiation as compared to skin fibroblasts from normal individuals. DNA repair studies indicated that the increased sensitivity of BCNS skin fibroblasts to killing by UV-B radiation was not due to a defect in the excision repair of pyrimidine dimers. These results indicate that there is an association between hypersensitivity of somatic cells to killing by UV-B radiation and the genetic predisposition to skin cancer in BCNS patients. In addition, these results suggest that DNA lesions (and repair processes) other than the pyrimidine dimer are also involved in the pathogenesis of sunlight-induced skin cancers in BCNS patients. More important, the UV-B sensitivity assay described here may be used as a diagnostic tool to identify presymptomatic individuals with BCNS.« less

Ultra-high-sensitive optical micro-angiography provides depth resolved visualization of microcirculations within human skin under psoriatic conditions

NASA Astrophysics Data System (ADS)

Qin, Jia; An, Lin; Wang, Ruikang

2011-03-01

Adequate functioning of the peripheral micro vascular in human skin is necessary to maintain optimal tissue perfusion and preserve normal hemodynamic function. There is a growing body of evidence suggests that vascular abnormalities may directly related to several dermatologic diseases, such as psoriasis, port-wine stain, skin cancer, etc. New in vivo imaging modalities to aid volumetric microvascular blood perfusion imaging are there for highly desirable. To address this need, we demonstrate the capability of ultra-high sensitive optical micro angiography to allow blood flow visualization and quantification of vascular densities of lesional psoriasis area in human subject in vivo. The microcirculation networks of lesion and non-lesion skin were obtained after post processing the data sets captured by the system. With our image resolution (~20 μm), we could compare these two types of microcirculation networks both qualitatively and quantitatively. The B-scan (lateral or x direction) cross section images, en-face (x-y plane) images and the volumetric in vivo perfusion map of lesion and non-lesion skin areas were obtained using UHS-OMAG. Characteristic perfusion map features were identified between lesional and non-lesional skin area. A statistically significant difference between vascular densities of lesion and non-lesion skin area was also found using a histogram based analysis. UHS-OMAG has the potential to differentiate the normal skin microcirculation from abnormal human skin microcirculation non-invasively with high speed and sensitivity. The presented data demonstrates the great potential of UHS-OMAG for detecting and diagnosing skin disease such as psoriasis in human subjects.

Patch-test reaction patterns in patients with a predisposition to atopic dermatitis.

PubMed

Brasch, Jochen; Schnuch, Axel; Uter, Wolfgang

2003-10-01

Patients with a predisposition to atopic dermatitis often need to be patch tested in order to detect possible contact sensitization. However, it is unknown whether immunologic or other peculiarities of atopic skin are related to altered patch-test reaction patterns. Our study was aimed at answering this question, because patch-test reaction patterns are of considerable practical importance in the reading and interpretation of patch tests. Therefore, we compared patterns of patch-test reactions in patients with a predisposition to atopic dermatitis and in control patients matched for sex, age, reason for testing and test centre. Patch-test results from 9 centres (2322 patients with a disposition to atopic dermatitis and 2126 matched controls) were evaluated retrospectively. All patients were tested with nickel sulfate, fragrance mix, potassium dichromate, lanolin alcohol, formaldehyde and mercury ammonium chloride. Patch tests applied for 1 day with readings on days 1, 2 and 3 were evaluated in order to cover the early phase of the reactions. Not unexpectedly, we found that, compared to the matched controls, patients with a predisposition to atopic dermatitis tended to have more doubtful and irritant reactions on day 1. As a new observation, it turned out that they had less reactions of crescendo pattern and more strong reactions on day 3. All these differences were slight/insignificant. A higher skin irritability in patients with a predisposition to atopic dermatitis is a likely explanation. In conclusion, standard methods for patch testing can be applied in patients with a predisposition to atopic dermatitis, but minor differences in reaction patterns should be considered.

Increased risk of horse sensitization in southwestern Iranian horse riders.

PubMed

Moghtaderi, Mozhgan; Farjadian, Shirin; Hosseini, Zeynab; Raayat, Alireza

2015-01-01

The aim of this study has been to investigate the frequency of sensitization to horse allergens and clinical symptoms in horse riders. A total of 42 horse riders and 50 healthy individuals were examined by means of skin prick tests for a panel of horse and common animal allergens, and pulmonary function tests were done by spirometry. The rate of sensitization to horse allergens was 31% as proven by the skin prick test in horse riders whereas horse sensitization was not seen in the control group. Occupational allergy symptoms were reported by 19 horse riders. Two horse riders with no history of clinical symptoms showed positive skin reactions to horse allergens. To decrease the high risk of occupational sensitization among horse riders, workplace conditions should be improved to reduce the load of airborne horse allergens. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Plasmonic light-sensitive skins of nanocrystal monolayers

NASA Astrophysics Data System (ADS)

Akhavan, Shahab; Gungor, Kivanc; Mutlugun, Evren; Demir, Hilmi Volkan

2013-04-01

We report plasmonically coupled light-sensitive skins of nanocrystal monolayers that exhibit sensitivity enhancement and spectral range extension with plasmonic nanostructures embedded in their photosensitive nanocrystal platforms. The deposited plasmonic silver nanoparticles of the device increase the optical absorption of a CdTe nanocrystal monolayer incorporated in the device. Controlled separation of these metallic nanoparticles in the vicinity of semiconductor nanocrystals enables optimization of the photovoltage buildup in the proposed nanostructure platform. The enhancement factor was found to depend on the excitation wavelength. We observed broadband sensitivity improvement (across 400-650 nm), with a 2.6-fold enhancement factor around the localized plasmon resonance peak. The simulation results were found to agree well with the experimental data. Such plasmonically enhanced nanocrystal skins hold great promise for large-area UV/visible sensing applications.

Gene expression profiles in auricle skin as a possible additional endpoint for determination of sensitizers: A multi-endpoint evaluation of the local lymph node assay.

PubMed

Tsuchiyama, Hiromi; Maeda, Akihisa; Nakajima, Mayumi; Kitsukawa, Mika; Takahashi, Kei; Miyoshi, Tomoya; Mutsuga, Mayu; Asaoka, Yoshiji; Miyamoto, Yohei; Oshida, Keiyu

2017-10-05

The murine local lymph node assay (LLNA) is widely used to test chemicals to induce skin sensitization. Exposure of mouse auricle skin to a sensitizer results in proliferation of local lymph node T cells, which has been measured by in vivo incorporation of H 3 -methyl thymidine or 5-bromo-2'-deoxyuridine (BrdU). The stimulation index (SI), the ratio of the mean proliferation in each treated group to that in the concurrent vehicle control group, is frequently used as a regulatory-authorized endpoint for LLNA. However, some non-sensitizing irritants, such as sodium dodecyl sulfate (SDS) or methyl salicylate (MS), have been reported as false-positives by this endpoint. In search of a potential endpoint to enhance the specificity of existing endpoints, we evaluated 3 contact sensitizers; (hexyl cinnamic aldehyde [HCA], oxazolone [OXA], and 2,4-dinitrochlorobenzene [DNCB]), 1 respiratory sensitizer (toluene 2,4-diisocyanate [TDI]), and 2 non-sensitizing irritants (MS and SDS) by several endpoints in LLNA. Each test substance was applied to both ears of female CBA/Ca mice daily for 3 consecutive days. The ears and auricle lymph node cells were analyzed on day 5 for endpoints including the SI value, lymph node cell count, cytokine release from lymph node cells, and histopathological changes and gene expression profiles in auricle skin. The SI values indicated that all the test substances induced significant proliferation of lymph node cells. The lymph node cell counts showed no significant changes by the non-sensitizers assessed. The inflammatory findings of histopathology were similar among the auricle skins treated by sensitizers and irritants. Gene expression profiles of cytokines IFN-γ, IL-4, and IL-17 in auricle skin were similar to the cytokine release profiles in draining lymph node cells. In addition, the gene expression of the chemokine CXCL1 and/or CXCL2 showed that it has the potential to discriminate sensitizers and non-sensitizing irritants. Our results suggest that multi-endpoint analysis in the LLNA leads to a better determination of the sensitizing potential of test substances. We also show that the gene expression of CXCL1 and/or CXCL2, which is involved in elicitation of contact hypersensitivity (CHS), can be a possible additional endpoint for discrimination of sensitizing compounds in LLNA. Copyright © 2017 Elsevier B.V. All rights reserved.

20170921 - An evaluation of selected (Q)SARs/expert systems for the Prediction of Skin Sensitization Potential (ASCCT)

EPA Science Inventory

Predictive testing to characterize substances for their skin sensitization potential has historically been based on animal models such as the Local Lymph Node Assay (LLNA) and the Guinea Pig Maximization Test (GPMT). In recent years, EU regulations have provided a strong incentiv...

Development of an in vitro skin sensitization test based on ROS production in THP-1 cells.

PubMed

Saito, Kazutoshi; Miyazawa, Masaaki; Nukada, Yuko; Sakaguchi, Hitoshi; Nishiyama, Naohiro

2013-03-01

Recently, it has been reported that reactive oxygen species (ROS) produced by contact allergens can affect dendritic cell migration and contact hypersensitivity. The aim of the present study was to develop a new in vitro assay that could predict the skin sensitizing potential of chemicals by measuring ROS production in THP-1 (human monocytic leukemia cell line) cells. THP-1 cells were pre-loaded with a ROS sensitive fluorescent dye, 5-(and 6-)-chloromethyl-2', 7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA), for 15min, then incubated with test chemicals for 30min. The fluorescence intensity was measured by flow cytometry. For the skin sensitizers, 25 out of 30 induced over a 2-fold ROS production at more than 90% of cell viability. In contrast, increases were only seen in 4 out of 20 non-sensitizers. The overall accuracy for the local lymph node assay (LLNA) was 82% for 50 chemicals tested. A correlation was found between the estimated concentration showing 2-fold ROS production in the ROS assay and the EC3 values (estimated concentration required to induce positive response) of the LLNA. These results indicated that the THP-1 cell-based ROS assay was a rapid and highly sensitive detection system able to predict skin sensitizing potentials and potency of chemicals. Copyright © 2012 Elsevier Ltd. All rights reserved.

In Vitro Reactivity of 3-M KC1-Solubilized Murine Histocompatibility (H-2) Antigens

DTIC Science & Technology

1974-01-01

experiment, varying concentra- mice were immunized with DBA/2 spleen tions of cells from day 5 BALB/c sensitized cells and subsequently skin grafted . Syn... skin grafts , spleen in MLC with mitomycin-C treated DBA/2 cells were removed and cultured with spleen cells. As seen in Table 4, increasing DBA/2...was solubilized antigens were assayed for levels produced by spleen cells from animals 5 of lymphotoxin (LT), it was seen that nor- days post skin graft sensitization

Cost-effectiveness of various methods of diagnosing hypersensitivity to Alternaria.

PubMed

Escudero, A I; Sánchez-Guerrero, I M; Mora, A M; Soriano, V; López, J D; García, F J; Negro, J M; Hernández, J; Pagán, J A

1993-01-01

This study was undertaken for two reasons: 1) It is more difficult to diagnose hypersensitivity to molds than to other allergens, so an evaluation of diagnostic tests was needed. 2) Alternaria is the principal cause of mold sensitization in our area. Sixty-six patients (20 +/- 4 years) were selected and divided into two groups. Group A was made up of patients with rhinitis and/or asthma due to Alternaria sensitization. Group B consisted of patients sensitized to other allergens and patients with nonrespiratory allergic disorders. Skin tests (prick and intradermal), challenge tests (conjunctival, nasal, and bronchial), and specific IgE determination were performed for all patients. A biologically standardized extract of Alternaria tenuis (Alergia e Inmunología Abelló, S. A., Madrid, Spain) obtained from a single batch was used for all tests. Our diagnostic criterion was a clinical history of rhinitis or asthma that coincided with the results of nasal/bronchial challenge. The diagnostic value of the other tests was compared to this criterion. In the group of rhinitic patients, skin tests and conjunctival challenge were more sensitive than specific IgE determination. In asthmatic patients, the most sensitive techniques were nasal and conjunctival challenges, followed by prick and intradermal skin tests, and, lastly, serum specific IgE determination. When rhinitis and asthma were considered jointly, the most sensitive test was conjunctival challenge, followed by skin-prick and intradermal tests. All tests had the same specificity, regardless of disorder. Nasal challenge was positive in all patients. Skin tests are easy to perform, cheap, non-traumatic for the patient, and sufficiently specific and sensitive for the diagnosis of Alternaria hypersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

DIFFERENTIAL RESPONSE TO ALLOGENIC AND XENOGENIC SKIN GRAFTS BY SUBLETHALLY IRRADIATED (670 RAD) AND NON-IRRADIATED MICE SENSITIZED BY VARIOUS MEANS

DTIC Science & Technology

consecutive BALB/c or rat skin tail grafts. One week following the last injection or the rejection of the second, skin graft , the mice either were grafted...resulted in prolonged survival of subsequent allogenic skin grafts in sublethally irradiated mice. The second-set response to a xenogenic skin graft was

[Respiratory allergies among symptomatic bakers and pastry cooks: initial results of a prevalence study].

PubMed

Bataille, A; Anton, M; Mollat, F; Bobe, M; Bonneau, C; Caramaniam, M N; Géraut, C; Dupas, D

1995-01-01

A survey was carried out on respiratory symptoms and skin prick response to common allergens, storage mite and occupational allergens. Among 178 symptomatics bakers and pastry workers from small businesses in western France, only 65 people underwent skin prick and specific-IgE. 12 (18%) workers were skin positive to at least one common or occupational allergens. The more often skin positive were D. Ptero. mite 36 (57%); Alpha amylase 23 (35%); wheat flour 17 (26%); saccharomyces cerevisiae 16 (25%); Ephestia 15 (24%). The sensitivity of skin test was better than specific IgE for D. Ptero. Mite 36 (57%); and Alpha amylase 23 (35%). The sensitivity of specific IgE was better than skin test for wheat flour 26 (45%) and rye flour 23 (40%). Occurrence of skin positive to occupational allergen among symptomatics with rhinitis and asthma is much more frequent in workers with skin positive to common allergens (40/36) than in workers with skin negative (8/20). Atopy must be regarded as an important predisposing factor for skin sensitisation to occupational allergens. We conclude in the necessity of a standardised allergologic exploration to be done in symptomatics bakers.

Usefulness of component resolved analysis of cat allergy in routine clinical practice.

PubMed

Eder, Katharina; Becker, Sven; San Nicoló, Marion; Berghaus, Alexander; Gröger, Moritz

2016-01-01

Cat allergy is of great importance, and its prevalence is increasing worldwide. Cat allergens and house dust mite allergens represent the major indoor allergens; however, they are ubiquitous. Cat sensitization and allergy are known risk factors for rhinitis, bronchial hyperreactivity and asthma. Thus, the diagnosis of sensitization to cats is important for any allergist. 70 patients with positive skin prick tests for cats were retrospectively compared regarding their skin prick test results, as well as their specific immunoglobulin E antibody profiles with regard to their responses to the native cat extract, rFel d 1, nFel d 2 and rFel d 4. 35 patients were allergic to cats, as determined by positive anamnesis and/or nasal provocation with cat allergens, and 35 patients exhibited clinically non-relevant sensitization, as indicated by negative anamnesis and/or a negative nasal allergen challenge. Native cat extract serology testing detected 100% of patients who were allergic to cats but missed eight patients who showed sensitization in the skin prick test and did not have allergic symptoms. The median values of the skin prick test, as well as those of the specific immunoglobulin E antibodies against the native cat extract, were significantly higher for allergic patients than for patients with clinically non-relevant sensitization. Component based diagnostic testing to rFel d 1 was not as reliable. Sensitization to nFel d 2 and rFel d 4 was seen only in individual patients. Extract based diagnostic methods for identifying cat allergy and sensitization, such as the skin prick test and native cat extract serology, remain crucial in routine clinical practice. In our study, component based diagnostic testing could not replace these methods with regard to the detection of sensitization to cats and differentiation between allergy and sensitization without clinical relevance. However, component resolved allergy diagnostic tools have individual implications, and future studies may facilitate a better understanding of its use and subsequently may improve the clinical management of allergic patients.

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

Goebel, Carsten, E-mail: goebel.c.1@pg.com; Troutman, John; Hennen, Jenny

The strong sensitizing potencies of the most important primary intermediates of oxidative hair dyes, p-phenylenediamine (PPD) and p-toluylenediamine (PTD, i.e. 2-methyl-PPD) are well established. They are considered as the key sensitizers in hair dye allergic contact dermatitis. While modification of their molecular structure is expected to alter their sensitizing properties, it may also impair their color performance. With introduction of a methoxymethyl side chain we found the primary intermediate 2-methoxymethyl-p-phenylenediamine (ME-PPD) with excellent hair coloring performance but significantly reduced sensitizing properties compared to PPD and PTD: In vitro, ME-PPD showed an attenuated innate immune response when analyzed for its proteinmore » reactivity and dendritic cell activation potential. In vivo, the effective concentration of ME-PPD necessary to induce an immune response 3-fold above vehicle control (EC3 value) in the local lymph node assay (LLNA) was 4.3%, indicating a moderate skin sensitizing potency compared to values of 0.1 and 0.17% for PPD and PTD, respectively. Finally, assessing the skin sensitizing potency of ME-PPD under consumer hair dye usage conditions through a quantitative risk assessment (QRA) indicated an allergy induction risk negligible compared to PPD or PTD. - Highlights: • Methoxymethyl side chain in p-phenylenediamine reduces its strong skin sensitizing properties. • Reduced protein reactivity and dendritic cell activation. • Reduced skin sensitizing potency in local lymph node assay (LLNA). • Negligible allergy induction risk under hair dye usage conditions.« less

Prediction of skin sensitization potency using machine learning approaches.

PubMed

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

2017-07-01

The replacement of animal use in testing for regulatory classification of skin sensitizers is a priority for US federal agencies that use data from such testing. Machine learning models that classify substances as sensitizers or non-sensitizers without using animal data have been developed and evaluated. Because some regulatory agencies require that sensitizers be further classified into potency categories, we developed statistical models to predict skin sensitization potency for murine local lymph node assay (LLNA) and human outcomes. Input variables for our models included six physicochemical properties and data from three non-animal test methods: direct peptide reactivity assay; human cell line activation test; and KeratinoSens™ assay. Models were built to predict three potency categories using four machine learning approaches and were validated using external test sets and leave-one-out cross-validation. A one-tiered strategy modeled all three categories of response together while a two-tiered strategy modeled sensitizer/non-sensitizer responses and then classified the sensitizers as strong or weak sensitizers. The two-tiered model using the support vector machine with all assay and physicochemical data inputs provided the best performance, yielding accuracy of 88% for prediction of LLNA outcomes (120 substances) and 81% for prediction of human test outcomes (87 substances). The best one-tiered model predicted LLNA outcomes with 78% accuracy and human outcomes with 75% accuracy. By comparison, the LLNA predicts human potency categories with 69% accuracy (60 of 87 substances correctly categorized). These results suggest that computational models using non-animal methods may provide valuable information for assessing skin sensitization potency. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Mild skin photosensitivity in cancer patients following injection of Photochlor (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a; HPPH) for photodynamic therapy.

PubMed

Bellnier, David A; Greco, William R; Nava, Hector; Loewen, Gregory M; Oseroff, Allan R; Dougherty, Thomas J

2006-01-01

To measure skin photosensitivity in cancer patients infused with the new second-generation photodynamic sensitizer Photochlor (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a). A major disadvantage of using the clinically approved photosensitizer Photofrin is potentially prolonged and sometimes severe cutaneous phototoxicity. Forty-eight patients enrolled in Phases 1 and 2 clinical trials underwent two or more exposures to four graded doses (44.4, 66.6, 88.8 or 133.2 J/cm2) of artificial solar-spectrum light (SSL) before and after administration of Photochlor at a dose of 2.5, 3, 4, 5 or 6 mg/m2 . The most severe skin response, experienced by only six of the subjects, was limited to erythema without edema and could only be elicited by exposure to the highest light dose. Conversely, eight subjects had no discernible reaction to SSL at any light dose. For nearly all the patients, the peak skin response was obtained when the interval between sensitizer injection and exposure to SSL was 1 day and, generally, their sensitivity to SSL decreased with increasing sensitizer-light interval. For example, a 2-day sensitizer-SSL interval resulted in less severe reactions than those obtained with the 1-day interval in 79% of the subjects, while 90% of the subjects exposed to SSL 3 days after Photochlor infusion had responses that were less severe than those obtained with either the 1- or 2-day sensitizer-SSL interval. Photochlor, at clinically effective antitumor doses, causes only mild skin photosensitivity that declines rapidly over a few days.

Validation and subsequent development of the DEREK skin sensitization rulebase by analysis of the BgVV list of contact allergens.

PubMed

Barratt, M D; Langowski, J J

1999-01-01

The DEREK knowledge-based computer system contains a subset of approximately 50 rules describing chemical substructures (toxophores) responsible for skin sensitization. This rulebase, based originally on Unilever historical in-house guinea pig maximization test data, has been subject to extensive validation and is undergoing refinement as the next stage of its development. As part of an ongoing program of validation and testing, the predictive ability of the sensitization rule set has been assessed by processing the structures of the 84 chemical substances in the list of contact allergens issued by the BgVV (German Federal Institute for Health Protection of Consumers). This list of chemicals is important because the biological data for each of the chemicals have been carefully scrutinized and peer reviewed, a key consideration in an area of toxicology in which much unreliable and potentially misleading data have been published. The existing DEREK rulebase for skin sensitization identified toxophores for skin sensitization in the structures of 71 out of the 84 chemicals (85%). The exercise highlighted areas of chemistry where further development of the rulebase was required, either by extension of the scope of existing rules or by generation of new rules where a sound mechanistic rationale for the biological activity could be established. Chemicals likely to be acting as photoallergens were identified, and new rules for photoallergenicity have subsequently been written. At the end of the exercise, the refined rulebase was able to identify toxophores for skin sensitization for 82 of the 84 chemicals in the BgVV list.

Evaluation of in silico tools to predict the skin sensitization potential of chemicals.

PubMed

Verheyen, G R; Braeken, E; Van Deun, K; Van Miert, S

2017-01-01

Public domain and commercial in silico tools were compared for their performance in predicting the skin sensitization potential of chemicals. The packages were either statistical based (Vega, CASE Ultra) or rule based (OECD Toolbox, Toxtree, Derek Nexus). In practice, several of these in silico tools are used in gap filling and read-across, but here their use was limited to make predictions based on presence/absence of structural features associated to sensitization. The top 400 ranking substances of the ATSDR 2011 Priority List of Hazardous Substances were selected as a starting point. Experimental information was identified for 160 chemically diverse substances (82 positive and 78 negative). The prediction for skin sensitization potential was compared with the experimental data. Rule-based tools perform slightly better, with accuracies ranging from 0.6 (OECD Toolbox) to 0.78 (Derek Nexus), compared with statistical tools that had accuracies ranging from 0.48 (Vega) to 0.73 (CASE Ultra - LLNA weak model). Combining models increased the performance, with positive and negative predictive values up to 80% and 84%, respectively. However, the number of substances that were predicted positive or negative for skin sensitization in both models was low. Adding more substances to the dataset will increase the confidence in the conclusions reached. The insights obtained in this evaluation are incorporated in a web database www.asopus.weebly.com that provides a potential end user context for the scope and performance of different in silico tools with respect to a common dataset of curated skin sensitization data.

Ultrahigh sensitive optical microangiography for in vivo imaging of microcirculations within human skin tissue beds

PubMed Central

An, Lin; Qin, Jia; Wang, Ruikang K

2010-01-01

In this paper, we demonstrate for the first time that the detailed cutaneous blood flow at capillary level within dermis of human skin can be imaged by optical micro-angiography (OMAG) technique. A novel scanning protocol, i.e. fast B scan mode is used to achieve the capillary flow imaging. We employ a 1310nm system to scan the skin tissue at an imaging rate of 300 frames per second, which requires only ∼5 sec to complete one 3D imaging of capillary blood flow within skin. The technique is sensitive enough to image the very slow blood flows at ∼4 μm/sec. The promising results show a great potential of OMAG's role in the diagnosis, treatment and management of human skin diseases. PMID:20588668

MEMS-based Force-clamp Analysis of the Role of Body Stiffness in C. elegans Touch Sensation

PubMed Central

Petzold, Bryan C.; Park, Sung-Jin; Mazzochette, Eileen A.; Goodman, Miriam B.; Pruitt, Beth L.

2013-01-01

Touch is enabled by mechanoreceptor neurons in the skin and plays an essential role in our everyday lives, but is among the least understood of our five basic senses. Force applied to the skin deforms these neurons and activates ion channels within them. Despite the importance of the mechanics of the skin in determining mechanoreceptor neuron deformation and ultimately touch sensation, the role of mechanics in touch sensitivity is poorly understood. Here, we use the model organism Caenorhabditis elegans to directly test the hypothesis that body mechanics modulate touch sensitivity. We demonstrate a microelectromechanical system (MEMS)-based force clamp that can apply calibrated forces to freely crawling C. elegans worms and measure touch-evoked avoidance responses. This approach reveals that wild-type animals sense forces < 1 μN and indentation depths < 1 μm. We use both genetic manipulation of the skin and optogenetic modulation of body wall muscles to alter body mechanics. We find that small changes in body stiffness dramatically affect force sensitivity, while having only modest effects on indentation sensitivity. We investigate the theoretical body deformation predicted under applied force and conclude that local mechanical loads induce inward bending deformation of the skin to drive touch sensation in C. elegans. PMID:23598612

Stress and skin disease quality of life: the moderating role of anxiety sensitivity social concerns.

PubMed

Dixon, L J; Witcraft, S M; McCowan, N K; Brodell, R T

2018-04-01

Stress is an important factor in the onset, exacerbation and reoccurrence of many skin diseases. Little is known about psychological risk factors that affect the association between stress and dermatological conditions. One relevant factor that may modulate this link is anxiety sensitivity (AS) social concerns - the propensity to respond fearfully to anxiety-related sensations (e.g. sweating, flushing) owing to perceived social consequences (e.g. rejection or humiliation). To gain insight into psychological factors affecting skin disease, we examined the moderating role of AS social concerns in the relationship between stress and skin disease quality of life (QoL). Participants [n = 237 (161 female), mean ± SD age 34·18 ± 9·57 years] with active skin disease symptoms were recruited online and completed questionnaires assessing stress, AS social concerns, skin disease QoL and global skin disease symptom severity. AS social concerns moderated the association between stress and skin-related emotional and social functioning in adults with skin disease. Stress was a significant predictor of the impairment associated with skin disease. Stress was linked to skin disease-related emotional and functional impairment associated with skin disease among individuals with high AS social concerns. These results highlight the potential for AS reduction interventions to break the vicious cycle of stress and skin disease symptoms and to improve psychosocial well-being in dermatology patients. © 2017 British Association of Dermatologists.

Is skin penetration a determining factor in skin sensitization ...

EPA Pesticide Factsheets

Summary:Background. It is widely accepted that substances that cannot penetrate through the skin will not be sensitisers. Thresholds based on relevant physicochemical parameters such as a LogKow > 1 and a MW 1 is a true requirement for sensitisation.Methods. A large dataset of substances that had been evaluated for their skin sensitisation potential, together with measured LogKow values was compiled from the REACH database. The incidence of skin sensitisers relative to non-skin sensitisers below and above the LogKow = 1 threshold was evaluated. Results. 1482 substances with associated skin sensitisation outcomes and measured LogKow values were identified. 305 substances had a measured LogKow < 0 and of those, 38 were sensitisers.Conclusions. There was no significant difference in the incidence of skin sensitisation above and below the LogKow = 1 threshold. Reaction chemistry considerations could explain the skin sensitisation observed for the 38 sensitisers with a LogKow < 0. The LogKow threshold is a self-evident truth borne out from the widespread misconception that the ability to efficiently penetrate the stratum corneum is a key determinant of skin sensitisation potential and potency. Using the REACH data extracted to test out the validity of common assumptions in the skin sensitization AOP. Builds on trying to develop a proof of concept IATA

Effect of skin temperature on the cholinergic sensitivity of the human eccrine sweat gland.

PubMed

DiPasquale, Dana M; Buono, Michael J; Kolkhorst, Fred W

2003-12-01

Although sweat gland activity is directly controlled by the central nervous system, which detects changes in core body temperature, sweat glands can also be influenced by local cutaneous thermal conditions. The present study sought to determine the effect of local skin temperature on pilocarpine-induced sweating within a range of typical skin temperatures. Thirteen subjects (30 +/- 6 years; 172 +/- 11 cm; 72.8 +/- 11.0 kg) had forearm sweat rates measured at rest following pilocarpine iontophoresis at each of three skin temperatures in randomized order: warm (T(warm) = 37.1 +/- 0.9 degrees C), control (T(con) = 32.3 +/- 1.4 degrees C), and cool (T(cool) = 26.6 +/- 1.3 degrees C). T(skin) was raised and lowered with an electric heating pad and gel ice pack, respectively. Forearm T(skin) was measured with a skin temperature probe. Pilocarpine iontophoresis was used on an approximately 7 cm(2) area of the anterior forearm to stimulate localized sweating. Following stimulation, sweat was collected from the area for 15 min with a Macroduct Sweat Collection System. There was a higher sweat rate at T(warm) (p = 0.001) and T(con) (p = 0.006) compared to that at T(cool). However, there was no difference between the sweat rate at T(warm) and that at T(con) (p = 0.127). These results indicated that skin temperatures below approximately 32 degrees C affect local sweat production primarily by altering glandular sensitivity to the neurotransmitter, whereas skin temperatures above approximately 32 degrees C predominantly affect neurotransmitter release. Furthermore, sweat glands display maximal or near maximal cholinergic sensitivity at resting skin temperature in a thermoneutral environment.

Pharmacologic induction of epidermal melanin and protection against sunburn in a humanized mouse model.

PubMed

Amaro-Ortiz, Alexandra; Vanover, Jillian C; Scott, Timothy L; D'Orazio, John A

2013-09-07

Fairness of skin, UV sensitivity and skin cancer risk all correlate with the physiologic function of the melanocortin 1 receptor, a Gs-coupled signaling protein found on the surface of melanocytes. Mc1r stimulates adenylyl cyclase and cAMP production which, in turn, up-regulates melanocytic production of melanin in the skin. In order to study the mechanisms by which Mc1r signaling protects the skin against UV injury, this study relies on a mouse model with "humanized skin" based on epidermal expression of stem cell factor (Scf). K14-Scf transgenic mice retain melanocytes in the epidermis and therefore have the ability to deposit melanin in the epidermis. In this animal model, wild type Mc1r status results in robust deposition of black eumelanin pigment and a UV-protected phenotype. In contrast, K14-Scf animals with defective Mc1r signaling ability exhibit a red/blonde pigmentation, very little eumelanin in the skin and a UV-sensitive phenotype. Reasoning that eumelanin deposition might be enhanced by topical agents that mimic Mc1r signaling, we found that direct application of forskolin extract to the skin of Mc1r-defective fair-skinned mice resulted in robust eumelanin induction and UV protection (1). Here we describe the method for preparing and applying a forskolin-containing natural root extract to K14-Scf fair-skinned mice and report a method for measuring UV sensitivity by determining minimal erythematous dose (MED). Using this animal model, it is possible to study how epidermal cAMP induction and melanization of the skin affect physiologic responses to UV exposure.

Further development of LLNA:DAE method as stand-alone skin-sensitization testing method and applied for evaluation of relative skin-sensitizing potency between chemicals.

PubMed

Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Itagaki, Hiroshi

2015-04-01

To date, there has been no well-established local lymph node assay (LLNA) that includes an elicitation phase. Therefore, we developed a modified local lymph node assay with an elicitation phase (LLNA:DAE) to discriminate true skin sensitizers from chemicals that gave borderline positive results and previously reported this assay. To develop the LLNA:DAE method as a useful stand-alone testing method, we investigated the complete procedure for the LLNA:DAE method using hexyl cinnamic aldehyde (HCA), isoeugenol, and 2,4-dinitrochlorobenzene (DNCB) as test compounds. We defined the LLNA:DAE procedure as follows: in the dose-finding test, four concentrations of chemical applied to dorsum of the right ear on days 1, 2, and 3 and dorsum of both ears on day 10. Ear thickness and skin irritation score were measured on days 1, 3, 5, 10, and 12. Local lymph nodes were excised and weighed on day 12. The test dose for the primary LLNA:DAE study was selected as the dose that gave the highest left ear lymph node weight in the dose-finding study, or the lowest dose that produced a left ear lymph node of over 4 mg. This procedure was validated using nine different chemicals. Furthermore, qualitative relationship was observed between the degree of elicitation response in the left ear lymph node and the skin sensitizing potency of 32 chemicals tested in this study and the previous study. These results indicated that LLNA:DAE method was as first LLNA method that was able to evaluate the skin sensitizing potential and potency in elicitation response.

Evaluation of a topical treatment for the relief of sensitive skin

PubMed Central

Heinicke, Ingrid R; Adams, Damian H; Barnes, Tanya M; Greive, Kerryn A

2015-01-01

Background Approximately, 50% of the population claim to have sensitive skin, which has created an important challenge for dermatologists and the cosmetic industry. This study evaluates the properties of QV Face Rescue Gel (Rescue Gel) that contains a combination of moisturizing and anti-irritant ingredients, and which is used to relieve the symptoms of sensitive facial skin. Methods The ability of Rescue Gel to induce collagen types I and III in cultured neonatal human foreskin fibroblasts compared to transforming growth factor beta 1, a known potent inducer of collagen types I and III, was measured using immunofluorescence staining. Furthermore, healthy volunteers were recruited to measure the potential for Rescue Gel to reduce erythema induced by solar-simulated ultraviolet radiation on the skin compared to 0.5% hydrocortisone cream (positive control) as well as it’s ability to decrease transepidermal water loss compared to baseline levels. In addition, the formulation was tested for its potential to be 1) nonstinging using a facial sting/discomfort assay performed on volunteers who reacted positively to lactic acid, 2) nonirritating as determined by repeat insult patch tests, and 3) noncomedogenic. Results Rescue Gel significantly induced collagen types I and III in cultured human foreskin fibroblasts similarly to transforming growth factor beta 1. In volunteers, Rescue Gel was shown to significantly reduce erythema induced by solar-simulated ultraviolet radiation similarly to 0.5% hydrocortisone, and to significantly reduce transepidermal water loss compared to baseline levels. Further, the formulation was found to be nonstinging, nonirritating, and noncomedogenic. No adverse events were observed. Conclusion In this study, Rescue Gel has been shown to exhibit properties that make it effective for use on sensitive or irritated facial skin, without exacerbation of the symptoms associated with sensitive skin. PMID:26251625

Application of IATA - A case study in evaluating the global and local performance of a Bayesian Network model for Skin Sensitization

EPA Science Inventory

Since the publication of the Adverse Outcome Pathway (AOP) for skin sensitization, there have been many efforts to develop systematic approaches to integrate the information generated from different key events for decision making. The types of information characterizing key event...

An evaluation of selected (Q)SARs/expert systems for the Prediction of Skin Sensitization Potential (WC10)

EPA Science Inventory

One of the alternative approaches to assessing skin sensitization hazard is through the use of (Q)SARs/expert systems. Here we evaluate the predictive performance of two expert systems (TIMES-SS and VEGA) and two SAR rulebases (OASIS protein binding alerts and Toxtree’s reactivit...

Eye-independent, light-activated chromatophore expansion (LACE) and expression of phototransduction genes in the skin of Octopus bimaculoides

PubMed Central

Ramirez, M. Desmond; Oakley, Todd H.

2015-01-01

ABSTRACT Cephalopods are renowned for changing the color and pattern of their skin for both camouflage and communication. Yet, we do not fully understand how cephalopods control the pigmented chromatophore organs in their skin and change their body pattern. Although these changes primarily rely on eyesight, we found that light causes chromatophores to expand in excised pieces of Octopus bimaculoides skin. We call this behavior light-activated chromatophore expansion (or LACE). To uncover how octopus skin senses light, we used antibodies against r-opsin phototransduction proteins to identify sensory neurons that express r-opsin in the skin. We hypothesized that octopus LACE relies on the same r-opsin phototransduction cascade found in octopus eyes. By creating an action spectrum for the latency to LACE, we found that LACE occurred most quickly in response to blue light. We fit our action spectrum data to a standard opsin curve template and estimated the λmax of LACE to be 480 nm. Consistent with our hypothesis, the maximum sensitivity of the light sensors underlying LACE closely matches the known spectral sensitivity of opsin from octopus eyes. LACE in isolated preparations suggests that octopus skin is intrinsically light sensitive and that this dispersed light sense might contribute to their unique and novel patterning abilities. Finally, our data suggest that a common molecular mechanism for light detection in eyes may have been co-opted for light sensing in octopus skin and then used for LACE. PMID:25994633

mHealth App for Risk Assessment of Pigmented and Nonpigmented Skin Lesions-A Study on Sensitivity and Specificity in Detecting Malignancy.

PubMed

Thissen, Monique; Udrea, Andreea; Hacking, Michelle; von Braunmuehl, Tanja; Ruzicka, Thomas

2017-12-01

With the advent of smartphone devices, an increasing number of mHealth applications that target melanoma identification have been developed, but none addresses the general context of melanoma and nonmelanoma skin cancer identification. In this study a smartphone application using fractal and classical image analysis for the risk assessment of skin lesions is systematically evaluated to determine its sensitivity and specificity in the diagnosis of melanoma and nonmelanoma skin cancer along with actinic keratosis and Bowen's disease. In the Department of Dermatology, Catharina Hospital Eindhoven, The Netherlands, 341 melanocytic and nonmelanocytic lesions were imaged using SkinVision app; 239 underwent histopathological examination, while the rest of 102 lesions were clinically diagnosed as clearly benign and not removed. The algorithm has been calibrated using the images of the first 233 lesions. The calibrated version of the algorithm was used in a subset of 108 lesions, and the obtained results were compared with the medical findings. On the 108 cases used for evaluation the algorithm scored 80% sensitivity and 78% specificity in detecting (pre)malignant conditions. Although less accurate than the dermatologist's clinical eye, the app may offer support to other professionals who are less familiar with differentiating between benign and malignant lesions. An mHealth application for the risk assessment of skin lesions was evaluated. It adds value to diagnosis tools of its type by taking into consideration pigmented and nonpigmented lesions all together and detecting signs of malignancy with high sensitivity.

Prediction of Chemical Respiratory and Contact Sensitizers by OX40L Expression in Dendritic Cells Using a Novel 3D Coculture System.

PubMed

Mizoguchi, Izuru; Ohashi, Mio; Chiba, Yukino; Hasegawa, Hideaki; Xu, Mingli; Owaki, Toshiyuki; Yoshimoto, Takayuki

2017-01-01

The use of animal models in chemical safety testing will be significantly limited due to the recent introduction of the 3Rs principle of animal experimentation in research. Although several in vitro assays to predict the sensitizing potential of chemicals have been developed, these methods cannot distinguish chemical respiratory sensitizers and skin sensitizers. In the present study, we describe a novel in vitro assay that can discriminate respiratory sensitizers from chemical skin sensitizers by taking advantage of the fundamental difference between their modes of action, namely the development of the T helper 2 immune response, which is critically important for respiratory sensitization. First, we established a novel three-dimensional (3D) coculture system of human upper airway epithelium using a commercially available scaffold. It consists of human airway epithelial cell line BEAS-2B, immature dendritic cells (DCs) derived from human peripheral blood CD14 + monocytes, and human lung fibroblast cell line MRC-5. Respective cells were first cultured in individual scaffolds and subsequently assembled into a 3D multi-cell tissue model to more closely mimic the in vivo situation. Then, three typical chemicals that are known respiratory sensitizers (ortho-phthaldialdehyde, hexamethylene diisocyanate, and trimellitic anhydride) and skin sensitizers (oxazolone, formaldehyde, and dinitrochlorobenzene) were added individually to the 3D coculture system. Immunohistochemical analysis revealed that DCs do not migrate into other scaffolds under the experimental conditions. Therefore, the 3D structure was disassembled and real-time reverse transcriptase-PCR analysis was performed in individual scaffolds to analyze the expression levels of molecules critical for Th2 differentiation such as OX40 ligand (OX40L), interleukin (IL)-4, IL-10, IL-33, and thymic stromal lymphopoietin. Both sensitizers showed similarly augmented expression of DC maturation markers (e.g., CD86), but among these molecules, OX40L expression in DCs was most consistently and significantly enhanced by respiratory sensitizers as compared to that by skin sensitizers. Thus, we have established a 3D coculture system mimicking the airway upper epithelium that may be successfully applied to discriminate chemical respiratory sensitizers from skin sensitizers by measuring the critical molecule for Th2 differentiation, OX40L, in DCs.

Detection theory for accurate and non-invasive skin cancer diagnosis using dynamic thermal imaging

PubMed Central

Godoy, Sebastián E.; Hayat, Majeed M.; Ramirez, David A.; Myers, Stephen A.; Padilla, R. Steven; Krishna, Sanjay

2017-01-01

Skin cancer is the most common cancer in the United States with over 3.5M annual cases. Presently, visual inspection by a dermatologist has good sensitivity (> 90%) but poor specificity (< 10%), especially for melanoma, which leads to a high number of unnecessary biopsies. Here we use dynamic thermal imaging (DTI) to demonstrate a rapid, accurate and non-invasive imaging system for detection of skin cancer. In DTI, the lesion is cooled down and the thermal recovery is recorded using infrared imaging. The thermal recovery curves of the suspected lesions are then utilized in the context of continuous-time detection theory in order to define an optimal statistical decision rule such that the sensitivity of the algorithm is guaranteed to be at a maximum for every prescribed false-alarm probability. The proposed methodology was tested in a pilot study including 140 human subjects demonstrating a sensitivity in excess of 99% for a prescribed specificity in excess of 99% for detection of skin cancer. To the best of our knowledge, this is the highest reported accuracy for any non-invasive skin cancer diagnosis method. PMID:28736673

Blebbistatin, a myosin II inhibitor, suppresses Ca(2+)-induced and "sensitized"-contraction of skinned tracheal muscles from guinea pig.

PubMed

Yumoto, Masatoshi; Watanabe, Masaru

2013-01-01

Blebbistatin, a potent inhibitor of myosin II, has inhibiting effects on Ca(2+)-induced contraction and contractile filament organization without affecting the Ca(2+)-sensitivity to the force and phosphorylation level of myosin regulatory light chain (MLC20) in skinned (cell membrane permeabilized) taenia cecum from the guinea pig (Watanabe et al., Am J Physiol Cell Physiol. 2010; 298: C1118-26). In the present study, we investigated blebbistatin effects on the contractile force of skinned tracheal muscle, in which myosin filaments organization is more labile than that in the taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca(2+)-induced tension development at any given Ca(2+) concentration, but had little effects on the Ca(2+)- induced myosin light chain phosphorylation. Also blebbistatin at 10 μM and higher significantly suppressed GTP-γS-induced "sensitized" force development. Since the force inhibiting effects of blebbistatin on the skinned trachea were much stronger than those in skinned taenia cecum, blebbistatin might directly affect myosin filaments organization.

Diagnostic value of the basophil activation test in evaluating Hymenoptera venom sensitization.

PubMed

Peternelj, Andreja; Silar, Mira; Bajrovic, Nissera; Adamic, Katja; Music, Ema; Kosnik, Mitja; Korosec, Peter

2009-01-01

Diagnosis of allergy to Hymenoptera venom is usually confirmed with skin testing and measurement of specific serum IgE antibody, tests which are sometimes inconclusive. In these cases, additional in vitro tests are necessary. The aim of this study was to show the applicability of the basophil activation test in detecting sensitization to Hymenoptera venom and to compare the test sensitivity and clinical positive-predictive value with skin prick tests and measurement of allergen-specific serum IgE. This prospective study was conducted between June 2004 and December 2007 and included a large group of 204 patients. All patients had a history of at least one systemic allergic reaction of Müller grades II-IV after a Hymenoptera sting. We compared results of the basophil activation test, specific serum IgE and skin prick tests with patients' clinical history and data on culprit insects. The overall clinical sensitivities of the basophil activation test, specific serum IgE and skin prick tests were 90%, 76% and 64%, respectively; the clinical positive-predictive values of the three tests were 79%, 73% and 78% for bee venom, 86%, 59% and 43% for wasp venom; and 84%, 77% and 22% for both venoms. Our results revealed a higher clinical sensitivity and comparable or better clinical positive-predictive value of basophil activation tests than skin prick tests and allergen-specific serum IgE in the detection of allergy to Hymenoptera venom.

Actively Perceiving and Responsive Soft Robots Enabled by Self-Powered, Highly Extensible, and Highly Sensitive Triboelectric Proximity- and Pressure-Sensing Skins.

PubMed

Lai, Ying-Chih; Deng, Jianan; Liu, Ruiyuan; Hsiao, Yung-Chi; Zhang, Steven L; Peng, Wenbo; Wu, Hsing-Mei; Wang, Xingfu; Wang, Zhong Lin

2018-06-04

Robots that can move, feel, and respond like organisms will bring revolutionary impact to today's technologies. Soft robots with organism-like adaptive bodies have shown great potential in vast robot-human and robot-environment applications. Developing skin-like sensory devices allows them to naturally sense and interact with environment. Also, it would be better if the capabilities to feel can be active, like real skin. However, challenges in the complicated structures, incompatible moduli, poor stretchability and sensitivity, large driving voltage, and power dissipation hinder applicability of conventional technologies. Here, various actively perceivable and responsive soft robots are enabled by self-powered active triboelectric robotic skins (tribo-skins) that simultaneously possess excellent stretchability and excellent sensitivity in the low-pressure regime. The tribo-skins can actively sense proximity, contact, and pressure to external stimuli via self-generating electricity. The driving energy comes from a natural triboelectrification effect involving the cooperation of contact electrification and electrostatic induction. The perfect integration of the tribo-skins and soft actuators enables soft robots to perform various actively sensing and interactive tasks including actively perceiving their muscle motions, working states, textile's dampness, and even subtle human physiological signals. Moreover, the self-generating signals can drive optoelectronic devices for visual communication and be processed for diverse sophisticated uses. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pyridoxylamine reactivity kinetics as an amine based nucleophile for screening electrophilic dermal sensitizers

PubMed Central

Chipinda, Itai; Mbiya, Wilbes; Adigun, Risikat Ajibola; Morakinyo, Moshood K.; Law, Brandon F.; Simoyi, Reuben H.; Siegel, Paul D.

2015-01-01

Chemical allergens bind directly, or after metabolic or abiotic activation, to endogenous proteins to become allergenic. Assessment of this initial binding has been suggested as a target for development of assays to screen chemicals for their allergenic potential. Recently we reported a nitrobenzenethiol (NBT) based method for screening thiol reactive skin sensitizers, however, amine selective sensitizers are not detected by this assay. In the present study we describe an amine (pyridoxylamine (PDA)) based kinetic assay to complement the NBT assay for identification of amine-selective and non-selective skin sensitizers. UV-Vis spectrophotometry and fluorescence were used to measure PDA reactivity for 57 chemicals including anhydrides, aldehydes, and quinones where reaction rates ranged from 116 to 6.2 × 10−6 M−1 s−1 for extreme to weak sensitizers, respectively. No reactivity towards PDA was observed with the thiol-selective sensitizers, non-sensitizers and prohaptens. The PDA rate constants correlated significantly with their respective murine local lymph node assay (LLNA) threshold EC3 values (R2 = 0.76). The use of PDA serves as a simple, inexpensive amine based method that shows promise as a preliminary screening tool for electrophilic, amine-selective skin sensitizers. PMID:24333919

Skylab

NASA Image and Video Library

1973-05-01

The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows the damaged meteoroid shield being held by a thin aluminum strap entangled with green-hued remnants of the lost heat shield. The Marshall Space Flight Center (MSFC) developed, tested, rehearsed, and approved three repair options. These options included a parasol sunshade and a twin-pole sunshade to restore the temperature inside the workshop, and a set of metal cutting tools to free the jammed solar panel.

An unexpected advantage of whiteness in horses: the most horsefly-proof horse has a depolarizing white coat

PubMed Central

Horváth, Gábor; Blahó, Miklós; Kriska, György; Hegedüs, Ramón; Gerics, Balázs; Farkas, Róbert; Åkesson, Susanne

2010-01-01

White horses frequently suffer from malign skin cancer and visual deficiencies owing to their high sensitivity to the ultraviolet solar radiation. Furthermore, in the wild, white horses suffer a larger predation risk than dark individuals because they can more easily be detected. In spite of their greater vulnerability, white horses have been highly appreciated for centuries owing to their natural rarity. Here, we show that blood-sucking tabanid flies, known to transmit disease agents to mammals, are less attracted to white than dark horses. We also demonstrate that tabanids use reflected polarized light from the coat as a signal to find a host. The attraction of tabanids to mainly black and brown fur coats is explained by positive polarotaxis. As the host's colour determines its attractiveness to tabanids, this parameter has a strong influence on the parasite load of the host. Although we have studied only the tabanid–horse interaction, our results can probably be extrapolated to other host animals of polarotactic tabanids, as the reflection–polarization characteristics of the host's body surface are physically the same, and thus not species-dependent. PMID:20129982

Molecular mechanisms of temperature adaptation

PubMed Central

Bagriantsev, Sviatoslav N; Gracheva, Elena O

2015-01-01

Thermal perception is a fundamental physiological process pertaining to the vast majority of organisms. In vertebrates, environmental temperature is detected by the primary afferents of the somatosensory neurons in the skin, which express a ‘choir’ of ion channels tuned to detect particular temperatures. Nearly two decades of research have revealed a number of receptor ion channels that mediate the perception of several temperature ranges, but most still remain molecularly orphaned. Yet even within this well-researched realm, most of our knowledge largely pertains to two closely related species of rodents, mice and rats. While these are standard biomedical research models, mice and rats provide a limited perspective to elucidate the general principles that drive somatosensory evolution. In recent years, significant advances have been made in understanding the molecular mechanism of temperature adaptation in evolutionarily distant vertebrates and in organisms with acute thermal sensitivity. These studies have revealed the remarkable versatility of the somatosensory system and highlighted adaptations at the molecular level, which often include changes in biophysical properties of ion channels from the transient receptor potential family. Exploiting non-standard animal models has the potential to provide unexpected insights into general principles of thermosensation and thermoregulation, unachievable using the rodent model alone. PMID:25433072

Biodosimetric quantification of short-term synchrotron microbeam versus broad-beam radiation damage to mouse skin using a dermatopathological scoring system

PubMed Central

Priyadarshika, R C U; Crosbie, J C; Kumar, B; Rogers, P A W

2011-01-01

Objectives Microbeam radiotherapy (MRT) with wafers of microscopically narrow, synchrotron generated X-rays is being used for pre-clinical cancer trials in animal models. It has been shown that high dose MRT can be effective at destroying tumours in animal models, while causing unexpectedly little damage to normal tissue. The aim of this study was to use a dermatopathological scoring system to quantify and compare the acute biological response of normal mouse skin with microplanar and broad-beam (BB) radiation as a basis for biological dosimetry. Method The skin flaps of three groups of mice were irradiated with high entrance doses (200 Gy, 400 Gy and 800 Gy) of MRT and BB and low dose BB (11 Gy, 22 Gy and 44 Gy). The mice were culled at different time-points post-irradiation. Skin sections were evaluated histologically using the following parameters: epidermal cell death, nuclear enlargement, spongiosis, hair follicle damage and dermal inflammation. The fields of irradiation were identified by γH2AX-positive immunostaining. Results The acute radiation damage in skin from high dose MRT was significantly lower than from high dose BB and, importantly, similar to low dose BB. Conclusion The integrated MRT dose was more relevant than the peak or valley dose when comparing with BB fields. In MRT-treated skin, the apoptotic cells of epidermis and hair follicles were not confined to the microbeam paths. PMID:21849367

C/EBPα expression is downregulated in human nonmelanoma skin cancers and inactivation of C/EBPα confers susceptibility to UVB-induced skin squamous cell carcinomas.

PubMed

Thompson, Elizabeth A; Zhu, Songyun; Hall, Jonathan R; House, John S; Ranjan, Rakesh; Burr, Jeanne A; He, Yu-Ying; Owens, David M; Smart, Robert C

2011-06-01

Human epidermis is routinely subjected to DNA damage induced by UVB solar radiation. Cell culture studies have revealed an unexpected role for C/EBPα (CCAAT/enhancer-binding protein-α) in the DNA damage response network, where C/EBPα is induced following UVB DNA damage, regulates the G(1) checkpoint, and diminished or ablated expression of C/EBPα results in G(1) checkpoint failure. In the current study we observed that C/EBPα is induced in normal human epidermal keratinocytes and in the epidermis of human subjects exposed to UVB radiation. The analysis of human skin precancerous and cancerous lesions (47 cases) for C/EBPα expression was conducted. Actinic keratoses, a precancerous benign skin growth and precursor to squamous cell carcinoma (SCC), expressed levels of C/EBPα similar to normal epidermis. Strikingly, all invasive SCCs no longer expressed detectable levels of C/EBPα. To determine the significance of C/EBPα in UVB-induced skin cancer, SKH-1 mice lacking epidermal C/EBPα (CKOα) were exposed to UVB. CKOα mice were highly susceptible to UVB-induced SCCs and exhibited accelerated tumor progression. CKOα mice displayed keratinocyte cell cycle checkpoint failure in vivo in response to UVB that was characterized by abnormal entry of keratinocytes into S phase. Our results demonstrate that C/EBPα is silenced in human SCC and loss of C/EBPα confers susceptibility to UVB-induced skin SCCs involving defective cell cycle arrest in response to UVB.

C/EBPα Expression Is Downregulated in Human Nonmelanoma Skin Cancers and Inactivation of C/EBPα Confers Susceptibility to UVB-Induced Skin Squamous Cell Carcinomas

PubMed Central

Thompson, Elizabeth A.; Zhu, Songyun; Hall, Jonathan R.; House, John S.; Ranjan, Rakesh; Burr, Jeanne A.; He, Yu-Ying; Owens, David M.; Smart, Robert C.

2012-01-01

Human epidermis is routinely subjected to DNA damage induced by UVB solar radiation. Cell culture studies have revealed an unexpected role for C/EBPα (CCAAT/enhancer-binding protein-α) in the DNA damage response network, where C/EBPα is induced following UVB DNA damage, regulates the G1 checkpoint, and diminished or ablated expression of C/EBPα results in G1 checkpoint failure. In the current study we observed that C/EBPα is induced in normal human epidermal keratinocytes and in the epidermis of human subjects exposed to UVB radiation. The analysis of human skin precancerous and cancerous lesions (47 cases) for C/EBPα expression was conducted. Actinic keratoses, a precancerous benign skin growth and precursor to squamous cell carcinoma (SCC), expressed levels of C/EBPα similar to normal epidermis. Strikingly, all invasive SCCs no longer expressed detectable levels of C/EBPα. To determine the significance of C/EBPα in UVB-induced skin cancer, SKH-1 mice lacking epidermal C/EBPα (CKOα) were exposed to UVB. CKOα mice were highly susceptible to UVB-induced SCCs and exhibited accelerated tumor progression. CKOα mice displayed keratinocyte cell cycle checkpoint failure in vivo in response to UVB that was characterized by abnormal entry of keratinocytes into S phase. Our results demonstrate that C/EBPα is silenced in human SCC and loss of C/EBPα confers susceptibility to UVB-induced skin SCCs involving defective cell cycle arrest in response to UVB. PMID:21346772

Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy

PubMed Central

Brough, Helen A.; Liu, Andrew H.; Sicherer, Scott; Makinson, Kerry; Douiri, Abdel; Brown, Sara J.; Stephens, Alick C.; Irwin McLean, W.H.; Turcanu, Victor; Wood, Robert A.; Jones, Stacie M.; Burks, Wesley; Dawson, Peter; Stablein, Donald; Sampson, Hugh; Lack, Gideon

2015-01-01

Background History and severity of atopic dermatitis (AD) are risk factors for peanut allergy. Recent evidence suggests that children can become sensitized to food allergens through an impaired skin barrier. Household peanut consumption, which correlates strongly with peanut protein levels in household dust, is a risk factor for peanut allergy. Objective We sought to assess whether environmental peanut exposure (EPE) is a risk for peanut sensitization and allergy and whether markers of an impaired skin barrier modify this risk. Methods Peanut protein in household dust (in micrograms per gram) was assessed in highly atopic children (age, 3-15 months) recruited to the Consortium of Food Allergy Research Observational Study. History and severity of AD, peanut sensitization, and likely allergy (peanut-specific IgE, ≥5 kUA/mL) were assessed at recruitment into the Consortium of Food Allergy Research study. Results There was an exposure-response relationship between peanut protein levels in household dust and peanut skin prick test (SPT) sensitization and likely allergy. In the final multivariate model an increase in 4 log2 EPE units increased the odds of peanut SPT sensitization (1.71-fold; 95% CI, 1.13- to 2.59-fold; P = .01) and likely peanut allergy (PA; 2.10-fold; 95% CI, 1.20- to 3.67-fold; P < .01). The effect of EPE on peanut SPT sensitization was augmented in children with a history of AD (OR, 1.97; 95% CI, 1.26-3.09; P < .01) and augmented even further in children with a history of severe AD (OR, 2.41; 95% CI, 1.30-4.47; P < .01); the effect of EPE on PA was also augmented in children with a history of AD (OR, 2.34; 95% CI, 1.31-4.18; P < .01). Conclusion Exposure to peanut antigen in dust through an impaired skin barrier in atopically inflamed skin is a plausible route for peanut SPT sensitization and PA. PMID:25457149

Skin cancer in skin of color: an update on current facts, trends, and misconceptions.

PubMed

Battie, Claire; Gohara, Mona; Verschoore, Michèle; Roberts, Wendy

2013-02-01

For many fair-skinned individuals around the world, skin cancer is the leading malignancy. Although skin cancer comprises only 1% to 2% of all malignancies in those with darker complexions, the mortality rates in this subgroup are substantially higher when compared with their Caucasian counterparts. This discrepancy is largely as a result of delayed detection/treatment, and a false perception among patient and physician that brown skin confers complete protection against skin cancer. Recent studies show that 65% of surveyed African Americans never wore sunscreen, despite living in sunny climates, and that more than 60% of minority respondents erroneously believed that they were not at risk for skin cancer. Dark skin offers some protection from ultraviolet (UV) light. However, there is considerable heterogeneity in skin of color, a phenomenon that is accentuated by mixed heritage. Ethnicity does not confer skin type anymore. People of color do experience sunburn, and from a biological point of view, all skin types appear to be sensitive to UV-induced DNA damage, with an inverse relationship between skin color and sensitivity to UV light. Our population is changing rapidly, and within the next few decades minority populations will become the majority. It is therefore imperative to educate both physicians and patients on the perceived immunity against cutaneous malignancies, the need for sun protection, and the clinical signs of skin cancer in non-Caucasian people, so that future unnecessary mortality can be avoided.

Human relevance of an in vitro gene signature in HaCaT for skin sensitization.

PubMed

van der Veen, Jochem W; Hodemaekers, Henny; Reus, Astrid A; Maas, Wilfred J M; van Loveren, Henk; Ezendam, Janine

2015-02-01

The skin sensitizing potential of chemicals is mainly assessed using animal methods, such as the murine local lymph node assay. Recently, an in vitro assay based on a gene expression signature in the HaCaT keratinocyte cell line was proposed as an alternative to these animal methods. Here, the human relevance of this gene signature is assessed through exposure of freshly isolated human skin to the chemical allergens dinitrochlorobenzene (DNCB) and diphenylcyclopropenone (DCP). In human skin, the gene signature shows similar direction of regulation as was previously observed in vitro, suggesting that the molecular processes that drive expression of these genes are similar between the HaCaT cell line and freshly isolated skin, providing evidence for the human relevance of the gene signature. Copyright © 2014 Elsevier Ltd. All rights reserved.

Probing Neutron-Skin Thickness of Unstable Nuclei with Total Reaction Cross Sections

NASA Astrophysics Data System (ADS)

Horiuchi, Wataru; Suzuki, Yasuyuki; Inakura, Tsunenori

We present our recent analysis of the total reaction cross sections, σR, of unstable nuclei and discuss their sensitivity to the neutron-skin thickness. The σR is calculated with the Glauber model using projectile densities obtained with the Skyrme-Hartree-Fock method on the three-dimensional coordinate space. We cover 91 nuclei of O, Ne, Mg, Si, S, Ca, and Ni isotopes. Defining a reaction radius, aR = √{σ R/π } , to characterize the nuclear size and target (proton or 12C) dependence, we see the 12C target probes the matter radius while the proton target is sensitive to the skin-thickness. We find an empirical formula for expressing aR with the point matter radius and the skin thickness, which can be used to determine the skin thickness.

An updated review of mechanotransduction in skin disorders: transcriptional regulators, ion channels, and microRNAs.

PubMed

Wang, Jing; Zhang, Yifan; Zhang, Ning; Wang, Chuandong; Herrler, Tanja; Li, Qingfeng

2015-06-01

The skin is constantly exposed and responds to a wide range of biomechanical cues. The mechanobiology of skin has already been known and applied by clinicians long before the fundamental molecular mechanisms of mechanotransduction are elucidated. Despite increasing knowledge on the mediators of biomechanical signaling such as mitogen-associated protein kinases, Rho GTPases or FAK-ERK pathways, the key elements of mechano-responses transcription factors, and mechano-sensors remain unclear. Recently, canonical biochemical components of Hippo and Wnt signaling pathway YAP and β-catenin were found to exhibit undefined mechanical sensitivity. Mechanical forces were identified to be the dominant regulators of YAP/TAZ activity in a multicellular context. Furthermore, different voltage or ligand sensitive ion channels in the cell membrane exhibited their mechanical sensitivity as mechano-sensors. Additionally, a large number of microRNAs have been confirmed to regulate cellular behavior and contribute to various skin disorders under mechanical stimuli. Mechanosensitive (MS) microRNAs could not only be activated by distinct mechanical force pattern, but also responsively target MS sensors such as e-cadherin and cytoskeleton constituent RhoA. Thus, a comprehensive understanding of this regulatory network of cutaneous mechanotransduction will facilitate the development of novel approaches to wound healing, hypertrophic scar formation, skin regeneration, and the progression or initiation of skin diseases.

SKIN SENSITIZATION AND ALLERGIC CONTACT DERMATITIS (BASIC COURSE): THE GLOBAL REGULATORY ENVIRONMENT - CONTINUING EDUCATION COURSE; 1 OF 4 SPEAKERS FOR AN SOT BASIC COURSE

EPA Science Inventory

New regulations have emerged in recent years giving guidance on how best to conduct skin sensitization testing on new chemical entities. For example, recently The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) in the U.S. and the European Ce...

What happens after the activation of ascaridole? Reactive compounds and their implications for skin sensitization

USDA-ARS?s Scientific Manuscript database

To replace animal testing and to improve the prediction of skin sensitization, significant attention has been directed to the use of alternative methods. Along with induction of Nrf2 target gene and upregulation of CD86 and C54 markers, the direct peptide reactivity assay (DPRA), the regulatory agen...

Simulation of a sensor array for multiparameter measurements at the prosthetic limb interface

NASA Astrophysics Data System (ADS)

Rowe, Gabriel I.; Mamishev, Alexander V.

2004-07-01

Sensitive skin is a highly desired device for biomechanical devices, wearable computing, human-computer interfaces, exoskeletons, and, most pertinent to this paper, for lower limb prosthetics. The measurement of shear stress is very important because shear effects are key factors in developing surface abrasions and pressure sores in paraplegics and users of prosthetic/orthotic devices. A single element of a sensitive skin is simulated and characterized in this paper. Conventional tactile sensors are designed for measurement of the normal stress only, which is inadequate for comprehensive assessment of surface contact conditions. The sensitive skin discussed here is a flexible array capable of sensing shear and normal forces, as well as humidity and temperature on each element.

Epoxy resin monomers with reduced skin sensitizing potency.

PubMed

O'Boyle, Niamh M; Niklasson, Ida B; Tehrani-Bagha, Ali R; Delaine, Tamara; Holmberg, Krister; Luthman, Kristina; Karlberg, Ann-Therese

2014-06-16

Epoxy resin monomers (ERMs), especially diglycidyl ethers of bisphenol A and F (DGEBA and DGEBF), are extensively used as building blocks for thermosetting polymers. However, they are known to commonly cause skin allergy. This research describes a number of alternative ERMs, designed with the aim of reducing the skin sensitizing potency while maintaining the ability to form thermosetting polymers. The compounds were designed, synthesized, and assessed for sensitizing potency using the in vivo murine local lymph node assay (LLNA). All six epoxy resin monomers had decreased sensitizing potencies compared to those of DGEBA and DGEBF. With respect to the LLNA EC3 value, the best of the alternative monomers had a value approximately 2.5 times higher than those of DGEBA and DGEBF. The diepoxides were reacted with triethylenetetramine, and the polymers formed were tested for technical applicability using thermogravimetric analysis and differential scanning calorimetry. Four out of the six alternative ERMs gave polymers with a thermal stability comparable to that obtained with DGEBA and DGEBF. The use of improved epoxy resin monomers with less skin sensitizing effects is a direct way to tackle the problem of contact allergy to epoxy resin systems, particularly in occupational settings, resulting in a reduction in the incidence of allergic contact dermatitis.

The local lymph node assay and the assessment of relative potency: status of validation.

PubMed

Basketter, David A; Gerberick, Frank; Kimber, Ian

2007-08-01

For the prediction of skin sensitization potential, the local lymph node assay (LLNA) is a fully validated alternative to guinea-pig tests. More recently, information from LLNA dose-response analyses has been used to assess the relative potency of skin sensitizing chemicals. These data are then deployed for risk assessment and risk management. In this commentary, the utility and validity of these relative potency measurements are reviewed. It is concluded that the LLNA does provide a valuable assessment of relative sensitizing potency in the form of the estimated concentration of a chemical required to produce a threefold stimulation of draining lymph node cell proliferation compared with concurrent controls (EC3 value) and that all reasonable validation requirements have been addressed successfully. EC3 measurements are reproducible in both intra- and interlaboratory evaluations and are stable over time. It has been shown also, by several independent groups, that EC3 values correlate closely with data on relative human skin sensitization potency. Consequently, the recommendation made here is that LLNA EC3 measurements should now be regarded as a validated method for the determination of the relative potency of skin sensitizing chemicals, a conclusion that has already been reached by a number of independent expert groups.

Automated Sensitivity Analysis of Interplanetary Trajectories

NASA Technical Reports Server (NTRS)

Knittel, Jeremy; Hughes, Kyle; Englander, Jacob; Sarli, Bruno

2017-01-01

This work describes a suite of Python tools known as the Python EMTG Automated Trade Study Application (PEATSA). PEATSA was written to automate the operation of trajectory optimization software, simplify the process of performing sensitivity analysis, and was ultimately found to out-perform a human trajectory designer in unexpected ways. These benefits will be discussed and demonstrated on sample mission designs.

Correlation between experimental human and murine skin sensitization induction thresholds.

PubMed

Api, Anne Marie; Basketter, David; Lalko, Jon

2015-01-01

Quantitative risk assessment for skin sensitization is directed towards the determination of levels of exposure to known sensitizing substances that will avoid the induction of contact allergy in humans. A key component of this work is the predictive identification of relative skin sensitizing potency, achieved normally by the measurement of the threshold (the "EC3" value) in the local lymph node assay (LLNA). In an extended series of studies, the accuracy of this murine induction threshold as the predictor of the absence of a sensitizing effect has been verified by conduct of a human repeated insult patch test (HRIPT). Murine and human thresholds for a diverse set of 57 fragrance chemicals spanning approximately four orders of magnitude variation in potency have been compared. The results confirm that there is a useful correlation, with the LLNA EC3 value helping particularly to identify stronger sensitizers. Good correlation (with half an order of magnitude) was seen with three-quarters of the dataset. The analysis also helps to identify potential outlier types of (fragrance) chemistry, exemplified by hexyl and benzyl salicylates (an over-prediction) and trans-2-hexenal (an under-prediction).

Polyvalent type IV sensitizations to multiple fragrances and a skin protection cream in a metal worker.

PubMed

Tanko, Zita; Shab, Arna; Diepgen, Thomas Ludwig; Weisshaar, Elke

2009-06-01

Fragrances are very common in everyday products. A metalworker with chronic hand eczema and previously diagnosed type IV sensitizations to epoxy resin, balsam of Peru, fragrance mix and fragrance mix II was diagnosed with additional type IV sensitizations to geraniol, hydroxycitronellal, lilial, tree moss, oak moss absolute, citral, citronellol, farnesol, Lyral, fragrance mix II and fragrance mix (with sorbitan sesquioleate). In addition, a type IV sensitization to the skin protection cream containing geraniol and citronellol used at the workplace was detected, and deemed occupationally relevant in this case. The patient could have had contact to fragrances through private use of cosmetics and detergents. On the other hand, the fragrance-containing skin protection cream supports occupational exposure. This case report demonstrates that fragrance contact allergy has to be searched for and clarified individually, which requires a thorough history and a detailed analysis of the work place.

LC-MS-based characterization of the peptide reactivity of chemicals to improve the in vitro prediction of the skin sensitization potential.

PubMed

Natsch, Andreas; Gfeller, Hans

2008-12-01

A key step in the skin sensitization process is the formation of a covalent adduct between skin sensitizers and endogenous proteins and/or peptides in the skin. Based on this mechanistic understanding, there is a renewed interest in in vitro assays to determine the reactivity of chemicals toward peptides in order to predict their sensitization potential. A standardized peptide reactivity assay yielded a promising predictivity. This published assay is based on high-performance liquid chromatography with ultraviolet detection to quantify peptide depletion after incubation with test chemicals. We had observed that peptide depletion may be due to either adduct formation or peptide oxidation. Here we report a modified assay based on both liquid chromatography-mass spectrometry (LC-MS) analysis and detection of free thiol groups. This approach allows simultaneous determination of (1) peptide depletion, (2) peptide oxidation (dimerization), (3) adduct formation, and (4) thiol reactivity and thus generates a more detailed characterization of the reactivity of a molecule. Highly reactive molecules are further discriminated with a kinetic measure. The assay was validated on 80 chemicals. Peptide depletion could accurately be quantified both with LC-MS detection and depletion of thiol groups. The majority of the moderate/strong/extreme sensitizers formed detectable peptide adducts, but many sensitizers were also able to catalyze peptide oxidation. Whereas adduct formation was only observed for sensitizers, this oxidation reaction was also observed for two nonsensitizing fragrance aldehydes, indicating that peptide depletion might not always be regarded as sufficient evidence for rating a chemical as a sensitizer. Thus, this modified assay gives a more informed view of the peptide reactivity of chemicals to better predict their sensitization potential.

Chemical and engineering approaches to enable organic field-effect transistors for electronic skin applications.

PubMed

Sokolov, Anatoliy N; Tee, Benjamin C-K; Bettinger, Christopher J; Tok, Jeffrey B-H; Bao, Zhenan

2012-03-20

Skin is the body's largest organ and is responsible for the transduction of a vast amount of information. This conformable material simultaneously collects signals from external stimuli that translate into information such as pressure, pain, and temperature. The development of an electronic material, inspired by the complexity of this organ is a tremendous, unrealized engineering challenge. However, the advent of carbon-based electronics may offer a potential solution to this long-standing problem. In this Account, we describe the use of an organic field-effect transistor (OFET) architecture to transduce mechanical and chemical stimuli into electrical signals. In developing this mimic of human skin, we thought of the sensory elements of the OFET as analogous to the various layers and constituents of skin. In this fashion, each layer of the OFET can be optimized to carry out a specific recognition function. The separation of multimodal sensing among the components of the OFET may be considered a "divide and conquer" approach, where the electronic skin (e-skin) can take advantage of the optimized chemistry and materials properties of each layer. This design of a novel microstructured gate dielectric has led to unprecedented sensitivity for tactile pressure events. Typically, pressure-sensitive components within electronic configurations have suffered from a lack of sensitivity or long mechanical relaxation times often associated with elastomeric materials. Within our method, these components are directly compatible with OFETs and have achieved the highest reported sensitivity to date. Moreover, the tactile sensors operate on a time scale comparable with human skin, making them ideal candidates for integration as synthetic skin devices. The methodology is compatible with large-scale fabrication and employs simple, commercially available elastomers. The design of materials within the semiconductor layer has led to the incorporation of selectivity and sensitivity within gas-sensing devices and has enabled stable sensor operation within aqueous media. Furthermore, careful tuning of the chemical composition of the dielectric layer has provided a means to operate the sensor in real time within an aqueous environment and without the need for encapsulation layers. The integration of such devices as electronic mimics of skin will require the incorporation of biocompatible or biodegradable components. Toward this goal, OFETs may be fabricated with >99% biodegradable components by weight, and the devices are robust and stable, even in aqueous environments. Collectively, progress to date suggests that OFETs may be integrated within a single substrate to function as an electronic mimic of human skin, which could enable a large range of sensing-related applications from novel prosthetics to robotic surgery.

β-adrenergic blockade does not impair the skin blood flow sensitivity to local heating in burned and non-burned skin under neutral and hot environments in children

PubMed Central

Rivas, Eric; McEntire, Serina J.; Herndon, David N.; Mlcak, Ronald P.; Suman, Oscar E.

2017-01-01

Objective Tested the hypothesis that propranolol, a drug given to burn patients to reduce hypermetabolism/cardiac stress, may inhibit heat dissipation by changing the sensitivity of skin blood flow (SkBF) to local heating under neutral and hot conditions. Methods In a randomized double-blind study, a placebo was given to 8 burned children while propranolol was given to 13 burned children with similar characteristics (mean ± SD: 11.9±3y, 147±20cm, 45±23kg, 56±12% TBSA). Non-burned children (n=13, 11.4±3y, 152±15cm, 52±13kg) served as healthy controls. A progressive local heating protocol characterized SkBF responses in burned and unburned skin and non-burned control skin under the two environmental conditions (23°C and 34°C) via laser-Doppler flowmetry. Results Resting SkBF was greater in burned and unburned skin compared to the non-burned control (main effect: skin, P<0.0001; 57±32 burned; 38±36 unburned vs 9±8 control %SkBFmax). No difference was found for maximal SkBF capacity to local heating between groups. Additionally, dose response curves for the sensitivity of SkBF to local heating were not different among burned or unburned skin, and non-burned control skin (EC50, P>0.05) under either condition. Conclusion Therapeutic propranolol does not negatively affect SkBF under neutral or hot environmental conditions and further compromise temperature regulation in burned children. PMID:28071840

The development of a 3D immunocompetent model of human skin.

PubMed

Chau, David Y S; Johnson, Claire; MacNeil, Sheila; Haycock, John W; Ghaemmaghami, Amir M

2013-09-01

As the first line of defence, skin is regularly exposed to a variety of biological, physical and chemical insults. Therefore, determining the skin sensitization potential of new chemicals is of paramount importance from the safety assessment and regulatory point of view. Given the questionable biological relevance of animal models to human as well as ethical and regulatory pressure to limit or stop the use of animal models for safety testing, there is a need for developing simple yet physiologically relevant models of human skin. Herein, we describe the construction of a novel immunocompetent 3D human skin model comprising of dendritic cells co-cultured with keratinocytes and fibroblasts. This model culture system is simple to assemble with readily-available components and importantly, can be separated into its constitutive individual layers to allow further insight into cell-cell interactions and detailed studies of the mechanisms of skin sensitization. In this study, using non-degradable microfibre scaffolds and a cell-laden gel, we have engineered a multilayer 3D immunocompetent model comprised of keratinocytes and fibroblasts that are interspersed with dendritic cells. We have characterized this model using a combination of confocal microscopy, immuno-histochemistry and scanning electron microscopy and have shown differentiation of the epidermal layer and formation of an epidermal barrier. Crucially the immune cells in the model are able to migrate and remain responsive to stimulation with skin sensitizers even at low concentrations. We therefore suggest this new biologically relevant skin model will prove valuable in investigating the mechanisms of allergic contact dermatitis and other skin pathologies in human. Once fully optimized, this model can also be used as a platform for testing the allergenic potential of new chemicals and drug leads.

β-Adrenergic blockade does not impair the skin blood flow sensitivity to local heating in burned and nonburned skin under neutral and hot environments in children.

PubMed

Rivas, Eric; McEntire, Serina J; Herndon, David N; Mlcak, Ronald P; Suman, Oscar E

2017-05-01

We tested the hypothesis that propranolol, a drug given to burn patients to reduce hypermetabolism/cardiac stress, may inhibit heat dissipation by changing the sensitivity of skin blood flow (SkBF) to local heating under neutral and hot conditions. In a randomized double-blind study, a placebo was given to eight burned children, while propranolol was given to 13 burned children with similar characteristics (mean±SD: 11.9±3 years, 147±20 cm, 45±23 kg, 56±12% Total body surface area burned). Nonburned children (n=13, 11.4±3 years, 152±15 cm, 52±13 kg) served as healthy controls. A progressive local heating protocol characterized SkBF responses in burned and unburned skin and nonburned control skin under the two environmental conditions (23 and 34°C) via laser Doppler flowmetry. Resting SkBF was greater in burned and unburned skin compared to the nonburned control (main effect: skin, P<.0001; 57±32 burned; 38±36 unburned vs 9±8 control %SkBF max ). No difference was found for maximal SkBF capacity to local heating between groups. Additionally, dose-response curves for the sensitivity of SkBF to local heating were not different among burned or unburned skin, and nonburned control skin (EC 50 , P>.05) under either condition. Therapeutic propranolol does not negatively affect SkBF under neutral or hot environmental conditions and further compromise temperature regulation in burned children. © 2017 John Wiley & Sons Ltd.

The use of ex vivo human skin tissue for genotoxicity testing

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

Reus, Astrid A.; Usta, Mustafa; Krul, Cyrille A.M., E-mail: cyrille.krul@tno.nl

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 positivemore » 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 is suitable for evaluation of chemicals that are in contact with skin.« less

Roughness based perceptual analysis towards digital skin imaging system with haptic feedback.

PubMed

Kim, K

2016-08-01

To examine psoriasis or atopic eczema, analyzing skin roughness by palpation is essential to precisely diagnose skin diseases. However, optical sensor based skin imaging systems do not allow dermatologists to touch skin images. To solve the problem, a new haptic rendering technology that can accurately display skin roughness must be developed. In addition, the rendering algorithm must be able to filter spatial noises created during 2D to 3D image conversion without losing the original roughness on the skin image. In this study, a perceptual way to design a noise filter that will remove spatial noises and in the meantime recover maximized roughness is introduced by understanding human sensitivity on surface roughness. A visuohaptic rendering system that can provide a user with seeing and touching digital skin surface roughness has been developed including a geometric roughness estimation method from a meshed surface. In following, a psychophysical experiment was designed and conducted with 12 human subjects to measure human perception with the developed visual and haptic interfaces to examine surface roughness. From the psychophysical experiment, it was found that touch is more sensitive at lower surface roughness, and vice versa. Human perception with both senses, vision and touch, becomes less sensitive to surface distortions as roughness increases. When interact with both channels, visual and haptic interfaces, the performance to detect abnormalities on roughness is greatly improved by sensory integration with the developed visuohaptic rendering system. The result can be used as a guideline to design a noise filter that can perceptually remove spatial noises while recover maximized roughness values from a digital skin image obtained by optical sensors. In addition, the result also confirms that the developed visuohaptic rendering system can help dermatologists or skin care professionals examine skin conditions by using vision and touch at the same time. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The physicochemical characterization and in vitro/in vivo evaluation of natural surfactants-based emulsions as vehicles for diclofenac diethylamine.

PubMed

Vucinić-Milanković, Nada; Savić, Snezana; Vuleta, Gordana; Vucinić, Slavica

2007-03-01

Two sugar-based emulsifiers, cetearyl alcohol & cetearyl glycoside and sorbitan stearate & sucrose cocoate, known as potential promoters of lamellar liquid crystals/gel phases, were investigated in order to formulate an optimal vehicle for amphiphilic drug - diclofenac diethylamine (DDA). Physico-chemical characterization and study of vehicle's physical stability were performed. Then, the in vitro DDA liberation profile, dependent on the mode of drug incorporation to the system, and the in vivo, short-term effects of chosen samples on skin parameters were examined. Droplets size distribution and rheological behavior indicated satisfying physical stability of both types of vehicles. Unexpectedly, the manner of DDA incorporation to the system had no significant influence on DDA release. In vivo study pointed to emulsion's favorable potential for skin hydration and barrier improvement, particularly in cetearyl glycoside-based vehicle.

Eye-independent, light-activated chromatophore expansion (LACE) and expression of phototransduction genes in the skin of Octopus bimaculoides.

PubMed

Ramirez, M Desmond; Oakley, Todd H

2015-05-15

Cephalopods are renowned for changing the color and pattern of their skin for both camouflage and communication. Yet, we do not fully understand how cephalopods control the pigmented chromatophore organs in their skin and change their body pattern. Although these changes primarily rely on eyesight, we found that light causes chromatophores to expand in excised pieces of Octopus bimaculoides skin. We call this behavior light-activated chromatophore expansion (or LACE). To uncover how octopus skin senses light, we used antibodies against r-opsin phototransduction proteins to identify sensory neurons that express r-opsin in the skin. We hypothesized that octopus LACE relies on the same r-opsin phototransduction cascade found in octopus eyes. By creating an action spectrum for the latency to LACE, we found that LACE occurred most quickly in response to blue light. We fit our action spectrum data to a standard opsin curve template and estimated the λmax of LACE to be 480 nm. Consistent with our hypothesis, the maximum sensitivity of the light sensors underlying LACE closely matches the known spectral sensitivity of opsin from octopus eyes. LACE in isolated preparations suggests that octopus skin is intrinsically light sensitive and that this dispersed light sense might contribute to their unique and novel patterning abilities. Finally, our data suggest that a common molecular mechanism for light detection in eyes may have been co-opted for light sensing in octopus skin and then used for LACE. © 2015. Published by The Company of Biologists Ltd.

Sensitivity, predictive values, pretest-posttest probabilities, and likelihood ratios of presurgery clinical diagnosis of nonmelanoma skin cancers.

PubMed

Ermertcan, Aylin Türel; Oztürk, Ferdi; Gençoğlan, Gülsüm; Eskiizmir, Görkem; Temiz, Peyker; Horasan, Gönül Dinç

2011-03-01

The precision of clinical diagnosis of skin tumors is not commonly measured and, therefore, very little is known about the diagnostic ability of clinicians. This study aimed to compare clinical and histopathologic diagnoses of nonmelanoma skin cancers with regard to sensitivity, predictive values, pretest-posttest probabilities, and likelihood ratios. Two hundred nineteen patients with 241 nonmelanoma skin cancers were enrolled in this study. Of these patients, 49.4% were female and 50.6% were male. The mean age ± standard deviation (SD) was 63.66 ± 16.44 years for the female patients and 64.77 ± 14.88 years for the male patients. The mean duration of the lesions was 20.90 ± 32.95 months. One hundred forty-eight (61.5%) of the lesions were diagnosed as basal cell carcinoma (BCC) and 93 (38.5%) were diagnosed as squamous cell carcinoma (SCC) histopathologically. Sensitivity, positive predictive value, and posttest probability were calculated as 75.96%, 87.77%, and 87.78% for BCC and 70.37%, 37.25%, and 37.20% for SCC, respectively. The correlation between clinical and histopathologic diagnoses was found to be higher in BCC. Knowledge of sensitivity, predictive values, likelihood ratios, and posttest probabilities may have implications for the management of skin cancers. To prevent unnecessary surgeries and achieve high diagnostic accuracies, multidisciplinary approaches are recommended.

Integrated Computational Solution for Predicting Skin Sensitization Potential of Molecules

PubMed Central

Desai, Aarti; Singh, Vivek K.; Jere, Abhay

2016-01-01

Introduction 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. Results 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). Conclusions 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. PMID:27271321

A Flexible and Wearable Human Stress Monitoring Patch

PubMed Central

Yoon, Sunghyun; Sim, Jai Kyoung; Cho, Young-Ho

2016-01-01

A human stress monitoring patch integrates three sensors of skin temperature, skin conductance, and pulsewave in the size of stamp (25 mm × 15 mm × 72 μm) in order to enhance wearing comfort with small skin contact area and high flexibility. The skin contact area is minimized through the invention of an integrated multi-layer structure and the associated microfabrication process; thus being reduced to 1/125 of that of the conventional single-layer multiple sensors. The patch flexibility is increased mainly by the development of flexible pulsewave sensor, made of a flexible piezoelectric membrane supported by a perforated polyimide membrane. In the human physiological range, the fabricated stress patch measures skin temperature with the sensitivity of 0.31 Ω/°C, skin conductance with the sensitivity of 0.28 μV/0.02 μS, and pulse wave with the response time of 70 msec. The skin-attachable stress patch, capable to detect multimodal bio-signals, shows potential for application to wearable emotion monitoring. PMID:27004608

Personalized skincare: from molecular basis to clinical and commercial applications.

PubMed

Markiewicz, Ewa; Idowu, Olusola Clement

2018-01-01

Individual responses of human skin to the environmental stress are determined by differences in the anatomy and physiology that are closely linked to the genetic characteristics such as pigmentation. Ethnic skin phenotypes can be distinguished based on defined genotypic traits, structural organization and compartmentalized sensitivity to distinct extrinsic aging factors. These differences are not only responsible for the variation in skin performance after exposure to damaging conditions, but can also affect the mechanisms of drug absorption, sensitization and other longer term effects. The unique characteristics of the individual skin function and, particularly, of the ethnic skin type are currently considered to shape the future of clinical and pharmacologic interventions as a basis for personalized skincare. Individual approaches to skincare render a novel and actively growing area with a range of biomedical and commercial applications within cosmetics industry. In this review, we summarize the aspects of the molecular and clinical manifestations of the environmental stress on human skin and proposed protective mechanisms that are linked to ethnic differences and pathophysiology of extrinsic skin aging. We subsequently discuss the possible applications and translation of this knowledge into personalized skincare.

Personalized skincare: from molecular basis to clinical and commercial applications

PubMed Central

Markiewicz, Ewa; Idowu, Olusola Clement

2018-01-01

Individual responses of human skin to the environmental stress are determined by differences in the anatomy and physiology that are closely linked to the genetic characteristics such as pigmentation. Ethnic skin phenotypes can be distinguished based on defined genotypic traits, structural organization and compartmentalized sensitivity to distinct extrinsic aging factors. These differences are not only responsible for the variation in skin performance after exposure to damaging conditions, but can also affect the mechanisms of drug absorption, sensitization and other longer term effects. The unique characteristics of the individual skin function and, particularly, of the ethnic skin type are currently considered to shape the future of clinical and pharmacologic interventions as a basis for personalized skincare. Individual approaches to skincare render a novel and actively growing area with a range of biomedical and commercial applications within cosmetics industry. In this review, we summarize the aspects of the molecular and clinical manifestations of the environmental stress on human skin and proposed protective mechanisms that are linked to ethnic differences and pathophysiology of extrinsic skin aging. We subsequently discuss the possible applications and translation of this knowledge into personalized skincare. PMID:29692619

UV Tanning Equipment | Radiation Protection | US EPA

EPA Pesticide Factsheets

2017-08-07

Sun lamps and tanning equipment emit ultraviolet (UV) rays. People who are exposed to UV rays over a long period of time are more likely to develop skin cancer. People with light skin are in more danger because their skin is more sensitive to UV rays.

Acute irritant threshold correlates with barrier function, skin hydration and contact hypersensitivity in atopic dermatitis and rosacea.

PubMed

Darlenski, Razvigor; Kazandjieva, Jana; Tsankov, Nikolai; Fluhr, Joachim W

2013-11-01

The aim of the study was to disclose interactions between epidermal barrier, skin irritation and sensitization in healthy and diseased skin. Transepidermal water loss (TEWL) and stratum corneum hydration (SCH) were assessed in adult patients with atopic dermatitis (AD), rosacea and healthy controls. A 4-h patch test with seven concentrations of sodium lauryl sulphate was performed to determine the irritant threshold (IT). Contact sensitization pattern was revealed by patch testing with European baseline series. Subjects with a lower IT had higher TEWL values and lower SCH. Subjects with positive allergic reactions had significantly lower IT. In AD, epidermal barrier deterioration was detected on both volar forearm and nasolabial fold, while in rosacea, impeded skin physiology parameters were observed on the facial skin only, suggesting that barrier impediment is restricted to the face in rosacea, in contrast with AD where the abnormal skin physiology is generalized. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Radiation sensitivity of bacteria and virus in porcine xenoskin for dressing agent

NASA Astrophysics Data System (ADS)

Jo, Eu-Ri; Jung, Pil-Mun; Choi, Jong-il; Lee, Ju-Woon

2012-08-01

In this study, gamma irradiation sensitivities of bacteria and viruses in porcine skin were evaluated to establish the optimum sterilization condition for the dressing material and a xenoskin graft. Escherichia coli and Bacillus subtilis were used as model pathogens and inoculated at 106-107 log CFU/g. As model viruses, porcine parvovirus (PPV), bovine viral diarrhea virus (BVDV), and poliovirus were used and inoculated at 105-106 TCID50/g into porcine skin. The D10 value of E. coli was found to be 0.25±0.1 kGy. B. subtilis endospores produced under stressful environmental conditions showed lower radiation sensitivity as D10 was 3.88±0.3 kGy in porcine skin. The D10 values of PPV, BVDV, and poliovirus were found to be 1.73±0.2, 3.81±0.2, and 6.88±0.3 kGy, respectively. These results can offer the basic information required for inactivating pathogens by gamma irradiation and achieving dressing material and porcine skin grafts.

Sensitization to Food Additives in Patients with Allergy: A Study Based on Skin Test and Open Oral Challenge.

PubMed

Moghtaderi, Mozhgan; Hejrati, Zinatosadat; Dehghani, Zahra; Dehghani, Faranak; Kolahi, Niloofar

2016-06-01

There has been a great increase in the consumption of various food additives in recent years. The purpose of this study was to identify the incidence of sensitization to food additives by using skin prick test in patients with allergy and to determine the concordance rate between positive skin tests and oral challenge in hypersensitivity to additives. This cross-sectional study included 125 (female 71, male 54) patients aged 2-76 years with allergy and 100 healthy individuals. Skin tests were performed in both patient and control groups with 25 fresh food additives. Among patients with allergy, 22.4% showed positive skin test at least to one of the applied materials. Skin test was negative to all tested food additives in control group. Oral food challenge was done in 28 patients with positive skin test, in whom 9 patients showed reaction to culprit (Concordance rate=32.1%). The present study suggested that about one-third of allergic patients with positive reaction to food additives showed positive oral challenge; it may be considered the potential utility of skin test to identify the role of food additives in patients with allergy.

Near infrared spectroscopy for body fat sensing in neonates: quantitative analysis by GAMOS simulations.

PubMed

Mustafa, Fatin Hamimi; Jones, Peter W; McEwan, Alistair L

2017-01-11

Under-nutrition in neonates is closely linked to low body fat percentage. Undernourished neonates are exposed to immediate mortality as well as unwanted health impacts in their later life including obesity and hypertension. One potential low cost approach for obtaining direct measurements of body fat is near-infrared (NIR) interactance. The aims of this study were to model the effect of varying volume fractions of melanin and water in skin over NIR spectra, and to define sensitivity of NIR reflection on changes of thickness of subcutaneous fat. GAMOS simulations were used to develop two single fat layer models and four complete skin models over a range of skin colour (only for four skin models) and hydration within a spectrum of 800-1100 nm. The thickness of the subcutaneous fat was set from 1 to 15 mm in 1 mm intervals in each model. Varying volume fractions of water in skin resulted minimal changes of NIR intensity at ranges of wavelengths from 890 to 940 nm and from 1010 to 1100 nm. Variation of the melanin volume in skin meanwhile was found to strongly influence the NIR intensity and sensitivity. The NIR sensitivities and NIR intensity over thickness of fat decreased from the Caucasian skin to African skin throughout the range of wavelengths. For the relationship between the NIR reflection and the thickness of subcutaneous fat, logarithmic relationship was obtained. The minimal changes of NIR intensity values at wavelengths within the ranges from 890 to 940 nm and from 1010 to 1100 nm to variation of volume fractions of water suggests that wavelengths within those two ranges are considered for use in measurement of body fat to solve the variation of hydration in neonates. The stronger influence of skin colour on NIR shows that the melanin effect needs to be corrected by an independent measurement or by a modeling approach. The logarithmic response obtained with higher sensitivity at the lower range of thickness of fat suggests that implementation of NIRS may be suited for detecting under-nutrition and monitoring nutritional interventions for malnutrition in neonates in resource-constrained communities.

Enhanced scratching evoked by PAR-2 agonist and 5-HT but not histamine in a mouse model of chronic dry skin itch.

PubMed

Akiyama, T; Carstens, M Iodi; Carstens, E

2010-11-01

Chronic itch is a symptom of many skin conditions and systemic disease, and it has been hypothesized that the chronic itch may result from sensitization of itch-signaling pathways. We induced experimental chronic dry skin on the rostral back of mice, and observed a significant increase in spontaneous hindlimb scratches directed to the dry skin. Spontaneous scratching was significantly attenuated by a PAR-2 antibody and 5-HT2A receptor antagonist, indicating activation of these receptors by endogenous mediators released under dry skin conditions. We also observed a significant increase in the number of scratch bouts evoked by acute intradermal injections of a protease-activated receptor (PAR)-2 agonist and serotonin (5-HT), but not histamine. We additionally investigated if pruritogen-evoked activity of dorsal root ganglion (DRG) neurons is enhanced in this model. DRG cells from dry skin mice exhibited significantly larger responses to the PAR-2 agonist and 5-HT, but not histamine. Spontaneous scratching may reflect ongoing itch, and enhanced pruritogen-evoked scratching may represent hyperknesis (enhanced itch), both potentially due to sensitization of itch-signaling neurons. The correspondence between enhanced behavioral scratching and DRG cell responses suggest that peripheral pruriceptors that respond to proteases and 5-HT, but not histamine, may be sensitized in dry skin itch. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Expression of CD73 slows down migration of skin dendritic cells, affecting the sensitization phase of contact hypersensitivity reactions in mice.

PubMed

Neuberger, A; Ring, S; Silva-Vilches, C; Schrader, J; Enk, A; Mahnke, K

2017-09-01

Application of haptens to the skin induces release of immune stimulatory ATP into the extracellular space. This "danger" signal can be converted to immunosuppressive adenosine (ADO) by the action of the ectonucleotidases CD39 and CD73, expressed by skin and immune cells. Thus, the expression and regulation of CD73 by skin derived cells may have crucial influence on the outcome of contact hypersensitivity (CHS) reactions. To investigate the role of CD73 expression during 2,4,6-trinitrochlorobenzene (TNCB) induced CHS reactions. Wild type (wt) and CD73 deficient mice were subjected to TNCB induced CHS. In the different mouse strains the resulting ear swelling reaction was recorded along with a detailed phenotypic analysis of the skin migrating subsets of dendritic cells (DC). In CD73 deficient animals the motility of DC was higher as compared to wt animals and in particular after sensitization we found increased migration of Langerin + DC from skin to draining lymph nodes (LN). In the TNCB model this led to a stronger sensitization as indicated by increased frequency of interferon-γ producing T cells in the LN and an increased ear thickness after challenge. CD73 derived ADO production slows down migration of Langerin + DC from skin to LN. This may be a crucial mechanism to avoid over boarding immune reactions against haptens. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

76 FR 61587 - Prothioconazole; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... toxicity by oral, dermal, and inhalation routes. It is not a dermal sensitizer, or a skin or eye irritant... routes. It is not a dermal sensitizer, or a skin irritant, but it is a slight eye irritant. The... barley at 0.2 ppm; oats, rye, and wheat at 0.05 ppm each; in the fodder (dry) of cereal grains at 5 ppm...

Skin inspired fractal strain sensors using a copper nanowire and graphite microflake hybrid conductive network.

PubMed

Jason, Naveen N; Wang, Stephen J; Bhanushali, Sushrut; Cheng, Wenlong

2016-09-22

This work demonstrates a facile "paint-on" approach to fabricate highly stretchable and highly sensitive strain sensors by combining one-dimensional copper nanowire networks with two-dimensional graphite microflakes. This paint-on approach allows for the fabrication of electronic skin (e-skin) patches which can directly replicate with high fidelity the human skin surface they are on, regardless of the topological complexity. This leads to high accuracy for detecting biometric signals for applications in personalised wearable sensors. The copper nanowires contribute to high stretchability and the graphite flakes offer high sensitivity, and their hybrid coating offers the advantages of both. To understand the topological effects on the sensing performance, we utilized fractal shaped elastomeric substrates and systematically compared their stretchability and sensitivity. We could achieve a high stretchability of up to 600% and a maximum gauge factor of 3000. Our simple yet efficient paint-on approach enabled facile fine-tuning of sensitivity/stretchability simply by adjusting ratios of 1D vs. 2D materials in the hybrid coating, and the topological structural designs. This capability leads to a wide range of biomedical sensors demonstrated here, including pulse sensors, prosthetic hands, and a wireless ankle motion sensor.

Gold thread implantation promotes hair growth in human and mice

PubMed Central

Kim, Jong-Hwan; Cho, Eun-Young; Kwon, Euna; Kim, Woo-Ho; Park, Jin-Sung; Lee, Yong-Soon

2017-01-01

Thread-embedding therapy has been widely applied for cosmetic purposes such as wrinkle reduction and skin tightening. Particularly, gold thread was reported to support connective tissue regeneration, but, its role in hair biology remains largely unknown due to lack of investigation. When we implanted gold thread and Happy Lift™ in human patient for facial lifting, we unexpectedly found an increase of hair regrowth in spite of no use of hair growth medications. When embedded into the depilated dorsal skin of mice, gold thread or polyglycolic acid (PGA) thread, similarly to 5% minoxidil, significantly increased the number of hair follicles on day 14 after implantation. And, hair re-growth promotion in the gold threadimplanted mice were significantly higher than that in PGA thread group on day 11 after depilation. In particular, the skin tissue of gold thread-implanted mice showed stronger PCNA staining and higher collagen density compared with control mice. These results indicate that gold thread implantation can be an effective way to promote hair re-growth although further confirmatory study is needed for more information on therapeutic mechanisms and long-term safety. PMID:29399026

Transdermal transport pathway creation: Electroporation pulse order.

PubMed

Becker, Sid; Zorec, Barbara; Miklavčič, Damijan; Pavšelj, Nataša

2014-11-01

In this study we consider the physics underlying electroporation which is administered to skin in order to radically increase transdermal drug delivery. The method involves the application of intense electric fields to alter the structure of the impermeable outer layer, the stratum corneum. A generally held view in the field of skin electroporation is that the skin's drop in resistance (to transport) is proportional to the total power of the pulses (which may be inferred by the number of pulses administered). Contrary to this belief, experiments conducted in this study show that the application of high voltage pulses prior to the application of low voltage pulses result in lower transport than when low voltage pulses alone are applied (when less total pulse power is administered). In order to reconcile these unexpected experimental results, a computational model is used to conduct an analysis which shows that the high density distribution of very small aqueous pathways through the stratum corneum associated with high voltage pulses is detrimental to the evolution of larger pathways that are associated with low voltage pulses. Copyright © 2014 Elsevier Inc. All rights reserved.

The Way of Love and Trust: The Sensitivity/Encounter Movement

ERIC Educational Resources Information Center

Back, Kurt W.

1972-01-01

Describes the unexpected revelations, conflict, despair and joy, spontaneous love-feasts, and sudden enthusiasms that happen at weekend encounter centers around the country--all under the mantle of science. (RJ)

Potential for local and systemic bacterial infection in some occupational groups in Benin City, Nigeria.

PubMed

Hugbo, P G; Okonkwo, J O

1992-06-01

Many Third World countries may not have adequate facilities for rapid sensitivity testing of antibiotics as an aid to diagnosis and chemotherapy. It may therefore be valuable to relate bacterial carriage on the skin to type of work a person does. Given areas of skin in workers from 10 occupational groups were sampled. The bacteria obtained were analyzed after growth on appropriate media. The sensitivity profiles of potential pathogens isolated from these groups, as well as of those (Staphylococcus aureus only) isolated from patients with certified infections, were carried out and the results were analyzed. Staphylococcus aureus constituted the most widely and frequently isolated potential pathogen. Proteus mirabilis, Escherichia coli, and Klebsiella species were also frequent colonizers of skin. There was a statistical relationship between work type and overall prevalence of bacteria on skin (p less than 0.01). Most isolates of the work groups were highly sensitive to gentamicin and cefuroxine but not to penicillin G, ampicillin, and trimethoprim plus sulfamethoxazole; isolates from infected persons were generally more resistant than were the community-acquired ones. A relationship may exist between the types of bacteria carried on the skin and the type of work in which a person is engaged.

Imperceptible magnetoelectronics

PubMed Central

Melzer, Michael; Kaltenbrunner, Martin; Makarov, Denys; Karnaushenko, Dmitriy; Karnaushenko, Daniil; Sekitani, Tsuyoshi; Someya, Takao; Schmidt, Oliver G.

2015-01-01

Future electronic skin aims to mimic nature’s original both in functionality and appearance. Although some of the multifaceted properties of human skin may remain exclusive to the biological system, electronics opens a unique path that leads beyond imitation and could equip us with unfamiliar senses. Here we demonstrate giant magnetoresistive sensor foils with high sensitivity, unmatched flexibility and mechanical endurance. They are <2 μm thick, extremely flexible (bending radii <3 μm), lightweight (≈3 g m−2) and wearable as imperceptible magneto-sensitive skin that enables proximity detection, navigation and touchless control. On elastomeric supports, they can be stretched uniaxially or biaxially, reaching strains of >270% and endure over 1,000 cycles without fatigue. These ultrathin magnetic field sensors readily conform to ubiquitous objects including human skin and offer a new sense for soft robotics, safety and healthcare monitoring, consumer electronics and electronic skin devices. PMID:25607534

Imperceptible magnetoelectronics

NASA Astrophysics Data System (ADS)

Melzer, Michael; Kaltenbrunner, Martin; Makarov, Denys; Karnaushenko, Dmitriy; Karnaushenko, Daniil; Sekitani, Tsuyoshi; Someya, Takao; Schmidt, Oliver G.

2015-01-01

Future electronic skin aims to mimic nature’s original both in functionality and appearance. Although some of the multifaceted properties of human skin may remain exclusive to the biological system, electronics opens a unique path that leads beyond imitation and could equip us with unfamiliar senses. Here we demonstrate giant magnetoresistive sensor foils with high sensitivity, unmatched flexibility and mechanical endurance. They are <2 μm thick, extremely flexible (bending radii <3 μm), lightweight (≈3 g m-2) and wearable as imperceptible magneto-sensitive skin that enables proximity detection, navigation and touchless control. On elastomeric supports, they can be stretched uniaxially or biaxially, reaching strains of >270% and endure over 1,000 cycles without fatigue. These ultrathin magnetic field sensors readily conform to ubiquitous objects including human skin and offer a new sense for soft robotics, safety and healthcare monitoring, consumer electronics and electronic skin devices.

Epicutaneous challenge of orally immunized mice redirects antigen-specific gut-homing T cells to the skin.

PubMed

Oyoshi, Michiko K; Elkhal, Abdallah; Scott, Jordan E; Wurbel, Marc-Andre; Hornick, Jason L; Campbell, James J; Geha, Raif S

2011-06-01

Patients with atopic dermatitis (AD) often suffer from food allergy and develop flares upon skin contact with food allergens. However, it is unclear whether T cells sensitized to allergens in the gut promote this skin inflammation. To address this question, we orally immunized WT mice and mice lacking the skin-homing chemokine receptor Ccr4 (Ccr4-/- mice) with OVA and then challenged them epicutaneously with antigen. Allergic skin inflammation developed in the WT mice but not in the mutants and was characterized by epidermal thickening, dermal infiltration by eosinophils and CD4+ T cells, and upregulation of Th2 cytokines. T cells purified from mesenteric lymph nodes (MLNs) of orally immunized WT mice transferred allergic skin inflammation to naive recipients cutaneously challenged with antigen, but this effect was lost in T cells purified from Ccr4-/- mice. In addition, the ability of adoptively transferred OVA-activated T cells to home to the skin following cutaneous OVA challenge was ablated in mice that lacked lymph nodes. These results indicate that cutaneous exposure to food antigens can reprogram gut-homing effector T cells in LNs to express skin-homing receptors, eliciting skin lesions upon food allergen contact in orally sensitized AD patients.

Global Gene Expression Profiling of Hyperkeratotic Skin Lesions from Inner Mongolians Chronically Exposed to Arsenic

EPA Science Inventory

The skin is an organ that is highly sensitive to chronic arsenic exposure. Skin lesions such as hyperkeratoses (HKs), which are characterized by hyperproliferation and aberrations in terminal epidermal differentiation, are common early manifestations of arsenicosis in humans. H...

Novel dermaseptin, adenoregulin and caerin homologs from the Central American red-eyed leaf frog, Agalychnis callidryas, revealed by functional peptidomics of defensive skin secretion.

PubMed

Wang, Lei; Zhou, Mei; McClelland, Ann; Reilly, Aislinn; Chen, Tianbao; Gagliardo, Ron; Walker, Brian; Shaw, Chris

2008-10-01

By integrating systematic peptidome and transcriptome studies of the defensive skin secretion of the Central American red-eyed leaf frog, Agalychnis callidryas, we have identified novel members of three previously described antimicrobial peptide families, a 27-mer dermaseptin-related peptide (designated DRP-AC4), a 33-mer adenoregulin-related peptide (designated ARP-AC1) and most unusually, a 27-mer caerin-related peptide (designated CRP-AC1). While dermaseptin and adenoregulin were originally isolated from phyllomedusine leaf frogs, the caerins, until now, had only been described in Australian frogs of the genus, Litoria. Both the dermaseptin and adenoregulin were C-terminally amidated and lacked the C-terminal tripeptide of the biosynthetic precursor sequence. In contrast, the caerin-related peptide, unlike the majority of Litoria analogs, was not C-terminally amidated. The present data emphasize the need for structural characterization of mature peptides to ensure that unexpected precursor cleavages and/or post-translational modifications do not produce mature peptides that differ in structure to those predicted from cloned biosynthetic precursor cDNA. Additionally, systematic study of the secretory peptidome can produce unexpected results such as the CRP described here that may have phylogenetic implications. It is thus of the utmost importance in the functional evaluation of novel peptides that the primary structure of the mature peptide is unequivocally established -- something that is often facilitated by cloning biosynthetic precursor cDNAs but obviously not reliable using such data alone.

Esophageal Cancer Metastases to Unexpected Sites: A Systematic Review

PubMed Central

2017-01-01

The most common pattern of esophageal cancer metastases (ECM) is to the lymph nodes, lung, liver, bones, adrenal glands, and brain. On the other hand, unexpected metastasis (UM) spread to uncommon sites has increasingly reported and consequently affected the pathway of diagnosis, staging, and management. Using the PubMed database, a systematic search of the following headings “Esophageal” and “Metastasis” or “Metastases” was performed, 10049 articles were identified, and the articles were included if they demonstrated unexpected ECM. 84% of cases were men with an average age of 60.7 years. EC was located in the lower third in 65%. Two-thirds of the UM originated from the lower esophagus, and the two major histological types were adenocarcinoma 40% and squamous cell carcinoma 60%. Metastases were disseminated toward five main anatomical sites: the head and neck (42%), thoracic (17%), abdomen and pelvis (25%), extremities (9%), and multiple skin and muscle metastases (7%). The EC metastases were found to be synchronous 42% and metachronous 58%, isolated in 53.5% and multiple in 46.5%. The overall survival rate was 10.2 months. Since distant metastases are responsible for most EC-related deaths, understanding of ECM dissemination patterns needs more extensive studies. These critical data are the cornerstone of optimal cancer approach and treatment. PMID:28659974

Highly polymorphic colour vision in a New World monkey with red facial skin, the bald uakari (Cacajao calvus).

PubMed

Corso, Josmael; Bowler, Mark; Heymann, Eckhard W; Roos, Christian; Mundy, Nicholas I

2016-04-13

Colour vision is highly variable in New World monkeys (NWMs). Evidence for the adaptive basis of colour vision in this group has largely centred on environmental features such as foraging benefits for differently coloured foods or predator detection, whereas selection on colour vision for sociosexual communication is an alternative hypothesis that has received little attention. The colour vision of uakaris (Cacajao) is of particular interest because these monkeys have the most dramatic red facial skin of any primate, as well as a unique fission/fusion social system and a specialist diet of seeds. Here, we investigate colour vision in a wild population of the bald uakari,C. calvus, by genotyping the X-linked opsin locus. We document the presence of a polymorphic colour vision system with an unprecedented number of functional alleles (six), including a novel allele with a predicted maximum spectral sensitivity of 555 nm. This supports the presence of strong balancing selection on different alleles at this locus. We consider different hypotheses to explain this selection. One possibility is that trichromacy functions in sexual selection, enabling females to choose high-quality males on the basis of red facial coloration. In support of this, there is some evidence that health affects facial coloration in uakaris, as well as a high prevalence of blood-borne parasitism in wild uakari populations. Alternatively, the low proportion of heterozygous female trichromats in the population may indicate selection on different dichromatic phenotypes, which might be related to cryptic food coloration. We have uncovered unexpected diversity in the last major lineage of NWMs to be assayed for colour vision, which will provide an interesting system to dissect adaptation of polymorphic trichromacy. © 2016 The Author(s).

Automated Sensitivity Analysis of Interplanetary Trajectories for Optimal Mission Design

NASA Technical Reports Server (NTRS)

Knittel, Jeremy; Hughes, Kyle; Englander, Jacob; Sarli, Bruno

2017-01-01

This work describes a suite of Python tools known as the Python EMTG Automated Trade Study Application (PEATSA). PEATSA was written to automate the operation of trajectory optimization software, simplify the process of performing sensitivity analysis, and was ultimately found to out-perform a human trajectory designer in unexpected ways. These benefits will be discussed and demonstrated on sample mission designs.

Alkaloids from single skins of the Argentinian toad Melanophryniscus rubriventris (ANURA, BUFONIDAE): An unexpected variability in alkaloid profiles and a profusion of new structures.

PubMed

Garraffo, H Martin; Andriamaharavo, Nirina R; Vaira, Marcos; Quiroga, María F; Heit, Cecilia; Spande, Thomas F

2012-12-01

GC-MS analysis of single-skins of ten Melanophryniscus rubriventris toads (five collections of two toads each) captured during their breeding season in NW Argentina has revealed a total of 127 alkaloids of which 56 had not been previously detected in any frog or toad. Included among these new alkaloids are 23 new diastereomers of previously reported alkaloids. What is particularly distinguishing about the alkaloid profiles of these ten collections is the occurrence of many of the alkaloids, whether known or new to us, in only one of the ten skins sampled, despite two skins being obtained from each breeding site of the five populations. Many of the alkaloids are of classes known to have structures with branched-chains (e.g. pumiliotoxins and tricyclic structures) that are considered to derive from dietary mites. A large number of previously reported and new alkaloids are also of unclassified structures. Only a very few 3,5-disubstituted-indolizidine or -pyrrolizidine alkaloids are observed that have a straight-chain carbon skeleton and are likely derived from ant prey. The possible relationship of these collections made during the toad's brief breeding episodes to sequestration of dietary arthropods and individual alkaloid profiles is discussed.

Spontaneous Development of Cutaneous Squamous Cell Carcinoma in Mice with Cell-specific Deletion of Inhibitor of κB Kinase 2

PubMed Central

Kirkley, Kelly S; Walton, Kelly D; Duncan, Colleen; Tjalkens, Ronald B

2017-01-01

The deletion of NFκB in epithelial tissues by using skin-specific promoters can cause both tumor formation and severe inflammatory dermatitis, indicating that this signaling pathway is important for the maintenance of immune homeostasis in epithelial tissues. In the present study, we crossed mice transgenic for loxP-Ikbk2 and human Gfap-cre to selectively delete IKK2 in CNS astrocytes. Unexpectedly, a subset of mice developed severe and progressive skin lesions marked by hyperplasia, hyperkeratosis, dysplasia, inflammation, and neoplasia with a subset of lesions diagnosed as squamous cell carcinoma (SCC). The development of lesions was monitored over a 3.5-y period and over 4 filial generations. Average age of onset of was 4 mo of age with 19.5% of mice affected with frequency increasing in progressive generations. Lesion development appeared to correlate not only with unintended IKK2 deletion in GFAP expressing cells of the epidermis, but also with increased expression of TNF in lesioned skin. The skins changes described in these animals are similar to those in transgenic mice with an epidermis-specific deletion of NFκB and thus represents another genetic mouse model that can be used to study the role of NFκB signaling in regulating the development of SCC. PMID:28935002

In vitro micro-physiological immune-competent model of the human skin.

PubMed

Ramadan, Qasem; Ting, Fiona Chia Wan

2016-05-21

Skin allergy, in particular, allergic contact dermatitis and irritant contact dermatitis, are common occupational and environmental health problems affecting the quality of life of a significant proportion of the world population. Since all new ingredients to be incorporated into a product are potential skin allergens, it is essential that these ingredients be first tested for their allergenic potential. However, despite the considerable effort using animal models to understand the underlying mechanism of skin sensitization, to date, the molecular and cellular responses due to skin contact with sensitizers are still not fully understood. To replace animal testing and to improve the prediction of skin sensitization, significant attention has been directed to the use of reconstructed organotypic in vitro models of human skin. Here we describe a miniaturized immune competent in vitro model of human skin based on 3D co-culture of immortalized human keratinocytes (HaCaT) as a model of the epidermis barrier and human leukemic monocyte lymphoma cell line (U937) as a model of human dendritic cells. The biological model was fitted in a microfluidic-based cell culture system that provides a dynamic cellular environment that mimics the in vivo environment of skin. The dynamic perfusion of culture media significantly improved the tight junction formation as evidenced by measuring higher values of TEER compared to static culture. This setting also maintained the high viability of cells over extended periods of time up to 17 days. The perfusion-based culture also allows growth of the cells at the air-liquid interface by exposing the apical side of the cells to air while providing the cell nutrients through a basolateral fluidic compartment. The microsystem has been evaluated to investigate the effect of the chemical and physical (UV irradiation) stimulation on the skin barrier (i.e. the TJ integrity). Three-tiered culture differential stimulation allowed the investigation of the role of the keratinocyte layer as a protection barrier to chemical/biological hazards.

Changes in skin reactivity and associated factors in patients sensitized to house dust mites after 1 year of allergen-specific immunotherapy.

PubMed

Son, Jeong-Yeop; Jung, Mann-Hong; Koh, Kwang-Wook; Park, Eun-Kee; Heo, Jeong-Hoon; Choi, Gil-Soon; Kim, Hee-Kyoo

2017-04-01

Allergen-specific immunotherapy (SIT) can significantly improve symptoms and reduce the need for symptomatic medication. The aim of this study was to investigate changes in skin reactivity to house dust mites (HDMs) as an immunologic response and associated factors after 1 year of immunotherapy. A total of 80 patients with allergic airway diseases who received subcutaneous SIT with HDMs from 2009 to 2014 were evaluated. The investigated parameters were basic demographic characteristics, skin reactivity and specific IgE for HDM, serum total IgE level, blood eosinophil counts, and medication score. The mean levels of skin reactivity to HDMs, blood eosinophil counts, and medication scores after 1 year were significantly reduced from baseline. In univariate comparison of the changes in skin reactivity to HDMs, age ≤30 years, HDMs only as target of immunotherapy, and high initial skin reactivity (≥2) to HDMs were significantly associated with the reduction in skin test reactivity. In multivariate analysis, high initial skin reactivity and HDMs only as target allergens were significantly associated with changes in skin reactivity to HDMs. In the receiver operating characteristic curve of the initial mean skin reactivity to HDMs for more than 50% reduction, the optimal cutoff value was 2.14. This study showed significant reductions in allergen skin reactivity to HDMs after 1 year of immunotherapy in patients sensitized to HDMs. The extent of initial allergen skin reactivity and only HDMs as target allergen were important predictive factors for changes in skin reactivity.

Antimicrobial efficacy of preoperative skin antisepsis and clonal relationship to postantiseptic skin-and-wound flora in patients undergoing clean orthopedic surgery.

PubMed

Daeschlein, G; Napp, M; Layer, F; von Podewils, S; Haase, H; Spitzmueller, R; Assadian, O; Kasch, R; Werner, G; Jünger, M; Hinz, P; Ekkernkamp, A

2015-11-01

Nosocomial surgical site infections (SSI) are still important complications in surgery. The underlying mechanisms are not fully understood. The aim of this study was to elucidate the possible role of skin flora surviving preoperative antisepsis as a possible cause of SSI. We conducted a two-phase prospective clinical trial in patients undergoing clean orthopedic surgery at a university trauma center in northern Germany. Quantitative swab samples were taken from pre- and postantiseptic skin and, additionally, from the wound base, wound margin, and the suture of 137 patients. Seventy-four patients during phase I and 63 during phase II were investigated. Microbial growth, species spectrum, and antibiotic susceptibility were analyzed. In phase two, the clonal relationship of strains was additionally analyzed. 18.0 % of the swab samples were positive for bacterial growth in the wound base, 24.5 % in the margin, and 27.3 % in the suture. Only 65.5 % of patients showed a 100 % reduction of the skin flora after antisepsis. The microbial spectrum in all postantiseptic samples was dominated by coagulase-negative staphylococci (CoNS). Clonally related staphylococci were detected in ten patients [nine CoNS, one methicillin-susceptible Staphylococcus aureus (MSSA)]. Six of ten patients were suspected of having transmitted identical clones from skin flora into the wound. Ethanol-based antisepsis results in unexpected high levels of skin flora, which can be transmitted into the wound during surgery causing yet unexplained SSI. Keeping with the concept of zero tolerance, further studies are needed in order to understand the origin of this flora to allow further reduction of SSI.

In search of the Golden Fleece: Unraveling principles of morphogenesis by studying the integrative biology of skin appendages

PubMed Central

Hughes, Michael W.; Wu, Ping; Jiang, Ting-Xin; Lin, Sung-Jan; Dong, Chen-Yuan; Li, Ang; Hsieh, Fon-Jou; Widelitz, Randall B.; Choung, Cheng Ming

2013-01-01

Summary The mythological story of the Golden Fleece symbolizes the magical regenerative power of skin appendages. Similar to the adventurous pursuit of the Golden Fleece by the multi-talented Argonauts, today we also need an integrated multi-disciplined approach to understand the cellular and molecular processes during development, regeneration and evolution of skin appendages. To this end, we have explored several aspects of skin appendage biology that contribute to the Turing activator / inhibitor model in feather pattern formation, the topo-biological arrangement of stem cells in organ shape determination, the macro-environmental regulation of stem cells in regenerative hair waves, and potential novel molecular pathways in the morphological evolution of feathers. Here we show our current integrative biology efforts to unravel the complex cellular behavior in patterning stem cells and the control of regional specificity in skin appendages. We use feather / scale tissue recombination to demonstrate the timing control of competence and inducibility. Feathers from different body regions are used to study skin regional specificity. Bioinformatic analyses of transcriptome microarrays show the potential involvement of candidate molecular pathways. We further show Hox genes exhibit some region specific expression patterns. To visualize real time events, we applied time-lapse movies, confocal microscopy and multiphoton microscopy to analyze the morphogenesis of cultured embryonic chicken skin explants. These modern imaging technologies reveal unexpectedly complex cellular flow and organization of extracellular matrix molecules in three dimensions. While these approaches are in preliminary stages, this perspective highlights the challenges we face and new integrative tools we will use. Future work will follow these leads to develop a systems biology view and understanding in the morphogenetic principles that govern the development and regeneration of ectodermal organs. PMID:21437328

Kyphectomy improves sitting and skin problems in patients with myelomeningocele.

PubMed

Garg, Sumeet; Oetgen, Matthew; Rathjen, Karl; Richards, B Stephens

2011-05-01

Progressive kyphosis occurs in up to 20% of patients with myelomeningocele. Severely affected patients can develop recurrent skin breakdown, osteomyelitis, sitting imbalance, and poor cosmetic appearance. We (1) assessed the ability of kyphectomy to restore an intact skin envelope and allow comfortable seating in a wheelchair; (2) reviewed the complications of kyphectomy and spinal fusion in myelomeningocele; and (3) determined whether patients requiring unexpected reoperation had worse correction or more ulceration compared with those patients treated with a single surgery. We retrospectively reviewed the records of 23 children with thoracic-level myelomeningocele who were treated with kyphectomy and spinal fusion since 1980. Indications for surgery included recurrent skin breakdown (15 patients) and poor sitting balance or unacceptable cosmetic deformity (three patients). We evaluated operative technique, type of sacropelvic fixation, surgical complications, radiographic correction, and skin condition at followup. The minimum followup was 2 years (median, 4.1 years; range, 2.1-10 years); 18 of the 23 children had greater than 2 years followup and are reported here. Kyphectomy achieved a sitting balance and resolved in skin ulceration in 17 of 18 patients. Seven patients had complications requiring reoperation. Three patients had multiple reoperations for early deep infection and one patient each had reoperation for late infection, pseudarthrosis, implant-related sacral pressure sore, and planned extension of proximal fusion after growth. Patients requiring multiple operations had similar correction and relief of ulceration to those treated with a single procedure. Complications after kyphectomy are frequent and many children with myelomeningocele and severe hyperkyphosis require multiple procedures and lengthy hospital stays. Nonetheless, improved seating balance and resolution of skin problems was achieved in 17 of 18 patients.

Integrated decision strategies for skin sensitization hazard.

PubMed

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

2016-09-01

One of the top priorities of the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) is the identification and evaluation of non-animal alternatives for skin sensitization testing. Although skin sensitization is a complex process, the key biological events of the process have been well characterized in an adverse outcome pathway (AOP) proposed by the Organisation for Economic Co-operation and Development (OECD). Accordingly, ICCVAM is working to develop integrated decision strategies based on the AOP using in vitro, in chemico and in silico information. Data were compiled for 120 substances tested in the murine local lymph node assay (LLNA), direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT) and KeratinoSens assay. Data for six physicochemical properties, which may affect skin penetration, were also collected, and skin sensitization read-across predictions were performed using OECD QSAR Toolbox. All data were combined into a variety of potential integrated decision strategies to predict LLNA outcomes using a training set of 94 substances and an external test set of 26 substances. Fifty-four models were built using multiple combinations of machine learning approaches and predictor variables. The seven models with the highest accuracy (89-96% for the test set and 96-99% for the training set) for predicting LLNA outcomes used a support vector machine (SVM) approach with different combinations of predictor variables. The performance statistics of the SVM models were higher than any of the non-animal tests alone and higher than simple test battery approaches using these methods. These data suggest that computational approaches are promising tools to effectively integrate data sources to identify potential skin sensitizers without animal testing. Published 2016. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Published 2016. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

WE-DE-201-11: Sensitivity and Specificity of Verification Methods Based On Total Reference Air Kerma (TRAK) Or On User Provided Dose Points for Graphically Planned Skin HDR Brachytherapy

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

Damato, A; Devlin, P; Bhagwat, M

Purpose: To investigate the sensitivity and specificity of a novel verification methodology for image-guided skin HDR brachytherapy plans using a TRAK-based reasonableness test, compared to a typical manual verification methodology. Methods: Two methodologies were used to flag treatment plans necessitating additional review due to a potential discrepancy of 3 mm between planned dose and clinical target in the skin. Manual verification was used to calculate the discrepancy between the average dose to points positioned at time of planning representative of the prescribed depth and the expected prescription dose. Automatic verification was used to calculate the discrepancy between TRAK of themore » clinical plan and its expected value, which was calculated using standard plans with varying curvatures, ranging from flat to cylindrically circumferential. A plan was flagged if a discrepancy >10% was observed. Sensitivity and specificity were calculated using as a criteria for true positive that >10% of plan dwells had a distance to prescription dose >1 mm different than prescription depth (3 mm + size of applicator). All HDR image-based skin brachytherapy plans treated at our institution in 2013 were analyzed. Results: 108 surface applicator plans to treat skin of the face, scalp, limbs, feet, hands or abdomen were analyzed. Median number of catheters was 19 (range, 4 to 71) and median number of dwells was 257 (range, 20 to 1100). Sensitivity/specificity were 57%/78% for manual and 70%/89% for automatic verification. Conclusion: A check based on expected TRAK value is feasible for irregularly shaped, image-guided skin HDR brachytherapy. This test yielded higher sensitivity and specificity than a test based on the identification of representative points, and can be implemented with a dedicated calculation code or with pre-calculated lookup tables of ideally shaped, uniform surface applicators.« less

Self-organization process in newborn skin organoid formation inspires strategy to restore hair regeneration of adult cells

PubMed Central

Lei, Mingxing; Lai, Yung-Chih; Juan, Wen-Tau; Yeh, Chao-Yuan; Wu, Ping; Jiang, Ting-Xin; Widelitz, Randall Bruce; Yang, Li; Chuong, Cheng-Ming

2017-01-01

Organoids made from dissociated progenitor cells undergo tissue-like organization. This in vitro self-organization process is not identical to embryonic organ formation, but it achieves a similar phenotype in vivo. This implies genetic codes do not specify morphology directly; instead, complex tissue architectures may be achieved through several intermediate layers of cross talk between genetic information and biophysical processes. Here we use newborn and adult skin organoids for analyses. Dissociated cells from newborn mouse skin form hair primordia-bearing organoids that grow hairs robustly in vivo after transplantation to nude mice. Detailed time-lapse imaging of 3D cultures revealed unexpected morphological transitions between six distinct phases: dissociated cells, cell aggregates, polarized cysts, cyst coalescence, planar skin, and hair-bearing skin. Transcriptome profiling reveals the sequential expression of adhesion molecules, growth factors, Wnts, and matrix metalloproteinases (MMPs). Functional perturbations at different times discern their roles in regulating the switch from one phase to another. In contrast, adult cells form small aggregates, but then development stalls in vitro. Comparative transcriptome analyses suggest suppressing epidermal differentiation in adult cells is critical. These results inspire a strategy that can restore morphological transitions and rescue the hair-forming ability of adult organoids: (i) continuous PKC inhibition and (ii) timely supply of growth factors (IGF, VEGF), Wnts, and MMPs. This comprehensive study demonstrates that alternating molecular events and physical processes are in action during organoid morphogenesis and that the self-organizing processes can be restored via environmental reprogramming. This tissue-level phase transition could drive self-organization behavior in organoid morphogenies beyond the skin. PMID:28798065

Self-organization process in newborn skin organoid formation inspires strategy to restore hair regeneration of adult cells.

PubMed

Lei, Mingxing; Schumacher, Linus J; Lai, Yung-Chih; Juan, Wen-Tau; Yeh, Chao-Yuan; Wu, Ping; Jiang, Ting-Xin; Baker, Ruth E; Widelitz, Randall Bruce; Yang, Li; Chuong, Cheng-Ming

2017-08-22

Organoids made from dissociated progenitor cells undergo tissue-like organization. This in vitro self-organization process is not identical to embryonic organ formation, but it achieves a similar phenotype in vivo. This implies genetic codes do not specify morphology directly; instead, complex tissue architectures may be achieved through several intermediate layers of cross talk between genetic information and biophysical processes. Here we use newborn and adult skin organoids for analyses. Dissociated cells from newborn mouse skin form hair primordia-bearing organoids that grow hairs robustly in vivo after transplantation to nude mice. Detailed time-lapse imaging of 3D cultures revealed unexpected morphological transitions between six distinct phases: dissociated cells, cell aggregates, polarized cysts, cyst coalescence, planar skin, and hair-bearing skin. Transcriptome profiling reveals the sequential expression of adhesion molecules, growth factors, Wnts, and matrix metalloproteinases (MMPs). Functional perturbations at different times discern their roles in regulating the switch from one phase to another. In contrast, adult cells form small aggregates, but then development stalls in vitro. Comparative transcriptome analyses suggest suppressing epidermal differentiation in adult cells is critical. These results inspire a strategy that can restore morphological transitions and rescue the hair-forming ability of adult organoids: ( i ) continuous PKC inhibition and ( ii ) timely supply of growth factors (IGF, VEGF), Wnts, and MMPs. This comprehensive study demonstrates that alternating molecular events and physical processes are in action during organoid morphogenesis and that the self-organizing processes can be restored via environmental reprogramming. This tissue-level phase transition could drive self-organization behavior in organoid morphogenies beyond the skin.

A 3D-psoriatic skin model for dermatological testing: The impact of culture conditions.

PubMed

Duque-Fernandez, Alexandra; Gauthier, Lydia; Simard, Mélissa; Jean, Jessica; Gendreau, Isabelle; Morin, Alexandre; Soucy, Jacques; Auger, Michèle; Pouliot, Roxane

2016-12-01

Inadequate representation of the human tissue environment during a preclinical screen can result in inaccurate predictions of compound effects. Consequently, pharmaceutical investigators are searching for preclinical models that closely resemble original tissue for predicting clinical outcomes. The current research aims to compare the impact of using serum-free medium instead of complete culture medium during the last step of psoriatic skin substitute reconstruction. Skin substitutes were produced according to the self-assembly approach. Serum-free conditions have no negative impact on the reconstruction of healthy or psoriatic skin substitutes presented in this study regarding their macroscopic or histological appearances. ATR-FTIR results showed no significant differences in the CH 2 bands between psoriatic substitutes cultured with or without serum, thus suggesting that serum deprivation did not have a negative impact on the lipid organization of their stratum corneum . Serum deprivation could even lead to a better organization of healthy skin substitute lipids. Percutaneous analyses demonstrated that psoriatic substitutes cultured in serum-free conditions showed a higher permeability to hydrocortisone compared to controls, while no significant differences in benzoic acid and caffeine penetration profiles were observed. Results obtained with this 3D-psoriatic skin substitute demonstrate the potential and versatility of the model. It could offer good prediction of drug related toxicities at preclinical stages performed in order to avoid unexpected and costly findings in the clinic. Together, these findings offer a new approach for one of the most important challenges of the 21st century, namely, prediction of drug toxicity.

Skin sensitization potency of methyl methacrylate in the local lymph node assay: comparisons with guinea-pig data and human experience.

PubMed

Betts, Catherine J; Dearman, Rebecca J; Heylings, Jon R; Kimber, Ian; Basketter, David A

2006-09-01

There is compelling evidence that contact allergens differ substantially (by 4 or 5 orders of magnitude) with respect to their inherent skin-sensitizing potency. Relative potency can now be measured effectively using the mouse local lymph node assay (LLNA) and such data form the basis of risk assessment and risk management strategies. Such determinations also facilitate distinctions being drawn between the prevalence of skin sensitization to a particular contact allergen and inherent potency. The distinction is important because chemicals that are implicated as common causes of contact allergy are not necessarily potent sensitizers. One example is provided by nickel that is undoubtedly a common cause of allergic contact dermatitis, but is a comparatively weak sensitizer in predictive tests. In an attempt to explore other examples of contact allergens where there may exist a discrepancy between prevalence and potency, we describe here analyses conducted with methyl methacrylate (MMA). Results of LLNA studies have been interpreted in the context of historical clinical data on occupational allergic contact dermatitis associated with exposure to MMA.

[Allergological study of pollen of mango (Magnifera indica) and cross reactivity with pollen of piru (Schinus molle)].

PubMed

Vargas Correa, J B; Sánchez Solís, L; Farfán Ale, J A; Noguchi, H; Moguel Baños, M T; Vargas de la Peña, M I

1991-01-01

With immediate skin test, we studied hypersensitivity to pollen of mango (Magnifera indica), and its probability cross-sensitivity to pollen of pirú (Schinus molle), from anacardaceae class. We have made one extract of Magnifera indica, with 0.485 mg per 100, of protein nitrogen. With this extract we carry out skin test on non-atopic subjects and atopic subjects with bronchial asthma and or allergy rhinitis and common stock of aerealergen. (Freeman stock). We studied seventy-one subjects, both sexes, from 14 to 40 years old. The prevalence of cutaneous sensitive to mango (Magnifera indica) were 66%, and sensitivity from Schinus molle were 31%. Those with sensitivity Schinus molle, were sensitivity from Magnifera, too. Statistical analyisis of correlation, with McNemar Test was p 0.001 under the conditions of the study we conclude that there are hypersensitivity to pollen of Magnifera, and there are cross-reactivity with Schinus molle. Therefore mangifera should be included within the stock of skin test in the areas were this anacardaceae is present.

Imiquimod Topical

MedlinePlus

... growths on the skin caused by too much sun exposure) on the face or scalp. Imiquimod cream ... have or have ever had unusual sensitivity to sunlight, any skin disease such as psoriasis, graft vs. ...

The Unique Molecular Signatures of Contact Dermatitis and Implications for Treatment.

PubMed

Leonard, Alexandra; Guttman-Yassky, Emma

2018-05-12

Irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) are common skin disorders that are characterized by inflammation, oozing, crusting, and pruritus. Atopic dermatitis (AD) is an inflammatory skin disease characterized by immune and barrier abnormalities and is additionally a risk factor for acquiring ICD and ACD. New work on allergic sensitization to common allergens (e.g., nickel and fragrance) in human skin has shown that different allergens have distinct molecular fingerprinting. For example, nickel promotes strong Th1/Th17 polarization, whereas fragrance allergy causes Th2/Th22 skewing, which is similar to the phenotype of AD. While ACD has previously been considered to be constant across all allergens, largely based on mouse models involving strong sensitizers, these new data suggest that ACD differs mechanistically according to allergen. Further, ACD in the setting of concurrent AD shows a different and attenuated phenotype as compared to healthy individuals with ACD, which influences the way AD patients respond to vaccination and other treatment modalities. As in contact sensitization, skin challenged by food patch testing shows that common food allergens (e.g., peanut and barley) also cause distinct immune polarizations in the skin. Additionally, house dust mite reactions in human skin have been profiled to show unique Th2, Th9, and Th17/22 activation as compared to controls, which are similar to the phenotype of psoriasis and contact responses to nickel. Given this information, ACD patients should be treated based on their unique allergen polarity. Refined understanding of the molecular behavior of contact dermatitis and related diseases translates to improved methods of inducing tolerance in sensitized allergic patients, such as with targeted drug therapy and epicutaneous immunotherapy.

Prevalence of Skin Sensitization to Pollen of Date Palm in Marrakesh, Morocco.

PubMed

Serhane, Hind; Amro, Lamyae; Sajiai, Hafsa; Alaoui Yazidi, Abdelhaq

2017-01-01

Background . Date palm's pollen has been identified as a source of allergy; the rate of sensitization of this pollen is between 6 and 29%. Objective . To determine the prevalence of sensitization to date palm in Marrakesh and to identify the clinical profile. Patients and Methods . This study is based on a questionnaire and the prick test on 7 allergens, in population aged 5 years and above with clinical symptoms suggesting allergic diseases, from November 2012 to February 2013 in Marrakech. Results . We included 468 patients (women: 79.5%). The prick tests were considered interpretable in 467 cases. The prevalence of skin sensitization to pollen of date palm was 6.6%. The 31 cases of sensitization to date palm involved 7 men and 24 women with an average age of 37.5 years. Cutaneous monosensitization to date palm's pollen was observed in 2 cases. Asthma, rhinitis, and conjunctivitis were recorded, respectively, in 48.4%, 93.5%, and 67.7%. Conclusion . Skin sensitization to pollen of date palm does not seem unusual among allergic patients in Marrakech and is comparable to that found in Casablanca (7%), Barcelona (6.6%), and Cartagena (6.1%).

Anaphylaxis to Gelofusine confirmed by in vitro basophil activation test: a case series.

PubMed

Apostolou, E; Deckert, K; Puy, R; Sandrini, A; de Leon, M P; Douglass, J A; Rolland, J M; O'hehir, R E

2006-03-01

The plasma expander Gelofusine (succinylated gelatin) is a recognised cause of peri-operative anaphylaxis. Current diagnosis of Gelofusine sensitivity is by skin testing, a procedure that itself carries a risk of allergic reaction. We evaluated the reliability of the in vitro basophil activation test as a diagnostic assay for Gelofusine sensitivity in subjects with a clinical history highly suggestive of Gelofusine allergy. Six patients with peri-operative anaphylaxis clinically attributed to Gelofusine were skin tested to confirm sensitivity. Control subjects included three healthy subjects and five subjects allergic to a neuromuscular blocking drug, all negative on Gelofusine skin testing. Whole blood basophil activation to Gelofusine was analysed by flow cytometry for CD63 surface expression. All of the Gelofusine sensitive patients and one of the control allergic subjects showed positive basophil activation to Gelofusine. In this series of subjects, the basophil activation test for Gelofusine allergy had a sensitivity of 100% and a specificity of 87.5%. Our findings suggest that basophil activation testing is a safe and reliable in vitro assay for prediction or confirmation of Gelofusine sensitivity in patients with high clinical suspicion of Gelofusine-induced anaphylaxis.

Nociceptive sensations evoked from 'spots' in the skin by mild cooling and heating.

PubMed

Green, Barry G; Roman, Carolyn; Schoen, Kate; Collins, Hannah

2008-03-01

It was recently found that nociceptive sensations (stinging, pricking, or burning) can be evoked by cooling or heating the skin to innocuous temperatures (e.g., 29 and 37 degrees C). Here, we show that this low-threshold thermal nociception (LTN) can be traced to sensitive 'spots' in the skin equivalent to classically defined warm spots and cold spots. Because earlier work had shown that LTN is inhibited by simply touching a thermode to the skin, a spatial search procedure was devised that minimized tactile stimulation by sliding small thermodes (16 and 1mm(2)) set to 28 or 36 degrees C slowly across the lubricated skin of the forearm. The procedure uncovered three types of temperature-sensitive sites (thermal, bimodal, and nociceptive) that contained one or more thermal, nociceptive, or (rarely) bimodal spots. Repeated testing indicated that bimodal and nociceptive sites were less stable over time than thermal sites, and that mechanical contact differentially inhibited nociceptive sensations. Intensity ratings collected over a range of temperatures showed that LTN increased monotonically on heat-sensitive sites but not on cold-sensitive sites. These results provide psychophysical evidence that stimulation from primary afferent fibers with thresholds in the range of warm fibers and cold fibers is relayed to the pain pathway. However, the labile nature of LTN implies that these low-threshold nociceptive inputs are subject to inhibitory controls. The implications of these findings for the roles of putative temperature receptors and nociceptors in innocuous thermoreception and thermal pain are discussed.

Cytochrome P450-mediated activation of the fragrance compound geraniol forms potent contact allergens

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

Hagvall, Lina; Baron, Jens Malte; Boerje, Anna

2008-12-01

Contact sensitization is caused by low molecular weight compounds which penetrate the skin and bind to protein. In many cases, these compounds are activated to reactive species, either by autoxidation on exposure to air or by metabolic activation in the skin. Geraniol, a widely used fragrance chemical, is considered to be a weak allergen, although its chemical structure does not indicate it to be a contact sensitizer. We have shown that geraniol autoxidizes and forms allergenic oxidation products. In the literature, it is suggested but not shown that geraniol could be metabolically activated to geranial. Previously, a skin-like CYP cocktailmore » consisting of cutaneous CYP isoenzymes, was developed as a model system to study cutaneous metabolism. In the present study, we used this system to investigate CYP-mediated activation of geraniol. In incubations with the skin-like CYP cocktail, geranial, neral, 2,3-epoxygeraniol, 6,7-epoxygeraniol and 6,7-epoxygeranial were identified. Geranial was the main metabolite formed followed by 6,7-epoxygeraniol. The allergenic activities of the identified metabolites were determined in the murine local lymph node assay (LLNA). Geranial, neral and 6,7-epoxygeraniol were shown to be moderate sensitizers, and 6,7-epoxygeranial a strong sensitizer. Of the isoenzymes studied, CYP2B6, CYP1A1 and CYP3A5 showed high activities. It is likely that CYP1A1 and CYP3A5 are mainly responsible for the metabolic activation of geraniol in the skin, as they are expressed constitutively at significantly higher levels than CYP2B6. Thus, geraniol is activated through both autoxidation and metabolism. The allergens geranial and neral are formed via both oxidation mechanisms, thereby playing a large role in the sensitization to geraniol.« less

Development of an artificial neural network model for risk assessment of skin sensitization using human cell line activation test, direct peptide reactivity assay, KeratinoSens™ and in silico structure alert parameter.

PubMed

Hirota, Morihiko; Ashikaga, Takao; Kouzuki, Hirokazu

2018-04-01

It is important to predict the potential of cosmetic ingredients to cause skin sensitization, and in accordance with the European Union cosmetic directive for the replacement of animal tests, several in vitro tests based on the adverse outcome pathway have been developed for hazard identification, such as the direct peptide reactivity assay, KeratinoSens™ and the human cell line activation test. Here, we describe the development of an artificial neural network (ANN) prediction model for skin sensitization risk assessment based on the integrated testing strategy concept, using direct peptide reactivity assay, KeratinoSens™, human cell line activation test and an in silico or structure alert parameter. We first investigated the relationship between published murine local lymph node assay EC3 values, which represent skin sensitization potency, and in vitro test results using a panel of about 134 chemicals for which all the required data were available. Predictions based on ANN analysis using combinations of parameters from all three in vitro tests showed a good correlation with local lymph node assay EC3 values. However, when the ANN model was applied to a testing set of 28 chemicals that had not been included in the training set, predicted EC3s were overestimated for some chemicals. Incorporation of an additional in silico or structure alert descriptor (obtained with TIMES-M or Toxtree software) in the ANN model improved the results. Our findings suggest that the ANN model based on the integrated testing strategy concept could be useful for evaluating the skin sensitization potential. Copyright © 2017 John Wiley & Sons, Ltd.

Cytochrome P450-mediated activation of the fragrance compound geraniol forms potent contact allergens.

PubMed

Hagvall, Lina; Baron, Jens Malte; Börje, Anna; Weidolf, Lars; Merk, Hans; Karlberg, Ann-Therese

2008-12-01

Contact sensitization is caused by low molecular weight compounds which penetrate the skin and bind to protein. In many cases, these compounds are activated to reactive species, either by autoxidation on exposure to air or by metabolic activation in the skin. Geraniol, a widely used fragrance chemical, is considered to be a weak allergen, although its chemical structure does not indicate it to be a contact sensitizer. We have shown that geraniol autoxidizes and forms allergenic oxidation products. In the literature, it is suggested but not shown that geraniol could be metabolically activated to geranial. Previously, a skin-like CYP cocktail consisting of cutaneous CYP isoenzymes, was developed as a model system to study cutaneous metabolism. In the present study, we used this system to investigate CYP-mediated activation of geraniol. In incubations with the skin-like CYP cocktail, geranial, neral, 2,3-epoxygeraniol, 6,7-epoxygeraniol and 6,7-epoxygeranial were identified. Geranial was the main metabolite formed followed by 6,7-epoxygeraniol. The allergenic activities of the identified metabolites were determined in the murine local lymph node assay (LLNA). Geranial, neral and 6,7-epoxygeraniol were shown to be moderate sensitizers, and 6,7-epoxygeranial a strong sensitizer. Of the isoenzymes studied, CYP2B6, CYP1A1 and CYP3A5 showed high activities. It is likely that CYP1A1 and CYP3A5 are mainly responsible for the metabolic activation of geraniol in the skin, as they are expressed constitutively at significantly higher levels than CYP2B6. Thus, geraniol is activated through both autoxidation and metabolism. The allergens geranial and neral are formed via both oxidation mechanisms, thereby playing a large role in the sensitization to geraniol.

Evaluation of the performance of the reduced local lymph node assay for skin sensitization testing.

PubMed

Ezendam, Janine; Muller, Andre; Hakkert, Betty C; van Loveren, Henk

2013-06-01

The local lymph node assay (LLNA) is the preferred method for classification of sensitizers within REACH. To reduce the number of mice for the identification of sensitizers the reduced LLNA was proposed, which uses only the high dose group of the LLNA. To evaluate the performance of this method for classification, LLNA data from REACH registrations were used and classification based on all dose groups was compared to classification based on the high dose group. We confirmed previous examinations of the reduced LLNA showing that this method is less sensitive compared to the LLNA. The reduced LLNA misclassified 3.3% of the sensitizers identified in the LLNA and misclassification occurred in all potency classes and that there was no clear association with irritant properties. It is therefore not possible to predict beforehand which substances might be misclassified. Another limitation of the reduced LLNA is that skin sensitizing potency cannot be assessed. For these reasons, it is not recommended to use the reduced LLNA as a stand-alone assay for skin sensitization testing within REACH. In the future, the reduced LLNA might be of added value in a weight of evidence approach to confirm negative results obtained with non-animal approaches. Copyright © 2013 Elsevier Inc. All rights reserved.

Contact sensitizers in commercial hair dye products sold in Thailand.

PubMed

Boonchai, Waranya; Bunyavaree, Monthathip; Winayanuwattikun, Waranaree; Kasemsarn, Pranee

2016-04-01

Hair dyes are known to contain potent contact allergens for which sensitization rates have increased over the last decade. To examine the type and frequency of potent contact sensitizers labelled on hair dyes sold in metropolitan Bangkok, Thailand. During the 2013-2014 study period, labelled ingredient information from home use and professional hair dye products was collected. Two hundred and fifty-two hair dye products were evaluated. One hundred and forty-nine products from 48 brands were domestically produced in Thailand, and 103 products were from 23 multinational brands produced in countries other than Thailand. Two hundred and fourteen of 252 (84.9%) hair dye products were found to contain strong skin sensitizers, with 118 (46.8%) being found in domestically produced products, and 96 (38.1%) being found in multinational brand products. Thirty-eight hair dye products (15.1%) were free of potent skin sensitizers. The number of domestically produced products (31, 20.8%) that were free of potent skin sensitizers was significantly higher (p = 0.002) than the number of multinational brand products (7, 6.8%). p-Phenylenediamine was the most prevalent potent sensitizer found among domestically produced hair dyes available on the market. Our findings indicate regional differences in hair dye allergen exposure. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Full skin quantitative optical coherence elastography achieved by combining vibration and surface acoustic wave methods

NASA Astrophysics Data System (ADS)

Li, Chunhui; Guan, Guangying; Huang, Zhihong; Wang, Ruikang K.; Nabi, Ghulam

2015-03-01

By combining with the phase sensitive optical coherence tomography (PhS-OCT), vibration and surface acoustic wave (SAW) methods have been reported to provide elastography of skin tissue respectively. However, neither of these two methods can provide the elastography in full skin depth in current systems. This paper presents a feasibility study on an optical coherence elastography method which combines both vibration and SAW in order to give the quantitative mechanical properties of skin tissue with full depth range, including epidermis, dermis and subcutaneous fat. Experiments are carried out on layered tissue mimicking phantoms and in vivo human forearm and palm skin. A ring actuator generates vibration while a line actuator were used to excited SAWs. A PhS-OCT system is employed to provide the ultrahigh sensitive measurement of the generated waves. The experimental results demonstrate that by the combination of vibration and SAW method the full skin bulk mechanical properties can be quantitatively measured and further the elastography can be obtained with a sensing depth from ~0mm to ~4mm. This method is promising to apply in clinics where the quantitative elasticity of localized skin diseases is needed to aid the diagnosis and treatment.

Proposed epidemiological case definition for serious skin infection in children.

PubMed

O'Sullivan, Cathryn E; Baker, Michael G

2010-04-01

Researching the rising incidence of serious skin infections in children is limited by the lack of a consistent and valid case definition. We aimed to develop and evaluate a good quality case definition, for use in future research and surveillance of these infections. We tested the validity of the existing case definition, and then of 11 proposed alternative definitions, by assessing their screening performance when applied to a population of paediatric skin infection cases identified by a chart review of 4 years of admissions to a New Zealand hospital. Previous studies have largely used definitions based on the International Classification of Diseases skin infection subchapter. This definition is highly specific (100%) but poorly sensitive (61%); it fails to capture skin infections of atypical anatomical sites, those secondary to primary skin disease and trauma, and those recorded as additional diagnoses. Including these groups produced a new case definition with 98.9% sensitivity and 98.8% specificity. Previous analyses of serious skin infection in children have underestimated the true burden of disease. Using this proposed broader case definition should allow future researchers to produce more valid and comparable estimates of the true burden of these important and increasing infections.

Grape seed and skin extract protects kidney from doxorubicin-induced oxidative injury.

PubMed

Mokni, Meherzia; Hamlaoui, Sonia; Kadri, Safwen; Limam, Ferid; Amri, Mohamed; Marzouki, Lamjed; Aouani, Ezzedine

2016-05-01

The study investigated the protective effect of grape seed and skin extract (GSSE) against doxorubicin-induced renal toxicity in healthy rats. Animals were treated with GSSE or not (control), for 8 days, administered with doxorubicin (20mg/kg) in the 4th day, and renal function as well as oxidative stress parameters were evaluated. Data showed that doxorubicin induced renal toxicity by affecting renal architecture and plasma creatinine. Doxorubicin also induced an oxidative stress characterized by an increase in malondialdehyde (MDA), calcium and H(2)O(2) and a decrease in catalase (CAT) and superoxide dismutase (SOD). Unexpectedly doxorubicin increased peroxidase (POD) and decreased carbonyl protein and plasma urea. Treatment with GSSE counteracted almost all adverse effects induced by doxorubicin. Data suggest that doxorubicin induced an oxidative stress into rat kidney and GSSE exerted antioxidant properties, which seem to be mediated by the modulation of intracellular calcium.

Initial results of finger imaging using photoacoustic computed tomography

NASA Astrophysics Data System (ADS)

van Es, Peter; Biswas, Samir K.; Moens, Hein J. Bernelot; Steenbergen, Wiendelt; Manohar, Srirang

2014-06-01

We present a photoacoustic computed tomography investigation on a healthy human finger, to image blood vessels with a focus on vascularity across the interphalangeal joints. The cross-sectional images were acquired using an imager specifically developed for this purpose. The images show rich detail of the digital blood vessels with diameters between 100 μm and 1.5 mm in various orientations and at various depths. Different vascular layers in the skin including the subpapillary plexus could also be visualized. Acoustic reflections on the finger bone of photoacoustic signals from skin were visible in sequential slice images along the finger except at the location of the joint gaps. Not unexpectedly, the healthy synovial membrane at the joint gaps was not detected due to its small size and normal vascularization. Future research will concentrate on studying digits afflicted with rheumatoid arthritis to detect the inflamed synovium with its heightened vascularization, whose characteristics are potential markers for disease activity.

Colonization of fish skin is vital for Vibrio anguillarum to cause disease.

PubMed

Weber, Barbara; Chen, Chang; Milton, Debra L

2010-02-01

Vibrio anguillarum causes a fatal haemorrhagic septicaemia in marine fish. During initial stages of infection, host surfaces are colonized; however, few virulence factors required for colonization of the host are identified. In this study, in vivo bioluminescent imaging was used to analyse directly the colonization of the whole rainbow trout animal by V. anguillarum. The wild type rapidly colonized both the skin and the intestines by 24 h; however, the bacterial numbers on the skin were significantly higher than in the intestines indicating that skin colonization may be important for disease to occur. Mutants defective for the anguibactin iron uptake system, exopolysaccharide transport, or Hfq, an RNA chaperone, were attenuated for virulence, did not colonize the skin, and penetrated skin mucus less efficiently than the wild type. These mutants, however, did colonize the intestines and were as resistant to 2% bile salts as is the wild type. Moreover, exopolysaccharide mutants were significantly more sensitive to lysozyme and antimicrobial peptides, while the Hfq and anguibactin mutants were sensitive to lysozyme compared with the wild type. Vibrio anguillarum encodes several mechanisms to protect against antimicrobial components of skin mucus enabling an amazingly abundant growth on the skin enhancing its disease opportunities. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

Advances in tumor diagnosis using OCT and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Zakharov, V. P.; Bratchenko, I. A.; Kozlov, S. V.; Moryatov, A. A.; Kornilin, D. V.; Myakinin, O. O.; Artemyev, D. N.

2014-05-01

Complex investigation of malignant tumors was performed with combined optical coherence tomography (OCT) and Raman spectroscopy (RS) setup: 22 ex vivo lung tissue samples and 23 in vivo experiments with skin tumors. It was shown that combined RS-OCT unit may be used for precise tissue morphology visualization with simultaneous tumor type determination (BCC, malignant melanoma of skin tissues, adenocarcinoma and squamous cell carcinoma of lung). Fast RS phase method for skin and lung tumors identification was proposed. It is based on alteration of Raman spectral intensity in 1300-1340, 1440-1460 and 1640-1680 cm-1 bands for healthy and malignant tissue. Complex method could identify: malignant melanoma with 88.9% sensitivity and 87.8% specificity; adenocarcinoma with 100% sensitivity and 81.5% specificity; squamous cell carcinomas with 90.9% sensitivity and 77.8% specificity.

Usefulness and limitations of various guinea-pig test methods in detecting human skin sensitizers-validation of guinea-pig tests for skin hypersensitivity.

PubMed

Marzulli, F; Maguire, H C

1982-02-01

Several guinea-pig predictive test methods were evaluated by comparison of results with those obtained with human predictive tests, using ten compounds that have been used in cosmetics. The method involves the statistical analysis of the frequency with which guinea-pig tests agree with the findings of tests in humans. In addition, the frequencies of false positive and false negative predictive findings are considered and statistically analysed. The results clearly demonstrate the superiority of adjuvant tests (complete Freund's adjuvant) in determining skin sensitizers and the overall superiority of the guinea-pig maximization test in providing results similar to those obtained by human testing. A procedure is suggested for utilizing adjuvant and non-adjuvant test methods for characterizing compounds as of weak, moderate or strong sensitizing potential.

Critical Examination of the Article Impulse Noise Injury Prediction Based on the Cochlear Energy by Zagadou, Chan, Ho, and Shelly

DTIC Science & Technology

2017-04-01

unexpected effects, given that skin on the scalp and hair are not normally part of an ATF. Also, at the very high pressures used in these studies (up to...where N represents the number of shots . One of the strong observations for a CL is that the rate at which loss accumulates goes from linear in log...ARL-TR-7958 ● APR 2017 US Army Research Laboratory Critical Examination of the Article Impulse Noise Injury Prediction Based on

78 FR 68076 - Request for Information on Alternative Skin Sensitization Test Methods and Testing Strategies and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-13

... INFORMATION: Background: Allergic contact dermatitis (ACD), a skin reaction characterized by localized redness, swelling, blistering, or itching after direct contact with a skin allergen, is an important public health.... Web site: http://ntp.niehs.nih.gov/go/niceatm . FOR FURTHER INFORMATION CONTACT: Dr. Warren S. Casey...

In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy

PubMed Central

Jang, Won Hyuk; Shim, Sehwan; Wang, Taejun; Yoon, Yeoreum; Jang, Won-Suk; Myung, Jae Kyung; Park, Sunhoo; Kim, Ki Hean

2016-01-01

Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis. PMID:26755422

Safety, efficacy, and usage compliance of home-use device utilizing RF and light energies for treating periorbital wrinkles.

PubMed

Gold, Michael H; Biron, Julie; Levi, Liora; Sensing, Whitney

2017-03-01

The aging process is often associated with undesirable effects on facial skin such as skin redundancy, reduction of elasticity, and increased wrinkling. Radiofrequency (RF) and light-emitting diodes (LEDs) are widely used, clinically proven technologies for skin rejuvenation. This study aimed to evaluate the safety, efficacy, and usage compliance of the home-use device, utilizing RF and LED energies, for self-treatment of periorbital wrinkles and improvement of skin appearance. Thirty-three subjects performed 21 treatment sessions every other day, over 6 weeks on the periorbital areas. In addition, two maintenance treatments were conducted 1 and 2 months following treatment end. Each subject served as his/her own control, comparing results before treatment, and 3 months following treatment end. Thirty subjects completed the study. A blinded, independent photographs assessment of three dermatologists demonstrated an average reduction of 1.49 Fitzpatrick scores (P < 0.001). Analysis revealed improvement (downgrade of at least 1 score) in almost all subjects. No unexpected adverse events were reported. Post-treatment erythema was seen in all subjects and disappeared within 1 h. In some subjects, post-treatment edema was detected and resolved within 24 h. High satisfaction with the device operation, ease of treatments, safety, and wrinkle reduction was reported. The Silk'n Home Skin Tightening (HST) device offers a safe and effective in-home noninvasive technique to improve the appearance of age-related periorbital wrinkles. © 2016 Wiley Periodicals, Inc.

Contribution of impaired myofibril and ryanodine receptor function to prolonged low-frequency force depression after in situ stimulation in rat skeletal muscle.

PubMed

Watanabe, Daiki; Kanzaki, Keita; Kuratani, Mai; Matsunaga, Satoshi; Yanaka, Noriyuki; Wada, Masanobu

2015-06-01

The aim of this study was to examine whether prolonged low-frequency force depression (PLFFD) that occurs in situ is the result of decreased myofibrillar Ca(2+) sensitivity and/or reduced sarcoplasmic reticulum (SR) Ca(2+) release. Intact rat gastrocnemius muscles were electrically stimulated via the sciatic nerve until force was reduced to ~50% of the initial and dissected 30 min following the cessation of stimulation. Skinned fibre and whole muscle analyses were performed in the superficial region composed exclusively of type IIB fibres. Fatiguing stimulation significantly reduced the ratio of force at low frequency to that at high frequency to 65% in skinned fibres (1 vs. 50 Hz) and 73% in whole muscles (20 vs. 100 Hz). In order to evaluate changes in myofibrillar Ca(2+) sensitivity and ryanodine receptor caffeine sensitivity, skinned fibres were activated in Ca(2+)- and caffeine-containing solutions, respectively. Skinned fibres from fatigued muscles displayed decreased caffeine sensitivity together with increased myofibrillar Ca(2+) sensitivity. Treatment with 2,2'-dithiodipyridine and reduced glutathione induced a smaller increase in myofibrillar Ca(2+)sensitivity in fatigued than in rested fibres. In fatigued muscles, S-glutathionylation of troponin I was increased and submaximal SR Ca(2+) release, induced by 4-chloro-m-cresol, was decreased. These findings suggest that in the early stage of PLFFD that occurs in fast-twitch muscles of exercising animals and humans, S-glutathionylation of troponin I may attenuate PLFFD by increasing myofibrillar Ca(2+) sensitivity and that under such a circumstance, PLFFD may be ascribable to failure of SR Ca(2+) release.

Glucocorticoid effects on contact hypersensitivity and on the cutaneous response to ultraviolet light in the mouse

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

Ross, P.M.; Walberg, J.A.; Bradlow, H.L.

1988-03-01

A single exposure to 254 nm ultraviolet irradiation (UV) can systemically suppress experimental sensitization to the simple allergen 2,4-dinitro, 1-chlorobenzene (DNCB) in the mouse. We show here that topical application at the site of irradiation of the 21-oic acid methyl ester derivative of the synthetic glucocorticoid triamcinolone acetonide (TAme) prevents UV suppression of sensitization. That is, mice painted with TAme at the site of UV exposure developed normal contact hypersensitivity (CH); mice exposed to UV only, like mice treated with the parent compound triamcinolone acetonide (TA), failed to be sensitized by DNCB applied to a distal site. TAme is inactivatedmore » rapidly by plasma esterases, so its effect is thought to be confined to the skin. Apparently, TAme blocked the cutaneous signal(s) for systemic suppression of CH. Histologically, irradiated skin exhibited mild inflammation and hyperproliferation, but these effects were greatly exaggerated and prolonged in the UV + TAme-treated skin, independent of sensitization at the distal site. The infiltrate consisted mostly of neutrophils and lacked the round cells characteristic of cell-mediated immunity. Apparently, normal immune suppression by UV prevented this vigorous reaction to irradiated skin. Applied together with DNCB. TAme blocked sensitization. It also prevented response to challenge by DNCB in previously sensitized animals. However, unlike the parent compound triamcinolone acetonide (TA), Budesonide or Beclomethasone diproprionate, each of which can penetrate the epidermis in active form, TAme had no effect on sensitization when applied at a distal site. Likewise, TAme did not affect plasma B (17-desoxycortisol) levels, whereas the other three compounds reduced plasma B tenfold, as expected of compounds causing adrenal-pituitary suppression.« less

Optical skin friction measurement technique in hypersonic wind tunnel

NASA Astrophysics Data System (ADS)

Chen, Xing; Yao, Dapeng; Wen, Shuai; Pan, Junjie

2016-10-01

Shear-sensitive liquid-crystal coatings (SSLCCs) have an optical characteristic that they are sensitive to the applied shear stress. Based on this, a novel technique is developed to measure the applied shear stress of the model surface regarding both its magnitude and direction in hypersonic flow. The system of optical skin friction measurement are built in China Academy of Aerospace Aerodynamics (CAAA). A series of experiments of hypersonic vehicle is performed in wind tunnel of CAAA. Global skin friction distribution of the model which shows complicated flow structures is discussed, and a brief mechanism analysis and an evaluation on optical measurement technique have been made.

The impact of vehicle on the relative potency of skin-sensitizing chemicals in the local lymph node assay.

PubMed

Jowsey, Ian R; Clapp, Catherine J; Safford, Bob; Gibbons, Ben T; Basketter, David A

2008-01-01

The identification and characterization of chemicals that possess skin-sensitizing potential are typically performed using predictive tests. However, human exposure to skin-sensitizing chemicals often occurs via a matrix (vehicle) that differs from that used in these tests. It is thus important to account for the potential impact of vehicle differences when undertaking quantitative risk assessment for skin sensitization. This is achieved through the application of a specific sensitization assessment factor (SAF), scaled between 1 and 10, when identifying an acceptable exposure level. The objective of the analysis described herein is to determine the impact of vehicle differences on local lymph node assay (LLNA) EC3 values (concentrations of test chemical required to provoke a 3-fold increase in lymph node cell proliferation). Initially, the inherent variability of the LLNA was investigated by examining the reproducibility of EC3 values for 14 chemicals that have been tested more than once in the same vehicle (4:1 acetone:olive oil, AOO). This analysis reveals that the variability in EC3 value for these chemicals following multiple assessments is <5-fold. Next, data from the literature and previously unpublished studies were compiled for 18 chemicals that had been assessed in the LLNA using at least 2 of 15 different vehicles. These data demonstrate that often the variability in EC3 values observed for a given chemical in different vehicles is no greater than the 5-fold inherent variability observed when assessing a chemical in the same vehicle on multiple occasions. However, there are examples where EC3 values for a chemical differ by a factor of more than 10 between different vehicles. These observations were often associated with an apparent underestimation of potency (higher EC3 values) with predominantly aqueous vehicles or propylene glycol. These data underscore the need to consider vehicle effects in the context of skin-sensitization risk assessments.

Allergy to cow's milk proteins: what contribution does hypersensitivity in skin tests have to this diagnosis?

PubMed

Costa, Aldo José Fernandes; Sarinho, Emanuel Sávio Cavalcanti; Motta, Maria Eugênia Farias Almeida; Gomes, Priscila Nogueira; de Oliveira de Melo, Sabrina Maria; da Silva, Giselia Alves Pontes

2011-02-01

Food allergy is an immunologically mediated adverse reaction to food protein. Cow's milk protein allergy (CMPA) is the most frequent type and is the one that is most difficult to diagnose. This study had the objective of analyzing the accuracy of hypersensitivity and specific IgE skin tests among children with CMPA and predominantly gastrointestinal clinical manifestations. The participants in this study were 192 children aged one and five (median of 2 yr). Among these, 122 underwent open oral challenge to the suspected food. After evaluating the sensitivity, specificity and positive and negative predictive values (respectively, PPV and NPV) of skin and specific IgE tests in relation to the gold standard (open oral challenge); all the children underwent the skin prick test (SPT), specific IgE test and atopy patch test (APT) for cow's milk, eggs, wheat and peanuts and the open oral challenge for the food to which the child was sensitive or had suspected sensitivity. Presence of food allergy was confirmed for 50 children (40.9%). Among these cases, 44/50 (88%) were of allergy to cow's milk protein. Children who presented a positive response to an oral challenge to cow's milk protein were considered to be cases, while the controls were children with negative response. Twenty-two of the 44 cases (50.0%) presented symptoms within the first 4 h after the challenge. The SPT presented 31.8% sensitivity, 90.3% specificity, 66.7% PPV and 68.4% NPV. The APT presented 25.0% sensitivity, 81.9% specificity, 45.8% PPV and 64.1% NPV. The specific IgE test presented, respectively, 20.5%, 88.9%, 52.9% and 64.6%. Despite the operational difficulty and the possible exposure risk, oral challenge is the best method for diagnosing CMPA, because of the low sensitivity and PPV of skin and specific IgE tests. © 2011 John Wiley & Sons A/S.

The relationship between CD86/CD54 expression and THP-1 cell viability in an in vitro skin sensitization test--human cell line activation test (h-CLAT).

PubMed

Sakaguchi, Hitoshi; Ashikaga, Takao; Miyazawa, Masaaki; Kosaka, Nanae; Ito, Yuichi; Yoneyama, Katsurako; Sono, Sakiko; Itagaki, Hiroshi; Toyoda, Hidekazu; Suzuki, Hiroyuki

2009-04-01

Recent regulations for cosmetics in Europe prohibit animal testing for evaluating the sensitization potential of chemicals to improve animal welfare. Yet, there is not an acceptable Organization for Economic Co-operation and Development non-animal skin sensitization test method. Several in vitro skin sensitization methods that focus on the activation of Langerhans cells, including human cell lines, are being evaluated as possible alternatives. In our previous study, we optimized our human cell line activation test (h-CLAT) using THP-1 cells (monocytic leukemia cell line) and conducted an inter-laboratory study. We found that measuring CD86/CD54 expression may be useful for predicting skin sensitization. The aim of this study was to confirm the relationship between CD86/CD54 expression and THP-1 cell viability in the h-CLAT. In this study, 21 allergens (e.g., dinitrochlorobenzene, p-phenylenediamine, Ni) and 8 non-allergens (e.g., SLS, lactic acid) were evaluated. For each chemical, more than 10 concentrations that gave a predicted cell viability range of 20-95% were used. The data showed that expression patterns of CD86/CD54 differed depending on chemical. For most allergens, cytotoxicity (65-90% cell viability) was needed for enhancement of CD86/CD54 expression. The criteria of "CD86 > or = 150 or CD54 > or = 200" resulted in an accuracy of 93%, which confirms appropriate cut-off criteria for h-CLAT. Furthermore, a good correlation was observed between EC3 of local lymph node assay and EC150(CD86) or EC200(CD54) of h-CLAT (12 or 16 chemicals, respectively), which would provide a useful estimate of allergic potency. These findings suggest that h-CLAT would be a good robust in vitro skin sensitization test.

Cutaneous sensitivity in unilateral trans-tibial amputees

PubMed Central

Templeton, Cale A.; Strzalkowski, Nicholas D. J.; Galvin, Patti

2018-01-01

Aim To examine tactile sensitivity in the leg and foot sole of below-knee amputees (diabetic n = 3, traumatic n = 1), and healthy control subjects (n = 4), and examine the association between sensation and balance. Method Vibration perception threshold (VPT; 3, 40, 250Hz) and monofilaments (MF) were used to examine vibration and light touch sensitivity on the intact limb, residual limb, and homologous locations on controls. A functional reach test was performed to assess functional balance. Results Tactile sensitivity was lower for diabetic amputee subjects compared to age matched controls for both VPT and MF; which was expected due to presence of diabetic peripheral neuropathy. In contrast, the traumatic amputee participant showed increased sensitivity for VPT at 40Hz and 250Hz vibration in both the intact and residual limbs compared to controls. Amputees with lower tactile sensitivity had shorter reach distances compared to those with higher sensitivity. Conclusion Changes in tactile sensitivity in the residual limb of trans-tibial amputees may have implications for the interaction between the amputee and the prosthetic device. The decreased skin sensitivity observed in the residual limb of subjects with diabetes is of concern as changes in skin sensitivity may be important in 1) identification/prevention of excessive pressure and 2) for functional stability. Interestingly, we saw increased residual limb skin sensitivity in the individual with the traumatic amputation. Although not measured directly in the present study, this increase in tactile sensitivity may be related to cortical reorganisation, which is known to occur following amputation, and would support similar findings observed in upper limb amputees. PMID:29856766

Sensitivity to bites by the bedbug, Cimex lectularius.

PubMed

Reinhardt, K; Kempke, D; Naylor, R A; Siva-Jothy, M T

2009-06-01

Bedbugs are a public health problem and can cause significant economic losses, but little is known about the effects of bites on humans. We reviewed case reports and published papers on bedbug bites to assess the empirical basis of the commonly cited figure that only approximately 80% of the population are sensitive to bedbug bites. We found the sensitivity estimate to be based on only one study carried out 80 years ago. However, this study did not account for the now well-established fact that only repeated exposure to external allergens leads to skin reactions. In our sample, 18 of 19 persons showed a skin reaction after bedbug exposure, but in most cases only after repeated controlled exposure. With repeated exposure, the latency between bite and skin reactions decreased from approximately 10 days to a few seconds. Our results are relevant for the hospitality industry, where apparently increasing infestation rates are likely to lead to an increase in the number of tourists and hotel employees exposed to bedbugs. Medical and public health professionals may expect to see an increase in the prevalence of people with bedbug bite sensitivity. The significance of the delayed reaction time of skin to bites may also have implications in litigation cases where people seek compensation.

Skin-Inspired Hierarchical Polymer Architectures with Gradient Stiffness for Spacer-Free, Ultrathin, and Highly Sensitive Triboelectric Sensors.

PubMed

Ha, Minjeong; Lim, Seongdong; Cho, Soowon; Lee, Youngoh; Na, Sangyun; Baig, Chunggi; Ko, Hyunhyub

2018-04-24

The gradient stiffness between stiff epidermis and soft dermis with interlocked microridge structures in human skin induces effective stress transmission to underlying mechanoreceptors for enhanced tactile sensing. Inspired by skin structure and function, we fabricate hierarchical nanoporous and interlocked microridge structured polymers with gradient stiffness for spacer-free, ultrathin, and highly sensitive triboelectric sensors (TESs). The skin-inspired hierarchical polymers with gradient elastic modulus enhance the compressibility and contact areal differences due to effective transmission of the external stress from stiff to soft layers, resulting in highly sensitive TESs capable of detecting human vital signs and voice. In addition, the microridges in the interlocked polymers provide an effective variation of gap distance between interlocked layers without using the bulk spacer and thus facilitate the ultrathin and flexible design of TESs that could be worn on the body and detect a variety of pressing, bending, and twisting motions even in humid and underwater environments. Our TESs exhibit the highest power density (46.7 μW/cm 2 ), pressure (0.55 V/kPa), and bending (∼0.1 V/°) sensitivities ever reported on flexible TESs. The proposed design of hierarchical polymer architectures for the flexible and wearable TESs can find numerous applications in next-generation wearable electronics.

Clinical Anaemia Detection in Children of Varied Skin Complexion: A Community-based Study in Southeast, Nigeria.

PubMed

Ughasoro, Maduka Donatus; Madu, Anazoeze Jude; Kela-Eke, Iheoma Clara

2017-02-01

Clinicians rely on clinical detection of pallor to diagnose anaemia. This makes it important to evaluate the effect of different skin complexions on the accuracy of the pallor in diagnosing anaemia in children. Clinicians conducted blind-independent physical examination, and their reports were compared with HemoCue 301 haemoglobin estimated with. The sensitivity and specificity were calculated. A total of 573 children were reviewed by 27 healthcare workers. The prevalence of anaemia was high. The highest prevalence was among children between the age of 4 and 12 months (urban 63.4% and rural 69.2%). Anaemia was detected better among dark-skinned children. Conjunctivae and palm pallor had the highest sensitivity (78.6% and 69.2%, respectively). Clinical pallor is a good screening assessment for anaemia but not diagnostic. Its sensitivity and specificity vary among different sites and skin complexions. Thus combining findings at any of the sites can improve detection of anaemia in children. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Two-step Raman spectroscopy method for tumor diagnosis

NASA Astrophysics Data System (ADS)

Zakharov, V. P.; Bratchenko, I. A.; Kozlov, S. V.; Moryatov, A. A.; Myakinin, O. O.; Artemyev, D. N.

2014-05-01

Two-step Raman spectroscopy phase method was proposed for differential diagnosis of malignant tumor in skin and lung tissue. It includes detection of malignant tumor in healthy tissue on first step with identification of concrete cancer type on the second step. Proposed phase method analyze spectral intensity alteration in 1300-1340 and 1640-1680 cm-1 Raman bands in relation to the intensity of the 1450 cm-1 band on first step, and relative differences between RS intensities for tumor area and healthy skin closely adjacent to the lesion on the second step. It was tested more than 40 ex vivo samples of lung tissue and more than 50 in vivo skin tumors. Linear Discriminant Analysis, Quadratic Discriminant Analysis and Support Vector Machine were used for tumors type classification on phase planes. It is shown that two-step phase method allows to reach 88.9% sensitivity and 87.8% specificity for malignant melanoma diagnosis (skin cancer); 100% sensitivity and 81.5% specificity for adenocarcinoma diagnosis (lung cancer); 90.9% sensitivity and 77.8% specificity for squamous cell carcinoma diagnosis (lung cancer).

Medications as causes of intraluminal hyperdensities: what radiologists need to know.

PubMed

Sin, Francesca Nga Yee; Tsang, Jane Pui Ki; Siu, Kwong Lok; Ma, Johnny Ka Fai; Yung, Alfred Wei Tak

2012-07-01

In computed tomography (CT) angiogram or some dedicated CT studies of the abdomen, the use of positive enteric contrast should be avoided as its presence could decrease the sensitivity of the test. There are, however, cases of CT scans with unexpected hyperdense intraluminal contents detected due to the use of certain oral or rectal medications. Reports on medications as causes of intraluminal hyperdensities are sparse in the English literature. We have studied several commonly used medications and revealed that many drugs appear hyperdense in CT scans. The presence of unexpected intraluminal hyperdensities can potentially cause erroneous interpretation of images and in some cases decrease the sensitivity of the test. The hyperdense bowel contents may be mistaken as acute hemorrhage in CT angiogram for detection of GI bleeding. Active GI bleeding, presented as intraluminal extravasation of contrast material, can also be obscured. Certain intra-abdominal pathologies could be masked, for example, in plain CT scan for detection of urinary tract stones or in contrast CT study for suspected bowel ischaemia. It is important for radiologists and clinicians to be aware of this situation in order to prevent misinterpretation of images and to select the most appropriate imaging modality when such unexpected intraluminal hyperdensities are encountered. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A Graphene-Based Resistive Pressure Sensor with Record-High Sensitivity in a Wide Pressure Range

PubMed Central

Tian, He; Shu, Yi; Wang, Xue-Feng; Mohammad, Mohammad Ali; Bie, Zhi; Xie, Qian-Yi; Li, Cheng; Mi, Wen-Tian; Yang, Yi; Ren, Tian-Ling

2015-01-01

Pressure sensors are a key component in electronic skin (e-skin) sensing systems. Most reported resistive pressure sensors have a high sensitivity at low pressures (<5 kPa) to enable ultra-sensitive detection. However, the sensitivity drops significantly at high pressures (>5 kPa), which is inadequate for practical applications. For example, actions like a gentle touch and object manipulation have pressures below 10 kPa, and 10–100 kPa, respectively. Maintaining a high sensitivity in a wide pressure range is in great demand. Here, a flexible, wide range and ultra-sensitive resistive pressure sensor with a foam-like structure based on laser-scribed graphene (LSG) is demonstrated. Benefitting from the large spacing between graphene layers and the unique v-shaped microstructure of the LSG, the sensitivity of the pressure sensor is as high as 0.96 kPa−1 in a wide pressure range (0 ~ 50 kPa). Considering both sensitivity and pressure sensing range, the pressure sensor developed in this work is the best among all reported pressure sensors to date. A model of the LSG pressure sensor is also established, which agrees well with the experimental results. This work indicates that laser scribed flexible graphene pressure sensors could be widely used for artificial e-skin, medical-sensing, bio-sensing and many other areas. PMID:25721159

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

PubMed Central

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

Evaluation of high throughput gene expression platforms using a genomic biomarker signature for prediction of skin sensitization.

PubMed

Forreryd, Andy; Johansson, Henrik; Albrekt, Ann-Sofie; Lindstedt, Malin

2014-05-16

Allergic contact dermatitis (ACD) develops upon exposure to certain chemical compounds termed skin sensitizers. To reduce the occurrence of skin sensitizers, chemicals are regularly screened for their capacity to induce sensitization. The recently developed Genomic Allergen Rapid Detection (GARD) assay is an in vitro alternative to animal testing for identification of skin sensitizers, classifying chemicals by evaluating transcriptional levels of a genomic biomarker signature. During assay development and biomarker identification, genome-wide expression analysis was applied using microarrays covering approximately 30,000 transcripts. However, the microarray platform suffers from drawbacks in terms of low sample throughput, high cost per sample and time consuming protocols and is a limiting factor for adaption of GARD into a routine assay for screening of potential sensitizers. With the purpose to simplify assay procedures, improve technical parameters and increase sample throughput, we assessed the performance of three high throughput gene expression platforms--nCounter®, BioMark HD™ and OpenArray®--and correlated their performance metrics against our previously generated microarray data. We measured the levels of 30 transcripts from the GARD biomarker signature across 48 samples. Detection sensitivity, reproducibility, correlations and overall structure of gene expression measurements were compared across platforms. Gene expression data from all of the evaluated platforms could be used to classify most of the sensitizers from non-sensitizers in the GARD assay. Results also showed high data quality and acceptable reproducibility for all platforms but only medium to poor correlations of expression measurements across platforms. In addition, evaluated platforms were superior to the microarray platform in terms of cost efficiency, simplicity of protocols and sample throughput. We evaluated the performance of three non-array based platforms using a limited set of transcripts from the GARD biomarker signature. We demonstrated that it was possible to achieve acceptable discriminatory power in terms of separation between sensitizers and non-sensitizers in the GARD assay while reducing assay costs, simplify assay procedures and increase sample throughput by using an alternative platform, providing a first step towards the goal to prepare GARD for formal validation and adaption of the assay for industrial screening of potential sensitizers.

Body temperature and cold sensation during and following exercise under temperate room conditions in cold-sensitive young trained females.

PubMed

Fujii, Naoto; Aoki-Murakami, Erii; Tsuji, Bun; Kenny, Glen P; Nagashima, Kei; Kondo, Narihiko; Nishiyasu, Takeshi

2017-11-01

We evaluated cold sensation at rest and in response to exercise-induced changes in core and skin temperatures in cold-sensitive exercise trained females. Fifty-eight trained young females were screened by a questionnaire, selecting cold-sensitive (Cold-sensitive, n  = 7) and non-cold-sensitive (Control, n  = 7) individuals. Participants rested in a room at 29.5°C for ~100 min after which ambient temperature was reduced to 23.5°C where they remained resting for 60 min. Participants then performed 30-min of moderate intensity cycling (50% peak oxygen uptake) followed by a 60-min recovery. Core and mean skin temperatures and cold sensation over the whole-body and extremities (fingers and toes) were assessed throughout. Resting core temperature was lower in the Cold-sensitive relative to Control group (36.4 ± 0.3 vs. 36.7 ± 0.2°C). Core temperature increased to similar levels at end-exercise (~37.2°C) and gradually returned to near preexercise rest levels at the end of recovery (>36.6°C). Whole-body cold sensation was greater in the Cold-sensitive relative to Control group during resting at a room temperature of 23.5°C only without a difference in mean skin temperature between groups. In contrast, cold sensation of the extremities was greater in the Cold-sensitive group prior to, during and following exercise albeit this was not paralleled by differences in mean extremity skin temperature. We show that young trained females who are sensitive to cold exhibit augmented whole-body cold sensation during rest under temperate ambient conditions. However, this response is diminished during and following exercise. In contrast, cold sensation of extremities is augmented during resting that persists during and following exercise. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Deciphering the Complexities of Atopic Dermatitis: Shifting Paradigms in Treatment Approaches

PubMed Central

Leung, Donald Y. M.; Guttman-Yassky, Emma

2014-01-01

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It often precedes the development of food allergy and asthma. Recent insights into AD reveal abnormalities in terminal differentiation of the epidermal epithelium leading to a defective stratum corneum, which allows enhanced allergen penetration and systemic IgE sensitization. Atopic skin is also predisposed to colonization or infection by pathogenic microbes, most notably Staphylococcus aureus and herpes simplex virus (HSV). Causes of this abnormal skin barrier are complex and driven by a combination of genetic, environmental and immunologic factors. These factors likely account for the heterogeneity of AD onset, severity and natural history of this skin disease. Recent studies suggest prevention of AD can be achieved by early interventions protecting the skin barrier. Onset of lesional AD requires effective control of local and systemic immune activation for optimal management. Early intervention may improve long term outcomes for AD and reduce the systemic allergen sensitization leading to associated allergic diseases in the gastrointestinal and respiratory tract. PMID:25282559

Albinism

MedlinePlus

... normal skin and hair Patches of missing skin color Many forms of albinism are associated with the following symptoms: Crossed eyes Light sensitivity Rapid eye movements Vision problems, or functional blindness Exams and Tests Genetic testing offers the most ...

Skin, Hair, and Nails

MedlinePlus

... as asthma and seasonal, environmental, and food allergies. Contact dermatitis. This occurs when the skin comes into contact ... or sensitive to. The best-known cause of contact dermatitis is poison ivy, but there are many others, ...

Molecular diagnosis of canine visceral leishmaniasis: a comparative study of three methods using skin and spleen from dogs with natural Leishmania infantum infection.

PubMed

Reis, Levi Eduardo Soares; Coura-Vital, Wendel; Roatt, Bruno Mendes; Bouillet, Leoneide Érica Maduro; Ker, Henrique Gama; Fortes de Brito, Rory Cristiane; Resende, Daniela de Melo; Carneiro, Mariângela; Giunchetti, Rodolfo Cordeiro; Marques, Marcos José; Carneiro, Cláudia Martins; Reis, Alexandre Barbosa

2013-11-08

Polymerase chain reaction (PCR) and its variations represent highly sensitive and specific methods for Leishmania DNA detection and subsequent canine visceral leishmaniasis (CVL) diagnosis. The aim of this work was to compare three different molecular diagnosis techniques (conventional PCR [cPCR], seminested PCR [snPCR], and quantitative PCR [qPCR]) in samples of skin and spleen from 60 seropositive dogs by immunofluorescence antibody test and enzyme-linked immunosorbent assay. Parasitological analysis was conducted by culture of bone marrow aspirate and optical microscopic assessment of ear skin and spleen samples stained with Giemsa, the standard tests for CVL diagnosis. The primers L150/L152 and LINR4/LIN17/LIN19 were used to amplify the conserved region of the Leishmania kDNA minicircle in the cPCR, and snPCR and qPCR were performed using the DNA polymerase gene (DNA pol α) primers from Leishmania infantum. The parasitological analysis revealed parasites in 61.7% of the samples. Sensitivities were 89.2%, 86.5%, and 97.3% in the skin and 81.1%, 94.6%, and 100.0% in spleen samples used for cPCR, snPCR, and qPCR, respectively. We demonstrated that the qPCR method was the best technique to detect L. infantum in both skin and spleen samples. However, we recommend the use of skin due to the high sensitivity and sampling being less invasive. Copyright © 2013 Elsevier B.V. All rights reserved.

Hybrid optimal descriptors as a tool to predict skin sensitization in accordance to OECD principles.

PubMed

Toropova, Alla P; Toropov, Andrey A

2017-06-05

Skin sensitization (allergic contact dermatitis) is a widespread problem arising from the contact of chemicals with the skin. The detection of molecular features with undesired effect for skin is complex task owing to unclear biochemical mechanisms and unclearness of conditions of action of chemicals to skin. The development of computational methods for estimation of this endpoint in order to reduce animal testing is recommended (Cosmetics Directive EC regulation 1907/2006; EU Regulation, Regulation, 1223/2009). The CORAL software (http://www.insilico.eu/coral) gives good predictive models for the skin sensitization. Simplified molecular input-line entry system (SMILES) together with molecular graph are used to represent the molecular structure for these models. So-called hybrid optimal descriptors are used to establish quantitative structure-activity relationships (QSARs). The aim of this study is the estimation of the predictive potential of the hybrid descriptors. Three different distributions into the training (≈70%), calibration (≈15%), and validation (≈15%) sets are studied. QSAR for these three distributions are built up with using the Monte Carlo technique. The statistical characteristics of these models for external validation set are used as a measure of predictive potential of these models. The best model, according to the above criterion, is characterized by n validation =29, r 2 validation =0.8596, RMSE validation =0.489. Mechanistic interpretation and domain of applicability for these models are defined. Copyright © 2017 Elsevier B.V. All rights reserved.

Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma.

PubMed

Demehri, Shadmehr; Morimoto, Mitsuru; Holtzman, Michael J; Kopan, Raphael

2009-05-19

Asthma is a common allergic lung disease frequently affecting individuals with a prior history of eczema/atopic dermatitis (AD); however, the mechanism underlying the progression from AD to asthma (the so-called "atopic march") is unclear. Here we show that, like humans with AD, mice with skin-barrier defects develop AD-like skin inflammation and are susceptible to allergic asthma. Furthermore, we show that thymic stromal lymphopoietin (TSLP), overexpressed by skin keratinocytes, is the systemic driver of this bronchial hyper-responsiveness. As an AD-like model, we used mice with keratinocyte-specific deletion of RBP-j that sustained high systemic levels of TSLP. Antigen-induced allergic challenge to the lung airways of RBP-j-deficient animals resulted in a severe asthmatic phenotype not seen in similarly treated wild-type littermates. Elimination of TSLP signaling in these animals blocked the atopic march, demonstrating that high serum TSLP levels were required to sensitize the lung to allergic inflammation. Furthermore, we analyzed outbred K14-TSLP(tg) mice that maintained high systemic levels of TSLP without developing any skin pathology. Importantly, epidermal-derived TSLP was sufficient to trigger the atopic march, sensitizing the lung airways to inhaled allergens in the absence of epicutaneous sensitization. Based on these findings, we propose that in addition to early treatment of the primary skin-barrier defects, selective inhibition of systemic TSLP may be the key to blocking the development of asthma in AD patients.

Skin sensitization potency of isoeugenol and its dimers evaluated by a non-radioisotopic modification of the local lymph node assay and guinea pig maximization test.

PubMed

Takeyoshi, Masahiro; Iida, Kenji; Suzuki, Keiko; Yamazaki, Shunsuke

2008-05-01

Allergic contact dermatitis is the serious unwanted effect arising from the use of consumer products such as cosmetics. Isoeugenol is a fragrance chemical with spicy, carnation-like scent, is used in many kinds of cosmetics and is a well-known moderate human sensitizer. It was previously reported that the dimerization of eugenol yielded two types of dimer possessing different sensitization potencies. This study reports the differences in skin sensitization potencies for isoeugenol and two types of dimer, beta-O-4-dilignol and dehydrodiisoeugenol (DIEG), as evaluated by the non-radioisotopic local lymph node assay (non-RI LLNA) and guinea pig maximization test. In the guinea pig maximization test, isoeugenol, beta-O-4-dilignol and DIEG were classified as extreme, weak and moderate sensitizers, respectively. As for the results of non-RI LLNA, the EC3 for isoeugenol, beta-O-4-dilignol and DIEG were calculated as 12.7%, >30% and 9.4%, respectively. The two types of isoeugenol dimer showed different sensitizing activities similar to the case for eugenol dimers. A reduction of sensitization potency achieved by dimerization may lead to developing safer cosmetic ingredients. Isoeugenol dimers are not currently used for fragrance chemicals. However, the dimerization of isoeugenol may yield a promising candidate as a cosmetic ingredient with low sensitization risk. The data may also provide useful information for the structure-activity relationship (SAR) in skin sensitization. Copyright (c) 2007 John Wiley & Sons, Ltd.

Suitability of macrophage inflammatory protein-1beta production by THP-1 cells in differentiating skin sensitizers from irritant chemicals.

PubMed

Lim, Yeon-Mi; Moon, Seong-Joon; An, Su-Sun; Lee, Soo-Jin; Kim, Seo-Young; Chang, Ih-Seop; Park, Kui-Lea; Kim, Hyoung-Ah; Heo, Yong

2008-04-01

Worldwide restrictions in animal use for research have driven efforts to develop alternative methods. The study aimed to test the efficacy of the macrophage inflammatory protein-1beta (MIP-1beta) assay for testing chemicals' skin-sensitizing capacity. The assay was performed using 9 chemicals judged to be sensitizing and 7 non-sensitizing by the standard in vivo assays. THP-1 cells were cultured in the presence or absence of 4 doses, 0.01x, 0.1x, 0.5x, or 1x IC(50) (50% inhibitory concentration for THP-1 cell proliferation) of these chemicals for 24 hr, and the MIP-1beta level in the supernatants was determined. Skin sensitization by the test chemicals was determined by MIP-1beta production rates. The MIP-1beta production rate was expressed as the relative increase in MIP-1beta production in response to chemical treatment compared with vehicle treatment. When the threshold MIP-1beta production rate used was 100% or 105% of dimethyl sulfoxide, all the sensitizing chemicals tested (dinitrochlorobenzene, hexyl cinnamic aldehyde, eugenol, hydroquinone, dinitrofluorobenzene, benzocaine, nickel, chromium, and 5-chloro-2-methyl-4-isothiazolin-3-one) were positive, and all the non-sensitizing chemicals (methyl salicylate, benzalkonium chloride, lactic acid, isopropanol, and salicylic acid), with the exception of sodium lauryl sulfate, were negative for MIP-1beta production. These results indicate that MIP-1beta could be a biomarker for classification of chemicals as sensitizers or non-sensitizers.

Bi-Directional Tuning of Amygdala Sensitivity in Combat Veterans Investigated with fMRI

PubMed Central

Brashers-Krug, Tom; Jorge, Ricardo

2015-01-01

Objectives Combat stress can be followed by persistent emotional consequences. It is thought that these emotional consequences are caused in part by increased amygdala reactivity. It is also thought that amygdala hyper-reactivity results from decreased inhibition from portions of the anterior cingulate cortex (ACC) in which activity is negatively correlated with activity in the amygdala. However, experimental support for these proposals has been inconsistent. Methods We showed movies of combat and civilian scenes during a functional magnetic resonance imaging (fMRI) session to 50 veterans of recent combat. We collected skin conductance responses (SCRs) as measures of emotional arousal. We examined the relation of blood oxygenation-level dependent (BOLD) signal in the amygdala and ACC to symptom measures and to SCRs. Results Emotional arousal, as measured with SCR, was greater during the combat movie than during the civilian movie and did not depend on symptom severity. As expected, amygdala signal during the less-arousing movie increased with increasing symptom severity. Surprisingly, during the more-arousing movie amygdala signal decreased with increasing symptom severity. These differences led to the unexpected result that amygdala signal in highly symptomatic subjects was lower during the more-arousing movie than during the less-arousing movie. Also unexpectedly, we found no significant inverse correlation between any portions of the amygdala and ACC. Rather, signal throughout more than 80% of the ACC showed a strong positive correlation with signal throughout more than 90% of the amygdala. Conclusions Amygdala reactivity can be tuned bi-directionally, either up or down, in the same person depending on the stimulus and the degree of post-traumatic symptoms. The exclusively positive correlations in BOLD activity between the amygdala and ACC contrast with findings that have been cited as evidence for inhibitory control of the amygdala by the ACC. The conceptualization of post-traumatic changes in neural function should be reconsidered. PMID:26120848

Skin sensitizers differentially regulate signaling pathways in MUTZ-3 cells in relation to their individual potency

PubMed Central

2014-01-01

Background Due to the recent European legislations posing a ban of animal tests for safety assessment within the cosmetic industry, development of in vitro alternatives for assessment of skin sensitization is highly prioritized. To date, proposed in vitro assays are mainly based on single biomarkers, which so far have not been able to classify and stratify chemicals into subgroups, related to risk or potency. Methods Recently, we presented the Genomic Allergen Rapid Detection (GARD) assay for assessment of chemical sensitizers. In this paper, we show how the genome wide readout of GARD can be expanded and used to identify differentially regulated pathways relating to individual chemical sensitizers. In this study, we investigated the mechanisms of action of a range of skin sensitizers through pathway identification, pathway classification and transcription factor analysis and related this to the reactive mechanisms and potency of the sensitizing agents. Results By transcriptional profiling of chemically stimulated MUTZ-3 cells, 33 canonical pathways intimately involved in sensitization to chemical substances were identified. The results showed that metabolic processes, cell cycling and oxidative stress responses are the key events activated during skin sensitization, and that these functions are engaged differently depending on the reactivity mechanisms of the sensitizing agent. Furthermore, the results indicate that the chemical reactivity groups seem to gradually engage more pathways and more molecules in each pathway with increasing sensitizing potency of the chemical used for stimulation. Also, a switch in gene regulation from up to down regulation, with increasing potency, was seen both in genes involved in metabolic functions and cell cycling. These observed pathway patterns were clearly reflected in the regulatory elements identified to drive these processes, where 33 regulatory elements have been proposed for further analysis. Conclusions This study demonstrates that functional analysis of biomarkers identified from our genomics study of human MUTZ-3 cells can be used to assess sensitizing potency of chemicals in vitro, by the identification of key cellular events, such as metabolic and cell cycling pathways. PMID:24517095

Biological Evaluation of the Copper/Low-density Polyethylene Nanocomposite Intrauterine Device

PubMed Central

Wang, Hong; Li, Jun; Xie, Changsheng; Duan, Zhuo; Sun, Li-Kui; Wang, Xin; Zhu, Changhong

2013-01-01

Devices and materials intended for clinical applications as medical and implant devices should be evaluated to determine their biocompatibility in physiological systems. This article presents results from cytotoxicity assay of L929 mouse fibroblasts culture, tests for skin irritation, intracutaneous reactivity and sensitization, and material implantation tests for the novel copper/low-density polyethylene nanocomposite intrauterine device (nano-Cu/LDPE IUD) with potential for future clinical utilization. Cytotoxicity test in vitro was conducted to evaluate the change in morphology, growth and proliferation of cultured L929 mouse fibroblasts, which in vivo examination for skin irritation (n = 6) and intracutaneous reactivity (n = 6) were carried out to explore the irritant behavior in New Zealand White rabbits. Skin sensitization was implemented to evaluate the potential skin sensitizing in Hartley guinea pigs (n = 35). The materials were implanted into the spinal muscle of rabbits (n = 9). The cytotoxicity grade of the nano-Cu/LDPE IUD was 0–1, suggested that the composite was nontoxic or mildly cytotoxic; no irritation reaction and skin sensitization were identified in any animals of specific extracts prepared from the material under test; similarly to the control sides, the inflammatory reaction was observed in the rabbits living tissue of the implanted material in intramuscular implantation assay. They indicated that the novel composite intrauterine device presented potential for this type of application because they meet the requirements of the standard practices recommended for evaluating the biological reactivity. The nano-Cu/LDPE IUD has good biocompatibility, which is biologically safe for the clinical research as a novel contraceptive device. PMID:24058521

Biological evaluation of the copper/low-density polyethylene nanocomposite intrauterine device.

PubMed

Hu, Li-Xia; He, Jing; Hou, Li; Wang, Hong; Li, Jun; Xie, Changsheng; Duan, Zhuo; Sun, Li-Kui; Wang, Xin; Zhu, Changhong

2013-01-01

Devices and materials intended for clinical applications as medical and implant devices should be evaluated to determine their biocompatibility in physiological systems. This article presents results from cytotoxicity assay of L929 mouse fibroblasts culture, tests for skin irritation, intracutaneous reactivity and sensitization, and material implantation tests for the novel copper/low-density polyethylene nanocomposite intrauterine device (nano-Cu/LDPE IUD) with potential for future clinical utilization. Cytotoxicity test in vitro was conducted to evaluate the change in morphology, growth and proliferation of cultured L929 mouse fibroblasts, which in vivo examination for skin irritation (n = 6) and intracutaneous reactivity (n = 6) were carried out to explore the irritant behavior in New Zealand White rabbits. Skin sensitization was implemented to evaluate the potential skin sensitizing in Hartley guinea pigs (n = 35). The materials were implanted into the spinal muscle of rabbits (n = 9). The cytotoxicity grade of the nano-Cu/LDPE IUD was 0-1, suggested that the composite was nontoxic or mildly cytotoxic; no irritation reaction and skin sensitization were identified in any animals of specific extracts prepared from the material under test; similarly to the control sides, the inflammatory reaction was observed in the rabbits living tissue of the implanted material in intramuscular implantation assay. They indicated that the novel composite intrauterine device presented potential for this type of application because they meet the requirements of the standard practices recommended for evaluating the biological reactivity. The nano-Cu/LDPE IUD has good biocompatibility, which is biologically safe for the clinical research as a novel contraceptive device.

TRPV1, but not TRPA1, in primary sensory neurons contributes to cutaneous incision-mediated hypersensitivity

PubMed Central

2013-01-01

Background Mechanisms underlying postoperative pain remain poorly understood. In rodents, skin-only incisions induce mechanical and heat hypersensitivity similar to levels observed with skin plus deep incisions. Therefore, cutaneous injury might drive the majority of postoperative pain. TRPA1 and TRPV1 channels are known to mediate inflammatory and nerve injury pain, making them key targets for pain therapeutics. These channels are also expressed extensively in cutaneous nerve fibers. Therefore, we investigated whether TRPA1 and TRPV1 contribute to mechanical and heat hypersensitivity following skin-only surgical incision. Results Behavioral responses to mechanical and heat stimulation were compared between skin-incised and uninjured, sham control groups. Elevated mechanical responsiveness occurred 1 day post skin-incision regardless of genetic ablation or pharmacological inhibition of TRPA1. To determine whether functional changes in TRPA1 occur at the level of sensory neuron somata, we evaluated cytoplasmic calcium changes in sensory neurons isolated from ipsilateral lumbar 3–5 DRGs of skin-only incised and sham wild type (WT) mice during stimulation with the TRPA1 agonist cinnamaldehyde. There were no changes in the percentage of neurons responding to cinnamaldehyde or in their response amplitudes. Likewise, the subpopulation of DRG somata retrogradely labeled specifically from the incised region of the plantar hind paw showed no functional up-regulation of TRPA1 after skin-only incision. Next, we conducted behavior tests for heat sensitivity and found that heat hypersensitivity peaked at day 1 post skin-only incision. Skin incision-induced heat hypersensitivity was significantly decreased in TRPV1-deficient mice. In addition, we conducted calcium imaging with the TRPV1 agonist capsaicin. DRG neurons from WT mice exhibited sensitization to TRPV1 activation, as more neurons (66%) from skin-incised mice responded to capsaicin compared to controls (46%), and the sensitization occurred specifically in isolectin B4 (IB4)-positive neurons where 80% of incised neurons responded to capsaicin compared to just 44% of controls. Conclusions Our data suggest that enhanced TRPA1 function does not mediate the mechanical hypersensitivity that follows skin-only surgical incision. However, the heat hypersensitivity is dependent on TRPV1, and functional up-regulation of TRPV1 in IB4-binding DRG neurons may mediate the heat hypersensitivity after skin incision injury. PMID:23497345

Ultrathin flexible piezoelectric sensors for monitoring eye fatigue

NASA Astrophysics Data System (ADS)

Lü, Chaofeng; Wu, Shuang; Lu, Bingwei; Zhang, Yangyang; Du, Yangkun; Feng, Xue

2018-02-01

Eye fatigue is a symptom induced by long-term work of both eyes and brains. Without proper treatment, eye fatigue may incur serious problems. Current studies on detecting eye fatigue mainly focus on computer vision detect technology which can be very unreliable due to occasional bad visual conditions. As a solution, we proposed a wearable conformal in vivo eye fatigue monitoring sensor that contains an array of piezoelectric nanoribbons integrated on an ultrathin flexible substrate. By detecting strains on the skin of eyelid, the sensors may collect information about eye blinking, and, therefore, reveal human’s fatigue state. We first report the design and fabrication of the piezoelectric sensor and experimental characterization of voltage responses of the piezoelectric sensors. Under bending stress, the output voltage curves yield key information about the motion of human eyelid. We also develop a theoretical model to reveal the underlying mechanism of detecting eyelid motion. Both mechanical load test and in vivo test are conducted to convince the working performance of the sensors. With satisfied durability and high sensitivity, this sensor may efficiently detect abnormal eyelid motions, such as overlong closure, high blinking frequency, low closing speed and weak gazing strength, and may hopefully provide feedback for assessing eye fatigue in time so that unexpected situations can be prevented.

Complex Regional Pain Syndrome

MedlinePlus

Complex regional pain syndrome (CRPS) is a chronic pain condition. It causes intense pain, usually in the arms, hands, legs, or feet. ... in skin temperature, color, or texture Intense burning pain Extreme skin sensitivity Swelling and stiffness in affected ...

In vivo immunomodulatory, cumulative skin irritation, sensitization and effect of d-limonene on permeation of 6-mercaptopurine through transdermal drug delivery.

PubMed

Chandrashekar, N S; Hiremath, Shobha Rani Rajeev

2008-04-01

Using skin as a port for systemic drug administration, transdermal drug delivery has expanded greatly over the last two decades. Our aim was to formulate the single layer drug-in-adhesive transdermal patch for 6-mercaptopurine (6-MP). In vitro permeation study was carried out using modified Franz diffusion cell with and without of different concentration of d-limonene in human cadaver skin. In vivo immunomodulatory was carried out in mice, cumulative skin irritation, sensitization and patch adherence study was done in both mice and human subjects. 6-MP flux increased from 43+/-12.2 microg/cm2h (control) to 162.8+/-32.2 microg/cm2h (6% w/v d-limonene) data was significant (p<0.05), with decrease in the lag time to 35+/-9.3 min compared to control of 90 +/-15.3 min. In vivo immunomodulatory effect was shown in the Balb/c mice with 100 mumol/kg/body wt of animal for 5d (one dose/d) of d-limonene. WBC count of 13469 cells/mm peak was observed on 12th day, bone marrow cells of 26.3 x 10(6) cells/femur and alpha-esterase positive cells of 1259+/-328.4 cells/4000 bone marrow cells. Cumulative skin irritation, sensitisation and patch adherence in animals and human subjects showed no skin irritation and sensitization. Patch adhesion was greater than 90.0% respectively in both human subjects and mice. The percentage of human subjects with adhesive residue was significantly less with scores of zero. d-Limonene proved as good chemical enhancer by increasing in the skin permeability with shortened the lag time. It proved that therapeutic amount of 6-MP can be delivered through transdermal drug delivery.

Aeroallergen sensitization predicts acute chest syndrome in children with sickle cell anaemia.

PubMed

Willen, Shaina M; Rodeghier, Mark; Strunk, Robert C; Bacharier, Leonard B; Rosen, Carol L; Kirkham, Fenella J; DeBaun, Michael R; Cohen, Robyn T

2018-02-01

Asthma is associated with higher rates of acute chest syndrome (ACS) and vaso-occlusive pain episodes among children with sickle cell anaemia (SCA). Aeroallergen sensitization is a risk factor for asthma. We hypothesized that aeroallergen sensitization is associated with an increased incidence of hospitalizations for ACS and pain. Participants in a multicentre, longitudinal cohort study, aged 4-18 years with SCA, underwent skin prick testing to ten aeroallergens. ACS and pain episodes were collected from birth until the end of the follow-up period. The number of positive skin tests were tested for associations with prospective rates of ACS and pain. Multivariable models demonstrated additive effects of having positive skin tests on future rates of ACS (incidence rate ratio (IRR) for each positive test 1·23, 95% confidence interval [CI] 1·11-1·36, P < 0·001). Aeroallergen sensitization was not associated with future pain (IRR 1·14, 95%CI 0·97-1·33, P = 0·11). Our study demonstrated that children with SCA and aeroallergen sensitization are at increased risk for future ACS. Future research is needed to determine whether identification of specific sensitizations and allergen avoidance and treatment reduce the risk of ACS for children with SCA. © 2018 John Wiley & Sons Ltd.

The local lymph node assay and skin sensitization: a cut-down screen to reduce animal requirements?

PubMed

Kimber, Ian; Dearman, Rebecca J; Betts, Catherine J; Gerberick, G Frank; Ryan, Cindy A; Kern, Petra S; Patlewicz, Grace Y; Basketter, David A

2006-04-01

The local lymph node assay (LLNA), an alternative approach to skin-sensitizing testing, has made a significant contribution to animal welfare by permitting a reduction and refinement of animal use. Although there is clearly an aspiration to eliminate the use of animals in such tests, it is appropriate also to consider other opportunities for refinement and reduction of animal use. We have therefore explored the use of a modified version of the LLNA for screening purposes when there is a need to evaluate the sensitizing activity of a large number of chemicals, as will be the case under the auspices of registration, evaluation and authorization of chemicals (REACH). Using an existing LLNA database of 211 chemicals, we have examined whether a cut-down assay comprising a single high-dose group and a concurrent vehicle control would provide a realistic approach for screening chemicals for sensitizing potential. The analyses reported here suggest this is the case. We speculate that the animal welfare benefits may be enhanced further by reducing the number of animals per experimental group. However, a detailed evaluation will be necessary to provide reassurance that a reduction in group size would provide adequate sensitivity across a range of skin sensitization potencies.

Can currently available non-animal methods detect pre and pro-haptens relevant for skin sensitization?

PubMed

Patlewicz, Grace; Casati, Silvia; Basketter, David A; Asturiol, David; Roberts, David W; Lepoittevin, Jean-Pierre; Worth, Andrew P; Aschberger, Karin

2016-12-01

Predictive testing to characterize substances for their skin sensitization potential has historically been based on animal tests such as the Local Lymph Node Assay (LLNA). In recent years, regulations in the cosmetics and chemicals sectors have provided strong impetus to develop non-animal alternatives. Three test methods have undergone OECD validation: the direct peptide reactivity assay (DPRA), the KeratinoSens™ and the human Cell Line Activation Test (h-CLAT). Whilst these methods perform relatively well in predicting LLNA results, a concern raised is their ability to predict chemicals that need activation to be sensitizing (pre- or pro-haptens). This current study reviewed an EURL ECVAM dataset of 127 substances for which information was available in the LLNA and three non-animal test methods. Twenty eight of the sensitizers needed to be activated, with the majority being pre-haptens. These were correctly identified by 1 or more of the test methods. Six substances were categorized exclusively as pro-haptens, but were correctly identified by at least one of the cell-based assays. The analysis here showed that skin metabolism was not likely to be a major consideration for assessing sensitization potential and that sensitizers requiring activation could be identified correctly using one or more of the current non-animal methods. Published by Elsevier Inc.

Skin deposition of nickel, cobalt, and chromium in production of gas turbines and space propulsion components.

PubMed

Julander, Anneli; Skare, Lizbet; Mulder, Marie; Grandér, Margaretha; Vahter, Marie; Lidén, Carola

2010-04-01

Skin exposure to nickel, cobalt, and chromium may cause sensitization and allergic contact dermatitis and it is known that many alloys and platings may release significant amounts of the metals upon contact with skin. Occupational exposure to these sensitizing metals has been studied in different settings with regards to airborne dust and different biological end points, but little is known about deposition on skin from airborne dust and direct contact with materials containing the metals. In this study, skin deposition was studied in 24 workers in an industry for development and manufacturing of gas turbines and space propulsion components. The workers were employed in three departments, representing different exposure scenarios: tools sharpening of hard metal items, production of space propulsion structures, and thermal application of different metal-containing powders. A novel acid wipe sampling technique was used to sample metals from specific skin surfaces on the hands and the forehead of the workers. Total amounts of nickel, cobalt, and chromium were measured by inductively coupled plasma mass spectrometry. The result showed that nickel, cobalt, and chromium could be detected on all skin surfaces sampled. The highest level of nickel was 15 microg cm(-2) h(-1), the highest for cobalt was 4.5 microg cm(-2) h(-1), and for chromium 0.6 microg cm(-2) h(-1). The three departments had different exposures regarding the metals. The highest levels of nickel on the skin of the workers were found in the thermal applications department, cobalt in the tools sharpening department, and chromium in the space propulsion components department. In conclusion, the workers' exposure to the metals was more likely to come from direct skin contact with items, rather than from airborne dust, based on the fact that the levels of metals were much higher on the fingers than on the back side of the hands and the forehead. The skin exposure levels of nickel and cobalt detected are judged capable to induce sensitization and elicit allergic contact dermatitis.

Response perseveration and sensitivity to reward and punishment in boys with oppositional defiant disorder.

PubMed

Matthys, Walter; van Goozen, Stephanie H M; Snoek, Heddeke; van Engeland, Herman

2004-12-01

Response perseveration is the tendency to continue a response set for reward despite punishment. In the present study, response perseveration and sensitivity to reward and punishment were assessed in boys with oppositional defiant disorder (ODD). The study also examined the relation between punishment sensitivity and autonomic arousal. Nineteen ODD boys (mean age 9.8 years) and 20 normal control boys (NC) (mean age 9.7 years) were administered the door-opening task. In this task, the subject chooses either to open the next door or to stop playing; the opening of doors is initially rewarded and then increasingly punished. ODD boys opened more doors than NC boys. Following punishment, ODD boys took less time than NC boys before opening the next door, but did not differ from NC boys in time after reward. Mean skin conductance level was lower in ODD boys than in NC boys. The correlation coefficient between time after punishment and skin conductance level was moderately positive in the total sample. These results suggest that response perseveration in ODD boys is related to low punishment sensitivity and that skin conductance level is a marker of punishment sensitivity.

An All-Silk-Derived Dual-Mode E-skin for Simultaneous Temperature-Pressure Detection.

PubMed

Wang, Chunya; Xia, Kailun; Zhang, Mingchao; Jian, Muqiang; Zhang, Yingying

2017-11-15

Flexible skin-mimicking electronics are highly desired for development of smart human-machine interfaces and wearable human-health monitors. Human skins are able to simultaneously detect different information, such as touch, friction, temperature, and humidity. However, due to the mutual interferences of sensors with different functions, it is still a big challenge to fabricate multifunctional electronic skins (E-skins). Herein, a combo temperature-pressure E-skin is reported through assembling a temperature sensor and a strain sensor in both of which flexible and transparent silk-nanofiber-derived carbon fiber membranes (SilkCFM) are used as the active material. The temperature sensor presents high temperature sensitivity of 0.81% per centigrade. The strain sensor shows an extremely high sensitivity with a gauge factor of ∼8350 at 50% strain, enabling the detection of subtle pressure stimuli that induce local strain. Importantly, the structure of the SilkCFM in each sensor is designed to be passive to other stimuli, enabling the integrated E-skin to precisely detect temperature and pressure at the same time. It is demonstrated that the E-skin can detect and distinguish exhaling, finger pressing, and spatial distribution of temperature and pressure, which cannot be realized using single mode sensors. The remarkable performance of the silk-based combo temperature-pressure sensor, together with its green and large-scalable fabrication process, promising its applications in human-machine interfaces and soft electronics.

Comparing the diagnostic properties of skin scraping, adhesive tape, and dermoscopy in diagnosing scabies.

PubMed

Abdel-Latif, Azmy A; Elshahed, Ahmad R; Salama, Omar A; Elsaie, Mohamed L

2018-06-01

Scabies is a contagious skin infestation that mainly presents with itching at night and skin burrows that are visible to the naked eye. Diagnosing scabies with dermoscopy is still a matter of controversy. The aim of our study was to compare the diagnostic properties of adhesive tape, skin scraping, and dermoscopy in diagnosing scabies. One hundred patients with clinical presumptive diagnoses of scabies underwent skin scraping, adhesive tape testing, and dermoscopic examination. Each diagnostic procedure was performed on three different areas. Comparing the diagnostic properties of the three methods, the adhesive tape test was the most sensitive method for diagnosing scabies. Sixteen cases (16.0%) were definitely diagnosed as scabies using the adhesive tape test detecting the presence of mites or their eggs. Only 10 cases (10.0%) were definitely diagnosed as scabies using the skin scraping test detecting mites or their eggs. Dermoscopic examination suggested a diagnosis of scabies in 22 cases (22.0%), of which only 10 were definitely diagnosed as scabies by detecting mites using the adhesive tape test, skin scraping, or both. The diagnosis of scabies can only be confirmed by seeing mites. The adhesive tape test and skin scraping procedure have high specificity in diagnosing scabies, but their low sensitivity cannot exclude the possibility of scabies. Dermoscopy-guided tape testing can be a helpful tool for better diagnosis of scabies.

Skin interaction with absorbent hygiene products.

PubMed

Runeman, Bo

2008-01-01

Skin problems due to the use of absorbent hygiene products, such as diapers, incontinence pads, and feminine sanitary articles, are mostly due to climate or chafing discomfort. If these conditions are allowed to prevail, these may develop into an irritant contact dermatitis and eventually superficial skin infections. Skin humidity and aging skin are among the most significant predisposing and aggravating factors for dermatitis development. Improved product design features are believed to explain the decline in observed diaper dermatitis among infants. Where adult incontinence-related skin problems are concerned, it is very important to apply a holistic perspective to understand the influences due to the individual's incontinence level and skin condition, as well as the hygiene and skin care measures provided. Individuals with frail, sensitive skin or with skin diseases may preferably have to use high-quality products, equipped with superabsorbent polymers and water vapor-permeable back sheets, to minimize the risk of skin complications.

Performance of mid infrared spectroscopy in skin cancer cell type identification

NASA Astrophysics Data System (ADS)

Kastl, Lena; Kemper, Björn; Lloyd, Gavin R.; Nallala, Jayakrupakar; Stone, Nick; Naranjo, Valery; Penaranda, Francisco; Schnekenburger, Jürgen

2017-02-01

Marker free optical spectroscopy is a powerful tool for the rapid inspection of pathologically suspicious skin lesions and the non-invasive detection of early skin tumors. This goal can be reached by the combination of signal localization and the spectroscopical detection of chemical cell signatures. We here present the development and application of mid infrared spectroscopy (midIR) for the analysis of skin tumor cell types and three dimensional tissue phantoms towards the application of midIR spectroscopy for fast and reliable skin diagnostics. We developed standardized in vitro skin systems with increasing complexity, from single skin cell types as fibroblasts, keratinocytes and melanoma cells, to mixtures of these and finally three dimensional skin cancer phantoms. The cell systems were characterized with different systems in the midIR range up to 12 μm. The analysis of the spectra by novel data processing algorithms demonstrated the clear separation of all cell types, especially melanoma cells. Special attention and algorithm training was required for closely related mesenchymal cell types as dedifferentiated melanoma cells and fibroblasts. Proof of concept experiments with mixtures of in vivo fluorescence labelled skin cell types allowed the test of the new algorithms performance for the identification of specific cell types. The intense training of the software systems with various samples resulted in a increased sensitivity and specificity of the combined midIR and software system. These data highlight the potential of midIR spectroscopy as sensitive and specific future optical biopsy technology.

Skin Bleaching and Dermatologic Health of African and Afro-Caribbean Populations in the US: New Directions for Methodologically Rigorous, Multidisciplinary, and Culturally Sensitive Research.

PubMed

Benn, Emma K T; Alexis, Andrew; Mohamed, Nihal; Wang, Yan-Hong; Khan, Ikhlas A; Liu, Bian

2016-12-01

Skin-bleaching practices, such as using skin creams and soaps to achieve a lighter skin tone, are common throughout the world and are triggered by cosmetic reasons that oftentimes have deep historical, economic, sociocultural, and psychosocial roots. Exposure to chemicals in the bleaching products, notably, mercury (Hg), hydroquinone, and steroids, has been associated with a variety of adverse health effects, such as Hg poisoning and exogenous ochronosis. In New York City (NYC), skin care product use has been identified as an important route of Hg exposure, especially among Caribbean-born blacks and Dominicans. However, surprisingly sparse information is available on the epidemiology of the health impacts of skin-bleaching practices among these populations. We highlight the dearth of large-scale, comprehensive, community-based, clinical, and translational research in this area, especially the limited skin-bleaching-related research among non-White populations in the US. We offer five new research directions, including investigating the known and under-studied health consequences among populations for which the skin bleach practice is newly emerging at an alarming rate using innovative laboratory and statistical methods. We call for conducting methodologically rigorous, multidisciplinary, and culturally sensitive research in order to provide insights into the root and the epidemiological status of the practice and provide evidence of exposure-outcome associations, with an ultimate goal of developing potential intervention strategies to reduce the health burdens of skin-bleaching practice.

Experimental skin deposition of chromium on the hands following handling of samples of leather and metal.

PubMed

Bregnbak, David; Thyssen, Jacob P; Jellesen, Morten S; Zachariae, Claus; Johansen, Jeanne D

2016-08-01

Chromium is an important skin sensitizer. Exposure to it has been regulated in cement, and recently in leather. Studies on the deposition of chromium ions on the skin as a result of handling different chromium-containing materials are sparse, but could improve the risk assessment of contact sensitization and allergic contact dermatitis caused by chromium. To determine whether the handling of chromium-containing samples of leather and metal results in the deposition of chromium onto the skin. Five healthy volunteers participated. For 30 min, they handled samples of leather and metal known to contain and release chromium. Skin deposition of chromium was assessed with the acid wipe sampling technique. Acid wipe sampling of the participants' fingers showed chromium deposition on the skin in all participants who had been exposed to leather (range 0.01-0.20 µg/cm(2) ) and in 3 of 5 participants after they had manually handled metal discs (range 0.02-0.04 µg/cm(2) ). We found that samples of leather and metal had the ability to deposit chromium on the skin at significant levels, in spite of a short duration of exposure. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The influence of body mass index on skin susceptibility to sodium lauryl sulphate.

PubMed

Löffler, H; Aramaki, J U N; Effendy, Isaak

2002-02-01

The influence of nutrition on the physiological functions of man is well studied. Numerous diseases can be exacerbated by obesity. However, it has not yet been determined whether body weight and body mass index (BMI), as an indicator of a high body fat store, can influence skin sensitivity. This study investigates the correlation between body mass index and the epidermal functions, evaluated by bioengineering methods, before and after an irritant patch test with sodium lauryl sulphate (SLS). Epidermal functions were evaluated using an evaporimeter, chromameter and laser-Doppler-flowmeter. Patch testing was conducted for 48 h with two different concentrations of SLS (0.25% and 0.5%) on the forearms of healthy volunteers. Measurements were performed 24h after patch removal. Obese individuals showed significantly increased transepidermal water loss (TEWL), skin blood flow and skin colour (red) as compared to a control group. However, the degree of skin sensitivity to SLS was not correlated with BMI. Basal biophysical parameters of the skin are primarily correlated with the BMI. This may be caused by obesity-induced physiological changes, e.g. increased sweat gland activity, high blood pressure and physiological temperature-regulating system. The epidermal barrier function, as evaluated after SLS patch testing is, however, not correlated with a high BMI, indicating a normal skin barrier.

Transferability and within- and between-laboratory reproducibilities of EpiSensA for predicting skin sensitization potential in vitro: A ring study in three laboratories.

PubMed

Mizumachi, Hideyuki; Sakuma, Megumi; Ikezumi, Mayu; Saito, Kazutoshi; Takeyoshi, Midori; Imai, Noriyasu; Okutomi, Hiroko; Umetsu, Asami; Motohashi, Hiroko; Watanabe, Mika; Miyazawa, Masaaki

2018-05-03

The epidermal sensitization assay (EpiSensA) is an in vitro skin sensitization test method based on gene expression of four markers related to the induction of skin sensitization; the assay uses commercially available reconstructed human epidermis. EpiSensA has exhibited an accuracy of 90% for 72 chemicals, including lipophilic chemicals and pre-/pro-haptens, when compared with the results of the murine local lymph node assay. In this work, a ring study was performed by one lead and two naive laboratories to evaluate the transferability, as well as within- and between-laboratory reproducibilities, of EpiSensA. Three non-coded chemicals (two lipophilic sensitizers and one non-sensitizer) were tested for the assessment of transferability and 10 coded chemicals (seven sensitizers and three non-sensitizers, including four lipophilic chemicals) were tested for the assessment of reproducibility. In the transferability phase, the non-coded chemicals (two sensitizers and one non-sensitizer) were correctly classified at the two naive laboratories, indicating that the EpiSensA protocol was transferred successfully. For the within-laboratory reproducibility, the data generated with three coded chemicals tested in three independent experiments in each laboratory gave consistent predictions within laboratories. For the between-laboratory reproducibility, 9 of the 10 coded chemicals tested once in each laboratory provided consistent predictions among the three laboratories. These results suggested that EpiSensA has good transferability, as well as within- and between-laboratory reproducibility. Copyright © 2018 John Wiley & Sons, Ltd.

An intradermal skin test for determination of immunity to varicella

PubMed Central

Somekh, E; Bujanover, Y; Tal, G; Dalal, I; Tanay, A; Lehman, D

2001-01-01

AIMS—To evaluate the usefulness of a diluted, inactivated solution of attenuated varicella vaccine in predicting susceptibility to varicella and its correlation with specific antibody titre to varicella.
METHODS—In a prospective blinded study, 63 healthy subjects (aged 2-43 years) were studied. Skin test solution was prepared from vials of OKA strain virus which was inactivated by exposure of the vials to room temperature for 10 days; solution was diluted at 1/50 with normal saline and kept at 4°C until used for skin testing. The material was injected intradermally. Serum samples were drawn prior to skin testing and kept at −70°C until analysis for antibody assay by the indirect fluorescent antibody (IFA) method.
RESULTS—Forty three patients were IFA antibody positive; 41 of them reacted to the skin test. One of the 20 IFA negative patients reacted to the skin test. Sixteen patients had two serological tests performed, one month apart. Four out of these 16 patients tested negative with the skin test. All four had negative serology on both samples. Six of the 12 IFA positive patients showed a boost in the antibody titre one month after application of the skin test. The specificity and sensitivity of the skin test compared to the IFA assay were both 95%, and the positive and negative predictive values were 97% and 90% respectively.
CONCLUSIONS—Results suggest that a varicella skin test prepared using this simple and relatively cheap method is a safe, sensitive, and specific tool by which to assess immunity to varicella.

 PMID:11719333

Latest advances in confocal microscopy of skin cancers toward guiding patient care: a Mohs surgeon's review and perspective (Conference Presentation)

NASA Astrophysics Data System (ADS)

Nehal, Kishwer S.; Rajadhyaksha, Milind

2016-02-01

Latest advances in confocal microscopy of skin cancers toward guiding patient care: a Mohs surgeon's review and perspective About 350 publications worldwide have reported the ability of reflectance confocal microscopy (RCM) imaging to detect melanocytic skin lesions in vivo with specificity of 84-88% and sensitivity of 71-92%, and non-melanocytic skin lesions with specificity of 85-97% and sensitivity 100-92%. Lentigo maligna melanoma can be detected with sensitivity of 93% and specificity 82%. While the sensitivity is comparable to that of dermoscopy, the specificity is 2X superior, especially for lightly- and non-pigmented lesions. Dermoscopy combined with RCM imaging is proving to be both highly sensitive and highly specific. Recent studies have reported that the ratio of equivocal (i.e., would have been biopsied) lesions to detected melanomas dropped by ~2X when guided by dermoscopy and RCM imaging, compared to that with dermoscopy alone. Dermoscopy combined with RCM imaging is now being implemented to guide noninvasive diagnosis (to rule out malignancy and biopsy) and to also guide treatment, with promising initial impact: thus far, about 3,000 patients have been saved from biopsies of benign lesions. These are currently under follow-up monitoring. With fluorescence confocal microscopy (FCM) mosaicing, residual basal cell carcinomas can be detected in Mohs surgically excised fresh tissue ex vivo, with sensitivity of 94-97% and specificity 89-94%. FCM mosaicing is now being implemented for guiding Mohs surgery. To date, about 600 Mohs procedures have been performed, guided with mosaicing, and with pathology being performed in parallel to confirm the final outcome. These latest advances demonstrate the promising ability of RCM and FCM to guide patient care.

TESTS TO ASSESS SENSITIZATION TO ASPERGILLUS FUMIGATUS IN CYSTIC FIBROSIS

PubMed Central

Aguiar, Simone Santana; Damaceno, Neiva; Forte, Wilma Carvalho Neves

2017-01-01

ABSTRACT Objective: To evaluate the results of the tests used to identify the IgE mediated sensitization to Aspergillus fumigatus in patients with cystic fibrosis. Methods: This is a cross-sectional descriptive study with a convenience sample of 86 patients diagnosed with cystic fibrosis in the Reference Service in Cystic Fibrosis at a tertiary teaching hospital. The following tests were performed to assess the sensitization to A. fumigatus in patients with cystic fibrosis: Total serum IgE, eosinophil count, fungus detection through oropharyngeal swab or sputum culture, serum-specific IgE, and immediate-type hypersensitivity (IgE) skin tests. We compared the results of the different tests performed. Results: In 33 (38.4%) patients with cystic fibrosis, with ages ranging from 1 to 33 years (median of 8 years), the IgE-mediated A. fumigatus sensitization test results were: in 16 patients, there was an increase in serum-specific IgE (>0.35 kU/L); in 23, skin tests were positive; and six had sensitization in both tests. We observed two patients with eosinophilia (>1,000 eosinophils/mm3) and seven with increasing total serum IgE (>1,000 IU/mL), all of whom obtained negative results in skin tests and had no IgE increase specific to A. fumigatus. A. fumigatus was not detected in oropharyngeal swabs and/or sputum culture of any patients. Conclusions: We conclude that, among the tests used to assess sensitization to A. fumigatus in cystic fibrosis patients, both serum-specific IgE and immediate-type hypersensitivity (IgE) skin tests are required. Serum eosinophilia and respiratory secretion culture were not essential in this study. PMID:28977288

Visible and Extended Near-Infrared Multispectral Imaging for Skin Cancer Diagnosis

PubMed Central

Rey-Barroso, Laura; Burgos-Fernández, Francisco J.; Delpueyo, Xana; Ares, Miguel; Malvehy, Josep; Puig, Susana

2018-01-01

With the goal of diagnosing skin cancer in an early and noninvasive way, an extended near infrared multispectral imaging system based on an InGaAs sensor with sensitivity from 995 nm to 1613 nm was built to evaluate deeper skin layers thanks to the higher penetration of photons at these wavelengths. The outcomes of this device were combined with those of a previously developed multispectral system that works in the visible and near infrared range (414 nm–995 nm). Both provide spectral and spatial information from skin lesions. A classification method to discriminate between melanomas and nevi was developed based on the analysis of first-order statistics descriptors, principal component analysis, and support vector machine tools. The system provided a sensitivity of 78.6% and a specificity of 84.6%, the latter one being improved with respect to that offered by silicon sensors. PMID:29734747

Hyperspectral imaging for melanoma screening

NASA Astrophysics Data System (ADS)

Martin, Justin; Krueger, James; Gareau, Daniel

2014-03-01

The 5-year survival rate for patients diagnosed with Melanoma, a deadly form of skin cancer, in its latest stages is about 15%, compared to over 90% for early detection and treatment. We present an imaging system and algorithm that can be used to automatically generate a melanoma risk score to aid clinicians in the early identification of this form of skin cancer. Our system images the patient's skin at a series of different wavelengths and then analyzes several key dermoscopic features to generate this risk score. We have found that shorter wavelengths of light are sensitive to information in the superficial areas of the skin while longer wavelengths can be used to gather information at greater depths. This accompanying diagnostic computer algorithm has demonstrated much higher sensitivity and specificity than the currently commercialized system in preliminary trials and has the potential to improve the early detection of melanoma.

Ca2+ and MgATP2- dependence of shortening in skinned single smooth muscle cells.

PubMed

Warshaw, D M; McBride, W J; Hubbard, M S

1987-04-01

Most studies of skinned smooth muscle have been performed in whole tissue preparations. In this study, we report the development of a chemically skinned single smooth muscle cell preparation from the toad, Bufo marinus, stomach. Isolated smooth muscle cells were skinned using saponin. The effect of various ionic environments (i.e., changing free Ca2+ and MgATP2-) on skinned cell contractile response was assessed by measuring cell lengths from populations of cells using a computer-assisted length-measuring system. Comparison of cell length histograms were used to determine the extent of cell shortening in response to a given ionic perturbation. Once skinned, the single cells shortened with a sensitivity to free calcium (ED50 = 1.5 microM Ca2+) that was three orders of magnitude lower than potassium depolarized cells (ED50 = 1.5 mM Ca2+). In addition to the calcium sensitivity, the effect of free MgATP2- on the extent of cell shortening was investigated. The extent of cell shortening was dependent on free MgATP2- with the maximum shortening response occurring at MgATP2- greater than 1 mM.

Transparent, flexible, and stretchable WS2 based humidity sensors for electronic skin.

PubMed

Guo, Huayang; Lan, Changyong; Zhou, Zhifei; Sun, Peihua; Wei, Dapeng; Li, Chun

2017-05-18

Skin-mountable chemical sensors using flexible chemically sensitive nanomaterials are of great interest for electronic skin (e-skin) application. To build these sensors, the emerging atomically thin two-dimensional (2D) layered semiconductors could be a good material candidate. Herein, we show that a large-area WS 2 film synthesized by sulfurization of a tungsten film exhibits high humidity sensing performance both in natural flat and high mechanical flexible states (bending curvature down to 5 mm). The conductivity of as-synthesized WS 2 increases sensitively over a wide relative humidity range (up to 90%) with fast response and recovery times in a few seconds. By using graphene as electrodes and thin polydimethylsiloxane (PDMS) as substrate, a transparent, flexible, and stretchable humidity sensor was fabricated. This senor can be well laminated onto skin and shows stable water moisture sensing behaviors in the undeformed relaxed state as well as under compressive and tensile loadings. Furthermore, its high sensing performance enables real-time monitoring of human breath, indicating a potential mask-free breath monitoring for healthcare application. We believe that such a skin-activity compatible WS 2 humidity sensor may shed light on developing low power consumption wearable chemical sensors based on 2D semiconductors.

[Penicillin allergy as a diagnostic problem. Overview and personal studies].

PubMed

Walker, T; Jung, E G; Bayerl, C

2000-11-01

Penicillin allergy is a common clinical problem. The distinction between penicillin and para-infectious exanthems is difficult. We investigated the reliability of the history, as well as the sensitivity and specificity of skin tests and specific IgE levels. 160 patients with a history of penicillin allergy were retrospectively evaluated in the outpatient department of a dermatological clinic. Nearly 50% were diagnosed as allergic to penicillin by detection of specific IgE or skin test. About 60% of the patients with immediate type reactions, and 72% with maculo-papular erythema showed positive reactions in skin tests. Significantly more patients were diagnosed as allergic to penicillin by intradermal testing than by prick testing (p < 0.05). The sensitivity of the specific IgE RAST was 17.9%; the specifity, 89.5%. For the prick test the sensitivity was 8.2%; the specificity 90.8%. For the intradermal test the sensitivity was 26%; the specifity 69.7%. We suggest a step by step procedure to detect penicillin allergy making the diagnostic results as valid as possible.

Biocompatibility of hyaluronic acid hydrogels prepared by porous hyaluronic acid microbeads

NASA Astrophysics Data System (ADS)

Kim, Jin-Tae; Lee, Deuk Yong; Kim, Tae-Hyung; Song, Yo-Seung; Cho, Nam-Ihn

2014-05-01

Hyaluronic acid hydrogels (HAHs) were synthesized by immersing HA microbeads crosslinked with divinyl sulfone in a phosphate buffered saline solution to evaluate the biocompatibility of the gels by means of cytotoxicity, genotoxicity ( in vitro chromosome aberration test, reverse mutation assay, and in vivo micronucleus test), skin sensitization, and intradermal reactivity. The HAHs induced no cytotoxicity or genotoxicity. In guinea pigs treated with grafts and prostheses, no animals died and there were no abnormal clinical signs. The sensitization scores were zero in all guinea pigs after 24 h and 48 h challenge, suggesting that the HAHs had no contact allergic sensitization in the guinea pig maximization test. No abnormal signs were found in New Zealand White rabbits during the 72 h observation period after the injection. There was no difference between the HAHs and negative control mean scores because skin reaction such as erythema or oedema was not observed after injection. Experimental results suggest that the HAHs would be suitable for soft tissue augmentation due to the absence of cytotoxicity, genotoxicity, skin sensitization, and intradermal reactivity.

A wearable diffuse reflectance sensor for continuous monitoring of cutaneous blood content

NASA Astrophysics Data System (ADS)

Zakharov, P.; Talary, M. S.; Caduff, A.

2009-09-01

An optical diffuse reflectance sensor for characterization of cutaneous blood content and optimized for continuous monitoring has been developed as part of a non-invasive multisensor system for glucose monitoring. A Monte Carlo simulation of the light propagation in the multilayered skin model has been performed in order to estimate the optimal geometrical separation of the light source and detector for skin and underlying tissue. We have observed that the pathlength within the upper vascular plexus of the skin which defines the sensor sensitivity initially grows with increasing source-detector distance (SDD) before reaching a maximum at 3.5 mm and starts to decay with further increase. At the same time, for distances above 2.4 mm, the sensor becomes sensitive to muscle blood content, which decreases the specificity to skin perfusion monitoring. Thus, the SDDs in the range from 1.5 mm to 2.4 mm satisfy the requirements of sensor sensitivity and specificity. The hardware implementation of the system has been realized and tested in laboratory experiments with a venous occlusion procedure and in an outpatient clinical study in 16 patients with type 1 diabetes mellitus. For both testing procedures, the optical sensor demonstrated high sensitivity to perfusion change provoking events. The general build-up of cutaneous blood under the sensor has been observed which can be associated with pressure-induced vasodilation as a response to the sensor application.

The diagnostic performance of expert dermoscopists vs a computer-vision system on small-diameter melanomas.

PubMed

Friedman, Robert J; Gutkowicz-Krusin, Dina; Farber, Michele J; Warycha, Melanie; Schneider-Kels, Lori; Papastathis, Nicole; Mihm, Martin C; Googe, Paul; King, Roy; Prieto, Victor G; Kopf, Alfred W; Polsky, David; Rabinovitz, Harold; Oliviero, Margaret; Cognetta, Armand; Rigel, Darrell S; Marghoob, Ashfaq; Rivers, Jason; Johr, Robert; Grant-Kels, Jane M; Tsao, Hensin

2008-04-01

To evaluate the performance of dermoscopists in diagnosing small pigmented skin lesions (diameter

Evaluation of PCR for cutaneous leishmaniasis diagnosis and species identification using filter paper samples in Panama, Central America.

PubMed

Miranda, A; Saldaña, A; González, K; Paz, H; Santamaría, G; Samudio, F; Calzada, J E

2012-09-01

Cutaneous leishmaniasis (CL) is a major vectorborne disease in Panama. In this study, the diagnostic performance and usefulness of two DNA extraction procedures from skin scraping samples collected on FTA filter paper for subsequent PCR diagnosis of CL was evaluated. A positive CL laboratory diagnosis was based on a positive parasitological test (Giemsa-stained smears or in vitro culture) and/or positive PCR test performed from skin scrapings collected in TE buffer (PCR-TE). Of 100 patients with skin lesions suggestive of CL, 82 (82%) were confirmed as CL positive. The sensitivity was calculated for each of the PCR approaches from samples collected on filter paper. The highest sensitivity was achieved by PCR-FTA processed by Chelex 100 (PCR-Chelex) (0.94). PCR-FTA extracted using the FTA purification reagent presented a lower sensitivity (0.60). Good concordance between routine PCR-TE and PCR-Chelex was observed (percent agreement=0.88, κ index=0.65). In conclusion, use of FTA filter paper for skin scraping collection combined with PCR is a reliable and convenient method for CL diagnosis in Panama, with comparable performance to the routine PCR method and with improved sensitivity compared with those of conventional parasitological methods. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

[Sensitivity and specificity of prick skin test with two concentrations of standardized extract of Culex quinquefasciatus in allergic children].

PubMed

Castro-Almarales, Raúl Lázaro; Álvarez-Castelló, Mirta; Ronquillo-Díaz, Mercedes; Rodríguez-Canosa, José S; González-León, Mayda; Navarro-Viltre, Bárbara I; Betancourt-Mesia, Daniel; Enríquez-Domínguez, Irene; Reyes-Zamora, Mary Carmen; Oliva-Díaz, Yunia; Mateo-Morejón, Maytee; Labrada-Rosado, Alexis

2016-01-01

Diagnostic options for immune reactions to mosquito bites are limited. In Cuba, IgE-mediated reactions are frequently related to Culex quinquefasciatus bite. To determine the sensitivity and specificity of skin prick test with two doses of standardized extract in nitrogen protein units (PNU of Culex quinquefasciatus (BIOCEN, Cuba). An analytical study was conducted on 100 children between 2 and 15 years old. Fifty atopic patients with a history of allergy to mosquito bite and positive specific serum IgE Culex quinquefasciatus and fifty atopic patients without a history of allergy to mosquito bite and negative specific serum IgE to Culex quinquefasciatus. Skin prick tests (SPT) were performed by duplicates on the forearms of the patients. Investigated doses were 100 PNU/mL and 10 PNU/mL. SPT with the highest concentration obtained a mean wheal size of 22.09 mm2 and for lower doses of 8.09 mm2, a statistically significant difference (p=0.001, Student's t test). Positive skin test correlated in 100% of patients with the presence of specific IgE. Testing with both doses showed a 94% of specificity and 88% of sensitivity. The diagnostic accuracy of SPT using both doses of standardized extract was similar, which justifies its use for diagnosis of sensitization to Culex quinquefasciatus in patients with symptoms of allergy to mosquito bite.

Effect of photodynamic therapy using benzoporphyrin derivative on the cutaneous immune response

NASA Astrophysics Data System (ADS)

Simkin, Guillermo O.; Obochi, Modestus; Hunt, David W. C.; Chan, Agnes H.; Levy, Julia G.

1995-05-01

In this study, the effect of transdermal photodynamic therapy (PDT) using benzoporphyrin derivative monoacid ring A (BPD) on the development of the immunologically mediated contact hypersensitivity (CHS) response against the hapten dinitrofluorobenzene (DNFB) and on the duration of skin allograft acceptance has been evaluated. In the CHS model it was found that the treatment of hairless strain mice with whole-body transdermal PDT using BPD (1 mg/kg) and LED light (15 J/cm2) resulted in a profound suppression of the CHS reaction if treatment was applied either 48 or 24 hours prior or up to 72 hours after sensitization of abdominal skin with DNFB. Less inhibition of the CHS response was observed if PDT was given one day before the ear challenge with DNFB which was applied 5 days following the initial DNFB sensitization. However, DNFB-exposed, PDT-treated mice retained the capacity to respond maximally to the unrelated contact sensitizer oxazolone. These results are consistent with other models of experimentally induced immune tolerance. allogeneic skin graft studies demonstrated that pretreatment of skin with BPD and light, at levels that did not cause significant tissue damage, significantly enhanced the length of engraftment. Using a separate protocol, photodynamic treatment of recipient mice at various times after transplant had no significant effect on allograft acceptance. Irradiation of skin in the presence of BPD may significantly inhibit the initiation of certain immunological responses within these tissues.

The respiratory local lymph node assay as a tool to study respiratory sensitizers.

PubMed

Arts, Josje H E; de Jong, Wim H; van Triel, Jos J; Schijf, Marcel A; de Klerk, Arja; van Loveren, Henk; Kuper, C Frieke

2008-12-01

The local lymph node assay (LLNA) is used to test the potential of low molecular weight (LMW) compounds to induce sensitization via the skin. In the present study, a respiratory LLNA was developed. Male BALB/c mice were exposed head/nose-only during three consecutive days for 45, 90, 180, or 360 min/day to various LMW allergens. Ear application (skin LLNA) was used as a positive control. Negative controls were exposed to the vehicle. Three days after the last exposure, proliferation was determined in the draining mandibular lymph nodes, and the respiratory tract was examined microscopically. Upon inhalation, the allergens trimellitic anhydride, phthalic anhydride, hexamethylene diisocyanate, toluene diisocyanate, isophorone diisocyanate (IPDI), dinitrochlorobenzene, and oxazolone were positive and showed stimulation indices (SIs) up to 11, whereas trimeric IPDI, formaldehyde, and methyl salicylate were negative (viz. SI < 3). All compounds, except trimeric IPDI, induced histopathological lesions predominantly in the upper respiratory tract. Exposure by inhalation is a realistic approach to test respiratory allergens. However, based on the local toxicity, the dose that can be applied is (generally) much lower than can be achieved by skin application. It is concluded that strong LMW allergens, regardless their immunological nature, besides the skin can also sensitize the body via the respiratory tract. In addition, the contact allergens were as potent as the respiratory allergens, although the potency ranking differed from that in a skin LLNA.

Development, validation and testing of a skin sampling method for assessment of metal exposure.

PubMed

Erfani, Behnaz; Midander, Klara; Lidén, Carola; Julander, Anneli

2017-07-01

Nickel, cobalt and chromium are frequent skin sensitizers. Skin exposure results in eczema in sensitized individuals, the risk being related to the skin dose. To develop a self-sampling method for quantification of skin exposure to metals, to validate the method, and to assess its feasibility. Defined metal doses (0.01-5 µg) were applied to the fingers of 5 participants. Skin areas (2 cm 2 ) were sampled with 1% HNO 3 , either as 0.1 ml on a swab, or as 0.5 ml on a wipe. Furthermore, 17 participants performed self-sampling by swab after 2 h of leisure activity. Samples were extracted in 1% HNO 3 and analysed by inductively coupled plasma mass spectrometry. The sampling efficiency by swab was 46%, as compared with 93% for acid wipe sampling, for all tested doses. Most metal from the skin dose was detected in the first swab (33-43%). Despite lower sampling efficiency by swab, skin doses of metals following 2 h of leisure activity without hand washing were quantified in all participants, and ranged from 0.0016 to 0.15 µg/cm 2 , from 0.00014 to -0.0020 µg/cm 2 and from 0.00048 to -0.027 µg/cm 2 for nickel, cobalt, and chromium, respectively. The results indicate a future potential of skin sampling by swab to detect and monitor metals on skin by self-sampling. This will contribute to better knowledge of metal skin exposure among dermatitis patients, workers, and the general population. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Topically applied ZnO nanoparticles suppress allergen induced skin inflammation but induce vigorous IgE production in the atopic dermatitis mouse model

PubMed Central

2014-01-01

Background Metal oxide nanoparticles such as ZnO are used in sunscreens as they improve their optical properties against the UV-light that causes dermal damage and skin cancer. However, the hazardous properties of the particles used as UV-filters in the sunscreens and applied to the skin have remained uncharacterized. Methods Here we investigated whether different sized ZnO particles would be able to penetrate injured skin and injured allergic skin in the mouse atopic dermatitis model after repeated topical application of ZnO particles. Nano-sized ZnO (nZnO) and bulk-sized ZnO (bZnO) were applied to mechanically damaged mouse skin with or without allergen/superantigen sensitization. Allergen/superantigen sensitization evokes local inflammation and allergy in the skin and is used as a disease model of atopic dermatitis (AD). Results Our results demonstrate that only nZnO is able to reach into the deep layers of the allergic skin whereas bZnO stays in the upper layers of both damaged and allergic skin. In addition, both types of particles diminish the local skin inflammation induced in the mouse model of AD; however, nZnO has a higher potential to suppress the local effects. In addition, especially nZnO induces systemic production of IgE antibodies, evidence of allergy promoting adjuvant properties for topically applied nZnO. Conclusions These results provide new hazard characterization data about the metal oxide nanoparticles commonly used in cosmetic products and provide new insights into the dermal exposure and hazard assessment of these materials in injured skin. PMID:25123235

Attenuated noradrenergic sensitivity during local cooling in aged human skin

PubMed Central

Thompson, Caitlin S; Holowatz, Lacy A; Kenney, W. Larry

2005-01-01

Reflex-mediated cutaneous vasoconstriction (VC) is impaired in older humans; however, it is unclear whether this blunted VC also occurs during local cooling, which mediates VC through different mechanisms. We tested the hypothesis that the sensitization of cutaneous vessels to noradrenaline (NA) during direct skin cooling seen in young skin is blunted in aged skin. In 11 young (18–30 years) and 11 older (62–76 years) men and women, skin blood flow was monitored at two forearm sites with laser Doppler (LD) flowmetry while local skin temperature was cooled and clamped at 24°C. Cutaneous vascular conductance (CVC; LD flux/mean arterial pressure) was expressed as percentage change from baseline (%ΔCVCbase). At one site, five doses of NA (10−10–10−2m) were sequentially infused via intradermal microdialysis during cooling while the other 24°C site served as control (Ringer solution + cooling). At control sites, VC due to cooling alone was similar in young versus older (−54 ± 5 versus −56 ± 3%ΔCVCbase, P= 0.46). In young, NA infusions induced additional dose-dependent VC (10−8, 10−6, 10−4 and 10−2m: −70 ± 2, −72 ± 3, −78 ± 3 and −79 ± 4%ΔCVCbase; P < 0.05 versus control). In older subjects, further VC did not occur until the highest infused dose of NA (10−2m: −70 ± 5%ΔCVCbase; P < 0.05 versus control). When cutaneous arterioles are sensitized to NA by direct cooling, young skin exhibits the capacity to further constrict to NA in a dose-dependent manner. However, older skin does not display enhanced VC capacity until treated with saturating doses of NA, possibly due to age-associated decrements in Ca2+ availability or α2C-adrenoceptor function. PMID:15705648

Skin Temperature Rhythms in Humans Respond to Changes in the Timing of Sleep and Light.

PubMed

Cuesta, Marc; Boudreau, Philippe; Cermakian, Nicolas; Boivin, Diane B

2017-06-01

Body temperature is known to vary with circadian phase and to be influenced by factors that can mask its circadian expression. We wanted to test whether skin temperature rhythms were sensitive to an abrupt shift of the sleep schedule and to the resetting effects of light. Nineteen healthy subjects spent 6 days in time isolation and underwent a simulated night-shift procedure. They were assigned to either a control group ( n = 10) or bright light group ( n = 9) and measurements were taken under a baseline day-oriented schedule and during the 4 th cycle of a night-oriented schedule. In the bright light group, participants were exposed to a 3-cycle 8-h exposure of ~6,500 lux at night, while the control group remained in dim light conditions (~3 lux). Skin temperature was recorded in 10 and 4 participants from the control and bright light groups, respectively. We found significant circadian rhythms of plasma melatonin, core body temperature (CBT), and skin temperature at baseline for both groups ( p < 0.001 for all). Rhythms of melatonin, CBT, and skin temperature following night shifts were significantly phase delayed by about 7 to 9 h ( p < 0.05) in response to bright light at night, whereas there was no shift in the control group. In addition, we found that at bedtime melatonin does not consistently increase before the increase in distal skin temperature and subsequent decrease in CBT, in contrast to what has been previously reported. The present study shows that, in constant posture conditions, skin temperature rhythms have an evoked component sensitive to abrupt changes in the timing of sleep. They also comprise an endogenous component that is sensitive to the resetting effects of bright light exposure. These results have applications for the determination of circadian phase, as skin temperature is less intrusive than rectal temperature recordings.

In vitro methods for hazard assessment of industrial chemicals – opportunities and challenges

PubMed Central

Wong, Chin Lin; Ghassabian, Sussan; Smith, Maree T.; Lam, Ai-Leen

2015-01-01

Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity immune reaction mediated by T-lymphocytes as a result of repeated exposure of an allergen primarily on skin. ACD accounts for up to 95% of occupational skin diseases, with epoxy resins implicated as one of the most common causes of ACD. Efficient high-throughput in vitro screening for accurate identification of compounds and materials that may pose hazardous risks in the workplace is crucial. At present, the murine local lymph node assay is the ‘method of choice’ for predicting the sensitizing potency of contact allergens. As the 3Rs principles of reduction, refinement, and replacement in animal testing has gained political and economic momentum, several in vitro screening methods have been developed for identifying potential contact allergens. To date, these latter methods have been utilized primarily to assess the skin sensitizing potential of the chemical components of cosmetic products with scant research attention as to the applicability of these methods to industrial chemicals, particularly epoxy resins. Herein we review the currently utilized in vitro methods and identify the knowledge gaps with regard to assessing the generalizability of in vitro screening methods for assessing the skin sensitizing potential of industrial chemicals. PMID:25999858

Occupational allergy to Artemia fish fry feed in aquaculture.

PubMed

Granslo, Jens-Tore; Van Do, Thien; Aasen, Tor B; Irgens, Agot; Florvaag, Erik

2009-06-01

Artemia (brine shrimp) is used as feed for fish fry and shrimp in aquaculture. Two employees in a Norwegian aquaculture research farm reported having chest symptoms when working in an Artemia hatch room. To determine the presence and prevalence of Artemia sensitization at the farm and the extent of any Artemia-related respiratory and hand skin symptoms and to identify the allergens involved. Participants completed a questionnaire and structured interview. Skin prick tests (SPTs) were performed, and immunoglobulin E (IgE) antibodies to Artemia, shrimp and recombinant tropomyosin were determined. Gel electrophoresis and immunoblots of Artemia extracts were also carried out. Thirty of 42 employees (71%) participated. Among the 24 subjects exposed to Artemia, four (17%) reported chest and/or hand skin symptoms during exposure and three of them were IgE sensitized to Artemia. Five (21%) of those exposed demonstrated IgE antibodies to Artemia and four (17%) had immediate-positive SPTs. A serum pool from these subjects exhibited IgE binding to a protein of approximately 97 kDa in the Artemia extract. Occupational exposure to the Artemia fish fry feed can cause IgE sensitization and allergic symptoms affecting airways and skin.

Assessment of Irritation and Sensitization Potential of Eight Baby Skin Care Products.

PubMed

Galzote, Carlos; Thomas, Mini; Sachdev, Mukta

2016-10-01

Ethnic differences in skin sensitivity suggest that greater emphasis be focused on understanding a product's effect in diverse populations. The irritation and/or sensitization potential of 8 baby skin care products in Indian adults were evaluated using cumulative irritation tests (CIT) and human repeat insult patch testing (HRIPT) protocols. Healthy males or females aged 18 to 65 years of Indian ethnicity were treated with each of 6 products (cream, hair oil, lotion, body wash, shampoo, and baby soap) using CIT (n = 25) and HRIPT (n = 200). Baby powder and baby oil were evaluated by CIT (n = 25) and HRIPT (n = 107) in separate studies. CITs were conducted over 14 days; HRIPTs were conducted over 10 weeks. In both CIT and HRIPT, most products were considered mild, with no irritation. Baby soap and powder elicited reactions in the HRIPT induction phase, with positive challenge phase reactions (3 subjects), but were affirmed to be nonallergenic in the rechallenge phase. In these studies, 8 baby skin care products were evaluated by both CIT and HRIPT in Indian adults. The results of the studies indicated that all of the tested products were nonallergenic and nonirritating.

J Drugs Dermatol. 2016;15(10):1244-1248.

In vitro methods for hazard assessment of industrial chemicals - opportunities and challenges.

PubMed

Wong, Chin Lin; Ghassabian, Sussan; Smith, Maree T; Lam, Ai-Leen

2015-01-01

Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity immune reaction mediated by T-lymphocytes as a result of repeated exposure of an allergen primarily on skin. ACD accounts for up to 95% of occupational skin diseases, with epoxy resins implicated as one of the most common causes of ACD. Efficient high-throughput in vitro screening for accurate identification of compounds and materials that may pose hazardous risks in the workplace is crucial. At present, the murine local lymph node assay is the 'method of choice' for predicting the sensitizing potency of contact allergens. As the 3Rs principles of reduction, refinement, and replacement in animal testing has gained political and economic momentum, several in vitro screening methods have been developed for identifying potential contact allergens. To date, these latter methods have been utilized primarily to assess the skin sensitizing potential of the chemical components of cosmetic products with scant research attention as to the applicability of these methods to industrial chemicals, particularly epoxy resins. Herein we review the currently utilized in vitro methods and identify the knowledge gaps with regard to assessing the generalizability of in vitro screening methods for assessing the skin sensitizing potential of industrial chemicals.

Application of principal component analysis to multispectral imaging data for evaluation of pigmented skin lesions

NASA Astrophysics Data System (ADS)

Jakovels, Dainis; Lihacova, Ilze; Kuzmina, Ilona; Spigulis, Janis

2013-11-01

Non-invasive and fast primary diagnostics of pigmented skin lesions is required due to frequent incidence of skin cancer - melanoma. Diagnostic potential of principal component analysis (PCA) for distant skin melanoma recognition is discussed. Processing of the measured clinical multi-spectral images (31 melanomas and 94 nonmalignant pigmented lesions) in the wavelength range of 450-950 nm by means of PCA resulted in 87 % sensitivity and 78 % specificity for separation between malignant melanomas and pigmented nevi.

Traditional Therapies for Skin Wound Healing.

PubMed

Pereira, Rúben F; Bártolo, Paulo J

2016-05-01

Significance: The regeneration of healthy and functional skin remains a huge challenge due to its multilayer structure and the presence of different cell types within the extracellular matrix in an organized way. Despite recent advances in wound care products, traditional therapies based on natural origin compounds, such as plant extracts, honey, and larvae, are interesting alternatives. These therapies offer new possibilities for the treatment of skin diseases, enhancing the access to the healthcare, and allowing overcoming some limitations associated to the modern products and therapies, such as the high costs, the long manufacturing times, and the increase in the bacterial resistance. This article gives a general overview about the recent advances in traditional therapies for skin wound healing, focusing on the therapeutic activity, action mechanisms, and clinical trials of the most commonly used natural compounds. New insights in the combination of traditional products with modern treatments and future challenges in the field are also highlighted. Recent Advances: Natural compounds have been used in skin wound care for many years due to their therapeutic activities, including anti-inflammatory, antimicrobial, and cell-stimulating properties. The clinical efficacy of these compounds has been investigated through in vitro and in vivo trials using both animal models and humans. Besides the important progress regarding the development of novel extraction methods, purification procedures, quality control assessment, and treatment protocols, the exact mechanisms of action, side effects, and safety of these compounds need further research. Critical Issues: The repair of skin lesions is one of the most complex biological processes in humans, occurring throughout an orchestrated cascade of overlapping biochemical and cellular events. To stimulate the regeneration process and prevent the wound to fail the healing, traditional therapies and natural products have been used with promising results. Although these products are in general less expensive than the modern treatments, they can be sensitive to the geographic location and season, and exhibit batch-to-batch variation, which can lead to unexpected allergic reactions, side effects, and contradictory clinical results. Future Directions: The scientific evidence for the use of traditional therapies in wound healing indicates beneficial effects in the treatment of different lesions. However, specific challenges remain unsolved. To extend the efficacy and the usage of natural substances in wound care, multidisciplinary efforts are necessary to prove the safety of these products, investigate their side effects, and develop standard controlled trials. The development of good manufacturing practices and regulatory legislation also assume a pivotal role in order to improve the use of traditional therapies by the clinicians and to promote their integration into the national health system. Current trends move to the development of innovative wound care treatments, combining the use of traditional healing agents and modern products/practices, such as nanofibers containing silver nanoparticles, Aloe vera loaded into alginate hydrogels, propolis into dressing films, and hydrogel sheets containing honey.

Traditional Therapies for Skin Wound Healing

PubMed Central

Pereira, Rúben F.; Bártolo, Paulo J.

2016-01-01

Significance: The regeneration of healthy and functional skin remains a huge challenge due to its multilayer structure and the presence of different cell types within the extracellular matrix in an organized way. Despite recent advances in wound care products, traditional therapies based on natural origin compounds, such as plant extracts, honey, and larvae, are interesting alternatives. These therapies offer new possibilities for the treatment of skin diseases, enhancing the access to the healthcare, and allowing overcoming some limitations associated to the modern products and therapies, such as the high costs, the long manufacturing times, and the increase in the bacterial resistance. This article gives a general overview about the recent advances in traditional therapies for skin wound healing, focusing on the therapeutic activity, action mechanisms, and clinical trials of the most commonly used natural compounds. New insights in the combination of traditional products with modern treatments and future challenges in the field are also highlighted. Recent Advances: Natural compounds have been used in skin wound care for many years due to their therapeutic activities, including anti-inflammatory, antimicrobial, and cell-stimulating properties. The clinical efficacy of these compounds has been investigated through in vitro and in vivo trials using both animal models and humans. Besides the important progress regarding the development of novel extraction methods, purification procedures, quality control assessment, and treatment protocols, the exact mechanisms of action, side effects, and safety of these compounds need further research. Critical Issues: The repair of skin lesions is one of the most complex biological processes in humans, occurring throughout an orchestrated cascade of overlapping biochemical and cellular events. To stimulate the regeneration process and prevent the wound to fail the healing, traditional therapies and natural products have been used with promising results. Although these products are in general less expensive than the modern treatments, they can be sensitive to the geographic location and season, and exhibit batch-to-batch variation, which can lead to unexpected allergic reactions, side effects, and contradictory clinical results. Future Directions: The scientific evidence for the use of traditional therapies in wound healing indicates beneficial effects in the treatment of different lesions. However, specific challenges remain unsolved. To extend the efficacy and the usage of natural substances in wound care, multidisciplinary efforts are necessary to prove the safety of these products, investigate their side effects, and develop standard controlled trials. The development of good manufacturing practices and regulatory legislation also assume a pivotal role in order to improve the use of traditional therapies by the clinicians and to promote their integration into the national health system. Current trends move to the development of innovative wound care treatments, combining the use of traditional healing agents and modern products/practices, such as nanofibers containing silver nanoparticles, Aloe vera loaded into alginate hydrogels, propolis into dressing films, and hydrogel sheets containing honey. PMID:27134765

Occupational Exposure to Ultraviolet Radiation and Risk of Non-Melanoma Skin Cancer in a Multinational European Study

PubMed Central

Surdu, Simona; Fitzgerald, Edward F.; Bloom, Michael S.; Boscoe, Francis P.; Carpenter, David O.; Haase, Richard F.; Gurzau, Eugen; Rudnai, Peter; Koppova, Kvetoslava; Févotte, Joëlle; Leonardi, Giovanni; Vahter, Marie; Goessler, Walter; Kumar, Rajiv; Fletcher, Tony

2013-01-01

Background Studies suggest that ambient sunlight plays an important role in the pathogenesis of non-melanoma skin cancers (NMSC). However, there is ongoing controversy regarding the relevance of occupational exposure to natural and artificial ultraviolet radiation (UV) radiation. Objectives We investigated potential associations between natural and artificial UV radiation exposure at work with NMSC in a case-control study conducted in Hungary, Romania, and Slovakia. Methods Occupational exposures were classified by expert assessment for 527 controls and 618 NMSC cases (515 basal cell carcinoma, BCC). Covariate information was collected via interview and multiple logistic regression models were used to assess associations between UV exposure and NMSC. Results Lifetime prevalence of occupational exposure in the participants was 13% for natural UV radiation and 7% for artificial UV radiation. Significant negative associations between occupational exposure to natural UV radiation and NMSC were detected for all who had ever been exposed (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.27–0.80); similar results were detected using a semi-quantitative metric of cumulative exposure. The effects were modified by skin complexion, with significantly decreased risks of BCC among participants with light skin complexion. No associations were observed in relation to occupational artificial UV radiation exposure. Conclusions The protective effect of occupational exposure to natural UV radiation was unexpected, but limited to light-skinned people, suggesting adequate sun-protection behaviors. Further investigations focusing on variations in the individual genetic susceptibility and potential interactions with environmental and other relevant factors are planned. PMID:23638051

Consistency of the Proteome in Primary Human Keratinocytes With Respect to Gender, Age, and Skin Localization*

PubMed Central

Sprenger, Adrian; Weber, Sebastian; Zarai, Mostafa; Engelke, Rudolf; Nascimento, Juliana M.; Gretzmeier, Christine; Hilpert, Martin; Boerries, Melanie; Has, Cristina; Busch, Hauke; Bruckner-Tuderman, Leena; Dengjel, Jörn

2013-01-01

Keratinocytes account for 95% of all cells of the epidermis, the stratified squamous epithelium forming the outer layer of the skin, in which a significant number of skin diseases takes root. Immortalized keratinocyte cell lines are often used as research model systems providing standardized, reproducible, and homogenous biological material. Apart from that, primary human keratinocytes are frequently used for medical studies because the skin provides an important route for drug administration and is readily accessible for biopsies. However, comparability of these cell systems is not known. Cell lines may undergo phenotypic shifts and may differ from the in vivo situation in important aspects. Primary cells, on the other hand, may vary in biological functions depending on gender and age of the donor and localization of the biopsy specimen. Here we employed metabolic labeling in combination with quantitative mass spectrometry-based proteomics to assess A431 and HaCaT cell lines for their suitability as model systems. Compared with cell lines, comprehensive profiling of the primary human keratinocyte proteome with respect to gender, age, and skin localization identified an unexpected high proteomic consistency. The data were analyzed by an improved ontology enrichment analysis workflow designed for the study of global proteomics experiments. It enables a quick, comprehensive and unbiased overview of altered biological phenomena and links experimental data to literature. We guide through our workflow, point out its advantages compared with other methods and apply it to visualize differences of cell lines compared with primary human keratinocytes. PMID:23722187

Classification of skin cancer images using local binary pattern and SVM classifier

NASA Astrophysics Data System (ADS)

Adjed, Faouzi; Faye, Ibrahima; Ababsa, Fakhreddine; Gardezi, Syed Jamal; Dass, Sarat Chandra

2016-11-01

In this paper, a classification method for melanoma and non-melanoma skin cancer images has been presented using the local binary patterns (LBP). The LBP computes the local texture information from the skin cancer images, which is later used to compute some statistical features that have capability to discriminate the melanoma and non-melanoma skin tissues. Support vector machine (SVM) is applied on the feature matrix for classification into two skin image classes (malignant and benign). The method achieves good classification accuracy of 76.1% with sensitivity of 75.6% and specificity of 76.7%.

Complement activation and liver impairment in trichloroethylene-sensitized BALB/c mice.

PubMed

Zhang, Jiaxiang; Zha, Wansheng; Wang, Feng; Jiang, Tao; Xu, Shuhai; Yu, Junfeng; Zhou, Chengfan; Shen, Tong; Wu, Changhao; Zhu, Qixing

2013-01-01

Our recent studies have shown that trichloroethylene (TCE) was able to induce multisystem injuries in the form of occupational medicamentosa-like dermatitis, including skin, kidney, and liver damages. However, the role of complement activation in the immune-mediated liver injury is not known. This study examined the role of complement activation in the liver injury in a mouse model of TCE-induced sensitization. Treatment of female BALB/c mice with TCE under specific dosing protocols resulted in skin inflammation and sensitization. Skin edema and erythema occurred in TCE-sensitized groups. Trichloroethylene sensitization produced liver histopathological lesions, increased serum alanine aminotransferase, aspartate transaminase activities, and the relative liver weight. The concentrations of serum complement components C3a-desArg, C5a-desArg, and C5b-9 were significantly increased in 24-hour, 48-hour, and 72-hour sensitization-positive groups treated with TCE and peaked in the 72-hour sensitization-positive group. Depositions of C3a, C5a, and C5b-9 into the liver tissue were also revealed by immunohistochemistry. Immunofluorescence further verified high C5b-9 expression in 24-hour, 48-hour, and 72-hour sensitization-positive groups in response to TCE treatment. Reverse transcription-polymerase chain reaction detected C3 messenger RNA expression in the liver, and this was significantly increased in 24-hour and 48-hour sensitization-positive groups with a transient reduction at 72 hours. These results provide the first experimental evidence that complement activation may play a key role in the generation and progression of immune-mediated hepatic injury by exposure to TCE.

IATA for skin sensitization potential – 1 out of 2 or 2 out of 3? ...

EPA Pesticide Factsheets

To meet EU regulatory requirements and to avoid or minimize animal testing, there is a need for non-animal methods to assess skin sensitization potential. Given the complexity of the skin sensitization endpoint, there is an expectation that integrated testing and assessment approaches (IATA) will need to be developed which rely on assays representing key events in the pathway. Three non-animal assays have been formally validated: the direct peptide reactivity assay (DPRA), the KeratinoSensTM assay and the h-CLAT assay. At the same time, there have been many efforts to develop IATA with the “2 out of 3” approach attracting much attention whereby a chemical is classified on the basis of the majority outcome. A set of 271 chemicals with mouse, human and non-animal sensitization test data was evaluated to compare the predictive performances of the 3 individual non-animal assays, their binary combinations and the ‘2 out of 3’ approach. The analysis revealed that the most predictive approach was to use both the DPRA and h-CLAT: 1. Perform DPRA – if positive, classify as a sensitizer; 2. If negative, perform h-CLAT – a positive outcome denotes a sensitizer, a negative, a non-sensitizer. With this approach, 83% (LLNA) and 93% (human) of the non-sensitizer predictions were correct, in contrast to the ‘2 out of 3’ approach which had 69% (LLNA) and 79% (human) of non-sensitizer predictions correct. The views expressed are those of the authors and do not ne

A novel in chemico method to detect skin sensitizers in highly diluted reaction conditions.

PubMed

Yamamoto, Yusuke; Tahara, Haruna; Usami, Ryota; Kasahara, Toshihiko; Jimbo, Yoshihiro; Hioki, Takanori; Fujita, Masaharu

2015-11-01

The direct peptide reactivity assay (DPRA) is a simple and versatile alternative method for the evaluation of skin sensitization that involves the reaction of test chemicals with two peptides. However, this method requires concentrated solutions of test chemicals, and hydrophobic substances may not dissolve at the concentrations required. Furthermore, hydrophobic test chemicals may precipitate when added to the reaction solution. We previously established a high-sensitivity method, the amino acid derivative reactivity assay (ADRA). This method uses novel cysteine (NAC) and novel lysine derivatives (NAL), which were synthesized by introducing a naphthalene ring to the amine group of cysteine and lysine residues. In this study, we modified the ADRA method by reducing the concentration of the test chemicals 100-fold. We investigated the accuracy of skin sensitization predictions made using the modified method, which was designated the ADRA-dilutional method (ADRA-DM). The predictive accuracy of the ADRA-DM for skin sensitization was 90% for 82 test chemicals which were also evaluated via the ADRA, and the predictive accuracy in the ADRA-DM was higher than that in the ADRA and DPRA. Furthermore, no precipitation of test compounds was observed at the initiation of the ADRA-DM reaction. These results show that the ADRA-DM allowed the use of test chemicals at concentrations two orders of magnitude lower than that possible with the ADRA. In addition, ADRA-DM does not have the restrictions on test compound solubility that were a major problem with the DPRA. Therefore, the ADRA-DM is a versatile and useful method. Copyright © 2015 John Wiley & Sons, Ltd.

Estimation of the safe use concentrations of the preservative 1,2-benzisothiazolin-3-one (BIT) in consumer cleaning products and sunscreens.

PubMed

Novick, Rachel M; Nelson, Mindy L; Unice, Kenneth M; Keenan, James J; Paustenbach, Dennis J

2013-06-01

1,2-Benzisothiazolin-3-one (BIT; CAS # 2634-33-5) is a preservative used in consumer products. Dermal exposure to BIT at sufficient dose and duration can produce skin sensitization and allergic contact dermatitis in animals and susceptible humans.The purpose of this study is to derive a maximal concentration of BIT in various consumer products that would result in exposures below the No Expected Sensitization Induction Level (NESIL), a dose below which skin sensitization should not occur. A screening level exposure estimate was performed for several product use scenarios with sunscreen, laundry detergent, dish soap, and spray cleaner. We calculated that BIT concentrations below the following concentrations of 0.0075%, 0.035%, 0.035%, 0.021% in sunscreen, laundry detergent, dish soap, and spray cleaner, respectively, are unlikely to induce skin sensitization. We completed a pilot study consisting of bulk sample analysis of one representative product from each category labelled as containing BIT, and found BIT concentrations of 0.0009% and 0.0027% for sunscreen and dish soap, respectively. BIT was not detected in the laundry detergent and spray cleaner products above the limit of detection of 0.0006%. Based on publically available data for product formulations and our results, we were able to establish that cleaning products and sunscreens likely contain BIT at concentrations similar to or less than our calculated maximal safe concentrations and that exposures are unlikely to induce skin sensitization in most users. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cocamidopropyl betaine.

PubMed

Jacob, Sharon E; Amini, Sadegh

2008-01-01

Cocamidopropyl betaine (CAPB) is an amphoteric synthetic detergent that has been increasingly used in cosmetics and personal hygiene products (eg, shampoos, contact lens solutions, toothpaste detergents, makeup removers, bath gels, skin care products, cleansers, liquid soaps, antiseptics, and gynecologic and anal hygiene products) because it induces relatively mild skin irritation. Delayed T-cell-mediated type IV hypersensitivity reactions to CAPB have been reported, and contact sensitization prevalence is estimated at between 3.0 and 7.2%. The increasing rates of sensitization led to CAPB's being named Allergen of the Year in 2004. Related impurities rendered during the manufacturing process (such as amidoamine and dimethylaminopropylamine) are thought to play a role in sensitization.

Effects of automobile steering characteristics on driver/vehicle system performance in discrete maneuvers

NASA Technical Reports Server (NTRS)

Klein, R. H.; Mcruer, D. T.

1975-01-01

A series of discrete maneuver tasks were used to evaluate the effects of steering gain and directional mode dynamic parameters on driver/vehicle responses. The importance and ranking of these parameters were evaluated through changes in subjective driver ratings and performance measures obtained from transient maneuvers such as a double lane change, an emergency lane change, and an unexpected obstacle. The unexpected obstacle maneuver proved more sensitive to individual driver differences than to vehicle differences. Results were based on full scale tests with an experienced test driver evaluating many different dynamic configurations plus seventeen ordinary drivers evaluating six key configurations.

Haemangiosarcoma in a captive Asiatic lion (Panthera leo persica)

PubMed Central

Vercammen, F.; Brandt, J.; Brantegem, L. Van; Bosseler, L.; Ducatelle, R.

2015-01-01

A 2.7-year-old male captive Asiatic lion (Panthera leo persica) died unexpectedly without preceding symptoms. Gross necropsy revealed liver and lung tumours, which proved to be haemangiosarcomas by histopathology. Some of the liver tumours were ruptured, leading to massive intra-abdominal haemorrhage and death. Haemangiosarcomas are rare in domestic and exotic felids, occurring in skin, thoracic-abdominal cavity and bones. Although these tumours mainly appear to be occurring in older cats, they are sometimes observed in younger animals, as in the present case. This is the first description of haemangiosarcoma in a young Asiatic lion. PMID:26623366

In vivo imaging of human burn injuries with polarization-sensitive optical coherence tomography

NASA Astrophysics Data System (ADS)

Kim, Ki Hean; Pierce, Mark C.; Maguluri, Gopi; Park, B. Hyle; Yoon, Sang June; Lydon, Martha; Sheridan, Robert; de Boer, Johannes F.

2012-06-01

The accurate determination of burn depth is critical in the clinical management of burn wounds. Polarization-sensitive optical coherence tomography (PS-OCT) has been proposed as a potentially non-invasive method for determining burn depth by measuring thermally induced changes in the structure and birefringence of skin, and has been investigated in pre-clinical burn studies with animal models and ex vivo human skin. In this study, we applied PS-OCT to the in-vivo imaging of two pediatric burn patients. Deep and superficial burned skins along with contralateral controls were imaged in 3D. The imaging size was 8 mm×6 mm×2 mm in width, length, and depth in the air respectively, and the imaging time was approximately 6 s per volume. Superficially burned skins exhibited the same layered structure as the contralateral controls, but more visible vasculature and reduced birefringence compared to the contralateral controls. In contrast, a deeply burned skin showed loss of the layered structure, almost absent vasculature, and smaller birefringence compared to superficial burns. This study suggested the vasculature and birefringence as parameters for characterizing burn wounds.

Immunological studies in patients with Crohn's disease.

PubMed Central

MacPherson, B R; Albertini, R J; Beeken, W L

1976-01-01

An investigation of immunological parameters was conducted in 38 patients with Crohn's disease. The immunological tests employed included skin tests with dinitrochlorobenzene and a battery of common skin test antigens, lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen, serum immunoglobulins, and absolute lymphocyte counts. Crohn's disease patients were divided into two groups, those treated with immunosuppressive drugs and those not receiving immunosuppressive medications. The latter group was subdivided into patients with active and inactive disease. Immunosuppressed patients with Crohn's disease did not develop sensitivity to dinitrochlorobenzene and had mildly depressed skin test reactivity to common skin test procedures. Non-immunosuppressed patients with active Crohn's disease also reacted less frequently to common skin test antigens, but 16 of 17 such patients developed sensitivity to dinitrochlorobenzene. Lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen was normal in all groups of patients with Crohn's disease. However, when suboptimal incubation periods were used with phytohaemagglutinin stimulation, there was a significant difference between Crohn's disease patients and controls. Serum immunoglobulin levels and absolute lymphocyte counts were normal in all Crohn's disease patients. We conclude that immunity in Crohn's disease is qualitatively normal. PMID:1261880

Changes in force and calcium sensitivity in the developing avian heart.

PubMed

Godt, R E; Fogaça, R T; Nosek, T M

1991-11-01

The aim of this study was to characterize the development of the contractile properties of intact and chemically skinned muscle from chicken heart and to compare these characteristics with those of developing mammalian heart reported by others. Small trabeculae were dissected from left ventricles of Arbor Acre chickens between embryonic day 7 and young adulthood (7 weeks post-hatching). At all ages, increasing extracellular calcium (0.45-3.6 mM) progressively increased twitch force of electrically stimulated trabeculae. Twitch force at 1.8 mM extracellular calcium, normalized to cross-sectional area, increased to a maximum at 1 day post-hatching, remained constant through 3 weeks post-hatching, but then decreased at 7 weeks post-hatching. The maximal calcium-activated force of trabeculae chemically skinned with Triton X-100 detergent increased to a maximum 2 days before the time of hatching and was not significantly changed up to 7 weeks post-hatching. Over the ages studied, average twitch force in 1.8 mM calcium was between 26 and 66% of maximal calcium-activated force after skinning, suggesting that the contractile apparatus is not fully activated during the twitch in normal Ringer. In skinned trabeculae, the calcium sensitivity of the contractile apparatus was higher in the embryo than in the young adult. These age-dependent changes in calcium sensitivity are correlated with isoform switching in troponin T. A decrease in pH from 7.0 to 6.5 decreased the calcium sensitivity of the contractile apparatus to a greater degree in skinned trabeculae from young adult hearts than in those from embryonic hearts. This change in susceptibility to acidosis is temporally associated with isoform switching in troponin I.(ABSTRACT TRUNCATED AT 250 WORDS)

The male beard hair and facial skin - challenges for shaving.

PubMed

Maurer, M; Rietzler, M; Burghardt, R; Siebenhaar, F

2016-06-01

The challenge of shaving is to cut the beard hair as closely as possible to the skin without unwanted effects on the skin. To achieve this requires the understanding of beard hair and male facial skin biology as both, the beard hair and the male facial skin, contribute to the difficulties in obtaining an effective shave without shaving-induced skin irritation. Little information is available on the biology of beard hairs and beard hair follicles. We know that, in beard hairs, the density, thickness, stiffness, as well as the rates of elliptical shape and low emerging angle, are high and highly heterogeneous. All of this makes it challenging to cut it, and shaving techniques commonly employed to overcome these challenges include shaving with increased pressure and multiple stroke shaving, which increase the probability and extent of shaving-induced skin irritation. Several features of male facial skin pose problems to a perfect shave. The male facial skin is heterogeneous in morphology and roughness, and male skin has a tendency to heal slower and to develop hyperinflammatory pigmentation. In addition, many males exhibit sensitive skin, with the face most often affected. Finally, the hair follicle is a sensory organ, and the perifollicular skin is highly responsive to external signals including mechanical and thermal stimulation. Perifollicular skin is rich in vasculature, innervation and cells of the innate and adaptive immune system. This makes perifollicular skin a highly responsive and inflammatory system, especially in individuals with sensitive skin. Activation of this system, by shaving, can result in shaving-induced skin irritation. Techniques commonly employed to avoid shaving-induced skin irritation include shaving with less pressure, pre- and post-shave skin treatment and to stop shaving altogether. Recent advances in shaving technology have addressed some but not all of these issues. A better understanding of beard hairs, beard hair follicles and male facial skin is needed to develop novel and better approaches to overcome the challenge of shaving. This article covers what is known about the physical properties of beard hairs and skin and why those present a challenge for blade and electric shaving, respectively. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Cross-well slug testing in unconfined aquifers: A case study from the Sleepers River Watershed, Vermont

USGS Publications Warehouse

Belitz, K.; Dripps, W.

1999-01-01

Normally, slug test measurements are limited to the well in which the water level is perturbed. Consequently, it is often difficult to obtain reliable estimates of hydraulic properties, particularly if the aquifer is anisotropic or if there is a wellbore skin. In this investigation, we use partially penetrating stress and observation wells to evaluate specific storage, radial hydraulic conductivity and anisotropy of the aquifer, and the hydraulic conductivity of the borehole skin. The study site is located in the W9 subbasin of the Sleepers River Research Watershed, Vermont. At the site, ~3 m of saturated till are partially penetrated by a stress well located in the center of the unconfined aquifer and six observation wells located above, below, and at the depth of the stress well at radial distances of 1.2 and 2.4 m. The observation wells were shut in with inflatable packers. The semianalytical solution of Butler (1995) was used to conduct a sensitivity analysis and to interpret slug test results. The sensitivity analysis indicates that the response of the stress well is primarily sensitive to radial hydraulic conductivity, less sensitive to anisotropy and the conductivity of the borehole skin, and nearly insensitive to specific storage. In contrast, the responses of the observation wells are sensitive to all four parameters. Interpretation of the field data was facilitated by generating type curves in a manner analogous to the method of Cooper et al. (1967). Because the value of radial hydraulic conductivity is obtained from a match point, the number of unknowns is reduced to three. The estimated values of radial hydraulic conductivity and specific storage are comparable to those derived from the methods of Bouwer and Rice (1976) and Cooper et al. (1967). The values and skin conductivity, however, could not have been obtained without the use of observation wells.Normally, slug test measurements are limited to the well in which the water level is perturbed. Consequently, it is often difficult to obtain reliable estimates of hydraulic properties, particularly if the aquifer is anisotropic or if there is a wellbore skin. In this investigation, we use partially penetrating stress and observation wells to evaluate specific storage, radial hydraulic conductivity and anisotropy of the aquifer, and the hydraulic conductivity of the borehole skin. The study site is located in the W9 subbasin of the Sleepers River Research Watershed, Vermont. At the site, approximately 3 m of saturated till are partially penetrated by a stress well located in the center of the unconfined aquifer and six observation wells located above, below, and at the depth of the stress well at radial distances of 1.2 and 2.4 m. The observation wells were shut in with inflatable packers. The semianalytical solution of Buffer (1995) was used to conduct a sensitivity analysis and to interpret slug test results. The sensitivity analysis indicates that the response of the stress well is primarily sensitive to radial hydraulic conductivity, less sensitive to anisotropy and the conductivity of the borehole skin, and nearly insensitive to specific storage. In contrast, the responses of the observation wells are sensitive to all four parameters. Interpretation of the field data was facilitated by generating type curves in a manner analogous to the method of Cooper et al. (1967). Because the value of radial hydraulic conductivity is obtained from a match point, the number of unknowns is reduced to three. The estimated values of radial hydraulic conductivity and specific storage are comparable to those derived from the methods of Bouwer and Rice (1976) and Cooper et al. (1967). The values and skin conductivity, however, could not have been obtained without the use of observation wells.

Imaging of biophoton emission from electrostimulated skin acupuncture point jg4: effect of light enhancers.

PubMed

Slawinski, Janusz; Gorski, Zbigniew

2008-05-01

Using an ultrasensitive CCD camera, an extremely low light intensity from the acupuncture-sensitive point JG4 at the left hand was recorded. As the intensity of the light was very weak and the time of electrostimulation exceeded the recommended period, the quality of biophoton images was poor. Chemiluminescent and fluorescent hydrophilic, hydrophobic and amphyphilic molecular probes were used to: (i) ensure penetration of probes into skin, (ii) enhance the intensity of BP emission, (iii) shorten time and (iv) obtain information about mechanisms of biophotons generation in EAP-sensitive points and channels. The results obtained partially fulfilled expectations and indicate on the necessity to elaborate special techniques of probes deposition on the skin.

Validation of the cephalosporin intradermal skin test for predicting immediate hypersensitivity: a prospective study with drug challenge.

PubMed

Yoon, S-Y; Park, S Y; Kim, S; Lee, T; Lee, Y S; Kwon, H-S; Cho, Y S; Moon, H-B; Kim, T-B

2013-07-01

Cephalosporin is a major offending agent in terms of drug hypersensitivity along with penicillin. Cephalosporin intradermal skin tests (IDTs) have been widely used; however, their validity for predicting immediate hypersensitivity has not been studied. This study aimed to determine the predictive value of cephalosporin intradermal skin testing before administration of the drug. We prospectively conducted IDTs with four cephalosporins, one each of selected first-, second-, third-, or fourth-generation cephalosporins: ceftezol; cefotetan or cefamandole; ceftriaxone or cefotaxime; and flomoxef, respectively, as well as with penicillin G. After the skin test, whatever the result, one of the tested cephalosporins was administered intravenously and the patient was carefully observed. We recruited 1421 patients who required preoperative cephalosporins. Seventy-four patients (74/1421, 5.2%) were positive to at least one cephalosporin. However, none of responders had immediate hypersensitivity reactions after a challenge dose of the same or different cephalosporin, which were positive in the skin test. Four patients who suffered generalized urticaria and itching after challenge gave negative skin tests for the corresponding drug. The IDT for cephalosporin had a sensitivity of 0%, a specificity of 97.5%, a negative predictive value of 99.7%, and a positive predictive value (PPV) of 0%, when challenged with the same drugs that were positive in the skin test. Routine skin testing with a cephalosporin before its administration is not useful for predicting immediate hypersensitivity because of the extremely low sensitivity and PPV of the skin test (CRIS registration no. KCT0000455). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detecting skin malignancy using elastic light scattering spectroscopy

NASA Astrophysics Data System (ADS)

Canpolat, Murat; Akman, Ayşe; Çiftçioğlu, M. Akif; Alpsoy, Erkan

2007-07-01

We have used elastic light scattering spectroscopy to differentiate between malign and benign skin lesions. The system consists of a UV spectrometer, a single optical fiber probe and a laptop. The single optical fiber probe was used for both delivery and detection of white light to tissue and from the tissue. The single optical fiber probe received singly scattered photons rather than diffused photons in tissue. Therefore, the spectra are correlated with morphological differences of the cells. It has been shown that spectra of malign skin lesions are different than spectra of benign skin lesions. While slopes of the spectra taken on benign lesions or normal skin tissues were positive, slopes of the spectra taken on malign skin lesions tissues were negative. In vivo experiments were conducted on 20 lesions from 18 patients (11 men with mean age of 68 +/- 9 years and 7 women with mean age of 52 +/- 20 years) applied to the Department of Dermatology and Venerology. Before the biopsy, spectra were taken on the lesion and adjacent (approximately 1 cm distant) normal-appearing skin. Spectra of the normal skin were used as a control group. The spectra were correlated to the pathology results with sensitivity and specificity of 82% and 89%, respectively. Due to small diameter of fiber probe and limited number of sampling (15), some positive cases are missed, which is lowered the sensitivity of the system. The results are promising and could suggest that the system may be able to detect malignant skin lesion non-invasively and in real time.

Triclosan Induces Thymic Stromal Lymphopoietin in Skin Promoting Th2 Allergic Responses

PubMed Central

Marshall, Nikki B.; Lukomska, Ewa; Long, Carrie M.; Kashon, Michael L.; Sharpnack, Douglas D.; Nayak, Ajay P.; Anderson, Katie L.; Meade, B. Jean; Anderson, Stacey E.

2016-01-01

Triclosan is an antimicrobial chemical incorporated into many personal, medical and household products. Approximately, 75% of the U.S. population has detectable levels of triclosan in their urine, and although it is not typically considered a contact sensitizer, recent studies have begun to link triclosan exposure with augmented allergic disease. We examined the effects of dermal triclosan exposure on the skin and lymph nodes of mice and in a human skin model to identify mechanisms for augmenting allergic responses. Triclosan (0%–3%) was applied topically at 24-h intervals to the ear pinnae of OVA-sensitized BALB/c mice. Skin and draining lymph nodes were evaluated for cellular responses and cytokine expression over time. The effects of triclosan (0%–0.75%) on cytokine expression in a human skin tissue model were also examined. Exposure to triclosan increased the expression of TSLP, IL-1β, and TNF-α in the skin with concomitant decreases in IL-25, IL-33, and IL-1α. Similar changes in TSLP, IL1B, and IL33 expression occurred in human skin. Topical application of triclosan also increased draining lymph node cellularity consisting of activated CD86+GL-7+ B cells, CD80+CD86+ dendritic cells, GATA-3+OX-40+IL-4+IL-13+ Th2 cells and IL-17 A+ CD4 T cells. In vivo antibody blockade of TSLP reduced skin irritation, IL-1β expression, lymph node cellularity, and Th2 responses augmented by triclosan. Repeated dermal exposure to triclosan induces TSLP expression in skin tissue as a potential mechanism for augmenting allergic responses. PMID:26048654

Safety and efficacy of personal care products containing colloidal oatmeal.

PubMed

Criquet, Maryline; Roure, Romain; Dayan, Liliane; Nollent, Virginie; Bertin, Christiane

2012-01-01

Colloidal oatmeal is a natural ingredient used in the formulation of a range of personal care products for relief of skin dryness and itchiness. It is also used as an adjunctive product in atopic dermatitis. The safety of personal care products used on vulnerable skin is of particular importance and the risk of developing further skin irritations and/or allergies should be minimized. In a series of studies, we tested the safety of personal care products containing oatmeal (creams, cleansers, lotions) by assessing their irritant/allergenic potential on repeat insult patch testing, in safety-in-use and ocular studies using subjects with nonsensitive and sensitive skin. We also tested the skin moisturizing and repair properties of an oatmeal-containing skin care product for dry skin. We found that oatmeal-containing personal care products had very low irritant potential as well as a very low allergenic sensitization potential. Low-level reactions were documented in 1.0% of subjects during the induction phase of repeat insult patch testing; one of 2291 subjects developed a persistent but doubtful low-level reaction involving edema during the challenge phase in repeat insult patch testing. No allergies were reported by 80 subjects after patch testing after in-use application. Sustained skin moisturizing was documented in subjects with dry skin that lasted up to 2 weeks after product discontinuation. Our results demonstrate that colloidal oatmeal is a safe and effective ingredient in personal care products. No allergies were reported by consumers of 445,820 products sold during a 3-year period.

Safety and efficacy of personal care products containing colloidal oatmeal

PubMed Central

Criquet, Maryline; Roure, Romain; Dayan, Liliane; Nollent, Virginie; Bertin, Christiane

2012-01-01

Background Colloidal oatmeal is a natural ingredient used in the formulation of a range of personal care products for relief of skin dryness and itchiness. It is also used as an adjunctive product in atopic dermatitis. The safety of personal care products used on vulnerable skin is of particular importance and the risk of developing further skin irritations and/or allergies should be minimized. Methods In a series of studies, we tested the safety of personal care products containing oatmeal (creams, cleansers, lotions) by assessing their irritant/allergenic potential on repeat insult patch testing, in safety-in-use and ocular studies using subjects with nonsensitive and sensitive skin. We also tested the skin moisturizing and repair properties of an oatmeal-containing skin care product for dry skin. Results We found that oatmeal-containing personal care products had very low irritant potential as well as a very low allergenic sensitization potential. Low-level reactions were documented in 1.0% of subjects during the induction phase of repeat insult patch testing; one of 2291 subjects developed a persistent but doubtful low-level reaction involving edema during the challenge phase in repeat insult patch testing. No allergies were reported by 80 subjects after patch testing after in-use application. Sustained skin moisturizing was documented in subjects with dry skin that lasted up to 2 weeks after product discontinuation. Conclusion Our results demonstrate that colloidal oatmeal is a safe and effective ingredient in personal care products. No allergies were reported by consumers of 445,820 products sold during a 3-year period. PMID:23204849

Measuring the penetration of a skin sensitizer and its delivery vehicles simultaneously with confocal Raman spectroscopy.

PubMed

Bonnist, E Y M; Gorce, J-P; Mackay, C; Pendlington, R U; Pudney, P D A

2011-01-01

Among the factors determining the propensity of a chemical to induce skin allergy are the penetration into skin and the kinetics of ingress. Confocal Raman spectroscopy can provide such information as it enables direct, spatially resolved measurement of the skin and of any chemical uptake. Several chemicals can be monitored at once, and the method is non-destructive (light in, light out) so that the skin can be kept intact for repeated and continuous measurement. Raman spectroscopy was used to follow the penetration of 2.5 weight percent trans-cinnamaldehyde and its delivery vehicle into skin in vitro, up to 24 h after topical application. A custom-made Bronaugh-type diffusion cell that was suitable for the Raman experiment was used. Four different vehicles were tested: absolute ethanol, 50% aqueous ethanol, propylene glycol and acetone:olive oil (4:1); these gave different time scales for cinnamaldehyde penetration. The acetone:olive oil vehicle phase-separated on the skin surface and the cinnamaldehyde penetrated at different rates in the different phases, which may be of significance since this is the preferred solvent for the local lymph node assay (an in vivo animal test used to generate hazard information on skin sensitization). In conclusion, the Raman method gives valuable detailed information on chemical ingress, clearly differentiates between different delivery rates and allows solvent monitoring alongside the chemical of interest. Copyright © 2011 S. Karger AG, Basel.

What we miss if standard panel is used for skin prick testing?

PubMed

Cavkaytar, Ozlem; Buyuktiryaki, Betul; Sag, Erdal; Soyer, Ozge; Sekerel, Bulent E

2015-09-01

Although standard skin prick test (SPT) panels are crucial for routine investigation of sensitization in daily clinical practice, it has limitations in terms of missing allergens. To find out sensitization rates (SR)s to additional panel of allergens and their relative contributions in allergic diseases. SPTs with a battery of aeroallergens [tree pollen (A.glutinosa, C.arizonica, J.communis, T.platyphyllos, R.pseudoacacia), weed pollen (R.acetosa, U.dioica, A.artemisifolia), smut mix, yeast mix, storage mites (SM) (B.tropicalis, L.destructor, T.putrescentiae, A.siro), mouse and budgerigar epithelia], were performed to 318 participants (6-18 years) who were previously identified to be sensitized to at least one of the aeroallergens found in standard battery. Forty percent of participants were sensitized to at least one additional aerollergen. Three most frequent sensitizations were to B.tropicalis (11.3%), R.pseudoacacia (9.7%) and L.destructor (8.2%). SR for tree pollen increased from 6.9% to 19.8%, for mites increased from 26.3% to 31.6% and for moulds increased from 5.3% to 9.4% with addition of respective group of other allergens to battery. Furthermore, higher rates for additional tree pollen sensitization was found among patients with "only AR" (21%) compared to patients with "only asthma" (4.6%, p =0.006), contrarily higher rates for SM sensitization was found among patients with "only asthma" (20%) compared to patients with "only AR" (3.2%, p =0.003) CONCLUSIONS: Though some of sensitizations may occur due to cross-reactivity, almost 40% of sensitized children were also co-sensitized to the additional allergens tested. Physicians should consider further steps when a negative or inconsistent result is achieved through a standard skin test panel.

SENSITIZATION AND TOLERANCE WITH EPISODIC (WEEKLY) NICOTINE ON MOTOR ACTIVITY IN RATS.

EPA Science Inventory

These studies grew out of an unexpected finding from investigations of the neurobehavioral toxicity of PCBs. This paper shows that episodic, or recurring intermittent acute exposures to nicotine produce dramatic and long-lasting changes in the motor activity of laboratory rats. ...

Amoxicillin rash in patients with infectious mononucleosis: evidence of true drug sensitization.

PubMed

Ónodi-Nagy, Katinka; Kinyó, Ágnes; Meszes, Angéla; Garaczi, Edina; Kemény, Lajos; Bata-Csörgő, Zsuzsanna

2015-01-01

It hasn't been clearly understood yet whether sensitization to antibiotics, the virus itself or transient loss of drug tolerance due to the virus, is responsible for the development of maculopapular exanthems following amoxicillin intake in patients with infectious mononucleosis. We aimed to examine whether sensitization to penicillin developed among patients with skin rash following amoxicillin treatment within infectious mononucleosis. Ten patients were investigated for drug sensitization by lymphocyte transformation test and six patients were further tested by prick-, intradermal and patch tests employing the penicillin's main antigens. Lymphocyte transformation test showed negative results with amoxicillin, while one patient had positive reaction to cefixime. Six patients with suspected sensitization to amoxicillin were then investigated by in vivo tests. Prick tests were negative in all six patients, but the intradermal tests showed positive reactions in four patients. Our data demonstrate that in vitro testing is not sensitive enough in determining drug sensitization to penicillin. In vivo tests should be performed to detect sensitization and indeed with skin tests our results confirmed that sensitization to aminopenicillin may develop within infectious mononucleosis.

Quantitation of peptides from non-invasive skin tapings using isotope dilution and tandem mass spectrometry.

PubMed

Reisdorph, Nichole; Armstrong, Michael; Powell, Roger; Quinn, Kevin; Legg, Kevin; Leung, Donald; Reisdorph, Rick

2018-05-01

Previous work from our laboratories utilized a novel skin taping method and mass spectrometry-based proteomics to discover clinical biomarkers of skin conditions; these included atopic dermatitis, Staphylococcus aureus colonization, and eczema herpeticum. While suitable for discovery purposes, semi-quantitative proteomics is generally time-consuming and expensive. Furthermore, depending on the method used, discovery-based proteomics can result in high variation and inadequate sensitivity to detect low abundant peptides. Therefore, we strove to develop a rapid, sensitive, and reproducible method to quantitate disease-related proteins from skin tapings. We utilized isotopically-labeled peptides and tandem mass spectrometry to obtain absolute quantitation values on 14 peptides from 7 proteins; these proteins had shown previous importance in skin disease. The method demonstrated good reproducibility, dynamic range, and linearity (R 2  > 0.993) when n = 3 standards were analyzed across 0.05-2.5 pmol. The method was used to determine if differences exist between skin proteins in a small group of atopic versus non-atopic individuals (n = 12). While only minimal differences were found, peptides were detected in all samples and exhibited good correlation between peptides for 5 of the 7 proteins (R 2  = 0.71-0.98). This method can be applied to larger cohorts to further establish the relationships of these proteins to skin disease. Copyright © 2017. Published by Elsevier B.V.

Effects of pressure, cold and gloves on hand skin temperature and manual performance of divers.

PubMed

Zander, Joanna; Morrison, James

2008-09-01

Cold water immersion and protective gloves are associated with decreased manual performance. Although neoprene gloves slow hand cooling, there is little information on whether they provide sufficient protection when diving in cold water. Nine divers wearing three-fingered neoprene gloves and dry suits were immersed in water at 25 and 4 degrees C, at depths of 0.4 msw (101 kPa altitude adjusted) and 40 msw (497 kPa) in a hyperbaric chamber. Skin temperatures were measured at the fingers, hand, forearm, chest and head. Grip strength, tactile sensitivity and manual dexterity were measured at three time intervals. There was an exponential decay in finger and back of hand skin temperatures with exposure time in 4 degrees C water. Finger and back of hand skin temperatures were lower at 40 msw than at 0.4 msw (P < 0.05). There was no effect of pressure or temperature on grip strength. Tactile sensitivity decreased linearly with finger skin temperature at both pressures. Manual dexterity was not affected by finger skin temperature at 0.4 msw, but decreased with fall in finger skin temperature at 40 msw. Results show that neoprene gloves do not provide adequate thermal protection in 4 degrees C water and that impairment of manual performance is dependent on the type of task, depth and exposure time.

Skin sensitization quantitative risk assessment for occupational exposure of hairdressers to hair dye ingredients.

PubMed

Goebel, Carsten; Diepgen, Thomas L; Blömeke, Brunhilde; Gaspari, Anthony A; Schnuch, Axel; Fuchs, Anne; Schlotmann, Kordula; Krasteva, Maya; Kimber, Ian

2018-06-01

Occupational exposure of hairdressers to hair dyes has been associated with the development of allergic contact dermatitis (ACD) involving the hands. p-Phenylenediamine (PPD) and toluene-2,5-diamine (PTD) have been implicated as important occupational contact allergens. To conduct a quantitative risk assessment for the induction of contact sensitization to hair dyes in hairdressers, available data from hand rinsing studies following typical occupational exposure conditions to PPD, PTD and resorcinol were assessed. By accounting for wet work, uneven exposure and inter-individual variability for professionals, daily hand exposure concentrations were derived. Secondly, daily hand exposure was compared with the sensitization induction potency of the individual hair dye defined as the No Expected Sensitization Induction Levels (NESIL). For PPD and PTD hairdresser hand exposure levels were 2.7 and 5.9 fold below the individual NESIL. In contrast, hand exposure to resorcinol was 50 fold below the NESIL. Correspondingly, the risk assessment for PPD and PTD indicates that contact sensitization may occur, when skin protection and skin care are not rigorously applied. We conclude that awareness of health risks associated with occupational exposure to hair dyes, and of the importance of adequate protective measures, should be emphasized more fully during hairdresser education and training. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of Phototoxic and Skin Sensitization Potentials of PLA2-Free Bee Venom

PubMed Central

Heo, Yunwi; Pyo, Min-Jung; Bae, Seong Kyeong; Lee, Hyunkyoung; Kwon, Young Chul; Kim, Je Hein; Kim, Bokyung; Kim, Choul Goo; Kang, Changkeun; Kim, Euikyung

2015-01-01

Bee venom (BV) from honey bee (Apis mellifera L.) has been used in oriental medicine and cosmetic ingredients because of its diverse pharmacological activities. In many studies, among BV components, phospholipase A2 (PLA2) is known as a major player in BV-induced allergic reaction. Therefore, we removed PLA2 from BV using ultrafiltration and then investigated in vitro phototoxicity and in vivo skin sensitization of PLA2-free BV (PBV) in comparison with regular BV. The 3T3 neutral red uptake phototoxicity assay can be appropriated to identify the phototoxic effect of a test substance upon the exposure of ultraviolet A. Chlorpromazine, a positive control, showed high levels of photoirritation factor and mean photo effect values, while BV and PBV had less of these values. Local lymph node assay is an alternative method to evaluate skin sensitization potential of chemicals. BALB/c mice were treated with p-phenylenediamine (PPD, positive control), BV, or PBV. In all of PPD concentrations, stimulation indexes (SI) as sensitizing potential of chemicals were ≥1.6, determined to be sensitizer, while SI levels of BV and PBV were below 1.6. Thus, based on these findings, we propose that both BV and PBV are nonphototoxic compounds and nonsensitizers. PMID:26347784

Skin Testing for Allergic Rhinitis: A Health Technology Assessment

PubMed Central

Kabali, Conrad; Chan, Brian; Higgins, Caroline; Holubowich, Corinne

2016-01-01

Background Allergic rhinitis is the most common type of allergy worldwide. The accuracy of skin testing for allergic rhinitis is still debated. This health technology assessment had two objectives: to determine the diagnostic accuracy of skin-prick and intradermal testing in patients with suspected allergic rhinitis and to estimate the costs to the Ontario health system of skin testing for allergic rhinitis. Methods We searched All Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database for studies that evaluated the diagnostic accuracy of skin-prick and intradermal testing for allergic rhinitis using nasal provocation as the reference standard. For the clinical evidence review, data extraction and quality assessment were performed using the QUADAS-2 tool. We used the bivariate random-effects model for meta-analysis. For the economic evidence review, we assessed studies using a modified checklist developed by the (United Kingdom) National Institute for Health and Care Excellence. We estimated the annual cost of skin testing for allergic rhinitis in Ontario for 2015 to 2017 using provincial data on testing volumes and costs. Results We meta-analyzed seven studies with a total of 430 patients that assessed the accuracy of skin-prick testing. The pooled pair of sensitivity and specificity for skin-prick testing was 85% and 77%, respectively. We did not perform a meta-analysis for the diagnostic accuracy of intradermal testing due to the small number of studies (n = 4). Of these, two evaluated the accuracy of intradermal testing in confirming negative skin-prick testing results, with sensitivity ranging from 27% to 50% and specificity ranging from 60% to 100%. The other two studies evaluated the accuracy of intradermal testing as a stand-alone tool for diagnosing allergic rhinitis, with sensitivity ranging from 60% to 79% and specificity ranging from 68% to 69%. We estimated the budget impact of continuing to publicly fund skin testing for allergic rhinitis in Ontario to be between $2.5 million and $3.0 million per year. Conclusions Skin-prick testing is moderately accurate in identifying subjects with or without allergic rhinitis. The diagnostic accuracy of intradermal testing could not be well established from this review. Our best estimate is that publicly funding skin testing for allergic rhinitis costs the Ontario government approximately $2.5 million to $3.0 million per year. PMID:27279928

Skin Testing for Allergic Rhinitis: A Health Technology Assessment.

PubMed

2016-01-01

Allergic rhinitis is the most common type of allergy worldwide. The accuracy of skin testing for allergic rhinitis is still debated. This health technology assessment had two objectives: to determine the diagnostic accuracy of skin-prick and intradermal testing in patients with suspected allergic rhinitis and to estimate the costs to the Ontario health system of skin testing for allergic rhinitis. We searched All Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database for studies that evaluated the diagnostic accuracy of skin-prick and intradermal testing for allergic rhinitis using nasal provocation as the reference standard. For the clinical evidence review, data extraction and quality assessment were performed using the QUADAS-2 tool. We used the bivariate random-effects model for meta-analysis. For the economic evidence review, we assessed studies using a modified checklist developed by the (United Kingdom) National Institute for Health and Care Excellence. We estimated the annual cost of skin testing for allergic rhinitis in Ontario for 2015 to 2017 using provincial data on testing volumes and costs. We meta-analyzed seven studies with a total of 430 patients that assessed the accuracy of skin-prick testing. The pooled pair of sensitivity and specificity for skin-prick testing was 85% and 77%, respectively. We did not perform a meta-analysis for the diagnostic accuracy of intradermal testing due to the small number of studies (n = 4). Of these, two evaluated the accuracy of intradermal testing in confirming negative skin-prick testing results, with sensitivity ranging from 27% to 50% and specificity ranging from 60% to 100%. The other two studies evaluated the accuracy of intradermal testing as a stand-alone tool for diagnosing allergic rhinitis, with sensitivity ranging from 60% to 79% and specificity ranging from 68% to 69%. We estimated the budget impact of continuing to publicly fund skin testing for allergic rhinitis in Ontario to be between $2.5 million and $3.0 million per year. Skin-prick testing is moderately accurate in identifying subjects with or without allergic rhinitis. The diagnostic accuracy of intradermal testing could not be well established from this review. Our best estimate is that publicly funding skin testing for allergic rhinitis costs the Ontario government approximately $2.5 million to $3.0 million per year.

Effect of friction on vibrotactile sensation of normal and dehydrated skin.

PubMed

Chen, S; Ge, S; Tang, W; Zhang, J

2016-02-01

Vibrotactile sensation mediated is highly dependent on surface mechanical and frictional properties. Dehydration of skin could change these properties. To investigate the relationship between friction and vibrotactile sensation of normal and dehydrated skin. Vibrations were firstly measured during surface exploration using a biomimetic sensor. Piglet skin was used as human skin model to study frictional properties for both normal and dehydrated skin using an atomic force microscope on nanoscale and a pin-on-disk tribometer on macroscale. Effect of vibrational frequency on friction and vibrotactile perception was also observed on nano and macro scale for normal and dehydrated skin. The result indicated that dehydrated skin was less sensitive than normal skin. The coefficient of friction of dehydrated skin is smaller than that of normal skin on both nano and macro scale. The coefficient of friction increases as increasing scanning frequencies. There is a positive correlation between coefficient of friction and vibrotactile sensation on nanoscale and macroscale. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Different sensitization to storage mites depending on the co-exposure to house dust mites.

PubMed

Morales, María; Iraola, Victor; Leonor, José Ramón; Bartra, Joan; Rodríguez, Fernando; Boquete, Manuel; Huertas, Ángel Julio; Paniagua, María Josefa; Pinto, Helder; Carnés, Jerónimo

2015-01-01

Co-sensitization to house dust mites (HDMs) and storage mites (SMs) is very frequent, although the clinical relevance is not well established. To describe the pattern of sensitization and immunologic characterization of patients with positive skin prick test reactions to HDMs and SMs in 4 areas of Spain, selected according to high exposure to HDMs and variable exposure to SMs. One hundred sixty-nine individuals with positive skin prick test reactions to HDMs and SMs were included. Specific IgE levels to different mite species and to Der p 1, Der p 2, and Der p 10 were determined. Immunoblots to Dermatophagoides pteronyssinus, Lepidoglyphus destructor, and Tyrophagus putrescentiae extracts were carried out, and allergograms were obtained. Results of different areas were compared. A high rate of polysensitization to SMs was observed, although 12% of participants did not have specific IgE to any SM species. Sensitization to Dermatophagoides species, Der p 2, and L destructor were predominant, although significant differences were observed among areas depending on the grade of exposure to SMs. In areas with high exposure, the SM allergogram showed greater recognition of group 2 allergen. Sensitization patterns to SMs in patients sensitized to HDMs and SMs differ depending on the exposure to SMs. Sensitization, mainly to L destructor, seems to exist in areas with high exposure, possibly with group 2 allergens mainly involved. However, in areas with low SM populations, sensitizations observed by skin prick testing appear to be related to HDM exposure. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Quantifying human susceptibility to contact sensitization; risk assessments now and in the future.

PubMed

Friedmann, Peter S; Pickard, Christopher

2010-11-01

Assessment and quantification of the risk that a chemical will induce allergic contact sensitization presently depend heavily on background data from animal tests. Following the banning of animal testing of chemicals used in cosmetics and personal products in Europe after 2013, alternative approaches will be required. The chemical properties likely to make a given compound a sensitizer can be determined in vitro with reasonable certainty, but confirmation that it is a sensitizer comes only from in vivo exposure to it. Assessment of the sensitization risks involves consideration of how much of the compound will be applied to skin, for how long, and at which sites. However, the in vivo interactions of the chemical with the skin, with regard to its permeability, and biochemical and immune defences, cannot be predicted from a theoretical position. The xenobiotic-metabolizing enzymes and antioxidant defences may degrade chemicals or may generate potentially immunogenic haptens. Many factors can modify the skin and the immune response, including sex, race, age, genetic programming of epidermal permeability, and/or antioxidant and drug-metabolizing pathways. The only certain way to evaluate whether a chemical will sensitize is in vivo exposure, and the nature of the hazard is revealed by determination of the dose-response relationship. This review shows there is still a serious gap in our understanding of the biological factors and variables involved in conferring resistance or susceptibility to the development of allergic sensitization by chemicals. We are not yet in a position to predict sensitization by chemicals from a theoretical starting point. © 2010 John Wiley & Sons A/S.

Influence of skin cold sensation threshold in the occurrence of dental sensitivity during dental bleaching: a placebo controlled clinical trial.

PubMed

Rahal, Vanessa; Gallinari, Marjorie de Oliveira; Barbosa, Juliana Stuginski; Martins-Junior, Reynaldo Leite; Santos, Paulo Henrique Dos; Cintra, Luciano Tavares Angelo; Briso, André Luiz Fraga

2018-01-18

This study verified the occurrence of dental sensitivity in patients submitted to a 35% hydrogen peroxide based product (Whiteness HP Maxx 35% - FGM), skin cold sensation threshold (SCST) and its influence on dental sensitivity. Sixty volunteers were divided into 4 groups (n = 15), according to SCST (low: GI and GIII, and high: GII and IV) and bleaching treatment (hydrogen peroxide: GI and GII, and placebo: GIII and GIV). SCST was determined in the inner forearm for 6 different times using a neurosensory analyzer, the TSA II (Medoc Advanced Medical Systems, Ramat Yishai, Northern District, Israel). Dental sensitivity measurements were performed 10 different times using a thermal stimulus and an intraoral device attached to TSA II, positioned in the buccal surface of the upper right central incisor. Spontaneous dental sensitivity was also determined using the Visual Analogue Scale (VAS). Data were submitted to Student's t-test and Pearson's Correlation Test (α=0.05). SCST remained the same during bleaching treatment. Distinct responses of dental sensitivity were found in patients with low and high SCST during the first and third bleaching session (p≤0.05). The teeth submitted to the bleaching treatment became more sensitive to cold than those treated with placebo. Moreover, data obtained with TSA and VAS presented moderate correlation. Bleaching treatment increased dental sensitivity and skin cold sensation threshold might represent a determining factor in this occurrence, since low and high SCST patients had different responses to the thermal stimulus in the teeth.

Egg hypersensitivity and measles-mumps-rubella vaccine administration.

PubMed

Beck, S A; Williams, L W; Shirrell, M A; Burks, A W

1991-11-01

Because reports have described egg-sensitive individuals in whom anaphylaxis developed after measles vaccination, current recommendations include delaying administration of egg-derived vaccines until skin testing can be performed. Specifically, the 1988 Red Book recommends skin testing via scratch, prick, or puncture with 1:10 dilution of the vaccine and, if the result is negative, intradermal testing is suggested. The purpose of this study was to evaluate the likelihood of reaction to measles-mumps-rubella (MMR) vaccine in patients with documented egg sensitivity and to delineate the efficacy of skin-prick testing (SPT) to MMR as a predictor of hypersensitivity to the vaccine. Egg sensitivity was documented by initial SPT to egg and then, if possible, double-blind placebo-controlled food challenge (DBPCFC). Patients with a positive DBPCFC to egg or a history of anaphylactic egg sensitivity had a SPT with the MMR vaccine and then were given the MMR vaccine. Additionally, children with atopic dermatitis who had been previously proven egg sensitive via DBPCFCs were evaluated retrospectively for sensitivity to the MMR vaccine. Sixteen children with a history of egg sensitivity underwent SPT to egg, with a positive result 3 mm greater than the negative control found in 12 patients. Eight of these children had a positive DBPCFC to egg. The SPT to MMR vaccine was negative in all 16 children; vaccine administration followed with no resultant systemic problems. Three children had a local reaction at the site of injection. Twelve additional children with atopic dermatitis and egg sensitivity were reviewed. Each child had a positive SPT and DBPCFC to egg.(ABSTRACT TRUNCATED AT 250 WORDS)

Advances in understanding and managing atopic dermatitis

PubMed Central

Barton, Michael; Sidbury, Robert

2015-01-01

Atopic dermatitis is a chronic, pruritic skin disease characterized by an improperly functioning skin barrier and immune dysregulation. We review proposed atopic dermatitis pathomechanisms, emphasizing how these impact current perspectives on natural history, role of allergic sensitization, and future therapeutic targets. PMID:26918129

Pilot clinical study for quantitative spectral diagnosis of non-melanoma skin cancer.

PubMed

Rajaram, Narasimhan; Reichenberg, Jason S; Migden, Michael R; Nguyen, Tri H; Tunnell, James W

2010-12-01

Several research groups have demonstrated the non-invasive diagnostic potential of diffuse optical spectroscopy (DOS) and laser-induced fluorescence (LIF) techniques for early cancer detection. By combining both modalities, one can simultaneously measure quantitative parameters related to the morphology, function and biochemical composition of tissue and use them to diagnose malignancy. The objective of this study was to use a quantitative reflectance/fluorescence spectroscopic technique to determine the optical properties of normal skin and non-melanoma skin cancers and the ability to accurately classify them. An additional goal was to determine the ability of the technique to differentiate non-melanoma skin cancers from normal skin. The study comprised 48 lesions measured from 40 patients scheduled for a biopsy of suspected non-melanoma skin cancers. White light reflectance and laser-induced fluorescence spectra (wavelength range = 350-700 nm) were collected from each suspected lesion and adjacent clinically normal skin using a custom-built, optical fiber-based clinical instrument. After measurement, the skin sites were biopsied and categorized according to histopathology. Using a quantitative model, we extracted various optical parameters from the measured spectra that could be correlated to the physiological state of tissue. Scattering from cancerous lesions was significantly lower than normal skin for every lesion group, whereas absorption parameters were significantly higher. Using numerical cut-offs for our optical parameters, our clinical instrument could classify basal cell carcinomas with a sensitivity and specificity of 94% and 89%, respectively. Similarly, the instrument classified actinic keratoses and squamous cell carcinomas with a sensitivity of 100% and specificity of 50%. The measured optical properties and fluorophore contributions of normal skin and non-melanoma skin cancers are significantly different from each other and correlate well with tissue pathology. A diagnostic algorithm that combines these extracted properties holds promise for the potential non-invasive diagnosis of skin cancer. Copyright © 2010 Wiley-Liss, Inc.

Effects of chronic acceleration on body composition

NASA Technical Reports Server (NTRS)

Pitts, G. C.

1982-01-01

Studies of the centrifugation of adult rats showed an unexpected decrease in the mass of fat-free muscle and bone, in spite of the added load induced by centrifugation. It is suggested that the lower but constant fat-free body mass was probably regulated during centrifugation. Rats placed in weightless conditions for 18.5 days gave indirect but strong evidence that the muscle had increased in mass. Other changes in the rats placed in weightless conditions included a smaller fraction of skeletal mineral, a smaller fraction of water in the total fat-free body, and a net shift of fluid from skin to viscera. Adult rats centrifuged throughout the post-weaning growth period exhibited smaller masses of bone and central nervous system (probably attributable to slower growth of the total body), and a larger mass of skin than controls at 1 G. Efforts at simulating the effects of weightlessness or centrifugation on the body composition of rats by regimens at terrestrial gravity were inconclusive.

Thermal effusivity: a promising imaging biomarker to predict radiation-induced skin injuries.

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

Chu, J. C. H.; Templeton, A.; Yao, R.

An effective screening technology is needed to triage individuals at the time of radiation incidents involving a large population. Three-dimensional thermal tomography is a relatively new development in active thermal imaging technology that produces cross-sectional images based on the subject's ability to transfer heat thermal effusivity at the voxel level. This noninvasive imaging modality has been used successfully in nondestructive examination of complex materials; also it has been shown to predict the severity of radiation-induced skin injuries several days before the manifestation of severe moist desquamations or blister formation symptoms in mice at 40 Gy. If these results are confirmedmore » at lower dose levels in human subjects, a thermal tomography imaging device may be an ideal screening tool in radiation emergencies. This imaging method is non-invasive, relatively simple, easily adaptable for field use, and when properly deployed, it will enhance public emergency preparedness for incidents involving unexpected radiation exposure.« less

Thermo-and pH-sensitive hydrogel membranes composed of poly(N-isopropylacrylamide)-hyaluronan for biomedical applications: Influence of hyaluronan incorporation on the membrane properties.

PubMed

Kamoun, Elbadawy A; Fahmy, Alaa; Taha, Tarek H; El-Fakharany, Esmail M; Makram, Mohamed; Soliman, Hesham M A; Shehata, Hassan

2018-01-01

Interpenetrating hydrogel membranes consisting of pH-sensitive hyaluronan (HA) and thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAM) were synthesized using redox polymerization, followed by N,N-methylenebisacrylamide (BIS) and epichlorohydrin (EPI) were added as chemical crosslinkers. The interaction between membrane compositions has been characterized by FTIR spectroscopy and discussed intensively. The result indicates that HA incorporation in membranes increase the gel fraction, swelling uptake, and the flexibility/elasticity of crosslinked membranes, however it reduced oppositely the mechanical elongation of membranes. PNIPAAm-HA hydrogels responded to both temperature and pH changes and the stimuli-responsiveness was reversible. However, in vitro bioevaluation results revealed that the released ampicillin during the burst release time was sharply influenced and increased with increasing HA contents in membranes; afterwards it became sustainable. Whereas, high HA contents in hydrogels unexpectedly impacted negatively on the cells viability, owing to the viscosity of cell culture media changed. A big resistance was observed against microbial growth of Staphylococcus aureus, Salmonella typhi, and Candida albicans in case of pure PNIPAAm hydrogel membranes without HA or ampicillin. However, HA incorporation or the loaded ampicillin in membranes showed unexpected easily microbial growth. The fast release performance with dual pH-thermo-sensitive hydrogels were suggested as promising materials for quick drug carrier in the biomedical field. Copyright © 2017 Elsevier B.V. All rights reserved.

Respiratory allergy to moth: the importance of sensitization to Bombyx mori in children with asthma and rhinitis.

PubMed

Araujo, Laura M L; Rosário Filho, Nelson A; Riedi, Carlos A

2014-01-01

this study aimed to prepare a silkworm moth (Bombyx mori) antigenic extract and to perform skin prick tests with this extract in patients with allergic respiratory diseases; to evaluate serum specific immunoglobulin E (IgE) to Bombyx mori using ImmunoCAP® system and to report the frequency of positivity between the two methods and with clinical data. this was a cross-sectional study with 99 children and adolescents diagnosed with asthma and/or allergic rhinitis, who had skin reactivity to at least one of the six aeroallergens tested. Clinical data were evaluated: skin prick tests with Bombyx mori in-house extract, and total and specific IgE analysis using ImmunoCAP® were performed. the frequency of Bombyx mori specific IgE was found to be 52.5% and 60% using the skin prick test and ImmunoCAP®, respectively. An association between a positive skin test for Bombyx mori and the presence of allergic rhinitis, atopic dermatitis, and urticaria was observed, but the same was not true for asthma or allergic conjunctivitis. There was no relation with the severity of asthma or rhinitis symptoms. a high frequency of sensitization to Bombyx mori was observed in a selected population of patients with respiratory allergic diseases in the city of Curitiba, state of Paraná, Brazil. The extract prepared from the wings of this moth species is effective in demonstrating this sensitivity. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Common bacterial skin infections.

PubMed

Trent, J T; Federman, D; Kirsner, R S

2001-08-01

Skin infections account for a significant portion of dermatologic disease, often resulting in or as a consequence of a disruption in the skin's integrity. This article covers the presentation, diagnosis, and treatment of the more common bacterial infections. The infections presented herein include impetigo, ecthyma, folliculitis, carbuncles/furuncles, cellulitis, toxic shock syndrome, and ecthyma gangrenosum. Once a diagnosis is made, treatment is based on the culture and antibiotic sensitivities of the offending organisms.

Novel antibacterial activity of monolaurin compared with conventional antibiotics against organisms from skin infections: an in vitro study.

PubMed

Carpo, Beatriz G; Verallo-Rowell, Vermén M; Kabara, Jon

2007-10-01

A cross-sectional laboratory study to determine the in vitro sensitivity and resistance of organisms in culture isolates from skin infections and mechanisms of action of monolaurin, a coconut lauric acid derivative, compared with 6 common antibiotics: penicillin, oxacillin, fusidic acid, mupirocin, erythromycin, and vancomycin. Skin culture samples were taken from newborn to 18-year-old pediatric patients with primary and secondarily infected dermatoses. Samples were collected and identified following standard guidelines, then sent to the laboratory for sensitivity testing against the 6 selected antibiotics and monolaurin. Sensitivity rates of Gram-positive Staphylococcus aureus, Streptococcus spp., and coagulase-negative Staphylococcus, Gram-negative E. vulneris, Enterobacter spp., and Enterococcus spp. to 20 mg/ml monolaurin was 100% and of Klebsiella rhinoscleromatis was 92.31%. Escherichia coli had progressively less dense colony growths at increasing monolaurin concentrations, and at 20 mg/ml was less dense than the control. Staphylococcus aureus, coagulase-negative Staphylococcus, and Streptococcus spp. did not exhibit any resistance to monolaurin and had statistically significant (P <.05) differences in resistance rates to these antibiotics. Monolaurin has statistically significant in vitro broad-spectrum sensitivity against Gram-positive and Gram-negative bacterial isolates from superficial skin infections. Most of the bacteria did not exhibit resistance to it. Monolaurin needs further pharmacokinetic studies to better understand its novel mechanisms of action, toxicity, drug interactions, and proper dosing in order to proceed to in vivo clinical studies.

Physicochemical properties of pH-sensitive hydrogels based on hydroxyethyl cellulose-hyaluronic acid and for applications as transdermal delivery systems for skin lesions.

PubMed

Kwon, Soon Sik; Kong, Bong Ju; Park, Soo Nam

2015-05-01

We investigated the physicochemical properties of pH-sensitive hydroxyethyl cellulose (HEC)/hyaluronic acid (HA) complex hydrogels containing isoliquiritigenin (ILTG), and discussed potential applications as transdermal delivery systems for the treatment of skin lesions caused by pH imbalance. HA has skin compatibility and pH functional groups and HEC serves as scaffold to build hydrogels with varied HCE:HA mass ratio. Hydrogels were synthesized via chemical cross-linking, and three-dimensional network structures were characterized via scanning electron microscopy (SEM). The swelling properties and polymer ratios of the hydrogels were investigated at pH values in the range 1-13. HECHA13 (i.e., an HEC:HA mass ratio of 1:3) was found to have optimal rheological and adhesive properties, and was used to investigate the drug release efficiency as a function of pH; the efficiency was greater than 70% at pH 7. Antimicrobial activity assays against Propionibacterium acnes were conducted to take advantage of the pH-sensitive properties of HECHA13. At pH 7, we found that HECHA13, which contained ILTG, inhibited the growth of P. acnes. Furthermore, HECHA13 was found to exhibit excellent permeability into the skin, which penetrated mostly via the hair follicle. These results indicate that this pH-sensitive hydrogel is effective as a transdermal delivery system for antimicrobial therapeutics, with potential applications in the treatment of acne. Copyright © 2015 Elsevier B.V. All rights reserved.

Further evaluation of quantitative structure--activity relationship models for the prediction of the skin sensitization potency of selected fragrance allergens.

PubMed

Patlewicz, Grace Y; Basketter, David A; Pease, Camilla K Smith; Wilson, Karen; Wright, Zoe M; Roberts, David W; Bernard, Guillaume; Arnau, Elena Giménez; Lepoittevin, Jean-Pierre

2004-02-01

Fragrance substances represent a very diverse group of chemicals; a proportion of them are associated with the ability to cause allergic reactions in the skin. Efforts to find substitute materials are hindered by the need to undertake animal testing for determining both skin sensitization hazard and potency. One strategy to avoid such testing is through an understanding of the relationships between chemical structure and skin sensitization, so-called structure-activity relationships. In recent work, we evaluated 2 groups of fragrance chemicals -- saturated aldehydes and alpha,beta-unsaturated aldehydes. Simple quantitative structure-activity relationship (QSAR) models relating the EC3 values [derived from the local lymph node assay (LLNA)] to physicochemical properties were developed for both sets of aldehydes. In the current study, we evaluated an additional group of carbonyl-containing compounds to test the predictive power of the developed QSARs and to extend their scope. The QSAR models were used to predict EC3 values of 10 newly selected compounds. Local lymph node assay data generated for these compounds demonstrated that the original QSARs were fairly accurate, but still required improvement. Development of these QSAR models has provided us with a better understanding of the potential mechanisms of action for aldehydes, and hence how to avoid or limit allergy. Knowledge generated from this work is being incorporated into new/improved rules for sensitization in the expert toxicity prediction system, deductive estimation of risk from existing knowledge (DEREK).

In vivo MR imaging of the human skin at subnanoliter resolution using a superconducting surface coil at 1.5 Tesla.

PubMed

Laistler, Elmar; Poirier-Quinot, Marie; Lambert, Simon A; Dubuisson, Rose-Marie; Girard, Olivier M; Moser, Ewald; Darrasse, Luc; Ginefri, Jean-Christophe

2015-02-01

To demonstrate the feasibility of a highly sensitive superconducting surface coil for microscopic MRI of the human skin in vivo in a clinical 1.5 Tesla (T) scanner. A 12.4-mm high-temperature superconducting coil was used at 1.5T for phantom and in vivo skin imaging. Images were inspected to identify fine anatomical skin structures. Signal-to-noise ratio (SNR) improvement by the high-temperature superconducting (HTS) coil, as compared to a commercial MR microscopy coil was quantified from phantom imaging; the gain over a geometrically identical coil made from copper (cooled or not) was theoretically deduced. Noise sources were identified to evaluate the potential of HTS coils for future studies. In vivo skin images with isotropic 80 μm resolution were demonstrated revealing fine anatomical structures. The HTS coil improved SNR by a factor 32 over the reference coil in a nonloading phantom. For calf imaging, SNR gains of 380% and 30% can be expected over an identical copper coil at room temperature and 77 K, respectively. The high sensitivity of HTS coils allows for microscopic imaging of the skin at 1.5T and could serve as a tool for dermatology in a clinical setting. © 2013 Wiley Periodicals, Inc.

[Hygienic study and evaluation of textile materials with reduced combustibility with reference to the use of the new anti-inflammable preparations Pyrofix 2 and Torflam].

PubMed

Uzunova, S; Baĭnova, A; Iordanova, I; Dolova, D

1986-01-01

The new anti-flammable preparations, proposed by the Higher Chemical Technology Institute (Sofia), were studied, namely: Pyrofix 2--for treatment of textile materials and Torflam--for production of anti-inflammable polyester fibres. The following parameters were studied: skin-irritating and skin-sensitizing effect of both preparations, skin toxic effect of Pyrofix 2 and migration of chemicals from the anti-inflammable textile materials (from the composition of the preparations used). The results obtained revealed the absence of skin-irritating and skin-sensitizing effect of both preparations and cumulative dermal toxicity of Pyrofix 2. The textile materials with reduced combustibility are chemically stable and do not release compounds in the contact aqueous medium, imitating the underclothes space. Formaldehyde from recipe for the treatment of Pyrofix 2 migrates in the air environment. In conclusion, Pyrofix 2 could be applied for the final anti-inflammable treatment of the textile materials for industrial needs, working garments and everyday textile (with the elimination of formaldehyde compound from the recipe). Torflam could be used in the production of anti-inflammable polyester fibres for textile materials intended for industry and everyday life without immediate contact with the skin of the consumers.

Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhao, Jianhua; Zeng, Haishan; Kalia, Sunil; Lui, Harvey

2017-02-01

Background: Raman spectroscopy is a non-invasive optical technique which can measure molecular vibrational modes within tissue. A large-scale clinical study (n = 518) has demonstrated that real-time Raman spectroscopy could distinguish malignant from benign skin lesions with good diagnostic accuracy; this was validated by a follow-up independent study (n = 127). Objective: Most of the previous diagnostic algorithms have typically been based on analyzing the full band of the Raman spectra, either in the fingerprint or high wavenumber regions. Our objective in this presentation is to explore wavenumber selection based analysis in Raman spectroscopy for skin cancer diagnosis. Methods: A wavenumber selection algorithm was implemented using variably-sized wavenumber windows, which were determined by the correlation coefficient between wavenumbers. Wavenumber windows were chosen based on accumulated frequency from leave-one-out cross-validated stepwise regression or least and shrinkage selection operator (LASSO). The diagnostic algorithms were then generated from the selected wavenumber windows using multivariate statistical analyses, including principal component and general discriminant analysis (PC-GDA) and partial least squares (PLS). A total cohort of 645 confirmed lesions from 573 patients encompassing skin cancers, precancers and benign skin lesions were included. Lesion measurements were divided into training cohort (n = 518) and testing cohort (n = 127) according to the measurement time. Result: The area under the receiver operating characteristic curve (ROC) improved from 0.861-0.891 to 0.891-0.911 and the diagnostic specificity for sensitivity levels of 0.99-0.90 increased respectively from 0.17-0.65 to 0.20-0.75 by selecting specific wavenumber windows for analysis. Conclusion: Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels.

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

PubMed Central

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

2011-01-01

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

A new discussion of the cutaneous vascular reactivity in sensitive skin: A sub-group of SS?

PubMed

Chen, S Y; Yin, J; Wang, X M; Liu, Y Q; Gao, Y R; Liu, X P

2018-02-02

Sensitive skin (SS) seems not to be a one-dimensional condition and many scholars concentrate on skin barrier disruption or sensorineural change, but few focus on its increased vascular reactivity. This study explored the possibility of using the different selection methods and measurement methods to verify a high vascular reactivity in SS without an impaired cutaneous barrier function. Sixty "self-perceived sensitive skin" volunteers were enlisted and each one completed three kinds of screening tests: assess cutaneous sensory using questionnaire survey and Lactic Acid Sting Test (LAST); assess barrier function using Sodium lauryl sulphate (SLS) skin irritation test and assess cutaneous vascular reactivity using 98% DMSO test and non-invasive measurement. Volunteers were divided into different groups based on response to SLS. The DMSO clinical score and the biophysical parameters obtained by non-invasive measurement were subsequently analysed. (1) The positive correlations could be seen between sum LAST score and sum DMSO score regardless of the observation time; (2) The biological parameters (CBF、a*values and L* values) are all keeping with DMSO score; (3) If the participants were divided into SLS reactors and non-reactors, a composition ratio of DMSO score was significant difference in these two groups and in SLS non-reactors, there were still seven participants showed high reaction to DMSO. There is a sub-group of SS for characteristics of a high vascular reactivity without an impaired cutaneous barrier function. The DMSO test and novel non-invasive measurements which are conducive to assess cutaneous vascular reactivity, combined with SLS skin irritation test could help us to screen this kind of SS. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Correlation between pH and irritant effect of cleansers marketed for dry skin.

PubMed

Baranda, Lourdes; González-Amaro, Roberto; Torres-Alvarez, Bertha; Alvarez, Carmen; Ramírez, Victoria

2002-08-01

Although it is important that dermatologists and the general population know the irritation potential of products marketed for dry skin used for body cleansing, this information is not usually available. To assess the irritative effect of different soaps and liquid cleansers recommended for sensitive skin. To study the correlation of the irritation effect of each substance with its pH and with the presence or absence of syndet in the product. Seventeen products marketed for dry skin and 12 common soaps used by the general population were studied. Fresh soap emulsions (8%) were applied to the volar side of the right forearm of 30 individuals with sensitive skin for 5 consecutive days using aluminum chambers. The appearance of irritation (erythema, scaling and fissures) was recorded, scored, and expressed in an Irritation index (IrIn). The pH of each solution was measured. Products with a low IrIn were White Dove (Dove, Lever Pond's, Toronto, Ontario, Canada), Dove Baby, Cetaphil (bar) (Cetaphil, Gulderma Lab., Forth Worth, TX, USA), Dove liquid cleanser for hands, Dove pink, and Aderma (Adenma, Pierre Fabre, Dermo-Cosmetique, Boulagne, France). Most corresponded to syndet products. Among the most used brand-name soap, Camay Classic (Camay, Procter & Gamble de Mexico, México, U.F.) had the lowest IrIn. Dove Baby was the only product with a neutral pH. A significant correlation between pH and the IrIn of cleansers was found (P < 0.006). Most products recommended for sensitive skin have a considerable irritation effect, which is related to the pH of the product. Better regulation of advertisement specifications including the pH level and type of cleanser contained is necessary for the majority of soaps and cleansers.

Combining skin prick, immediate skin application and specific-IgE testing in the diagnosis of peanut allergy in children.

PubMed

Wainstein, Brynn Kevin; Yee, Anthony; Jelley, Donna; Ziegler, Mary; Ziegler, John B

2007-05-01

Previous studies have suggested various diagnostic cut-offs of allergy tests for the diagnosis of clinical peanut allergy in children. There are few data relating to the use of combinations of these tests in children. We aimed to determine the validity of previously reported diagnostic cut-off levels of peanut allergen skin tests and peanut specific-immunoglobulin (Ig) E, as well as the usefulness of combinations of these, for predicting clinical peanut allergy in our Allergy Clinic. Children attending the Allergy Clinic with a positive peanut skin prick test (SPT; n = 84) were included in the study. Immediate skin application food tests (I-SAFT) using 1 g of peanut butter (positive if any wheals were detected at 15 min), peanut specific-IgE levels and open-label peanut food challenges were performed. Fifty-two of 85 peanut challenges were positive. Skin prick test specificity was 67% at >or=8 mm and 100% at >or=15 mm. The I-SAFT was 82% specific. A peanut specific-IgE level of 0.37 kU/l was 98% sensitive but 33% specific. A level of 10 kU/l was 100% specific. Combinations of a SPT of >or=8 mm with a positive I-SAFT and a peanut specific-IgE >or=0.37 kU/l were 88% specific with a sensitivity of 38%. Using challenge outcomes as the standard, available in vitro and in vivo diagnostic tests for peanut allergy have poor sensitivity and specificity and combining them does not significantly improve their clinical usefulness. Previously described diagnostic cut-off levels do not have general applicability. Allergy practitioners may need to interpret results of allergy tests in the context of their own practices.

Quantification of changes in skin hydration and sebum after tape stripping using infrared spectroscopy

NASA Astrophysics Data System (ADS)

Ezerskaia, A.; Pereira, S. F.; Urbach, H. P.; Varghese, B.

2017-02-01

Skin barrier function relies on well balanced water and lipid system of stratum corneum. Optimal hydration and oiliness levels are indicators of skin health and integrity. We demonstrate an accurate and sensitive depth profiling of stratum corneum sebum and hydration levels using short wave infrared spectroscopy in the spectral range around 1720 nm. We demonstrate that short wave infrared spectroscopic technique combined with tape stripping can provide morequantitative and more reliable skin barrier function information in the low hydration regime, compared to conventional biophysical methods.

The unique and cooperative roles of the Grainy head-like transcription factors in epidermal development reflect unexpected target gene specificity.

PubMed

Boglev, Yeliz; Wilanowski, Tomasz; Caddy, Jacinta; Parekh, Vishwas; Auden, Alana; Darido, Charbel; Hislop, Nikki R; Cangkrama, Michael; Ting, Stephen B; Jane, Stephen M

2011-01-15

The Grainy head-like 3 (Grhl3) gene encodes a transcription factor that plays essential roles in epidermal morphogenesis during embryonic development, with deficient mice exhibiting failed skin barrier formation, defective wound repair, and loss of eyelid fusion. Despite sharing significant sequence homology, overlapping expression patterns, and an identical core consensus DNA binding site, the other members of the Grhl family (Grhl1 and -2) fail to compensate for the loss of Grhl3 in these processes. Here, we have employed diverse genetic models, coupled with biochemical studies, to define the inter-relationships of the Grhl factors in epidermal development. We show that Grhl1 and Grhl3 have evolved complete functional independence, as evidenced by a lack of genetic interactions in embryos carrying combinations of targeted alleles of these genes. In contrast, compound heterozygous Grhl2/Grhl3 embryos displayed failed wound repair, and loss of a single Grhl2 allele in Grhl3-null embryos results in fully penetrant eyes open at birth. Expression of Grhl2 from the Grhl3 locus in homozygous knock-in mice corrects the wound repair defect, but these embryos still display a complete failure of skin barrier formation. This functional dissociation is due to unexpected differences in target gene specificity, as both GRHL2 and GRHL3 bind to and regulate expression of the wound repair gene Rho GEF 19, but regulation of the barrier forming gene, Transglutaminase 1 (TGase1), is unique to GRHL3. Our findings define the mechanisms underpinning the unique and cooperative roles of the Grhl genes in epidermal development. Copyright © 2010 Elsevier Inc. All rights reserved.

Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: A cross-sectional study.

PubMed

Flohr, Carsten; Tuyen, Luc Nguyen; Lewis, Sarah; Quinnell, Rupert; Minh, Truong Tan; Liem, Ho Thanh; Campbell, Jim; Pritchard, David; Hien, Tran Tinh; Farrar, Jeremy; Williams, Hywel; Britton, John

2006-12-01

Geohelminth infection and poor hygiene may be protective against allergic sensitization. To determine whether current helminth infection is associated with a reduced prevalence of allergen skin test sensitization in a Southeast Asian population of children with a high prevalence of hookworm infection. A total of 1742 Vietnamese schoolchildren were invited to take part in a cross-sectional survey. Allergen skin sensitization to house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae) and American cockroach (Periplaneta americana) were measured and stool samples for qualitative and quantitative geohelminth estimation collected. A total of 1601 children age 6 to 18 participated. Sensitization to dust mites was present in 14.4% and to cockroach in 27.6% of children. In a mutually adjusted model, the risk of sensitization to dust mites was reduced in those with higher hookworm burden (adjusted odds ratio [OR] for 350+ vs no eggs per gram, 0.61; 95% CI, 0.39-0.96) and with Ascaris infection (adjusted OR, 0.28; 0.10-0.78), and increased in those using flush toilets (adjusted OR for flush toilet vs none/bush/pit, 2.51; 1.00-6.28). In contrast, sensitization to cockroach was not independently related to geohelminth infection but was increased in those regularly drinking piped or well water rather than from a stream (adjusted OR, 1.33; 1.02-1.75). Geohelminth infection, sanitation, and water supply influence the risk of allergic sensitization in Vietnamese children. This is consistent with a protective effect against allergy by geohelminth or other gastrointestinal infection. If the inverse relationship between geohelminth infection, poor sanitation, and allergic sensitization proves to be causal, drugs derived from parasite products may help to alleviate clinical allergic disease.

Assessment of the sensitizing potency of preservatives with chance of skin contact by the loose-fit coculture-based sensitization assay (LCSA).

PubMed

Sonnenburg, Anna; Schreiner, Maximilian; Stahlmann, Ralf

2015-12-01

Parabens, methylisothiazolinone (MI) and its derivative methylchloroisothiazolinone (MCI), are commonly used as preservatives in personal care products. They can cause hypersensitivity reactions of the human skin. We have tested a set of nine parabens, MI alone and in combination with MCI in the loose-fit coculture-based sensitization assay (LCSA). The coculture of primary human keratinocytes and allogenic dendritic cell-related cells (DC-rc) in this assay emulates the in vivo situation of the human skin. Sensitization potency of the test substances was assessed by flow cytometric analysis of the DC-rc maturation marker CD86. Determination of the concentration required to cause a half-maximal increase in CD86-expression (EC50sens) allowed a quantitative evaluation. The cytotoxicity of test substances as indicator for irritative potency was measured by 7-AAD (7-amino-actinomycin D) staining. Parabens exhibited weak (methyl-, ethyl-, propyl- and isopropylparaben) or strong (butyl-, isobutyl-, pentyl- and benzylparaben) effects, whereas phenylparaben was found to be a moderate sensitizer. Sensitization potencies of parabens correlated with side chain length. Due to a pronounced cytotoxicity, we could not estimate an EC50sens value for MI, whereas MI/MCI was classified as sensitizer and also showed cytotoxic effects. Parabens showed no (methyl- and ethylparaben) or weak irritative potencies (propyl-, isopropyl-, butyl-, isobutyl-, phenyl- and benzylparaben), only pentylparaben was rated to be irritative. Overall, we were able to demonstrate and compare the sensitizing potencies of parabens in this in vitro test. Furthermore, we showed an irritative potency for most of the preservatives. The data further support the usefulness of the LCSA for comparison of the sensitizing potencies of xenobiotics.

Non-animal assessment of skin sensitization hazard: Is an integrated testing strategy needed, and if so what should be integrated?

PubMed

Roberts, David W; Patlewicz, Grace

2018-01-01

There is an expectation that to meet regulatory requirements, and avoid or minimize animal testing, integrated approaches to testing and assessment will be needed that rely on assays representing key events (KEs) in the skin sensitization adverse outcome pathway. Three non-animal assays have been formally validated and regulatory adopted: the direct peptide reactivity assay (DPRA), the KeratinoSens™ assay and the human cell line activation test (h-CLAT). There have been many efforts to develop integrated approaches to testing and assessment with the "two out of three" approach attracting much attention. Here a set of 271 chemicals with mouse, human and non-animal sensitization test data was evaluated to compare the predictive performances of the three individual non-animal assays, their binary combinations and the "two out of three" approach in predicting skin sensitization potential. The most predictive approach was to use both the DPRA and h-CLAT as follows: (1) perform DPRA - if positive, classify as sensitizing, and (2) if negative, perform h-CLAT - a positive outcome denotes a sensitizer, a negative, a non-sensitizer. With this approach, 85% (local lymph node assay) and 93% (human) of non-sensitizer predictions were correct, whereas the "two out of three" approach had 69% (local lymph node assay) and 79% (human) of non-sensitizer predictions correct. The findings are consistent with the argument, supported by published quantitative mechanistic models that only the first KE needs to be modeled. All three assays model this KE to an extent. The value of using more than one assay depends on how the different assays compensate for each other's technical limitations. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

2013 American College of Rheumatology/European League against rheumatism classification criteria for systemic sclerosis outperform the 1980 criteria: data from the Canadian Scleroderma Research Group.

PubMed

Alhajeri, Hebah; Hudson, Marie; Fritzler, Marvin; Pope, Janet; Tatibouet, Solène; Markland, Janet; Robinson, David; Jones, Niall; Khalidi, Nader; Docherty, Peter; Kaminska, Elzbieta; Masetto, Ariel; Sutton, Evelyn; Mathieu, Jean-Pierre; Ligier, Sophie; Grodzicky, Tamara; LeClercq, Sharon; Thorne, Carter; Gyger, Geneviève; Smith, Douglas; Fortin, Paul R; Larché, Maggie; Baron, Murray

2015-04-01

The goal of this study was to determine the sensitivity of the new 2013 classification criteria for systemic sclerosis (SSc; scleroderma) in an independent cohort of SSc subjects and to assess the contribution of individual items of the criteria to the overall sensitivity. SSc subjects from the Canadian Scleroderma Research Group cohort were assessed. Sensitivity was determined in several subgroups of patients. In patients without the criterion of skin thickening proximal to the metacarpophalangeal (MCP) joints, we recalculated sensitivity after removing the individual criterion. A total of 724 SSc patients were included. Most were women (86%), mean age was 55.8 years, mean disease duration was 10.9 years, and 59% had limited cutaneous SSc (lcSSc). Overall, the sensitivity of the 2013 criteria was 98.3% compared to 88.3% for the 1980 criteria. This pattern was consistent among those with lcSSc (98.8% versus 85.6%), anticentromere antibodies (98.9% versus 79.8%), disease duration ≤3 years (98.7% versus 84.7%), and no skin involvement proximal to the MCP joints (97% versus 60%). In the latter subgroup, removing Raynaud's phenomenon and sclerodactyly from the criteria reduced the sensitivity to 77% and 79%, respectively. Removing both sclerodactyly and puffy fingers reduced the sensitivity to 62%. The 2013 SSc classification criteria classify more SSc patients than the 1980 criteria. The improvement in sensitivity is most striking in those with lcSSc, especially those without skin involvement proximal to the MCP joints. The addition of Raynaud's phenomenon and puffy fingers to the 2013 criteria accounts for important gains in sensitivity. Copyright © 2015 by the American College of Rheumatology.

Diagnosing environmental allergies: Comparison of skin-prick, intradermal, and serum specific immunoglobulin E testing

PubMed Central

Shtessel, Maria; Lobell, Elizabeth; Hudes, Golda; Rosenstreich, David; de Vos, Gabriele

2017-01-01

Background: Allergists commonly perform intradermal skin testing (IDST) after negative skin-prick testing (SPT) to comprehensively diagnose environmental allergic sensitization. However, with the availability of modern methods to detect serum-specific immunoglobulin E (ssIgE), it is unclear if ssIgE testing could substitute for IDST. Objective: To determine the efficacy of ssIgE testing and IDST when added to SPT in diagnosing environmental allergic sensitizations. Methods: SPT, IDST, and ssIgE testing to nine common environmental allergens were analyzed in 75 patients with oculonasal symptoms who presented to our allergy clinics in the Bronx, New York, between January 2014 and May 2015. Results: A total of 651 SPT and 499 ssIgE tests were independently performed and revealed 162 (25%) and 127 (25%) sensitizations, respectively. When SPT results were negative, IDST results revealed 108 of 452 additional sensitizations (24%). In contrast, when SPT results were negative, ssIgE test results only revealed 9% additional sensitizations. When both SPT and IDST results were negative, ssIgE testing only detected 3% of additional sensitizations, and ssIgE levels were typically low in these cases (median, 1.25 kU/L; range, 0.357–4.47 kU/L). When both SPT and ssIgE test results were negative, IDST results detected 15% additional sensitizations. Conclusion: IDST detected more additional environmental sensitizations compared with ssIgE testing. IDST, therefore, may be useful when the SPT and/or ssIgE testing results were negative, but the exposure history indicated relevant allergic sensitization. Serology added only a little more information if both SPT and IDST results were negative but may be useful in combination with SPT if IDST cannot be performed. PMID:28583228

Diagnosing environmental allergies: Comparison of skin-prick, intradermal, and serum specific immunoglobulin E testing.

PubMed

Ferastraoaru, Denisa; Shtessel, Maria; Lobell, Elizabeth; Hudes, Golda; Rosenstreich, David; de Vos, Gabriele

2017-06-01

Allergists commonly perform intradermal skin testing (IDST) after negative skin-prick testing (SPT) to comprehensively diagnose environmental allergic sensitization. However, with the availability of modern methods to detect serum-specific immunoglobulin E (ssIgE), it is unclear if ssIgE testing could substitute for IDST. To determine the efficacy of ssIgE testing and IDST when added to SPT in diagnosing environmental allergic sensitizations. SPT, IDST, and ssIgE testing to nine common environmental allergens were analyzed in 75 patients with oculonasal symptoms who presented to our allergy clinics in the Bronx, New York, between January 2014 and May 2015. A total of 651 SPT and 499 ssIgE tests were independently performed and revealed 162 (25%) and 127 (25%) sensitizations, respectively. When SPT results were negative, IDST results revealed 108 of 452 additional sensitizations (24%). In contrast, when SPT results were negative, ssIgE test results only revealed 9% additional sensitizations. When both SPT and IDST results were negative, ssIgE testing only detected 3% of additional sensitizations, and ssIgE levels were typically low in these cases (median, 1.25 kU/L; range, 0.357-4.47 kU/L). When both SPT and ssIgE test results were negative, IDST results detected 15% additional sensitizations. IDST detected more additional environmental sensitizations compared with ssIgE testing. IDST, therefore, may be useful when the SPT and/or ssIgE testing results were negative, but the exposure history indicated relevant allergic sensitization. Serology added only a little more information if both SPT and IDST results were negative but may be useful in combination with SPT if IDST cannot be performed.

CORSSTOL: Cylinder Optimization of Rings, Skin, and Stringers with Tolerance sensitivity

NASA Technical Reports Server (NTRS)

Finckenor, J.; Bevill, M.

1995-01-01

Cylinder Optimization of Rings, Skin, and Stringers with Tolerance (CORSSTOL) sensitivity is a design optimization program incorporating a method to examine the effects of user-provided manufacturing tolerances on weight and failure. CORSSTOL gives designers a tool to determine tolerances based on need. This is a decisive way to choose the best design among several manufacturing methods with differing capabilities and costs. CORSSTOL initially optimizes a stringer-stiffened cylinder for weight without tolerances. The skin and stringer geometry are varied, subject to stress and buckling constraints. Then the same analysis and optimization routines are used to minimize the maximum material condition weight subject to the least favorable combination of tolerances. The adjusted optimum dimensions are provided with the weight and constraint sensitivities of each design variable. The designer can immediately identify critical tolerances. The safety of parts made out of tolerance can also be determined. During design and development of weight-critical systems, design/analysis tools that provide product-oriented results are of vital significance. The development of this program and methodology provides designers with an effective cost- and weight-saving design tool. The tolerance sensitivity method can be applied to any system defined by a set of deterministic equations.

Estimating skin sensitization potency from a single dose LLNA.

PubMed

Roberts, David W

2015-04-01

Skin sensitization is an important aspect of safety assessment. The mouse local lymph node assay (LLNA) developed in the 1990 s is an in vivo test used for skin sensitization hazard identification and characterization. More recently a reduced version of the LLNA (rLLNA) has been developed as a means of identifying, but not quantifying, sensitization hazard. The work presented here is aimed at enabling rLLNA data to be used to give quantitative potency information that can be used, inter alia, in modeling and read-across approaches to non-animal based potency estimation. A probit function has been derived enabling estimation of EC3 from a single dose. This has led to development of a modified version of the rLLNA, whereby as a general principle the SI value at 10%, or at a lower concentration if 10% is not testable, is used to calculate the EC3. This version of the rLLNA has been evaluated against a selection of chemicals for which full LLNA data are available, and has been shown to give EC3 values in good agreement with those derived from the full LLNA. Copyright © 2015 Elsevier Inc. All rights reserved.

Gum Arabic as a Cause of Occupational Allergy

PubMed Central

Viinanen, Arja; Salokannel, Maija; Lammintausta, Kaija

2011-01-01

Background. Gum arabic is a potential sensitizer in food industry. Methods. We examined 11 candy factory workers referred to examinations due to respiratory and skin symptoms paying attention to exposure and sensitization to gum arabic. Skin tests, pulmonary function tests, and respiratory provocation tests were carried out as indicated by the symptoms and findings. Results. Occupational asthma, caused by gum arabic was diagnosed in 4/11 candy factory workers and two of them had also occupational contact urticaria and one had occupational rhinitis. One of them had oral symptoms associated with ingestion of products containing gum arabic. Conclusions. Airborne exposure to gum arabic may cause sensitization leading to allergic rhinitis, asthma, and urticaria. PMID:21747872

The local lymph node assay: current position in the regulatory classification of skin sensitizing chemicals.

PubMed

Basketter, David A; Gerberick, G Frank; Kimber, Ian

2007-01-01

The local lymph node assay (LLNA) is being used increasingly in the identification of skin sensitizing chemicals for regulatory purposes. In the context of new chemicals legislation (REACH) in Europe, it is the preferred assay. The rationale for this is that the LLNA quantitative and objective approach to skin sensitization testing allied with the important animal welfare benefits that the method offers. However, as with certain guinea pig sensitization tests before it, this increasing use also brings experience with an increasingly wide range of industrial and other chemicals where the outcome of the assay does not always necessarily meet with the expectations of those conducting it. Sometimes, the result appears to be a false negative, but rather more commonly, the complaint is that the chemical represents a false positive. Against this background we have here reviewed a number of instances where false positive and false negative results have been described and have sought to reconcile science with expectation. Based on these analyses, it is our conclusion that false positives and false negatives do occur in the LLNA, as they do with any other skin sensitization assay (and indeed with all tests used for hazard identification), and that this occurs for a number of reasons. We further conclude, however, that false positive results in the LLNA, as with the guinea pig maximization test, arise most commonly via failure to distinguish what is scientifically correct from that which is unpalatable. The consequences of this confusion are discussed in the article, particularly in relation to the need to integrate both potency measurement and risk assessments into classification and labelling schemes that aim to manage potential risks to human health.

qPCR detection of Mycobacterium leprae in biopsies and slit skin smear of different leprosy clinical forms.

PubMed

Azevedo, Michelle de Campos Soriani; Ramuno, Natália Mortari; Fachin, Luciana Raquel Vincenzi; Tassa, Mônica; Rosa, Patrícia Sammarco; Belone, Andrea de Faria Fernandes; Diório, Suzana Madeira; Soares, Cleverson Teixeira; Garlet, Gustavo Pompermaier; Trombone, Ana Paula Favaro

Leprosy, whose etiological agent is Mycobacterium leprae, is a chronic infectious disease that mainly affects the skin and peripheral nervous system. The diagnosis of leprosy is based on clinical evaluation, whereas histopathological analysis and bacilloscopy are complementary diagnostic tools. Quantitative PCR (qPCR), a current useful tool for diagnosis of infectious diseases, has been used to detect several pathogens including Mycobacterium leprae. The validation of this technique in a robust set of samples comprising the different clinical forms of leprosy is still necessary. Thus, in this study samples from 126 skin biopsies (collected from patients on all clinical forms and reactional states of leprosy) and 25 slit skin smear of leprosy patients were comparatively analyzed by qPCR (performed with primers for the RLEP region of M. leprae DNA) and routine bacilloscopy performed in histological sections or in slit skin smear. Considering clinical diagnostic as the gold standard, 84.9% of the leprosy patients were qPCR positive in skin biopsies, resulting in 84.92% sensitivity, with 84.92 and 61.22% positive (PPV) and negative (NPV) predictive values, respectively. Concerning bacilloscopy of histological sections (BI/H), the sensitivity was 80.15% and the PPV and NPV were 80.15 and 44.44%, respectively. The concordance between qPCR and BI/H was 87.30%. Regarding the slit skin smear, 84% of the samples tested positive in the qPCR. Additionally, qPCR showed 100% specificity, since all samples from different mycobacteria, from healthy individuals, and from other granulomatous diseases presented negative results. In conclusion, the qPCR technique for detection of M. leprae using RLEP primers proved to be specific and sensitive, and qPCR can be used as a complementary test to diagnose leprosy irrespective of the clinical form of disease. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Volumetric cutaneous microangiography of human skin in vivo by VCSEL swept-source optical coherence tomography

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

Woo June Choi; Wang, R K

2014-08-31

We demonstrate volumetric cutaneous microangiography of the human skin in vivo that utilises 1.3-μm high-speed sweptsource optical coherence tomography (SS-OCT). The swept source is based on a micro-electro-mechanical (MEMS)-tunable vertical cavity surface emission laser (VCSEL) that is advantageous in terms of long coherence length over 50 mm and 100 nm spectral bandwidth, which enables the visualisation of microstructures within a few mm from the skin surface. We show that the skin microvasculature can be delineated in 3D SS-OCT images using ultrahigh-sensitive optical microangiography (UHS-OMAG) with a correlation mapping mask, providing a contrast enhanced blood perfusion map with capillary flow sensitivity.more » 3D microangiograms of a healthy human finger are shown with distinct cutaneous vessel architectures from different dermal layers and even within hypodermis. These findings suggest that the OCT microangiography could be a beneficial biomedical assay to assess cutaneous vascular functions in clinic. (laser biophotonics)« less

The atopic dog as a model of peanut and tree nut food allergy.

PubMed

Teuber, Suzanne S; Del Val, Gregorio; Morigasaki, Susumu; Jung, Hye Rim; Eisele, Pamela H; Frick, Oscar L; Buchanan, Bob B

2002-12-01

Animal models are needed that mimic human IgE-mediated peanut and tree nut allergy. Atopic dogs have been previously used in a model of food allergy to cow's milk, beef, wheat, and soy, with the demonstration of specific IgE production and positive oral challenges similar to those seen in human subjects. We sought to sensitize dogs to peanut, walnut, and Brazil nut and to assess whether sensitization is accompanied by clinical reactions and whether there is cross-reactivity among the different preparations. Eleven dogs were sensitized subcutaneously by using an established protocol with 1 microg each of peanut, English walnut, or Brazil nut protein extracts in alum first at birth and then after modified live virus vaccinations at 3, 7, and 11 weeks of age. The dogs were sensitized to other allergens, including soy and either wheat or barley. Intradermal skin tests, IgE immunoblotting to nut proteins, and oral challenges were performed with ground nut preparations. At 6 months of age, the dogs' intradermal skin test responses were positive to the nut extracts. IgE immunoblotting to peanut, walnut, and Brazil nut showed strong recognition of proteins in the aqueous preparations. Each of the 4 peanut- and the 3 Brazil nut-sensitized dogs and 3 of the 4 walnut-sensitized dogs reacted on oral challenge with the corresponding primary immunogen at age 2 years. None of the peanut-sensitized dogs reacted clinically with walnut or Brazil nut challenges. One of the walnut-sensitized dogs had delayed (overnight) vomiting to Brazil nut. On the basis of measurements of the mean amount of allergen eliciting a skin test response in dogs, the hierarchy of reactivity by skin testing is similar to the clinical experience in human subjects (peanut > tree nuts > wheat > soy > barley). Cross-reactivity, which was not apparent between soy and peanut or tree nuts or between peanut and tree nuts, was slight between walnut and Brazil nut. The results give further support to the dog as a model of human food allergy.

Preventative and Therapeutic Probiotic Use in Allergic Skin Conditions: Experimental and Clinical Findings

PubMed Central

Özdemir, Öner; Göksu Erol, Azize Yasemin

2013-01-01

Probiotics are ingested live microbes that can modify intestinal microbial populations in a way that benefits the host. The interest in probiotic preventative/therapeutic potential in allergic diseases stemmed from the fact that probiotics have been shown to improve intestinal dysbiosis and permeability and to reduce inflammatory cytokines in human and murine experimental models. Enhanced presence of probiotic bacteria in the intestinal microbiota is found to correlate with protection against allergy. Therefore, many studies have been recently designed to examine the efficacy of probiotics, but the literature on the allergic skin disorders is still very scarce. Here, our objective is to summarize and evaluate the available knowledge from randomized or nonrandomized controlled trials of probiotic use in allergic skin conditions. Clinical improvement especially in IgE-sensitized eczema and experimental models such as atopic dermatitis-like lesions (trinitrochlorobenzene and picryl chloride sensitizations) and allergic contact dermatitis (dinitrofluorobenzene sensitization) has been reported. Although there is a very promising evidence to recommend the addition of probiotics into foods, probiotics do not have a proven role in the prevention or the therapy of allergic skin disorders. Thus, being aware of possible measures, such as probiotics use, to prevent/heal atopic diseases is essential for the practicing allergy specialist. PMID:24078929

Potential natural sensitizers extracted from the skin of Canarium odontophyllum fruits for dye-sensitized solar cells

NASA Astrophysics Data System (ADS)

Lim, Andery; Kumara, N. T. R. N.; Tan, Ai Ling; Mirza, Aminul Huq; Chandrakanthi, R. L. N.; Petra, Mohammad Iskandar; Ming, Lim Chee; Senadeera, G. K. R.; Ekanayake, Piyasiri

2015-03-01

Possibility of use of dye extract from skin samples of a seasonal, indigenous fruit from Borneo, namely Canarium odontophyllum, in dye sensitized solar cells (DSSCs) are explored. Three main groups of flavonoid pigments are detected and these pigments exhibit different UV-vis absorption properties, and hence showing different light harvesting capabilities. When applied in DSSCs. The detected pigment constituents of the extract consist of aurone (maritimein), anthocyanidin (pelargonidin) and anthocyanidin (cyanidin derivatives). When tested in DSSC, the highest conversion efficiency of 1.43% is exhibited by cyanidin derivatives, and this is followed by conversion efficiencies of 0.51% and 0.79% for aurone and pelargonidin, respectively. It is shown that individual pigments, like cyanidin derivatives and pelargonidin, exhibit higher power conversion efficiency when compared to that of C.odontophyllum skin pigment mixture (with a conversion efficiency of only 0.68%). The results indicate a possibility of masking effects of the pigments when used as a mixture. The acidification of C.odontophyllum skin pigments with concentrated hydrochloric acid improves the conversion efficiency of the mixture from 0.68% to 0.99%. The discussion in this paper will draw data and observations from the variation in absorption and adsorption properties, the HOMO-LUMO levels, the energy band gaps and the functional group compositions of the detected flavonoids.

Structure-activity relationships for selected fragrance allergens.

PubMed

Patlewicz, G Y; Wright, Z M; Basketter, D A; Pease, C K; Lepoittevin, J-P; Arnau, E Giménez

2002-10-01

Fragrance substances represent a very diverse group of chemicals, a proportion of them providing not only desirable aroma characteristics, but also being associated with adverse effects, notably the ability to cause allergic reactions in the skin. However, efforts to find substitute materials are hampered by the need to undertake animal testing to evaluate both the presence and the degree of skin sensitization hazard. One potential route to avoid such testing is to understand the relationships between chemical structure and skin sensitization. In the present work we have evaluated two groups of fragrance chemicals, saturated aldehydes (aryl substituted and aliphatic aldehydes) and alpha,beta-unsaturated aldehydes. Data on their skin sensitization potency defined using the local lymph node assay has been evaluated in relation to their physicochemical properties. The initial outcome has been consistent with the concept that alpha,beta-unsaturated aldehydes react largely via Michael addition, whilst the group of saturated aldehydes form Schiff bases with proteins. Simple models of chemical reactivity based on these mechanisms suggest that it may be possible to predict allergenic potency. Accordingly, the evaluation of an additional group of similar aldehydes is now underway to assess the robustness of these models, with some emphasis being based on ensuring a wider spread of chemical reactivity.

Consumption of cosmetic products by the French population. Third part: Product exposure amount.

PubMed

Dornic, N; Ficheux, A S; Roudot, A C

2017-08-01

A recent study in France provided valuable data on the frequency and amount of use of cosmetic products (Ficheux et al., 2015, 2016a). The aim of the present study was to generate Product Exposure Amount data, i.e. the amounts of cosmetics applied to the skin among the French population using the raw data collected during the previous enquiry. These data are useful to derive Consumer exposure level data which are paramount for skin sensitization risk assessments. Exposure data were generated for 69 different cosmetics, classified as products for the hair, face, buccal hygiene, hands, feet, body, shaving and depilation, sunscreens as well as products specifically intended for babies. Exposure was calculated using a probabilistic Monte Carlo method. The main strength of this work was the break-down of data by age and sex. The results showed that some data used by the International Fragrance Association in skin sensitization risk assessments, in particular facial care products and deodorants, could be unsuitable for the protection of French consumers. For the first time, data were also generated for products intended for babies' nappy area. These data will be useful for the implementation of the Quantitative Risk Assessment for skin sensitization among the French population. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Assessment of the sensitizing potency of cosmetic ingredients and commodities. How will the ingredients of cosmetics and commodities be tested in Europe today and tomorrow?].

PubMed

Peiser, M; Platzek, T; Luch, A

2012-03-01

Cosmetics and certain commodities are applied or used by consumers directly on the skin. Creams may remain on the skin for longer periods, hair is dyed multiple times per year, nickel ions can be released from studs and piercings in areas of skin damage or migrate from toy materials into the skin of children. Accordingly, using or handling such products always entails a risk for developing a contact allergy. Moreover, daily usage and repeated contacts to certain cosmetics and commodities might lead to repeated elicitation of contact eczema in people already sensitized against allergenic ingredients. Unfortunately, contact allergy is not curable. For the assessment of the allergenic potential of chemicals, only testing based on animal experiments was available in the past. In 2003, the 7(th) amendment of the Cosmetics Directive 76/768/EWG laid down a ban on animal testing of cosmetic ingredients and from 2013 a general marketing ban of such products as well. Therefore, the development and validation of non-animal methods for assessing the toxicological endpoint sensitization/allergenic potency of chemicals is a major task for the years ahead and remains equally a challenge for industry and regulatory agencies.

Role of pressure-sensitive adhesives in transdermal drug delivery systems.

PubMed

Lobo, Shabbir; Sachdeva, Sameer; Goswami, Tarun

2016-01-01

Transdermal drug delivery systems (TDDS) are employed for the delivery of drugs across skin into the systemic circulation. Pressure-sensitive adhesive (PSA) is one of the most critical components used in a TDDS. The primary function of PSA is to help in adhesion of patch to skin, but more importantly it acts as a matrix for the drug and other excipients. Hence, apart from adhesion of the patch, PSA also affects other critical quality attributes of the TDDS such as drug delivery, flux through skin and physical and chemical stability of the finished product. This review article provides a summary of the adhesives used in various types of TDDS. In particular, this review will cover the design types of TDDS, categories of PSAs and their evaluation and regulatory aspects.

Experimental Eczema. 16. Diminution of the Eczematous Reaction in Preirradiated Guinea Pigs (in French)

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

Maggiora, A.; Lozeron, H.

1962-01-01

Irradiation of small areas of guinea pig skin with 1600 r produced persistent alopecia and acanthosis, without any other subsequent histologic or macroscopic changes in skin. Forty days after such local irradiation of skin, the animals were sensitized to chlorodinitrobenzene and skin reactions were tested with the same compound 7 days later on both the irradiated and control areas. In contrast to the intense eczema developing in control skin, irradiated skin showed a complete lack of reactivity to the allergen. lt was shown that the absence of reactivity in irradiated skin was not the result of the existing acanthosis, sincemore » acanthosis induced by applications of erucic acid did not block the eczematous response to the allergen. Nor was the lack of reactivity due to the absence of hair, since radiationinduced inhibition of eczema could be demonstrated in skin normally lacking hair (nipples).« less

CON4EI: SkinEthic™ Human Corneal Epithelium Eye Irritation Test (SkinEthic™ HCE EIT) for hazard identification and labelling of eye irritating chemicals.

PubMed

Van Rompay, A R; Alépée, N; Nardelli, L; Hollanders, K; Leblanc, V; Drzewiecka, A; Gruszka, K; Guest, R; Kandarova, H; Willoughby, J A; Verstraelen, S; Adriaens, E

2018-06-01

Assessment of ocular irritancy is an international regulatory requirement and a necessary step in the safety evaluation of industrial and consumer products. Although a number of in vitro ocular irritation assays exist, none are capable of fully categorizing chemicals as a stand-alone assay. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was developed with the goal of assessing the reliability of eight in vitro/alternative test methods as well as establishing an optimal tiered-testing strategy. One of the in vitro assays selected was the validated SkinEthic™ Human Corneal Epithelium Eye Irritation Test method (SkinEthic™ HCE EIT). The SkinEthic™ HCE EIT has already demonstrated its capacity to correctly identify chemicals (both substances and mixtures) not requiring classification and labelling for eye irritation or serious eye damage (No Category). The goal of this study was to evaluate the performance of the SkinEthic™ HCE EIT test method in terms of the important in vivo drivers of classification. For the performance with respect to the drivers all in vivo Cat 1 and No Cat chemicals were 100% correctly identified. For Cat 2 chemicals the liquids and the solids had a sensitivity of 100% and 85.7%, respectively. For the SkinEthic™ HCE EIT test method, 100% concordance in predictions (No Cat versus No prediction can be made) between the two participating laboratories was obtained. The accuracy of the SkinEthic™ HCE EIT was 97.5% with 100% sensitivity and 96.9% specificity. The SkinEthic™ HCE EIT confirms its excellent results of the validation studies. Copyright © 2017. Published by Elsevier Ltd.

Association between ultraviolet radiation, skin sun sensitivity and risk of pancreatic cancer.

PubMed

Tran, Bich; Whiteman, David C; Webb, Penelope M; Fritschi, Lin; Fawcett, Jonathan; Risch, Harvey A; Lucas, Robyn; Pandeya, Nirmala; Schulte, Annaka; Neale, Rachel E

2013-12-01

Ecological studies showing an inverse association between pancreatic cancer incidence and mortality and levels of ultraviolet radiation (UVR), suggest that higher levels of sun exposure may reduce risks of pancreatic cancer but there has been only one individual-level study that examined this issue. We aimed to examine the association between pancreatic cancer and markers of exposure to solar UVR, namely skin type, treatment of skin lesions, ambient UVR and time outdoors on work days. We used data from an Australian case-control study. Location at birth, residential location during adulthood, outdoors work, history of skin lesion treatment and sensitivity of the skin to the sun were obtained by questionnaire. We limited the analyses to Caucasians who answered the questionnaire about UVR (controls=589/711 recruited; cases=496/705 recruited). We used NASA's Total Ozone Mapping Spectrometer to estimate ambient UVR. Being born in or living in areas of higher ambient UVR (compared to lower ambient UVR) was associated with about 30-40% lower risk of pancreatic cancer. People with fair skin colour had 47% lower risk of pancreatic cancer than those with dark skin colour (95% CI 0.37-0.75). There was some suggestion of increased risk with increased average number of hours spent outside at work. This study suggests that people with light skin colour or those born or living in areas of high ambient UVR have lower risk of pancreatic cancer. Our analysis supports an association between UVR and pancreatic cancer, possibly mediated through production of vitamin D. Copyright © 2013 Elsevier Ltd. All rights reserved.

Raman spectroscopy reveals biophysical markers in skin cancer surgical margins

NASA Astrophysics Data System (ADS)

Feng, Xu; Moy, Austin J.; Nguyen, Hieu T. M.; Zhang, Yao; Fox, Matthew C.; Sebastian, Katherine R.; Reichenberg, Jason S.; Markey, Mia K.; Tunnell, James W.

2018-02-01

The recurrence rate of nonmelanoma skin cancer is highly related to the residual tumor after surgery. Although tissueconserving surgery, such as Mohs surgery, is a standard method for the treatment of nonmelanoma skin cancer, they are limited by lengthy and costly frozen-section histopathology. Raman spectroscopy (RS) is proving to be an objective, sensitive, and non-destructive tool for detecting skin cancer. Previous studies demonstrated the high sensitivity of RS in detecting tumor margins of basal cell carcinoma (BCC). However, those studies rely on statistical classification models and do not elucidate the skin biophysical composition. As a result, we aim to discover the biophysical differences between BCC and primary normal skin structures (including epidermis, dermis, hair follicle, sebaceous gland and fat). We obtained freshly resected ex vivo skin samples from fresh resection specimens from 14 patients undergoing Mohs surgery. Raman images were acquired from regions containing one or more structures using a custom built 830nm confocal Raman microscope. The spectra were grouped using K-means clustering analysis and annotated as either BCC or each of the five normal structures by comparing with the histopathology image of the serial section. The spectral data were then fit by a previously established biophysical model with eight primary skin constituents. Our results show that BCC has significant differences in the fit coefficients of nucleus, collagen, triolein, keratin and elastin compared with normal structures. Our study reveals RS has the potential to detect biophysical changes in resection margins, and supports the development of diagnostic algorithms for future intraoperative implementation of RS during Mohs surgery.

Dermoscopy improves accuracy of primary care physicians to triage lesions suggestive of skin cancer.

PubMed

Argenziano, Giuseppe; Puig, Susana; Zalaudek, Iris; Sera, Francesco; Corona, Rosamaria; Alsina, Mercè; Barbato, Filomena; Carrera, Cristina; Ferrara, Gerardo; Guilabert, Antonio; Massi, Daniela; Moreno-Romero, Juan A; Muñoz-Santos, Carlos; Petrillo, Gianluca; Segura, Sonia; Soyer, H Peter; Zanchini, Renato; Malvehy, Josep

2006-04-20

Primary care physicians (PCPs) constitute an appropriate target for new interventions and educational campaigns designed to increase skin cancer screening and prevention. The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard clinical examination improves the accuracy of PCPs to triage lesions suggestive of skin cancer. PCPs in Barcelona, Spain, and Naples, Italy, were given a 1-day training course in skin cancer detection and dermoscopic evaluation, and were randomly assigned to the dermoscopy evaluation arm or naked-eye evaluation arm. During a 16-month period, 73 physicians evaluated 2,522 patients with skin lesions who attended their clinics and scored individual lesions as benign or suggestive of skin cancer. All patients were re-evaluated by expert dermatologists at clinics for pigmented lesions. Referral accuracy of both PCP groups was calculated by their scores, which were compared to those tabulated for dermatologists. Referral sensitivity, specificity, and positive and negative predictive values were 54.1%, 71.3%, 11.3%, and 95.8%, respectively, in the naked-eye arm, and 79.2%, 71.8%, 16.1%, and 98.1%, respectively, in the dermoscopy arm. Significant differences were found in terms of sensitivity and negative predictive value (P = .002 and P = .004, respectively). Histopathologic examination of equivocal lesions revealed 23 malignant skin tumors missed by PCPs performing naked-eye observation and only six by PCPs using dermoscopy (P = .002). The use of dermoscopy improves the ability of PCPs to triage lesions suggestive of skin cancer without increasing the number of unnecessary expert consultations.

Critical comparison of diffuse reflectance spectroscopy and colorimetry as dermatological diagnostic tools for acanthosis nigricans: a chemometric approach.

PubMed

Devpura, Suneetha; Pattamadilok, Bensachee; Syed, Zain U; Vemulapalli, Pranita; Henderson, Marsha; Rehse, Steven J; Hamzavi, Iltefat; Lim, Henry W; Naik, Ratna

2011-06-01

Quantification of skin changes due to acanthosis nigricans (AN), a disorder common among insulin-resistant diabetic and obese individuals, was investigated using two optical techniques: diffuse reflectance spectroscopy (DRS) and colorimetry. Measurements were obtained from AN lesions on the neck and two control sites of eight AN patients. A principal component/discriminant function analysis successfully differentiated between AN lesion and normal skin with 87.7% sensitivity and 94.8% specificity in DRS measurements and 97.2% sensitivity and 96.4% specificity in colorimetry measurements.

Allergic Responses Induced by the Immunomodulatory Effects of Nanomaterials upon Skin Exposure

PubMed Central

Yoshioka, Yasuo; Kuroda, Etsushi; Hirai, Toshiro; Tsutsumi, Yasuo; Ishii, Ken J.

2017-01-01

Over the past decade, a vast array of nanomaterials has been created through the development of nanotechnology. With the increasing application of these nanomaterials in various fields, such as foods, cosmetics, and medicines, there has been concern about their safety, that is, nanotoxicity. Therefore, there is an urgent need to collect information about the biological effects of nanomaterials so that we can exploit their potential benefits and design safer nanomaterials, while avoiding nanotoxicity as a result of inhalation or skin exposure. In particular, the immunomodulating effect of nanomaterials is one of most interesting aspects of nanotoxicity. However, the immunomodulating effects of nanomaterials through skin exposure have not been adequately discussed compared with the effects of inhalation exposure, because skin penetration by nanomaterials is thought to be extremely low under normal conditions. On the other hand, the immunomodulatory effects of nanomaterials via skin may cause severe problems for people with impaired skin barrier function, because some nanomaterials could penetrate the deep layers of their allergic or damaged skin. In addition, some studies, including ours, have shown that nanomaterials could exhibit significant immunomodulating effects even if they do not penetrate the skin. In this review, we summarize our current knowledge of the allergic responses induced by nanomaterials upon skin exposure. First, we discuss nanomaterial penetration of the intact or impaired skin barrier. Next, we describe the immunomodulating effects of nanomaterials, focusing on the sensitization potential of nanomaterials and the effects of co-exposure of nanomaterials with substances such as chemical sensitizers or allergens, on the onset of allergy, following skin exposure. Finally, we discuss the potential mechanisms underlying the immunomodulating effects of nanomaterials by describing the involvement of the protein corona in the interaction of nanomaterials with biological components and by presenting recent data about the adjuvant effects of well-characterized particle adjuvant, aluminum salt, as an example of immunomodulatory particulate. PMID:28261221

Homeopathic Treatment of Vitiligo: A Report of Fourteen Cases

PubMed Central

Mahesh, Seema; Mallappa, Mahesh; Tsintzas, Dionysios; Vithoulkas, George

2017-01-01

Case series Patient: — Final Diagnosis: — Symptoms: Skin lesions Medication: — Clinical Procedure: — Specialty: Dermatology Objective: Unusual or unexpected effect of treatment Background: Vitiligo, also known as leukoderma, is an autoimmune skin condition that results in the loss of melanin pigment. Vitiligo is not a rare condition but is difficult to treat and is associated with psychological distress. Case Reports: A series of 14 cases of vitiligo are presented that were treated with individualized homeopathic remedies that were based on plant, animal, or mineral compounds. There were 13 women and one man in the case series, with a mean age 29.8 years, and a mean follow-up from treatment of 58 months. The mean time between the onset of the appearance of vitiligo and the first consultation at our clinic was 96 months. Homeopathic treatment for patients is holistic and was performed on an individualized basis as described in this case series. Photographic images of the skin are presented before and after treatment. Conclusions: In 14 patients with vitiligo treated with individualized homeopathy, the best results were achieved in the patients who were treated in the early stages of the disease. We believe that homeopathy may be effective in the early stages of vitiligo, but large controlled clinical studies are needed in this area. PMID:29196612

Effect of chemical peeling on the skin in relation to UV irradiation.

PubMed

Funasaka, Yoko; Abdel-Daim, Mohamed; Kawana, Seiji; Nishigori, Chikako

2012-07-01

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. However, it needs to be clarified whether the repetitive procedure of chemical peeling on photodamaged skin is safe and whether the different chemicals used for peeling results in similar outcomes or not. In this article, we reviewed the effect of peeling or peeling agents on the skin in relation to ultraviolet (UV) radiation. The pretreatment of peeling agents usually enhance UV sensitivity by inducing increased sunburn cell formation, lowering minimum erythematous dose and increasing cyclobutane pyrimidine dimers. However, this sensitivity is reversible and recovers to normal after 1-week discontinuation. Using animals, the chronic effect of peeling and peeling agents was shown to prevent photocarcinogenesis. There is also an in vitro study using culture cells to know the detailed mechanisms of peeling agents, especially on cell proliferation and apoptotic changes via activating signalling cascades and oxidative stress. It is important to understand the effect of peeling agents on photoaged skin and to know how to deal with UV irradiation during the application of peeling agents and treatment of chemical peeling in daily life. © 2012 John Wiley & Sons A/S.

Detection of canine skin and subcutaneous tumors by visible and near-infrared diffuse reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Cugmas, Blaž; Plavec, Tanja; Bregar, Maksimilijan; Naglič, Peter; Pernuš, Franjo; Likar, Boštjan; Bürmen, Miran

2015-03-01

Cancer is the main cause of canine morbidity and mortality. The existing evaluation of tumors requires an experienced veterinarian and usually includes invasive procedures (e.g., fine-needle aspiration) that can be unpleasant for the dog and the owner. We investigate visible and near-infrared diffuse reflectance spectroscopy (DRS) as a noninvasive optical technique for evaluation and detection of canine skin and subcutaneous tumors ex vivo and in vivo. The optical properties of tumors and skin were calculated in a spectrally constrained manner, using a lookup table-based inverse model. The obtained optical properties were analyzed and compared among different tumor groups. The calculated parameters of the absorption and reduced scattering coefficients were subsequently used for detection of malignant skin and subcutaneous tumors. The detection sensitivity and specificity of malignant tumors ex vivo were 90.0% and 73.5%, respectively, while corresponding detection sensitivity and specificity of malignant tumors in vivo were 88.4% and 54.6%, respectively. The obtained results show that the DRS is a promising noninvasive optical technique for detection and classification of malignant and benign canine skin and subcutaneous tumors. The method should be further investigated on tumors with common origin.

Local lymph node assay (LLNA): comparison of different protocols by testing skin-sensitizing epoxy resin system components.

PubMed

Gamer, Armin O; Nies, Eberhard; Vohr, Hans-Werner

2008-12-01

Thirteen epoxy resin system components were tested in the LLNA with regard to their sensitizing potency. Lymph node stimulation was quantified not only by measuring the incorporation of [3H]-thymidine into the ear lymph nodes but also the counts of cells recovered from these organs. Equivalent figures were obtained with both endpoints used for the evaluation of lymph node cell proliferation if the reference stimulation indices were adjusted. When dissolved in acetone, all test substances showed skin-sensitizing potential, mainly on the boundary between "strong" and "moderate" according to common potency evaluation schemes. Replacing acetone with acetone/olive oil (4:1) as a vehicle for four selected test items, resulted in considerably lower estimated concentrations for sensitization induction. The challenges in comparing the results obtained by different LLNA variations are discussed.

In vitro assessment of skin sensitization, photosensitization and phototoxicity potential of commercial glyphosate-containing formulations.

PubMed

de Ávila, Renato Ivan; Teixeira, Gabriel Campos; Veloso, Danillo Fabrini Maciel Costa; Moreira, Larissa Cleres; Lima, Eliana Martins; Valadares, Marize Campos

2017-12-01

This study evaluated the applicability of a modified Direct Peptide Reactivity Assay (DPRA) (OECD N° 442C, 2015) through the 10-fold reduction of reaction volume (micro-DPRA, mDPRA) for skin sensitization evaluation of six commercial glyphosate-containing formulations. In addition, another modification of DPRA was proposed by adding a UVA (5J/cm 2 ) irradiation step, namely photo-mDPRA, to better characterize (photo)sensitizer materials. The phototoxicity profile of pesticides was also evaluated using the 3T3 Neutral Red Uptake Phototoxicity Test (3T3-NRU-PT) (OECD N° 432, 2004). The mDPRA could represent an environmentally acceptable test approach, since it reduces costs and organic waste. Peptide depletion was greater in photo-mDPRA and changed the reactivity class of each test material, in comparison to mDPRA. Thus, the association of mDPRA with photo-mDPRA was better for correctly characterizing human (photo)sensitizer substances and pesticides. In general, cysteine depletion was greater than that of lysine for all materials tested in both mDPRA and photo-mDPRA. Furthermore, while 3T3-NRU-PT is unable to predict (photo)sensitizers, it was capable of correctly identifying the phototoxic potential of the tested agrochemical formulations. In conclusion, mDPRA plus photo-mDPRA and 3T3-NRU-PT seem to be preliminary non-animal test batteries for skin (photo)sensitization/phototoxicity assessment of chemicals, agrochemical formulations and their ingredients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dolichandrone platycalyx: New entomophilous pollen--A report on pollen sensitization in allergic individuals.

PubMed

Mridula, P A; Mahesh, P A; Abraham, Jacob N; Amrutha, D H; Agashe, S N; Sitesh, Roy; Vedanthan, P K

2011-01-01

Dolichandrone platycalyx, commonly known as Nile trumpet tree, is believed to have originated in East Africa. However, this and the variants of this tree are found in Europe, Asia, and America (California and Florida). The tree mostly grows in tropical climates, but temperate species are also found. This study was designed to evaluate the allergenicity of D. platycalyx, one of the most common entomophilous avenue trees in Karnataka state, and to determine the pollen production of D. platycalyx. All of the patients with allergic rhinitis and asthma attending a tertiary care center in South India during August 2007 to March 2008 underwent a detailed clinical evaluation and skin-prick testing to common allergens along with D. platycalyx. Control subjects without any symptoms of respiratory allergy also underwent skin testing. The pollen counts were determined for a mature unopened flower of D. platycalyx. A total of 317 subjects with respiratory allergy and 30 controls were included in the study. A significant percentage (16.1%) of patients evaluated were observed to be sensitive to Dolichandrone pollen extract by skin-prick testing, whereas none of the control subjects were found to be sensitized. D. platycalyx was the fourth most common sensitizer after Parthenium hysterophorus, Prosopis juliflora, and Artemesia vulgaris. D. platycalyx was found to be a moderate pollen producer at 66,000 pollens/flower. Sensitization to D. platycalyx is common in subjects with respiratory allergies. The clinical relevance of this sensitization and other entomophilous plants needs additional study.

A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers.

PubMed

Avonto, Cristina; Chittiboyina, Amar G; Rua, Diego; Khan, Ikhlas A

2015-12-01

Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization, integrated approaches combining different chemical, biological and in silico methods are recommended to replace conventional animal tests. Chemical methods are intended to characterize the potential of a sensitizer to induce earlier molecular initiating events. The presence of an electrophilic mechanistic domain is considered one of the essential chemical features to covalently bind to the biological target and induce further haptenation processes. Current in chemico assays rely on the quantification of unreacted model nucleophiles after incubation with the candidate sensitizer. In the current study, a new fluorescence-based method, 'HTS-DCYA assay', is proposed. The assay aims at the identification of reactive electrophiles based on their chemical reactivity toward a model fluorescent thiol. The reaction workflow enabled the development of a High Throughput Screening (HTS) method to directly quantify the reaction adducts. The reaction conditions have been optimized to minimize solubility issues, oxidative side reactions and increase the throughput of the assay while minimizing the reaction time, which are common issues with existing methods. Thirty-six chemicals previously classified with LLNA, DPRA or KeratinoSens™ were tested as a proof of concept. Preliminary results gave an estimated 82% accuracy, 78% sensitivity, 90% specificity, comparable to other in chemico methods such as Cys-DPRA. In addition to validated chemicals, six natural products were analyzed and a prediction of their sensitization potential is presented for the first time. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of computer systems and ranking criteria for automatic melanoma detection in dermoscopic images.

PubMed

Møllersen, Kajsa; Zortea, Maciel; Schopf, Thomas R; Kirchesch, Herbert; Godtliebsen, Fred

2017-01-01

Melanoma is the deadliest form of skin cancer, and early detection is crucial for patient survival. Computer systems can assist in melanoma detection, but are not widespread in clinical practice. In 2016, an open challenge in classification of dermoscopic images of skin lesions was announced. A training set of 900 images with corresponding class labels and semi-automatic/manual segmentation masks was released for the challenge. An independent test set of 379 images, of which 75 were of melanomas, was used to rank the participants. This article demonstrates the impact of ranking criteria, segmentation method and classifier, and highlights the clinical perspective. We compare five different measures for diagnostic accuracy by analysing the resulting ranking of the computer systems in the challenge. Choice of performance measure had great impact on the ranking. Systems that were ranked among the top three for one measure, dropped to the bottom half when changing performance measure. Nevus Doctor, a computer system previously developed by the authors, was used to participate in the challenge, and investigate the impact of segmentation and classifier. The diagnostic accuracy when using an automatic versus the semi-automatic/manual segmentation is investigated. The unexpected small impact of segmentation method suggests that improvements of the automatic segmentation method w.r.t. resemblance to semi-automatic/manual segmentation will not improve diagnostic accuracy substantially. A small set of similar classification algorithms are used to investigate the impact of classifier on the diagnostic accuracy. The variability in diagnostic accuracy for different classifier algorithms was larger than the variability for segmentation methods, and suggests a focus for future investigations. From a clinical perspective, the misclassification of a melanoma as benign has far greater cost than the misclassification of a benign lesion. For computer systems to have clinical impact, their performance should be ranked by a high-sensitivity measure.

Melanoma Is Skin Deep: A 3D Reconstruction Technique for Computerized Dermoscopic Skin Lesion Classification

PubMed Central

Satheesha, T. Y.; Prasad, M. N. Giri; Dhruve, Kashyap D.

2017-01-01

Melanoma mortality rates are the highest amongst skin cancer patients. Melanoma is life threating when it grows beyond the dermis of the skin. Hence, depth is an important factor to diagnose melanoma. This paper introduces a non-invasive computerized dermoscopy system that considers the estimated depth of skin lesions for diagnosis. A 3-D skin lesion reconstruction technique using the estimated depth obtained from regular dermoscopic images is presented. On basis of the 3-D reconstruction, depth and 3-D shape features are extracted. In addition to 3-D features, regular color, texture, and 2-D shape features are also extracted. Feature extraction is critical to achieve accurate results. Apart from melanoma, in-situ melanoma the proposed system is designed to diagnose basal cell carcinoma, blue nevus, dermatofibroma, haemangioma, seborrhoeic keratosis, and normal mole lesions. For experimental evaluations, the PH2, ISIC: Melanoma Project, and ATLAS dermoscopy data sets is considered. Different feature set combinations is considered and performance is evaluated. Significant performance improvement is reported the post inclusion of estimated depth and 3-D features. The good classification scores of sensitivity = 96%, specificity = 97% on PH2 data set and sensitivity = 98%, specificity = 99% on the ATLAS data set is achieved. Experiments conducted to estimate tumor depth from 3-D lesion reconstruction is presented. Experimental results achieved prove that the proposed computerized dermoscopy system is efficient and can be used to diagnose varied skin lesion dermoscopy images. PMID:28512610