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

Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing following Hurricanes

PubMed Central

Hurst, David

2017-01-01

Objective. To report on changes in sensitivity to mold allergens determined by changes in intradermal skin testing reactivity, after exposure to two severe hurricanes. Methods. A random, retrospective allergy charts review divided into 2 groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior to hurricanes, and Group B, patients tested in 2014 and 2015 following hurricanes. Reactivity to eighteen molds was determined by intradermal skin testing. Test results, age, and respiratory symptoms were recorded. Chi-square test determined reactivity/sensitivity differences between groups. Results. Posthurricane patients had 34.6 times more positive results (p < 0.0001) at weaker dilutions, all tested molds were found to be more reactive, and 95% had at least one positive test versus only 62% before the hurricanes (p < 0.0001); average mold reactivity was 55% versus 16% while 17% of patients reacted to the entire panel versus none before the hurricanes (p < 0.0001). The posthurricane population was younger (p < 0.001) and included more patients with asthma or lower respiratory symptoms (p < 0.05). Conclusion. Reactivity and sensitization to mold allergens increased compared to patients before the hurricanes. This supports climatologists' hypothesis that environmental changes resulting from hurricanes can be a health risk as reflected in increased allergic sensitivities and symptoms and has significant implications for physicians treating patients from affected areas. PMID:28491100

Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing following Hurricanes.

PubMed

Saporta, Diego; Hurst, David

2017-01-01

Objective . To report on changes in sensitivity to mold allergens determined by changes in intradermal skin testing reactivity, after exposure to two severe hurricanes. Methods . A random, retrospective allergy charts review divided into 2 groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior to hurricanes, and Group B, patients tested in 2014 and 2015 following hurricanes. Reactivity to eighteen molds was determined by intradermal skin testing. Test results, age, and respiratory symptoms were recorded. Chi-square test determined reactivity/sensitivity differences between groups. Results . Posthurricane patients had 34.6 times more positive results ( p < 0.0001) at weaker dilutions, all tested molds were found to be more reactive, and 95% had at least one positive test versus only 62% before the hurricanes ( p < 0.0001); average mold reactivity was 55% versus 16% while 17% of patients reacted to the entire panel versus none before the hurricanes ( p < 0.0001). The posthurricane population was younger ( p < 0.001) and included more patients with asthma or lower respiratory symptoms ( p < 0.05). Conclusion . Reactivity and sensitization to mold allergens increased compared to patients before the hurricanes. This supports climatologists' hypothesis that environmental changes resulting from hurricanes can be a health risk as reflected in increased allergic sensitivities and symptoms and has significant implications for physicians treating patients from affected areas.

Skin irritability to sodium lauryl sulfate is associated with increased positive patch test reactions.

PubMed

Schwitulla, J; Brasch, J; Löffler, H; Schnuch, A; Geier, J; Uter, W

2014-07-01

As previous observations have indicated an inter-relationship between irritant and allergic skin reactions we analysed data of synchronous allergen and sodium lauryl sulfate (SLS) patch tests in terms of a relationship between SLS responsiveness and allergic patch test reactions. To analyse differences in terms of allergen-specific and overall reaction profiles between patients with vs. those without an irritant reaction to SLS. Clinical data of 26 879 patients patch tested from 2008 to 2011 by members of the Information Network of Departments of Dermatology were analysed. After descriptive analyses, including the MOAHLFA index, the positivity ratio and the reaction index, a negative binomial hurdle model was adopted to investigate the correlation between SLS reactivity and positive patch test reactions. Men, patients aged ≥ 40 years and patients with an occupational dermatitis background were over-represented in the SLS-reactive group. Patients with an irritant reaction to SLS showed a higher proportion of weak positive reactions, as well as more questionable and irritant reactions to contact allergens than patients not reactive to SLS. The risk of an additional positive patch test reaction increased by 22% for SLS-reactive patients compared with those who were SLS negative. The marked association between SLS reactivity and the number of positive reactions in patch test patients may be due to nonspecific increased skin reactivity at the moment of patch testing only. However, increased SLS reactivity could also be due to longer-lasting enhanced skin irritability, which may have promoted (poly-)sensitization. Further studies, for example with longitudinal data on patients repeatedly patch tested with SLS and contact allergens, are necessary. © 2014 British Association of Dermatologists.

Use of recombinant purified protein derivative (PPD) antigens as specific skin test for tuberculosis.

PubMed

Stavri, Henriette; Bucurenci, Nadia; Ulea, Irina; Costache, Adriana; Popa, Loredana; Popa, Mircea Ioan

2012-11-01

Purified protein derivative (PPD) is currently the only available skin test reagent used worldwide for the diagnosis of tuberculosis (TB). The aim of this study was to develop a Mycobacterium tuberculosis specific skin test reagent, without false positive results due to Bacillus Calmette-Guerin (BCG) vaccination using recombinant antigens. Proteins in PPD IC-65 were analyzed by tandem mass spectrometry and compared to proteins in M. tuberculosis culture filtrate; 54 proteins were found in common. Top candidates MPT64, ESAT 6, and CFP 10 were overexpressed in Escherichia coli expression strains and purified as recombinant proteins. To formulate optimal immunodiagnostic PPD cocktails, the antigens were evaluated by skin testing guinea pigs sensitized with M. tuberculosis H37Rv and BCG. For single antigens and a cocktail mixture of these antigens, best results were obtained using 3 μg/0.1 ml, equivalent to 105 TU (tuberculin units). Each animal was simultaneously tested with PPD IC-65, 2 TU/0.1 ml, as reference. Reactivity of the multi-antigen cocktail was greater than that of any single antigen. The skin test results were between 34.3 and 76.6 per cent the level of reactivity compared to that of the reference when single antigens were tested and 124 per cent the level of reactivity compared to the reference for the multi-antigen cocktail. Our results showed that this specific cocktail could represent a potential candidate for a new skin diagnostic test for TB.

Skin testing for immediate hypersensitivity to corticosteroids: a case series and literature review.

PubMed

Baker, A; Empson, M; The, R; Fitzharris, P

2015-03-01

Immediate hypersensitivity to corticosteroids is reported to occur with an incidence of 0.1%. The largest previous case series reporting corticosteroid skin testing has seven patients. We identified 23 patients (mean age 50 years, 65% female) from Auckland City Hospital who underwent skin testing (ST) for suspected corticosteroid hypersensitivity between July 2005 and April 2012. We performed a retrospective clinical case note review detailing clinical history of reaction, skin test results and subsequent management. Most patients (21/23) had a standard panel of testing with prednisolone, triamcinolone, methylprednisolone, hydrocortisone and dexamethasone. Skin tests used a 10% steroid stock concentration for skin prick tests (SPT) and dilutions of 1 : 1000, 1 : 100 and 1 : 10 for subsequent intradermal testing. A weal 3 mm greater than the negative control was considered positive. A total of 23 patients were identified who had skin testing for suspected acute hypersensitivity to corticosteroids, eight of which had a history of anaphylaxis. From 28 reactions (in 23 patients), the most common route of administration was intra-articular (13), followed by oral (7), intravenous (3) and other (5). Skin tests were positive in 8/23 patients, and 7/8 of these patients had a history of corticosteroid-associated anaphylaxis. Skin tests were positive at either the skin prick test or intradermal stages. There was evidence suggesting clinical and skin test cross-reactivity between corticosteroids in one patient. One patient had a positive skin test, but negative oral challenge suggesting the skin test was false positive. Skin tests were negative in 15/23 patients. One patient had a negative prednisolone skin test and positive unblinded oral challenge, suggesting a false-negative skin test. Skin testing can provide sufficient evidence to diagnose allergy in patients with a clear history of immediate hypersensitivity to corticosteroids such as anaphylaxis. Both skin prick

Comparison between sensitivity of autologous skin serum test and autologous plasma skin test in patients with Chronic Idiopathic Urticaria for detection of antibody against IgE or IgE receptor (FcεRIα).

PubMed

Sajedi, Vahid; Movahedi, Masoud; Aghamohammadi, Asghar; Aghamohamadi, Asghar; Gharagozlou, Mohammad; Ghareguzlou, Mohammad; Shafiei, Alireza; Soheili, Habib; Sanajian, Nahal

2011-06-01

Intradermal injection of autologous serum and plasma elicit a cutaneous reactivity in almost 45-60% of patients with Chronic Idiopathic Urticaria (CIU). This reactivity is associated with the presence of auto antibodies against IgE or IgE receptors. This study was carried out to compare the cutaneous reactivity of autologous serum and plasma skin tests in a series of patients with CIU for diagnosis of auto antibodies against IgE or IgE receptor. Fifty eight patients with CIU were injected intradermally with autologous serum and plasma (anticoagulated by citrate). Histamine was used as positive control and normal saline as negative control. The study group was checked by routine laboratory tests (CBC, U/A etc), allergens with skin prick tests, and serum IgE level, and auto antibodies against thyroid as well. Duration of urticaria was another factor which was assessed.There was no significant difference between positive ASST and positive APST patients for the above mentioned tests. 77.6% of the patients were Positive for APST and 65.5% were ASST positive. Duration of urticaria was longer in patients with positive ASST and APST than ASST and APST negative patients, although the difference was not statistically significant.Autologus serum skin test (ASST) and autologous plasma skin test (APST) could be used for estimation of duration and severity of urticaria and planning for the treatment.

Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme.

PubMed

Bodensteiner, David; Scott, C Ronald; Sims, Katherine B; Shepherd, Gillian M; Cintron, Rebecca D; Germain, Dominique P

2008-05-01

To determine if enzyme replacement therapy, involving intravenous infusions of recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme), could be safely continued in patients with Fabry disease who had been withdrawn from a previous clinical trial as a precautionary, protocol-specified measure due to detection of serum IgE antibodies or skin-test reactivity to agalsidase beta. The rechallenge infusion protocol specified strict patient monitoring conditions and graded dosing and infusion-rate schemes that were adjusted according to each patient's tolerance to the infusion. Six males (age: 26-66 years) were enrolled. During rechallenge, five patients received between 4 and 27 infusions; one patient voluntarily withdrew after one infusion because of recurrence of infusion-associated reactions. No anaphylactic reactions occurred. All adverse events, including four serious adverse events, were mild or moderate in intensity. Most treatment-related adverse events occurred during infusions (most commonly urticaria, vomiting, nausea, chills, pruritus, hypertension) and were resolved by infusion rate reductions and/or medication. After participation in the study, all patients, including the one who withdrew after one infusion, transitioned to commercial drug. Agalsidase beta therapy can be successfully reinstated in patients with Fabry disease who have developed IgE antibodies or skin test reactivity to the recombinant enzyme.

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.

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...

Peptide Reactivity of Isothiocyanates - Implications for Skin Allergy

NASA Astrophysics Data System (ADS)

Karlsson, Isabella; Samuelsson, Kristin; Ponting, David J.; Törnqvist, Margareta; Ilag, Leopold L.; Nilsson, Ulrika

2016-02-01

Skin allergy is a chronic condition that affects about 20% of the population of the western world. This disease is caused by small reactive compounds, haptens, able to penetrate into the epidermis and modify endogenous proteins, thereby triggering an immunogenic reaction. Phenyl isothiocyanate (PITC) and ethyl isothiocyanate (EITC) have been suggested to be responsible for allergic skin reactions to chloroprene rubber, the main constituent of wetsuits, orthopedic braces, and many types of sports gear. In the present work we have studied the reactivity of the isothiocyanates PITC, EITC, and tetramethylrhodamine-6-isothiocyanate (6-TRITC) toward peptides under aqueous conditions at physiological pH to gain information about the types of immunogenic complexes these compounds may form in the skin. We found that all three compounds reacted quickly with cysteine moieties. For PITC and 6-TRITC the cysteine adducts decomposed over time, while stable adducts with lysine were formed. These experimental findings were verified by DFT calculations. Our results may suggest that the latter are responsible for allergic reactions to isothiocyanates. The initial adduct formation with cysteine residues may still be of great importance as it prevents hydrolysis and facilitates the transport of isothiocyanates into epidermis where they can form stable immunogenic complexes with lysine-containing proteins.

[An analysis of skin prick test reactivity to dust mite in overweight and normal weight children with allergic asthma before and after specific immunotherapy].

PubMed

Wang, Jian; Huang, Ying; Zhang, Xue-Li; Huang, Xia; Xu, Xiao-Wen; Liang, Fan-Mei

2016-04-01

To study the skin prick test (SPT) reactivity to house dust mite allergens in overweight and normal weight children with allergic asthma before and after standard subcutaneous specific immunotherapy. Two hundred and fifteen children with allergic asthma who had positive SPT responses to Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF) were enrolled. According to the weight index, they were classified into overweight (n=63) and normal weight groups (n=152). Skin indices (SI) to DP and DF were compared between the two groups at 6 months and 1 year after standard subcutaneous specific immunotherapy. The overweight group had a significantly larger histamine wheal diameter than the normal weight group after controlling the variation in testing time (P<0.05). After controlling the variation in weights, there were significant differences in the SIs to DP and DF before specific immunotherapy and at 6 months and 1 year after specific immunotherapy. At 6 months and 1 year after specific immunotherapy, the SIs to DP and DF were significantly reduced in both groups (P<0.05), and the overweight group had greater decreases in the SIs to DP and DF than the normal weight group. The overweight children with allergic asthma have stronger responses to histamine than the normal weight patients. Specific immunotherapy can reduce the reactivity to dust mite allergens in children with allergic asthma. Within one year after specific immunotherapy, the overweight children with allergic asthma have a significantly greater decrease in the reactivity to dust mite allergens than the normal weight patients.

Skin microdialysis coupled with laser speckle contrast imaging to assess microvascular reactivity.

PubMed

Cracowski, J L; Gaillard-Bigot, F; Cracowski, C; Roustit, M; Millet, C

2011-11-01

Laser speckle contrast imaging (LSCI) can be used to assess real-time responses of skin microcirculation to pharmacological interventions. The main objective of this study was to determine whether intradermal or subdermal microdialysis fiber insertion, coupled with skin flux recording using LSCI, can be used to assess baseline cutaneous flux and the post-occlusive reactive hyperemic response. The microdialysis sites were compared to control area without microdialysis fibers. One dermal and two subdermal microdialysis fibers were randomly inserted in the right forearm skin of six healthy volunteers. We performed consecutively tests of post-occlusive hyperemia, infusion of 29 mM sodium nitroprusside (SNP), local thermal hyperemia at 43°C and a second 29 mM SNP infusion at the end of the experiment. Two hours after fiber insertion, cutaneous vascular conductances (CVC) at the subdermal fiber sites were not different from their respective control regions of interest, while at the dermal site CVC remained higher (0.48+/-0.15 versus 0.37+/-0.1 PU.mm Hg(-1), P=0.003). The peak CVC and area under the curve observed during post-occlusive reactive hyperemia were similar at all fiber sites and their respective controls. We observed a similar increase in CVC using 29 mM SNP infusion, 40 min local heating at 43°C, and their combination. Finally, physiological and pharmacological responses of the subdermal sites were reproducible in terms of amplitude, whether expressed as raw CVC or as % CVCmax. We showed that studying skin microvascular physiological or pharmacological responses using inserted subdermal microdialysis fibers coupled with LSCI is feasible and reproducible, and provides two-dimensional information. This technique will be useful for future mechanistic studies of skin microcirculation. Copyright © 2011 Elsevier Inc. All rights reserved.

PPD skin test

MedlinePlus

... is a method used to diagnose silent (latent) tuberculosis (TB) infection. PPD stands for purified protein derivative. ... skin test; Tuberculin skin test; Mantoux test Images Tuberculosis in the kidney Tuberculosis in the lung Positive ...

Pollen food allergy syndrome in Turkey: Clinical characteristics and evaluation of its association with skin test reactivity to pollens.

PubMed

Özdemir, Seςil Kepil; Özgüςlü, Selcan

2017-09-17

There is limited data regarding pollen food allergy syndrome (PFAS) in Turkey. To investigate the clinical characteristics and possible risk factors of PFAS in Turkey, and to evaluate if there was an association between skin test reactivity to pollens and presence of PFAS. A total of 254 consecutive adult patients with pollen sensitivity were prospectively recruited. Patients were interviewed with a questionnaire including a list of pollen-associated foods. Patients were classified as having PFAS if they reported clear allergic symptoms compatible with PFAS. All participants underwent skin prick tests (SPT) to a panel of common aeroallergens, prick-to-prick tests with culprit fresh foods were performed in patients who gave consent. Self-reported PFAS was observed in 49 patients (19.3%). The most common culprit foods were kiwi, peach, tomato, melon and watermelon. Multiple logistic regression analysis showed that potential risk factors for PFAS were having asthma (OR=2.392, P=0.044) and tree pollen sensitization (OR=2.904, P=0.004). There were no significant differences in the SPT wheal sizes to individual pollen extracts between patients with and without PFAS with a positive SPT result for that pollen extract (P> 0.05). PFAS is frequent in pollen sensitized adults in Turkey. The most commonly implicated foods are kiwi, peach,tomato, melon and watermelon, in our geographical region. SPT wheal sizes to pollen extracts seems to be similar in patients with and without PFAS.

Skin sensitisation: the Colipa strategy for developing and evaluating non-animal test methods for risk assessment.

PubMed

Maxwell, Gavin; Aeby, Pierre; Ashikaga, Takao; Bessou-Touya, Sandrine; Diembeck, Walter; Gerberick, Frank; Kern, Petra; Marrec-Fairley, Monique; Ovigne, Jean-Marc; Sakaguchi, Hitoshi; Schroeder, Klaus; Tailhardat, Magali; Teissier, Silvia; Winkler, Petra

2011-01-01

Allergic contact dermatitis is a delayed-type hypersensitivity reaction induced by small reactive chemicals (haptens). Currently, the sensitising potential and potency of new chemicals is usually characterised using data generated via animal studies, such as the local lymph node assay (LLNA). There are, however, increasing public and political concerns regarding the use of animals for the testing of new chemicals. Consequently, the development of in vitro, in chemico or in silico models for predicting the sensitising potential and/or potency of new chemicals is receiving widespread interest. The Colipa Skin Tolerance task force currently collaborates with and/or funds several academic research groups to expand our understanding of the molecular and cellular events occurring during the acquisition of skin sensitisation. Knowledge gained from this research is being used to support the development and evaluation of novel alternative approaches for the identification and characterisation of skin sensitizing chemicals. At present three non-animal test methods (Direct Peptide Reactivity Assay (DPRA), Myeloid U937 Skin Sensitisation Test (MUSST) and human Cell Line Activation Test (hCLAT)) have been evaluated in Colipa interlaboratory ring trials for their potential to predict skin sensitisation potential and were recently submitted to ECVAM for formal pre-validation. Data from all three test methods will now be used to support the study and development of testing strategy approaches for skin sensitiser potency prediction. This publication represents the current viewpoint of the cosmetics industry on the feasibility of replacing the need for animal test data for informing skin sensitisation risk assessment decisions.

Histoplasma skin test

MedlinePlus

Histoplasmosis skin test ... health care provider cleans an area of your skin, usually the forearm. An allergen is injected just below the cleaned skin surface. An allergen is a substance that causes ...

Evaluation of autologous serum skin test and skin prick test reactivity to house dust mite in patients with chronic spontaneous urticaria.

PubMed

Song, Zhiqiang; Zhai, Zhifang; Zhong, Hua; Zhou, Ziyuan; Chen, WenChieh; Hao, Fei

2013-01-01

Chronic spontaneous urticaria (CSU) is a common skin disorder with etiology that is not well understood. In this study, we evaluated the prevalence of autologous serum skin test (ASST) and skin prick testing (SPT) to house dust mite (HDM) in 862 CSU cases in China. Clinical features, courses and treatment responses were also recorded. The prevalence of positive ASST was 46.3%, and patients aged 30-39 years had the highest positive rate (52.1%). Positive SPT to HDM was seen in 153 patients (17.7%) with the highest positive rate (34.2%) in patients aged 20 or less. Patients with positive ASST had higher urticaria activity scores (UAS) (4.18±0.65 vs. 3.67±0.53) but lower positive rates of HDM (24.6% vs. 37.6%), as compared with those with negative ASST (odds ratio (OR) 1.84, 95% CI 1.38-2.47). Patients could be categorized into four groups based on the results of ASST and SPT to HDM and patients with positive ASST and positive SPT to HDM had the highest disease activity scores, experienced higher frequencies of angioedema, diseases duration, and required higher dosage of loratadine every month, compared with other subgroups (P<0.0001). Patients with CSU showed varied responses of positive ASST and varied sensitivity to HDM, Patients with positive ASST and/or positive SPT had more disease activity compared with patients with negative ASST and/or negative SPT. Further classification can be made based on the result of SPT and ASST.

Evaluation of Autologous Serum Skin Test and Skin Prick Test Reactivity to House Dust Mite in Patients with Chronic Spontaneous Urticaria

PubMed Central

Song, Zhiqiang; Zhai, Zhifang; Zhong, Hua; Zhou, Ziyuan; Chen, WenChieh; Hao, Fei

2013-01-01

Background Chronic spontaneous urticaria (CSU) is a common skin disorder with etiology that is not well understood. Methods In this study, we evaluated the prevalence of autologous serum skin test (ASST) and skin prick testing (SPT) to house dust mite (HDM) in 862 CSU cases in China. Clinical features, courses and treatment responses were also recorded. Results The prevalence of positive ASST was 46.3%, and patients aged 30–39 years had the highest positive rate (52.1%). Positive SPT to HDM was seen in 153 patients (17.7%) with the highest positive rate (34.2%) in patients aged 20 or less. Patients with positive ASST had higher urticaria activity scores (UAS) (4.18±0.65 vs. 3.67±0.53) but lower positive rates of HDM (24.6% vs. 37.6%), as compared with those with negative ASST (odds ratio (OR) 1.84, 95% CI 1.38–2.47). Patients could be categorized into four groups based on the results of ASST and SPT to HDM and patients with positive ASST and positive SPT to HDM had the highest disease activity scores, experienced higher frequencies of angioedema, diseases duration, and required higher dosage of loratadine every month, compared with other subgroups (P<0.0001). Conclusions Patients with CSU showed varied responses of positive ASST and varied sensitivity to HDM, Patients with positive ASST and/or positive SPT had more disease activity compared with patients with negative ASST and/or negative SPT. Further classification can be made based on the result of SPT and ASST. PMID:23741306

Integrating non-animal test information into an adaptive testing strategy - skin sensitization proof of concept case.

PubMed

Jaworska, Joanna; Harol, Artsiom; Kern, Petra S; Gerberick, G Frank

2011-01-01

There is an urgent need to develop data integration and testing strategy frameworks allowing interpretation of results from animal alternative test batteries. To this end, we developed a Bayesian Network Integrated Testing Strategy (BN ITS) with the goal to estimate skin sensitization hazard as a test case of previously developed concepts (Jaworska et al., 2010). The BN ITS combines in silico, in chemico, and in vitro data related to skin penetration, peptide reactivity, and dendritic cell activation, and guides testing strategy by Value of Information (VoI). The approach offers novel insights into testing strategies: there is no one best testing strategy, but the optimal sequence of tests depends on information at hand, and is chemical-specific. Thus, a single generic set of tests as a replacement strategy is unlikely to be most effective. BN ITS offers the possibility of evaluating the impact of generating additional data on the target information uncertainty reduction before testing is commenced.

Human Herpesvirus-6 cytopathic inclusions: an exceptional and recognizable finding on skin biopsy during HHV6 reactivation after autologous stem-cell transplantation.

PubMed

Roux, Jennifer; Battistella, Maxime; Fornecker, Luc; Legoff, Jérôme; Deau, Bénédicte; Houhou, Nadira; Bouaziz, Jean-David; Thieblemont, Catherine; Janin, Anne

2012-08-01

Skin rash are common in immunocompromised patients, particularly after bone marrow transplantation. Human herpes virus 6 (HHV6) reactivation is often suspected, but its clinical presentation and the routine laboratory tests may be unspecific, thus leading to late diagnosis. In this case, we report specific intralymphocytic cytopathic inclusions on skin biopsy as a sign of systemic HHV6 reactivation. A 56-year-old patient presented progressive erythroderma and fever occurring after autologous hematopoietic stem-cell transplantation for mantle cell lymphoma. The skin biopsy showed a perivascular infiltrate of medium-to-large lymphocytes with irregular nuclei containing a large central basophilic inclusion surrounded by a clear halo. High levels of HHV-6 genomic in skin biopsy confirm HHV-6-induced cytopathic effect. The clinical course improved with intravenous foscavir. The specific histopathological findings encountered in this case are exceptional but recognizable, and along with HHV-6 DNA detection allow a prompt recognition of HHV6 skin rash.

Radiocontrast media-associated exanthema: identification of cross-reactivity and tolerability by allergologic testing.

PubMed

Seitz, Cornelia S; Pfeuffer, Petra; Raith, Petra; Bröcker, Eva-B; Trautmann, Axel

2009-10-01

All iodinated radiocontrast media (RCM) may cause hypersensitivity reactions, either immediate-type within 5-10 min of RCM injection or delayed-type, which become apparent more than 1h after RCM exposure. Delayed-type hypersensitivity to RCM may pose a problem for future radiologic investigations because due to possible immunological cross-reactivity all iodinated RCM are usually avoided. The aim of this study was not only to identify the causal RCM for the exanthema but also to demonstrate that patients may receive alternative iodinated RCM despite a history of RCM-induced allergic exanthema. We evaluated 32 patients with a history of exanthema after RCM application using standardized patch, prick and intradermal skin testing. In case of positive skin tests intravenous challenges with skin-test-negative RCM were performed to identify non-ionic monomer RCM which are tolerated. In 6 out of 32 patients skin tests strongly suggested a delayed-type non-IgE-mediated allergic hypersensitivity to the RCM iomeprol (3x), iopromide (2x), and iopamidol. In 4 patients alternative non-ionic monomer RCM (2x iosarcol, iopromide, and iomeprol) were identified by controlled challenge tests. The evaluation of patients with RCM-associated exanthema should always include appropriate skin tests ensuring that patients with a delayed-type allergic RCM-induced exanthema are not missed. Moreover, allergologic testing may identify alternative RCM of the group of non-ionic monomers, which are tolerated in future radiologic investigations.

Reactive skin decontamination lotion (RSDL) for the decontamination of chemical warfare agent (CWA) dermal exposure.

PubMed

Schwartz, M D; Hurst, C G; Kirk, M A; Reedy, S J D; Braue, E H

2012-08-01

Rapid decontamination of the skin is the single most important action to prevent dermal absorption of chemical contaminants in persons exposed to chemical warfare agents (CWA) and toxic industrial chemicals (TICs) as a result of accidental or intentional release. Chemicals on the skin may be removed by mechanical means through the use of dry sorbents or water. Recent interest in decontamination systems which both partition contaminants away from the skin and actively neutralize the chemical has led to the development of several reactive decontamination solutions. This article will review the recently FDA-approved Reactive Skin Decontamination Lotion (RSDL) and will summarize the toxicity and efficacy studies conducted to date. Evidence of RSDL's superior performance against vesicant and organophosphorus chemical warfare agents compared to water, bleach, and dry sorbents, suggests that RSDL may have a role in mass human exposure chemical decontamination in both the military and civilian arenas.

Allergy Skin Tests

MedlinePlus

... allergic rhinitis) Allergic asthma Dermatitis (eczema) Food allergies Penicillin allergy Bee venom allergy Latex allergy Skin tests ... check for an allergy to insect venom or penicillin. Patch test Patch testing is generally done to ...

Vulnerability of reactive skin to electric current perception--a pilot study implicating mast cells and the lymphatic microvasculature.

PubMed

Quatresooz, Pascale; Piérard-Franchimont, Claudine; Piérard, Gérald E

2009-09-01

Sensitive/reactive skin is regarded as a manifestation of sensory irritation. This susceptibility condition to various exogenous factors suggests the intervention of some neuropeptides and other neurobiological mediators. Mast cells are among the putative implicated cells. The present immunohistochemical and morphometric study was performed on two groups of 36 gender- and age-matched subjects complaining or not from reactive skin as determined by electric current perception. In the mid upper part of the dermis, the numerical density in mast cells and the size of the microvasculature were assessed distinguishing the blood and lymphatic vessels. Globally, the distributions of data were large in reactive skin. This condition was characterized by a prominent increase in both the numerical density in mast cells and the overall size of the lymphatics. By contrast, no difference was found in the size of cutaneous blood vessels. More precisely, it appeared that a subgroup of people with reactive skin exhibited these changes contrasting with some other individuals whose data remained close to the normal range. Mast cells and lymphatics are probably involved in the process of sensory irritation affecting a subgroup of the population.

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.

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.

Hypersensitivity reactions to penicillins: studies in a group of patients with negative benzylpenicillin G skin test.

PubMed

Qiao, H-L; Li, Z; Yang, J; Tian, X; Gao, N; Jia, L-J

2009-06-01

Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. The rate of positive reactions for the specific IgE antibodies was 59.40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39.10% (52) and 42.86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7.5%), were significantly fewer than the cross-reacting positive cases (36) to PG (P < 0.01). In the RAST inhibition studies all drugs exhibited good inhibitory potencies, and in some instances the side-chain of the penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. Radioallergosorbent test is a good complementary test in persons who are skin-test negative with PG, and the sensitivity of RAST increases with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross-reactivity.

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.

Decreased Reactivity of Skin Microcirculation in Response to l-Arginine in Later-Onset Type 1 Diabetes

PubMed Central

Neubauer-Geryk, Jolanta; Kozera, Grzegorz M.; Wolnik, Bogumil; Szczyrba, Sebastian; Nyka, Walenty M.; Bieniaszewski, Leszek

2013-01-01

OBJECTIVE The aim of our study was to evaluate the vasodilatory effect of l-arginine infusion on the skin microcirculation and to assess the relationship between this effect and the presence of microangiopathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Capillaroscopy was performed before and after l-arginine infusion in 48 diabetic patients (26 women and 22 men; age, 39.8 ± 6.3 years) and 24 volunteers free of any chronic disease (13 women and 11 men; age, 38.0 ± 6.7 years). The skin microcirculation reactivity, as expressed by the percentage of area covered by capillaries (coverage) and the distance between capillaries (distance), and the relationship between microcirculation reactivity and the presence of microangiopathic complications were assessed. RESULTS The distance before l-arginine infusion was significantly lower in patients than in controls (221 [153–311] vs. 240 [185–356] µm; P = 0.02) and did not differ after l-arginine infusion (223.5 [127–318] vs. 242.5 [181–341] µm; P = 0.27). The difference between the coverage values obtained before and after l-arginine infusion (Δcoverage) was significantly different from zero in the control group but not in the diabetes group. Patients with later onset of diabetes were characterized by decreased skin microcirculation reactivity when compared with patients with earlier onset of diabetes (−1.18 [−5.07 to 11.60] vs. 1.36 [−6.00 to 8.06]; P = 0.02) despite the higher prevalence of retinopathy in patients with earlier onset of diabetes (64% vs. 26%; P = 0.02). CONCLUSIONS Skin microvascular reactivity is impaired in patients with later onset of type 1 diabetes. Capillaroscopy with l-arginine infusion is useful for the identification of skin microangiopathy in type 1 diabetes. PMID:23150282

Tuberculin skin testing: determinants and reaction.

PubMed

Lao, L Y; De Guia, T

1999-09-01

Mantoux purified protein derivative (PPD) skin testing was performed in schoolchildren who were grouped according to positive (Group I, n = 205) and negative (Group II, n = 79) exposure to recent acid-fast bacilli (AFB) smear-positive tuberculosis (TB) family contact. A prospective case-control study was undertaken to evaluate whether repeat bacille Calmette-Guérin (BCG) vaccination, nutritional state, presence/absence of BCG scar, and degree of AFB positivity of sputum of adult TB cases affect PPD skin reactivity in these two groups. Group I with TB contacts had larger induration (13.00 +/- 11.29 mm) than the Group II control group of 4.52 +/- 6.20; P = 0.000. Purified protein derivative reaction as to the number of BCG vaccination(s) received showed an increase in size as the BCG vaccination is repeated with significantly larger induration in Group I than in Group II (P = 0.048). The nutritional status was subgrouped into A (weight < 10 percentile), B (weight 50-75 percentile), and C (weight > 90 percentile), which were comparable for both groups. The mean PPD induration of subgroup A in Groups I and II was not statistically different. However, the mean PPD induration was highly significant between Groups I and II in subgroup B (12.46 +/- 10.70 vs 3.80 +/- 5.71 mm; P = 0.000) and subgroup C (14.31 +/- 11.54 vs 5.42 +/- 6.70 mm; P = 0.000). Children in group I with the BCG scar were noted to have significantly greater PPD induration size than in group II (14.14 +/- 11.23 vs 5.05 +/- 6.24 mm; P = 0.000). The degree of AFB positivity of sputum of TB adult cases (1+ to 4+ and cavitary TB) has no effect on PPD size (P = 0.766). Close contact with individuals with active TB (AFB smear positive) is a very important factor for PPD skin conversion. Repeat BCG vaccination, malnutrition, and BCG with scars present difficulties in making a diagnosis of TB infection but did not affect PPD reactivity and did highlight the need for thorough clinical evaluation.

[Hypersensitivity to platinum salts and taxanes: The value of skin tests and tolerance induction procedures].

PubMed

Brault, F; Waton, J; Poreaux, C; Schmutz, J-L; Barbaud, A

2017-11-01

The rate of hypersensitivity reactions to platinum salts (PS) and taxanes (TX) is on the increase. The aim of our study was to show the value of skin testing and efficacy of rapid drug desensitization. This was a retrospective study conducted between January 2007 and February 2016 in patients consulting for immediate or delayed hypersensitivity to PS and TX. Skin prick tests (pT) and intradermal reaction tests (IDR) were performed according to the ENDA/EAACI recommendations. We used a 12-step desensitization protocol for rapid drug desensitization. Among the 99 patients included (30 men, 69 women, age 60.4) PS were suspected in 86 cases and taxanes in 13 cases. Skin tests were positive in 25 patients (7 pT, 18 IDR), 23 for platinum salts and 2 for taxanes. Rapid drug desensitization was proposed in 50 patients and performed in 33 (30 PS and 3 TX), proved effective in 29 patients, with protocol adaptation being necessary in 7 cases, and was ineffective in 4 patients. The skin tests for the latter 4 patients were positive. Seventy-five percent of patients with positive skin tests to oxaliplatin presented hypersensitivity reactions during desensitization, i.e. twice as many as patients having negative skin tests. Two percent of patient for PS and 7% for TX had cross reactivity. This French study confirms the efficacy of the 12-step protocol that allows patients to receive chemotherapy after hypersensitivity reaction. Skin test permits the detection of cross-reactions but their practice must be considered based on the patient's history. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Efficacy studies of Reactive Skin Decontamination Lotion, M291 Skin Decontamination Kit, 0.5% bleach, 1% soapy water, and Skin Exposure Reduction Paste Against Chemical Warfare Agents, part 2: guinea pigs challenged with soman.

PubMed

Braue, Ernest H; Smith, Kelly H; Doxzon, Bryce F; Lumpkin, Horace L; Clarkson, Edward D

2011-03-01

This report, the second in a series of five, directly compares the efficacy of Reactive Skin Decontamination Lotion (RSDL), the M291 Skin Decontamination Kit (SDK), 0.5% bleach (sodium or calcium hypochlorite solution), 1% soapy water, and Skin Exposure Reduction Paste Against Chemical Warfare Agents (SERPACWA) in the haired guinea pig model following exposure to soman (GD). In all experiments, guinea pigs were close-clipped and given anesthesia. In the decontamination experiments, the animals were challenged with GD and decontaminated after a 2-minute delay for the standard procedure or at longer times for the delayed-decontamination experiments. Positive control animals were challenged with GD in the same manner as the treated animals, except that they received no treatment. All animals were observed during the first 4 hours and again at 24 hours after exposure for signs of toxicity and death. The protective ratio (PR, defined as the median lethal dose [LD(50)] of the treatment group divided by the LD(50) of the untreated positive control animals) was calculated from the derived probit dose-response curves established for each treatment group and nontreated control animals. SERPACWA was applied as a thin coating (0.1 mm thick), allowed to dry for 15 minutes, and challenged with GD. After a 2-hour challenge, any remaining GD was blotted off the animal, but no additional decontamination was done. Significance in this report is defined as p <.05. Neat (undiluted) GD was used to challenge all animals in these studies. In the standard 2-minute GD decontamination experiments, the calculated PRs for RSDL, 0.5% bleach, 1% soapy water, and M291 SDK were 14, 2.7, 2.2, and 2.6, respectively. RSDL was by far the most effective decontamination product tested and significantly better than any of the other products. Bleach, soapy water, and the M291 SDK provided equivalent and modest protection. Since only RSDL provided at least good protection (PR > 5), it was the only

In vitro and in vivo characterization of hazelnut skin prick test extracts.

PubMed

Akkerdaas, Jaap H; Wensing, Marjolein; Knulst, André C; Aalberse, Rob C; Hefle, Susan L; van Ree, Ronald

2003-01-01

Hazelnut allergy ranks among the most frequently observed food allergies. Clinical symptoms range from the oral allergy syndrome to life threatening anaphylaxis. Diagnosis of hazelnut allergy partially relies on in vivo testing by means of skin prick testing (SPT). The aim of this study was to characterize hazelnut SPT extracts both in vitro and in vivo. Hazelnut SPT extracts were investigated for protein concentration and composition. The major hazelnut allergen Cor a 1, lipid transfer protein (LTP) and thaumatin-like-protein (TLP) were monitored by competitive RIA and immunoblotting. SPT extracts (n = 6) were analyzed for skin reactivity and the correlation between the SPT extract protein concentration and the mean skin reactivity (HEIC) was determined in a group of hazelnut-allergic patients (n = 30). For one SPT extract, the threshold level for Cor a 1 was determined in Cor a 1-monosensitized patients (n = 5). Protein concentrations ranged from 0.2-14 mg/ml. Although some proteins were present in most extracts (bands at 10, 22-28, 32 and around 48 kDa), clear differences in composition were observed (both intra- and inter-variability). The concentration of the major hazelnut allergen Cor a 1 differed up to a factor 50 (0.6-32 micrograms/ml). LTP was virtually absent in 3/9 SPT extracts and variable quantities of TLP were detected by immunoblotting. Some patients (6/30) had a false-negative SPT with 3/6 SPT extracts. There was a clear correlation between the protein concentration and the mean HEIC (RPearson = 0.87). The threshold level for Cor a 1 was +/- 3.2 ng/ml as assessed with one of the products investigated. Heterogeneous protein concentration/composition of SPT extracts results in variable skin test responses. The absence of potentially severe allergens like LTP may lead to false-negative SPT results that jeopardize a patient's safety. From these results it can be concluded that there is a strong need for standardization of products for SPT.

5-HTTLPR Expression Outside the Skin: An Experimental Test of the Emotional Reactivity Hypothesis in Children.

PubMed

Weeland, Joyce; Slagt, Meike; Brummelman, Eddie; Matthys, Walter; de Castro, Bram Orobio; Overbeek, Geertjan

2015-01-01

There is increasing evidence that variation in the promoter region of the serotonin transporter gene SLC6A4 (i.e., the 5-HTTLPR polymorphism) moderates the impact of environmental stressors on child psychopathology. Emotional reactivity -the intensity of an individual's response to other's emotions- has been put forward as a possible mechanism underlying these gene-by-environment interactions (i.e., G×E). Compared to children homozygous for the L-allele (LL-genotypes), children carrying an S-allele (SS/SL-genotypes), specifically when they have been frequently exposed to negative emotions in the family environment, might be more emotionally reactive and therefore more susceptible to affective environmental stressors. However, the association between 5-HTTLPR and emotional reactivity in children has not yet been empirically tested. Therefore, the goal of this study was to test this association in a large-scale experiment. Children (N = 521, 52.5% boys, Mage = 9.72 years) were genotyped and randomly assigned to happy, angry or neutral dynamic facial expressions and vocalizations. Motor and affective emotional reactivity were assessed through children's self-reported negative and positive affect (n = 460) and facial electromyography activity (i.e., fEMG: the zygomaticus or "smile" muscle and the corrugator or "frown" muscle, n = 403). Parents reported on their negative and positive parenting behaviors. Children mimicked and experienced the emotion they were exposed to. However, neither motor reactivity nor affective reactivity to these emotions depended on children's 5-HTTLPR genotype: SS/SL-genotypes did not manifest any stronger response to emotional stimuli than LL-genotypes. This finding remained the same when taking the broader family environment into account, controlling for kinship, age, gender and genetic ancestry, and when including a tri-allelic factor. We found no evidence for an association between the 5-HTTLPR polymorphism and children's emotional

5-HTTLPR Expression Outside the Skin: An Experimental Test of the Emotional Reactivity Hypothesis in Children

PubMed Central

Weeland, Joyce; Slagt, Meike; Brummelman, Eddie; Matthys, Walter; de Castro, Bram Orobio; Overbeek, Geertjan

2015-01-01

Background There is increasing evidence that variation in the promoter region of the serotonin transporter gene SLC6A4 (i.e., the 5-HTTLPR polymorphism) moderates the impact of environmental stressors on child psychopathology. Emotional reactivity −the intensity of an individual’s response to other’s emotions− has been put forward as a possible mechanism underlying these gene-by-environment interactions (i.e., G×E). Compared to children homozygous for the L-allele (LL-genotypes), children carrying an S-allele (SS/SL-genotypes), specifically when they have been frequently exposed to negative emotions in the family environment, might be more emotionally reactive and therefore more susceptible to affective environmental stressors. However, the association between 5-HTTLPR and emotional reactivity in children has not yet been empirically tested. Therefore, the goal of this study was to test this association in a large-scale experiment. Methods Children (N = 521, 52.5% boys, Mage = 9.72 years) were genotyped and randomly assigned to happy, angry or neutral dynamic facial expressions and vocalizations. Motor and affective emotional reactivity were assessed through children’s self-reported negative and positive affect (n = 460) and facial electromyography activity (i.e., fEMG: the zygomaticus or “smile” muscle and the corrugator or “frown” muscle, n = 403). Parents reported on their negative and positive parenting behaviors. Results Children mimicked and experienced the emotion they were exposed to. However, neither motor reactivity nor affective reactivity to these emotions depended on children’s 5-HTTLPR genotype: SS/SL-genotypes did not manifest any stronger response to emotional stimuli than LL-genotypes. This finding remained the same when taking the broader family environment into account, controlling for kinship, age, gender and genetic ancestry, and when including a tri-allelic factor. Conclusions We found no evidence for an association

Asthma, rhinitis, and dermatitis in workers exposed to reactive dyes.

PubMed Central

Nilsson, R; Nordlinder, R; Wass, U; Meding, B; Belin, L

1993-01-01

A survey was conducted at 15 textile plants with dyehouses in western Sweden. Employees with a history of work related rhinitis, asthma, or skin symptoms were offered a clinical and immunological investigation including skin prick tests, skin patch tests, and radioallergosorbent tests (RASTs) to detect specific allergy to reactive dyes. Among the 1142 employees, 162 were exposed to reactive dyes and 10 of these (6%) reported work related respiratory or nasal symptoms. An allergy to reactive dyes could be confirmed in five (3%, 95% confidence interval 1-7%). All but one had been exposed to reactive dyes for one year or less before the onset of symptoms. Positive RASTs could be detected in four of the five patients. All of the RAST positive patients were positive to remazol black B, but six out of eight additional remazol dyes also elicited positive results. RAST and RAST inhibition showed a cross reactivity between some of the dyes. Seven persons with work related dermatitis and three with urticaria or Quincke oedema were found. In one patient contact dermatitis to a monoazo dye was shown, but no positive patch test reactions to reactive dyes. IgE-mediated allergy to reactive dyes seems to be an important cause of respiratory and nasal symptoms among dyehouse employees exposed to dust from reactive dyes. PMID:8431393

Up-regulation of A1M/α1-microglobulin in skin by heme and reactive oxygen species gives protection from oxidative damage.

PubMed

Olsson, Magnus G; Allhorn, Maria; Larsson, Jörgen; Cederlund, Martin; Lundqvist, Katarina; Schmidtchen, Artur; Sørensen, Ole E; Mörgelin, Matthias; Akerström, Bo

2011-01-01

During bleeding the skin is subjected to oxidative insults from free heme and radicals, generated from extracellular hemoglobin. The lipocalin α(1)-microglobulin (A1M) was recently shown to have reductase properties, reducing heme-proteins and other substrates, and to scavenge heme and radicals. We investigated the expression and localization of A1M in skin and the possible role of A1M in the protection of skin tissue from damage induced by heme and reactive oxygen species. Skin explants, keratinocyte cultures and purified collagen I were exposed to heme, reactive oxygen species, and/or A1M and investigated by biochemical methods and electron microscopy. The results demonstrate that A1M is localized ubiquitously in the dermal and epidermal layers, and that the A1M-gene is expressed in keratinocytes and up-regulated after exposure to heme and reactive oxygen species. A1M inhibited the heme- and reactive oxygen species-induced ultrastructural damage, up-regulation of antioxidation and cell cycle regulatory genes, and protein carbonyl formation in skin and keratinocytes. Finally, A1M bound to purified collagen I (K(d) = 0.96×10(-6) M) and could inhibit and repair the destruction of collagen fibrils by heme and reactive oxygen species. The results suggest that A1M may have a physiological role in protection of skin cells and matrix against oxidative damage following bleeding.

Harsh Parenting and Child Externalizing Behavior: Skin Conductance Level Reactivity as a Moderator

ERIC Educational Resources Information Center

Erath, Stephen A.; El-Sheikh, Mona; Cummings, E. Mark

2009-01-01

Skin conductance level reactivity (SCLR) was examined as a moderator of the association between harsh parenting and child externalizing behavior. Participants were 251 boys and girls (8-9 years). Mothers and fathers provided reports of harsh parenting and their children's externalizing behavior; children also provided reports of harsh parenting.…

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 Four Skin Decontamination Procedures Using Reactive Skin Decontamination Lotion (RSDL) Following Cutaneous VX Exposure in Guinea Pigs

DTIC Science & Technology

2016-01-01

DC) product following cutaneous exposure to VX was affected by the DC procedure. Fur-clipped, male, unanesthetized guinea pigs were used as subjects...RSDL) Following Cutaneous VX Exposure in Guinea Pigs Irwin Koplovitz Susan Schulz Julia Morgan Robert Reed Edward Clarkson C. Gary Hurst...Decontamination Procedures Using Reactive Skin 5a. CONTRACT NUMBER Decontamination Lotion (RSDL) Following Cutaneous VX Exposure in Guinea Pigs 5b

Epidermal-skin-test 1,000 (EST-1,000)--a new reconstructed epidermis for in vitro skin corrosivity testing.

PubMed

Hoffmann, J; Heisler, E; Karpinski, S; Losse, J; Thomas, D; Siefken, W; Ahr, H-J; Vohr, H-W; Fuchs, H W

2005-10-01

The determination of a possible corrosive or irritative potential of certain products and ingredients is necessary for their classification and labeling requirements. Reconstructed skin as a model system provides fundamental advantages to single cell culture testing and leads to promising results as shown by different validation studies (for review: Fentem, J.H., Botham, P.A., 2002. ECVAM's activities in validating alternative tests for skin corrosion and irritation. ATLA 30(Suppl. 2), 61-67). In this study we introduce our new reconstructed epidermis "Epidermal-Skin-Test" (EST-1,000). This fully grown epidermis consists of proliferating as well as differentiating keratinocytes. EST-1,000 shows a high comparability to normal human skin as shown by histological and immunohistochemical data. Characteristic markers (KI-67, CK 1/10/5/14, transglutaminase, collagen IV, involucrin, beta 1 integrin) can be identified easily. The main focus of this work was to characterize EST-1,000 especially with respect to its barrier function by testing several substances of known corrosive potential. Skin corrosion was detected by the cytotoxic effect of the substances on a reconstructed epidermis after short-term application to the stratum corneum. The effect was determined by standard MTT assay and accompanying histological analysis. Hence EST-1,000 shows a very high predictive potential and closes the gap between animal testing and the established full-thickness model Advanced-Skin-Test 2,000 (AST-2,000) (Noll, M., Merkle, M.-L., Kandsberger, M., Matthes, T., Fuchs, H., Graeve, T., 1999. Reconstructed human skin (AST-2,000) as a tool for pharmaco-toxicology. ATLA 27, 302).

Irradiation of skin with visible light induces reactive oxygen species and matrix-degrading enzymes.

PubMed

Liebel, Frank; Kaur, Simarna; Ruvolo, Eduardo; Kollias, Nikiforos; Southall, Michael D

2012-07-01

Daily skin exposure to solar radiation causes cells to produce reactive oxygen species (ROS), which are a primary factor in skin damage. Although the contribution of the UV component to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology. Solar radiation comprises <10% of UV, and thus the purpose of this study was to examine the physiological response of skin to visible light (400-700 nm). Irradiation of human skin equivalents with visible light induced production of ROS, proinflammatory cytokines, and matrix metalloproteinase (MMP)-1 expression. Commercially available sunscreens were found to have minimal effects on reducing visible light-induced ROS, suggesting that UVA/UVB sunscreens do not protect the skin from visible light-induced responses. Using clinical models to assess the generation of free radicals from oxidative stress, higher levels of free radical activity were found after visible light exposure. Pretreatment with a photostable UVA/UVB sunscreen containing an antioxidant combination significantly reduced the production of ROS, cytokines, and MMP expression in vitro, and decreased oxidative stress in human subjects after visible light irradiation. Taken together, these findings suggest that other portions of the solar spectrum aside from UV, particularly visible light, may also contribute to signs of premature photoaging in skin.

Degradation of pesticides with RSDL® (reactive skin decontamination lotion kit) lotion: LC-MS investigation.

PubMed

Fentabil, Messele; Gebremedhin, Mulu; Purdon, J Garfield; Cochrane, Laura; Goldman, Virginia Streusand

2018-09-01

This study examined the degradation of organophosphate (OP) and carbamate pesticides using RSDL ® (Reactive Skin Decontamination Lotion Kit) lotion. Degradation occurs from a nucleophilic substitution (SN) reaction between an ingredient in the RSDL lotion, potassium 2,3-butanedione monoximate (KBDO), with susceptible sites in the pesticides. Evaluation at several molar ratios of KBDO:test articles using liquid chromatography-mass spectrometry (LC-MS) techniques was performed. The OP test articles, parathion, paraoxon, parathion-methyl, paraoxon-methyl and chlorpyrifos were effectively degraded at molar ratios of four and above in less than 6min contact time. Malathion and malaoxon were similarly converted to inactive by-products at molar ratios as low as two in less than 4min. A minimum molar ratio of nine was found to be effective against the carbamate pesticide carbofuran. In the case of aldicarb, complete destruction was achieved at a molar ratio of fifteen and a reaction time of one hour. It is important to note that these studies are based on a direct liquid phase RSDL lotion reaction with the toxic chemicals without the added physical removal decontamination efficacy component provided by the sponge component of the RSDL kit. The RSDL kit is intended to be used to remove or neutralize chemical warfare agents (CWA) and T-2 toxin from the skin. In actual use, the majority of the CWA decontamination occurs through the combined action of the sponge in both removing the chemical from the skin, and in rapidly mixing the chemicals at a high molar ratio of KBDO:CWA within the pores of the sponge to enhance rapid neutralization of the chemical. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of cephalosporins in patients with immediate penicillin hypersensitivity: cross-reactivity revisited.

PubMed

Lee, Q U

2014-10-01

A 10% cross-reactivity rate is commonly cited between penicillins and cephalosporins. However, this figure originated from studies in the 1960s and 1970s which included first-generation cephalosporins with similar side-chains to penicillins. Cephalosporins were frequently contaminated by trace amount of penicillins at that time. The side-chain hypothesis for beta-lactam hypersensitivity is supported by abundant scientific evidence. Newer generations of cephalosporins possess side-chains that are dissimilar to those of penicillins, leading to low cross-reactivity. In the assessment of cross-reactivity between penicillins and cephalosporins, one has to take into account the background beta-lactam hypersensitivity, which occurs in up to 10% of patients. Cross-reactivity based on skin testing or in-vitro test occurs in up to 50% and 69% of cases, respectively. Clinical reactivity and drug challenge test suggest an average cross-reactivity rate of only 4.3%. For third- and fourth-generation cephalosporins, the rate is probably less than 1%. Recent international guidelines are in keeping with a low cross-reactivity rate. Despite that, the medical community in Hong Kong remains unnecessarily skeptical. Use of cephalosporins in patients with penicillin hypersensitivity begins with detailed history and physical examination. Clinicians can choose a cephalosporin with a different side-chain. Skin test for penicillin is not predictive of cephalosporin hypersensitivity, while cephalosporin skin test is not sensitive. Drug provocation test by experienced personnel remains the best way to exclude or confirm the diagnosis of drug hypersensitivity and to find a safe alternative for future use. A personalised approach to cross-reactivity is advocated.

Use of intradermal dilutional testing and skin prick testing: clinical relevance and cost efficiency.

PubMed

Seshul, Merritt; Pillsbury, Harold; Eby, Thomas

2006-09-01

The objective was to determine the agreement of the positive results from a multiple skin prick test (SPT) device with the ability to determine a definable endpoint through intradermal dilutional testing (IDT) to compare semiquantitatively the degree of positivity of SPT results with quantitative results from IDT and to analyze the cost of immunotherapy based on SPT compared with IDT guided by SPT. Retrospective review of clinical data (random accrual). One hundred thirty-four patients underwent allergy screening using a multiple SPT device. Antigens testing positive by skin prick device were tested using IDT on a separate day. Antigens testing negative by SPT were not evaluated by IDT. Regional allergy testing practice patterns were determined, and a cost analysis using Medicare rates was performed There was good agreement between an antigen testing positive by SPT and the determination of a definable endpoint (93.33%, n = 1,334 antigens). The degree of positivity from the SPT correlated poorly with the final endpoint concentration (r = 0.40, P < .0001). Blended testing techniques were similar in cost when compared with several commonly used allergy testing protocols. Antigens which show reactivity to a multiple SPT device usually have a treatable endpoint that is independent of the degree of positivity of the SPT result. IDT is an important step in the determination of the strongest starting dose of immunotherapy that may be safely administered. Initiating immunotherapy in this manner may potentially create significant health care savings by shortening the time required for a patient to reach their individual maximally tolerated dose. The use of a relatively large screening panel is cost effective and does not increase the average number of antigens treated by immunotherapy. Blended allergy testing techniques that include IDT in their protocol are comparable in cost with commonly used allergy testing protocols.

Chemical Reactivity Test (CRT)

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

Zaka, F.

The Chemical Reactivity Test (CRT) is used to determine the thermal stability of High Explosives (HEs) and chemical compatibility between (HEs) and alien materials. The CRT is one of the small-scale safety tests performed on HE at the High Explosives Applications Facility (HEAF).

Association between alcohol consumption and skin prick test reactivity to aeroallergens.

PubMed

Assing, Kristian; Bodtger, Uffe; Linneberg, Allan; Malling, Hans Jørgen; Poulsen, Lars K

2007-01-01

A few studies have indicated a positive association between consumption of alcohol and allergic sensitization in age and socioeconomically heterogeneous populations. To investigate the association between consumption of alcohol and allergic sensitization in a young homogenous population of high social class (a group with a suspected high prevalence of sensitization). A total of 1,668 students aged 18 to 35 years recruited from universities in Copenhagen, Denmark, underwent skin prick testing (SPT) in October or November 2002 and completed a questionnaire about respiratory disease and lifestyle habits, including alcohol consumption. SPT positivity was defined as a positive reaction (> or =3 mm) against at least 1 of 10 common inhalant allergens. Before and after adjustment for sex, age, smoking, atopic predisposition, and pet keeping, no significant association was found between alcohol consumption (including type of beverage) and SPT positivity. Increasing alcohol consumption was significantly negatively associated with asthma symptoms and hay fever symptoms. Alcohol consumption does not favor SPT positivity, but cumulated effects were not addressed in the present study. Individuals with asthma or hay fever symptoms seem to reduce alcohol intake (a healthy drinkers' effect).

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

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

Avonto, Cristina; Chittiboyina, Amar G.; Rua, Diego

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 aftermore » 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. - Highlights: • A novel fluorescence-based method to detect electrophilic sensitizers is proposed. • A model fluorescent thiol was used to directly quantify the reaction products. • A discussion of the reaction

Skin prick tests and allergy diagnosis.

PubMed

Antunes, João; Borrego, Luís; Romeira, Ana; Pinto, Paula

2009-01-01

Skin testing remains an essential diagnostic tool in modern allergy practice. A significant variability has been reported regarding technical procedures, interpretation of results and documentation. This review has the aim of consolidating methodological recommendations through a critical analysis on past and recent data. This will allow a better understanding on skin prick test (SPT) history; technique; (contra-) indications; interpretation of results; diagnostic pitfalls; adverse reactions; and variability factors.

[Allergens used in skin tests in Mexico].

PubMed

Larenas Linnemann, Désirée; Arias Cruz, Alfredo; Guidos Fogelbach, Guillermo Arturo; Cid del Prado, Mari Lou

2009-01-01

Immunotherapy is the only recognized causal treatment for allergies. It is prepared on an individual basis, based on the patient's clinical history and the result of the skin prick test (SPT). An adequate composition of the allergens with which to test the patient is crucial for an optimal diagnosis. To know allergens used in tests in allergy practices in Mexico. A national survey among all members of the Colegio Mexicano de Inmunología Clínica y Alergia (CMICA) and of the Colegio Mexicano de Pediatras Especialistas en Inmunología Clínica y Alergia (COMPEDIA) was carried out. In a second phase respondents were asked to send in the composition of a routine SPT in their clinic. The results are presented descriptively and the frequency is calculated by which certain allergen is tested in the interviewed practices. A survey response rate of 61 (17%) was obtained and 54% showed their SPT content. Weeds' representation in the SPT seems adequate; Atriplex is tested in all allergy practices. Some trees that show cross-reactivity might be eliminated from the SPT, but 20% doesn't test for Cynodon nor Holcus, and 25% doesn't for important allergens as cat, dog and cockroach. House dust and tobacco are still tested with certain frequency. The selection of which allergens to test in a SPT is based on multiple data, that change continuously with new investigations and discoveries. Our specialty is the most indicated--and obligated--to adjust constantly to these changes to have the best diagnostic tool to detect specific allergies.

Clinical history as a predictor of penicillin skin test outcome.

PubMed

Wong, Benjamin B L; Keith, Paul K; Waserman, Susan

2006-08-01

Up to 10% of the population reports an "allergy" to penicillin, whereas approximately 1.1% has positive penicillin skin test results. Where penicillin skin tests are unavailable, some have advocated using history to decide whether to use a penicillin-related antibiotic. To determine if clinical history predicts penicillin skin test results. Retrospective medical record review of 94 consecutive patients who had previously taken penicillin referred for penicillin allergy. Case histories were taken, penicillin skin tests performed, and an oral challenge recommended if skin test results were negative. Of 91 cases studied, the average patient age was 27 years (range, 6 months to 82 years; 36% female). Fifty-two (57%) experienced hives as their main adverse reaction. Sixteen (18%) had at least 1 positive test result. Of this group, 9 had hives as their main symptom, whereas 1 had respiratory problems and 1 had angioedema. Most patients with positive skin test results had experienced their reaction at least 3 years ago. Regression analysis showed that age, sex, and clinical history, including type of reaction, time of reaction after penicillin ingestion, or time since the last reaction, were not associated with skin test positivity. Seventy-two (96%) of the 75 patients who had negative skin test results underwent oral challenge. Seventy had negative challenge results. The negative predictive value of a negative penicillin skin test result was 97%. Clinical history was not predictive of subsequent penicillin skin test results.

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

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

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

Quantitative skin prick and bronchial provocation tests with platinum salt.

PubMed Central

Merget, R; Schultze-Werninghaus, G; Bode, F; Bergmann, E M; Zachgo, W; Meier-Sydow, J

1991-01-01

Occupational asthma due to platinum salts is a frequent disease in platinum refineries. The diagnosis is based upon a history of work related symptoms and a positive skin prick test with platinum salts. Bronchial provocation tests have not been performed in epidemiological studies because the skin test is believed to be highly specific and sensitive. As no reliable data about this issue currently exist, this study assesses the use of skin prick and bronchial provocation tests with methacholine and platinum salt in platinum refinery workers. Twenty seven of 35 workers, who were referred to our clinic with work related symptoms and nine control subjects with bronchial hyperreactivity underwent a skin prick test and bronchial provocation with methacholine and platinum salt. For skin prick and bronchial provocation tests with platinum salt a 10(-2)-10(-8) mol/l hexachloroplatinic acid solution, in 10-fold dilutions was used. Four of the 27 subjects and all controls showed neither a bronchial reaction nor a skin reaction. Twenty three subjects were considered allergic to platinum salt; 22 of these showed a fall of 50% or more in specific airway conductance after inhalation of the platinum salt solution. Four workers experienced a positive bronchial reaction despite a negative skin prick test. No correlation of responsiveness to methacholine with responsiveness to platinum salt was found, but the skin prick test correlated with the bronchial reaction to platinum salt (rs = 0.50, p less than 0.023, n = 22). One dual reaction was seen in bronchial provocation tests. Side effects of both skin tests and bronchial provocation tests with platinum salt were rare and were not encountered in workers without a skin reaction to platinum salt. It is concluded that bronchial provocation tests with platinum salts should be performed on workers with work related symptoms but negative skin tests with platinum salts. PMID:1772797

Diagnosis of penicillin allergy by skin testing: the Manitoba experience.

PubMed Central

Warrington, R. J.; Simons, F. E.; Ho, H. W.; Gorski, B. A.

1978-01-01

The reliability of skin testing in the diagnosis of penicillin allergy was studied in 86 adults and 167 children with a history of possible hypersensitivity reactions to penicillin. Skin testing was done with the major antigenic determinant of benzylpenicillin and minor determinants of benzylpenicillin, ampicillin, cloxacillin, methicillin and cephalothin. The overall frequency of positive skin reactions was 11.5%. Among the patients with positive skin reactions about half had a history of immediate or accelerated reactions to penicillins, but 2 of 11 adults and 50% of the children in this group had a history of maculopapular rash of delayed onset. There was a low frequency of positive skin reactions when there was a long interval between the times of clinical reaction and skin testing. Of 169 patients reacting negatively to skin testing who received a specific drug challenge only 2 manifested mild urticaria; this indicates the reliability of the skin tests in predicting penicillin allergy. The major and minor determinants of benzylpenicillin were the most useful reagents. One fifth of the patients with penicillin hypersensitivity would have been missed if the major determinant of benzylpenicillin alone had been used for skin testing. The additional use of the minor determinants of other penicillin derivatives, however, did not increase substantially the clinical reliability of the skin testing procedure. PMID:638909

Mental Reactivation and Pleasantness Judgment of Experience Related to Vision, Hearing, Skin Sensations, Taste and Olfaction

PubMed Central

2016-01-01

Language acquisition is based on our knowledge about the world and forms through multiple sensory-motor interactions with the environment. We link the properties of individual experience formed at different stages of ontogeny with the phased development of sensory modalities and with the acquisition of words describing the appropriate forms of sensitivity. To test whether early-formed experience related to skin sensations, olfaction and taste differs from later-formed experience related to vision and hearing, we asked Russian-speaking participants to categorize or to assess the pleasantness of experience mentally reactivated by sense-related adjectives found in common dictionaries. It was found that categorizing adjectives in relation to vision, hearing and skin sensations took longer than categorizing adjectives in relation to olfaction and taste. In addition, experience described by adjectives predominantly related to vision, hearing and skin sensations took more time for the pleasantness judgment and generated less intense emotions than that described by adjectives predominantly related to olfaction and taste. Interestingly the dynamics of skin resistance corresponded to the intensity and pleasantness of reported emotions. We also found that sense-related experience described by early-acquired adjectives took less time for the pleasantness judgment and generated more intense and more positive emotions than that described by later-acquired adjectives. Correlations were found between the time of the pleasantness judgment of experience, intensity and pleasantness of reported emotions, age of acquisition, frequency, imageability and length of sense-related adjectives. All in all these findings support the hypothesis that early-formed experience is less differentiated than later-formed experience. PMID:27400090

The skin prick test.

PubMed

Frati, F; Incorvaia, C; Cavaliere, C; Di Cara, G; Marcucci, F; Esposito, S; Masieri, S

2018-01-01

The skin prick test (SPT) is the most common test for the diagnosis of allergy. SPT is performed by pricking the skin, usually in the volar surface of the forearm, with a lancet through a drop of an allergen extract and is usually the first choice test in the diagnostic workup for allergic diseases because of its reliability, safety, convenience and low cost. SPT is minimally invasive and has the advantage of testing multiple allergens in 15 to 20 min. In children, SPT is far less disturbing than venipuncture and is used to obtain a sample of serum to measure specific IgE through in vitro tests. There is a good correlation (about 85-95%) between SPT and in vitro tests. Globally, SPT is an excellent diagnostic tool, with a positive predictive value ranging from 95-100%. SPTs can identify sensitivity to inhalants, foods, some drugs, occupational allergens, hymenoptera venom and latex. However, the relevance of such sensitivity to allergens should always be carefully interpreted in the light of the clinical history, because sensitization and clinical allergy may not coincide. In regards to safety, though the reports of systemic reactions, and particularly anaphylaxis, are very rare, in vitro IgE tests should be preferred if previous severe reactions emerge from the patient’s clinical history.

Reactive fluxes delivered by dielectric barrier discharge filaments to slightly wounded skin

NASA Astrophysics Data System (ADS)

Babaeva, Natalia Yu; Kushner, Mark J.

2013-01-01

The application of atmospheric-pressure plasmas to human tissue has been shown to have therapeutic effects for wound healing and in treatment of skin diseases. In this paper, we report on a computational study of the intersection of plasma filaments in a dielectric barrier discharge (DBD) with a small wound in human skin in the context of plasma medicine. The wound is represented as a small cut in the epidermal layer of cells. Intracellular structures and their electrical properties were incorporated into the two-dimensional computational mesh in order to self-consistently couple gas phase plasma transport with the charging of the surface of the wound. We quantify the fluxes of reactive oxygen and nitrogen species, ions and photons produced in or diffusing into the wound as might occur during the first few discharge pulses of treatment. Comparison is made to fluxes predicted by global modelling. We show that the relative location of the plasma filament with respect to the wound is important on plasma time scales (ns) for ions and photons, and for radicals directly produced by electron impact processes. On the longer-term diffusion time scales (ms) the position of the plasma filament relative to the wound is not so critical. For typical DBD conditions, the magnitude of these fluxes to the cellular surfaces corresponds to fluences of radicals nearly equal to the surface site density. These results imply that the biological reactivity is limited by reaction probabilities and not the availability of radical fluxes.

Pressure sensitivity of flow oscillations in postocclusive reactive skin hyperemia.

PubMed

Strucl, M; Peterec, D; Finderle, Z; Maver, J

1994-05-01

Skin blood flow was monitored using a laser-Doppler (LD) flowmeter in 21 healthy volunteers after an occlusion of the digital arteries. The peripheral vascular bed was exposed to occlusion ischemia of varying duration (1, 4, or 8 min) and to a change in digital arterial pressure produced by different positions of the arm above heart level to characterize the pattern of LD flow oscillations in postocclusive reactive hyperemia (PRH) and to elucidate the relevance of metabolic and myogenic mechanisms in governing its fundamental frequency. The descending part of the hyperemic flow was characterized by the appearance of conspicuous periodic oscillations with a mean fundamental frequency of 7.2 +/- 1.5 cycles/min (SD, n = 9), as assessed by a Fourier transform frequency analysis of 50-s sections of flow. The mean respiratory frequency during the periods of flow frequency analysis was 17.0 +/- 2.2 (SD, n = 9), and the PRH oscillations remained during apnea in all tested subjects. The area under the maximum flow curve increased significantly with prolongation of the occlusion (paired t test, P < 0.001; n = 9), but showed no dependence on the estimated blood pressure in the digital arteries, which suggests the predominant role of a metabolic component in this part of the PRH response. In contrast, the fundamental frequency of PRH oscillations exhibited a significant decrease with a reduction in the estimated digital arterial pressure (linear regression, b = 0.08, P < 0.001; n = 12), but did not change with the prolongation of arterial occlusion despite a significant increase in mean LD flow (paired t test, P < 0.001; n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up.

PubMed

Macy, E; Burchette, R J

2002-12-01

Long-term follow-up data on adverse drug reactions after oral antibiotic use in penicillin allergy history positive individuals with penicillin skin test done in advance of need are rare. Oral antibiotic associated adverse drug reactions in 83 penicillin skin test positive individuals were compared to a sex, age, and length of follow-up matched sample of 166 penicillin skin test negative individuals, all of whom had at least one post penicillin skin test oral antibiotic. The mean post penicillin skin test follow-up interval was 34.5 +/- 16.6 months. There were 1655 total oral antibiotic exposures. In penicillin skin test positive individuals, the adverse drug reaction rate was not significantly different with cephalosporin or non-beta-lactam use (P = 0.12). In penicillin skin test negative individuals the adverse drug reaction rate was significantly lower with cephalosporin vs. non-beta-lactam use (P = 0.005). Penicillin was safely used in penicillin skin test negative individuals. Overall cephalosporins caused fewer adverse drug reactions independent of penicillin skin test status (P = 0.005). Penicillin skin testing was only able to predict penicillin associated adverse drug reactions in penicillin skin test positive individuals. Excluding accidental penicillin exposure in penicillin skin test positive individuals, non-beta-lactams were associated with adverse drug reactions more often than penicillins or cephalosporins, independent of the penicillin skin test result. Cephalosporins were used as or more safely than non-beta-lactams in both penicillin skin test positive and negative individuals.

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

Children's Skin Conductance Reactivity as a Mechanism of Risk in the Context of Parental Depressive Symptoms

ERIC Educational Resources Information Center

Cummings, E. Mark; El-Sheikh, Mona; Kouros, Chrystyna D.; Keller, Peggy S.

2007-01-01

Background: Children's physiological reactivity was examined as a moderator of relations between parental dysphoria and child adjustment problems, addressing gaps in the study of child characteristics as risk processes. Method: One hundred fifty-seven children (86 boys, 71 girls) were assessed twice over a two-year interval. Skin conductance level…

Differences in tuberculin reactivity as determined in a veterans administration employee health screening program.

PubMed

Mehta, Sanjay R; MacGruder, Cathy; Looney, David; Johns, Scott; Smith, Davey M

2009-04-01

In response to a difference in pricing, the San Diego Veterans Administration Medical Center changed its tuberculin preparation from Tubersol to Aplisol in the fall of 2006. Following the change, an increased number of employee skin test conversions was noted. Employee tuberculin skin test converters from 2006 were screened with the QuantiFERON Gold (QFT-G) gamma interferon release assay. Those employees who tested negative by QFT-G were asked to repeat their skin test with both Tubersol and Aplisol tuberculin preparations. Of the new purified protein derivative converters, 12 of 14 returned for repeat testing with QFT-G, and the assay was negative for 83% (10/12), positive for 8% (1/12), and indeterminate for 8% (1/12) of the individuals. Nine of the individuals who were QFT-G negative agreed to repeat skin testing with both tuberculin preparations, and 7/8 (87.5%) demonstrated reactivity with the Aplisol preparation, while 0/8 (0%) reacted to the Tubersol preparation. A change from Tubersol to Aplisol resulted in elevated tuberculin skin test conversion rates that may be due to false-positive reactions. The differences in skin test reactivity between preparations support CDC guidelines that recommend that institutions should not change tuberculin preparations, as doing so may falsely increase the number of positive reactions.

Delayed-type hypersensitivity skin test responses to PPD and other antigens among BCG-vaccinated HIV-1-infected and healthy children and adolescents.

PubMed

Costa, Natalia Moriya Xavierda; Albuquerque, Maly de; Lins, Janaína Bacelar Acioli; Alvares-Junior, João Teixeira; Stefani, Mariane Martins de Araújo

2011-10-01

Among HIV-1-infected patients, CD4+ T cell counts are well-established markers of cell-mediated immunity. Delayed-type hypersensitivity (DTH) skin tests can be used to evaluate in vivo cell-mediated immunity to common antigens. DTH responses to tuberculin purified protein derivative (PPD), sporotrichin, trichophytin, candidin and streptokinase/streptodornase antigens were assessed. Thirty-six HIV-1-infected children/adolescents and 56 age- and sex-matched HIV-1/HIV-2-seronegative participants were tested. All participants had a BCG scar. Fisher's exact test was used to evaluate significant differences between groups (p<0.05). The main characteristics of the HIV-1 patients were as follows: median age 8.1 years; 20/36 were males; 35 were vertical transmission cases; 34 were AIDS cases under antiretroviral therapy; median viral load = 3.04 log10 copies/ml; median CD4+ T cell count = 701 cells/μl. A total of 25% (9/36) and 87.5% (49/56) of HIV-1-infected and healthy participants, respectively, displayed DTH reactivity to at least one antigen (p<0.001). Among HIV-1-infected participants, reactivity to candidin predominated (8/36, 22.2%), while PPD positivity prevailed among healthy participants (40/56, 71.4%). PPD reactivity in the HIV-1-positive group was 8.3% (p<0.01). The median PPD induration was 2.5mm (range: 2-5mm) in the HIV-1 group and 6.0 mm among healthy participants (range: 3-15 mm). There was no correlation between PPD positivity and age. No correlation between CD4+ T cell counts and DTH reactivity was observed among HIV-1-infected patients. DTH skin test responses, including PPD reactivity, were significantly lower among HIV-1-infected participants compared to healthy controls, which likely reflects advanced disease and T cell depletion.

Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes

PubMed Central

Beer, Sandra; Feihl, François; Ruiz, Juan; Juhan-Vague, Irène; Aillaud, Marie-Françoise; Wetzel, Sandrine Golay; Liaudet, Lucas; Gaillard, Rolf C; Waeber, Bernard

2008-01-01

Aim: Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at increased cardiovascular risk due to an accelerated atherosclerotic process. The present study aimed to compare skin microvascular function, pulse wave velocity (PWV), and a variety of hemostatic markers of endothelium injury [von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and the soluble form of thrombomodulin (s-TM)] in patients with NIDDM. Methods: 54 patients with NIDDM and 38 sex- and age-matched controls were studied. 27 diabetics had no overt micro- and/or macrovascular complications, while the remainder had either or both. The forearm skin blood flow was assessed by laser-Doppler imaging, which allowed the measurement of the response to iontophoretically applied acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation), as well as the reactive hyperemia triggered by the transient occlusion of the circulation. Results: Both endothelial and non-endothelial reactivity were significantly blunted in diabetics, regardless of the presence or the absence of vascular complications. Plasma vWF, TFPI and s-TM levels were significantly increased compared with controls only in patients exhibiting vascular complications. Concentrations of t-PA and PAI-1 were significantly increased in the two groups of diabetics versus controls. Conclusion: In NIDDM, both endothelium-dependent and -independent microvascular skin reactivity are impaired, whether or not underlying vascular complications exist. It also appears that microvascular endothelial dysfunction is not necessarily associated in NIDDM with increased circulating levels of hemostatic markers of endothelial damage known to reflect a hypercoagulable state. PMID:19337558

Chemical stability and in chemico reactivity of 24 fragrance ingredients of concern for skin sensitization risk assessment.

PubMed

Avonto, Cristina; Wang, Mei; Chittiboyina, Amar G; Vukmanovic, Stanislav; Khan, Ikhlas A

2018-02-01

Twenty-four pure fragrance ingredients have been identified as potential concern for skin sensitization. Several of these compounds are chemically unstable and convert into reactive species upon exposure to air or light. In the present work, a systematic investigation of the correlation between chemical stability and reactivity has been undertaken. The compounds were subjected to forced photodegradation for three months and the chemical changes were studied with GC-MS. At the end of the stability study, two-thirds of the samples were found to be unstable. The generation of chemically reactive species was investigated using the in chemico HTS-DCYA assay. Eleven and fourteen compounds were chemically reactive before and after three months, respectively. A significant increase in reactivity upon degradation was found for isoeugenol, linalool, limonene, lyral, citronellol and geraniol; in the same conditions, the reactivity of hydroxycitronellal decreased. The non-reactive compounds α-isomethyl ionone, benzyl alcohol, amyl cinnamal and farnesol became reactive after photo-oxidative degradation. Overall, forced degradation resulted in four non-reactive fragrance compounds to display in chemico thiol reactivity, while ten out of 24 compounds remained inactive. Chemical degradation does not necessarily occur with generation of reactive species. Non-chemical activation may be involved for the 10 stable unreactive compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of sex-related changes in skin topography and structure using innovative skin testing equipment.

PubMed

Dąbrowska, M; Mielcarek, A; Nowak, I

2018-04-29

Evaluation of skin condition on the basis of parametrization and objective measurements of the parameters has become obligatory. The aim of this study was to assess sex-related changes in skin topography and structure using the skin testing equipment. The study was carried out on the group of 40 volunteers (20 females and 20 males) of the mean age 24 ± 3 years. The skin parameters were measured using 3 devices: Visioscan ®  VC 98 (skin topography), Visioline ® VL 650 (skin macro relief) and Ultrascan UC22 (ultrasound imaging of the skin). All measurements were performed on the inner part of the left forearm. The skin parameters measured revealed significant differences in skin surface and structure between females and males. The skin of all women subjects was more homogenous in its structure with the presence of more abundant superficial skin lines and wrinkles in comparison to male skin. The higher number of skin furrows in the skin of women is in agreement with literature reports claiming that men's skin has lower number of wrinkles which are deeper and more pronounced. Ultrasound imaging of the skin indicated greater thickness and lower density of the dermis of men subjects compared to those of females. Non-invasive methods of skin testing using new and advanced equipment have provided a possibility of objective parametrization and evaluation of sex-related changes in skin topography and structure. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Differences among heat-treated, raw, and commercial peanut extracts by skin testing and immunoblotting.

PubMed

Maleki, Soheila J; Casillas, Adrian M; Kaza, Ujwala; Wilson, Brian A; Nesbit, Jacqueline B; Reimoneqnue, Chantrel; Cheng, Hsiaopo; Bahna, Sami L

2010-12-01

Peanut allergenicity has been reported to be influenced by heat treatment, yet the commonly available extracts for skin prick testing (SPT) are derived from raw extracts. To assess the effect of heat treatment on the SPT reactivity and specific IgE binding to peanut. Three commercial extracts and 3 laboratory-prepared extracts, including raw, roasted, and boiled, were used for SPT in 19 patients with suspected peanut allergy and in 4 individuals who eat peanut without any symptoms. Serum samples were obtained to measure total IgE in addition to specific IgE binding to the study extracts by immunoblotting. Peanut allergy was confirmed with challenge test unless the individual had a convincing history of a severe reaction. Eleven study participants were considered peanut allergic based on a strong history or positive challenge test result. SPT with the prepared and commercial reagents showed that the boiled extract had the highest specificity (67% vs 42%-63% for the other extracts). The prepared extracts showed similar SPT sensitivity (81%). Three patients with a history of severe reaction and elevated specific IgE levels to peanut to the 3 study extracts had variable SPT reactivity to 1 or more of the commercial extracts. IgE binding to Ara h 2 was found in nearly all patients, regardless of their clinical reactivity. None of the extracts tested showed optimal diagnostic reliability regarding both sensitivity and specificity. Perhaps testing should be performed with multiple individual extracts prepared by different methods. Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Skin Conductance Level Reactivity Moderates the Association between Harsh Parenting and Growth in Child Externalizing Behavior

ERIC Educational Resources Information Center

Erath, Stephen A.; El-Sheikh, Mona; Hinnant, J. Benjamin; Cummings, E. Mark

2011-01-01

Skin conductance level reactivity (SCLR) was examined as a moderator of the association between harsh parenting at age 8 years and growth in child externalizing behavior from age 8 to age 10 (N = 251). Mothers and fathers provided reports of harsh parenting and their children's externalizing behavior; children also provided reports of harsh…

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

PubMed

Fox, Stephanie; Park, Miguel A

2011-01-01

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

Development of a forensic skin colour predictive test.

PubMed

Maroñas, Olalla; Phillips, Chris; Söchtig, Jens; Gomez-Tato, Antonio; Cruz, Raquel; Alvarez-Dios, José; de Cal, María Casares; Ruiz, Yarimar; Fondevila, Manuel; Carracedo, Ángel; Lareu, María V

2014-11-01

There is growing interest in skin colour prediction in the forensic field. However, a lack of consensus approaches for recording skin colour phenotype plus the complicating factors of epistatic effects, environmental influences such as exposure to the sun and unidentified genetic variants, present difficulties for the development of a forensic skin colour predictive test centred on the most strongly associated SNPs. Previous studies have analysed skin colour variation in single unadmixed population groups, including South Asians (Stokowski et al., 2007, Am. J. Hum. Genet, 81: 1119-32) and Europeans (Jacobs et al., 2013, Hum Genet. 132: 147-58). Nevertheless, a major challenge lies in the analysis of skin colour in admixed individuals, where co-ancestry proportions do not necessarily dictate any one person's skin colour. Our study sought to analyse genetic differences between African, European and admixed African-European subjects where direct spectrometric measurements and photographs of skin colour were made in parallel. We identified strong associations to skin colour variation in the subjects studied from a pigmentation SNP discovery panel of 59 markers and developed a forensic online classifier based on naïve Bayes analysis of the SNP profiles made. A skin colour predictive test is described using the ten most strongly associated SNPs in 8 genes linked to skin pigmentation variation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

Cross-reactivity and tolerability of aztreonam and cephalosporins in subjects with a T cell-mediated hypersensitivity to penicillins.

PubMed

Romano, Antonino; Gaeta, Francesco; Valluzzi, Rocco Luigi; Maggioletti, Michela; Caruso, Cristiano; Quaratino, Donato

2016-07-01

The few studies performed in adults with T cell-mediated hypersensitivity to penicillins have found a rate of cross-reactivity with cephalosporins ranging from 2.8% to 31.2% and an absence of cross-reactivity with aztreonam. We sought to evaluate the possibility of using cephalosporins and aztreonam in subjects with documented delayed hypersensitivity to penicillins who especially require them. We conducted a prospective study of 214 consecutive subjects who had 307 nonimmediate reactions to penicillins (almost exclusively aminopenicillins) and had positive patch test and/or delayed-reading skin test responses to at least 1 penicillin reagent. To assess cross-reactivity with cephalosporins and aztreonam and the tolerability of such alternative β-lactams, all subjects underwent skin tests with cephalexin, cefaclor, cefadroxil, cefuroxime, ceftriaxone, and aztreonam. Subjects with negative responses were challenged with the alternative β-lactams concerned. All subjects had negative skin test results to cefuroxime, ceftriaxone, and aztreonam and tolerated challenges. Forty (18.7%) of the 214 subjects had positive skin test responses to at least 1 aminocephalosporin. Of the 174 subjects with negative responses, 170 underwent challenges; 1 reacted to cefaclor. These data demonstrate a rate of cross-reactivity between aminopenicillins and aminocephalosporins (ie, cephalexin, cefaclor, and cefadroxil) of around 20%, as well as the absence of cross-reactivity between penicillins and cefuroxime, ceftriaxone, and aztreonam in all subjects with T cell-mediated hypersensitivity to penicillins, almost exclusively aminopenicillins. Therefore these subjects could be treated with cefuroxime, ceftriaxone, and aztreonam. In those who especially require cephalosporin or aztreonam treatment, however, we recommend pretreatment skin tests because negative responses indicate tolerability. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc

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.

Allergic reactions during allergy skin testing with food allergens.

PubMed

Pitsios, C; Dimitriou, A; Kontou-Fili, K

2009-08-01

Skin testing is a reliable and safe way to diagnose IgE-mediated allergies, with rare side-effects. Two cases of systemic allergic reactions during skin testing to food allergens are hereby reported. A 28-year-old male reported allergic reactions, mild to moderate in severity, each time he tasted fish in the frame of his professional duties. During SPT and prick-to-prick to raw and cooked fishes, he presented urticaria and tachycardia. A 59-year-old male had a long history of urticaria-angioedema and asthma attacks, following the consumption of mammalian meat. He was skin-tested to various meats and during the 5 last minutes of the test he developed generalized urticaria, allergic rhinitis and conjunctivitis. They were both advised to completely avoid the relative allergens. In conclusion, skin testing, particularly prick-to-prick, may cause anaphylaxis. Tests should be performed only by physicians with proper training in allergy, experienced in treating promptly and properly episodes of anaphylaxis.

An analysis of skin prick test reactions in 656 asthmatic patients.

PubMed Central

Hendrick, D J; Davies, R J; D'Souza, M F; Pepys, J

1975-01-01

Of 656 asthmatic patients referred specifically for allergy assessments, 544 (84 percent) gave positive immediate skin prick tests to at least one of 22 common allergens used routinely. Comparison of these skin test positive patients with the 102 (16 percent) who were skin test negative showed a number of significant differences. The majority of the skin test positive patients (52 percent) were less than 10 years old at the time of onset of the asthma, whereas, of the skin test negative patients, 56 percent were aged over 30 years at the time of onset. Seventy per cent report rhinitis compared with 48 per cent of the skin test negative patients, and 29 per cent reported infantile eczema compared with 9 per cent. Symptoms attributed to house dust, pollens, and animals were noted two to three times more frequently by the skin test positive patients, while corticosteroid drugs had been used more commonly by the skin test negative patients (45 percent compared with 35 percent). No significant differences were observed with the other factors studied, namely, history of urticaria or angio-oedema, family history of "allergic" disease, and awareness of sensitivity to foods, aspirin or penicillin. Prick test reactions in the skin test positive patients were most commonly seen to house dust or the acarine mite, Dermatophagoides farinae (82 percent), followed by pollens (66 percent), animal danders (38 percent), foods (16 percent), Aspergillus fumigatus (16 percent), and other moulds (21 percent). There was a highly significant association of positive history with positive prick test for all allergens studied. Images PMID:1168378

An analysis of skin prick test reactions in 656 asthmatic patients.

PubMed

Hendrick, D J; Davies, R J; D'Souza, M F; Pepys, J

1975-02-01

Of 656 asthmatic patients referred specifically for allergy assessments, 544 (84 percent) gave positive immediate skin prick tests to at least one of 22 common allergens used routinely. Comparison of these skin test positive patients with the 102 (16 percent) who were skin test negative showed a number of significant differences. The majority of the skin test positive patients (52 percent) were less than 10 years old at the time of onset of the asthma, whereas, of the skin test negative patients, 56 percent were aged over 30 years at the time of onset. Seventy per cent report rhinitis compared with 48 per cent of the skin test negative patients, and 29 per cent reported infantile eczema compared with 9 per cent. Symptoms attributed to house dust, pollens, and animals were noted two to three times more frequently by the skin test positive patients, while corticosteroid drugs had been used more commonly by the skin test negative patients (45 percent compared with 35 percent). No significant differences were observed with the other factors studied, namely, history of urticaria or angio-oedema, family history of "allergic" disease, and awareness of sensitivity to foods, aspirin or penicillin. Prick test reactions in the skin test positive patients were most commonly seen to house dust or the acarine mite, Dermatophagoides farinae (82 percent), followed by pollens (66 percent), animal danders (38 percent), foods (16 percent), Aspergillus fumigatus (16 percent), and other moulds (21 percent). There was a highly significant association of positive history with positive prick test for all allergens studied.

Development of methods for skin barrier peeling tests.

PubMed

Omura, Yuko; Kazuharu, Seki; Kenji, Oishi

2006-01-01

We sought to develop a more effective method to evaluate the adhesive properties of skin barriers. The experimental design used was based on 3 principles: partial control, randomization, and repetition. Using these principles, the 180-degree peeling tests were conducted as specified in a standardized methodology (JIS Z0297) to the extent possible. However, the use of a stainless steel plate as a proxy for skin barrier application may result in the stretching and breaking of the skin barrier, making it impossible to obtain suitable measurements. Tests were conducted in constant temperature/ humidity chambers using a Tensilon Automatic Elongation Tester, where a sample was fixed on the side of a sample immobilization device, a sturdy metal (aluminum) box from which the air in the box was drawn off with a vacuum pump. A fluorocarbon polymer film was applied to the adhesive surface of a sample skin barrier. The film was peeled off in the volte-face (180-degree) direction in order to measure adhesive strengths. The films exhibit such properties as (a) ease of removal from the adhesive surface, (b) no resistance to a 180-degree fold back due to the thinness and flexibility of the material, and (c) tolerance of elongation. The adhesive properties of skin barriers were measured by peeling the fluorocarbon polymers in a 180-degree direction. Twelve specimen skin barrier products were selected for measurement, providing results with satisfactory reproducibility. Results based on the conventional stainless steel plate-based testing method acted as a control. The newly developed testing method enables chronological measurement results for skin barriers applied to fluorocarbon polymer films after 24 hours, 48 hours, and longer period.

Flu Vaccine Skin Patch Tested

MedlinePlus

... Subscribe September 2017 Print this issue Health Capsule Flu Vaccine Skin Patch Tested En español Send us ... Each year, millions of people nationwide catch the flu. The best way to protect yourself is to ...

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

Skin Prick Test in Patients with Chronic Allergic Skin Disorders

PubMed Central

Bains, Pooja; Dogra, Alka

2015-01-01

Background: Chronic allergic skin disorders are the inflammatory and proliferative conditions in which both genetic and environmental factors play important roles. Chronic idiopathic urticaria (CIU) and atopic dermatitis (AD) are among the most common chronic allergic skin disorders. These can be provoked by various food and aeroallergens. Skin prick tests (SPTs) represent the cheapest and most effective method to diagnose type I hypersensitivity. Positive skin tests with a history suggestive of clinical sensitivity strongly incriminate the allergen as a contributor to the disease process. Aims and Objectives: To determine the incidence of positive SPT in patients with chronic allergic skin disorders and to identify the various allergens implicated in positive SPT. Methods: Fifty patients of chronic allergic disorders were recruited in this study. They were evaluated by SPT with both food and aeroallergens. Results: In our study, SPT positivity in patients of CIU was 63.41% and in AD was 77.78%. Out of the 41 patients of CIU, the most common allergen groups showing SPT positivity were dust and pollen, each comprising 26.83% patients. SPT reaction was positive with food items (21.6%), insects (17.07%), fungus (12.20%), and Dermatophagoides farinae, that is, house dust mite (HDM) (7.32%). The allergen which showed maximum positivity was grain dust wheat (19.51%). Among nine patients of AD, maximum SPT positivity was seen with Dermatophagoides farinae, pollen Amaranthus spinosus, grain dust wheat, and cotton mill dust; each comprising 22.22% of patients. Conclusion: Our study showed that a significant number of patients of CIU and AD showed sensitivity to dust, pollen, insects, Dermatophagoides farinae, and fungi on SPT. Thus, it is an important tool in the diagnosis of CIU and AD. PMID:25814704

Bacterial cellulose skin masks-Properties and sensory tests.

PubMed

Pacheco, Guilherme; de Mello, Carolina Véspoli; Chiari-Andréo, Bruna Galdorfini; Isaac, Vera Lucia Borges; Ribeiro, Sidney José Lima; Pecoraro, Édison; Trovatti, Eliane

2017-09-29

Bacterial cellulose (BC) is a versatile material produced by microorganisms in the form of a membranous hydrogel, totally biocompatible, and endowed with high mechanical strength. Its high water-holding capacity based on its highly porous nanofibrillar structure allows BC to incorporate and to release substances very fast, thus being suitable for the preparation of skincare masks. The preparation and characterization of cosmetic masks based on BC membranes and active cosmetics. The masks were prepared by the simple incorporation of the cosmetic actives into BC membranes, used as a swelling matrix. The masks were characterized by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), sensory tests, and skin moisture tests on volunteers. The results of sensory tests revealed the good performance of BC, being considered effective by the panel of volunteers, specially for adhesion to the skin (7.7 at the score scale), and improvement of the skin moisture (the hydration effect increased 76% in 75% of the volunteers that used vegetable extract mask formulation [VEM]), or a decrease in skin hydration (80% of the volunteers showed 32.6% decrease on skin hydration using propolis extract formulation [PEM] treatment), indicating the BC nanofiber membranes can be used to skincare applications. The results demonstrate the BC can be used as an alternative support for cosmetic actives for skin treatment. © 2017 Wiley Periodicals, Inc.

Variation in aluminium patch test reactivity over time.

PubMed

Siemund, Ingrid; Mowitz, Martin; Zimerson, Erik; Bruze, Magnus; Hindsén, Monica

2017-11-01

Contact allergy to aluminium has been reported more frequently in recent years. It has been pointed out that positive patch test reactions to aluminium may not be reproducible on retesting. To investigate possible variations in patch test reactivity to aluminium over time. Twenty-one adults, who had previously reacted positively to aluminium, were patch tested with equimolar dilution series in pet. of aluminium chloride hexahydrate and aluminium lactate, four times over a period of 8 months. Thirty-six of 84 (43%) serial dilution tests with aluminium chloride hexahydrate and 49 of 84 (58%) serial dilution tests with aluminium lactate gave negative results. The range of reactivity varied between a negative reaction to aluminium chloride hexahydrate at 10% and/or to aluminium lactate at 12%, and a positive reaction to aluminium chloride hexahydrate at 0.1% and/or to aluminium lactate at 0.12%. The highest individual difference in test reactivity noticed was 320-fold when the two most divergent minimal eliciting concentrations were compared. The patch test reactivity to aluminium varies over time. Aluminium-allergic individuals may have false-negative reactions. Therefore, retesting with aluminium should be considered when there is a strong suspicion of aluminium contact allergy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Herbal supplements and skin testing: the lack of effect of commonly used herbal supplements on histamine skin prick testing.

PubMed

More, D R; Napoli, D C; Hagan, L L

2003-06-01

The use of herbal supplements is common, yet little is known about their pharmacologic properties. The purpose of this study was to assess the effects of 23 commonly used herbal supplements on histamine skin prick testing (SPT). Fifteen healthy volunteers participated in a double-blind, placebo-controlled, single-dose, crossover study. Wheal and flare responses to SPT with histamine phosphate (1 mg/ml) were measured before and 4 h after administration of each of the 23 popular herbal supplements, fexofenadine (60 mg) and placebo. Wheal and flare areas were recorded with tracings performed 10 min after the prick test and measured with a PC-digitizer using stereometric software. Fexofenadine significantly suppressed the wheal (P < 0.001) and flare (P = 0.02) areas compared with placebo. None of the herbal supplements caused significant suppression of the wheal and flare areas compared with placebo (P > 0.10). When taken in single-doses, the popular herbal supplements tested did not significantly affect the histamine skin response. Therefore, it seems unnecessary for clinicians to ask patients to discontinue these herbal supplements prior to allergy skin testing.

Skin prick testing in atopic eczema: atopic to what and at what age?

PubMed

Hon, Kam Lun; Wang, Shuxin Susan; Wong, Wing Lam; Poon, Wing Kwan; Mak, Ka Yi; Leung, Ting Fan

2012-05-01

Atopic eczema is a common and distressing disease. This study aimed to review the age-dependent pattern of atopic sensitization to food and aeroallergens in patients with eczema by skin prick testing. The results of skin prick test (SPT), serum IgE, bronchial challenge test, and family history of atopy in eczema patients seen at a pediatric dermatology clinic were reviewed. SPT results were available in 816 eczema patients. In these patients, 90% had atopic sensitization to at least one aeroallergen, 69% to at least one food allergen, and 94% to at least one allergen by SPT. Together with a family history of atopy in parents or siblings and a personal history of airway atopies, 97% and 99.8% of the patients were atopic, respectively. Bronchial hyper-reactivity (BHR) was demonstrated in 44% of 339 patients. Aeroallergen was more prevalent than food allergen sensitization among children older than 10 years. The mites (D. pteronysissnus, D. farinae and Blomia Tropicalis) were the most prevalent allergens regardless of age and BHR, but D. pteronysissnus and D. farinae sensitization were more prevalent among BHR-positive patients. Beef is the least sensitized food protein in all ages. The majority of patients with eczema are atopic to aeroallergens. The mites (D. pteronysissnus, D. farinae and Blomia Tropicalis) are the most prevalent allergens regardless of age and BHR.

Improved wheal detection from skin prick test images

NASA Astrophysics Data System (ADS)

Bulan, Orhan

2014-03-01

Skin prick test is a commonly used method for diagnosis of allergic diseases (e.g., pollen allergy, food allergy, etc.) in allergy clinics. The results of this test are erythema and wheal provoked on the skin where the test is applied. The sensitivity of the patient against a specific allergen is determined by the physical size of the wheal, which can be estimated from images captured by digital cameras. Accurate wheal detection from these images is an important step for precise estimation of wheal size. In this paper, we propose a method for improved wheal detection on prick test images captured by digital cameras. Our method operates by first localizing the test region by detecting calibration marks drawn on the skin. The luminance variation across the localized region is eliminated by applying a color transformation from RGB to YCbCr and discarding the luminance channel. We enhance the contrast of the captured images for the purpose of wheal detection by performing principal component analysis on the blue-difference (Cb) and red-difference (Cr) color channels. We finally, perform morphological operations on the contrast enhanced image to detect the wheal on the image plane. Our experiments performed on images acquired from 36 different patients show the efficiency of the proposed method for wheal detection from skin prick test images captured in an uncontrolled environment.

Xenobiotic metabolizing enzyme activities in cells used for testing skin sensitization in vitro.

PubMed

Fabian, E; Vogel, D; Blatz, V; Ramirez, T; Kolle, S; Eltze, T; van Ravenzwaay, B; Oesch, F; Landsiedel, R

2013-09-01

For ethical and regulatory reasons, in vitro tests for scoring potential toxicities of cosmetics are essential. A test strategy for investigating potential skin sensitization using two human keratinocytic and two human dendritic cell lines has been developed (Mehling et al. Arch Toxicol 86:1273–1295, 2012). Since prohaptens may be metabolically activated in the skin, information on xenobiotic metabolizing enzyme (XME) activities in these cell lines is of high interest. In this study, XME activity assays, monitoring metabolite or cofactor, showed the following: all three passages of keratinocytic (KeratinoSens® and LuSens) and dendritic (U937 und THP-1) cells displayed N-acetyltransferase 1 (NAT1) activities (about 6–60 nmol/min/mg S9-protein for acetylation of para-aminobenzoic acid). This is relevant since reactive species of many cosmetics are metabolically controlled by cutaneous NAT1. Esterase activities of about 1–4 nmol fluorescein diacetate/min/mg S9-protein were observed in all passages of investigated keratinocytic and about 1 nmol fluorescein diacetate/min/mg S9-protein in dendritic cell lines. This is also of practical relevance since many esters and amides are detoxified and others activated by cutaneous esterases. In both keratinocytic cell lines, activities of aldehyde dehydrogenase (ALDH) were observed (5–17 nmol product/min/mg cytosolic protein). ALDH is relevant for the detoxication of reactive aldehydes. Activities of several other XME were below detection, namely the investigated cytochrome P450-dependent alkylresorufin O-dealkylases 7-ethylresorufin O-deethylase, 7-benzylresorufin O-debenzylase and 7-pentylresorufin O-depentylase (while NADPH cytochrome c reductase activities were much above the limit of quantification), the flavin-containing monooxygenase, the alcohol dehydrogenase as well as the UDP glucuronosyl transferase activities.

Evaluation of a High-Throughput Peptide Reactivity Format Assay for Assessment of the Skin Sensitization Potential of Chemicals

PubMed Central

Wong, Chin Lin; Lam, Ai-Leen; Smith, Maree T.; Ghassabian, Sussan

2016-01-01

The direct peptide reactivity assay (DPRA) is a validated method for in vitro assessment of the skin sensitization potential of chemicals. In the present work, we describe a peptide reactivity assay using 96-well plate format and systematically identified the optimal assay conditions for accurate and reproducible classification of chemicals with known sensitizing capacity. The aim of the research is to ensure that the analytical component of the peptide reactivity assay is robust, accurate, and reproducible in accordance with criteria that are used for the validation of bioanalytical methods. Analytical performance was evaluated using quality control samples (QCs; heptapeptides at low, medium, and high concentrations) and incubation of control chemicals (chemicals with known sensitization capacity, weak, moderate, strong, extreme, and non-sensitizers) with each of three synthetic heptapeptides, viz Cor1-C420 (Ac-NKKCDLF), cysteine- (Ac-RFAACAA), and lysine- (Ac-RFAAKAA) containing heptapeptides. The optimal incubation temperature for all three heptapeptides was 25°C. Apparent heptapeptide depletion was affected by vial material composition. Incubation of test chemicals with Cor1-C420, showed that peptide depletion was unchanged in polypropylene vials over 3-days storage in an autosampler but this was not the case for borosilicate glass vials. For cysteine-containing heptapeptide, the concentration was not stable by day 3 post-incubation in borosilicate glass vials. Although the lysine-containing heptapeptide concentration was unchanged in both polypropylene and borosilicate glass vials, the apparent extent of lysine-containing heptapeptide depletion by ethyl acrylate, differed between polypropylene (24.7%) and glass (47.3%) vials. Additionally, the peptide-chemical complexes for Cor1-C420-cinnamaldehyde and cysteine-containing heptapeptide-2, 4-dinitrochlorobenzene were partially reversible during 3-days of autosampler storage. These observations further highlight

Intradermal Skin Testing in Allergic Rhinitis and Asthma with Negative Skin Prick Tests.

PubMed

Erel, Fuat; Sarioglu, Nurhan; Kose, Mehmet; Kaymakci, Mustafa; Gokcen, Mucahide; Kepekci, Ahmet Hamdi; Arslan, Mehmet

2017-06-01

Taking medical history, physical examination, and performing some in vivo and in vitro tests are necessary for the diagnosis of allergy. Skin prick test (SPT) is considered as the standard method and first-line approach for the detection of allergic sensitization. Although mainly SPT is used for the detection of allergic sensitization, intradermal skin test (IDST) may be necessary, especially in patients with a negative SPT result. IDST is quite safe; however, is nowadays seldom used for detection of inhalant allergy and its value remains controversial. We aimed to investigate whether IDST is useful and necessary in diagnosis of respiratory allergies or not. This study involved 4223 patients with allergic rhinitis (AR) and/or bronchial asthma (BA). SPT results were positive in 2419 patients (57%) and negative in 1804 (43%). IDST was applied to 344 patients with marked allergic symptoms and with negative SPT results. Out of 344 patients, 152 (44%) showed allergic sensitization to IDST. The most commonly encountered allergic response was against the house dust mite (HDM) (32.6%). Allergic response against fungal spores was also relatively high (22%), while the pollen allergy rate (4.3%) was quite low. In BA patients with negative prick test, IDST made a significant contribution to the diagnosis of HDM allergy (p=0.003). To avoid missed diagnosis of AR and BA, particularly regarding  the HDM allergy, application of IDST may be beneficial; therefore, IDST should be considered as the next step after SPT for diagnosis of allergy prior to in vitro or provocation tests.

Feasibility, Benefits, and Limitations of a Penicillin Allergy Skin Testing Service.

PubMed

Narayanan, Prasanna P; Jeffres, Meghan N

2017-06-01

To critically examine the feasibility, benefits, and limitations of an inpatient penicillin skin testing service and how pharmacists can be utilized. A PubMed search was performed from July 2016 through September 2016 using the following search terms: penicillin skin testing, penicillin allergy, β-lactam allergy. Additional references were identified from a review of literature citations. All English-language studies assessing the use of penicillin skin testing as well as management and clinical outcomes of patients with a β-lactam allergy were evaluated. The prevalence of people self-identifying as penicillin allergic ranges from 10% to 20% in the United States. Being improperly labeled as penicillin allergic is associated with higher health care costs, worse clinical outcomes, and an increased prevalence of multidrug-resistant infections. Penicillin skin testing can be a tool used to clarify penicillin allergies and has been demonstrated to be a successful addition to antimicrobial stewardship programs in multiple health care settings. Prior to implementing a penicillin skin testing service, institutions will need to perform a feasibility analysis of who will supply labor and accept the financial burden as well as identify if the positive benefits of a penicillin skin testing service overcome the limitations of this diagnostic test. We conclude that institutions with high percentages of patients receiving non-β-lactams because of penicillin allergy labels would likely benefit the most from a penicillin skin testing service.

Efficacy studies of Reactive Skin Decontamination Lotion, M291 Skin Decontamination Kit, 0.5% bleach, 1% soapy water, and Skin Exposure Reduction Paste Against Chemical Warfare Agents, part 1: guinea pigs challenged with VX.

PubMed

Braue, Ernest H; Smith, Kelly H; Doxzon, Bryce F; Lumpkin, Horace L; Clarkson, Edward D

2011-03-01

This report, first in a series of five, directly compares the efficacy of 4 decontamination products and Skin Exposure Reduction Paste Against Chemical Warfare Agents (SERPACWA) in the haired guinea pig model following exposure to VX. In all experiments, guinea pigs were close-clipped and given anesthesia. In the decontamination experiments, the animals were challenged with VX and decontaminated after a 2-minute delay for the standard procedure or at longer times for the delayed-decontamination experiments. Skin Exposure Reduction Paste Against Chemical Warfare Agents was applied as a thin coating (0.1 mm thick), allowed to dry for 15 minutes, and challenged with VX. After a 2-hour challenge, any remaining VX was blotted off the animal, but no additional decontamination was done. Positive control animals were challenged with VX in the same manner as the treated animals, except that they received no treatment. In addition, the positive control animals were always challenged with 5% VX in isopropyl alcohol (IPA) solution, whereas the treatment animals received either neat (undiluted) VX or 5% VX in IPA solution. All animals were observed during the first 4 hours and again at 24 hours after exposure for signs of toxicity and death. The protective ratio (PR, defined as the median lethal dose [LD(50)] of the treatment group divided by the LD(50) of the untreated positive control animals) was calculated from the probit dose-response curves established for each treatment group and nontreated control animals. Significance in this report was defined as p < .05. In the standard 2-minute neat VX decontamination experiments, the calculated PRs for Reactive Skin Decontamination Lotion (RSDL), 0.5% bleach, 1% soapy water, and the M291 Skin Decontamination Kit (SDK) were 66, 17, 16, and 1.1, respectively. Reactive Skin Decontamination Lotion was by far the most effective decontamination product tested and was significantly better than any of the other products. Bleach and

Controlling reactive oxygen species in skin at their source to reduce skin aging.

PubMed

Kern, Dale G; Draelos, Zoe D; Meadows, Christiaan; James Morré, D; Morré, Dorothy M

2010-01-01

Activity of an age-related, superoxide-forming, cell-surface oxidase (arNOX) comparing dermis, epidermis, serum, and saliva from female and male subjects ages 28-72 years measured spectrophotometrically using reduction of ferricytochrome c correlated with oxidative skin damage as estimated from autofluoresence of skin using an Advanced Glycation End products Reader (AGE-Reader; DiagnOptics B.V., Netherlands). By reducing arNOX activity in skin with arNOX-inhibitory ingredients (NuSkin's ageLOC technology), skin appearance was improved through decreased protein cross-linking and an accelerated increase in collagen.

Estimating Skin Cancer Risk: Evaluating Mobile Computer-Adaptive Testing.

PubMed

Djaja, Ngadiman; Janda, Monika; Olsen, Catherine M; Whiteman, David C; Chien, Tsair-Wei

2016-01-22

Response burden is a major detriment to questionnaire completion rates. Computer adaptive testing may offer advantages over non-adaptive testing, including reduction of numbers of items required for precise measurement. Our aim was to compare the efficiency of non-adaptive (NAT) and computer adaptive testing (CAT) facilitated by Partial Credit Model (PCM)-derived calibration to estimate skin cancer risk. We used a random sample from a population-based Australian cohort study of skin cancer risk (N=43,794). All 30 items of the skin cancer risk scale were calibrated with the Rasch PCM. A total of 1000 cases generated following a normal distribution (mean [SD] 0 [1]) were simulated using three Rasch models with three fixed-item (dichotomous, rating scale, and partial credit) scenarios, respectively. We calculated the comparative efficiency and precision of CAT and NAT (shortening of questionnaire length and the count difference number ratio less than 5% using independent t tests). We found that use of CAT led to smaller person standard error of the estimated measure than NAT, with substantially higher efficiency but no loss of precision, reducing response burden by 48%, 66%, and 66% for dichotomous, Rating Scale Model, and PCM models, respectively. CAT-based administrations of the skin cancer risk scale could substantially reduce participant burden without compromising measurement precision. A mobile computer adaptive test was developed to help people efficiently assess their skin cancer risk.

21 CFR 866.5270 - C-reactive protein immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5270 C-reactive protein immuno-logical test system. (a) Identification. A C-reactive protein... 21 Food and Drugs 8 2010-04-01 2010-04-01 false C-reactive protein immuno-logical test system. 866...

Marital Conflict and Risk for Child Maladjustment over Time: Skin Conductance Level Reactivity as a Vulnerability Factor

ERIC Educational Resources Information Center

El-Sheikh, Mona; Keller, Peggy S.; Erath, Stephen A.

2007-01-01

Skin conductance level reactivity (SCLR) was examined as a longitudinal mediator and moderator of relations between parental marital conflict and psychopathology among children and young adolescents. Participants were 157 boys and girls (M age at T1 = 9.31 years; SD = 1.97); there was a 2-year lag between T1 and T2 assessments. At T1,…

Food-specific serum IgE and IgG reactivity in dogs with and without skin disease: lack of correlation between laboratories.

PubMed

Hardy, Jonathan I; Hendricks, Anke; Loeffler, Anette; Chang, Yu-Mei; Verheyen, Kristien L; Garden, Oliver A; Bond, Ross

2014-10-01

Despite conflicting data on their utility and no reports on interlaboratory reproducibility, serum food-specific antibodies are commonly assayed in first-opinion canine practice. To determine both the variability of test results between two laboratories and the frequencies and magnitudes of food reactivity in dogs of different disease status. Sera were obtained from eight dogs with cutaneous adverse food reaction (Group A), 22 with nonfood-induced atopic dermatitis (Group B), 30 with an allergic/inflammatory phenotype (Group C), 12 with miscellaneous skin diseases (Group D) and nine healthy dogs (Group E). Paired sera were submitted to two laboratories (A and B) for assays of food-specific IgE and IgG antibodies. Numbers of positive IgE and IgG tests determined by each laboratory in Groups A, B, D and E were comparable (Group C not included). Significant differences in the magnitude of IgE reactivity between groups for each allergen were seen only for lamb (Laboratory A, P = 0.003); lamb reactivity in Group D exceeded Group E (P = 0.004) but was comparable between all other groups. Agreement (kappa statistic) between the two laboratories' tests was 'moderate' for one antigen (potato IgE), 'fair' for four (corn IgE, rice IgE and IgG and soya bean IgG), 'slight' for eight (six IgE and two IgG) and 'less than chance' for the remaining six antigens (three IgE and three IgG). These laboratories' tests appear to have dubious predictive clinical utility because they neither correlate nor distinguish between dogs of different disease status. © 2014 ESVD and ACVD.

Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose.

PubMed

Sesé, L; Gaouar, H; Autegarden, J-E; Alari, A; Amsler, E; Vial-Dupuy, A; Pecquet, C; Francès, C; Soria, A

2016-03-01

The diagnosis of HSR to iodinated contrast media (ICM) is challenging based on clinical history and skin tests. This study evaluates the negative predictive value (NPV) of skin tests and intravenous provocation test (IPT) with low-dose ICM in patients with suspected immediate hypersensitivity reaction (HSR) to ICM. Thirty-seven patients with suspected immediate hypersensitivity reaction to ICM were included retrospectively. Skin tests and a single-blind placebo-controlled intravenous provocation test (IPT) with low-dose iodinated contrast media (ICM) were performed. Skin tests with ICM were positive in five cases (one skin prick test and five intradermal test). Thirty-six patients were challenged successfully by IPT, and only one patient had a positive challenge result, with a grade I reaction by the Ring and Messmer classification. Ten of 23 patients followed up by telephone were re-exposed to a negative tested ICM during radiologic examination; two experienced a grade I immediate reaction. For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44-97%). © 2016 John Wiley & Sons Ltd.

A new alternative method for testing skin irritation using a human skin model: a pilot study.

PubMed

Miles, A; Berthet, A; Hopf, N B; Gilliet, M; Raffoul, W; Vernez, D; Spring, P

2014-03-01

Studies assessing skin irritation to chemicals have traditionally used laboratory animals; however, such methods are questionable regarding their relevance for humans. New in vitro methods have been validated, such as the reconstructed human epidermis (RHE) model (Episkin®, Epiderm®). The comparison (accuracy) with in vivo results such as the 4-h human patch test (HPT) is 76% at best (Epiderm®). There is a need to develop an in vitro method that better simulates the anatomo-pathological changes encountered in vivo. To develop an in vitro method to determine skin irritation using human viable skin through histopathology, and compare the results of 4 tested substances to the main in vitro methods and in vivo animal method (Draize test). Human skin removed during surgery was dermatomed and mounted on an in vitro flow-through diffusion cell system. Ten chemicals with known non-irritant (heptylbutyrate, hexylsalicylate, butylmethacrylate, isoproturon, bentazon, DEHP and methylisothiazolinone (MI)) and irritant properties (folpet, 1-bromohexane and methylchloroisothiazolinone (MCI/MI)), a negative control (sodiumchloride) and a positive control (sodiumlaurylsulphate) were applied. The skin was exposed at least for 4h. Histopathology was performed to investigate irritation signs (spongiosis, necrosis, vacuolization). We obtained 100% accuracy with the HPT model; 75% with the RHE models and 50% with the Draize test for 4 tested substances. The coefficients of variation (CV) between our three test batches were <0.1, showing good reproducibility. Furthermore, we reported objectively histopathological irritation signs (irritation scale): strong (folpet), significant (1-bromohexane), slight (MCI/MI at 750/250ppm) and none (isoproturon, bentazon, DEHP and MI). This new in vitro test method presented effective results for the tested chemicals. It should be further validated using a greater number of substances; and tested in different laboratories in order to suitably

Skin Testing With Water Buffalo's Milk in Children With Cow's Milk Allergy.

PubMed

Sheehan, William J; Gardynski, Andrea; Phipatanakul, Wanda

2009-09-01

BACKGROUND: Cow's milk allergy is the most common food allergy in young children. In areas outside the United States, milk from other mammals has been studied as a possible and desirable alternative for children with cow's milk allergy. OBJECTIVES: We chose to further investigate water buffalo's milk as an alternative for cow's milk allergic children in the United States. METHODS: Children with cow's milk allergy were skin prick tested with water buffalo's milk. Additionally, subjects were followed clinically for 1 year after the test to determine how many of the subjects had persistent cow's milk allergy. RESULTS: In total, 30 children, age 8 months to 8 years, were skin prick tested to water buffalo's milk with 73% (22/30) having a positive test. All children with a negative water buffalo's milk skin test also had a negative cow's milk skin test. In follow-up, most (7 of 8) of the children with a negative skin prick test (SPT) to water buffalo's milk were found to have outgrown their cow's milk allergy. In comparison, all of the subjects with a positive skin test to water buffalo's milk had persistent cow's milk allergy. After adjusting for this, we determined that 96% (22/23) of the children with persistent cow's milk allergy were positive on skin testing to water buffalo's milk. CONCLUSIONS: In this population, the vast majority of children with persistent cow's milk allergy were positive on skin prick testing to water buffalo's milk. These results indicate that water buffalo's milk is unlikely to be a successful alternative for children with cow's milk allergy.

A comparison of skin prick tests, intradermal skin tests, and specific IgE in the diagnosis of mouse allergy.

PubMed

Sharma, Hemant P; Wood, Robert A; Bravo, Andrea R; Matsui, Elizabeth C

2008-04-01

Mouse sensitization is assessed by using skin testing and serum levels of mouse allergen-specific IgE (m-IgE). However, it is unknown whether a positive skin test response or m-IgE result accurately identifies those with clinically relevant mouse sensitization. We sought to compare skin testing and m-IgE measurement in the diagnosis of mouse allergy. Sixty-nine mouse laboratory workers underwent skin prick tests (SPTs), intradermal tests (IDTs), and serum IgE measurements to mouse allergen, followed by nasal challenge to increasing concentrations of mouse allergen. Challenge response was assessed by nasal symptom score. Thirty-eight women and 31 men with a mean age of 30 years were studied. Forty-nine workers reported mouse-related symptoms, of whom 10 had positive m-IgE results and 12 had positive SPT responses. Fifteen had negative SPT responses but positive IDT responses. Positive nasal challenges were observed in 70% of workers with positive m-IgE results, 83% of workers with positive SPT responses, 33% of workers with negative SPT responses/positive IDT responses, and 0% of workers with negative IDT responses. SPTs performed best, having the highest positive and negative predictive values. Among participants with a positive challenge result, those with a positive SPT response or m-IgE result had a significantly lower challenge threshold than those with a positive IDT response (P = .01). Workers with a positive challenge result were more likely to have an increase in nasal eosinophilia after the challenge compared with those with a negative challenge result (P = .03). SPTs perform best in discriminating patients with and without mouse allergy. Mouse-specific IgE and IDTs appear to be less useful than SPTs in the diagnosis of mouse allergy.

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.

Nummular eczema: An addition of senile xerosis and unique cutaneous reactivities to environmental aeroallergens.

PubMed

Aoyama, H; Tanaka, M; Hara, M; Tabata, N; Tagami, H

1999-01-01

The pathogenesis of nummular eczema (NE) is still unknown. It often develops on the lower legs of elderly individuals with xerotic changes during the winter months. Such winter exacerbation is also observed in atopic dermatitis, in which there is a high incidence of cutaneous immune reactivities against environmental aeroallergens. Because of the total lack of information about skin reactivities in NE patients, we performed immunological as well as functional studies in their uninvolved skin. Prick tests and chamber scarification patch tests for representative aeroallergens were conducted on the flexor surface of the forearm in 26 NE patients, in 21 age-matched elderly persons without NE and in 43 healthy young controls. We found that the elderly subjects, regardless of their background, showed a significantly higher immediate skin reactivity to Candida albicans than the young controls. In contrast, patch testing revealed that, unlike the age-matched elderly subjects who showed a decrease in incidence of positive patch test reactions, the NE patients retained delayed contact sensitivity at a level comparable to that of the young healthy controls. They showed a significantly higher percentage of positive patch test reactions to Dermatophagoides farinae allergen (46%) and house dust allergen (35%) than the age-matched controls. Moreover, they also showed a significantly higher percentage of delayed hypersensitive reactions to C. albicans allergen (85%) than the age-matched controls (48%). Noninvasive functional assessment of the stratum corneum (SC) in unaffected skin areas of the lower legs in 8 NE patients demonstrated that, though the water barrier function of the SC was comparable to that of the age-matched controls, they showed a significantly lower hydration state of the SC than the age-matched controls. The xerotic skin of elderly individuals facilitates the development of cracking and fissuring of the skin surface in dry and cold winter. Such damage in the SC

Skin test hypersensitivity for childhood asthma in Istanbul during a period of 16 years.

PubMed

Akcakaya, N; Cokugras, H; Camcioglu, Y; Ozdemir, M

2005-01-01

For diagnosis of allergic disorders, besides history and physical examination, many in vivo and in vitro laboratory tests are used. Skin prick test (SPT) is an easily performed and valuable test in children. Our aim was to evaluate the SPT results of asthmatic children according to age and gender, in Istanbul and its neighborhood, followed for a period of 16 years. Consecutive 5080 asthmatic children, aged 1 to 18 years, admitted to Pediatric Allergy Policlinics of Istanbul University Cerrahpasa Medicine Faculty from 1987 to 2003, were screened retrospectively for 10 frequently exposed allergens. 3086 cases (61 %) had SPT reactivity for one and/or for multiple allergens; the SPT reactivity percentages of the exposed allergens was 50 % (2554 cases) for house dust mites DP, 49 % (2462 cases) for house dust mites DF, 15 % (784 cases) for cat dander, 10 % (525 cases) for dog dander, 4 % (228 cases) for lamb wool, 10 % (504 cases) for wheat, 3 % (162 cases) for egg white, 6 % (345 cases) for hazelnut pollen, 6 % (318 cases) for Candida Albicans, 6 % (326 cases) for Aspergillus Fumigatus. While house dust mites were determined as the predominant allergen for each age groups in this study, allergy against cat dander was the third important allergen in sequence, as cat is a domestic pet which is frequently kept at home in Turkey.

Echo: skin stress test

NASA Image and Video Library

1960-05-14

Photographed in 1960. -- Skin Stress Test of the 12-foot satellite built as a prototype of the full-scale Echo satellite. The 12-foot diameter of the sphere was chosen because that was the ceiling height in the Langley model shop. The proposal to build the 12-foot satellite was made in November 1957. -- Published in James R. Hansen, Spaceflight Revolution: NASA Langley Research Center From Sputnik to Apollo, NASA SP-4308, pp. 170-171.

Predictive value of the cow's milk skin prick test in infantile colic.

PubMed

Moravej, Hossein; Imanieh, Mohammad H; Kashef, Sara; Handjani, Farhad; Eghterdari, Fardin

2010-01-01

Infantile colic is a common problem among young infants. Cow's milk allergy has been suggested as one of the causes. We aimed to investigate the value of the cow's milk skin test for the diagnosis of cow's milk allergy in exclusively breast-fed infants with infantile colic. Exclusively breast-fed infants with infantile colic were enrolled in this study. On the first visit, the average hours of crying of the infant in a 24-h period were recorded and the cow's milk skin test was performed. If the infant had a positive skin test, elimination of cow's milk from the mothers' diet was advised. Infants with negative skin tests were divided into case and control groups. Cow's milk was eliminated from the diet of mothers in the case group. After 2 weeks, the number of hours of crying were recorded again. The reduction in the crying hours was compared between the two groups using the chi-square test. Skin tests were positive in 3 of 114 cases (2.6%) of infantile colic. All three cases recovered completely following elimination of cow's milk from the mother's diet. Among the 111 patients with negative skin tests, 77 patients completed the study: 35 in the case group and 42 in the control group. The reduction in crying hours in infants in the case group was not significantly different from that in the control group. Elimination of cow's milk from the mothers' diet is not beneficial for infants with a negative skin test. Infants with a positive skin test may benefit from this management.

Penicillin skin testing: potential implications for antimicrobial stewardship.

PubMed

Unger, Nathan R; Gauthier, Timothy P; Cheung, Linda W

2013-08-01

As the progression of multidrug-resistant organisms and lack of novel antibiotics move us closer toward a potential postantibiotic era, it is paramount to preserve the longevity of current therapeutic agents. Moreover, novel interventions for antimicrobial stewardship programs are integral to combating antimicrobial resistance worldwide. One unique method that may decrease the use of second-line antibiotics (e.g., fluoroquinolones, vancomycin) while facilitating access to a preferred β-lactam regimen in numerous health care settings is a penicillin skin test. Provided that up to 10% of patients have a reported penicillin allergy, of whom ~10% have true IgE-mediated hypersensitivity, significant potential exists to utilize a penicillin skin test to safely identify those who may receive penicillin or a β-lactam antibiotic. In this article, we provide information on the background, associated costs, currently available literature, pharmacists' role, antimicrobial stewardship implications, potential barriers, and misconceptions, as well as future directions associated with the penicillin skin test. © 2013 Pharmacotherapy Publications, Inc.

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.

Reactivity measurement in estimation of benzoquinone and benzoquinone derivatives’ allergenicity

PubMed Central

Mbiya, Wilbes; Chipinda, Itai; Simoyi, Reuben H.; Siegel, Paul D.

2015-01-01

Benzoquinone (BQ) and benzoquinone derivatives (BQD) are used in the production of dyes and cosmetics. While BQ, an extreme skin sensitizer, is an electrophile known to covalently modify proteins via Michael Addition (MA) reaction whilst halogen substituted BQD undergo nucleophilic vinylic substitution (SNV) mechanism onto amine and thiol moieties on proteins, the allergenic effects of adding substituents on BQ have not been reported. The effects of inserting substituents on the BQ ring has not been studied in animal assays. However, mandated reduction/elimination of animals used in cosmetics testing in Europe has led to an increased need for alternatives for the prediction of skin sensitization potential. Electron withdrawing and electron donating substituents on BQ were assessed for effects on BQ reactivity toward nitrobenzene thiol (NBT). The NBT binding studies demonstrated that addition of EWG to BQ as exemplified by the chlorine substituted BQDs increased reactivity while addition of EDG as in the methyl substituted BQDs reduced reactivity. BQ and BQD skin allerginicity was evaluated in the murine local lymph node assay (LLNA). BQD with electron withdrawing groups had the highest chemical potency followed by unsubstituted BQ and the least potent were the BQD with electron donating groups. The BQD results demonstrate the impact of inductive effects on both BQ reactivity and allergenicity, and suggest the potential utility of chemical reactivity data for electrophilic allergen identification and potency ranking. PMID:26612505

Assessment of a Protein Cocktail-Based Skin Test for Bovine Tuberculosis in a Double-Blind Field Test in Cattle

PubMed Central

Xin, Ting; Jia, Hong; Ding, Jiabo; Li, Pingjun; Yang, Hongjun; Hou, Shaohua; Yuan, Weifeng; Guo, Xiaoyu; Wang, Haichun; Liang, Qianqian; Li, Ming

2013-01-01

Bovine tuberculosis (bTB) is a worldwide zoonosis caused mainly by Mycobacterium bovis. The traditional diagnostic method used often is the tuberculin skin test, which uses bovine purified protein derivatives (PPD-B). However, it is difficult to maintain uniformity of PPD-B from batch to batch, and it shares common antigens with nonpathogenic environmental mycobacteria. To overcome these problems, M. bovis-specific antigens that showed good T cell stimulation, such as CFP-10, ESAT-6, Rv3615c, etc., have been used in the skin test, but there have been no large-scale clinical studies on these antigens. In this study, two combinations (CFP-10/ESAT-6/TB10.4 protein cocktail and CFP-10/ESAT-6/Rv3872/MPT63 protein cocktail) were developed and used as stimuli in the skin test. Cattle were double-blind tested to assess the efficiency of the protein cocktail-based skin tests. The results showed that the CFP-10/ESAT-6/TB10.4 protein cocktail-based skin test can differentiate TB-infected cattle from Mycobacterium avium-infected ones and that it shows a high degree of agreement with the traditional tuberculin skin test (κ = 0.8536) and gamma interferon (IFN-γ) release assay (κ = 0.8154). Compared to the tuberculin skin test, the relative sensitivity and relative specificity of the CFP-10/ESAT-6/TB10.4-based skin test were 87% and 97%, respectively., The relative sensitivity and relative specificity of the CFP-10/ESAT-6/TB10.4-based skin test were 93% and 92%, respectively, on comparison with the IFN-γ release assay. The correlation between the increases in skin thickness observed after the inoculation of stimuli was high (PPD-B versus CFP-10/ESAT-6/TB10.4, Spearman r of 0.8435). The correlation between the optical density at 450 nm (OD450) obtained after blood stimulation with PPD-B and the increase in skin thickness observed after inoculation of the CFP-10/ESAT-6/TB10.4 protein cocktail was high (Spearman r = 0.7335). Therefore, the CFP-10/ESAT-6/TB10.4-based skin test

[Assessment of hypersensitivity to honey-bee venom in beekeepers by skin tests].

PubMed

Becerril-Ángeles, Martín; Núñez-Velázquez, Marco; Marín-Martínez, Javier

2013-01-01

Beekeepers are exposed to frequent honey-bee stings, and have the risk to develop hypersensitivity to bee venom, but long-term exposure can induce immune tolerance in them. Up to 30% of beekeepers show positive skin tests with honey-bee venom. The prevalence of systemic reactions to bee stings in beekeepers is from 14% to 42%. To know the prevalence of hypersensitivity to honeybee venom in Mexican beekeepers and non-beekeepers by the use of skin tests. A group of 139 beekeepers and a group of 60 non-beekeeper volunteers had a history and physical related to age, sex, family and personal atopic history and time of exposure to bee stings. Both groups received intradermal skin tests with honey-bee venom, 0.1 mcg/mL and 1 mcg/mL, and histamine sulphate 0.1 mg/mL and Evans solution as controls. The skin tests results of both groups were compared by chi-squared test. Of the group of beekeepers, 116 were men (83%) and 23 women, average age was 39.3 years, had atopic family history 28% and personal atopy 13%, average time of exposure to bee stings was 10.9 years, skin tests with honey-bee venom were positive in 16.5% and 11% at 1 mcg/mL and 0.1 mcg/mL, respectively. In the non-beekeepers group venom skin tests were positive in 13.3% and 6.7% at 1 mcg/mL and 0.1 mcg/mL. We did not find significant differences between the two venom concentrations tested in both groups, neither in the number of positive skin tests between the two groups. We found hypersensivity to honey-bee venom slightly higher in the beekeepers than in the group apparently not exposed. Both honey-bee venom concentrations used did not show difference in the results of the skin tests. The similarity of skin tests positivity between both groups could be explained by immune tolerance due to continued exposure of beekeepers.

8-Oxo-2'-deoxyguanosine ameliorates UVB-induced skin damage in hairless mice by scavenging reactive oxygen species and inhibiting MMP expression.

PubMed

Lee, Jin-Ku; Ko, Seong-Hee; Ye, Sang-Kyu; Chung, Myung-Hee

2013-04-01

Skin is uniquely vulnerable to damage caused by reactive oxygen species (ROS), which are most commonly produced in response to ultraviolet (UV) light. ROS generated at injury sites play an important role in modulating the inflammatory response. Besides inhibiting Rac, 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) has also shown notable antioxidant action. We tested whether 8-oxo-dG could protect skin from UVB-induced damage by scavenging ROS. HaCaT cells and hairless mice were irradiated with 15 and 180 mJ/cm(2) narrow-spectrum UVB, respectively. ROS generation was detected through incubation with DCFDA and confocal microscopy. Western blot analyses and immunohistochemistry were performed to verify the activities of ERK, JNK, p38, ATF-2, and c-Jun, and the expression of matrix metalloproteinases (MMPs), in UVB-irradiated HaCaT cells and murine skin. Hydrogen peroxide production and protein carbonyl concentrations were measured in UVB-damaged mouse skin. MMP-1 and MMP-9 expression in UVB-irradiated HaCaT cells was measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). In UVB-irradiated HaCaT cells, 8-oxo-dG inhibited ROS production, subsequent activation of mitogen-activated protein kinase (MAPK), ATF-2, and c-Jun, and MMP expression. It also prevented UV-induced skin reactions in hairless mice, inhibiting the increase in protein carbonyl content, activation of MAPKs, ATF-2, and c-Jun, the increases in MMP-9 and -13 expression, and epidermal hyperplasia. 8-oxo-dG can be considered an endogenous antioxidant and its potent antioxidant activity might be a beneficial property that could be exploited to protect skin from ROS-associated photodamage. Copyright © 2013. Published by Elsevier Ireland Ltd.

Cosmetics Europe multi-laboratory pre-validation of the SkinEthic™ reconstituted human corneal epithelium test method for the prediction of eye irritation.

PubMed

Alépée, N; Bessou-Touya, S; Cotovio, J; de Smedt, A; de Wever, B; Faller, C; Jones, P; Le Varlet, B; Marrec-Fairley, M; Pfannenbecker, U; Tailhardat, M; van Goethem, F; McNamee, P

2013-08-01

Cosmetics Europe, The Personal Care Association, known as Colipa before 2012, conducted a program of technology transfer and assessment of Within/Between Laboratory (WLV/BLV) reproducibility of the SkinEthic™ Reconstituted Human Corneal Epithelium (HCE) as one of two human reconstructed tissue eye irritation test methods. The SkinEthic™ HCE test method involves two exposure time treatment procedures - one for short time exposure (10 min - SE) and the other for long time exposure (60 min - LE) of tissues to test substance. This paper describes pre-validation studies of the SkinEthic™ HCE test method (SE and LE protocols) as well as the Eye Peptide Reactivity Assay (EPRA). In the SE WLV study, 30 substances were evaluated. A consistent outcome with respect to viability measurement across all runs was observed with all substances showing an SD of less than 18%. In the LE WLV study, 44 out of 45 substances were consistently classified. These data demonstrated a high level of reproducibility within laboratory for both the SE and LE treatment procedures. For the LE BLV, 19 out of 20 substances were consistently classified between the three laboratories, again demonstrating a high level of reproducibility between laboratories. The results for EPRA WLV and BLV studies demonstrated that all substances analysed were categorised similarly and that the method is reproducible. The SkinEthic™ HCE test method entered into the experimental phase of a formal ECVAM validation program in 2010. Copyright © 2013. Published by Elsevier Ltd.

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

Prevalence of IgE reactivities in mold-allergic subjects to commercially available fungal enzymes.

PubMed

Horner, W Elliott; Armstrong, Maricelis; El-Dahr, Jane; McCants, Marjorie; Reese, Gerald; Kobernick, Aaron K; Lehrer, Samuel B

2008-01-01

Fungi are important aeroallergens. However, fungal allergen sources of consistent quality for clinical testing are not readily available. Because some allergens have been identified as enzymes, we assessed the prevalence of IgE reactivity to commercially available fungal enzymes. The purpose of this study was to determine IgE antibody reactivity by radioallergosorbent assay (RAST) to commercially available fungal enzymes in mold-allergic individuals. Sera from 20 subjects with symptoms of respiratory allergies and skin test reactivity to 2 or more fungal allergens (4 conidial [imperfecti] fungi and/or 8 basidiomycetes) were selected. Controls were six atopic individuals with neither history of fungal allergy nor skin test reactivity to fungi. Seventeen commercial fungal enzymes were used as antigens to evaluate the subjects' IgE antibody reactivity by RAST. Sera from most fungus-allergic individuals showed substantial IgE antibody reactivity to enzymes; control sera showed little or no reactivity. The mean reactivity to all commercial enzymes of all subjects tested was RAST > or = 3% with only one exception. The most reactive fungal enzymes were invertase (bakers' yeast, Saccharomyces cerevisiae), cellulase (Trichoderma viride), and glucosidase (brewers yeast, S. cerevisiae) with mean binding of 14.6, 9.5, and 8.8%, respectively. Using RAST results with a combination of four enzymes from S. cerevisiae (brewers yeast glucosidase, bakers' yeast maltase, invertase, and invertase V), a sensitivity of 100% was shown for detecting mold-allergic patients. The studies suggest that fungal enzymes may be useful source materials for the identification of fungal allergens and may also provide readily available source materials to produce improved diagnostic and therapeutic reagents.

Tuberculin skin test conversion among health sciences students: A retrospective cohort study

PubMed Central

Pérez-Lu, José E.; Cárcamo, Cesar P.; García, Patricia J.; Bussalleu, Alejandro; Bernabé-Ortiz, Antonio

2014-01-01

SUMMARY Previous studies have reported that health sciences students are at greater risk for tuberculosis infection, especially in developing countries. The objective of this study was to estimate the prevalence, incidence, and factors associated with latent tuberculosis infection among Health Sciences students in Peru. Students enrolled at private university (in Lima – Peru) are tested annually for tuberculosis infection by tuberculin skin test. Data on tuberculin skin test results between 2002 and 2009 was used in this retrospective cohort study, a total of 4842 students were included. Tuberculin skin test conversion was defined as the change of tuberculin skin test from negative (<10 mm) to positive (≥10 mm) after 48 –72 h of inoculation. Baseline tuberculin skin test positivity was 1.0% (95%CI: 0.6%–1.3%), whereas tuberculin skin test conversion incidence was 12.4 per 100 person-years (95%CI: 11.8–13.0). This study showed that students from clinical careers in close contact with patients had an increased risk of tuberculosis infection in the internship, especially Medicine, Dentistry, Medical Technology and Nursing. Administrative, environmental and personal protection measures should be implemented and evaluated periodically in order to reduce the risk of exposure. PMID:23116653

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.

Utility of minor determinants for skin testing in inpatient penicillin allergy evaluation.

PubMed

Geng, Bob; Eastman, Jacqueline J; Mori, Karen; Braskett, Melinda; Riedl, Marc A

2017-09-01

Most patients with a history of penicillin allergy can tolerate penicillin. Skin testing can identify tolerant patients, but not all known allergenic determinants are commercially available. Protocols exist that use only available reagents, but the sensitivity and safety of these protocols, particularly for hospitalized patients, are controversial. To determine the number of hospitalized patients referred for penicillin skin testing who showed unique positivity to the minor determinants penicilloate and penilloate. A retrospective chart review was conducted of all inpatients who underwent penicillin skin testing at 1 institution. Patients were referred by their treating physician. All patients underwent skin prick testing to benzylpenicilloyl polylysine (major determinant), penicillin G, penicilloate, penilloate (minor determinants), amoxicillin, and positive and negative controls. If the result was negative, then intradermal testing was done with the same penicillin determinants and the negative control. A 4-mm wheal with flare was considered a positive reaction. Inpatient penicillin skin testing was done in 528 subjects. Any positive test reaction was found in 107 subjects (20%). Three subjects (3%) reacted to penilloate only, 25 (23%) reacted to penicilloate only, 2 (2%) reacted to penicillin G only, and 8 (8%) reacted to amoxicillin only. Sixty-eight subjects (64%) reacted to a compound other than the major determinant. This study found a high rate of exclusively positive skin test reactions to the minor determinants penicilloate and penilloate. Because patients with positive test reactions are at increased risk of reaction to drug challenge, these data support the use of these reagents for penicillin skin testing in hospitalized patients. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Sleep deprived and sweating it out: the effects of total sleep deprivation on skin conductance reactivity to psychosocial stress.

PubMed

Liu, Jean C J; Verhulst, Silvan; Massar, Stijn A A; Chee, Michael W L

2015-01-01

We examined how sleep deprivation alters physiological responses to psychosocial stress by evaluating changes in skin conductance. Between-subjects design with one group allocated to 24 h of total sleep deprivation and the other to rested wakefulness. The study took place in a research laboratory. Participants were 40 healthy young adults recruited from a university. Sleep deprivation and feedback. Electrodermal activity was monitored while participants completed a difficult perceptual task with false feedback. All participants showed increased skin conductance levels following stress. However, compared to well-rested participants, sleep deprived participants showed higher skin conductance reactivity with increasing stress levels. Our results suggest that sleep deprivation augments allostatic responses to increasing psychosocial stress. Consequentially, we propose sleep loss as a risk factor that can influence the pathogenic effects of stress. © 2014 Associated Professional Sleep Societies, LLC.

Cutaneous Microvascular Blood Flow and Reactivity in Hypoxia

PubMed Central

Treml, Benedikt; Kleinsasser, Axel; Stadlbauer, Karl-Heinz; Steiner, Iris; Pajk, Werner; Pilch, Michael; Burtscher, Martin; Knotzer, Hans

2018-01-01

As is known, hypoxia leads to an increase in microcirculatory blood flow of the skin in healthy volunteers. In this pilot study, we investigated microcirculatory blood flow and reactive hyperemia of the skin in healthy subjects in normobaric hypoxia. Furthermore, we examined differences in microcirculation between hypoxic subjects with and without short-term acclimatization, whether or not skin microvasculature can acclimatize. Fourty-six healthy persons were randomly allocated to either short-term acclimatization using intermittent hypoxia for 1 h over 7 days at an FiO2 0.126 (treatment, n = 23) or sham short-term acclimatization for 1 h over 7 days at an FiO2 0.209 (control, n = 23). Measurements were taken in normoxia and at 360 and 720 min during hypoxia (FiO2 0.126). Microcirculatory cutaneous blood flow was assessed with a laser Doppler flowmeter on the forearm. Reactive hyperemia was induced by an ischemic stimulus. Measurements included furthermore hemodynamics, blood gas analyses and blood lactate. Microcirculatory blood flow increased progressively during hypoxia (12.3 ± 7.1–19.0 ± 8.1 perfusion units; p = 0.0002) in all subjects. The magnitude of the reactive hyperemia was diminished during hypoxia (58.2 ± 14.5–40.3 ± 27.4 perfusion units; p = 0.0003). Short-term acclimatization had no effect on microcirculatory blood flow. When testing for a hyperemic response of the skin's microcirculation we found a diminished signal in hypoxia, indicative for a compromised auto-regulative circulatory capacity. Furthermore, hypoxic short-term acclimatization did not affect cutaneous microcirculatory blood flow. Seemingly, circulation of the skin was unable to acclimatize using a week-long short-term acclimatization protocol. A potential limitation of our study may be the 7 days between acclimatization and the experimental test run. However, there is evidence that the hypoxic ventilatory response, an indicator of acclimatization, is increased for 1 week after

Electroencephalographic reactivity testing in unconscious patients: a systematic review of methods and definitions.

PubMed

Admiraal, M M; van Rootselaar, A-F; Horn, J

2017-02-01

Electroencephalographic (EEG) reactivity testing is often presented as a clear-cut element of electrophysiological testing. Absence of EEG reactivity is generally considered an indicator of poor outcome, especially in patients after cardiac arrest. However, guidelines do not clearly describe how to test for reactivity and how to evaluate the results. In a quest for clear guidelines, we performed a systematic review aimed at identifying testing methods and definitions of EEG reactivity. We systematically searched the literature between 1970 and May 2016. Methodological quality of the studies was assessed using the QUality In Prognostic Studies tool. Quality of the descriptions of stimulus protocol and reactivity definition was rated on a four-category grading scale based on reproducibility. We found that protocols for EEG reactivity testing vary greatly and descriptions of protocols are almost never replicable. Furthermore, replicable definitions of presence or absence of EEG reactivity are never provided. In order to draw firm conclusions on EEG reactivity as a prognostic factor, future studies should include a precise stimulation protocol and reactivity definition to facilitate guideline formation. © 2016 EAN.

Non-immediate reactions to beta-lactams: diagnostic value of skin testing and drug provocation test.

PubMed

Padial, A; Antunez, C; Blanca-Lopez, N; Fernandez, T D; Cornejo-Garcia, J A; Mayorga, C; Torres, M J; Blanca, M

2008-05-01

beta-Lactam (BL) antibiotics can induce non-immediate skin reactions, frequently manifested as exanthema or urticaria. The time between drug intake and the reaction appearance is generally 24-48 h. Because the mechanisms involved are not completely understood, diagnostic tests for these reactions have still to be fully validated. To evaluate the role of skin and drug provocation tests (DPTs) in the diagnosis of patients with non-immediate reactions to BL. We evaluated a group of 22 patients who developed maculopapular exanthema or urticarial exanthema after BL intake. Diagnosis was confirmed by DPT with BL. Intradermal/patch testing was performed with benzylpenicilloyl, minor determinant mixture, amoxicillin (AX), ampicillin (AMP) and the culprit drug in patients and in 22 negative controls. Immunohistochemical studies were done in the affected skin at the acute phase of the reaction and after a delayed positive skin test/DPT. IFN-gamma and IL-4 were quantified in peripheral mononuclear cells, obtained during the positive response to DPT and after resolution of the symptoms. From the total number of cases, 12 patients developed urticarial exanthema and 10 maculopapular exanthema after DPT. Only two of the 22 patients (9%) had a positive delayed intradermal skin test: one to AX/AMP and the other to cloxacillin. Biopsies showed a mononuclear CD4, CD8 infiltrate and activated and memory cells. The cytokine expression showed a Th1 pattern in patients, in contrast with the Th0 pattern in controls. In patients with non-immediate reactions to BLs (maculopapular exathema or urticarial exanthema), the sensitivity of skin testing is low and DPT may be required to establish the diagnosis. The reproducibility of the reactions and the cytokine pattern expressed during the acute episode support a T cell-induced non-immediate response.

Systematic evaluation of non-animal test methods for skin sensitisation safety assessment.

PubMed

Reisinger, Kerstin; Hoffmann, Sebastian; Alépée, Nathalie; Ashikaga, Takao; Barroso, Joao; Elcombe, Cliff; Gellatly, Nicola; Galbiati, Valentina; Gibbs, Susan; Groux, Hervé; Hibatallah, Jalila; Keller, Donald; Kern, Petra; Klaric, Martina; Kolle, Susanne; Kuehnl, Jochen; Lambrechts, Nathalie; Lindstedt, Malin; Millet, Marion; Martinozzi-Teissier, Silvia; Natsch, Andreas; Petersohn, Dirk; Pike, Ian; Sakaguchi, Hitoshi; Schepky, Andreas; Tailhardat, Magalie; Templier, Marie; van Vliet, Erwin; Maxwell, Gavin

2015-02-01

The need for non-animal data to assess skin sensitisation properties of substances, especially cosmetics ingredients, has spawned the development of many in vitro methods. As it is widely believed that no single method can provide a solution, the Cosmetics Europe Skin Tolerance Task Force has defined a three-phase framework for the development of a non-animal testing strategy for skin sensitization potency prediction. The results of the first phase – systematic evaluation of 16 test methods – are presented here. This evaluation involved generation of data on a common set of ten substances in all methods and systematic collation of information including the level of standardisation, existing test data,potential for throughput, transferability and accessibility in cooperation with the test method developers.A workshop was held with the test method developers to review the outcome of this evaluation and to discuss the results. The evaluation informed the prioritisation of test methods for the next phase of the non-animal testing strategy development framework. Ultimately, the testing strategy – combined with bioavailability and skin metabolism data and exposure consideration – is envisaged to allow establishment of a data integration approach for skin sensitisation safety assessment of cosmetic ingredients.

Comparison of subject-reported allergy versus skin test results in a common cold trial.

PubMed

Krahnke, Jason S; Gentile, Deborah A; Cordoro, Kelly M; Angelini, Betty L; Cohen, Sheldon A; Doyle, William J; Skoner, David P

2003-01-01

Few studies have examined the relationship between subject-reported allergy and results of allergy skin testing in large unselected or unbiased cohorts. The objective of this study was to compare the results of self-reported allergy via verbal questioning with the results of allergy skin testing by the puncture method in 237 healthy adult subjects enrolled in a common cold study. On enrollment, all subjects were verbally asked if they had a history of allergy and then underwent puncture skin testing to 19 relevant aeroallergens, as well as appropriate positive and negative controls. A skin test was considered positive if its wheal diameter was at least 3 mm larger than that obtained with the negative control. Forty-eight (20%) subjects reported a history of allergy and 124 (52%) subjects had at least one positive skin test response. A history of allergy was reported in 40 (32%) of the skin test-positive subjects and 8 (7%) of the skin test-negative subjects. At least one positive skin test response was found in 40 (83%) of those subjects reporting a history of allergy and 84 (44%) of those subjects denying a history of allergy. These data indicate that there is a relatively poor correlation between self-reported history of allergy and skin test results in subjects enrolled in a common cold study. These results have implications in both clinical practice and research settings.

Parameters estimation for reactive transport: A way to test the validity of a reactive model

NASA Astrophysics Data System (ADS)

Aggarwal, Mohit; Cheikh Anta Ndiaye, Mame; Carrayrou, Jérôme

The chemical parameters used in reactive transport models are not known accurately due to the complexity and the heterogeneous conditions of a real domain. We will present an efficient algorithm in order to estimate the chemical parameters using Monte-Carlo method. Monte-Carlo methods are very robust for the optimisation of the highly non-linear mathematical model describing reactive transport. Reactive transport of tributyltin (TBT) through natural quartz sand at seven different pHs is taken as the test case. Our algorithm will be used to estimate the chemical parameters of the sorption of TBT onto the natural quartz sand. By testing and comparing three models of surface complexation, we show that the proposed adsorption model cannot explain the experimental data.

Skin testing only with penicillin G in children with a history of penicillin allergy.

PubMed

Picard, Matthieu; Paradis, Louis; Bégin, Philippe; Paradis, Jean; Des Roches, Anne

2014-07-01

The absence of commercially available penicilloyl-polylysine (PPL) for most of the last decade severely hampered the practice of penicillin allergy evaluation because skin testing without PPL is reported to have a poor negative predictive value (NPV). To determine the safety and NPV of skin testing without PPL using only penicillin G followed by a 3-dose graded challenge to the incriminated penicillin in children with a history of penicillin allergy. Patients evaluated for a history of penicillin allergy at the CHU Sainte-Justine Allergy Clinic between December 2006 and December 2009 were skin tested only with penicillin G and underwent a 3-dose graded challenge to the culprit penicillin if the skin test result was negative. Among 563 patients skin tested to penicillin G, 185 (33%) had a positive skin test result. These patients had a shorter interval between the initial reaction and skin testing compared with patients with a negative skin test result (P = .03). A total of 375 of 378 patients (99%) with a negative skin test result were challenged and 18 (4.8%) reacted, translating into a NPV of 95.2% (95% confidence interval [CI], 92.5%-97.1%). Three of 17 patients with a history of anaphylaxis and a negative skin test result reacted to challenge (NPV, 82.4%; 95% CI, 59.0-93.8%). All challenge reactions were mild and resolved promptly with treatment. Among children with a history of penicillin allergy, skin testing only with penicillin G followed by a 3-dose graded challenge to the incriminated penicillin is safe and yields a good NPV. This approach could be useful when PPL is unavailable. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The skin prick test – European standards

PubMed Central

2013-01-01

Skin prick testing is an essential test procedure to confirm sensitization in IgE-mediated allergic disease in subjects with rhinoconjunctivitis, asthma, urticaria, anapylaxis, atopic eczema and food and drug allergy. This manuscript reviews the available evidence including Medline and Embase searches, abstracts of international allergy meetings and position papers from the world allergy literature. The recommended method of prick testing includes the appropriate use of specific allergen extracts, positive and negative controls, interpretation of the tests after 15 – 20 minutes of application, with a positive result defined as a wheal ≥3 mm diameter. A standard prick test panel for Europe for inhalants is proposed and includes hazel (Corylus avellana), alder (Alnus incana), birch (Betula alba), plane (Platanus vulgaris), cypress (Cupressus sempervirens), grass mix (Poa pratensis, Dactilis glomerata, Lolium perenne, Phleum pratense, Festuca pratensis, Helictotrichon pretense), Olive (Olea europaea), mugwort (Artemisia vulgaris), ragweed (Ambrosia artemisiifolia), Alternaria alternata (tenuis), Cladosporium herbarum, Aspergillus fumigatus, Parietaria, cat, dog, Dermatophagoides pteronyssinus, Dermatophagoides farinae, and cockroach (Blatella germanica). Standardization of the skin test procedures and standard panels for different geographic locations are encouraged worldwide to permit better comparisons for diagnostic, clinical and research purposes. PMID:23369181

Comparison of human skin irritation patch test data with in vitro skin irritation assays and animal data.

PubMed

Jírová, Dagmar; Basketter, David; Liebsch, Manfred; Bendová, Hana; Kejlová, Kristina; Marriott, Marie; Kandárová, Helena

2010-02-01

Efforts to replace the rabbit skin irritation test have been underway for many years, encouraged by the EU Cosmetics Directive and REACH. Recently various in vitro tests have been developed, evaluated and validated. A key difficulty in confirming the validity of in vitro methods is that animal data are scarce and of limited utility for prediction of human effects, which adversely impacts their acceptance. This study examines whether in vivo or in vitro data most accurately predicted human effects. Using the 4-hr human patch test (HPT) we examined a number of chemicals whose EU classification of skin irritancy is known to be borderline, or where in vitro methods provided conflicting results. Of the 16 chemicals classified as irritants in the rabbit, only five substances were found to be significantly irritating to human skin. Concordance of the rabbit test with the 4-hr HPT was only 56%, whereas concordance of human epidermis models with human data was 76% (EpiDerm) and 70% (EPISKIN). The results confirm observations that rabbits overpredict skin effects in humans. Therefore, when validating in vitro methods, all available information, including human data, should be taken into account before making conclusions about their predictive capacity.

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

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

Harsh parenting and child externalizing behavior: skin conductance level reactivity as a moderator.

PubMed

Erath, Stephen A; El-Sheikh, Mona; Mark Cummings, E

2009-01-01

Skin conductance level reactivity (SCLR) was examined as a moderator of the association between harsh parenting and child externalizing behavior. Participants were 251 boys and girls (8-9 years). Mothers and fathers provided reports of harsh parenting and their children's externalizing behavior; children also provided reports of harsh parenting. SCLR was assessed in response to a socioemotional stress task and a problem-solving challenge task. Regression analyses revealed that the association between harsh parenting and externalizing behavior was stronger among children with lower SCLR, as compared to children with higher SCLR. SCLR may be a more robust moderator among boys compared to girls. Results are discussed with regard to theories on antisocial behavior and multiple-domain models of child development.

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.

Skin corrosion test: a comparison between reconstructed human epidermis and full thickness skin models.

PubMed

Catarino, Carolina Motter; do Nascimento Pedrosa, Tatiana; Pennacchi, Paula Comune; de Assis, Silvia Romano; Gimenes, Fabrícia; Consolaro, Márcia Edilaine Lopes; de Moraes Barros, Silvia Berlanga; Maria-Engler, Silvya Stuchi

2018-04-01

Currently, there is a strong global trend towards the development of in vitro models to replace the use of animals in safety evaluation tests. Reconstructed Human Epidermis (RHE) models have been employed as an alternative method to animal testing of skin corrosion and irritation potential of chemical compounds. However, the consequences of an absence of the dermal compartment in these models should be considered since the cross-talk between fibroblasts and keratinocytes is fundamental for promoting proper epidermal stratification, homeostasis, inflammatory response and wound healing. In this study, we compare in-house developed models of Reconstructed Human Epidermis (i.e. USP-RHE) and full thickness skin (i.e. USP-FTS) regarding their response when submitted to skin corrosion assays, based on Guideline 431 (OECD). The results show that both models correctly classified the four substances tested (2-phenylethyl bromide, benzylacetone, lactic acid, octanoic acid) as corrosive or non-corrosive. Furthermore, we have demonstrated higher cell viability of the USP-FTS model compared to the USP-RHE model, a sign of its improved barrier function, following the exposure to the substances test on the corrosion assay. This emphasizes the importance of employing in vitro models that are more physiologically relevant and that better mimic the in vivo situation for the toxicological screening of substances. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of action levels for MED/MPD skin-testing units in ultraviolet phototherapy

NASA Astrophysics Data System (ADS)

O'Connor, Una M.; O'Hare, Neil J.

2003-03-01

Ultraviolet (UV) Phototherapy is commonly used for treatment of skin diseases such as psoriasis and eczema. Treatment is carried out using UV phototherapy units, exposing all or part of the body for a certain exposure time. Prior to exposure in treatment units, an unaffected area of skin may be tested using UV skin-testing units in order to determine a suitable treatment regime. The exposure time at which barely perceptible erythema has developed is known as the Minimal Erythemal Dose (MED) for UVB therapy and Minimal Phototoxic Dose (MPD) for UVA therapy. This is used to determine the starting dose in the treatment regime. The presence of 'hotspots' and 'coldspots' in UV skin-testing units can result in inaccurate determination of MED/MPD. This could give rise to severe burns during treatment, or in a sub-optimal dose regime being used. Quality assurance protocols for UV phototherapy equipment have recently been developed and these protocols have highlighted the need for action levels for skin-testing units. An action level is a reference value, which is used to determine whether the difference in irradiance output level across a UV unit is acceptable. Current methodologies for skin-testing in Ireland have been characterised and errors introduced during testing have been estimated. Action levels have been developed based on analysis of errors and requirements of skin-testing.

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.

Immediate Wheal Reactivity to Autologous Sweat in Atopic Dermatitis Is Associated with Clinical Severity, Serum Total and Specific IgE and Sweat Tryptase Activity.

PubMed

Ilves, Tiina; Virolainen, Anu; Harvima, Ilkka Tapani

2016-01-01

Sweating can worsen atopic dermatitis (AD). The purpose of this work was to study the associations between reactivity to autologous sweat and the clinical severity of AD as well as investigate the possible wheal-inducing factors of sweat. Intracutaneous skin tests with autologous sweat were performed on 50 AD patients and 24 control subjects. In skin biopsies, tryptase and PAR-2 were enzyme and immunohistochemically stained. The associations between skin test reactivity and sweat histamine concentration, tryptase or chymase activity levels, tryptase or PAR-2 expression and AD clinical severity or IgE levels were investigated. The wheal reactions in the intracutaneous tests with autologous sweat were positive, weakly positive and negative in 38, 34 and 28% of the AD patients, respectively, and in 4, 46 and 50% of the healthy controls, respectively (p = 0.008). In AD, the wheal reaction was associated significantly with clinical severity, serum total and specific IgE levels and sweat tryptase activity, but not with sweat histamine and chymase. In nonlesional AD skin, the percentage of PAR-2+ mast cells (MCs) or the number of tryptase+ MCs did not differ significantly between the intracutaneous test reactivity groups. Reactivity to autologous sweat correlates with the clinical severity of AD, and tryptase may be one of the factors involved in the sweat-induced wheal. © 2016 S. Karger AG, Basel.

Postocclusive reactive hyperemia in hand-arm vibration syndrome.

PubMed

Stoyneva, Zlatka

2016-01-01

To assess laser Doppler-recorded postocclusive reactive hyperemic responses in vibration-induced Raynaud's phenomenon and compare it with primary and secondary to sclerodermy Raynaud's phenomenon. Thirty patients with vibration-induced Raynaud's phenomenon and 30 healthy controls and patients with primary and secondary to sclerodermy Raynaud's phenomenon were investigated. Fingerpulp skin blood flow was monitored by laser Doppler flowmetry during postocclusive reactive hyperemia test. Lower initial perfusion values were established in all the patients with Raynaud's phenomenon compared to the healthy controls (p < 0.0001). The postocclusive reactive hyperemic peak was lower in all the Raynaud's phenomenon groups compared to the controls (p < 0.0001). The postocclusive and basal perfusions were lower in the secondary Raynaud's phenomenon groups compared to the control and the primary Raynaud's phenomenon groups (p < 0.0001). The velocities to postocclusive hyperemic peak were lower in all the Raynaud's phenomenon patients (p < 0.0001), so were in the vibration-induced (p < 0.002) and the sclerodermy Raynaud's phenomenon (p < 0.004) groups in relation to the primary Raynaud's phenomenon group. The perfusion values and the velocities were significantly influenced by the initial superficial skin temperatures and perfusions, while the velocities were dependent also on gender, and the hyperemic peak on age. Postocclusive reactive hyperemia is abnormal in all Raynaud's phenomenon patients. Laser Doppler-recorded reactive hyperemia test contributes to diagnosing Raynaud's phenomenon and has proved to be valuable for group analysis. The applied method is not sensitive enough to discriminate adequately the type of Raynaud's phenomenon among individual cases. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Correcting for possible tissue distortion between provocation and assessment in skin testing: the divergent beam UVB photo-test.

PubMed

O'Doherty, Jim; Henricson, Joakim; Falk, Magnus; Anderson, Chris D

2013-11-01

In tissue viability imaging (TiVi), an assessment method for skin erythema, correct orientation of skin position from provocation to assessment optimizes data interpretation. Image processing algorithms could compensate for the effects of skin translation, torsion and rotation realigning assessment images to the position of the skin at provocation. A reference image of a divergent, UVB phototest was acquired, as well as test images at varying levels of translation, rotation and torsion. Using 12 skin markers, an algorithm was applied to restore the distorted test images to the reference image. The algorithm corrected torsion and rotation up to approximately 35 degrees. The radius of the erythemal reaction and average value of the input image closely matched that of the reference image's 'true value'. The image 'de-warping' procedure improves the robustness of the response image evaluation in a clinical research setting and opens the possibility of the correction of possibly flawed images performed away from the laboratory setting by the subject/patient themselves. This opportunity may increase the use of photo-testing and, by extension, other late response skin testing where the necessity of a return assessment visit is a disincentive to performance of the test. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

New strategy to improve quality control of Montenegro skin test at the production level.

PubMed

Guedes, Deborah Carbonera; Minozzo, João Carlos; Pasquali, Aline Kuhn Sbruzzi; Faulds, Craig; Soccol, Carlos Ricardo; Thomaz-Soccol, Vanete

2017-01-01

The production of the Montenegro antigen for skin test poses difficulties regarding quality control. Here, we propose that certain animal models reproducing a similar immune response to humans may be used in the quality control of Montenegro antigen production. Fifteen Cavia porcellus (guinea pigs) were immunized with Leishmania amazonensis or Leishmania braziliensis , and, after 30 days, they were skin tested with standard Montenegro antigen. To validate C. porcellus as an animal model for skin tests, eighteen Mesocricetus auratus (hamsters) were infected with L. amazonensis or L. braziliensis , and, after 45 days, they were skin tested with standard Montenegro antigen. Cavia porcellus immunized with L. amazonensis or L. braziliensis , and hamsters infected with the same species presented induration reactions when skin tested with standard Montenegro antigen 48-72h after the test. The comparison between immunization methods and immune response from the two animal species validated C. porcellus as a good model for Montenegro skin test, and the model showed strong potential as an in vivo model in the quality control of the production of Montenegro antigen.

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.

Diagnostic performance of the "MESACUP anti-Skin profile TEST".

PubMed

Horváth, Orsolya N; Varga, Rita; Kaneda, Makoto; Schmidt, Enno; Ruzicka, Thomas; Sárdy, Miklós

2016-01-01

The "MESACUP anti-Skin profile TEST" is a new, commercially available ELISA kit to detect circulating IgG autoantibodies against desmoglein 1, desmoglein 3, BP180, BP230, and type VII collagen, both simultaneously and more rapidly than previous assays. The aim of this study was to evaluate the diagnostic accuracy of this kit for the diagnosis of pemphigus foliaceus, pemphigus vulgaris, bullous pemphigoid and epidermolysis bullosa acquisita. Dual-centre retrospective study in which 138 patients with autoimmune blistering diseases were compared to 40 controls Using the MESACUP anti-Skin profile TEST, both sensitivities and specificities for desmoglein 1, desmoglein 3, BP180, BP230, and type VII collagen autoantibodies were similar to those obtained using previous, specific ELISA systems and 88% of the results were concordant without any significant difference. The MESACUP anti-Skin profile TEST had a similar performance to previously produced ELISA systems. The novel kit can be used for rapid diagnosis of most common autoimmune blistering diseases and is especially suitable for identifying overlapping disorders.

Autonomic stress reactivity and craving in individuals with problematic Internet use.

PubMed

Moretta, Tania; Buodo, Giulia

2018-01-01

The link between autonomic stress reactivity and subjective urge/craving has been less systematically examined in behavioral addictions (i.e. problematic Internet use) than in substance use disorders. The present study investigated whether problematic Internet users (PU) show enhanced autonomic stress reactivity than non-PU, indexed by lower Heart Rate Variability (HRV) and higher Skin Conductance Level (SCL) reactivity during the Trier Social Stress Test (TSST), whether greater reactivity is related to stronger Internet craving, and whether problematic Internet usage is associated with some dysfunctional psychological features. Based on their Internet Addiction Test scores, participants were divided into PU (N = 24) and non-PU (N = 21). Their heart rate and skin conductance were continuously recorded during baseline, social stressors, and recovery. Craving for Internet usage were collected using a Likert scale before and after the TSST. The SDNN, an overall measure of HRV, was significantly lower in PU than non-PU during baseline, but not during and after stressful task. Furthermore, only among PU a significant negative correlation emerged between SDNN during recovery and craving ratings after the test. No group differences emerged for SCL. Lastly, PU endorsed more mood, obsessive-compulsive, and alcohol-related problems. Our findings suggest that problems in controlling one's use of the Internet may be related to reduced autonomic balance at rest. Moreover, our results provide new insights into the characterization of craving in PIU, indicating the existence of a relationship between craving for Internet usage and reduced autonomic flexibility.

Penicillin skin testing is a safe and effective tool for evaluating penicillin allergy in the pediatric population.

PubMed

Fox, Stephanie J; Park, Miguel A

2014-01-01

Penicillin skin testing has been validated in the evaluation of adult patients with penicillin allergy. However, the commercially available benzylpenicilloyl polylysine (Pre-Pen) is not indicated in the pediatric population. Moreover, the safety and validity of penicillin skin testing in the pediatric population has not been well studied. We describe the safety and validity of penicillin skin testing in the evaluation of children with a history of penicillin allergy. Children (<18 years) with a history of penicillin allergy were evaluated with penicillin skin tests and were reviewed for basic demographics, penicillin skin test results, adverse drug reaction to penicillin after penicillin skin test, and adverse reaction to penicillin skin test. By using the χ(2) test, we compared the differences in the proportion of children and adults with a positive penicillin skin test. P value (<.05) was considered statistically significant. The institutional review board approved the study, and all the subjects signed written informed consents. A total of 778 children underwent penicillin skin testing; 703 of 778 patients had a negative penicillin skin test (90.4%), 66 had a positive test (8.5%), and 9 had an equivocal test (1.1%). Children were more likely to have a positive penicillin skin test (P < .0001) compared with adults (64 of 1759 [3.6%]); 369 of 703 patients with negative penicillin skin test (52%) were challenged with penicillin, and 14 of 369 patients (3.8%) had an adverse drug reaction. No adverse reactions to penicillin skin testing were observed. Penicillin skin testing was safe and effective in the evaluation of children with a history of penicillin allergy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

CAT SCRATCH DISEASE: RESULTS OF COMPLEMENT-FIXATION AND SKIN TESTS

DTIC Science & Technology

Serologic and skin-testing data on a group of patients having cat scratch disease are presented to demonstrate a possible relationship to the psitt...indicate that the incidence of positive serologic reactions with the psitt-LGV group antigen is consistently higher in patients with cat scratch disease...patients, 2 of 5 did not respond with positive skin reactions when tested with cat scratch antigen, and at least 2 of the remaining 3 responded in a manner difficult to interpret.

[The tuberculin skin test in BCG-vaccinated individualse].

PubMed

Miret Cuadras, P; Pina Gutiérrez, J M

1998-10-01

The aim of this study was to evaluate the tuberculin skin test in individuals vaccinated with bacillus Calmette-Guérin (BCG) using 2 IU of RT-23. One hundred ninety-six individuals aged 22-40 years-old who had been vaccinated with BCG between 1965 and 1974 were enrolled along with 375 non-vaccinated individuals of the same age and with similar level of risk of infection. The positive predictive value of the test was assessed for three levels of response as indicated by areas of thickening in three diameters: 5, 10 and 15 mm. Vaccinated individuals with negative results were given a second skin test 7 days later to detect a booster effect. Positive diameters 5 mm were observed in 66% of the vaccinated individuals and 24% of the non-vaccinated subjects. Positive diameters 10 mm were observed in 51% of the vaccinated individuals and 19% of the non vaccinated ones. Positive diameters 15 mm were observed in 29% of the vaccinated subjects and in 13% of the non vaccinated ones. The differences were significant for all diameters. The positive predictive value of the test was 36.4% for a diameter 5 mm, 37.6% for diameter 10 mm and 44.8% for diameter 15 mm. The booster effect was detected in 25.8% of the vaccinated individuals who had tested negative at first. In vaccinated individuals, no guidelines can be established to guarantee that a positive reaction is due to infection by Mycobacterium tuberculosis infection, although the likelihood of infection (increased positive predictive value) increases with diameter. It is also impossible to fix a time limit. A second skin test is needed to detect a booster effect in all vaccinated individuals whose first test is negative.

Factors influencing and modifying the decision to pursue genetic testing for skin cancer risk.

PubMed

Fogel, Alexander L; Jaju, Prajakta D; Li, Shufeng; Halpern-Felsher, Bonnie; Tang, Jean Y; Sarin, Kavita Y

2017-05-01

Across cancers, the decision to pursue genetic testing is influenced more by subjective than objective factors. However, skin cancer, which is more prevalent, visual, and multifactorial than many other malignancies, may offer different motivations for pursuing such testing. The primary objective was to determine factors influencing the decision to receive genetic testing for skin cancer risk. A secondary objective was to assess the impact of priming with health questions on the decision to receive testing. We distributed anonymous online surveys through ResearchMatch.org to assess participant health, demographics, motivations, and interest in pursuing genetic testing for skin cancer risk. Two surveys with identical questions but different question ordering were used to assess the secondary objective. We received 3783 responses (64% response rate), and 85.8% desired testing. Subjective factors, including curiosity, perceptions of skin cancer, and anxiety, were the most statistically significant determinants of the decision to pursue testing (P < .001), followed by history of sun exposure (odds ratio 1.85, P < .01) and history of skin cancer (odds ratio 0.5, P = .01). Age and family history of skin cancer did not influence this decision. Participants increasingly chose testing if first queried about health behaviors (P < .0001). The decision to pursue hypothetical testing may differ from in-clinic decision-making. Self-selected, online participants may differ from the general population. Surveys may be subject to response bias. The decision to pursue genetic testing for skin cancer is primarily determined by subjective factors, such as anxiety and curiosity. Health factors, including skin cancer history, also influenced decision-making. Priming with consideration of objective health factors can increase the desire to pursue testing. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Skin testing and oral penicillin challenge in patients with a history of remote penicillin allergy.

PubMed

Goldberg, Arnon; Confino-Cohen, Ronit

2008-01-01

Penicillin administration is usually contraindicated in penicillin-allergic patients with positive skin test results. To examine whether penicillin oral challenge for patients with a history of remote non-life-threatening allergic reaction to penicillin can be well tolerated irrespective of skin test results. In a prospective open-label trial, 8,702 individuals were screened between November 1998 and January 2000. Of 687 patients with a non-life-threatening allergic reaction to penicillin, occurring longer than 3 years earlier, 169 were enrolled. Regardless of the response to penicillin skin testing, patients received the usual 1-day dosage of penicillin and amoxicillin, on 2 separate occasions. Two to 6 years later, a follow-up was conducted to assess the outcomes of further penicillin administration. A total of 272 combined skin tests and oral challenges were performed on 169 patients. Among 137 challenges with a positive skin test result and 135 patients with a negative skin test result, 9 (6.6%) and 5 (3.7%) (P = .29), respectively, developed a mild rash to oral challenge. At follow-up, 2 to 6 years afterward, 3 of 55 patients (5.5%) who were given a full treatment course of penicillin developed a mild skin eruption. Positive penicillin skin test results for patients with a remote history of non-life-threatening allergic reaction to penicillin were not associated with a greater prevalence of adverse reactions to oral challenge with penicillin than negative results. Because skin testing is considered the gold standard and the safest method for predicting tolerance to penicillin administration, oral penicillin challenge may be used as a diagnostic method only in these specific patients when skin testing is not feasible.

Functional testing of topical skin formulations using an optimised ex vivo skin organ culture model.

PubMed

Sidgwick, G P; McGeorge, D; Bayat, A

2016-07-01

A number of equivalent-skin models are available for investigation of the ex vivo effect of topical application of drugs and cosmaceuticals onto skin, however many have their drawbacks. With the March 2013 ban on animal models for cosmetic testing of products or ingredients for sale in the EU, their utility for testing toxicity and effect on skin becomes more relevant. The aim of this study was to demonstrate proof of principle that altered expression of key gene and protein markers could be quantified in an optimised whole tissue biopsy culture model. Topical formulations containing green tea catechins (GTC) were investigated in a skin biopsy culture model (n = 11). Punch biopsies were harvested at 3, 7 and 10 days, and analysed using qRT-PCR, histology and HPLC to determine gene and protein expression, and transdermal delivery of compounds of interest. Reduced gene expression of α-SMA, fibronectin, mast cell tryptase, mast cell chymase, TGF-β1, CTGF and PAI-1 was observed after 7 and 10 days compared with treated controls (p < 0.05). Histological analysis indicated a reduction in mast cell tryptase and chymase positive cell numbers in treated biopsies compared with untreated controls at day 7 and day 10 (p < 0.05). Determination of transdermal uptake indicated that GTCs were detected in the biopsies. This model could be adapted to study a range of different topical formulations in both normal and diseased skin, negating the requirement for animal models in this context, prior to study in a clinical trial environment.

Anaphylaxis during skin testing with food allergens in children.

PubMed

Pitsios, Constantinos; Dimitriou, Anastasia; Stefanaki, Efthalia C; Kontou-Fili, Kalliopi

2010-05-01

Skin testing is the diagnostic cornerstone for allergies and is considered extremely safe. It is usually performed with the prick and the prick-to-prick method. The aim of this study is to report the first two pediatric cases of systemic allergic reactions during skin prick tests (SPT) with commercial food allergens. Both patients had a history of fish allergy. A 5-year-old girl, with a history of atopic dermatitis and asthma, reported an episode of urticaria and angioedema due to ingestion of fish, which had occurred 2 years before consultation. Ten minutes after having completed SPT to fish extracts, which had resulted positive, she suffered from generalized pruritus, nausea, stomach pain, and loss of consciousness. A 9-year-old boy, with a history of asthma and two episodes of acute urticaria and angioedema upon eating fish during infancy, reported a recent episode of oropharyngeal pruritus after tasting salmon. He was evaluated for fish allergy with SPT but developed conjunctivitis and acute urticaria during the first 10 min of the test. Anaphylaxis appears to be a rare side effect of skin testing in pediatric patients. Children with a history of asthma and atopic dermatitis are more likely to react.

Skin testing of guinea pigs and footpad testing of mice with a new antigen for detecting delayed hypersensitivity to Cryptococcus neoformans.

PubMed

Murphy, J W; Gregory, J A; Larsh, H W

1974-02-01

This study was undertaken to evaluate the potential of a cryptococcal culture filtrate antigen, cryptococcin C184, for detecting delayed hypersensitivity in Cryptococcus neoformans-injected animals. The antigen was tested on guinea pigs which had received saline or C. neoformans and on animals sensitized to Histoplasma capsulatum, Blastomyces dermatitidis, Candida albicans, or Sporothrix schenckii. A delayed-type hypersensitivity response was elicited by cryptococcin C184 in C. neoformans-injected guinea pigs, whereas no indurations or erythemas were seen at 48 h after skin testing of saline controls or heterologously sensitized guinea pigs. Besides being specific for Cryptococcus, the antigen showed a high degree of sensitivity and was reproducible. Footpad tests were conducted with the antigen on mice which had previously received either 10(5) viable C. neoformans cells or saline. Delayed hypersensitivity was indicated in the C. neoformans-injected mice by the increase in thickness of antigen-injected footpads when compared with the saline-injected footpads. In control mice, antigen- and saline-injected footpads were comparable in thickness 24 h after injection. Mice sensitized to B. dermatitidis were footpad tested with C184, and no cross-reactivity was demonstrated.

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs.

PubMed

Sachs, B; Al Masaoudi, T; Merk, H F; Erdmann, S

2004-10-01

Amino-penicillins are a major cause of delayed-type reactions to penicillins. The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.

Testing of Raman spectroscopy method for assessment of skin implants

NASA Astrophysics Data System (ADS)

Timchenko, E. V.; Timchenko, P. E.; Volova, L. T.; Pershutkina, S. V.; Shalkovskaya, P. Y.

2016-11-01

Results of studies of testing of Raman spectroscopy (RS) method for assessment of skin implants are presented. As objects of study were used samples of rat's skin material. The main spectral differences of implants using various types of their processing appear at wavenumbers 1062 cm-1, 1645 cm-1, 1553 cm-1, 851 cm-1, 863 cm-1, 814 cm-1 and 1410 cm-1. Optical coefficients for assessment of skin implants were introduced. The research results are confirmed by morphological analysis.

Utility and limitations of a peptide reactivity assay to predict fragrance allergens in vitro.

PubMed

Natsch, A; Gfeller, H; Rothaupt, M; Ellis, G

2007-10-01

A key step in the skin sensitization process is the formation of a covalent adduct between the skin sensitizer and endogenous proteins and/or peptides in the skin. A published peptide depletion assay was used to relate the in vitro reactivity of fragrance molecules to LLNA data. Using the classical assay, 22 of 28 tested moderate to strong sensitizers were positive. The prediction of weak sensitizers proved to be more difficult with only 50% of weak sensitizers giving a positive response, but for some compounds this could also be due to false-positive results from the LLNA. LC-MS analysis yielded the expected mass of the peptide adducts in several cases, whereas in other cases putative oxidation reactions led to adducts of unexpected molecular weight. Several moderately sensitizing aldehydes were correctly predicted by the depletion assay, but no adducts were found and the depletion appears to be due to an oxidation of the parent peptide catalyzed by the test compound. Finally, alternative test peptides derived from a physiological reactive protein with enhanced sensitivity for weak Michael acceptors were found, further increasing the sensitivity of the assay.

An overview about oxidation in clinical practice of skin aging*

PubMed Central

Silva, Silas Arandas Monteiro e; Michniak-Kohn, Bozena; Leonardi, Gislaine Ricci

2017-01-01

Free radicals are unstable chemical species, highly reactive, being formed by cellular entities of different tissues. Increased production of these species without proper effective action of endogenous and exogenous antioxidant systems, generates a condition of oxidative stress, potentially provider of skin disorders that extend from functional impairments (skin cancer, dermatitis, chronic and acute inflammatory processes) even aesthetic character, with the destruction of structural proteins and cellular changes with the appearance of stains, marks and lines of expressions and other signs inherent to the intrinsic and extrinsic skin aging process. The antioxidants are chemical substances commonly used in clinical practice for topical application and may contribute in the fight against the radical species responsible for many skin damage. This paper summarized the main evidence of the benefits brought by the topical application of antioxidants in the skin, considering the amplitude of the indicative performance of antioxidant activity by in vitro and ex-vivo tests as well as in vivo tests. It is recognized that a breadth of product performance tests should be explored to truly identify the effectiveness of antioxidant products for an anti-aging effect. PMID:29186250

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.

584 Frequency of Autoreactivity Demonstrated by Autologous Serum Skin Test in Patients with Chronic Urticaria in the Valley of Mexico During a Period of 8 Years

PubMed Central

Rojo Gutiérrez, María Isabel; Mellado-Abrego, Jaime; Gonzalez-Ibarra, Misael; Sandoval, Teresa; Bermejo, Mario-Alberto

2012-01-01

Background Urticaria is a skin disease characterized by rapid emergence of hives, accompanied or not with angioedema. Usually lasts less than 24 hours. Approximately 12 to 24 per cent of the population will have hives or angioedema at least once in their life. Some patients with chronic urticaria has been classified as autoimmune. The autologous serum skin test (ASST) has been used to show pro-inflammatory circulating endogenous factors and it is regarded as a test for autorreactividad. The autorreactividad does not define an autoimmune urticaria, but may be an indicator of the presence of auto- reactive antibodies with the capacity of to activate the mast cells however functional antibodies need to be confirmed through of release of basophils histamine test from basophils (BHRA) and its specificity immunoassay (Western Blot or ELISA)-confirmed. Objective: to evaluate the auto-reactivity by autologous serum skin test in patients with chronic urticaria idiopathic in a study of 8 years. Material and methods: we made 216 ASST and autologous plasma skin test (APST) in patients with chronic urticaria without specific cause identified, of any age, during the period of 2003 to 2011. Results Thirty five thousand patients were evaluated only 261 patients not identified the cause (0.6%) and we realized ASST, of these 190 (88%) were negative, and 26 (12%) were positive, 20 (76.9 %) were female and 6 (23.1%) male, the median of age for women was 30 years ago with medium of 28 and men average 29 years and median 20. Of the 26 patients one was positive for anti-thyroglobulin senior titles (1: 170) .dos with positive anti unclears and one with pANCA and cANCA positive of a total of 216 patients, 156 (72.2) had APST and 60 (27.8%) were positive, 46 (76.6%) women and 14 (23.3 %) men. Mc Neman concordance between tests P < 0.0001 and Kappa index gives us a highly significant concordance P < 0.0001. The correlation between ASST and APST by Sperman was high significance value of P < 0

Relationships between skin test, specific IgE and levels of cytokines in patients with penicillin allergy.

PubMed

Qiao, H-L; Liu, J-H; Yang, J; Dong, Z-M

2005-08-01

The aim of this study was to investigate the relationships between skin test, specific immunoglobulin (Ig) E and cytokines in penicillin allergy. We collected the sera of 259 patients with historical positive skin test to penicillins, with immediate positive skin test and with a negative skin test results. The positive rate of specific IgE antibodies in 259 patients was 62.2% (161) by using radioallergosorbent test (RAST). Of the eight kinds of antigenic determinants, the positive rates of specific IgE to major and minor determinants were 43.63% (113) and 52.51% (136), respectively (p < 0.05). In 122 patients with immediate positive skin test, when the degrees of skin test were +, 2+, 3+ and 4+, the positive rates of specific IgE were 45.7, 57.1, 85.2 and 100%, respectively. The levels of interleukin (IL)-4, IL-13 and interferon (IFN)-gamma in the sera of patients with positive skin test were significantly increased with the degree of positive skin test (p < 0.05). The combined use of major and minor determinants in RAST offers the better test for the detection of penicillin-specific IgE antibodies. IL-4, IL-13 and IFN-gamma play important roles in penicillin allergy.

Sporotrichin Skin Test for the Diagnosis of Sporotrichosis.

PubMed

Bonifaz, Alexandro; Toriello, Conchita; Araiza, Javier; Ramírez-Soto, Max C; Tirado-Sánchez, Andrés

2018-05-09

Sporotrichosis is the most common implantation mycosis caused by several species of the Sporothrix schenckii complex. The gold standard for diagnosis is concerned with the isolation of the fungus; although, fresh examinations, staining, and biopsies are also helpful for this purpose. The sporotrichin is an antigenic complex comprised of a peptide-rhamnomannan, which is relevant with respect to pathogenic fungi; it is primarily used for serological and skin testing. We present a study regarding the use of sporotrichin as a diagnostic aid for cutaneous sporotrichosis. Furthermore, 138 cases with suspicion of sporotrichosis were included, 55 of which were proven through cultures. Moreover, out of these 55 cases, 52 (94.5%) tested positive for sporotrichin, while the negative cases corresponded to the disseminated cutaneous forms. We observed a sensitivity of 94.5% and a specificity of 95.2%. We consider that the use of sporotrichin as a skin test helps us as an auxiliary diagnosis before a positive sample culture.

Ethanol extract of Dalbergia odorifera protects skin keratinocytes against ultraviolet B-induced photoaging by suppressing production of reactive oxygen species.

PubMed

Ham, Sun Ah; Hwang, Jung Seok; Kang, Eun Sil; Yoo, Taesik; Lim, Hyun Ho; Lee, Won Jin; Paek, Kyung Shin; Seo, Han Geuk

2015-01-01

Dalbergia odorifera T. Chen (Leguminosae), an indigenous medicinal herb, has been widely used in northern and eastern Asia to treat diverse diseases. Here, we investigated the anti-senescent effects of ethanolic extracts of Dalbergia odorifera (EEDO) in ultraviolet (UV) B-irradiated skin cells. EEDO significantly inhibited UVB-induced senescence of human keratinocytes in a concentration-dependent manner, concomitant with inhibition of reactive oxygen species (ROS) generation. UVB-induced increases in the levels of p53 and p21, biomarkers of cellular senescence, were almost completely abolished in the presence of EEDO. Sativanone, a major constituent of EEDO, also attenuated UVB-induced senescence and ROS generation in keratinocytes, indicating that sativanone is an indexing (marker) molecule for the anti-senescence properties of EEDO. Finally, treatment of EEDO to mice exposed to UVB significantly reduced ROS levels and the number of senescent cells in the skin. Thus, EEDO confers resistance to UVB-induced cellular senescence by inhibiting ROS generation in skin cells.

[Practice patterns in Mexican allergologists about skin tests with allergens during 2005-2006].

PubMed

Larenas Linnemann, Désirée; Fogelbach, Guillermo Arturo Guidos; Cruz, Alfredo Arias

2008-01-01

Immunotherapy has been practiced since over a hundred years. The exact composition of the immunotherapy concentrate, with which the patient is treated, depends partly on the results of the skin prick tests applied to the allergic patient. As such, the effectiveness of the immunotherapy depends heavily on the quality of the skin prick test. The detailed recommendations for the realization of the skin prick tests have evolved and changed over the years, leading to multiple variations in its application in Mexico. We tried to get a picture of the daily practice patterns of the members of CMICA and CoMPedIA concerning the application of skin prick tests. Aquestionnaire was sent in various occasions to all members of the Colegio Mexicano de Inmunologia Clinica y Alergia (CMICA) and of the Colegio Mexicano de Pediatras, Especialistas en Inmunologia y Alergia (CoMPedIA). The results are presented descriptively and by calculation of the frequency/percentages of intervals of replies, in the case of numerical responses. A response rate of 61 (17%) was obtained of the College members, showing consistency in some replies but a wide variation in others, for example in the time certain medication has to be suspended before the execution of the skin prick test. Comparing the replies obtained with recent recommendations in international publications, some discrepancy can be detected. In some aspects of the survey there is coincidence of the skin test practices among the participants; however, in other items there is an important variation.

An approach for development of alternative test methods based on mechanisms of skin irritation.

PubMed

Osborne, R; Perkins, M A

1994-02-01

Recent advances in techniques for culture of human skin cells have led to their potential for use as in vitro models for skin irritation testing to augment or replace existing rabbit skin patch tests. Our work is directed towards the development of cultured human skin cells, together with endpoints that can be linked to in vivo mechanisms of skin irritation, as in vitro models for prediction of human skin irritation, and for study of mechanisms of contact irritant dermatitis. Three types of commercial human skin cell cultures have been evaluated, epidermal keratinocytes and partially or fully cornified keratinocyte-dermal fibroblast co-cultures. Human epidermal keratinocyte cultures (Clonetics) were treated with product ingredients and formulations, and the extent of cell damage was assessed by incorporation of the vital dye neutral red. Cell damage correlated with human skin patch data for ingredient chemicals with the exception of acids and alkalis, but did not correlate with skin irritation to surfactant-containing product formulations. Cultures of human skin equivalents were evaluated as potential models for measurement of responses to test materials that could not be measured in the keratinocyte/neutral red assay. We developed a battery of in vitro endpoints to measure responses to prototype ingredients and formulations in human epidermal keratinocyte-dermal fibroblast co-cultures grown on a nylon mesh ('Skin2' from Advanced Tissue Sciences) or on a collagen gel ('Testskin' from Organogenesis). The endpoints measure cytotoxicity (neutral red and MTT vital dye staining, lactate dehydrogenase and N-acetyl glucosaminidase release, glucose utilization) and inflammatory mediator (prostaglandin E2) release. Initial experiments indicate a promising correlation between responses of the Skin2 model to prototype surfactants and in vivo human skin irritation. The responses of Testskin cultures to acids and alkalis help to prove the concept that a topical application

Healing rate and autoimmune safety of full-thickness wounds treated with fish skin acellular dermal matrix versus porcine small-intestine submucosa: a noninferiority study.

PubMed

Baldursson, Baldur Tumi; Kjartansson, Hilmar; Konrádsdóttir, Fífa; Gudnason, Palmar; Sigurjonsson, Gudmundur F; Lund, Sigrún Helga

2015-03-01

A novel product, the fish skin acellular dermal matrix (ADM) has recently been introduced into the family of biological materials for the treatment of wounds. Hitherto, these products have been produced from the organs of livestock. A noninferiority test was used to compare the effect of fish skin ADM against porcine small-intestine submucosa extracellular matrix in the healing of 162 full-thickness 4-mm wounds on the forearm of 81 volunteers. The fish skin product was noninferior at the primary end point, healing at 28 days. Furthermore, the wounds treated with fish skin acellular matrix healed significantly faster. These results might give the fish skin ADM an advantage because of its environmental neutrality when compared with livestock-derived products. The study results on these acute full-thickness wounds might apply for diabetic foot ulcers and other chronic full-thickness wounds, and the shorter healing time for the fish skin-treated group could influence treatment decisions. To test the autoimmune reactivity of the fish skin, the participants were tested with the following ELISA (enzyme-linked immunosorbent assay) tests: RF, ANA, ENA, anti ds-DNA, ANCA, anti-CCP, and anticollagen I and II. These showed no reactivity. The results demonstrate the claims of safety and efficacy of fish skin ADM for wound care. © The Author(s) 2015.

Validation of artificial skin equivalents as in vitro testing systems

NASA Astrophysics Data System (ADS)

Schmitt, Robert; Marx, Ulrich; Walles, Heike; Schober, Lena

2011-03-01

With the increasing complexity of the chemical composition of pharmaceuticals, cosmetics and everyday substances, the awareness of potential health issues and long term damages for humanoid organs is shifting into focus. Artificial in vitro testing systems play an important role in providing reliable test conditions and replacing precarious animal testing. Especially artificial skin equivalents ASEs are used for a broad spectrum of studies like penetration, irritation and corrosion of substances. One major challenge in tissue engineering is the qualification of each individual ASE as in vitro testing system. Due to biological fluctuations, the stratum corneum hornified layer of some ASEs may not fully develop or other defects might occur. For monitoring these effects we developed an fully automated Optical Coherence Tomography device. Here, we present different methods to characterize and evaluate the quality of the ASEs based on image and data processing of OCT B-scans. By analysing the surface structure, defects, like cuts or tears, are detectable. A further indicator for the quality of the ASE is the morphology of the tissue. This allows to determine if the skin model has reached the final growth state. We found, that OCT is a well suited technology for automatically characterizing artificial skin equivalents and validating the application as testing system.

'Wanting' and 'liking' skin picking: A validation of the Skin Picking Reward Scale.

PubMed

Snorrason, Ivar; Olafsson, Ragnar P; Houghton, David C; Woods, Douglas W; Lee, Han-Joo

2015-12-01

Excoriation (skin-picking) disorder (SPD) is often conceptualized as a behavioral addiction in which aberrant reward processing may play an important role. The current study sought to develop a self-report instrument--the Skin Picking Reward Scale (SPRS)--that measures how strongly skin picking is 'liked' (i.e., the degree of pleasurable feelings while receiving the reward) and 'wanted' (i.e., the degree of the motivation to seek the reward). We administered the SPRS to individuals who endorsed excessive skin picking in online surveys and examined the scale's factor structure (Studies 1 and 2). We then asked individuals with documented pathological skin picking to complete the SPRS and other relevant questionnaires on two occasions one week apart (Study 3). Exploratory (Study 1; n = 330) and confirmatory (Study 2; n = 144) factor analyses consistently supported a two-factor structure reflecting the 'liking' and 'wanting' constructs. Results from Study 3 (N = 36) indicated that the Wanting and the Liking scales had adequate internal consistency and test-retest reliability. Additionally, consistent with predictions, the Wanting scale, but not the Liking scale, was associated with picking urges the following week, greater cue-reactivity, and more picking-related routines/habits. These initial findings suggest that SPRS is a psychometrically sound measure of 'wanting' and 'liking' in pathological skin picking. The SPRS may facilitate research on reward processing anomalies in SPD and serve as a useful clinical instrument (e.g., to identify those at risk for cue-induced relapse).

Reactivity of cosmetic UV filters towards skin proteins: model studies with Boc-lysine, Boc-Gly-Phe-Gly-Lys-OH, BSA and gelatin.

PubMed

Stiefel, C; Schwack, W

2014-12-01

Organic UV filters are used as active ingredients in most sunscreens and also in a variety of daily care products. Their good (photo) stability is of special interest to guarantee protective function and to prevent interactions with the human skin. Due to the mostly electrophilic character of the UV filters, reactions with nucleophilic protein moieties like lysine side chains are conceivable. Prior studies showed that the UV filters octocrylene (OCR), butyl methoxydibenzoylmethane (BM-DBM), ethylhexyl salicylate (EHS), ethylhexyl methoxycinnamate (EHMC), benzophenone-3 (BP-3), ethylhexyl triazone (EHT) and dibenzoylmethane (DBM) were able to covalently bind to an HPTLC amino phase and the amino acid models ethanolamine and butylamine after slightly heating and/or radiation. Boc-protected lysine, the tetrapeptide Boc-Gly-Phe-Gly-Lys-OH, bovine serum albumin (BSA) and porcine gelatin were used as more complex models to determine the reactivity of the mentioned UV filters towards skin proteins under thermal or UV irradiation conditions. After gentle heating at 37°C, benzophenone imines were identified as reaction products of BP-3 and OCR with Boc-lysine and the tetrapeptide, whereas DBM and BM-DBM yielded enamines. For EHMC, a Michael-type reaction occurred, which resulted in addition of Boc-lysine or the tetrapeptide to the conjugated double bond. Ester aminolysis of EHS and EHT mainly afforded the corresponding amides. Reactions of the UV filters with BSA changed the UV spectrum of BSA, generally associated with an increase of the absorption strength in the UVA or UVB range. For all protein models, the UV filters showed an increasing reactivity in the order EHT < EHMC < EHS < BP-3 < OCR < DBM < BM-DBM. Especially the UV absorbers BM-DBM, OCR and BP-3, which are seen as common allergens or photoallergens, showed a high reactivity towards the different skin protein models. As the formation of protein adducts is recognized as important key element in the induction of

Reactions to prick and intradermal skin tests.

PubMed

Bagg, Andrew; Chacko, Thomas; Lockey, Richard

2009-05-01

Allergy skin testing is a common procedure for the diagnosis of atopic diseases with a small risk of systemic reactions. To determine the 12-month incidence of systemic reactions (SRs) to skin prick testing (SPT) and intradermal skin testing (ST) and the symptoms and response to immediate treatment with epinephrine intramuscularly. A prospective study was conducted to evaluate SRs from ST in 1,456 patients. A standard form was used to record symptoms, signs, and treatment. The SRs are defined as any sign or symptom other than a local reaction thought to be secondary to ST. No vasovagal reactions were included. Nurses, as instructed by attending physicians, administered epinephrine (0.2 mL of a 1:1,000 dilution) intramuscularly in the deltoid as soon as any remote signs or symptoms occurred. Fifty-two patients (3.6%) had SRs (6 SPT and 46 intradermal): 43 (83%) were female, and 17 (33%) had asthma. Systemic symptoms included (SPT/intradermal) pruritic eyes, nose, or pharynx (0%/46%); worsening cough (50%/26%); sensation of difficulty swallowing (0%/20%); worsening nasal congestion (17%/15%); rhinorrhea (17%/13%); chest tightness or shortness of breath (33%/11%); generalized pruritus (17%/11%); sneezing (33%/9%); wheeze (0%/4%); and urticaria (17%/2%). No severe asthma, shock, hypotension, unconsciousness, or biphasic reactions occurred. All 52 patients received epinephrine intramuscularly, 48 (92%) oral prednisone, 9 (17%) oral prednisone to take 6 to 8 hours after a reaction, 50 (96%) oral antihistamine, and 6 (12%) nebulized beta-agonist. Of patients who underwent ST, SRs occurred in 3.6% (0.4% for SPT and 3.2% for intradermal ST), all of whom readily responded to epinephrine intramuscularly in the deltoid. This immediate administration of epinephrine seems to prevent more serious and biphasic reactions.

Positive tuberculin skin tests in nursing home residents in Southern Taiwan.

PubMed

Chang, Chia-Ming; Lee, Nan-Yao; Lee, Hsin-Chun; Wu, Chi-Jung; Chen, Po-Lin; Lee, Ching-Chi; Shih, Hsin-I; Ko, Wen-Chien

2010-01-01

In Taiwan, the tuberculin skin test (TST) is not recommended as a screening test for Mycobacterium tuberculosis (TB) infections. The aim of this study is to determine the prevalence and predictors of positive tuberculin reactivity and its association with TB infections among nursing home residents in Taiwan. A cross-sectional study and review of medical records were conducted at four nursing homes in Tainan City. A one-stage TST was performed by study nurses using two tuberculin units of purified protein derivative (PPD) of the RT23 strain. An induration ≥10 mm at 72 h was considered to be a positive reaction. Chest radiographs, acid-fast stains and mycobacterial cultures of three sputum samples were performed for those with a positive TST result. Of 115 residents (66.5% participation, mean age 73.1 years) who underwent a TST, 26 (22.6%) had a positive reaction. One woman was microbiologically diagnosed to have pulmonary TB. On multivariate analysis, a Bacille Calmette-Guérin (BCG) scar and a history of myocardial infarction were significantly associated with a positive TST. In conclusions, this study shows a considerable rate of positive TST among nursing home residents in southern Taiwan. A BCG scar and a history of myocardial infarction were associated with a positive TST. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical stability of reactive skin decontamination lotion (RSDL®).

PubMed

Bogan, R; Maas, H J; Zimmermann, T

2018-09-01

Reactive Skin Decontamination Lotion (RSDL ® ) is used for the decontamination of Chemical Warfare Agents and Toxic Industrial Compounds after dermal exposure. It has to be stockpiled over a long period and is handled in all climatic zones. Therefore stability is an essential matter of concern. In this work we describe a study to the chemical stability of RSDL ® as basis for an estimation of shelf life. We analysed RSDL ® for the active ingredient 2,3-butandione monoxime (diacetylmonooxime, DAM), the putative degradation product dimethylglyoxime (DMG) and unknown degradation products by means of a reversed phase high pressure liquid chromatography (HPLC). Calculations were done according to the Arrhenius equation. Based on the temperature dependent rate constants, the time span was calculated, until defined threshold values for DAM and DMG subject to specification and valid regulations were exceeded. The calculated data were compared to the ones gathered from stockpiled samples and samples exposed during foreign mission. The decline of DAM followed first order kinetics, while formation of DMG could be described by zero order kinetics. The rate constants were distinctively temperature dependent. Calculated data were in good accordance to the measured ones from stockpile and mission. Based on a specified acceptable DAM-content of 90% and a valid threshold value of 0.1% (w/w) for the degradation product DMG, RSDL ® proved to be stable for at least four years if stored at the recommended conditions of 15°C-30°C. If continuously stored at higher temperatures shelf life will decrease markedly. Therefore RSDL ® is an object for risk orientated quality monitoring during storage. Copyright © 2017 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

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

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

Educational case series: β-lactam allergy and cross-reactivity.

PubMed

Atanasković-Marković, Marina

2011-12-01

Penicillins and cephalosporins are the most widely used antibiotics for the treatment of common infections, and they are the two main classes of β-lactams. On the basis of the time of appearance of the reaction after drug intake and for diagnostic purposes, hypersensitivity reactions to β-lactams have been classified as immediate or non-immediate. The diagnostic evaluation of allergic reactions to β-lactams has changed over the last decade, for several reasons. In many countries, major and minor determinants for skin testing are not available. In immediate allergic reactions, the sensitivity of skin testing is decreasing. For non-immediate reactions, skin testing appears to be less sensitive than previously reported. The drug provocation test is still necessary for diagnosis. In this education review series, we described three cases of β-lactam allergy: first, a child with an IgE-mediated allergy to benzyl-penicillin; second, a child with a non-allergic hypersensitivity to amoxicillin; and in the third patient, we will discuss about cross-reactivity between penicillins and cephalosporins. These cases are correlated with the practical management of evaluating β-lactam allergy. © 2011 John Wiley & Sons A/S.

Sub-categorisation of skin corrosive chemicals by the EpiSkin™ reconstructed human epidermis skin corrosion test method according to UN GHS: revision of OECD Test Guideline 431.

PubMed

Alépée, N; Grandidier, M H; Cotovio, J

2014-03-01

The EpiSkin™ skin corrosion test method was formally validated and adopted within the context of OECD TG 431 for identifying corrosive and non-corrosive chemicals. The EU Classification, Labelling and Packaging Regulation (EU CLP) system requires the sub-categorisation of corrosive chemicals into the three UN GHS optional subcategories 1A, 1B and 1C. The present study was undertaken to investigate the usefulness of the validated EpiSkin™ test method to identify skin corrosive UN GHS Categories 1A, 1B and 1C using the original and validated prediction model and adapted controls for direct MTT reduction. In total, 85 chemicals selected by the OECD expert group on skin corrosion were tested in three independent runs. The results obtained were highly reproducible both within (>80%) and between (>78%) laboratories when compared with historical data. Moreover the results obtained showed that the EpiSkin™ test method is highly sensitive (99%) and specific (80%) in discriminating corrosive from non-corrosive chemicals and allows reliable and relevant identification of the different skin corrosive UN GHS subcategories, with high accuracies being obtained for both UN GHS Categories 1A (83%) and 1B/1C (76%) chemicals. The overall accuracy of the test method to subcategorise corrosive chemicals into three or two UN GHS subcategories ranged from 75% to 79%. Considering those results, the revised OECD Test Guideline 431 permit the use of EpiSkin™ for subcategorising corrosive chemicals into at least two classes (Category 1A and Category 1B/1C). Copyright © 2013. Published by Elsevier Ltd.

Gremlin inhibits UV-induced skin cell damages via activating VEGFR2-Nrf2 signaling

PubMed Central

Xu, Qiu-yun; Zhang, Jing; Lin, Meng-ting; Tu, Ying; He, Li; Bi, Zhi-gang; Cheng, Bo

2016-01-01

Ultra Violet (UV) radiation induces reactive oxygen species (ROS) production, DNA oxidation and single strand breaks (SSBs), which will eventually lead to skin cell damages or even skin cancer. Here, we tested the potential activity of gremlin, a novel vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) agonist, against UV-induced skin cell damages. We show that gremlin activated VEGFR2 and significantly inhibited UV-induced death and apoptosis of skin keratinocytes and fibroblasts. Pharmacological inhibition or shRNA-mediated knockdown of VEGFR2 almost abolished gremlin-mediated cytoprotection against UV in the skin cells. Further studies showed that gremlin activated VEGFR2 downstream NF-E2-related factor 2 (Nrf2) signaling, which appeared required for subsequent skin cell protection. Nrf2 shRNA knockdown or S40T dominant negative mutation largely inhibited gremlin-mediated skin cell protection against UV. At last, we show that gremlin dramatically inhibited UV-induced ROS production and DNA SSB formation in skin keratinocytes and fibroblasts. We conclude that gremlin protects skin cells from UV damages via activating VEGFR2-Nrf2 signaling. Gremlin could be further tested as a novel anti-UV skin protectant. PMID:27713170

Gremlin inhibits UV-induced skin cell damages via activating VEGFR2-Nrf2 signaling.

PubMed

Ji, Chao; Huang, Jin-Wen; Xu, Qiu-Yun; Zhang, Jing; Lin, Meng-Ting; Tu, Ying; He, Li; Bi, Zhi-Gang; Cheng, Bo

2016-12-20

Ultra Violet (UV) radiation induces reactive oxygen species (ROS) production, DNA oxidation and single strand breaks (SSBs), which will eventually lead to skin cell damages or even skin cancer. Here, we tested the potential activity of gremlin, a novel vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) agonist, against UV-induced skin cell damages. We show that gremlin activated VEGFR2 and significantly inhibited UV-induced death and apoptosis of skin keratinocytes and fibroblasts. Pharmacological inhibition or shRNA-mediated knockdown of VEGFR2 almost abolished gremlin-mediated cytoprotection against UV in the skin cells. Further studies showed that gremlin activated VEGFR2 downstream NF-E2-related factor 2 (Nrf2) signaling, which appeared required for subsequent skin cell protection. Nrf2 shRNA knockdown or S40T dominant negative mutation largely inhibited gremlin-mediated skin cell protection against UV. At last, we show that gremlin dramatically inhibited UV-induced ROS production and DNA SSB formation in skin keratinocytes and fibroblasts. We conclude that gremlin protects skin cells from UV damages via activating VEGFR2-Nrf2 signaling. Gremlin could be further tested as a novel anti-UV skin protectant.

Comparison of wheat and rye flour solutions for skin prick testing: a multi-centre study (Stad 1).

PubMed

van Kampen, V; Merget, R; Rabstein, S; Sander, I; Bruening, T; Broding, H C; Keller, C; Muesken, H; Overlack, A; Schultze-Werninghaus, G; Walusiak, J; Raulf-Heimsoth, M

2009-12-01

Skin prick testing (SPT) is the basic method for diagnosing IgE-mediated allergies. However, skin reactivity is related to the quality of allergen extracts, which are often poorly defined for occupational allergens. To compare wheat and rye flour SPT solutions from different producers. Standardized SPTs were performed in seven allergy centres with wheat and rye flour solutions from four producers in 125 symptomatic bakers. Optimal cut-off levels for weal sizes were assessed with the Youden Index. Comparisons between SPT results of different solutions were made with flour-specific IgE (sIgE) as the gold standard. Sensitivities, specificities, positive and negative predictive values, and test efficiencies were calculated and compared with McNemar and chi(2)-tests. The influence of the choice of the gold standard (sIgE or challenge) test was examined for 95 subjects. Additionally, SPT solutions were analysed for protein and antigen content. The optimal cut-off level for all SPT solutions was a weal size of >or=1.5 mm. While differences between wheat and rye flours were small, differences between producers were important. Variability of sensitivities (0.31-0.96), negative predictive values (0.42-0.91), and test efficiencies (0.54-0.90) were higher than variations of specificities (0.74-1.00) and positive predictive values (0.88-1.00). Similar results were obtained when using challenge test results as the gold standard. Variability could be explained by the different antigen contents of the SPT solutions. There is a wide variability of SPT solutions for wheat and rye flour from different producers, mainly with respect to sensitivities, negative predictive values, and test efficiencies. Improvement and standardization of SPT solutions used for the diagnosis of baker's asthma are highly recommended.

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.

The development and testing of a skin tear risk assessment tool.

PubMed

Newall, Nelly; Lewin, Gill F; Bulsara, Max K; Carville, Keryln J; Leslie, Gavin D; Roberts, Pam A

2017-02-01

The aim of the present study is to develop a reliable and valid skin tear risk assessment tool. The six characteristics identified in a previous case control study as constituting the best risk model for skin tear development were used to construct a risk assessment tool. The ability of the tool to predict skin tear development was then tested in a prospective study. Between August 2012 and September 2013, 1466 tertiary hospital patients were assessed at admission and followed up for 10 days to see if they developed a skin tear. The predictive validity of the tool was assessed using receiver operating characteristic (ROC) analysis. When the tool was found not to have performed as well as hoped, secondary analyses were performed to determine whether a potentially better performing risk model could be identified. The tool was found to have high sensitivity but low specificity and therefore have inadequate predictive validity. Secondary analysis of the combined data from this and the previous case control study identified an alternative better performing risk model. The tool developed and tested in this study was found to have inadequate predictive validity. The predictive validity of an alternative, more parsimonious model now needs to be tested. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

The colour of blood in skin: a comparison of Allen's test and photonics simulations.

PubMed

Välisuo, Petri; Kaartinen, Ilkka; Kuokkanen, Hannu; Alander, Jarmo

2010-11-01

The colour of the skin reflects many physiological and pathological states of an individual. Usually, the skin colour is examined by the bare eye alone. Several scaling systems have been developed to quantify the sensory evaluation of skin colour. In this work, the reflectance of the skin is measured directly using an objective instrument. Haemoglobin inside the dermal circulation is one of the key factors of skin colour and it also has a major role in the appearance of many skin lesions and scars. To quantitatively measure and analyse such conditions, the relation between the skin colour and the haemoglobin concentration in the skin needs to be resolved. To examine the effect of blood concentration on the skin colour, five Allen's tests were performed on 20 persons. The skin colour change was measured using a spectrophotometer by changing the blood concentration by the Allen's test. Light interaction with the skin was simulated with a Monte Carlo model, tuning the blood concentration parameter until the simulated and the measured spectra matched, yielding the relationship between the skin colour and the blood concentration. The simulation produced spectra similar to those measured. The change in the blood concentration in the simulation model and in the skin produced changes similar to the spectra. The reflectance of the skin was found to be a nonlinear function of the blood concentration. The relationship found between skin colour and blood concentration makes it possible to quantify those skin conditions expressed by blood volume better than plain colour. © 2010 John Wiley & Sons A/S.

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

12-OH-nevirapine sulfate, formed in the skin, is responsible for nevirapine-induced skin rash.

PubMed

Sharma, Amy M; Novalen, Maria; Tanino, Tadatoshi; Uetrecht, Jack P

2013-05-20

Nevirapine (NVP) treatment is associated with a significant incidence of skin rash in humans, and it also causes a similar immune-mediated skin rash in Brown Norway (BN) rats. We have shown that the sulfate of a major oxidative metabolite, 12-OH-NVP, covalently binds in the skin. The fact that the sulfate metabolite is responsible for covalent binding in the skin does not prove that it is responsible for the rash. We used various inhibitors of sulfation to test whether this reactive sulfate is responsible for the skin rash. Salicylamide (SA), which depletes 3'-phosphoadenosine-5'-phosphosulfate (PAPS) in the liver, significantly decreased 12-OH-NVP sulfate in the blood, but it did not prevent covalent binding in the skin or the rash. Topical application of 1-phenyl-1-hexanol, a sulfotransferase inhibitor, prevented covalent binding in the skin as well as the rash, but only where it was applied. In vitro incubations of 12-OH-NVP with PAPS and cytosolic fractions from the skin of rats or from human skin also led to covalent binding that was inhibited by 1-phenyl-1-hexanol. Incubation of 12-OH-NVP with PAPS and sulfotransferase 1A1*1, a human isoform that is present in the skin, also led to covalent binding, and this binding was also inhibited by 1-phenyl-1-hexanol. We conclude that salicylamide did not deplete PAPS in the skin and was unable to prevent covalent binding or the rash, while topical 1-phenyl-1-hexanol inhibited sulfation of 12-OH-NVP in the skin and did prevent covalent binding and the rash. These results provide definitive evidence that 12-OH-NVP sulfate formed in skin is responsible for NVP-induced skin rashes. Sulfotransferase is one of the few metabolic enzymes with significant activity in the skin, and it may be responsible for the bioactivation of other drugs that cause skin rashes.

Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants.

PubMed

Martino, David; Dang, Thanh; Sexton-Oates, Alexandra; Prescott, Susan; Tang, Mimi L K; Dharmage, Shyamali; Gurrin, Lyle; Koplin, Jennifer; Ponsonby, Anne-Louise; Allen, Katrina J; Saffery, Richard

2015-05-01

The diagnosis of food allergy (FA) can be challenging because approximately half of food-sensitized patients are asymptomatic. Current diagnostic tests are excellent makers of sensitization but poor predictors of clinical reactivity. Thus oral food challenges (OFCs) are required to determine a patient's risk of reactivity. We sought to discover genomic biomarkers of clinical FA with utility for predicting food challenge outcomes. Genome-wide DNA methylation (DNAm) profiling was performed on blood mononuclear cells from volunteers who had undergone objective OFCs, concurrent skin prick tests, and specific IgE tests. Fifty-eight food-sensitized patients (aged 11-15 months) were assessed, half of whom were clinically reactive. Thirteen nonallergic control subjects were also assessed. Reproducibility was assessed in an additional 48 samples by using methylation data from an independent population of patients with clinical FA. Using a supervised learning approach, we discovered a DNAm signature of 96 CpG sites that predict clinical outcomes. Diagnostic scores were derived from these 96 methylation sites, and cutoffs were determined in a sensitivity analysis. Methylation biomarkers outperformed allergen-specific IgE and skin prick tests for predicting OFC outcomes. FA status was correctly predicted in the replication cohort with an accuracy of 79.2%. DNAm biomarkers with clinical utility for predicting food challenge outcomes are readily detectable in blood. The development of this technology in detailed follow-up studies will yield highly innovative diagnostic assays. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Effects of different base agents on prediction of skin irritation by sodium lauryl sulfate using patch testing and repeated application test.

PubMed

Horita, Kotomi; Horita, Daisuke; Tomita, Hiroyuki; Yasoshima, Mitsue; Yagami, Akiko; Matsunaga, Kayoko

2017-05-01

Animal testing for cosmetics was banned in the European Union (EU) in 2013; therefore, human tests to predict and ensure skin safety such as the patch test or usage test are now in demand in Japan as well as in the EU. In order to investigate the effects of different bases on the findings of tests to predict skin irritation, we performed patch testing (PT) and the repeated application test (RAT) using sodium lauryl sulfate (SLS), a well-known irritant, dissolved in 6 different base agents to examine the effects of these bases on skin irritation by SLS. The bases for PT were distilled water, 50% ethanol, 100% ethanol, a gel containing 50% ethanol, white petrolatum, and hydrophilic cream. The concentrations of SLS were 0.2% and 0.5%. Twelve different base combinations were applied to the normal back skin of 19 individuals for 24h. RAT was performed with distilled water, 50% ethanol, 100% ethanol, a gel containing 50% ethanol, white petrolatum, and hydrophilic cream containing SLS at concentrations of 0.2%, 2%, and 5%, being applied to the arms of the same PT subjects. The test preparation of each base was applied at the same site, with 0.2% SLS being used in the first week, 2% SLS in the following week, and 5% SLS in the final week. The results of PT revealed that skin irritation scores varied when SLS at the same concentration was dissolved in a different base. The results of RAT showed that although skin irritation appeared with every base at a concentration of 5%, the positive rate was approximately the same. In conclusion, our results suggest that skin irritation elicited in PT depends on the base, while in RAT, it does not depend on the type of base employed. Copyright © 2017 Elsevier B.V. All rights reserved.

Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies.

PubMed

Wilkinson, Simon C; Maas, Wilfred J M; Nielsen, Jesper Bo; Greaves, Laura C; van de Sandt, Johannes J M; Williams, Faith M

2006-05-01

To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Percutaneous penetration of caffeine (log P -0.01), testosterone (log P 3.32), propoxur (log P 1.52) (finite dose in ethanol to water vehicle ratio) and butoxyethanol (log P 0.83) (undiluted finite dose or as an infinite dose 50% [v/v] aqueous solution) through skin of varying thicknesses under occluded conditions was measured using flow through cells for 8-24 h. Saline (adjusted to pH 7.4) was used as receptor fluid, with BSA added for studies with testosterone and propoxur. Following exposure, the remaining surface dose was removed by swabbing and the skin digested prior to scintillation counting. The maximum flux of caffeine was increased with decreasing skin thickness, although these differences were found to be non-significant. The presence of caffeine in the skin membrane was not altered by skin thickness. Maximum flux and cumulative dose absorbed of testosterone and butoxyethanol (in both finite and infinite doses) were markedly reduced with full thickness (about 1 mm thick) skin compared with split thickness skin (about 0.5 mm). Maximum flux of propoxur (dissolved in 60% ethanol) was clearly higher through skin of 0.71 mm than through skin of 1.36 mm, but no difference was found between 0.56 and 0.71 mm. The proportion of propoxur present in the membrane after 24 h increased significantly over the complete range of thicknesses tested (0.56-1.36 mm). A complex relationship exists between skin thickness, lipophilicity and percutaneous penetration and distribution. This has implications for risk assessment studies and for the validation of models with data from different sources.

Assessment of the human epidermal model LabCyte EPI-MODEL for In vitro skin corrosion testing according to the OECD test guideline 431.

PubMed

Katoh, Masakazu; Hamajima, Fumiyasu; Ogasawara, Takahiro; Hata, Ken-Ichiro

2010-06-01

A new OECD test guideline 431 (TG431) for in vitro skin corrosion tests using human reconstructed skin models was adopted by OECD in 2004. TG431 defines the criteria for the general function and performance of applicable skin models. In order to confirm that the new reconstructed human epidermal model, LabCyte EPI-MODEL is applicable for the skin corrosion test according to TG431, the predictability and repeatability of the model for the skin corrosion test was evaluated. The test was performed according to the test protocol described in TG431. Based on the knowledge that LabCyte EPI-MODEL is an epidermal model as well as EpiDerm, we decided to adopt the the Epiderm prediction model of skin corrosion for the LabCyte EPI-MODEL, using twenty test chemicals (10 corrosive chemicals and 10 non-corrosive chemicals) in the 1(st) stage. The prediction model results showed that the distinction of non-corrosion to corrosion corresponded perfectly. Therefore, it was judged that the prediction model of EpiDerm could be applied to the LabCyte EPI-MODEL. In the 2(nd) stage, the repeatability of this test protocol with the LabCyte EPI-MODEL was examined using twelve chemicals (6 corrosive chemicals and 6 non-corrosive chemicals) that are described in TG431, and these results recognized a high repeatability and accurate predictability. It was concluded that LabCyte EPI-MODEL is applicable for the skin corrosive test protocol according to TG431.

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.

EVALUATION OF DIAGNOSTIC ACCURACY OF THE COMPARATIVE TUBERCULIN SKIN TEST IN REHABILITANT BORNEAN ORANGUTANS (PONGO PYGMAEUS).

PubMed

Dench, Rosalie; Sulistyo, Fransiska; Fahroni, Agus; Philippa, Joost

2015-12-01

The tuberculin skin test (TST) has been the mainstay of tuberculosis (TB) testing in primates for decades, but its interpretation in orangutans (Pongo spp.) is challenging, because many animals react strongly, without evidence of infection with Mycobacterium tuberculosis complex. One explanation is cross-reactivity with environmental nontuberculous mycobacteria (NTM). The use of a comparative TST (CTST), comparing reactivity to avian (representing NTM) and bovine (representing tuberculous mycobacteria) tuberculins aids in distinguishing cross-reactivity due to sensitization by NTM from shared antigens. The specificity of the TST can be increased with the use of CTST. We considered three interpretations of the TST in rehabilitant Bornean orangutans ( Pongo pygmaeus ) using avian purified protein derivative (APPD; 25,000 IU/ml) and two concentrations of bovine purified protein derivative (BPPD; 100,000 and 32,500 IU/ml). The tests were evaluated for their ability to identify accurately seven orangutans previously diagnosed with and treated for TB from a group of presumed negative individuals (n = 288 and n = 161 for the two respective BPPD concentrations). BPPD at 32,500 IU/ml had poor diagnostic capacity, whereas BPPD at 100,000 IU/ml performed better. The BPPD-only interpretation had moderate sensitivity (57%) and poor specificity (40%) and accuracy (41%). The comparative interpretation at 72 hr had similar sensitivity (57%) but improved specificity (95%) and accuracy (94%). However, best results were obtained by a comparative interpretation incorporating the 48- and 72-hr scores, which had good sensitivity (86%), specificity (95%) and accuracy (95%). These data reinforce recommendations that a CTST be used in orangutans and support the use of APPD at 25,000 IU/ml and BPPD at 100,000 IU/ml. The highest score at each site from the 48- and 72-hr checks should be considered the result for that tuberculin. If the bovine result is greater than the avian result, the

Atopy, non-allergic bronchial reactivity, and past history as determinants of work related symptoms in seasonal grain handlers.

PubMed Central

Cookson, W O; Ryan, G; MacDonald, S; Musk, A W

1986-01-01

One hundred and five young subjects with little or no previous exposure to grain dust were studied before and after a seven week period of grain handling work to determine if there was an association between symptoms experienced at work and pre-employment respiratory symptoms, allergy skin test responses, and non-allergic bronchial reactivity. The incidence of work related symptoms was cough 18%, wheeze 13%, and dyspnoea 14%. The results showed that pre-employment history of respiratory symptoms, positive allergy skin test responses, and a high level of non-allergic bronchial reactivity were significantly associated with these symptoms. These measurements may be useful to predict symptoms associated with exposure to grain dust in new employees and the results suggest that these work related symptoms may be due to allergen induced asthma. PMID:3718884

Bioactive nitric oxide concentration does not increase during reactive hyperemia in human skin.

PubMed

Zhao, J L; Pergola, P E; Roman, L J; Kellogg, D L

2004-02-01

This study examined whether nitric oxide (NO) is involved in the cutaneous response to reactive hyperemia (RH) in the human forearm. We enrolled seven healthy volunteers. NO concentrations were monitored using a NO selective amperometric electrode (ISO-NOP200, World Precision Instruments) inserted into the skin of the forearm. Laser-Doppler flowmetry (Moor Instruments) was used for monitoring skin blood flow (SkBF) at the same site. SkBF and NO levels were monitored and recorded continuously throughout the experiment. An intradermal microdialysis probe was inserted adjacent to the NO electrode for drug delivery. Data collection began 140 min after the NO electrodes and microdialysis probes were inserted. RH was achieved by the inflation of a blood pressure cuff to 25 mmHg above systolic pressure for 7 min after which the pressure in the cuff was abruptly released. Acetylcholine (ACh) was given by microdialysis probe at the end of RH study to verify the ability of the electrode system to detect changes in the NO concentration. SkBF and NO data before RH and immediately, 2, 5, 7, and 10 min after cuff deflation were used for analysis. SkBF increased immediately after release of the occlusion (P < 0.0001) and remained elevated for 2 min. No significant NO changes occurred with the increases in LDF. ACh induced increases in both SkBF and NO (P < 0.000 and P < 0.037, respectively). We conclude that RH increases SkBF by mechanisms that do not require a measurable increase in NO concentrations.

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

Skin-prick testing as a diagnostic aid for childhood asthma.

PubMed

Chan, E Y; Dundas, I; Bridge, P D; Healy, M J R; McKenzie, S A

2005-06-01

Diagnosing asthma is problematic when based solely on reported symptoms. The purpose of this study was to evaluate skin-prick testing as a diagnostic aid for asthma in children. Skin-prick testing (SPT) was undertaken in children aged 2-10 years with either no history of wheeze (n = 149) or recent doctor-observed wheeze which responded to treatment with a bronchodilator, the "gold standard" (n = 164). Children with moderate or severe asthma were excluded. SPT positivity increased sharply at age 5 years in wheezers. Data were therefore divided into two age groups: 2- < 5 years (57 controls, 97 wheezers) and 5-10 years (92 controls, 67 wheezers). The sensitivity, specificity, and likelihood ratios of SPT positivity for wheeze were 32%, 89%, and 2.9, respectively, in the younger children, and 82%, 85%, and 5.5, respectively, in the older children. For a prevalence of 30% for asthma, the positive predictive values of a positive SPT were 55% and 70% for the younger and older age groups, respectively. The test characteristics of SPT for helping diagnose asthma in schoolchildren are good. The prevalence of wheeze in preschool children is high, and so SPT should be helpful even in this group. We suggest that clinicians consider skin-prick testing as a diagnostic aid for asthma. Copyright 2005 Wiley-Liss, Inc.

Allergy testing - skin

MedlinePlus

... if you're allergic to bee venom or penicillin. Or it may be used if the skin ... sore, or swollen after contact with the substance Penicillin allergy Venom allergy Allergies to penicillin and related ...

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.

Sesame allergy: role of specific IgE and skin-prick testing in predicting food challenge results.

PubMed

Permaul, Perdita; Stutius, Lisa M; Sheehan, William J; Rangsithienchai, Pitud; Walter, Jolan E; Twarog, Frank J; Young, Michael C; Scott, Jordan E; Schneider, Lynda C; Phipatanakul, Wanda

2009-01-01

There are conflicting data regarding the diagnostic value of sesame-specific IgE and sesame skin test. Currently, there are no established thresholds that predict clinical reactivity. We examined the correlation of sesame ImmunoCAP and skin-prick test (SPT) results with oral challenge outcomes in children suspected of having a sesame food allergy. We conducted a retrospective chart review of children, aged 2-12 years, receiving a sesame ImmunoCAP level, SPT, and food challenge from January 2004 to August 2008 at Children's Hospital Boston and affiliated allergy clinics. Food challenges were conducted in cases of questionable clinical history or a negative ImmunoCAP and/or negative SPT despite a convincing history. Thirty-three oral sesame challenges were conducted. Of the 33 challenges performed, 21% (n = 7) failed and 79% (n = 26) passed. A sesame-specific IgE level of > or = 7 kU(A)/L showed specificity of >90%. An SPT wheal size of > or = 6 mm showed specificity of >90%. Receiver operator characteristic (ROC) curve analysis for sesame-specific IgE revealed an area under the curve (AUC) of 0.56. ROC curve analysis for SPT wheal size revealed an AUC of 0.67. To our knowledge, this study represents the largest number of sesame challenges performed to evaluate the diagnostic value of both sesame-specific IgE and SPT. Based on our sample, both tests are not good predictors of true sesame allergy as determined by an oral challenge. We were unable to establish a threshold with a 95% positive predictive value for both sesame-specific IgE and SPT.

Occupational Rhinoconjunctivitis due to Maize in a Snack Processor: A Cross-Reactivity Study Between Lipid Transfer Proteins From Different Cereals and Peach.

PubMed

Guillen, Daiana; Barranco, Pilar; Palacín, Arantxa; Quirce, Santiago

2014-09-01

We report the case of a snack processor who developed occupational rhinoconjunctivitis due to maize brand exposure during the extrusion process, and who experienced abdominal pain upon drinking beer. The allergens implicated and the cross-reactivity between non-specific lipid transfer proteins (LTPs) from different cereals and peach were investigated. Skin prick tests and specific IgE to cereal flours, pulmonary functions tests and specific conjunctival and inhalation challenges to maize extract were performed. In vitro studies included IgE immunoblotting and ELISA inhibition assays. Skin prick tests with maize flour, maize brand and wheat flour extracts were positive, whereas serum specific IgE was positive only to maize flour. Specific inhalation challenge (SIC) to maize flour did not elicit an asthmatic reaction; however, conjunctival challenge test with the same extract was positive. Patient's serum recognized IgE-binding bands in the maize and beer extracts corresponding to LTPs. In the ELISA inhibition assays, a significant degree of allergenic cross-reactivity was found between maize and beer LTPs, whereas no cross-reactivity was observed between maize LTP and wheat and peach LTPs.

Surprisingly high specificity of the PPD skin test for M. tuberculosis infection from recent exposure in The Gambia.

PubMed

Hill, Philip C; Brookes, Roger H; Fox, Annette; Jackson-Sillah, Dolly; Lugos, Moses D; Jeffries, David J; Donkor, Simon A; Adegbola, Richard A; McAdam, Keith P W J

2006-12-20

Options for intervention against Mycobacterium tuberculosis infection are limited by the diagnostic tools available. The Purified Protein Derivative (PPD) skin test is thought to be non-specific, especially in tropical settings. We compared the PPD skin test with an ELISPOT test in The Gambia. Household contacts over six months of age of sputum smear positive TB cases and community controls were recruited. They underwent a PPD skin test and an ELISPOT test for the T cell response to PPD and ESAT-6/CFP10 antigens. Responsiveness to M. tuberculosis exposure was analysed according to sleeping proximity to an index case using logistic regression. 615 household contacts and 105 community controls were recruited. All three tests assessed increased significantly in positivity with increasing M. tuberculosis exposure, the PPD skin test most dramatically (OR 15.7; 95% CI 6.6-35.3). While the PPD skin test positivity continued to trend downwards in the community with increasing distance from a known case (61.9% to 14.3%), the PPD and ESAT-6/CFP-10 ELISPOT positivity did not. The PPD skin test was more in agreement with ESAT-6/CFP-10 ELISPOT (75%, p = 0.01) than the PPD ELISPOT (53%, p<0.0001). With increasing M. tuberculosis exposure, the proportion of ESAT-6/CFP-10 positive contacts who were PPD skin test positive increased (p<0.0001), and the proportion of ESAT-6/CFP-10 negative contacts that were PPD skin test negative decreased (p<0.0001); the converse did not occur. The PPD skin test has surprisingly high specificity for M. tuberculosis infection from recent exposure in The Gambia. In this setting, anti-tuberculous prophylaxis in PPD skin test positive individuals should be revisited.

Mini Review - Phenolics for skin photo-aging.

PubMed

Ali, Atif

2017-07-01

Photo-aging is one of the foremost problems caused by generation of reactive oxygen species when skin is exposed on UV irradiation. In view of that, generation of reactive oxygen species intermingle with proteins, DNA, saccharides and fatty acids triggering oxidative mutilation and effects are in the appearance of distressed cell metabolism, morphological and ultra-structural changes, mistreat on the routes and revisions in the demarcation, propagation and skin apoptosis living cells which leads to photo-aging. Plant phenolics are universally found in both edible and inedible plants and have extended substantial interest as photo-protective for human skin due to their antioxidant activities. The objective of this review is to highlight the use of plant phenolics for their antioxidant activities against photo-aging.

Dual skin tests with Mycobacterium avium sensitin and PPD to detect misdiagnosis of latent tuberculosis infection.

PubMed

Larson, E M; O'Donnell, M; Chamblee, S; Horsburgh, C R; Marsh, B J; Moreland, J D; Johnson, L S; von Reyn, C Fordham

2011-11-01

A positive tuberculin skin test (TST) may indicate cross-reacting immunity to non-tuberculous mycobacteria (NTM) and not latent tuberculosis infection (LTBI). To assess misclassification of LTBI, as assessed by skin testing with Mycobacterium avium sensitin (MaS), and to determine how this misclassification affects the analysis of risk factors for LTBI. In a population-based survey, participants underwent skin testing with M. tuberculosis purified protein derivative (PPD) and MaS. A PPD-dominant skin test was a reaction that was ≥ 3 mm larger than the MaS reaction; a MaS-dominant skin test was a reaction that was ≥ 3 mm larger than the PPD reaction. Of 447 randomly selected persons, 135 (30%) had a positive PPD test. Of these, 21 (16%) were MaS- dominant, and were therefore attributable to NTM and misclassified as LTBI. PPD reactions of 5-14 mm were more likely to be misclassified than those ≥ 15 mm (OR = 5.0, 95%CI 1.9-13.2). Adjusting for misclassification had only a small impact on the analysis of risk factors for LTBI. A substantial number of individuals who are diagnosed with LTBI are actually sensitized to NTM. Using dual skin testing would reduce misdiagnosis and prevent unnecessary treatment.

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

Exploring the cause of initially reactive bovine brains on rapid tests for BSE

PubMed Central

Dudas, Sandor; James, Jace; Anderson, Renee; Czub, Stefanie

2015-01-01

ABSTRACT Bovine spongiform encephalopathy (BSE) is an invariably fatal prion disease of cattle. The identification of the zoonotic potential of BSE prompted safety officials to initiate surveillance testing for this disease. In Canada, BSE surveillance is primarily focused on high risk cattle including animals which are dead, down and unable to rise, diseased or distressed. This targeted surveillance results in the submission of brain samples with a wide range of tissue autolysis and associated contaminants. These contaminants have the potential to interfere with important steps of surveillance tests resulting in initially positive test results requiring additional testing to confirm the disease status of the animal. The current tests used for BSE screening in Canada utilize the relative protease resistance of the prion protein gained when it misfolds from PrPC to PrPSc as part of the disease process. Proteinase K completely digests PrPC in normal brains, but leaves most of the PrPSc in BSE positive brains intact which is detected using anti-prion antibodies. These tests are highly reliable but occasionally give rise to initially reactive/false positive results. Test results for these reactive samples were close to the positive/negative cut-off on a sub set of test platforms. This is in contrast to all of the previous Canadian positive samples whose numeric values on these same test platforms were 10 to 100 fold greater than the test positive/negative cut-off. Here we explore the potential reason why a sample is repeatedly positive on a sub-set of rapid surveillance tests, but negative on other test platforms. In order to better understand and identify what might cause these initial reactions, we have conducted a variety of rapid and confirmatory assays as well as bacterial isolation and identification on BSE positive, negative and initially reactive samples. We observed high levels of viable bacterial contamination in initially reactive samples suggesting that the

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.

Evaluation of carotenoids and reactive oxygen species in human skin after UV irradiation: a critical comparison between in vivo and ex vivo investigations.

PubMed

Meinke, Martina C; Müller, Robert; Bechtel, Anne; Haag, Stefan F; Darvin, Maxim E; Lohan, Silke B; Ismaeel, Fakher; Lademann, Jürgen

2015-03-01

UV irradiation is one of the most harmful exogenous factors for the human skin. In addition to the development of erythema, free radicals, that is reactive oxygen species (ROS), are induced under its influence and promote the development of oxidative stress in the skin. Several techniques are available for determining the effect of UV irradiation. Resonance Raman spectroscopy (RRS) measures the reduction of the carotenoid concentration, while electron paramagnetic resonance (EPR) spectroscopy enables the analysis of the production of free radicals. Depending on the method, the skin parameters are analysed in vivo or ex vivo. This study provides a critical comparison between in vivo and ex vivo investigations on the ROS formation and carotenoid depletion caused by UV irradiation in human skin. The oxygen content of tissue was also determined. It was shown that the antioxidant status measured in the skin samples in vivo and ex vivo was different. The depletion in the carotenoid concentration in vivo exceeded the value determined ex vivo by a factor of about 1.5, and the radical formation after UV irradiation was significantly greater in vivo by a factor of 3.5 than that measured in excised human skin, which can be explained by the lack of oxygen ex vivo. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: skin irritation.

PubMed

Macfarlane, Martin; Jones, Penny; Goebel, Carsten; Dufour, Eric; Rowland, Joanna; Araki, Daisuke; Costabel-Farkas, Margit; Hewitt, Nicola J; Hibatallah, Jalila; Kirst, Annette; McNamee, Pauline; Schellauf, Florian; Scheel, Julia

2009-07-01

Evaluation of the skin irritancy and corrosivity potential of an ingredient is a necessity in the safety assessment of cosmetic ingredients. To date, there are two formally validated alternatives to the rabbit Draize test for skin corrosivity in place, namely the rat skin transcutaneous electrical resistance (TER) assay and the Human Skin Model Test using EpiSkin, EpiDerm and SkinEthic reconstructed human epidermal equivalents. For skin irritation, EpiSkin, EpiDerm and SkinEthic are validated as stand-alone test replacements for the rabbit Draize test. Data from these tests are rarely considered in isolation and are evaluated in combination with other factors to establish the overall irritating or corrosive potential of an ingredient. In light of the deadlines established in the Cosmetics Directive for cessation of animal testing for cosmetic ingredients, a COLIPA scientific meeting was held in Brussels on 30th January, 2008 to review the use of alternative approaches and to set up a decision tree approach for their integration into tiered testing strategies for hazard and safety assessment of cosmetic ingredients and their use in products. In conclusion, the safety assessments for skin irritation/corrosion of new chemicals for use in cosmetics can be confidently accomplished using exclusively alternative methods.

Intradermal testing after negative skin prick testing for patients with high suspicion of allergy.

PubMed

Larrabee, Yuna C; Reisacher, William

2015-06-01

Skin testing is a widely accepted method for identifying inhalant allergies. Intradermal (ID) testing is often performed after negative skin prick testing (SPT) when a practitioner has a high level of clinical suspicion for a particular allergen. A retrospective chart review study was performed over a 5-year period in patients with negative SPT for airborne allergens who also underwent ID testing based on a high level of suspicion for clinical allergy. Eighty-seven patients had negative SPT and went on to receive an average of 7 ID tests per patient. A total of 592 ID tests were performed after negative SPT. Of these, 20.8% (123/592) had a positive ID result with negative SPT. The allergens with the greatest percentage of positive ID results with negative SPTs were dog, cat, D. farinae, and D. pteronyssinus (33.3%, 34.3%, 39.4%, and 39.6%, respectively). The allergens least likely to test positive on ID testing after negative SPT were red maple, Cladosporium, and Alternaria (0%, 6.3%, and 6.5%, respectively). Approximately 20% of all negative results on SPT will have a positive ID test, more likely for indoor allergens. If a high suspicion for allergy exists in a patient with a negative SPT result, it may be useful to proceed with ID testing. However, the clinical significance of a positive ID test after negative SPT still needs to be elucidated. © 2015 ARS-AAOA, LLC.

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.

Proof of concept testing of a positive reference material for in vivo and in vitro skin irritation testing.

PubMed

Nomura, Yusuke; Lee, Michelle; Fukui, Chie; Watanabe, Kayo; Olsen, Daniel; Turley, Audrey; Morishita, Yuki; Kawakami, Tsuyoshi; Yuba, Toshiyasu; Fujimaki, Hideo; Inoue, Kaoru; Yoshida, Midori; Ogawa, Kumiko; Haishima, Yuji

2017-12-11

In vivo and in vitro irritation testing is important for evaluating the biological safety of medical devices. Here, the performance of positive reference materials for skin irritation testing was evaluated. Four reference standards, referred to as Y-series materials, were analyzed: a polyvinyl chloride (PVC) sheet spiked with 0 (Y-1), 1.0 (Y-2), 1.5 (Y-3), or 10 (Y-4) parts of Genapol X-080 per 100 parts of PVC by weight. Y-1, Y-2, and Y-3 did not induce skin irritation responses in an in vitro reconstructed human epidermis (RhE) tissue model, as measured by tissue viability or interleukin-1α release, or in an in vivo intracutaneous response test using rabbits. In contrast, Y-4 extracts prepared with saline or sesame oil at 37°C and 50°C clearly elicited positive irritation responses, including reduced viability (< 50%) and significantly higher interleukin-1α release compared with the solvent alone group, in the RhE tissue model and an intracutaneous response test, where substantial necrosis was observed by histopathology. The positive skin irritation responses induced in vitro under various extraction conditions, as well as those elicited in vivo, indicate that Y-4 is an effective extractable positive control material for in vivo and in vitro skin irritation tests of medical devices. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

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

PubMed

Lönnqvist, Susanna; Briheim, Kristina; Kratz, Gunnar

2016-02-01

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

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.

Humoral immunity in tuberculin skin test anergy and its role in high-risk persons exposed to active tuberculosis.

PubMed

Encinales, Liliana; Zuñiga, Joaquin; Granados-Montiel, Julio; Yunis, Maria; Granados, Julio; Almeciga, Ingrid; Clavijo, Olga; Awad, Carlos; Collazos, Vilma; Vargas-Rojas, María Inés; Bañales-Mendez, José Luis; Vazquez-Castañeda, Lilia; Stern, Joel N; Romero, Viviana; Fridkis-Hareli, Masha; Frindkis-Hareli, Masha; Terreros, Daniel; Fernandez-Viña, Marcelo; Yunis, Edmond J

2010-02-01

The most common test to identify latent tuberculosis is the tuberculin skin test that detects T cell responses of delayed type hypersensitivity type IV. Since it produces false negative reactions in active tuberculosis or in high-risk persons exposed to tuberculosis patients as shown in this report, we studied antibody profiles to explain the anergy of such responses in high-risk individuals without active infection. Our results showed that humoral immunity against tuberculin, regardless of the result of the tuberculin skin test is important for protection from active tuberculosis and that the presence of high antibody titers is a more reliable indicator of infection latency suggesting that latency can be based on the levels of antibodies together with in vitro proliferation of peripheral blood mononuclear cells in the presence of the purified protein derivative. Importantly, anti-tuberculin IgG antibody levels mediate the anergy described herein, which could also prevent reactivation of disease in high-risk individuals with high antibody titers. Such anti-tuberculin IgG antibodies were also found associated with blocking and/or stimulation of in vitro cultures of PBMC with tuberculin. In this regard, future studies need to establish if immune responses to Mycobacterium tuberculosis can generate a broad spectrum of reactions either toward Th1 responses favoring stimulation by cytokines or by antibodies and those toward diminished responses by Th2 cytokines or blocking by antibodies; possibly involving mechanisms of antibody dependent protection from Mtb by different subclasses of IgG. Published by Elsevier Ltd.

Comparison of the results of intradermal test reactivity and serum allergen-specific IgE measurement for Malassezia pachydermatis in atopic dogs.

PubMed

Oldenhoff, Willam E; Frank, Glenn R; DeBoer, Douglas J

2014-12-01

Malassezia pachydermatis is part of the normal flora of canine skin. Malassezia hypersensitivity is recognized as a trigger for clinical signs of atopic dermatitis (AD) in some dogs. Determinations of Malassezia hypersensitivity are often made with intradermal testing (IDT), which may have limited availability in a first-opinion veterinary practice. The purpose of this study was to compare immediate IDT reactivity to M. pachydermatis with results of an enzyme-linked immunosorbent assay (ELISA) designed to detect anti-Malassezia IgE. Eighty-four dogs with a clinical diagnosis of AD. Multi-allergen IDT was performed on all dogs. Serum testing for allergen-specific IgE against a panel of common environmental allergens and M. pachydermatis was performed by ELISA using the FcεRIα receptor fragment as a detection reagent, with results reported as adjusted optical density (OD). A receiver operating characteristic (ROC) curve was used to analyse the results of the two tests. The median adjusted OD of the anti-Malassezia IgE ELISA for dogs reactive and nonreactive to M. pachydermatis on IDT was 0.137 and 0.024, respectively. Analysis of the ROC curve suggested a cut-off point for the anti-Malassezia ELISA that yielded a sensitivity of 77.0% and a specificity of 89% relative to IDT results. Substantial agreement was demonstrated between IDT reactivity and anti-Malassezia IgE as detected by the FcεRIα receptor reagent. Although correlation with a clinical diagnosis of Malassezia dermatitis was not attempted in this study, the results indicate that the ELISA may be used to demonstrate the presence of immediate-type Malassezia hypersensitivity in dogs with AD. © 2014 ESVD and ACVD.

The identification and classification of skin irritation hazard by a human patch test.

PubMed

Basketter, D A; Whittle, E; Griffiths, H A; York, M

1994-08-01

There exist various regulatory instruments the purpose of which is to ensure that the intrinsic toxic hazards associated with substances and preparations are identified. In the context of identification of skin irritation potential, the method is normally the Draize test. Guidance notes provided by the OECD and the EEC expect that corrosive substances will have been screened out by a variety of methods. Substances or preparations which cause a sufficient degree of skin irritation will be classified as skin irritants. The primary motivation behind the present work was to introduce the concept that it is possible to assess the hazard potential of a substance or preparation to produce skin irritation in a human study. In the example presented here, 20% sodium lauryl sulfate (SLS) has been chosen as the positive control. With the protocol currently devised, occluded patch treatment with 20% SLS for up to 4 hr produces an irritant response in just over half of the panel. An irritant response is taken as a clinically evident and significant increase in erythema, oedema or dryness--a minimum of a+ reaction on the ICDRG scale. At such a level of response with the positive control (both in terms of intensity and in proportion of the panel), it is then possible to judge and/or to determine statistically, whether the test material has produced a level of skin irritation which is similar to, greater, or lower than the positive control. In this way a human patch test protocol can form a fundamental component of a strategy for the replacement of animals in determination of skin irritation and corrosion potential. By use of a careful and progressive protocol and by comparison of test data against a positive control it is both possible and practical to classify substances and preparations in terms of their skin irritation potential using that endpoint in the species of concern, man.

Anaphylaxis to Spirulina confirmed by skin prick test with ingredients of Spirulina tablets.

PubMed

Le, Thuy-My; Knulst, André C; Röckmann, Heike

2014-12-01

Spirulina (Arthrospira platensis), blue-green microalgae, has high content in proteins, γ-linoleic acid and vitamins and therefore gained popularity as food supplement. According to the Food and Agriculture Organization of the United Nations Spirulina is also an interesting alternative and sustainable protein source with the growing world population. We present a case of a 17-year-old male, who developed anaphylaxis the first time he ingested a Spirulina tablet. Skin prick test with diluted Spirulina tablet was positive. Further skin prick testing with separated ingredients (Spirulina platensis algae, silicon dioxide, inulin and magnesium stearate) was only positive for Spirulina platensis algae and negative in controls, confirming the allergy was caused by Spirulina and not by one of the additives. This case report shows that diagnosis of Spirulina allergy can safely be made by skin prick test with dilutions of the A. platensis or even more simple by skin prick test with the diluted tablet. Since Spirulina has gained popularity as food and nutritional supplement, it is important to realize the potential risk of this dietary supplement. Before Spirulina is produced and consumed on a wider scale, allergenicity risk assessment should be performed, including investigation of potential crossreactivity with well-known inhalant allergens and foods.

Acute generalized exanthematous pustulosis to amoxicillin associated with parvovirus B19 reactivation.

PubMed

Calistru, Ana Maria; Lisboa, Carmen; Cunha, Ana Paula; Bettencourt, Herberto; Azevedo, Filomena

2012-09-01

We report the case of a 22-year-old male patient with 2 episodes, 4 months apart, of acute generalized exanthematous pustulosis (AGEP) associated with oral intake of amoxicillin and simultaneous reactivation of parvovirus B19 infection proven by positive polymerase chain reaction test in the skin fragment and blood sample and elevation of the IgG antibodies titer. To our knowledge, this is the first report of AGEP resulting from the interaction between drug hypersensitivity and the reactivation of parvovirus B19. A combination of an immunological reaction to the drug and virus infection could be responsible for the clinical picture.

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.

Determination of total iron-reactive phenolics, anthocyanins and tannins in wine grapes of skins and seeds based on near-infrared hyperspectral imaging.

PubMed

Zhang, Ni; Liu, Xu; Jin, Xiaoduo; Li, Chen; Wu, Xuan; Yang, Shuqin; Ning, Jifeng; Yanne, Paul

2017-12-15

Phenolics contents in wine grapes are key indicators for assessing ripeness. Near-infrared hyperspectral images during ripening have been explored to achieve an effective method for predicting phenolics contents. Principal component regression (PCR), partial least squares regression (PLSR) and support vector regression (SVR) models were built, respectively. The results show that SVR behaves globally better than PLSR and PCR, except in predicting tannins content of seeds. For the best prediction results, the squared correlation coefficient and root mean square error reached 0.8960 and 0.1069g/L (+)-catechin equivalents (CE), respectively, for tannins in skins, 0.9065 and 0.1776 (g/L CE) for total iron-reactive phenolics (TIRP) in skins, 0.8789 and 0.1442 (g/L M3G) for anthocyanins in skins, 0.9243 and 0.2401 (g/L CE) for tannins in seeds, and 0.8790 and 0.5190 (g/L CE) for TIRP in seeds. Our results indicated that NIR hyperspectral imaging has good prospects for evaluation of phenolics in wine grapes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of intradermal dilutional testing, skin prick testing, and modified quantitative testing for common allergens.

PubMed

Peltier, Jacques; Ryan, Matthew W

2007-08-01

To compare and correlate wheal size using the Multi-Test II applicator with the endpoint obtained by intradermal dilutional testing (IDT) for 5 common allergens. To examine the safety of modified quantitative testing (MQT) for determining immunotherapy starting doses. Prospective comparative clinical study. A total of 134 subjects were simultaneously skin tested for immediate hypersensitivity using the Multi-Test II device and IDT. There was a 77% concordance between results from IDT and results from MQT. When there was a difference, MQT predicted a safer endpoint for starting immunotherapy in all but 2 cases. Wheal size by SPT is predictive of endpoint by IDT. MQT is nearly as effective as formal IDT in determining endpoint. Modified quantitative testing appears to be a safe alternative to IDT for determining starting doses for immunotherapy.

Usefulness of In Vivo and In Vitro Diagnostic Tests in the Diagnosis of Hypersensitivity Reactions to Quinolones and in the Evaluation of Cross-Reactivity: A Comprehensive Study Including the Latest Quinolone Gemifloxacin

PubMed Central

Gelincik, Asli; Akdeniz, Nilgun; Aktas-Cetin, Esin; Olgac, Muge; Unal, Derya; Ertek, Belkis; Coskun, Raif; Colakoğlu, Bahattin; Deniz, Gunnur; Buyukozturk, Suna

2017-01-01

Purpose Reports evaluating diagnosis and cross reactivity of quinolone hypersensitivity have revealed contradictory results. Furthermore, there are no reports investigating the cross-reactivity between gemifloxacin (GFX) and the others. We aimed to detect the usefulness of diagnostic tests of hypersensitivity reactions to quinolones and to evaluate the cross reactivity between different quinolones including the latest quinolone GFX. Methods We studied 54 patients (mean age 42.31±10.39 years; 47 female) with 57 hypersensitivity reactions due to different quinolones and 10 nonatopic quinolone tolerable control subjects. A detailed clinical history, skin test (ST), and single-blind placebo-controlled drug provocation test (SBPCDPT), as well as basophil activation test (BAT) and lymphocyte transformation test (LTT) were performed with the culprit and alternative quinolones including ciprofloxacin (CFX), moxifloxacin (MFX), levofloxacin (LFX), ofloxacin (OFX), and GFX. Results The majority (75.9%) of the patients reported immediate type reactions to various quinolones. The most common culprit drug was CFX (52.6%) and the most common reaction type was urticaria (26.3%). A quarter of the patients (24.1%) reacted to SBPCDPTs, although their STs were negative; while false ST positivity was 3.5% and ST/SBPCDPTs concordance was only 1.8%. Both BAT and LTT were not found useful in quinolone hypersensitivity. Cross-reactivity was primarily observed between LFX and OFX (50.0%), whereas it was the least between MFX and the others, and in GFX hypersensitive patients the degree of cross-reactivity to the other quinolones was 16.7%. Conclusions These results suggest that STs, BAT, and LTT are not supportive in the diagnosis of a hypersensitivity reaction to quinolone as well as in the prediction of cross-reactivity. Drug provocation tests (DPTs) are necessary to identify both culprit and alternative quinolones. PMID:28497922

Main approaches for delivering antioxidant vitamins through the skin to prevent skin ageing.

PubMed

Gašperlin, Mirjana; Gosenca, Mirjam

2011-07-01

One of the major contributions to skin photoageing and diseases is oxidative stress, caused by UV radiation inducing reactive oxygen and nitrogen species. Successful prophylaxis and therapy would necessitate control of the oxidant/antioxidant balance at the affected site, which can be achieved through the external supply of endogenous antioxidants. This review discusses possible strategies for dermal delivery of the antioxidant vitamins E and C, as oral supplementation has proved insufficient. These antioxidants have low skin bioavailability, owing to their poor solubility, inefficient skin permeability, or instability during storage. These drawbacks can be overcome by various approaches, such as chemical modification of the vitamins and the use of new colloidal drug delivery systems. New knowledge is included about the importance of: enhancing the endogenous skin antioxidant defense through external supply; the balance between various skin antioxidants; factors that can improve the skin bioavailability of antioxidants; and new delivery systems, such as microemulsions, used to deliver vitamins C and E into the skin simultaneously. A promising strategy for enhancing skin protection from oxidative stress is to support the endogenous antioxidant system, with antioxidants containing products that are normally present in the skin.

Menstrual cycle and cue reactivity in women smokers.

PubMed

Gray, Kevin M; DeSantis, Stacia M; Carpenter, Matthew J; Saladin, Michael E; LaRowe, Steven D; Upadhyaya, Himanshu P

2010-02-01

Emerging research suggests potential effects of the menstrual cycle on various aspects of smoking behavior in women, but results to date have been mixed. The present study sought to explore the influence of menstrual cycle phase on reactivity to smoking in vivo and stressful imagery cues in a sample of non-treatment-seeking women smokers. Via a within-subjects design, nicotine-dependent women (N = 37) participated in a series of four cue reactivity sessions, each during a distinct biologically verified phase of the menstrual cycle (early follicular [EF], mid-follicular [MF], mid-luteal [ML], and late luteal [LL]). Subjective (Questionnaire of Smoking Urges-Brief; QSU-B) and physiological (skin conductance and heart rate) measures of craving and reactivity were collected and compared across phases. Subjective reactive craving (QSU-B) to smoking in vivo cues varied significantly across the menstrual cycle (p = .02) and was higher in both EF and MF phases versus ML and LL phases, but this finding was not sustained when controlling for reactivity to neutral cues. Heart rate reactivity to stressful imagery cues (p = .01) and skin conductance reactivity to smoking in vivo cues (p = .05) varied significantly across the menstrual cycle upon controlling for reactivity to neutral cues, with highest reactivity during the MF phase. Menstrual cycle phase may have an effect on reactivity to smoking-related and stressful cues among women smokers. These findings contribute to an expanding literature, suggesting menstrual cycle effects on smoking behaviors in women.

Testing and Analysis of Composite Skin/Stringer Debonding Under Multi-Axial Loading

NASA Technical Reports Server (NTRS)

Krueger, Ronald; Cvitkovich, Michael K.; O'Brien, T. Kevin; Minguet, Pierre J.

2000-01-01

A consistent step-wise approach is presented to investigate the damage mechanism in composite bonded skin/stringer constructions under uniaxial and biaxial (in-plane/out-of-plane) loading conditions. The approach uses experiments to detect the failure mechanism, computational stress analysis to determine the location of first matrix cracking and computational fracture mechanics to investigate the potential for delamination growth. In a first step, tests were performed on specimens, which consisted of a tapered composite flange, representing a stringer or frame, bonded onto a composite skin. Tests were performed under monotonic loading conditions in tension, three-point bending, and combined tension/bending to evaluate the debonding mechanisms between the skin and the bonded stringer. For combined tension/bending testing, a unique servohydraulic load frame was used that was capable of applying both in-plane tension and out-of-plane bending loads simultaneously. Specimen edges were examined on the microscope to document the damage occurrence and to identify typical damage patterns. For all three load cases, observed failure initiated in the flange, near the flange tip, causing the flange to almost fully debond from skin. In a second step, a two dimensional plane-strain finite element model was developed to analyze the different test cases using a geometrically nonlinear solution. For all three loading conditions, computed principal stresses exceeded the transverse strength of the material in those areas of the flange where the matrix cracks had developed during the tests. In a third step, delaminations of various lengths were simulated in two locations where delaminations were observed during the tests. The analyses showed that at the loads corresponding to matrix ply crack initiation computed strain energy release rates exceeded the values obtained from a mixed mode failure criterion in one location, Hence. Unstable delamination propagation is likely to occur as

Testing and Analysis of Composite Skin/Stringer Debonding under Multi-Axial Loading

NASA Technical Reports Server (NTRS)

Krueger, Ronald; Cvitkovich, Michael; OBrien, Kevin; Minguet, Pierre J.

2000-01-01

A consistent step-wise approach is presented to investigate the damage mechanism in composite bonded skin/stringer constructions under uniaxial and biaxial (in-plane/out-of-plane) loading conditions. The approach uses experiments to detect the failure mechanism, computational stress analysis to determine the location of first matrix cracking and computational fracture mechanics to investigate the potential for delamination growth. In a first step, tests were performed on specimens, which consisted of a tapered composite flange, representing a stringer or frame, bonded onto a composite skin. Tests were performed under monotonic loading conditions in tension, three-point bending, and combined tension/bending to evaluate the debonding mechanisms between the skin and the bonded stringer. For combined tension/bending testing, a unique servohydraulic load frame was used that was capable of applying both in-plane tension and out-of-plane bending loads simultaneously. Specimen edges were examined on the microscope to document the damage occurrence and to identify typical damage patterns. For all three load cases, observed failure initiated in the flange, near the flange tip, causing the flange to almost fully debond from the skin. In a second step, a two-dimensional plane-strain finite element model was developed to analyze the different test cases using a geometrically nonlinear solution. For all three loading conditions, computed principal stresses exceeded the transverse strength of the material in those areas of the flange where the matrix cracks had developed during the tests. In a third step, delaminations of various lengths were simulated in two locations where delaminations were observed during the tests. The analyses showed that at the loads corresponding to matrix ply crack initiation computed strain energy release rates exceeded the values obtained from a mixed mode failure criterion in one location. Hence, unstable delamination propagation is likely to occur as

Antibiotic-induced immediate type hypersensitivity is a risk factor for positive allergy skin tests for neuromuscular blocking agents.

PubMed

Hagau, Natalia; Gherman, Nadia; Cocis, Mihaela; Petrisor, Cristina

2016-01-01

Skin tests for neuromuscular blocking agents (NMBAs) are not currently recommended for the general population undergoing general anaesthesia. In a previous study we have reported a high incidence of positive allergy tests for NMBAs in patients with a positive history of non-anaesthetic drug allergy, a larger prospective study being needed to confirm those preliminary results. The objective of this study was to compare the skin tests results for patients with a positive history of antibiotic-induced immediate type hypersensitivity reactions to those of controls without drug allergies. Ninety eight patients with previous antibiotic hypersensitivity and 72 controls were prospectively included. Skin tests were performed for atracurium, pancuronium, rocuronium, and suxamethonium. We found 65 positive skin tests from the 392 tests performed in patients with a positive history of antibiotic hypersensitivity (1 6.58%) and 23 positive skin tests from the 288 performed in controls (7.98%), the two incidences showing significant statistical difference (p = 0.0011). The relative risk for having a positive skin test for NMBAs for patients versus controls was 1.77 (1.15-2.76). For atracurium, skin tests were more often positive in patients with a positive history of antibiotic hypersensitivity versus controls (p = 0.02). For pancuronium, rocuronium and suxamethonium the statistical difference was not attained (p-values 0.08 for pancuronium, 0.23 for rocuronium, and 0.26 for suxamethonium). Patients with a positive history of antibiotic hypersensitivity seem to have a higher incidence of positive skin tests for NMBAs. They might represent a group at higher risk for developing intraoperative anaphylaxis compared to the general population. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

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

PubMed

Oesch, F; Fabian, E; Landsiedel, Robert

2018-06-18

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

Skin sensitization potency and cross-reactivity of p-phenylenediamine and its derivatives evaluated by non-radioactive murine local lymph node assay and guinea-pig maximization test.

PubMed

Yamano, Tetsuo; Shimizu, Mitsuru

2009-04-01

p-Phenylenediamine (PPD)-related chemicals have been used as antioxidants in rubber products, and many cases of contact dermatitis caused by these chemicals have been reported. The aim of this study was to investigate relative sensitizing potency and cross-reactivity among PPD derivatives. Five PPD derivatives, p-aminodiphenylamine (PADPA), N,N'-diphenyl-p-phenylenediamine (DPPD), N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (DMBPPD), N-(1-methylheptyl)-N'-phenyl-p-phenylenediamine (MHPPD), and the core chemical PPD were evaluated for their sensitizing potency and cross-reactivity using the non-radioactive murine local lymph node assay (LLNA) and the guinea-pig maximization test (GPMT). PPD and all the derivatives were identified as primary sensitizers in both tests. The order of potency in the LLNA was as follows: IPPD and PADPA > PPD > DMBPPD and MHPPD > DPPD. In the GPMT, all six groups of animals sensitized with one of these chemicals cross-reacted to four other derivatives. Specifically, the five groups that have a common basic PADPA structure, that is PADPA, DPPD, IPPD, DMBPPD, and MHPPD, all reacted to each other at almost the same scores, while none of them reacted to PPD. The cross-reactivity profile found in the study was to some extent different from that in previous human data, where distinction between cross-reaction and concomitant primary sensitization is not always clear.

Measurement and interpretation of skin prick test results.

PubMed

van der Valk, J P M; Gerth van Wijk, R; Hoorn, E; Groenendijk, L; Groenendijk, I M; de Jong, N W

2015-01-01

There are several methods to read skin prick test results in type-I allergy testing. A commonly used method is to characterize the wheal size by its 'average diameter'. A more accurate method is to scan the area of the wheal to calculate the actual size. In both methods, skin prick test (SPT) results can be corrected for histamine-sensitivity of the skin by dividing the results of the allergic reaction by the histamine control. The objectives of this study are to compare different techniques of quantifying SPT results, to determine a cut-off value for a positive SPT for histamine equivalent prick -index (HEP) area, and to study the accuracy of predicting cashew nut reactions in double-blind placebo-controlled food challenge (DBPCFC) tests with the different SPT methods. Data of 172 children with cashew nut sensitisation were used for the analysis. All patients underwent a DBPCFC with cashew nut. Per patient, the average diameter and scanned area of the wheal size were recorded. In addition, the same data for the histamine-induced wheal were collected for each patient. The accuracy in predicting the outcome of the DBPCFC using four different SPT readings (i.e. average diameter, area, HEP-index diameter, HEP-index area) were compared in a Receiver-Operating Characteristic (ROC) plot. Characterizing the wheal size by the average diameter method is inaccurate compared to scanning method. A wheal average diameter of 3 mm is generally considered as a positive SPT cut-off value and an equivalent HEP-index area cut-off value of 0.4 was calculated. The four SPT methods yielded a comparable area under the curve (AUC) of 0.84, 0.85, 0.83 and 0.83, respectively. The four methods showed comparable accuracy in predicting cashew nut reactions in a DBPCFC. The 'scanned area method' is theoretically more accurate in determining the wheal area than the 'average diameter method' and is recommended in academic research. A HEP-index area of 0.4 is determined as cut-off value for a

In vitro characterization of cutaneous immunotoxicity of immortalized human keratinocytes (HaCaT) exposed to reactive and disperse textile dyes.

PubMed

Leme, Daniela Morais; Sehr, Andrea; Grummt, Tamara; Gonçalves, Jenifer Pendiuk; Jacomasso, Thiago; Winnischofer, Sheila Maria Brochado; Potrich, Francine Bittencourt; Oliveira, Carolina Camargo de; Trindade, Edvaldo da Silva; de Oliveira, Danielle Palma

2018-05-01

Several synthetic dyes are used by textile industry for supplying the market of colored clothes. However, these chemicals have been associated with a variety of adverse human health effects, including textile dermatitis. Thus, there is a growing concern to identify textile dyes potentially as skin immunotoxicants. The aim of this in vitro study was to characterize the immunotoxic potential of reactive (Reactive Green 19 [RG19], Reactive Blue 2 [RB2], Reactive Black 5 [RB5]) and disperse (Disperse Red 1 [DR1]) textile dyes using a dermal cell line. For this purpose, a cell-based approach was conducted with immortalized human keratinocytes (KC) (HaCaT) using selected biomarkers of cutaneous inflammation including modulation of matrix metalloproteinases (MMP), oxidative stress such as reactive oxygen species (ROS) generation, and inflammatory cytokine profile. DR1 was the only dye able to trigger an immune response such as release of IL-12 cytokine, a potent co-stimulator of T helper 1 cell, which may be considered as a skin immunotoxicant. The reactive dyes including RB5 that were previously reported as skin sensitizers failed to induce inflammatory reactions under the conditions tested. The reactive dyes studied may pose a risk to human KC by induction of effects related to modulation of MMP-2 (RB5) and -9 (RB5 and RB2) and generation of ROS (RG19 and RB2). Thus, all these dyes need to be used with caution to avoid undesirable effects to consumers who may be exposed dermally.

Tests of Flammability of Cotton Fabrics and Expected Skin Burns in Microgravity

NASA Technical Reports Server (NTRS)

Cavanagh, Jane M.; Torvi, David A.; Gabriel, Kamiel S.; Ruff, Gary A.

2004-01-01

During a shuttle launch and other portions of space flight, astronauts wear specialized flame resistant clothing. However during most of their missions on board the Space Shuttle or International Space Station, astronauts wear ordinary clothing, such as cotton shirts and pants. As the behaviour of flames is considerably different in microgravity than under earth's gravity, fabrics are expected to burn in a different fashion in microgravity than when tested on earth. There is interest in determining how this change in burning behaviour may affect times to second and third degree burn of human skin, and how the results of standard fabric flammability tests conducted under earth's gravity correlate with the expected fire behaviour of textiles in microgravity. A new experimental apparatus was developed to fit into the Spacecraft Fire Safety Facility (SFSF), which is used on NASA's KC-135 low gravity aircraft. The new apparatus was designed to be similar to the apparatus used in standard vertical flammability tests of fabrics. However, rather than using a laboratory burner, the apparatus uses a hot wire system to ignite 200 mm high by 80 mm wide fabric specimens. Fabric temperatures are measured using thermocouples and/or an infrared imaging system, while flame spread rates are measured using real time observations or video. Heat flux gauges are placed between 7 and 13 mm away from the fabric specimen, so that heat fluxes from the burning fabric to the skin can be estimated, along with predicted times required to produce skin burns. In November of 2003, this new apparatus was used on the KC-135 aircraft to test cotton and cotton/polyester blend fabric specimens in microgravity. These materials were also been tested using the same apparatus in 1-g, and using a standard vertical flammability test that utilizes a flame. In this presentation, the design of the test apparatus will be briefly described. Examples of results from the KC-135 tests will be provided, including

The potential utility of iodinated contrast media (ICM) skin testing in patients with ICM hypersensitivity.

PubMed

Ahn, Young-Hwan; Koh, Young-Il; Kim, Joo-Hee; Ban, Ga-Young; Lee, Yeon-Kyung; Hong, Ga-Na; Jin, U-Ram; Choi, Byung-Joo; Shin, Yoo-Seob; Park, Hae-Sim; Ye, Young-Min

2015-03-01

Both immediate and delayed hypersensitivity reactions to iodinated contrast media (ICM) are relatively common. However, there are few data to determine the clinical utility of immunologic evaluation of ICM. To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity, 23 patients (17 immediate and 6 delayed reactions) were enrolled from 3 university hospitals in Korea. With 6 commonly used ICM including iopromide, iohexol, ioversol, iomeprol, iopamidol and iodixanol, skin prick (SPT), intradermal (IDT) and patch tests were performed. Of 10 patients with anaphylaxis, 3 (30.0%) and 6 (60.0%) were positive respectively on SPTs and IDTs with the culprit ICM. Three of 6 patients with urticaria showed positive IDTs. In total, 11 (64.7%) had positive on either SPT or IDT. Three of 6 patients with delayed rashes had positive response to patch test and/or delayed IDT. Among 5 patients (3 anaphylaxis, 1 urticaria and 1 delayed rash) taken subsequent radiological examinations, 3 patients administered safe alternatives according to the results of skin testing had no adverse reaction. However, anaphylaxis developed in the other 2 patients administered the culprit ICM again. With 64.7% (11/17) and 50% (3/6) of the sensitivities of corresponding allergic skin tests with culprit ICM for immediate and delayed hypersensitivity reactions, the present study suggests that skin tests is useful for the diagnosis of ICM hypersensitivity and for selecting safe ICM and preventing a recurrence of anaphylaxis caused by the same ICM.

Towards label-free evaluation of oxidative stress in human skin exposed to sun filters (Conference Presentation)

NASA Astrophysics Data System (ADS)

Osseiran, Sam; Wang, Hequn; Suita, Yusuke; Roider, Elisabeth; Fisher, David E.; Evans, Conor L.

2016-02-01

Skin cancer, including basal cell carcinoma, squamous cell carcinoma, and melanoma, is the most common form of cancer in North America. Paradoxically, skin cancer incidence is steadily on the rise even despite the growing use of sunscreens over the past decades. One potential explanation for this discrepancy involves the sun filters in sunscreen, which are responsible for blocking harmful ultraviolet radiation. It is proposed that these agents may produce reactive oxygen species (ROS) at the site of application, thereby generating oxidative stress in skin that gives rise to genetic mutations, which may explain the rising incidence of skin cancer. To test this hypothesis, ex vivo human skin was treated with five common chemical sun filters (avobenzone, octocrylene, homosalate, octisalate, and oxybenzone) as well as two physical sun filters (zinc oxide compounds), both with and without UV irradiation. To non-invasively evaluate oxidative stress, two-photon excitation fluorescence (2PEF) and fluorescence lifetime imaging microscopy (FLIM) of the skin samples were used to monitor levels of NADH and FAD, two key cofactors in cellular redox metabolism. The relative redox state of the skin was assessed based on the fluorescence intensities and lifetimes of these endogenous cofactors. While the sun filters were indeed shown to have a protective effect from UV radiation, it was observed that they also generate oxidative stress in skin, even in the absence of UV light. These results suggest that sun filter induced ROS production requires more careful study, especially in how these reactive species impact the rise of skin cancer.

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.

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

Systemic Allergy to Corticosteroids: Clinical Features and Cross Reactivity.

PubMed

Barbaud, Annick; Waton, Julie

2016-01-01

Systemic hypersensitivity (HS) to corticosteroids (CS) is paradoxical but does exist. Some patients with a previous contact allergy to topical CS may develop a systemic contact dermatitis (SCD) while receiving CS orally or intravenously. However, a previous contact sensitization is not mandatory for developing a systemic HS to CS. Acute or delayed urticaria can occur in immediate HS. Immediate HS can be due to excipients, mainly carboxymethylcellulose or to CS themselves. Delayed reactions, mainly maculopapular rash and acute generalized exanthematous pustulosis can occur. Skin tests with systemic CS have to be standardized. It is necessary to determine if IDT with CS frequently induce skin atrophy or not and if such skin atrophy is transient by doing prospective studies using an standardized method and a limited injected volume (0.02 ml). Patch tests can be done in delayed HS, with readings at day 2, 4 and 7. In SCD, the Baeck's classification of CS in 3 chemical groups could explain cross reactivity between systemic CS. However, this classification is not applicable to explain cross-reactions between in systemic HS. According to the literature, 52/79 patients had a HS reaction to a group confirmed by a positive allergological investigations, but had a negative provocation test with another CS belonging to the same group. In case of non-severe cutaneous adverse reactions and when skin tests are negative, provocation tests have to be performed to find an alternative CS, even if it belongs to the same chemical group as those responsible for the initial reaction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Tuberculin reactivity and tuberculosis epidemiology in the Pakaanóva (Wari') Indians of Rondônia, south-western Brazilian Amazon.

PubMed

Escobar, A L; Coimbra, C E A; Camacho, L A B; Santos, R V

2004-01-01

To investigate the characteristics of tuberculin skin test reactivity in the Pakaanóva Indians, in Amazonia, Brazil, after revaccination of all study participants with bacille Calmette-Guerin (BCG). The investigation was designed as a post-BCG vaccination purified protein derivative (PPD) survey. Data included PPD readings, age, sex, nutritional status, place of residence, previous tuberculosis, physical examinations and BCG status. Bivariate and multivariate logistic regression analyses were conducted. About 90% (n = 505) of the total population participated. One third (32.1%) of the subjects presented induration > or = 10 mm at 72 h. Induration sizes showed weak linear correlation with age; differences between sexes were not observed. Skin reaction was not associated with nutritional status. Individuals with a history of tuberculosis were six times more likely to test positive. History of tuberculosis, age, and previous BCG vaccination were significantly associated with PPD reactivity in the multivariate analyses. The Pakaanóva showed a high proportion (58.4%) of non-reactors, even with a recent BCG booster. Sex differences in PPD reactivity were either not present or could not be demonstrated. The association between age and PPD reactivity resembles that observed in other Amazonian populations. The authors discuss the potential of PPD testing as a screening tool to enhance tuberculosis detection, especially in indigenous populations in Amazonia with limited access to health services.

Quiz: Test Your Skin Cancer IQ

MedlinePlus

... three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma, and melanoma. They can develop from the uncontrolled growth of three different types of skin cells: basal cells, squamous cells, and melanocytes, respectively. A is the correct answer. ...

Effect of Topical Steroids on Skin Prick Test: A Randomized Controlled Trial.

PubMed

Ebbesen, Anne R; Riis, Lene A; Gradman, Josefine

2018-05-04

Topically applied corticosteroids on the skin can significantly inhibit the wheal response to allergens in skin prick test (SPT). The duration of this effect is unknown. The aim of this study is to investigate the duration of the inhibitory effect of topical corticosteroids on SPT. Twenty-two healthy subjects were included in a single-blinded randomized study. All subjects were skin prick tested using a standard inhalant allergen panel. The subjects were randomized to treat either the left or right forearm with Betnovat ® cream (group III steroid) once a day for 10 days. Subsequently, the subjects were skin prick tested the following 5 days and at day 8 on both forearms. At baseline, the 22 individuals had positive SPT for a total of 72 allergens. Compared with the untreated arm, the mean size of the wheals was significantly reduced on day 1 (12 h after end of treatment) by 0.56 mm (95 % confidence interval (CI) [0.06; 1.06], p = 0.03) for allergens and 0.70 mm [0.32; 1.09] (p = 0.001) for histamine. On day 2 (36 h after end of treatment), the mean difference between treated and untreated arm was 0.47 mm [-0.08; 0.85] (p = 0.02) for allergen-induced wheals and 0.22 mm [-0.21; 0.64] (p = 0.31) for histamine-induced wheal. On day 3, 4, 5, and 8, there was no significant difference. Treatment with topical steroid significantly inhibited the response to SPT for 36 h but for less than 3 days. In addition, we demonstrated that topical applied corticosteroids inhibit the mean wheal size of the positive histamine control for a shorter time than for the allergens. Consequently, positive response to histamine control is not a valid marker for reliable skin prick test in steroid-treated patients. Plain language summary available for this article.

Physiological correlates of emotional reactivity and regulation in early adolescents.

PubMed

Latham, Melissa D; Cook, Nina; Simmons, Julian G; Byrne, Michelle L; Kettle, Jonathan W L; Schwartz, Orli; Vijayakumar, Nandita; Whittle, Sarah; Allen, Nicholas B

2017-07-01

Few studies have examined physiological correlates of emotional reactivity and regulation in adolescents, despite the occurrence in this group of significant developmental changes in emotional functioning. The current study employed multiple physiological measures (i.e., startle-elicited eyeblink and ERP, skin conductance, facial EMG) to assess the emotional reactivity and regulation of 113 early adolescents in response to valenced images. Reactivity was measured while participants viewed images, and regulation was measured when they were asked to discontinue or maintain their emotional reactions to the images. Adolescent participants did not exhibit fear-potentiated startle blink. However, they did display affect-consistent zygomatic and corrugator activity during reactivity, as well as inhibition of some of these facial patterns during regulation. Skin conductance demonstrated arousal dependent activity during reactivity, and overall decreases during regulation. These findings suggest that early adolescents display reactivity to valenced pictures, but not to startle probes. Psychophysiological patterns during emotion regulation indicate additional effort and/or attention during the regulation process. Copyright © 2017 Elsevier B.V. All rights reserved.

[Characteristics of allergic conjunctivitis with positive skin prick test].

PubMed

Yang, S; Jiang, Y; Jin, Y M; Zhang, J Y; Li, Y

2017-09-11

Objective: To observe the clinical characteristics of allergic conjunctivitis, and the correlations with skin prick test results. Methods: A retrospective study. Forty patients with positive skin prick test result were included. Patients underwent an ophthalmologic examination to identify their primary presenting signs and symptoms. The allergy types were divided into 5 groups. All dates were analyzed for the dependence, normality and homogeneity of variance. Chi-square test, Mann-Whitney U test, Kruskal-Wallis H test and Spearman correlation analysis were performed accordingly. Results: Among 40 patients, 18(45.0%) had a clinical diagnosis of seasonal allergic conjunctivitis, 14(35.0%) had perennial allergic conjunctivitis, 5(12.5%) had vernal keratoconjunctivitis, and 2(5.0%) had atopic keratoconjunctivits, and 1(2.5%) had giant papillary conjunctivitis. There was no significant difference in the number of symptoms and signs score among different types of allergic conjunctivitis, the score of itching and hyperemia had a positive relationship with the number of positive allergens ( r =0.74, P< 0.05. r =0.96, P< 0.05). The primary symptoms and signs are itching and hyperemia; dust and pollens are the most common allergens. The more positive result of the test of the allergen, the more symptoms and signs encountered in terms of severity. Conclusion: Seasonal allergic conjunctivitis was the most prevalent disorder, the most important clinical characteristics of allergic conjunctivitis are itching and conjunctival congestion, the main allergens are dust and pollens, patients may be sensitive to multiple allergens. (Chin J Ophthalmol, 2017, 53: 689-693) .

Executive functioning performance predicts subjective and physiological acute stress reactivity: preliminary results.

PubMed

Hendrawan, Donny; Yamakawa, Kaori; Kimura, Motohiro; Murakami, Hiroki; Ohira, Hideki

2012-06-01

Individual differences in baseline executive functioning (EF) capacities have been shown to predict state anxiety during acute stressor exposure. However, no previous studies have clearly demonstrated the relationship between EF and physiological measures of stress. The present study investigated the efficacy of several well-known EF tests (letter fluency, Stroop test, and Wisconsin Card Sorting Test) in predicting both subjective and physiological stress reactivity during acute psychosocial stress exposure. Our results show that letter fluency served as the best predictor for both types of reactivity. Specifically, the higher the letter fluency score, the lower the acute stress reactivity after controlling for the baseline stress response, as indicated by lower levels of state anxiety, negative mood, salivary cortisol, and skin conductance. Moreover, the predictive power of the letter fluency test remained significant for state anxiety and cortisol indices even after further adjustments for covariates by adding the body mass index (BMI) as a covariate. Thus, good EF performance, as reflected by high letter fluency scores, may dampen acute stress responses, which suggests that EF processes are directly associated with aspects of stress regulation. Copyright © 2012 Elsevier B.V. All rights reserved.

Penicillin skin testing in cardiac surgery.

PubMed

Cook, David J; Barbara, David W; Singh, Karen E; Dearani, Joseph A

2014-06-01

Penicillin is the most commonly reported allergy in cardiac surgical patients and a history of penicillin allergy frequently results in the use of vancomycin for antibiotic prophylaxis. However, clinical history is unreliable and true allergy is rare. Penicillin allergy testing has the potential to reduce vancomycin use and indirectly the potential for selection of vancomycin-resistant organisms, a national priority. After the publication of the 2007 Society of Thoracic Surgeons practice guideline report, we initiated a penicillin allergy testing service for cardiac surgical patients in 2009. We sought to determine the true incidence of penicillin allergy in the tested population, whether testing availability reduced vancomycin use in those tested, and if vancomycin use was reduced in the entire cardiac surgical population as a whole. A total of 276 patients were skin tested for allergy to penicillin or cephalosporin. Testing recommended no penicillin use in 13.8% of those tested giving a true penicillin allergy incidence of 0.9%. Only 24 of the 276 patients tested (9%) received vancomycin. However, given the small percentage of the total population that underwent allergy testing, the overall use of vancomycin in the cardiac surgery practice was not reduced in the posttesting period. The true rate of contraindication to penicillin in a cardiac surgical population is very low. Penicillin allergy testing can reduce vancomycin use in the tested population, but better means of conducting the testing and making the results available are necessary to reduce unnecessary vancomycin use in a broader cardiac surgical population. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

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

Development and psychometric testing of the 'Motivation and Self-Efficacy in Early Detection of Skin Lesions' index.

PubMed

Dyson, Judith; Cowdell, Fiona

2014-12-01

To develop and psychometrically test the Motivation and Self-Efficacy in Early Detection of Skin Lesions Index. Skin cancer is the most frequently diagnosed cancer worldwide. The primary strategy used to prevent skin cancer is promotion of sun avoidance and the use of sun protection. However, despite costly and extensive campaigns, cases of skin cancer continue to increase. If found and treated early, skin cancer is curable. Early detection is, therefore, very important. The study was conducted in 2013. Instrument Development. A literature review and a survey identified barriers (factors that hinder) and levers (factors that help) to skin self-examination. These were categorized according to a the Theoretical Domains Framework and this formed the basis of an instrument, which was tested for validity and reliability using confirmatory factor analysis and Cronbach's alpha respectively. A five-factor 20-item instrument was used that tested well for reliability and construct validity. Test-retest reliability was good for all items and domains. The five factors were: (i) Outcome expectancies; (ii) Intention; (iii) Self-efficacy; (iv) Social influences; (v) Memory. The Motivation and Self-Efficacy in Early Detection of Skin Lesions Index provides a reliable and valid method of assessing barriers and levers to skin self-examination. The next step is to design a theory-based intervention that can be tailored according to individual determinants to behaviour change identified by this instrument. © 2014 John Wiley & Sons Ltd.

Instability of delayed-type hypersensitivity skin test anergy in human immunodeficiency virus infection.

PubMed

Caiaffa, W T; Graham, N M; Galai, N; Rizzo, R T; Nelson, K E; Vlahov, D

1995-10-23

To evaluate stability of delayed-type hypersensitivity (DTH) skin test over time in human immunodeficiency virus (HIV)-seropositive and HIV-seronegative injecting drug users. A community-based cohort of injecting drug users who had serial skin testing with purified protein derivative tuberculin, mumps, and Candida albicans antigen. Delayed-type hypersensitivity anergy was defined as a skin test result of less than 3 mm for all three antigens; DTH positivity was a skin test result of 3 mm or greater for at least one antigen (Centers for Disease Control and Prevention, Atlanta, Ga, 1993). At baseline, 36% of HIV-seropositive subjects (n = 401) were anergic as compared with 14% of HIV-seronegative subjects (n = 552; P < .001). During follow-up, fewer HIV-seropositive subjects remained DTH positive (42%) and more remained anergic (19%) than of HIV-seronegative subjects (67% and 7%, respectively). Twenty-four percent of HIV-seropositive subjects who were initially DTH positive became anergic as compared with 15.3% of the HIV-seronegative subjects. However, the proportion changing from anergy to DTH positivity was greater among HIV-seropositive subjects (15%) than HIV-seronegative subjects (12%). In comparison to those who remained DTH positive, HIV-seropositive subjects with CD4 cell counts of less than 0.50 x 10(9)/L (odds ratio = 6.4) and less than 0.35 x 10(9)/L (odds ratio = 11.2) were more likely to remain anergic than those who had CD4 cell counts above 0.50 x 10(9)/L or were HIV seronegative. Although the prevalence and incidence of DTH anergy were higher in HIV-seropositive subjects, high rates of change in DTH status occurred in both directions. This suggests that instability of DTH skin testing is substantial and only partially dependent on HIV status. Although a single test may be an unreliable indicator of HIV-induced immunosuppression, two consecutive anergic readings were strongly associated with a CD4 cell count below 0.50 x 10(9)/L and particularly below

A computerized test battery for the assessment of cardiovascular reactivity.

PubMed

Debski, T T; Kamarck, T W; Jennings, J R; Young, L W; Eddy, M J; Zhang, Y X

1991-01-01

Recent evidence has suggested a possible relationship between the tendency to exhibit excessive cardiovascular reactions during psychological challenge and the risk of cardiovascular disease. Valid techniques for reliably assessing such reactions are, however, minimally available. A test battery for the assessment of cardiovascular reactivity to experimental challenge is currently being developed at the University of Pittsburgh in conjunction with the University of Miami and Duke University. An IBM-AT compatible microcomputer is being used for the concurrent collection of physiological data and presentation of the laboratory stressors. Digitized cardiovascular data being collected include EKG, Impedance Cardiogram (ICG), phonocardiogram, and a peripheral pulse wave measure. Blood pressure readings are also being collected and stored on disk. The computer presents three challenging video games, each designed to elicit cardiovascular reactions. Processing programs are being used and developed for the standardized scoring of the digitized signals. To assist in epidemiological research a mobile testing unit has been assembled for the easy administration of the test battery in varying geographical locations. The test battery being developed will increase the feasibility of epidemiological and clinical assessment of stress-induced cardiovascular responses which may substantiate a link between reactivity and cardiovascular disease.

Identification of danger signals in nevirapine-induced skin rash.

PubMed

Zhang, Xiaochu; Sharma, Amy M; Uetrecht, Jack

2013-09-16

Nevirapine (NVP) can cause serious skin rashes and hepatotoxicity. It also causes an immune-mediated skin rash in rats but not hepatotoxicity. This rash is caused by a metabolite of NVP; specifically, NVP is oxidized in the liver to a benzylic alcohol (12-OH-NVP), which travels to the skin where it forms a reactive benzylic sulfate. This could both act as a hapten and induce a danger signal. In contrast, most of the covalent binding in the liver involves oxidation of the methyl group leading to a reactive quinone methide. In this study, we examined the effects of NVP and 12-OH-NVP on gene expression in the liver and skin. Both NVP and 12-OH-NVP induced changes in the liver, but the list of genes was different, presumably reflecting different bioactivation pathways. In contrast, many more genes were up-regulated in the skin by 12-OH-NVP than by NVP, which is consistent with the fact that 12-OH-NVP is an obligate intermediate in the formation of the reactive sulfate in the skin. Genes up-regulated by 12-OH-NVP in the skin included TRIM63 (18-fold increase), S100a7a (7-fold increase), IL22-RA2 (4-fold increase), and DAPK1 (3-fold increase). TRIM63 acts as a ubiquitin ligase, which is consistent with protein damage leading to an increase in protein turnover. In addition, TRIM proteins are involved in inflammasome activation, and it appears that inflammasome activation is an essential step in the induction of NVP-induced skin rash. S100A7 is considered a danger signal, and its upregulation supports the danger hypothesis. Upregulation of the IL-22 RA2 gene marks an immune response. DAPK1 is involved with inflammasome assembly through binding directly to NLRP3, a NOD-like receptor expressed in keratinocytes. These results provide important clues to how NVP causes the induction of an immune response, in this case leading to skin rash.

De-labelling self-reported penicillin allergy within the emergency department through the use of skin tests and oral drug provocation testing.

PubMed

Marwood, Joseph; Aguirrebarrena, Gonzalo; Kerr, Stephen; Welch, Susan A; Rimmer, Janet

2017-10-01

Self-reported penicillin allergy is common among patients attending the ED, but is a poor predictor of true immunoglobulin E-mediated hypersensitivity to penicillin. We hypothesise that with a combination of skin testing and drug provocation testing, selected patients can be safely de-labelled of their allergy. This prospective study enrolled a sample of patients presenting to an urban academic ED between 2011 and 2016 with a self-reported allergy to penicillin. Standardised skin prick and intradermal testing with amoxicillin and both major and minor determinants of penicillin was performed in the department. If negative, testing was followed by a graded oral challenge of amoxicillin over 9 days. The primary end point was the allergy status of participants at the end of the study. A total of 100 patients (mean age 42; standard deviation 14 years; 54% women) completed the testing. Of these, 81% (95% confidence interval 71.9-88.2) showed no hypersensitivity to penicillin and were labelled non-allergic. The majority (16/19) of allergies were confirmed by skin testing, with three suspected allergies detected by the oral challenge. Women were more likely than men to have a true penicillin allergy, with odds ratio of 4.0 (95% confidence interval 1.23-13.2). There were no serious adverse events. Selected patients in the ED who self-report an allergy to penicillin can be safely tested there for penicillin allergy, using skin tests and oral drug provocation testing. This testing allows a significant de-labelling of penicillin allergy, with the majority of these patients able to tolerate penicillin without incident. © 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Apparatus for testing skin samples or the like

DOEpatents

Holland, J.M.

1982-08-31

An apparatus for testing the permeability of living skin samples has a flat base with a plurality of sample-holding cavities formed in its upper surface, the samples being placed in counterbores in the cavities with the epidermis uppermost. O-rings of Teflon washers are respectively placed on the samples and a flat cover is connected to the base to press the rings against the upper surfaces of the samples. Media to maintain tissue viability and recovery of metabolites is introduced into the lower portion of the sample-holding cavities through passages in the base. Test materials are introduced through holes in the cover plate after assembly of the chamber.

Application of a Virtual Reactivity Feedback Control Loop in Non-Nuclear Testing of a Fast Spectrum Reactor

NASA Technical Reports Server (NTRS)

Bragg-Sitton, Shannon M.; Forsbacka, Matthew

2004-01-01

For a compact, fast-spectrum reactor, reactivity feedback is dominated by core deformation at elevated temperature. Given the use of accurate deformation measurement techniques, it is possible to simulate nuclear feedback in non-nuclear electrically heated reactor tests. Implementation of simulated reactivity feedback in response to measured deflection is being tested at the NASA Marshall Space Flight Center Early Flight Fission Test Facility (EFF-TF). During tests of the SAFE-100 reactor prototype, core deflection was monitored using a high resolution camera. "virtual" reactivity feedback was accomplished by applying the results of Monte Carlo calculations (MCNPX) to core deflection measurements; the computational analysis was used to establish the reactivity worth of van'ous core deformations. The power delivered to the SAFE-100 prototype was then dusted accordingly via kinetics calculations, The work presented in this paper will demonstrate virtual reactivity feedback as core power was increased from 1 kilowatt(sub t), to 10 kilowatts(sub t), held approximately constant at 10 kilowatts (sub t), and then allowed to decrease based on the negative thermal reactivity coefficient.

Assuring consumer safety without animal testing: a feasibility case study for skin sensitisation.

PubMed

Maxwell, Gavin; Aleksic, Maja; Aptula, Aynur; Carmichael, Paul; Fentem, Julia; Gilmour, Nicola; Mackay, Cameron; Pease, Camilla; Pendlington, Ruth; Reynolds, Fiona; Scott, Daniel; Warner, Guy; Westmoreland, Carl

2008-11-01

Allergic Contact Dermatitis (ACD; chemical-induced skin sensitisation) represents a key consumer safety endpoint for the cosmetics industry. At present, animal tests (predominantly the mouse Local Lymph Node Assay) are used to generate skin sensitisation hazard data for use in consumer safety risk assessments. An animal testing ban on chemicals to be used in cosmetics will come into effect in the European Union (EU) from March 2009. This animal testing ban is also linked to an EU marketing ban on products containing any ingredients that have been subsequently tested in animals, from March 2009 or March 2013, depending on the toxicological endpoint of concern. Consequently, the testing of cosmetic ingredients in animals for their potential to induce skin sensitisation will be subject to an EU marketing ban, from March 2013 onwards. Our conceptual framework and strategy to deliver a non-animal approach to consumer safety risk assessment can be summarised as an evaluation of new technologies (e.g. 'omics', informatics), leading to the development of new non-animal (in silico and in vitro) predictive models for the generation and interpretation of new forms of hazard characterisation data, followed by the development of new risk assessment approaches to integrate these new forms of data and information in the context of human exposure. Following the principles of the conceptual framework, we have been investigating existing and developing new technologies, models and approaches, in order to explore the feasibility of delivering consumer safety risk assessment decisions in the absence of new animal data. We present here our progress in implementing this conceptual framework, with the skin sensitisation endpoint used as a case study. 2008 FRAME.

Missed opportunities: refusal to confirm reactive rapid HIV tests in the emergency department.

PubMed

Ganguli, Ishani; Collins, Jamie E; Reichmann, William M; Losina, Elena; Katz, Jeffrey N; Arbelaez, Christian; Donnell-Fink, Laurel A; Walensky, Rochelle P

2013-01-01

HIV infection remains a major US public health concern. While HIV-infected individuals now benefit from earlier diagnosis and improved treatment options, progress is tempered by large numbers of newly diagnosed patients who are lost to follow-up prior to disease confirmation and linkage to care. In the randomized, controlled USHER trial, we offered rapid HIV tests to patients presenting to a Boston, MA emergency department. Separate written informed consent was required for confirmatory testing. In a secondary analysis, we compared participants with reactive results who did and did not complete confirmatory testing to identify factors associated with refusal to complete the confirmation protocol. Thirteen of 62 (21.0%, 95% CI (11.7%, 33.2%)) participants with reactive rapid HIV tests refused confirmation; women, younger participants, African Americans, and those with fewer HIV risks, with lower income, and without primary care doctors were more likely to refuse. We projected that up to four true HIV cases were lost at the confirmation stage. These findings underscore the need to better understand the factors associated with refusal to confirm reactive HIV testing and to identify interventions that will facilitate confirmatory testing and linkage to care among these populations. ClinicalTrials.gov NCT00502944; NCT01258582.

TIMES-SS--recent refinements resulting from an industrial skin sensitisation consortium.

PubMed

Patlewicz, G; Kuseva, C; Mehmed, A; Popova, Y; Dimitrova, G; Ellis, G; Hunziker, R; Kern, P; Low, L; Ringeissen, S; Roberts, D W; Mekenyan, O

2014-01-01

The TImes MEtabolism Simulator platform for predicting Skin Sensitisation (TIMES-SS) is a hybrid expert system, first developed at Bourgas University using funding and data from a consortium of industry and regulators. TIMES-SS encodes structure-toxicity and structure-skin metabolism relationships through a number of transformations, some of which are underpinned by mechanistic 3D QSARs. The model estimates semi-quantitative skin sensitisation potency classes and has been developed with the aim of minimising animal testing, and also to be scientifically valid in accordance with the OECD principles for (Q)SAR validation. In 2007 an external validation exercise was undertaken to fully address these principles. In 2010, a new industry consortium was established to coordinate research efforts in three specific areas: refinement of abiotic reactions in the skin (namely autoxidation) in the skin, refinement of the manner in which chemical reactivity was captured in terms of structure-toxicity rules (inclusion of alert reliability parameters) and defining the domain based on the underlying experimental data (study of discrepancies between local lymph node assay Local Lymph Node Assay (LLNA) and Guinea Pig Maximisation Test (GPMT)). The present paper summarises the progress of these activities and explains how the insights derived have been translated into refinements, resulting in increased confidence and transparency in the robustness of the TIMES-SS predictions.

Factors associated with negative histamine control for penicillin allergy skin testing in the inpatient setting.

PubMed

Geng, Bob; Thakor, Ami; Clayton, Elisabeth; Finkas, Lindsay; Riedl, Marc A

2015-07-01

Identification of factors adversely affecting the utility of allergy skin testing is important in optimizing patient care. Inpatient penicillin skin test data from 1997 through 2007 demonstrate that up to 20% of attempted penicillin skin tests are indeterminate owing to a negative histamine test response, despite exclusion of H1 antagonists. Critical illness, vasopressors, steroid use, and psychotropic medications have been postulated to influence outcomes, but large studies are lacking. To identify factors associated with a negative histamine test response for the inpatient setting. Fifty-two cases were identified with a negative histamine response after penicillin skin testing in the absence of antihistamine therapy for 72 hours before testing. One hundred twenty-five controls with a normal histamine response were randomly selected from same population. Independent variables assessed included stay in the intensive care unit (ICU), skin color, diabetes, age, use of vasopressors, H2 blocker, steroids, other immunosuppressive drugs, thyroid replacement, proton pump inhibitors, diuretics, 5 categories of psychotropic medications, and amiodarone. Mean age was 68 years for cases vs 60 years for controls (P = .002). Bivariate analysis showed ICU stay was more frequent in cases than in controls (73.1% vs 33.6%, P < .001). Regression analysis yielded odds ratios (ORs) of 8.18 (95% confidence interval 3.22-20.76) for ICU status, 3.76 (1.30-10.92) for systemic corticosteroids, and 4.90 (1.17-20.62) for H2 blockers as associated with lack of histamine response. For every additional year in age, there was increase in the OR of 1.04 (1.01-1.07). Regression analysis supports ICU stay during skin testing as associated with a high OR for a negative histamine response independent of age. Systemic corticosteroids, H2 blockers, and older age are associated with a significant OR for a negative histamine response. This is one of largest studies on factors associated with a negative

[Atopic eczema: psychophysiological reactivity with standardized stressors].

PubMed

Münzel, K; Schandry, R

1990-11-01

In 18 atopic eczema patients with active symptomatology and 15 control subjects a comparison of reactivity to psychological stressors was made. The physiological measures were heart rate, peripheral vasomotor response, skin resistance level, spontaneous fluctuations of the skin resistance, and forearm skin temperature. In addition, self-ratings of subjective state, situational anxiety, and social anxiety were assessed. Mental arithmetic performed undisturbed and in distracting conditions, and anticipation of the latter and of having to speak in public served as stressors. The results show higher reaction values of the eczema patients for heart rate, peripheral vasomotor response, fluctuations of skin resistance and subjective tension. A subgroup of patients with extreme skin irritation (itching) reacted with an elevation of skin temperature, in contrast to control subjects and patients with less marked itching, in whom skin temperature dropped slightly. The results suggest that atopic eczema may have a psychophysiological component.

Craving by imagery cue reactivity in opiate dependence following detoxification

PubMed Central

Behera, Debakanta; Goswami, Utpal; Khastgir, Udayan; Kumar, Satindra

2003-01-01

Background: Frequent relapses in opioid addiction may be a result of abstinentemergent craving. Exposure to various stimuli associated with drug use (drug cues) may trigger craving as a conditioned response to ′drug cues′. Aims: The present study explored the effects of imagery cue exposure on psychophysiological mechanisms of craving, viz. autonomic arousal, in detoxified opiate addicts. Methodology: Opiate dependent subjects (N=38) following detoxification underwent imagery cue reactivity trials.The subjects were asked to describe verbally and then imagine their craving experiences. Results: Craving was measured subjectively by using Visual Analogue Scale and autonomic parameters of galvanic skin resistance (GSR), pulse rate (PR), and skin temperature (ST) was taken during cue imagery. Spearman′s r and Wilcoxon signed ranks test were employed in analysis. Multivariate repeated measurement analysis (wilk′s Lambda) was employed wherever appropriate. Subjective measures of craving, GSR and PR increased significantly whereas ST decreased significantly during drug related cue imagery as compared to neutral cues. Conclusions: The results support that cue imagery is a powerful tool in eliciting craving. Hence, it can be used as a screening manoeuvre for detecting individuals with high cue reactivity, as well as for extinction of craving. PMID:21206851

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.

Testing and Analysis of Composite Skin/Stringer Debonding Under Multi-Axial Loading

NASA Technical Reports Server (NTRS)

Krueger, Ronald; Cvitkovich, Michael K.; OBrien, T. Kevin; Minguet, Pierre J.

1999-01-01

Damage mechanisms in composite bonded skin/stringer constructions under uniaxial and biaxial (in-plane/out- of-plane) loading conditions were examined. Specimens consisted of a tapered composite flange bonded onto a composite skin. Tests were performed under monotonic loading conditions in tension, three-point bending, and combined tension/bending . For combined tension/bending testing, a unique servohydraulic load frame was used that was capable of applying both in-plane tension and out-of-plane bending loads simultaneously. Specimen edges were examined on the microscope to document the damage occurrence and to identify typical damage patterns. The observations showed that, for all three load cases, failure initiated in the flange, near the flange tip, causing the flange to almost fully debond from the skin. A two-dimensional plane-strain finite element model was developed to analyze the different test cases using a geometrically nonlinear solution. For all three loading conditions, principal stresses exceeded the transverse strength of the material in the flange area. Additionally, delaminations of various lengths were simulated in two locations where delaminations were observed. The analyses showed that unstable delamination propagation is likely to occur in one location at the loads corresponding to matrix ply crack initiation for all three load cases.

A comparison of skin endpoint titration and skin-prick testing in the diagnosis of allergic rhinitis.

PubMed

Gungor, Anil; Houser, Steven M; Aquino, Benjamin F; Akbar, Imran; Moinuddin, Rizwan; Mamikoglu, Bulent; Corey, Jacquelynne P

2004-01-01

Among the many methods of allergy diagnosis are intradermal testing (IDT) and skin-prick testing (SPT). The usefulness of IDT has been called into question by some authors, while others believe that studies demonstrating that SPT was superior might have been subject to bias. We conducted a study to compare the validity of SPT and IDT--specifically, the skin endpoint titration (SET) type of IDT--in diagnosing allergic rhinitis. We performed nasal provocation testing on 62 patients to establish an unbiased screening criterion for study entry. Acoustic rhinometric measurements of the nasal responses revealed that 34 patients tested positive and 28 negative. All patients were subsequently tested by SET and SPT. We found that SPT was more sensitive (85.3 vs 79.4%) and more specific (78.6 vs 67.9%) than SET as a screening procedure. The positive predictive value of SPT was greater than that of SET (82.9 vs 75.0%), as was the negative predictive value (81.5 vs 73.0%). None of these differences was statistically significant; because of the relatively small sample size, our study was powered to show only equivalency. The results of our study suggest that the information obtained by the SET method of IDT is comparable to that obtained by SPT in terms of sensitivity, specificity, and overall performance and that both SET and SPT correlate well with nasal provocation testing for ragweed. Therefore, the decision as to which to use can be based on other factors, such as the practitioner's training, the desire for quantitative results, the desire for rapid results, and the type of treatment (i.e., immunotherapy or pharmacotherapy) that is likely to be chosen on the basis of test results.

Increased matriptase zymogen activation in inflammatory skin disorders

PubMed Central

Chen, Cheng-Jueng; Wu, Bai-Yao; Tsao, Pai-In; Chen, Chi-Yung; Wu, Mei-Hsuan; Chan, Yee Lam E.; Lee, Herng-Sheng; Johnson, Michael D.; Eckert, Richard L.; Chen, Ya-Wen; Chou, Fengpai; Lin, Chen-Yong

2011-01-01

Matriptase, a type 2 transmembrane serine protease, and its inhibitor hepatocyte growth factor activator inhibitor (HAI)-1 are required for normal epidermal barrier function, and matriptase activity is tightly regulated during this process. We therefore hypothesized that this protease system might be deregulated in skin disease. To test this, we examined the level and activation state of matriptase in examples of 23 human skin disorders. We first examined matriptase and HAI-1 protein distribution in normal epidermis. Matriptase was detected at high levels at cell-cell junctions in the basal layer and spinous layers but was present at minimal levels in the granular layer. HAI-1 was distributed in a similar pattern, except that high-level expression was retained in the granular layer. This pattern of expression was retained in most skin disorders. We next examined the distribution of activated matriptase. Although activated matriptase is not detected in normal epidermis, a dramatic increase is seen in keratinocytes at the site of inflammation in 16 different skin diseases. To gain further evidence that activation is associated with inflammatory stimuli, we challenged HaCaT cells with acidic pH or H2O2 and observed matriptase activation. These findings suggest that inflammation-associated reactive oxygen species and tissue acidity may enhance matriptase activation in some skin diseases. PMID:21123732

Melatonin and human skin aging

PubMed Central

Kleszczynski, Konrad; Fischer, Tobias W.

2012-01-01

Like the whole organism, skin follows the process of aging during life-time. Additional to internal factors, several environmental factors, such as solar radiation, considerably contribute to this process. While fundamental mechanisms regarding skin aging are known, new aspects of anti-aging agents such as melatonin are introduced. Melatonin is a hormone produced in the glandula pinealis that follows a circadian light-dependent rhythm of secretion. It has been experimentally implicated in skin functions such as hair cycling and fur pigmentation, and melatonin receptors are expressed in many skin cell types including normal and malignant keratinocytes, melanocytes and fibroblasts. It possesses a wide range of endocrine properties as well as strong antioxidative activity. Regarding UV-induced solar damage, melatonin distinctly counteracts massive generation of reactive oxygen species, mitochondrial and DNA damage. Thus, there is considerable evidence for melatonin to be an effective anti-skin aging compound, and its various properties in this context are described in this review. PMID:23467217

Bioactivation of drugs in the skin: relationship to cutaneous adverse drug reactions.

PubMed

Sharma, Amy M; Uetrecht, Jack

2014-02-01

Drug-induced skin rashes are poorly understood idiosyncratic reactions, and current methods cannot predict their occurrence. Most idiosyncratic drug reactions are thought to be caused by chemically reactive metabolites, and the skin is a frequent site of idiosyncratic reactions; however, the skin has a very limited capacity to metabolize drugs. To balance this, the skin represents a protective barrier with a very active immune response against pathogens and other types of skin injury. Therefore its response to reactive metabolites is quite different from that of the liver. The purpose of this review is to integrate emerging findings into proposed mechanisms of drug and carcinogen metabolism in the skin that are likely responsible for rashes and other immune responses of the skin. Current evidence suggests the skin possesses significant sulfotransferase and flavin monooxygenases activities, but very low cytochromes P450 activity. However, there are skin-specific P450s that are not present in the liver. The manner in which the skin responds to neoantigens through local antigen presentation and innate immune sensing is reviewed with a focus on insights gained from the contact hypersensitivity (CHS) field. The roles of keratinocytes and Langerhans cells, and the emerging function of NOD-like receptors, are highlighted.

HSP27 as a biomarker for predicting skin irritation in human skin and reconstructed organotypic skin model.

PubMed

Chen, Hongxia; Li, Shuhua; Meng, Tian; Zhang, Lei; Dai, Taoli; Xiang, Qi; Su, Zhijian; Zhang, Qihao; Huang, Yadong

2014-04-21

In vitro alternative tests aiming at replacing the traditional animal test for predicting the irritant potential of chemicals have been developed, but the assessing parameters or endpoints are still not sufficient. To discover novel endpoints for skin irritation responses, 2DE-based proteomics was used to analyze the protein expression in human skin exposed to sodium lauryl sulfate (SLS) following the test protocol of the European Centre for the Validation of Alternative Methods (ECVAM) in the present study. HSP27 was up-regulated most significantly among the eight identified proteins, consistent with our previous reports. Acid and basic chemicals were applied on human skin for further validation and results showed that the up-regulated expression of HSP27 was induced in 24h after the exposure. Skin-equivalent constructed with fibroblasts, basement membrane and keratinocytes was used to investigate the potential of HSP27 as a biomarker or additional endpoint for the hazard assessment of skin irritation. Our skin-equivalent (Reconstructed Organotypic Skin Model, ROSM) had excellent epidermal differentiation and was suitable for the skin irritation test. HSP27 also displayed an up-regulated expression in the ROSM in 24h after the irritants exposure for 15min. All these results suggest that HSP27 may represent a potential marker or additional endpoint for the hazard assessment of skin irritation caused by chemical products. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Are allergen batch differences and the use of double skin prick test important?

PubMed

Thomsen, Gert F; Schlünssen, Vivi; Skadhauge, Lars R; Malling, Tine Halsen; Sherson, David L; Omland, Øyvind; Sigsgaard, Torben

2015-04-09

Skin prick tests (SPT) are widely used both in clinical diagnostics and in research. The standardization of allergen extracts is well documented to be crucial for the validity of SPT, whereas less emphasis has been placed on reproducibility and the SPT procedure itself. The objectives of this study are to clarify how the double skin prick test procedure influence the sensitivity and specificity of the test and to analyse the differences in weal size in skin prick tests between two batches of allergen extracts from the same vendor. The association between rhinitis and SPT was assessed among 1135 persons from a general population sample. SPT was performed twice with 10 common aeroallergens. In a subsample of 90 persons SPT was performed simultaneously with five of the allergens using different batches. Thirty percent had at least one positive SPT. Among asthmatics this number was 62%. Only minor differences were seen between the sizes of two weals from the same batch. A second SPT with the same batch did not change the association between rhinitis and sensitization. When performing SPT with two different batches disagreement was observed in 2% (Birch) to 11% (Cat) of the subjects. Performing SPT twice with the same allergen batch does not enhance the validity of the test, and value of double testing can be questioned. Considerable differences in SPT response with different batches from the same manufacturer were observed. Thus inter batch differences in allergen extracts might be a source of variability.

Emotional and physiological reactivity in Complicated Grief.

PubMed

LeBlanc, Nicole J; Unger, Leslie D; McNally, Richard J

2016-04-01

Grief is a psychobiological response to the loss of a loved one. Some grief theorists suggest that this predictable response may arise from withdrawal of psychobiological regulation previously provided by the deceased (e.g. assistance with emotion regulation). Accordingly, recovery from loss may require bereaved individuals to re-establish self-regulatory control to avoid developing Complicated Grief (CG). This model implies that adults with CG may exhibit aberrant emotional responding to environmental stimuli. The present study was designed to test this hypothesis. We recruited a sample of 23 bereaved adults with CG and 26 healthy bereaved adults to complete an emotional reactivity paradigm. Participants watched a series of emotional film clips and provided measures of their self-reported emotional response. We also assessed their heart rate, respiratory sinus arrhythmia (RSA), and skin conductance level in response to these clips. Though emotional and physiological differences between the groups were rare, the CG group exhibited attenuated RSA reactivity to some emotional film clips, suggesting blunted parasympathetic nervous system reactivity in those with the disorder. Limitations include the modest sample size and unequal group sizes. Individuals with CG do not exhibit pervasive differences in emotional and physiological reactivity compared to healthy bereaved individuals. However, we did observe evidence of blunted parasympathetic nervous system reactivity in individuals with CG, which may mediate emotional inflexibility among those who develop the disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

A SKIN TEST FOR DETECTING GROUP C HEMOLYTIC STREPTOCOCCAL INFECTION CAUSING EPIZOOTIC LYMPHADENITIS IN GUINEA PIGS

PubMed Central

Moen, Johannes K.

1936-01-01

1. A skin test with a crude bacterial extract prepared from group C (Lancefield) hemolytic streptococci was used as a means of detecting possible carriers of the streptococcus causing epizootic lymphadenitis in guinea pigs. A positive test similar to a positive tuberculin reaction was considered presumptive evidence of present or recent infection with this streptococcus. 2. 20 positive reactors were found in 330 supposedly normal guinea pigs. 3. 195 negatively reacting animals were used as a breeding stock which yielded 1,296 progeny over a period of 15 months. None of the breeding stock or their progeny showed evidence of spontaneous lymphadenitis. Skin tests of 100 of the progeny were all negative. 4. The use of this skin test as a means of obtaining guinea pig breeding stock free of the streptococcus causing spontaneous lymphadenitis is suggested. PMID:19870552

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.

Assessment of test method variables for in vitro skin irritation testing of medical device extracts.

PubMed

Olsen, Daniel S; Lee, Michelle; Turley, Audrey P

2018-08-01

Skin irritation is an important component of the biological safety evaluation of medical devices. This testing has typically been performed using in vivo models. However, in an effort to reduce the need for in vivo testing, alternative methods for assessing skin irritation potential in vitro have been developed using a Reconstructed Human Epidermis (RhE) model. During the development of the protocol for the round robin validation of in vitro irritation testing for medical device extracts, it became clear that there were three points in the procedure where different options may be validated within each laboratory for routine testing: sample exposure time (18 vs 24h), SDS positive control concentration, and cytokine (IL-1α) release testing. The goal of our study was to evaluate the effect of these variables. EpiDerm™ tissues were exposed to extracts of three plain polymer samples, and four polymers embedded with known irritant chemicals. Exposures were performed for 18 and 24h. Resulting tissue viability was assessed by MTT reduction and IL-1α release was assessed by ELISA. Testing was also performed using various concentrations of SDS ranging from 0.5 to 1% (w/v). Overall, results were similar for samples tested and 18 and 24h, but the 18h exposure time has the potential to have an impact on the results of some sample types. IL-1α testing was shown to be useful to clarify conflicting tissue viability results. Use of a lower concentration of SDS as a positive control can help prevent issues that arise from excessive tissue damage often caused by 1% SDS. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

[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.

Positive Skin Test or Specific IgE to Penicillin Does Not Reliably Predict Penicillin Allergy.

PubMed

Tannert, Line Kring; Mortz, Charlotte Gotthard; Skov, Per Stahl; Bindslev-Jensen, Carsten

According to guidelines, patients are diagnosed with penicillin allergy if skin test (ST) result or specific IgE (s-IgE) to penicillin is positive. However, the true sensitivity and specificity of these tests are presently not known. To investigate the clinical relevance of a positive ST result and positive s-IgE and to study the reproducibility of ST and s-IgE. A sample of convenience of 25 patients with positive penicillin ST results, antipenicillin s-IgE results, or both was challenged with their culprit penicillin. Further 19 patients were not challenged, but deemed allergic on the basis of a recent anaphylactic reaction or delayed reactions to skin testing. Another sample of convenience of 18 patients, 17 overlapping with the 25 challenged, with initial skin testing and s-IgE (median, 25; range, 3-121), months earlier (T -1 ), was repeat skin tested and had s-IgE measured (T 0 ), and then skin tested and had s-IgE measured 4 weeks later (T 1 ). Only 9 (36%) of 25 were challenge positive. There was an increased probability of being penicillin allergic if both ST result and s-IgE were positive at T 0 . Positive ST result or positive s-IgE alone did not predict penicillin allergy. Among the 18 patients repeatedly tested, 46.2% (12 of 25) of positive ST results at T -1 were reproducibly positive at T 0 . For s-IgE, 54.2% (14 of 24) positive measurements were still positive at T 0 and 7 converted to positive at T 1 . The best predictor for a clinically significant (IgE-mediated) penicillin allergy is a combination of a positive case history with simultaneous positive ST result and s-IgE or a positive challenge result. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Allergenic components of a novel food, Micronesian nut Nangai (Canarium indicum), shows IgE cross-reactivity in pollen allergic patients.

PubMed

Sten, Eva; Stahl Skov, P; Andersen, S B; Torp, A M; Olesen, A; Bindslev-Jensen, U; Poulsen, L K; Bindslev-Jensen, C

2002-05-01

New foods may present a risk for food hypersensitive patients. Several examples exist of allergic reactions caused by cross-reactive plant-derived foods, and new foods should be scrutinised before introducing them to the market. We have evaluated the clinical and serological relevance of cross-reactivity between Nangai and pollen allergens. Cross-reactivity was examined with Maxisorp RAST (radioallergosorbent test), RAST inhibition and Western blot, using sera from patients allergic to grass, birch and mugwort pollen. None of the patients reported having seen or eaten Nangai previously. To determine the biological and clinical relevance of the cross-reactivity, histamine release (HR) test, skin prick test (SPT) and food challenge were used. There was prevalence for reactivity against Nangai in the group of pollen allergic patients. This cross-reactivity seems to be related--at least in part--to carbohydrate epitopes. Three out of 12 patients tested with Nangai were positive upon open challenge, but using double blind placebo controlled food challenge (DBPCFC) this could not be confirmed in two patients. The biological effects of Nangai on allergic patients were confirmed using HR and SPT. The Nangai specific IgE found among pollen allergic patients addresses the need for control of new or changed foods before introduction to the market.

Optical coherence tomography applied to tests of skin care products in humans--a case study.

PubMed

Vasquez-Pinto, L M C; Maldonado, E P; Raele, M P; Amaral, M M; de Freitas, A Z

2015-02-01

When evaluating skin care products for human skin, quantitative test methods need to be simple, precise and reliable. Optical coherence tomography (OCT), provides high-resolution sectional images of translucent materials to a depth of a few millimeters, a technique usually applied to medical measurements in ophthalmology and dermatology. This study aimed to demonstrate the application of OCT as the main technique for monitoring changes in skin topography during tests of a wrinkle-reduction product in humans. We used a commercial OCT apparatus to perform clinical examinations of skin roughness in treated and non-treated sites in the periorbital region of thirty human voluntaries who were using an anti-aging product commercially available: Natura Chronos® Flavonóides de Passiflora 45+ FPS15, from Natura Cosméticos, Brazil. Measurements were performed days 0, 7, 14 and 28 of treatment. Equipment and software allowed real-time recording of skin roughness parameters and wrinkle depths. The OCT measurements have allowed the monitoring of changes in skin roughness, which have shown reduction in treated sites around 10%. The obtained depth distributions also indicate reduction in the occurrence of wrinkles deeper than 170 μm. The verified results are consistent with those typically obtained after successful treatment with modern anti-aging products. By using the OCT technique, it was possible to quantify changes in skin roughness and in the distribution of depths of skin wrinkles, with adequate sensitivity. OCT imaging allows the direct visualization of the skin topography with resolution of micrometers, a reliable and interactive tool for clinical use. Therefore, for the first time, we demonstrated the use of OCT technique to verify the efficacy of cosmetic products in real time. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Penicillin allergy: value of including amoxicillin as a determinant in penicillin skin testing.

PubMed

Lin, Erina; Saxon, Andrew; Riedl, Marc

2010-01-01

Allergy to penicillins remains an important issue. Penicillin skin testing (PST) with major and minor determinants has been shown to be a highly valuable tool for identifying IgE-mediated penicillin allergy. The value of additional testing with side-chain-specific moieties from semisynthetic penicillins such as amoxicillin is not well-established in spite of the widespread use of these medications. A retrospective review of all consecutive inpatient PST results from 1995 to 2007 comprising 1,068 patients was performed in our institution on individuals with a self-reported history of beta-lactam allergy to assess the importance of including the amoxicillin determinant in a previously validated PST panel. Descriptive statistics were performed. The PST panel included penicilloyl-polylysine, penicillin G, penicilloate, penilloate and amoxicillin. Of 1,068 patients, 243 (23%) had a positive skin test reaction on the PST panel. Testing with amoxicillin was positive in 30.9% of patients, the majority of whom (81%) were also positive to 1 or more standard penicillin reagents. Fourteen of the 243 positive patients (5.8%) had a positive skin test reaction only to amoxicillin. Additionally, the use of penicilloate and penilloate minor determinants in combination with penicillin G identified a greater percentage of penicillin-allergic individuals compared to using only penicillin G (22.6 vs. 6.6%), demonstrating their importance in the PST panel. These data indicate that the inclusion of the amoxicillin determinant appears to identify a small but important group of allergic individuals who may otherwise test negative on a PST panel. Copyright 2010 S. Karger AG, Basel.

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.

Comparison of the Skin Penetration of 3 Metabolically Stable Chemicals Using Fresh and Frozen Human Skin.

PubMed

Jacques-Jamin, Carine; Duplan, Hélène; Rothe, Helga; Vaillant, Ophelie; Eilstein, Joan; Grégoire, Sebastien; Cubberley, Richard; Lange, Daniela; Ellison, Corie; Klaric, Martina; Hewitt, Nicola; Schepky, Andreas

2017-01-01

The Cosmetics Europe ADME Task Force is developing in vitro and in silico tools for predicting skin and systemic concentrations after topical application of cosmetic ingredients. There are conflicting reports as to whether the freezing process affects the penetration of chemicals; therefore, we evaluated whether the storage of human skin used in our studies (8-12 weeks at -20°C) affected the penetration of model chemicals. Finite doses of trans-cinnamic acid (TCA), benzoic acid (BA), and 6-methylcoumarin (6MC) (non-volatile, non-protein reactive and metabolically stable in skin) were applied to fresh and thawed frozen skin from the same donors. The amounts of chemicals in different skin compartments were analysed after 24 h. Although there were some statistical differences in some parameters for 1 or 2 donors, the penetration of TCA, BA, and 6MC was essentially the same in fresh and frozen skin, i.e., there were no biologically relevant differences in penetration values. Statistical differences that were evident indicated that penetration was marginally lower in frozen than in fresh skin, indicating that the barrier function of the skin was not lost. The penetration of the 3 chemicals was essentially unaffected by freezing the skin at -20°C for up to 12 weeks. © 2017 S. Karger AG, Basel.

Oxidative stress and skin diseases: possible role of physical activity.

PubMed

Kruk, Joanna; Duchnik, Ewa

2014-01-01

The skin is the largest body organ that regulates excretion of metabolic waste products, temperature, and plays an important role in body protection against environmental physical and chemical, as well as biological factors. These include agents that may act as oxidants or catalysts of reactions producing reactive oxygen species (ROS), reactive nitrogen species (RNS), and other oxidants in skin cells. An increased amount of the oxidants, exceeding the antioxidant defense system capacity is called oxidative stress, leading to chronic inflammation, which, in turn, can cause collagen fragmentation and disorganization of collagen fibers and skin cell functions, and thus contribute to skin diseases including cancer. Moreover, research suggests that oxidative stress participates in all stages of carcinogenesis. We report here a summary of the present state of knowledge on the role of oxidative stress in pathogenesis of dermatologic diseases, defensive systems against ROS/RNS, and discuss how physical activity may modulate skin diseases through effects on oxidative stress. The data show duality of physical activity actions: regular moderate activity protects against ROS/RNS damage, and endurance exercise with a lack of training mediates oxidative stress. These findings indicate that the redox balance should be considered in the development of new antioxidant strategies linked to the prevention and therapy of skin diseases.

Delayed tuberculin reactivity in persons of Indochinese origin: implications for preventive therapy.

PubMed

Robertson, J M; Burtt, D S; Edmonds, K L; Molina, P L; Kiefe, C I; Ellner, J J

1996-05-01

To 1) study a variant delayed reaction to tuberculin testing as a way to enhance screening for tuberculosis among high-risk persons and 2) correlate the delayed reaction with lymphocyte blastogenesis. Cross-sectional study. 2 public health department clinics in North Carolina. 121 adults who had recently emigrated from Vietnam to North Carolina and who were ethnic Vietnamese and ethnic Dega, a minority population group from the central highlands region of Vietnam. Medical history, physical examination, laboratory evaluation, and standard purified protein derivative (PPD) testing (Mantoux method). Skin test results were read at 72 hours and again at 6 days. Variant reactivity was defined as induration of less than 10 mm at 72 hours that, when reassessed at 6 days, had increased in size to 10 mm or greater. Persons with negative (n=54) and variant (n=32) PPD results also had booster testing at 10 to 12 weeks. Serum samples were obtained from 57 participants for lymphocyte blastogenesis studies. 26% of participants had variant tuberculin reactivity. Variant reactivity was strongly associated with booster positivity: Sixty-five percent of persons with variant PPD results had booster positivity compared with 16% of persons with negative PPD results (P<0.001). The lymphocyte blastogenesis response of persons with variant PPD results was between the response of persons with negative PPD results and that of persons with positive PPD results. Variant reactivity in this high-risk group was a predictor of booster positivity. Together with the blastogenic response pattern, this association strongly suggests that variant reactivity has a high positive predictive value for tuberculous infection. Clinicians should incorporate these findings into their approach for choosing candidates for preventive therapy.

Detectability of bovine TB using the tuberculin skin test does not vary significantly according to pathogen genotype within Northern Ireland.

PubMed

Wright, David M; Allen, Adrian R; Mallon, Thomas R; McDowell, Stanley W J; Bishop, Stephen C; Glass, Elizabeth J; Bermingham, Mairead L; Woolliams, John A; Skuce, Robin A

2013-10-01

Strains of many infectious diseases differ in parameters that influence epidemic spread, for example virulence, transmissibility, detectability and host specificity. Knowledge of inter-strain variation can be exploited to improve management and decrease disease incidence. Bovine tuberculosis (bTB) is increasingly prevalent among farmed cattle in the UK, exerting a heavy economic burden on the farming industry and government. We aimed to determine whether strains of Mycobacterium bovis (the causative agent of bTB) identified and classified using genetic markers (spoligotyping and multi-locus VNTR analysis) varied in response to the tuberculin skin test; this being the primary method of bTB detection used in the UK. Inter-strain variation in detectability of M. bovis could have important implications for disease control. The skin test is based on a differential delayed type hypersensitivity (DTH) response to intradermal injections of purified protein derivative (PPD) from M. bovis (PPD-B) and Mycobacterium avium (PPD-A). We searched for an association between skin test response (PPD-B skin rise minus PPD-A skin rise) and M. bovis genotype at the disclosing test in culture-confirmed cases using a field dataset consisting of 21,000 isolates belonging to 63 genotypes of M. bovis from cattle in Northern Ireland. We found no substantial variation among genotypes (estimated responses clustered tightly around the mean) controlling for animal sex, breed and test effects. We also estimated the ratio of skin test detected to undetected cases (i.e. cases only detected at abattoir). The skin test detection ratio varied among abattoirs with some detecting a greater proportion of cases than others but this variation was unrelated to the community composition of genotypes within each abattoir catchment. These two lines of evidence indicate that M. bovis genotypes in Northern Ireland have similar detectability using the skin test. Crown Copyright © 2013. Published by Elsevier B

Debates in Allergy Medicine: Allergy skin testing cannot be replaced by molecular diagnosis in the near future.

PubMed

Larenas-Linnemann, Désirée; Luna-Pech, Jorge A; Mösges, Ralph

2017-01-01

Percutaneous skin prick tests (SPT) have been considered the preferred method for confirming IgE-mediated sensitization. This reliable and minimally invasive technique correlates with in vivo challenges, has good reproducibility, is easily quantified, and allows analyzing multiple allergens simultaneously. Potent extracts and a proficient tester improve its accuracy. Molecular-based allergy diagnostics (MA-Dx) quantifies allergenic components obtained either from purification of natural sources or recombinant technology to identify the patient's reactivity to those specific allergenic protein components. For a correct allergy diagnosis, the patient selection is crucial. MA-Dx has been shown to have a high specificity, however, as MA-Dx testing can be ordered by any physician, the pre-selection of patients might not always be optimal, reducing test specificity. Also, MA-Dx is less sensitive than in vitro testing with the whole allergen or SPT. Secondly, no allergen-specific immunotherapy (AIT) trial has yet shown efficacy with patients selected on the basis of their MA-Dx results. Thirdly, why would we need molecular diagnosis, as no molecular treatment can yet be offered? Then there are the practical arguments of costs (SPT highly cost-efficient), test availability for MA-Dx still lacking in wide areas of the world and scarce in others. As such, it is hard physicians can build confidence in the test and their interpretation of the MA-Dx results. as of now these techniques should be reserved for situations of complex allergies and polysensitization; in the future MA-Dx might help to reduce the number of allergens for AIT, but trials are needed to prove this concept.

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.

Distress tolerance and physiological reactivity to stress predict women's problematic alcohol use.

PubMed

Holzhauer, Cathryn Glanton; Wemm, Stephanie; Wulfert, Edelgard

2017-06-01

Research has shown that measures of reactivity to distress-including distress tolerance and physiological reactivity to stress-are dysregulated in women who misuse alcohol. These variables may interact and create a risk profile for young adult women, reflecting patterns of stress reactivity that confer a risk for alcohol misuse. The current study tested this hypothesis by examining the independent and interactive associations of subjective distress tolerance, behavioral distress tolerance, and physiological stress reactivity with women's alcohol misuse. The study was conducted with a sample of 91 college women recruited on a large northeastern university campus. Results showed that subjective levels of distress tolerance and physiological reactivity to stress (skin conductance reactivity, SCR), but not behavioral distress tolerance, were independently associated with alcohol misuse. In addition, subjective distress tolerance moderated the relationship between SCR and negative alcohol-related consequences. Specifically, women with low physiological reactivity (SCR) to a stressful task and greater urge to quickly rid themselves of distress (low subjective distress tolerance) endorsed a significantly greater number of adverse consequences from their alcohol use. These results extend prior findings by showing that, even among a nonclinical sample of women, lower stress reactivity in combination with low subjective distress tolerance is associated with increased risk for various drinking-related negative consequences. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Repeat tuberculin skin testing leads to desensitisation in naturally infected tuberculous cattle which is associated with elevated interleukin-10 and decreased interleukin-1 beta responses.

PubMed

Coad, Michael; Clifford, Derek; Rhodes, Shelley G; Hewinson, R Glyn; Vordermeier, H Martin; Whelan, Adam O

2010-01-01

The principal surveillance tool used to control bovine tuberculosis in cattle is the removal of animals that provide a positive response to the tuberculin skin-test. In this study we performed a longitudinal investigation of the immunological and diagnostic consequences of repeated short-interval skin-tests in cattle naturally infected with Mycobacterium bovis. Tuberculin skin-test positive cattle were subjected to up to four further intradermal comparative cervical skin-tests at approximately 60-day intervals. A significant progressive reduction in the strength of the skin-test was observed after successive tests. In contrast, the magnitude of interferon-gamma (IFN-gamma) responses was not influenced by repeat skin-testing either transiently around the time of each skin-test or longitudinally following repeated tests. A significant boost in blood interleukin-10 (IL-10) production was observed within 3 days following each skin-test although the magnitude of this boosted response returned to lower levels by day 10 post-test. The application of a novel multiplex assay to simultaneously measure seven cytokines and chemokines also identified that skin-testing resulted in a significant and progressive reduction in antigen specific interleukin-1beta (IL-1beta) whilst confirming stable IFN-gamma and elevated IL-10 responses in the blood. Therefore, we have demonstrated that in cattle naturally infected with M. bovis, repeat short-interval skin-testing can lead to a progressive reduction in skin-test responsiveness which has potential negative consequences for the detection of infected animals with marginal or inconclusive skin-test responses. The desensitising effect is associated with decreased IL-1beta and elevated IL-10 responses, but importantly, does not influence antigen specific IFN-gamma responses. INRA, EDP Sciences, 2009

Formulation and evaluation on human skin of a water-in-oil emulsion containing Muscat hamburg black grape seed extract.

PubMed

Sharif, A; Akhtar, N; Khan, M S; Menaa, A; Menaa, B; Khan, B A; Menaa, F

2015-04-01

Vitis vinifera 'muscat hamburg' (Vitaceae) is a blue-black grape variety commonly found in Pakistan. It has been consumed and used in traditional medicine for centuries. Compared to other grapes, M. hamburg records one of the greatest amount of polyphenols and displays potent antioxidant activities, which make it a great candidate for its exploitation in the development of stable cream emulsions destined to improve the skin appearance. Evaluate the effects of stable water-in-oil (W/O) emulsion containing 2% M. hamburg grape seed extract ('formulation') on human cheek skin in comparison with the placebo ('base'). An occlusive patch test, containing either the formulation or the base, was topically tested for 8 weeks during a winter period in young adult and healthy Pakistani male volunteers. The subjects were instructed to use twice a day the base and the formulation on their right and left cheek skin, respectively. Non-invasive measurements on these skin areas were carried out every week to assess any effects produced on melanin, elasticity and sebum. Skin compatibility assay (Burchard test) was used to report any potential skin reactivity. ANOVA, paired sample t-test and LSD test were applied to determine the statistical data significance. Significant differences (P ≤ 0.05) were found between the placebo and the formulation in terms of their respective skin effects elicited on melanin, elasticity and sebum content. Nevertheless, placebo and formulation exerted similar effects on skin erythema and moisture contents. Importantly, no skin hypersensitivity cases were reported during the whole course of the study. The developed grape-based cream could be efficiently and safely applied to improve a number of skin conditions (e.g. hyper-pigmentation, premature ageing, acne). © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

A feasibility study of Q-sort to determine recall of skin test results and environmental remediation education.

PubMed

Townsend, Kristen; Corry, James M; Quigley, Beth Hogan; George, Maureen

2012-02-01

Allergic asthma is common in urban minority children and evidence suggests that remediation tailored to the child's allergic profile is the most effective management strategy. The purpose of this pilot study therefore was to examine the caregiver's recall of their child's skin test results and the accuracy of planned remediation ∼4 months after testing. Caregivers were asked to recall their child's skin test results ∼4 months after their skin testing but before any follow-up visit. A Q-sort was then used to determine the knowledge of the recommended remediation. In this Q-sort, caregivers placed 52 cards, each representing one intervention for an indoor allergen, on a response board that prioritized the interventions. At the conclusion of the Q-sort, caregivers received feedback on the accuracy of their recall and prioritization. African American caregivers (5 females; mean age 33.6) of 5 children (4 males; mean age 7.8) were enrolled. No caregiver's recall of skin test results was concordant with the actual results for type or number of allergens. Caregiver's accuracy in prioritizing strategies was 33-100% for cat dander, 40-70% for molds, 70-87% for dust mite allergens, and 100% for the one dog allergic child. Subjects preferred Q-sort to traditional methods of receiving remediation education. Caregivers do not accurately recall skin test results and this may, in part, impede their ability to implement appropriate interventions. A low-literacy game-style approach is a novel strategy to provide complex teaching that warrants further investigation.

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

PubMed

Sharma, Rakesh

2010-07-21

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

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

NASA Astrophysics Data System (ADS)

Sharma, Rakesh

2010-07-01

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

Tannins from Potentilla officinalis display antiinflammatory effects in the UV erythema test and on atopic skin.

PubMed

Hoffmann, Julia; Wölfle, Ute; Schempp, Christoph M; Casetti, Federica

2016-09-01

Rich in tannins, the rhizome of Potentilla officinalis (PO) has traditionally been used in the topical treatment of inflammatory disorders of the skin and mucous membranes. The objective of the present study was to examine the antiinflammatory effects of PO in the UV erythema test as well as in patients with atopic skin. Using the UV erythema test, the antiinflammatory effects of a PO extract (2 %) - compared to 1 % hydrocortisone acetate - were assessed in a randomized, prospective, placebo-controlled double-blind study of 40 healthy volunteers. In the context of a prospective non-controlled trial, the efficacy and tolerability of 2 % PO cream (applied to defined test areas twice daily for two weeks) was evaluated in twelve adults and twelve children with atopic skin using a partial SCORAD. In addition, the effects on the degree of erythema in the test areas was measured photometrically. In the UV erythema test, PO cream significantly reduced the erythema index compared to the vehicle. The antiinflammatory effects of PO cream were comparable to those of 1 % hydrocortisone acetate cream. The clinical study with atopic patients revealed a significant reduction in the partial SCORAD as well as erythema in the test areas. No adverse events were recorded. PO cream displays antiinflammatory effects in vivo. It is effective in and well tolerated by patients with atopic skin. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Agreement between the skin prick test and specific serum IgE for egg white and cow's milk allergens in young infant with atopic dermatitis.

PubMed

Yang, Hyeon-Jong; Park, Min-Ju; Youn, Seo Young; Yoo, Sangsoo; Min, Taek Ki; Jeon, You Hoon; Lee, Hae Won; Lee, Ji Sung; Pyun, Bok Yang

2014-06-01

The skin prick test (SPT) for detecting atopic sensitization is not preferred in young infants with atopic dermatitis (AD) because of concerns about poor skin reactivity. This study aimed to evaluate whether the results of SPT agreed well with those of specific serum immunoglobulin E (sIgE) antibody test in young infants with AD. This study included 2,077 eligible infants (age, <12 months) with AD who were tested by either SPT or sIgE between 2007 and 2011. Among them, 199 infants tested for egg white (EW) and 192 infants tested for cow's milk (CM), by both SPT and sIgE on the same day were identified and reviewed retrospectively. Kappa statistics and tests for equal kappa statistics were used to evaluate the agreement between the SPT and sIgE. The mean wheal diameter and the allergen-to-histamine ratio of SPT showed substantial agreement with those of sIgE for EW (κ = 0.62, 0.69) and CM (κ = 0.34, 0.47). The agreement for EW was significantly higher <6-month-old than in ≥6-month-old infants (κ = 0.79 vs. 0.54, P = 0.02), and that for CM was similar (P = 0.60). The mean wheal diameters for EW and CM were evenly distributed, and did not show increasing trends regardless of age in months (Ptrend = 0.13 and 0.06, respectively). The results of SPT agreed well with those of sIgE. This finding provides a rationale for using SPT, and suggests that SPT can be used along with sIgE to detect food sensitization in young infants with AD.

The Tritiated Water Skin Barrier Integrity Test: Considerations for Acceptance Criteria with and Without 14C-Octanol.

PubMed

Lehman, Paul A; Beatch, Kacie; Raney, Sam G; Franz, Thomas J

2017-01-01

A study was designed to assess barrier integrity simultaneously using separate compounds (probes) for polar and non-polar pathways through the skin, 3 H 2 O and 14 C-octanol, respectively; and to determine whether the two probe approach could better define barrier integrity. A 5-min dose of water containing 3 H 2 O and 14 C -octanol was applied to ex vivo human skin mounted in Franz diffusion cells. The receptor solution was sampled at 30 min, analyzed for 3 H and 14 C content, and the correlation between water and octanol absorption was determined by statistical tests suitable for non-normally distributed data. This study was conducted on skin from 37 donors with from 3 to 30 replicate skin sections per donor (a total of 426 sections). The correlation between 3 H 2 O and 14 C-octanol absorption was low (Pearson correlation coefficient = 0.3485). The 3 H 2 O absorption cutoff used in this study to select for a normal skin barrier rejected some sections in which 14 C-octanol absorption was within normal limits and accepted others in which 14 C-octanol absorption was abnormally high. The converse was true for 3 H 2 O absorption when the 14 C-octanol-based cutoff was used. The results of the 3 H 2 O test or of similar tests that primarily assess the permeability of polar pathways through the skin may not necessarily provide information relevant to the absorption of highly lipophilic compounds. Octanol, or another molecule that more closely matches the physicochemical attributes of the test compound, may characterize properties of the skin barrier that are more relevant to compounds of low water solubility.

Patch test reactivity to metal allergens following regulatory interventions: a 33-year retrospective study.

PubMed

Thyssen, Jacob Pontoppidan; Ross-Hansen, Katrine; Menné, Torkil; Johansen, Jeanne Duus

2010-08-01

Contact allergy epidemics to chromate and nickel were addressed in Denmark in 1983 and 1990 by regulatory interventions. To evaluate whether regulatory interventions on nickel and chromate exposure have reduced the proportion of strong patch test reactions. 22 506 patients with dermatitis aged 4-99 years were patch tested with nickel sulfate, potassium dichromate, or cobalt chloride between 1977 and 2009. The proportion of 3+ reactions to nickel sulfate was reduced and almost disappeared after the mid- and late 1980s (P-trend = 0.001). Today, 1+ and 2+ nickel reactions occur equally frequent. Cobalt chloride patch test reactivity reflected the nickel development to some degree. The proportion of 3+ reactions to potassium dichromate was reduced during the 1980s (P-trend = 0.13), whereas the proportion of 2+ reactions to potassium dichromate have increased in recent years. The decrease in nickel sulfate and cobalt chloride 3+ patch test reactivity began long before the Danish nickel regulation came into effect. This could be because of research activity at the time as well as political attention in Northern Europe. The chromate content in cement regulation may have changed the epidemiology of patch test reactivity; however, in recent years, 2+ reactions to chromate have increased markedly, a development that should be carefully followed.

Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing.

PubMed

Torres, M J; Romano, A; Mayorga, C; Moya, M C; Guzman, A E; Reche, M; Juarez, C; Blanca, M

2001-09-01

Penicillin is no longer the most commonly prescribed beta-lactam, and the pattern of reactions has changed. We studied the diagnostic value of skin testing in penicillin-allergic subjects from a population where benzylpenicillin is not now the most frequently used beta-lactam. Patients with a history of immediate allergic reactions to penicillins were studied with: skin tests with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin, and ampicillin; in vitro determination of specific IgE; and controlled administration for those with a positive history but negative skin and in vitro tests. A reaction was considered immediate when symptoms appeared within a maximum of 1 h after drug intake. After testing, 290 patients (71% having anaphylaxis and 29% having urticaria) proved to be allergic. Amoxicillin was involved in 64.8% and benzylpenicillin in 2.8% of the patients. Skin test positivity to at least one determinant appeared in 70% of cases, amoxicillin being the most frequent. The overall sensitivity decreased markedly when only BPO and MDM were considered. In 13.1% of patients, the diagnosis was established by in vitro test and in 16.9% by controlled administration. Of the 290 patients, 42.1% were positive to determinants generated from benzylpenicillin and 57.9% were selective responders. Sensitivity of skin tests to BPO was lower than reported, being partly replaced by minor determinants, mostly amoxicillin. The incorporation of additional reagents and the development of new tests are required, and these will probably change as the patterns of consumption vary.

Stability and potency of raw and boiled shrimp extracts for skin prick test.

PubMed

Pariyaprasert, Wipada; Piboonpocanun, Surapon; Jirapongsananuruk, Orathai; Visitsunthorn, Nualanong

2015-06-01

The difference of stability between raw and boiled shrimp extracts used in prick tests has never been investigated despite its potential consequences in tests development. The aim of this study was to compare the raw and boiled shrimp extracts of two species; Macrobrachium rosenbergii (freshwater shrimp) and Penaeus monodon (seawater shrimp) held at 4 ?C for different periods of time for their stability and potency in vivo by using the skin prick test (SPT) method. Raw and boiled M. rosenbergii and P. monodon extracts were prepared and stored at 4 ?C for 1, 7, 14 and 30 days. Thirty patients were pricked with raw and boiled shrimp extracts at all storage times, as well as prick to prick skin test (PTP) to fresh raw and boiled shrimps of both species. The mean wheal diameter (MWD) resulting from prick tests for all shrimp extracts was measured and compared. The shrimp extracts of all storage times yielded positive skin test results in the range of 90% - 100%. Raw P. monodon extracts induced larger wheals than boiled extracts at all storage times. There was no significant difference of MWD between raw and boiled M. rosenbergii extracts on day 1, 7, and 14. Significant correlations between MWD of PTP to fresh shrimps and SPT to all shrimp extracts were observed. All shrimp extracts were sterile at all storage times. Raw and boiled M. rosenbergii and P. monodon extracts were stable and sterile at 4 ?C for at most 30 days. SPT with these extracts induced more than 10 mm in shrimp allergy patients and the results were comparable with PTP to fresh shrimps.

Depressive symptoms and attenuated physiological reactivity to laboratory stressors.

PubMed

Schwerdtfeger, Andreas; Rosenkaimer, Ann-Kathrin

2011-07-01

There is evidence that depressive symptoms are associated with attenuated physiological reactivity to active stressors. However, it is not known whether blunted reactivity in depressed individuals is stressor-specific. We examined cardiovascular and electrodermal reactivity in non-clinical participants with varying levels of depressive symptoms to different active and passive stressors. Depressive symptoms were inversely related to both blood pressure and skin conductance reactivity during a public speaking task and the viewing of the speech video. However, no effects were found during a cold pressor task. Together these findings suggest that depressive symptoms are related to attenuated sympathetic nervous system reactivity in response to self-relevant stressors. Copyright © 2011 Elsevier B.V. All rights reserved.

Skin reactions to histamine of healthy subjects after hypnotically induced emotions of sadness, anger, and happiness.

PubMed

Zachariae, R; Jørgensen, M M; Egekvist, H; Bjerring, P

2001-08-01

The severity of symptoms in asthma and other hypersensitivity-related disorders has been associated with changes in mood but little is known about the mechanisms possibly mediating such a relationship. The purpose of this study was to examine the influence of mood on skin reactivity to histamine by comparing the effects of hypnotically induced emotions on flare and wheal reactions to cutaneous histamine prick tests. Fifteen highly hypnotically susceptible volunteers had their cutaneous reactivity to histamine measured before hypnosis at 1, 2, 3, 4, 5, 10, and 15 min after the histamine prick. These measurements were repeated under three hypnotically induced emotions of sadness, anger, and happiness presented in a counterbalanced order. Skin reactions were measured as change in histamine flare and wheal area in mm2 per minute. The increase in flare reaction in the time interval from 1 to 3 min during happiness and anger was significantly smaller than flare reactions during sadness (P<0.05). No effect of emotion was found for wheal reactions. Hypnotic susceptibility scores were associated with increased flare reactions at baseline (r=0.56; P<0.05) and during the condition of happiness (r=0.56; P<0.05). Our results agree with previous studies showing mood to be a predictor of cutaneous immediate-type hypersensitivity and histamine skin reactions. The results are also in concordance with earlier findings of an association between hypnotic susceptibility and increased reactivity to an allergen.

Sensitization to cereals and peanut evidenced by skin prick test and specific IgE in food-tolerant, grass pollen allergic patients

PubMed Central

2011-01-01

Background The botanical relation between grass and cereal grains may be relevant when diagnosing food allergy to cereals. The aim was to investigate the diagnostic specificity of skin prick test (SPT) and specific immunoglobulin E (sIgE) tests to cereals and peanut in grass pollen allergic subjects without history of, and clinically reactions to foods botanically related to grass. Methods 70 subjects (41 females; mean age 32 years) and 20 healthy controls (13 females; mean age 24 years) were tested by open food challenge (OFC) with cereals and peanut. SPT and sIgE both with Immulite® (Siemens) and ImmunoCAP® (Phadia) to grass and birch pollen, cereals, peanut and bromelain were performed. Results Of the 65 OFC-negative subjects 29-46% (SPT, depending on cut-off), 20% (Immulite) and 38% (ImmunoCAP) had positive results to one or more of the foods tested. Controls were negative in all tests. Cross-reactive carbohydrate determinants (CCD) as evidenced by reaction to bromelain could explain only a minority of the measured IgE-sensitizations. Conclusion Grass pollen allergic patients with documented food tolerance to cereals and peanut may express significant sensitization. False-positive cereal or peanut allergy diagnoses may be a quantitatively important problem both in routine clinical work and epidemiological studies. PMID:22409998

Reactive perforating collagenosis associated with scabies in a diabetic.

PubMed

Brinkmeier, T; Herbst, R A; Frosch, P J

2004-09-01

Reactive perforating collagenosis (RPC) in adults commonly manifests in patients with diabetes mellitus. Pruritus and consequent induced scratching have been identified as the bases for the evolution of this skin disease. We present the unusual case of a 55-year-old female diabetic with characteristic umbilicated skin lesions and a long history of scabies. Histology from a crusty nodule revealed transepidermal elimination of collagen. Following antiscabietic treatment, two courses of oral doxycycline demonstrated beneficial effects in controlling the perforating skin disorder. Copyright 2004 European Academy of Dermatology and Venereology

[IFN-gamma enzyme-linked immunospot assay versus PPD tuberculin skin test in the diagnosis of tuberculous epididymitis].

PubMed

Huang, Hao; Yang, Xi-Fei; Deng, Qun-Yi; Li, Bing; Liu, Guo-Hui; Zhang, Jie-Yun; Yang, Da-Fei

2012-06-01

To explore the potential application of IFN-gamma enzyme-linked immunospot (ELISPOT) assay in the diagnosis of tuberculous epididymitis (TE) by comparing ELISPOT assay with the traditional purified protein derivative (PPD) tuberculin skin test. We examined 13 TE patients using an in-house ELISPOT kit, another 11 TE patients by PPD skin testing, and 57 healthy male volunteers by parallel test with both the methods. Twelve (92.3%) of the 13 TE cases were positive on ELISPOT assay, and 10 (90.9%) of the 11 TE cases positive on PPD skin test, with no statistically significant differences between the two groups (P > 0.05). Among the 57 healthy male volunteers, 8 (14.0%) were positive on ELISPOT, and 28 (49.1%) positive on PPD test, the latter significantly higher than the former (P < 0.001). In terms of sensitivity, ELISPOT assay is similar to PPD test in the examination of tuberculous epididymitis. As for specificity, ELISPOT assay seems better than PPD test in differentiating tuberculous epididymitis patients from healthy males.

Skin models for the testing of transdermal drugs

PubMed Central

Abd, Eman; Yousef, Shereen A; Pastore, Michael N; Telaprolu, Krishna; Mohammed, Yousuf H; Namjoshi, Sarika; Grice, Jeffrey E; Roberts, Michael S

2016-01-01

The assessment of percutaneous permeation of molecules is a key step in the evaluation of dermal or transdermal delivery systems. If the drugs are intended for delivery to humans, the most appropriate setting in which to do the assessment is the in vivo human. However, this may not be possible for ethical, practical, or economic reasons, particularly in the early phases of development. It is thus necessary to find alternative methods using accessible and reproducible surrogates for in vivo human skin. A range of models has been developed, including ex vivo human skin, usually obtained from cadavers or plastic surgery patients, ex vivo animal skin, and artificial or reconstructed skin models. Increasingly, largely driven by regulatory authorities and industry, there is a focus on developing standardized techniques and protocols. With this comes the need to demonstrate that the surrogate models produce results that correlate with those from in vivo human studies and that they can be used to show bioequivalence of different topical products. This review discusses the alternative skin models that have been developed as surrogates for normal and diseased skin and examines the concepts of using model systems for in vitro–in vivo correlation and the demonstration of bioequivalence. PMID:27799831

Evaluation of Food Allergy in Children by Skin Prick Tests with Commercial Extracts and Fresh Foods, Specific IgE and, Open Oral Food Challenge-Our Five Years Experience in Food Allergy Work-up.

PubMed

Zivanovic, Mirjana; Atanasković-Marković, Marina; Medjo, Biljana; Gavrović-Jankulović, Marija; Smiljanić, Katarina; Tmušić, Vladimir; Djurić, Vojislav

2017-04-01

IgE- mediated food allergy affects 6-8% of children. Our study aimed to define the correlations between the results obtained with skin prick tests (SPTs) using commercial extracts and fresh foods, and the correlations between these result and those obtained with specific IgE (sIgE) and/ or challenge. Children aged from 2 months to 6 years were recruited prospectively. Overall 571 children were positive to one food. In all children we performed  SPT using commercial extracts of suspected food and fresh foods and sIgE. If SPT and sIgE test results did not correspond to the history, we performed open oral food challenge. Sensitivity of SPT with commercial extracts for all tested food was poor (3-35%), while  sensitivity of fresh food skin prick tests (FFSPT) was excellent (50-100%), and showed correlation with open oral food challenge (p<0.001). Our results suggest that fresh food extracts are more effective in detecting sensitization and with levels of sIgE greater than class 3 could predict clinical reactivity, without the need for potentially hazardous food challenges.

[Efficacy of the treatment for latent tuberculosis infection and delayed reactivation of tuberculosis].

PubMed

Toyota, Makoto

2013-09-01

To evaluate the efficacy of treatment for latent tuberculosis infection and delayed reactivation of tuberculosis. During a large tuberculosis outbreak, 129 individuals who were in close contact with tuberculosis patients and subsequently tested strongly positive by the tuberculin skin test were followed up for 10 years after identification of the source case. Of the 129 individuals, 105 received treatment for latent tuberculosis infection for 6 months as per recommendation, while the remaining 24 did not receive treatment, because most of them were above 30 years of age and were therefore discouraged from receiving treatment, as was done in the earlier times in Japan. Of the 105 individuals, 5 (4.8%) were newly diagnosed with tuberculosis, and the average duration from identification of the source case to reactivation of tuberculosis was 53 months. Of the 24 individuals who did not receive treatment for latent tuberculosis infection, 6 (25.0%) were newly diagnosed with tuberculosis, and the average duration from identification of the source case to reactivation of tuberculosis was 8.2 months. The risk of active tuberculosis was reduced by 81.0% with treatment for latent tuberculosis infection, compared with that without treatment. Delayed reactivation of tuberculosis was observed among patients treated with isoniazid for latent tuberculosis infection for 6 months.

Intradermal skin tests for rocuronium and cisatracurium in patients with a history of allergy: a retrospective study.

PubMed

Kim, Yu Yil; Kim, Ik Thae; Shin, Sung In; Yim, So Mang

2018-04-24

Neuromuscular blocking agents (NMBAs) are a leading cause of perioperative anaphylaxis. However, the performance of systematic screening skin tests to detect reactions for NMBAs prior to general anesthesia is not recommended. We retrospectively examined intradermal tests (IDTs) for rocuronium and cisatracurium in patients with a history of allergy. We reviewed the records of patients who underwent IDTs for NMBAs between January 1 and December 31, 2016. We analyzed the patients' allergy histories and skin test results for NMBAs. The overall prevalence of positive IDTs was 5.8% (26/451), and there was no significant difference in prevalence among allergy types (P = 0.655). In logistic regression analysis, there was no allergy history that had a significant effect on positive IDT for NMBAs. We found no association between allergy history and positive skin test for NMBAs. Therefore, a systematic screening test for NMBAs or other anesthetic agents before anesthesia is not considered necessary even in patients with an allergy history.

Water immersion decreases sympathetic skin response during color–word Stroop test

PubMed Central

Yamazaki, Yudai; Takahashi, Akari; Uetake, Yoshihito; Nakano, Saki; Iguchi, Kaho; Baba, Yasuhiro; Nara, Rio; Shimoyama, Yoshimitsu

2017-01-01

Water immersion alters the autonomic nervous system (ANS) response in humans. The effect of water immersion on executive function and ANS responses related to executive function tasks was unknown. Therefore, this study aimed to determine whether water immersion alters ANS response during executive tasks. Fourteen healthy participants performed color–word-matching Stroop tasks before and after non-immersion and water immersion intervention for 15 min in separate sessions. The Stroop task-related skin conductance response (SCR) was measured during every task. In addition, the skin conductance level (SCL) and electrocardiograph signals were measured over the course of the experimental procedure. The main findings of the present study were as follows: 1) water immersion decreased the executive task-related sympathetic nervous response, but did not affect executive function as evaluated by Stroop tasks, and 2) decreased SCL induced by water immersion was maintained for at least 15 min after water immersion. In conclusion, the present results suggest that water immersion decreases the sympathetic skin response during the color–word Stroop test without altering executive performance. PMID:28742137

Water immersion decreases sympathetic skin response during color-word Stroop test.

PubMed

Sato, Daisuke; Yamazaki, Yudai; Takahashi, Akari; Uetake, Yoshihito; Nakano, Saki; Iguchi, Kaho; Baba, Yasuhiro; Nara, Rio; Shimoyama, Yoshimitsu

2017-01-01

Water immersion alters the autonomic nervous system (ANS) response in humans. The effect of water immersion on executive function and ANS responses related to executive function tasks was unknown. Therefore, this study aimed to determine whether water immersion alters ANS response during executive tasks. Fourteen healthy participants performed color-word-matching Stroop tasks before and after non-immersion and water immersion intervention for 15 min in separate sessions. The Stroop task-related skin conductance response (SCR) was measured during every task. In addition, the skin conductance level (SCL) and electrocardiograph signals were measured over the course of the experimental procedure. The main findings of the present study were as follows: 1) water immersion decreased the executive task-related sympathetic nervous response, but did not affect executive function as evaluated by Stroop tasks, and 2) decreased SCL induced by water immersion was maintained for at least 15 min after water immersion. In conclusion, the present results suggest that water immersion decreases the sympathetic skin response during the color-word Stroop test without altering executive performance.

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

PubMed

Kostal, Jakub; Voutchkova-Kostal, Adelina

2016-01-19

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

Monitoring skin microvascular dysfunction of type 1 diabetic mice using in vivo skin optical clearing

NASA Astrophysics Data System (ADS)

Feng, Wei; Shi, Rui; Zhu, Dan

2018-02-01

To monitor skin microvascular dysfunction of alloxan-induced type 1 diabetic mice model. In this work, we used laser speckle contrast imaging and hyperspectral imaging through in vivo skin optical clearing method to simultaneously monitor the noradrenaline-induced response of microvascular blood flow and blood oxygen with the development of diabetes. The main results showed that venous and arterious blood flow steadily decreased without recovery after injecting noradrenaline (NE), furthermore the influence of NE-induced arterious blood oxygen response greatly decreased, especially for 2-weeks and 4-weeks diabetic mice. This study demonstrated that skin microvascular function was a potential research biomarker for early warning in the occurrence and development of diabetes. And it provides a feasible solution to realize visualization of cutaneous microvessels for monitoring microvascular reactivity.

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.

Sweating under pressure: skin conductance level reactivity moderates the association between peer victimization and externalizing behavior.

PubMed

Gregson, Kim D; Tu, Kelly M; Erath, Stephen A

2014-01-01

This study examined whether the association between peer victimization and externalizing behavior may be illuminated by individual differences in skin conductance level reactivity (SCLR) in the context of peer stress. Participants included 123 fifth and sixth graders (Mean age = 12.03 years, 50% females; 42% ethnic minorities). SCLR was assessed in the context of an ecologically relevant, lab-based peer-evaluative stress experience in preadolescence. As hypothesized, self-reported peer victimization was linked with parent- and teacher-reported externalizing behavior, and SCLR consistently moderated these associations. Peer victimization was associated with parent- and teacher-reported externalizing behavior among preadolescents who exhibited lower SCLR, but not among preadolescents who exhibited higher SCLR. Results suggest that promoting engagement with peer stress experiences and enhancing inhibitory control are potential intervention targets that may reduce externalizing behavior in the context of peer victimization (or reduce peer victimization among preadolescents who exhibit externalizing behavior). © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

High Prevalence of Latent Tuberculosis Infection in Dialysis Patients Using the Interferon-γ Release Assay and Tuberculin Skin Test

PubMed Central

Lee, Susan Shin-Jung; Chou, Kang-Ju; Dou, Horng-Yunn; Huang, Tsi-Shu; Ni, Yen-Yun; Fang, Hua-Chang; Tsai, Hung-Chin; Sy, Cheng-Len; Chen, Jui-Kuang; Wu, Kuang-Sheng; Wang, Yung-Hsin; Lin, Hsi-Hsun

2010-01-01

Background and objectives: Patients in ESRD on hemodialysis with latent tuberculosis (TB) infection have 10 to 25 times the risk of reactivation into active disease compared with healthy adults. This study investigates the prevalence of latent TB infection in dialysis patients from a country with an intermediate burden of TB and its associated risk factors using the QuantiFERON-TB Gold in-tube test (QGIT) and the tuberculin skin test (TST). Design, setting, participants, & measurements: This was a prospective, cross-sectional study performed at a medical center in Taiwan on dialysis patients. Each patient underwent QGIT, two-step TST using 2 tuberculin units (TU) of PPD RT-23, a chest x-ray to exclude active TB, and an interview to determine TB risk factors. Results: Ninety-three of 190 eligible patients were enrolled: 35 men and 58 women. 64.8% were vaccinated with the Bacille-Calmette-Guérin (BCG) vaccination. Overall, 34.4% were positive by QGIT and 10.8% were indeterminate. Using a 10-mm TST cutoff, 53.9% were positive. There was poor correlation between TST and QGIT at any TST cutoff criteria. There was a significant increasing trend of QGIT positivity with age in those younger than 70 years, and, conversely, a decreasing trend of TST reactivity with age. Significant risk factors for QGIT positivity included age and past TB disease. Conclusions: This study shows a high prevalence of latent TB infection in dialysis patients in a country with an intermediate burden of TB. QGIT in dialysis patients correlated better than TST with the risk of TB infection and past TB disease. PMID:20538837

Generalized reactions during skin testing with clindamycin in drug hypersensitivity: a report of 3 cases and review of the literature.

PubMed

Papakonstantinou, Eleni; Müller, Sabine; Röhrbein, Jan H; Wieczorek, Dorothea; Kapp, Alexander; Jakob, Thilo; Wedi, Bettina

2018-04-01

The diagnostic approach to drug hypersensitivity includes a detailed medical history, clinical examination, and skin testing and/or oral challenge with a culprit or alternative drug, depending on the type of reaction and the suspected drugs. Although skin testing is considered to be rather safe, cutaneous and systemic, including fatal, reactions have been described. To report 3 cases with generalized delayed reactions after skin testing with clindamycin, and to review the existing literature. Thorough clinical examination, blood tests and prick, intradermal and patch tests were performed in 3 patients. All patients experienced generalized maculopapular exanthema after intradermal and patch testing with clindamycin and amoxicillin in the first patient, and clindamycin alone in the second and third patient. None of the patients showed immediate reactions to skin tests, while positive intradermal reactions after 24 h to amoxicillin and clindamycin were observed in the first patient, and positive intradermal reactions after 24 h to clindamycin were observed in the second and third patients. Skin testing with clindamycin in the diagnosis of drug hypersensitivity carries some risk of adverse reactions. A stepwise and individual diagnostic work-up, considering potential risk factors, and testing in a specialized centre with emergency equipment available is highly recommended. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The role of non-covalent protein binding in skin sensitisation potency of chemicals.

PubMed

Aleksic, Maja; Thain, Emma; Gutsell, Stephen J; Pease, Camilla K; Basketter, David A

2007-01-01

Skin sensitisation is a delayed hypersensitivity reaction caused by repeated exposure to common natural and synthetic chemical allergens. It is thought that small chemical sensitisers (haptens) are required to form a strong irreversible bond with a self protein/peptide and generate an immunogenic hapten-protein complex in order to be recognised by the immune system and stimulate T cell proliferation. The sensitisers are usually electrophilic chemicals that are directly reactive with proteins or reactive intermediates (metabolites) of chemically inert compounds (prohaptens). Sensitising chemicals are also capable of weak, non-covalent association with proteins and there is an ongoing debate about the role of weak interactions of chemicals and proteins in the chemistry of allergy. The non-covalent interactions are reversible and thus have a major impact on skin/epidermal bioavailability of chemical/reactive metabolites. We investigated the relationship between the relative level of non-covalent association to a model protein and their relative potencies as determined by the EC3 values in the murine local lymph node assay (LLNA) for a number of chemicals. Using human serum albumin as a model protein, we determined that no observable relationship exists between the two parameters for the chemicals tested. Therefore, at least for this model protein, non-covalent interactions appear not to be a key determinant of allergen potency.

Bioconvertible vitamin antioxidants improve sunscreen photoprotection against UV-induced reactive oxygen species.

PubMed

Hanson, Kerry M; Clegg, Robert M

2003-01-01

The ability of sunscreens and antioxidants to deactivate highly destructive reactive oxygen species in human skin has remained inconclusive. Two-photon fluorescence imaging microscopy was used to determine the effect of sunscreen/antioxidant combinations upon UV-induced ROS generation in ex vivo human skin. A sunscreen combination containing octylmethoxycinnamate (Parsol MCX) and avobenzone (Parsol 1789) at SPF 8 and SPF 15 was tested for its ability to prevent UV radiation from generating ROS in the viable epidermal strata of ex vivo human skin. A UV dose equivalent to two hours of North American solar UV was used to irradiate the skin. Each sunscreen reduced the amount of ROS induced in the viable strata by a value consistent with the SPF level. UV photons that were not absorbed/scattered by the sunscreen formulations generated ROS within the viable epidermal layers. The addition of the bioconvertible antioxidants vitamin E acetate and sodium ascorbyl phosphate (STAY-C 50) improves photoprotection by converting to vitamins E and C, respectively, within the skin. The bioconversion forms an antioxidant reservoir that deactivates the ROS generated (within the strata granulosum, spinosum, and basale) by the UV photons that the sunscreens do not block in the stratum corneum.

The adverse outcome pathway for skin sensitisation: Moving closer to replacing animal testing.

PubMed

Schultz, Terry W; Dimitrova, Gergana; Dimitrov, Sabcho; Mekenyan, Ovanes G

2016-10-01

This article outlines the work of the Organisation for Economic Co-operation and Development (OECD) that led to being jointly awarded the 2015 Lush Black Box Prize. The award-winning work centred on the development of 'The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins'. This Adverse Outcome Pathway (AOP) has provided the mechanistic basis for the integration of skin sensitisation-related information. Recent developments in integrated approaches to testing and assessment, based on the AOP, are summarised. The impact of the AOP on regulatory policy and on the Three Rs are discussed. An overview of the next generation of the skin sensitisation AOP module in the OECD QSAR Toolbox, based on more-recent work at the Laboratory of Mathematical Chemistry, is also presented. 2016 FRAME.

Resveratrol Prevents High Fluence Red Light-Emitting Diode Reactive Oxygen Species-Mediated Photoinhibition of Human Skin Fibroblast Migration.

PubMed

Mamalis, Andrew; Koo, Eugene; Isseroff, R Rivkah; Murphy, William; Jagdeo, Jared

2015-01-01

Skin fibrosis is a significant medical problem that leads to a functional, aesthetic, and psychosocial impact on quality-of-life. Light-emitting diode-generated 633-nm red light (LED-RL) is part of the visible light spectrum that is not known to cause DNA damage and is considered a safe, non-invasive, inexpensive, and portable potential alternative to ultraviolet phototherapy that may change the treatment paradigm of fibrotic skin disease. The goal of our study was to investigate the how reactive oxygen species (ROS) free radicals generated by high fluence LED-RL inhibit the migration of skin fibroblasts, the main cell type involved in skin fibrosis. Fibroblast migration speed is increased in skin fibrosis, and we studied cellular migration speed of cultured human skin fibroblasts as a surrogate measure of high fluence LED-RL effect on fibroblast function. To ascertain the inhibitory role of LED-RL generated ROS on migration speed, we hypothesized that resveratrol, a potent antioxidant, could prevent the photoinhibitory effects of high fluence LED-RL on fibroblast migration speed. High fluence LED-RL generated ROS were measured by flow cytometry analysis using dihydrorhodamine (DHR). For purposes of comparison, we assessed the effects of ROS generated by hydrogen peroxide (H2O2) on fibroblast migration speed and the ability of resveratrol, a well known antioxidant, to prevent LED-RL and H2O2 generated ROS-associated changes in fibroblast migration speed. To determine whether resveratrol could prevent the high fluence LED-RL ROS-mediated photoinhibition of human skin fibroblast migration, treated cells were incubated with resveratrol at concentrations of 0.0001% and 0.001% for 24 hours, irradiated with high fluences LED-RL of 480, 640, and 800 J/cm2. High fluence LED-RL increases intracellular fibroblast ROS and decreases fibroblast migration speed. LED-RL at 480, 640 and 800 J/cm2 increased ROS levels to 132.8%, 151.0%, and 158.4% relative to matched controls

Tests of Flammability of Cotton Fabrics and Expected Skin Burns in Microgravity

NASA Technical Reports Server (NTRS)

Cavanagh, Jane M.; Torvi, David A.; Gabriel, Kamiel S.; Ruff, Gary A.

2004-01-01

During a shuttle launch and other portions of space flight, astronauts wear specialized flame resistant clothing. However during most of their missions on board the Space Shuttle or International Space Station, astronauts wear ordinary clothing, such as cotton shirts and pants. As the behaviour of flames is considerably different in microgravity than under earth s gravity, fabrics are expected to burn in a different fashion in microgravity than when tested on earth. There is interest in determining how this change in burning behaviour may affect times to second and third degree burn of human skin, and how the results of standard fabric flammability tests conducted under earth s gravity correlate with the expected fire behaviour of textiles in microgravity. A new experimental apparatus was developed to fit into the Spacecraft Fire Safety Facility (SFSF), which is used on NASA s KC-135 low gravity aircraft. The new apparatus was designed to be similar to the apparatus used in standard vertical flammability tests of fabrics. However, rather than using a laboratory burner, the apparatus uses a hot wire system to ignite 200 mm high by 80 mm wide fabric specimens. Fabric temperatures are measured using thermocouples and/or an infrared imaging system, while flame spread rates are measured using real time observations or video. Heat flux gauges are placed between 7 and 13 mm away from the fabric specimen, so that heat fluxes from the burning fabric to the skin can be estimated, along with predicted times required to produce skin burns.

Estimation of the viscous properties of skin and subcutaneous tissue in uniaxial stress relaxation tests.

PubMed

Wu, John Z; Cutlip, Robert G; Welcome, Daniel; Dong, Ren G

2006-01-01

Knowledge of viscoelastic properties of soft tissues is essential for the finite element modelling of the stress/strain distributions in finger-pad during vibratory loading, which is important in exploring the mechanism of hand-arm vibration syndrome. In conventional procedures, skin and subcutaneous tissue have to be separated for testing the viscoelastic properties. In this study, a novel method has been proposed to simultaneously determine the viscoelastic properties of skin and subcutaneous tissue in uniaxial stress relaxation tests. A mathematical approach has been derived to obtain the creep and relaxation characteristics of skin and subcutaneous tissue using uniaxial stress relaxation data of skin/subcutaneous composite specimens. The micro-structures of collagen fiber networks in the soft tissue, which underline the tissue mechanical characteristics, will be intact in the proposed method. Therefore, the viscoelastic properties of soft tissues obtained using the proposed method would be more physiologically relevant than those obtained using the conventional method. The proposed approach has been utilized to measure the viscoelastic properties of soft tissues of pig. The relaxation curves of pig skin and subcutaneous tissue obtained in the current study agree well with those in literature. Using the proposed approach, reliable material properties of soft tissues can be obtained in a cost- and time-efficient manner, which simultaneously improves the physiological relevance.

Allergic contact dermatitis associated with reactive dyes in a dark garment: a case report.

PubMed

Moreau, Linda; Goossens, An

2005-09-01

In this study, we present a case of a patient who has not been occupationally exposed to reactive dyes, but did present with a dermatitis from wearing a dark cotton garment. The patient experienced reactivation of his dermatitis when rewearing a new unwashed dark T-shirt made of 100% cotton (in fact, the patient reported that it had to be washed at least 3 times before the skin reaction disappeared). He presented positive patch tests to 6 reactive dyes from Chemotechnique textile series. The clothing could not be proved as the true cause of the dermatitis, but resolution occurred upon removal of the suspected garment. This suggests that contact allergy to the reactive dyes (he did not react to any other dyes and his garment was a natural fabric) was likely responsible. With this report, we would like to emphasize that reactive dyes, as a class, should be considered as potential allergens, both occupationally and from non-occupational exposure such as garments. If garments containing reactive dyes are not properly rinsed in the manufacturing process, we believe that excess of dye can be retained that may cause allergic contact dermatitis (ACD). As the reactive dyes and their hydrolysis products are very water-soluble, they can be easily washed off to prevent ACD.

Non-animal methods to predict skin sensitization (I): the Cosmetics Europe database.

PubMed

Hoffmann, Sebastian; Kleinstreuer, Nicole; Alépée, Nathalie; Allen, David; Api, Anne Marie; Ashikaga, Takao; Clouet, Elodie; Cluzel, Magalie; Desprez, Bertrand; Gellatly, Nichola; Goebel, Carsten; Kern, Petra S; Klaric, Martina; Kühnl, Jochen; Lalko, Jon F; Martinozzi-Teissier, Silvia; Mewes, Karsten; Miyazawa, Masaaki; Parakhia, Rahul; van Vliet, Erwin; Zang, Qingda; Petersohn, Dirk

2018-05-01

Cosmetics Europe, the European Trade Association for the cosmetics and personal care industry, is conducting a multi-phase program to develop regulatory accepted, animal-free testing strategies enabling the cosmetics industry to conduct safety assessments. Based on a systematic evaluation of test methods for skin sensitization, five non-animal test methods (DPRA (Direct Peptide Reactivity Assay), KeratinoSens TM , h-CLAT (human cell line activation test), U-SENS TM , SENS-IS) were selected for inclusion in a comprehensive database of 128 substances. Existing data were compiled and completed with newly generated data, the latter amounting to one-third of all data. The database was complemented with human and local lymph node assay (LLNA) reference data, physicochemical properties and use categories, and thoroughly curated. Focused on the availability of human data, the substance selection resulted nevertheless resulted in a high diversity of chemistries in terms of physico-chemical property ranges and use categories. Predictivities of skin sensitization potential and potency, where applicable, were calculated for the LLNA as compared to human data and for the individual test methods compared to both human and LLNA reference data. In addition, various aspects of applicability of the test methods were analyzed. Due to its high level of curation, comprehensiveness, and completeness, we propose our database as a point of reference for the evaluation and development of testing strategies, as done for example in the associated work of Kleinstreuer et al. We encourage the community to use it to meet the challenge of conducting skin sensitization safety assessment without generating new animal data.

Observational, Physiological, and Self-Report Measures of Children's Anger: Relations to Reactive versus Proactive Aggression.

ERIC Educational Resources Information Center

Hubbard, Julie A.; Smithmyer, Catherine M.; Ramsden, Sally R.; Parker, Elizabeth H.; Flanagan, Kelly D.; Dearing, Karen F.; Relyea, Nicole; Simons, Robert F.

2002-01-01

This study examined relations of reactive versus proactive aggression to second-graders' anger after losing in a board game to a cheating confederate. Found that reactive aggression, but not proactive aggression, was positively related to skin conductance reactivity and observed angry nonverbal behaviors, both at an aggregated level and in terms…

Comparative Evaluation of a Silicone Membrane as an Alternative to Skin for Testing Mosquito Repellents.

PubMed

Agramonte, Natasha M; Gezan, Salvador A; Bernier, Ulrich R

2017-05-01

Repellents prevent mosquito bites and help reduce mosquito-borne disease, a global public health issue. Laboratory-based repellent bioassays predict the ability of compounds to deter mosquito feeding, but the variety of repellent bioassays and statistical analysis methods makes it difficult to compare results across methodologies. The most realistic data are collected when repellents are applied on the skin; however, this method exposes volunteers to chemicals and mosquito bites. Silicone membranes were investigated as an alternative to human skin in assays of repellent efficacy. Results from module system bioassays conducted in vitro with a silicone membrane were compared with in vivo bioassays conducted with N,N-diethyl-3-methylbenzamide (referred to as DEET), 1-piperidinecarboxylic acid 2-(2-hydroxyethyl)-1-methylpropylester (referred to as Picaridin), ethyl 3-[acetyl(butyl)amino]propanoate (referred to as IR3535), and para-menthane-3,8-diol (referred to as PMD) applied directly on the skin of the leg. No significant difference in mosquito feeding was found when comparing skin and volunteer-worn membrane controls using blood; however, feeding was significantly lower in unworn membrane controls using either 10% sucrose or blood, indicating that worn membranes are a possible surrogate for untreated human skin. Pooled data from six volunteers were used to generate dose-response curves of blood-feeding activity. Results from skin-applied repellents were modeled to determine if membranes could provide a predictive correlate for skin. Goodness-of-fit comparisons indicated that the nonlinear dose-response curves for the skin and membrane differed significantly for DEET and Picaridin, but did not differ significantly for IR3535 and PMD. With knowledge of the dose-response relationships and further modifications to this system, the membrane-based tests could be used for standardized repellent testing with infected vectors. Published by Oxford University Press on behalf

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

PubMed

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

2014-12-01

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

How Stress and Anxiety Can Alter Immediate and Late Phase Skin Test Responses in Allergic Rhinitis

PubMed Central

Kiecolt-Glaser, Janice K.; Heffner, Kathi L.; Glaser, Ronald; Malarkey, William B.; Porter, Kyle; Atkinson, Cathie; Laskowski, Bryon; Lemeshow, Stanley; Marshall, Gailen D.

2010-01-01

Summary Allergic rhinitis (AR) is the fifth most common chronic disease, and the association between allergic disorders and anxiety is well-documented. To investigate how anxiety and stressors modulate skin prick test (SPT) responses and associated inflammatory responses, 28 men and women with AR were selected by clinical history and skin test responses. The participants were admitted twice to a hospital research unit for 4 hours in a crossover trial. Changes in SPT wheals were assessed before and after a standardized laboratory speech stressor, as well as again the following morning; skin responses assessed twice during a lab session without a stressor and again the following morning served as the contrast condition. Anxiety heightened the magnitude of allergen-induced wheals following the stressor. As anxiety increased, SPT wheal diameters increased after the stressor, compared to a slight decrease following the control task. Anxiety also substantially enhanced the effects of stress on late phase responses: even skin tests performed the day after the stressor reflected the continuing impact of the speech stressor among the more anxious participants. Greater anxiety was associated with more IL-6 production by Con A-stimulated leukocytes following the stressor compared to the control visit. The data suggest that stress and anxiety can enhance and prolong AR symptoms. PMID:19150180

In vitro human skin permeation and decontamination of 2-chloroethyl ethyl sulfide (CEES) using Dermal Decontamination Gel (DDGel) and Reactive Skin Decontamination Lotion (RSDL).

PubMed

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

2018-07-01

This study compared the efficiency for in vitro human skin decontamination using DDGel and RSDL. Experiments were performed using in vitro human skin models, in which skin was mounted onto Flow-Through diffusion cells. The mass of 14 -C CEES removed from skin surface after decontamination was quantitated by measuring radioactivity with a liquid scintillation spectrometer. Both decontaminants removed more than 82% of CEES from skin. DDGel skin decontamination significantly reduced toxicant amount when compared to RSDL. Mean CEES remaining in stratum corneum (SC), viable epidermis, dermis, and systemic absorption of DDGel and RSDL were, 0.12 and 0.55% (P < 0.01), 0.31 and 0.95% (p < 0.01), 1.08 and 2.92% (p < 0.05), 3.13 and 6.34% (p < 0.05), respectively. DDGel showed higher decontamination efficiency (twice decontamination efficacy factor, DEF) than RSDL and efficiently removed chemicals from the skin surface, importantly back-extracted from the SC, and significantly reduced both chemical penetration into skin and systemic absorption. Thus, DDGel can offer a potential as a next generation skin decontamination platform technology for military and civilian applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Rapid screening method to study the reactivity of UV filter substances towards skin proteins by high-performance thin-layer chromatography.

PubMed